{
 "meta": {
  "title": "Epilepsy Board Review — High-Yield Notes",
  "source": "Original notes; ILAE 2025/2022/2021, ACNS 2021",
  "parts": 5
 },
 "parts": [
  {
   "id": "i",
   "title": "The Normal EEG",
   "pages": [
    3,
    15
   ],
   "sections": [
    {
     "id": "i-overview",
     "n": "",
     "title": "Overview",
     "blocks": [
      {
       "type": "p",
       "text": "Scope: the physiologic basis of the EEG, instrumentation and localization, normal variants and artifacts, and neonatal EEG."
      },
      {
       "type": "p",
       "text": "Original notes written for the current exam."
      },
      {
       "type": "p",
       "text": "Terminology follows ILAE 2025 (seizures), ILAE 2022 (syndromes), ACNS 2021 (EEG patterns), and ILAE 2020 medication nomenclature — antiseizure medication (ASM) , not AED."
      },
      {
       "type": "p",
       "text": "Items flagged as recently changed are where guidance or terminology has moved on. Older sources — and a lot of older teaching — still carry the previous version."
      }
     ],
     "tags": [
      "eeg-fundamentals",
      "seizure-management",
      "ilae-classification"
     ],
     "updated": false,
     "words": 77
    },
    {
     "id": "i-where-the-signal-comes-from",
     "n": "1",
     "title": "Where the Signal Comes From",
     "blocks": [
      {
       "type": "h3",
       "text": "The generator"
      },
      {
       "type": "p",
       "text": "Scalp EEG records summated excitatory and inhibitory postsynaptic potentials in the apical dendrites of cortical pyramidal neurons — not action potentials . Postsynaptic potentials last long enough (tens to hundreds of milliseconds) to summate; action potentials are too brief and asynchronous to contribute meaningfully."
      },
      {
       "type": "p",
       "text": "Three conditions must be met for cortical activity to reach the scalp:"
      },
      {
       "type": "li",
       "text": "Synchrony — thousands of neurons firing together Geometry — pyramidal neurons in layers III, V and VI aligned perpendicular to the cortical surface, forming an open field. Randomly oriented cells cancel out."
      },
      {
       "type": "li",
       "text": "Area — roughly 6 cm² of synchronously active cortex is needed to produce a recognizable scalp spike"
      },
      {
       "type": "p",
       "text": "The cortex has six horizontal layers : layer I most superficial (beneath the pia), layer IV receives thalamic input , layer VI deepest against the subcortical white matter."
      },
      {
       "type": "li",
       "text": "Why so much cortex disappears. Because a scalp spike needs ~6 cm², most interictal activity — and many seizures confined to a sulcus, the mesial temporal structures, or the insula — is invisible on scalp EEG. This single fact explains why depth electrodes exist."
      },
      {
       "type": "h3",
       "text": "Polarity and what surface negativity means"
      },
      {
       "type": "li",
       "text": "Superficial EPSPs and deep IPSPs both produce surface negativity . Superficial IPSPs and deep EPSPs both produce surface positivity. Polarity alone tells you nothing about excitation versus inhibition."
      },
      {
       "type": "li",
       "text": "Epileptic spikes are most commonly surface negative , but not exclusively. A spike generated on a sulcal wall produces a dipole parallel to the scalp and can record as surface positive;"
      },
      {
       "type": "li",
       "text": "positive discharges also appear after craniotomy and in neonates with germinal matrix hemorrhage."
      },
      {
       "type": "h3",
       "text": "Membrane biophysics"
      },
      {
       "type": "li",
       "text": "Resting membrane potential ≈ −70 mV , inside negative."
      },
      {
       "type": "li",
       "text": "The Nernst equation gives the equilibrium potential for a single ion. The Goldman– Hodgkin–Katz equation gives the resting membrane potential, because it accounts for the relative permeability of sodium, potassium and chloride together."
      },
      {
       "type": "li",
       "text": "Ion distribution: potassium higher intracellularly; sodium and chloride higher extracellularly."
      },
      {
       "type": "li",
       "text": "Voltage-gated sodium channels generate and propagate the action potential; potassium channels repolarize."
      },
      {
       "type": "li",
       "text": "A trap worth knowing. Henderson–Hasselbalch is a pH and buffer equation with no role in membrane physiology, and it turns up as a distractor on exactly this question. The answer is Goldman–Hodgkin–Katz."
      },
      {
       "type": "h3",
       "text": "The interictal spike, intracellularly"
      },
      {
       "type": "p",
       "text": "The paroxysmal depolarizing shift (PDS) is the cellular correlate of an interictal epileptiform discharge: a large, sustained membrane depolarization carrying a burst of action potentials, terminated by a prominent after-hyperpolarization . That after-hyperpolarization is generated by surrounding inhibitory interneurons — surround inhibition — and its failure is one route from an interictal spike to a seizure."
      },
      {
       "type": "h3",
       "text": "Slowing versus attenuation"
      },
      {
       "type": "li",
       "text": "Focal slowing reflects white matter disturbance — cortical deafferentation from subcortical structures."
      },
      {
       "type": "li",
       "text": "Attenuation (voltage reduction) reflects cortical disturbance, or something interposed between cortex and electrode (subdural fluid, blood)."
      },
      {
       "type": "h3",
       "text": "Fast oscillations"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — frequency bands. Current convention defines ripples at 80–250 Hz and fast ripples at 250–500 Hz ; the older figures (100–200 and >200 Hz) have been superseded. Ripples occur physiologically and pathologically; fast ripples are more specific to epileptogenic tissue . Recording them requires intracranial electrodes and a sampling rate of at least 2 kHz."
      }
     ],
     "tags": [
      "eeg-fundamentals",
      "ilae-classification",
      "epilepsy-surgery"
     ],
     "updated": true,
     "words": 510
    },
    {
     "id": "i-instrumentation-montage-and-localization",
     "n": "2",
     "title": "Instrumentation, Montage and Localization",
     "blocks": [
      {
       "type": "h3",
       "text": "The differential amplifier"
      },
      {
       "type": "p",
       "text": "Every EEG channel displays the difference in potential between two inputs . By convention, when input 1 is negative relative to input 2 , the pen deflects upward ."
      },
      {
       "type": "p",
       "text": "Common mode rejection cancels signals that arrive equally at both inputs — which is how 60 Hz line noise is removed. It fails when electrode impedances are mismatched , because the interference then arrives unequally. Impedance imbalance, not the ground electrode, is the reason 60 Hz artifact appears in a single channel."
      },
      {
       "type": "h3",
       "text": "Montages"
      },
      {
       "type": "table",
       "head": [
        "",
        "BIPOLAR (CHAINED)",
        "REFERENTIAL"
       ],
       "rows": [
        [
         "Measures",
         "Difference between adjacent electrodes",
         "Each electrode against a common reference"
        ],
        [
         "Localizes by",
         "Phase reversal",
         "Amplitude (highest at the source)"
        ],
        [
         "Strength",
         "Cancels distant/common noise; sharpens local detail",
         "Detects broad or far-field potentials; preserves true waveform"
        ],
        [
         "Weakness",
         "Misses widespread or far-field activity; can cancel a signal shared by both inputs",
         "Reference contamination"
        ]
       ]
      },
      {
       "type": "p",
       "text": "A phase reversal in a bipolar chain marks the electrode of maximum negativity (or positivity) — it is a localizing finding, not an abnormality in itself."
      },
      {
       "type": "figure",
       "n": 1,
       "src": "fig-10-20-array.png",
       "caption": "The 10–20 array. The four electrodes renamed under modified combinatorial"
      },
      {
       "type": "p",
       "text": "nomenclature are highlighted."
      },
      {
       "type": "figure",
       "n": 2,
       "src": "fig-bipolar-vs-referential.png",
       "caption": "The same left mid-temporal spike in a bipolar chain and a referential montage."
      },
      {
       "type": "h3",
       "text": "Filters"
      },
      {
       "type": "table",
       "head": [
        "FILTER",
        "ALSO CALLED",
        "EFFECT"
       ],
       "rows": [
        [
         "Low-frequency filter",
         "High-pass",
         "Removes slow activity (sweat, movement, respiration)"
        ],
        [
         "High-frequency filter",
         "Low-pass",
         "Removes fast activity (muscle)"
        ],
        [
         "Notch",
         "Band-stop",
         "Removes a narrow band — 60 Hz (50 Hz outside North America)"
        ]
       ]
      },
      {
       "type": "li",
       "text": "The time constant is the time for a capacitor to discharge to 36.8% of its initial charge; it is inversely related to the low-frequency cutoff."
      },
      {
       "type": "li",
       "text": "Filters cannot preferentially amplify epileptiform activity. They can only make it easier to see by removing competing frequencies — and aggressive filtering creates artifactual sharp transients."
      },
      {
       "type": "h3",
       "text": "Digitization"
      },
      {
       "type": "li",
       "text": "Nyquist theorem: the sampling rate must be at least twice the highest frequency of interest."
      },
      {
       "type": "li",
       "text": "Sampling below that produces aliasing — a 60 Hz sine wave sampled at 100 Hz appears as a spurious low-frequency wave."
      },
      {
       "type": "li",
       "text": "Practical rule: sample at 3–5× the high-frequency filter setting. Routine EEG at 256–512 Hz;"
      },
      {
       "type": "li",
       "text": "HFO recording needs ≥2 kHz ."
      },
      {
       "type": "li",
       "text": "An anti-aliasing (analog low-pass) filter must be applied before analog-to-digital conversion — you cannot remove aliasing after the fact."
      },
      {
       "type": "li",
       "text": "Order of the acquisition chain: differential amplification → anti-alias filtering → analog- to-digital conversion → digital filtering and display ."
      },
      {
       "type": "h3",
       "text": "Electrodes and safety"
      },
      {
       "type": "li",
       "text": "Electrode nomenclature: RECENTLY CHANGED modified combinatorial nomenclature replaced the old labels — T3/T4 → T7/T8 , T5/T6 → P7/P8 . Older figures and question stems still use the legacy names."
      },
      {
       "type": "li",
       "text": "10–20 system: inter-electrode distance is 10% or 20% of the measured skull distance; average ~6 cm in adults."
      },
      {
       "type": "li",
       "text": "Electrode material is typically chloride-treated silver (Ag/AgCl) ; a properly applied electrode shows a resistance of a few hundred ohms."
      },
      {
       "type": "li",
       "text": "Impedance: keep below ~5 kΩ for routine recording (and above 100 Ω, since near-zero impedance suggests a salt bridge). For electrocerebral inactivity protocols, ACNS specifies 100–10,000 Ω ."
      },
      {
       "type": "li",
       "text": "Electrical safety: minimize leakage current, keep cords short, use a single common ground per patient, and use a three-pronged hospital-grade outlet. Grounding the patient through appliances increases the risk of electrocution — it does not reduce it."
      },
      {
       "type": "h3",
       "text": "Recording for suspected electrocerebral inactivity (ACNS)"
      },
      {
       "type": "p",
       "text": "Minimum 8 scalp electrodes with ear reference; inter-electrode distances ≥10 cm; sensitivity increased to 2 µV/mm; recording at least 30 minutes; reactivity to pain, sound and light must be tested ; and system integrity documented."
      }
     ],
     "tags": [
      "eeg-fundamentals",
      "acns-terminology"
     ],
     "updated": true,
     "words": 531
    },
    {
     "id": "i-normal-variants-and-artifacts",
     "n": "3",
     "title": "Normal Variants and Artifacts",
     "blocks": [
      {
       "type": "p",
       "text": "RECENTLY CHANGED Terminology. ACNS now prefers \"normal variant\" over \"benign variant\" — \"benign\" implies a clinical judgement the waveform itself does not carry."
      },
      {
       "type": "h3",
       "text": "Variants that get mistaken for epileptiform activity"
      },
      {
       "type": "table",
       "head": [
        "VARIANT",
        "RECOGNITION"
       ],
       "rows": [
        [
         "Mu rhythm",
         "Central (rolandic) arciform 7–11 Hz; attenuates with contralateral movement or thought of movement; asymmetric and asynchronous"
        ],
        [
         "Lambda waves",
         "Occipital positive sharp transients, awake with eyes open , evoked by scanning a patterned field; disappear with eye closure"
        ],
        [
         "POSTS",
         "Positive occipital sharp transients of sleep — the sleep counterpart of lambda"
        ],
        [
         "Wicket spikes",
         "Temporal, arciform 6–11 Hz, drowsiness; no after-going slow wave, no background disruption"
        ],
        [
         "Rhythmic mid-temporal theta of drowsiness (RMTD)",
         "5–7 Hz notched/flat-topped trains, temporal, drowsiness; formerly \"psychomotor variant\""
        ],
        [
         "Small sharp spikes (BETS)",
         "Low amplitude (<50 µV), very brief (<50 ms), mono/diphasic, no after- going slow wave , light sleep, often bilateral; vanish in deep sleep"
        ],
        [
         "6 Hz phantom spike-wave",
         "Very low-amplitude spike with 6 Hz wave, brief bursts"
        ],
        [
         "14 & 6 Hz positive bursts",
         "Posterior temporal, adolescents, drowsiness"
        ],
        [
         "SREDA",
         "Subclinical rhythmic electrographic discharge of adults — sudden rhythmic theta, usually >40 years, no clinical correlate , no postictal slowing"
        ],
        [
         "Breach rhythm",
         "Higher-amplitude, sharply contoured activity over a skull defect — a craniotomy sign, not epileptiform"
        ],
        [
         "Hypnagogic hypersynchrony",
         "High-voltage rhythmic 3–5 Hz in drowsy young children — normal"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The three questions that separate a spike from a variant: does it have an after-going slow wave, does it disrupt the background, and does it have a plausible physiologic field?"
      },
      {
       "type": "h3",
       "text": "Artifacts"
      },
      {
       "type": "li",
       "text": "Lateral rectus spike — a brief spike at F7 or F8 at the onset of horizontal eye movement, immediately followed by the eye-movement deflection. The cornea is a positive dipole: on looking left, the cornea approaches F7, producing positivity there."
      },
      {
       "type": "li",
       "text": "Blink (Bell phenomenon) — the eyes roll up, producing frontal positivity at Fp1/Fp2."
      },
      {
       "type": "li",
       "text": "Chewing/myogenic — rhythmic high-frequency muscle over temporalis; glossokinetic artifact is slower (the tongue is also a dipole)."
      },
      {
       "type": "li",
       "text": "ECG and pulse — time-locked to the QRS; pulse artifact is a slow wave following it by ~200 ms, usually one electrode over an artery."
      },
      {
       "type": "li",
       "text": "Electrode pop — abrupt vertical transient confined to a single electrode, with no field."
      },
      {
       "type": "li",
       "text": "Sweat — very slow (<0.5 Hz) undulations."
      },
      {
       "type": "h3",
       "text": "Maturation of the normal EEG"
      },
      {
       "type": "table",
       "head": [
        "AGE",
        "LANDMARK"
       ],
       "rows": [
        [
         "~2 months (6–8 weeks)",
         "Sleep spindles appear — asynchronous until ~2 years"
        ],
        [
         "~4 months",
         "Posterior dominant rhythm ~4 Hz"
        ],
        [
         "~1 year",
         "PDR ~6 Hz"
        ],
        [
         "~3 years",
         "PDR ~8 Hz"
        ],
        [
         "~8 years onward",
         "Adult PDR 8–13 Hz"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Sleep spindles are generated by the thalamus , paced by the reticular nucleus, and are the first sign of EEG synchronization in early sleep."
      }
     ],
     "tags": [
      "eeg-fundamentals",
      "acns-terminology",
      "ilae-classification"
     ],
     "updated": true,
     "words": 430
    },
    {
     "id": "i-neonatal-eeg-and-neonatal-seizures",
     "n": "4",
     "title": "Neonatal EEG and Neonatal Seizures",
     "blocks": [
      {
       "type": "h3",
       "text": "Normal patterns by conceptional age"
      },
      {
       "type": "table",
       "head": [
        "PATTERN",
        "AGE WINDOW"
       ],
       "rows": [
        [
         "Tracé discontinu",
         "<30 weeks — bursts of mixed frequency separated by long attenuations"
        ],
        [
         "Delta brushes",
         "Appear ~26 weeks, peak 32–34 weeks , largely gone by term"
        ],
        [
         "Temporal theta (\"sawtooth\")",
         "~26–32 weeks"
        ],
        [
         "Encoches frontales (frontal sharp transients)",
         "34–46 weeks , peak ~35 weeks; blunt, biphasic , symmetric and synchronous , normal in transitional sleep"
        ],
        [
         "Tracé alternant",
         "Term quiet sleep — bursts alternating with lower-voltage (not flat) interburst intervals"
        ],
        [
         "Continuity",
         "Continuous by term in wakefulness and active sleep"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Maturational changes appear first in active sleep , then wakefulness (~2 weeks later), then quiet sleep."
      },
      {
       "type": "p",
       "text": "Multifocal sharp transients in a premature infant are usually a nonspecific marker of cerebral dysfunction , not evidence of epileptogenicity — the opposite of how they are read in adults."
      },
      {
       "type": "p",
       "text": "A 60-minute recording is the recommended minimum, long enough to sample a full sleep–wake cycle."
      },
      {
       "type": "figure",
       "n": 3,
       "src": "fig-neonatal-patterns.png",
       "caption": "Normal neonatal EEG patterns by conceptional age."
      },
      {
       "type": "h3",
       "text": "Neonatal seizures"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — the ILAE 2021 neonatal classification. Neonates are now classified separately from the main seizure framework, and the change is fundamental:"
      },
      {
       "type": "li",
       "text": "EEG confirmation is required. Because most neonatal seizures are electrographic-only or have unreliable clinical correlates, the diagnosis is defined electrographically."
      },
      {
       "type": "li",
       "text": "Seizure types relevant to this age: automatisms, autonomic, clonic, epileptic spasms, myoclonic, sequential, tonic , and electrographic-only ."
      },
      {
       "type": "li",
       "text": "The old category of \"subtle seizures\" is gone; events without an EEG correlate should not be called seizures."
      },
      {
       "type": "p",
       "text": "Other essentials:"
      },
      {
       "type": "li",
       "text": "Hypoxic-ischemic encephalopathy is the most common cause in term neonates. Others:"
      },
      {
       "type": "li",
       "text": "stroke, intracranial hemorrhage, infection, metabolic derangement, inborn errors, and genetic channelopathies."
      },
      {
       "type": "li",
       "text": "Ictal discharges most often arise in the central region, then temporal. They are typically focal or multifocal — the immature brain does not readily generalize."
      },
      {
       "type": "li",
       "text": "Electroclinical uncoupling — after an ASM is given, clinical signs disappear while electrographic seizures persist. This is why continuous EEG must continue after treatment."
      },
      {
       "type": "li",
       "text": "Benign familial neonatal epilepsy (now self-limited neonatal epilepsy) — KCNQ2/KCNQ3 potassium channel mutations, day 2–8 onset, normal development, good outcome."
      },
      {
       "type": "li",
       "text": "Pyridoxine-dependent epilepsy (ALDH7A1) — refractory neonatal seizures that stop within minutes of IV pyridoxine. Give it with EEG running and be ready for apnea and hypotension."
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — treatment. The ILAE 2023 neonatal seizure guideline recommends phenobarbital as first-line , on the strength of head-to-head data (including NEOLEV2, where phenobarbital outperformed levetiracetam), with the important caveat that it be used for the shortest duration possible and discontinued early in acute provoked seizures."
      },
      {
       "type": "p",
       "text": "Second-line options are phenytoin, levetiracetam, midazolam or lidocaine."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management",
      "epilepsy-surgery"
     ],
     "updated": true,
     "words": 405
    },
    {
     "id": "i-technical-standards-and-recording-practice",
     "n": "5",
     "title": "Technical Standards and Recording Practice",
     "blocks": [
      {
       "type": "h3",
       "text": "Display conventions"
      },
      {
       "type": "table",
       "head": [
        "PARAMETER",
        "STANDARD"
       ],
       "rows": [
        [
         "Sensitivity (gain)",
         "7 µV/mm routine; 2 µV/mm for suspected electrocerebral inactivity"
        ],
        [
         "Paper speed / time base",
         "30 mm/s (10 s per page); 15 mm/s for neonates and long-term review"
        ],
        [
         "Low-frequency filter",
         "1 Hz (time constant 0.16 s)"
        ],
        [
         "High-frequency filter",
         "70 Hz"
        ],
        [
         "Notch",
         "60 Hz — use sparingly; it hides impedance problems rather than fixing them"
        ],
        [
         "Sampling rate",
         "≥3× the HFF; ≥2 kHz for high-frequency oscillations"
        ],
        [
         "Recording duration",
         "≥20 min of technically satisfactory recording; ≥30 min for ECI protocol; 60 min for neonates"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Supplementary electrodes"
      },
      {
       "type": "p",
       "text": "The 10–20 array under-samples the inferomesial temporal region. Options:"
      },
      {
       "type": "li",
       "text": "T1/T2 (anterior temporal) — simple surface electrodes, modest gain 10–10 (modified combinatorial) inferior chain: F9/F10, T9/T10, P9/P10 — now the preferred non-invasive approach; better yield than T1/T2 and no discomfort Sphenoidal electrodes — inserted below the zygomatic arch toward the foramen ovale;"
      },
      {
       "type": "li",
       "text": "higher yield for mesial temporal spikes but invasive and largely superseded by the inferior 10– 10 chain Nasopharyngeal electrodes — obsolete; poorly tolerated and artifact-prone"
      },
      {
       "type": "h3",
       "text": "Activation procedures"
      },
      {
       "type": "li",
       "text": "Hyperventilation — 3–5 minutes, ideally with the patient supine and eyes closed. Physiologic buildup is normal in children and resolves within a minute of stopping. Contraindicated in sickle cell disease or trait, recent stroke or TIA, moyamoya, significant cardiopulmonary disease, and raised intracranial pressure. Enhanced by hypoglycaemia;"
      },
      {
       "type": "li",
       "text": "blunted by older age and by having eaten."
      },
      {
       "type": "li",
       "text": "Photic stimulation — flash frequencies typically 1–30 Hz in ascending and descending trains, eyes open and closed. Eye closure (the first 1–2 seconds) is the most provocative moment."
      },
      {
       "type": "li",
       "text": "Sleep deprivation — increases yield independently of the sleep it produces."
      },
      {
       "type": "li",
       "text": "Response testing during any event is the single most valuable thing the technologist does;"
      },
      {
       "type": "li",
       "text": "without it, awareness cannot be assessed retrospectively."
      },
      {
       "type": "h3",
       "text": "More artifacts"
      },
      {
       "type": "table",
       "head": [
        "ARTIFACT",
        "RECOGNITION"
       ],
       "rows": [
        [
         "Photoelectric",
         "Sharp transients time-locked to the photic flash, from light striking the electrode — vanishes when the electrode is covered"
        ],
        [
         "Salt bridge",
         "Conductive paste bridging two electrodes — a channel becomes flat or near-isoelectric with abnormally low impedance"
        ],
        [
         "Dissimilar metals",
         "Two electrode types in one array create a battery effect and slow drift"
        ],
        [
         "Bruxism",
         "Rhythmic high-frequency temporal muscle bursts during sleep"
        ],
        [
         "Ventilator",
         "Rhythmic slow waves at the respiratory rate, often widespread — check the rate against the ventilator"
        ],
        [
         "IV drip / bed percussion",
         "Regular sharp transients at a mechanical frequency, no physiologic field"
        ],
        [
         "Fluid collection",
         "Focal attenuation from subdural fluid or blood interposed between cortex and electrode"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Sleep architecture"
      },
      {
       "type": "p",
       "text": "Vertex sharp waves (Cz maximal) and K complexes with spindles define N2; POSTS appear in N1–N2. Slow-wave sleep is high-voltage delta. REM shows a desynchronized low-voltage mixed- frequency background with sawtooth waves and no spindles. Sleep activates focal epileptiform discharges — NREM increases spike frequency and field; REM restricts the field and is the most localizing state."
      },
      {
       "type": "h3",
       "text": "Age-related normal findings not to over-read"
      },
      {
       "type": "li",
       "text": "Posterior slow waves of youth — 2.5–4.5 Hz slow waves intermixed with the posterior rhythm in children and adolescents, attenuating with eye opening Alpha variants — slow alpha variant (half the alpha frequency) and fast alpha variant (double); both react like alpha Squeak phenomenon — a transient rise in alpha frequency on eye closure Alpha asymmetry — up to ~50% higher amplitude on the right is normal; a frequency asymmetry of >1 Hz is not Midline theta (Ciganek) rhythm — rhythmic Cz theta during drowsiness Elderly — benign temporal theta/delta slowing, mild alpha slowing (but a posterior rhythm below 8 Hz is abnormal at any adult age)"
      },
      {
       "type": "h3",
       "text": "Electrocerebral inactivity and brain death"
      },
      {
       "type": "p",
       "text": "The EEG is ancillary , never the diagnosis. Brain death is a clinical determination — irreversible coma of known cause, absent brainstem reflexes, and apnea testing — with confounders (hypothermia, sedatives, neuromuscular blockade, severe metabolic or endocrine derangement, hypotension) excluded first. ECI requires the full ACNS technical protocol: ≥8 electrodes, inter- electrode distance ≥10 cm, impedance 100–10,000 Ω, sensitivity 2 µV/mm, ≥30 minutes, documented absence of reactivity to intense somatosensory, auditory and visual stimulation , and demonstration of system integrity."
      }
     ],
     "tags": [
      "eeg-fundamentals",
      "acns-terminology"
     ],
     "updated": false,
     "words": 654
    }
   ],
   "selftest": [
    {
     "q": "Roughly how much synchronously active cortex is needed to produce a scalp spike, and what follows from that number?",
     "a": "About 6 cm² . It follows that sulcal, mesial temporal and insular activity is often invisible on scalp EEG — the reason intracranial recording exists.",
     "section": "i-where-the-signal-comes-from",
     "match": 3.73
    },
    {
     "q": "Which equation gives the resting membrane potential, and which gives the equilibrium potential for one ion?",
     "a": "Goldman–Hodgkin–Katz for resting membrane potential (it weights sodium, potassium and chloride permeability); Nernst for a single ion's equilibrium potential.",
     "section": "i-where-the-signal-comes-from",
     "match": 4.51
    },
    {
     "q": "A 60 Hz sine wave is sampled at 100 Hz. What happens, and what prevents it?",
     "a": "Aliasing — the signal is misrepresented as a spurious lower frequency. An analog anti-aliasing low-pass filter applied before digitization prevents it; nothing can fix it afterwards.",
     "section": "i-instrumentation-montage-and-localization",
     "match": 3.53
    },
    {
     "q": "Name three features that distinguish small sharp spikes from a true epileptiform discharge.",
     "a": "Amplitude <50 µV, duration <50 ms, no after-going slow wave (also: no background disruption, disappear in deep sleep, often bilateral).",
     "section": "i-normal-variants-and-artifacts",
     "match": 3.96
    },
    {
     "q": "What are the current frequency bands for ripples and fast ripples, and which is more specific for epileptogenic tissue?",
     "a": "Ripples 80–250 Hz , fast ripples 250–500 Hz ; fast ripples are the more specific biomarker.",
     "section": "i-where-the-signal-comes-from",
     "match": 3.71
    },
    {
     "q": "Under the ILAE 2021 neonatal classification, what is required before an event can be called a seizure?",
     "a": "An electrographic correlate on EEG. Clinical events without an EEG correlate are no longer classified as neonatal seizures.",
     "section": "i-neonatal-eeg-and-neonatal-seizures",
     "match": 3.54
    }
   ]
  },
  {
   "id": "ii",
   "title": "The Abnormal EEG",
   "pages": [
    16,
    27
   ],
   "sections": [
    {
     "id": "ii-interictal-epileptiform-discharges",
     "n": "1",
     "title": "Interictal Epileptiform Discharges",
     "blocks": [
      {
       "type": "h3",
       "text": "Definitions"
      },
      {
       "type": "li",
       "text": "Spike: 20–70 ms. Sharp wave: 70–200 ms. The distinction is duration only and has no clinical significance on its own."
      },
      {
       "type": "li",
       "text": "A genuine epileptiform discharge has an after-going slow wave , disrupts the background , stands out from ongoing activity, and has a physiologic electrical field across several electrodes."
      },
      {
       "type": "h3",
       "text": "What location predicts"
      },
      {
       "type": "p",
       "text": "The clinical weight of a discharge depends heavily on where it sits:"
      },
      {
       "type": "li",
       "text": "Anterior temporal spikes — roughly 90% of children with them have seizures Centrotemporal (rolandic) spikes — only about 40% have seizures; the classic mismatch between an alarming EEG and a mild syndrome Generalized 3 Hz spike-wave — even brief, subclinical bursts cause transient cognitive impairment , which is why \"just a few discharges\" is not reassuring in a child struggling at school Multifocal discharges — associated with encephalopathy, and with both cognitive and motor deficits"
      },
      {
       "type": "p",
       "text": "Epileptiform discharges appear in roughly 2–4% of healthy children and a smaller fraction of healthy adults, so an isolated discharge in an asymptomatic child is not a diagnosis of epilepsy."
      },
      {
       "type": "p",
       "text": "Yield of the first routine EEG in people who have epilepsy is roughly 30–50%; sleep deprivation, repeat studies and prolonged recording raise it substantially."
      }
     ],
     "tags": [
      "ilae-classification"
     ],
     "updated": false,
     "words": 196
    },
    {
     "id": "ii-ictal-eeg",
     "n": "2",
     "title": "Ictal EEG",
     "blocks": [
      {
       "type": "h3",
       "text": "The defining feature is evolution"
      },
      {
       "type": "p",
       "text": "An electrographic seizure is recognized by evolution — a progressive change in frequency, morphology, amplitude, or spatial field . A monomorphic, unchanging rhythm is not a seizure."
      },
      {
       "type": "p",
       "text": "This is the single most useful discriminator against artifact and against rhythmic patterns of encephalopathy."
      },
      {
       "type": "h3",
       "text": "Onset patterns"
      },
      {
       "type": "li",
       "text": "Low-voltage fast activity (LVFA) at onset is the hallmark of the true seizure-onset zone and correlates with better surgical outcome when resected."
      },
      {
       "type": "li",
       "text": "Other onset patterns: electrodecrement, rhythmic spiking, and a burst of high-amplitude polyspikes."
      },
      {
       "type": "li",
       "text": "Onset involving many contacts simultaneously, clinical onset preceding EEG onset, or focal slowing without evolution all suggest you are recording propagated rather than onset activity."
      },
      {
       "type": "h3",
       "text": "Scalp ictal patterns worth memorizing"
      },
      {
       "type": "li",
       "text": "Rhythmic 5–7 Hz theta over the temporal region evolving within 30 seconds predicts mesial temporal onset with high reliability."
      },
      {
       "type": "li",
       "text": "Seizures without alteration of awareness show a scalp ictal correlate only about 20% of the time — rising to roughly a third if there are motor phenomena, falling further if purely subjective. A normal ictal scalp EEG never excludes a focal aware seizure."
      },
      {
       "type": "li",
       "text": "Postictal slowing and postictal aphasia are localizing; postictal aphasia points to the dominant temporal lobe."
      },
      {
       "type": "figure",
       "n": 6,
       "src": "fig-ilae-2025-classification.png",
       "caption": "The ILAE 2025 seizure classification and its two classifiers."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "acns-terminology",
      "eeg-fundamentals"
     ],
     "updated": false,
     "words": 192
    },
    {
     "id": "ii-generalized-epilepsies",
     "n": "3",
     "title": "Generalized Epilepsies",
     "blocks": [
      {
       "type": "h3",
       "text": "EEG signatures"
      },
      {
       "type": "table",
       "head": [
        "PATTERN",
        "FREQUENCY",
        "SYNDROME"
       ],
       "rows": [
        [
         "Generalized spike-wave",
         "3 Hz , abrupt onset and offset, normal background",
         "Childhood/juvenile absence epilepsy"
        ],
        [
         "Generalized polyspike-wave",
         "4–6 Hz",
         "Juvenile myoclonic epilepsy"
        ],
        [
         "Slow spike-wave",
         "1–2.5 Hz , activated by sleep, abnormal background",
         "Lennox–Gastaut syndrome"
        ],
        [
         "Generalized paroxysmal fast activity (GPFA)",
         "~10–20 Hz bursts, mostly in NREM sleep",
         "Tonic seizures of Lennox– Gastaut"
        ],
        [
         "Hypsarrhythmia",
         "Chaotic high-voltage delta with multifocal spikes",
         "Infantile epileptic spasms syndrome"
        ],
        [
         "Electrodecrement",
         "Abrupt generalized attenuation",
         "Epileptic spasms; tonic seizures"
        ]
       ]
      },
      {
       "type": "p",
       "text": "In idiopathic generalized epilepsy the background is normal — an abnormal background argues for a developmental and epileptic encephalopathy instead."
      },
      {
       "type": "h3",
       "text": "Activating procedures"
      },
      {
       "type": "li",
       "text": "Hyperventilation — activates absence seizures reliably; produces physiologic buildup (slowing) in children that must not be over-read. Enhanced by hypoglycemia ; diminished by older age. Contraindicated in sickle cell disease, recent stroke, significant cardiopulmonary disease, and moyamoya."
      },
      {
       "type": "li",
       "text": "Photic stimulation — a photoparoxysmal (photoconvulsive) response is generalized spike- wave, a cortical and epileptic phenomenon. A photomyogenic (photomyoclonic) response is time-locked frontal muscle activity that increases with flash frequency and stops when stimulation stops — it reflects anxiety, arousal or alcohol/sedative withdrawal , not epilepsy."
      },
      {
       "type": "li",
       "text": "Photosensitivity is most common in juvenile myoclonic epilepsy (~30%) and in eyelid myoclonia with absences."
      },
      {
       "type": "h3",
       "text": "Semiology pitfalls"
      },
      {
       "type": "li",
       "text": "Asymmetric or focal features at the onset of a myoclonic or tonic-clonic seizure do not exclude a genetic generalized epilepsy."
      },
      {
       "type": "li",
       "text": "Eyelid myoclonia with absences (Jeavons) — eye-closure sensitivity plus photosensitivity, often refractory."
      },
      {
       "type": "li",
       "text": "Epilepsy with myoclonic-atonic seizures (EMAtS , formerly Doose) — normal development then drop attacks; strong family history of generalized epilepsy."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management",
      "eeg-fundamentals"
     ],
     "updated": false,
     "words": 250
    },
    {
     "id": "ii-focal-epilepsy-semiology-to-localization",
     "n": "4",
     "title": "Focal Epilepsy — Semiology to Localization",
     "blocks": [
      {
       "type": "h3",
       "text": "Auras by lobe"
      },
      {
       "type": "table",
       "head": [
        "AURA",
        "LOCALIZATION"
       ],
       "rows": [
        [
         "Epigastric rising",
         "Mesial temporal (limbic) — ~90% specific for temporal lobe"
        ],
        [
         "Fear, déjà vu, olfactory",
         "Mesial temporal (amygdala, uncus)"
        ],
        [
         "Auditory",
         "Lateral temporal (Heschl's gyrus) — think LGI1/ADEAF if familial"
        ],
        [
         "Vertiginous",
         "Temporo-parietal junction; more often extratemporal"
        ],
        [
         "Simple visual (flashes, colours, geometric)",
         "Occipital"
        ],
        [
         "Complex visual (formed scenes, faces)",
         "Temporo-occipital association cortex"
        ],
        [
         "Somatosensory",
         "Parietal (postcentral)"
        ],
        [
         "Throat constriction, hypersalivation, viscerosensory",
         "Insula — frequently mimics temporal or even gastroenterologic disease"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Lateralizing signs"
      },
      {
       "type": "table",
       "head": [
        "SIGN",
        "SIDE"
       ],
       "rows": [
        [
         "Dystonic posturing of a limb",
         "Contralateral to seizure onset"
        ],
        [
         "Manual automatisms",
         "Ipsilateral"
        ],
        [
         "Postictal nose-wiping (hand used)",
         "Ipsilateral"
        ],
        [
         "Versive head turn (forced, sustained, unnatural)",
         "Contralateral"
        ],
        [
         "Postictal aphasia",
         "Dominant hemisphere"
        ],
        [
         "Preserved ictal speech",
         "Non-dominant"
        ],
        [
         "Ictal vomiting/emesis",
         "Non-dominant (usually right) temporal"
        ],
        [
         "Ictal piloerection",
         "Temporal, more often left"
        ],
        [
         "Unilateral eye blinking",
         "Ipsilateral"
        ],
        [
         "Figure-of-4 sign (extended arm)",
         "Extended arm contralateral"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The classic combination — ipsilateral automatisms with contralateral dystonic posturing — localizes with high confidence."
      },
      {
       "type": "h3",
       "text": "Regional signatures"
      },
      {
       "type": "li",
       "text": "Mesial temporal: epigastric aura, motionless stare, oroalimentary then manual automatisms, gradual onset, postictal confusion, no early clonic activity . Slow evolution, longer duration (1–2 min)."
      },
      {
       "type": "li",
       "text": "Lateral (neocortical) temporal: auditory or vertiginous aura, earlier contralateral clonic activity , faster spread."
      },
      {
       "type": "li",
       "text": "Frontal: brief, frequent, nocturnal, clustered, hypermotor with bicycling or pelvic thrusting, minimal postictal confusion, rapid recovery — commonly mistaken for parasomnia or functional seizures. Nocturnal enuresis is not a frontal feature."
      },
      {
       "type": "li",
       "text": "Dorsolateral frontal convexity: forced head and eye turning, unilateral clonic activity, preserved consciousness; not olfactory hallucinations."
      },
      {
       "type": "li",
       "text": "Supplementary motor area: asymmetric tonic posturing (fencer), preserved awareness, vocalization."
      },
      {
       "type": "li",
       "text": "Cingulate/ventral prefrontal: hypermotor seizures with prominent fearful facial expression ."
      },
      {
       "type": "li",
       "text": "Parietal: somatosensory aura, distortion of body image, vertigo; prominent autonomic features are not typical — those point to insula."
      },
      {
       "type": "li",
       "text": "Occipital: elementary visual hallucinations, ictal blindness, forced eye deviation, eyelid flutter."
      },
      {
       "type": "li",
       "text": "Complex visual hallucinations arise at the temporo-occipital junction, not primary visual cortex."
      },
      {
       "type": "li",
       "text": "Insular: laryngeal constriction, dysphonia, hypersalivation, unpleasant somatosensory or gustatory sensations, preserved awareness — but contralateral head version is not an insular aura ."
      }
     ],
     "tags": [
      "acns-terminology"
     ],
     "updated": false,
     "words": 323
    },
    {
     "id": "ii-status-epilepticus",
     "n": "5",
     "title": "Status Epilepticus",
     "blocks": [
      {
       "type": "p",
       "text": "Covered in full in Part IV, section 7 — definitions, the receptor-trafficking basis of pharmacoresistance, and the ESETT-era treatment sequence. What belongs here is the electrographic side."
      },
      {
       "type": "h3",
       "text": "EEG in status"
      },
      {
       "type": "li",
       "text": "Nonconvulsive status is found in roughly 20% of ICU patients with unexplained altered mental status who undergo continuous EEG — and in most of them the seizures are exclusively nonconvulsive ."
      },
      {
       "type": "li",
       "text": "48 hours of continuous monitoring captures the large majority of seizures in comatose patients (24 hours is usually adequate in non-comatose patients)."
      },
      {
       "type": "li",
       "text": "Treatment target in refractory status: seizure suppression, or burst-suppression, guided by continuous EEG. Optimal burst-suppression parameters have never been established; an interburst interval on the order of 5–10 seconds is commonly used."
      },
      {
       "type": "li",
       "text": "MRI during or after status may show reversible T2/FLAIR and diffusion hyperintensity — at the focus, and remotely in the ipsilateral pulvinar , contralateral cerebellum , and splenium . Recognizing this prevents a mistaken diagnosis of stroke or encephalitis."
      },
      {
       "type": "li",
       "text": "Metabolic consequences: lactic acidosis (never alkalosis), hyperthermia, hypoglycemia after an initial hyperglycemia, hyperkalemia, rhabdomyolysis, acute kidney injury, neurogenic pulmonary edema, DIC."
      }
     ],
     "tags": [
      "seizure-management",
      "acns-terminology"
     ],
     "updated": false,
     "words": 177
    },
    {
     "id": "ii-encephalopathy-coma-and-the-icu",
     "n": "6",
     "title": "Encephalopathy, Coma and the ICU",
     "blocks": [
      {
       "type": "h3",
       "text": "ACNS 2021 nomenclature — the biggest change in this chapter"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED The old \"epileptiform\" periodic labels are gone:"
      },
      {
       "type": "table",
       "head": [
        "LEGACY",
        "CURRENT"
       ],
       "rows": [
        [
         "PLEDs",
         "LPDs — lateralized periodic discharges"
        ],
        [
         "BIPLEDs",
         "BIPDs — bilateral independent periodic discharges"
        ],
        [
         "GPEDs",
         "GPDs — generalized periodic discharges"
        ],
        [
         "Triphasic waves",
         "GPDs with triphasic morphology (± anterior–posterior lag)"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The word epileptiform was removed deliberately: these patterns sit on an ictal–interictal continuum and describing them should not presuppose that they are ictal."
      },
      {
       "type": "p",
       "text": "Other ACNS main terms: LRDA (lateralized rhythmic delta activity), GRDA (generalized rhythmic delta activity), SIRPIDs (stimulus-induced rhythmic, periodic or ictal discharges)."
      },
      {
       "type": "p",
       "text": "\"Plus\" modifiers (+F fast, +R rhythmic, +S sharp) mark superimposed features that raise the probability a pattern is ictal."
      },
      {
       "type": "figure",
       "n": 7,
       "src": "fig-acns-2021-naming.png",
       "caption": "How ACNS 2021 pattern names are built, and which patterns carry seizure risk."
      },
      {
       "type": "h3",
       "text": "Which patterns predict seizures"
      },
      {
       "type": "li",
       "text": "LPDs at any frequency , LRDA , BIPDs , and GPDs with plus features all carry increased seizure risk."
      },
      {
       "type": "li",
       "text": "GRDA — including frontally predominant GRDA (the old FIRDA) — does not. It is a nonspecific marker of encephalopathy or deep structural pathology."
      },
      {
       "type": "li",
       "text": "FIRDA correlates with toxic-metabolic disturbance and structural lesions, not with epilepsy."
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — the 2HELPS2B score. Seizure risk over the next 24 hours can be quantified from the first hour of EEG. One point each for: any rhythmic or periodic pattern >2 Hz (excluding GRDA), plus features , sporadic epileptiform discharges , LPDs / LRDA / BIPDs , and a prior clinical seizure — and two points for BIRDs (brief potentially ictal rhythmic discharges). Range 0–7."
      },
      {
       "type": "table",
       "head": [
        "SCORE",
        "RISK",
        "MONITORING"
       ],
       "rows": [
        [
         "0",
         "<5%",
         "~1 hour may suffice"
        ],
        [
         "1",
         "~12%",
         "~12 hours"
        ],
        [
         "≥2",
         "25% to >80%",
         "≥24 hours"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Triphasic morphology"
      },
      {
       "type": "p",
       "text": "Classically metabolic — hepatic and renal failure — but not specific . Also seen with lithium toxicity, other toxic-metabolic states, hyponatremia, white matter disease, and neurodegenerative disease. Features favouring a metabolic (rather than ictal) reading: anterior-to-posterior lag , frontal predominance, and reactivity to stimulation. Improvement after a benzodiazepine trial is suggestive of a nonconvulsive seizure but is confounded by the sedative effect on the background."
      },
      {
       "type": "h3",
       "text": "Coma patterns and prognosis"
      },
      {
       "type": "table",
       "head": [
        "PATTERN",
        "SIGNIFICANCE"
       ],
       "rows": [
        [
         "Burst-suppression",
         "Bursts of mixed-frequency high-voltage activity alternating with suppression <10 µV. Anoxia, deep anesthesia, hypothermia, severe encephalopathy. Identical, highly epileptiform bursts after cardiac arrest is a highly malignant pattern"
        ],
        [
         "Alpha coma",
         "Widespread nonreactive alpha; overall mortality ~75%; worst with anoxia and brainstem infarction"
        ],
        [
         "Spindle coma",
         "Sleep-like spindles in coma; generally better prognosis, often after trauma or drug effect"
        ],
        [
         "Electrocerebral inactivity",
         "No activity >2 µV with the ACNS technical protocol satisfied"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Post-cardiac-arrest prognostication rests on multiple modalities — EEG background continuity and reactivity, absent N20 SSEPs, neuron-specific enolase, and imaging — never EEG alone, and never before the effects of sedation and hypothermia have cleared."
      },
      {
       "type": "h3",
       "text": "A few situation-specific patterns"
      },
      {
       "type": "li",
       "text": "Carotid endarterectomy — intraoperative EEG that stays symmetric after clamping means a shunt can be avoided ; shunting itself carries a several-fold increase in embolic risk."
      },
      {
       "type": "li",
       "text": "Dialysis — hemodialysis increases seizure risk (dysequilibrium syndrome); peritoneal dialysis does not . Chronic dialysis encephalopathy is now rare."
      },
      {
       "type": "li",
       "text": "Celiac disease — bilateral occipital calcifications with occipital seizures (CEC syndrome)."
      },
      {
       "type": "li",
       "text": "Nonketotic hyperglycemia — focal motor seizures or epilepsia partialis continua, often refractory to ASMs until the glucose is corrected."
      }
     ],
     "tags": [
      "acns-terminology",
      "ilae-classification",
      "epilepsy-surgery"
     ],
     "updated": true,
     "words": 515
    },
    {
     "id": "ii-periodic-patterns-by-etiology",
     "n": "7",
     "title": "Periodic Patterns by Etiology",
     "blocks": [
      {
       "type": "p",
       "text": "Periodicity itself is nonspecific, but the interval narrows the differential sharply:"
      },
      {
       "type": "table",
       "head": [
        "PATTERN",
        "INTERVAL",
        "SETTING"
       ],
       "rows": [
        [
         "LPDs over the temporal region",
         "~1–2 s",
         "Herpes simplex encephalitis — with fever, aphasia and temporal T2 change, this is the classic triad. Also stroke, tumor, abscess"
        ],
        [
         "Generalized periodic sharp waves",
         "~1 Hz (0.5–2 s) , often with startle myoclonus",
         "Creutzfeldt–Jakob disease ; appears as the illness progresses, and disappears in terminal stages and in sleep"
        ],
        [
         "Long-interval periodic complexes",
         "4–15 s , high amplitude, stereotyped, with time-locked myoclonic jerks",
         "SSPE (subacute sclerosing panencephalitis)"
        ],
        [
         "GPDs, often with identical epileptiform bursts",
         "variable",
         "Post-anoxic injury — a highly malignant pattern"
        ],
        [
         "Bilateral independent PDs (BIPDs)",
         "",
         "Bilateral structural disease, anoxia, CNS infection; worse prognosis than unilateral LPDs"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Metabolic patterns: hepatic encephalopathy progresses from alpha slowing → theta → GPDs with triphasic morphology → delta → suppression, roughly paralleling clinical stage. Uremia adds prominent triphasic activity and, with dialysis, the dysequilibrium syndrome ."
      },
      {
       "type": "p",
       "text": "Drug and treatment effects: benzodiazepines and barbiturates produce enhanced beta ;"
      },
      {
       "type": "p",
       "text": "therapeutic hypothermia slows the background and can produce burst-suppression independent of injury — a critical confounder when prognosticating after cardiac arrest."
      }
     ],
     "tags": [
      "acns-terminology",
      "ilae-classification",
      "epilepsy-surgery"
     ],
     "updated": false,
     "words": 187
    },
    {
     "id": "ii-birds-and-the-ictal-interictal-continuum",
     "n": "8",
     "title": "BIRDs and the Ictal–Interictal Continuum",
     "blocks": [
      {
       "type": "p",
       "text": "BIRDs — brief potentially ictal rhythmic discharges. Focal or generalized rhythmic activity >4 Hz lasting <10 seconds (too brief to be a seizure by definition) without clinical correlate."
      },
      {
       "type": "p",
       "text": "They carry a high association with seizures and are worth two points on the 2HELPS2B score — the heaviest single item."
      },
      {
       "type": "p",
       "text": "The ictal–interictal continuum is the grey zone where a periodic or rhythmic pattern is neither clearly ictal nor clearly interictal — typically GPDs or LPDs at 1–2.5 Hz, or with plus features. Practical approach:"
      },
      {
       "type": "li",
       "text": "Look for evolution — if present it is a seizure, not a continuum pattern."
      },
      {
       "type": "li",
       "text": "Weigh plus features and frequency; faster and sharper leans ictal."
      },
      {
       "type": "li",
       "text": "Consider a benzodiazepine trial : resolution of the pattern with clinical improvement supports an ictal interpretation. Resolution of the pattern with background suppression and no clinical change proves nothing."
      },
      {
       "type": "li",
       "text": "Correlate with imaging, lactate, and clinical trajectory; treat the patient, not the tracing."
      }
     ],
     "tags": [
      "acns-terminology"
     ],
     "updated": false,
     "words": 154
    },
    {
     "id": "ii-focal-motor-status-todd-paralysis-and-other-status",
     "n": "9",
     "title": "Focal Motor Status, Todd Paralysis and Other Status",
     "blocks": [
      {
       "type": "h3",
       "text": "Subtypes"
      },
      {
       "type": "li",
       "text": "Epilepsia partialis continua — continuous focal motor jerking, often for days, with preserved consciousness. Causes: Rasmussen encephalitis (children), nonketotic hyperglycemia , stroke, tumor, mitochondrial disease (MELAS, POLG). Notoriously ASM-refractory; treat the cause."
      },
      {
       "type": "li",
       "text": "Todd paralysis — postictal focal deficit (usually weakness, sometimes aphasia or hemianopia) lasting minutes to ~48 hours. Mimics stroke; the discriminator is a preceding seizure and gradual resolution."
      },
      {
       "type": "li",
       "text": "Tonic status epilepticus — a hazard in Lennox–Gastaut, where intravenous benzodiazepines can precipitate or worsen tonic seizures . A specific and testable exception to benzodiazepine-first management."
      },
      {
       "type": "li",
       "text": "Absence status — prolonged confusional state with continuous or near-continuous generalized spike-wave; may be precipitated in genetic generalized epilepsy by carbamazepine or by benzodiazepine withdrawal . Highly responsive to IV benzodiazepine."
      },
      {
       "type": "li",
       "text": "Febrile status epilepticus — see Part III."
      },
      {
       "type": "li",
       "text": "Refractory status = failure of a benzodiazepine plus one second-line agent. Super-refractory = continuing or recurring 24 hours or more after the start of anesthesia, including on weaning. Consider NORSE/FIRES , autoimmune and paraneoplastic causes, and the ketogenic diet."
      },
      {
       "type": "h3",
       "text": "Quantitative EEG and trending"
      },
      {
       "type": "p",
       "text": "Compressed spectral arrays, amplitude-integrated EEG, rhythmicity spectrograms and seizure- detection trends let a reviewer scan hours quickly. They are a screening adjunct : every flagged event must be confirmed on the raw tracing, and aEEG in neonates misses brief and focal seizures."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 218
    }
   ],
   "selftest": [
    {
     "q": "What single feature distinguishes an electrographic seizure from a rhythmic pattern of encephalopathy?",
     "a": "Evolution — progressive change in frequency, morphology, amplitude or field.",
     "section": "ii-ictal-eeg",
     "match": 3.36
    },
    {
     "q": "Give the current ACNS terms for PLEDs, GPEDs and triphasic waves.",
     "a": "LPDs , GPDs , and GPDs with triphasic morphology . \"Epileptiform\" was dropped because these patterns lie on the ictal–interictal continuum.",
     "section": "ii-encephalopathy-coma-and-the-icu",
     "match": 4.05
    },
    {
     "q": "Which rhythmic ICU pattern is not associated with increased seizure risk?",
     "a": "GRDA , including frontally predominant GRDA (the old FIRDA) — a nonspecific encephalopathy marker.",
     "section": "ii-encephalopathy-coma-and-the-icu",
     "match": 4.01
    },
    {
     "q": "Which EEG onset pattern best marks the true seizure-onset zone?",
     "a": "Low-voltage fast activity.",
     "section": "ii-ictal-eeg",
     "match": 2.77
    },
    {
     "q": "A patient has ipsilateral hand automatisms and contralateral dystonic posturing. Which is which, and what does the pair tell you?",
     "a": "Automatisms are ipsilateral to the onset; dystonic posturing is contralateral . Together they localize with high confidence — the dystonic limb is opposite the seizure.",
     "section": "ii-focal-epilepsy-semiology-to-localization",
     "match": 3.08
    },
    {
     "q": "On the 2HELPS2B score, which single finding is worth two points?",
     "a": "BIRDs — brief potentially ictal rhythmic discharges.",
     "section": "ii-birds-and-the-ictal-interictal-continuum",
     "match": 3.33
    }
   ]
  },
  {
   "id": "iii",
   "title": "Epilepsy Syndromes and Genetics",
   "pages": [
    28,
    43
   ],
   "sections": [
    {
     "id": "iii-the-2022-framework-read-this-first",
     "n": "1",
     "title": "The 2022 Framework — Read This First",
     "blocks": [
      {
       "type": "p",
       "text": "RECENTLY CHANGED. The ILAE published a complete syndrome classification in 2022, across four position papers (neonatal/infantile, childhood, variable age, and idiopathic generalized epilepsies). Almost every syndrome name in the previous classification has changed. Three principles drive it:"
      },
      {
       "type": "li",
       "text": "\"Benign\" is gone , replaced by self-limited (likely to remit spontaneously) and pharmacoresponsive . \"Malignant\" and \"catastrophic\" were removed entirely."
      },
      {
       "type": "li",
       "text": "Epileptic encephalopathy → developmental and epileptic encephalopathy (DEE) where both the underlying cause and the epileptic activity contribute to impairment. Where only the epileptic activity is responsible, \"epileptic encephalopathy\" alone still applies."
      },
      {
       "type": "li",
       "text": "Syndromes are defined by age at onset , then by seizure types, EEG, imaging and genetics."
      },
      {
       "type": "h3",
       "text": "The rename table"
      },
      {
       "type": "table",
       "head": [
        "LEGACY NAME",
        "CURRENT NAME"
       ],
       "rows": [
        [
         "Benign familial neonatal seizures",
         "Self-limited neonatal epilepsy (SeLNE)"
        ],
        [
         "Benign familial infantile epilepsy",
         "Self-limited infantile epilepsy (SeLIE)"
        ],
        [
         "Ohtahara syndrome / early myoclonic encephalopathy",
         "Early infantile DEE (EIDEE) — the two merged"
        ],
        [
         "West syndrome / infantile spasms",
         "Infantile epileptic spasms syndrome (IESS)"
        ],
        [
         "Severe myoclonic epilepsy of infancy",
         "Dravet syndrome (unchanged)"
        ],
        [
         "Benign/childhood epilepsy with centrotemporal spikes; benign rolandic",
         "Self-limited epilepsy with centrotemporal spikes (SeLECTS)"
        ],
        [
         "Panayiotopoulos syndrome",
         "Self-limited epilepsy with autonomic seizures (SeLEAS)"
        ],
        [
         "Gastaut-type late-onset occipital epilepsy",
         "Childhood occipital visual epilepsy (COVE)"
        ],
        [
         "Doose / myoclonic-astatic epilepsy",
         "Epilepsy with myoclonic-atonic seizures (EMAtS)"
        ],
        [
         "CSWS / Landau–Kleffner",
         "DEE-SWAS and EE-SWAS (spike-wave activation in sleep)"
        ],
        [
         "Epilepsy with GTCs on awakening",
         "Epilepsy with generalized tonic-clonic seizures alone (GTCA)"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The four idiopathic generalized epilepsies — and the only place \"idiopathic\" survives — are childhood absence epilepsy (CAE) , juvenile absence epilepsy (JAE) , juvenile myoclonic epilepsy (JME) , and GTCA ."
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED IESS no longer requires the full triad. Spasms plus either hypsarrhythmia or developmental arrest is enough — because hypsarrhythmia and regression may not be present at onset, and waiting for them delays treatment."
      },
      {
       "type": "figure",
       "n": 8,
       "src": "fig-syndromes-by-age.png",
       "caption": "Epilepsy syndromes by age at onset, under ILAE 2022 names."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": true,
     "words": 295
    },
    {
     "id": "iii-syndromes-by-age",
     "n": "2",
     "title": "Syndromes by Age",
     "blocks": [
      {
       "type": "h3",
       "text": "Neonatal and infantile"
      },
      {
       "type": "table",
       "head": [
        "SYNDROME",
        "KEY FEATURES"
       ],
       "rows": [
        [
         "SeLNE",
         "KCNQ2/KCNQ3; onset days 2–8; normal development; excellent outcome"
        ],
        [
         "SeLIE",
         "PRRT2 ; clusters of focal seizures at 3–20 months; normal development; the same gene causes paroxysmal kinesigenic dyskinesia and hemiplegic migraine in the family"
        ],
        [
         "EIDEE",
         "Onset first weeks; tonic spasms; burst-suppression ; structural or genetic (STXBP1, KCNQ2, SCN2A, ARX); poor prognosis"
        ],
        [
         "IESS",
         "Peak 4–8 months; epileptic spasms in clusters; hypsarrhythmia ; ~75% have an identifiable cause. Vigabatrin first-line if tuberous sclerosis , otherwise hormonal therapy (ACTH or high-dose prednisolone) ± vigabatrin"
        ],
        [
         "Dravet syndrome",
         "SCN1A loss-of-function in >80% ; onset ~5–15 months with prolonged febrile hemiclonic seizures, then myoclonic, atypical absence and focal seizures with developmental slowing after year one. Avoid sodium channel blockers — carbamazepine, oxcarbazepine, lamotrigine, phenytoin all worsen it"
        ],
        [
         "EIMFS",
         "Epilepsy of infancy with migrating focal seizures — KCNT1"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Childhood"
      },
      {
       "type": "table",
       "head": [
        "SYNDROME",
        "KEY FEATURES"
       ],
       "rows": [
        [
         "SeLECTS",
         "15% of childhood epilepsy. Nocturnal hemifacial motor seizures, speech arrest, drooling, secondary spread. Centrotemporal spikes with a horizontal dipole , markedly activated by sleep. Remits by mid-adolescence; most have <5 lifetime seizures. Treatment is optional. Associated with reading and language-based learning difficulty"
        ],
        [
         "SeLEAS",
         "Age 3–6. Prolonged nocturnal autonomic seizures — vomiting, pallor, then eye deviation and unresponsiveness. Occipital spikes, but the EEG is variable. Often a single event; treatment usually unnecessary"
        ],
        [
         "COVE",
         "Elementary visual hallucinations, ictal blindness, postictal migraine; occipital spikes with fixation-off sensitivity"
        ],
        [
         "CAE",
         "Age 4–10, 3 Hz spike-wave provoked by hyperventilation, OIRDA is supportive. Ethosuximide first-line. ADHD is a common comorbidity"
        ],
        [
         "EMAtS",
         "Normal development, then myoclonic-atonic drop attacks age 2–6; family history of generalized epilepsy in 15–30%; ketogenic diet often effective"
        ],
        [
         "Lennox– Gastaut",
         "Multiple seizure types (tonic, atonic, atypical absence), slow spike-wave <2.5 Hz , GPFA in sleep, intellectual impairment. ~70% have a structural or metabolic cause; 10–25% evolve from IESS"
        ],
        [
         "DEE-SWAS / EE-SWAS",
         "Spike-wave activation in ≥85% of NREM sleep with cognitive or language regression. The Landau–Kleffner phenotype is acquired auditory agnosia . Avoid carbamazepine; use valproate, benzodiazepines, or steroids"
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Variable age"
      },
      {
       "type": "li",
       "text": "Familial focal epilepsy with variable foci — DEPDC5 , NPRL2, NPRL3 (GATOR1 complex, mTOR pathway); strongly associated with focal cortical dysplasia and with SUDEP."
      },
      {
       "type": "li",
       "text": "Sleep-related hypermotor epilepsy (SHE , formerly ADNFLE) — CHRNA4, CHRNB2, CHRNA2 nicotinic acetylcholine receptor subunits, also KCNT1 and DEPDC5 . Clusters of brief nocturnal hypermotor seizures with preserved awareness; routinely misdiagnosed as parasomnia."
      },
      {
       "type": "li",
       "text": "Autosomal dominant epilepsy with auditory features (ADEAF) — LGI1 ; auditory aura, sometimes distorted speech."
      },
      {
       "type": "li",
       "text": "Genetic epilepsy with febrile seizures plus (GEFS+) — SCN1A, SCN1B, GABRG2; a family spectrum from simple febrile seizures to Dravet."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management",
      "eeg-fundamentals"
     ],
     "updated": false,
     "words": 422
    },
    {
     "id": "iii-genetics",
     "n": "3",
     "title": "Genetics",
     "blocks": [
      {
       "type": "h3",
       "text": "What causes what"
      },
      {
       "type": "table",
       "head": [
        "GENE",
        "PHENOTYPE"
       ],
       "rows": [
        [
         "SCN1A",
         "Dravet (loss of function), GEFS+"
        ],
        [
         "SCN2A / SCN8A",
         "Gain-of-function → early-onset DEE, responds to sodium channel blockers ; loss-of- function → later onset, avoid them"
        ],
        [
         "KCNQ2 / KCNQ3",
         "SeLNE; KCNQ2 also causes a severe DEE"
        ],
        [
         "PCDH19",
         "X-linked, affects heterozygous girls and spares hemizygous boys (cellular interference); fever-sensitive seizure clusters"
        ],
        [
         "STXBP1, CDKL5, ARX",
         "Early DEEs. CDKL5 has an approved therapy (ganaxolone)"
        ],
        [
         "KCNT1",
         "EIMFS; sleep-related hypermotor epilepsy"
        ],
        [
         "DEPDC5 / NPRL2 / NPRL3",
         "Familial focal epilepsy, FCD, mTOR pathway"
        ],
        [
         "CHRNA4 / B2 / A2",
         "Sleep-related hypermotor epilepsy"
        ],
        [
         "LGI1",
         "ADEAF (and, as an autoantibody target, limbic encephalitis)"
        ],
        [
         "TSC1 / TSC2",
         "Tuberous sclerosis complex"
        ],
        [
         "SLC2A1",
         "GLUT1 deficiency — early-onset absence, movement disorder, low CSF glucose"
        ],
        [
         "ALDH7A1",
         "Pyridoxine-dependent epilepsy"
        ],
        [
         "POLG",
         "Alpers–Huttenlocher — valproate causes fatal hepatic failure"
        ],
        [
         "MECP2",
         "Rett syndrome"
        ],
        [
         "GLRA1",
         "Hyperekplexia (stiff baby syndrome)"
        ],
        [
         "CSTB",
         "Unverricht–Lundborg progressive myoclonus epilepsy"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Inheritance traps: ADEAF/LGI1, SeLNE, SeLIE, SHE and familial focal epilepsy are all autosomal dominant . Sialidosis and most other progressive myoclonus epilepsies are autosomal recessive . PCDH19 is X-linked with an inverted sex pattern."
      },
      {
       "type": "h3",
       "text": "Recently changed — how to test"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED The ILAE Genetics Commission now recommends offering genetic testing to everyone with unexplained epilepsy, regardless of age . Testing strategy has shifted decisively toward broad sequencing:"
      },
      {
       "type": "table",
       "head": [
        "TEST",
        "DIAGNOSTIC YIELD"
       ],
       "rows": [
        [
         "Genome sequencing",
         "~48%"
        ],
        [
         "Exome sequencing",
         "~24%"
        ],
        [
         "Multigene panel (>25 genes)",
         "~20%"
        ],
        [
         "Multigene panel (<25 genes)",
         "~7%"
        ],
        [
         "Chromosomal microarray",
         "~9%"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Exome or genome sequencing is preferred as first-tier , with panels reserved for a clearly defined syndrome or where cost and coverage make sequencing impractical."
      },
      {
       "type": "h3",
       "text": "Why the result matters — precision therapy"
      },
      {
       "type": "li",
       "text": "GLUT1 deficiency → ketogenic diet Tuberous sclerosis → vigabatrin for spasms; everolimus for refractory focal seizures SCN1A/Dravet → avoid sodium channel blockers; use valproate, clobazam, stiripentol, cannabidiol, fenfluramine SCN2A/SCN8A gain-of-function → sodium channel blockers (often high-dose phenytoin) CDKL5 deficiency → ganaxolone Pyridoxine-dependent (ALDH7A1) → pyridoxine, lifelong POLG → avoid valproate absolutely"
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": true,
     "words": 314
    },
    {
     "id": "iii-imitators-of-epilepsy",
     "n": "4",
     "title": "Imitators of Epilepsy",
     "blocks": [
      {
       "type": "table",
       "head": [
        "IMITATOR",
        "DISCRIMINATING FEATURES"
       ],
       "rows": [
        [
         "Convulsive syncope",
         "Prodromal lightheadedness, pallor, tunnel vision, tinnitus; triggered by standing, heat, pain; brief (<15 s) irregular jerks after the collapse; rapid reorientation. Treat with salt and water, not ASMs"
        ],
        [
         "Functional (dissociative) seizures",
         "Forced eye closure with resistance to opening is the strongest single sign. Also: side-to-side head movement, asynchronous out-of-phase limb movements, pelvic thrusting, waxing and waning, long duration, ictal crying, memory for the event. Arising from confirmed EEG sleep effectively excludes them"
        ],
        [
         "Parasomnias / confusional arousal",
         "First third of the night, out of slow-wave sleep, variable and non-stereotyped, infrequent, amnestic. Contrast with sleep-related hypermotor epilepsy: brief, stereotyped, clustered, many per night"
        ],
        [
         "Paroxysmal kinesigenic dyskinesia",
         "Movement-triggered, no loss of awareness, PRRT2 , exquisitely responsive to carbamazepine"
        ],
        [
         "Sandifer syndrome",
         "Infant with reflux; arching and stiffening after feeds; treat the reflux"
        ],
        [
         "Hyperekplexia",
         "Neonatal stiffness with exaggerated startle, nose-tap reflex; GLRA1 glycine receptor; responds to clonazepam"
        ],
        [
         "Benign myoclonus of infancy",
         "Clusters of jerks, normal development, normal ictal EEG — observation, not ACTH"
        ],
        [
         "Breath-holding spells",
         "Provoked by crying or anger; cyanotic or pale (the pale type is reflex asystolic)"
        ],
        [
         "REM sleep behaviour disorder",
         "Older adults, dream enactment in the last third of the night; a prodrome of Parkinson disease and synucleinopathy"
        ],
        [
         "Migraine with aura",
         "Slow march over minutes (versus seconds for a seizure), positive then negative phenomena, headache"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Laboratory adjuncts. Serum prolactin rises and peaks 10–20 minutes after a convulsive or focal impaired-awareness seizure, then falls — so it must be drawn early. It has reasonable specificity but poor sensitivity, and syncope also raises it , so it cannot separate seizure from syncope. Creatine kinase rises later (6–12 h) and is more specific but also insensitive. Lateral tongue biting favours an epileptic seizure."
      },
      {
       "type": "p",
       "text": "Outcome in functional seizures. Better: male sex, shorter duration of illness, independent living, absence of psychiatric comorbidity, normal neuropsychological testing. Worse: long illness duration, personality disorder, ongoing litigation. Never discharge these patients from care — deliver the diagnosis clearly and hand off to psychiatry, CBT and neuropsychology."
      }
     ],
     "tags": [
      "ilae-classification"
     ],
     "updated": false,
     "words": 333
    },
    {
     "id": "iii-epilepsy-from-specific-mechanisms",
     "n": "5",
     "title": "Epilepsy from Specific Mechanisms",
     "blocks": [
      {
       "type": "h3",
       "text": "Post-traumatic"
      },
      {
       "type": "li",
       "text": "Early seizures (<7 days) are provoked; late seizures (>7 days) essentially define post- traumatic epilepsy, with a high recurrence risk."
      },
      {
       "type": "li",
       "text": "Risk factors: severity of injury, penetrating trauma, depressed skull fracture , intracranial hematoma, early seizures, prolonged post-traumatic amnesia, and family history of epilepsy ."
      },
      {
       "type": "li",
       "text": "Prophylaxis with phenytoin or levetiracetam for the first 7 days reduces early seizures only. No ASM prevents epileptogenesis — treating early seizures does not lower the risk of later epilepsy."
      },
      {
       "type": "li",
       "text": "Risk declines with time from injury but stays elevated for well over a decade."
      },
      {
       "type": "h3",
       "text": "Post-stroke"
      },
      {
       "type": "li",
       "text": "Stroke is the most common identifiable cause of epilepsy after 60."
      },
      {
       "type": "li",
       "text": "Hemorrhagic and cortical strokes carry higher risk than deep or lacunar ones; large infarcts and early seizures predict epilepsy."
      },
      {
       "type": "li",
       "text": "Pediatric stroke presents with seizures far more often than adult stroke and has a higher rate of subsequent epilepsy."
      },
      {
       "type": "h3",
       "text": "Tumors"
      },
      {
       "type": "li",
       "text": "Low-grade, slow-growing tumors are the most epileptogenic. DNET has nearly a 100% association with seizures , followed by ganglioglioma. High-grade tumors such as glioblastoma present with seizures much less often."
      },
      {
       "type": "li",
       "text": "Metastases are the most common neoplastic cause of new-onset seizures in older adults."
      },
      {
       "type": "li",
       "text": "No prophylaxis before a first seizure (AAN guideline); treat after one occurs, and consider perioperative prophylaxis around craniotomy."
      },
      {
       "type": "h3",
       "text": "Infection and immune"
      },
      {
       "type": "li",
       "text": "Neurocysticercosis is the leading cause of acquired epilepsy worldwide — multiple cystic lesions in varying stages; treat with albendazole plus corticosteroids, with an ASM."
      },
      {
       "type": "li",
       "text": "Autoimmune causes are covered in Part IV, section 5 ."
      },
      {
       "type": "h3",
       "text": "Metabolic and other"
      },
      {
       "type": "li",
       "text": "Nonketotic hyperglycemia → focal motor seizures, often refractory until glucose is corrected."
      },
      {
       "type": "li",
       "text": "Hyponatremia, hypoglycemia, hypocalcemia, hypomagnesemia — correct the derangement first."
      },
      {
       "type": "li",
       "text": "Isoniazid competes with pyridoxine and causes refractory seizures — the antidote is high-dose pyridoxine."
      },
      {
       "type": "li",
       "text": "Celiac disease → bilateral occipital calcifications and occipital seizures."
      },
      {
       "type": "li",
       "text": "Whipple disease → diarrhoea, weight loss, arthropathy, oculomasticatory myorhythmia."
      },
      {
       "type": "li",
       "text": "Hypothalamic hamartoma → gelastic seizures ; sporadic, or part of Pallister–Hall syndrome (GLI3) ."
      },
      {
       "type": "li",
       "text": "Septo-optic dysplasia → optic nerve hypoplasia, absent septum pellucidum, and hypopituitarism — check cortisol ."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": false,
     "words": 327
    },
    {
     "id": "iii-febrile-seizures",
     "n": "6",
     "title": "Febrile Seizures",
     "blocks": [
      {
       "type": "p",
       "text": "The single most common seizure disorder of childhood — 2–5% of children — and a reliable exam topic."
      },
      {
       "type": "table",
       "head": [
        "",
        "SIMPLE",
        "COMPLEX"
       ],
       "rows": [
        [
         "Duration",
         "<15 min",
         "≥15 min"
        ],
        [
         "Type",
         "Generalized",
         "Focal features"
        ],
        [
         "Number in 24 h",
         "One",
         "More than one"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Age window 6 months to 5 years, with fever and without CNS infection, metabolic derangement, or prior afebrile seizure."
      },
      {
       "type": "li",
       "text": "Recurrence of febrile seizures ~30% overall. Risk rises with younger age at first seizure (<12–18 months) , lower peak temperature , shorter fever-to-seizure interval , and family history of febrile seizures . Frequency of febrile illnesses also correlates."
      },
      {
       "type": "li",
       "text": "Risk of later epilepsy: ~1–2% after simple febrile seizures — barely above the general population. It rises with complex features , family history of epilepsy , pre-existing neurodevelopmental abnormality , and febrile status epilepticus ."
      },
      {
       "type": "li",
       "text": "Workup: lumbar puncture if meningeal signs, or in an infant under 6–12 months where examination is unreliable or immunization status is incomplete. Neither EEG nor neuroimaging is indicated after a simple febrile seizure."
      },
      {
       "type": "li",
       "text": "Treatment: none. Continuous prophylaxis is not justified — the risks outweigh a benefit that does not include preventing epilepsy. Antipyretics do not prevent recurrence. Intermittent benzodiazepine at fever onset works but is rarely worth the sedation."
      },
      {
       "type": "li",
       "text": "Febrile status epilepticus (FEBSTAT) is the exception: prolonged febrile seizures are associated with acute hippocampal T2 signal change and later hippocampal sclerosis. An abnormality on MRI is the strongest predictor of subsequent problems."
      },
      {
       "type": "li",
       "text": "Genetics: GEFS+ (SCN1A, SCN1B, GABRG2) spans simple febrile seizures to Dravet within one family."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 247
    },
    {
     "id": "iii-neurocutaneous-and-chromosomal-disorders",
     "n": "7",
     "title": "Neurocutaneous and Chromosomal Disorders",
     "blocks": [
      {
       "type": "h3",
       "text": "Neurocutaneous"
      },
      {
       "type": "table",
       "head": [
        "SYNDROME",
        "SKIN",
        "NEUROLOGIC",
        "EPILEPSY NOTES"
       ],
       "rows": [
        [
         "Tuberous sclerosis (TSC1/TSC2)",
         "Hypopigmented ash- leaf macules (Wood lamp), shagreen patch, facial angiofibroma, ungual fibroma",
         "Cortical tubers, subependymal nodules, SEGA , cardiac rhabdomyoma, renal angiomyolipoma",
         "Presents with infantile epileptic spasms . Vigabatrin is first-line for spasms here. Everolimus for refractory focal seizures. AMT-PET distinguishes epileptogenic from silent tubers"
        ],
        [
         "Sturge-Weber",
         "Port-wine stain in V1 distribution",
         "Leptomeningeal angioma, \"tram-track\" gyriform calcification , hemiatrophy, glaucoma",
         "Early refractory focal seizures, hemiparesis, stroke-like episodes; hemispherotomy for unilateral disease. Sporadic — somatic GNAQ mutation"
        ],
        [
         "Neurofibromatosis 1",
         "Café-au-lait macules , axillary freckling, neurofibromas, Lisch nodules",
         "Optic pathway glioma, T2 hyperintensities",
         "Seizures in ~5%; look for a structural cause"
        ],
        [
         "Incontinentia pigmenti (IKBKG)",
         "Vesicular → verrucous → hyperpigmented whorls along Blaschko lines",
         "X-linked dominant, lethal in males ; neonatal seizures, stroke-like lesions",
         ""
        ],
        [
         "Hypomelanosis of Ito",
         "Hypopigmented whorls",
         "Hemimegalencephaly, cortical dysplasia",
         ""
        ],
        [
         "Ataxia- telangiectasia (ATM)",
         "Oculocutaneous telangiectasia",
         "Cerebellar ataxia, immunodeficiency, malignancy risk, elevated AFP",
         ""
        ]
       ]
      },
      {
       "type": "h3",
       "text": "Chromosomal and imprinting disorders"
      },
      {
       "type": "table",
       "head": [
        "DISORDER",
        "RECOGNITION"
       ],
       "rows": [
        [
         "Angelman syndrome",
         "Maternal 15q11-q13 deletion (~70%), also maternal UPD, imprinting defect, or UBE3A mutation. Happy demeanour with inappropriate laughter, ataxic gait, microcephaly, absent speech, prominent jaw and wide-spaced teeth. EEG: high-amplitude rhythmic 2–3 Hz \"notched delta\" , often with posterior discharges on eye closure"
        ],
        [
         "Prader-Willi",
         "Paternal 15q11-q13 deletion — hypotonia, hyperphagia; seizures uncommon"
        ],
        [
         "Ring chromosome 20",
         "Refractory frontal-type seizures, prolonged nonconvulsive status with confusion , terrifying nocturnal events; EEG shows long runs of frontally dominant slow waves with spikes. Mosaic — needs karyotype, not microarray"
        ],
        [
         "Down syndrome (trisomy 21)",
         "Bimodal: infantile spasms in infancy, late-onset myoclonic epilepsy with Alzheimer pathology in adulthood"
        ],
        [
         "Fragile X (FMR1)",
         "Centrotemporal-spike-like EEG; seizures in ~15%"
        ],
        [
         "Wolf-Hirschhorn (4p−)",
         "\"Greek warrior helmet\" facies; seizures often triggered by fever, atypical absences"
        ],
        [
         "Miller-Dieker (17p13.3)",
         "Lissencephaly with facial dysmorphism — contiguous gene deletion including LIS1"
        ]
       ]
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management",
      "acns-terminology"
     ],
     "updated": false,
     "words": 294
    },
    {
     "id": "iii-progressive-myoclonus-epilepsies",
     "n": "8",
     "title": "Progressive Myoclonus Epilepsies",
     "blocks": [
      {
       "type": "p",
       "text": "Suspect a PME when myoclonus, generalized seizures, and progressive cognitive and cerebellar decline occur together — the combination that separates it from juvenile myoclonic epilepsy, where cognition and gait stay normal."
      },
      {
       "type": "table",
       "head": [
        "DISEASE",
        "GENE / DEFECT",
        "DISTINGUISHING FEATURE"
       ],
       "rows": [
        [
         "Unverricht- Lundborg (EPM1)",
         "CSTB dodecamer repeat expansion",
         "Baltic myoclonus; the most benign PME, near-normal lifespan; severe stimulus-sensitive myoclonus"
        ],
        [
         "Lafora disease (EPM2)",
         "EPM2A (laforin) / NHLRC1 (malin)",
         "Adolescent onset, occipital seizures with visual hallucinations and blindness , rapid dementia, death within ~10 years. Periodic acid-Schiff-positive Lafora bodies on axillary skin biopsy"
        ],
        [
         "MERRF",
         "mtDNA m. 8344A>G tRNA- Lys",
         "Maternal inheritance, ragged red fibers , lactic acidosis, deafness, lipomas"
        ],
        [
         "Neuronal ceroid lipofuscinosis",
         "CLN genes",
         "Visual failure early (especially juvenile CLN3), retinal degeneration; curvilinear/fingerprint inclusions on EM"
        ],
        [
         "Sialidosis type I",
         "NEU1 , autosomal recessive",
         "Cherry-red spot , myoclonus, no dementia early; increased urinary oligosaccharides"
        ],
        [
         "DRPLA",
         "ATN1 CAG repeat",
         "Ataxia, choreoathetosis, dementia; anticipation; more common in Japan"
        ]
       ]
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED Careful with inheritance. Almost all PMEs are autosomal recessive (MERRF is maternal, DRPLA autosomal dominant) — in contrast with the dominantly inherited focal epilepsies (LGI1/ADEAF, CHRNA4/SHE, DEPDC5, KCNQ2/SeLNE)."
      }
     ],
     "tags": [
      "ilae-classification"
     ],
     "updated": true,
     "words": 182
    },
    {
     "id": "iii-reflex-situation-related-and-catastrophic-syndromes",
     "n": "9",
     "title": "Reflex, Situation-Related and Catastrophic Syndromes",
     "blocks": [
      {
       "type": "li",
       "text": "Reflex epilepsies — seizures reliably provoked by a specific stimulus. Photosensitivity is the commonest (JME, Jeavons, photosensitive occipital lobe epilepsy). Others: reading-induced (jaw myoclonus while reading aloud, usually in adolescence), hot-water , startle (often in pre- existing hemiparesis), musicogenic , eating , and praxis induction — thinking, calculating or manipulating objects, characteristic of JME ."
      },
      {
       "type": "li",
       "text": "Hemiconvulsion–hemiplegia–epilepsy (HHE) — prolonged febrile hemiconvulsive status in a young child → acute hemispheric oedema → permanent hemiplegia with hemiatrophy → focal epilepsy years later."
      },
      {
       "type": "li",
       "text": "FIRES (febrile infection-related epilepsy syndrome) — a previously healthy school-age child develops refractory status days after a banal febrile illness. Sits within NORSE (new- onset refractory status epilepticus), where FIRES is the febrile-prodrome subtype. Extensive workup for autoimmune and infectious causes is usually negative. The ketogenic diet is one of the few interventions with reported benefit ; anakinra and tocilizumab are used."
      },
      {
       "type": "li",
       "text": "Outcome is poor — chronic refractory epilepsy and cognitive impairment."
      },
      {
       "type": "li",
       "text": "Eclampsia — seizures in pregnancy or postpartum with hypertension and proteinuria."
      },
      {
       "type": "li",
       "text": "Magnesium sulfate is the treatment , superior to phenytoin and diazepam; delivery is definitive. Consider PRES on imaging."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 186
    },
    {
     "id": "iii-metabolic-and-vitamin-responsive-epilepsies",
     "n": "10",
     "title": "Metabolic and Vitamin-Responsive Epilepsies",
     "blocks": [
      {
       "type": "table",
       "head": [
        "DISORDER",
        "CLUE",
        "TREATMENT"
       ],
       "rows": [
        [
         "Pyridoxine-dependent (ALDH7A1)",
         "Neonatal refractory seizures; elevated α-AASA",
         "IV pyridoxine with EEG running — watch for apnea and hypotension; lifelong"
        ],
        [
         "PNPO deficiency (pyridox(am)ine 5′- phosphate oxidase)",
         "Same picture but does not respond to pyridoxine",
         "Pyridoxal-5′-phosphate (PLP)"
        ],
        [
         "Folinic acid–responsive seizures",
         "Allelic with ALDH7A1",
         "Folinic acid"
        ],
        [
         "Biotinidase deficiency",
         "Alopecia, rash, hearing loss, seizures",
         "Biotin"
        ],
        [
         "GLUT1 deficiency (SLC2A1)",
         "Early absence, movement disorder, low CSF glucose, CSF:blood ratio <0.4",
         "Ketogenic diet"
        ],
        [
         "Nonketotic hyperglycinemia",
         "Neonatal burst-suppression, hiccups; high CSF:plasma glycine",
         "Poor; sodium benzoate, dextromethorphan"
        ],
        [
         "Menkes (ATP7A)",
         "Kinky hair, hypothermia, low copper and ceruloplasmin",
         "Copper histidine"
        ],
        [
         "Canavan disease (ASPA)",
         "Macrocephaly, leukodystrophy, elevated urinary N- acetylaspartate ; EEG shows diffuse polymorphic delta — leukodystrophies slow the background rather than producing spikes",
         "Supportive"
        ],
        [
         "Creatine deficiency syndromes",
         "Absent creatine peak on MRS",
         "Creatine supplementation (GAMT/AGAT)"
        ]
       ]
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": false,
     "words": 132
    },
    {
     "id": "iii-nonepileptic-paroxysmal-events-extended-differential",
     "n": "11",
     "title": "Nonepileptic Paroxysmal Events — Extended Differential",
     "blocks": [
      {
       "type": "p",
       "text": "Beyond the common imitators in section 4:"
      },
      {
       "type": "li",
       "text": "Cardiac and autonomic Long QT syndrome — exertional or startle-triggered syncope with convulsive features; a family history of sudden death or drowning demands an ECG ."
      },
      {
       "type": "p",
       "text": "Regularly misdiagnosed and treated as epilepsy for years. - Reflex anoxic seizures — vagally mediated asystole in toddlers after pain or fright, with pallor then stiffening. - Orthostatic intolerance / POTS , hyperventilation syncope, compulsive Valsalva."
      },
      {
       "type": "li",
       "text": "Movement disorders Paroxysmal nonkinesigenic dyskinesia (PNKD) — triggered by caffeine, alcohol, stress; longer attacks. - Paroxysmal exercise-induced dyskinesia — a classic"
      },
      {
       "type": "p",
       "text": "GLUT1 presentation. - Episodic ataxia type 1 (KCNA1, myokymia, brief) and type 2 (CACNA1A, hours, responds to acetazolamide). - Alternating hemiplegia of childhood ( ATP1A3 ) — alternating hemiplegic episodes resolving in sleep. - Benign paroxysmal tonic upgaze , spasmus nutans (head nodding, nystagmus, torticollis), opsoclonus-myoclonus (look for neuroblastoma)."
      },
      {
       "type": "li",
       "text": "Sleep-related Benign neonatal sleep myoclonus — jerks only in sleep, stop on waking, normal EEG. - Hypnic jerks , rhythmic movement disorder (head banging/body rocking), periodic limb movements. - Narcolepsy with cataplexy — emotion-triggered atonia with preserved awareness; hypocretin deficiency."
      },
      {
       "type": "p",
       "text": "Migraine spectrum in children — benign paroxysmal torticollis, benign paroxysmal vertigo, cyclical vomiting, and migraine with aura (slow march over minutes, positive then negative phenomena)."
      }
     ],
     "tags": [
      "acns-terminology"
     ],
     "updated": false,
     "words": 210
    }
   ],
   "selftest": [
    {
     "q": "Give the current names for West syndrome, benign rolandic epilepsy, Doose syndrome, and Landau–Kleffner.",
     "a": "IESS (infantile epileptic spasms syndrome), SeLECTS , EMAtS , and EE-SWAS (the Landau– Kleffner phenotype sits within spike-wave activation in sleep).",
     "section": "iii-the-2022-framework-read-this-first",
     "match": 4.16
    },
    {
     "q": "Which four syndromes still carry the label \"idiopathic generalized epilepsy\"?",
     "a": "CAE, JAE, JME, and GTCA (epilepsy with generalized tonic-clonic seizures alone).",
     "section": "iii-the-2022-framework-read-this-first",
     "match": 3.77
    },
    {
     "q": "Which ASM class must be avoided in Dravet syndrome, and which gene explains why?",
     "a": "Sodium channel blockers — carbamazepine, oxcarbazepine, lamotrigine, phenytoin. SCN1A loss-of-function predominantly affects inhibitory interneurons, so blocking sodium channels further reduces inhibition.",
     "section": "iii-syndromes-by-age",
     "match": 2.41
    },
    {
     "q": "What is the first-tier genetic test for unexplained epilepsy, and roughly what yield does it have?",
     "a": "Exome or genome sequencing — genome ~48%, exome ~24%, well above gene panels (~20% for large panels) and microarray (~9%).",
     "section": "iii-genetics",
     "match": 3.2
    },
    {
     "q": "A 4-year-old has nocturnal events with vomiting and pallor, then eye deviation. Syndrome and treatment?",
     "a": "SeLEAS (self-limited epilepsy with autonomic seizures, formerly Panayiotopoulos). Seizures are infrequent — most children need no ASM .",
     "section": "iii-syndromes-by-age",
     "match": 3.14
    },
    {
     "q": "Which single clinical sign most strongly favours functional seizures, and which finding most strongly argues against them?",
     "a": "Forced eye closure with active resistance favours functional seizures. An event arising from confirmed EEG sleep effectively excludes them.",
     "section": "iii-imitators-of-epilepsy",
     "match": 3.47
    },
    {
     "q": "Define a complex febrile seizure, and give the approximate risk of later epilepsy after a simple one.",
     "a": "≥15 minutes, focal features, or more than one in 24 hours — any one qualifies. Risk of later epilepsy after a simple febrile seizure is only about 1–2% .",
     "section": "iii-febrile-seizures",
     "match": 4.09
    },
    {
     "q": "Which PME presents with occipital seizures and blindness, and how is it diagnosed on biopsy?",
     "a": "Lafora disease — adolescent onset, occipital seizures with visual hallucinations and blindness, rapid dementia. PAS-positive Lafora bodies on axillary skin biopsy (EPM2A/NHLRC1).",
     "section": "iii-progressive-myoclonus-epilepsies",
     "match": 4.04
    },
    {
     "q": "A neonate has refractory seizures unresponsive to IV pyridoxine. What next?",
     "a": "Give pyridoxal-5′-phosphate — this is PNPO deficiency , which does not respond to pyridoxine itself.",
     "section": "iii-metabolic-and-vitamin-responsive-epilepsies",
     "match": 2.75
    },
    {
     "q": "Which chromosomal disorder shows high-amplitude notched delta on EEG, and which parental allele is deleted?",
     "a": "Angelman syndrome ; the maternal 15q11-q13 allele is deleted (paternal deletion gives Prader- Willi).",
     "section": "iii-neurocutaneous-and-chromosomal-disorders",
     "match": 3.54
    }
   ]
  },
  {
   "id": "iv",
   "title": "Management of Epilepsy",
   "pages": [
    44,
    60
   ],
   "sections": [
    {
     "id": "iv-diagnosis-and-treatment-principles",
     "n": "1",
     "title": "Diagnosis and Treatment Principles",
     "blocks": [
      {
       "type": "h3",
       "text": "Defining the disease"
      },
      {
       "type": "p",
       "text": "Epilepsy (ILAE 2014 practical definition) — any one of:"
      },
      {
       "type": "li",
       "text": "Two unprovoked (or reflex) seizures more than 24 hours apart One unprovoked seizure plus a recurrence risk ≥60% over the next 10 years — practically, a remote symptomatic lesion, epileptiform EEG, or both Diagnosis of an epilepsy syndrome"
      },
      {
       "type": "p",
       "text": "Resolved — past the applicable age of an age-dependent syndrome, or seizure-free for 10 years with the last 5 off medication. \"Resolved\" deliberately avoids \"cured\": the underlying predisposition may persist."
      },
      {
       "type": "p",
       "text": "Drug-resistant epilepsy (ILAE 2010) — failure of two tolerated, appropriately chosen and adequately used ASM schedules (monotherapy or combination) to achieve sustained seizure freedom. Sustained means 12 months, or three times the longest pre-treatment interseizure interval, whichever is longer."
      },
      {
       "type": "li",
       "text": "Why the number two matters. Kwan and Brodie's cohort showed ~47% become seizure-free on the first ASM, ~13% on the second, and only ~4% on anything after that. The curve flattens hard, which is the entire justification for referring at drug two rather than drug five. A 30-year follow-up of the same cohort reproduced this (~50% / ~12% / ~4%)."
      },
      {
       "type": "h3",
       "text": "Working up a first seizure"
      },
      {
       "type": "li",
       "text": "Imaging: epilepsy-protocol MRI at 3T. CT only for the acute emergency question — bleed, mass effect, trauma — or when MRI is contraindicated."
      },
      {
       "type": "li",
       "text": "EEG: first routine EEG captures epileptiform activity in roughly a third to a half of people who have epilepsy. Sleep deprivation and repeat studies raise the yield; a normal EEG never excludes epilepsy."
      },
      {
       "type": "li",
       "text": "Labs: glucose, electrolytes (sodium, calcium, magnesium), toxicology. Lumbar puncture if febrile, immunocompromised, or persistently altered."
      },
      {
       "type": "li",
       "text": "Recurrence risk after one unprovoked seizure: ~21–45% within two years (AAN/AES 2015). Independent predictors: prior brain insult, epileptiform EEG, significant imaging abnormality, and nocturnal seizure."
      },
      {
       "type": "li",
       "text": "Treating the first seizure reduces recurrence over the next 1–2 years but does not change long-term remission or quality of life. This makes it a shared decision — driving, occupation, and patient risk tolerance drive it more than the neurology does."
      },
      {
       "type": "h3",
       "text": "Choosing and monitoring"
      },
      {
       "type": "p",
       "text": "Match the drug to seizure type and syndrome first, then to the person — childbearing potential, psychiatric and cognitive comorbidity, bone health, renal and hepatic function, interactions, and cost. Start monotherapy, titrate to effect or intolerance, then substitute rather than add. Add-on therapy is for after two failed monotherapies."
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — SANAD II (2021). For focal epilepsy, lamotrigine remains first choice; levetiracetam and zonisamide did not beat it on time-to-treatment-failure. For generalized and unclassified epilepsy, levetiracetam was not non-inferior to valproate — valproate remains the most effective drug, which is precisely the tension in treating people who can become pregnant."
      },
      {
       "type": "p",
       "text": "Therapeutic drug monitoring is not a routine ritual. Use it for phenytoin (saturable kinetics), suspected non-adherence or toxicity, pregnancy, renal or hepatic impairment, and drug interactions. In stable, seizure-free, side-effect-free patients, a level changes nothing."
      },
      {
       "type": "p",
       "text": "Withdrawal — consider after ≥2 years seizure-free. Relapse runs 11–41%. Higher risk:"
      },
      {
       "type": "p",
       "text": "abnormal EEG at withdrawal, structural etiology, adolescent onset, longer time to control."
      },
      {
       "type": "p",
       "text": "Juvenile myoclonic epilepsy is the classic lifelong exception — only ~10–20% come off successfully."
      },
      {
       "type": "figure",
       "n": 9,
       "src": "fig-asm-by-mechanism.png",
       "caption": "Antiseizure medications grouped by mechanism of action."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": true,
     "words": 502
    },
    {
     "id": "iv-established-antiseizure-medications",
     "n": "2",
     "title": "Established Antiseizure Medications",
     "blocks": [
      {
       "type": "h3",
       "text": "Phenytoin / fosphenytoin"
      },
      {
       "type": "li",
       "text": "Mechanism: use- and voltage-dependent sodium channel blockade (fast inactivation)."
      },
      {
       "type": "li",
       "text": "Kinetics: the exam favorite — saturable (Michaelis–Menten) kinetics. Above the saturation point, small dose increases cause large concentration jumps and half-life lengthens. ~90% albumin-bound; check a free level in hypoalbuminemia, uremia, pregnancy, or with displacing drugs like valproate."
      },
      {
       "type": "li",
       "text": "Interactions: potent CYP3A4 inducer; substrate of CYP2C9/2C19."
      },
      {
       "type": "li",
       "text": "Chronic toxicity: gingival hyperplasia, hirsutism, coarse facies, cerebellar atrophy with ataxia, peripheral neuropathy, osteopenia, folate deficiency."
      },
      {
       "type": "li",
       "text": "Acute: nystagmus → ataxia → encephalopathy as levels climb. IV phenytoin causes purple glove syndrome and hypotension (propylene glycol vehicle)."
      },
      {
       "type": "li",
       "text": "Fosphenytoin is a water-soluble prodrug dosed in phenytoin equivalents (PE) ; less phlebitis and no purple glove, but still hypotension if pushed fast. Paresthesia and pruritus (groin) are characteristic and benign."
      },
      {
       "type": "li",
       "text": "HLA-B*15:02 raises SJS/TEN risk in people of Han Chinese and Southeast Asian ancestry."
      },
      {
       "type": "h3",
       "text": "Carbamazepine"
      },
      {
       "type": "li",
       "text": "Mechanism: sodium channel blockade. Active 10,11-epoxide metabolite drives much of the toxicity."
      },
      {
       "type": "li",
       "text": "Autoinduction over 2–4 weeks — the half-life shortens with continued use, so the dose that worked in week one is under-dosed by week four."
      },
      {
       "type": "li",
       "text": "Hyponatremia via SIADH-like effect; more common in older adults."
      },
      {
       "type": "li",
       "text": "Idiosyncratic: aplastic anemia and agranulocytosis (rare but real), DRESS, SJS/TEN."
      },
      {
       "type": "li",
       "text": "Pharmacogenetics: HLA-B*15:02 → SJS/TEN (screen before starting in at-risk ancestries — FDA recommendation). HLA-A*31:01 → DRESS and maculopapular rash, relevant in European and Japanese populations."
      },
      {
       "type": "li",
       "text": "Aggravates absence and myoclonic seizures — a common way to worsen a genetic generalized epilepsy misdiagnosed as focal."
      },
      {
       "type": "h3",
       "text": "Valproate"
      },
      {
       "type": "li",
       "text": "Mechanism: broad — sodium channels, T-type calcium channels, GABA turnover."
      },
      {
       "type": "li",
       "text": "Interactions: inhibits UGT and CYP2C9. Roughly doubles lamotrigine levels (halve the lamotrigine dose and titrate slowly). Displaces phenytoin from albumin, raising the free fraction."
      },
      {
       "type": "li",
       "text": "Toxicity: dose-dependent thrombocytopenia and tremor; hyperammonemia (worse with topiramate, and can cause encephalopathy with a normal LFT panel); weight gain; alopecia;"
      },
      {
       "type": "li",
       "text": "pancreatitis; hepatotoxicity."
      },
      {
       "type": "li",
       "text": "RECENTLY CHANGED POLG contraindication. Valproate precipitates fatal hepatic failure in POLG- related mitochondrial disease (Alpers–Huttenlocher). Test POLG before valproate in a child with unexplained refractory seizures and hepatic or developmental concerns — this is the reasoning behind the \"avoid valproate in explosive occipital status in a toddler\" question stem."
      },
      {
       "type": "li",
       "text": "Teratogenicity is the dominant modern issue — see §6."
      },
      {
       "type": "h3",
       "text": "Phenobarbital and primidone"
      },
      {
       "type": "li",
       "text": "Primidone is metabolized to phenobarbital and PEMA , both active."
      },
      {
       "type": "li",
       "text": "Potent enzyme inducers; sedation and cognitive blunting limit use; paradoxical hyperactivity in children."
      },
      {
       "type": "li",
       "text": "Connective-tissue effects: Dupuytren's contracture, plantar fibromatosis, frozen shoulder — the distinctive chronic signature."
      },
      {
       "type": "li",
       "text": "Still the most widely used ASM globally on cost grounds."
      },
      {
       "type": "h3",
       "text": "Ethosuximide"
      },
      {
       "type": "li",
       "text": "T-type calcium channel blockade in thalamocortical relay neurons — interrupts the 3-Hz oscillation."
      },
      {
       "type": "li",
       "text": "Absence seizures only. No efficacy against tonic-clonic seizures, so it is not a solution for juvenile absence epilepsy where convulsions are expected."
      },
      {
       "type": "li",
       "text": "GI upset, hiccups, headache; rarely aplastic anemia and drug-induced lupus."
      },
      {
       "type": "li",
       "text": "Childhood Absence Epilepsy trial: ethosuximide and valproate were equally effective and both beat lamotrigine; ethosuximide caused fewer attentional adverse effects than valproate, making it first-line for absence-only disease."
      },
      {
       "type": "h3",
       "text": "Benzodiazepines"
      },
      {
       "type": "li",
       "text": "Clobazam is a 1,5-benzodiazepine (all the others are 1,4) — less sedation, and the source of the brand name Onfi."
      },
      {
       "type": "li",
       "text": "Active metabolite N-desmethylclobazam is cleared by CYP2C19; poor metabolizers accumulate it, and CYP2C19 inhibitors (including cannabidiol) raise it."
      },
      {
       "type": "li",
       "text": "Tolerance limits chronic use; abrupt withdrawal precipitates status."
      },
      {
       "type": "li",
       "text": "Lorazepam and clonazepam have no active metabolites ; diazepam and clobazam do (desmethyldiazepam, N-desmethylclobazam)."
      },
      {
       "type": "li",
       "text": "Lorazepam is preferred to diazepam in status despite diazepam's longer elimination half- life. Diazepam is highly lipophilic and redistributes out of the brain within ~20 minutes, so its anticonvulsant effect is short; the less lipophilic lorazepam stays in the CNS longer."
      },
      {
       "type": "li",
       "text": "Elimination half-life and duration of anticonvulsant action are not the same thing — a classic exam trap."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": true,
     "words": 597
    },
    {
     "id": "iv-newer-antiseizure-medications",
     "n": "3",
     "title": "Newer Antiseizure Medications",
     "blocks": [
      {
       "type": "h3",
       "text": "The ones that carry the most exam weight"
      },
      {
       "type": "p",
       "text": "Lamotrigine — sodium channel blocker, broad spectrum."
      },
      {
       "type": "li",
       "text": "Rash and SJS risk scales with titration speed and with valproate co-therapy. Halve the starting dose and titration rate on valproate; double it on enzyme inducers."
      },
      {
       "type": "li",
       "text": "Estrogen-containing contraceptives induce glucuronidation and drop lamotrigine ~50% — breakthrough seizures during active-pill weeks and toxicity during the placebo week."
      },
      {
       "type": "li",
       "text": "A breakthrough seizure in a woman stable for years on lamotrigine should send you straight to her contraceptive history."
      },
      {
       "type": "li",
       "text": "Can aggravate myoclonus in juvenile myoclonic epilepsy despite being broad-spectrum."
      },
      {
       "type": "p",
       "text": "Levetiracetam — SV2A binding; renally cleared; essentially no interactions. Behavioral and irritability effects are the limiting factor, particularly in intellectual disability and psychiatric comorbidity."
      },
      {
       "type": "p",
       "text": "Brivaracetam — higher-affinity SV2A analog with additional sodium channel activity; CYP2C19 substrate; usually better tolerated behaviorally than levetiracetam and can be switched to directly."
      },
      {
       "type": "p",
       "text": "Topiramate — multiple mechanisms. Weight loss, word-finding difficulty, paresthesias, nephrolithiasis, acute angle-closure glaucoma , metabolic acidosis, and oligohidrosis with hyperthermia in children (shared with zonisamide — both are weak carbonic anhydrase inhibitors). Reduces oral contraceptive efficacy above ~200 mg/day."
      },
      {
       "type": "p",
       "text": "Zonisamide — sulfonamide structure, so avoid in sulfonamide allergy . Stones, weight loss, oligohidrosis. Long half-life allows once-daily dosing but it has no FDA once-daily label."
      },
      {
       "type": "p",
       "text": "Oxcarbazepine / eslicarbazepine — sodium channel blockers with more hyponatremia than carbamazepine . Eslicarbazepine is once daily with a flatter concentration curve, which is the fix for peak-dose toxicity on immediate-release oxcarbazepine."
      },
      {
       "type": "p",
       "text": "Lacosamide — enhances slow inactivation of sodium channels (distinct from the classic agents' fast inactivation). PR interval prolongation — get an ECG in cardiac conduction disease."
      },
      {
       "type": "p",
       "text": "Minimal interactions."
      },
      {
       "type": "p",
       "text": "Perampanel — the only marketed AMPA receptor antagonist . Very long half-life (~105 h), dosed nightly. Black box warning for serious psychiatric and behavioral reactions , including aggression and homicidal ideation."
      },
      {
       "type": "p",
       "text": "Vigabatrin — irreversible GABA transaminase inhibitor. Causes permanent, usually irreversible peripheral visual field constriction in up to a third of patients, related to dose and cumulative duration; central vision is spared. REMS programme with periodic perimetry."
      },
      {
       "type": "p",
       "text": "First-line for infantile epileptic spasms syndrome, and the drug of choice when the cause is tuberous sclerosis."
      },
      {
       "type": "p",
       "text": "Felbamate — effective in Lennox–Gastaut but carries aplastic anemia and hepatic failure ;"
      },
      {
       "type": "p",
       "text": "requires informed consent and monitoring. Reserved for refractory cases."
      },
      {
       "type": "p",
       "text": "Rufinamide — Lennox–Gastaut; shortens the QT interval and is contraindicated in familial short QT syndrome. Somnolence and vomiting are the common adverse effects."
      },
      {
       "type": "h3",
       "text": "Approved recently"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED"
      },
      {
       "type": "table",
       "head": [
        "DRUG",
        "APPROVED",
        "INDICATION",
        "WHAT TO KNOW"
       ],
       "rows": [
        [
         "Cannabidiol (Epidiolex)",
         "2018; TSC added 2020",
         "Dravet, Lennox– Gastaut, tuberous sclerosis",
         "Raises N-desmethylclobazam; transaminitis, especially with valproate ; diarrhea, somnolence, decreased appetite"
        ],
        [
         "Cenobamate",
         "2019",
         "Focal seizures",
         "12-week titration to prevent DRESS ; inhibits CYP2C19 ( cut phenytoin ~50% ), induces CYP3A4 (lowers contraceptive levels)"
        ],
        [
         "Fenfluramine (Fintepla)",
         "2020; LGS added 2022",
         "Dravet, Lennox– Gastaut",
         "5-HT and sigma-1 activity; REMS with echocardiography before, every 6 months, and 3–6 months after stopping (valvulopathy, pulmonary hypertension)"
        ],
        [
         "Ganaxolone (Ztalmy)",
         "2022",
         "CDKL5 deficiency disorder",
         "Neuroactive steroid acting at extrasynaptic GABA-A receptors"
        ],
        [
         "Stiripentol",
         "2018 (US)",
         "Dravet, with clobazam ± valproate",
         "Potent CYP inhibitor — raises clobazam metabolite substantially"
        ],
        [
         "Everolimus",
         "2018",
         "TSC-associated focal seizures",
         "mTOR inhibitor; the first genuinely mechanism- targeted ASM"
        ]
       ]
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED Withdrawn. Ezogabine (retigabine) was taken off the market worldwide in 2017 — retinal pigment changes and blue skin discoloration. Any question keying it as a live treatment option is historical. Its mechanism (Kv7 potassium channel opening) is worth keeping, because the successor drug uses it."
      },
      {
       "type": "h3",
       "text": "On the horizon (know the names, not the details)"
      },
      {
       "type": "li",
       "text": "Azetukalner (XEN1101) — Kv7.2/7.3 opener with positive phase 3 results in focal and generalized tonic-clonic seizures; an approval decision is anticipated."
      },
      {
       "type": "li",
       "text": "Zorevunersen (STK-001) — antisense oligonucleotide that upregulates Nav1.1 from the healthy SCN1A allele in Dravet syndrome. The first serious disease-modifying candidate rather than a symptomatic one."
      },
      {
       "type": "li",
       "text": "RECENTLY CHANGED Comparative effectiveness (JAMA Neurology, 2026). In real-world drug-resistant focal epilepsy, cenobamate outperformed brivaracetam, lacosamide, and perampanel (~84% responder rate, ~32% seizure-free at 12 months) but had the highest adverse-event rate ; lacosamide had the lowest."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification",
      "acns-terminology"
     ],
     "updated": true,
     "words": 659
    },
    {
     "id": "iv-dietary-therapy",
     "n": "4",
     "title": "Dietary Therapy",
     "blocks": [
      {
       "type": "h3",
       "text": "The diets"
      },
      {
       "type": "table",
       "head": [
        "DIET",
        "COMPOSITION",
        "NOTES"
       ],
       "rows": [
        [
         "Classic ketogenic (",
         "4:1 or 3:1 ratio — grams of fat : grams of protein + carbohydrate ) combined",
         "Most restrictive, most ketogenic; weighed meals"
        ],
        [
         "Modified Atkins (MAD)",
         "Carbohydrate restricted (~10–20 g/day), fat encouraged, protein unlimited",
         "No weighing, outpatient initiation, better adherence in teens and adults"
        ],
        [
         "Medium-chain triglyceride (MCT)",
         "MCT oil supplies ketones more efficiently, allowing more carbohydrate",
         "GI intolerance limits it"
        ],
        [
         "Low glycemic index treatment (LGIT)",
         "Carbohydrates limited and restricted to GI <50",
         "Least restrictive"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The classic-ratio question is a reliable one: 4:1 means 4 g fat for every 1 g of protein plus carbohydrate , not 4 g fat per gram of carbohydrate."
      },
      {
       "type": "h3",
       "text": "When it is the treatment, not an option"
      },
      {
       "type": "p",
       "text": "Absolute indications — the diet corrects the metabolic defect rather than suppressing seizures:"
      },
      {
       "type": "li",
       "text": "GLUT1 deficiency syndrome — ketones bypass the defective glucose transporter at the blood–brain barrier Pyruvate dehydrogenase deficiency — ketones enter the TCA cycle downstream of the block"
      },
      {
       "type": "p",
       "text": "Strong indications: infantile epileptic spasms syndrome, Dravet, Lennox–Gastaut, epilepsy with myoclonic-atonic seizures, tuberous sclerosis, FIRES, and super-refractory status epilepticus."
      },
      {
       "type": "h3",
       "text": "Contraindications — screen before starting"
      },
      {
       "type": "p",
       "text": "Anything that depends on fat oxidation for energy:"
      },
      {
       "type": "li",
       "text": "Fatty acid oxidation defects — carnitine deficiency (primary), CPT I and II deficiency, carnitine translocase deficiency, β-oxidation defects Pyruvate carboxylase deficiency (impaired gluconeogenesis/anaplerosis — contrast with pyruvate dehydrogenase , where the diet is indicated) Porphyria"
      },
      {
       "type": "p",
       "text": "Pre-diet screen: acylcarnitine profile, urine organic acids, serum carnitine."
      },
      {
       "type": "h3",
       "text": "Practicalities"
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — the 2018 International Ketogenic Diet Study Group consensus update: consider the diet after two ASMs have failed (earlier in the absolute- indication syndromes), fasting is no longer required at initiation, and outpatient initiation is acceptable for MAD. Supplement vitamins, minerals, calcium, vitamin D, and oral citrates."
      },
      {
       "type": "li",
       "text": "Give it ~3 months before judging efficacy, though most responders declare themselves within 2 weeks."
      },
      {
       "type": "li",
       "text": "Early adverse effects: acidosis, hypoglycemia, dehydration, GI upset, lethargy."
      },
      {
       "type": "li",
       "text": "Late: nephrolithiasis (citrate prophylaxis), dyslipidemia, growth restriction, reduced bone mineral density, constipation."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": true,
     "words": 322
    },
    {
     "id": "iv-hormonal-immune-and-investigational-therapy",
     "n": "5",
     "title": "Hormonal, Immune, and Investigational Therapy",
     "blocks": [
      {
       "type": "h3",
       "text": "Catamenial epilepsy"
      },
      {
       "type": "p",
       "text": "Three patterns, defined by at least a twofold increase in seizure frequency during the phase:"
      },
      {
       "type": "li",
       "text": "C1 — perimenstrual. Withdrawal of progesterone and its neurosteroid metabolite allopregnanolone (a positive allosteric GABA-A modulator) removes inhibition. The most common pattern."
      },
      {
       "type": "li",
       "text": "C2 — periovulatory. The estrogen surge without progesterone opposition; estrogen is proconvulsant."
      },
      {
       "type": "li",
       "text": "C3 — luteal. Inadequate luteal phase, typically anovulatory cycles."
      },
      {
       "type": "p",
       "text": "Treatment: the NIH Progesterone Trial was negative overall , with a post-hoc signal in C1 patients who had a marked (≥3-fold) perimenstrual increase. In practice, cyclic clobazam, acetazolamide, or a temporary ASM dose increase around menses are used, all on thin evidence."
      },
      {
       "type": "h3",
       "text": "Immunotherapy"
      },
      {
       "type": "p",
       "text": "Autoimmune causes are now a formal etiologic category in the ILAE framework. The antibodies worth knowing:"
      },
      {
       "type": "table",
       "head": [
        "ANTIBODY",
        "CLINICAL SIGNATURE"
       ],
       "rows": [
        [
         "NMDA receptor",
         "Young women, psychiatric prodrome, dyskinesias, autonomic instability, extreme delta brush on EEG; ovarian teratoma — image the pelvis"
        ],
        [
         "LGI1",
         "Older adults, faciobrachial dystonic seizures (very brief, very frequent), hyponatremia , rapid memory decline"
        ],
        [
         "CASPR2",
         "Morvan syndrome, neuromyotonia, limbic encephalitis"
        ],
        [
         "GAD65",
         "Slower course, poorer immunotherapy response, often coexists with type 1 diabetes and stiff- person spectrum"
        ]
       ]
      },
      {
       "type": "li",
       "text": "First-line: corticosteroids, IVIG, plasma exchange. Second-line: rituximab, cyclophosphamide."
      },
      {
       "type": "li",
       "text": "LGI1 faciobrachial dystonic seizures respond dramatically to steroids and poorly to ASMs — recognizing them early prevents the fixed amnestic syndrome."
      },
      {
       "type": "li",
       "text": "Screening tools (APE2, ACES) help decide who to test."
      },
      {
       "type": "h3",
       "text": "Animal models — how the drugs got found"
      },
      {
       "type": "table",
       "head": [
        "MODEL",
        "WHAT IT PREDICTS"
       ],
       "rows": [
        [
         "Maximal electroshock (MES)",
         "Generalized tonic-clonic and focal seizures; sodium channel drugs"
        ],
        [
         "Subcutaneous pentylenetetrazole (PTZ)",
         "Myoclonic and absence seizures"
        ],
        [
         "6-Hz psychomotor",
         "Drug-resistant focal seizures — the screen that finds drugs the others miss"
        ],
        [
         "Kindling",
         "Focal seizures with progression; a model of epileptogenesis"
        ],
        [
         "Pilocarpine and kainate",
         "Chronic temporal lobe epilepsy with spontaneous recurrent seizures"
        ],
        [
         "GAERS / WAG-Rij rats",
         "Genetic absence epilepsy"
        ]
       ]
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": false,
     "words": 293
    },
    {
     "id": "iv-special-populations",
     "n": "6",
     "title": "Special Populations",
     "blocks": [
      {
       "type": "h3",
       "text": "Contraception and drug interactions"
      },
      {
       "type": "p",
       "text": "Enzyme inducers that reduce contraceptive efficacy: carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, eslicarbazepine, topiramate (>200 mg/day), perampanel (≥12 mg), rufinamide, felbamate, cenobamate."
      },
      {
       "type": "p",
       "text": "No meaningful interaction: levetiracetam, brivaracetam, lacosamide, gabapentin, pregabalin, vigabatrin, zonisamide, valproate."
      },
      {
       "type": "p",
       "text": "Lamotrigine is the bidirectional special case — it does not reduce contraceptive efficacy, but estrogen halves lamotrigine levels."
      },
      {
       "type": "h3",
       "text": "Pregnancy"
      },
      {
       "type": "li",
       "text": "Preconception folic acid , started 3 months before conception. 0.4–1 mg for standard risk; 4– 5 mg with a prior neural tube defect or on valproate. In women with epilepsy specifically, periconceptional folate is associated with better neurodevelopmental outcomes in offspring."
      },
      {
       "type": "li",
       "text": "Valproate — dose-dependent major congenital malformations (~10% overall, higher above 700–1000 mg/day), neural tube defects, reduced verbal IQ, and increased autism risk. Folate does not neutralize it. Avoid in anyone who could become pregnant unless nothing else controls the epilepsy."
      },
      {
       "type": "li",
       "text": "RECENTLY CHANGED Topiramate. The EMA introduced a pregnancy prevention programme in 2023 over malformations, low birth weight, and possible neurodevelopmental harm. Note the nuance: a large 2024 cohort study found the autism signal for topiramate largely disappeared after adjusting for confounding by indication, while the valproate signal persisted . Intellectual disability risk remains a concern. Treat topiramate as second-tier in pregnancy, valproate as last resort."
      },
      {
       "type": "li",
       "text": "Lamotrigine and levetiracetam have the lowest malformation rates (~2–3%) and are the preferred agents."
      },
      {
       "type": "li",
       "text": "Clearance rises substantially in pregnancy — most dramatically for lamotrigine (up to 2–3 fold) and levetiracetam. Get a preconception baseline level, monitor each trimester, and taper back down postpartum to avoid toxicity."
      },
      {
       "type": "li",
       "text": "Breastfeeding is encouraged. Most ASMs are compatible; the MONEAD and NEAD data are reassuring for neurodevelopment. Watch for sedation and poor feeding with phenobarbital, primidone, and benzodiazepines."
      },
      {
       "type": "h3",
       "text": "Older adults"
      },
      {
       "type": "li",
       "text": "Stroke is the most common identifiable cause of new-onset epilepsy after 60."
      },
      {
       "type": "li",
       "text": "Physiology: reduced albumin (higher free fraction of bound drugs), reduced renal and hepatic clearance, and heavy polypharmacy."
      },
      {
       "type": "li",
       "text": "Preferred: lamotrigine, levetiracetam, gabapentin — the VA Cooperative Study found lamotrigine and gabapentin better tolerated than carbamazepine at equal efficacy."
      },
      {
       "type": "li",
       "text": "Avoid: topiramate (cognitive), phenytoin (saturable kinetics plus interactions), and enzyme inducers generally (bone density, lipids, and interference with anticoagulants and statins)."
      },
      {
       "type": "li",
       "text": "Lower starting doses, slower titration, and lower target concentrations than in younger adults."
      },
      {
       "type": "h3",
       "text": "Organ dysfunction"
      },
      {
       "type": "li",
       "text": "Renally cleared (reduce in CKD): levetiracetam, gabapentin, pregabalin, vigabatrin, topiramate (partly), lacosamide (partly)."
      },
      {
       "type": "li",
       "text": "Hepatically cleared (caution in liver disease): valproate, carbamazepine, phenytoin, lamotrigine, perampanel."
      },
      {
       "type": "h3",
       "text": "Psychiatric comorbidity"
      },
      {
       "type": "li",
       "text": "Depression affects at least a third of people with epilepsy and is the strongest driver of poor quality of life — often more than seizure frequency."
      },
      {
       "type": "li",
       "text": "SSRIs are safe at therapeutic doses (sertraline, citalopram are the usual choices)."
      },
      {
       "type": "li",
       "text": "Avoid bupropion — dose-dependent proconvulsant. Also avoid clomipramine and maprotiline."
      },
      {
       "type": "li",
       "text": "Screen with a validated instrument; validity against a reference standard matters more than brevity or cost."
      },
      {
       "type": "h3",
       "text": "Bone health"
      },
      {
       "type": "p",
       "text": "Enzyme inducers and valproate both reduce bone mineral density. Check vitamin D and supplement calcium and vitamin D in anyone on long-term therapy."
      }
     ],
     "tags": [
      "seizure-management"
     ],
     "updated": true,
     "words": 478
    },
    {
     "id": "iv-status-epilepticus",
     "n": "7",
     "title": "Status Epilepticus",
     "blocks": [
      {
       "type": "h3",
       "text": "Operational definitions (ILAE 2015)"
      },
      {
       "type": "table",
       "head": [
        "SEIZURE TYPE",
        "T1 — TREAT NOW",
        "T2 — LONG-TERM CONSEQUENCES LIKELY"
       ],
       "rows": [
        [
         "Tonic-clonic",
         "5 min",
         "30 min"
        ],
        [
         "Focal with impaired consciousness",
         "10 min",
         ">60 min"
        ],
        [
         "Absence",
         "10–15 min",
         "unknown"
        ]
       ]
      },
      {
       "type": "p",
       "text": "The 2015 classification has four axes: semiology, etiology, EEG correlates, and age."
      },
      {
       "type": "p",
       "text": "Duration sets the thresholds but is not one of the axes — a frequently tested distinction."
      },
      {
       "type": "figure",
       "n": 4,
       "src": "fig-status-ladder.png",
       "caption": "Operational thresholds and the treatment ladder in status epilepticus."
      },
      {
       "type": "h3",
       "text": "Why speed matters mechanistically"
      },
      {
       "type": "p",
       "text": "Seizure activity drives internalization of synaptic GABA-A receptors and simultaneous trafficking of AMPA and NMDA receptors to the synapse . Inhibition falls and excitation rises as the minutes pass, which is why benzodiazepine efficacy decays with time and why late status is pharmacoresistant. This is also the rationale for early ketamine (an NMDA antagonist) in refractory cases."
      },
      {
       "type": "h3",
       "text": "The sequence"
      },
      {
       "type": "p",
       "text": "First line — a benzodiazepine, adequately dosed. Under-dosing is the single most common management error."
      },
      {
       "type": "li",
       "text": "No IV access: IM midazolam 10 mg for ≥40 kg (RAMPART trial — non-inferior, and faster overall because you skip the line) IV: lorazepam 0.1 mg/kg (max 4 mg) or diazepam 0.15–0.2 mg/kg"
      },
      {
       "type": "p",
       "text": "Second line — ESETT (2019) settled this. Levetiracetam, fosphenytoin, and valproate are equivalent , each stopping roughly 45–47% of benzodiazepine-refractory status:"
      },
      {
       "type": "table",
       "head": [
        "DRUG",
        "DOSE",
        "CAP"
       ],
       "rows": [
        [
         "Levetiracetam",
         "60 mg/kg",
         "4500 mg"
        ],
        [
         "Fosphenytoin",
         "20 mg PE/kg",
         "1500 mg PE"
        ],
        [
         "Valproate",
         "40 mg/kg",
         "3000 mg"
        ]
       ]
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED. Choose on patient factors, not presumed potency — valproate or levetiracetam if hemodynamically fragile or with cardiac conduction disease; avoid valproate in hepatic disease, suspected mitochondrial disease, and pregnancy."
      },
      {
       "type": "p",
       "text": "Third line — anesthetic infusion with continuous EEG. Midazolam, propofol, or ketamine, titrated to seizure suppression or burst-suppression."
      },
      {
       "type": "li",
       "text": "Propofol infusion syndrome — bradyarrhythmia, rhabdomyolysis with myoglobinuria, metabolic acidosis, hepatic dysfunction. Higher risk in children, with high doses, and with prolonged infusion. Stop the propofol."
      },
      {
       "type": "li",
       "text": "RECENTLY CHANGED Ketamine has moved into mainstream practice since 2017, including in non- intubated patients, and is increasingly used earlier rather than as a last resort."
      },
      {
       "type": "p",
       "text": "Throughout: treat the cause. Give thiamine before glucose in alcohol use, pyridoxine in a neonate with refractory seizures, and correct sodium, glucose, and calcium — a focal motor seizure with a glucose of 45 needs dextrose, not another ASM."
      }
     ],
     "tags": [
      "seizure-management",
      "ilae-classification"
     ],
     "updated": true,
     "words": 354
    },
    {
     "id": "iv-sudep-and-mortality",
     "n": "8",
     "title": "SUDEP and Mortality",
     "blocks": [
      {
       "type": "h3",
       "text": "SUDEP"
      },
      {
       "type": "p",
       "text": "Definition. Sudden, unexpected, witnessed or unwitnessed, non-traumatic and non-drowning death in a person with epilepsy, with or without evidence of a seizure, excluding documented status epilepticus, and in which post-mortem examination does not reveal a structural or toxicologic cause ."
      },
      {
       "type": "table",
       "head": [
        "CATEGORY",
        "REQUIREMENT"
       ],
       "rows": [
        [
         "Definite",
         "All criteria met with autopsy excluding other causes"
        ],
        [
         "Probable",
         "All criteria met but no autopsy performed"
        ],
        [
         "Possible",
         "A competing cause of death cannot be excluded"
        ],
        [
         "Near-SUDEP",
         "Cardiorespiratory arrest with survival >1 hour after resuscitation"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Incidence (AAN/AES 2017 guideline):"
      },
      {
       "type": "li",
       "text": "Adults ~1.2 per 1,000 patient-years (roughly 1 in 1,000 per year) Children ~0.22 per 1,000 (roughly 1 in 4,500 per year) Drug-resistant epilepsy ~1 in 100 per year — a hundredfold spread across the population"
      },
      {
       "type": "p",
       "text": "Risk factors, in order of weight:"
      },
      {
       "type": "li",
       "text": "Frequent generalized tonic-clonic seizures — the single strongest, dose-dependent risk factor. Three or more per year raises risk roughly 15-fold; seizure freedom nearly abolishes it Nocturnal seizures and being unattended or unmonitored at night Sleeping prone Long epilepsy duration, early onset, intellectual disability Polytherapy — largely a marker of severity rather than a cause Non-adherence and subtherapeutic levels Genetic contributors: SCN1A (Dravet), DEPDC5 , and cardiac channelopathy overlap genes"
      },
      {
       "type": "p",
       "text": "Mechanism. Monitored cases (MORTEMUS) show a stereotyped cascade after a generalized convulsion: postictal tachypnea , then central apnea , generalized EEG suppression , bradycardia and terminal asystole — usually within minutes, and almost always in sleep and prone."
      },
      {
       "type": "p",
       "text": "Prevention and counselling:"
      },
      {
       "type": "li",
       "text": "Optimize control of convulsive seizures — this is the only intervention with strong evidence Nocturnal supervision , room-sharing, or a listening/monitoring device reduces risk Address adherence; avoid triggers including sleep deprivation and alcohol Consider epilepsy surgery earlier in drug-resistant convulsive epilepsy — seizure freedom lowers SUDEP mortality Discuss SUDEP with patients and families. The guideline supports disclosure; most patients want to know, and non-disclosure removes the main motivator for adherence and supervision"
      },
      {
       "type": "h3",
       "text": "Mortality in epilepsy generally"
      },
      {
       "type": "li",
       "text": "Overall mortality is 2–3 times the general population."
      },
      {
       "type": "li",
       "text": "SUDEP is the leading cause of epilepsy-related death in chronic refractory epilepsy, ahead of status epilepticus, accidents and suicide."
      },
      {
       "type": "li",
       "text": "Drowning carries the highest relative risk versus the general population (standardized mortality ratio in the range of 15–20×) — the basis for bathing and swimming counselling:"
      },
      {
       "type": "li",
       "text": "shower rather than bathe, never swim alone, supervision in open water."
      },
      {
       "type": "li",
       "text": "Suicide risk is elevated roughly 3-fold, driven largely by comorbid depression."
      },
      {
       "type": "li",
       "text": "Highest near-term mortality: ongoing drug-resistant epilepsy with a structural cause ;"
      },
      {
       "type": "li",
       "text": "lowest: sustained seizure freedom."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 402
    },
    {
     "id": "iv-safety-counselling-and-practical-management",
     "n": "9",
     "title": "Safety Counselling and Practical Management",
     "blocks": [
      {
       "type": "li",
       "text": "Bathing — showers rather than baths; never bathe an infant or child with epilepsy unsupervised."
      },
      {
       "type": "li",
       "text": "Swimming and water sports — permitted with a dedicated, informed observer; never alone."
      },
      {
       "type": "li",
       "text": "Sports — most sports are safe and should be encouraged. Restrict activities where a seizure causes a fall from height or immersion: climbing, scuba diving, solo cycling in traffic, gymnastics on apparatus. Contact sports are not contraindicated."
      },
      {
       "type": "li",
       "text": "Sleep deprivation and alcohol are the two most common avoidable precipitants in young adults."
      },
      {
       "type": "li",
       "text": "Piloting — private and commercial licences generally require prolonged seizure freedom off medication; standards are stricter than for driving."
      },
      {
       "type": "li",
       "text": "School — an individualized education plan (IEP) or 504 plan, a written seizure action plan, and a trained staff member. Where the school nurse is untrained, arrange training (the Epilepsy Foundation runs programmes) rather than restricting attendance or defaulting to home schooling."
      },
      {
       "type": "li",
       "text": "Genetic counselling — offer when a monogenic cause is found, for recurrence risk and reproductive planning; remember mosaicism and incomplete penetrance in apparently sporadic dominant disease."
      },
      {
       "type": "h3",
       "text": "Other therapies to recognize"
      },
      {
       "type": "li",
       "text": "Acetazolamide — carbonic anhydrase inhibitor used intermittently for catamenial exacerbation; tolerance develops."
      },
      {
       "type": "li",
       "text": "Rescue medications for seizure clusters — intranasal midazolam , intranasal diazepam , rectal diazepam, buccal midazolam. Contraindicated in acute narrow-angle glaucoma."
      },
      {
       "type": "li",
       "text": "ACTH and high-dose prednisolone — infantile epileptic spasms (vigabatrin first if tuberous sclerosis)."
      },
      {
       "type": "li",
       "text": "IVIG, corticosteroids, plasma exchange — autoimmune epilepsy and some DEEs."
      },
      {
       "type": "li",
       "text": "TMS — repetitive transcranial magnetic stimulation has modest evidence in focal epilepsy; not standard care."
      },
      {
       "type": "li",
       "text": "ECT — not a treatment for epilepsy; used for severe comorbid depression, and it is not contraindicated by epilepsy."
      }
     ],
     "tags": [
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 265
    }
   ],
   "selftest": [
    {
     "q": "A woman stable on lamotrigine for years has a breakthrough seizure during the third week of her pill pack. Why?",
     "a": "Estrogen in the active pills induces glucuronidation and drops lamotrigine by roughly half; levels rebound in the placebo week (sometimes into toxicity).",
     "section": "iv-newer-antiseizure-medications",
     "match": 4.02
    },
    {
     "q": "Which two metabolic diseases make the ketogenic diet the treatment rather than an option — and which similarly-named disease makes it dangerous?",
     "a": "GLUT1 deficiency and pyruvate dehydrogenase deficiency. Pyruvate carboxylase deficiency is a contraindication, as are fatty acid oxidation defects.",
     "section": "iv-dietary-therapy",
     "match": 3.78
    },
    {
     "q": "Under ILAE 2015, how long must a focal seizure with impaired consciousness last before it is status?",
     "a": "10 minutes (t1). Tonic-clonic status is 5 minutes.",
     "section": "iv-status-epilepticus",
     "match": 3.64
    },
    {
     "q": "Name the second-line status drugs and their weight-based doses and caps.",
     "a": "Levetiracetam 60 mg/kg (cap 4500 mg), fosphenytoin 20 mg PE/kg (cap 1500 mg PE), valproate 40 mg/kg (cap 3000 mg) — all equivalent per ESETT.",
     "section": "iv-status-epilepticus",
     "match": 2.77
    },
    {
     "q": "Which ASM needs a 12-week titration, and what is it preventing?",
     "a": "Cenobamate, to prevent DRESS.",
     "section": "iv-newer-antiseizure-medications",
     "match": 2.12
    },
    {
     "q": "A toddler with explosive occipital-onset status — which second-line agent do you avoid, and why?",
     "a": "Valproate — the presentation suggests POLG-related mitochondrial disease, where valproate can precipitate fatal hepatic failure.",
     "section": "iv-established-antiseizure-medications",
     "match": 3.27
    }
   ]
  },
  {
   "id": "v",
   "title": "Presurgical Evaluation and Surgery",
   "pages": [
    61,
    72
   ],
   "sections": [
    {
     "id": "v-who-gets-referred-and-when",
     "n": "1",
     "title": "Who Gets Referred, and When",
     "blocks": [
      {
       "type": "p",
       "text": "Two failed ASMs. Drug-resistant epilepsy is defined by failure of two tolerated, appropriately chosen regimens — and the chance that a third drug delivers seizure freedom is only about 4%."
      },
      {
       "type": "p",
       "text": "Referral at drug two is not aggressive; it is the evidence-based threshold."
      },
      {
       "type": "p",
       "text": "Surgery beats continued medical therapy in drug-resistant temporal lobe epilepsy — the Wiebe randomized trial found ~58% seizure-free at one year with surgery versus ~8% with medication, and the ERSET trial reproduced the effect in patients with shorter disease duration."
      },
      {
       "type": "p",
       "text": "Patients treated surgically are several times more likely to become seizure-free than those managed medically."
      },
      {
       "type": "p",
       "text": "Epilepsy surgery remains badly underused. Median delay from onset to surgery runs close to two decades. Documented disparities: Medicaid and Medicare coverage (versus private insurance) is associated with lower likelihood of surgery, and Black patients undergo surgery less often than White patients — the causal drivers have not been definitively identified."
      },
      {
       "type": "p",
       "text": "A normal MRI is not a contraindication. Non-lesional temporal lobe epilepsy has lower seizure-freedom rates than lesional disease, but the patient still warrants a full presurgical evaluation."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "seizure-management"
     ],
     "updated": false,
     "words": 180
    },
    {
     "id": "v-structural-imaging",
     "n": "2",
     "title": "Structural Imaging",
     "blocks": [
      {
       "type": "p",
       "text": "RECENTLY CHANGED — the HARNESS-MRI protocol. The ILAE Neuroimaging Task Force defined a Harmonized Neuroimaging of Epilepsy Structural Sequences protocol that every centre can run on a standard scanner:"
      },
      {
       "type": "li",
       "text": "3D isotropic T1 at 1 mm³ or better 3D high-resolution FLAIR 2D coronal T2 angled perpendicular to the long axis of the hippocampus"
      },
      {
       "type": "p",
       "text": "The task force recommends structural imaging in all new-onset epilepsy — generalized as well as focal. Reading an epilepsy-protocol study is a different act from reading a routine brain MRI, and a substantial number of \"MRI-negative\" patients become lesional when the images are reacquired and reviewed properly."
      },
      {
       "type": "h3",
       "text": "Mesial temporal sclerosis"
      },
      {
       "type": "p",
       "text": "Findings: hippocampal atrophy with T2/FLAIR hyperintensity and loss of internal architecture , often with ipsilateral atrophy of the fornix, mammillary body, amygdala and temporal lobe white matter — and extratemporal atrophy of the caudate , not enlargement."
      },
      {
       "type": "p",
       "text": "Sensitivity for detection: hippocampal volumetry ~97% , ahead of T2 relaxometry and qualitative visual inspection."
      },
      {
       "type": "p",
       "text": "Pitfalls that produce a false diagnosis of bilateral MTS: - The hippocampus is normally hyperintense on FLAIR — that alone is not sclerosis - Choroid fissure cysts expand the fissure and compress the hippocampus, mimicking atrophy - Incomplete hippocampal inversion, and oblique slice angulation Pathology. ILAE type 1 (most common) — predominant neuronal loss in CA1 and CA4 , with CA2 relatively spared ; type 2 is CA1-predominant, type 3 CA4-predominant. Granule cell dispersion and mossy fiber sprouting — dentate granule cell axons forming aberrant recurrent excitatory circuits back onto the granule cell layer, not onto CA1 — are characteristic. In MRI- negative temporal lobe epilepsy, changes are often confined to CA4 (the endfolium) ."
      },
      {
       "type": "figure",
       "n": 5,
       "src": "fig-hippocampal-subfields.png",
       "caption": "Hippocampal subfields and the ILAE hippocampal sclerosis types."
      },
      {
       "type": "h3",
       "text": "Focal cortical dysplasia"
      },
      {
       "type": "li",
       "text": "ILAE classification: Type I = architectural abnormality alone (radial = Ia, tangential = Ib, both = Ic). Type IIa = dysmorphic neurons. Type IIb = dysmorphic neurons plus balloon cells . Type III = dysplasia adjacent to a principal lesion — IIIa with hippocampal sclerosis , IIIb with a tumor, IIIc with a vascular malformation, IIId with an early-life injury."
      },
      {
       "type": "li",
       "text": "MRI: grey–white junction blurring, cortical thickening, abnormal sulcal or gyral pattern, and the transmantle sign — a T2/FLAIR hyperintense band tapering toward the ventricle, characteristic of type IIb."
      },
      {
       "type": "li",
       "text": "MRI is unrevealing in up to a third of FCD, especially type I (architectural) dysplasia ."
      },
      {
       "type": "li",
       "text": "In neonates and young infants , an FCD is typically T2 hyperintense and T1 hypointense — the reverse of the older-child appearance, and easy to miss before myelination completes."
      },
      {
       "type": "h3",
       "text": "Other lesions worth recognizing"
      },
      {
       "type": "table",
       "head": [
        "LESION",
        "POINTS"
       ],
       "rows": [
        [
         "DNET",
         "Nearly 100% associated with seizures; \"bubbly\" cortical mass, minimal mass effect, usually no enhancement"
        ],
        [
         "Ganglioglioma",
         "Second most epileptogenic; cystic with an enhancing mural nodule; temporal predilection"
        ],
        [
         "Cavernoma",
         "\"Popcorn\" with a hemosiderin rim; blooming on gradient echo/SWI. An incidental cavernoma with no epilepsy needs neither prophylactic ASM nor surgery — surveillance MRI is enough"
        ],
        [
         "AVM",
         "Seizures in 24–69% — the vascular malformation most associated with seizures"
        ],
        [
         "Polymicrogyria",
         "Bilateral perisylvian is the most common topography — oromotor dysfunction, dysarthria, feeding difficulty, epilepsy"
        ],
        [
         "Periventricular nodular heterotopia",
         "Nodules isointense to grey matter on all sequences and non-enhancing — the discriminator from subependymal tuberous sclerosis nodules, which calcify and may enhance"
        ],
        [
         "Band heterotopia / lissencephaly",
         "Arrested radial migration; LIS1 (autosomal dominant, classic lissencephaly) versus DCX (X-linked; lissencephaly in boys, band heterotopia in girls)"
        ],
        [
         "Dyke–Davidoff–Masson",
         "Unilateral hemispheric atrophy with compensatory calvarial thickening and enlarged frontal sinus"
        ],
        [
         "Hemimegalencephaly",
         "Enlarged dysplastic hemisphere with increased and abnormal white matter ; mTOR pathway"
        ]
       ]
      },
      {
       "type": "p",
       "text": "CT has a narrow role: acute emergencies, calcification, and bony detail. It reliably shows haemorrhage, calcification, subacute infarct and large tumors — and misses hippocampal sclerosis and dysplasia entirely."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "ilae-classification"
     ],
     "updated": true,
     "words": 596
    },
    {
     "id": "v-functional-and-metabolic-imaging",
     "n": "3",
     "title": "Functional and Metabolic Imaging",
     "blocks": [
      {
       "type": "table",
       "head": [
        "MODALITY",
        "WHAT IT SHOWS",
        "NOTES"
       ],
       "rows": [
        [
         "FDG-PET",
         "Interictal hypometabolism in and around the epileptogenic zone",
         "Most useful in MRI-negative temporal lobe epilepsy; the hypometabolic field is typically larger than the epileptogenic zone. False lateralization ~1–2% , usually from unrecognized ictal activity during tracer uptake"
        ],
        [
         "Ictal SPECT / SISCOM",
         "Ictal hyperperfusion ; subtraction co-registered to MRI",
         "Requires fast injection — the tracer must be given within seconds of onset. Ictal hyperperfusion at the focus with surrounding hypoperfusion; postictally the focus becomes hypoperfused"
        ],
        [
         "Flumazenil PET",
         "Reduced benzodiazepine receptor binding ipsilateral to the focus",
         "More restricted field than FDG"
        ],
        [
         "AMT PET",
         "α-[¹¹C]-methyl-L-tryptophan uptake",
         "Distinguishes epileptogenic from non-epileptogenic tubers in tuberous sclerosis"
        ],
        [
         "Diffusion MRI",
         "Peri-ictal ADC changes",
         "ADC falls at onset (cytotoxic), then rises in the later ictal and postictal period; DWI signal is increased postictally at the focus"
        ]
       ]
      }
     ],
     "tags": [
      "epilepsy-surgery"
     ],
     "updated": false,
     "words": 138
    },
    {
     "id": "v-magnetoencephalography",
     "n": "4",
     "title": "Magnetoencephalography",
     "blocks": [
      {
       "type": "li",
       "text": "MEG measures neuromagnetic fields on the order of femtoteslas (10⁻¹⁵ T) — a billionth of the earth's field, hence the magnetically shielded room."
      },
      {
       "type": "li",
       "text": "MEG is preferentially sensitive to tangential sources — activity in sulcal walls — while EEG favours radial sources at the gyral crown. The two are complementary , not redundant."
      },
      {
       "type": "li",
       "text": "MEG signals are not distorted by skull and scalp conductivity, so source localization is more straightforward than with EEG."
      },
      {
       "type": "li",
       "text": "Magnetic source imaging (MSI) = MEG source localization co-registered onto MRI. It solves the \"ill-posed\" inverse problem — determining generators from surface measurements — which has no unique solution but an infinite number of possible solutions , so it requires constraining assumptions."
      },
      {
       "type": "li",
       "text": "The forward model predicts the fields a given source would produce; the head model is a component of it."
      },
      {
       "type": "li",
       "text": "Inverse solutions: equivalent current dipole (ECD), minimum norm estimate (MNE), MUSIC, synthetic aperture magnetometry (SAM) and other beamformers. \"Standardized evoked response\" is not a real inverse method."
      },
      {
       "type": "li",
       "text": "Clinical indications: localizing interictal spikes in presurgical evaluation, and functional mapping (somatosensory, motor, auditory, language). Language lateralization by MEG concordance with the Wada test exceeds 70%."
      },
      {
       "type": "li",
       "text": "Limitations: it usually records interictal activity, and may capture no spikes at all in a given session; it is not indicated to confirm a diagnosis of epilepsy in a patient with a negative EEG, and not for routine new-onset seizures."
      }
     ],
     "tags": [
      "epilepsy-surgery"
     ],
     "updated": false,
     "words": 226
    },
    {
     "id": "v-neuropsychology-and-functional-lateralization",
     "n": "5",
     "title": "Neuropsychology and Functional Lateralization",
     "blocks": [
      {
       "type": "li",
       "text": "The neuropsychologist characterizes cognitive strengths and deficits, contributes to localization, establishes a baseline for postoperative comparison , and predicts risk."
      },
      {
       "type": "li",
       "text": "Diagnosing and treating psychiatric comorbidity is not their role — that belongs to psychiatry."
      },
      {
       "type": "li",
       "text": "Material-specific memory: dominant (usually left) temporal → verbal memory; non-dominant → visual/figural memory."
      },
      {
       "type": "li",
       "text": "Predictors of postoperative verbal memory decline after dominant temporal resection:"
      },
      {
       "type": "li",
       "text": "high baseline memory performance , late age at seizure onset , absence of hippocampal sclerosis , and a normal-appearing hippocampus on MRI. In short — the more functional the tissue you are removing, the more you stand to lose. Early onset allows functional reorganization and protects against decline."
      },
      {
       "type": "li",
       "text": "White matter tracts relevant to verbal memory: uncinate fasciculus and inferior longitudinal fasciculus ."
      },
      {
       "type": "li",
       "text": "Wada (intracarotid amobarbital) testing lateralizes language and memory and estimates the risk of postoperative amnesia. It does not localize the seizure focus."
      },
      {
       "type": "li",
       "text": "RECENTLY CHANGED. Language fMRI has largely displaced Wada for language lateralization; the AAN concluded it may be considered an alternative to the IAP in appropriate candidates. Memory fMRI is less established, and Wada retains a role where bilateral or crossed dominance is suspected or memory reserve is in doubt. fMRI results depend on task design, patient performance, and analysis method — duration of epilepsy is not a principal technical consideration."
      },
      {
       "type": "li",
       "text": "New cognitive complaints on stable therapy warrant formal neuropsychological assessment rather than a reflexive medication change."
      },
      {
       "type": "figure",
       "n": 10,
       "src": "fig-presurgical-zones.png",
       "caption": "The cortical zones of presurgical evaluation."
      }
     ],
     "tags": [
      "epilepsy-surgery"
     ],
     "updated": true,
     "words": 231
    },
    {
     "id": "v-intracranial-monitoring",
     "n": "6",
     "title": "Intracranial Monitoring",
     "blocks": [
      {
       "type": "p",
       "text": "When it is needed: discordant non-invasive data, MRI-negative epilepsy, suspected bitemporal or bilateral onset, extratemporal or multilobar networks, and proximity to eloquent cortex requiring mapping."
      },
      {
       "type": "p",
       "text": "RECENTLY CHANGED — SEEG has become the default. Stereo-EEG depth electrodes have largely replaced subdural grids in North America. Advantages: sampling of deep, mesial, insular and bilateral structures; no craniotomy; lower infection and haemorrhage rates;"
      },
      {
       "type": "p",
       "text": "better tolerated. Trade-off: no continuous coverage of the cortical surface , so extensive functional mapping over a convexity still favours grids."
      },
      {
       "type": "li",
       "text": "Complication risk with subdural grids rises with the number of electrodes and extent of coverage — more than with age, duration of monitoring, or side."
      },
      {
       "type": "li",
       "text": "Extratemporal epilepsy far more often requires invasive recording than temporal lobe epilepsy."
      },
      {
       "type": "li",
       "text": "High-frequency oscillations — resection of tissue generating fast ripples is associated with better outcome, making them a candidate biomarker of the epileptogenic zone. Recording requires high sampling rates."
      },
      {
       "type": "li",
       "text": "Electrical stimulation mapping in children: thresholds for both clinical responses and afterdischarges are higher than in adults, cooperation is limited, and shorter sessions spread over more visits work better. Individual finger movements are difficult to elicit in young children."
      },
      {
       "type": "li",
       "text": "Electrically induced seizures are most predictive of a good resection outcome when their semiology is identical to the patient's habitual seizures."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "eeg-fundamentals",
      "ilae-classification"
     ],
     "updated": true,
     "words": 208
    },
    {
     "id": "v-procedures",
     "n": "7",
     "title": "Procedures",
     "blocks": [
      {
       "type": "table",
       "head": [
        "PROCEDURE",
        "INDICATION",
        "OUTCOME AND RISK"
       ],
       "rows": [
        [
         "Anterior temporal lobectomy",
         "Mesial temporal sclerosis; the best-validated epilepsy operation",
         "~60–70% seizure-free long term. Risks: superior quadrantanopia from Meyer's loop, verbal memory decline (dominant side), transient psychosis, depression and suicidality"
        ],
        [
         "Selective amygdalohippocampectomy",
         "Discrete mesial temporal focus",
         "Seizure-freedom rates similar to ATL ; a clear neurocognitive advantage has not been established"
        ],
        [
         "LITT (laser interstitial thermal therapy)",
         "Mesial temporal sclerosis, hypothalamic hamartoma, small deep lesions, cavernoma",
         "Minimally invasive, short stay, lower risk of verbal memory decline ; seizure freedom somewhat below open resection. Low intralesional haemorrhage risk"
        ],
        [
         "Lesionectomy",
         "DNET, ganglioglioma, cavernoma, focal dysplasia",
         "Excellent when the lesion is discrete and concordant"
        ],
        [
         "Functional hemispherotomy",
         "Hemispheric pathology with pre- existing hemiparesis — Rasmussen, hemimegalencephaly, perinatal infarct, Sturge-Weber",
         "70–80% seizure-free. Expect persistent homonymous hemianopia and loss of fine finger movement; gross motor function usually returns toward baseline. Preferred over anatomical hemispherectomy — lower risk of hydrocephalus and superficial hemosiderosis"
        ],
        [
         "Corpus callosotomy",
         "Atonic and tonic drop attacks , usually in Lennox– Gastaut",
         "Palliative. Anterior two-thirds first; may worsen focal seizures and cause transient disconnection syndrome"
        ],
        [
         "Multiple subpial transection",
         "Eloquent cortex that cannot be resected",
         "Limited and declining use"
        ],
        [
         "Gamma knife radiosurgery",
         "Hypothalamic hamartoma with gelastic seizures",
         "Effective and minimally invasive; delayed benefit"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Rasmussen encephalitis — progressive unihemispheric inflammation with T-cell infiltrates and microglial nodules , epilepsia partialis continua, progressive hemiparesis and cognitive decline."
      },
      {
       "type": "p",
       "text": "Bilateral disease is rare. Immunotherapy may slow progression but hemispherotomy is the only definitive treatment — multilobar resection is not an adequate substitute. Children reorganize function better than adolescents and adults."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "seizure-management",
      "ilae-classification"
     ],
     "updated": false,
     "words": 254
    },
    {
     "id": "v-neuromodulation",
     "n": "8",
     "title": "Neuromodulation",
     "blocks": [
      {
       "type": "p",
       "text": "DEVICE TARGET EFFICACY KEY FACTS"
      },
      {
       "type": "li",
       "text": "VNS Left cervical vagus nerve ~35% median Hoarseness is the most common adverse effect ;"
      },
      {
       "type": "li",
       "text": "reduction at 1 also cough, dyspnea, voice change. Can worsen year, improving obstructive sleep apnea — lower the frequency and beyond 2 years duty cycle. Leads must sit below the superior and inferior cervical cardiac branches ; stimulating them during lead testing causes bradycardia or asystole . Frequent magnet activation at high frequency (>50 Hz) with ON time > OFF time risks nerve injury RNS Cortical or hippocampal ~44% at 1 year, Closed-loop. Blinded phase: 37.9% reduction versus foci; increasingly ~75% median 17.3% sham. Haemorrhage and infection each ~2%."
      },
      {
       "type": "li",
       "text": "thalamic reduction at 9 Mood and cognition do not worsen; quality of years ; 50% life improves. Suited to bilateral mesial temporal responder rate onset or eloquent cortex. No clinical factor reliably ~55% at 2 years predicts response in mesial temporal epilepsy DBS Anterior nucleus of the ~40% at 1 year Paresthesia is the most common device-related thalamus (SANTE); rising to ~69% at 5 adverse event ; depression (~15%) and centromedian nucleus years and ~75% at subjective memory impairment (~13%) are the for generalized epilepsy 7 years notable stimulation-related effects. Open-loop, and Lennox–Gastaut continuous cycling RECENTLY CHANGED. VNS and MRI — blanket \"turn off both modes\" advice has been replaced by device- and coil-specific MR-conditional labeling ; check the generator model and the specific MRI conditions. - Thalamic RNS now has encouraging data in generalized epilepsy, and centromedian DBS in Lennox–Gastaut, blurring the old \"RNS for focal, DBS for network\" division. Recent comparisons find the two broadly comparable, with RNS efficacy appearing to depend more on long-term network neuromodulation than on aborting individual seizures."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "ilae-classification"
     ],
     "updated": true,
     "words": 284
    },
    {
     "id": "v-quality-of-life-driving-and-employment",
     "n": "9",
     "title": "Quality of Life, Driving and Employment",
     "blocks": [
      {
       "type": "li",
       "text": "Depression is the strongest determinant of quality of life in epilepsy — a stronger predictor than seizure frequency. It affects at least a third of patients and is under-treated."
      },
      {
       "type": "li",
       "text": "QOLIE-31 is the standard instrument."
      },
      {
       "type": "li",
       "text": "Psychosis is most common in temporal lobe epilepsy; postictal psychosis follows a lucid interval of hours to days after a seizure cluster and responds to atypical antipsychotics."
      },
      {
       "type": "li",
       "text": "Suicidality is elevated, driven mainly by coexisting depression."
      },
      {
       "type": "li",
       "text": "Driving: seizure-free intervals are set by state and vary widely (commonly 3–12 months)."
      },
      {
       "type": "li",
       "text": "Restrictions apply to provoked as well as unprovoked seizures. Commercial licences (US DOT) require being seizure-free and off ASMs for a prolonged period — the standard teaching is ~10 years. In mandatory-reporting jurisdictions patients are more likely to conceal driving from their physician , and stricter laws have not been shown to reduce unlicensed driving or fatal crashes. Comorbid obstructive sleep apnea is a major and modifiable crash risk."
      },
      {
       "type": "li",
       "text": "Employment and the ADA: an employer may not ask about the existence or severity of a disability , and may not ask health questions until after a job offer . They may ask whether the applicant can perform the essential functions of the job. An offer may only be withdrawn, or an employee excluded, on documented evidence of a direct threat to health or safety. Free workplace accommodation advice comes from the Job Accommodation Network (JAN) ."
      },
      {
       "type": "li",
       "text": "Orphan Drug Act (1983) — designation requires a disease affecting fewer than 200,000 people in the US."
      },
      {
       "type": "li",
       "text": "Self-management programmes with evidence for improving mood: HOBSCOTCH, PACES, TIME ."
      }
     ],
     "tags": [
      "seizure-management"
     ],
     "updated": false,
     "words": 262
    },
    {
     "id": "v-outcome-classification",
     "n": "10",
     "title": "Outcome Classification",
     "blocks": [
      {
       "type": "p",
       "text": "Two scales, and the exam expects you to tell them apart."
      },
      {
       "type": "p",
       "text": "Engel classification (the older, outcome-focused scale):"
      },
      {
       "type": "table",
       "head": [
        "CLASS",
        "MEANING"
       ],
       "rows": [
        [
         "I",
         "Free of disabling seizures (IA = completely seizure-free since surgery; IB = non-disabling auras only; IC = some disabling seizures after surgery but free ≥2 years; ID = generalized convulsion with ASM withdrawal only)"
        ],
        [
         "II",
         "Rare disabling seizures (\"almost seizure-free\")"
        ],
        [
         "III",
         "Worthwhile improvement"
        ],
        [
         "IV",
         "No worthwhile improvement"
        ]
       ]
      },
      {
       "type": "p",
       "text": "ILAE outcome scale (1–6, counts seizure days per year and is more granular):"
      },
      {
       "type": "table",
       "head": [
        "CLASS",
        "MEANING"
       ],
       "rows": [
        [
         "1",
         "Completely seizure-free, no auras"
        ],
        [
         "2",
         "Auras only, no other seizures"
        ],
        [
         "3",
         "1–3 seizure days per year"
        ],
        [
         "4",
         "4 seizure days per year to 50% reduction from baseline"
        ],
        [
         "5",
         "Less than 50% reduction to 100% increase"
        ],
        [
         "6",
         "More than 100% increase over baseline"
        ]
       ]
      },
      {
       "type": "p",
       "text": "Auras are the key difference : Engel IB counts non-disabling auras as a good outcome; ILAE separates them into class 2."
      },
      {
       "type": "p",
       "text": "Outcome predictors. Favourable: a discrete concordant lesion on MRI (especially hippocampal sclerosis or a benign tumor), concordant EEG and semiology, shorter duration of epilepsy, unilateral interictal discharges, complete resection of the lesion. Unfavourable: MRI-negative epilepsy, extratemporal onset, bilateral or non-localized discharges, need for invasive monitoring, incomplete resection, and generalized tonic-clonic seizures."
      },
      {
       "type": "p",
       "text": "Repeat surgery is reasonable after a failed resection where re-evaluation identifies residual or unresected epileptogenic tissue — outcomes are less good than first-time surgery but seizure freedom remains achievable in a substantial minority."
      }
     ],
     "tags": [
      "epilepsy-surgery",
      "ilae-classification",
      "seizure-management"
     ],
     "updated": false,
     "words": 232
    }
   ],
   "selftest": [
    {
     "q": "Name the three sequences of the HARNESS-MRI protocol.",
     "a": "3D isotropic T1 (≤1 mm³), 3D high-resolution FLAIR , and 2D coronal T2 perpendicular to the hippocampal long axis .",
     "section": "v-structural-imaging",
     "match": 3.47
    },
    {
     "q": "Which hippocampal subfield is relatively spared in ILAE type 1 hippocampal sclerosis?",
     "a": "CA2. The predominant loss is in CA1 and CA4.",
     "section": "v-structural-imaging",
     "match": 3.33
    },
    {
     "q": "Which patient is at highest risk of verbal memory decline after dominant temporal lobectomy?",
     "a": "The patient with high baseline verbal memory, late seizure onset, and no hippocampal sclerosis — functional tissue is being resected, and there has been no time for reorganization.",
     "section": "v-neuropsychology-and-functional-lateralization",
     "match": 3.9
    },
    {
     "q": "Why are MEG and EEG complementary rather than redundant?",
     "a": "MEG preferentially detects tangential (sulcal) sources; EEG favours radial (gyral crown) sources. They sample different generator geometries.",
     "section": "v-magnetoencephalography",
     "match": 3.27
    },
    {
     "q": "What is the most common device-related adverse event of anterior thalamic DBS, and what is the most common stimulation-related one?",
     "a": "Paresthesia is the most common device-related event; depression is the most common stimulation-related one (with subjective memory impairment close behind).",
     "section": "v-neuromodulation",
     "match": 3.41
    },
    {
     "q": "A patient has an incidental cavernoma and one remote febrile seizure. What do you do?",
     "a": "Neither ASM nor surgery — surveillance imaging. An incidental cavernoma without epilepsy does not warrant prophylactic treatment.",
     "section": "v-structural-imaging",
     "match": 2.65
    }
   ]
  }
 ]
}