Seizures & Epilepsy

General Information

Classification: Nervous
Figure 1 Absence (petit mal) seizure EEG. Note the 3 Hz spike-and-wave discharge waveforms characteristic of absence seizures. (Source: Wikimedia Commons)

What is it?

Abnormal neuronal excitatory activity

Epilepsy: two or more unprovoked seizures within 24 hours or 60% recurrence rate after the first

Risk Factors: trauma to the affected bone, young age ([extreme] sports), old age (osteoporosis, brittle bones)

Evaluation:

  • Symptoms
    1. Trigger
    2. Aura (present only in focal seizures): sense of deja vu (disconnect with temporal lobe), nausea, automatisms (rapid blinking, lip smacking/chewing)
    3. Ictal event: seizure
    4. Post-ictal phase (in focal seizures with impairment, full generalized seizures, or focal to bilateral generalized): confusion, lethargy, amnesia, Todd’s paralysis (unilateral weakness)
  • Physical exam
    • Obtain history (mechanism of injury, timing/progression, prior injury)
    • Inspection, palpation, evaluate range of motion (ROM)
  • Imaging: x-ray (first line, include joint), CT (complex fractures), MRI (stress)
  • Lab biomarkers:
    • Bio formation markers (alkaline phosphatase, calcium, phosphate)
    • CBC: increased WBC recruitment
    • CRP/ESR: elevated due to inflammation

Classification(see below)

  1. Focal seizures
  2. Generalized seizures

Pathophysiology:

Greater electrical activity can be attributed to decrease in inhibitory pathway (GABA) or increase in stimulatory (glutamate)

Glutamate pathways

  • Increased production
  • Increased AMPA/NMDA receptor activity

GABA pathways

  • Dysfunctional GABA-A receptors (which facilitates hyperpolerization), diminishing GABA’s inhibitory effects
Physiological Blurb: AMPA vs NMDA Receptors

AMPA

  • Ionotropic: Na+, K+
  • Phasic
  • Activation: voltage-independent glutamate binding

NMDA

  • Ionotropic: Na+, K+, Ca2+
    • Has Mg2+ block at RMP (thus not open)
  • Tonic
  • Activation: glutamate-induced depolarization (removing Mg2+ block)

Etiology

VITAMIN D N E mnemonic for seizure causes:

Vascular, Infectious, Traumatic, Autoimmune, Metabolic, Idiopathic, Neoplastic, Drugs, Extra

Vascular: ischemic/hypoxic brain injuries, hemorrhage

Infections (CNS)

Traumatic brain injuries: epidural/subdural hematoma

Autoimmune: lupus, neoplasias

Metabolic: Na+, Ca2+, Mg2+ imbalances, increased T3/T4, ammonia

Idiopathic: see Epileptic syndromes

Neoplastic: gliobastomamultiforme, meningioma, metastasized malignancies

Drugs (Otis Campbel): opioids, tricyclic antidepressants, isoniazid, salicyclic toxicity, cocaine, amphetamines, metronidazole, penicillin, benzo withdrawal, ethanol, lithium

Extra/other: ecclampsia, genetic/family history

Classification

Focal seizures

Consciousness

Focal aware (simple partial): retain consciousness

Focal impaired awareness (complex partial): lose consciousness

Motor

Focal clonic: rhythmic jerking

Focal myoclonic: brief, shocking jerk

Focal clonic (Jacksonian March): jerking spreads along motor homunculus, starting distally and moving proximally (ex. jerking originates in hand but moves up to full arm)

  • EEG findings: contralateral motor spikes

Non-motor

Focal sensory (originating in parietal/occipital/temporal lobes): pain, parasthesias, hallucinations, ringing, abnormal, intense smells

Focal autonomic (originating in insula): SNS symptoms (increased HR, TA, HT), urinary incontinence, salivation

Focal cognitive/emotional: deja vu, hypersexual, depersonalization

Generalized seizures

Motor

Grand Mal (tonic-clonic) classic convulsive: starts tonic (stiffening) then clonic (jerking) with extreme contractions

  • EEG findings: polyspike-and-waves, high amplitude spikes
  • Contractions: lungs (involuntary scream), eyes (extreme upgaze), mouth (pooling of oral secretions), mastication (jaw clenching, tongue biting), sphincters (incontinence)

Focal secondarily generalized (focal to bilateral tonic-clonic): focal hemisphere origins then progress to tonic-clonic

Tonic: see above

Clonic: see above

Myoclonic*: asynchronous rapid jerking

  • EEG findings: 10-16 Hz polyspike wave bursts

Atonic: no movement, drop attacks

Non-motor

Petit mal (absence): “star-gazing” (dazed, unresponsive), no post-ictal phase

  • EEG findings: 3 Hz spike-wave (Figure 1)

*Note: all generalized seizures, except myoclonic, present with complete/brief impairment

Epilepsy

Definition: two or more unprovoked seizures within 24hrs OR 60% recurrence rate after the first

Epileptic syndromes

  • West syndrome: severe, brief jerky spasms in infants (linked to developmental encephalopathy)
  • Lennox-Gastaut syndrome: severe, childhood onset of multiple seizure forms (tonic, atonic)
  • Juvenile myoclonic epilepsy: jerking movements in waking, generalized seizures
  • Dravet syndrome: severe infantile epilepsy (often fever-triggered)

Status epilepticus: extremely urgent, >5 min continuous seizures OR recurrent seizures without return to normal electrical activity

Treatment

To counter glutamate’s excitatory effects

Anti-epileptics

  • Na+ channel blockers (very problematic to let phosphenytoin cuddle): valproic acid, phosphenytoin, topiramate, lamotrigine, fosphenytoin, carbamazepine
    • Prevent positive influx of ions, reducing rate of depolarization
  • Ca2+ channel blockers: gabapentin, ethosuximide (especially for absence)
    • Prevent Sv2a-mediated vesicular exocytosis of glutamate
  • Sv2a blockers: levatiracetam
  • AMPA/NMDA antagonists: ketamine

To increase GABA’s inhibitory effects

  • GABA-A agonists (mimic GABA activity): benzodiabepines, propofol, phenobarbital
  • GABA reuptake inhibitors: tiagabine
  • GABA-transaminase inhibitors (which normally inactivates GABA): vigabatrin, valproate

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