All about seizures! – 6.5.2018

Today, Hugo presented a case of a middle aged man with schizophrenia and recently diagnosed seizure disorder who presented with worsening seizures, found to have toxic levels of clozapine!

  • Etiologies of seizures:
    • Idiopathic
      • >75% of seizure disorders
    • Primary neurological condition
      • Structural brain lesion
        • Stroke
        • Hemorrhage
        • Tumor
        • Head trauma
        • Abscess
        • Neurocystercircosis
        • AVM
      • Meningitis/encephalitis
      • HIV encephalopathy
      • Global cerebral ischemia (post cardiac arrest)
    • Systemic disorder
      • Metabolic
        • Hypo/hyperglycemia
        • Hypo/hypernatremia
        • Hypo/hypercalcemia
        • Hypomagnesemia
        • Uremia
        • Vitamin B6 deficiency
      • Drug
        • Intoxication
          • Cocaine
          • Phencyclidine
          • Methamphetamines
        • Withdrawal
          • ETOH
          • Benzos
          • Barbiturates
          • Baclofen
        • Med-induced lowered seizure threshold
          • Bupropion
          • Abx: cefepime, Cipro, imipenem, INH
          • Clozapine
          • Cyclosporine
          • Tacrolimus
          • Theophylline
          • TCAs
          • Tramadol
        • Eclampsia
        • Hyperthermia
        • Hypertensive encephalopathy
        • Hepatic encephalopathy
        • Porphyria
      • Etiology by age
        • 10-40 years
          • Idiopathic, trauma, drugs/withdrawal, metabolic
        • 40-60 years
          • Tumor, trauma, drugs/withdrawal
        • >60 years
          • Vascular, tumor, subdural, infection

DDx for seizure:

  • Syncope
  • Movement disorder
  • Tremor
  • Psychogenic nonepileptic seizure
    • Forced eye closure
    • Long duration
    • Hypermotor activity that starts and stops
    • Pelvic thrusting
    • Dx?
      • Inpatient video EEG
      • Strong association with PTSD
    • Narcolepsy

 

Clozaril toxicity:

  • Metabolic syndrome
  • Sedation
  • Anticholinergic side effects
    • Especially urinary retention
  • Orthostatic hypotension
  • QTc prolongation
  • Prolactin elevation (+)
  • EPS/TD (+)
  • Seizures (lower threshold, 3% incidence per year, highest of any other secong gen antipsychotic, dose dependent)
  • Agranulocytosis (1%)
  • Myocarditis and cardiomyopathy (fatal, within few weeks or months of treatment)
  • Gastrohypomotility (usually bowel)

 

Epilepsy

  • Defined as two or more unprovoked seizures

 

Seizure Classifications:

Seizure Type Characteristics
Simple partial Normal consciousness/awareness

Single neurologic modality involving single region of body

Complex partial Conscious but not aware

May have an aura

Automatism (lip smacking, swallowing, or manipulating objects)

Postictal confusion

Primary generalized LOC

No prodromal or localizing symptoms

Whole-body stiffening (tonic) and/or jerking (clonic) seizures

 

Other:

  • When is continuous EEG needed?
    • If patient is not returning toward baseline in 15 mins after a seizure, goal is to rule out nonconvulsive seizures
  • How to define status?
    • > 5 mins

 

Treatment:

  • Start AED after > 2 unprovoked seizures
  • Start AED after first unprovoked seizure if
    • Age > 65
    • h/o significant head trauma
    • h/o partial seizure
    • h/o post-ictal weakness or paralysis
    • focal findings on neuroimaging
    • focal findings on EEG
  • If therapy is unsuccessful:
    • D/c first drug and start second drug as single agent

 

Which AED to initiate:

Drug Seizure type Side effects Notes
Lamotrigine Both SJS, SI  
Keppra Both Few DDIs, well tolerated

SJS, SI

Safe in pregnancy
Topamax Both Kidney stones

SJS, SI

 
Depakote Both Weight gain, HLD, PCOS, teratogenic

SJS, SI

Superior to other AEDs for generalized seizures
Zonisamide Both Kidney stoNes

SJS, SI

 
Carbamazepine Partial Interacts with other hepatically metabolized drugs, osteoporosis, HLD, hyponatremia

SJS, SI

Cost-effective

 

Refractory disease?

  • Temporal lobectomy:
    • Mesial temporal lobe sclerotic lesion resection
  • PNES?
    • Refer to psych

 

Symptom free in 2-5 years?

  • Withdraw AEDs

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