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