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)
- Structural brain lesion
- 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
- Intoxication
- Etiology by age
- 10-40 years
- Idiopathic, trauma, drugs/withdrawal, metabolic
- 40-60 years
- Tumor, trauma, drugs/withdrawal
- >60 years
- Vascular, tumor, subdural, infection
- 10-40 years
- Metabolic
- Idiopathic
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
