Treatment

DEPENDS on the underlying cause Metabolic : correction Structural abnormality: seizure control + consider surgery Tumor Vascular Idiopathic : seizure control

Diagnosis and Classification of seizure disorder choose Anti-epileptic drug of choice Main Goal: Adequate seizure control monitoring of response (seizure-free) and side effects therapeutic monitoring drug interactions

Principles of Treatment Individualized treatment Selection of specific drug for initial therapy is based on specific clinical seizure type Monotherapy is preferred Dose is increased gradually Enough time for steady state to be reached must be allowed Prompt substitution when serious adverse reaction develops If poor seizure control-gradually withdraw first drug while replacing with second drug of choice for seizure type (should not be stopped abruptly) Treatment failures may be due to poor compliance or misdiagnosis Continue treatment to achieve minimum seizure-free period of 3-5 years Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Absence seizures Ethosuximide is the drug of choice for typical absence seizure Valproic Acid is the drug of choice for atypical absence seizure used only when treatment tolerance or failure appear with Ethosuximide Wide spectrum AED Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Anti Epileptic DrugGlutamate Antagonist GABA agonist Na channel blocker Ca channel blocker Phenobarbital* Phenytoin* Carbamazepine* Valproic Acid** Gabapentin* Topiramate**** Oxcarbazepine** Ethosuximide* Lamotrigine**

Ethosuximide Primary indication: First-line or adjunctive therapy of generalized absence seizures Mechanisms of action: Inhibition of neuronal T-type calcium channels in the thalamus (Type III AED) Usual preparations: Capsules: 250 mg; syrup: 250 mg/5 mL Usual dosages: Initial: 250 mg (adults); 10–15 mg/kg/day (children) Maintenance: 750–1500 mg/day (adults); 15–40 mg/kg/day (children) Dosing frequency: 2–3 times/day Significant drug interactions: – Ethosuximide levels are reduced by co-medication with carbamazepine, phenytoin, phenobarbital and rifampicin. – Valproic acid may exert synergistic effects with ethosuximide in patients refractory to either drug given alone, and may have variable and inconsistent effects on ethosuximide levels. Serum valproic acid levels may be decreased by ethosuximide. Ethosuximide levels are increased by isoniazid Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Serum level monitoring: usually optimized based on clinical and EEG response. Main advantages: Well-established treatment for absence epilepsy without the risk of hepatic toxicity carried by valproic acid Main disadvantages: Adverse effects common. Unlike valproic acid, ethosuximide does not protect against generalized tonic– clonic seizures Common/important adverse effects: Gastrointestinal symptoms, drowsiness, ataxia, diplopia, headache, dizziness, hiccoughs, sedation, behavioural disturbances, acute psychotic reactions, extrapyramidal symptoms, blood dyscrasias, rash, lupus-like syndrome, other severe idiosyncratic reactions Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Valproic Acid Primary indications: First line for atypical absence seizures. First-line therapy of idiopathic generalized epilepsies. First-line or adjunctive therapy of cryptogenic or symptomatic generalized epilepsies. Valuable but not generally first-line therapy for partialseizures Mechanisms of action: Increases brain GABA activity by increasing activity of glutamic acid decarboxylase, inhibition of GABA transaminase, inhibition of succinic semialdehyde dehydrogenase Usual dosages: Initial: 400–500 mg/day (adults); 15 mg/kg/day (children) Maintenance: 500–2500 mg/day (adults); 20–40 mg/day (children under 20 kg); 20–30 mg/kg/day (children over 20 kg) Dosing frequency: 2-3 times a day Serum level monitoring: Dosage usually can be adjusted on the basis of clinical response, but monitoring serum valproic acid levels may be useful in selected cases Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Significant drug interactions : Enzyme-inducing drugs and imipenem antibiotics reduce serum valproic acid levels. Felbamate, stiripentol, isoniazid and other drugs may increase valproic acid levels. Valproic acid inhibits the metabolism of a number of drugs, most notably phenobarbital, lamotrigine and rufinamide. Valproic acid displaces phenytoin from plasma protein binding sites and may inhibit phenytoin metabolism at the same time Common/important adverse effects: Tremor, sedation, asthenia, encephalopathy, extrapyramidal symptoms, nausea, vomiting, hyperammonaemia, weight gain, polycystic ovary syndrome, hair loss, platelet and coagulation disorders, liver toxicity, pancreatitis, teratogenic effects (including spina bifi da) Main advantages: Unsurpassed effi cacy in most generalized epilepsy syndromes. Broadspectrum efficacy in different seizure types Main disadvantages: Weight gain, severe liver toxicity (particularly in children), teratogenicity Katzung Basic and Clinical Pharmacology, 9 th ed. The Treatment of Epilepsy, 3 rd ed.

Other Modalities Surgical Management – surgical excision of epileptic foci in simple and complex partial epilepsies that have not responded to intensive and prolonged medical therapy may be beneficial for some Regulation of Physical and Mental Activity – precipitating factors needs to be modified and stressed to the patient – moderate amount of physical exercise can also be advised – psychosocial difficulties needs to be identified and addressed early The Treatment of Epilepsy, 3 rd ed.

Ketogenic Diet – biochemical alteration both in the blood and in the brain – possible GABA-mimetic effects of ketosis given the structural similarities of GABA,  -hydroybutyrate and acetoacetate Vagal Nerve Stimulation – vagal stimulation produces its effects are unclear and it is done through attachment of electrodes to the vagus nerve at the left carotid bifurcation The Treatment of Epilepsy, 3 rd ed.

Management American Academy of Neurology Guidelines on CESSATION OF TREATMENT Stopping the treatment may be considered when: – The patient has been seizure-free for 2 to 5 years – The patient has a single type of seizure – The patient has no abnormalities on neurologic examination and has a normal IQ – The patient’s electroencephalogram (EEG) has become normal