Epilepsy and Niazy B Hussam Aldin

DEFINTION DEFINITIONS • Epilepsy implies a periodic recurrence of seizures with or without convulsions. A seizure results from an excessive discharge of cortical neurons and is characterized by changes in electrical activity as measured by the electroencephalogram (EEG). A convulsion implies violent, involuntary contraction(s) of the voluntary muscles.

Pathophysiology Then normal membrane conductances and inhibitory synaptic currents break down, excitability spreads locally (focal seizure) or more widely (generalized seizure). • Mechanisms that may contribute to synchronous hyper excitability include: ✓ Alterations of ion channels in neuronal membranes ✓ Biochemical modifications of receptors ✓ Modulation of second messaging systems and gene expression ✓ Changes in extracellular ion concentrations ✓ Alterations in neurotransmitter uptake and metabolism in glial cells ✓ Modification in the ratio and function of inhibitory circuits ✓ Local neurotransmitter imbalances (e.g., glutamate, aaminobutyric acid [GABA]), acetylcholine, norepinephrine, and serotonin)

Clinical Manifestation SYMPTOMS • Symptoms of a specific seizure depend on seizure type. Although seizures can vary between patients, they tend to be stereo typed within an individual. • CP seizures may include somatosensory or focal motor features. They are associated with altered consciousness • Absence seizures have only very brief (seconds) periods of altered consciousness.• GTC seizures are major convulsive episodes and are always associated with a loss of consciousness. SIGNS • Intricately (between seizure episodes), there are typically no objective, pathognomonic signs of epilepsy.

Seizures Partial Generalized Simple Partial Complex Partial Secondarily Absence Myoclonic Atonic Tonic Tonic-Clonic

LABORATORY TESTS There are currently no diagnostic laboratory tests for epilepsy. In some cases, particularly following GTC (or perhaps CP) seizures, serum prolactin levels may be transiently elevated. Laboratory tests may be done to rule out treatable causes of seizures (e.g., hypoglycemia, altered serum electrolyte concentrations, infections, etc.) that do not represent epilepsy

Aim of treatment DESIRED OUTCOME • The goal of treatment is to control or reduce the frequency of seizures, minimize side effects, and ensure compliance, allowing the patient to lives normal a life as possible. Complete suppression of seizures must be balanced against tolerability of side effects, and the patient should be involved in defining the balance.

General approach The treatment of choice depends on the type of epilepsy (Table 52-2) and on drug-specific adverse effects and patient preferences. Fig. 52-1 is a suggested algorithm for treatment of epilepsy. • Begin with monotherapy; about 50% to 70% of patients can be maintained on one antiepileptic drug (AED), but all are not seizure free. • Up to 60% of patients with epilepsy are noncompliant, and this is the most common reason for treatment failure. • Drug therapy may not be indicated in patients who have had only one seizure or those whose seizures have minimal impact on their lives. Patients who have had two or more seizures should generally be started on AEDs.

Mechanism of action The mechanism of action of most AEDs includes effects on ion channels (sodium and Ca), inhibitory neurotransmission (increasing CNS GABA), or excitatory neurotransmission (decreasing or antagonizing glutamate and aspartate). AEDs that are effective against GTC and partial seizures probably work by delaying recovery of sodium channels from activation. Drugs that reduce corticothalamic T-type Ca currents are effective against generalized absence seizures.

AED monotherapy is preferred in pregnancy. Clearance of Phenytoin carbamazepine, phenobarbital, ethosuximide, lamotrigine, And clorazepate increases during pregnancy, and protein binding may be altered. There is a higher incidence of adverse pregnancy outcomes in women with epilepsy, and the risk of congenital malformations is 4% to 6% (twice as high as in non epileptic women). Barbiturates and phenytoin are associated with congenital heart malformations and facial clefts. Valproic acid and carbamazepine are associated with spina bifida (0.5% to 1%) and hypospadias.

Newer AEDs The newer AEDs are generally used as second-line drugs when treatment with established first-line drugs has failed. Exceptions to this are lamotrigine, levetiracetam, topiramate and oxcarbazepine, which have indications for first-line use in the UK. Lamotrigine is considered the first-line option in women of child-bearing potential who have idiopathic generalised epilepsy because of the teratogenic profile of sodium valproate,

Gabapentin, levetiracetam, tiagabine and vigabatrin are generally used in combination with another drug. • Newer drugs can be used where older drugs are unsuitable for the person, for example, liver disease, or where unwanted effects cannot be tolerated.

Withdrawal of drugs AEDs should not be withdrawn abruptly. With barbiturates and benzodiazepines, in particular, rebound seizures may occur. Withdrawal of individual AEDs should be carried out in a slow stepwise fashion to avoid the precipitation of withdrawal seizures (e.g. over 2–3 months). This risk is particularly great with barbiturates, for example, phenobarbital and primidone, and benzodiazepines, for example, clobazam and clonazepam. If a drug needs to be withdrawn rapidly, for example, if there are life-threatening side effects, then diazepam or another benzodiazepine can be used to cover the Withdrawal phase. Examples of withdrawal regimens are given below. • Carbamazepine 100–200 mg every 2 weeks (as part of a drug change) 100–200 mg every 4 weeks (total withdrawal

Status epilepticus Initial management of status epilepticus is supportive and may include: • positioning the person to avoid injury • supporting respiration • maintaining blood pressure • correcting hypoglycaemia Drugs used include intravenous lorazepam or diazepam. Alternative medicines include midazolam in cases where the person has not responded to first-line drugs. Alternatively, buccal midazolam has been advocated and is increasingly being used, although it is not licensed in the UK. In severe cases, phenytoin, clonazepam or phenobarbital sodium may be required.

Febrile convulsions Convulsions associated with fever are termed febrile convulsions and may occur in the young. Brief febrile convulsions are managed conservatively with the primary aim of reducing the temperature of the child. Tepid sponging and use of paracetamol is usual. Prolonged febrile convulsions lasting 10–15 min or longer or in a child with risk factors require active management to avoid brain damage. The drug of choice is diazepam by intravenous or rectal (rectal solution) administration. Prophylactic management of febrile convulsions may be required in some children, such as those with pre-existing risk factors or a history of previous prolonged seizures