Combating epilepsy

The stigma associated with epilepsy is slowly giving way to a better understanding of this neurological problem. Dr. GIGI KURUTTUKULAM examines new strategies to deal with this disorder.

EPILEPSY affects a small percentage of the world's population; but it can occur at any age, affect all races and may be more common in men than in women. Early seizure control is important for physiologic as well as social reasons, as untreated seizures can lead to neuronal damage and intellectual decline.

The stigma of epilepsy used to be an obstacle to appropriate care in developing countries. But now it has been realised that it is more a neurological, than a psychiatric, brain disorder. The past decade has seen the introduction of eight new anti-convulsant drugs worldwide and many more are being developed.

Surgical management of epilepsies continues to expand in tandem with the growing number of specialised treatment centres worldwide. Greater education and awareness about this often highly effective mode of treatment, advances in computerised digital EEG and anatomical and functional brain imaging like MRI, SPECT have made the surgical option popular and safe. Other therapies have also become available in the past few years, particularly vagus nerve stimulation and refinements in the ketogenic diet. New treatments under investigation include bilateral deep brain stimulation of the thalamus and new drug delivery systems.

Epilepsy is clinically defined as recurrent, unprovoked seizures. Seizures are characterised by spontaneous behavioural changes caused by an abnormal hypersynchronous discharge of neurons within the brain. Specific behavioural changes that occur relate to the location of the abnormality causing the seizure and the pattern of spread of the seizure. Thus, epilepsy is not a single disease entity but a condition with many different causes and types. Seizures and epilepsy are symptoms of underlying brain dysfunction that may be inherited or may result from brain infections, trauma, tumours and stroke. Looking at this complex picture, it is not surprising that now no single therapy is effective against all forms of epilepsy.

Epilepsy is broadly categorised as either idiopathic generalised epilepsy (which has a strong genetic basis) or partial (or focal) epilepsy, in which a local disturbance of neuronal function in one part of the brain acts as an epileptogenic "focus." The underlying etiology of partial epilepsy is often critical in guiding therapy and prognosis. Partial epilepsy may also be categorised according to the site of the focus within different parts of the brain ("location-related"), such as temporal lobe epilepsy and frontal lobe epilepsy. Simple partial seizures occur without changes in awareness or consciousness; an aura of deja-vu is an example of a simple partial seizure of temporal lobe origin. Complex partial seizures also arise from one brain locus but are associated with changes in or loss of awareness. A partial seizure can evolve into a tonic-clonic convulsion (a grand-mal seizure), a process referred to as secondary generalisation. Most tonic-clonic convulsions in adults occur in the setting of partial epilepsy.

The first part of any management plan depends on an accurate diagnosis. This involves a full clinical history (from both the patient and a reliable witness), a physical and neurologic examination, and appropriate and intelligent use of EEG and neuro-imaging technology. For patients who have new-onset seizure (s), it is important to rule out underlying secondary causes such as proconvulsant medication use and alcohol withdrawal. Most neurologists begin anti-convulsant therapy after two seizures have occurred and no underlying correctable cause has been found.

However, in some circumstances it may be desirable to begin treatment following a single seizure; this is decided on a case by case basis, and depends on the patient's circumstances and preference.

In conjunction with initiating anti-epileptic drug (AED) therapy, modification of one's life style is important in optimising the chances of achieving and maintaining freedom from seizures. Such factors include an adequate and regular sleep, avoiding or minimising alcohol intake, drug compliance (a pill box is often helpful), and minimising stress.

Why early seizure control? From a patient's perspective, seizures themselves are unpleasant, often embarrassing and potentially dangerous. Frequent seizures often engender a secondary social phobia in some and thus affects the quality of life. Poorly controlled epilepsy may lead patients to learn and maintain a dependent sick role and thus prevent them from leading full and productive lives. In addition, recent studies lend credence to the controversial hypothesis that the more a patient has seizures, the more difficult it may be to control the underlying epilepsy. Also, repeated seizures, especially generalised tonic- clonic convulsions, may lead to cognitive dysfunction, particularly memory impairment in some.

Research on and development of better anti-epileptic agents is a complex task reflecting the underlying processes of both epileptogenesis and seizure initiation, some of which are still unknown or poorly understood. Further, the mechanisms of action of many AEDs - both traditional agents and newer ones - are not completely delineated. Nonetheless, several targets have been identified, the modulation of which is likely to effect improved seizure control. These targets include voltage-dependent sodium channels and synaptic inhibitory and excitatory pathways.

Traditional AEDs still in widespread use are phenobarbital, primidone, phenytoin, ethosuximide, carbamazepine, and sodium valproate. Newer AEDs introduced in the past decade are felbamate, gabapentin, lamptrigine, topiramate, tiagabine, oxcarbazepine, vigabatrin and zonisamide. Out of this, Lamotrigine, Gabapentin and topiramate are available in India. As time goes on, the distinction between the older and newer AEDs begins to blur.

Several specific mechanisms have been identified as those through which the traditional AEDs exert their activity: inhibition of voltage-dependent sodium channels, inhibition of voltage- dependent calcium channels, and enhancement of the actions of gamma-amino-butyric acid (GABA), an important endogenous inhibitory transmitter.

The goal of therapy in epilepsy is to achieve freedom from seizures without significant adverse effects ("no seizures and no side-effects"). Once diagnosis is established, the physician chooses the most appropriate AED to treat the patient's specific problem, at the same time, taking care to choose a drug that will be least likely to cause adverse side-effects that might interfere with the quality of life. The first consideration is to establish whether the diagnosis is a generalised or partial epilepsy syndrome, as this is critical in guiding initial drug therapy.

In primary generalised epilepsy associated with tonic-clonic convulsions or epileptic myoclonus, the traditional drug of choice is sodium valproate. However, recent experience with the new drugs suggests that both lamotrigine and topiramate may be effective. Although most AEDs are effective against the generalised tonic-clonic convulsions seen in patients with primary generalised epilepsy, some AEDs may have no effect or indeed may worsen other seizure types, such as absence or myoclonus. Such drugs include carbamazepine, phenytoin, gabapentin, and tiagabine.

The choice of drug of patients with partial epilepsy is broader. However, the main problem associated with prescribing AED is the inability to predict the response to individual drugs in persons. Traditionally, many neurologists would use carbamazepine as the first-line agent in partial epilepsy.

The advent of the new generation of AEDs in the 1990s has challenged our traditional approach to initial seizure control. These drugs offer advantages over older agents, including fewer drug interactions, wider therapeutic windows, lack of hepatic enzyme induction, less sedation, and usually twice-a-day dosing. These drugs also broaden the choice of therapies for individual patients.

Many factors unrelated to direct efficacy considerations influence the choice of AED (both old and new) in an individual patient with epilepsy. These include age, sex, weight, cosmetic factors, pre-existing illnesses, concomitant medications, cost, and individual physician and patient preference. The initial pharmacotherapeutic approach to early seizure control continues to evolve. The availability of new AEDs has widened the choice, leading to improved control and quality of life for many individual patients. No drug is clearly superior, although individual patients often exhibit a differential, superior response to a particular drug. Unfortunately, it is impossible to predict which drug is the best choice for a person, particularly in those with partial epilepsy. Research may pave the way for a more rational individualised therapy.

Surgery is a safe and effective in patients with intractable epilepsy. Among 900 million people in India, there would be about 9,00,000 people with 30,000 patients in Kerala (30 million population) who might benefit from surgery. Success depends on a meticulous presurgical evaluation to identify the seizure focus (epileptogenic zone).

Focal or localisation related epilepsy is the most common seizure disorder encountered in patients with intractable epilepsy. Initial steps in the assessment of a patient with presumed medically refractory epilepsy is to establish the diagnosis of a seizure disorder, classify the type of seizures and to identify the seizure focus (epileptogenic zone).

Most patients with intractable epilepsy can benefit significantly from a systematic, comprehensive diagnostic and therapeutic management programme. The neurologist, neurosurgeon, neuro- physiologist neuroradiologist, psychologist, psychiatrist and medico-social workers constitute a coordinated team in the comprehensive epilepsy management programme. Psycho-social intervention may help the patient cope better with the chronic handicap and have an improved quality of life. Counselling and education about epilepsy will help to demystify the disease.

Appropriate counselling for patients and family about the diagnosis of epilepsy is the first step in the management. Questions concerning schooling, employment, driving, parenting, children and the cost of medical and surgical management should be addressed. The assistance of medico-social worker in the counselling process is valuable.

The goal of an epilepsy education programme is to provide patients and the family members with the information needed to enhance their knowledge, to dispel misconceptions about epilepsy, to ensure compliance with the treatment, to minimise the effects of this chronic disorder on their daily activities and to promote optimal quality of life.

Till now most patients with refractory epilepsy had nothing much to look forward in their life, other than to wait for the next seizure. Till recently these newer treatment options were available only in the advanced centres abroad, but now many comprehensive epilepsy management centres have started functioning in India.

The writer is a consultant neurologist, Lourdes Hospital, Kochi.

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