Avoiding pitfalls in the management of epilepsy

A C F Hui許志輝, H M Yeung楊漢明

HK Pract 2001;23:246-250

Summary

Epilepsy is a common disorder. There is a substantial literature on its management. This article summarises practical information for family physicians. It highlights the common mistakes in the care of patients with recurrent seizures by emphasing the importance of making a correct and specific diagnosis, the use of appropriate anticonvulsants and treatment of refractory epilepsy.

摘要

癲癇是一種常見疾病，有關其治療的文獻甚多。 本文的目的在於對家庭醫生治療癲癇病人時可用的實 用信息加以總結。通過強調對患頑固性癲癇的病人的 正確和明確的診斷、抗痙攣藥物的選擇和應用、治療 方案的選擇和應用的重要性，我們突出了在癲癇反覆 發作的病人之治療中的常見錯誤。

Introduction

There have been great advances in understanding the aetiology, investigation and management of epilepsies.^1-3 However, about a fifth of patients with seizures are still poorly controlled worldwide. It is important for the findings from research to be translated into clinical practice.

Establish the correct diagnosis

Not all paroxysmal events are epileptic. Inappropriate treatment with anticonvulsants is a frequent error. Ten to twenty percent of patients referred to neurology clinics with epilepsy have alternative diagnoses. One should ask whether the patient has experienced seizures before, as episodes of myoclonic jerks or partial seizures may not be volunteered.

Conditions that mimic seizures should be considered. Syncope has characteristic precipitating factors: premonitory features such as nausea, sweating and palpitations; a transient unconsciousness of less than 25 seconds without disorientation or exhaustion support this diagnosis. If the person cannot lie supine, for example when propped up by bystanders, cerebral circulation is re-established more slowly and convulsive syncope is more likely to occur.⁴

In epilepsy monitoring units, non-epileptic attack disorders (NEAD) such as "psychogenic seizures" account for 30% of cases studied.⁵ Pelvic-thrusting, back arching, side to side head movements, biting of the tip rather than the edge of the tongue and tonic retrocollis are suggestive of NEAD.⁶ Although attacks may have a strong emotional or psychological component, it is difficult to confirm this from the history alone. Careful analysis of the patient's behaviour during a typical attack and electroencephalogram (EEG) correlation can distinguish these from epileptic seizures.⁷ Some patients may have combination of genuine convulsions and psychogenic seizures. Parasomnias such as REM-sleep behaviour disorder or somnambulism may be misinterpreted as nocturnal seizures.⁸

The physical examination may reveal subtle focal brain dysfunction which suggests a diagnosis of partial or localisation-related epilepsy. These include facial asymmetry, asymmetry of thumb size and pronation of outstretched hands. Skin abnormalities are present in conditions with combined dermatological features and epilepsy, such as tuberous sclerosis.⁹

Identify patients who require treatment

Antiepileptic drugs (AEDs) may be reasonably deferred after a first unprovoked seizure. However the patient should be told that there is a chance of recurrence which is about 40% in the subsequent two years.¹⁰

Patients with a first tonic-clonic seizure precipitated by factors such as exhaustion or sleep deprivation do not need therapy. Lifestyle modifications may be sufficient to prevent further attacks. Long term treatment should not be started in seizures with a primary cause which is temporary such as hypoglycaemia or alcoholic withdrawal.¹¹

When the benefits of treatment outweigh the problems of treatment-related side effects or inconvenience, treatment should be initiated. AEDs may be prescribed after a single unprovoked seizure if specific risk factors are present. These include presence of structural brain lesion, a history of insult such as significant head trauma or cerebral infection or status epilepticus at onset. In these conditions, the risk of further seizures is much higher. There is no evidence that early treatment alters the long-term prognosis for extended remission.¹² In general, the use of an AED as a diagnostic test is not recommended because of its placebo effect and the availability of alternative tests to reach a positive diagnosis, such as sleep EEG or video-telemetry.

Select the most appropriate drug

The choice of medication depends on the type of seizure.^13,14 Carbamazepine, phenytoin and lamotrigine have a strong action on the sodium channel and they are employed for treating seizures which are focal in onset, based on clinical or EEG findings.^14-17 These include simple partial motor, complex partial and tonic-clonic seizures. The side effect profile may also influence the choice of drug. Carbamazepine may cause hyponatraemia and cardiac arrhythmias while phenytoin is associated with cosmetic and cognitive side effects. (The seizure disorder of some patients can be classified under a syndrome which may be responsive to a particular AED. For example patients with juvenile myoclonic epilepsy respond well to valproate but their symptoms are worsened with carbamazepine).^18,19 Children or adolescents, with generalised epilepsies may present with absences. They experience a sudden onset of unresponsiveness and appear blank. The attack lasts for a few seconds and terminates rapidly. Valproate and lamotrigine are used to treat this type of seizure.^19,20

Treatment should start with a single drug at a low dosage. This is particularly important in elderly patients in whom seizures are usually partial in onset. For example, carbamazepine should be started at 100 mg twice a day for one to two weeks and then titrated to 200 mg twice a day.²¹

The dose should be increased as necessary to produce seizure control or until side effects develop. The drug cannot be said to be ineffective until appropriate dosages have been tried. It would be an error to substitute or add a new drug without an adequate trial.^19,22

Avoid unnecessary investigations

Therapeutic efficacy is judged by seizure control and the appearance of toxic effects. Asymptomatic patients do not require regular blood tests if initial screening tests were negative.²³ Laboratory tests should be performed only when indicated. (For example to help determine compliance in a patient with poor control or to review drug levels in patients with altered pharmacokinetics). Routine blood tests are ineffective in preventing serious toxicity.^23,24

Drug levels should be interpreted with caution. Diagnosis of drug-induced side-effects is based on clinical features. Some patients may have side effects even at low dose of AED.

Avoid misinterpretion of EEG report

A normal EEG does not exclude epilepsy. The prevalence of a normal initial EEG in persons with epilepsy is 50%. The likelihood of detecting inter-ictal epileptiform discharges (IED) is influenced by age, the frequency and type of seizures (less common in simple partial seizures) and the underlying neurological condition.²⁵ A sleep study may demonstrate IEDs in 40% of epileptic patients with a normal recording while awake. With serial recordings, the number of abnormal EEG increase to 60%. In healthy individuals without a personal or family history of epilepsy, the probability of an EEG showing epileptiform discharges such as spike or sharp waves is 0.5%.²⁵ Artifacts, normal variants or normal physiological phenomena, such as vertex sharps or ECG potentials may resemble epileptic discharges but are not pathological. When epileptiform discharges are recorded, it is important to note whether the abnormal activity is focal or generalised at onset. If the onset is focal, the epilepsy may be due to an underlying structural pathology and would respond best to the drugs mentioned above.

There is no association between EEG changes and clinical improvement. Routine follow-up recordings at regular intervals are not useful. Any follow-up EEG should be performed to address a specific clinical problem, such as to determine if a decline in cognitive function is a result of subclinical seizures, drug toxicity or a progressive neurological disease.

Avoid overtreatment

The lowest effective dose is generally recommended. In patients who continue to have seizures on monotherapy, a second agent can be introduced. The initial drug can be tapered off in most cases without an increase in seizure frequency.^19,26 The maximum tolerated dose should be maintained only if there is significant reduction in the intensity or frequency of seizures; otherwise the dose increments can be reversed.

Treatment with unnecessarily high dosages may result in chronic drug toxicity.²⁷ This is particularly important in women of child-bearing age. Pre-conceptual counselling should be given and if possible converted to monotherapy, reduced to the lowest effective dose and add folic acid, 2 to 5 mg per day to reduce the possibility of teratogenicity.²⁸

There is a lack of clinical evidence on whether AED working on different mechanisms have an additive effect.

Identify psychosocial problems

Seizures are intermittent but the psycho-social burden is always present. Patients may have misconceptions of their illness. Parents of the sufferers may be over-protective. Pregnancy issues are a common concern. Although the commonly used AEDs may cause malformations, over 90-95% of women with epilepsy have a normal pregnancy. Epilepsy is not a contraindication to pregnancy. In general there should be few restrictions on recreational activities. Television, computer and video games should be restricted only when these are found to be a precipitating factor. Unsupervised swimming should be avoided.

Refer patients with refractory epilepsy

Frequent generalised seizures, evidence of brain damage, low intelligence, failure to achieve control readily are predictors of intractability. Ideally a magnetic resonance scan (MRI) of the brain should be performed in all patients with uncontrolled seizures.²⁹ MRI may detect underlying lesions such as hippocampal atrophy or cortical dysplasia which are beyond the resolution of CT scanning.³⁰ Those with refractory epilepsy despite good compliance with one or two AEDs should be referred for specialist assessment. Video-monitoring may clarify the diagnosis and second-line AEDs can be introduced.^31-33 Patients can also be evaluated for non-pharmacological interventions such as vagal nerve stimulator implantation or epilepsy surgery, consisting of anterior temporal lobectomy with amygdalo-hippocampectomy, corpuscallosotmy and lesionectomy.^34-39 In properly selected patients the success rate in controlling seizure is approximately 70%.

Consider stopping antiepileptic drugs

In adults, the factors which are associated with successful drug withdrawal include normal neurological examination and intelligence, normalisation of the EEG following treatment, normal neuroimaging and the presence of only one type of seizure previously.⁴⁰ The risk of relapse and the benefits of discontinuing AEDs (fewer side effects, psychosocial benefits) should be discussed with the patient.⁴¹ Treatment may be discontinued in patients with the above characteristics if they have been free from seizures for two to three years. Seizure recurrence is about 25% in patients without and over 50% in those with risk factors.

Key messages

1. Magnetic resonance scan and Video-EEG are recommended investigational tools in patients with refractory epilepsy.
2. Push the first anti-epileptic drug tried and avoid polypharmacy as far as possible.
3. Anticipate and address psychological and social consequences of epilepsy in addition to seizure control.
4. If patients are not responsive to one or two firstline drugs, consider referral to neurologist in order to assess surgical amenability.