Introduction

Epilepsy is a diagnosis that evokes fear and stigma, as evidenced by the commonly used phrase, ‘I wouldn’t do it in a fit!’. The definition of epilepsy is a tendency to recurrence of seizures, which is as broad a definition as are the variety of seizures.

Extrapolating from this, epilepsy is not a satisfactory diagnosis. It represents a symptom of another underlying diagnosis that has provoked the seizures. This has translated into an internationally accepted classification of seizures (see Fig 7.1),¹ which offers the road map to provide treatment options.

There is also an internationally accepted classification of the epilepsies² (note the plural) provided to allow the clinician to acknowledge that one type of epilepsy may incorporate numerous seizure types (see Box 7.1).

The classification of the epilepsies also permits prediction of prognosis, thereby making both classifications part and parcel of a better understanding of the condition. An easier way to describe this is that the description of seizures offers phenomenology of the event, and description of the epilepsies provides a syndromal approach. As these classifications should mirror current knowledge, the leaders in the field are constantly trying to improve their content and suggesting enhanced pedagogy.³

It can be seen that the study and management of epilepsy is a vibrant and complex endeavour. It encompasses many other illnesses that can themselves provoke seizures, fits, turns or any other such term that may be in vogue. The aim of this chapter is not to turn the family physician into an ‘epileptologist’ but rather to offer epilepsy’s ‘travel guide’ to better understanding and an appreciation of the pitfalls.

Diagnosis of Epilepsy

The diagnosis of epilepsy rests completely on a convincing history. If the patient satisfies the above definition, then the diagnosis is confirmed even in the absence of any positive tests. The tests provide an adjunct to clinical skill rather than a substitute.

A comprehensive history is the principal tool of all neurology. The patient often is unable to report exactly what happened during the seizure due to loss of consciousness, but the doctor should not capitulate at this point. The patient should be able to describe what they were doing just before the seizure and any preliminary symptoms, such as the perception of bad smell (e.g. burning rubber), bad taste (e.g. metallic taste), or a feeling that the unfamiliar is familiar (déjà vu—I have seen it before) or the opposite (jamais vu—the familiar is unfamiliar—I have not seen it before). The patient may be able to identify flashing lights as a photic stimulation that provoked the seizure, but this only occurs in approximately 10% of people with epilepsy.⁴ Stress, fatigue, sleep deprivation, drugs, alcohol or even sleep itself can provoke seizures. Menstruation and hormonal changes may cause seizures. Most of this information is readily available from the patient if the right questions are asked (see Table 7.1).

TABLE 7.1 Questions and answers that help diagnose epilepsy

Question	Answers pointing to epilepsy
When and where did the seizure occur?	• when asleep • when sleep deprived • with excess alcohol • with alcohol withdrawal • at times of stress • related to menstrual cycle • at time of flashing lights (e.g. at a dance or while playing video games)

Were there any warning symptoms or signs that occurred before the seizure? What do you recall from the seizure? What have others told you about your seizure? How did you feel after the seizure? Is there a family history? Were there febrile convulsions? Is there a history of brain trauma?

The patient will know if they bit their tongue, buccal mucosa or injured themselves in a seizure. Similarly, they can report if they were incontinent of urine or faeces. The patient will also know how they felt in the post-ictal period, whether they were confused, disoriented, exhausted and had to sleep, or if they had a headache. Thus the history from the patient is very helpful (see Table 7.1).

In addition, a history from any eyewitness will help the doctor to ascertain a word picture of what occurred during the seizure. Questions should include: did the patient appear absent; were there automatisms (automatic behaviour such as smacking lips, fiddling with clothing, involuntary behaviour or apparently purposeful activity for which the patient has no recall); did the patient turn the head to one or the other side; where, if identified, did the seizure start (such as in one hand or in the face to then move throughout the body); were the eyes open or shut (often used to differentiate non-epileptic, pseudo-seizures from truly epileptic phenomena where eyes are open); did the patient shake, twitch, talk, writhe, flail or do anything else during the episode? (See Table 7.2.)

TABLE 7.2 Description of seizures

Seizure type	Description
Simple partial seizure (SPS)	Consciousness retained but focal features determined by site of seizure, such as perception of a smell, a sound or a vision. Uncontrolled movement or twitching of a part of the body, such as a thumb or hand, without loss of consciousness, which may spread (such as Jacksonian march in focal motor seizure).
Complex partial seizure (CPS)	Differentiated from SPS by altered state of consciousness. Patient may be unaware or poorly relate to the surrounding environment as with déjà vu (false memory) or jamais vu (blocked real memory). The patient, while non-responsive, may have automatisms—automatic behaviour that can be quite complex—such as driving a car. The appearance may be of a patient on automatic pilot. The patient has post-ictal features of fatigue, headache or confusion. ‘Absence’ with post-ictal features may be CPS rather than generalised absence.
Secondarily generalised seizure	This is a convulsive seizure that follows focal onset. A convulsion in which the patient reports an aura (representing a focal seizure) is experiencing secondary generalisation (2° gend) throughout the brain.
Typical absence	The patient has generalised absence that is short lived and often multiple, possibly provoked by hyperventilation. There is often no post-ictal feature.
Atypical absence	Similar to typical absence but may have automatisms. Differentiation from CPS may be difficult. EEG with typical 3 Hz spike and wave pattern may be necessary to differentiate from CPS, which will have more focal, often temporal lobe abnormality.
Tonic seizure	Drop attacks with hands and arms often coming up in front of the body and the head dropping forward as the patient becomes stiff and falls down, usually forward.
Myoclonic seizure	Sudden jerking of limbs and head—often first thing in the morning after waking. A form of generalised seizure without focal features.
Tonic clonic seizure	Primarily generalised convulsive seizure starting abruptly without focal features. Similar features to 2° gend but without focality—no aura at onset.

After spending considerable effort to define the seizure the next step is to determine if there are precipitating factors, such as illness, genetic influences (with family history), or exposure to toxins. An obstetric history looking for birth trauma is important, as is any other history of brain damage from accidents, assaults or trauma. An educational history gives a clue regarding poor cognition and possible impaired function. A past history of febrile convulsions is worth seeking as is the detailed past medical and surgical history.

After history taking the patient should undergo a full medical examination, particularly a neurological assessment. In general, the patient with only epilepsy and an otherwise unremarkable history will have no focal neurological signs. If signs are found then further questions seeking cause for focal cerebral damage must be asked. The doctor must accept that seizures, and hence epilepsy, are the physical manifestation of what is occurring in the brain and must question what that might be, such as a space-occupying lesion, congenital abnormality, ischaemic lesion, cerebral bleed or site of infection, such as an abscess.

Investigation of the Patient with Epilepsy

Differential Diagnosis

Epilepsy is itself not a stand-alone diagnosis. In many cases it is secondary to some other underlining condition, so the doctor must be acutely aware of alternative diagnoses (see Table 7.3).

TABLE 7.3 Differential diagnoses

Syncope

Cardiac causes: • dysrhythmia • prolonged QT • valvular heart disease • cardiomyopathy Situational causes: • micturition • defecation syncope • cough syncope • carotid sinus hypersensitivity • valsalva manoeuvre

Orthostatic hypotension Dysautonomia Cerebrovascular disease Brainstem compression Nocturnal parasomnias Psychiatric disorders

These may also exclude epilepsy altogether. The most common ‘mimic’ of a seizure is syncope. Syncope will be accompanied by negative ‘epilepsy’ tests, although it may reveal abnormal lead-2 rhythm ECG tracing during the EEG. Syncope will usually start abruptly, arrest spontaneously and be devoid of para-ictal features, such as confusion, fatigue or incontinence. There may be some epileptiform twitches due to cerebral hypoxia, which may create a diagnostic dilemma.⁷

Nocturnal parasomnias may mimic epilepsy. Somnambulism may be confused with ictal automatisms. Conversely, frontal lobe epilepsy, often with bizarre writhing and even mastibatory movements, particularly in female patients who are shown to rhythmically gyrate their pelvis in epilepsy telemetry, may be considered non-epileptic phenomena until the diagnosis is confirmed by the neurologist.⁸ Concurrent with this recognition that sleep-related phenomena may be confused with epilepsy, it is also important to respect that such phenomena may also provoke seizures due to sleep disturbance and possible additional hypoxaemia affecting the brain. Obstructive sleep apnoea (OSA) with twitching, jerking and gasping for air may be confused with epilepsy. OSA was first diagnosed as a consequence of epilepsy with overnight video monitoring. It should not be ignored that sleep is a neurological state and it is only with the advent of therapeutic interventions, such as continuous positive air pressure (CPAP), that respiratory physicians have claimed sleep medicine. Judicious use of CPAP, averting hypoxaemia and sleep deprivation in cases of OSA, has proven efficacious in seizure control, thereby recognising that epilepsy and OSA can co-exist, necessitating proper management of both.⁹

Transient global amnesia (TGA) in which the patient lacks recall of recent events may be confused with epilepsy.¹⁰ Even if the diagnosis of TGA is suspected, many clinicians will still investigate the patient for epilepsy.

Transient ischaemic attack (TIA),¹¹ due to short-lived cerebral ischaemia, may be confused with epilepsy because of potentially short duration with possible post-ictal features and general good recovery. Acute index of suspicion is needed for such diagnoses.

Migraine is also within the differential and was discussed in an earlier review of headache (see Ch 6).

Briefly, anything that results in short-lived, altered cerebral function may resemble a seizure. Some events that are devoid of organicity, so called ‘non-epileptic seizures’ or ‘pseudo-seizures’, may resemble epilepsy. Some of the features have been discussed but the differentiation often requires involvement of a neurologist. Even the neurologist may be confused and misdiagnose non-epileptic seizures as the real thing. Two important features should be sought, namely, the potential gain for the patient and the source of the model for the featured behaviour. Even competent psychiatrists may have difficulty teasing these out, thereby making treatment difficult. One must remember that the same patient may demonstrate both real seizures and hence epilepsy, as well as non-epileptic phenomena, thus truly confounding the picture.¹²

Treating the Seizures

As already discussed, seizures are divided into those with focal or generalised onset. This differentiation determines the choice of optimal anti-epileptic medication (AEM). Carbamazepine (CBZ) [Tegretol®] is the choice for focal seizures, also known as partial seizures, and valproate (VPA) [Epilim®] is the choice for generalised seizures. These belong to the older generation of AEM, with both being first published in the 1960s. Phenytoin (PHT) [Dilantin®] is no longer a first-line agent because of saturable metabolism, which causes potential for a large increase in blood levels with minor dosage adjustment and a wide range of unwanted effects¹³ that can affect all bodily functions from pseudolymphoma to cardiac dysrhythmia and heart block. The reason for favouring the older AEMs is that none of the newer AEMs has surpassed them in head-to-head trials and they are far cheaper.¹⁴ There is evidence suggesting newer AEMs have a better side-effect profile¹⁵ but their cost precludes their initial use.¹⁴

It would be remiss not to mention generic AEMs. Many specialists argue against generics in epilepsy because one cannot be certain of absolute bio-equivalence. Allowing the pharmacist to switch from standard AEM to generics, recognising there may be more than one generic per AEM, could result in the patient continuously changing AEM, thus placing seizure control in jeopardy.¹⁶

Over the last few decades there has been an explosion of newer AEMs. Some, like vigabatrin, felbamate or tiagabine, have already largely fallen out of favour due to unacceptable adverse effects. They are only used in niche markets, such as vigabatrin for West’s syndrome.

If the patient does not respond to the initial AEM, be it CBZ or VPA, the likelihood of responding to subsequent AEM is less favourable.¹⁷ This does not exclude trying other AEM but this is probably the time to call in reinforcements (if the general practitioner initiated treatment without consultant input). Seizure control has become more complicated with respect to choosing AEM or combinations thereof. Competition between monotherapy (preferred) and rational polypharmacy, where certain combinations (such as VPA with lamotrigine (LTG)) have a mutually beneficial pharmacokinetic and pharmaco-dynamic interaction,¹⁸ is a hot topic.

AEM thought efficacious for generalised epilepsies include VPA, LTG, levetiracetam (LVT), topiramate (TPM) and maybe gabapentin (GBP) (see Table 7.4). These are ‘broad-spectrum’ AEM that can also be used for partial onset (focal) seizures.

TABLE 7.4 Selection of medications

Generalised seizures	Partial seizures [focal]
Epilim® (valproate [VPA])	Tegretol® (carbamazepine [CBZ])
Lamictal® (lamotrigine [LTG])	Epilim® (valproate [VPA])
Keppra® (levetiracetam [LVT])	Dilantin® (phenytoin [PHT])
Topamax® (topiramate [TPM])	Trileptil® (oxcarbazepine [OXC])
Maybe Neurontin® (gabapentin [GBP])	Lamictal® (lamotrigine [LTG])
Zarontin® (ethosuximide [ETX]) • only for absence seizures

Keppra® (levetiracetam [LVT]) Topamax® (topiramate [TPM]) Neurontin® (gabapentin [GBP])   Lyrica® (pregabalin [PGB])      

Less broad spectrum AEM can usually only be used to treat focal seizures (see Table 7.4). They are either ineffective for generalised seizures or they may exacerbate some forms, such as CBZ exacerbating myoclonic seizures. Ethosuximide (Zarontin®) is an AEM only suitable for generalised absences but may exacerbate tonic–clonic seizures and largely has been replaced with VPA.

Other AEM within the newer generation available for focal seizures include oxcarbazepine (similar efficacy to CBZ with less central nervous system unwanted effects). Pregabalin, a new AEM developed after GBP, may have good efficacy although personal experience has not been encouraging (see Table 7.4). It is advisable to involve an epilepsy specialist if CBZ and VPA fail to achieve seizure control. Personal preference would advocate involvement of a neurologist to validate the diagnosis even before prescribing the first AEM, to choose the best AEM.

Treating the Epilepsy

Epilepsy is more than seizures. It is a condition with stigma, social implications and potential lifelong impact even if seizures are controlled. No-one is better placed to deal with these issues than is the general practitioner.

People have an established self-image, and adult or even adolescent onset epilepsy may threaten that image. Epilepsy invokes a lack of predictability—there is always the threat of another seizure without knowing exactly when, or even if, it will occur. The person who has had a first seizure has approximately 35–70% chance of a second seizure, and after a second seizure the risk is approximately 80% continuing to rise with each subsequent seizure.^19,20

The patient must deal with a reliance on medications, which reduces independence. There is reliance both on pills and the doctor who prescribes them. The doctor must supervise compliance with treatment and adjust lifestyle issues to accommodate the epilepsy.

Seizures and driving are incompatible, such that the patient must be seizure free for predetermined periods of time to be permitted to drive. While the doctor advises the licensing authority on ‘fitness to drive’, the licensing authority is responsible for the final decision established within the Austroads Guidelines.²¹ This is not absolute and the doctor needs to acknowledge a duty of care both to the patient and the wider community. If a doctor does not stop a person with uncontrolled epilepsy from driving, there is potential for an injured third party to litigate against that doctor.

Psychosocial Issues

Driving is not the only psychosocial issue requiring the general practitioner’s attention. Recreational activities, such as swimming, surfing and sporting activities, dictate that the person with epilepsy should not swim alone. Someone present should be aware of the epilepsy and be capable of rendering assistance if necessary.

Social interaction in school and even special schooling needs may require general practitioner involvement. A letter seeking special consideration from the Department of Education and the school principal may determine the difference between achieving optimal results or failing. Generalised epilepsy may hinder concentration, while focal epilepsy may impact on recall. Once teachers are aware of this, they might tailor teaching to the student’s idiosyncratic needs.

Juvenile myoclonic epilepsy (JME) is exacerbated by alcohol, lack of sleep, stress and poor compliance. The general practitioner should assist the patient to adopt a lifestyle that accommodates the epilepsy (with ample sleep and avoiding alcohol) while also encouraging the patient to strive to achieve maximal potential. Quality of life demands realistic expectations. Some career choices are impracticable, such as airline pilot, bus driver, soldier, working at heights or with dangerous equipment. The general practitioner needs to ensure that the patient’s aspirations are compatible with their epilepsy. Self-employment avoids potential for discrimination but is not always practicable for the person with epilepsy.

Teratogenicity needs to be considered, and folate may protect the neural axis during development. High doses of some AEM, such as VPA, are to be avoided if possible. Should pregnancy be planned then it is advisable, where possible, to wean out AEM prior to the pregnancy. It is generally too late to wean out medications after the pregnancy has been confirmed, as this is usually well into the first trimester. By this time potential teratogenicity, if it is to occur, will have happened and removal of AEM increases the risk of seizures.

Blood levels of AEM may change dramatically during pregnancy and should be monitored. This is very much the case with LTG where levels fall dramatically during pregnancy and doses need to be increased during the pregnancy and reduced thereafter.

Oral contraception may be affected by AEM, especially those metabolised by the liver. It is important to advise the patient accordingly to obviate the traumas of an unwanted pregnancy. If liver metabolism is increased then so is metabolism of the contraceptive pill, which may render it ineffective. If contraception is important then one of the newer AEM may be better to avoid interaction with contraceptive metabolism.

Recurrence of seizures in previously controlled epilepsy should alert the doctor to possible infection. This is especially important for women with possible urinary tract infection. By far the most common reason for recurrence of seizures in previously controlled epilepsy is lack of compliance or, more correctly, lapse of compliance. This can be confirmed by determining blood levels of the prescribed AEM.

Conclusion

Management of epilepsy requires both the correct diagnosis and appropriate choice of treatment—both pharmacological and psychosocial. The most important diagnostic tool is the taking of an accurate and comprehensive history, which is complemented by suitable investigations, all of which may be normal without disturbing a history-based diagnosis. The early involvement of a consultant assists both diagnosis and treatment, but there is little reason to bypass the established AEM of CBZ for focal epilepsy and VPA for generalised epilepsy as first-line agents. The general practitioner is by far the best placed to address the psychosocial issues.