Differential Diagnosis of Paroxysmal Events: Epileptic and Nonepileptic Seizures

The first step towards the correct diagnosis of epilepsies is to establish whether a paroxysmal clinical event was actually an epileptic seizure or something else. The differential diagnosis includes all causes of episodic impairment of awareness, aberrations of mental function, falls, sensory/motor phenomena and generalised convulsive movements, which are common presenting symptoms of epileptic seizures. This is often easy for physicians adequately trained in the recognition of the various forms of epileptic seizures, who are able to obtain a clear history of the events from the patient and witnesses. However, even the most experienced epileptologists time and again have great difficulties in reaching an unequivocal diagnosis for reasons such as atypical seizure presentations, inadequate historical data or overlapping symptom manifestations.

Misdiagnosis in epilepsies, when considering its dimensions and consequences, is a colossal medical problem. Common disorders and even normal phenomena may imitate epileptic seizures and, conversely, certain types of epileptic seizures may imitate symptoms of other diseases. Misdiagnosis has serious repercussions. Patients with nonepileptic disorders incorrectly diagnosed as having epileptic seizures are likely to be mistreated with antiepileptic drugs and also denied specific and possibly life-saving treatment (Figure 1.1). Similarly, patients with epileptic seizures erroneously diagnosed as migraine, encephalitis or other nonepileptic paroxysmal events are likely to be mismanaged with inappropriate treatments and also deprived of specific therapies.

Figure 1.1

Potentially Life-Threatening Cardiogenic Syncopes Imitating Epileptic Generalised Convulsive Seizures. A 34-year-old man was referred for routine EEG because of ‘two episodes of GTCS in the last (more...)

Epileptic Seizures and Their Classification

Having established that a paroxysmal event is genuinely epileptic, the next step, not the final step, is to define the type of seizure or seizures, which is a prerequisite for the correct diagnosis and management.

There are numerous types of epileptic seizures, which in their presentation may be minor or dramatic, brief or long, frequent or sparse or singular. Clinical manifestations of seizures range from the dramatic events of a GTCS to the mild myoclonic flickering of the eyelids or a focal numbness of the thumb and mouth. Minor seizures are often overlooked although they are more important than a GTCS in the diagnosis of epilepsies.⁵⁴ The same patient may suffer from different types of minor and major seizures, independently or evolving from one to the other.

Minor Seizures Are More Important than Major Seizures for Diagnostic Procedures, Correct Diagnosis and Appropriate Management Strategies

Minor seizures include myoclonic jerks, absences and simple or complex focal seizures. Minor seizures should be thoroughly sought during the clinical evaluation (Figure 1.2). Patients are unlikely to report minor seizures because they do not appreciate that these are epileptic events and their significance. It is the physician’s responsibility to detect and evaluate them.

Figure 1.2

Video EEG of a 16-Year-Old Girl Referred for an EEG Because of ‘a First Generalised Tonic Clonic Seizure’ at Age 16 Years. This happened in the morning on her way to school (more...)

A single GTCS does not require medication, but if the patient also has other even minor seizures treatment is usually mandatory (Figure 1.2). Similarly, it is a medical error to advise the withdrawal of medication for a patient with minor seizures even if free of convulsive seizures for many years.

Minor seizures, such as brief myoclonic jerks, mild absences and simple or even complex focal seizures, may go unnoticed for many years or be ignored as normal variations in a person’s life. Typical examples in this respect are patients with juvenile myoclonic epilepsy who may have frequent myoclonic jerks many years prior to a GTCS (Figure 1.2) or patients with temporal lobe epilepsy who may have frequent classical simple focal seizures (auras) many years prior to a GTCS. Even if frequent, these seizure events are unlikely to raise concerns and promote a medical consultation. Conversely, a major seizure such as a GTCS invariably draws medical attention.

Clarification on the ILAE Seizure and Syndrome Classifications

The standardised classification and terminology for epileptic seizures⁵⁶ and syndromes ⁵⁷ by the ILAE provides a fundamental framework for organising and differentiating them. This categorisation is essential in clinical practice and research on epilepsies. The currently valid classification of Epileptic Seizures is used from 1981⁵⁶ and the last revision of the Classification of Epilepsies and Epileptic Syndromes was in 1989.⁵⁷ The ILAE Task Force recently proposed a new diagnostic scheme³ the basic concepts of which were accepted by the ILAE General Assembly in 2001 but “none of these proposals are yet complete, nor are any intended to constitute a classification… ”.⁵⁸ The relevant editorials inEpilepsia on ‘Cabbages and Kings in the Classification of Seizures and the Epilepsies’ are authoritative and well-presented views on the different methodologies, approaches, targets and philosophies of these classifications.^58–63

Definitions

Focal (synonym=partial) seizure: a seizure that has an initial semiology which indicates or is consistent with initial activation of only part of one cerebral hemisphere.⁴ See also another ILAE definition in page 10.

Generalised (synonym = bilateral) seizure: a seizure that has an initial semiology which indicates or is consistent with more than minimal involvement of both cerebral hemispheres.⁴.

Aura: a subjective ictal phenomenon that, in a given patient, may precede an observable seizure; if alone it constitutes a sensory seizure.⁴

Prodrome: a preictal phenomenon, i.e. a subjective or objective clinical alteration (e.g. ill-localised sensation or agitation) that heralds the onset of an epileptic seizure but does not form part of it.⁴

Aura is not synonymous to prodrome: aura is a seizure itself while prodrome is not a seizure.

Ictus: a sudden neurological occurrence such as a stroke or an epileptic seizure.⁴

Ictal: the seizure period or events due to a seizure.

Interictal: the interval between seizures.

Postictal: a transient clinical abnormality of central nervous system function that appears or becomes accentuated when clinical signs of the ictus have ended.⁴

Impaired consciousness is defined as the inability to respond normally to exogenous stimuli by virtue of altered awareness and/or responsiveness. Aberrations of behaviour (automatisms) may occur in patients with impaired consciousness. There is considerable evidence that simple partial seizures usually have unilateral hemispheric involvement and only rarely have bilateral hemispheric involvement; however, complex partial seizures frequently have bilateral hemispheric involvement.⁵⁶

Patients may often suffer many minor seizures long before the reported ‘first seizure’ or long after what is considered as their ‘last seizure’.⁵⁴

Important note

Three-quarters (74%) of patients with ‘newly identified unprovoked seizures’ (mainly GTCS) had experienced multiple seizure episodes prior to their first medical contact.⁵⁵ Yet, studies on the prognosis and treatment of the ‘first seizure’ mainly refer to a GTCS although this may not be the first seizure in the patient’s life.

Epileptic Seizures in Accordance with the ILAE Classification of 1981⁵⁶

The currently valid ILAE seizure classification of 1981⁵⁶ is an old updated version of the classification proposed by Gastaut in 1970.⁶⁴ It is based on clinical and EEG (ictal and interictal) manifestations (Tables 1.1 and 1.2). Seizures are primarily divided into the following types.

Table 1.1

ILAE Classification of focal (partial, local) seizures

Table 1.2

ILAE Classification of generalised seizures (convulsive and nonconvulsive)

• Partial (focal or local) seizures (with great variation in clinical expression and severity).
• Generalised seizures (tonic, clonic or tonic-clonic, myoclonic and typical or atypical absences).

Such a dichotomy is necessary because an abnormal paroxysmal discharge of cerebral neurons may be localised (partial seizures) or simultaneously affect the whole cerebral cortex from onset to termination (generalised seizures).⁵⁶ This classification also recognises the following types of seizure.

• Unclassified epileptic seizures, which cannot be classified because of inadequate or incomplete data and some that defy classification in hitherto described categories. This includes some neonatal seizures, e.g. rhythmic eye movements, chewing and swimming movements.⁵⁶
• Prolonged or repetitive seizures (status epilepticus).

Partial (Or Focal) Seizures (Table 1.1)

Partial seizures are those in which, in general, the first clinical and EEG changes indicate initial activation of a system of neurons limited to a part of one cerebral hemisphere.⁵⁶ Partial seizures are classified primarily on the basis of whether or not consciousness is impaired during the attack and whether or not progression to generalised convulsions occurs.

Terminological Changes in the New Diagnostic Scheme

The old term ‘focal’ is reintroduced to replace ‘partial’ and ‘localisation-related’ epileptic seizures, which is understandable.

However, this new scheme abandons the division of focal seizures into ‘simple’ (without impairment of consciousness) and ‘complex’ (with impairment of consciousness).³ The reason given is that this ‘inappropriately created the impression that impairment of consciousness had certain mechanistic implications related to limbic system involvement’ and that ‘complex partial seizures’ has been erroneously used as a synonym of ‘temporal lobe epilepsy’. ³ Though these are correct, there are significant practical reasons (medico-legal cases, driving and job-related performance) for distinguishing seizures with or without impairment of consciousness. Therefore, I keep using the terms ‘simple’ and ‘complex’ focal seizures in this book, while emphasising that (1) ictal impairment of consciousness is a symptom of either neocortical or limbic seizures and (2) complex focal seizures may originate from any cerebral lobe and therefore they are not synonymous with temporal lobe epilepsy.

The scheme also introduces the terms ‘continuous seizure types’ for status epilepticus and ‘self-limited seizure types’ for briefer seizures. These terms are unlikely to find any support and I do not use them in this book.

1. Simple partial seizures (when consciousness is not impaired).
2. Complex partial seizures (when consciousness is impaired). Impairment of consciousness may be the first clinical sign or simple partial seizures may evolve into complex partial seizures.
   A partial seizure may not terminate, but instead progress to a generalised motor seizure.
3. Partial seizures evolving to secondarily generalised (tonic-clonic or tonic or clonic) seizures.

Generalised Seizures (Table 1.2)

‘Generalised seizures are those in which the first clinical changes indicate initial involvement of both hemispheres. Consciousness may be impaired and this impairment may be the initial manifestation. Motor manifestations are bilateral. The ictal EEG patterns initially are bilateral and presumably reflect neuronal discharge, which is widespread in both hemispheres’. ⁵⁶ Generalised seizures may be convulsive or nonconvulsive and vary considerably: mild or severe myoclonic jerks, inconspicuous or severe typical and atypical absences and generalised clonic, tonic or tonic clonic convulsions. ⁵⁶ Generalised seizures may be primarily or secondarily generalised.

• Primarily generalised seizures are generalised from the onset.
• Secondarily generalised seizures are partial (focal) at onset but do not remain localised. They spread and trigger a generalised fit.

Important note

Important note on the terminology of primarily and secondarily generalised seizures
I purposely highlighted the words primarily and secondarily generalised seizures because these are often confused with primary (= idiopathic) and secondary (= symptomatic or cryptogenic) which are often used as adjuncts to ‘epilepsy’ (see also page. 281).

The ILAE classification of generalised seizures is presented in Table 1.2 with the following broad categories.⁵⁶

• A1. Absence seizures.
• A2. Atypical absence seizures.
• B. Myoclonic seizures.
• C. Clonic seizures.
• D. Tonic seizures.
• E. Tonic-clonic seizures.
• F. Atonic seizures.

Precipitated (Reflex) Seizures

Reflex epileptic seizures are detailed in Chapter 13.

They are consistently precipitated by environmental or internal stimuli and are differentiated from spontaneous epileptic attacks in which precipitating factors cannot be identified. In individual patients, the precipitating stimuli are usually limited to a single specific stimulus or a limited number of closely related stimuli.

Reflex seizures may, like spontaneous seizures, be:

• generalised, primarily or secondarily
• focal, simple or complex.

Seizure Classification in the New Diagnostic ILAE Scheme

The new diagnostic scheme of the ILAE Task Force is divided into five parts or axes, organised to facilitate a logical clinical approach to the development of hypotheses necessary to determine the diagnostic studies and therapeutic strategies to be undertaken in individual patients (Table 1.3).^3,65

Table 1.3

Proposed diagnostic scheme for people with epileptic seizures and with epilepsy

Table 1.4 is the list of seizures as provided by the ILAE Task Force.³

Table 1.4

Epileptic seizure types and precipitating stimuli for reflex seizures

For didactic purposes, I describe the various types of seizures when appropriate in the relevant epileptic syndromes.

Epileptic Syndromes and Their Classification

Having established that a paroxysmal event is epileptic, the diagnosis by the nonspecialist is often limited to excluding structural abnormalities of the brain or predisposing medical disease. However, simply diagnosing ‘epilepsy’ or ‘seizures, is insufficient. Symptom/seizure diagnosis cannot provide guidance on important items such as severity of the disease, prognosis, short- and long-term therapeutic decisions and genetics (research and counselling), which are all factors that crucially affect family and social life and the education and career choices of patients. Defining the type of epilepsy should now be considered mandatory as it offers the best guide to both management and prognosis.^66–69

Syndromic diagnosis of epilepsies provides a firm foundation for short- and long-term therapeutic decisions and enables natural history, inheritance, treatment efficacy and prognosis of epilepsies to be studied scientifically. The benefits of syndromic diagnosis over seizure/symptom diagnosis or an inclusive diagnosis such as ‘epilepsy’ far outweigh any morbidity from miscategorisation that may arise in difficult cases.

Important note

Imprecise syndromic diagnosis commonly results in avoidable morbidity and sometimes mortality.⁵⁷

The most important milestone in modern epileptology has been the recognition of epileptic syndromes and diseases, most of which are well defined and easy to diagnose. The concept of epilepsies as specific syndromes is old (see for example pyknolepsy = childhood absence epilepsy)⁷⁰ and the first attempt to formalise them in an international classification was published in 1970.⁷¹ The current classification⁵⁷ originated from a meeting in the Centre Saint-Paul, Marseilles, France, in July 1983 and has been the basis of the book Epileptic Syndromes in Infancy, Childhood and Adolescence, also known as Guide Bleu, which is now published as an updated third edition.⁷²

The classification and definitions from this meeting were adopted in 1985 by the Commission on Classification and Terminology of the ILAE⁷⁴ and remained essentially the same in the revised proposal of 1989.⁵⁷

Medical diagnosis is defined as ‘The identification of a disease by investigation of its symptoms and history, which provides a solid basis for the treatment and prognosis of the individual patient’.⁷⁰

Similarly, in the epilepsies the recognition of non-fortuitous clustering of symptoms and signs requires the study of detailed clinical and laboratory data.

Important clinical features of a syndrome include the type of seizures, their localisation, frequency, sequence of events, circadian distribution, precipitating factors, response to treatment, age at onset, mode of inheritance and physical or mental symptoms and signs.

Although some symptoms predominate and may indicate the underlying disease, no single symptom or sign can be considered entirely pathognomonic. The process of differential diagnosis requires close scrutiny of the clinical data before a list of possible diagnoses can be drawn up and the final diagnosis reached. It should be realised that some epilepsies are easy to diagnose and some more difficult, but this is not unusual in medicine. Molecular genetics are already making decisive discoveries in the identification of epilepsies (Chapter 11).

Some parts of the current ILEA classification^3,57 remain contentious and some syndromes are ill or broadly defined and require further clarification.^{59,67–69,75} There are patients whose clinical and EEG features do not appear to fit neatly into any recognised category or erroneously appear to evolve from one syndrome to another. Some may represent new or ‘overlap’ syndromes, others may be unusual or atypical forms of known syndromes or cases where clinical history is misleading. However, many syndromes are common, well characterised and easily diagnosed.

Epileptic Syndromes in Accordance with Currently Valid ILAE Classification of 1989 ⁵⁷

The currently valid 1989 syndromic classification of the ILAE⁵⁷ is presented in Table 1.5.

Table 1.5

Syndromic Classification of the ILAE

Two divisions are widely used to shape the major classes.

• The first separates epilepsies with generalised seizures (generalised epilepsy) from epilepsies with partial seizures (localisation related, partial or focal epilepsies).
• The other separates epilepsies of known aetiology (symptomatic or ‘secondary’ epilepsies) from those that are idiopathic (or ‘primary’) and those that are cryptogenic.

The following are the four major classes in this 1989 classification as defined by the ILAE;⁵⁷

1. Localisation-related (focal, local and partial) epilepsies and syndromes
2. Generalised epilepsies and syndromes
3. Epilepsies and syndromes undetermined as to whether they are focal or generalised
4. Special syndromes

Localisation-Related Epilepsies and Syndromes

The description and definitions of epileptic seizures and syndromes in this chapter are based entirely on the currently valid ILEA proposals.^{56, 57}

Clarification on Primary/Primarily and Secondary/Secondarily Seizures or Syndromes

There is significant confusion regarding the words primary and secondary as adjuncts to seizures or syndromes. In syndromes, primary is synonymous to idiopathic and secondary is synonymous to symptomatic or probably symptomatic (cryptogenic).

In seizures, primary denotes seizures that are generalised from onset (primarily generalised) while secondary denotes generalised seizures that are generated from a cortical focus (secondarily generalised seizures).

In this book these terms primary/primarily and secondary/secondarily are used only in relation to seizures. In syndromes, only the terms idiopathic, symptomatic and cryptogenic (or probably symptomatic) are used.

Localisation-related epilepsies and syndromes are epileptic disorders in which seizure semiology or findings at investigation disclose a localised origin of the seizures. This includes not only patients with small, circumscribed, constant epileptogenic lesions (anatomic or functional), i.e. true focal epilepsies, but also patients with less well-defined lesions, whose seizures may originate from variable loci. In most symptomatic localisation-related epilepsies, the epileptogenic lesions can be traced to one part of one cerebral hemisphere, but in idiopathic age-related epilepsies with focal seizures corresponding regions of both hemispheres may be functionally involved.⁵⁷

Localisation-related (focal, local and partial) epilepsies and syndromes are

1.1 Idiopathic

1.2 Symptomatic

1.3 Cryptogenic

The symptomatic sydromes are anatomically classified as:

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– Temporal lobe epilepsies – Parietal lobe epilepsies

– Frontal lobe epilepsies – Occipital lobe epilepsies

Idiopathic localisation-related epilepsies are childhood epilepsies with partial seizures and focal EEG abnormalities. They are age related, without demonstrable anatomic lesions and are subject to spontaneous remission. Clinically, patients have neither neurological nor intellectual deficit nor a history of antecedent illness, but frequently have a family history of benign epilepsy. The seizures are usually brief and rare, but may be frequent early in the course of the disorder. The seizure patterns may vary from case to case, but usually remain constant in the same child. The EEG is characterised by normal background activity and localised high voltage repetitive spikes, which are sometimes independently multifocal. Brief bursts of generalised spike and wave can occur. Focal abnormalities are increased by sleep and are without change in morphology.⁵⁷

Symptomatic localisation-related epilepsies: apart from the rare conditions of Kozhevnikov–Rasmussen syndrome and focal reflex epilepsies, the symptomatic category comprises syndromes of great individual variability which are based mainly on seizure types and other clinical features as well as anatomic localisation and aetiology – as far as these are known. The seizure types refer to the ILAE classification. Inferences regarding anatomic localisation must be drawn carefully. The scalp EEG (both interictal and ictal) may be misleading and even local morphological findings detected by neuroimaging techniques are not necessarily identical with an epileptogenic lesion. Seizure symptomatology and, sometimes, additional clinical features often provide important clues. The first sign or symptom of a seizure is often the most important indicator of the site of origin of seizure discharge, whereas the following sequence of ictal events can reflect its further propagation through the brain. However, this sequence can still be of high localising importance. One must bear in mind that a seizure may start in a clinically silent region, so that the first clinical event occurs only after spread to a site more or less distant from the locus of initial discharge. The tentative descriptions of syndromes related to anatomic localisations are based on data that include findings in studies with depth electrodes.⁵⁷

Generalised Epilepsies and Syndromes

Generalised epilepsies and syndromes are epileptic disorders with generalised seizures, i.e. seizures in which the first clinical changes indicate initial involvement of both hemispheres. The ictal encephalographic patterns initially are bilateral.⁵⁷ Generalised epilepsies and syndromes are

2.1 Idiopathic

2.2 Cryptogenic

2.3 Symptomatic

2.3.1 Non-Specific Aetiology

2.3.2 Specific Syndrome

Idiopathic generalised epilepsies are forms of generalised epilepsies in which all seizures are initially generalised, with an EEG expression that is a generalised, bilateral, synchronous, symmetrical discharge (such as is described in the seizure classification of the corresponding type). The patient usually has a normal interictal state, without neurological or neuroradiological signs. In general, interictal EEGs show normal background activity and generalised discharges, such as spikes, polyspike, spike and wave and polyspike waves of about 3 Hz. The discharges are increased by non-REM sleep. The various syndromes of idiopathic generalised epilepsies differ mainly in age of onset.⁵⁷

Symptomatic generalised epilepsies, most often occurring in infancy and childhood, are characterised by generalised seizures with clinical and EEG features different from those of idiopathic generalised epilepsies. There may be only one type, but more often there are several types, including myoclonic jerks, tonic seizures, atonic seizures and atypical absences. EEG expression is bilateral but less rhythmical than in idiopathic generalised epilepsies and is more or less asymmetrical. Interictal EEG abnormalities differ from idiopathic generalised epilepsies, appearing as suppression bursts, hypsarrhythmia, slow spike and wave or generalised fast rhythms. Focal abnormalities may be associated with any of the above. There are clinical, neuropsychological and neuroradiological signs of a usually diffuse, specific or nonspecific encephalopathy.⁵⁷

Symptomatic generalised epilepsies of specific aetiologies are “only diseases in which epileptic seizures are the presenting or a prominent feature”. ⁵⁷ These diseases often have epileptic features that resemble symptomatic generalised epilepsies without specific aetiology, appearing at similar ages and include diseases such as Aicardi syndrome, Lissencephaly-pachygyria, Sturge-Webber syndrome, hypothalamic hamartomas, disorders of inborn error of metabolism, Lafora disease and others.

Epilepsies and Syndromes Undetermined as to Whether They Are Focal or Generalised

There may be two reasons why a determination of whether seizures are focal or generalised cannot be made. ⁵⁷

• The patient has both focal and generalised seizures together or in succession (e.g. partial seizures plus absences) and has both focal and generalised EEG seizure discharges (e.g. temporal spike focus plus independent bilateral spike and wave discharges). ⁵⁷
• There are no positive signs of either focal or generalised seizure onset. The most common reasons for this are that the seizures occur during sleep, the patient recalls no aura and ancillary investigations including EEG are not revealing.⁵⁷

Therefore, epilepsies and syndromes undetermined as to whether they are focal or generalised may be:

3.1 with Both Generalised and Focal Seizures

3.2 without Unequivocal Generalised or Focal Features

Special Syndromes

These manifest with situation-related seizures (Gelegenheitsanfälle) such as

• febrile seizures
• isolated seizures or isolated status epilepticus
• seizures occurring only when there is an acute metabolic or toxic event due to factors such as alcohol, drugs, eclampsia and nonketotic hyperglycaemia.⁵⁷

Epilepsies with Seizures Precipitated by Specific Modes of Activation

Reflex epileptic syndromes are detailed in Chapter 13. They are characterised by reflex seizures which are consistently related to specific modes of precipitations such as primary reading epilepsy. Seizures also occur spontaneously in most reflex epilepsies. ⁵⁷

Diseases and Syndromes of Specific Aetiologies

The ILAE classification also recognises certain diseases and syndromes where epileptic seizures are the presenting or a prominent feature such as progressive myoclonic epilepsies and inherited metabolic disorders.

Syndromic Classification of the New Diagnostic ILAE Scheme³

Recent advances in the clinical EEG manifestations of previously recognised and newly described syndromes, video EEG information, functional and structural imaging, investigative procedures and genetics mandated a new thorough and realistic revision of this classification and the definitions of epileptic syndromes.³ The proposed diagnostic scheme for people with epileptic seizures and with epilepsy is such an attempt by the ILAE Task Force.³ Table 1.6 shows the epileptic syndromes and related conditions as listed in the new diagnostic scheme³ and Table 1.7 is an example of their group classification. Table 1.8 lists diseases which are frequently associated with epileptic seizures.

Table 1.6

Epilepsy syndromes and related conditions

Table 1.7

An example of a classification of epilepsy syndromes

Table 1.8

An example of a classification of diseases frequently associated with epileptic seizures or syndromes

Gardeners and Botanists, Splitters and Lumpers

In epileptological literature there is frequent comparison of physicians and classifications to gardeners and botanists or splitters and lumbers. This should not be misunderstood. Neither of these paradigms advocates or justifies a unification of all epilepsies under a single diagnostic category.

Gardeners and Botanists

An outstanding scientific account of the principles and terminology of classification systems is the recent lead Editorial by Peter Wolf in Epilepsia.⁶⁰ He also refers to John Hughlings Jackson who is the first to compare the classification systems needed for epilepsies to the classification of plants for botanists and gardeners.⁷⁶ The botanists, like all scientists, need a taxonomy, while the gardeners, like all practising physicians need something to use in daily work.

Patient note

“There are two ways of investigating diseases, and two kinds of classification corresponding thereto, the empirical and the scientific. The former is to be illustrated by the way in which a gardener classifies plants, the latter by the way in which a botanist classifies them. The former is, strictly speaking, only an arrangement. The gardener arranges his plants as they are fit for food, for ornament, etc. One of his classifications of ornamental plants is into trees, shrubs, and flowers. His object is the direct application of knowledge to utilitarian purposes. It is, so to speak, practical. The other kind of classification (the classification properly so-called) is rather for the better organization of existing knowledge, and for discovering the relations of new facts; its principles are methodical guides to further investigation. It is of great utilitarian value, but not directly.” John Hughlings Jackson (1874)⁷⁶

Splitters and Lumpers

There are two main schools of thought in the classifications. The ‘splitters’ try to identify specific epileptic syndromes while recognising the existence of borderline cases. The ‘lumpers’ do not recognise specific syndromes within the spectrum of epilepsies.

Berg and Blackstone⁶² have provided an excellent and objective debate on classification systems and I quote them regarding lumping and splitting in epilepsies:

Patient note

“Related to differentiation is the debate about lumping together what may or may not be similar forms of epilepsy or splitting apart groups that may represent minor variations of the same form of epilepsy. Ideally any method for classifying the epilepsies should require identification and measurement of all potentially relevant characteristics (be they phenotypic characteristics, gene mutations, etc.) and appropriate analyses to determine which characteristics truly define and differentiate between ‘syndromes’. Implicitly, one must be prepared to split before one can lump. Thus we must always be on guard against unwittingly lumping because we are unaware of certain characteristics on which we should have split.” ⁶²

The Significance of Specifying the Type of ‘Epilepsy’

The significance of the syndromic diagnosis of epilepsies has been emphasised on many occasions.^67–69 The results to be expected of syndromic diagnosis of epilepsies can be compared with the advances, which have accrued from the widespread acceptance of syndromic diagnosis of other medical disorders such as neuromuscular diseases. If diagnosed on a few symptoms alone, distinction would be impossible even between the broad categories of muscular dystrophies, inflammatory myopathies and motor neurone diseases which all manifest with muscle weakness and muscle atrophy. Similarly, if diagnosed on a few symptoms alone, distinction would be often impossible even between the broad categories of focal or generalised, idiopathic or symptomatic epilepsies which all manifest with seizures. Despite the occasional occurrence of ‘overlap syndromes’, syndromic classification allows the scientific analysis of the underlying disease processes and their specific clinicopathological features and genetics and provides a framework for clinical trials aimed at optimising treatment.^77,78

Terminological Changes in the New Diagnostic Scheme

The new diagnostic scheme maintains focal and generalised epilepsies, does not specify on syndromes of uncertain origin and replaces ‘seizures with a specific situation’ to ‘seizures that do not require the diagnosis of epilepsy’.³ In addition, the scheme rightly maintains and lists the ‘diseases frequently associated with epileptic seizures or syndromes’ (Table 1.8).

Traditional medical teaching and attitudes to the diagnosis and management of epilepsies often differ from those applied in other medical conditions.^54,66

Accurate diagnosis is the golden rule in medicine and epilepsies should not be an exception to this.

Physicians who rightly seek bedside confirmation of muscle fatigability in a patient with a clear-cut history of myasthenia gravis, should also request to view the seizures which if frequent can be easily captured with modern digital recorders. Physicians who rightly emphasise the differential diagnosis between spinal muscular atrophy and polymyositis should give the same emphasis to the differentiation between absences of idiopathic generalised epilepsies and complex focal seizures. Major paediatric journals which often emphasise rare disease should at least give the same space to highlight that childhood autonomic status epilepticus is a common and costly cause of misdiagnosis and mismanagement adversely affecting thousands of children around the world (page 240).⁷⁹

The danger of a unified diagnosis of ‘epilepsy’ or a symptomatic diagnosis of ‘seizures’ is exemplified by three common epileptic syndromes: benign childhood focal seizures, juvenile myoclonic epilepsy (JME) and hippocampal epilepsy, which comprise more than one-third of all epilepsies. They are entirely different in presentation, causes, investigative procedures, short- and long-term treatment strategies and prognosis.

Benign childhood focal seizures (Chapter 9), like febrile seizures, are age-related, show genetic predisposition, may manifest as a single seizure, remit within a few years of onset and may or may not require a short course of antiepileptic drug (AED) treatment. The risk of recurrent seizures in adult life (1–2%) is less than in febrile seizures (4%). Recognition of the characteristic clinical and EEG features of benign childhood focal epilepsies will enable the parents to be reassured of the invariably benign prognosis with spontaneous resolution of the disorder by the middle teens.

Juvenile myoclonic epilepsy, an easy to diagnose syndrome of idiopathic generalised epilepsies, has a prevalence of 8–10% among adult patients with seizures. It manifests with myoclonic jerks on awakening, GTCS and, more rarely, absences. The management of JME differs from standard medical practice for the treatment of seizures in several important respects. Recommendations not to treat after the first seizure are usually inappropriate, not only because affected patients have usually experienced other epileptic events (e.g. myoclonic jerks and absences) for many months or years before their first GTCS, but also because JME is a lifelong disease with a high risk of major and minor seizures, particularly after sleep deprivation, fatigue and alcohol indulgence. Emphasising avoidance of precipitating factors in JME is part of the management strategy. Many AED such as carbamazepine or gabapentin worsen JME. Withdrawal of appropriate AED after 2–3 years seizure free is inappropriate because relapses are inevitable.

Hippocampal epilepsy is the commoner focal epileptic disorder affecting around 20% of patients with epilepsies. It is of defined pathology that can be documented in vivo with high resolution MRI in nearly all patients. If carbamazepine alone or in combination with another one or two of the main AEDs fails, the chances of achieving medical control are negligible. These patients, even in childhood, need urgent evaluation for neurosurgical treatment for which they are the best candidates and the most likely to have excellent and sustained benefit.^80,81

Epilepsy or Epilepsies?

Even the most sceptical physicians among those who doubt the clinical or practical significance of the syndromic diagnosis of epilepsies have to accept that benign childhood focal epilepsies, JME and hippocampal epilepsy have nothing in common other than the fact that they may all be complicated by GTCS, which are primarily GTCS in JME and secondarily GTCS in benign childhood focal epilepsies and hippocampal epilepsy. Furthermore, the short- and long-term treatment strategies are entirely different for each disorder: benign childhood focal epilepsies may or may not require medication for a few years, appropriate AED treatment is lifelong in JME while neurosurgery may be life saving for patients with hippocampal epilepsy. What may be a saviour drug for one may be deleterious for another type of epilepsy.

It should not be difficult to distinguish an intelligent child with benign focal seizures or childhood absence epilepsy from a child with Kozhevnikov–Rasmussen, Lennox–Gastaut, Down or Sturge–Weber syndrome or a child with severe post-traumatic cerebral damage, brain anoxia or catastrophic progressive myoclonic epilepsy. Diagnosing all these children as simply having epilepsy just because they have seizures offers no more benefit than a diagnosis of a febrile illness irrespective of cause, which may be a mild viral illness, bacterial meningitis or malignancy. Describing all these children as simply having epilepsy just because they have seizures offers no more benefit than a diagnosis of muscle atrophy, irrespective of whether it is localised or generalised, post-traumatic or genetically determined, static, reversible or progressive, or whether the underlying cause is in the muscle, nerve or spinal cord, and is treatable or untreatable.

The treatment of epilepsies will change, but their correct diagnosis will always be the golden rule. We should discourage randomised control trials that lump all patients with any type of seizures as a ‘universe of epilepsy’ or recommendations such as ‘start with valproate and if this does not work change it to carbamazepine’, ‘an EEG is not needed after the first seizure because treatment is after the second seizure’ (not even specifying the type of seizure and the need to specifically inquire for minor fits).

The Web and New Avenues for Information and Communication

There has been an explosive growth of the Internet and Web as tools for seeking and communicating health and medical information. An increasing number of physicians and patients use Web search engines to seek very detailed advice and solicit or share specific medical and health information. More specialised medical or health websites, such as WebMD, are becoming available.

There is a rapid growth in the literature addressing the role of the Internet in medicine and in particular patient education, patient support networks, education and communication among health providers, and communication between providers and patients.

In this shared-decision-making medical environment, immediate access to such information has been of great benefit to health-care professionals and patients. However, there is growing concern that a substantial proportion of clinical information on the Web might be inaccurate, erroneous, misleading, or fraudulent, and thereby pose a threat to public health. Medical website quality is being tested through many sources and guidelines for quality criteria are being developed. With e-mail use patients also have easy, direct and fast access to experts around the world. Parents and patients often use the wide information provided on the Internet for formulating their own opinion regarding diagnosis and management. They are entitled to do so and this is often useful. The following is an example from many e-mails that I receive from non-medically qualified parents and patients:

Clinical note

… For years her condition has gone undiagnosed and to this day it still is. I have searched extensively on the Web and PubMed for vomiting and seizures because I understand that the aura and the way a seizure starts can be very informative.....I finally found out about Panayiotopoulos syndrome which perfectly matched her symptoms. Upon forwarding the articles to our neurologist, I was told that her EEG did not fit the pattern.

Author’s note: the EEG was a typical example of multifocal EEG in this syndrome.

Significant progress is expected if emphasis is directed on ‘how to diagnose the epilepsies’ rather than the current theme of ‘how to treat epilepsy’.

Important note

Inappropriate generalisations regarding terminology, diagnosis and treatment is the single most important cause of mismanagement in epilepsies.

References

1.

Commission on Epidemiology and Prognosis. International League Against Epilepsy. Guidelines for epidemiologic studies on epilepsy. Epilepsia. 1993;34:592–6. [PubMed: 8330566]

2.

ILAE Commission Report. The epidemiology of the epilepsies: future directions. International League Against Epilepsy. Epilepsia. 1997;38:614–8. [PubMed: 9184609]

3.

Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42:796–803. [PubMed: 11422340]

4.

Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde BW, Engel J Jr. Glossary of descriptive terminology for ictal semiology: report of the ILAE task force on classification and terminology. Epilepsia. 2001;42:1212–8. [PubMed: 11580774]

5.

Stephenson JB. Fits and faints. London: MacKeith Press; 1990.

6.

Murtagh J. Fits, faints and funny turns. A general diagnostic approach. Aust Fam Physician. 2003;32:203–6. [PubMed: 12735258]

7.

Benditt D, Blanc JJ, Brignole M, Sutton R. Evaluation and Treatment of Syncope. London: Blackwell Publishing; 2003.

8.

Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, et al. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J. 2001;22:1256–306. [PubMed: 11465961]

9.

Lesser RP. Psychogenic seizures. Neurology. 1996;46:1499–507. [PubMed: 8649537]

10.

Gumnit RJ. Psychogenic seizures. In: Wyllie E, editor. The treatment of epilepsy: Principles and practices. Philadelphia: Lippincott Williams & Wilkins; 2001. pp. 699–703.

11.

Gates JR, Rowan AJ. Nonepileptic seizures. Boston: Butterworth-Heinemann; 2000.

12.

Gates JR. Nonepileptic seizures:Classification, coexistence with epilepsy, diagnosis, therapeutic approaches, and consensus. Epilepsy Behav. 2002;3:28–33.

13.

Reuber M, Elger CE. Psychogenic nonepileptic seizures: review and update. Epilepsy Behav. 2003;4:205–16. [PubMed: 12791321]

14.

de Timary P, Fouchet P, Sylin M, Indriets JP, De Barsy T, Lefebvre A, et al. Non-epileptic seizures: delayed diagnosis in patients presenting with electroencephalographic (EEG) or clinical signs of epileptic seizures. Seizure. 2002;11:193–7. [PubMed: 12018963]

15.

Nowack WJ. Epilepsy: a costly misdiagnosis. Clin Electroencephalogr. 1997;28:225–8. [PubMed: 9343716]

16.

Fisher RS. Imitators of epilepsy. New York: Demos Publications, Inc.; 1994.

17.

Francis P, Baker GA. Non-epileptic attack disorder (NEAD): a comprehensive review. Seizure. 1999;8:53–61. [PubMed: 10091850]

18.

Guerrini R, Aicardi J, Andermann F, Hallett M. Epilepsy and movement disorder. Cambridge: Cambridge University Press; 2001.

19.

Foldvary N. Sleep and Epilepsy. Curr Treat Options Neurol. 2002;4:129–35. [PubMed: 11827645]

20.

Beran RG, Plunkett MJ, Holland GJ. Interface of epilepsy and sleep disorders. Seizure. 1999;8:97–102. [PubMed: 10222301]

21.

Scher MS. Applying classifications of sleep disorders to children with neurologic conditions. J Child Neurol. 1998;13:525–36. [PubMed: 9853644]

22.

Shouse MN, da Silva AM, Sammaritano M. Sleep. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook. Vol. 42. Philadelphia: Lippincott-Raven Publishers; 1929. 1997.

23.

Bourgeois B. The relationship between sleep and epilepsy in children. Semin Pediatr Neurol. 1996;3:29–35. [PubMed: 8795839]

24.

Barthlen GM, Stacy C. Dyssomnias, parasomnias, and sleep disorders associated with medical and psychiatric diseases. Mt Sinai J Med. 1994;61:139–59. [PubMed: 8022426]

25.

Stephenson JB. Anoxic seizures: self-terminating syncopes. Epileptic Disord. 2001;3:3–6. [PubMed: 11313215]

26.

Drigo P, Carli G, Laverda AM. Benign paroxysmal vertigo of childhood. Brain Dev. 2001;23:38–41. [PubMed: 11226728]

27.

Li BU. Cyclic vomiting syndrome: age-old syndrome and new insights. Semin Pediatr Neurol. 2001;8:13–21. [PubMed: 11332860]

28.

Li BU, Balint JP. Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. Adv Pediatr. 2000;47:117–60. [PubMed: 10959442]

29.

Meadow R. Different interpretations of Munchausen Syndrome by Proxy. Child Abuse Negl. 2002;26:501–8. [PubMed: 12079086]

30.

Meadow R. What is, and what is not, ‘Munchausen syndrome by proxy’? Arch Dis Child. 1995;72:534–8. [PMC free article: PMC1511135] [PubMed: 7618944]

31.

Schreier H. Munchausen by proxy defined. Pediatrics. 2002;110:985–8. [PubMed: 12415040]

32.

Thomas K. Munchausen syndrome by proxy: identification and diagnosis. J Pediatr Nurs. 2003;18:174–80. [PubMed: 12796859]

33.

Golden GS. Nonepileptic paroxysmal events in childhood. Pediatr Clin North Am. 1992;39:715–25. [PubMed: 1635803]

34.

Andriola MR, Ettinger AB. Pseudoseizures and other nonepileptic paroxysmal disorders in children and adolescents. Neurology. 1999;53:S89–S95. [PubMed: 10496239]

35.

Bye AM, Kok DJ, Ferenschild FT, Vles JS. Paroxysmal non-epileptic events in children: a retrospective study over a period of 10 years. J Paediatr Child Health. 2000;36:244–8. [PubMed: 10849225]

36.

Villanueva-Gomez F. A video-EEG description of non-epileptic paroxysmal seizures. Rev Neurol. 2000;30(Suppl 1):S9–15. [PubMed: 10904964]

37.

Pellock JM. Other nonepileptic paroxysmal disorders. In: Wyllie E, editor. The treatment of epilepsy: Principles and practices. Philadelphia: Lippincott Williams & Wilkins; 2001. pp. 705–16.

38.

Kotagal P, Costa M, Wyllie E, Wolgamuth B. Paroxysmal nonepileptic events in children and adolescents. Pediatrics. 2002;110:e46. [PubMed: 12359819]

39.

Lempert T. Recognizing syncope: pitfalls and surprises. J R Soc Med. 1996;89:372–5. [PMC free article: PMC1295849] [PubMed: 8774533]

40.

Kapoor WN. Syncope. N Engl J Med. 2000;343:1856–62. [PubMed: 11117979]

41.

McLeod KA. Syncope in childhood. Arch Dis Child. 2003;88:350–3. [PMC free article: PMC1719534] [PubMed: 12651770]

42.

Stephenson JB. Differentiating convulsive syncope and epilepsy. Ann Intern Med. 1992;116:777–8. [PubMed: 1558356]

43.

Stephenson J, Breningstall G, Steer C, Kirkpatrick M, Horrocks I, Nechay A, et al. Anoxic-epileptic seizures: home video recordings of epileptic seizures induced by syncopes. Epileptic Disord. 2004;6:15–9. [PubMed: 15075063]

44.

Ferrie CD. Reflex anoxic seizures. Gilman S, editor. Medlink Neurology; San Diego SA: 2005.

45.

Lempert T, von Brevern M. The eye movements of syncope. Neurology. 1996;46:1086–8. [PubMed: 8780096]

46.

Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol. 1994;36:233–7. [PubMed: 8053660]

47.

Alper K, Devinsky O, Perrine K, Vazquez B, Luciano D. Psychiatric classification of nonconversion nonepileptic seizures. Arch Neurol. 1995;52:199–201. [PubMed: 7848132]

48.

Howell SJ, Owen L, Chadwick DW. Pseudostatus epilepticus. Q J Med. 1989;71:507–19. [PubMed: 2602547]

49.

Carmant L, Kramer U, Holmes GL, Mikati MA, Riviello JJ, Helmers SL. Differential diagnosis of staring spells in children: a video- EEG study. Pediat Neurol. 1996;14:199–202. [PubMed: 8736402]

50.

Opherk C, Hirsch LJ. Ictal heart rate differentiates epileptic from non-epileptic seizures. Neurology. 2002;58:636–8. [PubMed: 11865145]

51.

Carton S, Thompson PJ, Duncan JS. Non-epileptic seizures: patients’ understanding and reaction to the diagnosis and impact on outcome. Seizure. 2003;12:287–94. [PubMed: 12810341]

52.

Meyer MA, Zimmerman AW, Miller CA. Temporal lobe epilepsy presenting as panic attacks: detection of interictal hypometabolism with positron emission tomography. J Neuroimaging. 2000;10:120–2. [PubMed: 10800267]

53.

Cragar DE, Berry DT, Fakhoury TA, Cibula JE, Schmitt FA. A review of diagnostic techniques in the differential diagnosis of epileptic and nonepileptic seizures. Neuropsychol Rev. 2002;12:31–64. [PubMed: 12090718]

54.

Panayiotopoulos CP. Benign childhood partial seizures and related epileptic syndromes. London: John Libbey & Company Ltd; 1999.

55.

Hauser WA, Rich SS, Annegers JF, Anderson VE. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology. 1990;40:1163–70. [PubMed: 2381523]

56.

Commission of Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981;22:489–501. [PubMed: 6790275]

57.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389–99. [PubMed: 2502382]

58.

Engel J Jr. Reply to “ Cabbages and Kings in the classification of seizures and the epilepsies “ Epilepsia. 2003;44:4–6.

59.

Fisher RS, Wolf P, Engel J Jr, Luders H, Najm I, Wyllie E, et al. Cabbages and Kings in the classification of seizures and the epilepsies. Epilepsia. 2003;44:1–13.

60.

Wolf P. Of cabbages and kings: some considerations on classifications, diagnostic schemes, semiology, and concepts. Epilepsia. 2003;44:1–4. [PubMed: 12581219]

61.

Luders HO, Najm I, Wyllie E. Reply to “ Cabbages and Kings in the classification of seizures and the epilepsies “ Epilepsia. 2003;44:6–8.

62.

Berg A, Blackstone NW. Reply to “Cabbages and Kings in the classification of seizures and the epilepsies “ Epilepsia. 2003;44:8–12.

63.

Avanzini G. Reply to “ Cabbages and Kings in the classification of seizures and the epilepsies “ Epilepsia. 2003;44:12–3.

64.

Gastaut H. Clinical and electroencephalographical classification of epileptic seizures. Epilepsia. 1970;11:102–13. [PubMed: 5268244]

65.

Nicholl JS. Of Cabbages and Kings: Some considerations on classifications, diagnostic schemes, semiology, and concepts. Epilepsia. 2003;44:988. [PubMed: 12823587]

66.

Panayiotopoulos CP. Importance of specifying the type of epilepsy. Lancet. 1999;354:2002–3. [PubMed: 10622332]

67.

Grunewald RA, Panayiotopoulos CP. The diagnosis of epilepsies. JRCPhys London. 1996;30:122–7. [PMC free article: PMC5401546] [PubMed: 8709057]

68.

Benbadis SR, Luders HO. Epileptic syndromes: an underutilized concept [editorial] Epilepsia. 1996;37:1029–34. [PubMed: 8917051]

69.

Nordli DR Jr. Diagnostic difficulty in infants and children. J Child Neurol. 2002;17(Suppl 1):S28–S35. [PubMed: 11918460]

70.

Adie WJ. Pyknolepsy:a form of epilepsy occurring in children with a good prognosis. Brain. 1924;47:96–102. [PMC free article: PMC2201422] [PubMed: 19983793]

71.

Merlis JK. Proposal for an international classification of the epilepsies. Epilepsia. 1970;11:114–9. [PubMed: 5268245]

72.

Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. 3. London: John Libbey & Co Ltd; 2002.

73.

Wolf P. Historical aspects: the concept of idiopathy. In: Malafose A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalised epilepsies:clinical, experimental and genetic aspects. London: John Libbey & Company; 1994. pp. 3–6.

74.

Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for classification of epilepsy and epileptic syndromes. Epilepsia. 1985;26:268–278. [PubMed: 3924589]

75.

Camfield P, Camfield C. Childhood epilepsy: what is the evidence for what we think and what we do? J Child Neurol. 2003;18:272–87. [PubMed: 12760431]

76.

Jackson HJ. On Classification and on Methods of Investigation (1874). In: Taylor J, editor. Selected writing of John Hughlings Jackson. London: Hodder and Stoughton; 1952.

77.

Commission on Antiepileptic Drugs of the International League Against Epilepsy. Guidelines for clinical evaluation of antiepileptic drugs. Epilepsia. 1989;30:400–8. [PubMed: 2752994]

78.

Commission on Antiepileptic Drugs of the International League Against Epilepsy. Guidelines for antiepileptic drug trials in children. Epilepsia. 1994;35:94–100. [PubMed: 8112263]

79.

Panayiotopoulos CP. Autonomic seizures and autonomic status epilepticus peculiar to childhood: diagnosis and management. Epilepsy Behav. 2004;5:286–95. [PubMed: 15145296]

80.

Engel J Jr, Wiebe S, French J, Sperling M, Williamson P, Spencer D, et al. Practice parameter: temporal lobe and localized neocortical resections for epilepsy. Epilepsia. 2003;44:741–51. [PubMed: 12790886]

81.

Wieser HG. ILAE Commission Report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2004;45:695–714. [PubMed: 15144438]