CLINICAL SPECTRUM

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CHAPTER 50 CLINICAL SPECTRUM

The clinical spectrum of epilepsy is vast. In terms of symptomatology, the expression of epileptic seizures is very diverse and depends on the function of the part of the brain that is involved by the abnormal neuronal discharge. The age of the affected individual at disease onset and during its evolution ranges from neonates to elderly persons, leading to multiple clinical scenarios. Certain epileptic disorders that occur early in life may have severe consequences on the developing brain. Another key determinant of epileptic diseases is the etiological background, which may include genetic factors, acquired brain lesions, or progressive brain dysfunction but may also remain unknown. This diversity and sometimes complexity are well reflected by the classifications—classification of epileptic seizures on the one hand and classification of epilepsies and epileptic syndromes on the other. All of these parameters should be analyzed by a clinician in a syndromic approach to the patient’s condition. This type of approach facilitates development of a rational management strategy, with selection of the most appropriate drugs as a function of their spectrum of efficacy, and establishes a reasonably reliable prognosis. The severity of the different epileptic syndromes varies from very benign and transient conditions to devastating diseases.

DEFINITIONS AND EPIDEMIOLOGY

Any epidemiological approach requires solid definitions of the events and conditions that are under study. Consensual agreement on even the definition of the terms seizure and epilepsy has proved difficult.

An epileptic seizure can be defined as a transient occurrence of signs and/or symptoms due to abnormal or excessive synchronous brain activity.

Epilepsy is a family of disorders of the brain characterized by an enduring predisposition to epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition.

Epileptic seizures are pleomorphic, although usually stereotyped for a given individual. Unlike most neurological disorders, the majority of patients with epileptic seizures do not have permanent physical signs and can be diagnosed only by taking a history or by the chance observation of a seizure. Diagnosis is a discretionary judgment that may vary depending on the skill and experience of clinicians and the quality of available information from witnesses. Electroencephalographic and other complementary investigations are useful in classifying epilepsy but are of limited help in making the diagnosis. Some patients with seizures may never seek medical attention because they ignore or misinterpret their symptoms, or indeed they may be unaware of them. In practice, both false-positive and false-negative diagnoses are common.

The definitions of epilepsy have often included the notion of unprovoked seizures and of recurrence. Epileptic seizures may occur as a result of a variety of acute brain insults or metabolic disorders. Those seizures triggered by clear precipitants are termed “acute symptomatic seizures” but, despite exhibiting clear epileptiform phenomenology, they are not classified as epilepsy. The distinction between provoked and unprovoked seizures, however, is not always clear-cut or reliable for epilepsy diagnosis. Indeed, precipitating factors such as lack of sleep or alcohol may facilitate seizures in well-established epileptic diseases.

The notion of recurrence, which theoretically implies at least two seizures, is not a necessary characteristic for epilepsy diagnosis. The occurrence of one seizure may be sufficient when clinical or paraclinical elements suggest that there is an enduring alteration in the brain that increases the likelihood of future seizures. More than recurrence, it is the potential for recurrence of seizures that defines epilepsy. All of these distinctions and evolving concepts increase the difficulty of diagnostic accuracy and case ascertainment necessary for the accurate study of epilepsy epidemiology.

The overall annual incidence of epilepsy is generally believed to be around 50 per 100 000 (range, 40 to 70 per 100 000/year) in industrialized countries, but socioeconomically deprived people are at greater risk. First seizures are estimated to be around 70 per 100 000 annually. There is a mild predominance in males. The specific incidence as a function of age shows a bimodal curve, with two peaks, one in childhood, with figures of more than 100 per 100,000 during the first year of life, although there is evidence of a decrease in childhood incidence in recent decades. A second peak is observed in elderly people with an estimate of 150 per 100,000 over the age of 80 years, which is attributed to the many prevalent causes of brain damage at that age, with cardiovascular diseases being the most frequent (Fig. 50-1).

Figure 50-1 Epidemiology of epilepsy in terms of incidence and lifetime cumulative risk.

In terms of prevalence, several studies conducted in different regions of the world have suggested that epilepsy affects 5 to 8 per 1000 population. These estimates are based on individuals with active epilepsy, defined as patients with a seizure in the previous 5 years or still receiving antiepileptic drug treatment.

When isolated seizures are included, the cumulative risk or incidence, which measures the lifetime risk of having a nonfebrile seizure, is very high, ranging from 2% to 8% between 40 and 80 years of age.

From the difference between incidence and prevalence of active epilepsy, it is apparent that most patients with epilepsy cease to have seizures or die. It is also likely that the condition remits in many patients. However, epilepsy is associated with increased mortality, particularly but not exclusively in patients with brain lesions.

CLINICAL APPROACH TO EPILEPTIC DISORDERS

The clinical approach should consist of a description of the ictal semiology, using as far as possible a standardized terminology. A description of the ictal event(s) should be carefully obtained from the patient and relatives without reference to etiology, anatomy, or mechanisms. Detailed descriptions of the onset and evolution of focal ictal phenomena are not always necessary to make a diagnosis of partial seizure, but they are useful in patients who are candidates for surgical treatment or for research designed to elucidate the anatomical substrates or pathophysiological mechanisms underlying specific clinical behaviors. Electroencephalographic video monitoring, including direct interaction with the patient during an event, is the investigation that permits the most accurate and detailed analysis of symptoms.

The next step is to characterize the epileptic seizure type relative to the list of different types defined by the International Classification of Seizures (Table 50-1). It is essential to identify or rule out seizure types by detailed questioning of patients and relatives. Localization within the brain should be specified when this is appropriate; in the case of reflex or provoked seizures, the specific stimulus should also be specified. Electroencephalographic data are often incorporated at this stage of the diagnostic process, as many seizures are also associated with specific electroclinical characteristics. Age at onset is also a critical piece of information. Certain specific seizure types may by themselves be more or less indicative of diagnostic entities with etiological, therapeutic, and/or prognostic implications.

TABLE 50-1 International Classification of Seizures (1981)

Generalized Seizures

Tonic-clonic seizures

Atonic seizures

Unclassified Seizures

A syndromic diagnosis should then be made whenever possible, again using the common terms proscribed by the International Classification of Epilepsies and Epileptic Syndromes. This syndromic diagnosis relies on the grouping of information: on seizure type or types, pattern of recurrence or frequency, age at onset, personal and familial antecedents, natural history, and other neurological and extraneurological manifestations. The electroencephalographic data, both interictal and sometimes ictal, are essential, as is a brain imaging examination. Magnetic resonance imaging is indicated in the majority of situations but can be omitted when certitude is reached about the diagnosis of an idiopathic generalized syndrome.

Clinical and paraclinical investigations can also help to identify specific etiologies. The etiology can consist of a specific disease frequently associated with epileptic seizures or syndromes, a genetic defect, or a specific pathological substrate, for instance, for the symptomatic focal epilepsies.

Finally, it is essential to evaluate the degree of impairment caused by the epileptic condition and to try to establish a prognosis in parallel to making decisions about the therapeutic measures to be exhibited. These steps are strongly influenced by analysis of seizure type and the syndromic diagnosis.

EPILEPTIC SEIZURES

Three great categories have been identified—generalized, partial or focal seizures, and unclassified seizures. Here they are described as individual events, with a well-defined temporal course from onset to termination. Almost every type of seizure can occur continuously or repetitively, thus constituting status epilepticus. In this case, some of the seizure characteristics may become less readily identifiable.

Generalized Seizures

In generalized seizures, the paroxysmal discharge involves both hemispheres simultaneously and in a diffuse manner. Clinical manifestations are usually bilateral and symmetrical. The electroencephalographic correlates consist of spikes, polyspikes, spikes and waves, or polyspikes and waves that are typically bilateral, synchronous, and symmetrical in the two hemispheres.

Partial Seizures

Partial seizures are very polymorphic, they reflect the function of the brain area where they take origin—the focus or the epileptogenic zone and of the pattern of spread of epileptic activity. They are, however, remarkably stereotyped in individual patients. The first clinical symptoms of a seizure have strong localizing value. When they are perceived by the patient, they define the aura. A postictal deficit can be observed, resulting from acute dysfunction of some brain areas that have been involved by the epileptic discharge. A postictal deficit may be motor, a hemianopsia, or an aphasia. Clinically, these are generally of good lateralizing value.

Interictal and ictal scalp electroencephalographic abnormalities may correlate more or less with the brain areas invaded by the discharge, but they can be difficult to detect when epileptic neuronal activity remains confined within small or deep brain areas. Intracerebral recordings with stereotaxically implanted electrodes performed in candidates for surgical treatment have contributed considerably to an understanding of anatomical-clinical correlations in partial seizures.

The terminology of simple partial seizure is used when the patient remains conscious, whereas complex partial is used when some degree of altered consciousness can be identified. The latter generally implies that larger or bilateral brain areas are involved by the ictal discharge. In the absence of video-electroencephalographic monitoring and direct interaction with the patient during a seizure, it is not always possible to ascertain the presence or absence of brief, partial alterations of consciousness. Although the dichotomy of simple versus complex may be useful in terms of appreciating seizure severity, its significance otherwise is questionable. Recent classifications give priority to associated features.

Simple Partial Seizures

With Motor Symptoms

In somatomotor seizures with a jacksonian march, the epileptic discharge moves along the precentral motor strip, although it remains confined to the rolandic cortex. Clinically, a tonic contraction is followed by clonic jerks that initially affect a specific part of a limb or one half of the face, which then propagate to adjacent body parts as a function of the somatotopic representation.

Other types of somatomotor seizures combine various patterns of clonic and/or tonic and postural manifestations that affect a more or less extensive part of one half of the body. The contralateral discharge involves simultaneously the primary motor cortex and premotor areas. A rotation of the head and/or of the eyes is frequent. Oculomotor symptoms may also result from an occipital lobe discharge. When head deviation is associated with an elevation in abduction of the ipsilateral arm, speech arrest, or vocalization, the supplementary motor area is often implicated. Paroxysmal speech disorders such as speech arrest, vocalization, and pallilalia can be observed with seizures affecting the third frontal gyrus. Jargon phasia evokes the possible implication of the superior temporal gyrus.

With Somatosensory or Special Sensory Symptoms

Somatosensory seizures result from a discharge affecting the postcentral gyrus. Contralateral manifestations involving more or less extensive parts of one half of the body may include sensations of tingling, numbness, paraesthesias, or pain.

Visual seizures corresponding to a discharge in the occipital cortex are characterized by elementary hallucinations that can be positive (flashing lights, colored dots, etc.) or negative in the form of scotomas. More complex or elaborate visual hallucinations such as brief scenarios, macropsia, and the like generally result from implication of occipital and temporal regions.

Auditory seizures may include sound or voice distortions or hallucinations (noise, music). They result from discharges in the superior temporal gyrus (Heschl’s gyrus).

Olfactory hallucinations are usually described as the sudden perception of an unpleasant odor. They result from involvement of the region of the uncus of the temporal lobe but sometimes of the orbitofrontal cortex.

Gustatory seizures, sometimes difficult to differentiate from olfactory manifestations, have their origin in the posterior supra-sylvian cortex.

Vertiginous symptoms may rarely be an epileptic manifestation, sometimes associated with a floating sensation, implicating the inferior parietal region.

With Autonomic Symptoms

Autonomic symptoms (pallor, sweating, flushing, piloerection, pupillary dilation) can be generated by many areas of the brain, both cortical and subcortical. They have little localizing value and are frequently associated with other manifestations of partial seizures. An ascending epigastric sensation, frequently of mesial temporal origin, may also be generated by the insula and mesial frontal regions. Many components of the autonomic system can be involved—digestive, ocular, urinary, respiratory, and cardiovascular. Some symptoms result from disturbance of the thermoregulatory system.

With Psychic Symptoms

These are characterized by conscious disturbances of higher cortical functions expressed by perceptive, mnesic, or affective manifestations. The term “dreamy state” covers diverse phenomena or illusions, including feelings of strangeness, unreality, reminiscence of past experiences, and familiarity (déjà vu, déjà vécu). They often result from paroxysmal disorganization of mesial temporal lobe structures, leading to false interpretations of normally encoded notions.

Affective symptoms include fear, anxiety, even terror, and, more rarely, euphoria or sensations of pleasure.

Phenomena of forced thinking are also encountered, generally implicating the frontal lobes. Gelastic (laughter) seizures, generally occurring without any affective component, are highly suggestive of a hypothalamic origin and hamartomatous pathology.

Complex Partial Seizures

These are defined by a disturbance of consciousness, either at onset or after an initial phase of simple partial manifestations (aura). They are often accompanied by automatisms, gestural, oroalimentary (masticatory, swallowing), verbal, or more or less elaborated or adapted behavioral sequences. All of these automatisms, taken separately, have very little localizing value. Their sequence or combination of such diverse automatisms with other manifestations, however, may have some localizing value. A masticatory automatism is a good indicator of involvement of the amygdala in the context of temporal lobe seizures. The mesial temporal lobe is frequently at the origin of complex partial seizures that include an aura, often an ascending epigastric sensation with autonomic or psychic symptoms, with fear being frequent. Alteration of consciousness begins with an arrest or staring reaction, followed by oroalimentary automatisms, gestual automatisms, and limb dystonia (most often contralateral to the focus). A postictal dysphasia may be present if the dominant hemisphere is implicated. However, complex partial seizures may take their origin in other regions of the brain. The frontal lobes can generate either absence-like seizures or prominent motor automatisms.

Unclassified Seizures

Many seizures remain difficult to classify in the absence of other data (interictal electroencephalography, brain imaging). For instance, nocturnal convulsive events may correspond to primary or secondary generalized tonic-clonic seizures. Many neonatal seizures are difficult to analyze. Spasms, most often infantile, consist of brief muscular contractions in flexion or extension that occur in clusters. Whether they should be considered as generalized seizures or as unclassified seizures is unclear.

Reflex Seizures

Seizures can also be characterized by a specific mode of precipitation, independent of their classification into partial or generalized. Many precipitating stimuli eliciting reflex seizures have been described:

Visual stimuli, flickering light—color, particular patterns (black-white contrast)

Diverse stimuli: eating, reading, somatosensory, proprioceptive, contact with water, audiogenic, thinking music

Startle seizures

EPILEPSIES AND EPILEPTIC SYNDROMES

A classification system is extremely useful from many points of view—the determination of diagnosis criteria, the elaboration of a strategy for organizing complementary investigations, the rationalization of therapeutic options based on the efficacy profile of the different drugs, the establishment of a prognosis, and the facilitation of clinical research.

The international classification (Table 50-2) may give the impression that it is simply a very long list of diseases, without providing the reader with some essential organizing notions like frequency or severity. Some syndromes are very frequent, whereas others correspond to orphan diseases, emphasizing an extraordinarily vast and diversified spectrum.

TABLE 50-2 International Classification of Epilepsies and Epileptic Syndromes