Limbic Epilepsies

Mesial temporal lobe epilepsy with hippocampal sclerosis

Mesial temporal lobe epilepsy defined by specific aetiologies

Other types defined by location and aetiology

Neocortical Epilepsies (See Pages 207–221)

Rasmussen syndrome (page 207)

Hemiconvulsion-hemiplegia syndrome (page 215)

Lateral temporal lobe epilepsy

Migrating focal seizures of early childhood (page 217)

Other types defined by location and aetiology

Simple and complex focal seizures may account for 60–70 % of all epilepsies and nearly half originate from temporal lobe structures.^3–5 There are numerous causes of focal symptomatic and probably symptomatic focal epilepsies, such as benign or malignant tumours, viral and other infectious and parasitic diseases, cerebrovascular disorders, malformations of cortical development, genetically determined brain and metabolic disorders, trauma and other injuries. The exact prevalence of these aetiological factors in various types of focal epilepsies has not been estimated precisely, and certainly varies significantly between developed and developing countries. For example, cysticercosis and tuberculomas are among the commonest causes of epilepsies in developing countries, but have a minimal prevalence in Western industrialised countries. Malformations of cortical development, which are a significant cause of focal epilepsies, are often revealed only by high resolution MRI.⁶

The other idiopathic and hereditary forms of focal epilepsies have been detailed mainly in Chapters 10 and 11.

Temporal Lobe Epilepsies

Temporal lobe epilepsies comprise a heterogeneous group of disorders sharing the same topographical seizure onset (the temporal lobe), but often of diverse aetiology, age at onset, prognosis, and response to medical or surgical management. Anatomically they are broadly divided into those originating from the lateral or mesial regions of the temporal lobe (Figures 12.1 and 12.2). Mesial (or medial) is far more common (accounting for two-thirds of cases) than lateral temporal lobe epilepsy (LTLE). The most common of all is hippocampal epilepsy, which probably constitutes a disease with known pathology rather than a syndrome. Other causes of temporal lobe epilepsy, mesial or lateral, are benign or malignant tumours, viral and other infectious and parasitic diseases, cerebrovascular disorders, malformations of cortical development, trauma and other injuries.⁷ The other idiopathic and hereditary forms of temporal lobe epilepsy have been detailed in Chapters 10 and 11. Onset, progress and response to treatment largely depend on causative factors. Ictal manifestations distinguishing lateral from MTLE are often, but not always, pathognomonic. Seizures from other anatomical brain locations may present with similar semiology, mainly because of spread to temporal lobe structures.

Figure 12.1

MRIs of two patients with mesial (right) and lateral (left) temporal lobe epilepsy due to dysembryoplastic neuroepithelial tumours (DNET). Left: Coronal FLAIR MRI showing a discrete ring-like lesion in the lateral aspects of the (more...)

Figure 12.2

Ictal EEG of 2 patients with hippocampal epilepsy. Top and middle: This was the first EEG of a boy aged 6 referred for episodes of panic attacks and a recent GTCS. The resting EEG was entirely normal but one of his (more...)

Clinical Manifestations of Temporal Lobe Seizures

Temporal lobe epilepsy manifests with:

• Simple focal seizures
• Complex focal seizures
• Secondarily generalised tonic clonic seizures (GTCS)
• Focal non-convulsive status epilepticus (limbic or neocortical)
• Secondarily convulsive status epilepticus

Ictal clinical symptoms of temporal lobe epilepsy can be subjective, objective or both. They have been accurately localised and studied in neurosurgical series of patients. Simple focal seizures manifest with subjective symptoms of illusions, hallucinations or both (also called auras). These last from a few seconds to 1–2 min. They may be the only seizure type, but commonly progress to complex focal seizures during which objective symptoms, such as automatisms and motor manifestations, appear. Autonomic disturbances are common at any stage of the ictus. Secondarily GTCS may be frequent or rare and one-tenth of patients may never experience GTCS. Postictal fatigue and drowsiness are common.

The clinical manifestations of temporal lobe epilepsy are well described in relevant textbooks. Excellent descriptions can be found in old^12–27 and relatively newer reports^28–34 and reviews^35–39 devoted to this vast subject.

Subjective Ictal Clinical Manifestations

Subjective ictal clinical manifestations constitute a galaxy of various simple or complex sensations of illusions, hallucinations or both. They are also called auras because they are the first subjective symptom of an epileptic seizure prior to the impairment of consciousness. These symptoms are experienced by nearly all patients (> 90%) with temporal lobe epilepsy.^{28,31,35,37,39–41} They can be the only ictal symptom of a focal seizure, but frequently progress to other manifestations of complex focal seizures.^42,43

Epigastric aura and fear are the commonest and often the initial manifestations of mesial temporal lobe seizures. Simple or complex auditory hallucinations mainly characterise LTLE. Mental hallucinations and illusions are common in both. Olfactory and gustatory hallucinations are less common.

Subjective ictal symptoms of temporal lobe seizures, in order of prevalence, include:

• ascending epigastric aura
• experiential (mental or psychic) symptoms
• fear and panic
• déjà vu or jamais vu and their variations
• auditory hallucinations and illusions
• olfactory and gustatory hallucinations
• other symptoms.

Epigastric or Visceral Aura

Clinical note

Epigastric or visceral aura is by far the commonest symptom of mesial temporal lobe seizures.^40,44,45 It is defined by location, quality, duration, movement and associated symptoms in progression.

Location

It is usually felt in the upper half of the abdomen⁴⁴ with most patients pointing with the palm of one or both hands to a wide area between the end of the sternum and the umbilicus. Of hundreds of patients I have interrogated, I do not recall anyone pointing with a finger instead of the palm or lateralising to one side or the other. Less than 10% of 100 patients thoroughly studied by Van Buren (1963) pointed slightly lateral to the midline.⁴⁴

Quality

Epigastric aura is often initially described as pain, but on further questioning is rarely pain. It is a strange ‘difficult-to-describe’ sensation in that area for which the most common description I get is as ‘if the organs inside are squeezed and twisted’. Other descriptions are of emptiness, rolling, turning, whirling, tenderness, fluttering, butterflies, pressure, burning, nausea, emptiness and their variations.⁴⁴ Genuine pain, sometimes excruciating, is exceptional, but does occur.

Duration

This is usually short, a few seconds, but becomes longer with the appearance of other symptoms as the seizure progresses. I am not aware of any report of ‘epigastric status epilepticus’, but it may occur:

Patient note

A patient with typical MRI and PET scan evidence of right-sided hippocampal sclerosis had frequent seizures starting with an ascending abdominal sensation of discomfort in the stomach “as though being in a lift that stops abruptly”. This often progressed to a feeling of disorientation and “shivering”, and sometimes déjà vu prior to losing consciousness witnessed as: “stares and fiddles or drums with his fingers on a table”. He also had clusters of the same “intense abdominal discomfort and a feeling of shivering” lasting for 2–5 minutes, becoming repetitive at intervals of 1 hour for approximately half a day to 2 days. Within that period lengthy attacks of more than half an hour occurred.

Movement

An ascending epigastric sensation is probably the most characteristic feature of this type of epileptic seizure. Irrespective of quality, this sensation often moves upwards in a slow or fast fashion (within seconds) and, interestingly, it is when it reaches the level of the throat that the patient loses consciousness. Downward movement towards the feet is exceptional.

Fear

Fear is the commonest aura after epigastric sensations in mesial temporal lobe seizures. It is an affective mental symptom. There are two aspects to this. Firstly, fear may be a symptom of a seizure itself. Secondly, fear may be the realistic and natural reaction to an impending convulsion heralded by an aura. In some cases, the one cannot be disentangled from the other, although in most patients fear is an evidenced ictal event.

The intensity and quality of ictal fear varies considerably between patients, though it is stereotypical in each individual. Most patients use the terms ‘fear’ and ‘panic’ synonymously. It is not directed towards any particular circumstance, event or person. It is just fear or panic that may be the first, and sometimes the only, ictal symptom.

Patient note

“I am scared, I have my panic” a 5-year-old boy said during a 2-min video-EEG recorded seizure without other subjective or objective symptoms (Figure 12.2).

More often, fear appears with other symptoms at the beginning or during the course of the seizure.

Patient note

It starts with my panic and that stomach feeling, and then I pass out.

Fear is not specific to only mesial temporal lobe seizures. Although it is mainly associated with amygdaloid, periamygdaloid and hippocampal stimulation, neocortical areas can also be responsible. A typical example is the fear of frontal lobe seizures. However, there is a major difference between the fear of temporal versus frontal lobe epilepsy:

Patient note

Fear in mesial temporal lobe seizures is predominantly subjective “I am scared, I am in a terrible panic”, which is not apparent to the observer. Conversely, in frontal seizures, ‘fear’ is predominantly expressive, such as ‘his face is fearful’.

I have reached this conclusion after comparing relevant video EEG recordings of a significant number of patients. In temporal lobe seizures, patients feel intense fear or panic while, at the same time, they look relatively calm or their ‘fearful’ expression is disproportional to the intensity of their panic. Conversely, patients with frontal lobe seizures look so very terrified, which is disproportional to the actual subjective experience of fear. This differentiation should be expected: the temporal lobe is dealing with emotions/memory, while the frontal lobe dictates expression/movement.

Important note

Briefly, ‘fear’ is mainly felt emotionally in mesial temporal lobe seizures and mainly expressed facially in frontal seizures.

Experiential Symptoms (Mental, Intellectual or Psychic Symptoms, Dreamy States)

Experiential symptoms (also described as mental, intellectual or psychic symptoms, or dreamy states) of temporal lobe seizures are hallucinations, illusions or both. They may involve any faculty of the human mind: thinking, emotion, memory and recollection, chronological order, speed, sensation, reality and unreality, and their interactions with past, present and imaginary experiences. Events and experiences may be reproduced intact or disturbed: the present may be misplaced to the past, and the past to the present; real may be seen as unreal and vice versa; time may be speeded up or slowed down; and shape and other morphology may be natural or unnatural, and deformed or undistorted. Mental ictal symptoms may be very simple and natural, such as the ‘déjà vu’ phenomenon, a sensation of ‘fear and panic’ or a mild sense of depersonalisation such as “who am I?”, that may also be experienced by normal people who do not have seizures. On other occasions, these symptoms may be more complicated with a complete distortion of time, space, morphology, direction, experience and normality.

The mental ictal manifestations of temporal lobe seizures typically combine elements of perception, memory and affect that, as in real life, are often encompassed together in a unified subjective symptom.²⁸ Perceptual, mnemonic or affective aberrations usually cluster in various combinations and various degrees of disturbance. However, one aberration may be more involved than another; sometimes, one may be exclusively affected and may occur in isolation. Depending on the predominant mental aberration, they are subdivided under various names, such as: ideational (impairment of thoughts), dysmnesic (impairment of memory), affective (emotional impairment)⁴⁶ and dyscognitive (impairment of perception, cognition).

Déjà Vu

Déjà vu is another common symptom that is experienced exclusively as an ictal phenomenon in temporal lobe seizures. Déjà vu is a natural event that has been experienced by most normal people and the term is used in everyday life. In temporal lobe epilepsy, déjà vu is signified by the presence and the sequence of other epileptic events that may precede, coincide or follow it.

Nomenclature Issues

‘Dreamy states’, ‘psychic or mental symptoms’, ‘intellectual aura’ and ‘experiential phenomena’ are the terms most widely used to denote symptoms of temporal lobe seizures that uniquely relate to the patient’s personality regarding identity, experience, emotion, thought and memory. These terms are not necessarily synonymous, because they are used in the relevant literature to encompass either limited or much wider ictal manifestations.

Hughlings Jackson^14;15;47;48 introduced the term ‘dreamy state’ in favour of ‘intellectual aura’ or ‘psychical state’. He also used the word ‘psychical’ not as synonymous to the ‘dreamy state’, but to differentiate it from physical symptoms.

‘Peculiar mental state’ are the words used by Holmes.¹⁶

Of these terms, ‘psychic symptoms’¹ became popular first and ‘dreamy state’ second. Other terms used are ‘mental aura’ or ‘mental symptoms’ that may be illusionary or hallucinatory. ‘Psychic’ has inappropriate connotations and implications. Furthermore, these symptoms are transient mental, not psychic, aberrations. Patients have a clear insight that these are pathological symptoms for which they themselves seek medical advice. ‘Experiential phenomena’, introduced by Penfield⁴⁹ and masterly detailed by Gloor (1993)³¹ and Bancaud et al. (1994),³³ may be an appropriate term for only those manifestations that are based on previously experienced events. It is of limited value for ictal mental symptoms that are not related to previous experiences or in certain common circumstances that defy such experiential links.

Definition

Déjà vu is defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. Different mental components, such as memory, attention and perception, are associated with this distinct experience.

‘Déjà vu’ (already seen) is commonly used in a much broader sense, to include ‘déjà entendu’ (already heard) and ‘déjà veçu’ (already lived, experienced), as a false feeling of having experienced, seen and heard something before that is actually happening now. In déjà vu, the physical recognition is correct, but it is inappropriately connected with mental, emotional, experiential and timing processes that are associated with other physical presentations. The feeling of familiarity supervenes. It is mainly, a feeling of immense and vivid familiarity with the present situation irrespective of whether the content is visual, auditory or of any other physical presentation. The patient may say “that it is as if I have seen, heard or lived this before”, but more often the expression is “it was so familiar to me”.^33,50

Patient note

Extreme familiarity with people and surroundings, as if I knew them well, as if they were close friends or relatives, intimate relations, as if it was my everyday experience. It is more of a feeling of knowing them well than of visual or auditory recognition and experience.

Seizures start with a strong feeling of extreme familiarity with what he sees, hears or happens at the moment. The feeling is so intense and vivid that on one occasion when this happened while playing cards with his wife, he thought that he knew exactly the next sequence of cards to be played.

The precise origin of déjà vu is still controversial (see for review ref ⁵⁰). On the basis of intracranial EEG monitoring and stimulation studies, three possible sites of dysfunction have been proposed: (a) the mesial temporal lobe especially in the non-dominant hemisphere; (b) the superior lateral temporal cortex; and (c) a neuronal network that engages both mesial and lateral aspects of the temporal lobe. However, it is uncertain whether the temporal lobe disturbance is sufficient and necessary for the generation of déjà vu, since it is difficult to evaluate wider cortical regions using intracranial recordings. Based on PET scan studies, Adachi et al. (1999)⁵⁰ proposed that extensive cortical areas beyond the temporal lobe, such as the parietal and possibly other association areas, may be involved in the network that integrates the déjà vu experience. Involvement of the left hemisphere, irrespective of the side of ictal onset, seems to be of particular importance for the generation of the déjà vu experience.

Jamais Vu, Jamais Entendu and Jamais Veçu

Jamais vu (never seen), jamais entendu (never heard) and jamais veçu (never experienced before) are similar as the jamais vu expressions for illusions “during which the subject’s surroundings even when familiar are no longer recognised, although they are clearly perceived by the subject”. Jamais vu is commonly used in a much broader sense to include jamais entendu and jamais veçu. It is a false feeling of unfamiliarity (has not been experienced, seen or heard) with something that has been previously encountered.

Jamais vu is much rarer than déjà vu, but it is well described by some patients with temporal lobe epilepsy. Similar to ‘déjà vu/familiarity’, in ‘jamais vu/unfamiliarity’, the feeling of unfamiliarity is stronger than the visual, auditory or other sensorial component. Visual, auditory and any other physical recognition is correct, but the connections to the mental and emotional processes associated with them are missing.

Patient note

I know that she is my mother but I do not feel that she is. Her features do not change. She is still my mother but I do not have the same human attachment to her. She is a stranger with the looks, the voice and the manners of my mother. She is a stranger.

Auditory Hallucinations and Illusions

Auditory hallucinations are attributed to lateral temporal lobe seizures, which are much less common than mesial temporal lobe seizures. They may be elementary or complex auditory hallucinations.

Elementary auditory hallucinations are crude and described as buzzing, ringing, hissing, fizzing, whistling, humming, shrilling, sizzling or clicking auditory sensations. High pitch noises are more frequently reported. They mainly originate from the activation of Heschl’s auditory cortex in the superior temporal gyrus. For many patients, this ‘buzz’ is the aura and the start of the seizure itself.

Patient note

Here it is again. That buzzing in both ears. It is just buzz. I cannot describe it. A buzz. There is nothing else. No voice, no identifiable noise that simulates anything else, just a buzz.

Complex auditory hallucinations consist of voices, music or other sounds that may be familiar or unfamiliar, friendly or aggressive and offensive, clear or indefinable, meaningful or incomprehensible. Complex auditory hallucinations are rarely the first ictal symptom and they usually combine with other visual or mental ictal symptoms of the ‘dreamy state’. These are mainly elicited by activation of the associated auditory cortex. Auditory hallucinations of hearing a voice are almost always without semantic content, even though the voice may sound familiar and may be identifiable.³¹ The affective tone of the voice is, however, often recognised.

Patient note

“It is a clear voice of a woman, she says something that I do not remember”, “conversations of people talking next door”, “a hoarse voice of a man saying that I have to go”, “sounds of human voices and animals”, “I hear the same voice saying the same thing. I know it at the time but I can not recall it afterwards”, “a voice filtered as if spoken through a handkerchief”, “it is my own voice talking to myself”, “voices through an amplifier or a loud speaker.”

Hearing music, often the same piece for every seizure, is uncommon though it is frequently cited in the literature and can be reproduced during electrical stimulation studies. ^18,51–53 A song, usually a nursery rhyme, may be more common than music.

Auditory illusions are altered perceptions and interpretations of sounds, voices and conversations in the actual environment during the seizure. This may refer to simple changes of intensity, resonance, spatial orientation, tone, echo and clarity or be more complicated. Sounds and voices may appear louder/deafening/earsplitting or dim/faded, nearer or further away, clearer or disturbed, higher or lower pitched, echoed and variations of all of these.

Patient note

“the voices fade away”, “my hearing is heightened so I can hear everything loud and high pitched”, “as if talking from a distance”, “the voices become hoarse”, “a woman’s voice sounds like a man’s voice or like that of an animal”, “the sounds become so intense as if somebody has put the radio at maximum volume next to your ears”, “I hear the echo of the voices”, “as if you are in an empty church, you hear the sounds and their echoes.”

Olfactory and Gustatory Hallucinations

Olfactory epileptic auras are rare, constituting about 0.9% of all auras, and are typically, but not necessarily, unpleasant.^54–56 The amygdala is the most likely symptomatogenic zone of olfactory auras. Tumours⁵⁴ and hippocampal sclerosis⁵⁶ are common causes.

Patient note

“a strong smell of gas or something like this”, “a smell of rotten leaves”, “a smell of perfume”, “a peculiar odour that I can not describe”.

Gustatory epileptic auras are hallucinations of taste that are usually unpleasant (rotten food) or a strange taste. They are usually generated in the insula or superior Sylvian bank.^55,57,58

Patient note

“a strange taste of food in my mouth”, “a taste of burnt food”, “a taste of rotten food”, “taste of funny food in my mouth.”

Visual Hallucinations and Illusions

Visual hallucinations and visual illusions are detailed in the discussion of occipital lobe epilepsies.

Elementary visual hallucinations originate in the visual cortex. They do not feature in temporal lobe seizures except after secondary spread to the occipital lobes.

Complex visual hallucinations originate from the occipito-parietal-temporal junction and therefore may be part of any seizure that starts from or spreads to this area.

Complex visual hallucinations may take the form of persons, animals, objects, figures or scenes. They may be static or moving, real or unreal, normal or distorted in size, shape and dimension. They often progress to more complex visual hallucinatory experiences. They may be familiar or unfamiliar, friendly, frightening or grotesque. They may or may not be related with a past visual experience or connected with past events. In two patients reported by Penfield and associates,^59,60 habitual complex visual hallucinations could be elicited by stimulation of the right posterior temporal regions.

An influential report on this subject has been written by Lance (1976)⁶¹ and the topic has been effectively reviewed by Kolmel (1993).⁶²

Gordon Holmes (1927),¹⁶ in differentiating visual hallucinations of occipital from temporal lobe epilepsy, clearly stated:

Patient note

“More complicated subjective visual phenomena associated with local lesions in the neighbourhood of the uncus of the temporal lobe are different in origin and nature to those of occipital epilepsy. These uncinate epileptic seizures frequently begin with subjective smells and tastes, which are almost invariably of an unpleasant, usually of an extremely disagreeable, character; often there is, too, an epigastric sensation which may account to actual nausea. Then comes that peculiar mental state which Jackson called the ‘dreamy state’ or ‘intellectual aura’ characterised by a feeling of unreality of the present or familiarity with the events of the moment as though they had been experienced before. Often visions, which the patient associates with the past come up. A patient whom I had under observation always saw, in this stage a woman with a red cloak approaching nearer and nearer until, as the spectre reached her, she lost consciousness. In other cases, the vision may be of a scene tinted with a tone of familiarity, a building or a similar object. In such cases the visual hallucinations, for to these the term hallucination can be applied, is only part of the intellectual aura of Jackson and is obviously the result of more complicated cerebral and psychological processes than the perception and projection of lights and colour.”

Usually, auditory and visual hallucinations occur together. These are complex hallucinations of a scene, people, animals, objects, voices, music or the noise of a train. The content of these hallucinations usually appears familiar, but it may be entirely strange or unidentifiable.

Ictal Urinary Urge

Ictal urinary urge indicates seizure onset in the non-dominant temporal lobe.⁶³ Six patients with temporal lobe seizures characterised by an aura of ictal urinary urge were recently described.⁶³ In ictal single photon emission computed tomography (SPECT) of two patients, there was hyperperfusion of the insular cortex, indicating a critical role of the insula in the generation of the urinary urge.

Objective Ictal Symptoms

Objective ictal symptoms of temporal lobe epilepsy usually occur when consciousness is impaired. The patient is seldom aware of them. They are described by witnesses or captured on video recordings.

Objective ictal symptoms in order of prevalence include:

• Automatisms
• Autonomic disturbances
• Speech disturbances
• Head and eye deviation as well as dystonic postures
• Motor arrest with staring
• Unilateral ictal paresis
• Unilateral eyelid blinking
• Ictal vomiting

In general, nearly all of these ictal symptoms are not specific to temporal lobe seizures. Recent reviews and reports of temporal lobe epilepsy have emphasised objective symptoms only because of their lateralising value.

Automatisms

Oro-alimentary automatisms, which are often followed by simple gestural automatisms, are characteristic of MTLE only if preceded by epigastric aura, fear and mental symptoms of the ‘dreamy state’ of Jackson, alone or in combination.^{34,37,39,64–67} Oro-alimentary automatisms are more likely to begin in the first part of a complex focal seizure after the aura. They are attributed to seizures originating from the amygdala and periamygdaloid region, and not from the hippocampus. However, hippocampal after-discharges invariably spread to the amygdala, which explains the high prevalence of these automatisms in MTLE.

Important note

Simple automatisms, devoid of behavioural changes, are of no diagnostic significance in temporal lobe epilepsy. They are among the commonest symptoms in childhood and juvenile absence epilepsy. They are differentiated by clustering of other symptoms, duration and EEG manifestations.

Verbal automatisms of coherent speech are associated with seizure onset in the non-dominant hemisphere.^38,70 Ictal vocalisation probably has no lateralising value.⁷⁰ Both ictal vocalisation and verbal automatisms can occur in extratemporal epilepsies, such as frontal lobe seizures; they often occur in childhood and juvenile absence epilepsy.⁷¹

Definitions of Automatisms

Automatisms are coordinated involuntary simple movements or more complex acts performed by a patient who is unaware of them, because consciousness is sufficiently impaired. The patient is totally amnesic of this behaviour.

Automatisms are defined by the ILAE as “A more or less coordinated, repetitive, motor activity usually occurring when cognition is impaired and for which the subject is usually amnesic afterwards. This often resembles a voluntary movement, and may consist of inappropriate continuation of ongoing preictal motor activity.”⁶⁸

According to Jackson “They have one common character –they are automatic; they are done unconsciously, and the agent is irresponsible. Hence, I use the term mental automatism.”^47;69 In the Dictionary of Epilepsy ⁴⁶ automatisms are “more or less coordinated adapted (eupractic or dyspractic) involuntary motor activity occurring during the state of clouding of consciousness either in the course of, or after an epileptic seizure, and usually followed by amnesia for the event. The automatism may be simply a continuation of an activity that was going on when the seizure occurred, or, conversely, a new activity developed in association with the ictal impairment of consciousness. Usually, the activity is commonplace in nature, often provoked by the subject’s environment, or by his sensations during the seizure: exceptionally, fragmentary, primitive, infantile, or antisocial behaviour may occur.”

Automatisms may be simple or complex.

I. Simple automatisms, devoid of behavioural changes, manifest with simple involuntary movements and include: Oro-alimentary automatisms: lip smacking, lip pursing, chewing, licking, tooth grinding or swallowing

Vocal: single or repetitive utterances consisting of sounds such as grunts or shrieks

Verbal: single or repetitive utterances consisting of words, phrases or brief sentences, such as uttering, shouting, talking or singing words, sentences or phrases

Gestural: often unilateral: (a) fumbling or exploratory movements with the hand directed towards self or environment; fiddling, fumbling, picking, tapping, patting or plucking, rubbing or scratching the face and other gestural movements; and (b) movements resembling those intended to lend further emotional tone to speech

Ambulatory automatisms: well coordinated acts, such as walking straight or in circles, continuing cycling or even driving

Manual or pedal: bilateral or unilateral fumbling, tapping, manipulating movements

Mimetic: facial expression suggesting an emotional state, often fear⁶⁸

II. Complex (behavioural)automatisms: rich in behavioural changes with complex acts performed without apparent awareness. Semi-purposeful or well-organised exploratory or inappropriate behavioural manifestations, such as embarrassing actions, undressing in public, chewing objects that are not edible, wandering or running inappropriately, or aggressive behavioural acts.

Automatisms may also be spontaneous or interactive

Spontaneous: stereotyped, involve only self, and are virtually independent of environmental influences Interactive: not stereotyped, involve more than self, and are environmentally influenced.

Complex automatisms rich in behavioural aberrations are also common in temporal lobe epilepsy, and also occur in extratemporal seizures; they are exceptional in typical absence seizures.

Spitting, either as an ictal or postictal event,⁷² and bicycling movements⁷³ are also common in extratemporal seizures.

Automatisms involving masturbation or other sexually related behaviour are uncommon, though often mentioned even in brief textbook reviews; I have never encountered them. Ictal penile erection and ejaculation are autonomic disturbances.^74,75

It is generally considered that unilateral automatisms are ipsilateral to the seizure onset.³⁸ However, this has been debated by Elger (2000)⁷⁶ and it is not applicable in patients with bilateral independent temporal spikes.⁷⁷

Language and Speech Ictal Disturbances

In addition to vocal and verbal automatisms, speech arrest and language disturbances are frequent manifestations of temporal lobe seizures. The commonest of all is the inability to speak.

Patient note

“I know what is going on and I understand what they are saying, but I can not speak” is much more common than “I know what it is but I can not find the word”.

Ictal aphasia and ictal speech arrest have been attributed to seizure onset in the language-dominant temporal lobe.⁷⁸ Clear ictal speech and quick recovery mainly characterise seizures of the non-dominant temporal lobe,^38,65 while postictal aphasia and prolonged recovery are mainly features of seizures of the dominant temporal lobe.³⁸

Motor Arrest, Staring and Temporal Lobe Absence

Motor and speech arrest together with staring and loss of consciousness may be the first objective symptom of a temporal lobe seizure. As a rule, they follow other subjective symptoms, but in around 10% of patients, they may occur alone from the beginning of the seizure. These symptoms are clinically similar to those of generalised absence seizures when examined in isolation. For this reason, this type of focal seizure is also called ‘temporal lobe absence’, a term that should be discouraged to avoid confusion with ‘generalised absence seizures’, which are completely different if other symptoms and duration are considered in their entirety.

The duration of motor arrest, staring and loss of consciousness varies, but usually lasts for 1 min. Occasionally, this may be the only manifestation of the seizure. The patient usually recovers without other concurrent symptoms, such as automatisms.

Motor Manifestations

Motor manifestations include eye and head deviation, as well as dystonic postures that occur in around one-fifth of patients. These symptoms, which are also detailed in other chapters, are not specific to temporal lobe seizures. Thus, eye and head deviation is a common symptom in frontal and occipital lobe seizures. Dystonic postures are more often related to the frontal than temporal lobe.

Motor manifestations, despite their insignificance for pure anatomical localisation, are of value with respect to possible lateralisation:

Early and casual deviation of the eyes and head, in the setting of other more typical mesial temporal lobe ictal symptoms, may be ipsilateral to the epileptogenic focus.^38,79–81 Conversely, it is almost always contralateral if it occurs during the progression of the seizure, when it is also more violent and often followed by secondarily GTCS.³⁷

Unilateral tonic or dystonic posturing of arm, leg and face was described by Ajmone-Marsan and Ralston¹⁹ who called it ‘larval M2e’ to differentiate it from that of frontal lobe seizures. It is often associated with ipsilateral automatisms. It is reliably contralateral to the epileptogenic focus.³⁸

Unilateral eyelid blinking is ipsilateral to the epileptogenic focus.⁸²

Unilateral ictal paresis is contralateral to the origin of the seizure.⁸³

Autonomic Disturbances and Ictus Emeticus

Autonomic disturbances of any type are among the most frequent ictal symptoms of temporal lobe epilepsy.^84–88

Cardiovascular symptoms, mainly tachycardia and arrhythmias, less often bradycardia, asystole or hypertension, are very common and may be a common cause of sudden death in temporal lobe epilepsies (Figure 12.3).^{75,84,88–93}

Figure 12.3

Cardiac asystole soon after the onset of a right-sided temporal lobe seizure. The patient is a 60-year-old man with seizures of MTLE of recent onset. Seizures start with a vague feeling of ascending epigastric sensation. He never had GTCS. (more...)

A brief respiratory arrest, a sigh or a gasp is common in the initial part of complex focal seizures. Hyperpnoea, hypopnoea or even apnoea may occur in the late seizure phase.⁷⁵

Mydriasis, sometimes asymmetrical, is a frequent symptom associated with the arrest reaction.^38,75 Miosis and hippus pupillae are also common.⁷⁵

A feeling of ‘shivering cold’ is sometimes associated with piloerection.⁷⁵ Salivation is common, but lacrimation and nasal secretion are rare.⁷⁵

There are occasional reports of penile erection, and even ejaculation or other sexual ictal manifestations.⁷⁴

Flushing or more often pallor are commonly encountered.⁷⁵

Ictus emeticus (nausea, retching and vomiting), and particularly ictal vomiting, is exceptional in adult patients with temporal lobe seizures, but very common in children with Panayiotopoulos syndrome.

Important Clinical Note on Ictus Emeticus in Adults and Children

In adults, there are no more than 30 reported cases of ictal vomiting, which predominantly emanates from the non-dominant temporal lobe and usually occurs after seizure onset, concurrently with other symptoms, and the patient is amnesic of the events.^77,94–97 Conversely, ictus emeticus in children is very common, usually occurs at the onset of the seizures and the patient has a good recollection of the event (see ictus emeticus in Panayiotopoulos syndrome page 235).^98–100

Gelastic Seizures of Temporal Lobe Epilepsy

Ictal laughter is rare, but has been well documented in over 34 cases of temporal lobe epilepsy.¹⁰¹ It has been attributed mainly to right-⁷⁶ and less often to left-sided^102–104 extramesial seizures. Age at onset is variable with several cases starting in childhood. Gelastic seizures have been produced by stimulation of the temporobasal cortex in two candidates for surgery for non-gelastic seizures and explored with subdural electrodes.¹⁰⁵

The clinical descriptions are variable; the laughter being natural or forced, unmotivated, associated or even reactional to a pleasant event or feeling.

The laughter commonly is devoid of any sensation and is accompanied by a break of contact. A few patients have described feelings of mirth associated with laughter^105–108 or an immediate environment felt to be amusing or distorted.^105,107 In one case, the seizures could be triggered by hyperextension of the back and, in another case, sexual sensation was reported prior to the development of laughter.¹⁰⁸

In 50% of cases, other types of seizures occur concomitantly or precede the gelastic seizures.¹⁰¹

See also hypothalamic (gelastic) epilepsy.

Amnesic Seizures

In pure amnesic seizures, the only clinical manifestation is an inability to retain in memory what occurs during the seizure. Other cognitive functions are preserved and patients interact normally with their physical and social environment.¹⁰⁹ Pure amnesic seizures of patients with temporal lobe epilepsy never represent the only type of seizure. This may suggest that they result from selective ictal inactivation of mesial temporal structures without neocortical involvement. Amnesic seizures occur most often in patients with neuropsychological and EEG evidence of bilateral dysfunction of mesial temporal lobe structures. More rarely, in unilateral dysfunction, amnesic seizures may be due to seizure discharge limited to the mesial temporal structures of both sides, probably as a result of contralateral spread from one to the other through the dorsal hippocampal commissure.¹⁰⁹

Diagnostic Procedures

Brain MRI is the most important diagnostic test required for all patients with temporal lobe epilepsy to detect symptomatic causes.^114–118 High resolution MRI may detect abnormalities in 90% of patients in neurosurgical series.

Magnetic resonance spectroscopy (MRS) offers valuable insights and is useful in the presurgical evaluation of patients. PET scanning and other functional brain imaging modalities are helpful for localisation.

The serum prolactin concentration may rise markedly 10 min after seizure onset in three-quarters of patients.¹¹⁹

Electroencephalography

Interictal EEG of MTLE is identical to that detailed in hippocampal epilepsy (see page 378), irrespective of aetiology.^120–122 Briefly, in one-third of patients, the classical spike or sharp and slow wave is shown by the anterior temporal electrode (Figure 12.4), and the yield is increased with prolonged EEG recordings and sleep EEG.

Figure 12.4

EEG samples from two patients with hippocampal epilepsy. Left: Discrete runs of monomorphic theta activity are localised in the left anterior temporal regions in this patient with left hippocampal sclerosis. There were (more...)

In LTLE, spike and sharp wave complexes may be seen in the middle temporal electrode (Figure 12.5), but this is often indistinguishable from MTLE.

Figure 12.5

EEG of a woman aged 24 with LTLE. Note the marked focal abnormalities of slow waves and sharp–slow wave complexes around the right anterior-midtemporal regions.

“Please, exclude temporal lobe epilepsy” is the commonest reason for requesting an EEG for any kind of transient behavioural aberration; it is often an impossible task.

About two-thirds of patients have a normal routine interictal EEG or show non-specific abnormalities with an excess of slow waves in one temporal lobe. Runs of monomorphic slow waves may be important for lateralisation and appear ipsilateral to seizure onset (Figure 12.4).^123–125 Furthermore, in patients with temporal lobe epilepsy whose MRI is either normal or suggestive of hippocampal sclerosis, interictal temporal delta activity has a lateralising value similar to that of temporal spiking.¹²⁵

Ictal EEG as detailed in hippocampal epilepsy is not significantly different in either MTLE or LTLE.^126–128 It mainly consists of regional ipsilateral rhythmic 4–7-Hz activity (Figures 12.2 and 12.3). Less often, there is attenuation of the background rhythms and remission of the interictal spikes. In one study, the ictal EEG in LTLE revealed a lower mean frequency of lateralised rhythmic activity that frequently had a hemispheric distribution, whereas in MTLE seizures this was maximal over the ipsilateral temporal region.¹¹³

Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (Hippocampal Epilepsy)

MTLE with hippocampal sclerosis (MTLE-HS) or hippocampal epilepsy is the commonest and one of the most distinct epileptic diseases/syndromes with defined underlying hippocampal pathology shown on MRI, clinical seizure types and post-resection seizure relief.^133,134 MTLE-HS has been the subject of a recent state-of-the art ILAE report.¹³⁴ Experts discussed the definition, natural history, pathological features, pathogenesis, electroclinical, neurophysiological, neuropsychological, and structural and functional imaging findings of MTLE-HS.

The clinical features and prognosis of MTLE-HS derive almost exclusively from neurosurgical series of cases that are medically intractable.^{37,39,75,76,134–136} Therefore, they may not accurately represent the clinical spectrum of MTLE-HS, particularly with respect to severity and prognosis. The neurosurgical cases may represent the tip of the iceberg and the worst cases (about 20%). The vast majority of cases (80%) are not seen in these specialised neurosurgical centres, and some cases may be very mild and easily controlled with appropriate AEDs. I have seen an impressive number of professionals (physicians, nurses, solicitors, successful businessmen, teachers) and ordinary working class people that live a normal life, some with minor focal seizures, but others with an occasional secondary GTCS often controlled with AED monotherapy.

Patient note

A 35-year-old man had an excellent work and health record as a fire-fighter and driver for 11 years despite numerous seizures from 31 years of age.

The onset of seizures was inconspicuous with brief episodes (lasting a few seconds) of “an empty feeling in the stomach” with no other symptoms. However, 2 years later, these occurred on a daily basis and were associated with a “daydream, you disappear in your own world for a moment, a second”. He did not experience any overt loss of consciousness during these events, but he felt distant and he was told by his colleagues that he became aggressive. These episodes lasted a few seconds and rarely 1 min. He was investigated in a major teaching hospital for hypoglycaemia and cardiac dysrhythmia. EEG showed independent bitemporal abnormalities of slow and occasional sharp waves. MRI documented left-sided hippocampal atrophy. Nearly all the seizures were stopped with carbamazepine 400 mg daily. Following the diagnosis of temporal lobe epilepsy, he was made redundant from work.

A more complete clinical picture is expected to emerge now that MRI enables an in-vivo diagnosis of hippocampal sclerosis/atrophy (Figures 12.1 and 12.6).^137,138

Figure 12.6

MRI findings in hippocampal sclerosis. Left: Coronal T1-weighted MRI scan showing right hippocampal sclerosis (arrow).

Clinical Manifestations^{37,39,75,76,135,136}

Patients with MTLE-HS usually have a previous history of initial precipitating incidents, including febrile seizures, trauma, hypoxia and intracranial infections, before 5 years of age and prior to the onset of their habitual non-febrile seizures.^{40,134,142,144–149} Complex focal seizures or generalised convulsions are the initial non-febrile seizures that attract medical attention. As a rule, they are preceded by simple focal seizures that may have been considered, sometimes for years, as normal phenomena. Classically, the onset of habitual seizures occurs after a latent period from the initial precipitating incidents. However, some patients have no identifiable initial precipitating incidents, and some have habitual seizures that begin immediately after the initial precipitating incidents.¹³⁴

Epigastric aura, fear and oro-alimentary automatisms are the most common ictal symptoms.

Patient note

It starts with that strange stomach feeling and my panic, and then I pass out.

ILAE Classification and Definitions

The ILAE Commission (1989)¹ classifies MTLE-HS among other temporal lobe epilepsies under the name ‘Amygdalohippocampal (mesiobasal limbic or rhinencephalic) seizures’ and describes them as follows:

“Hippocampal seizures are the most common form; the symptoms are those described in the previous paragraphs except that auditory symptoms may not occur. The interictal scalp EEG may be normal, may show interictal unilateral temporal sharp or slow waves, may show bilateral sharp or slow waves, synchronous or asynchronous. The intracranial interictal EEG may show mesial anterior temporal spikes or sharp waves. Seizures are characterized by rising epigastric discomfort, nausea, marked autonomic signs, and other symptoms, including borborygmi, belching, pallor, fullness of the face, flushing of the face, arrest of respiration, papillary dilatation, fear, panic, and olfactory-gustatory hallucinations.”¹ The new ILAE diagnostic scheme classifies MTLE with hippocampal sclerosis in limbic epilepsies (page 21).² The majority of expert contributors in the 2004 ILAE report consider MTLE-HS to represent a sufficient cluster of signs and symptoms to make up a syndromic diagnostic entity, but not a disease (despite common pathology).¹³⁴

Clarifications on Nomenclature

MTLE-HS is usually described under the heading ‘MTLE’, though only 65% of patients have mesial temporal lobe seizures due to hippocampal atrophy. The remainder is due to mesial temporal lobe pathology other than hippocampal sclerosis.

The term ‘complex focal (partial) seizures’ has been erroneously used as a synonym of ‘temporal lobe epilepsy’.² Ictal impairment of consciousness in focal epilepsies is a symptom of either neocortical or limbic seizures.

Simple Focal Seizures

Simple focal seizures are the commonest and most frequent seizure type in MTLE-HS, and occur in more than 90% of patients.^{35,37,38,40–43,45,65,70,76,78,133,136,150,151} The first symptom is always an aura. They mainly start with an ascending epigastric aura and less often with fear. Mental hallucinations and illusions of déjà vu and their variations occur, but not as commonly as in other extra-hippocampal epilepsies. Olfactory and gustatory hallucinations occur less often.

Simple focal seizures may be the only seizure type, though they often progress to complex focal seizures.

Ascending epigastric or visceral aura is by far the more common aura (around 80% of cases), and the most characteristic of all other ictal symptoms of simple hippocampal seizures.

Ictal fear is in a distant second most common aura (around 20–30% of cases), but is not specific to hippocampal seizures alone.

Dreamy states, ⁴⁷ experiential phenomena, ²⁸ intellectual aura, mental or psychic symptoms. These events occur less often than epigastric aura and fear, and the patient may also have other subjective ictal symptoms, such as mental illusions and hallucinations of déjà vu, depersonalisation and their variations.

Unspecified somatic sensations or olfactory and gustatory hallucinations may occur. Elementary or complex visual and auditory hallucinations do not occur.³⁷

Urgency to urinate is exceptional and is associated with right-sided foci.⁶³

Language impairment during simple focal seizures has not been examined thoroughly. Most patients are able to understand conversations fully, but they are unable to speak or carry on conversations; they answer monosyllabically or with movements of the head or hands.

Patient note

I know well what they say, but I can not speak or I reply in the simplest possible way with ‘yes’ or ‘no’ until I am back to normal again in a minute or so.

Simple focal seizures may be the only seizure type, sometimes for years, and can vary in duration from “a few seconds to rarely 1–2 minutes”. They may be entirely inconspicuous to the observer, though close relatives or friends are able to say when it happens.

Patient note

“He has it now”, the relative points out. The patient and the EEG confirms it, but nothing significant can be detected on the video record of events.

Simple focal seizures frequently progress to complex focal seizures with mainly oro-alimentary automatisms.

Complex Focal Seizures

In MTLE-HS, complex focal seizures usually emerge as a progression of simple focal seizures with gradual or abrupt impairment of consciousness that typically associates with oro-alimentary automatisms in about 70% of cases.^{35,37–43,45,65,70,76,78,133,136,150–153}

The initial objective symptoms in this stage of impairment of consciousness are staring, motor restlessness or motor arrest, oro-alimentary automatisms and unforced head deviation. The patient has no recollection of this phase, but may still be responsive (70% of cases in one study).⁷⁶ Gestural automatisms, other forms of automatisms, vocalisations and dystonic posturing may occur soon after. Hypersalivation (left sided) is exceptional.

Complex focal seizures last for 2–3 min, occur on average once or twice a week and usually appear in clusters of two or three. They may also occur during sleep and, in some women, they are exclusively or predominantly catamenial.

Oro-alimentary automatisms consist of lip smacking, chewing, swallowing, licking and tooth-grinding movements. They are often followed by simple gestural automatisms. Oro-alimentary automatisms are characteristic of MTLE only if preceded by epigastric aura, fear and mental symptoms of the ‘dreamy state’ of Jackson, alone or in combination.

Gestural automatisms consist of fiddling, fumbling, picking, tapping, patting or plucking, rubbing or scratching the face and other gestural movements.

Autonomic manifestations of any type are among the most frequent ictal symptoms of MTLE-HS.^{75,84–88,134} These manifestations include: pupillary dilatation and less commonly miosis;^38,75 cardiovascular symptoms, mainly tachycardia and arrhythmias and less often bradycardia, asystole or hypertension;^{75,84,88–93} pallor and less commonly flushing;⁷⁵ and changes in respiratory rate and depth, mainly in the late seizure phase.⁷⁵

There are occasional reports of penile erection, or even ejaculation, and other sexual ictal manifestations.^74,75

Lateralising Signs of Ictal Symptoms

Dystonic posturing occurs in 20–30% of patients and is contralateral to the side of seizure onset.^38,136,154

Head deviation early in the seizure is usually ipsilateral to the seizure focus, but head deviation late in the seizure is contralateral and often a prelude to generalisation.³⁸

Ictal or postictal aphasia and prolonged recovery is mainly seen following seizures in the dominant temporal lobe,³⁸ while clear ictal speech and quick recovery mainly characterise seizures of the non-dominant temporal lobe.^38,65

It is generally considered that unilateral automatisms are ipsilateral to the seizure onset.³⁸

Although non-specific for right or left disease, impaired consciousness,⁷⁶ motion arrest,⁷⁶ escape automatisms⁷⁶ and fear^87,155 occur more often in patients with left rather than right mesial temporal sclerosis.

Hyperventilation during the seizure is rare and occurs in left mesial onset.⁷⁶

Vocalisations,⁷⁶ motor restlessness,⁷⁶ staring,⁷⁶ oral automatisms,³⁸ pupillary dilatation,³⁸ impaired consciousness³⁸ or generalised rigidity³⁸ do not predict side of origin.

Generalised Tonic Clonic Seizures

Secondarily GTCS are usually infrequent in patients receiving appropriate AEDs.¹³⁴ They are not uniform in their clinical presentation, but are more stereotyped in their final phases than the initial clinical signs of generalisation.¹⁵⁶ Some patients (probably around 10%) may never have GTCS.

Psychomotor Complex Focal Status Epilepticus

Psychomotor complex focal status epilepticus features particularly in untreated patients with temporal lobe epilepsy. It is less common than the absence status epilepticus of idiopathic generalised epilepsy, but its prevalence may be underestimated.^157–159 It may be confused with transient global amnesia.^160,161

Postictal Symptoms

Postictal symptoms of the mainly complex focal seizures in MTLE-HS are very frequent and often severe. They comprise mental and physical fatigue, drowsiness, headache, language aberrations, inability to concentrate and confusion of various degrees that may be severe and associated with automatic behaviour of which the patient may be amnesic.

Patient note

I am more concerned by what follows than the fit itself.

Definitions

Psychomotor (complex focal) status epilepticus is characterised by continuous or rapidly recurring psychomotor (complex focal) seizures that may involve temporal or extratemporal regions. Cyclic disturbance of consciousness is characteristic of psychomotor status epilepticus of temporal lobe origin. The differential diagnosis from complex focal status epilepticus of frontal lobe origin remains a challenge (Figure 12.11).¹⁶² In one-third of cases, a frontal lesion is revealed.¹⁶³

Figure 12.11

Video EEG of a 43-year-old man during complex focal status epilepticus of frontal lobe origin. He was confused, disorientated in time and place, with bizarre behaviour, laughing and making inappropriate jokes. Note: (more...)

Neurological, Mental State and Behaviour

Neurological examination is usually normal; facial asymmetry contralateral to the epileptogenic zone may be apparent in some patients. Specific baseline and follow-up memory testing are necessary. The only clearly defined behavioural disturbance in MTLE-HS is a material-specific memory deficit, but this may also be seen in MTLE due to other mesial temporal lesions.¹³⁴ Many other psychiatric and psychological problems, especially depression, have been reported to be more prevalent in MTLE-HS, but inadequate information exists to determine the extent to which these disturbances are a direct biological result of either the hippocampal sclerosis or the mesial temporal seizures, a non-specific biological result of brain injury, or a consequence of external psychological and social factors.¹³⁴

Febrile Convulsions and Other Initial Precipitating Events

One-third of patients with MTLE-HS have a previous history of prolonged febrile convulsions and many others have a history of cerebral insults in early life.^{40,134,142,144–149}

Mathern et al. (1995)¹⁴⁷ found that 90% of patients have a history of complicated febrile convulsions or other initial precipitating events. The type of initial precipitating events and the patient’s age at which it occurred are related to the clinicopathological features. Thus, patients with a prolonged febrile seizure before 5 years of age are likely to have unilateral hippocampal atrophy and a good neurosurgical response.^147,149

Differential Diagnosis

MTLE-HS needs to be differentiated from non-epileptic conditions and from seizures arising from other brain locations (Table 12.1).

Table 12.1

Mesial versus lateral temporal lobe epilepsy

• Non-epileptic conditions. The diagnosis of hippocampal seizures should be suspected from their very brief duration, the ascending character of the epigastric sensations, the occasional nocturnal appearance and often an associated feeling of depersonalisation. However, simple focal seizures of epigastric aura and ‘panic attacks’ are unlikely to raise suspicion of epilepsy in either the patient or the general physician (Figure 12.2). These patients are often investigated for gastroenterological and psychological disorders²¹⁵ or hypoglycaemia until more salient seizure features appear with the development of complex focal seizures and secondarily GTCS. Patients are often reassured by normal relevant tests or told that their symptoms are the result of anxiety. It is rare, at this stage, that a general physician would request an EEG, but again, if this normal (as is the case in two-thirds of patients), a diagnosis of stress-related events would be reinforced.

Clinical note

Pseudo-seizures may be difficult to differentiate. An increase in serum prolactin level postictally may be helpful in differentiating between epileptic seizures and ‘pseudo-seizures’.²¹⁶

• Mesial temporal epilepsy with aetiologies other than hippocampal sclerosis: The differential diagnosis of hippocampal from other MTLE is practically impossible without MRI, with the possible exception of olfactory-gustatory hallucinations, which may be more often associated with tumoural MTLE.¹³⁴
• Hippocampal versus other temporal lobe seizures: The epigastric aura and early oro-alimentary automatisms predominate in MTLE compared with other neocortical temporal lesions. Conversely, MTLE-HS is unlikely when seizures manifest with early focal motor, somatosensory, visual or auditory ictal symptoms, frequent secondarily GTCS or occur in patients with neurological or cognitive deficits other than memory impairment.
• Hippocampal versus mesial familial temporal lobe epilepsy (MFTLE): The main differentiating features in favour of mesial familial temporal lobe epilepsy are:
  • – onset in teenage or early adult life and familial occurrence
  • – no febrile convulsions or other initial precipitating events
  • – no ictal symptoms of rising epigastric aura
  • – mild and infrequent seizures that may remit
  • – usually normal MRI.
• Typical absence seizures are more likely to be misdiagnosed as complex focal seizures than vice versa.

Mesial Temporal Lobe Epilepsy Defined by Specific Aetiologies Other than Hippocampal Sclerosis

Clinical note

In MTLE with aetiologies other than hippocampal sclerosis,^{37,39,75,76,135,136} seizure symptomatology is the same irrespective of cause and location within the mesial temporal lobe structures. MRI commonly identifies structural causes.

Lateral Temporal Lobe Epilepsy

Lateral temporal lobe epilepsy ^1,76,113,136 is neocortical as opposed to MTLE, which is limbic.

Diagnostic Procedures

MRI often determines structural causes of LTLE (Figure 12.7).

Figure 12.7

Axial proton density-weighted MRI showing left temporal lobe cavernoma in a patient with LTLE. Figure courtesy of Professor John S Duncan and the National Society for Epilepsy MRI Unit.

Scalp interictal EEG shows unilateral or bilateral midtemporal or posterior temporal spikes (Figure 12.5).^1,76

Frontal Lobe Epilepsies

Frontal lobe epilepsies manifest with seizures originating from a primary epileptic focus anywhere within the frontal lobe. The clinical and EEG manifestations vary greatly and depend on the origin and spread of the epileptogenic focus.^230–240 The frontal lobe occupies 40% of the cerebral cortex and is the largest of the brain lobes. On the basis of cyto-architectural and functional studies, the frontal lobe can be subdivided into the primary motor cortex, premotor cortex, prefrontal cortex, and the limbic and paralimbic cortices,²³⁶ with distinct cortico-subcortical organisations and immense connections with the temporal and parietal cortices.^233,241 Complex and varied patterns in the spread of seizure discharges explain the variability in the clinical and EEG manifestations of frontal lobe seizures.^232,242 Also, exact localisation is often hindered because of the rapid propagation of seizures within the frontal lobe from and to extrafrontal areas. It is difficult to assign the origin of seizures with pre- and post-central symptomatology to the frontal or parietal lobe. Such overlap to adjacent anatomical regions also occurs in opercular epilepsy.¹

Seizures arising from the primary motor cortex and the supplementary motor area (SMA; Figures 12.8 and 12.9) have been relatively well defined, but seizures generated in other regions of the frontal lobe are less well specified.

Figure 12.8

MRI in two patients with symptomatic frontal lobe epilepsy. Left: Coronal FLAIR MRI showing focal cortical dysplasia in the supplementary motor area of the left frontal lobe. Note the tail extending down towards the frontal horn of (more...)

Figure 12.9

Hypermotor seizure of the sensorimotor supplementary area. Sample from one of 10 stereotypical hypermotor seizures recorded during an all-night video EEG. Note the abrupt and explosive character of the seizure, which lasted for only (more...)

Clinical Manifestations

According to their origin within the frontal lobe, various seizure patterns have been recognised though multiple frontal areas may be involved. Rapid and specific seizure types may not be discernible.¹ Motor manifestations are more common and the most characteristic ictal symptom occurring in 90% of seizures.

The following are the most common frontal lobe seizures.

Seizures from the Motor Cortex

Seizures from the motor cortex are mainly simple focal motor seizures. Symptoms depend on the side and topography of the area involved. Focal motor seizures (with or without march) originate from the contralateral precentral gyrus. In the lower pre-Rolandic area, there may be speech arrest, vocalisation or dysphasia, tonic-clonic movements of the face on the contralateral side, or swallowing. In the paracentral lobule, tonic movements of the foot may occur, which may be ipsilateral or contralateral. Seizures often progress to secondarily generalisation. Postictal Todd’s paralysis is frequent.

Simple Focal Motor Clonic or Tonic-Clonic Seizures with or without Jacksonian March

These seizures manifest with localised, rhythmic or arrhythmic, clonic movements that may affect the thumb only, the thumb and ipsilateral side of the lips, the hand, the whole arm or any other body part contralateral to the focus. Distal segments are more frequently affected than proximal segments. The hand (mainly the thumb) and face (mainly the lips) are preferentially affected because of their larger cortical representation (homunculus of Penfield). These ictal motor manifestations may remain highly localised for the whole of the seizure or march in an ordinary anatomical fashion to neighbouring motor regions, which constitute the classical Jacksonian (or Bravais-Jackson) seizure.

Patient note

Usually there are a few jerks of the right corner of my mouth and the right thumb. That is all. However, the jerks may become more intense and spread gradually to my eye and my fingers on the same side. Then my elbow and shoulder also start jerking violently and this may also go to my leg. The whole right side of my body is jerking and jerking, and there is nothing I can do before this stops suddenly or I lose consciousness and I have whole body convulsions.

Myoclonic seizures that may be unilateral or bilateral are predominantly facial or distal in the limbs. Epilepsia partialis continua of Kozhevnikov is one type of myoclonic seizure.

Tonic postural motor seizures associated with clonic movements are asymmetric, unilateral or bilateral.

ILAE Classification and Definitions

The seizures and some syndromes of frontal lobe epilepsy have been well described in the 1989 ILAE classification among the localisation-related (focal, local, partial) epilepsies and epileptic syndromes, and defined as follows: ¹

“Frontal lobe epilepsies are characterized by simple partial, complex partial, secondarily generalized seizures or combinations of these. Seizures often occur several times a day and frequently occur during sleep. Frontal lobe partial seizures are sometimes mistaken for psychogenic seizures. Status epilepticus is a frequent complication.

General characteristics

Features strongly suggestive of the diagnosis include:

1. Generally short seizures.

2. Complex partial seizures arising from the frontal lobe, often with minimal or no postictal confusion.

3. Rapid secondary generalization (more common in seizures of frontal than of temporal lobe epilepsy).

4. Prominent motor manifestations which are tonic or postural.

5. Complex gestural automatisms frequent at onset. 6. Frequent falling when the discharge is bilateral. A number of seizure types are described below; however, multiple frontal areas may be involved rapidly and specific seizure types may not be discernible.

Supplementary motor seizures. In supplementary motor seizures, the seizure patterns are postural, focal tonic, with vocalization, speech arrest, and fencing postures.

Cingulate. Cingulate seizure patterns are complex partial with complex motor gestural automatisms at onset. Autonomic signs are common, as are changes in mood and affect.

Anterior frontopolar region. Anterior frontopolar seizure patterns include forced thinking or initial loss of contact and adversive movements of head and eyes, with possible evolution including contraversive movements and axial clonic jerks and falls and autonomic signs.

Orbitofrontal. The orbitofrontal seizure pattern is one of complex partial seizures with initial motor and gestural automatisms, olfactory hallucinations and illusions, and autonomic signs.

Dorsolateral. Dorsolateral seizure patterns may be tonic or, less commonly, clonic with versive eye and head movements and speech arrest.

Opercular. Opercular seizure characteristics include mastication, salivation, swallowing, laryngeal symptoms, speech arrest, epigastric aura, fear, and autonomic phenomena. Simple partial seizures, particularly partial clonic facial seizures, are common and may be ipsilateral. If secondary sensory changes occur, numbness may be a symptom, particularly in the hands. Gustatory hallucinations are particularly common in this area.

Motor cortex. Motor cortex epilepsies are mainly characterized by simple partial seizures, and their localization depends on the side and topography of the area involved. In cases of the lower prerolandic area there may be speech arrest, vocalization or dysphasia, tonic-clonic movements of the face on the contralateral side, or swallowing. Generalization of the seizure frequently occurs. In the rolandic area, partial motor seizures without march or jacksonian seizures occur, particularly beginning in the contralateral upper extremities. In the case of seizures involving the paracentral lobule, tonic movements of the ipsilateral foot may occur as well as the expected contralateral leg movements. Postictal or Todd’s paralysis is frequent.”¹ “In frontal lobe epilepsies, the interictal scalp recordings may show (a) no abnormality; (b) sometimes background asymmetry, frontal spikes or sharp waves; or (c) sharp waves or slow waves (either unilateral or frequently bilateral or unilateral multiobar. Intracranial recordings can sometimes distinguish unilateral from bilateral involvement.

In frontal lobe seizures, various EEG patterns can accompany the initial clinical symptomatology. Uncommonly, the EEG abnormality precedes the seizure onset and then provides important localizing information, such as: (a) frontal or multilobar, often bilateral, low-amplitude fast activity, mixed spikes, rhythmic spikes, rhythmic spike waves, or rhythmic slow waves; or (b) bilateral high amplitude single sharp waves followed by diffuse flattening. Depending on the methodology, intracranial recordings may provide additional information regarding the chronologic and spatial evolution of the discharges; localization may be difficult.” ¹ Frontal lobe epilepsies other than epilepsia partialis continua and Kozhevnikov-Rasmussen syndrome have not been detailed in the new ILAE diagnostic scheme. ¹⁰

Seizures from the Supplementary Sensorimotor Area

Seizures from the SMA have distinct and characteristic clustering of symptoms, and are usually stereotyped (Figure 12.9).^244–249

Hypermotor seizures²⁵⁰ of bizarre bilateral, asymmetric tonic posturing and movements

The characteristic hypermotor seizure of SMA consists of sudden and explosive, bilateral and asymmetric tonic posturing of limb girdles at shoulder and pelvis often with contraversion of the eyes and head, vocalisation or speech arrest.

‘Fencing posturing’²⁵¹ is the best known descriptive term for these SMA seizures, though it may not be common.²⁴⁹ In fencing posturing, one arm is raised and semi-extended above the head, while the other remains by the body semi-flexed at the elbow. Bilateral asymmetrical posturing is the most common.

M²E posture is another term used to describe flexion of the elbow of one arm, abduction of the shoulder to 90⁰, with associated external rotation.¹⁹ The head looks at the postured hand, and the opposite arm shows slight flexion. The leg ipsilateral to the involved arm extends, while the opposite leg flexes at the hip and knee.

Clinical note

Posturing is extremely variable among patients with SMA seizures, but it is stereotypical for each individual patient.

This variability of hypermotor seizures is reflected well by other descriptive terms of SMA seizures, such as:

• – complex gestural automatisms,
• – extreme motor restlessness,
• – complex motor automatisms and agitation,
• – frenetic complex motor automatisms of both arms and legs,
• – intensely affective vocal and facial expression associated with powerful bimanual-bipedal and axial activity,
• – repetitive rhythmical and postural movements accompanied by bizarre vocalisation,
• – complex motor automatisms with kicking and thrashing, complex and global gesticulations.

Clinical note

Somatosensory or other ill-defined auras (not epigastric), vocalisations and speech arrest are common ictal manifestations of SMA seizures.

Somatosensory auras are described by more than half and probably about 80%²⁵³ of patients, mainly at onset. Unilateral somatosensory sensations usually accurately predict contralateral lateralisation.²⁵⁴ Cephalic sensations are probably more common.²⁵³ Auras are described as:

Patient note

pressure on the chest, difficult to breathe, floating away, paraesthesia of a hand, dizziness and light headedness, cephalalgia or electrical sensation in the head, discharge in the whole body, sensation of body heat, feeling of coldness or heat in the back and the head, vertebral column shivering, moving outside oneself, crawling sensation in both, one leg or somewhere in the body.^{250,253,255,256}

Important note

Epigastric auras do not occur.

Vocalisations

One-third of patients manifest with vocalisations that may vary from a brief deep breath or air expiration and palilalic vocalisations to the most bizarre, loud and scaring noises.

Definition of Hypermotor Seizures

Hypermotor seizures consist of “complex, organised movements which affect mainly the proximal portions of the limbs and lead to a marked increase in motor activity. Consciousness may be preserved. They are most frequently associated with frontal lobe epilepsy”.^250,252

Speech arrest is a well-documented and frequent ictal manifestation. Pure paroxysmal speech arrest without other motor activity is exceptional.

Consciousness is usually well preserved; as a rule, these are simple focal seizures.

Other characteristics of seizures from the SMA are:

• abrupt onset and abrupt termination
• nocturnal circadian distribution; rarely occur in awake states
• high frequency, sometimes many per night
• lack of postictal confusion.

Seizures from Other Frontal Lobe Regions

Seizures from other frontal lobe regions are less common and are, topographically: cingulate, anterior frontopolar, orbitofrontal, dorsolateral and opercular seizures.¹

Other Frontal Lobe Seizures of Particular Clinical Interest

The following frontal seizures are of particular clinical interest:

1. ‘Frontal absences’ are similar and often indistinguishable from generalised absence seizures in their clinical and EEG manifestations (Figure 12.10).^257,258
2. Seizures characterised by unusual symptoms of ‘forced thinking’ and ‘forced acts’. The patient is forced into an obsessive thought (forced thinking) associated with a fairly well-adapted attempt to act on this thought (forced acts),^49,49,51,51 with ‘eye-directed automatisms’ and ‘pseudo-compulsive behaviour’. These seizures emanate from the dorsolateral intermediate frontal lobe. French investigators vividly described the seizures as follows:^{232,238,259–261}

Figure 12.10

Typical absence seizures of late onset due to frontal lobe glioma. Left: Brain imaging showing a right-sided frontal glioma in a woman who started having absences at 28 years of age (1989). Middle right and left: Initially, the EEG (more...)

“Gaze and gestures of the upper limbs appear to be attracted by some object in the immediate environment, which orients a pseudo-intentional sequence of catching, touching, putting in order, or playing with the hands. Aggressive facial expression and complex vocalisation (menaces, insults, obscenities) precede a sequential gestural pattern such as standing up, then running around the table, spitting, tapping on the table, seemingly speaking to somebody; or jumping or pedalling movements with rhythmic joyful vocalisation. Their onset is often marked by alternating head deviations as if oriented towards an external stimulus… In other cases, they consist of much more complex and bizarre gesticulations, seemingly aimless, or apparently running away from some frightening situation, possibly as a reaction to ‘unconscious’ hallucinations. Often occurring during sleep, they are characterised by a facial expression of fear or terror, a powerful vocalisation (screaming), agitation of the upper limbs as if struggling or tearing out something, manipulation of the genitals accompanying pelvic movements, pedalling movements, or kicking.”^{232,238,259–261}

Tonic deviation of the eyes preceding head deviation (frontal eye field involvement) may occur independently or in association with these strange symptoms.^232,238,261

Patient note

The patient is compulsively ‘forced to fix on something with the eyes’, ‘the brain commands him to do something that he should not do’, ‘a sensation of being forced to open the eyes’. This is often associated with forced bizarre actions of hypermotor seizures.

A 30-year-old man, holder of a karate black belt, had a cluster of 30–50 such seizures while dozing in the waiting room of my clinic. Each seizure, which lasted for 10–15 s, was of sudden onset and termination. His facial expression was very aggressive and he would perform various karate acts, often kicking or punching objects in the office (without damaging them), with simultaneous and irregular roaring and other vocalisations. Immediately, after each attack, he would go back and sit in his chair, and fully aware of what was happening he would then apologise, “I can not resist doing this. It will be OK after a while”, before jumping off again to perform a similar enforced act. The staff and the other patients were terrified and maintained a safe distance from him, while I had to put on a brave face to approach him until he recovered.

c. Gelastic seizures of frontal lobe origin. ^101,262 There are around 15 well-documented cases of gelastic seizures originating from the frontal lobe. Onset is usually before the age of 6 years, but may start in adulthood in one-third of patients. Most lesions commonly involve the cingulate gyrus. Laughter is described as unnatural and mirthless. The duration of the seizure is brief, lasting from less than 30 s to less than 2 min. Other types of seizures may predate or follow the gelastic attacks.

See also hypothalamic (gelastic) epilepsy on page 193.

d. Negative motor seizures manifest with ictal loss of localised muscle power or inability to produce a voluntary movement.

Focal Status Epilepticus of Frontal Lobe Origin

Focal (non-convulsive) status epilepticus of frontal lobe origin is of undetermined prevalence.^162,163 It manifests with prolonged impairment of consciousness and inappropriate behaviours (Figure 12.11). Symptoms fluctuate in intensity and severity over time. Concurrent turning of the head and focal jerking may occur. It commonly ends with GTCS. Ictal EEG shows repetitive frontopolar, frontocentral and frontotemporal epileptiform discharges with unilateral emphasis. It is difficult to differentiate from frontal or idiopathic absence status epilepticus without EEG (Figure 12.11).

Thomas et al. (1999)¹⁶³ described two types of frontal lobe status epilepticus. The first and more common type manifests with mood disturbances with affective disinhibition or affective indifference, which are associated with subtle impairment of cognitive functions without overt confusion. The EEG shows a unilateral frontal ictal pattern and normal background activity. In the second type, impaired consciousness is associated with bilateral, asymmetric frontal EEG discharges on an abnormal background. The response to intravenous benzodiazepines is poor, while intravenous phenytoin successfully controls seizures in most patients.¹⁶³

Diagnostic Procedures

High resolution brain MRI is mandatory. This reveals abnormalities in around two-thirds of patients.

Functional neuroimaging and magnetoencephalograpy are important for localisation.²⁶⁴

Ictal and interictal surface EEG has a notoriously low yield. Normal EEG is often misinterpreted as evidence of non-epileptic attacks.

Serum prolactin concentration (> 700 μU/ml) may be raised after frontal lobe seizures, with or without secondarily GTCS. However, failure of prolactin levels to rise does not help in the clinical differentiation of frontal lobe complex focal seizures from psychogenic attacks.

MRI

High resolution MRI detects abnormalities in 67% of patients with frontal lobe epilepsy as opposed to 79% in temporal lobe epilepsy. The overall sensitivity and accuracy of MRI is around 50% in neurosurgical series, but will become higher with new MRI technologies (Figure 12.8). This figure is similar to qualitative linear (routine) analysis of FDG-PET. Quantitative normalised analysis of FDG-PET scans have 96% sensitivity and 74–78% accuracy, and also detects 81% of abnormalities in non-lesional cases.²⁶⁵

MRS may be useful in the presurgical evaluation of patients with frontal lobe epilepsy.²⁶⁶

Electroencephalography

Interictal and ictal surface EEG is often unhelpful in the diagnosis of frontal lobe epilepsies. They are often normal (50–60% of cases), particularly when seizures originate from the medial frontal regions. The EEG of patients with lateral seizures is far more revealing than that of mesial frontal seizures (Figure 12.11). Prolonged video EEG recording increases the EEG yield.²⁶⁷

Patient note

The video EEG of one of my patients with tens of clinical SMA seizures was entirely normal over two nights, except for a single, left frontal, giant sharp and slow wave that occurred only once.

Important note

The EEG, both interictal and ictal, is usually normal in seizures originating from the mesial frontal regions, a factor that contributes to misdiagnosis.^{1,239,263,268}

If abnormal, interictal EEGs may show background asymmetry, frontal spikes or sharp waves (either unilateral or frequently bilateral or unilateral multilobar).¹ Generalised discharges of 3-Hz spike–waves may occur with or without evidence of secondary bilateral synchrony.

Abnormal Ictal EEG Patterns Consist of

• frontal or multilobar, often bilateral, low amplitude, fast activity, mixed spikes, rhythmic spikes, rhythmic spike waves, or rhythmic slow waves (Figure 12.12). Ictal, fast, rhythmic paroxysms may be of very high frequency (> 50 Hz) and low amplitude requiring specialised recording systems with fast sampling rates and high sensitivity.²⁶⁹
• bilateral high amplitude single sharp waves followed by diffuse flattening. sUncommonly, this EEG abnormality precedes the seizure onset providing important localising information.^1,270

Figure 12.12

Top: Interictal EEG of a 14-year-old child with malformations of cortical development in the dorsolateral aspect of the right frontal lobe. The same EEG sample is presented in different montages. Note frequent clusters (more...)

Even when EEG is abnormal, its localisation value is often unreliable without focal ictal paroxysmal patterns at seizure onset. This is probably because of

• – early seizure spread within and outside the frontal lobe
• – widespread distribution of the epileptogenic brain tissue
• – secondary bilateral synchrony and secondary epileptogenesis.

Though seizures predominate in sleep, sleep organisation is normal.

Epilepsia Partialis Continua of Kozhevnikov

Epilepsia partialis continua of Kozhevnikov is rightly considered as a type of seizure/status epilepticus caused by various heterogeneous conditions in children and adults.^292–299

Aetiology

There are multiple and diverse causes of epilepsia partialis continua, such as focal or multifocal brain lesions, systemic diseases affecting the brain and metabolic or other derangements (Table 12.2). Kozhevnikov-Rasmussen syndrome and malformations of cortical development are the main causes in children. Cerebrovascular disease and brain space-occupying lesions are the main causes in adults. Non-ketotic hyperglycaemia is the most common reversible cause. Other metabolic, mitochondrial or hereditary disorders are well described. Dereux (1955),³⁰⁸ in a thesis comprising 102 cases, found that more than 50% were caused by an ‘encephalitic process’. Rasmussen et al. (1958) described three children with epilepsia partialis continua, progressive hemiparesis, cognitive impairment and pathological changes of chronic encephalitis.

Table 12.2

Causes of epilepsia partialis continua

Russian spring-summer tick-borne encephalitis is a rare cause that occurs in endemic areas. This condition is overemphasised based on the erroneous assumption³⁰⁹ that it caused the cases of epilepsia partialis continua described by Kozhevnikov (see review in ref ³¹⁰).

Diagnostic Procedures

The yield of investigative procedures is cause dependent. Around two-thirds of patients have abnormal brain MRI scans and EEG, which get worse in progressive disorders such as Kozhevnikov-Rasmussen syndrome. Ictal EEG may or may not show epileptiform abnormalities concomitant with the jerks (Figures 12.13 and 12.14). Typically, jerk-locked back-averaged cortical potentials appear in the contralateral primary motor area preceding the jerks by a few milliseconds, sensory evoked potentials are of high amplitude (Figure 12.15) and there is a rostro-caudal pattern of muscle recruitment with co-contraction of agonist and antagonist muscles. PET and SPECT scans often localise the abnormal region, but they are not specific. Screening for metabolic and mitochondrial disorders may be necessary and a few cases are of unknown origin.

Figure 12.13

Epilepsia partialis continua of 3 days’ duration, ending with hemiconvulsions. Sample from a video EEG of a girl aged 12 years. She has epilepsia partialis continua, which started at the age of 4 years and continues (more...)

Figure 12.14

Epilepsia partialis continua of 3 days’ duration in an elderly woman in a coma. The right vastus medialis and right biceps brachius muscles were involved. Note that the only concurrent EEG abnormality during the jerking (more...)

Figure 12.15

Neurophysiological investigations in a man aged 26 years with onset of epilepsia partialis continua at the age of 25. This consisted of continuous and arrhythmic twitching of various muscles of the left leg and particularly (more...)

Parietal Lobe Epilepsies

Parietal lobe epilepsies manifest with seizures originating from a primary epileptic focus anywhere within the parietal lobe.^1,312–324

The clinical seizure characteristics, EEG findings and results of neuroimaging studies have been established mainly in neurosurgical series of patients with a carefully documented seizure of parietal lobe origin.^{312–314,318,319,321–324} The report by Kim et al. (2004)³²⁴ is an excellent description of the modern approach to parietal lobe epilepsies.

Aetiology

The aetiology is diverse and includes symptomatic (Figure 12.16), probably symptomatic and idiopathic causes.

Figure 12.16

Top: Coronal and axial T1-weighted MRI demonstrating parietal subcortical heterotopia (arrows). Bottom left: Coronal T2-weighted MRI demonstrating bilateral perisylvian polymicrogyria.

Of 82 non-tumoural patients with parietal lobe epilepsy, 43% had a history of head trauma, 16% a history of birth trauma and the cause was unknown in 20%.³¹⁸ The remaining 21% had a history of encephalitis, febrile convulsions, gunshot wounds to the head, forme fruste of tuberous sclerosis, hamartoma, vascular malformations, tuberculoma, arachnoid or porencephalic cysts, microgyria and post-traumatic thrombosis of the middle cerebral artery.³¹⁸ Of the tumours, astrocytomas (62%) were more common than meningiomas (14%), hemangiomas (9%), oligodendrogliomas (9%) and ependymoblastomas (3%).³¹⁹ However, patients with more aggressive tumours, such as glioblastomas, are unlikely to feature in these series.

In reports with MRI, lesions were small, indolent or non-progressive and could have been found only on pathological examination.^313,314 Malformations of cortical development, mild or severe, are probably the most common cause.^324,326

Diagnostic Procedures

Neurological examination is usually normal in patients with non-tumoural parietal lobe epilepsy or the abnormalities are mild. Sensory deficits, such as impaired two-point discrimination or stereoagnosia (of which patients may be unaware), mild limb atrophy and inferior quadrantic visual field defects, should be sought. Patients should also be examined for disturbances of written language, aphasia, spatial orientation and right-left disorientation.^325,326 Patients with tumoural parietal lobe epilepsy have similar neurological deficits, but mild contralateral weakness is common (38%), while unilateral limb atrophy is exceptional.³¹⁹

Brain imaging, preferably with high resolution MRI, is mandatory for any patient with parietal lobe epilepsy and may be abnormal in around 60% of patients (Figure 12.16).³¹⁹ Other brain imaging modalities, such as FDG-PET and ictal SPECT, are useful in neurosurgical evaluations.³²⁴

Electroencephalography

Interictal EEG

Surface interictal EEG may be normal, non-specific, or even misleading.^313,324 In symptomatic patients, localised slow waves may be the only interictal abnormality (Figure 12.17).^318,319 Epileptiform abnormalities, if they occur, may appear in areas other than the parietal regions, involving frontal, temporal or occipital electrodes.^{313–315,318,319,324} Of patients with intractable parietal lobe epilepsy, 16% do not have epileptiform discharges.³¹⁸ In these patients, secondary bilateral synchrony may be common (32%).³¹⁸ Interictal spikes, if present, should be interpreted cautiously regarding localisation.³⁴⁶

Figure 12.17

Interictal EEG of a 5-year-old girl with extensive right-sided porencephaly due to brain anoxia at birth. Severe right sided abnormalities of spikes, sharp and slow waves are mainly focused around the parietal regions. (more...)

In one report,³¹³ scalp EEGs correctly localised the side and region of seizure onset in only 1 of 11 patients in whom lesions had been detected with MRI. Three additional patients with congruent parietal localisation on scalp EEG had additional misleading EEG findings.

Ictal EEG

The ictal EEG may be normal in 80% of simple focal sensory seizures.³²⁶ The prevalence of scalp EEG changes in simple focal seizures with predominant sensory symptoms is only 15%, as opposed to 33% when motor symptoms are present.³⁵⁰

Localised parietal seizure onset is rare (11%).^313,318 Ictal onset may be distant from the area of the predominant interictal spiking,³²⁹ and ictal EEG patterns are occasionally difficult to interpret,³⁴⁶ particularly when seizures rapidly become generalised.

Postictal EEG

Postictal EEG may have some localising value when focal slow wave attenuation of background activity or spike activation occur.³⁵¹

Occipital Lobe Epilepsies^*

Clinical note

Occipital seizures originate from an epileptic occipital focus that is triggered spontaneously or by external visual stimuli.^{315,317,328,353–358} These epilepsies may be idiopathic, symptomatic or probably symptomatic.

Clinical Manifestations

Ictal clinical symptoms of occipital lobe epilepsies are subjective, objective or both. The cardinal symptoms are mainly visual and oculomotor. Visual subjective symptoms include:

• elementary and less often complex visual hallucinations
• blindness
• visual illusions
• pallinopsia
• sensory hallucinations of ocular movements.

Ocular subjective symptoms comprise:

• ocular pain.

Ictal objective oculomotor symptoms are:

• tonic deviation of the eyes (pursuit-like rather than oculotonic)
• oculoclonic movements or nystagmus
• repetitive eyelid closures or eyelid fluttering.

Some of these ictal manifestations, such as elementary visual hallucinations, are generated in the primary visual cortex; others, such as visual illusions, emanate from the neighbourhood of the occipital-parietal and occipito-temporal regions. Seizures may spread from the occipital to other more anterior regions of the brain generating symptoms from the temporal, parietal and frontal lobes and secondarily hemi- or generalised convulsions. Ictal or postictal headache is frequently associated with occipital seizures.

Elementary Visual Hallucinations

Elementary visual hallucinations are the most common, characteristic and well-defined ictal symptoms of occipital lobe seizures (Figure 12.18). They are usually the first, and often the only, ictal symptom during a seizure and may progress to other occipital and extra-occipital manifestations and convulsions.

Figure 12.18

Visual seizures as perceived and drawn by a patient with an interesting form of symptomatic occipital epilepsy (case detailed in ref ). From Panayiotopoulos (1999) with the permission of the Editor of Epileptic Disorders. (more...)

Important note

Elementary visual hallucinations of visual seizures are mainly coloured and circular, develop rapidly within seconds and are brief in duration (Figure 12.18). They often appear in the periphery of a temporal visual hemifield, becoming larger and multiplying in the course of the seizure, and frequently moving horizontally towards the other side. They are fundamentally different to the visual aura of migraine for which they are often mistaken.^357,363,364

Panayiotopoulos has studied the elementary visual hallucinations of idiopathic and symptomatic occipital seizures in a qualitative and quantitative chronological manner,^357,364 differentiated them from the visual aura of migraine^365,366 and reviewed them exhaustively from ancient times.³⁵⁹ The main conclusions of these studies are briefly described here.

Ictal elementary visual hallucinations (Figure 12.18) are defined by colour, shape, size, location, movement, speed of appearance and duration, frequency and associated symptoms of progression.

Colour, Shape and Size

The predominant patterns are coloured, usually multicoloured, and circular. Bright red, yellow, blue and green prevail. Shapes are mainly circular, spots, circles and balls. Individual elements are multiple and rarely single. Their size varies from ‘spots’ to rarely the size of a ‘small ball’. Coloured, square, triangular and rectangular or star-like shapes, alone or in combination with circular patterns are less frequent. Flashing or flickering achromatic lights, shades or non-circular patterns are rare. The components of visual hallucinations increase in number, size or both with progression of the seizure, particularly prior to other non-visual symptoms.

Patient note

Multicoloured blue, yellow and red, circular flickering patterns closely packed together and multiplying in the left lateral hemifield. Then it seems that the environment moves slowly and stepwise from left to right.

A ‘rainbow’ of all colours with dust blocks of shadow-like bricks in the periphery of the right eye.

Location

Their location at onset is usually unilateral, mainly in the temporal visual hemifield (Figure 12.18). They may appear in a normal, blind or damaged hemifield.³⁶⁷ Central or undefined localisation occurs in 10–30% of patients.

Movement

The components of elementary visual hallucinations usually multiply and become larger without any particular movement other than changing positions and luminance within their visual territory (Figure 12.18). Flickering or flashing is common. Movement towards the centre of vision or the other side is less common. Rarely, the movement is spinning, circling, rotatory, random, approaching or moving away from the patient.^51,367,368

Patient note

“Visual movement was more frequently present than absent. The image might remain still, but more often it moved slowly in a certain direction or it danced, flickered, or whirled.”³⁶⁹

“There are 3–4 concentric spherical rings of red and yellow moving from the left to the right of my vision, and repeating the same course again and again after their disappearance on the right”. ³²⁸

Lateralisation

The side of unilateral elementary visual hallucinations is contralateral to the epileptogenic focus (Figure 12.18). Conversely, this is ipsilateral to the epileptogenic focus for unilateral visual hallucinations moving horizontally towards the other side.^368,370

Vision

Ictally, vision may be obscured only in the area occupied by the visual hallucinations. However, some patients may be even able to read through them. Blurring of vision at onset, with or without visual hallucinations, may be a common mild form of visual seizure if investigated.

Patient note

The additional notable symptom that I suffer is clusters of momentary left visual field disturbances “like a momentary flickering or blurring of vision (always in the left temporal field only)”. Several of these moments can occur within, for example, a 10 min period and then several again over a similar period 1 or more hours later.

My sight deteriorates very slightly before the visual aura, but flashing does not start. It is a reduction of visual awareness of around 10%.

Duration

Visual seizures develop rapidly within seconds and they are usually brief, lasting from a few seconds to 1–3 min, rarely longer.^357,364,365 Exceptionally, they last for 20–150 minutes, sometimes constituting focal visual status epilepticus without other ictal symptoms.^{16,359,371,372}

As a rule, elementary visual hallucinations are longer prior to secondarily generalisation.

Frequency and Circadian Distribution

Visual seizures occur, often in multiple clusters, daily or weekly. Commonly, several may occur per day. They are usually diurnal, but some patients often wake up with elementary visual hallucinations.

Patient note

I would wake up from sleep either with elementary visual hallucinations or with white blindness (all white), before a generalised convulsion.

Stereotypic Appearance

Ictal symptoms of elementary visual hallucinations are stereotyped, particularly at onset, in all aspects other than duration. Exceptionally, the same patient may experience different types of seizures.

Progression to Other Occipital or Non-Occipital Seizure Manifestations

Elementary visual hallucinations may be the only seizure manifestation, but they often progress to other ictal symptoms, such as complex visual hallucinations, oculoclonic seizures, tonic deviation of the eyes, eyelid fluttering or repetitive eye closures, impairment of consciousness, experiential phenomena, hemi-anaesthesia, and unilateral or generalised convulsions. On other occasions, they progress to extra-occipital seizure manifestations by spread to the temporal, frontal or parietal regions.

Patient note

Bright, multicoloured, blue, red, yellow and green spots of light in the periphery of the right eye multiply rapidly and occupy the whole right visual field, though I can see through them. They cause me a pleasant feeling ‘because of the colours’. These are sometimes followed by distortion of the surrounding objects and persons as if ‘through the mirrors of a theme park’.

A spinning ball filled with mainly red and yellow colours on the right. This could be followed by visions of distorted bodies.

Complex Visual Hallucinations, Visual Illusions and Other Symptoms from More Anterior Ictal Spreading

Complex visual hallucinations, visual illusions and other symptoms from more anterior ictal spreading mainly occur in progression of the seizure that may terminate with hemiconvulsions or generalised convulsions. They may be the first ictal symptom, but more often follow elementary visual hallucinations.

Complex visual hallucinations may take the form of persons, animals, objects, figures or scenes. They may be familiar or unfamiliar, friendly or frightening, and simple or grotesque. They may appear in a small or large area of a hemifield, or in the centre and the whole of the visual field. They may be static, move horizontally, expand or shrink, approach or move away. In patients with visual field defects due to structural brain lesions, complex visual hallucinations appear in the defective visual field. Complex visual hallucinations of occipital seizures do not have the emotional and complicated character of temporal lobe seizures.^357,364,381

Patient note

Sudden awareness of rapidly oscillating, vague, dark, disproportionate, face-like, frightening figures moving forwards and backwards in the temporal field of my left eye.

An interesting, but extremely rare ictal complex visual hallucination is autoscopia (or heautoscopy), which means viewing his own image/viewing himself.^382,383 This mirror self image looks ‘real’ and is usually undistorted, silent, brief or recurrent, from the present time or from the past, framed or performing complex tasks.

Complex visual hallucinations including ictal autoscopia probably originate from occipito-parietal and occipito-temporal junction areas.

Visual illusions are misinterpretations, false percepts, of real external images. These distorted images (metamorphopsia) involve changes in size, dimension, shape, proportions, position, colour, illumination and movement, alone or in combination. Changes in perception of object size are common, the percepts being smaller (micropsia) or larger (macropsia) than the real image. Objects may be distorted in shape, pulled, compressed or rotated in lateral or vertical directions. They may appear in black and white (achromatopsia), in one colour (monochromopsia), hazy and dark or highly illuminated and bright. Motion and speed may be affected with or without distortion of direction (horizontal, vertical or rotated, approaching or moving away). Movement is faster or slower. Moving objects may appear stationary and vice versa.

Visual illusions also entail changes in spatial interpretation affecting stereoscopic vision.

Patient note

“Far objects appear near, near ones far, and convex ones concave, or vice versa.”³⁸⁴

Ictal visual illusions may occupy part or the whole visual field, and are probably more likely to be associated with symptomatic than with idiopathic occipital seizures.

Palinopsia

Palinopsia, that is persistence or recurrence of visual images after the exciting stimulus has been removed, is an interesting form of visual illusion associated with right posterior parieto-temporal lesions.

Patient note

He looked at a small video display unit and, after he looked away, the image of the screen persisted in the right upper corner of his vision and nearly simultaneously, started flashing at a rate of 3–5 Hz for 2 s. This was followed by visual illusions of the walls and the passengers closing in on him, ending within 5 s with GTCS.

Sensory Hallucinations of Ocular Movements

Sensory hallucinations of ocular movements, that is a sensation of ocular movement in the absence of detectable motion, is rare.

Patient note

“This involuntary movement of the eyes to the left and at a slight tilt upwards causes the pain described above. The motion to the left seems out of your control. It can be resisted but this adds to nausea and general pain.” Neither he nor the witnesses could confirm any such movement of the eyes.

Ictal Blindness (Ictal Amaurosis)

Ictal blindness (ictal amaurosis) may follow the visual hallucinations and progress to other epileptic symptoms, but often occurs as a starting or the only ictal seizure manifestation with abrupt onset.^{357,359,364,366,385}

Patient note

I usually have millions of small, very bright, mainly blue and green coloured, circular spots of light, which appear on the left side and sometimes move to the right, but on one occasion suddenly everything went black, I could not see and I had to ask other swimmers to show me the direction to the beach.^328,386

The duration of ictal blindness is usually longer (3–5 minutes) than ictal visual hallucinations; occasionally, blindness may last for hours or days (status epilepticus amauroticus).^387–389 Ictal blindness and less frequently ictal hemianopia occur in one-third of patients with symptomatic and two-thirds of patients with idiopathic occipital epilepsy.

Terminology

Autoscopia (or heautoscopy) means viewing his/her own image, viewing himself.^374,375

Fortification spectra in migraine are visual hallucinations with similarities to the bastioned, star-patterned, pentagonal fortifications and not of the castellated appearances of battlements.^376,377 A bastion is a projecting part of a fortification, consisting of an earthwork in the form of an irregular pentagon, having its base in the main line or at an angle of the fortification. Spectrum is used by Gowers³⁷⁸ “to mean apparition and not a coloured band of light.”

Pallinopsia (visual persevereness) is the persistence or recurrence of visual images after the exciting stimulus has been removed. Percept is the mental image or product of perception of any object in space.

Phosphenes are subjective sensations of light due to non-luminous stimulation of the retina. Phosphenes are also used to denote visual percepts from stimulation of the visual cortex with an electrical stimulus, in which case they are usually coloured spots or circles.³⁷⁹

Photopsias (phos = light, opsis = appearance) are unformed flashes of light and sparks.

Scintillating (scintilla = spark) scotoma (skotos = darkness) is also used because of the sparking appearance of the visual hallucinations of migraine (brilliant flashes of light in the periphery of dark areas in the visual fields).

Teichopsia (teichos = town wall, opsis = appearance) was coined by Airy³⁸⁰ “to represent the bastioned form of transient hemiopsia which I have been describing, not without a reminiscence of some words of Tennyson’s:

as yonder walls

Rose slowly to a music slowly breathed,

A cloud that gathered shape.”

Visual hallucinations are subjectively experienced images in the absence of an actual external stimulus:

Elementary visual hallucinations consist of simple, usually geometric forms, spots or lines.

Complex visual hallucinations consist of objects, faces or scenes.

Visual illusions are misinterpreted false percepts of real images.

An interesting rare variation of ictal blindness is ‘white ictal blindness’.^357,359 The patient can not see because everything is white.

Patient note

I can not see, like a white sheet in front of my eyes.

It is all white.

Blurring of vision as an initial seizure manifestation prior to visual hallucinations may be common if investigated.^357,364,381

Patient note

It starts with a momentary flickering or blurring of vision (always in the left temporal field only) (case 7.2 in ref ³²⁸).

My sight deteriorates very slightly as it does before the aura, but flashing does not start. It is a reduction of visual awareness of around 10% (case 30 in ref ³²⁸).

Tonic Deviation of the Eyes, Oculoclonic Seizures and Epileptic Nystagmus

Tonic deviation of the eyes often, but not necessarily, followed by ipsilateral turning of the head is the most common (40–50% of cases) non-visual symptom of occipital seizures. This is similar to a voluntary, pursuit-like turning of the eyes to one side. This usually follows visual symptoms and mainly elementary visual hallucinations, but it may also occur from seizure onset. Consciousness is often, but not invariably, impaired when eye deviation occurs.

The epileptogenic focus is more likely to be contralateral to the movement of the head and the eyes if consciousness is not impaired.

Ictal nystagmus (epileptic nystagmus) is mainly horizontal and rarely vertical. The quick phase of the nystagmus is opposite to the epileptic focus, in the same direction of eye and head deviation, which may coexist, precede or follow.

Repetitive Eyelid Closures, Eyelid Fluttering and Eyelid Blinking

Repetitive eyelid closures, eyelid fluttering and eyelid blinking is an interesting ictal clinical symptom of symptomatic and idiopathic occipital epilepsy. It usually occurs after the phase of visual hallucinations, at a stage when consciousness is impaired and heralds the impending secondarily generalised convulsions. However, it may also occur alone, be inconspicuous in appearance and not be suspected as a seizure event, documented only by video EEG recordings in occipital photosensitive patients.

Eyelid opening, or ‘eyes widely opened’, is another well-described symptom in occipital epilepsy, but may also be a symptom associated with other cerebral locations. Widened palpebral fissures with fixed staring and dilated pupils are among the typical symptoms of mesial temporal lobe seizures.³⁹⁰

Consciousness

Consciousness is not impaired during the elementary and complex visual hallucinations, blindness and other subjective occipital seizure symptoms, but may be disturbed or lost in the course of the seizure, usually at the time of eye deviation or eye closure, and generally prior to convulsions.

Ictal or Postictal Headache

Ictal or postictal headache is frequently associated with occipital seizures. ^{357,359,364,366} Ictal pain is mainly orbital. It is described as a sharp, stabbing, retro-orbital pain, a sensation of bifrontal pressure, a vague ache in the head or a sensation of electricity.

Patient note

The visual hallucinations consist of vivid, flashing multicoloured lights and circular patterns that occupy and obscure my vision. Severe unilateral throbbing headache follows 1–2 min later, lasts for hours and it is often associated with vomiting (case 7.1 in ref ³²⁸).

Important note

Postictal headache, often indistinguishable from migraine, is far more common in occipital (occurring in more than 50% of cases) than in any other focal epilepsy,^391,392 and may occur even after brief visual seizures.^357,364 Also, postictal headache often occurs 3–15 min from the end of the visual seizure, a situation known in migraine as the ‘asymptomatic interval’ between the end of migraine aura and the onset of headache.³⁹³

Postictal hemianopia may occur.

Patient note

When the visual hallucinations ceased completely, I had almost no vision in the left eye, only blackness (case 7.2 in ref ³²⁸).

Seizure Spreading

Seizures may spread from the occipital to other more anterior regions of the brain, generating symptoms from the temporal, parietal and frontal lobes and secondarily hemi- or generalised convulsions. Infra-calcarine occipital foci will propagate to the temporal lobe causing complex focal seizures, while supra-calcarine foci tend to propagate to the parietal and frontal areas giving rise to predominantly motor seizures.

Important note

Progression to temporal lobe seizure symptomatology is rather exceptional in idiopathic cases.

Diagnostic Procedures

The discovery of the underlying cause in symptomatic occipital epilepsies may require haematology and biochemistry screening for metabolic disorders, molecular DNA analysis, or even skin or other tissue biopsy.³²⁸ High resolution MRI is necessary in all patients with occipital lobe epilepsy (Figure 12.19).³²⁸ Unsuspected residual or progressive lesions, tumours, vascular malformations and malformations of cortical development are all detected by MRI. CT scanning is far inferior to MRI and insensitive to focal cortical dysplasia. Conversely, the calcifications of CD may be missed with MRI, but this is rare. Functional brain imaging for localisation is of practical value in neurosurgical cases.⁴¹⁰

Figure 12.19

Patient with visual seizures and focal status epilepticus of occipital lobe epilepsy. Three dimensional reconstruction of the brain demonstrating abnormal gyral patterns on the right. A. Surface rendering of cortex viewed (more...)

Electroencephalography

EEG is essential, but certain limitations should be recognised.

Interictal EEG

In symptomatic cases, the background EEG is usually abnormal with posterior lateralised slow waves. Unilateral occipital spikes or fast multiple spikes and, occasionally, occipital paroxysms occur. There may be occipital photosensitivity.³²⁸ Worsening of the background EEG is significant in the diagnosis of progressive causes.

In idiopathic cases, such as Gastaut-type idiopathic childhood occipital epilepsy and photosensitive occipital epilepsy, the background interictal EEG is normal.³²⁸ Occipital spikes and occipital paroxysms, spontaneous, evoked or both, are often abundant. They disappear with age frequently long after cessation of the occipital seizures.

Ictal EEG

Surface ictal EEG in occipital seizures, irrespective of cause, usually manifests with paroxysmal fast activity, fast spiking or both, localised in the occipital regions with occasional gradual anterior spreading and generalisation with irregular spike wave discharges or monomorphic spike and wave activity. Brief occipital flattening may be seen before the fast rhythmic pattern. Often, in patients with symptomatic occipital lobe epilepsy, the ictal discharge is more widespread (regional) rather than of a precise occipital localisation. Usually, there is no postictal localised slow activity unless the seizure is prolonged or progresses to secondarily GTCS.

Important note

In one-third of patients (30%), the ictal surface EEG does not show any appreciable changes in occipital seizures.³²⁸

Differential Diagnosis

Occipital seizures should not be difficult to diagnose, but should be first differentiated from migraine, normal phenomena and psychogenic or other causes unrelated to seizures.³²⁸

Differentiating Visual Seizures from Migraine

Visual Aura of Migraine

Patient note

“I was startled by a single, shadowy appearance at the outside corner of the field of vision of the left eye. It gradually advanced into the field of view and then appeared to be a pattern of straight-lined angular forms, very much in general aspects like the drawing of a fortification, with salient and re-entering angles, bastions and ravelins with some suspicion of faint lines of colour between the dark lines.” Sir JFW Herschel (1866)³⁷⁶

Visual Seizure

Patient note

“They commenced with the appearance of several small spheres, white in the centre with an intermediate zone of blue and outside this a ring of red, immediately to the left of the point at which the patient gazed; from here they moved either at a uniform rate or in jerks to the left and downwards…In all attacks the eyes deviated towards the left and the head turned in the same direction as soon as the visual spectra appeared.” G Holmes (1927)¹⁶

Misdiagnosis of visual seizures as migraine appears to be high though their differentiation should not be difficult.^328,357,364 Occipital seizures manifesting with elementary visual hallucinations, blindness and headache, alone or in combination, may imitate migraine, which is the reason that they are often mistaken as migraine with aura, acephalgic or basilar migraine (Table 12.3).^328,357,364 Even lesional occipital epilepsy is often misdiagnosed as migraine and, on many occasions, visual seizures are considered as visual aura of migraine, thus limiting their prognostic significance regarding continuation of treatment.³⁵⁷ The following are quotes from medical referrals of patients with visual seizures:

Table 12.3

Differential diagnosis of occipital seizures from basilar migraine or migraine with aura.

Patient note

“This patient has visual migraine-like disturbances, such as teichopsias.”

“Scintillating scotoma or sparkling scotoma of migraine.”

“Migrainous aura before the fit.”

There are two main reasons that visual seizures are misdiagnosed as migraine.^{357,359,364,366} Firstly, visual seizures are not examined in a comprehensive manner; instead they are abbreviated to terms such as ‘scintillating scotoma’ or ‘teichopsia’, which often do not represent the actual description of the patients. Secondly, their differential diagnostic criteria have only recently been adequately studied and addressed by Panayiotopoulos.^357,363,364 The diagnosis of visual seizures may comfortably rely on clinical criteria only; other investigative procedures are essential, but even ictal EEG may not identify one-third or more of cases.

Important note

Factors contributing to error in the diagnosis of visual seizures
The major contributory factor to error is that the description of visual hallucinations is often abbreviated in terms such as fortification spectrum, teichopsia, scintillating scotoma, phosphenes and their variations.³⁶³ Their meaning does not always represent the actual descriptions, which should be meticulously requested. Erroneously, they are frequently unquestionably equated with migraine.

The quality and the chronological sequence of ictal elementary visual hallucinations are markedly different from the visual aura of migraine. Visual seizures and the visual aura of migraine may imitate each other, but their true identity can not easily escape clinical scrutiny.

Though brief duration is significant, there are many more clinical manifestations to differentiate visual seizures from the visual aura of migraine (Table 12.3).

Clinical note

Diagnostic clues
As a rule, brief (< 1 min), elementary visual hallucinations that develop rapidly within seconds, with coloured and circular patterns and daily frequency are probably pathognomonic of visual seizures, despite severe headache and vomiting that may follow. EEG may be normal, show non-specific abnormalities or reveal slow focal or occipital spikes. A high resolution MRI is mandatory as it may detect a structural lesion requiring early attention and management.

The visual aura of migraine with aura and acephalgic migraine are adequately studied and illustrated in all relevant textbooks and publications. In one of the most detailed, a nosographic analysis⁴¹¹ describes migraine visual aura as:

Patient note

“started as a flickering, uncoloured, zigzag line in the centre of the visual field and affected the central vision. It gradually progressed over > 4 min, usually lasting < 30 min, towards the periphery of one hemifield and often left a scotoma. The total duration of visual auras was 60 min. Only four patients had exclusively acute onset visual aura.” ⁴¹¹

Furthermore, migraine visual aura:

• rarely has daily frequency
• non-visual ictal occipital symptoms, such as eye and head deviation, and repetitive eyelid repetitive do not occur
• it is debatable and probably exceptional to progress to non-visual epileptic seizures.

Less typical features of migraine visual aura, such as spots, circles and beads, with or without colours, may be experienced during the migraine visual aura, but usually they are not dominant. More importantly, clustering of other symptoms, as above, betrays their migraine nature.

Clarifications on Migraine and Epilepsy

Migraine and epilepsy are the commonest neurological disorders. The prevalence of migraine is probably around 6% in men and three times more common in women. The prevalence of epilepsy is around 0.5%, and men and women are equally affected. If there was a relation between them, this would be obvious in our everyday neurological practice. It would not be revealed only through obscure and complicated cases with bizarre symptomatology. It would be simple and common. It is not. The problem is that occipital seizures are not appropriately differentiated from migraine and, therefore, they are often erroneously diagnosed as migraine.

Seizures may be triggered from a migrainous event or caused by a migraine-stroke, but this is rare. There should be no doubt that a cerebral infarct due to severe migraine can be responsible for symptomatic seizures. Also, there should be no reason that epileptic seizures, so vulnerable to extrinsic and intrinsic precipitating factors, could not also be susceptible to cortical changes introduced by migraine. Thus a migrainous attack may also be able to trigger epileptic seizures in susceptible individuals. However, both these cases are rare. In my opinion, the commonest reason for their association is the coincidence of two of the more common neurological disorders, and an erroneous interpretation of epileptic seizures as migraine, and less often vice versa. The emerging and more realistic concept of occipital seizures triggering migrainous headache needs consideration and exploration. More importantly, patients with daily visual seizures that may progress to convulsions merit a precise diagnosis and appropriate treatment, probably with carbamazepine. Most of these patients with visual seizures are misdiagnosed as migraine with aura, basilar migraine, acephalgic migraine or migralepsy, simply because physicians are not properly informed about the differential diagnostic criteria. As a result, diagnosis, appropriate investigations and treatment may be delayed for years. There are numerous published reports of such misdiagnosis.

Based on the results of my studies, my thesis is that the visual aura of migraine is entirely different from that of visual seizures when all their components are synthesised together (Table 12.3).

Basilar migraine of Bickerstaff ^412,413 is characterised by transient and fully reversible symptoms of aura, indicating focal dysfunction of the brainstem, the occipital lobes or both, followed by headache.³⁶¹ Common neurological symptoms of aura include visual manifestations, dizziness, vertigo and tinnitus, ataxia, bilateral weakness and dysaesthesia, diplopia, dysarthria and decreased hearing. Visual symptoms mainly consist of dimming of vision, blindness, tunnel vision, hemianopia and scotomata. Elementary visual hallucinations are usually bilateral, described as ‘teichopsia’, ‘flashes or blobs of light’, ‘coloured figures’ or ‘dysmorphopsia’. Aura symptoms develop gradually over 4 min and last for less than 30 min to 1 hour. Impairment or loss of consciousness without convulsions may occur in one-quarter of patients between the aura and the headache phase.

Patient note

“The loss of consciousness is described as curiously slow in onset – never abrupt, and never causing the patient to fall or to be injured. A dreamlike state sometimes precedes impairment of consciousness. The degree of impairment of consciousness was never profound but the patients were never unrousable; on vigorous stimulation they could be aroused to cooperate but they returned to unconsciousness when the stimulation ceased.”⁴¹³

Attacks of basilar migraine are usually infrequent and, over the years, they may cease or be replaced by common migraine with or without aura.³⁶¹

Migralepsy versus Epilepsy-Migraine

Migralepsy, migra(ine) and (epi)lepsy, is a term used to denote “a seizure that may be a composite of symptoms encountered in epilepsy and migraine”.^18,414 The term intercalated seizures is used to denote epileptic seizures occurring between the migrainous aura and the headache phase of migraine.⁴¹⁵ There should be no reason that epileptic seizures, which are so vulnerable to precipitating factors, could not be susceptible to cortical changes induced by migraine. However, this is exceptional considering that migraine and epilepsy are the most common brain diseases. According to a recent review, most of the reported cases are likely to be genuine occipital seizures imitating migraine aura.^357,364 Of the most influential cases that I have detailed,^357,364 two of three ‘migralepsy’ patients,¹⁸ one case of ‘basilar migraine and epilepsy’ ⁴¹⁶ and one boy with ‘juvenile migraine with epilepsy’, ⁴¹⁷ all had symptoms of visual seizures as defined in this book, which were interpreted as migraine aura. The patient of Barlow⁴¹⁷ with symptomatic occipital epilepsy may be indicative.

Patient note

This boy at age 13 years, “While ski-ing he saw blue to the right associated with blurred vision that lasted for a few seconds”, after which he vomited, became confused for 30 minutes, followed by severe throbbing headache. Subsequently he had occasional “episodes of similar visual disturbance” diagnosed as juvenile migraine and successfully treated with phenytoin. An arteriovenous malformation was found in the left occipital lobe. “Visual scotomata accompanied by flashing lights that only occasionally were followed by headache” continued postoperatively.

None of 1550 patients I have studied had any evidence of seizures developing from migraine aura, though this was often the initial erroneous diagnosis on referral.³⁵⁷ Conversely, postictal headache and other migraine-like symptoms frequently occurred after occipital seizures. However, an incontrovertible diagnosis may be difficult in some equivocal cases.

Patient note

A 38-year-old man who, while working with the computer, saw flashing lights in between his eyes. They were moving for a few centimetres upwards and to the right repetitively. Gradually the intensity of the light and the area increased over the next 30 min obscuring his vision. This ended with a GTCS as he was entering the examination room of his general practitioner, which he had walked to for help. He had never had similar symptoms, seizures or migraine in the past. MRI was normal. EEG showed minor non-specific abnormalities.

Important note

The concept of migralepsy and its synonymous intercalated seizures or of a migraine-epilepsy sequence needs re-evaluation based on accurate diagnosis. In most instances, it is seizures imitating migraine or an epilepsy-migraine sequence.

Patient note

Misconceptions

There is a misconception that there is a syndrome of ‘basilar migraine with EEG occipital paroxysms’, which is perpetuated in every relevant publication and textbook to date. Retrospective analysis of cases described as “basilar migraine with occipital paroxysms” ^386,418,419 showed that these patients genuinely suffer from idiopathic occipital epilepsy.^328,420

Differentiating Ictal Deviation of the Eyes of Occipital versus Extra-Occipital Origin

I am not aware of any study that has compared ictal deviation of the eyes, head or both of occipital origin with that of extra-occipital origin. The following conclusions are derived from my personal experience, supplemented by relevant reports in the literature.

In occipital epilepsy, the deviation of the eyes is usually pursuit-like or tonic, rarely clonic and different to the oculoclonic ictal symptoms that are often seen in focal motor seizures of extra-occipital, mainly frontal origin. Occipital oculotonic seizures are similar to a voluntary, pursuit-like turning of the eyes to one side that, by itself, could not be considered as an abnormal movement by witnesses. They usually follow visual symptoms and mainly elementary visual hallucinations, but may also occur ab initio. At this stage, consciousness is often but not invariably impaired. This phase may progress to unilateral clonic seizures of the face and the extremities, with or without progressing to GTCS.

Conversely, ictal eye movements of extra-occipital origin are more violent and look unnatural. Ipsilateral eyelid tonic or clonic convulsions are commonly associated with upward deviation of the eyeballs. It is simultaneous, and precedes or follows tonic or clonic convulsions of other facial, neck and shoulder muscles of the same side (e.g. as in hemifacial Rolandic seizures).

Differentiating Idiopathic from Symptomatic Occipital Epilepsy

Differentiation between symptomatic and idiopathic occipital epilepsy is essential with regard to prognosis and management.

The visual seizures of symptomatic versus idiopathic occipital epilepsy are indistinguishable.³⁵⁷ The only difference is that symptomatic visual seizures more frequently progress to other extra-occipital seizure manifestations and mainly temporal lobe seizures. Though progression to ictal motor manifestations may be common in both, temporal lobe symptoms are nearly exclusively seen in symptomatic occipital epilepsy. A normal neurological state (including visual fields) and brain imaging may be misleading, and suggest an idiopathic cause without high resolution MRI using the new generation scanners.^328,355

The Drug Treatment of Focal Epilepsies

The treatment of focal epilepsies of any cause begins first with AEDs. If this fails, neurosurgical options are now becoming more widely available and are often life saving for symptomatic and probably symptomatic epilepsies (see individual syndromes).

Existing evidence indicates that 15⁴²²–30%⁴²³ of those with newly diagnosed focal epilepsy (of any cause) fail to achieve reasonably sustained remission with optimal antiepileptic medication. The figure is significantly higher (35%) for those with symptomatic focal epilepsy.⁴²² Of those failing to respond, 25–50% develop intractable disease, that is continuation of seizures beyond 2–3 years, despite optimal AED treatment. In one large study, complex focal seizures were controlled in only 16–43% of patients, compared with 48–53% in those with only secondarily GTCS at 1 year.⁴²⁴

AED treatment in focal epilepsies has been detailed in recent books^425–430 and reviews,^431–445 although the conclusions of experts sometimes differ significantly. My recommendations, based on the procedures explained in Chapter 4 (page 59), are fairly pragmatic, combining evidence-based medicine with clinical experience. Details for each AED can be found in Chapter 14 in the pharmacopoeia (page 497).

Antiepileptic Drugs Effective for Focal Seizures

Carbamazepine and phenytoin are the superior old AEDs in the treatment of focal seizures. According to evidence-based medicine, all new AEDs entered into randomised controlled trials (RCT) have approximately equal efficacy to carbamazepine, phenytoin and valproate in controlling focal seizures, but are better tolerated.^431,432,446 The reality in clinical practice often contradicts these conclusions for many reasons.^431,447,448 It is extremely difficult to find a balance. There is a significant and rapidly changing swing with the increasing experience obtained from the clinical application of licensed new drugs and the introduction of new antiepileptic agents. The following may be applicable at the present time.

Evidence-Based Medicine

Overall, RCTs in patients with focal seizures with or without secondarily GTCS have shown the following.

• In head-to-head comparisons of old AEDs (phenobarbitone, primidone, phenytoin and carbamazepine), overall treatment success was highest with carbamazepine or phenytoin, intermediate with phenobarbitone and lowest with primidone.⁴²⁴ Carbamazepine provided complete control of focal seizures more often than primidone or phenobarbitone. The control of GTCS and the proportion of patients rendered seizure free (48–63%) did not differ significantly with the various AEDs. The differences in the failure rates were explained primarily by their adverse reactions.⁴²⁴
• In head-to-head comparisons of carbamazepine with valproate, carbamazepine provided better control of complex focal seizures and had fewer long-term adverse effects than valproate.⁴⁴⁹ Both drugs were comparably effective for the control of secondarily GTCS.⁴⁴⁹ These conclusions have been confirmed in a recent meta-analysis report.⁴⁵⁰
• “The new AEDs gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide are of nearly equal efficacy to carbamazepine, phenytoin and valproate (phenobarbitone and clobazam have not been used in recent RCT).”^431,432,446 Comparatively, topiramate and levetiracetam have the highest efficacy, while lamotrigine and gabapentin are the least efficacious (Table 12.4 and Figure 12.20).

Table 12.4

Order of priority of new AEDs in intractable focal epilepsies.

Figure 12.20

Comparison of odds ratios, with 95% confidence intervals, for the efficacy (responder rates) and tolerability (withdrawal rates) of new AEDs in a meta-analysis of published RCTs. The numbers of patients included in the (more...)

New AEDs are “better tolerated, with few adverse effects, minimal drug interactions, and a broad spectrum of activity”.^{431,432,446,458} However, this generalisation needs clarification (Table 12.4). Only a few of the new AEDs, such as levetiracetam, fulfil these conclusions. Conversely, certain other new AEDs, such as topiramate have adverse reactions that are worse than those of carbamazepine. Lamotrigine, oxcarbamazepine and topiramate have clinically significant drug–drug interactions. Gabapentin and tiagabine have a narrow spectrum of antiepileptic activity and they are contraindicated in generalised epilepsies (Table 12.4).

There are no direct head-to-head comparisons between new AEDs. Therefore, the comparative efficacy and tolerability of new AEDs is deduced from meta-analyses of RCTs (Figure 12.21).^{430,459–461} A reliable way of comparing new AEDs is to display the odds ratios for efficacy and tolerability in the same graph (Figure 12.20). Efficacy is assessed by the odds ratio for a 50% seizure reduction, which is defined as the probability of a patient being a □50% responder with the test AED divided by the probability of being a □50% responder with placebo. The more effective the AED tested, the bigger is the numerical value of the odds ratio and the higher the position of the AED in the histogram in Figure 12.20. A numerical value of unity indicates that there is an equal probability of a patient being a □50% responder, either with the tested AED or placebo. The tolerability and safety of AEDs is usually assessed by the odds ratio of premature withdrawal from the RCT. AEDs with small odds ratios are better tolerated and further on the right in the histogram. An odds ratio of unity indicates that the probability for withdrawal is equal for the tested AED and the placebo.

Figure 12.21

Synaptic vesicle protein 2A, the binding site of levetiracetam. Levetiracetam is the first and only AED found to bind to synaptic vesicle protein 2A (SV2A). SV2A binding inhibits abnormal bursting in epileptic circuits, which (more...)

Clinical Practice in Developed Countries

Old Antiepileptic Drugs in Developed Countries

Carbamazepine is the superior drug for controlling focal seizures in more than 70% of patients (10% of patients develop idiosyncratic reactions). Valproate, a superior drug in generalised epilepsies, is inferior in focal epilepsies, with significant concerns in the treatment of women. Use of phenytoin, which is as effective as carbamazepine, is falling dramatically, mainly because of chronic toxicity. Phenobarbitone and primidone, which are less efficacious, have been practically eliminated, mainly because of their adverse effects on cognition. Clobazam, though often highly beneficial in selective cases, is rarely used as continuous AED treatment and it is not licensed in the USA.

New Antiepileptic Drugs in Developed Countries

Oxcarbazepine, which is probably of equal efficacy to carbamazepine and possibly with less idiosyncratic reactions, is gaining some ground.⁴⁷⁴ Levetiracetam has become increasingly more popular, because of a combined high efficacy, comparative poverty of adverse reactions, lack of drug–drug interactions and rapid titration. Topiramate is very efficacious, but with serious and numerous adverse reactions that reduce its value. Lamotrigine is relatively widely used despite relatively low efficacy in RCTs, often severe idiosyncratic reactions and drug–drug interactions. Gabapentin has very weak antiepileptic efficacy and rarely achieves satisfactory control of seizures,⁴³⁰ but it is has become popular in the USA, where it has been promoted for many off-label uses, mainly neurogenic pain. Zonisamide has been used widely in Japan in intractable focal epilepsies. Tiagabine is used cautiously, because of fears of adverse reactions, such as non-convulsive status epilepticus. Vigabatrin has been practically discarded in the treatment of epilepsies, because of common and often irreversible visual field defects. Currently, the use of vigabatrin is limited to infantile spasms.

Clinical Practice in Developing Countries

Phenytoin, carbamazepine and phenobarbitone are by far the most common main antiepileptic agents for treating focal epilepsies, either as monotherapy or polytherapy).

Note on the Use of Valproate and Clobazam in Focal Epilepsies

Valproate is the superior AED for generalised epilepsies, but its use as monotherapy in focal epilepsies is debated. The assessment of RCTs⁴⁵⁰ that valproate is of nearly equal efficacy to carbamazepine in focal epilepsies contradicts the experience in clinical practice that valproate is not the appropriate AED for focal seizures. There are many reasons for this contradiction. Firstly, in RCTs, “Misclassification of patients may have confounded the results … The age distribution of adults classified as having generalised seizures indicated that significant numbers of patients may have had their seizures misclassified.”⁴⁵⁰ Secondly, “systematic reviews cannot up-grade poor primary research. Also, a major hurdle is that of publication bias, as trials with a positive result are more likely to be published than those with a negative result.⁴⁶² It is not surprising that a review of trials with positive results will come up with a positive answer.”⁴⁶⁰

Personally, after consistent failures to introduce valproate as monotherapy in focal seizures, I rarely use it and only adjunctively in patients with focal and secondarily GTCS because of the following: effective required doses of valproate are much higher for focal than generalised epilepsies; side effects, particularly in some women, make its use extremely problematic;.currently, there are other more effective and safer drugs for focal seizures.

Clobazam in the treatment of focal epilepsies

Based on recent evidence, clobazam is a very useful AED both as monotherapy and polytherapy, though it is not licensed in the USA.^463–473 It is neglected in current clinical practice mainly because it is erroneously considered of high dependence for all patients, of similar effectiveness regarding seizure type to that of clonazepam and because it is a benzodiazepine.

Clobazam is a very useful drug that should be tried in all intractable patients with focal seizures that fail to respond to other AEDs. Tolerance to clobazam has been overemphasised. The truth is in between and many patients may remain seizure free despite continuing use.^464,473

A 23-year-old man with intractable temporal lobe epilepsy failed to respond to any appropriate medication. While waiting for neurosurgical evaluation, 20 mg of clobazam nocte was added with a miraculous effect. He has remained seizure free for 7 years.

Monotherapy of Focal Epilepsies

Monotherapy is the primary aim in all, and therefore also focal, epilepsies.

Carbamazepine remains the first choice AED in focal seizures, but over 10% of patients develop acute idiosyncratic reactions (mainly rash). In numerous comparative studies, no other drug showed better efficacy than carbamazepine in focal seizures, although some new AEDs were better tolerated.

If treatment with carbamazepine in maximal tolerated doses fails, other pragmatic options include, of the old AEDs, phenytoin and, of the new AEDs, oxcarbazepine, levetiracetam, lamotrigine, topiramate and zonisamide (in order of preference). Personally, I also use clobazam in selected cases and I do not recommend valproate.

Phenytoin, despite its high efficacy, may not be tolerated by 10–20% of patients, because of idiosyncratic reactions, which may be fatal in exceptional cases. Long-term use is associated with unacceptable adverse reactions, including dysmorphic features.

Phenobarbitone and primidone are still very useful AEDs, particularly when cost is of concern. Their use is often barred by cognitive adverse reactions.

All new AEDs have shown a variable degree of efficacy (Figure 12.20), tolerability (Figure 12.20), safety profile, pharmacokinetics and drug–drug interactions, which should be taken into account when choosing one drug over another and which may be in the following order of priority: oxcarbazepine, levetiracetam, lamotrigine, topiramate, gabapentin and zonisamide.

Oxcarbazepine should probably be the drug of first choice by virtue of similar efficacy to carbamazepine, evidence-based documentation and length of experience; it is the first of the new AEDs to achieve FDA approval as monotherapy in focal seizures.

Of all other new AEDs only levetiracetam, lamotrigine and topiramate have the potential to be monotherapy in focal seizures.

Rational Polytherapy

Rational polytherapy* is often needed for the treatment of intractable focal epilepsies. The decision for polytherapy should first examine the possible/probable reasons why the monotherapy failed. These should thoroughly examine the following possibilities, which often require re-evaluation of the diagnosis (genuine epileptic seizures? and what type of seizures?).

• The patient does not suffer from epileptic seizures.
• The patient has both genuine epileptic and non-epileptic seizures.
• The patient has generalised seizures and not focal seizures.
• The AED used as monotherapy was not suitable for the particular type of seizures or had weak efficacy.

Non-compliance, which varies from unwillingness to take medication to occasionally forgetting or missing the AED dose. The latter is often improved with the use of AED-monitored dosage systems, which are widely available through pharmacies. These are useful even for patients who comply well, but who often may be uncertain whether or not they have taken their medication.

Important note

* The word “rational” has been used in conjunction with “polytherapy” in order to emphasise that this can also be irrational and hazardous if a diagnosis is incorrect and anti-epileptic drug indications/contraindications are violated.⁴⁷⁵ Conversion from polytherapy to monotherapy should also be rational.⁴⁷⁶

In polytherapy, initially, a second drug is added to the first line agent, which had demonstrated acceptable but insufficient efficacy, tolerability or both in monotherapy. Adding a new AED with another one to three AEDs that have already partially or totally failed or have made the situation worse is a formidable physician’s task for a disappointed and frustrated patient. The choice of a second or sometimes a third AED depends on many factors such as efficacy, adverse effects, interactions with other drugs and mode of action (Table 12.4). Polytherapy with more than three drugs is discouraged because adverse reactions become more prominent with little if any seizure improvement.

Of the old AEDs, carbamazepine, phenytoin, valproate and phenobarbital (in that order of importance and priority) are the most valuable either as monotherapy or polytherapy and particularly when cost is of concern.

Carbamazepine is currently the gold standard for controlling focal seizures in more than 70% of patients (10% of the patients develop idiosyncratic reactions). Valproate, the gold standard in generalised epilepsies, is inferior in focal epilepsies, with significant concerns in the treatment of women. The usage of phenytoin, which is as effective as carbamazepine, is dramatically decreasing because of mainly chronic toxicity. Phenobarbitone and primidone, which are less efficacious, have been practically eliminated in developed countries, mainly because of their adverse effects on cognition.

Of the new AEDs, the consensus, including the recent American QS&TTA assessment,⁴⁷⁷ is that all of them are appropriate for adjunctive treatment in refractory focal epilepsies with or without secondarily GTCS.

Clinical note

It is appropriate to use gabapentin, lamotrigine, tiagabine, topiramate, oxcarbazepine, levetiracetam and zonisamide as add-on therapy in patients with refractory focal epilepsy.⁴⁷⁷

Guidance that gives the physician a list of options is unsatisfactory in practice. The clinician’s important question is:

‘In what order of priority the new AEDs should be used?’

The ideal profile of an antiepileptic drug for polytherapy purposes⁴⁷⁸ is that it:

1. is effective
2. has a low incidence of adverse effects
3. causes no pharmacokinetic interactions
4. favourably combines with drugs with different mechanisms of action
5. needs minimal laboratory monitoring
6. needs as little as possible titration.

Thus, the order of priority of the new add-on AED is determined by the following factors.

• Strength of efficacy. The more efficacious a drug the more likely it is to control seizures and, if successful, withdrawal of other concomitant AEDs may be possible without losing seizure control and, in some cases, with improved seizure control (Figure 12.20).⁴⁷⁶ Seizure-free status is the ultimate, often achievable, goal of treatment and this should be precisely evaluated in any RCT and relevant formal practice parameter recommendations. ⁴⁷⁹
• Safety and tolerability. This includes adverse reactions and particularly those that may be serious and may outweigh any beneficial effect achieved by a reduction in seizures (Table 12.4 and Figure 12.20). Topiramate is probably the worst of all new broad spectrum AEDs because of multiple and severe adverse reactions.
• Interactions with other antiepileptic drugs, whether pharmacokinetic, pharmacodynamic or both, are particularly unwanted in polytherapy (Table 12.4).⁴⁷⁸ Raising the levels of concomitant AEDs and pharmacodynamic interactions may lead to toxic effects. Conversely, decreasing their levels may increase and worsen seizures causing a vicious circle in clinical management. With the exception of levetiracetam and⁴⁵⁴ gabapentin, all other new AEDs exhibit sometimes complex undesirable drug–drug interactions.⁴⁵³ Lamotrigine is amongst the worst of all new AEDs from that point. It requires different dosage and titration schemes when combined with hepatic enzyme-inducers and when combined with valproate. Concomitant administration of carbamazepine with lamotrigine enhances each drug’s side-effect profile as the result of pharmacodynamic interactions.
• Different mechanisms of action in relation to other concurrent AEDs (Table 4.5, page 70).^478,480 Antiepileptic drug–drug interactions may be purely additive, antagonistic or synergistic. AEDs with the same mechanism of action would be expected to be additive, while combining AEDs with different mechanisms of action may have synergistic efficacy.^478,480 A review of clinical studies suggested that a combination of a sodium channel blocker with a drug that increases the GABAergic neurotransmission or that has multiple mechanisms is generally more effective than a combination of two sodium channel blockers.⁴⁸⁰ An AED is unlikely to have better success and more likely to have additive adverse reactions if added to another AED with the same mechanism of action.⁴⁸⁰ Levetiracetam appears to have a unique mode of action (Figure 12.21).
• Need for less laboratory monitoring (Table 12.4). This refers firstly to monitoring of the serum AED levels of the added AED or the co-medications that may be affected, such as with lamotrigine or topiramate added to carbamazepine and, secondly, blood or other tests needed for detecting possible adverse drug reactions such as hypernatraemia with oxcarbazepine, metabolic acidosis for topiramate and zonisamide. More laboratory testing may mean less compliance, more expenses and more uncomfortable situations for patients.
• The need for as little as possible titration (Table 12.4). Very slow titration may mean more seizures that may also be traumatic. Levetiracetam and gabapentin are nearly ideal from that point of view with their starting dose often equalling the effective maintenance dose. Conversely, lamotrigine and topiramate are inferior requiring 6–8 weeks of low dose and slow titration in order to reach reasonable therapeutic levels.

Taking all these parameters together levetiracetam is much superior to all other new AEDs (Tables 4.3, 4.4, 4.5, 4.6, 4.7 and 12.4 and Figure 12.20).

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Footnotes

*

The terms focal and partial seizures are synonymous and are interchangeable. Focal seizures or focal epilepsies are the preferred term.

*

This section is primarily based on an extensive review from ancient to current times, studies and numerous illustrative cases in a previous monograph of mine, which I have updated appropriately.^{328,359–361}