Myoclonus epilepsy with ragged-red fibers
Jun. 18, 2022
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Childhood occipital epilepsy of Gastaut is an epilepsy syndrome that manifests with frequent and brief visual seizures consisting of elementary visual hallucinations, blindness, or both. Postictal headache is common. Interictal EEG shows occipital spikes that may be activated by the elimination of fixation and central vision (fixation-off sensitivity); EEG may be normal. The syndrome is often misdiagnosed as basilar migraine or migraine with visual aura. Conversely, structural (symptomatic) epilepsies may imitate this syndrome. Prognosis is usually good, with remission of seizures and normalization of the EEG by the late teenage years. In this update, the author details developments in childhood occipital epilepsy of Gastaut and provides clues for its proper differential diagnosis in relation to migraine and other occipital epilepsies.
Onset is usually in late childhood or in the early teenage years.
It manifests mainly with typical visual seizures of elementary visual hallucinations or blindness that are usually of brief duration.
Seizures may be very frequent.
Postictal headache is common and it is often indistinguishable from migraine headache.
EEG often shows occipital spikes or occipital paroxysms that may demonstrate fixation-off sensitivity. However, some patients have consistently normal interictal EEG.
Treatment with appropriate antiseizure medication is often needed.
Gibbs and Gibbs documented that on EEG . . . seizure foci in one or both occipital lobes are most commonly found in young children. Occipital foci tend to disappear in adult life, and the subsidence of the electroencephalographic abnormality is usually accompanied by a cessation of seizures (29). Peak age at first discovery of occipital foci was 4 to 5 years, and they could occur in children without seizures. Gibbs and Gibbs also described an 8.5-year-old boy with onset of attacks 2 months before the recording, consisting of blindness, followed by holding both hands to eyes, rolling up of eyes, and loss of consciousness. . . severe headache after attack. . . no convulsions at any time (29). EEG showed independent bilateral occipital spikes. Although similar cases were later reported by other authors, the recognition of childhood occipital epilepsy of Gastaut was delayed. This was motivated in part by a report of several patients with occipital paroxysms on EEG with eye closure whose clinical features were interpreted as basilar migraine causing seizures (09).
Subsequently, Gastaut retrospectively identified 36 patients with occipital paroxysms and proposed them as a new type of epilepsy: benign partial epilepsy of childhood with occipital spike-waves (27; 28). The 1989 International League Against Epilepsy (ILAE) classification proposed this syndrome be called childhood epilepsy with occipital paroxysms (16). This was renamed as late-onset childhood occipital epilepsy (Gastaut type) in more recent ILAE proposals (20; 06). The ILAE 2017 operational classification of seizure types included this syndrome under self-limited focal epilepsies, meaning that it is an epilepsy syndrome that is likely to resolve over time.
The typical visual seizures consist of simple visual hallucinations or ictal blindness.
Motor seizures and hemiconvulsions can occur.
Postictal headache is common and in many cases difficult to distinguish from migraine.
Prognosis is variable. Seizure remission will occur in many patients but is not universal. Patients will often have associated deficits in attention, memory, and visuospatial skills.
Visual seizures are the cardinal symptoms of childhood occipital epilepsy of Gastaut. They are usually frequent and diurnal, and they usually last from seconds to 1 to 3 minutes. Ictal blindness may last longer than this. The seizures may progress and coexist with other occipital symptoms such as sensory illusions of ocular movements and ocular pain, tonic deviation of the eyes, eyelid fluttering, or repetitive eye closures. Complex visual hallucinations, visual illusions, and other symptoms from more anterior ictal spreading rarely occur. Consciousness is intact during the visual symptoms but may be disturbed or lost if the seizures progress. Postictal headache often occurs.
Simple visual hallucinations. Visual seizures are the most typical and usually the first ictal symptom (27; 28; 11; 10; 40; 51). In a study of 129 patients with childhood occipital epilepsy of Gastaut, visual hallucinations were the first symptom in 62% and the only manifestation in 39% of patients (51).
Elementary visual hallucinations are typically brief. They develop quickly, lasting for 5 to 15 seconds, and seldom exceeding 1 to 2 minutes if they occur alone without other occipital or extra-occipital spreading. Rarely, they may last 15 to 20 minutes or longer. They are usually multicolored and circular, appearing either in the periphery of a hemifield or centrally; they may multiply in number or size, or both; they may move horizontally to the other side; and they may be flashing or static.
They may be the only ictal manifestations, or progress to other seizure symptoms. They typically have a stereotyped appearance and progression. Patients may know at what stage of their visual hallucinations progression to secondary generalization is likely to occur (38; 11; 36; 39). Consciousness is not affected.
Blindness or partial visual loss. Blindness is probably as common an ictal symptom as elementary visual hallucinations. It can occur alone and can be the only ictal event in patients who may, in other times, have visual hallucinations without blindness (38; 39; 27; 28). Blindness is sudden and total, often lasting several minutes, with preserved consciousness (10; 04). Postictal blindness, hemianopia, and other partial visual loss are well established after visual seizures, with or without secondarily generalization.
Complex visual hallucinations and visual illusions. Complex visual hallucinations are much rarer, probably occurring in less than 10% of the patients and usually emerging from elementary visual hallucinations (28). These patients usually see the form of a face or figures, which may have the same location and movement sequence as that of the elementary visual hallucinations. They do not have the same emotional or other characteristics as those associated with temporal lobe semiology.
Ictal visual illusions such as micropsia, metamorphopsia, and palinopsia are most likely generated from the nondominant parietal regions (28). They are extremely rare and may be associated more with symptomatic occipital seizures (38).
Sensory hallucinations of ocular movements and pain. A sensation of ocular movement in the absence of detectable motion is a rare occurrence and mainly occurs as a progression of elementary visual hallucinations (38; 39).
Deviation of the eyes and oculoclonic seizures. Deviation of the eyes, usually following elementary visual hallucinations and often associated with ipsilateral turning of the head, is the most common (around 70%) nonvisual symptom (27; 28; 38; 39; 22; 11; 42). This focal motor seizure usually starts after visual hallucinations, but may also occur while the hallucinations still persist. It may progress to hemiconvulsions and generalized tonic clonic seizures (GTCS) (38; 10; 39).
Ictal clinical symptoms from occipital seizure propagation. Elementary visual hallucinations or other ictal symptoms may progress to hemiconvulsions or generalized convulsions. According to Gastaut and Zifkin, visual seizures are often followed by other nonvisual seizure symptoms such as hemiconvulsions (43%), complex focal seizures (14%), dysphasia, dysesthesia, aversive convulsions (25%), and generalized tonic-clonic seizures (13%) (28). Forced eyelid closure and eyelid blinking occur in approximately 10% of patients, usually at a stage in which consciousness is impaired. They signal impending secondarily generalized convulsions (27; 28; 38; 39).
Autonomic manifestations, ictal vomiting, and ictal syncope. These are the most prominent symptoms in Panayiotopoulos syndrome and are unusual in childhood occipital epilepsy of Gastaut (39). Ictal vomiting may sometimes occur after the end of the visual symptoms, with the patient having no recollection of it but does not occur at seizure onset in this condition. Ictal syncope is exceptional (38; 39). Respiratory arrest has been reported in the literature only once (25).
Headache. Postictal headache is a consistent symptom in about half of patients (28; 10). This occurs immediately, or 5 to 10 minutes after the end of the visual hallucinations. The duration and severity of the headache appears to be proportional to the duration and severity of the preceding seizures. The headache may be diffuse and of mild to moderate intensity, but in some patients it is strong and pulsating and may be associated with nausea, vomiting, photophobia, and phonophobia, which may make it indistinguishable from migraine (28; 04). Ictal headache, mainly orbital, is a rare occurrence.
Circadian distribution. Visual seizures are predominantly diurnal and occur at any time of the day. Longer seizures, with or without secondarily hemiconvulsions or generalized convulsions tend to occur either during sleep, causing the patient to wake, or after awakening.
Frequency of seizures. In untreated patients, brief visual seizures are frequent, occurring at a frequency of several per day or weekly. However, propagation to other seizure manifestations, such as focal or more generalized convulsions is much less frequent, occurring monthly, yearly, or exceptionally (11; 39).
Prognosis is unclear, though available data may indicate that remission occurs in more than 60% of patients (29; 28; 11; 51). Patients whose seizures continue into adulthood may be unlikely to have long-term remission at all (03).
This syndrome is often misdiagnosed as migraine, resulting in the delay of appropriate antiseizure medication, sometimes for years, which may affect prognosis (38; 22; 39). In a study of 19 patients with childhood epilepsy of Gastaut, only 4 patients had remission of seizures before the age of 17 years; 7 patients also developed other types of seizures (48). Prognosis was not associated with a specific EEG pattern whether abnormal or normal.
There have been reported cases of childhood occipital epilepsy of Gastaut that developed continuous spike-waves during slow-wave sleep with cognitive deterioration, which may be reversible with appropriate medication (37; 23).
Various studies have demonstrated intellectual and neuropsychological abnormalities in children with childhood occipital epilepsy. Gulgonen and colleagues tested intellectual functioning, attention, memory, academic achievement, visual-motor functioning, and executive functioning in 21 patients with childhood occipital epilepsy compared to controls (31). The case patients' performance scores were lower in attention and memory, as well as in intellectual functioning.
Language impairments, and in particular difficulties with semantic function, have also been demonstrated in children with childhood occipital epilepsy of Gastaut (47). In neuropsychological assessment with specific visuoperceptual testing of 6 patients, a deficit in facial discrimination was found in 4 patients and was associated with a line orientation deficit in 3 (14). Significant abnormalities have also been found in the domains of visuomotor coordination, memory, and attention (44).
Children with childhood occipital epilepsy of Gastaut have been demonstrated to have impairments in visuospatial processing and those who experienced a higher number of seizures or in whom interictal EEG discharges had been present for a longer time demonstrated a higher degree of impairment (07).
Comparative neuropsychological testing between patients with childhood occipital epilepsy of Gastaut and Panayiotopoulos syndrome showed impairments in psychomotor speed, writing and arithmetic skills, and verbal memory in both groups whereas children with Panayiotopoulos syndrome showed worse performance in terms of visual memory and reading problems (02).
An otherwise normal 8-year-old boy had onset of weekly episodes of elementary visual hallucinations. These were brief, lasting 5 seconds to 15 seconds, and consisted of 3 to 4 concentric spherical rings of red and yellow moving from the left to the right visual field, and repeating the same course again after their disappearance on the right. On other occasions, only 1 colored ball was moving continuously from left to right. The colors were faint at onset, becoming more intense as the seizure progressed. There was no impairment of consciousness, convulsion, or headache. An initial diagnosis of acephalgic migraine was made.
Beginning at 10 years of age, on 4 occasions, the same concentric rings were bigger (double in size), followed the same course from left to right, but the duration of the seizure was longer, lasting 1 minute. On 3 more occasions, visual seizures were longer, lasting 2 to 3 minutes, followed by left sided deviation of the head, and left hemiconvulsions. At this stage, the diagnosis of occipital lobe seizures was suspected. An initial routine EEG was normal in the awake state.
Carbamazepine 600 mg daily was initiated at 11 years of age. The head deviation and hemiconvulsions ceased but he continued to have infrequent, brief, elementary visual hallucinations like those mentioned above, which were more likely to occur after watching television or playing video games for long periods. These were occasionally followed by diffuse headache of moderate intensity for 10 to 15 minutes, and once he felt sick. A follow-up EEG was again normal in the awake state but showed occasional occipital spikes during sleep. A high-resolution MRI was normal.
At 17 years of age, he had 3 visual seizures lasting for nearly an hour each (focal visual status epilepticus). They started with left sided blurring of vision, whitish like a fog, together with small clouds of colors; mainly red, and mixed with small colored circles. Symptoms did not progress, but when the blurring of vision and the visual hallucinations cleared, he had left sided throbbing headache, which started 5 to 7 minutes after the cessation of the seizures, and lasted for half an hour. His carbamazepine dose was increased and he has had no further seizures of any type.
The exact etiology is not clear but a genetic predisposition is suspected.
There may be a relationship with other self-limited focal childhood epilepsies.
The etiology of childhood occipital epilepsy of Gastaut is unclear but genetic mechanisms are postulated. There is an increased family history of epilepsies (21% to 37%) or migraine (9% to 16%) (28; 10), but familial childhood occipital epilepsy of Gastaut appears to be rare (12). Genetic analysis of a series of patients with self-limited focal epilepsies of childhood found 1 patient with an atypical occipital epilepsy and a mutation involving EPHB6; no specific gene abnormalities were associated with classic childhood occipital epilepsy of Gastaut (46).
Childhood occipital epilepsy of Gastaut and other syndromes of self-limited childhood focal seizures may be linked together based on a common, genetically determined, functional derangement of the brain cortical maturational process, which Panayiotopoulos proposed to call benign childhood seizure susceptibility syndrome (39). EEG and seizure manifestations often follow an age-related localization and prevalence and the location of spikes may shift over time (19). That occipital paroxysms may be bilateral and synchronous can be explained by cortical occipital hyperexcitability, which is driven simultaneously by fixation-off sensitivity (39). Conversely, Gastaut and Zifkin hypothesized that the occipital paroxysms are due to a subcortical, thalamocortical, mechanism in order to explain the rhythmic spike and wave complexes seen with eye closure or intermittent photic stimulation over an intact occipital lobe" (28).
An association between childhood occipital epilepsy of Gastaut and typical absence seizures has been reported. Typical absences may appear at the same time as or after the onset of visual seizures (50).
The mechanisms of postictal headache, common even after minor visual seizures with or without a predisposition to migraine, are unknown. It is likely that the occipital seizure discharge triggers a genuine migraine headache through trigeminovascular or brain stem mechanisms (38; 39; 18).
Childhood occipital epilepsy of Gastaut is rare, with a probable prevalence of 0.2% to 0.9% of all epilepsies and 2% to 7% of benign childhood focal seizures (38; 39; 26). Childhood occipital epilepsy of Gastaut is much rarer than Panayiotopoulos syndrome. Boys and girls are equally affected. The onset is typically during childhood or adolescence, with a peak at 8 to 9 years of age. Gastaut and Zifkin reported age at onset from 15 months to 19 years (28).
The differential diagnosis of childhood occipital epilepsy of Gastaut is mainly from other occipital epilepsies and migraine syndromes. Occipital epilepsies include structural occipital epilepsy, Panayiotopoulos syndrome, and photosensitive occipital lobe epilepsy. Migraine syndromes that may mimic occipital epilepsy of Gastaut include migraine with aura, basilar, or acephalgic migraine (38; 39; 01).
Symptomatic occipital epilepsy often imitates childhood occipital epilepsy of Gastaut; neuro-ophthalmological examination and initial brain imaging may be normal, requiring high-resolution MRI for detection of subtle lesions. Occipital seizures of hyperglycemia, mitochondrial disorders (13), Lafora disease, and celiac disease should be considered (39). In a study from Turkey, 15.7% (6 out of 38) children with childhood epilepsy with occipital paroxysms had biopsy-proven celiac disease (32).
Panayiotopoulos syndrome often has similar interictal EEG recordings to childhood occipital epilepsy of Gastaut. However, onset and clinical progression of the seizures distinguishes the two. In Panayiotopoulos syndrome, seizures start with autonomic manifestations (emesis in 70%), and the whole seizure may be entirely autonomic, but commonly other more conventional symptoms occur in the progress of the seizures. These primarily include deviation of the eyes and impairment of consciousness; visual hallucinations and illusions may occur but not at onset. In childhood occipital epilepsy of Gastaut, seizures are exclusively occipital, and onset predominantly consists of elementary visual hallucinations. Deviation of the eyes is common; ictal vomiting may occur during the progression of seizures (22; 42; 39; 40).
Photosensitive occipital lobe epilepsy has been recognized as a syndrome of reflex epilepsy with age-related onset (20; 08). Photosensitive occipital seizures may start in adulthood (35), develop later in children with Rolandic seizures (38), or occur incidentally during intermittent photic stimulation of normal or migraine subjects (39). Occipital seizures may be induced by television, video games, and intermittent photic stimulation and can manifest with multicolored circular visual hallucinations that are often associated with blindness (30; 38; 22; 39; 43). Tonic deviation of the eyes, epigastric discomfort and vomiting, headache, and generalized convulsions may follow. Duration varies from 2 to 5 minutes or up to 2 hours. Prognosis is uncertain. Some children may have only 1 or 2 seizures, but others may not remit. Interictal EEG shows spontaneous and photically induced occipital spikes. Centrotemporal spikes may coexist. Ictal EEGs documented the occipital origin and the spreading of the discharges to the temporal regions (30; 43). Visual evoked potentials in this condition show higher amplitudes compared to both normal controls and patients with occipital epilepsy of Gastaut (08).
Visual seizures are often confused with migraine with aura, and basilar and acephalgic migraine, but their epileptic nature becomes apparent with careful scrutiny (38; 39; 18; 40; 15). A definite diagnosis can be made by experienced epileptologists even at the onset of this syndrome (26).
Paroxysmal tonic upgaze deviation, an uncommon neuro-ophthalmological syndrome characterized by episodes of sustained upward eye deviation, may be associated with occipital spikes on EEG (53). Of note, the spikes in this case occurred in the intervals between episodes. However, not all cases of paroxysmal tonic upgaze deviation are associated with epileptiform discharges.
The diagnosis is made by a combination of clinical history and EEG findings.
Interictal occipital spikes are typical; these often demonstrate fixation-off sensitivity.
A number of ictal EEG patterns may be present.
Brain imaging should be performed to rule out structural causes of seizures.
Neurologic exam is normal. Brain imaging is normal. All patients should have high resolution MRI to exclude static or progressive occipital lesions (01).
The interictal EEG can show occipital spikes or occipital paroxysms, often superimposed on an otherwise normal background (28; 36; 04). The spikes can be unilateral or bilateral and are often high in amplitude. Spike frequency is variable. Some patients may have a normal interictal EEG or may have spikes only during sleep; thus, prolonged EEG monitoring may be indicated when a routine study is unrevealing (10; 19). EEG abnormalities may be disproportional to clinical severity. The spikes may demonstrate fixation-off sensitivity, meaning that spikes can be induced by darkness, closing the eyes, or otherwise eliminating visual fixation. Conversely, spikes can sometimes be suppressed via visual fixation or eye opening (04). Occipital paroxysms may also be suppressed during various neuropsychological conditions (45).
In addition to the classic occipital spikes, a number of other abnormalities may be present on EEG. Generalized spikes, spike-wave or polyspike-wave discharges, centrotemporal spikes, and other focal spikes have all been reported (28; 48). Of 19 patients with this syndrome in 1 study, only 4 had the classical occipital paroxysms. Prognosis was not associated with a specific interictal EEG pattern whether abnormal or normal (48).
It should be emphasized that the characteristic occipital spikes are not by themselves diagnostic of this condition. Occipital spikes can also be seen in the setting of structural lesions, other epilepsy syndromes, patients with visual impairments, and a small number of normal children (10; 04). The presence of occipital spikes with associated frontal-central positivity and/or tangential dipoles may suggest one of the self-limited occipital epilepsies as opposed to these other etiologies of occipital spikes (17).
Although it is more common in occipital epilepsy of Gastaut, it should also be noted that fixation-off sensitivity is not specific and may occur in children and adult patients with or without occipital spikes with generalized and symptomatic focal epilepsies (34; 35; 39; 21; 33).
Simple focal occipital seizures with positive signs are characterized by fast rhythmic activities with intermixed spikes over the occipital region. Complex visual hallucinations, when they occur, can be accompanied by slower discharges. In oculoclonic seizures, slow spikes and spike-wave discharges are typical as the seizure progresses. A localized ictal fast spike rhythm may be observed before eye deviation.
Head deviation may be accompanied by rhythmic theta activity. The EEG during ictal blindness is characterized by pseudoperiodic slow waves and spikes. There are usually no postictal abnormalities or else they resolve quickly (05; 39; 24; 04).
Unlike Rolandic epilepsy and Panayiotopoulos syndrome, which often do not require treatment, childhood occipital epilepsy of Gastaut should be treated because seizures, though brief and mild, are frequent (49). Secondary generalization is probably common without medication. Most antiseizure medications used to treat focal seizures may be suitable. Seizures will frequently stop or be dramatically reduced within days after treatment with carbamazepine (38; 11). In 1 study, 12 patients with this syndrome became seizure free with levetiracetam monotherapy (52). Success has also been reported with valproate and phenobarbital (19). Slow reduction of medication 2 to 3 years after the last visual or other minor or major seizure may be advised, but if visual seizures reappear, treatment should be resumed (39).
The outcome of treatment with antiseizure medications is usually excellent with the exception of children with atypical evolutions (23; 51).
Jules C Beal MD
Dr. Beal of Weill Cornell Medicine and New York-Presbyterian Queens Hospital received honorariums from Neurelis as a speaker.See Profile
Solomon L Moshé MD
Dr. Moshé of Albert Einstein College of Medicine has no relevant financial relationships to disclose.See Profile
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