Defective visual inhibition in photosensitive idiopathic generalized epilepsy

Purpose: To assess the visual system excitability of photosensitive patients with idiopathic generalized epilepsy (IGE) with the paired‐pulse flash‐evoked potential (paired F‐VEP) technique. Methods: We studied 19 photosensitive patients with IGE (16 women) showing a photoparoxysmal electroencephalographic (EEG) response (PPR). Twenty‐two normal subjects of similar age and sex acted as controls (17 women). We recorded F‐VEPs from occipital and central electrodes. Stimuli were single flashes, intermingled to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 msec (i.e., at the internal frequency of 3, 8, 16, 20, 30, and 60 Hz). Recordings were done both with closed and open eyes. The single F‐VEP was split into a “main complex” and a “late response,” which were measured separately. As to paired stimuli, the “test” F‐VEP emerged from electronic subtraction of the single F‐VEP to the paired F‐VEP. Grouped data were analyzed by means of nonparametric analyses of variance (ANOVAs). Key Findings: In patients, the single F‐VEP showed some enhanced components in its early “main complex.” Then, the “test” F‐VEP behaved differently than controls, particularly if recorded with closed eyes, when the normal inhibition was abolished at given ISIs, corresponding to an internal frequency of 16–30 Hz. In patients with a posterior PPR, impaired inhibition was evident over the occipital region only, but in those with a widespread PPR, it also involved the central areas. Significance: The paired F‐VEP technique documents a defective inhibition in the visual system of photosensitive patients with IGE, whose features and timing likely underlie the PPR origin.     

EEG in adult-onset idiopathic generalized epilepsy

PURPOSE: It remains controversial whether adult-onset idiopathic generalized epilepsy (IGE) is a distinct syndrome or a continuum among IGE syndromes. EEG is the only known biologic marker of IGE and helps differentiate many of its classic subsyndromes. In this study, we looked for the differences in the EEG findings of IGE of classic adolescent onset versus adult onset that may suggest syndromic heterogeneity. METHODS: Seventy-six patients (47 adolescent-onset IGE, 29 adult-onset IGE) with a clinical and EEG diagnosis of IGE were included. We defined IGE with age at onset of 11-20 years as adolescent-onset IGE and age at onset of 20 years or after as adult-onset IGE. Patients with first-decade onset of seizures, delayed EEGs, and no EEG available for review were excluded. The first EEG was performed within 24 h of the seizure, and if negative, a sleep-deprived EEG was done. All EEGs were reviewed in detail with respect to the background activity and the generalized spike-wave (GSW) characteristic. RESULTS: EEGs (87; 56 adolescent-onset IGE, 31 adult-onset IGE) were systematically reviewed. Background was normal in all patients. The morphology, amplitude, duration, frequency, occurrence, or activation of the GSW pattern did not differ between these two groups. CONCLUSIONS: No differences of EEG features were found between the classic adolescent-onset and the adult-onset IGE. This supports the hypothesis that they share common biologic determinants and exist along a life-long age spectrum of classic IGE.     

Imaging idiopathic generalized epilepsy.

It has been traditionally held that there is no radiological abnormality in patients with idiopathic generalized epilepsy (IGE). Sophisticated image processing and quantitative magnetic resonance imaging (MRI) studies suggest that, in some cases, there may be a subtle structural abnormality. Magnetic resonance spectroscopy indicates neuronal dysfunction with differing patterns of abnormality in the IGE sub-syndromes, and high levels of glutamate and glutamine have been suggested in the frontal lobes, and low GABA levels in the occipital lobe. Studies reflecting cerebral blood flow at the time of absences have given complex results. The principal consensus is of an increase in the thalamus and broad decreases in the neocortex, reflecting a suppression of neuronal activity, but with the possibility of some increases, that could perhaps reflect focal areas of neuronal activation. PET ligand studies with an opioid tracer have implied neocortical release of endogenous opioids at the time of serial absences. In combination with high time-resolution neurophysiological methods, static and dynamic PET studies with specific ligands have the potential to elucidate the functional anatomy and neurochemical circuits that under-lie IGE.     

The coexistence of idiopathic generalized epilepsy and partial epilepsy

PURPOSE: To describe the clinical, EEG, and imaging data of a series of patients with features of both idiopathic generalized epilepsy (IGE) and partial epilepsy. METHODS: A computerized database of all patients attending the regional epilepsy clinic was used to identify all patients with IGE. Case notes were reviewed, and cases with clinical evidence of co-existing partial epilepsy identified. RESULTS: Nine cases with clinical features of a partial and generalized-onset epilepsy and with electrophysiological evidence of IGE are presented. This represented <1% of the overall IGE population in the clinic. Five (55.6%) patients are currently in remission, with successful epilepsy surgery in one patient. CONCLUSIONS: The coexistence of IGE and partial epilepsy is uncommon, and if appropriate treatment with a broad-spectrum antiepileptic drug is given, then the prognosis can be good. Surgery should be considered for those cases with medically intractable partial-onset seizures as part of this syndrome.     

The prognosis of idiopathic generalized epilepsy

Prognosis describes the trajectory and long‐term outcome of a condition. Most studies indicate a better prognosis in idiopathic generalized epilepsy (IGE) in comparison with other epilepsy syndromes. Studies looking at the long‐term outcome of different IGE syndromes are relatively scant. Childhood absence epilepsy appears to have a higher rate of remission compared to juvenile absence epilepsy. In absence epilepsies, development of myoclonus and generalized tonic–clonic seizures predicts lower likelihood of remission. Although most patients with juvenile myoclonic epilepsy (JME) achieve remission on antiepileptic drug therapy, <20% appear to remain in remission without treatment. Data on the prognosis of other IGE syndromes are scarce. There are contradictory findings reported on the value of electroencephalography as a predictor of prognosis. Comparisons are made difficult by study heterogeneity, particularly in methodology and diagnostic criteria.     

The electroencephalogram of idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes based on clinical and electroencephalography (EEG) features. The EEG signature of IGE is bisynchronous, symmetric, and generalized spike-wave complex; although focal, irregular, and so called "fragments" of discharges are not uncommon. Other characteristic EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, and photoparoxysmal response. Both human and animal data suggest involvement of the thalamus and the cortex in the generation of spike-wave discharges in IGE. Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. Those discharges tend to occur more often after awakening and during cyclic alternating pattern phase-A of non-rapid eye movement sleep. Activation procedures such as hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are useful techniques to increase the yield of both interictal and ictal EEG abnormalities. Although not in routine use, specific triggers such as pattern stimulation and cognitive tasks may also be of value in eliciting rare reflex seizure-related EEG abnormalities. Variations of EEG abnormalities are evident between different electroclinical syndromes. EEG is also affected by certain external as well as internal factors, which should be borne in mind when interpreting EEG studies in IGE.     

Visual auras in idiopathic generalized epilepsy]

Visual auras are reported to be uncommon or rare in patients with idiopathic generalized epilepsy. We describe three patients who experienced visual auras just before generalized tonic-clonic seizures. This study indicates that in idiopathic generalized epilepsy, visual auras manifest as flashes, lighting or the impression of seeing the sun. Unlike auras in occipital lobe epilepsy, they are very brief.     

Corpus callosotomy in refractory idiopathic generalized epilepsy

RATIONALE: A small percentage of patients with idiopathic generalized epilepsy (IGE) do not respond to medical therapy. Generalized tonic-clonic (GTC) seizures are especially debilitating and can be associated with severe injuries. The benefit, safety and effect of corpus callosotomy (CC) in patients with IGE have not been studied. METHODS: We reviewed patients with presumed IGE who underwent CC between 1991 and 2000. Criteria for selection included history, examination, brain imagining, interictal and ictal EEG. All patients had refractory and debilitating tonic-clonic seizures (GTCS) and had failed four or more antiepileptic drugs. Seizure frequency was calculated per month over the last year and pre-operative baseline was compared to last follow-up using paired t-tests. IQ, executive function, language and verbal, non-verbal memory and quality of life (QOL) was compared before and after surgery. Serial EEGs after surgery were reviewed. RESULTS: There were nine patients (seven men), mean age 37.9 (range: 22-49), mean IQ 87.3 (range: 75-107). All had anterior CC. Mean follow-up time was 5.4 years (range: 0.6-10.3 years). One patient died from sudden death in epilepsy 9 months after surgery. There was a significant reduction of GTC seizures from 6.3 to 1.1 (p<0.005). Four patients had more than 80% and eight more than 50% reduction. Of five patients with absence seizures, two became seizure free and one had more than 80% reduction and two worsened slightly, and of three with myoclonic seizures one had more than 90% reduction. One patient had completion of the CC with improvement of myoclonus and absence seizures, but not of GTC seizures and suffered a disconnection syndrome. Another had right frontal focal resection without improvement after new seizures of focal onset. Cognitive testing showed a good outcome (improved or no change) in all cognitive domains. Post-surgical EEG showed new focal slowing and sharp waves. There was no change in QOL. CONCLUSION: CC can be effective in reducing GTC, absence and myoclonic seizures in patients with refractory IGE. These findings suggest that interhemispheric communication of the cerebral cortices plays an important role in the generation of seizures in IGE. Anterior CC appears safe while complete callosotomy has a risk of disconnection syndrome.     

Subcortical nuclei volumetry in idiopathic generalized epilepsy

PURPOSE: The exact anatomic and neurophysiologic correlates of idiopathic generalized epilepsy (IGE) in humans are still not well understood, although the thalamus has frequently been invoked as the crucial structure in the generation of primary generalized seizures. The few in vivo magnetic resonance (MR)-based studies in IGE patients suggest an altered cortical/subcortical gray matter ratio, but with no evidence of structural alterations of the thalamus. In this study, we sought to determine the volumes of the other subcortical structures. METHODS: The volumes of the caudate nucleus, putamen, pallidum as well as the thalamus were each determined in both hemispheres in 11 patients with various IGE syndromes, normalized for whole-brain volumes and then compared with 15 age-matched controls. RESULTS: No differences were noted in thalamic volumes, confirming previous reports. However, smaller subcortical volumes were noted in the IGE patients (p < 0.009), mainly due to smaller putamen bilaterally (p < or = 0.015). CONCLUSIONS: It is speculated that the presence of discrete frontal dysfunction, as noted in neuropsychological studies in IGE patients, indirectly supports our results because the putamen projects predominantly to the frontal cortex. Larger studies with more homogeneous patient populations are needed to determine the robustness of these findings and whether they are specific for particular IGE syndromes.     

Auras are frequent in idiopathic generalized epilepsy

The occurrence of an aura is often considered evidence of a partial rather than an idiopathic generalized epilepsy syndrome. The authors examined this hypothesis by prospectively recording reports of auras by patients being admitted for video-EEG monitoring. Auras were equally common (70%) among patients with idiopathic generalized epilepsy as they were among those with localization-related epilepsy. Presence of an aura is not a reliable indicator of localization-related epilepsy.     

Antimyoclonic efficacy of piracetam in idiopathic generalized epilepsy

Piracetam, a derivative of gamma-aminobutyric acid (GABA), has been used extensively for treatment of myoclonus in a variety of conditions, but not in patients with idiopathic generalized epilepsy (IGE). We have treated a patient with juvenile myoclonic epilepsy who had frequent and inconvenient morning myoclonus with 3,200 mg of piracetam daily. She had had only two generalized tonic-clonic seizures, with the last seizure 10 years earlier. Her obesity precluded the use of sodium valproate. She had a dramatic response to piracetam with sustained cessation of myoclonus and no side effects during 1.5 years' follow-up. Further trials of piracetam for control of myoclonus in patients with IGE are justified.     

Cognitive function in idiopathic generalized epilepsy of childhood

This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well-controlled seizures. Twenty-four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic-clonic seizures (GTCS), mean age 14y 4mo, SD ly 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS]) mean age 14y 5mo, SD ly 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age-appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non-verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding non-verbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long-term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.     

Default mode network abnormalities in idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is associated with widespread cortical network abnormalities on electroencephalography. Resting state functional connectivity (RSFC), based on fMRI, can assess the brain's global functional organization and its disruption in clinical conditions. We compared RSFC associated with the 'default mode network' (DMN) between people with IGE and healthy controls. Strength of functional connectivity within the DMN associated with seeds in the posterior cingulate cortex (PCC) and medial prefrontal cortices (MPFC) was compared between people with IGE and healthy controls and was correlated with seizure duration, age of seizure onset and age at scan. Those with IGE showed markedly reduced functional network connectivity between anterior and posterior cortical seed regions. Seizure duration positively correlates with RSFC between parahippocampal gyri and the PCC but negatively correlates with connectivity between the PCC and frontal lobe. The observed pattern of disruption provides evidence for integration- and segregation-type network abnormalities and supports aberrant network organization among people with IGE.