The impact of prophylactic treatment on post-traumatic epilepsy after severe traumatic brain injury.

AIM: To assess the incidence of late post-traumatic epilepsy (PTE) in patients with very severe traumatic brain injury (TBI) who either received or did not receive anti-epileptic prophylactic treatment. METHODS: Two populations were studied: 55 patients retrospectively and 82 subjects prospectively. RESULTS: Ten patients (18%) in the first population showed late PTE. Although the incidence was lower in patients who did not receive prophylactic treatment, the difference between the treated and the non-treated group was not statistically significant. Sixty-nine patients in the second group (84%) had prophylactic treatment. Twenty-seven patients (39%) suffered from late PTE during the 2-year follow-up period and 17 of them (63%) showed EEG epileptic abnormalities. No patient who did not receive preventive therapy suffered from late PTE during the observation period. CONCLUSIONS: Due to the negative cognitive effects of anti-epileptic drugs, the preliminary results are of considerable interest for the rehabilitation of patients with very severe TBI.

Gabapentin-induced modulation of interictal epileptiform activity related to different vigilance levels.

OBJECTIVES: Gabapentin (GBP) is a novel antiepileptic drug (AED), currently used as add-on therapy in patients with partial seizures. Similar to other AEDs, little is known about its effects on nocturnal sleep, despite the strict relationship between sleep and epileptic discharges. The aim of our study was to evaluate the effects of chronic therapy with GBP on both nocturnal sleep and on interictal epileptiform abnormalities (IEA) in relation to the different sleep stages. METHODS: Eighteen patients affected by partial seizures resistant to common AEDs were submitted to nocturnal polygraphic recordings under baseline conditions and after 4 months of add-on GBP treatment. RESULTS: We observed a significant increase in unilateral/focal IEA during light NREM sleep and a significant reduction in bilateral/diffuse IEA during wakefulness after sleep onset (WASO) with respect to the baseline condition. A significant increase in REM sleep and slow wave sleep (SWS) associated with a reduction in the number of awakenings and Stage 1 was also observed after GBP chronic therapy. CONCLUSIONS: GBP therapy improves the sleep pattern of epileptic patients and it seems to modulate the expression of IEA with different effects in relation to the various vigilance levels.

Transcranial magnetic stimulation reveals an interhemispheric asymmetry of cortical inhibition in focal epilepsy.

Transcranial magnetic stimulation (TCS) was applied to both hemispheres of 16 patients affected by criptogenic focal epilepsy to evaluate the interhemispheric symmetry of the motor cortex excitability. The amplitude of the motor evoked potentials (MEPs) and the duration of the post-MEP silent period (SP) were measured at threshold (THR) and at increasing TCS stimulation intensities. The THR was significantly higher in patients than in 16 age-matched control subjects (p < 0.01). No interhemispheric differences were found in MEP amplitude. In controls, the correlation between SP duration and increasing TCS stimulus intensity was linear with a symmetrical progression of the SP duration over the two hemispheres. In patients this linear SP progression was lacking on the 'epileptic' hemisphere: the SP duration did not increase following TCS > 40% above THR, indicating abnormal interhemispheric asymmetry. This finding suggests a selective dysfunction of inhibition in the epileptic hemisphere as signaled by an abnormal SP duration in response to progressively higher TCS intensities.

Gabapentin as add-on therapy in focal epilepsy: a computerized EEG study.

OBJECTIVES: Gabapentin (GBP) possesses a well documented clinical efficacy in those types of focal epilepsy otherwise resistant to conventional antiepileptic drugs (AEDs); on the basis of this, it appears important to investigate the drug effects on the EEG epileptiform and background activity. METHODS: Twenty-five patients with cryptogenic or symptomatic partial epilepsy resistant to conventional AED treatment were included in the study. All patients underwent long-term video-EEG recordings before and after GBP addition (900-1200 mg/day). RESULTS: Quantitative analysis of the interictal EEG paroxysms revealed that GBP had no effect on the rate of occurrence of interictal and ictal EEG abnormalities. GBP was active in delimiting the spatial extent of the interictal spiking activity in those patients who displayed a significant reduction (> or =50%) in seizure occurrence (32% of the patients). EEG background activity recorded under rest condition from 18 out of 25 epileptic patients, before GBP therapy, was characterised by a higher content of the slow spectral components (delta and theta) with respect to control subjects. After GBP addition, the increase of theta relative power was also evident during task performance. CONCLUSIONS: These findings suggest that GBP does not interfere with the generation of interictal EEG spiking while it appears to reduce the susceptibility to seizures concomitantly with a limiting effect on the spiking activity spatial extent. The utilization of GBP in controlling focal seizures is reinforced by the absence of negative influence on cognitive functioning.

Neurophysiologic and neuropsychologic profiles of lamotrigine in epilepsy.

The anticonvulsant potential of lamotrigine (LTG) has been extensively assessed in open and double-blind clinical trials including patients with different types of epilepsy. In this review, the neurophysiologic and neuropsychologic profile of LTG is discussed. The electroencephalographic (EEG) findings reveal that the drug induces a decrease both in frequency and in probability of propagation of the EEG epileptiform abnormalities (interictal and ictal), whereas the background activity appears unmodified. In contrast with the traditional antiepileptic drugs (AEDs), LTG does not affect evoked responses (brainstem auditory evoked potentials and somatosensory and visual evoked potentials), indicating only a minor toxic effect on the nervous system. The neuropsychologic assessment shows that LTG does not alter the cognitive functions. In conclusion, the neurophysiologic and neuropsychologic data confirm the efficacy and safety of LTG and support its clinical use as monotherapy in epilepsy.

Changes of the EEG paroxysmal pattern during felbamate therapy in Lennox-Gastaut syndrome: a case report.

We report a case of a 43-year old woman with Lennox-Gastaut syndrome who exhibited atypical absence seizures, atonic seizures and generalized toniclonic seizures which were not controlled by antiepileptic drug (AED) treatment. Because of this, felbamate (FBM) (1800 mg per day) was progressively added to the pre-existent therapy. The patient underwent a 24-hour-video-EEG monitoring before and after 4 months of FBM therapy. Analysis of the video-EEG signal recorded during wakefulness revealed the presence of ictal activity represented by repetitive, bilateral, slow spike and wave bursts underlying atypical absence seizures; the ictal activity occurring during non-REM sleep was characterized by runs of bilateral, rapid, high-voltage spikes followed by slow spike and wave complexes corresponding to brief tonic seizures. FBM therapy induced disappearance of the EEG ictal slow, spike and wave complexes leaving rather unaffected the runs of spikes. Computerized analysis of both the EEG background activity and the sleep structure displayed a better organization of the global cerebral rhythms under FBM treatment. Our findings suggest a selective effect of FBM on the ictal atypical spike and wave pattern. The differential effect of FBM on ictal patterns may be a reflection of a different action on the excitatory and inhibitory systems.

Lamotrigine add-on therapy in focal epilepsy: electroencephalographic and neuropsychological evaluation.

The effect of lamotrigine (LTG) as add-on therapy on electroencephalogram (EEG) background activity was studied in 11 patients with refractory partial seizures with or without secondary generalization. The computerized EEG study was performed at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX), and mental arithmetic (MA) tasks. EEG spectral values were analyzed statistically using three-way ANOVA. The neuropsychological evaluation included a battery of six tests. Epileptic patients before LTG therapy, compared with control subjects, displayed at rest condition EEG changes consisting of higher delta and theta relative power coupled with lower alpha and beta power. During performance of attentive (BR) and cognitive (FIX) tasks, a decrease in alpha reactivity associated with a decrease of beta 1 and beta 2 power was found. The addition of LTG to previous therapy induced changes, although subtle, consisting of an increase in both alpha reactivity and beta power to attentive task. Neuropsychological evaluation did not evidence any impairment of cognitive functions. During LTG therapy, a decrease in seizure frequency occurred in 9 of the 11 patients whereas no changes were observed in the remaining 2. On the basis of these neurophysiologic and neuropsychological findings, LTG as add-on therapy does not seem to produce adverse side effects on mental activity; moreover, EEG data indicate a slight improvement in attentional processes.

Movement-induced seizures: a case report.

Reflex seizures induced by movement are typically evoked by sudden or unattended motor actions. However, tonic seizures may also be triggered by slow movements as observed in nonketotic hyperglycemia or in "praxis-induced epilepsy." We report the case of a young, nondiabetic patient affected by recurrent partial tonic postural seizures precipitated by slow movements which were unrelated to cognitive tasks. Ictal EEG did not permit location of the epileptogenic brain region. However, the clinical features suggest possible involvement of the supplementary motor area.

EEG changes induced by vigabatrin monotherapy in focal epilepsy.

The effect of vigabatrin (GVG) monotherapy on EEG interictal abnormalities and on background activity recorded at rest and during mental tasks was studied in 14 patients suffering from focal epilepsy. A long-term EEG monitoring was performed in each patient before and 3 months after the beginning of GVG therapy. Ictal and interictal EEG abnormalities (IEA) were quantified by specific computer programs. Background activity was evaluated by spectral analysis at rest with eyes closed (EC), during blocking reaction (BR) and during fixation of cartoons (FIX). During treatment, IEA was either decreased or unmodified independently from seizure occurrence, which clearly improved in the majority of patients. The only EEG modifications induced by GVG monotherapy were a more pronounced slowing of the background activity at rest with EC and a reduced responsiveness to BR. EEG data suggest a GVG monotherapy induced mild "sedative" action on attentive tasks rather than on cognitive function.

Relations between EEG seizure morphology, interhemispheric spread, and mesial temporal atrophy in bitemporal epilepsy.

PURPOSE: A strong relation exists between lateralization of seizure onset in temporal-lobe epilepsy and atrophic mesial structures measured by volumetric magnetic resonance imaging (MRI). We examined whether this relation extended to subregions of the mesial temporal lobe and whether the trend for seizures to spread contralaterally could be related to the localization of atrophy. METHODS: We analyzed 362 seizures (with and without clinical signs) from 23 patients having bitemporal epilepsy in whom intracerebral electrodes were implanted for presurgical evaluation. Patients had measurements of hippocampal and amygdala volumes, including comparison with normal controls. We assessed on EEG the lateralization and localization of seizure onset and the trend to spread to the contralateral side (proportion of seizures that spread for each patient). We included all seizures, independent of the presence of clinical manifestations. These features were related to presence and localization of atrophy. RESULTS: Among the 19 patients with mesial atrophy, agreement between side of prevalent seizure onset and predominant atrophy was found in 10 (53%). From 99 seizures starting in a temporal lobe with atrophy limited to the hippocampus, 67% started simultaneously in amygdala and hippocampus, 20% in hippocampus, and 13% in amygdala. From 137 seizures starting in a temporal lobe with amygdala and hippocampal atrophy, 47% started in amygdala and hippocampus, 48% in hippocampus, and 5% in amygdala. The trend to spread was 45% to the most atrophic side and 62% to the normal or less atrophic side. CONCLUSIONS: When examining amygdala and hippocampus in this group of patients with bitemporal epilepsy, regions of seizure onset did not correspond to regions of predominant atrophy. The likelihood that seizures spread contralaterally was not influenced by atrophy in the region targeted by the spread. Precise relation between mesial temporal atrophy and seizures remain to be elucidated.

Effect of lamotrigine on EEG paroxysmal abnormalities and background activity: a computerized analysis.

1. Little information is available about the action of lamotrigine (LTG) on EEG paroxysmal abnormalities and background activity. On the contrary, several clinical trials have shown the therapeutic efficacy of the drug in preventing partial and generalized seizures. 2. We performed computerized EEG monitoring in 21 patients suffering from focal and generalized epilepsy before and 4 months after addition of LTG. The anticonvulsant modified the EEG ictal events by reducing their frequency and duration. A statistically significant decrease of the interictal spikes was observed. The decrease involved mainly the spreading component of the interictal events leading to a better spatial definition of the epileptic focus. 3. In the presence of LTG, generalized tonic-clonic attacks were completely controlled, whereas partial seizures were decreased. 4. The EEG background activity was not modified by the addition of the drug. 5. Our findings suggest a specific role for LTG in the generation and propagation processes of epileptiform activity without interfering with the EEG background activity.

Primary CNS demyelinating diseases in childhood: multiple sclerosis.

We report on five children (three female and two male, age span 11-16 years) with laboratory-supported definite multiple sclerosis or clinically definite multiple sclerosis, diagnosed on the basis of Poser and Paty criteria. All patients were subjected to serial clinical examinations, magnetic resonance investigations, CSF biochemical and immunological studies, and neurophysiological and neuropsychological assessments. Four of the five examined subjects underwent steroid treatment. Over a period of 3 years relapses have been observed in three of them. The first symptoms and signs of multiple sclerosis may be subtle and misleading; careful assessment of them may be crucial for an early diagnosis of the disease.

Development of myoclonus in patients with partial epilepsy during treatment with vigabatrin: an electroencephalographic study.

In the context of a study of the effects of gamma-vinyl-GABA (GVG) on seizure occurrence and on EEG abnormalities we present three cases with focal epilepsy in which new clinical and EEG paroxysmal manifestations were observed during GVG therapy. At that time, whereas an amelioration or no change in patients' habitual seizures were observed, myoclonic jerks appeared with related changes in the EEG paroxysmal abnormalities, represented by generalized polyspike and wave complexes. An electroclinical correlation was recorded in one case. These data indicate that, although occurring rarely, it is possible to have epileptic myoclonus during GVG treatment. Mechanisms underlying these manifestations are difficult to explain. Probably a shift in the anti/proconvulsant GABAergic balance towards the latter may compromise the therapeutic effect of GVG.

Sodium valproate and mental processes in newly referred epileptic patients. A computerized EEG study.

Seventeen epileptic patients suffering from generalized idiopathic epilepsy who underwent antiepileptic treatment with sodium valproate (NaVPA) for the first time were studied. The EEG was recorded at rest with eyes closed (EC), during blocking reaction, fixation and mental arithmetic tasks. The computerized EEG study, performed before and after therapy, utilized spectral analysis; data underwent statistical evaluation including ANOVA and correlation analysis. Before NaVPA therapy, a significant decrease of beta 1 and beta 2 relative power, compared with control subjects, was observed in epileptic patients at rest with EC, whereas fast activity increased during mental tasks. After treatment, no significant variations in fast activity were observed during tasks, with a pattern similar to that observed in the control population. Therefore, considering the effect of NaVPA primarily on fast activity, which reflects rather well preserved mental functioning processes, it is possible to hypothesize that the drug interferes positively with mental activities.

Quantitative EEG evaluation in normal elderly subjects during mental processes: age-related changes.

Computerized EEG study was performed on 39 healthy elderly subjects (50-90 years), divided into two cohorts of increasing age (old, older) and on a group of 21 young controls. The EEG was recorded at rest, with eyes closed (EC) and during blocking reaction (BR), fixation (FIX) and mental arithmetic (MA) tasks. At rest with EC, the only significant variation was an increase of beta 1 relative power in old subjects which was positively correlated with age. During the performance of the mental tasks, in the elderly population when compared to young controls, the slow activity decreased slightly or was not significantly modified, while the alpha reactivity progressively decreased, showing a negative correlation with age in the older group. Beta 2 increased significantly in elderly subjects during BR and FIX but such change was less consistent with increasing age. Data show that at rest, the EEG in the elderly population differs only from that of young controls by showing a more pronounced fast activity, while only during mental processes is it possible to evidence changes that can be utilized as physiological "markers" of normal aging.