Epileptic Subjects Research Articles

GABA B1a, GABA B1b AND GABA B2 mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy

The aim of this study was to investigate the mRNA expression of the two GABA B1 receptor isoforms and the GABA B2 subunit, in human postmortem control hippocampal sections and in sections resected from epilepsy patients using quantitative in situ hybridisation autoradiography. Utilising human control hippocampal sections it was shown that the oligonucleotides employed were specific to the receptor. Hippocampal slices from surgical specimens obtained from patients with hippocampal sclerosis and temporal lobe epilepsy were compared with neurologically normal postmortem control subjects for neuropathology and GABA B mRNA expression. Neuronal loss was observed in most of the hippocampal subregions, but in the subiculum no significant difference was detected. The localisation of GABA B1a and GABA B1b isoform mRNAs in human control hippocampal sections supported and extended earlier studies using the GABA B1 pan probe, which does not distinguish between the two GABA B1 isoforms. Moreover, the GABA B2 mRNA location confirmed the heterodimerisation of the receptor. Thus, although there was an apparent correlation between GABA B1b and GABA B2, GABA B1a exhibited no such relationship. GABA B1b and GABA B2 showed a similar intensity of expression whilst GABA B1a displayed a lower hybridisation signal. Comparison of the expression of the three mRNAs between control and epileptic subjects showed significant decreases or increases in different hippocampal subregions. GABA B isoforms and subunit mRNA expression per remaining neuron was significantly increased in the hilus and dentate gyrus. These results demonstrate that altered GABA B receptor mRNA expression occurs in human TLE; possibly the observed changes may also serve to counteract ongoing hyperexcitability.

Basic mechanisms of central rhythms reactivity to preparation and execution of a voluntary movement: a stereoelectroencephalographic study.

To localize the sources of mu, beta and gamma rhythms and to explore the functional significance of their reactivity. We used the method of quantification of event-related desynchronization (ERD) and synchronization (ERS) to analyze the reactivity of intracerebral rhythms recorded in stereoelectroencephalography within the sensorimotor areas during the preparation and the execution of a simple self-paced hand movement. We recorded 3 epileptic subjects who were explored before a surgical treatment. An ERD of mu and beta rhythms has been recorded before the movement onset in the precentral gyrus, spreading then to the postcentral gyrus and to the frontal medial cortex. The frontal lateral cortex was inconstantly involved during the movement. The movement offset was followed by an important and focused beta ERS which was found within the pre- and post-central gyrus and the frontal medial cortex. Within the beta band, we observed several narrower bands with different reactivities and locations. Focused gamma reactivity was also found in the precentral and postcentral gyri. The reactivities of mu and beta rhythms are different but their locations overlap. Mu ERD is a diffuse phenomenon that reflects the activation of all the sensorimotor areas during a simple movement. Beta band is likely to be composed of different rhythms with different functional significance. The primary motor area seems to contain two distinct areas with different reactivity to the movement preparation and execution.

The Role of Hypnosis in the Detection of Psychogenic Seizures

In this preliminary clinical investigation, hypnosis was used in the differential diagnosis of epileptic versus psychogenic seizures (PS). Eight patients with a clinical profile suggesting the presence of PS were given a hypnotic suggestion in which they had to go back in time to the exact moment of their last seizure. They were then asked to concentrate their attention on any unusual feeling or bodily sensation. All 8 patients presented a PS during the age regression protocol. In 6 cases, independent testimony from family members corroborated the morphological similarity of the induced attack and the ones presented in their natural environment. Also, the seizures ended abruptly after a command was given to stop them. A control group of 5 epileptic subjects did not present any signs of discomfort or seizure behavior during the hypnotic protocol. It is argued that a simple procedure as the one described in this investigation can be useful as a diagnostic tool in the differentiation of epileptic from PS attacks.

Heart rate variability during sleep in children with partial epilepsy.

Alterations in autonomic control of cardiac activity in epileptic patients have been reported by several studies in the past, and both ictal and interictal modifications of heart rate regulation have been described. Alterations of autonomic control of cardiac activity can play an important role in sudden unexplained death in patients with epilepsy (SUDEP). However, the presence of specific changes in heart rate variability (HRV) during sleep, not correlated with seizures, has not been assessed in children with epilepsy; for this reason, we evaluated features of cardiac autonomic function during sleep without ictal epileptiform electroencephalogram (EEG) activity in a group of children with partial epilepsy. Eleven patients (five males and six females; mean age 11.5 years, SD: 3.65 years) affected by partial epilepsy were admitted to this study; 11 normal subjects (five males and six females; mean age 12.9 years, SD: 2.72 years) served as a control group. All subjects slept in the laboratory for two consecutive nights. The data were analyzed during the second night. Sleep was polygraphically recorded [including one electrocardiography (ECG) channel] and signals were digitally stored. A series of 5-min ECG epochs were chosen from each sleep stage, during periods without evident ictal epileptiform activity in the EEG. Electrocardiography signals were analyzed for automatic detection of R-waves and, subsequently, a series of time- and frequency-domain measures were calculated. Epileptic subjects tended to show an overall lower HRV in both time- and frequency-domain parameters, principally during rapid eye movement (REM) sleep and, to a lesser extent, during sleep stage 2. Among the different bands, this decrease was most evident for the high-frequency band (HF) absolute power. For this reason, the ratio between the low-frequency band (LF) and HF was always higher in epileptic patients than in normal controls and the difference was statistically significant during sleep stages 3 and/or 4 and REM sleep. Our results indicate that during sleep, a particular condition of basal modification in autonomic characteristics occurs (mostly during REM sleep) in partial epilepsy patients. This finding might represent an important factor contributing to the complex mechanism of SUDEP which takes place most often during sleep and supports the need of studying HRV specifically during this state in subjects with seizures.

Vagus nerve stimulation for treatment of medically intractable seizures. Evaluation of long-term outcome

Vagus nerve stimulation (VNS) constitutes an adjunctive, modern management of medically intractable seizures, especially when surgery is inadvisable. Objective: To evaluate the long-term results as regards efficacy, safety and tolerability of VNS in epileptic subjects, with focal and/or generalised seizures, refractory to old and new AEDs, without indication for resective surgery. Patients: 51 epileptic subjects (30 males, 21 females), aged 7–49 years, have been implanted so far. Results: The results refer to the 47 subjects with a follow-up longer than 6 months. 22 (46.8%) of them had a greater than 50% reduction in seizure frequency, with a more than 75% reduction in 6. No significant difference was found in relation to type of seizures. The efficacy maintained steadily over time during the follow-up (mean 26.4 months). Twelve out of the 47 subjects had an improvement in alertness, attention and psychomotor activity. Complications were observed in 5 cases, leading to removal of the stimulator in 2. A moderate vocal hoarseness (40.4%), paresthesia (6.3%), pharingodinia and cough (4.3%) were the registered adverse events. Conclusions: Our results confirm that VNS is effective, safe and well tolerated and constitutes an alternative treatment for pharmacoresistant epileptic seizures.

Psychostimulants and Epilepsy

The aim of this article is to review the literature on the effects of psychostimulants in epileptic subjects in order to reach a consensus statement regarding the use or abuse of these substances. Psychostimulant substances have been considered the drugs that share the ability to produce excitation of the CNS leading to convulsions. The stimulation may be at cortical, brainstem, or spinal levels. In this article, the following cortical stimulants are analyzed and discussed: cocaine, amphetamine and related agents, caffeine, cannabinoids, and psychedelic drugs. This review is based on research done using pharmacological textbooks and Medline. The use of cocaine is associated with the occurrence of seizures. The reported frequency varies from 1% to 40% of addicted subjects, based on the typology of the considered study. Amphetamines and related drugs rarely induce epileptic seizures at therapeutic doses, but seizures may occur after the first dosing. Caffeine at high doses may induce epileptic seizures because of its adenosine receptor-antagonizing properties. Marijuana, at variance with other psychostimulants, owing to its serotonin-mediated anticonvulsant action, could have a medical use for the treatment of epilepsy. Psychedelic compounds rarely induce epileptic seizures, but the most common clinical CNS complication after ingestion of ecstasy is the occurrence of seizures. The use of psychostimulants, except for marijuana, can induce single or multiple seizures in healthy subjects.

Changes in Lateralized Memory Performance in Subjects with Epilepsy Following Neurofeedback Training

Both seizure reduction and neuropsychological improvements have been reported following neurofeedback training directed to normalization of the sensorimotor EEG. These findings could be interpreted as nonspecific effects rather than specific changes brought about by EEG training. The present study demonstrated neuropsychological changes of a selective nature that would be difficult to interpret as nonspecific. Epileptic subjects with unilateral temporal lobe lesions were administered memory tests prior to EEG training, after control training, and after sensorimotor EEG normalization training. Successfully trained subjects showed exclusive improvement on memory tasks specific to the hemisphere contralateral to their lesion, and no improvement on memory tasks specific to the hemisphere with the lesion. Such selective changes are difficult to interpret as nonspecific effects of participating in a study, and would seem to require genuine alteration of neural substrates as a result of EEG training.

Generalized dimension of the intersection between EEGs.

The generalized dimension defined by [Mandelbrot (1995) J Fourier Anal Appl special J.P. Kahane issue: 409-432] was applied to studying the interrelationship between various parts of human cerebral cortex in different functional conditions. Taking EEG signals from different brain areas as different sets, the generalized dimensions of their intersections were calculated to describe the interrelationship between them. The results showed that the generalized dimensions of intersections in different brain states decreased according to the following order: rest with eyes open, closed, light sleep, and deep sleep. The generalized dimensions of intersections related to the left or right temporal lobe were higher than the others when the subjects was doing mental arithmetic, and there was a decrease when the subjects listened to soft classical music. In addition, it was found that there was a noticeable difference in singular spectra between epileptic patients and normal subjects, irrespective of whether the epileptic patient was experiencing a seizure or not.

Multiple microelectrode-recording system for human intracortical applications

The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred from multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system meeting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region.

Emotional Cognition without Awareness after Unilateral Temporal Lobectomy in Humans

To investigate the function of the amygdala in human emotional cognition, we investigated the electrodermal activity (EDA) in response to masked (unseen) visual stimuli. Six epileptic subjects were investigated after unilateral temporal lobectomy. Emotionally valenced photographic slides (10 negative, 10 neutral) from the International Affective Picture System were presented to their unilateral visual fields under either subliminal or supraliminal conditions. An interaction between hemispheres and emotional valences was found only under the subliminal conditions; greater EDA responses to negative stimuli compared with neutral ones were observed when stimuli were presented to the intact hemispheres. The findings suggest that nonconscious emotional processing is reflected in EDA in a different manner from conscious emotional processing. Medial temporal structures, including the amygdala, thus appear to play a critical role in the neural substrates for this automatic processing.

Genetically Epilepsy‐Prone Rats (GEPRs) in Drug Research

ABSTRACTTwo independently derived, inbred strains of genetically epilepsy‐prone rats (GEPRs) have been developed, the moderately epileptic GEPR‐3 and the more severely epileptic GEPR‐9. Seizures expressed by GEPRs model human generalized tonic/clonic seizures (GTCSs) and partial seizures secondarily generalized to tonic/clonic seizures. Several types of existing antiepileptic drugs have been tested in the GEPR model. Without exception, the seizure suppressing properties of these drugs occur both in GEPR‐3 s and GEPR‐9s. The differential responses of the two GEPR strains separate the antiepileptic drugs into three categories: (1) those effective in GTCSs and partial seizures; (2) those that are additionally effective in absence seizures; and (3) those effective in absence seizures but not in convulsive seizures. No known false positives have yet been detected in GEPR tests. In addition to the utility of the seizures expressed by GEPRs in drug development paradigms, these animals also have potential in the search for drugs that are specifically “antiseizure predisposition” rather than merely anticonvulsant. Heretofore, worldwide drug development efforts have emphasized the discovery of drugs that are anticonvulsant in nonepileptic animals. As might have been anticipated, these same drugs have proven to be anticonvulsant in epileptic subjects. Paradigms that would detect drugs with the capacity to correct the biological determinants of predisposition are in early stages of application. Kindling seizures provide a means to identify drugs that might be useful in correcting stimulus‐induced seizure predisposition. The GEPR and other genetic models of the epilepsies provide models for developing treatments to correct genetically determined seizure predisposition. Emerging evidence supports the hypothesis that GEPRs model comorbidity between the epilepsies and affective disorders. Understanding the basis of this comorbidity has the potential to enable the development of treatments that reverse the underlying abnormalities of the coexisting disorders. Because human epilepsies and affective disorders are environmentally and genetically complex, the abnormalities of the GEPR probably will not account for all predispositions leading to this comorbidity.

Evaluation of sleepiness in epilepsy

Excessive daytime sleepiness often complicates the clinical picture of epilepsy, facilitating the occurrence of seizures and aggravating cognitive disabilities and/or behavioral problems. Thus it further adversely affects social and working activities of epileptic subjects. Both unstructured and structured clinical reports documented a not negligible proportion of epilepsy patients suffering from excessive daytime sleepiness. Studies based on neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test revealed a degree of daytime sleepiness tendency in epilepsy patients greater than that they subjectively estimate. Antiepileptic drugs play a remarkable role in determining drowsiness in epilepsy patients and they are generally viewed as the only cause of sleepiness in these patients. However excessive daytime sleepiness has been documented in epilepsy patients before starting any drug treatment or after its discontinuation. Both clinical and neurophysiological studies have clearly documented the possible role of seizure occurrence and of co-morbidity as determinants of excessive daytime sleepiness in epilepsy patients. Nocturnal sleep fragmentation and daytime sleepiness have been reported in temporal lobe and frontal lobe epilepsy, namely nocturnal frontal lobe epilepsy. Some recent reports have stressed that obstructive sleep apnea and periodic limb movements during sleep can significantly account for sleepiness complaints in epilepsy patients; most of the antiepileptic drugs can worsen obstructive sleep apnea. To date the evaluation of daytime sleepiness of epilepsy patients in clinical practice has been based mainly or exclusively on clinical reports. To improve our understanding of this symptom in epilepsy patients, the use of standardized sleepiness scales should be encouraged. Patients with persistent daytime sleepiness without a clear cause-and-effect relationship with antiepiletic drugs treatment or in whom a coincident sleep pathology is suspected, should be investigated by means of neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test.

Agranulocytose liée à la prise de miansérine: une complication à redouter chez le sujet âgé

Epileptic men may experience hormonal changes that may alter semen quality and sexual function. Alterations in male sexual and reproductive parameters may also be due to treatment with antiepileptic drugs to control seizures.To evaluate serum hormone concentrations, semen quality, the frequency of sexual intercourse (FSI), and erectile function in men with epileptic seizures controlled by carbamazepine (CBZ).The five‐question form of the International Index of Erectile Function (IIEF‐5), and semi‐structured questionnaire.One hundred and eighteen men, aged 18–45 years, were included in this controlled, cross‐sectional study: 63 men taking CBZ (epileptic group) were compared to 55 healthy men (control group). Blood sample was collected to determine hormones concentrations. Erectile function and the frequency of sexual relations were assessed by using questionnaires. Sperm morphology was analyzed by examining the quality of the head, intermediate part and tail of the spermatozoa.Using the IIEF‐5, we observed a significant association between erectile dysfunction (ED) and groups (P < 0.01), where epileptic men had 17.33 (95% CI 3.59, 83.52) odds to have erectile dysfunction. Adjusted odds ratio to group considering luteinizing hormone, prolactin, Serum total testosterone, androstenedione, and dehydroepiandrosterone, androstenedione levels and free androgen index, we observed only group effect where epileptic men had 10.47 (95% CI 2.75, 39.83) odds to have FSI < 3 times a week. Sperm vitality was altered in 27% of the epileptic subjects compared with 5.4% of the control group (P < 0.002). Sperm motility differed significantly between groups, with A + B motility ≤50% observed in 98.4% of the epileptic group and in 85.4% of the control group (P < 0.01). Sperm morphology <14% was observed in 93.7% of the epileptic men, compared with 34.6% of the controls (P < 0.001). CBZ users, showed less sexual intercourse then controls (P ≤ 0.001).Epileptic men taking CBZ present with changes in hormonal levels, altered semen quality, ED, and a reduction in coital frequency. Reis RM, de Angelo AG, Sakamoto AC, Ferriani RA, and Lara LAS. Altered sexual and reproductive functions in epileptic men taking carbamazepine. J Sex Med **;**:**–**.

Burden of epilepsy: the Ontario Health Survey.

Few data exist on the frequency and burden of epilepsy in Canada and on the impact of self-reported epilepsy in the general population. We assess the frequency, general health, psychosocial function, and health care resource use among self-identified epileptic persons in the general population. The 1990 Ontario Health Survey is an omnibus, extensive health survey of 61,239 subjects representing the Ontario population. Self-reported epileptic subjects are compared with three groups, i.e., those with > or = 1 other chronic illnesses, the general population, and those with no health problems. The point prevalence of self-reported epilepsy was 5.8 per 1,000 population, a figure similar to that of active epilepsy in other studies. Quality of life, family function and social support were worse in epileptic than in other chronically ill subjects. Similarly, the epilepsy population had more disability days and limitations in activities, and lower annual income than all other groups, including the chronically ill. Accidents were no more common among epileptic subjects than among controls. Epileptic persons were high users of health care resources, including hospitalization, emergency room, psychological/social work, nursing services and telephone contact with health professionals. Barriers to health care were experienced infrequently. Small area variations in health status and care are explored. The health profile of self-reported epileptic subjects is similar to that obtained in studies involving defined epilepsy patients. In the general population, self-identification as having epilepsy carries a significant burden of illness, reflected in poorer health, psychosocial function, and quality of life, and higher health care resource use.

Enhanced gamma (30–150 Hz) frequency in the human medial temporal lobe

We performed fast Fourier transformation power spectral analysis of the electrocorticogram in human medial temporal lobe during wakeful rest in six epileptic subjects. Compared with the electrocorticogram wave in the basal temporal lobe, which showed monotonic decline of spectral power across the frequency axis, the electrocorticogram wave in the parahippocampal gyrus was enhanced (or did not decline) in the gamma frequency range (30–150 Hz) in all subjects. Although it has been suggested that electrical oscillations of the hippocampus have functional roles in higher brain functions, namely learning and memory, the knowledge of hippocampal oscillations is largely limited to animal studies. The present results demonstrate that fast frequency oscillation is also present in the human medial temporal lobe, which has been reported in animal hippocampi. They also demonstrate the importance of recording very fast field potentials in human electrocorticograms. This fast oscillation is likely to play important functional roles related to learning and memory, possibly to induce long-term potentiation in the human medial temporal lobe.

Repetitive sleep starts in neurologically impaired children: an unusual non‐epileptic manifestation in otherwise epileptic subjects

ABSTRACT Sleep starts, also called hypnagogic or hypnic jerks, are bilateral, sometimes asymmetric, usually single, brief body jerks that coincide with sleep onset. We describe sleep starts occurring repetitively in three epileptic children with spastic‐dystonic diplegia and mental retardation. Repetitive sleep starts began at age 18 months in two children and at 9 months in the third. All three children had had feto‐neonatal asphyxia; two presented with spastic and one with dystonic tetraparesis. One had West syndrome and two had partial motor seizures in the first year of life. Seizures were controlled in all three patients by antiepileptic drug therapy. Video/EEG recordings of all the children during the afternoon nap revealed clusters of sleep starts during the transition between wakefulness and sleep. Cluster lasted 4‐15 min and comprised from twenty to twenty‐nine contractions. The EEG counterpart of the event sometimes showed an arousal response, at times inducing complete awakening. Repetitive sleep starts should be recognized and clearly differentiated from epileptic seizures, especially if they appear in epileptic subjects. In neurologically compromised patients, they could represent an intensification of an otherwise normal event, due to the lack of strong inhibitory influence of the pyramidal tract resulting from the pyramidal lesion.

Age-related fractures in people with intellectual disability and epilepsy.

The present paper describes age-related fractures in 68 people with intellectual disability and epilepsy (39 females and 29 males). A higher incidence of fractures in epileptic subjects (26%) was noted when they were compared with non-epileptic patients (15%). In the sample of 263 epileptics (121 females and 142 males), a higher number of females (32%) sustained fractures than their male counterparts (20%). The peak period of all fractures is between 40 and 49 years of age. The highest incidence of fractures in females occurred during the periods from 10 to 19 and 40 to 49 years, while the peak was between 30 and 39 years for males. The causes of fractures and preventative measures are discussed, and further avenues for research are indicated.

Formal Thought Disorder and Psychopathology in Pediatric Primary Generalized and Complex Partial Epilepsy

To examine whether formal thought disorder and psychopathology occurred in children with complex partial seizures (CPS) rather than children with primary generalized epilepsy with absences (PGE) or nonepileptic children. Formal thought disorder was coded in 30 children with CPS, 24 children with PGE, and 61 nonepileptic children, and structured interview-based psychiatric diagnoses were obtained for the epileptic subjects. The CPS subjects had significantly more illogical thinking than the PGE and nonepileptic children. The severity of their illogical thinking was related to global cognitive dysfunction and a schizophrenia-like psychosis. Age of onset and seizure control, however, were significantly associated with the severity of illogical thinking in the PGE group. One or more psychiatric diagnoses were found in 63% of the CPS and 54% of the PGE patients, particularly if they had global cognitive deficits. Illogical thinking, associated with cognitive dysfunction or schizophrenia-like symptoms, might be a feature of pediatric CPS. Psychopathology might be related to global cognitive dysfunction in pediatric CPS and PGE.

Loss of Calbindin-D 28K immunoreactivity from dentate granule cells in human temporal lobe epilepsy

The loss of the calcium binding protein, Calbindin-D 28k, from dentate granule cells has been observed in different animal models of epilepsy and in ischaemia. This decrease is accompanied by alterations of calcium and N-methyl- d-aspartate currents, which may explain the hyperexcitability of the dentate gyrus. In the present study, we found a loss of Calbindin immunoreactivity from over 90% of the dentate granule cells in lobectomy samples from four of 10 temporal lobe epilepsy patients. In another four patients, over 50% of dentate granule cells were devoid of Calbindin immunoreactivity, whereas the remaining two cases showed a 20–30% decrease. Electron microscopy revealed a normal ultrastructure both in Calbindin-containing and Calbindin-negative granule cells. Both Calbindin-positive and -negative mossy fibre collaterals participated in supragranular sprouting. As inferred from data in animal models, the lack of Calbindin in dentate granule cells of human epileptic subjects is likely to result in hyperexcitability of the dentate gyrus, which may then function as a “motor” for seizures.

Transcranial magnetic stimulation in partial epilepsy: drug-induced changes of motor excitability.

Single-pulse transcranial magnetic stimulation (s-TMS) with recording of motor evoked potentials (MEPs) from thenar muscles of both hands was performed on 84 patients with cryptogenic partial epilepsy and 50 healthy controls. We analyzed the cortical latency (CL), central conduction time (CCT), and threshold intensity (TI) required to elicit liminal MEPs at rest. In the patients, CL and CCT were normal, but TI was significantly higher than in the controls. Of the 84 patients, 65 were taking one or more antiepileptic drugs and 19 were untreated. The untreated patients had a significantly lower TI than the treated patients. In the treated patients, the TI increase paralleled the number of drugs taken. Additionally, in 2 subgroups of patients undergoing major modifications of antiepileptic treatment, TI dropped after partial withdrawal of medication and increased following the commencement of therapy. The results suggest that anticonvulsants depress the excitability of human motor pathways in epileptic subjects.