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PubMed2004

Discontinuation and duration of antiepileptic drug therapy: a retrospective study of factors for specific epileptic syndromes.

PURPOSE: To study factors associated with discontinuation of antiepileptic drugs (AEDs) in idiopathic generalized epilepsy (IGE) and symptomatic/cryptogenic localization-related epilepsy (S/CLRE) METHODS: For the IGE study, 71 patients who were able to discontinue their AED (discontinued-IGE group) were compared to 71 patients who continued AED therapy (continued-IGE group) and 20 patients with seizure relapse after discontinuing AED (relapsed-IGE group). For S/CLRE, 90 patients who were able to discontinue AED (discontinued-S/CLRE group) were compared to 90 patients who continued AED (continued-S/CLRE group) and 76 patients with benign childhood epilepsy with centrotemporal spikes who were able to discontinue AED (discontinued-BECTS group). RESULTS: Compared to the continued-IGE group, the discontinued-IGE group showed a weaker seizure propensity, better response to AEDs, more frequent epileptiform discharge suppression, and lower frequency of generalized tonic-clonic seizures (GTCs). Compared to the relapse-IGE group, the discontinued-IGE group had more frequent epileptiform discharge suppression. The discontinued-S/CLRE group showed a weaker seizure propensity, better response to AEDs, more frequent epileptiform discharge suppression, and less frequent symptomatic signs compared to the continued-S/C LRE group. Notably, the age at epilepsy onset was not a critical factor for discontinuing AEDs in both IGE and S/CLRE. Although the discontinued-S/CLRE group had more frequent symptomatic signs, older age at epilepsy onset and less frequent epileptiform discharge suppression than the discontinued-BECTS group, no difference was found in seizure propensity and response to AEDs between the two groups. CONCLUSIONS: Seizure propensity, epileptiform discharge, and response to AEDs should be considered to predict the possibility of terminating AED therapy in IGE or S/CLRE. In addition, attention should be paid to seizure pattern in IGE and symptomatic signs in LRE.

Adolescent↗

PubMed1996

Eyelid myoclonia with absences in adults: a clinical and video-EEG study.

We report clinical and video-EEG findings in 11 adults with the syndro me of eyelid myoclonia with absences (EMA). Prevalence was 2.7% among all epilepsies and 12.9% among idiopathic generalized epilepsies (IGE) with typical absences. All patients with EMA were women, with a mean age of 30.9 years and a mean age of 7.8 years at reported onset of eyelid myoclonia. The characteristic seizures, studied with video-EEG in 10 patients, began with and were mainly manifested by eyelid myoclonia, either alone if brief (< or = 2 s) or with associated mild impairment of consciousness if longer. The ictal EEG was characterized by polyspike and slow waves at 3-6 Hz. Ictal clinical and EEG manifestations occurred mainly after eye closure and were inhibited by total darkness. All patients were photosensitive, but photosensitivity decreased with age; nonpatient had self-induced seizures. Infrequent generalized tonic-clonic seizures (GTCS) occurred in all but the youngest patient; they were usually infrequent and were precipitated mainly by flickering lights, sleep deprivation, fatigue, and menstruation. Mild myoclonic jerks of the upper limbs occurred in 6 patients. Eyelid myoclonia was resistant to medication and persisted despite control of other seizures.

Adolescent↗

PubMed1994

Central cardio-autonomic disorganization in interictal states of epilepsy detected by phase space analysis.

In a study of central autonomic organization in interictal states of idiopathic generalized epilepsy, we measured the spontaneous oscillations of the heart rate in 8 young epileptics with normal interictal electroencaphalograms (EEGs), 6 young epileptics with epileptiform discharges in the interictal EEGs and 8 healthy controls. The temporal structure of the heart rate (HR) dynamics was operationalized through the estimation of the largest Lyapunov exponent (LLE). For all patients and controls, the LLEs of the HR dynamics were positive, indicating chaotic oscillations. The patients with interictal epileptiform discharges showed significantly lower LLEs of the HR dynamics than the epileptics with normal EEGs and the healthy controls. By comparison, the values of the epileptics with normal EEGs und those of the healthy controls did not differ significantly. This finding suggests a more rigid and thus less adaptable central cardio-autonomic organization in epileptics with epileptiform discharges in the interictal EEG.

Adult↗

PubMed2001

A novel gene causing a mendelian audiogenic mouse epilepsy.

Frings mice are a model of generalized epilepsy and have seizures in response to loud noises. This phenotype is due to the autosomal recessive inheritance of a single gene on mouse chromosome 13. Here we report the fine genetic and physical mapping of the locus. Sequencing of the region led to identification of a novel gene; mutant mice are homozygous for a single base pair deletion that leads to premature termination of the encoded protein. Interestingly, the mRNA levels of this gene in various tissues are so low that the cDNA has eluded detection by standard library screening approaches. Study of the MASS1 protein will lead to new insights into regulation of neuronal excitability and a new pathway through which dysfunction can lead to epilepsy.

Amino Acid Sequence↗

PubMed2003

Absence of mutations in major GEFS+ genes in myoclonic astatic epilepsy.

Myoclonic astatic epilepsy (MAE) is a genetically determined condition of childhood onset characterized by multiple generalized types of seizures including myoclonic astatic seizures, generalized spike waves and cognitive deterioration. This condition has been reported in a few patients in generalized epilepsy with febrile seizures plus (GEFS+) families and MAE has been considered, like severe myoclonic epilepsy of infancy (SMEI), to be a severe phenotype within the GEFS+ spectrum. Four genes have been identified in GEFS+ families, but only three (SCN1A, SCNlB, GABRG2) were found in MAE patients within GEFS+ families. We analysed these three genes in a series of 22 sporadic patients with MAE and found no causal mutations. These findings suggest that MAE, unlike SMEI, is not genetically related to GEFS+. Although MAE and SMEI share the same types of seizures, only SMEI patients are sensitive to fever. This is probably its main link to GEFS+. A different family of genes is likely to account for MAE.

Child, Preschool↗

PubMed2001

Seizure frequency affects event-related potentials (P300) in epilepsy.

To analyse the effect of epilepsy an P300 event-related potentials we studied 27 patients with idiopathic generalized epilepsy (IGE), 13 patients with temporal lobe epilepsy (TLE) and 60 normal controls. The prolongation of P300 latencies was highly cor related with increasing age in controls but not epileptic patients. The age-corrected P300 latency used in this study was actual P300 latency-predicted P300 latency (predicted P300 (msec)=306.20+0.79 age, P=0.001, R2=0.32). By using ANOVA analysis, the age-corrected latencies of P300 were significantly longer in TLE patients (19.72+/-47.82 msec, mean+/-SD) than in IGE patients (10.97+/-36.97 msec) and controls (0.23+/-20.28 msec). Likewise, significantly prolonged P300 latencies were seen in the epileptic patients with a seizure frequency more than 400 times (37.21+/-47.50 msec). The multivariate-adjusted odds ratio for those who had TLE was 10.97 (95% CI=3.99 - 30.14 ) in the prolonged latencies of P300 compared with that of IGE patients. The odds ratio of longer latencies of P300 was 7.43 (95% CI=2.75 - 20.08) among those who had a high seizure frequency (> or =400 times) compared with those who had a low seizure frequency. No interaction between TLE and high frequency of attacks was found. The age at onset of seizure and duration of illness was not associated with P300 latency prolongation. From the above results, we might infer that the seizure type of TLE and a high frequency of seizure are two major independent precipitate factors for abnormal latencies of P300 in the epileptic patients.

Adult↗

PubMed1995

Preferences concerning epilepsy education: opinions of nurses, physicians, and persons with epilepsy.

The purpose of this study was to determine whether patients with epilepsy treated in outpatient settings would prefer to receive information about epilepsy and its treatment from physicians, nurses or other health care professionals. A second purpose of this study was to determine which health care professionals physicians and nurses believe are able to teach patients about epilepsy. Participants in this study included 59 persons with epilepsy, 73 nurses caring for people with epilepsy, and 38 neurologists and neurosurgeons. Results indicated that people with epilepsy generally prefer physicians to teach about epilepsy and its treatment. Nurses received the most responses about teaching general lifestyle information. Nurses and physicians provided very similar responses to inquiries about which health care professionals were able to teach information about epilepsy. Nurse and physician participants agreed that nurses are the preferred provider of information related to psychological concerns of patients and physicians are the preferred provider of information about the cause and treatment of epilepsy.

Adult↗

PubMed2000

[Cerebrogenic disorders of cardiac rhythm and conductivity in epilepsy patients].

51 epileptic patients aged 16-32 years without any signs of cardiovascular pathology were examined. The primary generalized epilepsy was diagnosed in 24 cases while a partial one--in 27 patients. Were examined a state of the heart (echo- and electrocardiography, Holter's monitoring of ECG), of the brain (computed echoencephalography, visual evoked potentials) and of the autonomic nervous system (variability of cardiac rhythm, autonomic tonus). A control group included 15 healthy individuals. Significantly higher prevalence of the disorders of the cardiac rhythm and conduction was found in patients with epilepsy as compared with a control group (p < 0.001). More frequently there were sino-atrial blocks of the II degree of the I type (p < 0.01), heterotopic rhythms (p < 0.05), supraventricular extrasystole (p < 0.1), supraventricular paroxysmal tachycardia (p < 0.05), supraventricular migration of the pacemaker (p < 0.01). It was found that close relationship between cardiac arrhythmias and epilepsy was mobided by a complex of pathophysiologic mechanisms. Among them a leading role belongs to dysfunction of suprasegmental autonomic centers with a predominant activation of sympathetic or parasympathetic departments of the autonomic nervous system. Significant arrhythmogenic factors appeared to be: presence of organic damages in the brain, frequency of epileptic fits, dysfunction of suprasegmental autonomic centers with activation of cerebral ergotropic systems.

Adolescent↗

PubMed2006

Phenotypes and genotypes in epilepsy with febrile seizures plus.

In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.

Adolescent↗

PubMed2006

A new paradigm of channelopathy in epilepsy syndromes: intracellular trafficking abnormality of channel molecules.

Mutations in genes encoding ion channels in brain neurons have been identified in various epilepsy syndromes. In neuronal networks, "gain-of-function" of channels in excitatory neurotransmission could lead to hyper-excitation while "loss-of-function" in inhibitory transmission impairs neuronal inhibitory system, both of which can result in epilepsy. A working hypothesis to view epilepsy as a disorder of channel or "channelopathy" seems rational to explore the pathogenesis of epilepsy. However, the imbalance resulting from channel dysfunction is not sufficient to delineate the pathogenesis of all epilepsy syndromes of which the underlying channel abnormalities have been verified. Mutations identified in epilepsy, mainly in genes encoding subunits of GABA(A) receptors, undermine intracellular trafficking, thus leading to retention of channel molecules in the endoplasmic reticulum (ER). This process may cause ER stress followed by apoptosis, which is a known pathomechanism of certain neurodegenerative disorders. Thus, the pathomechanism of "channel trafficking abnormality" may provide a new paradigm to channelopathy to unsolved questions underlying epilepsy, such as differences between generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy, which share the causative genetic abnormalities in the same genes and hence are so far considered to be within the spectrum of one disease entity or allelic variants.

Codon, Nonsense↗

PubMed2026

Valproate vs levetiracetam in juvenile myoclonic epilepsy: systematic review and meta-analysis.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome with onset typically in adolescence and a chronic course requiring long-term antiseizure medications (ASMs). Valproate (VPA) is the most effective treatment for seizure control in JME but use is limited by metabolic, cognitive, and teratogenic adverse effects (AEs). Levetiracetam (LEV) is an alternative ASM when VPA is contraindicated or not tolerated. Comparisons of the efficacy and long-term tolerability of VPA and LEV remain limited. METHODS: We conducted a systematic review and meta-analysis using PRISMA guidelines and the Cochrane Handbook. We searched PubMed, Embase, and the Cochrane Library from inception through January 2026 for studies in JME patients comparing LEV and VPA, and included randomized controlled trials and comparative observational studies with ≥ 6 months of follow-up. Primary outcomes were seizure remission and ASM failure or treatment discontinuation. Secondary outcomes included, memory impairment, weight gain or obesity, dizziness, and overall AEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven studies encompassing 1,009 patients were included. VPA was associated with higher pooled seizure remission rates compared with LEV (344 of 574 vs. 169 of 390; RR 1.44, 95% CI 1.27-1.63); however, substantial heterogeneity (I2 = 88.4%) limits confidence in this finding. VPA was associated with a lower risk of drug failure or treatment discontinuation (RR 0.68, 95% CI 0.54-0.86), with no heterogeneity (I2 = 0.0%). VPA was also associated with a higher risk of memory impairment (RR 5.37, 95% CI 2.05-14.04; I2 = 74.5%) and weight gain or obesity (RR 6.40, 95% CI 3.64-11.26; I2 = 35.9%). No significant differences were observed between treatments regarding dizziness (RR 0.91, 95% CI 0.61-1.37; I2 = 21.2%). Sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSION: VPA was associated with higher seizure remission rates and lower treatment discontinuation compared with LEV; however, these findings must be interpreted with caution given the substantial heterogeneity, the predominance of observational studies, and the serious risk of bias identified in most included studies VPA also demonstrated lower rates of treatment discontinuation, despite a higher burden of cognitive impairment and weight gain. No relevant differences were observed regarding dizziness. Large-scale randomized trials with standardized outcome definitions and longer follow-up are needed to define the comparative risk-benefit profiles of LEV and VPA in JME.

Humans↗

PubMed1994

Interictal language fluency in temporal lobe epilepsy.

Mild language production difficulties, particularly in confrontation naming, have been documented previously in patients with left temporal lobe epilepsy (LTLE). These difficulties, however, do not seem to be reflected in the conversational speech of these patients. In order to compare speech fluency in patients with left and right temporal lobe epilepsy (RTLE) experimentally, we studied global pause-to-speech ratios in patients with unilateral temporal lobe epilepsy, using cases with primary generalized epilepsy (PGE) as controls. We hypothesized that left-sides cases would exhibit longer pause durations than right-sided cases. Speech samples were elicited by asking subjects to describe five different New Yorker cartoons, with three repetitions of each description. Phonation was converted to graphic output, and pauses between 200 ms and 4000 ms were summated and divided by total phonation time. This measure did not discriminate significantly between the groups, although the LTLE group tended to pause longer than the RTLE or PGE groups. Increased variability in pause duration in the LTLE group during cycle 1 suggested that some individuals with LTLE are vulnerable to disruption when planning demands are high. A post hoc correlational analysis showed that variation in fluency was primarily explained by orthographically-based lexical retrieval, suggesting that individual differences in fluency are related to limitations in a high-level capacity relevant to the production of speech. It is unlikely that such limitations are specific to LTLE.

Adult↗

PubMed2002

Deficits in executive functions and motor coordination in children with frontal lobe epilepsy.

Frontal lobe dysfunction in adults has been associated with impairments of planning abilities, working memory, impulse control, attention and certain aspects of motor coordination. However, very few studies have attempted to assess these functions in children suffering from frontal lobe epilepsy. The aim of the present study was to determine whether some or all of the components of the frontal lobe syndrome are present in children with this disorder. For this purpose, a neuropsychological test battery was administered to 32 unresected epileptic children, aged 8-16 years: 16 with frontal lobe epilepsy (FLE), eight with temporal lobe epilepsy (TLE) and eight with generalized epilepsy whose principal manifestations were typical absences (GEA). The performances of the three epileptic groups were further compared to normative data derived from 200 French-speaking, healthy children aged 7-16 years, except for standardized tests for which the norms provided in the manual were used. The three epilepsy groups did not differ with respect to conceptual shift and recency memory. However, the FLE children showed deficits in planning and impulse control. Furthermore, they had significantly more coordination problems and exhibited greater rigidity than the other epilepsy groups on the motor tests. These problems were more marked in younger FLE children (8-12 years). The latter were also more impaired on verbal fluency measures. No differences were observed with respect to gender, localization of the epileptic abnormality (unilateral versus bilateral) or medication (monotherapy versus polytherapy). The findings reveal similarities between the neuropsychological profiles of FLE children and adults with frontal lobe lesions.

Adolescent↗

PubMed1981

[Epilepsies of the young adult (author's transl)].

Data on 614 epileptic patients whose first seizure occurred between the ages of 19 and 29 were reviewed and some clinical and electroencephalographical features compared, in order to clear up the semiology and etiology of this type of late-onset epilepsy. Partial epilepsies were more numerous than generalized epilepsies and post-traumatic epilepsies the more frequent. We could only study the evolution of 305 patients for 5 years or more: 60% were not stabilized but, probably, those who were free of seizures no longer consulted the physician. It seems difficult to compare our findings with other studies, the age periods in the latter being too broad (childhood epilepsy, late or very late onset epilepsy).

Adult↗

PubMed1981

[Seizures after the age of sixty (author's transl)].

Three percent of epileptic patients have their first seizure after the age of 60. More than at other ages, the real nature of such fits is very difficult to assert. Most of the reversible attacks occurring at this age are not of grave nature, syncopes are much more frequent. Some semeiological aspects are discussed. Focal seizures are more frequent after the age of 60. Absence status may be the first epileptic symptom in some rare cases (almost all of them being women). 100 patients whose ages ranged from 60 to 83 years, were examined after their first seizure and aetiological problems were examined. The following topics are discussed:--The possible onset of a primary epilepsy, extremely rare at that age;--The incidence of neoplasms, not exceeding 10% for patients whose late onset epilepsy is still an isolated symptom, and who have not been selected from specialized neurological or neurosurgical hospital departments;--The role of vascular epilepsy; in a very few cases, but of great practical interest, the epilepsy may announce a cerebrovascular accident which will occur later. It is, however, difficult to specify the vascular origin of a certain number of temporary unexplained late onset epilepsies. Some other aetiological factors are taken into account: antecedents of trauma, alcoholism, and dementia. The authors agree that in 50% of the cases the aetiology is not obvious. In this group of unknown aetiology it seemed interesting to isolate the following electroclinical form;--Epilepsy grand mal, with apparently generalized seizures; no special pathological antecedents; the neuropsychological and neurological examinations are normal, showing no intellectual disorders; the EEG generally shows slight modifications: quick rhythms, some sharp waves; a global cerebral atrophy is seen by the scanner. Such patients have been called victims of 'secondary late-onset generalized epilepsy'. They form 16% of a series of 156 epileptic patients who were over 65 years old, and 21% of our own 100 patients.

Age Factors↗

PubMed1998

Study on surgical treatment of intractable childhood epilepsy.

We studied the clinical details of 14 children with intractable epilepsies, all of whom underwent epilepsy surgery before age 18 years. All 14 suffered catastrophic seizures, which were resistant to the full range of available medical treatments. The ages at operation ranged from 4 years 7 months to 17 years 2 months, with a mean of 9 years 11 months. In nine patients, the age at onset of epilepsy was less than 2 years. The seizure disorders were classified as temporal lobe epilepsy in two patients, extratemporal lobe epilepsy in 10, and symptomatic generalized epilepsy in two. Eight patients had a hemicorporeal deficit (hemiparesis or hemiplegia) preoperatively. All 14 patients showed localized magnetic resonance imaging (MRI), single photon emission computer tomography (SPECT) and/or positron emission tomography (PET) abnormalities, providing crucial information regarding the epileptic focus. As to the surgical outcomes, four patients became seizure-free and the other 10 showed significant improvement during a mean follow-up period of 2 years 5 months. As to etiology, cortical dysplasia was identified in seven patients. Epilepsy surgery should be considered for intractable childhood epilepsy based on individual clinical characteristics, including seizure status, cognitive development, and evidence indicating location of the seizure focus, rather than age.

Adolescent↗

PubMed2002

Historical criteria that distinguish syncope from seizures.

OBJECTIVES: We prospectively sought evidence-based criteria that distinguished between seizures and syncope. BACKGROUND: Loss of consciousness is usually due to either seizures or syncope. There are no evidence-based historical diagnostic criteria that distinguish them. METHODS: A total of 671 patients with loss of consciousness completed a 118-item historical questionnaire. Data sets were complete for all subjects. The data set was randomly divided into two equal groups. The contributions of symptoms to diagnoses in one group were estimated with logistic regression and point scores were developed. The accuracy of the decision rule was then assessed using split-half analysis. Analyses were performed with and without inclusion of measures of symptom burden, which were the number of losses of consciousness and the duration of the history. The scores were tested using receiver-operator characteristic analysis. RESULTS: The causes of loss of consciousness were known satisfactorily in 539 patients and included seizures (n = 102; complex partial epilepsy [50 patients] and primary generalized epilepsy [52 patients]) and syncope (n = 437; tilt-positive vasovagal syncope [267 patients], ventricular tachycardia [90 patients] and other diagnoses such as complete heart block and supraventricular tachycardias [80 patients]). The point score based on symptoms alone correctly classified 94% of patients, diagnosing seizures with 94% sensitivity and 94% specificity. Including symptom burden did not significantly improve accuracy, indicating that the symptoms surrounding the loss of consciousness accurately discriminate between seizures and syncope. CONCLUSIONS: A simple point score of historical features distinguishes syncope from seizures with very high sensitivity and specificity.

Case-Control Studies↗

PubMed1994

Diagnosing juvenile myoclonic epilepsy in an elderly patient.

Juvenile myoclonic epilepsy is a common idiopathic generalized epilepsy with age-related onset of symptoms. We present an unusual case where definitive diagnosis was delayed until the patient was aged 66 years, despite early recognition of the clinical features. Although uncommon in the elderly, JME should be considered in all patients with seizures refractory to treatment.

Aged↗