Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy

PURPOSE: A few reports have described focal electroencephalographic or clinical features or both of juvenile myoclonic epilepsy (JME), but without video-EEG documentation. We examined focal clinical and EEG features in patients with JME who underwent video-EEG monitoring. METHODS: Twenty-six patients (nine males and 17 females) who had seizures recorded during video-EEG monitoring were included. Age at seizure onset was 0 to 22 years (mean, 12.3 years), and age at monitoring was 12 to 44 years (mean, 26.5 years). In one patient with left parietooccipital epilepsy, primary generalized tonic-clonic seizures developed after resection of the parietal tumor. Two patients had both temporal lobe epilepsy and JME. Videotaped seizures in each patient were analyzed. Interictal and ictal EEG also were analyzed for any focal features. RESULTS: Focal semiologic features were observed in 12 (46%) of 26 patients. Six patients had focal myoclonic seizures, and two had Figure 4 sign: one with version to the left, and another had left version followed by Figure 4 sign, and left arm clonic seizure. Their ictal EEGs were generalized at onset but with a lateralized evolution over the right hemisphere. The patient who had both JME and left parietooccipital epilepsy, right arm clonic seizure, and Figure 4 sign was seen during a generalized EEG seizure. Interictally, one patient had temporal sharp waves, and another had run of spikes in the right frontal region. CONCLUSIONS: Fourteen (54%) of 26 patients with JME exhibited focal semiologic or electroencephalographic features or both. Video-EEG was essential in reaching a correct diagnosis and choosing an appropriate antiepileptic drug regimen.     

31例青少年肌阵挛性癫痫临床表现脑电图特点及误诊分析

目的 回顾性分析31例青少年肌阵挛性癫痫(JME)患者的临床、脑电图特点及误诊原因.方法 收集2008年9月～2011年1月在我院癫痫诊治中心诊治的31例JME患者,对其临床表现、脑电图改变及药物治疗疗效进行总结性分析.结果 31例患者表现单纯肌阵挛发作者12例;肌阵挛伴全身强直-阵挛发作者15例;肌阵挛伴失神发作者4例.长程录像脑电图检查,24例患者于监测过程中出现肌阵挛发作,脑电见与发作同步的对称性、泛化性多棘慢波、棘慢波爆发.既往就诊中诊断为全身强直-阵挛发作者17例,抽动症者8例,部分性发作者4例,正常者2例.依据发作类型给予治疗后肌阵挛症状1w内消失者13人;2w内消失者11人;1个月内消失者6人,每月内均有3～4次肌阵挛发作者1人.继发的全身强直-阵挛性发作,半年内消失者20例;1年内消失者11例.结论 青少年肌阵挛性癫痫,以短暂的、无节律性、不规则的肌阵挛抽动为特点,由于症状不典型容易造成误诊,长程录像脑电图检查,附加闪光刺激、睡眠剥夺等诱发试验,提高阳性诊断率,对症治疗效果好.     

Characteristics of valproic acid resistant juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is often exquisitely responsive to treatment with valproic acid (VPA). However, a subset of patients does not respond to this medication and often has intractable seizures. We wanted to identify differences between these two subsets of JME patients. Charts of all JME patients followed at the Duke Epilepsy Center were reviewed. Clinical parameters, electroencephalogram (EEG) findings and magnetic resonance imaging (MRI) data were reviewed. These features were compared between patients with VPA sensitive and VPA resistant JME. Thirty-three patients with JME were identified: 23 (70%) were VPA sensitive (13 females, 10 males; mean age of onset 15.9 years) and 10 (30%) were VPA resistant (5 females, 5 males; mean age of onset 14.1 years). The VPA resistant group had a higher frequency of EEG asymmetries (40% vs. 10%); atypical seizure characteristics including auras and post-ictal confusion (30% vs. 4%); and intellectual deficiency (20% vs. 0%). Clinical characteristics combined with EEG data may help in predicting which JME patients will respond favorably to VPA. This study also raises the issue whether VPA resistant JME is in fact a localization-related epilepsy.     

Focal clinical and electroencephalographic features in patients with juvenile myoclonic epilepsy

Jayalakshmi SS, Srinivasa Rao B, Sailaja S. Focal clinical and electroencephalographic features in patients with juvenile myoclonic epilepsy.
Acta Neurol Scand: 2010: 122: 115–123.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To identify prevalence and factors associated with occurrence of focal clinical and electroencephalogram (EEG) abnormalities in patients with juvenile myoclonic epilepsy (JME). Materials and methods – Clinical asymmetries in the seizures and focal EEG abnormalities were analyzed in 266 patients with JME. Results – All the patients had myoclonic jerks (MJ) and generalized tonic‐clonic seizures (GTCS); 56 (21%) had absence seizures. Asymmetry in clinical seizures was reported in 45 (16.9%) and focal EEG abnormalities were noted in 92 (45.5%) patients. Amplitude asymmetry or focal onset of generalized discharges was noted in 41 (44.6%) and independent focal EEG abnormalities in 30 (32.6%) patients. A statistically significant association was seen with the presence of GTCS and MJ (P = 0.007), a family history of epilepsy (P = 0.001) and drug resistance (P = 0.04) and the occurrence of focal EEG abnormalities. Conclusion – Patients with JME showed focal clinical and EEG features. These features should not be misinterpreted as indicative of partial epilepsy.     

A clinical and electroencephalographic study of juvenile myoclonic epilepsy: its pathophysiological considerations based on the findings obtained from neuropsychological EEG activation

Juvenile myoclonic epilepsy (JME) is one of the idiopathic generalized epilepsies with age-related onset. Myoclonic seizures of JME often occur on awakening. On the other hand, patients with reflex epilepsy, whose seizures are particularly induced by activating higher cognitive functions, are thought to belong to the same category. As to the seizure precipitating factors of these patients with JME, however, few studies have ever been made. In this study, clinical and electroencephalographic findings of 25 patients with JME, on whom "neuropsychological EEG activation" (NPA) was performed, were carefully analyzed. After a routine EEG examination, NPA was carried out; this is a special method for EEG activation that requires the patients to speak, read, write, calculate and perform constructive acts (drawing figures and doing a block design test); in addition to EEG recording, simultaneous video-EEG monitoring was also made during these tasks. In the patients with JME, the sex ratio was about equal (11 males and 14 females). Eight patients (32%) had a family history of epilepsy but none of the patients had a positive past history responsible for epilepsy. The age at the onset of myoclonic seizures ranged between 10 and 20 years (mean: 15.3 years). A total of 18 patients (72%) had another type of seizures; 3 had absence seizures, 9 had generalized tonic-clonic seizures and 6 had both absence and generalized tonic-clonic seizures. Myoclonic seizures often occurred in the morning on awakening in 17 (68%) of 25 patients. As for EEG findings (all but one patient were receiving antiepileptic drugs when EEG was examined), paroxysmal discharges in a resting state were found in 12 patients (48%); most of them were either very brief generalized spike and wave complexes or bursts of generalized 3-5 Hz spike and wave complexes lasting for 1-3 seconds; generalized multiple spikes were observed only in 5 patients. These clinical and EEG findings were in accordance with those reported previously. Careful investigation of the histories obtained from the patients disclosed the following: Myoclonic seizures were induced (1) by mental activity associated with the use of hands in 20 patients (80%), (2) in a situation with psychic tension in 12 (48%), and (3) by decision making in 3 (12%). Interestingly, these findings could be confirmed by NPA with simultaneous video-EEG monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)     

Seizure Threshold in Juvenile Myoclonic Epilepsy with Graves Disease

Summary: Thyroxine lowers the seizure threshold in experimental animals and humans. We report juvenile myoclonic epilepsy (JME) in two female patients with Graves' disease who had exophthalmos at age 11 (patient 1) and age 12 years (patient 2) but remained untreated until onset of seizures at ages 15 and 13 years, respectively. Seizures were not controlled well despite administration of antiepileptic drugs (AEDs) during the periods of excess serum thyroid hormones in Graves disease. When the serum levels of T₃ were reduced to <220 ng/dl with antithyroid drug treatment, both clinical seizures and paroxysmal EEG abnormalities disappeared despite discontinuation of AEDs and sleep deprivation. JME was noted only during periods of excess thyroid hormone and low compliance with antithyroid drug treatment. The excessively high level of thyroid hormones may have been a factor in precipitating the onset of JME.     

Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic syndrome distinctively characterized by myoclonic jerks often associated to generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite of typical clinical and EEG profiles, JME is widely underdiagnosed. In the present study we retrospectively revised clinical and EEG data of JME patients referring to our Epilepsy Service. A diagnosis of JME could be made in 63 patients, that is 5.7% of all the epileptic patients referring to our Service and 25.9% of those suffering from an idiopathic generalized epilepsy. General features as well as modality of onset and course of the syndrome of our JME subjects were in accordance with literature. Regarding EEG findings, asymmetries were detected in 38.1% of cases. At referral to our Service only 31.7% of JME patients were correctly diagnosed. Main factors responsible for misdiagnosis were failure in eliciting a history of myoclonic jerks and misinterpretation of myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13 patients. In conclusion, a correct JME diagnosis is strictly dependent on the knowledge of the syndrome leading the interviewer to look for and correctly interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.     

Idiopathic generalized epilepsies misdiagnosed as partial epilepsies

Idiopathic generalized epilepsy (IGE) is often not recognized with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis of IGE in 41 adults attending our epilepsy clinic with diagnosis of partial epilepsy who had semiology or EEG findings suggesting a possible differential diagnosis. After careful re-evaluation, the diagnosis of IGE was established in 25 patients: 22 (88%) with JME, one with juvenile absence, one with perioral myoclonia with absences, one with eyelid myoclonia with typical absences. Myoclonic jerks, the hallmark of the JME and other IGE, were not usually reported by patients or misdiagnosed as focal motor seizures. Brief and infrequent absence seizures and focal EEG abnormalities were other factors contributing to not recognizing JME. All 25 patients did not achieve seizure control before re-evaluation of diagnosis. After appropriate diagnosis of IGE and change of AED to valproate or valproic acid, 19 (76%) became seizure free and six (24%) had a significant improvement on seizure control. Association with lamotrigine provided further improvement in three of these patients. An appropriate questioning to identify myoclonic and absence seizures and a proper interpretation in the context of whole clinical constellation are essential for a correct seizure classification and diagnosis of IGE in adults.     

Cognitive function in juvenile myoclonic epilepsy

In this study, we examined 35 patients with juvenile myoclonic epilepsy (JME) and 35 healthy volunteers. We used tests of cognitive performance (mini mental state examination, verbal and visual memory, visuospatial, frontal function, attention). In the JME group, we examined age, sex, family history, education level, age of seizure onset, seizure types, characteristics of EEG, duration of the therapy, drug dose and level, and verbal IQ level. Additionally, patients initially diagnosed as JME and patients who were initially under inappropriate drug therapy because of misdiagnosis were compared. As a result, we found statistically significant differences between JME patients and the control group with respect to verbal and visual memory. Furthermore, JME patients had impaired frontal and visuospatial function compared with the control group. We detected negative effects of younger age, family history, and absence seizures on cognitive function in JME patients.     

Juvenile Myoclonic Epilepsy: Factors of Error Involved in the Diagnosis and Treatment

Juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, has a distinct clinical and electroencephalographic profile. Often JME is not recognized, with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis even in an epilepsy clinic. Of 70 JME patients, 66 (91.4%) were not diagnosed on referral and 22 (33%) were not initially recognized in the epilepsy clinic. The correct diagnosis was established after a mean of 8.3 +/- 5.5 years from disease onset and an interval of 17.7 +/- 10.4 months from first evaluation in the epilepsy clinic. Myoclonic jerks, the hallmark of the disease, were not usually reported by patients. Similarly, relevant questioning may not be included in the history. Absence seizures antedating jerks by many years, myoclonic jerks reported as unilateral, generalized tonic-clonic seizures occurring during sleep and focal EEG abnormalities are other factors contributing to not recognizing JME. Our study reemphasizes the need to have not only a correct seizure diagnosis but also a correct epilepsy-disease diagnosis.     

The Seizure Prognosis of Juvenile Myoclonic Epilepsy

Abstract: Thirty-two patients with juvenile myoclonic epilepsy (JME) were studied to evaluate the seizure prognosis. The response to antiepileptic drugs ww excellent in 68%, but the patients, who had much more focal discharges on EEG and were sensitive to neuropsychological EEG activations at the beginning of treatment, had an unfavorable outcome. A combination of absence seizure alone resulted in the excellent prognosis for both absence and myoclonic seizures, and a combination of generalized tonic-clonic seizure on awakening related to rare myoclonic seizures. These findings suggest that the outcome of JME would be predicted by the EEG abnormality and the combination of the other types of seizures, which are probably determined by the pathophysiology at the beginning of treatment.     

A study of idiopathic generalised epilepsy in an Irish population.

Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on clinical and EEG features. PURPOSE: The aim of this study was to characterise all cases of IGE with supportive EEG abnormalities in terms of gender differences, seizure types reported, IGE syndromes, family history of epilepsy and EEG findings. We also calculated the limited duration prevalence of IGE in our cohort. METHODS: Data on abnormal EEGs were collected retrospectively from two EEG databases at two tertiary referral centres for neurology. Clinical information was obtained from EEG request forms, standardised EEG questionnaires and medical notes of patients. RESULTS: two hundred twenty-three patients met our inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic seizures were the most common seizure type reported, 162 (72.65%) having a generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA) was the most common syndrome in our cohort being present in 94 patients (34 male, 60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG studies in all patients showed generalised epileptiform activity. CONCLUSIONS: More women than men were diagnosed with generalised epilepsy. Tonic clonic seizures were the most common seizure type reported. EGTCSA was the most frequent syndrome seen. Gender differences were evident for JAE and JME as previously reported and for EGTCSA, which was not reported to date, and reached statistical significance for EGTCA and JME.     

Clinical genetic study in juvenile myoclonic epilepsy

PurposeTo evaluate clinical features of probands with juvenile myoclonic epilepsy (JME) and affected members of their families in order to study clinical genetics of JME.MethodThirteen unrelated families with at least two members with history of seizures were identified; clinical and genealogic data were collected from JME probands and family members.ResultsAll probands had myoclonic and generalized tonic–clonic seizures (GTCS), while absences occurred in 25% of them. The average age of seizure onset was 13 years. Totally 22 members from 13 families had history of seizures with average age of seizure onset at 18 years. Ten family members had JME, three had epilepsy with GTCS, two had juvenile absence epilepsy, one had adult onset myoclonic epilepsy and six of the affected individuals had unclassified type of epilepsy. In five families, JME was the solely clinical feature. JME dominated among siblings, while phenotypic heterogeneity was observed in second and third degree relatives. In three multi-generation families, members with adult onset genetic generalized epilepsies (GGE) were identified.ConclusionWe found phenotypic heterogeneity regarding epilepsy type and age of seizure onset. Using pedigree analysis, we found no evidence for preferential maternal or any other distinctive inheritance pattern. Further study is needed to confirm and clarify the results.     

青少年肌阵挛性癫(癎)的临床特点及误诊原因分析

目的研究青少年肌阵挛性癫痫（JME）的临床特点及导致误诊的主要原因。方法对61例JME患者的临床和脑电图（EEG）资料进行回顾性分析。结果肌阵孪是最常见的首发症状，其次为肌阵挛加全身强直一阵孪发作（GTCS）。导致误诊最常见的原因是医师对肌阵挛发作缺乏认识，其次是临床和EEG的非对称性表现。结论JME的正确诊断依赖于医师对此综合征的深刻了解，EEG只能作为辅助诊断工具。     

Predictors of seizure control in patients with juvenile myoclonic epilepsy (JME)

PurposeJuvenile myoclonic epilepsy (JME) is a widely accepted epilepsy syndrome. Factors that are potentially predictive for seizure outcome in JME are not entirely clear yet. In the current study, we tried to identify factors that are potentially predictive for seizure outcome in patients with JME.MethodIn this case–control study all patients with a clinical diagnosis of JME were recruited at the outpatient epilepsy clinic at Shiraz University of Medical Sciences from 2008 to 2012. All patients were followed for at least 18 months. We divided the patients into two groups: patients who were seizure free in the last 12 months of their follow-up period and those who had any seizures (i.e., generalized tonic-clonic (GTC), myoclonic or absences).Results116 patients were studied. Sixty-eight patients were seizure free in the last 12 months of their follow-up and 48 patients had at least one seizure of any type. Shorter follow-up period, drugs other than valproate in the drug regimen, and poor drug adherence were significantly more frequent among those who were not seizure free.ConclusionA correct diagnosis of JME does not guarantee an optimal response to therapy. Poorer drug adherence might result in more seizures; this should be highlighted for patients in every single visit. Longer follow-up gives the treating physician more time to adjust the drug(s) and formulate a plan that is appropriate for patients with difficult to treat seizures. We recommend valproate if seizure control is the main objective.     

Sleep disturbances in juvenile myoclonic epilepsy: a sleep questionnaire-based study

Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age- and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F=22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure- or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.     

Clinical expression and EEG features of patients with juvenile myoclonic epilepsy (JME) from North India.

We aimed to characterize the clinical profile, EEG features and response to treatment of juvenile myoclonic epilepsy (JME) patients. We studied 103 JME probands with a standard protocol recording age of onset, type, frequency of seizures, EEG data, detailed family history and response to treatment in a superspeciality university hospital in New Delhi. The mean age of onset of disease was 14.01 +/- 3.14 years with a male to female ratio of 1.19 : 1. The myoclonic jerks were present in all the probands, generalized tonic-clonic seizures (GTCS) were present in 75.72% and 11.65% probands had absence seizures. The incidence of febrile convulsion (FC) was higher (9.7%) in our JME probands reflecting some ethnic variation or ascertainment bias. There was a considerable delay (of approximately 5.26 +/- 4.61 years) in the diagnosis of JME in our probands because most of the patients were referred from private physicians who were possibly not familiar with this epileptic syndrome in this part of the world or thought it was a milder variety of GTCS. The family history was positive in 25.24% JME probands among first- and second-degree relatives. An interictal EEG was found to be abnormal in 81 (78.64%) patients with the predominant abnormality being generalized polyspike and wave (PSW) discharges (39.80% probands). The majority of patients (80.58%) showed a good response to treatment with valproate alone. There was a subset of patients (11.65%) who required the addition of other antiepileptic drugs (AEDs) for control of GTCS: 7.76% of JME patients were diagnosed as cases of GTCS by private practitioners before they were registered in our study and their seizures were well controlled on other AEDs (without valproate) prescribed by the referring physicians (carbamazepine-4, phenytoin-2, clobazam-2). It is concluded that the clinical features and EEG data of JME probands were comparable to reports from other parts of the world except for the fact that the incidence of FC was higher in our JME patients. There was a delay in the diagnosis of JME due to unfamiliarity with the epileptic syndrome among private practitioners in this part of the world. There was a subset of JME patients who had complete seizure control on other AEDs besides valproate.     

Seizure control in patients with idiopathic generalized epilepsies: EEG determinants of medication response

In a minority of patients with idiopathic generalized epilepsies (IGEs), seizures continue despite appropriate treatment. We sought to determine the clinical and EEG factors associated with medication response in these patients. All patients with IGEs evaluated by epilepsy specialists between 17 November 2008 and 16 November 2009 were included. We collected information on seizure freedom (dependent variable), EEG asymmetries, response to valproic acid (VPA), MRI characteristics, medication use, demographics, and seizure history (predictors). We identified 322 patients with IGEs; 45 (14%) were excluded from analyses because they had always had a normal EEG (N = 26), there were no EEG data (N = 3), or they were non-compliant with medication (N = 26). Patients with juvenile myoclonic epilepsy were more likely to respond to VPA than were patients with other IGEs, and VPA response was associated with seizure freedom. When EEG characteristics were considered, presence of any focal EEG abnormalities (focal slowing, focal epileptiform discharges, or both) was associated with decreased odds of seizure freedom. These findings suggest that patients with IGEs with poor seizure control may have atypical IGEs with possibly focal, for example, frontal, rather than thalamic onset.     

The prognostic significance of interictal epileptiform activity in postoperative EEGs of patients with mesial temporal lobe epilepsy.

It has not been established whether electroencephalography (EEG) is a contributing factor in predicting the outcome of surgery for epilepsy. We conducted a prospective study on 26 patients (M/F 14/12, age: 33 +/- 7.5 years, range 19-48) with mesial temporal lobe epilepsy (MTLE) who were followed for 2 years after surgery and who underwent routine EEG recordings 5.6 +/- 3 months (range 3-12) postoperatively. Interictal epileptiform activity (IEA) on the EEG was compared in 17 seizure-free patients to 9 patients with recurrent seizures. The two groups were similar in gender, age, febrile convulsions, trauma, family history, seizure frequency prior to surgery, epilepsy duration and number of antiepileptic drugs. Following surgery, 17 study patients (65%) became seizure free; 9 (35%) had seizure recurrence. Post-operative EEG recordings showed IEA in 8/26 study patients (31%), 3 of whom were from the seizure-free group (3/17, 18%); 5 had seizure recurrence (5/9, 56%) (p=0.078). IEAs in postoperative EEGs were less frequently demonstrated in patients who were seizure free, but the presence of postoperative IEAs does not preclude successful surgical outcome.     

Levetiracetam in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents

The aim of this study was to evaluate the efficacy and tolerability of levetiracetam (LEV) monotherapy in juvenile myoclonic epilepsy (JME). The study group consisted of 32 patients with epilepsy (20 males, 12 females) with a mean age of 13 years 3 months (SD 7y 11mo) at seizure onset. LEV was administered as the first drug; all patients were followed up at 6 and 12 months. The dose that achieved seizure control ranged from 1000 to 2500mg/daily. At 6-month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12-month evaluation: 29 patients were seizure free; three patients were responders. No patients reported adverse events. These data provide preliminary evidence that LEV may be effective for treating patients with newly diagnosed JME.