Video-Polygraphic Analysis of Myoclonic Seizures in Juvenile Myoclonic Epilepsy

Summary: We studied myoclonic seizures (MS) in 5 patients with juvenile myoclonic epilepsy (JME) using video polygraphic recordings to investigate the clinical characteristics of MS in this epileptic syndrome. The total number of MS analyzed was 302 (range 27–125, mean 60) seizures per patient. MS occurred either singly or repetitively (37 vs. 63%) and corresponded to generalized bilaterally synchronous single or multispike-and-wave complexes at 3–5 Hz. Video analysis of the myoclonic jerks demonstrated that either distal or proximal muscle involvement predominated. In the former, there was mild bilateral flexion and some external rotation of the forearms. In the latter, flexion of both arms at the elbow, flexion and abduction of the thighs, and extension of the back was observed. Asymmetry of MS was noted in 4 of 5 patients. Facial involvement of MS occurred infrequently in 2 patients. When the patients kept both arms outstretched, the arms dropped or there was sudden interruption of ongoing electromyographic (EMG) potentials immediately after myoclonic jerks (postmyoclonic inhibition) in all patients. One should inquire about these clinical characteristics of MS in JME when taking a thorough history in patients with primary generalized tonic-clonic seizures (GTC).     

Management Strategies for Refractory Localization-Related Seizures

Summary: Localization-related epilepsy, the most common type of seizure disorder, often provides major management problems. Five new antiepileptic drugs (AEDs) with different mechanisms of action have been licensed in the United Kingdom in the 1990s for adjunctive use in the management of poorly controlled partial seizures. These were, in chronologic order, vigabatrin, lamotrigine, gabapentin, topiramate, and tiagabine. Their practical deployment is explored here. Mention also is made of clobazam and acetazolamide. Combination therapy with two or even three AEDs having complementary pharmacologic effects can provide an essential contribution to the management of partial seizures. This article discusses some of the pharmacologic strategies used in treating patients with refractory localization-related epilepsy.     

Seizures in Series: Similarities Between Seizures of the West and Lennox-Gastaut Syndromes

We observed seizures resembling infantile spasms in patients with Lennox-Gastaut syndrome (LGS). Infantile spasms, the type of seizures that occurs in patients who have West syndrome, have been well characterized by video-EEG studies and typically occur as a series of sudden generalized flexor or extensor jerks. The seizure types that occur in LGS have not been as clearly delineated. Some patients with West syndrome (WS) in early infancy later develop LGS. Using intensive video-EEG monitoring, we evaluated 14 LGS patients who had seizures that occurred in series. Clinically, the seizures greatly resembled infantile spasms, and the ictal EEG changes were identical to those that occur with infantile spasms. These findings expand the number of features known to be shared by these two syndromes and strengthen the hypothesis that the two syndromes represent age-related manifestations of similar epileptogenic processes.     

Myoclonic Absence-Like Seizures and Chromosome Abnormality Syndromes

Summary: Purpose: We explored the relationship between myoclonic absence seizures (MAS) and underlying chromosome disorders.
Methods: Among 14 patients with MAS observed in three centers, 5 had typical cryptogenic myoclonic absence epilepsy (MAE), 2 had MAS associated with other seizure types (1 with signs of a neuronal migration abnormality and 1 with signs of a metabolic disorder), and 7 had MAS, with or without other seizure types, complicating a chromosome abnormality syndrome-2 with trisomy 12p, 4 with Angelman syndrome, and 1 with inv dup (15).
Results: In the 7 patients with chromosomopathy, MAS appeared at a mean age of 2.9 years (range 4 months to 6 years 6 months), had a duration of 4–20 s, and were accompanied by reduced awareness and rhythmic myoclonic jerks involving proximal limb muscles. Ictal EEG showed 2- to 3-Hz generalized spike-and-wave discharges.
Conclusions: In these patients, MAS differed slightly from those of typical MAE: age of onset was earlier, absences were of shorter duration, and no clear increase in muscular tone was noted. Abnormal expression of genes codifying for the subfamily of K⁺ channels and for γ-aminobutyric acid-3 subunit receptors (GABRBS), both located in the chromosome segments involved in the chromosomopathies presented by our patients, could be responsible for the same generalized seizure type. Chromosome analysis should be performed in patients with mental retardation and MAS, especially when the ictal pattern does not completely overlap that observed in MAE.     

Sleep architecture in patients with Juvenile Myoclonic Epilepsy

AimThe aim is to analyze the sleep architecture using polysomnography (PSG) in patients with Juvenile Myoclonic Epilepsy (JME): (newly diagnosed and those on valproate drug) attending epilepsy clinic at Alexandria University Hospitals.MethodsThis study involved 20 patients with JME on valproate (age: 22.40 ± 5.80 years; M:F = 6:14), 20 newly diagnosed patients (age: 18.55 ± 6.0 years; M:F = 6:14), and 20 matched healthy controls (age: 22.10 ± 5.0 years; M:F = 6:14). Clinical assessment, electroencephalogram (EEG), evaluation with comprehensive sleep questionnaire, and PSG were done for all patients.ResultsPSG showed significant alterations in sleep architecture in the total JME group in the form of reduced mean sleep efficiency (p = 0.001¹), increased mean Rapid eye movement (REM) onset latency (p = 0.046¹), decrease mean REM percentage (p = 0.011¹), increased mean wakefulness after sleep onset (p = 0.018¹), increase the index of total arousal (p = 0.005¹), increased mean periodic limb movement index (P = 0.001¹), and reduced apnea hypopnea index (P = <0.001) in comparison to control group. Valproate treated group showed increased sleep efficiency (p = 0.040¹), decreased REM arousal index (P = 0.012), longer stage 3 (P = 0.038), and prolonged stage 2 (P = 0.049¹) than the newly diagnosed group.ConclusionsSleep architecture was significantly disturbed in JME, with improvement in sleep efficiency in valproate treated patients.     

Video-EEG Analysis of Drop Seizures in Myoclonic Astatic Epilepsy of Early Childhood (Doose Syndrome)

We studied 36 drop seizures in 5 patients with myoclonic astatic epilepsy of early childhood (MAEE) with simultaneous split-screen video recording and polygraph. Sixteen were falling attacks and 20 were either less severe attacks exhibiting only deep head nodding or seizures equivalent to drop attacks in terms of ictal pattern but recorded in the supine position. All seizures except those that occurred in patients in the supine position showed sudden momentary head dropping or collapse of the whole body downward. Recovery to the preictal position was observed in 0.3-1 s. As a result of carefully repeated observations, the 36 seizures were classified as myoclonic flexor type in 9, myoclonic atonic type in 2, and atonic type, with and without transient preceding symptoms in the remaining 25. The MF seizure was characterized by sudden forward flexion of the head and trunk as well as both arms, which caused the patient to fall. In the myoclonic atonic seizure, patients showed brief myoclonic flexor spasms, immediately followed by atonic falling. The AT seizure showed abrupt atonic falling, with and without transient preceding facial expression change and/or twitching of extremities. The ictal EEGs of all 36 seizures exhibited generalized bilaterally synchronous single or multiple spike(s) and wave discharges. Atonic drop attacks appear to be a common cause of ictal epileptic falling in MAEE.     

Benign Myoclonic Epilepsy in Infancy (BMEI): A Longitudinal Electroclinical Study of 22 Cases

Summary:  Purpose: Benign myoclonic epilepsy in infancy (BMEI) is a nosologically well-defined entity, characterized by myoclonic seizures (MS) in normal children younger than 3 years and by a good long term prognosis. In some cases the seizures are reflex. We studied 22 cases to better define the electroclinical semeiology and evolution of the disorder.
Methods: Serial electroclinical and neuropsychological assessments, both during wakefulness and during sleep, were performed in 22 otherwise healthy children with spontaneous (17) or reflex (5) MS, recorded by video-EEG-polygraphy since clinical onset.
Results: Seizure onset was between 3 months and 4 years 10 months (50% during first year, 86% before the third year); in reflex cases onset, was earlier than the 14th month. MS recurred during wakefulness and slow sleep in all cases and during REM sleep in reflex cases. MS and related EEG discharges were synchronous or asynchronous. Often ictal EEG discharges were limited to the rolandic and vertex regions (falsely focal paroxysms). Several seizures were subtle and could have escaped recognition. Unusually frequent sleep startles were recorded mostly in reflex cases. MS were well controlled by treatment. At follow-up, between ages 3 and 19 years, four patients had occasional seizures; two had cognitive impairment and three had learning difficulties. No other seizures or cognitive deficits were observed in reflex cases.
Conclusions: Seizures associated with BMEI are rarely truly generalized and are often so subtle and related to falsely focal paroxysms that their frequency can be underestimated. The reflex form is a well-defined variant with an early onset, peculiar electroclinical features, and a good prognosis.     

Epidemiology of Severe Myoclonic Epilepsy of Infancy

Severe myoclonic epilepsy of infancy (SMEI) is a newly recognized epileptic syndrome. It is characterized by multiple febrile seizures, often prolonged, subsequent development of uncontrollable mixed-myoclonic seizures, and, eventually, psychomotor retardation. Drugs for myoclonic epilepsy--valproate (VPA), the suximides, and the benzodiazepines--have been shown to be useful in SMEI. Among children with seizures in the National Institute of Neurological and Communicative Disorders and Stroke Collaborative Perinatal Project (NCPP), one individual with SMEI was identified. This finding from the NCPP suggests that the incidence of SMEI is approximately 1 in 40,000 children. Such an incidence is supported by observations at the Texas Tech University Health Sciences Center.     

8例家族性皮质肌阵挛震颤性癫痫临床特点分析

目的分析家族性皮质肌阵挛震颤性癫痫(FCMTE)的临床特点。方法对8例FCMTE患者的临床资料进行回顾性分析,总结家系的临床特点、遗传特征。结果 8例FCMTE患者,连续3代发病,男女均受累,均30岁以后起病,先后出现震颤、全面强直-阵挛发作。其中,5例伴头痛,6例有肢体震颤,4例有情绪焦虑,1例有共济失调症状。8例均于30岁以后癫痫发作,呈强直-阵挛发作。4例刺激左右正中神经记录的躯体感觉诱发电位(SEPs)可见巨大电位,未见C-反射。结论 FCMTE呈常染色体显性遗传,均发生于成人,表现为四肢末端细微震颤、强直-阵挛性癫痫发作,光刺激、情绪激动或惊吓时可诱发。服抗癫痫药有效,服用β受体阻滞剂或饮酒无效,为非进展性病程。神经电生理检查提示肌阵挛或震颤来源于大脑皮质。     

Gene Mapping in the Idiopathic Generalized Epilepsies: Juvenile Myoclonic Epilepsy, Childhood Absence Epilepsy, Epilepsy with Grand Mai Seizures, and Early Childhood Myoclonic Epilepsy

Summary: Idiopathic generalized epilepsies, i.e., juvenile myoclonic epilepsy (JME), childhood absence epilepsy, and epilepsy with grand mal [generalized tonic-clonic seizures (GTCS)], are the most common genetic epilepsies. Linkage studies using Bf, HLA serologic, and DNA markers by three independent investigators, one from Los Angeles and two from Berlin, have localized the JME locus to the short arm of chromosome 6 (6p). Because members of the same JME family have the same JME phenotype of childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or early childhood myoclonic epilepsy (ECME), our observations give evidence for a single-locus etiology in 6p for JME and for at least some of the childhood absence seizures, epilepsy with grand mal (GTCS) seizures, and ECME. Studies should now address whether locus heterogeneity exists within childhood absence epilepsy, epilepsy with grand mal (GTCS) seizures, or ECME. Markers linked to JME (Bf, HLA serologic, and DNA markers in the DQ region) can be used to resolve etiologic heterogeneity. Using such markers, both linked and unlinked forms of phenotypes that are clinically indistinguishable may be detected and provide evidence for etiologic heterogeneity. Studies should also concentrate on narrowing the JME locus to 2 to 3 cm by screening families with recombinant events using RFLPs, candidate genes, and new expressed sequences on chromosome 6.     

Alcohol, Seizures, and Epilepsy

Summary: Seizures, epilepsy, and alcohol are complexly interrelated. Although it is commonly perceived that patients with epilepsy experience problems with seizure control if they use alcohol, this is not confirmed by the few experimental studies that have tested the hypothesis. The last 30 years have emphasized the role of withdrawal from alcohol as a mechanism of seizure production. However, this is but one of many potential mechanisms by which seizures and epilepsy may be related to alcohol use and abuse. The rare but clear situations in which alcohol can act as a convulsant drug need further study, and mechanisms by which the long-term neurotoxic effects of alcohol lead to chronic epilepsy also need further elucidation.     

Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis

PURPOSE: To survey the characteristics of epilepsy in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and determine the antiepileptic drug (AED) treatment most suitable for these patients. METHODS: The study included 60 patients with JNCL; their mean age was 16.5 years (range 5-33). The age at onset of epilepsy, type of seizures, effect of the first AED on seizures, and the current seizure frequency and AED therapy were studied. The side effects of the AEDs were also clarified. RESULTS: Fifty of the 60 patients had epilepsy. Patients' first epileptic seizure occurred at a mean age of 10.0 years (range 5-16), the most common type being generalized seizures. As the first AED tried, valproate (VPA) and lamotrigine (LTG) appeared equally effective, with 80% of the patients responding to these AEDs. During the study year, the median seizure frequency was four seizures a year (range 0-120), and 72% of the patients had good or satisfactory seizure control (0-6 seizures a year). In the different AED therapy groups, the proportion of patients with good or satisfactory seizure control ranged from 25% to 100%. LTG in monotherapy or in combination with clonazepam (CZP) was superior to other AEDs or combinations, but VPA also seemed effective. Adverse effects leading to the discontinuation of an AED were observed in 25% of the patients, most frequently in patients receiving phenobarbital (PB). No patient receiving LTG had to discontinue the drug due to adverse effects. CONCLUSION: Epilepsy in JNCL can usually be successfully treated with the current AEDs. In Finnish patients with JNCL, treatment is based on LTG, or, secondarily, VPA. In combination therapy, CZP seems a valuable add-on AED.     

Felbamate Levels in Patients with Epilepsy

The usefulness of felbamate (FBM) levels in managing epilepsy patients has not been determined. The purpose of the present study was to determine if FBM levels obtained at routine office visits correlated with side effects reported by patients. We determined FBM levels by high-pressure liquid chromatography (HPLC) of 46 epilepsy patient plasma specimens (41 patients) and assessed medication toxicity and seizure frequency by a questionnaire. Thirty-six patients were treated with other antiepileptic drugs (AEDs); concomitant AED levels not in ranges believed to cause toxicity. FBM levels ranged from 9 to 134 pg/ml, and were divided into three groups for analysis, resulting in low-range (9–36 pg/ml), mid-range (37–54 μg/ml), and high-level (44–134 pg/ml) groups. Anorexia and complaints of severe side effects were reported significantly more often in the high-level group as compared with the low- and midrange groups. Significantly more patients in the high-level group (1043) reported decreased seizure frequency, as compared with 12 of 30 of patients in the low-and midrange groups combined. FBM levels correlated linearly with doses overall, but most closely in FBM monotherapy patients.     

Circling Seizures in a Case of Juvenile Myoclonic Epilepsy

Summary: Circling seizures (CS) have been described in association with focal lesions as well as with generalized EEG discharges. We report 1 patient with juvenile myoclonic epilepsy (JME) who developed CS. There were no focal findings on clinical examination, EEG, or imaging studies. We propose that CS in this patient may represent a profound asymmetry in expression of an idiopathic generalized epilepsy rather than a partial condition.     

Juvenile Myoclonic Epilepsy – an experience from north western India

OBJECTIVES: The clinical data on cases of Juvenile Myoclonic Epilepsy (JME) were analysed. Response to initial small dosages (lower than usual) of sodium valproate and further lower maintenance dosages in patients who were seizure free for 2 years on drug were assessed. MATERIAL AND METHODS: Seventy-six patients who were diagnosed to have Juvenile Myoclonic Epilepsy on definite criteria were studied. All patients were put on sodium valproate in dosages (lower than usual) for initial control and further lower maintenance dosage and response evaluated. RESULTS: The clinical profile was found to be similar as in other parts of India. There was a female preponderance and average delay of 4.9 years in final diagnosis. Forty-eight (63.1%) patients showed good control on 15 mg/kg/day dosages of sodium valproate. After a seizure free interval of 2 years, 58% of patients could be maintained on small dosages ranging from 3-5 mg/kg/day to 6-8 mg/kg/day. CONCLUSION: The majority of JME patients responded well not only to sodium valproate in dosages lower than usually prescribed but required very small dosages for maintenance after a seizure free period of 2 years.     

De Novo Psychogenic Nonepileptic Seizures After Epilepsy Surgery

Summary: Purpose: The occurrence of de novo nonepileptic seizures (NES) after epilepsy surgery have been reported only twice in the literature (one article and one abstract).
Methods: We report three patients whose de novo NES were documented by video-EEG telemetry after epilepsy surgery. These patients were drawn from a sample of 166 consecutive patients who underwent epilepsy surgery at our center between 1989 and 1996.
Results: Two patients became seizure free after surgery, and one had significant improvement of her seizures. The interval between the date of surgery and the development of the symptoms was variable (8, 10, and 47 months, respectively). The clinical phenomena of NES differed from those of the epileptic seizures preceding surgery. Their diagnosis had not been suspected in two patients before the diagnostic video-EEG monitoring study. After the diagnosis of NES, spells stopped in two patients and recurred rarely in one.
Conclusions: We conclude that de novo NES appears to occur rarely after epilepsy surgery. Given that the possibility of NES was suspected in only one patient, its incidence after surgery may be higher than so far reported. Physicians should therefore consider NES in the differential diagnosis of recurrent seizures after a seizure-free period after epilepsy surgery.     

Emotion-Induced Myoclonic Absence-Like Seizures in a Patient with Inv-Dup(15) Syndrome: A Clinical, EEG, and Molecular Genetic Study

We have described a clinical EEG and molecular genetic study of a 9-year-old boy with inv-dup(15) syndrome in whom seizures were induced by emotionally gratifying stimuli. The reflex seizures began 5-20 s after the onset of repeated cheek-kissing from his mother or after viewing of pleasant or funny events. They were characterized by bilateral discharges involving mainly the temporal regions and evolving into myoclonic absence-like seizures. Nonemotional stimuli, such as a pinch, sucking or rubbing his cheeks, or the sound of the kiss alone, failed to provoke seizures. The seizures were resistant to antiepileptic (AED) treatments. Molecular genetic investigations revealed a correct methylation pattern of the chromosomes 15, and three copies (two maternal and one paternal) of the segment 15q11-q13, including the GABRb3 gene. We hypothesize that an overexpression of cerebral gamma-aminobutyric acid (GABA)-mediated inhibition accounts for the severe epilepsy that we observed in this patient.