Juvenile myoclonic epilepsy: clinical and EEG features

We aimed to characterize the clinical profile and EEG features of 43 patients with juvenile myoclonic epilepsy. In a retrospective design we studied the records of, and re-interviewed, 43 patients diagnosed with JME from the epilepsy clinic data base. Furthermore, available EEGs were re-evaluated. Of the patients 72% were female and 28% male. Average age of onset was 13 (5.5–22) years for absences, 16 (5.2–25) years for myoclonic seizures, and 16 (8–29) years for generalized tonic–clonic seizures. Forty-two percent reported asymmetric or unilateral myoclonic jerks. Commonly reported precipitating factors were sleep deprivation (84%), stress (70%), and alcohol consumption (51%). EEG findings included rapid spike-wave and polyspike-wave.     

Occurrence of only myoclonic jerks in juvenile myoclonic epilepsy

Objectives - The clinical data on individuals who were diagnosed to have juvenile myoclonic epilepsy (JME) on the basis of myoclonic jerks alone has been analysed. The points in favour and against individuals with only myoclonic jerks being classified as "affected" for research on JME are discussed.
Materials and methods - We studied 15 persons diagnosed with JME on the basis of only myoclonic jerks in a series of 161 patients with JME and their relatives. Detailed information on the seizure types in JME patients and their family members was collected. All affected individuals were examined by one person and had at least one conventional scalp EEG. CT/MRI of the brain was done as and when indicated.
Results - Nine of these were probands while 6 were the relatives of JME patients. The EEG was abnormal in 8 of 9 probands and 1 of 6 relatives with only myoclonic jerks. All the 9 probands and 2 relatives with only myoclonic jerks were treated with anti-epileptic drugs. Three of the 4 relatives had spontaneous remission of jerks after variable intervals. Four of 15 persons with only myoclonic jerks had a first degree relative with definite JME.
Conclusions - It appears that persons with myoclonic jerks alone may represent a benign subgroup of JME that may be genetically distinct from classic JME and the jerks may even spontaneously remit in a few cases. It is suggested that those persons with only myoclonic jerks and a first degree relationship with a definite diagnosis of JME can be classified as "affected" for inclusion into molecular studies, till molecular tools are available to settle the issue of phenotypic variations in hereditary neurological disorders like JME.     

Outcome of lamotrigine treatment in juvenile myoclonic epilepsy

Bodenstein‐Sachar H, Gandelman‐Marton R, Ben‐Zeev B, Chapman J, Blatt I. Outcome of lamotrigine treatment in juvenile myoclonic epilepsy.
Acta Neurol Scand: 2011: 124: 22–27.
© 2011 John Wiley & Sons A/S. Objectives – To determine the response rate of patients with juvenile myoclonic epilepsy (JME) to lamotrigine (LTG) and identify predictive factors for treatment response. Material and methods – Medical records of 62 patients with JME were reviewed for demographic, clinical, and EEG parameters. We determined clinical response to LTG and compared LTG responders with non‐responders. Results – There were 35 LTG responders (56%) and 27 non‐responders (44%). JME patients without generalized tonic clonic seizures (GTCS) responded better to LTG (P = 0.04). Valproic acid (VPA) failure because of adverse events rather than lack of efficacy (P = 0.069) and delay in diagnosis (P = 0.07) showed a tendency toward good response to LTG. Conclusions – LTG should be considered a drug of first choice for JME patients without GTCS. LTG as second‐line treatment after VPA failure seems more appropriate for those patients whose reason for VPA failure is poor tolerability rather than lack of efficacy.     

Some clinical and EEG aspects of benign juvenile myoclonic epilepsy

Twelve patients with benign juvenile myoclonic epilepsy (BJME) representing 4% of our population of epileptics (n = 275) are presented. Only two patients (17%) had myoclonic jerks as the only seizure type. Seven (58%) had generalized tonic-clonic seizures (GTCS) and myoclonus. Three patients (25%) had absence seizures (AS), GTCS, and myoclonic jerks. Electroencephalographic evidence of photosensitivity was found in four (33%). Auditory precipitation of seizures was found in one patient. As is the case with other primary generalized epilepsies, the onset of BJME seems to be age specific. In our series the mean age of onset in years was 4.3 for AS, 14.75 for myoclonic jerks, and 16.4 for GTCS. It took an average of 8.5 years from the onset of BJME (range, 2-20 years) and 6.5 years from the onset of GTCS (range, 2 months-6 years) until the condition was properly recognized. Five patients experienced at least one episode of myoclonic status epilepticus. Generalized, paroxysmal, symmetric polyspike and slow wave discharges are the typical EEG finding. These complexes, however, showed considerable interpatient variability. Sleep deprivation proved to be the most valuable activating procedure. Valproic acid monotherapy effectively controlled myoclonic jerks as well as associated GTCS in most patients.     

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.     

Juvenile myoclonic epilepsy – a generalized epilepsy syndrome?

Juvenile myoclonic epilepsy (JME) has been classified as a syndrome of idiopathic generalized epilepsy and is characterized by specific types of seizures, showing a lack of pathology using magnetic resonance imaging (MRI) and computed tomography scanning. However, JME is associated with a particular personality profile, and behavioral and neuropsychologic studies have suggested the possible involvement of frontal lobe dysfunction. The development of highly sensitive neuroimaging techniques has provided a means of elucidating the underlying mechanisms of JME. For example, positron emission tomography has demonstrated neurotransmitter changes in the cerebral cortex, quantitative MRI has revealed significant abnormalities of cortical gray matter in medial frontal areas, and ¹H-magnetic resonance spectroscopy has shown evidence of thalamic dysfunction, which appears to be progressive. Such techniques provide evidence of multi-focal disease mechanisms, suggesting that JME is a frontal lobe variant of a multi-regional, thalamocortical 'network' epilepsy, rather than a generalized epilepsy syndrome.     

Early childhood myoclonic epilepsy: An independent genetic generalized epilepsy with myoclonic seizures as the main seizure type

Objective

To elucidate the characteristics of the myoclonic seizures alone, or predominant myoclonus combined with generalized tonic-clonic seizures (GTCS) and/or absences, in early childhood, and discuss its classification.

Premature death in juvenile myoclonic epilepsy

OBJECTIVES: To report three cases of premature death in juvenile myoclonic epilepsy (JME), a benign form of idiopathic generalized epilepsy (IGE) in which no case of epilepsy-related death has been reported. MATERIAL AND METHODS: We retrospectively analyzed all medical records of JME patients first referred to two epilepsy centers (Marseilles, Nice) between 1981 and 1998. RESULTS: Among 170 consecutive JME cases, 3 female patients died prematurely. No autopsy was performed. The first had a history of severe anorexia nervosa (DSM IV: 307.1). She died at age 34 and 2 days, from severe inhalation pneumonia. The second is a woman with a history of infantile psychosis (DSM IV: 299.80) and with a case of IGE in her family. Her epilepsy was never controlled. At age 16, she was found cyanotic and unconscious one morning in the toilets. She died before resuscitation was undertaken. The third had a borderline personality (DSM IV: 301.83) and a history of alcoholism and low compliance. Her epilepsy was never well controlled. She also received neuroleptics. At age 42, she was found dead in her home. CONCLUSION: In the first case, death was apparently unrelated to epilepsy. In the second, an awakening seizure seems to be responsible. In the third, death is also possibly seizure-related. Cases two and three had persistent seizures and severe psychiatric disorders. Serious mental disorders seem to be risk factors for unexpected death. In JME, the overall death ratio was 1.4/1000 patient-years (or 0.9 if we exclude case 1).     

Phenotypic analysis of juvenile myoclonic epilepsy in Indian families

OBJECTIVES: Phenotypic analysis of juvenile myoclonic epilepsy (JME) is presented to document the variations in disease expression. MATERIAL AND METHODS: Information on seizure type and frequency, seizure precipitating factors, electro-encephalographic (EEG) data, response to antiepileptic drugs (AEDs) and family history was collected on 500 Indian probands and 61 relatives with JME. RESULTS: The overall clinical features, EEG characteristics, and familial occurrence were similar to other reports. JME probands and relatives having absences (56 of 561, 10%), those with only myoclonic jerks (MJ) or MJ with one generalized tonic clonic seizure (GTCS) in remission without treatment (five of 561, 1%) and those who required valproic acid (VPA) and another AED for seizure control (19 of 561, 3%) are examples of differential disease expression within JME. Seizures among those having photoparoxysmal response (PPR) on EEG responded very well to VPA alone while those with all three seizure types (MJ, GTCS and absences) were poor responders. CONCLUSIONS: Recognition of clinical 'subtypes' among JME could have therapeutic implications and help improve JME phenotypic characterization for molecular studies.     

Topiramate or valproate in patients with juvenile myoclonic epilepsy: a randomized open-label comparison

Few randomized, controlled trials evaluating antiepileptic drug (AED) efficacy and tolerability have focused solely on patients with juvenile myoclonic epilepsy (JME). We conducted a pilot, randomized controlled trial comparing topiramate (N=19) and valproate (N=9) in adolescents/adults with JME to evaluate clinical response when these broad-spectrum agents are titrated to optimal effect. Rating scales were used to systematically assess tolerability. Among patients completing 26 weeks of treatment, 8 of 12 (67%) in the topiramate group and 4 of 7 (57%) in the valproate group were seizure-free during the 12-week maintenance period. Median daily dose was 250mg topiramate or 750mg valproate. Two (11%) topiramate-treated patients and one (11%) valproate-treated patient discontinued due to adverse events. Systemic toxicity scores, but not neurotoxicity scores, differed substantially between the two groups; greater systemic toxicity was associated with valproate. Our preliminary findings that topiramate may be an effective, well-tolerated alternative to valproate warrant validation in a double-blind trial.     

How to diagnose and classify idiopathic (genetic) generalized epilepsies

Idiopathic or genetic generalized epilepsies (IGE) constitute an electroclinically well‐defined group that accounts for almost one third of all people with epilepsy. They consist of four well‐established syndromes and some other rarer phenotypes. The main four IGEs are juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilepsy and IGE with generalized tonic‐clonic seizures alone. There are three main seizure types in IGE, namely generalized tonic‐clonic seizures, typical absences and myoclonic seizures, occurring either alone or in any combination. Diagnosing IGEs requires a multidimensional approach. The diagnostic process begins with a thorough medical history with a specific focus on seizure types, age at onset, timing and triggers. Comorbidities and family history should be questioned comprehensively. The EEG can provide valuable information for the diagnosis, including specific IGE syndromes, and therefore contribute to their optimal pharmacological treatment and management.     

Focal epilepsy recruiting a generalised network of juvenile myoclonic epilepsy: a case report

We report a patient with juvenile myoclonic epilepsy who subsequently developed temporal lobe epilepsy, which gradually became clinically dominant. Video telemetry revealed both myoclonic seizures and temporal lobe seizures. The temporal lobe seizures were accompanied by a focal recruiting rhythm with rapid generalisation on EEG, in which the ictal EEG pattern during the secondary generalised phase was morphologically similar to the ictal pattern during myoclonic seizures. The secondary generalised seizures of the focal epilepsy responded to sodium valproate, similar to the myoclonic epilepsy. In this rare case of coexistent Juvenile Myoclonic Epilepsy and Temporal lobe epilepsy, the possibility of focal epilepsy recruiting a generalised epileptic network was proposed and discussed.     

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.     

CBF changes in drug naive juvenile myoclonic epilepsy patients

Abstract Purpose The role of thalamus and brainstem in generalized epilepsy has been suggested in previous studies. The aim of the present study was to assess regional cerebral blood flow (rCBF) abnormality in juvenile myoclonic epilepsy (JME) patients. Methods ^99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed in 19 drug naive JME patients and 25 normal controls with the similar age and gender distribution. Differences of rCBF between a JME group and a normal control group were examined by the statistical parametric mapping of brain SPECT images using independent t test. The regression analyses in SPM were also performed between rCBF and the age of seizure onset or the disease duration in JME group. Results Compared to normal controls, the JME group showed a significant rCBF reduction in bilateral thalami, red nucleus, midbrain, pons, left hippocampus, and in the cerebelli (FDR corrected p < 0.01) whereas rCBF increase in the left superior frontal gyrus (uncorrected p < 0.001 but FDR corrected p > 0.05). Disease duration was negatively correlated with rCBF in bilateral frontal cortices, caudate nuclei, brainstem and cerebellar tonsils. Conclusions Our results suggest that abnormal neural networks in the thalamus, hippocampus, brainstem and cerebellum are associated with JME.     

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors

ObjectiveOur goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases.MethodsWe retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria.ResultsStudy involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15–53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance.ConclusionJME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.     

Analysis of background EEG activity in patients with juvenile myoclonic epilepsy

PURPOSE: To analyze background EEG activity of patients with juvenile myoclonic epilepsy (JME) with and without antiepileptic drugs. METHODS: We studied the background EEG activity in 18 patients with JME. The qEEG analysis included absolute power (AP), relative power (RP) and mean frequency (MF) of delta, theta, alpha and beta bands. The Z scores were calculated by comparison with population parameters based on the age-dependent regression function. Seven patients were unmedicated (UM) and eleven medicated (M). RESULTS: The UM group presented 69 (4.32%) abnormal Z scores and 227 (9.05%) in the M group (P<0.001). In the UM group, AP delta abnormal Z scores were identified in frontotemporal and occipital leads. In AP alpha and beta bands an increase in Z scores was encountered in frontoparietal leads in three patients. In addition, in three patients, the AP theta Z scores were below -1.96 and distributed in all regions. In the M group, AP beta Z scores were above 1.96 in frontoparietal leads in 7 of 11 patients. The AP delta increased above 1.96 in frontotemporal and occipital leads in 6 patients of 11. The AP alpha showed an abnormal decrease in Z scores in 5 of 11 patients, whereas other 5 patients presented normal scores. The AP theta presented 7 normal Z scores out of 11; this band exhibited the lowest number of abnormalities of the 4. CONCLUSION: Patients with JME have an increase in AP delta, alpha and beta bands, which is more evident in frontoparietal regions.