Slow repetitive transcranial magnetic stimulation in refractory juvenile myoclonic epilepsies.

OBJECTIVE: The objective of the study was to investigate the effects of slow repetitive transcranial magnetic stimulation (rTMS) on patients with refractory juvenile myoclonic epilepsy (JME). METHODS: One thousand pulses with the intensity of 120% active motor threshold (AMT) at 0.2 Hz frequency were applied on 5 consecutive days in 10 patients with refractory JME. Sham rTMS was performed after 3 months. Electroencephalography (EEG) examinations were performed before rTMS, on the 5th day, and 1, 2, 4, and 8 weeks after rTMS. Resting motor threshold (RMT), AMT, and cortical silent periods (CSPs) were recorded before the application and at the end of day 5. The changes in the quality of life were evaluated using the Quality of Life in Epilepsy Inventory (QOLIE-31). RESULTS: No adverse effects were observed. The number of seizures decreased by 29-50%, and interictal discharge durations decreased 2 weeks after the real rTMS. No significant difference was observed between the AMT and RMT values recorded before and after the stimulations. Statistically significant increases in CSP duration and quality of life scores were found following real rTMS. Repetitive transcranial magnetic stimulation may be considered as a safe treatment option in refractory JME. CONCLUSION: This study provides some positive evidence that rTMS may be effective in resistant JME.

Prevalence and clinical characteristics of headache in juvenile myoclonic epilepsy: experience from a tertiary epilepsy center.

The comorbidity of headache and epilepsy is often seen in neurological practice. The objective of this study was to assess the prevalence, types of, and risk factors for headache in juvenile myoclonic epilepsy (JME). We assessed a total of 200 patients and 100 healthy controls in our study. Headache was classified in participants using a self-administered questionnaire. Demographical, clinical features and headache characteristics were recorded. Seizure and headache temporal profiles were noted. Headache was present in 111 (56%) patients and 50 (50%) healthy participants. From these patients, 47 (42.3%) JME patients had migraine [30 (27%) migraine without aura (MO), 17 (15.3%) migraine with aura (MA)], 52 (46.8%) had tension type headache (TTH), 4 (3.6%) had both migraine and TTH, and 8 (7.2%) had other non-primary headaches. In the healthy control group, migraine was detected in 16 (32%) subjects, TTH in 33 (66%), both migraine and TTH in 1 (2%) subject. A positive migraine family history and symptom relief with sleep were more frequent in JME patients (p = 0.01). Headache was classified as inter-ictal in 82 (79.6%) patients and peri-ictal in 21 (20.4%) patients. In conclusion, the present study revealed that headache frequency was not significantly different between JME patients and healthy controls (p > 0.05). However, migraine frequency was higher in JME patients than healthy controls. Some migraine and TTH characteristics were different in between groups. We suggest that our results support both genetic relationship and shared underlying hypothetical pathopysiological mechanisms between JME and headache, especially migraine.

Electroclinical and prognostic characteristics of epilepsy patients with photosensitivity.

BACKGROUND AND PURPOSE: Epilepsy with photosensitivity (PSE) is one of the reflex epilepsy types with pathophysiology still unexplained. In our study we aimed to evaluate the clinical, electroencephalogram (EEG) and prognosis of patients with PSE diagnosis. METHODS: A total of 44 patients with PSE diagnosis according to international classification were included in this retrospective and cross-sectional study. The age, gender, syndrome, clinical and EEG characteristics of patients, and treatment response were investigated. RESULTS: The mean age was 22.09±6.49 years for 28 females and 16 males included in the study. Of patients, 17 had idiopathic photosensitive occipital lobe epilepsy (IPOLE), 11 had juvenile myoclonic epilepsy (JME), 11 had other PSE and 5 had juvenile absence epilepsy (JAE), with the most common visual trigger factors television and sunlight. In terms of seizure type, the most common was generalized tonic clonic seizure (GTCS), with myoclonus, absence and other seizure types observed. There was family history present in 17 patients and valproic acid was most commonly used for treatment. CONCLUSION: As noted in the literature, our data show that PSE has defined age group and clinical presentation, good prognosis but requires correct choice of medication for treatment. It is thought that good description of these epilepsy types will reduce misdiagnosis and mistreatment rates.

Outcome of childhood-onset epilepsy from adolescence to adulthood: Transition issues.

This is the second of three papers that summarize the second symposium on Transition in Epilepsies held in Paris in June 2016. This paper addresses the outcome for some particularly challenging childhood-onset epileptic disorders with the goal of recommending the best approach to transition. We have grouped these disorders in five categories with a few examples for each. The first group includes disorders presenting in childhood that may have late- or adult-onset epilepsy (metabolic and mitochondrial disorders). The second group includes disorders with changing problems in adulthood (tuberous sclerosis complex, Rett syndrome, Dravet syndrome, and autism). A third group includes epilepsies that change with age (Childhood Absence Epilepsy, Juvenile Myoclonic Epilepsy, West Syndrome, and Lennox-Gastaut syndrome). A fourth group consists of epilepsies that vary in symptoms and severity depending on the age of onset (autoimmune encephalitis, Rasmussen's syndrome). A fifth group has epilepsy from structural causes that are less likely to evolve in adulthood. Finally we have included a discussion about the risk of later adulthood cerebrovascular disease and dementia following childhood-onset epilepsy. A detailed knowledge of each of these disorders should assist the process of transition to be certain that attention is paid to the most important age-related symptoms and concerns.

Clinical aspects of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a recognizable, frequent epileptic syndrome. The most typical ictal phenomenon is bilateral myoclonia without loss of consciousness (M), with most patients also presenting with generalized tonic-clonic seizures (GTCSs) and some with absence seizures (ASs). The most striking features of JME are its onset around the time of puberty and the fact that seizure episodes occur after awakening from a sleep period or in the evening relaxation period and are facilitated by sleep deprivation and sudden arousal. Photic sensitivity is common in the EEG laboratory but uncommon or unrecognized in daily life. The clinical features of JME make it easy to diagnose. In recent years, awareness of JME has increased, and patients are often accurately diagnosed clinically before confirmation by EEG. The typical circumstance at diagnosis is a first GTCS episode, and one learns during the interview that the patient has had M in the morning for some time before the GTCS episode. There are only few differential diagnoses: the adolescent-onset progressive myoclonus epilepsies, or other forms of idiopathic generalized epilepsies of adolescence. With JME being so common, we propose that a first GTCS episode in a teenager should be considered as revealing JME until proven otherwise.

Management of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common form of epilepsy and a fairly lifelong disorder that may significantly lower a patient's expectations and potential for a full life. Luckily, it is also a highly treatable disorder, and up to 85% of patients with JME will enjoy satisfactory seizure control. Among anticonvulsants, valproate still stands out as the most efficacious drug, but may be poorly tolerated by some, and is considered unsafe for the fetuses of pregnant women. Alternatives have emerged in recent years, especially levetiracetam, but also topiramate, zonisamide or lamotrigine. In some cases, combination therapy may be useful or even required. One should not forget the potential aggravation induced not only by some commonly used anticonvulsants, especially carbamazepine and oxcarbazepine, but also, in some patients, by lamotrigine. In special settings, older drugs like benzodiazepines and barbiturates may be useful. But the management of JME should also include intervention in lifestyle, with strict avoidance of sleep deprivation and the management of copathologies, including the cognitive and psychiatric problems that are often encountered. With adequate management, there will only remain a small proportion of patients with uncontrolled epilepsy and all of its related problems. Juvenile myoclonic epilepsy is a condition in which the clinician has a fair chance of significantly helping the patient with medication and counseling.

Consensus on diagnosis and management of JME: From founder's observations to current trends.

An international workshop on juvenile myoclonic epilepsy (JME) was conducted in Avignon, France in May 2011. During that workshop, a group of 45 experts on JME, together with one of the founding fathers of the syndrome of JME ("Janz syndrome"), Prof. Dr. Dieter Janz from Berlin, reached a consensus on diagnostic criteria and management of JME. The international experts on JME proposed two sets of criteria, which will be helpful for both clinical and scientific purposes. Class I criteria encompass myoclonic jerks without loss of consciousness exclusively occurring on or after awakening and associated with typical generalized epileptiform EEG abnormalities, with an age of onset between 10 and 25. Class II criteria allow the inclusion of myoclonic jerks predominantly occurring after awakening, generalized epileptiform EEG abnormalities with or without concomitant myoclonic jerks, and a greater time window for age at onset (6-25years). For both sets of criteria, patients should have a clear history of myoclonic jerks predominantly occurring after awakening and an EEG with generalized epileptiform discharges supporting a diagnosis of idiopathic generalized epilepsy. Patients with JME require special management because their epilepsy starts in the vulnerable period of adolescence and, accordingly, they have lifestyle issues that typically increase the likelihood of seizures (sleep deprivation, exposure to stroboscopic flashes in discos, alcohol intake, etc.) with poor adherence to antiepileptic drugs (AEDs). Results of an inventory of the different clinical management strategies are given. This article is part of a supplemental special issue entitled Juvenile Myoclonic Epilepsy: What is it Really?

Lifetime prognosis of juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is among the most common types of genetic epilepsies, displaying a good prognosis when treated with appropriate drugs, but with a well-known tendency to relapse after withdrawal. The majority of patients with JME have continuing seizures after a follow-up of two decades. However, 17% are able to discontinue medication and remain seizure-free thereafter. Clinicians should remember that there is a small but still considerable subgroup of JME patients whose seizures are difficult to treat before informing patients with newly-diagnosed JME about their "benign" prognosis. This resistant course is not fully explained, though there are many suggested factors. The dominating myoclonic seizures disappear or diminish in severity in the fourth decade of life. Despite the favorable seizure outcome in most of the cases, 3/4 of patients with JME have at least one major unfavorable social outcome. The possible subsyndromes of JME, its genetic background, and its pathophysiological and neuroimaging correlates should be further investigated.

Mania following vagus nerve stimulation: a case report and review of the literature.

Vagus nerve stimulation (VNS) is an increasingly used therapy for patients with treatment-refractory epilepsy and depression. Hypomanic and manic symptoms are a rare but recognized adverse effect of VNS treatment. Here we describe a case in which VNS treatment in a patient with epilepsy and unipolar depression was associated with the rapid development of manic symptoms. The patient's manic symptoms resolved with temporary discontinuation of the VNS current, and the patient was eventually able to resume VNS treatment with good effect and without further manic symptoms. Mania is a rare but serious side effect of VNS; however, in this case and in the majority of reported cases of VNS-associated mania, symptoms resolve and VNS can be safely administered.

Challenges in the treatment of a chronic disease: A study of narratives of people with juvenile myoclonic epilepsy.

PURPOSE: The purpose of this study was to explore how people with juvenile myoclonic epilepsy perceive the impact of treatment. METHODS: We conducted 14 interviews of participants with juvenile myoclonic epilepsy recruited with the support of the Brazilian Association of Epilepsy in 2018 in São Paulo. Thematic analysis was carried out by two investigators who independently coded the transcripts and reviewed the coding results to check for agreement. RESULTS: Participants' (n = 14, 8 female) mean age was 31.4 years (SD ± 8.3) and their onset of seizures occurred at mean age 13.4 (SD ± 2.9). The answers to the interview questions revealed the paths of participants through life as they dealt with difficulties and challenges. Three interrelated themes and seven sub-themes emerged from the answers of the participants: seizure control, impact of epilepsy and attitude of others. CONCLUSION: This investigation may be useful in providing insights for the interventions of health providers in caring for people with JME. Themes and sub-themes that emerged from this study are connected to important aspects of treatment that go beyond focusing solely on seizures.

Clinical profile and treatment outcome of epilepsy syndromes in children: A hospital-based study in Eastern Nepal.

Objective: It is often difficult to diagnose epilepsy syndromes in resource-limited settings. This study was aimed to investigate the prospect of ascertaining the diagnosis, clinical profile, and treatment outcomes of epilepsy syndromes (ESs) among children in a resource-limited setting. Methods: This was a descriptive study done from 01/07/2009 to 15/06/2017 among children (1-17 years of age) with unprovoked seizures presenting to the pediatric neurology clinic of a university hospital in eastern Nepal. Diagnosis, classification, and treatment of seizures were based upon International League Against Epilepsy guidelines. Results: Of 768 children with unprovoked seizures, 120 (15.6%) were diagnosed as ES. The age of onset of seizure was unique for each ES. Developmental delay and cerebral palsy were present in 47.5% and 28.3% children, respectively. Common ESs were West syndrome (WS)-26.7%, generalized tonic-clonic seizures alone (GTCSA)-21.7%, self-limited childhood epilepsy with centrotemporal spikes (SLCECTS)-12.5%, childhood absence epilepsy (CAE)-10.0%, Lennox-Gastaut syndrome (LGS)-10.0%, other developmental and epileptic encephalopathies (DEE)-5.8%, self-limited familial infantile epilepsy (SLFIE)-4.2%, and juvenile myoclonic epilepsy (JME)-3.3%. Among children with known outcomes (87/120), overall response to pharmacotherapy and to monotherapy was observed in 72.4% (63/87) and 57.5% (50/87) children, respectively. All children with GTCSA, SLFIE, genetic epilepsy with febrile seizure plus (GEFS+), CAE, SLCECTS, and JME responded to pharmacotherapy and they had normal computerized tomography scans of the brain. Seizures were largely pharmaco-resistant in progressive myoclonus epilepsy (PME)-100.0%, LGS-73.0%, WS-52.0%, and other DEEs-40%. Significance: A reasonable proportion (15.6%) of unprovoked seizures could be classified into specific ES despite limited diagnostic resources. WS was the most common ES. GTCSA, SLCECTS, CAE, and LGS were other common ESs. GTCSA, SLFIE, CAE, SLCECTS, GEFS+, and JME were largely pharmaco-responsive. PME, WS, and LGS were relatively pharmaco-resistant. Electro-clinical diagnosis of certain ES avoids the necessity of neuroimaging.

Epileptiform asymetries and treatment response in juvenile myoclonic epilepsy.

BACKGROUND: Epileptiform electroencephalogram (EEG) asymmetries are not uncommon in juvenile myoclonic epilepsy (JME) and can contribute to the misdiagnosis of this syndrome. The objective of this study is to further characterize patients with focal or asymmetric epileptiform electroencephalographic abnormalities and more specifically in terms of response to treatment. Controversial data exists in the literature concerning this issue. METHODS: We retrospectively reviewed clinical and EEG data of a group of consecutive JME patients followed at our Epilepsy Service. The first EEG available for each patient was reviewed blindly by two independent electroencephalographers. RESULTS: Twenty-eight patients with JME were identified: 11 (39.3%) were resistant to at least one appropriate anti-epileptic drug (AED), including valproate, lamotrigine, topiramate or levetiracetam. All patients except two had generalized epileptiform abnormalities. Overall, EEG asymmetries were detected in 57.1% of the cases. The proportion of EEG asymmetries between AED-sensitive group (52.9%) and AED-resistant group (63.5%) did not reach statistical significance. Concordance between examiners for identification of EEG asymmetries was good. Analysis of patients with and without asymmetries showed no statistically significant differences in comparisons of age, family history of seizure, presence of polyspike and slow wave, photosensitivity and timing of EEG related to the onset of treatment. CONCLUSION: Asymmetric electroencephalographic abnormalities are frequent in patients with JME. These features should not be misinterpreted as being indicative of partial epilepsy. In our group, asymmetries were not associated with resistance to treatment.

[Clinical factors related to treatment resistance in juvenile myoclonic epilepsy].

UNLABELLED: Juvenile myoclonic epilepsy (JME) is one of the most representative idiopathic generalized epilepsies occurring in adolescence. Although epileptic seizures in JME are easily controlled by appropriate antiepileptic drug (AED) treatment, there have recently been several reports that approximately 15-20% of patients with JME are resistant to such treatment, despite an accurate diagnosis and choice of AEDs. In this study, we sought to identify risk factors that may lead to treatment resistance in patients with JME. SUBJECTS AND METHODS: The subjects were 47 patients meeting the criteria of JME, and had been followed up for over 2 years. We retrospectively analyzed the response to treatment, and classified them into 3 groups: group 1 consisting of fully controlled cases (N = 33), group 2 of a true resistant case (N = 1), and group 3 of pseudoresistant cases (N = 13). The epileptic seizures in group 2 were difficult to control despite various AED treatments from the onset of epilepsy. Group 3 cases showed a recurrence of seizures despite excellent initial responses to AEDs. Among the group 3 cases, 4 patients showed a low compliance with AEDs because of poor recognition of their epilepsy, while the remaining 9 patients had serious psychosocial factors potentially aggravating the seizures. CONCLUSION: Approximately 30% of patients with JME experienced a recurrence of seizures despite an appropriate choice of AEDs. Most of them were categorized into refractory JME due to various psychosocial factors. Our results suggest that seizure control and the quality of life in this group are improved by education, psychological treatment, and favorable life-styles.

Tap seizures in infancy: A critical review.

Tap seizure is a type of reflex myoclonic epilepsy in which seizures are evoked mainly by unexpected tactile stimuli and which is classified among the electroclinical syndromes of infancy. This condition, whose onset is in the first two years of life, is characterized by excellent prognosis and is extremely rare. We reviewed all published articles and case reports on Reflex Myoclonic Epilepsies focusing on touch-induced seizures in order to clarify clinical and electroencephalographic findings. Our aim is to increase knowledge about this specific disorder in order to help pediatricians avoid extensive investigations when making their diagnosis and reassure parents regarding absence of long-term complications.

Dravet syndrome (severe myoclonic epilepsy in infancy): a retrospective study of 16 patients.

To report the authors' experience with diagnosis and management of Dravet syndrome, or severe myoclonic epilepsy in infancy, in the era of commercially available genetic testing, the authors performed a retrospective study of 16 patients diagnosed with Dravet syndrome at a tertiary care pediatric epilepsy center. They analyzed their clinical presentation, electroencephalographic findings, genetic (SCN1A gene) results, and treatment responses and compared the findings to previous reports. The patients presented with all the previously described characteristics of Dravet syndrome. Six of the 7 patients (86%) who were tested for SCN1A mutations had positive results. The best treatment combinations included topiramate, valproate, or the ketogenic diet. Dravet syndrome is a well-defined epileptic syndrome that needs larger recognition, particularly because commercial testing for SCN1A gene mutations is now available in the United States. Despite its reputation for seizure intractability, several treatment options may be particularly helpful, whereas others need to be avoided.

Juvenile myoclonic epilepsy: Challenges on its 60th anniversary.

PURPOSE: Since its initial 1957 description, juvenile myoclonic epilepsy (JME) has been recognized as a common epileptic syndrome worldwide. METHODS: We reviewed a series of articles on JME to clarify challenges in clinical and pathophysiological findings, treatment and outcome. RESULTS: Typical JME characteristics include: 1) the age at seizure onset between 10 and 25 years; 2) the triad of myoclonia, generalized tonic-clonic seizures, and absences, of which only myoclonia is a mandatory criterion; 3) cognitive dysfunction that may have impact on interpersonal relationships and social outcome; 4) possibility of seizure control in up to 80% of individuals, in particular with the use of sodium valproate; 5) a tendency for lifelong seizures with an early morning preponderance; 6) after decades from the clinical onset, a possibility to be off medications for a third of the patients, and 7) several prognostic factors. CONCLUSION: After 60 years, several challenges remain in this complex epileptic syndrome.

Orofacial reflex myocloni. Definition, relation to epilepsy syndromes, nosological and prognosis significance. A focused review.

PURPOSE: There is increasing awareness that reflex epileptic mechanisms provide unique insight into ictogenesis in human epilepsies. Among the complex triggers of seizures, this review considers orofacial reflex myocloni (ORM) from the aspects of history and delineation, clinical and electroencephalographic presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and nosological implications, treatment and prognosis. METHODS: We reviewed all published articles and case reports on ORM in order to clarify clinical and electroencephalographic findings, treatment and outcome. RESULTS: ORM, besides Reading Epilepsy (RE), is closely related to idiopathic generalized epilepsies especially Juvenile Myoclonic Epilepsy (JME) where hyperexcitability of the network supporting linguistic communication seems to provide the precondition for eliciting reflex myocloni in the perioral muscles active in the precipitating task. CONCLUSION: The conclusions on ictogenesis derived from ORM support the concept of both, RE and JME, as system disorders of the brain.

Terminal remission is possible in some patients with juvenile myoclonic epilepsy without therapy.

INTRODUCTION: Juvenile myoclonic epilepsy is considered to be a chronic disease requiring lifelong antiepileptic treatment. The aim of this study was both to identify factors predicting the kind of seizure control and to investigate the outcome in patients after therapy withdrawal. MATERIAL AND METHODS: The study included 87 patients (49 female, 38 male), aged from 17.5 to 43.5 years, referred to our Department between 1987 and 2008, with the seizure onset at the age of 14.3±2.9, and followed up for 13.3±5.8 years on average (from 5 to 23 years). RESULTS: Sixty seven (77.0%) patients were fully controlled; whereas 13.8% had persistent seizures and 9.2% showed pseudoresistance. The combination of three seizure types and focal electroencephalogram features were independent factors of poor seizure control. Therapy was discontinued in 34 patients either by the treating physician (in 21 patients) or by the patients themselves (in 13 cases). In 18 subjects, all seizure types relapsed after 1.1 year on average (from 7 days to 4 years) and therapy was resumed in them. All patients but three (10/13), who stopped the treatment themselves, experienced recurrences. Seizure freedom off drugs was recorded in 10.3% patients. Nonintrusive myoclonic seizures recurred in 0.5-3 years as their only seizure type in four patients, but without reintroducing medication in three patients. CONCLUSION: Combination of seizure types and focal electroencephalogram features are significant factors of pharmacoresistancy. Continuous pharmacotherapy is required in majority of patients, although about 10% of them appear to have permanent remission without therapy in adolescence.