Treatment Of Juvenile Myoclonic Epilepsy Research Articles

Challenges in the Treatment of Juvenile Myoclonic Epilepsy in Female Patients

Challenges in the Treatment of Juvenile Myoclonic Epilepsy in Female Patients

Trends in the choice of antiseizure medications in juvenile myoclonic epilepsy: A retrospective multi-center study from Turkey between 2010 and 2020

Purpose:Valproic acid (VPA) is frequently used and effective in juvenile myoclonic epilepsy (JME). Recently, levetiracetam (LEV) has been suggested as a monotherapy in JME. This study aimed to evaluate antiseizure medication (ASM) use in patients with JME.Methods: Treatment choices in a total of 257 patients (age range 8–18 years, 152 girls, 105 boys) with JME diagnosed and treated between 2010 and 2020 were evaluated retrospectively. Seizure remission was defined as complete seizure control for at least 12 months.Results: Across the study period and entire patient group, VPA was most commonly chosen as the initial ASM (50.9%), followed by LEV (44.4%), and lamotrigine (4.7%). VPA was also the most frequent first choice in the subgroup of boys (73.3%), while LEV was the commonest first choice in girls (57.9%). The sex difference regarding the ASM of the first choice was statistically significant (p<0.001). While VPA was the most frequent initial ASM in the first 5 years of the study period (2010–2015,n = 66, 64%), LEV had taken over as the most popular first ASM in the last 5 years (n = 83, 53.9%, p = 0.005). The most frequent reasons for discontinuation were inefficacy for LEV and adverse effects for VPA (p = 0.001). During follow-up, 237 patients (92.2%) were seizure-free for at least 12 months, and 159 (61.9%) were also in electrographic remission. Seizure remission occurred earlier than electroencephalographic remission (p<0.001).Conclusion: This study revealed that LEV has become the most frequently chosen initial ASM in the treatment of JME. Although LEV appears to have a better adverse effect profile, VPA seems more likely to be effective in achieving seizure control.

Safety and Efficacy of Clonazepam in the Treatment of Juvenile Myoclonic Epilepsy: A Meta-Analysis.

Juvenile myoclonic epilepsy (JME) is referred to as one of the most common epileptic syndromes. Several anti-epilepsy drugs (AEDs) have been developed and remain part of clinical intervention with varying safety and efficacy profiles. Comprehensive synthesis of the scientific evidence examining the safety and efficacy of clonazepam toward the treatment of JME was carried out in the study. A detailed scientific literature search was made utilizing the most relevant scientific studies published to date on the intervention of clonazepam in the management of JME. In this study, a detailed search was made in multiple databases, including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scielo databases. Confidence intervals among the studies and continuous measures, proportion, and risk factor analysis were determined using the MedCalC tool (Version 20.110) as per PRISMA guidelines. A total of 6 studies out of 70 were found eligible for meta-analysis, where 186 JME patients were subjected to clonazepam intervention with controls. Clonazepam was reported effective in comparative analysis among six studies where P < 0.001. The result also shows a higher prevalence of JME in the female population compared to males (male versus female; 86/110). Efficacy and safety of clonazepam were reported significant as well. Clonazepam is effective AEDs for the management of JME. However, more clinical evidence requires for statistical validation of clinical efficacy.

Topiramate for juvenile myoclonic epilepsy.

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019. To evaluate the efficacy and tolerability of topiramate in the treatment of JME. For the latest update, we searched the Cochrane Register of Studies (CRS Web) on 26 August 2021, and MEDLINE (Ovid 1946 to 26 August 2021). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy. We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs). Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality of the studies. We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or greater reduction in primarily generalized tonic-clonic seizures (PGTCS), compared with participants in the placebo group (RR 4.00, 95% CI 1.08 to 14.75; 1 study, 22 participants; very low-certainty evidence). There were no significant differences between topiramate and valproate for participants responding with a 50% or greater reduction in myoclonic seizures (RR 0.88, 95% CI 0.67 to 1.15; one study, 23 participants; very-low certainty evidence) or in PGTCS (RR 1.22, 95% CI 0.68 to 2.21; one study, 16 participants, very-low certainty evidence), or participants becoming seizure-free (RR 1.13, 95% CI 0.61 to 2.11; one study, 27 participants; very-low certainty evidence). Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints (2 studies, 61 participants; very low-certainty evidence). Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged the studies to be at low to unclear risk of bias for the remaining domains (selection bias, performance bias, detection bias and other bias). We judged the overall certainty of the evidence for the outcomes as very low using the GRADE approach. We have found no new studies since the last version of this review was published in 2019. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Treatment of Juvenile Myoclonic Epilepsy in Patients of Child-Bearing Potential.

Juvenile myoclonic epilepsy (JME) is both a frequent and a very characteristic epileptic syndrome with female preponderance. Treatment of JME in women of childbearing potential must consider multiple factors such as desire for pregnancy, use of contraception, seizure control and previously used antiepileptic drugs (AEDs). Approximately 85% of cases are well controlled with valproate, which remains the reference AED in JME but is nowadays considered unsafe for the expecting mother and her fetus. The prescription of valproate is now severely restricted in women of childbearing potential but may still be considered, at the lowest possible dose and when pregnancies can be reliably planned, with temporary alternatives to valproate prescribed before fertilization. Alternatives have emerged, especially lamotrigine and levetiracetam, but also topiramate, zonisamide, and recently perampanel, but none of these AEDs can be considered fully safe in the context of pregnancy. In special settings, benzodiazepines and barbiturates may be useful. In some cases, combination therapy, especially lamotrigine and levetiracetam, may be useful or even required. However, lamotrigine may have the potential to aggravate JME, with promyoclonic effects. Carbamazepine, oxcarbazepine and phenytoin must be avoided. Valproate, levetiracetam, zonisamide, topiramate if the daily dose is ≤ 200mg and perampanel if the daily dose is ≤ 10mg do not affect combined hormonal contraception. Lamotrigine ≥ 300mg/day has been shown to decrease levonorgestrel levels by 20% but does not compromise combined hormonal contraception. Patients with JME taking oral contraceptive should be counselled on the fact that the estrogenic component can reduce concentrations of lamotrigine by over 50%, putting patients at risk of increased seizures. Pregnancy is a therapeutic challenge, and the risk/benefit ratio for the mother and fetus must be considered when choosing the appropriate drug. Lamotrigine (< 325mg daily in the European Registry of Antiepileptic Drugs in Pregnancy) and levetiracetam seem to be comparatively safer in pregnancy than other AEDs, especially topiramate and valproate. Plasma concentration of lamotrigine and levetiracetam decreases significantly during pregnancy, and dosage adjustments may be necessary. With persisting generalized tonic-clonic seizures, the combination of lamotrigine and levetiracetam offer the chance of seizure control and lesser risks of major congenital malformations. The risk of malformation increases when valproate or topiramate are included in the drug combination. In one study, the relative risk of autism and autism spectrum disorders (ASD) in children born to women with epilepsy (WWE) treated with valproate were, respectively, 5.2 for autism and 2.9 for ASD versus 2.12 for autism and 1.6 for ASD in WWE not treated with valproate. More studies are needed to assess the risk of autism with AEDs other than valproate. The current knowledge is that the risk appears to be double that in the general population. In patients with JME, valproate remains an essential and life-changing agent. The consequences of a lifetime of poorly controlled epilepsy need to be balanced against the teratogenic risks of valproate during limited times in a woman's life. The management of JME in WWE should include lifestyle interventions, with avoidance of sleep deprivation, and planned pregnancy.

Topiramate for juvenile myoclonic epilepsy.

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2017. To evaluate the efficacy and tolerability of topiramate in the treatment of JME. For the latest update, on 10 July 2018 we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid 1946- ), and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies. We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs). Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data. We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate and valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS, or becoming seizure-free. Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group.Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged all three studies to be at low to unclear bias for the remaining risk of bias domains (random sequence, allocation, blinding). We judged the quality of the evidence from the studies to be very low. We have found no new studies since the last version of this review was published in 2017. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Topiramate monotherapy for juvenile myoclonic epilepsy.

Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015. To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME. For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies. We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs). Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data. We included three studies with 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low. Since the last version of this review we found no new studies. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Problems of juvenile myoclonic epilepsy. A view through the prism of time

The authors present a comparative analysis of the results of the study of 72 adolescent patients with juvenile myoclonic epilepsy (JME), which were published in 2010, and a new sample of patients over the last 5 years with the publications of domestic and foreign authors. Difficult clinical cases are described. These data indicate positive shifts in the diagnosis and treatment of JME. However, the question of diagnosis is still a hard problem for neurologists. The questions to be resolved are: gender aspect of the disease, to what extent levetiracetam could be a drug of first choice and to what extent valproats could be replaced; monitoring of children born to mothers with JME, a role of paternal inheritance.

Topiramate monotherapy for juvenile myoclonic epilepsy.

Topiramate is a newer broad-spectrum of antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. To determine the efficacy and tolerability of topiramate monotherapy in the treatment of JME. We searched the Cochrane Epilepsy Group Specialized Register (2 November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies CRSO, 2 November 2015), MEDLINE (Ovid, 2 November 2015), EMBASE (1 July 2015) and ClinicalTrials.gov (2 November 2015). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies. We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs). Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data. We included three studies with 83 participants. For the efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

Treatment of pediatric epilepsy in Poland

BackgroundThe many types of childhood epilepsies make the diagnosis and treatment difficult and the outcomes frequently poor. Furthermore, there are few clinical trials in pediatric epilepsy that provide useful results to guide daily practice. Therefore for pediatric neurologists expert opinion may be useful. AimsTo provide an overview of current practice in Poland and compare results with European and US clinical guidelines. MethodsPolish specialists in pediatric neurology were asked to participate in a survey about pediatric epilepsy. The focus of the questions was on the overall strategy and treatment options for different syndromic diagnoses. The survey was developed and performed according to a previous European survey (Wheless et al., 2007). ResultsFifty-one Polish specialists, working in academic or clinical settings, completed the questionnaire. They limited combination therapy to two or three antiepileptic drugs. Valproate was the treatment of choice for myoclonic, generalized tonic-clonic seizures and Lennox-Gastaut syndrome. For infantile spasms caused by tuberous sclerosis and of symptomatic etiology, vigabatrin was treatment of choice; valproate and ACTH were other first line options. Valproate and ethosuximide were chosen for childhood absence epilepsy and valproate for juvenile absence epilepsy. Carbamazepine was the first-line treatment option for benign partial epilepsy of childhood with centrotemporal spikes and complex partial seizures. In the treatment of juvenile myoclonic epilepsy for males valproate, for females lamotrigine were chosen. ConclusionPolish pediatric neurologists agreed on the majority of questions. Their views reflect the clinical utility and availability of treatment options in Poland. Results may provide direction for clinicians.

Burns from foul play? No – previously unsuspected epilepsy

SUMMARY Introduction. Injuries such as burns may occur from unwitnessed and unsuspected new onset epilepsy with forensic implications. Case report. A young woman was found with &gt;25% 2nd and 3rd degree body burns after an unwitnessed morning event in a shower. Discussion. The onset of tonic-clonic seizures and limb jerks in adolescence with a typical EEG recording of 3–4/second spike/polyspike-and-waves are diagnostic of Juvenile Myoclonic Epilepsy (JME). Worldwide there is a significant morbidity and mortality in epilepsy from burns. The treatment of JME and of burns was discussed.

Lacosamide treatment of juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy is the most common form of idiopathic generalized epilepsy with onset at puberty or late teenage years. About 80–90% of patients with juvenile myoclonic epilepsy respond to appropriate antiepileptic treatment and achieve seizure freedom, and about 15% of patients become intractable. Valproic acid, levetiracetam, lamotrigine, topiramate and zonisamide are used as first line or adjunctive therapy of this disorder. Lacosamide is approved for adjunctive treatment of partial onset epilepsies. The role of lacosamide in treatment of idiopathic generalized epilepsy including juvenile myoclonic epilepsy is unknown. We present three patients with classic clinical and electrographic features of juvenile myoclonic epilepsy that were maintained on lacosamide (one on monotherapy and two as adjuvant therapy). There were no special pharmacodynamic actions causing exacerbation or worsening of myoclonic jerks or generalized seizures in these three patients. In conclusion, although, the data from our three patients’ suggest that lacosamide may be effective in the treatment of juvenile myoclonic epilepsy, larger studies are needed to explore efficacy and role of lacosamide in the treatment of this disorder.

Migraine attack triggering a generalised seizure: is this a case of migralepsy or ictal epileptic headache?

We describe the electro-clinical, neuroimaging and treatment features of a 23-year-old woman patient who suffered of migraine and epilepsy. The historical based hypothesis that migraine and epilepsy are related dates back to the 19th century. Although, it is rare that a migraine attack triggered an epileptic seizure (phenomenon called migralepsy), headache develops very frequently prior or after an epileptic seizure [1, 2]. Migraine and epilepsy are strongly associated, independent of seizure type, aetiology, age at onset or family history of epilepsy [1, 2]. Although the association between migraine and epilepsy is independent from the epilepsy syndrome and the risk of migraine is evident within every type of epilepsy, it is reasonable to think that this relationship can be even more common among female patients. In fact, migraine is often encountered in female patients compared to males [2]. Juvenile myoclonic epilepsy (JME) is one of the most common idiopathic generalized epilepsy in women, and it is characterized by frequent bilateral myoclonic jerks of the arms associated at times with generalized tonic–clonic or absence seizures with a good response to antiepileptic drugs [3–5]. Habitually, menstrual period and sleep deprivation can trigger seizures. Seizures are very well controlled by appropriate therapy in up to 90% of subjects [3, 4]. Generalized 3–6 Hz polyspike-wave (PSW) discharges are the cornerstone in the diagnosis and treatment of JME [3–5]. According to the International Classification of Headache Disorders II (ICHD-II), the diagnosis of ‘‘migralepsy’’ should fulfil two diagnostic criteria: migraine fulfilling criteria for migraine with aura (MA) and a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within one hour after a migraine aura [6]. A 23-year-old woman referred to the epilepsy outpatients clinic of the University of Catanzaro, because of a reappearance of generalised tonic–clonic seizures (GTCS). The patient signed informed consent. She had unremarkable past medical history other than history of migraine attacks. At admission, her neurological examination was normal. She had either family history of epilepsy and migraine. At 13 years of age she began having very rare episodes of headaches preceded by visual aura lasting no longer than one hour usually around 20 min. These attacks had clinical features of migraine with aura according to ICHD-II [6]. At 15 years of age, she began having 2–3 min episodes of unprovoked myoclonic jerks mainly on awakening with or without GTCS and/or typical absence seizures. She had no evidence of intellectual or neurological deficit. The diagnosis of JME was made using the Classification of the International League Against Epilepsy (ILAE) [7]. She underwent to various EEG recordings performed during wakefulness in a soundproof room, with a Xltek machine, employing scalp electrodes placed A. Labate (&) F. Pucci A. Quattrone Institute of Neurology, University Magna Graecia, Catanzaro, Italy e-mail: labate@unicz.it

Treatment Options in Juvenile Myoclonic Epilepsy

Juvenile myoclonic epilepsy (JME) is characterized by excellent response to treatment, if diagnosed correctly. Lifestyle advice is an integral part of the treatment of JME; it should include recommendations on avoidance of common triggers such as sleep deprivation and alcohol excess and emphasis on the importance of compliance with medication. The drug of first choice in the treatment of JME is sodium valproate, which has a response rate of up to 80%. Valproate should be avoided in women of childbearing age because of significantly increased risks of fetal malformations and neurodevelopmental delay. Levetiracetam or lamotrigine are alternative first-line options if valproate is contraindicated. With limited data from trials to support either of these drugs, the choice should take into account comorbidity factors and patient priorities. Because of its low side effect profile, excellent tolerability, and lack of interactions with other drugs, levetiracetam is our preferred alternative first-line agent. Lamotrigine is another first-line option but may exacerbate myoclonus. The failure of valproate or failure of two first-line antiepileptic drugs suggests that combination therapy is indicated. Drug interactions and the patient's gender, age, and comorbidities need to be considered. Levetiracetam, lamotrigine, and valproate are suitable adjuncts, with a synergistic effect reported from the combination of valproate and lamotrigine. Clonazepam is a useful adjunct for myoclonus and can be used in combination with lamotrigine to avoid lamotrigine's myoclonic effects. In women of childbearing potential, valproate should be considered if levetiracetam and lamotrigine have failed to control seizures at this stage. Topiramate is a cost-effective alternative monotherapy, but because of its poor tolerability, we recommend it as add-on treatment only. Zonisamide should remain a second-line adjunct in the treatment of JME, owing to the lack of supportive data. Phenobarbital is the most cost-effective drug and can be used to control the seizures of JME when antiepileptic drugs are limited or too costly. Carbamazepine, oxcarbazepine, and phenytoin can exacerbate absences and myoclonus and are therefore contraindicated, although they can improve control of tonic-clonic seizures when these are refractory to other medication. Gabapentin, pregabalin, tiagabine, and vigabatrin are contraindicated and can worsen seizures. (Tiagabine and vigabatrin have been reported to induce absence status epilepticus.) Surgical alternatives in refractory cases are rarely contemplated but may include vagus nerve stimulation and callosotomy. Deep brain stimulation is an experimental technique that may prove useful in managing refractory cases of JME.

Use of Clonazepam and Avoidance of Sleep Deprivation in the Treatment of Juvenile Myoclonic Epilepsy

Objectives Juvenile Myoclonic Epilepsy(J.M.E.) needs life-long anti-epileptic drug (AED) treatment. Of various drugs tried in this condition, valproate effectively treats all types of seizures seen in J.M.E. Among valproate side effects, neural tube defects (NTD) in the offspring, is a deterring factor in its use in childbearing period. To avoid NTD, most authorities advise on switching to AED drug before conception.As well, the effects of valproate on male fertility is feared of. Clonazepam controls only the myoclonic jerks, leaving the patients unprotected and susceptible to generalized seizures, which mostly occur in the morning after sleep deprivation. Sleep deprivation is the most prevalent precipitating factor for generalized seizures in these patients. Materials M 4(26.6%) had breakthrough episodes of generalized seizures, provoked by sleep deprivation; the rest (11,73.4 %), were in full remission of their myoclonic and generalized seizures. In control group, 2(12.5 %), had episodes of breakthrough, sleep-deprived, generalized seizures;the rest(14, 87.5%) were in remission. Statistically, there was no significance between the results in both groups. Clonazepam side effects were limited to mild to moderate drowsiness in the morning, eliminated by giving the dose earlier at night. Conclusion The study suggests that if J.M.E. patients avoid sleep deprivation, they can be reated with clonazepam alone to avoid side effects of valproate.

Treatment of Juvenile Myoclonic Epilepsy

Drug treatment of juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are almost no head‐to‐head comparisons between old and new antiepileptic drugs (AEDs). Valproate is the drug of the first choice in men with JME. In women, lamotrigine (LTG) should be preferred regarding teratogenicity and side effects of valproate. Levetiracetam (LEV) is also effective. Recent data suggest that it may soon be used as first line treatment. Some AEDs can aggravate JME. In addition to AEDs, nonpharmacological treatments are important in JME. JME usually requires lifelong treatment because seizures nearly always return after withdrawal of therapy.

Treatment of Juvenile Myoclonic Epilepsy

Drug treatment of juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are almost no head-to-head comparisons between old and new antiepileptic drugs (AEDs). Valproate is the drug of the first choice in men with JME. In women, lamotrigine (LTG) should be preferred regarding teratogenicity and side effects of valproate. Levetiracetam (LEV) is also effective. Recent data suggest that it may soon be used as first line treatment. Some AEDs can aggravate JME. In addition to AEDs, nonpharmacological treatments are important in JME. JME usually requires lifelong treatment because seizures nearly always return after withdrawal of therapy.

Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy

A multicenter, prospective, long-term, open-label study to evaluate the effects of levetiracetam on electroencephalogram (EEG) abnormalities and photoparoxysmal response (PPR) of patients affected by juvenile myoclonic epilepsy (JME). Forty-eight patients with newly diagnosed JME (10) or resistant/intolerant (38) to previous antiepileptic drugs (AEDs) were enrolled. After an 8-week baseline period, levetiracetam was titrated in 2 weeks to 500 mg b.i.d. and then increased to up to 3,000 mg/day. Efficacy parameters were based on the comparison and analysis of EEG interictal abnormalities classified as spikes-and-waves, polyspikes-and-waves, and presence of PPR. Secondary end point was evaluation of EEG and PPR changes as predictive factors of 12-month seizure freedom. Overall, mean dose of levetiracetam was 2,208 mg/day. Mean study period was 19.3 +/- 11.5 months (range 0.3-38). During the baseline period, interictal EEG abnormalities were detected in 44/48 patients (91.6%) and PPR was determined in 17/48 (35.4%) of patients. After levetiracetam treatment, 27/48 (56.2%) of patients compared to 4/48 (8.3%) in the baseline period (p < 0.0001) had a normal EEG. Thirteen of 17 (76.4%) (p < 0.0003) patients showed suppression of PPR. Cumulative probability of days with myoclonia (DWM) 12-month remission was significantly higher (p < 0.05) in patients with a normal (normalized) EEG after levetiracetam treatment compared to those with an unchanged EEG. Levetiracetam appeared to be effective in decreasing epileptiform EEG abnormalities, and suppressing the PPR in JME patients. This effect, along with a good efficacy and tolerability profile in this population further supports a first-line role for levetiracetam in the treatment of JME.

Treatment of myoclonic seizures in patients with juvenile myoclonic epilepsy.

Drug treatment of Juvenile myoclonic epilepsy (JME) is mainly based on clinical experience and prospective and retrospective studies, with little evidence from randomized clinical trials. There are no head-to-head comparisons between old and new antiepileptic drugs (AEDs) and no drugs licensed specifically for JME. Valproate is unquestionably the drug of the first choice in men with JME. In women, lamotrigine should be preferred regarding teratogenicity and side effects of valproate. In addition, levetiracetam and topiramate are effective and can be use in combination or as second line treatment. Some AEDs can aggravate JME. In addition of AEDs, non-pharmacological treatments are important in JME. JME usually require lifelong treatment because seizures nearly always return after withdrawal of therapy.

Therapeutic Drug Monitoring of Levetiracetam by High-Performance Liquid Chromatography With Photodiode Array Ultraviolet Detection: Preliminary Observations on Correlation Between Plasma Concentration and Clinical Response in Patients With Refractory Epilepsy

Levetiracetam is a new antiepileptic drug prescribed for the treatment of patients with refractory partial seizures with or without secondary generalization as well as for the treatment of juvenile myoclonic epilepsy. A rapid and specific method by high-performance liquid chromatography diode array detection was developed to measure the concentration of levetiracetam in human plasma. The trough plasma concentrations measured in 69 epileptic patients treated with 500 to 3000 mg/d of levetiracetam ranged from 1.1 to 33.5 microg/mL. The mean (range) levetiracetam plasma concentrations in responders and nonresponders were 12.9 microg/mL (4.6-21 microg/mL) and 9.5 microg/mL (1.1-20.9 microg/mL), respectively. A wide variability in concentration-response relationships was observed in patients. Using a receiver operating characteristic curve, the threshold levetiracetam concentration for a therapeutic response was 11 microg/mL. The sensitivity and specificity for this threshold levetiracetam concentration were 73% and 71%, respectively. According to chi analysis, this finding was not significant probably because of the small number of patients and because of their refractory seizure type. Nevertheless, the levetiracetam plasma concentration could be used to help clinicians detect severe intoxication or to verify compliance by repeating the measurement in patients.