Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype. PED was characterized by choreoathetosis, dystonia or both, affecting mainly the legs. Predominant epileptic seizure types were primary generalized. A median CSF/blood glucose ratio of 0.52 (normal >0.60) in the patients and a reduced glucose uptake by mutated transporters compared with the wild-type as determined in Xenopus oocytes confirmed a pathogenic role of these mutations. Functional imaging studies implicated alterations in glucose metabolism in the corticostriate pathways in the pathophysiology of PED and in the frontal lobe cortex in the pathophysiology of epileptic seizures. Three patients were successfully treated with a ketogenic diet. In conclusion, co-occurring PED and epilepsy can be due to autosomal dominant heterozygous SLC2A1 mutations, expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for this clinical syndrome.

This study, supported by the Rwandan Ministry of Health and the World Health Organization, was conducted in 2005 to determine the prevalence of epilepsy and its sociocultural perception in Rwanda, as well as epilepsy-related knowledge and practices of health-care professionals (HCPs). A cross-sectional, nationally representative survey was conducted throughout Rwanda by trained investigators. Participants were recruited by random cluster sampling based on the organization of administrative units in the country. Overall, 1137 individuals (62% from rural areas) were interviewed. The prevalence of epilepsy was estimated to be 49 per 1000 people or 41 per 1000 for active epilepsy. Onset of epilepsy before the age of 2 years was reported in 32% of the cases. Family history of epilepsy, head trauma, and premature delivery were reported in 53%, 50%, and 68% of the cases, respectively. Most (68%) patients did not receive any medical treatment for epilepsy; 21.5% had received some form of traditional treatment. According to responses from the general population, people with epilepsy should not be entitled to schooling (according to 66%), to work (according to 72%), to the use of public places (according to 69%), or to marriage (according to 66%). Furthermore, 50% believed that epilepsy was untreatable, and 40% thought that it was transmissible. Of the 29 HCPs interviewed, the majority knew the definition of epilepsy and status epilepticus, as well as basic treatment options and side effects. However, 90% believed that treatment was only necessary in the first week after a seizure. Living with epilepsy was associated heavily with stigma, and a significant treatment gap (68%) was identified. Following this study, numerous actions have been taken by the Rwandan government, the Rwandan League Against Epilepsy, and several nongovernmental organizations to increase awareness about epilepsy and to close the treatment gap. An overview of these activities is provided.

SummaryObjectiveEvidence for the efficacy and safety of adjunctive lacosamide in the treatment of partial‐onset seizures (POS) was gained during placebo‐controlled clinical trials in patients with treatment‐resistant seizures who were taking one to three concomitant antiepileptic drugs (AEDs). The VITOBA study (NCT01098162) evaluated the effectiveness and tolerability of adjunctive lacosamide added to one baseline AED in real‐world clinical practice.MethodsWe conducted a 6‐month observational study at 112 sites across Germany. Adult patients (≥16 years) with POS received lacosamide adjunctive to only one baseline AED. Seizure frequency reduction at the end of the observation period was compared with a 3‐month retrospective baseline period.ResultsFive hundred seventy‐one patients received lacosamide at least once (Safety Set [SS]); 520 provided evaluable seizure records (Full Analysis Set [FAS]); and 499 took in‐label dosages of lacosamide (up to 400 mg) and were evaluated for effectiveness (modified FAS). Median baseline seizure frequency was 2.0 per 28 days: 47.1% of patients (235/499, mFAS) took a concomitant sodium channel–blocking (SCB) AED; 38.1% (190/499) had only one lifetime AED; and 18.4% (92/499) were aged ≥65 years (mFAS). At the final visit, 72.5% (358/494) of patients showed a ≥50% reduction in seizure frequency from baseline, 63.8% (315/494) showed a ≥75% reduction, and 45.5% (225/494) were seizure‐free. Seizure freedom rates were higher in patients aged ≥65 years (56.7%) compared with patients aged <65 years (43.1%), in patients with ≤5 years epilepsy duration (52.5%) versus >5 years duration (41.0%), and when added to first monotherapy (60.5%) rather than as a later therapy option. Treatment‐emergent adverse events (TEAEs) were reported by 48.5% (277/571) of patients (SS), with a profile similar to that observed in pivotal trials; 466 of patients (81.6%, SS) continued lacosamide therapy after the trial.SignificanceThese results suggest that lacosamide use, added to one concomitant AED, was effective at improving seizure control and was well tolerated in patients treated in routine clinical practice.

Lacosamide initiated as first add-on treatment was efficacious and well tolerated in patients with uncontrolled POS.

In this large-scale, multinational, descriptive survey, we sought to identify measures for improving treatment outcomes for individuals with epilepsy. As a framework, questions relating specifically to each of the five steps of the 'patient-physician journey', namely, patient identification (omitted in this survey), diagnosis, choice of drug, disease and drug information, and patient monitoring were asked. Overall, 337 physicians and 1150 patients across France, Germany, and the United States returned questionnaires. Results indicated that 16% of the patients were initially misdiagnosed. Treatment choice was driven by efficacy, safety, experience with a drug (physician only), and convenience (patient only). Physicians were identified as the primary source of information for patients, and, as expected, better informed patients were found to adhere better to their therapy than those who were less well informed. Approximately 50% of the patients had not seen their specialist in the last year, which indicates poor follow-up; furthermore, important topics such as seizures, treatment, and its side effects were not discussed at every visit. Specialists, but not primary care practitioners (PCPs), consistently reported discussing all topics more frequently than their patients, suggesting that specialists may overestimate the clarity of their questions. There was also substantial disparity in the reasons cited for nonadherence - patients overwhelmingly cited forgetfulness, while both PCPs and specialists cited complacency, forgetfulness, and tolerability. We also noted a disparity between physicians and their patients, as well as between PCPs and specialists, in their views on the impact of epilepsy on patients' lives. Our results indicate multiple opportunities to intervene at all stages of the patient-physician journey to improve treatment outcomes. We provide practical suggestions to achieve the most from these opportunities.

In patients with difficult-to-treat epilepsy, standard anti-epileptic drug therapy plus lacosamide appears to be a cost-effective option in Belgium.

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. MRI with intrathecal gadolinium to detect a CSF leak: a prospective open label cohort study