Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy.

OBJECTIVE: We aimed to test whether patients who died of sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation. METHODS: We conducted a retrospective, observational, case-control study of a group of patients who died of SUDEP and controls who were matched to the patients for epilepsy type, drug resistance, sex, age at EEG recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and HR variability (HRV) at rest and during and after hyperventilation performed during the patient's last EEG recording before SUDEP. In each group, changes over time in HRV indexes were analyzed with linear mixed models. RESULTS: Twenty patients were included in each group. In the control group, the HR increased and the root mean square of successive RR-interval differences (RMSSD) decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 minutes after its end discriminated well between patients with SUDEP and control patients (area under the receiver operating characteristic curve 0.870, sensitivity 85%, specificity 75%). CONCLUSION: Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in HR on hyperventilation might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.

Vitamin D status among patients with drug-resistant and non-drug-resistant epilepsy.

Background & Aims: Epilepsy affects nearly 70 million people worldwide. Vitamin D deficiency may influence the balance of certain epilepsies. The purpose of this study was to determine the vitamin D status and anthropometric measurements of people with epilepsy (PWE), according to their pharmacosensitivity. Methods: Forty-six PWE, with or without drug resistance, underwent nutritional assessment after giving consent. Weight, body mass index (BMI), triceps skinfold thickness (TSF), fat mass (FM) and free fat mass (FFM) by bioelectrical impedance analysis were measured. Serum vitamin D was determined without supplementation. Deficiency was defined as a level < 30 ng/mL. Statistical analysis involved Student t test, ANOVA and Chi2. Results: Patients were aged 44.5 ± 14.3 years, with 60.9% of drug-resistance. BMI was 28.7 ± 7.0, 2.2% were malnourished and 30.4% obese according to the BMI. The average vitamin D level was 15.3 ± 9.9 ng/mL, with 87.0% of deficiency, and 40.0% of severe deficiency (<10 ng/mL). The TSF was higher in drug-resistant cases (p = 0.03). There was no link between drug resistance and anthropometric measurements, FM, FFM or vitamin D concentration. Conclusions: Although limited in size, this study showed that PWE are more often obese. Vitamin D deficiency is more common than in the general population, with a much higher prevalence of severe deficiency.

[Drug Shortage May Have Serious Outcome: the French Exemple of Phenytoine]. / Des ruptures de stock aux conséquences parfois graves : l'exemple de la phénytoïne, à propos de 7 cas.

In 2012, in France, phenytoin sodium was used as a substitute for phenytoin base during a shortage at the dose of 100 mg for 100 mg, according to the French Health Agency recommendations. However, this substitution was problematic because the two specialties were not bioequivalent. We report here the case of a 29-year old woman who presented with severe epilepsy. The substitution of phenytoin base by phenytoin sodium induced an increase of seizure frequency leading to several hospitalizations and sick leave. Phenytoin base was finally available again in 2013 which allowed a reduction of seizure frequency. Six similar cases, including one death, were reported to the French pharmacovigilance system. Drug shortages are increasingly common and can have serious consequences. Reporting the difficulties that drug shortage causes to health authorities is important in order to improve their management and to better support patients.

Probable drug-induced liver injury associated with aliskiren: case report and review of adverse event reports from pharmacovigilance databases.

PURPOSE: A case of probable drug-induced liver injury (DILI) attributed to use of the antihypertensive agent aliskiren is reported. SUMMARY: A 61-year-old woman undergoing routine liver function monitoring in conjunction with long-term antiepileptic therapy was noted to have an asymptomatic acute hepatic cytolysis 1 month after the initiation of concomitant aliskiren therapy (150 mg/day). Liver enzyme testing showed dramatically elevated aspartate transaminase (AST) and alanine transaminase (ALT) concentrations, with substantial rises also noted in γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) levels. The calculated ALT:ALP value indicated hepatocellular injury. On discontinuation of aliskiren use, rapid biological improvement occurred, including normalization of serum AST and a sharp decline in serum ALT within one week and the return of GGT and ALP levels to baseline a few weeks later; the patient's AST and ALT concentrations remained normal during 18 months of subsequent monitoring. Using the algorithm of Naranjo et al. and a DILI-specific causality assessment instrument, it was determined that aliskiren use was the probable cause of the patient's liver injury. While this is believed to be the first report of aliskiren-associated DILI in the professional literature, a review of information from several European and North American pharmacovigilance databases (through October 2012) identified 117 reports of suspected aliskiren hepatotoxicity, including 6 reports of liver failure and 12 reports of deaths. CONCLUSION: Asymptomatic acute hepatic cytolysis was observed in a 61-year-old woman approximately one month after initiation of aliskerin for treatment of hypertension. Improvement in AST and ALT concentrations was observed shortly after the drug was discontinued.

Etiologies of epilepsy: a comprehensive review.

Epilepsy is a heterogeneous disorder, the symptoms of which are preventable and controllable to some extent. Significant inter- and intra-country differences in incidence and prevalence exist because multiple etiologic factors are implicated. Many past reviews have addressed sole etiologies. We considered a comprehensive view of all etiologies (genetic/structural/metabolic) to be significant for both the developing and the developed world as well as routine clinical/epidemiology practice. We therefore carried out a comprehensive search for peer-reviewed articles (irrespective of year, region and language; chosen based on novelty and importance) for each etiology. This article was felt to be essential since newer etiologic knowledge has emerged in recent years. Many new genetic links for rarer epilepsy forms have emerged. Epilepsy risk in limbic encephalitis, mechanisms of Alzheimer's-related epilepsy and the genetic basis of cortical malformations have been detailed. An etiological approach to epilepsy in combination with the conventional classification of epilepsy syndromes is required to gain knowledge.

Malnutrition and epilepsy: a two-way relationship.

BACKGROUND & AIMS: A link between malnutrition and epilepsy has been suspected for many years. METHODS: Different aspects of the question were studied with a review of previous published data. RESULTS: Several studies performed on animal models or humans highlight the possible adverse effects of malnutrition in the onset of seizures. Protein-energy, electrolyte, vitamin or trace element deficiencies may be involved. Conversely, several determinants of epilepsy could lead to malnutrition: food taboos and social exclusion in developing countries as well as some adverse effects of antiepileptic treatments. CONCLUSIONS: Two different hypotheses exist as a vicious circle: malnutrition predisposing to epilepsy or epilepsy predisposing to malnutrition. A better understanding of these interactions is necessary. In the mean time, malnutrition has to be prevented and treated.