Allelic heterogeneity in a patient with postzygotic MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

A case of mosaic MTOR-associated hemimegalencephaly and hypomelanosis of Ito, died at 33 probably because of sudden unexpected death in epilepsy. Assessment of the variant allele fraction (VAF) in different tissues postmortem showed high variability not correlated with clinical features, representing the most detailed assessment of VAFs in different tissues to date.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

OBJECTIVE: To assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. METHODS: Cross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected. Coffee consumption was collected using a standardized self-report questionnaire and classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day), and high (more than 4 cups/day). RESULTS: Six hundred and nineteen patients were included. There was no relation between coffee consumption and total seizure frequency (p = 0.902). In contrast, the number of FBTCS reported over the past year was significantly associated with usual coffee consumption (p = 0.029). Specifically, number of FBCTS in patients who reported moderate coffee consumption was lower than in others. In comparison with patients with moderate coffee consumption, the odds ratio (95%CI) for reporting at least 1 FBTCS per year was 1.6 (1.03-2.49) in patients who never take coffee, 1.62 (1.02-2.57) in those with rare consumption and 2.05 (1.24-3.4) in those with high consumption. Multiple ordinal logistic regression showed a trend toward an association between coffee consumption and number of FBTCS (p = 0.08). CONCLUSIONS AND RELEVANCE: Our data suggest that effect of coffee consumption on seizures might depend on dose with potential benefits on FBTCS frequency at moderate doses. These results will have to be confirmed by prospective studies.

Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease.

PURPOSE: Lafora disease (LD) is an autosomal recessive form of progressive myoclonus epilepsy with onset in childhood or adolescence and with fatal outcome caused by mutations in two genes: EPM2A and NHLRC1. The aim of this study was to characterize the mutation spectrum in a cohort of unrelated patients with presumed LD. METHODS: Sequencing of the two genes and search for large rearrangements was performed in 46 unrelated patients with suspected LD, 33 originating from France and the others from different countries. Patients were classified into two groups according to the clinical presentation. RESULTS: Mutations of various types were found in EPM2A in 10 patients and in NHLRC1 in 4 patients. Mutations were found in 14 (93%) of 15 patients with classical clinical and electroencephalography (EEG) presentation of LD and in no patients with an atypical presentation. Ten mutations were novel, including the first substitution reported in a donor splice site of EPM2A, leading to the deletion of exon 2 at the RNA level. Four large deletions, including two deletions of exon 2 with different sizes and breakpoints, were found in EPM2A, corresponding to 20% of the alleles of this gene. DISCUSSION: We described several novel mutations of EPM2A and NHLRC1 and brought additional data to the genetic epidemiology of LD. This study emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy.

Adherence to mental health care and caregiver-patient relationship after diagnosis of psychogenic non-epileptic seizures: Longitudinal follow-up study.

PURPOSE: This study aimed to describe the quality of adherence to mental health care follow-up and the mental health caregiver-patient relationship after diagnosis of psychogenic non-epileptic seizures (PNES). METHODS: We conducted an ancillary study of a multicenter prospective study. Patients (n = 108) received a standardized diagnostic explanation of PNES following video-EEG. They were referred to their community mental health centers or to a private psychiatrist/psychologist, who received written information about PNES and the study. Data collected about adherence to care (follow-up started or not, consensual and those who withdrew non-consensually, ongoing follow-up) were cross-tabulated from patients and care structures by telephone at 6, 12, 18 and 24 months after diagnosis. At M24, we collected reasons for stopping follow-up by phone using a predefined 9-item questionnaire. We also assessed the perception of the caregiver-patient relationship among patients who started follow-up and their mental health caregivers with a simple questionnaire based on five dimensions: feeling comfortable, continuity of care, content of therapy sessions, effectiveness of therapy sessions, and the patient's overall assessment of the follow-up. RESULTS: From M6 to M24, ongoing follow-up decreased from 64.8 to 25.8%, while the "not following initial recommandations" group of patients (those who never started follow-up and those who withdrew non-consensually) increased from 35.2 to 64.9%. We found two main reasons for stopping follow-up: lack of interest and feeling better. Adherent patients had an overall more positive view of their therapy than caregivers. CONCLUSION: Only a third of PNES patients adhered to a mental health care program and felt comfortable in the caregiver-patient relationship. Solutions need to be found to help patients understand the interest of follow-up therapy and help mental health caregivers improve their feeling of competence.

A time estimation task as a possible measure of emotions: difference depending on the nature of the stimulus used.

OBJECTIVE: Time perception is fundamental for human experience. A topic which has attracted the attention of researchers for long time is how the stimulus sensory modality (e.g., images vs. sounds) affects time judgments. However, so far, no study has directly compared the effect of two sensory modalities using emotional stimuli on time judgments. METHODS: In the present two studies, healthy participants were asked to estimate the duration of a pure sound preceded by the presentation of odors vs. emotional videos as priming stimuli (implicit emotion-eliciting task). During the task, skin conductance (SC) was measured as an index of arousal. RESULTS: Olfactory stimuli resulted in an increase in SC and in a constant time overestimation. Video stimuli resulted in an increase in SC (emotional arousal), which decreased linearly overtime. Critically, video stimuli resulted in an initial time underestimation, which shifted progressively towards a time overestimation. These results suggest that video stimuli recruited both arousal-related and attention-related mechanisms, and that the role played by these mechanisms changed overtime. CONCLUSIONS: These pilot studies highlight the importance of comparing the effect of different kinds on temporal estimation tasks, and suggests that odors are well suited to investigate arousal-related temporal distortions, while videos are ideal to investigate both arousal-related and attention-related mechanisms.

Prognostic value of early epileptic seizures on mortality and functional disability in acute stroke: the Dijon Stroke Registry (1985-2010).

We aimed to evaluate the prognostic value of early epileptic seizures after stroke. All consecutive patients with a first-ever stroke were prospectively identified within the population of Dijon, France, thanks to a population-based registry, from 1985 to 2010. Early epileptic seizures were defined as seizures occurring within 14 days after stroke onset. Outcomes were 1-month and 1-year mortality, and severe functional handicap at discharge. Of the 4,411 stroke patients included, data about seizures were available in 4,358 (98.8, 53.5 % women, mean age, 74.1 ± 14.8 years). Among these patients, 134 (3.1 %) had early seizures. Stroke patients with early seizures differed from those without seizures, as there was a higher proportion of hemorrhagic stroke, higher blood glucose level at admission, smoking status, and more frequent impaired. Higher risks of 1-month and 1-year mortality in patients with early seizures (unadjusted HR 1.45, 95 % CI 1.00-2.10; HR = 1.59, 95 % CI 1.21-2.09, respectively) disappeared (HR 0.71, 95 % CI 0.49-1.08 and HR 0.85, 95 % CI 0.64-1.17) after adjustment for stroke severity and other confounding factors. Early seizures were associated with severe handicap in unadjusted analyses (OR 2.07, 95 % CI 1.46-2.95) but the association was no longer significant after multivariable adjustment (OR 1.12, 95 % CI 0.69-1.83). Early epileptic seizures were not associated with higher risks of mortality at 1 month and 1 year or with unfavorable functional outcome after acute stroke. The adverse effects of epileptic seizures may not be distinguishable from stroke severity, which is strongly related to epileptic seizures.

Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H) in a French Family.

INTRODUCTION: Inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD) is a rare late-onset autosomal dominant disorder due to a mutation of the valosin-containing protein (VCP) gene. CASE REPORT: We report the case of a patient who developed progressive weakness of the limbs in his fifties, until he was confined to a wheelchair. At that time, he developed acute behavioural changes including irritability, severe anxiety and major depression, which led to him being hospitalised in a psychiatric hospital. He also suffered from aphasia and executive function impairment, which helped us to diagnose a behavioural form of frontotemporal dementia (FTD). The diagnosis of IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the VCP gene (R155H mutation). DISCUSSION: THE CLINICAL DIAGNOSIS OF IBMPFD IS SUGGESTED BY THE PRESENCE OF AT LEAST ONE OF THREE MAJOR MANIFESTATIONS AS FOLLOWS: inclusion body myopathy (mean onset at 42 years of age), Paget's disease of the bone and FTD (mean onset at 55 years of age). It is mostly the behavioural form of FTD (behavioural changes, executive dysfunction and aphasia). One interesting finding in our report is the predominance of the psychiatric symptoms at the beginning of the behavioural changes, which led to the diagnosis of FTD. The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in the VCP gene.

[Botulism has not disappeared]. / Le botulisme est toujours d'actualité

INTRODUCTION: Botulism is a potentially fatal infectious disease induced by a neurotoxin secreted by Clostridium botulinum, a sporulated species of obligate anaerobic bacteria. This neurotoxin inhibits the normal release of acetylcholine in the synaptic cleft, inducing presynaptic neuromuscular blockade. The diagnosis is often difficult because of the range and the lack of specificity of the symptoms. CASE: We report two cases of human botulism. The first case was easy to diagnose, with dysphagia, dysphonia, blurred vision, and xerostomia, associated with potentiation on electromyogram and B botulinum toxin in the serum. Symptoms in the second case included diplopia, blurred vision, dysphagia, dysphonia, with potentiation on electromyogram but no botulinum toxin. DISCUSSION: These two cases remind us of the necessity to keep botulism in mind when systemic atropinic symptoms are found together with generalized, progressive and extensive paralysis. The diagnosis is confirmed by electromyogram and serology. There is no specific treatment for botulism; only intensive care surveillance and symptomatic treatment improve survival.