Glial Fibrillary Acidic Protein Autoimmunity: A French Cohort Study.

BACKGROUND AND OBJECTIVES: To report the clinical, biological, and imaging features and clinical course of a French cohort of patients with glial fibrillary acidic protein (GFAP) autoantibodies. METHODS: We retrospectively included all patients who tested positive for GFAP antibodies in the CSF by immunohistochemistry and confirmed by cell-based assay using cells expressing human GFAPα since 2017 from 2 French referral centers. RESULTS: We identified 46 patients with GFAP antibodies. Median age at onset was 43 years, and 65% were men. Infectious prodromal symptoms were found in 82%. Other autoimmune diseases were found in 22% of patients, and coexisting neural autoantibodies in 11%. Tumors were present in 24%, and T-cell dysfunction in 23%. The most frequent presentation was subacute meningoencephalitis (85%), with cerebellar dysfunction in 57% of cases. Other clinical presentations included myelitis (30%) and visual (35%) and peripheral nervous system involvement (24%). MRI showed perivascular radial enhancement in 32%, periventricular T2 hyperintensity in 41%, brainstem involvement in 31%, leptomeningeal enhancement in 26%, and reversible splenial lesions in 4 cases. A total of 33 of 40 patients had a monophasic course, associated with a good outcome at last follow-up (Rankin Score ≤2: 89%), despite a severe clinical presentation. Adult and pediatric features are similar. Thirty-two patients were treated with immunotherapy. A total of 11/22 patients showed negative conversion of GFAP antibodies. DISCUSSION: GFAP autoimmunity is mainly associated with acute/subacute meningoencephalomyelitis with prodromal symptoms, for which tumors and T-cell dysfunction are frequent triggers. The majority of patients followed a monophasic course with a good outcome.

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.

Post-traumatic factors are involved in the evolution of the number of seizures in patients with PNES.

OBJECTIVE: The purpose of this prospective study was to identify predictive factors of the evolution of the number of seizures. METHODS: We included 85 individuals with a diagnosis of Psychogenic Nonepileptic Seizure (PNES) who completed at least two clinical interviews spaced by 6 months during a 24-month follow-up. Participants underwent a structured interview with an experimented clinician in PNES to complete standardized evaluation and validated scales. We collected sociodemographic and clinical data on PNES (number of seizures, duration of the disease), anxiety, depression, history of traumas, alexithymia, dissociation, and post-traumatic stress disorder (PTSD). We used a multivariate linear regression analysis to predict the characteristics independently associated with the evolution of the number of seizures in percentage. RESULTS: Dissociation score was significantly associated with a negative evolution of the number of seizures (p < 0.002). Conversely, the diagnosis of PTSD at inclusion was correlated to a positive evolution of the number of seizures (p < 0.029). CONCLUSION: Dissociation was related to a more pejorative evolution of the number of seizures while PTSD diagnosis was associated with a decreased number of seizures. It is therefore essential to improve detection and treatment of post-traumatic dissociation. Further studies are required to understand the impact of PTSD on the evolution of the number of seizures.

Explanatory factors of quality of life in psychogenic non-epileptic seizure.

OBJECTIVE: Previous studies showed that patients with Psychogenic Non-Epileptic Seizures (PNES) have poor quality of life (QoL). This study explored the explicative factors of the QoL at the time of diagnosis and monitored changes over the two years of follow-up. METHODS: We evaluated 107 participants with a diagnosis of Psychogenic Non-Epileptic Seizure (PNES), every 6 months for 24 months. Quality of life (QoL) was evaluated using the QOLIE-31 and SF-36 scales (respectively specific and generic scales of QoL). Positive evolution of QoL was defined by the increase in the score of overall QoL using QOLIE-31 sub-scale from baseline to the last interview of the patient. We also collected for each patient data on psychiatric dimensions (childhood abuse, history of traumatic events, post-traumatic stress disorder (PTSD), depression, anxiety, alexithymia, and dissociation), clinical evolution of seizures and the number of mental health consultations. RESULTS: According to the QOLIE-31 and the SF-36, depression (p ≤ 0.001), anxiety (p < 0.001), alexithymia (p ≤ 0.001), and dissociation (p ≤ 0.004) were related to QoL at the time of the diagnosis. According to SF-36 (mental and physical), PTSD was also significantly associated with QoL (p < 0.05). The number of seizures or the co-occurrence of epilepsy did not influence QoL. Positive evolution of QoL was linked to the number of consultations for mental health issues (p = 0.02). SIGNIFICANCE: Post-traumatic dimensions (PTSD, dissociation), alexithymia and psychiatric comorbidities (depression and anxiety disorders) seem to alter QoL in people with PNES. The current study suggests that mental health care improves QoL of patients with PNES.

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.

Differentiating PNES from epileptic seizures using conversational analysis on French patients: A prospective blinded study.

Psychogenic nonepileptic seizures (PNES) resemble epileptic seizures (ES) but are not caused by the occurrence of excessive cortical neuronal discharge. Previous studies in German-, English-, and Italian-speaking patients showed that patients used a different communicative style to talk about their seizures. They demonstrated that the diagnosis between PNES and ES could be predicted using qualitative assessment and a diagnostic scoring aid (DSA). The objective of our study was to evaluate the contribution of linguistic analysis in the differential diagnosis between ES and PNES in a French patient population. During an extended video-electroencephalogram (video-EEG) monitoring, 13 patients presented PNES and 19 patients with ES. Two neurologists blindly and independently analyzed the interview of each patient. Rater 1 predicted the correct diagnosis in 27 of 32 patients (84%) and Rater 2 in 28 of 32 patients (88%). Interrater reliability of qualitative analysis was satisfactory (k = 0.68, interrater agreement = 84.4%). Using a simplified DSA, Rater 1 and Rater 2 would have correctly diagnosed 88% (28/32 patients) and 91 % (29/32) of the cases, respectively. Our blinded prospective study confirms the diagnostic value of conversational analysis, performed by neurologists, to differentiate PNES from ES in French-speaking patients.

Development of permanent brain damage after subacute encephalopathy with seizures in alcoholics.

PURPOSE: To describe additional cases of subacute encephalopathy with seizures in alcoholics (SESA) syndrome, and to question the clinical and radiological course. METHODS: We retrospectively analyzed the clinical characteristics, electroencephalography (EEG), MRI studies at the admission and over the following 6 months of 5 cases of SESA syndrome visited our neurology department between 2010 and 2016. RESULTS: Five middle-aged males with history of chronic alcohol abuse were admitted for confusion, neurological deficit and seizures. Four patients had recurrent partial seizures requiring 2 or more antiepileptic drugs. EEG showed interictal periodic lateralized discharges in 4 patients and focal rhythmic delta activities in 1. Initial MRI studies revealed unilateral hemispheric cortical-subcortical areas of increased T2/ FLAIR signal and restricted diffusion. Follow up examination after 6 months, revealed persistent focal neurological deficits in 3 patients. Follow-up cerebral MRI at 6 months showed a resolution of the hyperintense lesions, but developing focal atrophic changes in all patients. CONCLUSION: SESA syndrome should be included among the alcohol-related encephalopathies as a particular pathophysiological entity. The possibility of permanent brain damage should encourage a better clinical awareness of this syndrome to establish prompt diagnosis, relevant investigation and appropriate treatment of recurrent seizures including, if necessary, intensive care unit treatment.

[Psychiatric comorbidities in epilepsy]. / Les comorbidités psychiatriques dans l'épilepsie.

Psychiatric comorbidities are overrepresented in people suffering from epilepsy in comparison to the general population. There is a two-way link between epilepsy and psychiatric disorders. Psychiatric symptomatology is specific in epilepsy, according to the chronology of symptoms in relation to the seizure (inter, pre- or postictal). Easy to use, fast and efficient self-administered questionnaires are available to evaluate depressive (NDDI-E) and generalized anxiety disorder (GAD-7) symptoms. Selective serotonin reuptake inhibitors (SSRIs) are not proconvulsant and can be safely used to treat depressive or anxious disorders.

Are the clinical classifications for psychogenic nonepileptic seizures reliable?

BACKGROUND: Psychogenic nonepileptic seizures (PNESs) are episodes that resemble epileptic seizures but are of psychological origin. A few studies have attempted to describe different types of PNES as a combination of clinical signs but their validation and robustness have not yet been reached. The aim of this study was to assess the inter-rater reliability (IRR) of five existing clinical PNES classifications. METHODS: A total of 107 PNESs from 54 patients were retrospectively analyzed independently by two trained epileptologists, who were blinded to each other's findings. The recorded events were grouped according to the five chosen classifications systems. The IRR was measured using a kappa (κ) coefficient for each PNES classification. We also report category-specific κ values. RESULTS: Our study demonstrated a mild to moderate IRR (κ from 0.44-0.68) for classifying PNES using the 5 proposed classification schemes. Within these classifications, the most reproducible classes are the subjective ones followed by the dialeptic group. Classes based on motor signs are the least reproducible. CONCLUSION: The IRR for current clinical classifications of PNES was only moderate. The difficulty to analyze motor signs could explain this poor reliability. It is necessary to ensure the reliability of clinical classifications of PNES in order for them to be a relevant tool in clinical practice or to explore correlations in clinical research. Future research would benefit from increased precision of diagnostic criteria specific to each class.

High incidence of obstructive sleep apnea syndrome in patients with late-onset epilepsy.

OBJECTIVES: The objective of the present study was to evaluate the prevalence of obstructive sleep apnea (OSA) in patients with late-onset epilepsy (LOE) who were considered at higher risk of cardiovascular disease. METHODS: Polysomnography was performed on 27 patients with LOE. Berlin questionnaires and Epworth sleepiness score were performed on all patients. We compared clinical, demographic and anthropometric characteristics, questionnaire scores on the patients with no or mild OSA (group 1) and the patients with moderate or severe OSA (group 2). Patients eligible for continuous positive airway pressure (CPAP) therapy were reviewed in consultation. RESULTS: Twenty-four patients (88.9%) had OSA and 55.6% had moderate or severe OSA. Patients in group 2 (n=15) were older than patients in group 1 (n=12). The two groups were similar in terms of body mass index (BMI), neck circumference, nocturnal seizure frequency, vascular cardiovascular risk factors and excessive daytime sleepiness. Leukoaraiosis in MRI was highly prevalent in our patients (40.7%), especially in group 2 patients. Eighty percent of the patients who had begun CPAP therapy experienced decreased seizure frequency. CONCLUSION: Patients with LOE should be screened for the presence of OSA and treated accordingly.

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours.

PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with learning disability and/or psychiatric comorbidity. METHOD: We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. RESULTS: One hundred and one patients were included (mean age: 41.2years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1months (range: 14days to 17months). On final evaluation, a >50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p=0.043). CONCLUSION: Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period.

Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.4 megabase CMT1A duplication and atypical presentation (electrophysiological, clinical or pathological): a 10 year-old girl with tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent paresthesiae and block conduction on the electrophysiological study; a 46 year-old woman with transient recurrent nerve palsies mimicking HNPP. These observations highlight the wide spectrum of CMT1A and the overlap between CMT1A and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases.

Association of a paraneoplastic motor neuron disease with anti-Ri antibodies and a novel SOD1 I18del mutation.

INTRODUCTION: Whether motor neuron diseases (MNDs) can be considered in some cases of paraneoplastic syndromes is controversial. We report a case of rapidly progressive motor neuronopathy following a diagnosis of breast carcinoma, with a presence of anti-Ri antibodies, and a novel SOD1 gene mutation. OBSERVATION: An 80-year-old woman with mucinous adenocarcinoma of the left breast for 4 years developed sub-acute quadriparesis. Myography revealed chronic denervation signs. The patient had serum anti-Ri onconeural antibodies. The diagnosis of paraneoplastic MND was established. Because of a familial history of ALS, a genetic analysis for familial ALS was performed. We identified a novel heterozygous mutation in SOD1 gene, SOD I18del. This mutation may reflect a genetic predisposition to develop a MND, inducing fragility of motor neurons. Neurological improvement was observed after three months of both intravenous gamma globulin and corticosteroids. CONCLUSION: The present observation supports the idea that MND can be considered as a paraneoplastic syndrome. A combination of anti-Ri onconeural antibodies and a particular SOD1 gene mutation, consisting in risk factor, might be in cause in the process of motor neuron death. When in doubt, paraneoplastic cause should be suspected in the differential diagnosis of MND. Immunotherapy treatment may lead to a favorable outcome.