Caffeine consumption outcomes on amyotrophic lateral sclerosis disease progression and cognition.

Caffeine consumption outcomes on Amyotrophic Lateral Sclerosis (ALS) including progression, survival and cognition remain poorly defined and may depend on its metabolization influenced by genetic variants. 378 ALS patients with a precise evaluation of their regular caffeine consumption were monitored as part of a prospective multicenter study. Demographic, clinical characteristics, functional disability as measured with revised ALS Functional Rating Scale (ALSFRS-R), cognitive deficits measured using Edinburgh Cognitive and Behavioural ALS Screen (ECAS), survival and riluzole treatment were recorded. 282 patients were genotyped for six single nucleotide polymorphisms tagging different genes involved in caffeine intake and/or metabolism: CYP1A1 (rs2472297), CYP1A2 (rs762551), AHR (rs4410790), POR (rs17685), XDH (rs206860) and ADORA2A (rs5751876) genes. Association between caffeine consumption and ALSFRS-R, ALSFRS-R rate, ECAS and survival were statistically analyzed to determine the outcome of regular caffeine consumption on ALS disease progression and cognition. No association was observed between caffeine consumption and survival (p = 0.25), functional disability (ALSFRS-R; p = 0.27) or progression of ALS (p = 0.076). However, a significant association was found with higher caffeine consumption and better cognitive performance on ECAS scores in patients carrying the C/T and T/T genotypes at rs2472297 (p-het = 0.004). Our results support the safety of regular caffeine consumption on ALS disease progression and survival and also show its beneficial impact on cognitive performance in patients carrying the minor allele T of rs2472297, considered as fast metabolizers, that would set the ground for a new pharmacogenetic therapeutic strategy.

Anti-disialosyl-immunoglobulin M chronic autoimmune neuropathies: a nationwide multicenter retrospective study.

BACKGROUND AND PURPOSE: In this retrospective study involving 14 university hospitals from France and Switzerland, the aim was to define the clinicopathological features of chronic neuropathies with anti-disialosyl ganglioside immunoglobulin M (IgM) antibodies (CNDA). RESULTS: Fifty-five patients with a polyneuropathy evolving for more than 2 months and with at least one anti-disialosyl ganglioside IgM antibody, that is, anti-GD1b, -GT1b, -GQ1b, -GT1a, -GD2 and -GD3, were identified. Seventy-eight percent of patients were male, mean age at disease onset was 55 years (30-76) and disease onset was progressive (82%) or acute (18%). Patients presented with limb sensory symptoms (94% of cases), sensory ataxia (85%), oculomotor weakness (36%), limb motor symptoms (31%) and bulbar muscle weakness (18%). Sixty-five percent of patients had a demyelinating polyradiculoneuropathy electrodiagnostic profile and 24% a sensory neuronopathy profile. Anti-GD1b antibodies were found in 78% of cases, whilst other anti-disialosyl antibodies were each observed in less than 51% of patients. Other features included nerve biopsy demyelination (100% of cases), increased cerebrospinal fluid protein content (75%), IgM paraprotein (50%) and malignant hemopathy (8%). Eighty-six percent of CNDA patients were intravenous immunoglobulins-responsive, and rituximab was successfully used as second-line treatment in 50% of cases. Fifteen percent of patients had mild symptoms and were not treated. CNDA course was progressive (55%) or relapsing (45%), and 93% of patients still walked after a mean disease duration of 11 years. CONCLUSION: Chronic neuropathies with anti-disialosyl ganglioside IgM antibodies have a recognizable phenotype, are mostly intravenous immunoglobulins-responsive and present with a good outcome in a majority of cases.

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.

Confirmed cases of Neuroborreliosis with involvement of peripheral nervous system: Description of a cohort.

The manifestations of borreliosis in the peripheral nervous system (PNS) remain poorly described. As the symptoms of neuroborreliosis can be reversed with timely introduction of antibiotics, early identification could avoid unnecessary axonal loss. Our aim was to describe the characteristics of confirmed neuroborreliosis cases involving the PNS diagnosed between 2007 and 2017 in our neuromuscular disease center in a nonendemic area (La Pitié-Salpêtrière Hospital, Paris, France).Neuroborreliosis was defined as follows: compatible neurological symptoms without other cause of neuropathy; cerebrospinal fluid and serum analysis (positive serological tests with ELISA, confirmed by Western Blot); and improvement of symptoms with adapted antibiotherapy. All the patients consulting in our center between 2007 and 2017 underwent electrophysiological study.Sixteen confirmed cases of neuroborreliosis involving the PNS were included: 10 cases of meningoradiculoneuritis, 4 of axonal neuropathy, and 2 of demyelinating neuropathy (one acute and one chronic). Only 4 (25%) patients reported tick bites. Meningoradiculoneuritis was characterized by lymphocytic meningitis, intense pain, cranial nerve palsy, and contrast enhancement of nerve roots on imagery. The patients with axonal neuropathy presented sensory symptoms with intense pain but no motor deficit and meningitis was rare. Nerve biopsy of 1 patient revealed lymphocytic vasculitis. Electrophysiological testing showed sensory or sensorimotor axonal neuropathy (3 subacute and 1 chronic) of the lower limbs, with asymmetrical neuropathy in 1 patients, symmetrical neuropathy in one and monomelic sensory mononeuritis multiplex in another. We also found 1 case of acute demyelinating neuropathy, treated with antibiotherapy and immunoglobulins, and 1 chronic demyelinating neuropathy. Overall, diaphragmatic paralysis was frequent (18.6%). Antibiotherapy (mostly ceftriaxone 3-4 weeks) resulted in symptom resolution.This series gives an updated overview of the peripheral complications of neuroborreliosis to help identify this disease so that timely treatment could avoid axonal loss.

Outcome of patients with large vessel occlusion stroke after first admission in telestroke spoke versus comprehensive stroke center.

INTRODUCTION: While telestroke allows early intravenous thrombolysis (IVT) for ischemic strokes in spoke centers, mechanical thrombectomy (MT) for large vessel occlusion (LVO) is mainly performed at comprehensive stroke centers (CSCs). We aimed to compare 3 month outcome in patients with LVO after admission to a spoke center using telestroke compared with first CSC admission in our large regional stroke network, irrespective of final treatment decision. METHODS: All consecutive LVO patients who were admitted to one of six spoke centers or to the regional CSC within 6 hours of symptom onset were prospectively included from September 1, 2015 to August 31, 2017. All patients admitted to spoke centers were assessed on site with cerebral and vessel imaging. Primary outcome was 3 month favorable outcome (modified Rankin Scale score of 0-2). RESULTS: Distances between spoke centers and CSC ranged from 36 to 77 miles. Among 207 included patients, 132 (63.8%) were first admitted to CSCs and 75 (36.2%) to spoke centers. IVT was administered more in spoke centers (81.3% vs 53.8%, p<0.0001) while MT was performed less (26.7% vs 49.2%, p=0.001) and with a longer time from onset (303 vs 200 min, p<0.0001). No difference was found in 3 month favorable outcome between spoke centers compared with CSCs (32.0% and 35.1%, respectively; OR=0.68; 95% CI 0.42 to 1.10; p=0.12). CONCLUSIONS: Despite different distribution of reperfusion therapies for LVO patients managed by telemedicine, we could not demonstrate a difference in functional outcome according to admission location in a large area with long distances between centers.