Neurofilament accumulations in amyotrophic lateral sclerosis patients' motor neurons impair axonal initial segment integrity.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease in adults with no curative treatment. Neurofilament (NF) level in patient' fluids have recently emerged as the prime biomarker of ALS disease progression, while NF accumulation in MNs of patients is the oldest and one of the best pathological hallmarks. However, the way NF accumulations could lead to MN degeneration remains unknown.

Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles.

Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology.

Efficacy and safety of mexiletine in non-dystrophic myotonias: A randomised, double-blind, placebo-controlled, cross-over study.

The MYOMEX study was a multicentre, randomised, double-blind, placebo-controlled, cross-over study aimed to compare the effects of mexiletine vs. placebo in patients with myotonia congenita (MC) and paramyotonia congenita (PC). The primary endpoint was the self-reported score of stiffness severity on a 100 mm visual analogic scale (VAS).

Anosognosia in amyotrophic lateral sclerosis: A cross-sectional study of 85 individuals and their relatives.

Background: Amyotrophic lateral sclerosis (ALS) has long been considered a pure motor neurodegenerative disease. However, now, extra-motor manifestations such as cognitive-behavioral disorders are considered not rare and are even a severity factor of the disease. Experiencing anosognosia (i.

Exome Sequencing Reveals Signal Transduction Genes Involved in Impulse Control Disorders in Parkinson's Disease.

Impulse control disorders (ICDs) frequently complicate dopamine agonist (DA) therapy in Parkinson's disease (PD). There is growing evidence of a high heritability for ICDs in the general population and in PD. Variants on genes belonging to the reward pathway have been shown to account for part of this heritability.

Absence of hyperexcitability of spinal motoneurons in patients with amyotrophic lateral sclerosis.

Key Points: •Amyotrophic lateral sclerosis (ALS) motoneurons become hypoexcitable with disease progression in experimental models, raising questions about the neural hyperexcitability supported by clinical observations. •A variant of the ∆F method, based on motor unit discharge frequency modulations during recruitment and derecruitment, has been developed to investigate the motoneuron capacity to self-sustained discharge in patients. •The modulation of motor unit firing rate during ramp contraction and vibration-induced recruitment are modified in ALS, suggesting lower motoneuron capacity to self-sustained discharge, which is a sign of hypoexcitability.

Examining the Reserve Hypothesis in Parkinson's Disease: A Longitudinal Study.

Background: Whether reserve plays a role in Parkinson's disease (PD) patients has received less attention than in dementia and has been mainly examined in relation with cognitive function.

Objective: To investigate whether reserve plays a role in the severity and progression of motor, cognitive, and nonmotor PD symptoms by examining whether education level (proxy of reserve) is associated with baseline performance and rate of progression.

Methods: We used data from a longitudinal cohort of PD patients (≤5-year disease duration at baseline) annually followed up to 5 years (n = 393; 41% women; mean age = 62.

Are PSP patients included in clinical trials representative of the general PSP population?

Background: Progressive supranuclear palsy (PSP) is a rare parkinsonian syndrome with a wide spectrum of clinical presentations. Recently, the MDS published revised diagnosis criteria to provide early and reliable diagnosis of PSP and its variants. Two large randomized clinical trials were initiated in 2017, but the question remains regarding the extrapolation of their results to the general PSP population.

Cursive Eye-Writing With Smooth-Pursuit Eye-Movement Is Possible in Subjects With Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder causing a progressive motor weakness of all voluntary muscles, whose progression challenges communication modalities such as handwriting or speech. The current study investigated whether ALS subjects can use Eye-On-Line (EOL), a novel eye-operated communication device allowing, after training, to voluntarily control smooth-pursuit eye-movements (SPEM) so as to eye-write in cursive. To that aim, ALS participants ( = 12) with preserved eye-movements but impaired handwriting were trained during six on-site visits.

Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients 60 Years of Age and Younger: Results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study.

Purpose: To determine the efficacy and toxicity of chemoimmunotherapy followed by either whole-brain radiotherapy (WBRT) or intensive chemotherapy and autologous stem-cell transplantation (ASCT) as a first-line treatment of primary CNS lymphoma (PCNSL).

Patients And Methods: Immunocompetent patients (18 to 60 years of age) with untreated PCNSL were randomly assigned to receive WBRT or ASCT as consolidation treatment after induction chemotherapy consisting of two cycles of R-MBVP (rituximab 375 mg/m day (D) 1, methotrexate 3 g/m D1; D15, VP16 100 mg/m D2, BCNU 100 mg/m D3, prednisone 60 mg/kg/d D1-D5) followed by two cycles of R-AraC (rituximab 375 mg/m D1, cytarabine 3 g/m D1 to D2). Intensive chemotherapy consisted of thiotepa (250 mg/m/d D9; D8; D7), busulfan (8 mg/kg D6 through D4), and cyclophosphamide (60 mg/kg/d D3; D2).

The spinal and cerebral profile of adult spinal-muscular atrophy: A multimodal imaging study.

Unlabelled: Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging.

Emotional feeling in patients suffering from amyotrophic lateral sclerosis.

Objective: Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disorder involving motor neurons of the cerebral cortex, brain stem and spinal cord. Besides the motor signs, cognitive disorders and apathy may be present and may impact the survival time. These elements are therefore to be taken into consideration for medical care because they can influence the disease evolution.

Atrophy, metabolism and cognition in the posterior cortical atrophy spectrum based on Alzheimer's disease cerebrospinal fluid biomarkers.

Introduction: In vivo clinical, anatomical and metabolic differences between posterior cortical atrophy (PCA) patients presenting with different Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers profiles are still unknown.

Methods: Twenty-seven PCA patients underwent CSF examination and were classified as 1) PCA with a typical CSF AD profile (PCA-tAD; abnormal amyloid and T-tau/P-tau biomarkers, n = 13); 2) PCA with an atypical AD CSF profile (PCA-aAD; abnormal amyloid biomarker only, n = 9); and 3) PCA not associated with AD (PCA-nonAD; normal biomarkers, n = 5). All patients underwent clinical and cognitive assessment, structural MRI, and a subset of them underwent brain F-FDG PET.

Naftazone in advanced Parkinson's disease: An acute L-DOPA challenge randomized controlled trial.

Introduction: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study.

Methods: We conducted a double-blind randomized placebo-controlled cross-over trial in PD patients with motor fluctuations and dyskinesia testing naftazone 160 mg/day versus placebo for 14 days.

The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy.

Objective: Objective of this study is the comprehensive characterisation of motor unit (MU) loss in type III and IV Spinal Muscular Atrophy (SMA) using motor unit number index (MUNIX), and evaluation of compensatory mechanisms based on MU size indices (MUSIX).

Methods: Nineteen type III and IV SMA patients and 16 gender- and age-matched healthy controls were recruited. Neuromuscular performance was evaluated by muscle strength testing and functional scales.

Extrapyramidal deficits in ALS: a combined biomechanical and neuroimaging study.

Introduction: Extrapyramidal deficits are poorly characterised in amyotrophic lateral sclerosis (ALS) despite their contribution to functional disability, increased fall risk and their quality-of-life implications. Given the concomitant pyramidal and cerebellar degeneration in ALS, the clinical assessment of extrapyramidal features is particularly challenging.

Objective: The comprehensive characterisation of postural instability in ALS using standardised clinical assessments, gait analyses and computational neuroimaging tools in a prospective study design.

Longitudinal analysis of impulse control disorders in Parkinson disease.

Objective: To investigate the longitudinal dose-effect relationship between dopamine replacement therapy and impulse control disorders (ICDs) in Parkinson disease (PD).

Methods: We used data from a multicenter longitudinal cohort of consecutive patients with PD with ≤5 years' disease duration at baseline followed up annually up to 5 years. ICDs were evaluated during face-to-face semistructured interviews with movement disorder specialists.

Posterior cortical atrophy: from vision to emotion.

In this review of the literature on posterior cortical atrophy (PCA), the history of the disease is first told through the studies of Frank Benson and Oliver Sacks. Then, we detail the possible underlying pathologies, Alzheimer's disease being the most common cause. Clinical, cognitive, and biological features are described, with a specific focus on the neuroimaging.

Sleep and REM sleep behaviour disorder in Parkinson's disease with impulse control disorder.

Introduction: Because the association between rapid eye movement sleep behaviour disorder (RBD) and impulse control disorders (ICDs) in Parkinson's disease (PD) has been debated, we assessed the sleep characteristics and the frequency of RBD using video-polysomnography (v-PSG) in patients with PD with versus without ICDs.

Methods: Eighty non-demented patients with PD consecutively identified during routine evaluation at three movement disorders centres were enrolled in a case-control study. Forty patients (22 men; mean age: 62.

Outcome of gastrostomy in parkinsonism: A retrospective study.

Objective: To investigate the indications and the outcomes of gastrostomy tube insertion in patients with parkinsonian syndromes.

Methods: Consecutive patients with Parkinson's disease or atypical parkinsonism, seen in two French tertiary referral movement disorders centers, that received gastrostomy tube insertion (GTI) for feeding between 2008 and 2014 were included in this retrospective study. Data regarding clinical status, indications and outcomes were retrieved from medical files.

Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study.

The central cholinergic system undergoes changes during the physiological process of aging and the pathologic process of Alzheimer disease (AD). We aimed to analyze the impairment of cholinergic pathways by positron emission tomography using the [F]-F-A-85380 (FA85) tracer, which has a high affinity for nicotinic acetylcholine receptors (nAChRs). Aging was assessed by comparing young (n=10) and elderly (n=4) healthy subjects, and the pathologic process of AD was assessed by comparing elderly controls and age-matched AD patients (n=8).

Correction: Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

[This corrects the article DOI: 10.1371/journal.pone.

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial.

Unlabelled: In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20).