Cognitive impairment in children and adults with cerebrotendinous xanthomatosis: A French cohort study.

Cerebrotendinous xanthomatosis is a rare and treatable metabolic disorder related to the accumulation of cholestanol. This disorder is primarily associated with motor and cognitive impairments, although the latter has not been extensively characterized. The objectives of this work were to define the cognitive profile found in cerebrotendinous xanthomatosis patients, investigate the progression of cognitive impairment over time, and search for radio-clinical correlations.

Pearls & Oy-sters: Spinal Cord Candidiasis Linked to CARD9 Deficiency Masquerading as a Longitudinally Extensive Transverse Myelitis.

spp. myelopathies are very rare. We report a case of subacute longitudinally extensive transverse myelitis in an apparently immunocompetent 55-year-old man.

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.

Clinical trials in pediatric ALS: a TRICALS feasibility study.

Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA). To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.

Impact of a frequent nearsplice variant in amyotrophic lateral sclerosis: optimising genetic screening for gene therapy opportunities.

Objective: Mutations in superoxide dismutase 1 gene (, encoding copper/zinc superoxide dismutase protein, are the second most frequent high penetrant genetic cause for amyotrophic lateral sclerosis (ALS) motor neuron disease in populations of European descent. More than 200 missense variants are reported along the SOD1 protein. To limit the production of these aberrant and deleterious SOD1 species, antisense oligonucleotide approaches have recently emerged and showed promising effects in clinical trials.

Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study.

Levels of chitotriosidase (CHIT1) are increased in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients reflecting microglial activation. Here, we determine the diagnostic and prognostic potential of CHIT1 for early symptomatic ALS. : Overall, 275 patients from 8 European neurological centers were examined.

Development of new outcome measures for adult SMA type III and IV: a multimodal longitudinal study.

Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials.

Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later.

Who and Why? Requests for Presymptomatic Genetic Testing for Amyotrophic Lateral Sclerosis/Frontotemporal Dementia vs Huntington Disease.

Objective: We aimed to describe the population of subjects seeking presymptomatic counseling for amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS/FTD) and compared them with those demanding the well-established presymptomatic test for Huntington disease (HD).

Methods: We retrospectively examined the requests of a cohort of individuals at risk of familial ALS/FTD and 1 at risk of HD over the same time frame of 11 years. The individuals were seen in the referral center of our neurogenetics unit.

Genetic screening of ANXA11 revealed novel mutations linked to amyotrophic lateral sclerosis.

ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.

Predictive factors for prognosis after gastrostomy placement in routine non-invasive ventilation users ALS patients.

Due to the expanding use of non-invasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS), the question of enteral nutrition is increasingly raised in NIV users ALS patients. Here, we aimed to determine the prognostic factors for survival after gastrostomy placement in routine NIV users, taking into consideration ventilator dependence. Ninety-two routine NIV users ALS patients, who underwent gastrostomy insertion for severe dysphagia and/or weight loss, were included.

Homoplasmic deleterious MT-ATP6/8 mutations in adult patients.

To address the frequency of complex V defects, we systematically sequenced MT-ATP6/8 genes in 512 consecutive patients. We performed functional analysis in muscle or fibroblasts for 12 out of 27 putative homoplasmic mutations and in cybrids for four. Fibroblasts, muscle and cybrids with known deleterious mutations underwent parallel analysis.

Four-dimensional digital subtraction angiography for exploration of spinal cord vascular malformations: preliminary experience.

Background: The precise understanding of the angioarchitecture of spinal vascular malformations (SVMs) is often difficult to reach with conventional digital subtraction angiography (DSA). The purpose of our study was to evaluate the potential of four-dimensional DSA (4D-DSA) (Siemens Healthcare) in the exploration of SVMs.

Methods: We retrospectively studied all patients who underwent spinal DSA, including 4D-DSA acquisition, from July 2018 to June 2019 at a single institution.

Spastic paraplegia due to recessive or dominant mutations in can convert to ALS.

Objective: The aim of this study was to evaluate whether mutations in , known to cause SPG18, a recessive hereditary spastic paraplegia (SP) responsible for the degeneration of the upper motor neurons leading to weakness and spasticity restricted to the lower limbs, could contribute to amyotrophic lateral sclerosis (ALS), a distinct and more severe motor neuron disease (MND), in which the lower motor neurons also profusely degenerates, leading to tetraplegia, bulbar palsy, respiratory insufficiency, and ultimately the death of the patients.

Methods: Whole-exome sequencing was performed in a large cohort of 200 familial ALS and 60 sporadic ALS after a systematic screening for hexanucleotide repeat expansion. variants identified by exome analysis were validated using Sanger analysis.

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.

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.

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.

Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare neurodegenerative disease related to sterols metabolism. It affects both central and peripheral nervous systems but treatment with chenodeoxycholic acid (CDCA) has been reported to stabilize clinical scores and improve nerve conduction parameters. Few quantitative brain structural studies have been conducted to assess the effect of CDCA in CTX.

Targeted versus untargeted omics - the CAFSA story.

Background: In 2009, untargeted metabolomics led to the delineation of a new clinico-biological entity called cerebellar ataxia with elevated cerebrospinal free sialic acid, or CAFSA. In order to elucidate CAFSA, we applied sequentially targeted and untargeted omic approaches.

Methods And Results: First, we studied five of the six CAFSA patients initially described.

Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis.

Objective: To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS).

Methods: We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures.

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.