Brain Diffusion Imaging and Tractography to Distinguish Clinical Severity of Human PLP1-Related Disorders.

AIMS: We performed quantitative diffusion tensor imaging and brain tractography to distinguish clinical severity in a series of 35 patients with hypomyelinating PLP1-related disorders classified using the Motor Developmental Score according to the best motor function acquired before the age of 5 years and the gross motor function measure (GMFM) at the time of magnetic resonance imaging acquisition. METHODS: We calculated fractional anisotropy and diffusivity values in 26 regions of interest and the numbers of fibers and volumes of hemisphere tractograms. Fiber bundles on tractograms were characterized according to 3 criteria: size, direction of main-stream fibers, and connectivity of bundles (extratelencephalic projections, commissural fibers, and intrahemispheric connections). RESULTS: Age-adjusted multivariate analysis in 3 severity groups revealed increased isotropic diffusion in the superior cerebellar peduncle and grey matter in the most severe group, and larger tractogram volumes and increased numbers of fibers in the least severely affected group. Tractogram patterns showed preserved extratelencephalic projections and a main anterior-posterior aspect of intrahemispheric fibers in most patients, whereas interhemispheric connectivity was variable. The most severely affected and intermediate patients had less intrahemispheric connectivity, with a frequent predominant anterior-posterior direction of main-stream fibers. INTERPRETATION: Diffusion tensor imaging and tractographic parameters can operate as biomarkers to distinguish clinical severity in PLP1-related disorders and could improve our understanding of hypomyelinating leukodystrophies.

Clinical features of 1487 COVID-19 patients with outpatient management in the Greater Paris: the COVID-call study.

Clinical features of COVID-19 have been mostly described in hospitalized patients with and without ICU admission. Yet, up to 80% of patients are managed in an outpatient setting. This population is poorly documented. In France, health authorities recommend outpatient management of patients presenting mild-to-moderate COVID-19 symptoms. The aim of this study was to describe their clinical characteristics. The study took place in an emergency medical dispatching center located in the Greater Paris region. Patients included in this survey met confirmed COVID-19 infection criteria according to the WHO definition. We investigated clinical features and classified symptoms as general, digestive, ear-nose-throat, thoracic symptoms, and eye disease. Patients were included between March 24 and April 6 2020. 1487 patients included: 700 (47%) males and 752 (51%) females, with a median age of 44 (32-57) years. In addition to dry cough and fever reported in more than 90% of cases, the most common symptoms were general symptoms: body aches/myalgia (N = 845; 57%), headache (N = 824; 55%), and asthenia (N = 886; 60%); shortness of breath (N = 479; 32%) and ear-nose-throat symptoms such as anosmia (N = 415; 28%) and ageusia (N = 422; 28%). Chest pain was reported in 320 (21%) cases and hemoptysis in 41 (3%) cases. The main difference between male and female patients was an increased prevalence of ear-nose-throat symptoms as well as diarrhea, chest pains, and headaches in female patients. General symptoms and ear-nose-throat symptoms were predominant in COVID-19 patients presenting mild-to-moderate symptoms. Shortness of breath and chest pain were remarkably frequent.

Scoliosis in Patients With Friedreich Ataxia: Results of a Consecutive Prospective Series.

STUDY DESIGN: Prospective monocentric study. OBJECTIVES: To describe the radiologic characteristics and evolution of spinal shapes in a pediatric cohort of patients with Friedreich ataxia (FA). SUMMARY OF BACKGROUND DATA: FA is a spinocerebellar degenerative disorder responsible for gait impairment in children and young adults, and several orthopedic deformities can occur during growth, including scoliosis. However, curves' characteristics and their natural evolution have been poorly described, and the subsequent therapeutic management remains controversial. METHODS: Sixty six FA patients were prospectively included between 2008 and 2017. Clinical, functional, and radiologic records were conducted twice a year. Coronal curve types, segmental measurements, and skeletal maturity were assessed. RESULTS: A scoliotic deformity was reported in 71% of the patients at a mean age of 11.7 ± 3.1 years. Average follow-up was 6 years, including 75% of patients with closed triradiate cartilage at latest examination. Mean Cobb angle was 34° ± 2°. Main right thoracic curves were the most frequent curves observed (36%), followed by double major (21%), thoracolumbar and left thoracic curves (13%), main lumbar (11%), and long C-shape curves (6%). Hyperkyphosis (>40°) was present in 66%, with an average kyphosis angle of 50° ± 3°, and anterior misalignment (>5°) occurred in 53%. The severity of the Cobb angle was neither correlated to the FA severity scores nor the age at FA diagnosis. An arthrodesis was performed in 9 patients, including 5 patients (45%) who were ambulatory at least 1 year after surgery. CONCLUSIONS: The prevalence of scoliosis in FA was high (71%), and thoracic hyperkyphosis, with anterior misalignment, was frequently observed, which might be related to the anterior imbalance frequently encountered in patients with an ataxia. Posterior fusion including sacral instrumentation was only performed in nonambulatory patients, and the loss of ambulation was not associated with spinal surgery. LEVEL OF EVIDENCE: Level IV.

Test-retest reliability of an instrumented electronic walkway system (GAITRite) for the measurement of spatio-temporal gait parameters in young patients with Friedreich's ataxia.

BACKGROUND: Friedreich ataxia (FRDA) affects the spatio-temporal parameters (STP) of gait. To our knowledge, proper tools to measure the variability of ataxic gait have not been validated yet. The aims of the present study were: (1) to measure the reproducibility of STP and gait scores in young patients with FRDA and (2) to describe the characteristics of gait parameters in this population. METHODS: Thirty-six patients (18 males, 18 females) with diagnosis of FRDA (mean age 16.4 ± 4.5 years) were asked to walk barefoot at a self-selected pace along the pressure sensitive walkway (GAITRite®). Three trials were recorded for each patient and repeated 48 h later. Collected data was put into statistical analysis tests to determine reliability and variability of STPs and two other gait scores: The Functional Ambulation Performance score (FAP) and the Gait Variability Index (GVI). RESULTS: All STPs showed strong or very strong reliability (ICC > 0.7) and a low variability. The two parameters showing the lowest reliability (0.71 and 0.74) were the base of support and the foot progression angle. The FAP score and the GVI showed strong reliability (ICC > 0.8). CONCLUSIONS: The GAITRite system allows feasible and reliable measurements of gait parameters in young patients with FRDA. Lower reliability found for the weakest parameters was attributed to the software automatic errors and the ankle laxity noted in every patient.

Limited benefits of presymptomatic cord blood transplantation in neurovisceral acid sphingomyelinase deficiency (ASMD) intermediate type.

Acid sphingomyelinase (ASM) deficient Niemann-Pick disease is a lysosomal storage disorder resulting from mutations in the SMPD1 gene. The clinical spectrum distinguishes a severe infantile neurological form (type A), a non-neurological visceral form (type B) and a rare intermediate neurovisceral form. We report the first case of presymptomatic cord blood transplantation in a child with the intermediate type of ASM deficiency due to a homozygous Tyr369Cys mutation, whose affected elder brother had developed neurodevelopmental delay from 19 months of age, and had died from severe visceral complications at the age of 3. In the transplanted propositus, neurological deterioration became evident by 4 years of age; the child was alive at age 8, although severely disabled. Whereas the transplant prevented visceral progression and early death, it could only delay neurocognitive deterioration.