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Background: Hereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition. Methods: A total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T0 and T1) and longitudinally (T0 vs. T1). Results: Statistically significant data showed that T0 mI/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA/Cr was reduced, and ml/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing "pure" and "complex" forms, NAA/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients (n = 30), showed an increase in mI/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI/Cr in the L precentral area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%. Conclusion: This pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP. [ABSTRACT FROM AUTHOR]

Background: A drug repositioning effort supported the possible use of the anti-HIV drug etravirine as a disease-modifying drug for Friedreich ataxia (FRDA). Etravirine increases frataxin protein and corrects the biochemical defects in cells derived from FRDA patients. Because of these findings, and since etravirine displays a favorable safety profile, we conducted a pilot open-label phase 2 clinical trial assessing the safety and potential efficacy of etravirine in FRDA patients. Methods: Thirty-five patients were stratified into three severity groups and randomized to etravirine 200 mg/day or 400 mg/day. They were treated for 4 months. Safety endpoints were the number and type of adverse events and number of dropouts. Efficacy endpoints were represented by changes in peak oxygen uptake and workload as measured by incremental exercise test, SARA score, cardiac measures, measures of QoL and disability. Data were collected 4 months before the start of the treatment (T − 4), at the start (T0), at the end (T4) and 4 months after the termination of the treatment (T + 4). Results: Etravirine was reasonably tolerated, and adverse events were generally mild. Four months of etravirine treatment did not significantly increase the peak oxygen uptake but was associated with a change in the progression of the SARA score (p value < 0.001), compared to the 4 months pre- and post-treatment. It also significantly increased peak workload (p value = 0.021). No changes in the cardiac measures were observed. Health and QoL measures showed a worsening at the suspension of the drug. Conclusions: In this open trial etravirine treatment was safe, reasonably well tolerated and appreciably improved neurological function and exercise performance. Even though a placebo effect cannot be ruled out, these results suggest that etravirine may represent a potential therapeutic agent in FRDA deserving testing in a randomized placebo-controlled clinical trial. [ABSTRACT FROM AUTHOR]

This paper presents an effort by the World Health Organization (WHO) to integrate the reference classifications of the Family of International Classifications (ICD, ICF, and ICHI) into a unified digital framework. The integration was accomplished via an expanded Content Model and a single Foundation that hosts all entities from these classifications, allowing the traditional use cases of individual classifications to be retained while enhancing their combined use. The harmonized WHO-FIC Content Model and the unified Foundation has streamlined the content management, enhanced the web-based tool functionalities, and provided opportunities for linkage with external terminologies and ontologies. This integration promises reduced maintenance cost, seamless joint application, complete representation of health-related concepts while enabling better interoperability with other informatics infrastructures. [ABSTRACT FROM AUTHOR]

Aim: Nodopathies and paranodopathies are autoimmune neuropathies associated with antibodies to nodal–paranodal antigens (neurofascin 140/186 and 155, contactin‐1, contactin‐associated protein 1 [Caspr1]) characterized by peculiar clinical features, poor response to standard immunotherapies (e.g., intravenous immunoglobulins, IVIg). Improvement after anti‐CD20 monoclonal antibody therapy has been reported. Data on Caspr1 antibodies pathogenicity are still preliminary, and longitudinal titers have been poorly described. Methods: We report on a young woman who developed a disabling neuropathy with antibodies to the Caspr1/contactin‐1 complex showing a dramatic improvement after rituximab therapy, mirrored by the decrease of antibody titers. Results: A 26‐year‐old woman presented with ataxic‐stepping gait, severe motor weakness at four limbs, and low frequency postural tremor. For neurophysiological evidence of demyelinating neuropathy, she was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg without benefit. MRI showed symmetrical hypertrophy and marked signal hyperintensity of brachial and lumbosacral plexi. Cerebrospinal fluid showed 710 mg/dL protein. Despite intravenous methylprednisolone, the patient progressively worsened, and became wheelchair‐bound. Antibodies to nodal–paranodal antigens were searched for by ELISA and cell‐based assay. Anticontactin/Caspr1 IgG4 antibodies resulted positive. The patient underwent rituximab therapy with slow progressive improvement that mirrored the antibodies titer, measured throughout the disease course. Conclusions: Our patient had a severe progressive course with early disability and axonal damage, and slow recovery starting only a few months after antibody‐depleting therapy. The close correlation between titer, disability, and treatment, supports the pathogenicity of Caspr1 antibodies, and suggest that their longitudinal evaluation might provide a potential biomarker to evaluate treatment response. [ABSTRACT FROM AUTHOR]

The Family of International Classifications of the World Health Organization (WHO-FIC) currently includes three reference classifications, namely International Classification of Diseases (ICD), International Classification of Functioning, Disability, and Health (ICF), and International Classification of Health Interventions (ICHI). Recently, the three classifications have been incorporated into a single WHO-FIC Foundation that serves as the repository of all concepts in the classifications. Each classification serves a specific classification need. However, they share some common concepts that are present, in different forms, in two or all of them. For the WHO-FIC Foundation to be a logically consistent repository without duplicates, these common concepts must be reconciled. One important set of shared concepts is the representation of human anatomy entities, which are not always modeled in the same way and with the same level of detail. To understand the relationships among the three anatomical representations, an effort is needed to compare them, identifying common areas, gaps, and compatible and incompatible modeling. The work presented here contributes to this effort, focusing on the anatomy representations in ICF and ICD-11. For this aim, three experts were asked to identify, for each entity in the ICF Body Structures, one or more entities in the ICD-11 Anatomic Detail that could be considered identical, broader or narrower. To do this, they used a specifically developed web application, which also automatically identified the most obvious equivalences. A total of 631 maps were independently identified by the three mappers for 218 ICF Body Structures, with an interobserver agreement of 93.5%. Together with 113 maps identified by the software, they were then consolidated into 434 relations. The results highlight some differences between the two classifications: in general, ICF is less detailed than ICD-11; ICF favors lumping of structures; in very few cases, the two classifications follow different anatomic models. For these issues, solutions have to be found that are compliant with the WHO approach to classification modeling and maintenance. [ABSTRACT FROM AUTHOR]

Children in a vegetative state (VS) and a minimally conscious state (MCS) experience severe limitations as a consequence of nervous system deficits and require consistent environmental support. However, disability in VS and MCS children has never been described following a model that accounts for the presence of the symptoms, limitations and the support required. Therefore, the aim of this paper is to describe the functioning and disability of children in VS and MCS using the International Classification of Functioning, Disability and Health--version for Children and Youth (ICF-CY). VS and MCS children were enrolled in postacute settings and at home. ICF-CY questionnaires were filled in using information available from clinical documentation, direct observation and from children's parents. ICF-CY categories were considered as relevant if used in at least one-third of the children. In total, 36 children and adolescents (22 in VS, 25 males) were enrolled. The majority developed VS and MCS following a nontraumatic event; the mean age was 114.8 months and the mean duration of condition was 50.1 months. A total of 94 ICF-CY categories were reported as relevant: 26 were from body functions, mostly from mental functions and mobility chapters; nine from body structures, 32 from activities and participation, mostly from learning, mobility and self-care chapters; and 27 from environmental factors. The use of ICF-CY enables to obtain a specific profile of functioning for each child that can be coupled with known issues, such as loss of brain functions and provision of life-sustaining interventions. (Contains 4 tables.)

Background: Spinal cord damage is a hallmark of Friedreich's ataxia (FRDA), but its progression and clinical correlates remain unclear. Objective: The objective of this study was to perform a characterization of cervical spinal cord structural damage in a large multisite FRDA cohort. Methods: We performed a cross‐sectional analysis of cervical spinal cord (C1–C4) cross‐sectional area (CSA) and eccentricity using magnetic resonance imaging data from eight sites within the ENIGMA‐Ataxia initiative, including 256 individuals with FRDA and 223 age‐ and sex‐matched control subjects. Correlations and subgroup analyses within the FRDA cohort were undertaken based on disease duration, ataxia severity, and onset age. Results: Individuals with FRDA, relative to control subjects, had significantly reduced CSA at all examined levels, with large effect sizes (d > 2.1) and significant correlations with disease severity (r < −0.4). Similarly, we found significantly increased eccentricity (d > 1.2), but without significant clinical correlations. Subgroup analyses showed that CSA and eccentricity are abnormal at all disease stages. However, although CSA appears to decrease progressively, eccentricity remains stable over time. Conclusions: Previous research has shown that increased eccentricity reflects dorsal column (DC) damage, while decreased CSA reflects either DC or corticospinal tract (CST) damage, or both. Hence our data support the hypothesis that damage to the DC and damage to CST follow distinct courses in FRDA: developmental abnormalities likely define the DC, while CST alterations may be both developmental and degenerative. These results provide new insights about FRDA pathogenesis and indicate that CSA of the cervical spinal cord should be investigated further as a potential biomarker of disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]