CANVAS, a rare disorder responsible for late-onset ataxia of autosomal recessive inheritance, can be misdiagnosed. We investigated a series of eight patients with sensory neuropathy and/or an unexplained cough, who appeared to suffer from CANVAS, and we emphasized the clinical clues for early diagnosis. Investigations included clinical and routine laboratory analyses, skin biopsy, nerve biopsy and molecular genetics. The eight patients had clinical and/or laboratory evidence of sensory neuronopathy. All but one had neuropathic pain that had started in an asymmetric fashion in two patients. A chronic cough was a prominent feature in our eight patients and had started years before neuropathic symptoms in all but one. The course of the disease was slow, and ataxia remained mild in all. Five patients were initially thought to have immune-mediated sensory neuronopathy and received immunotherapy. Skin biopsies showed a near complete and non-length-dependent loss of intraepidermal nerve fibers. Moreover, nerve biopsy findings suggested a prominent involvement of small myelinated and unmyelinated fibers. The burden of CANVAS extends far beyond cerebellar ataxia and vestibular manifestations. Indeed, our study shows that a chronic cough and neuropathic pain may represent a major source of impairment in these patients and should not be overlooked to allow an early diagnosis and prevent unnecessary immunotherapy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting adverse side effect of treatment. CIPN affects the oncological prognosis of patients, as well as their quality of life. To date, no specific pharmacological therapy has demonstrated effectiveness in preventing CIPN. Accumulating preclinical evidence suggests that renin-angiotensin system (RAS) inhibitors may have neuroprotective effects. One hundred and twenty patients were included in this observational study and were followed from the beginning of their neurotoxic chemotherapy schedule until their final assessment, at least one month after its cessation. The National Cancer Institute’s common toxicity criteria 4.0 (NCI-CTC 4.0) were used to grade the severity of adverse events. Follow-ups also included electrochemical skin conductance and scales for pain, quality of life and disability. Among patients receiving a platinum-based regimen, the mean grade of sensory neuropathy (NCI-CTC 4.0) was significantly lower in the RAS inhibitor group after the end of their anticancer treatment schedule. Because of the observational design of the study, patients in the RAS inhibitor group cumulated comorbidities at risk of developing CIPN. Randomized controlled trials in platinum-based regimens would be worth conducting in the future to confirm the neuroprotective potential of RAS inhibitors during chemotherapy.

BackgroundX‐Linked Charcot–Marie–Tooth disease type 1 (CMTX1) is characterized by gender differences in clinical severity. Women are usually clinically affected later and less severely than men. However, their clinical presentation appears to be heterogenous. Our aim was to extend the phenotypic description in a large series of women with CMTX1.MethodsWe retrospectively evaluated 263 patients with CMTX1 from 11 French reference centers. Demographic, clinical, and nerve conduction data were collected. The severity was assessed by CMT Examination Score (CMTES) and Overall Neuropathy Limitations Scale (ONLS) scores. We looked for asymmetrical strength, heterogeneous motor nerve conduction velocity (MNCV), and motor conduction blocks (CB).ResultsThe study included 137 women and 126 men from 151 families. Women had significantly more asymmetric motor deficits and MNCV than men. Women with an age of onset after 19 years were milder. Two groups of women were identified after 48 years of age. The first group represented 55%, with women progressing as severely as men, however, with a later onset age. The second group had mild or no symptoms. Some 39% of women had motor CB. Four women received intravenous immunoglobulin before being diagnosed with CMTX1.ConclusionsWe identified two subgroups of women with CMTX1 who were over 48 years of age. Additionally, we have demonstrated that women with CMTX can exhibit an atypical clinical presentation, which may result in misdiagnosis. Therefore, in women presenting with chronic neuropathy, the presence of clinical asymmetry, heterogeneous MNCV, and/or motor CB should raise suspicion for X‐linked CMT, particularly CMTX1, and be included in the differential diagnosis.

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN.