Objective: The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases.Methods: We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study.Results: In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10^–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10^–5) and all SCAs (p = 2.22 × 10^–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10^–5), all in the same direction as in the HD GWAS.Interpretation: We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990

Neuropsychiatric symptoms are common in multiple sclerosis (MS). They include two broad categories of disturbances: abnormalities in cognition, and abnormalities of mood, affect and behaviour. The present review deals with the epidemiology, clinical features, etiology and treatment of disturbances included in the second category, i.e., major depression, fatigue and sleep disorders, bipolar disorder, euphoria, pathological laughing and crying, anxiety, psychosis and personality changes. Major depression is one of the most common neuropsychiatric disorders in MS with an approximate 50% lifetime prevalence rate. Early recognition and management of depression in MS is of major importance because it is a key predictor of morbidity, mortality, quality of life, possibly physical outcome and disease exacerbations, adherence to immunomodulatory treatments and suicide risk in MS patients, as well as of the caregiver's distress and quality of life. The etiopathogenesis of neuropsychiatric disorders in MS has been incompletely investigated. It is postulated that a complex interplay of biological, disease-related, behavioural and psychosocial factors contribute to the pathophysiology of most of them. Management of neuropsychiatric symptoms in MS is often effective, although commonly based on evidence provided by case studies and uncontrolled trials. A comprehensive biopsychosocial neuropsychiatric approach is essential for the optimal care of patients with MS.

MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in length that play a pivotal role in post-transcriptional gene regulation by binding to complementary sites in the 3’-untranslated region of messenger RNAs. In the past decade, their role in several human diseases, from cancer to cardiovascular disease, has been established by a wealth of evidence. Stroke is responsible for 10% of deaths worldwide and is one of the leading causes of disability. MiRNAs are involved in stroke risk factors including hypertension, atherosclerosis, atrial fibrillation, diabetes and dyslipidemia. The role of miRNAs in the pathophysiology of stroke has been the subject of more recent investigations. Animal studies, which dominate the field, have demonstrated the differential expression of miRNAs in brain and blood following ischemic or hemorrhagic insult and the potential use of miRNA antagonists to reduce focal cerebral damage. In particular, antagomirs to miR-145, -497, -181a, -1 and let-7f have been found to be neuroprotective in vivo. The discovery of circulating miRNAs in peripheral blood, which are unexpectedly stable, has allowed the recent completion of several studies in human stroke patients that have confirmed the differential expression of specific miRNAs following stroke and have addressed their potential use as diagnostic and prognostic markers. With miRNA research in stroke still in its infancy, it is anticipated that in the next few years significant discoveries that may have important therapeutic implications will emerge.

Autonomic neuropathy, although common in Guillain–Barré syndrome, is considered rare in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and has not been systematically investigated in that disorder. The present study was aimed at determining the prevalence of autonomic dysfunction and investigating the integrity of autonomic nervous system (ANS) reflexes in CIDP. We studied 17 patients with idiopathic CIDP and 20 healthy controls. Six quantitative autonomic function tests (AFTs) were used: Valsalva ratio, 30/15 ratio, and inspiration–expiration difference for parasympathetic function; and tilt test, handgrip test, and sympathetic skin response for sympathetic function. Eleven patients had symptoms of autonomic dysfunction. AFTs were abnormal in 13 patients. Parasympathetic and sympathetic systems were affected with equal frequency. The tilt test was abnormal most frequently, followed by the 30/15 ratio. Three patients developed postural hypotension with loss of consciousness during the tilt test. Abnormality of AFTs did not correlate with the presence of dysautonomic symptoms; duration, severity, and clinical course of the disease; or with age or gender of patients. Our study suggests a higher frequency of clinical and subclinical involvement of the ANS in CIDP than previously estimated. Dysautonomic symptoms are frequent but are mild. However, upon prolonged passive standing, autonomic failure can lead to loss of consciousness. The subclinical involvement of the ANS affects mainly the sympathetic vasomotor and parasympathetic cardiovascular fibers. Muscle Nerve, 2005