Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers.

The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6 years (SCA1 +) aged 27.8 ± 8.

Levels of Neurofilament Light at the Preataxic and Ataxic Stages of Spinocerebellar Ataxia Type 1.

Background And Objectives: Neurofilament light (NfL) appears to be a promising fluid biomarker in repeat-expansion spinocerebellar ataxias (SCAs), with piloting studies in mixed SCA cohorts suggesting that NfL might be increased at the ataxic stage of SCA type 1 (SCA1). We here hypothesized that NfL is increased not only at the ataxic stage of SCA1, but also at its (likely most treatment-relevant) preataxic stage.

Methods: We assessed serum NfL (sNfL) and CSF NfL (cNfL) levels in both preataxic and ataxic SCA1, leveraging a multicentric cohort recruited at 6 European university centers, and clinical follow-up data, including actually observed (rather than only predicted) conversion to the ataxic stage.

Conversion of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 to manifest ataxia (RISCA): a longitudinal cohort study.

Background: Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative diseases. Our aim was to study the conversion to manifest ataxia among apparently healthy carriers of mutations associated with the most common SCAs (SCA1, SCA2, SCA3, and SCA6), and the sensitivity of clinical and functional measures to detect change in these individuals.

Methods: In this prospective, longitudinal, observational cohort study, based at 14 referral centres in seven European countries, we enrolled children or siblings of patients with SCA1, SCA2, SCA3, or SCA6.

Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice.

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH.

Prediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia.

Background: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death.

Objective: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival.

Methods: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed.

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes.

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP subtypes and other neurodegenerative disorders and the HSPs' dual mode of inheritance (both dominant and recessive) make the genetic diagnosis of HSPs complex and difficult. Out of the original HSP cohort comprising 306 index cases (familial and isolated) who had been tested according to "traditional workflow/guidelines" by Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing, 30 unrelated patients (all familial cases) with unsolved genetic diagnoses were tested using next-generation sequencing (NGS).

Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias.

Introduction: To study the long-term evolution of patient-reported outcome measures (PROMs) in the most common spinocerebellar ataxias (SCAs), we analyzed 8 years follow-up data of the EUROSCA Natural History Study, a cohort study of 526 patients with SCA1, SCA2, SCA3 and SCA6.

Methods: To assess the functional capacity in daily living, we used the functional assessment (part IV) of the Unified Huntington's Disease Rating Scale (UHDRS-IV), for health-related quality of life the visual analogue scale of the EuroQol Five Dimensions Questionnaire (EQ-5D VAS), and for depressive symptoms the Patient Health Questionnaire (PHQ-9). Severity of ataxia was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and neurological symptoms other than ataxia with the Inventory of Non-Ataxia Signs (INAS).

WITHDRAWN: Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.pjnns.

Are there clinical and neurophysiologic predictive factors for a positive response to HF-rTMS in patients with treatment-resistant depression?

Better selection of patients with treatment-resistant depression for high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) would make the procedure more efficient. The objective of this study was to search for clinical and neurophysiologic predictors of therapeutic response with a special focus on the bipolar population. Forty patients (30 bipolar) underwent 20 daily sessions of HF-rTMS.

Evidence for a relatively high proportion of DM2 mutations in a large group of Polish patients.

Introduction: Myotonic dystrophies (DMs) type 1 (DM1) and type 2 (DM2) are autosomal dominant, multisystem disorders, considered the most common dystrophies in adults. DM1 and DM2 are caused by dynamic mutations in the DMPK and CNBP genes, respectively.

Methods: Molecular analyses were performed by PCR and the modified RP-PCR in patients, in their at-risk relatives and prenatal cases.

Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study.

Background: Spinocerebellar ataxias are dominantly inherited progressive ataxia disorders that can lead to premature death. We aimed to study the overall survival of patients with the most common spinocerebellar ataxias (SCA1, SCA2, SCA3, and SCA6) and to identify the strongest contributing predictors that affect survival.

Methods: In this longitudinal cohort study (EUROSCA), we enrolled men and women, aged 18 years or older, from 17 ataxia referral centres in ten European countries; participants had positive genetic test results for SCA1, SCA2, SCA3, or SCA6 and progressive, otherwise unexplained, ataxias.

The influence of the repetitive transcranial magnetic stimulation on sleep quality in depression.

Objectives: Repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. In this study we investigated whether the depression-related insomnia is modulated by this therapeutic method.

Methods: We examined 13 patients (mean age 50.

Body Mass Index Decline Is Related to Spinocerebellar Ataxia Disease Progression.

Background: Spinocerebellar ataxias (SCAs) are dominantly inherited, progressive ataxia disorders. Disease progression could be preceded by weight loss.

Objectives: We aimed to study the course of weight loss in patients who had the most common SCAs (SCA1, SCA2 SCA3, and SCA6).

High relative frequency of SCA1 in Poland reflecting a potential founder effect.

Spinocerebellar ataxias (SCAs) have irregular distributions worldwide. SCA1 is the most frequent in Poland, and no cases of SCA3 of Polish origin has yet been identified. In view of such patterns of SCAs occurrence, the relative frequency, geographical distribution and a possible founder effect of SCA1 were investigated.

Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients.

Hereditary spastic paraplegias (HSPs) consist of a heterogeneous group of genetically determined neurodegenerative disorders. Progressive lower extremity weakness and spasticity are the prominent features of HSPs resulting from retrograde axonal degeneration of the corticospinal tracts. Three genetic types, SPG3 (ATL1), SPG4 (SPAST) and SPG31 (REEP1), appear predominantly and may account for up to 50% of autosomal dominant hereditary spastic paraplegias (AD-HSPs).

Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study.

Background: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated.

Morphological changes of skeletal muscle in spinal and bulbar muscular atrophy (SBMA), Kennedy's disease: a case report.

Spinal and bulbar muscular atrophy (SBMA, Kennedy's disease) is an X-linked recessive disease affecting lower motor neurons. In the present case report, we describe morphological changes in a muscle biopsy obtained from a 62-year-old patient with gynecomastia and with the following neurological symptoms: dysphagia, dysarthria, wasting and fasciculation of the tongue, proximal weakness, fasciculations in the limb muscles, and an absence of all tendon reflexes. Neurogenic alternations were predominantly observed using light and electron microscopy.

Modulation of the age at onset in spinocerebellar ataxia by CAG tracts in various genes.

Polyglutamine-coding (CAG)n repeat expansions in seven different genes cause spinocerebellar ataxias. Although the size of the expansion is negatively correlated with age at onset, it accounts for only 50-70% of its variability. To find other factors involved in this variability, we performed a regression analysis in 1255 affected individuals with identified expansions (spinocerebellar ataxia types 1, 2, 3, 6 and 7), recruited through the European Consortium on Spinocerebellar Ataxias, to determine whether age at onset is influenced by the size of the normal allele in eight causal (CAG)n-containing genes (ATXN1-3, 6-7, 17, ATN1 and HTT).

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

Background: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset.

Methods: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort.

Negative influence of L-dopa on subjectively assessed sleep but not on nocturnal polysomnography in Parkinson's disease.

Background: Sleep disorders are highly prevalent among patients with Parkinson's disease (PD). Chronic medication with L-dopa may be one of the factors that contributes to poor sleep quality. The aim of this study was to assess the effects of long term use of L-dopa on objective and subjective measures of sleep quality in PD patients.

Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data.

Background: Spinocerebellar ataxias (SCAs) are autosomal, dominantly inherited, fully penetrant neurodegenerative diseases. Our aim was to study the preclinical stage of the most common SCAs: SCA1, SCA2, SCA3, and SCA6.

Methods: Between Sept 13, 2008, and Dec 1, 2011, offspring or siblings of patients with SCA1, SCA2, SCA3, or SCA6 were enrolled into a prospective, longitudinal observational study at 14 European centres.

Corticomotor excitability in drug-naive patients with Parkinson disease.

Background And Purpose: This study aimed to assess the indices of corticomotor excitability (CE) in drug-naive Parkinson disease (PD) patients and to investigate its relationship with asymmetry and severity of clinical symptoms.

Material And Methods: Eleven (4 men) drug-naive PD patients (mean age: 53.1 ± 9.

The personal experience of parenting a child with juvenile Huntington's disease: perceptions across Europe.

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington's disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,.

Genotype-specific patterns of atrophy progression are more sensitive than clinical decline in SCA1, SCA3 and SCA6.

Spinocerebellar ataxias are dominantly inherited disorders that are associated with progressive brain degeneration, mainly affecting the cerebellum and brainstem. As part of the multicentre European integrated project on spinocerebellar ataxias study, 37 patients with spinocerebellar ataxia-1, 19 with spinocerebellar ataxia-3 and seven with spinocerebellar ataxia-6 were clinically examined and underwent magnetic resonance imaging at baseline and after a 2-year follow-up. All patients were compared with age-matched and gender-matched healthy control subjects.