Publications by authors named "Wolfgang Nachbauer"

Objective: Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterised by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2, however the evolution and pattern of whole-brain atrophy in SCA2 remain unclear. We undertook a multi-site, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.

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  • Non-polyglutamine CACNA1A variants are linked to a diverse range of symptoms including developmental delay, migraines, epilepsy, psychiatric issues, and chronic cerebellar signs, with most patients showing symptoms from childhood.
  • In a study over 20 years, 41 patients were monitored, revealing that 66% required interval therapy, which effectively managed their episodic symptoms.
  • The findings suggest that non-polyglutamine CACNA1A disease presents differently as patients age, and that targeted prophylaxis can significantly alleviate their symptoms.
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  • Early studies suggested that iron accumulation occurs in Friedreich's ataxia (FA), but data from actual patients was limited, prompting further investigation into systemic iron metabolism and regulation in FA patients.
  • The study involved 40 FA patients and matched healthy controls, analyzing serum iron parameters, hormones, and iron distribution in blood cells, while also using MRI to assess iron stores in organs like the liver and spleen.
  • Results indicated that FA patients had lower serum iron levels and certain iron-related proteins correlated inversely with genetic severity; there was also an unexpected discovery of iron deficiency and altered iron distribution within cells, suggesting that systemic iron-lowering treatments might not be ideal for FA patients.
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Background: Friedreich's ataxia (FA) is a rare multisystemic disorder which can cause premature death.

Objectives: To investigate predictors of survival in FA.

Methods: Within a prospective registry established by the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS; ClinicalTrials.

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Friedreich's ataxia (FRDA) is a severe multisystemic disorder caused by a deficiency of the mitochondrial protein frataxin. While some aspects of FRDA pathology are developmental, the causes underlying the steady progression are unclear. The inaccessibility of key affected tissues to sampling is a main hurdle.

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  • - Multiple system atrophy (MSA) is a severe disease with varying motor and autonomic symptoms, and previous studies have linked certain clinical factors to reduced survival rates.
  • - Researchers analyzed 210 MSA patients over 17 years to create a survival risk model using clinical factors like age at symptom onset and early autonomic failure.
  • - They developed a nomogram to predict individual survival probabilities over 7 years, which showed good accuracy and could enhance patient counseling and treatment strategies.
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Objective: The natural history of Friedreich ataxia is being investigated in a multi-center longitudinal study designated the Friedreich ataxia Clinical Outcome Measures Study (FACOMS). To understand the utility of this study in analysis of clinical trials, we performed a propensity-matched comparison of data from the open-label MOXIe extension (omaveloxolone) to that from FACOMS.

Methods: MOXIe extension patients were matched to FACOMS patients using logistic regression to estimate propensity scores based on multiple covariates: sex, baseline age, age of onset, baseline modified Friedreich Ataxia Rating scale (mFARS) score, and baseline gait score.

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Background: The Scale for Assessment and Rating of Ataxia (SARA) is widely used in different types of ataxias and has been chosen as the primary outcome measure in the European natural history study for Friedreich ataxia (FA).

Methods: To assess distribution and longitudinal changes of SARA scores and its single items, we analyzed SARA scores of 502 patients with typical-onset FA (<25 years) participating in the 4-year prospective European FA Consortium for Translational Studies (EFACTS). Pattern of disease progression was determined using linear mixed-effects regression models.

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Objective: In Friedreich's ataxia (FRDA), the most affected tissues are not accessible to sampling and available transcriptomic findings originate from blood-derived cells and animal models. Herein, we aimed at dissecting for the first time the pathophysiology of FRDA by means of RNA-sequencing in an affected tissue sampled in vivo.

Methods: Skeletal muscle biopsies were collected from seven FRDA patients before and after treatment with recombinant human Erythropoietin (rhuEPO) within a clinical trial.

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Background: Sporadic adult-onset ataxias without known genetic or acquired cause are subdivided into multiple system atrophy of cerebellar type (MSA-C) and sporadic adult-onset ataxia of unknown etiology (SAOA).

Objectives: To study the differential evolution of both conditions including plasma neurofilament light chain (NfL) levels and magnetic resonance imaging (MRI) markers.

Methods: SPORTAX is a prospective registry of sporadic ataxia patients with an onset >40 years.

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  • MOXIe was a two-part study that assessed the drug omaveloxolone for treating Friedreich's ataxia, a rare neurological disease, finding significant improvements in patient scores compared to a placebo.
  • The study included an open-label extension where patients previously on placebo were reassessed after receiving omaveloxolone, allowing for comparisons of their mFARS scores.
  • The results showed that the benefits of omaveloxolone persisted over time, indicating its positive impact on the disease's progression in affected patients.
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We explored whether disease severity of Friedreich ataxia can be predicted using data from clinical examinations. From the database of the European Friedreich Ataxia Consortium for Translational Studies (EFACTS) data from up to five examinations of 602 patients with genetically confirmed FRDA was included. Clinical instruments and important symptoms of FRDA were identified as targets for prediction, while variables such as genetics, age of disease onset and first symptom of the disease were used as predictors.

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Background: Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs). It is caused by bi-allelic mutations in the gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported.

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  • Cerebellar ataxia is a neurodegenerative disorder that disrupts motor functions, impacting balance, movement, speech, and fine motor skills.
  • The ALCAT trial aimed to evaluate the effectiveness, safety, and tolerance of the modified essential amino acid acetyl-DL-leucine in treating patients with this condition across multiple centers in Germany and Austria.
  • The study involved 108 participants, who were split into two groups to receive either acetyl-DL-leucine or a placebo, and the primary measure of efficacy was the change in their ataxia score after six weeks of treatment.
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Background: Gait disturbances are a frequent symptom in CACNA1A disorders. Even though, data about their severity and progression are lacking and no CACNA1A-specific scale or assessment for gait is available.

Methods: We applied a gait assessment protocol in 20 ambulatory patients with genetically confirmed CACNA1A disorders and 39 matched healthy controls.

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Objective: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA.

Methods: A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole-brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls.

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Dentatorubral-pallidoluysian atrophy (DRPLA) is a CAG trinucleotide repeat expansion disorder with an autosomal-dominant mode of inheritance and very low prevalence in Europe. We herein report the clinical characteristics of the first Austrian DRPLA family. Genetic analysis revealed the presence of a common European haplotype, suggesting a founder mutation in Europe.

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Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia.

Methods: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry.

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Objectives: CACNA1A variants underlie three neurological disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). EEG is applied to study their episodic manifestations, but findings in the intervals did not gain attention up to date.

Methods: We analyzed repeated EEG recordings performed between 1994 and 2019 in a large cohort of genetically confirmed CACNA1A patients.

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Objective: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.

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The spectrum of coenzyme Q (CoQ) deficiency syndromes comprises a variety of disorders, including a form of autosomal recessive cerebellar ataxia (ARCA2) caused by mutations in the AarF domain-containing kinase 3 gene (ADCK3). Due to the potential response to CoQ supplementation, a timely diagnosis is crucial. Herein, we describe two siblings with a novel homozygous ADCK3 variant and an unusual presentation consisting of isolated writer's cramp with adult-onset.

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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.

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Background: In rare disorders diagnosis may be delayed due to limited awareness and unspecific presenting symptoms. Herein, we address the issue of diagnostic delay in Friedreich's Ataxia (FRDA), a genetic disorder usually caused by homozygous GAA-repeat expansions.

Methods: Six hundred eleven genetically confirmed FRDA patients were recruited within a multicentric natural history study conducted by the EFACTS (European FRDA Consortium for Translational Studies, ClinicalTrials.

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Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress.

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