Predictors of Survival in Friedreich's Ataxia: A Prospective Cohort Study.

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.

Cerebral venous thrombosis, neutropenia and iron-deficiency anemia in Huntington disease.

Neurologic and nonneurologic manifestations have been shown for Huntington disease (HD) as a genetic neurodegenerative disorder. However, cerebral venous thrombosis (CVT), iron-deficiency anemia and neutropenia have not been reported as its presentations to date. We introduce the first case of a HD patient with CVT, iron-deficiency anemia and neutropenia.

Onset features and time to diagnosis in Friedreich's Ataxia.

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.

Aberrant functional connectivity of resting state networks related to misperceptions and intra-individual variability in Parkinson's disease.

Patients with Parkinson's disease (PD) frequently suffer from visual misperceptions and hallucinations, which are difficult to objectify and quantify. We aimed to develop an image recognition task to objectify misperceptions and to assess performance fluctuations in PD patients with and without self-reported hallucinations. Thirty-two non-demented patients with Parkinson's disease (16 with and 16 without self-reported visual hallucinations) and 25 age-matched healthy controls (HC) were tested.

Nonataxia symptoms in Friedreich Ataxia: Report from the Registry of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS).

Objective: To provide a systematic evaluation of the broad clinical variability in Friedreich ataxia (FRDA), a multisystem disorder presenting mainly with afferent ataxia but also a complex phenotype of nonataxia symptoms.

Methods: From the large database of the European Friedreich's Ataxia Consortium for Translational Studies, 650 patients with genetically confirmed FRDA were included. Detailed data of medical history documentation, questionnaires, and reports on clinical features were analyzed to provide in-depth description of the clinical profile and frequency rates of phenotypical features with a focus on differences between typical-onset and late-onset FRDA.

[Primary and Secondary Fall Prevention in the Rehabilitation: A Practical Approach to Fall Prevention].

Active fall prevention requires analysis of the mechanisms provoking falls and the subsequent initiation of appropriate counteracting measures. This is crucial for the quality management of all rehabilitation programs. There is primary and secondary fall prevention.

Scales for the clinical evaluation of cerebellar disorders.

Clinical scales represent an important tool not only for the initial grading/scoring of disease and assessment of progression, but also for the quantification of therapeutic effects in clinical trials. There are several scales available for the clinical evaluation of cerebellar symptoms. While some scales have been developed and evaluated for specific cerebellar disorders such as Friedreich ataxia, others reliably capture cerebellar symptoms with no respect to the underlying etiology.

Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

Background: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction.

Methods: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls.

Friedreich Ataxia: current status and future prospects.

Friedreich ataxia (FA) represents the most frequent type of inherited ataxia. Most patients carry homozygous GAA expansions in the first intron of the frataxin gene on chromosome 9. Due to epigenetic alterations, frataxin expression is significantly reduced.

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 2 year cohort study.

Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) is a prospective international registry investigating the natural history of Friedreich's ataxia. We used data from EFACTS to assess disease progression and the predictive value of disease-related factors on progression, and estimated sample sizes for interventional randomised clinical trials.

Methods: We enrolled patients with genetically confirmed Friedreich's ataxia from 11 European study sites in Austria, Belgium, France, Germany, Italy, Spain, and the UK.

Spinocerebellar ataxia 28: a novel AFG3L2 mutation in a German family with young onset, slow progression and saccadic slowing.

Background: Spinocerebellar ataxia type 28 (SCA28) is related to mutations of the ATPase family gene 3-like 2 gene (AFG3L2). To date, 13 private missense mutations have been identified in families of French, Italian, and German ancestry, but overall, the disorder seems to be rare in Europe. Here, we report a kindred of German ancestry with four affected family members presenting with slowly progressive ataxia, mild pyramidal tract signs and slow saccades.

No parkinsonism in SCA2 and SCA3 despite severe neurodegeneration of the dopaminergic substantia nigra.

See Klockgether (doi:10.1093/awv253) for a scientific commentary on this article.The spinocerebellar ataxias types 2 (SCA2) and 3 (SCA3) are autosomal dominantly inherited cerebellar ataxias which are caused by CAG trinucleotide repeat expansions in the coding regions of the disease-specific genes.

Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data.

Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry.

Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia.

A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression.

Spinocerebellar ataxia type 6 (SCA6), episodic ataxia type 2 (EA2) and familial hemiplegic migraine type 1 (FHM1) are allelic disorders of the gene CACNA1A encoding the P/Q subunit of a voltage gated calcium channel. While SCA6 is related to repeat expansions affecting the C-terminal part of the protein, EA2 and FHM phenotypes are usually associated with nonsense and missense mutations leading to impaired channel properties. In three unrelated families with dominant cerebellar ataxia, symptoms cosegregated with CACNA1A missense mutations of evolutionary highly conserved amino acids (exchanges p.

Monitoring progression in Friedreich ataxia (FRDA): the use of clinical scales.

Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder associated with ataxia, dysarthria, pyramidal tract signs, sensory loss, cardiomyopathy and diabetes. There is no cure for FRDA so far. Studies of the natural history of the disease and future therapeutic trials require development of appropriate outcome markers.

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.

Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology.

Multiple system atrophy (MSA) is a rapidly progressive sporadic α-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated.

Mesial temporal lobe epilepsy in a patient with spinocerebellar ataxia type 13 (SCA13).

We report a female patient of German descent with a molecular diagnosis of SCA13 who presented with a history of cerebellar ataxia and epilepsy. The underlying mutation R420H had been shown to cause a dominant negative effect on the functional properties of the voltage-gated potassium channel KCNC3. Despite widespread KCNC3 expression in the central nervous system, the patient presented with a left mesiotemporal electroencephalogram focus and left hippocampal sclerosis.

Antineuronal autoantibodies in neurological disorders.

Autoantibodies (abs) related to neurological disease are currently classified into two large groups depending on the site of the respective target antigen: Group I encompasses abs that recognise intracellular antigens (Hu, Yo, Ri, CV2/CRMP5, amphiphysin, Ma2, SOX, ZIC, GAD, adenylate kinase 5, homer 3), whereas group II abs are targeted against neuronal cell membrane antigens (VGKC, AMPA-R, GABAB-R, NMDA-R, Glycine-R, VGCC, metabotropic GluR1). Both abs groups can be further subdivided according to their diagnostic impact for paraneoplastic or non-paraneoplastic neurological disease. The review gives an overview of the common characteristics of each group and provides more detailed information on single abs and the associated clinical syndromes.

Treatment of paroxysmal dyskinesias.

Importance Of The Field: Paroxysmal dyskinesias represent a heterogeneous group of rare diseases sharing characteristics with two important groups of neurological disorders, the movement disorders and the epilepsies. Their common hallmark is the paroxysmal occurrence of dyskinesias including athetosis, ballism, chorea and dystonia. During the last two decades, various genetic abnormalities have been identified thereby providing insight into the underlying pathophysiology and offering therapeutic opportunities for many of these conditions.

KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients.

We recently identified KCNC3, encoding the Kv3.3 voltage-gated potassium channel, as the gene mutated in SCA13. One g.

Neurological symptoms in patients with biopsy proven celiac disease.

In celiac disease (CD), the gut is the typical manifestation site but atypical neurological presentations are thought to occur in 6 to 10% with cerebellar ataxia being the most frequent symptom. Most studies in this field are focused on patients under primary neurological care. To exclude such an observation bias, patients with biopsy proven celiac disease were screened for neurological disease.

Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2.

Background: The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (SETX). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions.