Active clinical trials for "Cerebellar Ataxia"

The study will consist of a prospective observation of subjects in a natural history design. Disease progression will be monitored through clinical scales and video-oculography. Participants will be stratified in three groups: ataxic carriers, pre-ataxic carriers and non-carriers (controls). The following clinical scales will be applied in all subjects at baseline and at months 12 and 24: SARA, SCAFI, CCFS, NESSCA, INAS and ICARS. Oculomotor function will be registered using video-oculography (EyeSeeCam, InterAcoustics) at the same time points. Progression rates, effect sizes and responsiveness to change will be established for all parameters and results will be compared between candidate biomarkers.

Cerebellar ataxia (CA) is a collection of signs and symptoms caused by cerebellar dysfunction, which can be the result of different disease processes including hereditary and acquired conditions. High incidence of falls is reported in people with CA due to poor balance while walking. Therefore, it is crucial to assess the balance of people with CA to identify potential fallers. There are some clinical tests commonly used for assessing the balance of people with CA, including both generic measures of balance and ataxia-specific rating scales. The current best balance outcome measures for CA includes Berg Balance Scale (BBS), Timed Up and Go test (TUG), and the balance related items in Scale for the assessment and rating of ataxia (SARA). TUG is commonly used in clinical settings for the assessment of mobility and fall risk of individuals. However, a study done by Winser et. al (2017) found that the correlation between TUG and ataxia rating scales (SARA and ICARS) is only moderate. This indicates that the gait speed and functional mobility findings of TUG might not truly reflect the balance deficits of CA. Therefore, our study will develop a modified TUG for the assessment of balance in people with CA. Circular TUG (cTUG) is a modified version of the standard TUG. cTUG is an equilibrium test that challenges subjects' ability to maintain balance in response to the constant change in direction of walking. In cTUG, the subject walks a semi-circular pathway instead of a straight line. Walking in a circular pathway targets at challenging the coordination of people with CA as walking in a circle requires constant change in directions and correction after feedback. It is speculated that the cTUG will have better accuracy in predicting the balance and falls risk among people with CA. We will target at recruiting 30 healthy volunteers and 30 individuals with cerebellar ataxia. Besides the cTUG we will also assess disease severity of ataxia using the Scale for the Assessment and Rating of Ataxia (SARA), balance using the Berg Balance Scale, Timed Up and Go test, Sensory Organization test, Limits of Stability test and functional independence using the Barthel Index. For validation of the cTUG, two types of reliability will be examined, including intra-rater reliability and interrater reliability and four types of validity will be assessed, including concurrent validity, convergent validity, discriminant validity, and external validity.

Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by gait disorders, neuromotor dysfunction, eye abnormalities and immune deficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already initiated. Until recently, AT patients were immunized with the pneumococcal polysaccharide vaccine (PPV23, Pneumovax® Aventis Pasteur MSD). However, data have shown that they do not respond well to these vaccines. Recently, the Israeli Ministry of Health has approved the pneumococcal 7-valent conjugate vaccine (PCV7, Prevenar®, Wyeth Lederle) for AT patients of all ages. This conjugate vaccine is known to stimulate the immune system through a different mechanism and the response is expected to be higher. The approved Israeli schedule for immunization of AT patients includes children older than 2 years that are entitled to receive 2 doses of PCV7 (8 weeks apart) boosted by PPV23, eight weeks after the second dose of PCV7. Assessment of the antibody response of such pneumococcal vaccination protocol in AT patients has never been performed. The "Safra" Children's Hospital is the national multi-disciplinary center caring for AT patients. Approximately 50 patients from all over the country (including Jewish, Druze, Bedouin and other Muslim patients - 3 of whom are Palestinians) are followed in the clinic on a monthly basis. Approximately 20 AT patients are not receiving IVIG replacement therapy, therefore are entitled to receive pneumococcal vaccination as stated above (mean age 10.6, 3 -23 years, 3 less than 5 years) The aim of this study is to evaluate the responsiveness, determined by specific antibody production, of AT patients receiving this new vaccine protocol.

Ataxia telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, immunodeficiency, chromosomal instability, and cancer susceptibility. Currently there are no curative therapy options. The clinical presentation of the disease has a wide variety is linked to the proven mutation, immunological status and residual ATM kinase activity. Apart from these prognostic markers, hardly any biomarker to predict disease course is available. Aim of the present proposal is to evaluate serum concentrations of neurofilament - light chain in the serum of whole blood as biomarker of neurodegeneration prospectively. In addition to that, the investigators will examine the evolution of neurofilament - light chain longitudinally by blood samples from our biobank as well as the concentration of neurofilament - light chain in cerebrospinal fluid (CSF) of affected A-T patients from our biobank. As in other neurodegenerative disorders and ataxias, the investigators expect that neurofilament- light chain levels are increased in the A-T cohort and correlated to the neurological status of A-T patients evaluated by means of AT-score.

Friedreich's ataxia (FA) is the most frequent recessive genetic ataxia with an estimated prevalence of 1/50 000. The first symptoms appear around the age of 10 years with a progressive course and the need for an armchair 10- 15 years after the first symptoms. More rarely the disease can present with a late onset (after the age of 25) with a picture characterized by spastic paraparesis and slower progression ("LOFA" for "Late Onset Friedreich Ataxia" or VLOFA for "Very Late Appearance of Friedreich's ataxia "). AF is caused in 96% of cases by an expansion of GAAN triplets (N> 100 repeats) located in intron 1 of the FXN gene, present on the two alleles, and, in the rest of the cases, by an associated expansion a point mutation or a deletion in trans. During molecular diagnostics, it is not uncommon to find the presence of interruptions within the GAA expansion. This results in the absence and / or the shift of peak (s) within the chromatogram. To date, only the partial correlation between the size of the expansion and the age of onset of Friedreich's ataxia has been established. In particular, very atypical forms of AF with a late onset (after the age of 25) are in particular explained by the low number of repetitions in the expansion, typically between 100 and 500 repetitions. However, the presence of an interruption could stabilize the size of the expansion and, therefore, be mainly associated with expansions of small sizes and therefore with a late onset of the disease. The objective of this study is therefore to analyse and caracterize the presence and the type of interruptions of the GAA expansions in a group of patients with FA ; this data will be correlated with the age at onset of FA.

Autoimmune encephalitis (AE) are characterized by subacute onset of memory deficits, altered mental status or psychiatric symptoms, frequently associated with seizures, inflammatory cerebrospinal fluid and in cases with prominent limbic involvement, typical magnetic resonance imaging. Several autoantibodies (Ab) may be detected in AE, although its detection is not mandatory to establish a diagnosis. These Ab mainly recognize different synaptic and cell-surface proteins in the central nervous system, and are thought to be pathogenic as they alter the normal location or function of its antigens. The primary trigger of the immune response is unknown for most of AE. In addition to acquired susceptibility, genetic predisposition may also be important in the pathogenesis of AE. Human leukocyte antigen (HLA) is the genetic factor most frequently associated with autoimmune diseases, due to its genetic complexity and key role in the adaptive immune response. The aim of the study is to describe HLA profile in three groups of autoimmune encephalitis and related disorders: anti-LGI1, anti-CASPR2 and anti-GAD neurological diseases.

Rationale: Forced spirometry maneuvers are not routinely performed in patients with Ataxia Telangiectasia (A-T), even though they suffer from respiratory illnesses. Objectives: To study the feasibility and validity of forced spirometry in A-T patients. Methods: Patients will perform spirometry during clinical visits. Parameters studied will be technical quality, relation to predicted values, age, pulmonary illness, body mass index, mutational status and mutation.

Cerebellar ataxias (CA) and spastic paraplegias (SP) are genetically and clinically very heterogeneous. More than 40 loci are already known but the number of phenotypes is even greater suggesting further genetic heterogeneity. These progressive disorders are often severe and fatal, due to the absence of specific therapy. The SPATAX network combines the experience of European clinicians and scientists working on these groups of diseases. Over the past year, they have assembled the largest collection of families and achieved a number of tasks (initiation of a clinical and genetic database, distribution of DNA to participating laboratories, mapping of three new loci, and refinement of several loci). In addition to clinicians from Europe and Mediterranean countries, who play a major role in collecting families according to evaluation tools developed and validated by the SPATAX members, the group includes major European laboratories devoted to the elucidation of the molecular basis of these disorders. Each laboratory will centralize all families with a subtype of autosomal recessive (AR) CA (n=116) or SP (n=207) in order to efficiently map and identify the responsible gene(s). Genome-wide scans are already underway in 61 families. Given the expertise of the participants, the researchers expect to map and identify several genes during the course of this project. The spectrum of mutations and phenotype/genotype correlations will be analysed thanks to this unique series of patients with various phenotypes. The knowledge gained will be immediately applicable to patients in terms of improved positive diagnosis, follow-up and appropriate genetic counselling. In the long term, models for genetic entity will be developed in order to understand the pathophysiology and to identify new targets for treatment. The series of patients assembled and the precise knowledge of natural history will facilitate the implantation of therapeutic trials based on rational approaches.