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Continuum (Minneapolis, Minn.) Aug 2019This article reviews the symptoms, laboratory and neuroimaging diagnostic tests, genetics, and management of cerebellar ataxia. (Review)
Review
PURPOSE OF REVIEW
This article reviews the symptoms, laboratory and neuroimaging diagnostic tests, genetics, and management of cerebellar ataxia.
RECENT FINDINGS
Recent advances in genetics have led to the identification of novel genetic causes for ataxia and a more comprehensive understanding of the biological pathways critical for normal cerebellar function. When these molecular pathways become dysfunctional, patients develop cerebellar ataxia. In addition, several ongoing clinical trials for Friedreich ataxia and spinocerebellar ataxia will likely result in novel symptomatic and disease-modifying therapies for ataxia. Antisense oligonucleotides for spinocerebellar ataxias associated with CAG repeat expansions might be a promising therapeutic strategy.
SUMMARY
Cerebellar ataxias include heterogeneous disorders affecting cerebellar function, leading to ataxic symptoms. Step-by-step diagnostic workups with genetic investigations are likely to reveal the underlying causes of ataxia. Some disease-specific therapies for ataxia exist, such as vitamin E for ataxia with vitamin E deficiency and thiamine for Wernicke encephalopathy, highlighting the importance of recognizing these forms of ataxia. Finally, genetic diagnosis for patients with ataxia will accelerate clinical trials for disease-modifying therapy and will have prognostic value and implications for family planning for these patients.
Topics: Ataxia; Cerebellar Ataxia; Dopamine Agents; Female; Friedreich Ataxia; Humans; Male; Middle Aged; Physical Therapy Modalities
PubMed: 31356292
DOI: 10.1212/CON.0000000000000753 -
Arquivos de Neuro-psiquiatria Mar 2019Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations... (Review)
Review
Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.
Topics: Acute Disease; Brain; Cerebellar Ataxia; Diagnosis, Differential; Humans; Magnetic Resonance Imaging
PubMed: 30970132
DOI: 10.1590/0004-282X20190020 -
Annals of Physical and Rehabilitation... Mar 2014Gait and balance disorders are often major causes of handicap in patients with cerebellar ataxia. Although it was thought that postural and balance disorders in... (Review)
Review
Gait and balance disorders are often major causes of handicap in patients with cerebellar ataxia. Although it was thought that postural and balance disorders in cerebellar ataxia were not treatable, recent studies have demonstrated the beneficial effects of rehabilitation programs. This article is the first systematic review on the treatment of postural disorders in cerebellar ataxia. Nineteen articles were selected, of which three were randomized, controlled trials. Various aetiologies of cerebellar ataxia were studied: five studies assessed patients with multiple sclerosis, four assessed patients with degenerative ataxia, two assessed stroke patients and eight assessed patients with various aetiologies. Accurate assessment of postural disorders in cerebellar ataxia is very important in both clinical trials and clinical practice. The Scale for the Assessment and Rating of Ataxia (SARA) is a simple, validated measurement tool, for which 18 of the 40 points are related to postural disorders. This scale is useful for monitoring ataxic patients with postural disorders. There is now moderate level evidence that rehabilitation is efficient to improve postural capacities of patients with cerebellar ataxia - particularly in patients with degenerative ataxia or multiple sclerosis. Intensive rehabilitation programs with balance and coordination exercises are necessary. Although techniques such as virtual reality, biofeedback, treadmill exercises with supported bodyweight and torso weighting appear to be of value, their specific efficacy has to be further investigated. Drugs have only been studied in degenerative ataxia, and the level of evidence is low. There is now a need for large, randomized, controlled trials testing rehabilitation programs suited to postural and gait disorders of patients with cerebellar ataxia.
Topics: Cerebellar Ataxia; Exercise Therapy; Humans; Postural Balance; Sensation Disorders
PubMed: 24582474
DOI: 10.1016/j.rehab.2014.01.002 -
International Journal of Molecular... May 2020Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main... (Review)
Review
Glutamic acid decarboxylase (GAD) is an intracellular enzyme whose physiologic function is the decarboxylation of glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter within the central nervous system. GAD antibodies (Ab) have been associated with multiple neurological syndromes, including stiff-person syndrome, cerebellar ataxia, and limbic encephalitis, which are all considered to result from reduced GABAergic transmission. The pathogenic role of GAD Ab is still debated, and some evidence suggests that GAD autoimmunity might primarily be cell-mediated. Diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid. Due to the relative rarity of these syndromes, treatment schemes and predictors of response are poorly defined, highlighting the unmet need for multicentric prospective trials in this population. Here, we reviewed the main clinical characteristics of neurological syndromes associated with GAD Ab, focusing on pathophysiologic mechanisms.
Topics: Autoimmune Diseases of the Nervous System; Autoimmunity; Cerebellar Ataxia; Glutamate Decarboxylase; Humans; Limbic Encephalitis; Neurons; Stiff-Person Syndrome
PubMed: 32456344
DOI: 10.3390/ijms21103701 -
Current Neuropharmacology 2019Immune-mediated cerebellar ataxias (IMCAs), a clinical entity reported for the first time in the 1980s, include gluten ataxia (GA), paraneoplastic cerebellar... (Review)
Review
Immune-mediated cerebellar ataxias (IMCAs), a clinical entity reported for the first time in the 1980s, include gluten ataxia (GA), paraneoplastic cerebellar degenerations (PCDs), antiglutamate decarboxylase 65 (GAD) antibody-associated cerebellar ataxia, post-infectious cerebellitis, and opsoclonus myoclonus syndrome (OMS). These IMCAs share common features with regard to therapeutic approaches. When certain factors trigger immune processes, elimination of the antigen( s) becomes a priority: e.g., gluten-free diet in GA and surgical excision of the primary tumor in PCDs. Furthermore, various immunotherapeutic modalities (e.g., steroids, immunoglobulins, plasmapheresis, immunosuppressants, rituximab) should be considered alone or in combination to prevent the progression of the IMCAs. There is no evidence of significant differences in terms of response and prognosis among the various types of immunotherapies. Treatment introduced at an early stage, when CAs or cerebellar atrophy is mild, is associated with better prognosis. Preservation of the "cerebellar reserve" is necessary for the improvement of CAs and resilience of the cerebellar networks. In this regard, we emphasize the therapeutic principle of "Time is Cerebellum" in IMCAs.
Topics: Animals; Autoimmune Diseases; Cerebellar Ataxia; Cerebellum; Disease Progression; Humans; Practice Guidelines as Topic
PubMed: 30221603
DOI: 10.2174/1570159X16666180917105033 -
Journal of Neurology Jan 2023This narrative review aims at providing an update on the management of inherited cerebellar ataxias (ICAs), describing main clinical entities, genetic analysis... (Review)
Review
This narrative review aims at providing an update on the management of inherited cerebellar ataxias (ICAs), describing main clinical entities, genetic analysis strategies and recent therapeutic developments. Initial approach facing a patient with cerebellar ataxia requires family medical history, physical examination, exclusions of acquired causes and genetic analysis, including Next-Generation Sequencing (NGS). To guide diagnosis, several algorithms and a new genetic nomenclature for recessive cerebellar ataxias have been proposed. The challenge of NGS analysis is the identification of causative variant, trio analysis being usually the most appropriate option. Public genomic databases as well as pathogenicity prediction software facilitate the interpretation of NGS results. We also report on key clinical points for the diagnosis of the main ICAs, including Friedreich ataxia, CANVAS, polyglutamine spinocerebellar ataxias, Fragile X-associated tremor/ataxia syndrome. Rarer forms should not be neglected because of diagnostic biomarkers availability, disease-modifying treatments, or associated susceptibility to malignancy. Diagnostic difficulties arise from allelic and phenotypic heterogeneity as well as from the possibility for one gene to be associated with both dominant and recessive inheritance. To complicate the phenotype, cerebellar cognitive affective syndrome can be associated with some subtypes of cerebellar ataxia. Lastly, we describe new therapeutic leads: antisense oligonucleotides approach in polyglutamine SCAs and viral gene therapy in Friedreich ataxia. This review provides support for diagnosis, genetic counseling and therapeutic management of ICAs in clinical practice.
Topics: Humans; Cerebellar Ataxia; Friedreich Ataxia; Mutation; Ataxia; Spinocerebellar Ataxias
PubMed: 36152050
DOI: 10.1007/s00415-022-11383-6 -
Neurologic Clinics Feb 2023Cerebellar ataxia results from damage to the cerebellum and presents as movement incoordination and variability, gait impairment, and slurred speech. Patients with... (Review)
Review
Cerebellar ataxia results from damage to the cerebellum and presents as movement incoordination and variability, gait impairment, and slurred speech. Patients with cerebellar ataxia can also have cognitive and mood changes. Although the identification of causes for cerebellar ataxia can be complex, age of presentation, chronicity, family history, and associated movement disorders may provide diagnostic clues. There are many genetic causes for cerebellar ataxia, and the common autosomal dominant and recessive ataxia are due to genetic repeat expansions. Step-by-step approach will lead to the identification of the causes. Symptomatic and potential disease-modifying therapies may benefit patients with cerebellar ataxia.
Topics: Humans; Cerebellar Ataxia; Ataxia; Cerebellum
PubMed: 36400556
DOI: 10.1016/j.ncl.2022.05.002 -
Italian Journal of Pediatrics Jan 2017Ataxia is a sign of different disorders involving any level of the nervous system and consisting of impaired coordination of movement and balance. It is mainly caused by... (Review)
Review
BACKGROUND
Ataxia is a sign of different disorders involving any level of the nervous system and consisting of impaired coordination of movement and balance. It is mainly caused by dysfunction of the complex circuitry connecting the basal ganglia, cerebellum and cerebral cortex. A careful history, physical examination and some characteristic maneuvers are useful for the diagnosis of ataxia. Some of the causes of ataxia point toward a benign course, but some cases of ataxia can be severe and particularly frightening.
METHODS
Here, we describe the primary clinical ways of detecting ataxia, a sign not easily recognizable in children. We also report on the main disorders that cause ataxia in children.
RESULTS
The causal events are distinguished and reported according to the course of the disorder: acute, intermittent, chronic-non-progressive and chronic-progressive.
CONCLUSIONS
Molecular research in the field of ataxia in children is rapidly expanding; on the contrary no similar results have been attained in the field of the treatment since most of the congenital forms remain fully untreatable. Rapid recognition and clinical evaluation of ataxia in children remains of great relevance for therapeutic results and prognostic counseling.
Topics: Cerebellar Ataxia; Child; Diagnosis, Differential; Early Diagnosis; Humans; Physical Examination; Prognosis; Severity of Illness Index
PubMed: 28257643
DOI: 10.1186/s13052-016-0325-9 -
Molecular Neurobiology Jun 2022Cerebellar ataxia is a form of ataxia that originates from dysfunction of the cerebellum, but may involve additional neurological tissues. Its clinical symptoms are... (Review)
Review
Cerebellar ataxia is a form of ataxia that originates from dysfunction of the cerebellum, but may involve additional neurological tissues. Its clinical symptoms are mainly characterized by the absence of voluntary muscle coordination and loss of control of movement with varying manifestations due to differences in severity, in the site of cerebellar damage and in the involvement of extracerebellar tissues. Cerebellar ataxia may be sporadic, acquired, and hereditary. Hereditary ataxia accounts for the majority of cases. Hereditary ataxia has been tentatively divided into several subtypes by scientists in the field, and nearly all of them remain incurable. This is mainly because the detailed mechanisms of these cerebellar disorders are incompletely understood. To precisely diagnose and treat these diseases, studies on their molecular mechanisms have been conducted extensively in the past. Accumulating evidence has demonstrated that some common pathogenic mechanisms exist within each subtype of inherited ataxia. However, no reports have indicated whether there is a common mechanism among the different subtypes of inherited cerebellar ataxia. In this review, we summarize the available references and databases on neurological disorders characterized by cerebellar ataxia and show that a subset of genes involved in lipid homeostasis form a new group that may cause ataxic disorders through a common mechanism. This common signaling pathway can provide a valuable reference for future diagnosis and treatment of ataxic disorders.
Topics: Ataxia; Cerebellar Ataxia; Cerebellum; Humans; Lipids; Spinocerebellar Degenerations
PubMed: 35420383
DOI: 10.1007/s12035-022-02826-2 -
Ugeskrift For Laeger May 2023CANVAS including its clinical components of cerebellar ataxia, sensory neuropathy and vestibular areflexia is presented in this review. An intronic biallelic... (Review)
Review
CANVAS including its clinical components of cerebellar ataxia, sensory neuropathy and vestibular areflexia is presented in this review. An intronic biallelic pentanucleotide expansion in RFC1 is the genetic cause of CANVAS. Several patients diagnosed with isolated "idiopathic" neurological or otological conditions might have a CANVAS spectrum disorder. The number of CANVAS patients may well increase considerably in the near future, making it important to consider the diagnostic set-up and infrastructure for counselling, treatment and follow-up in the Danish healthcare system.
Topics: Humans; Cerebellar Ataxia; Bilateral Vestibulopathy; Vestibular Diseases; Peripheral Nervous System Diseases; Syndrome
PubMed: 37170740
DOI: No ID Found