Treatment Options in Degenerative Cerebellar Ataxia: A Systematic Review

Abstract

The etiology of cerebellar ataxia (CA) is heterogeneous and includes easily identified and often reversible causes (i.e., drug toxicity and vitamin B12 deficiency) as well as irreversible degenerative conditions. It is the latter that poses a significant therapeutic challenge for practitioners treating this population of patients. To date, there are no U.S. Food and Drug Administration-approved medications for the treatment of CA. The literature, consisting mostly of case reports, case series, and small clinical trials, is sparse and scattered. These studies are difficult to translate clinically because they often describe diverse study populations with various identified and unidentified genetic etiologies. In addition, the reported treatment duration is often brief, and it is uncertain whether any of these options provide substantially lasting benefits. In this article, we review published reports and studies to aid the practitioner counseling patients with degenerative ataxias.Degenerative cerebellar ataxias (CAs) are a group of disorders associated with progressive degeneration of the cerebellum, and its afferent and efferent pathways, resulting in the impairment of both appendicular and axial motor control. Patients often present with complaints of clumsiness, speech changes, and unsteady gait. These disorders can be classified into three major groups. The first group is the acquired ataxias resulting from causes such as toxins (e.g., alcohol), immune-mediated disorders (e.g., paraneoplastic cerebellar degeneration), vitamin deficiency (e.g., vitamin E), chronic central nervous system (CNS) infections (e.g., Creutzfeld-Jakob disease), and superficial siderosis. The other two groups are the hereditary and nonhereditary degenerative ataxias. 1 The inheritance pattern of the known hereditary ataxia disorders includes autosomal-dominant, autosomal-recessive, X-linked, and mitochondrial transmission. However, many patients present without a family history and have an unidentifiable etiology.The neurochemistry of CA is complex, suggesting a variety of possible targets for ataxia treatment. Though gamma-aminobutyric acid (GABA) and glutamate are the primary neurotransmitters associated with motor control, neurotransmitters such as serotonin, norepinephrine, acetylcholine, dopamine, and histamine are also responsible for normal cerebellar function, including motor learning. 2 Unfortunately, current practice offers no recommendations for first-line medical or physical therapy (PT).Several variables may influence the mixed outcomes of treatment studies, including the heterogeneity of the studied populations and the small sample size. The scattered publications addressing ataxia treatment, in addition to the lack of widely accepted guidelines, make it challenging for physicians to guide management in patients seeking comprehensive treatment, including PT. In this article, we offer the clinician an overview of the literature.To identify relevant publications, a PubMed search using the terms "treatments of cer...

Spinocerebellar Ataxia 27: A Review and Characterization of an Evolving Phenotype

“…Amantadine slows the inactivation of sodium channels and thus may allow for increased excitation, helping to reverse the decreased cell firing of Purkinje and granule cells after depolarization that is associated with the genetic defect in FGF14. 28 – 30 Although amantadine has previously been shown to potentially help improve cerebellar ataxia, Friedreich’s ataxia, and parkinsonism, 31 , 32 there are no reports to date of amantadine or any other medication found to successfully reduce tremor and/or gait stability in SCA27. 5 – 17 Thus, research is needed to better determine if amantadine or levodopa may be reasonable treatment options to consider for SCA27.…”

Genetic Dystonia‐ataxia Syndromes: Clinical Spectrum, Diagnostic Approach, and Treatment Options

“…Physical, occupational, and speech rehabilitation therapy are usually combined with pharmacological treatment where appropriate . Unfortunately, there currently exists no medication that has been approved for the treatment of cerebellar ataxia or that can prevent or slow‐down neurodegenerative processes that are not related to metabolic diseases (with the exception of aminopyridines and acetazolamide for episodic ataxia in episodic ataxia type 2) .…”

“…Unfortunately, there currently exists no medication that has been approved for the treatment of cerebellar ataxia or that can prevent or slow‐down neurodegenerative processes that are not related to metabolic diseases (with the exception of aminopyridines and acetazolamide for episodic ataxia in episodic ataxia type 2) . Most drugs used to treat ataxia or other cerebellar features failed to achieve significant and sustained improvement . For patients with Friedreich ataxia or spinocerebellar ataxia, riluzole showed modest improvement in ataxia at 12 months in a Class I study (Supporting Table 2) .…”

Cerebellar Degeneration in Epilepsy: A Systematic Review

“…The causes of cerebellar degeneration can be broadly divided into two categories; acquired and genetic [ 13 ]. Acquired cerebellar degeneration has been attributed to endogenous or exogenous non-genetic causes [ 14 ], such as alcohol abuse and vitamin deficiencies [ 15 ], infections of the central nervous system (CNS) [ 16 ], autoimmune disorders [ 17 ], and primary or metastatic tumours [ 17 ], among others. Neuroimaging studies including magnetic resonance (MR) and nuclear medicine techniques such as single-photon emission computed tomography (SPECT) and positron emission tomography (PET) provide structural and functional assessments of cerebellar atrophy [ 18 ].…”