EC Neurology

Review Article Volume 15 Issue 7 - 2023

Ataxia: Neurological Condition with Intertwining Multifactorial Mechanisms

Marwan A Ebrahim, Moustafa S Gaber, Rami H Abdelghani, Mina M Ayoub, Amira Zaky and Ahmad R Bassiouny*

Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt

*Corresponding Author: Ahmad R Bassiouny, Professor, Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
Received: May 23, 2023; Published: June 12, 2023



Ataxia is a neurological disorder describes poor muscle control that causes clumsy voluntary movements, characterized by a lack of muscle coordination, leading to difficulties with voluntary movements such as walking, speaking, and controlling fine motor skills. It is usually results from malfunction of the “cerebellum”, located at the back of the brain beneath the occipital lobes, which fine tunes motor activity or movement via the flocculonodular lobe. Ataxia, is a physical finding, not a disease. The symptoms of ataxia can vary depending on the underlying cause and the specific areas of the brain affected. Common symptoms include unsteady gait, difficulty with balance, slurred speech, tremors, difficulty swallowing, and impaired fine motor skills.

In this review article we discuss the diverse disease types that lead to sporadic ataxia with adult onset. Medical imaging modalities comprise computed tomography (CT) scanners and magnetic resonance imaging (MRI), the most frequently performed imaging investigation in patients with ataxia, with clinical findings might reflect progressive disease changes such as cerebellar degeneration and other brain structures in people with ataxia. Recent advances in genetics have significantly contributed to our understanding of ataxia, particularly in identifying causative genes and uncovering underlying molecular mechanisms.

Keywords: Ataxia; Epidemiology; Molecular Mechanisms; Medical Interventions

  1. Pirker Walter and Regina Katzenschlager. “Gait disorders in adults and the elderly: A clinical guide”. Wiener Klinische Wochenschrift3-4 (2017): 81-95.
  2. Giladi Nir., et al. “Classification of gait disturbances: distinguishing between continuous and episodic changes”. Movement Disorders: Official Journal of the Movement Disorder Society11 (2013): 1469-1473.
  3. Ashizawa T and G Xia. “Ataxia”. Continuum (2016): 1208-1226.
  4. Ferreira-Pinto Manuel J., et al. “Functional diversity for body actions in the mesencephalic locomotor region”. Cell17 (2021): 4564-4578.e18.
  5. Fujisawa Haruki., et al. “Chronic Hyponatremia Causes Neurologic and Psychologic Impairments”. Journal of the American Society of Nephrology: JASN3 (2016): 766-780.
  6. Verkerk AJ., et al. “Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome”. Cell5 (1991): 905-914.
  7. La Spada AR., et al. “Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy”. Nature6330 (1991): 77-79.
  8. Hannan Anthony J. “Tandem repeats mediating genetic plasticity in health and disease”. Nature Reviews Genetics5 (2018): 286-298.
  9. Klockgether Thomas and Henry Paulson. “Milestones in ataxia”. Movement Disorders: Official Journal of the Movement Disorder Society6 (2011): 1134-1141.
  10. Cortese Andrea., et al. “Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia”. Nature Genetics4 (2019): 649-658.
  11. Cavallieri Francesco., et al. “Subacute copper-deficiency myelopathy in a patient with occult celiac disease”. The Journal of Spinal Cord Medicine4 (2017): 489-491.
  12. Kalia Lorraine V., et al. “Tremor in Spinocerebellar Ataxia Type 12”. Movement Disorders Clinical Practice (2014): 76-78.
  13. De Silva Rajith Nilantha., et al. “Diagnosis and Management of Progressive Ataxia in Adults”. And quot Practical Neurology (2019): 196-207.
  14. Choi Sung Won., et al. “Evaluation of Ataxia in Mild Ischemic Stroke Patients Using the Scale for the Assessment and Rating of Ataxia (SARA)”. Annals of Rehabilitation Medicine (2018): 375-383.
  15. Ferrarin M., et al. “Procedure for the Quantitative Evaluation of Motor Disturbances in Cerebellar Ataxic Patients”. Medical and Biological Engineering and Computing3 (2005): 349-356.
  16. Hartley Helen., et al. “Incidence and Prognostic Factors of Ataxia in Children with Posterior Fossa Tumors”. Neuro-Oncology Practice3 (2018): 185-193.
  17. Hermann Ruben., et al. “Bilateral Vestibulopathy: Vestibular Function, Dynamic Visual Acuity and Functional Impact”. Frontiers in Neurology 9 (2018).
  18. Mitoma Hiroshi., et al. “Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum”. International Journal of Environmental Research and Public Health16 (2021): 8678.
  19. “Spinocerebellar Ataxia - Getting a Diagnosis”. Genetic and Rare Diseases Information Center, U.S. Department of Health and Human Services (2023).
  20. Van Gaalen J., et al. “Drug-Induced Cerebellar Ataxia: A Systematic Review”. CNS Drugs12 (2014): 1139-1153.
  21. Wilkins Alastair. “Cerebellar Dysfunction in Multiple Sclerosis”. Frontiers in Neurology 8 (2017).
  22. Jayadev Suman and Thomas D Bird. “Hereditary Ataxias: Overview”. Genetics in Medicine9 (2013): 673-683.
  23. Bastian Amy J. “Mechanisms of Ataxia”. Physical Therapy6 (1997): 672-675.
  24. Tanburoğlu A., et al. “Pathogenesis, Types, Causes and Treatment;”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 4 (2017): 32-39.
  25. Hiraga Akiyuki. “Ataxic Hemiparesis”. Handbook of the Cerebellum and Cerebellar Disorders (2013): 1669-1686.
  26. Schuelke Markus. Ataxia with Vitamin E Deficiency. University of Washington, Seattle (2023).
  27. Lönnqvist Tuula. Infantile-Onset Spinocerebellar Ataxia. University of Washington, Seattle, (2018).
  28. Hadjivassiliou Marios., et al. “Gluten Ataxia”. The Cerebellum3 (2008): 494-498.
  29. Kanazawa I. “Dentatorubral-Pallidoluysian Atrophy or Naito-Oyanagi Disease”. Neurogenetics1 (1998): 1-17.
  30. Infante Jon., et al. “Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (Canvas) with Chronic Cough and Preserved Muscle Stretch Reflexes: Evidence for Selective Sparing of Afferent Ia Fibres”. Journal of Neurology6 (2018): 1454-1462.
  31. Coutinho Paula and Clara Barbot. “Ataxia with Oculomotor Apraxia Type 1”. University of Washington, Seattle (2015).
  32. Moreira Maria-Ceu and Michel Koenig. “Ataxia with Oculomotor Apraxia Type 2”. University of Washington, Seattle (2018).
  33. Salman Michael S. “Epidemiology of Cerebellar Diseases and Therapeutic Approaches”. Cerebellum1 (2018): 4-11.
  34. Paulson Henry. “Machado-Joseph disease/spinocerebellar ataxia type 3”. Handbook of Clinical Neurology 103 (2012): 437-449.
  35. Klockgether Thomas., et al. “Spinocerebellar ataxia”. Nature Reviews Disease Primers1 (2019): 24.
  36. Joo Byung-Euk., et al. “Prevalence rate and functional status of cerebellar ataxia in Korea”. Cerebellum3 (2012): 733-738.
  37. Chawla Jasvinder. “Friedreich Ataxia”. Background, Pathophysiology, Epidemiology, Medscape 2 (2023).
  38. Doerflinger N., et al. “Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families”. American Journal of Human Genetics5 (1995): 1116-1124.
  39. Cavalier Laurent., et al. “Ataxia with Isolated Vitamin E Deficiency: Heterogeneity of Mutations and Phenotypic Variability in a Large Number of Families”. The American Journal of Human Genetics2 (1998): 301-310.
  40. Eigentler Andreas., et al. “The Scale for the Assessment and Rating of Ataxia Correlates with Dysarthria Assessment in Friedreich’s Ataxia”. Journal of Neurology3 (2011): 420-426.
  41. Caplan Louis R. “Ataxia in patients with brain infarcts and hemorrhages”. Handbook of Clinical Neurology 103 (2012): 147-160.
  42. Duffy Joseph R. “Motor Speech Disorders: Substrates, Differential Diagnosis, and Management”. Elsevier (2020).
  43. Garofalo Maria., et al. “Alzheimer and Parkinson and Disease and Amyotrophic Lateral Sclerosis Gene Expression Patterns Divergence Reveals Different Grade of RNA Metabolism Involvement”. International Journal of Molecular Sciences24 (2020): 9500.
  44. “Adult Central Nervous System Tumors Treatment (PDQ®)–Patient Version”. National Cancer Institute (2023).
  45. Perlman S. “Hereditary Ataxia Overview”. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle 1993-2023 (1998).
  46. Schmahmann Jeremy D. “Disorders of the Cerebellum: Ataxia, Dysmetria of Thought, and the Cerebellar Cognitive Affective Syndrome”. The Journal of Neuropsychiatry and Clinical Neurosciences3 (2004): 367-378.
  47. “Ataxia and Cerebellar or Spinocerebellar Degeneration”. National Institute of Neurological Disorders and Stroke, U.S. Department of Health and Human Services (2023).
  48. Klockgether Thomas. “Sporadic adult-onset ataxia”. Handbook of Clinical Neurology 155 (2018): 217-225.
  49. Nip Ignatius and Carole R Roth. “Anarthria”. Encyclopedia of Clinical Neuropsychology (2017): 1-1.
  50. Naqvi Erum. “Dysphagia in Friedreich and Ataxia”. Friedreich and Ataxia News (2017).
  51. “Ataxia Telangiectasia”. National Institute of Neurological Disorders and Stroke, U.S. Department of Health and Human Services (2020).
  52. Rachael Zimlich BSN. “Telangiectasia: Causes, Symptoms, and Treatment”. Verywell Health, Verywell Health (2022).
  53. Naqvi Erum. “Symptoms of Friedreich and Ataxia”. Friedreich and Ataxia News (2022).
  54. Milbrandt Todd A., et al. “Friedreich and ataxia and scoliosis: the experience at two institutions”. Journal of Pediatric Orthopedics2 (2008): 234-238.
  55. Helmchen Christoph., et al. “Postural Ataxia in Cerebellar Downbeat Nystagmus: Its Relation to Visual, Proprioceptive and Vestibular Signals and Cerebellar Atrophy”. PLOS ONE1 (2017).
  56. Sandford Erin and Margit Burmeister. “Genes and genetic testing in hereditary ataxias”. Genes3 (2014): 586-603.
  57. Manto Mario., et al. “Consensus paper: roles of the cerebellum in motor control--the diversity of ideas on cerebellar involvement in movement”. Cerebellum2 (2012): 457-487.
  58. Greenlee JE and HR Brashear. “Antibodies to cerebellar Purkinje cells in patients with paraneoplastic cerebellar degeneration and ovarian carcinoma”. Annals of Neurology6 (1983): 609-613.
  59. Mitoma Hiroshi., et al. “Immune-Mediated Cerebellar Ataxias: Clinical Diagnosis and Treatment Based on Immunological and Physiological Mechanisms”. Journal of Movement Disorders1 (2021): 10-28.
  60. Maréchal Alexandre and Lee Zou. “DNA damage sensing by the ATM and ATR kinases”. Cold Spring Harbor Perspectives in Biology9 (2013): a012716.
  61. Ziv Y., et al. “The ATC (ataxia-telangiectasia complementation group C) locus localizes to 11q22-q23”. Genomics2 (1991): 373-375.
  62. Shackelford Rodney E., et al. “Desferrioxamine treatment increases the genomic stability of Ataxia-telangiectasia cells”. DNA Repair9 (2003): 971-981.
  63. Delatycki Martin B and Sanjay I Bidichandani. “Friedreich ataxia- pathogenesis and implications for therapies”. Neurobiology of Disease 132 (2019): 104606.
  64. Rowland Tennille J., et al. “Role of occupational therapy after stroke”. Annals of Indian Academy of Neurology 111 (2008): S99-S107.
  65. Perlman Susan L. “Update on the Treatment of Ataxia: Medication and Emerging Therapies”. Neurotherapeutics: The Journal of the American Society for Experimental Neuro Therapeutics4 (2020): 1660-1664.
  66. Kotagal Vikas. “Acetazolamide-responsive ataxia”. Seminars in Neurology5 (2012): 533-537.
  67. Berntsson Shala Ghaderi., et al. “Cerebellar ataxia and intrathecal baclofen therapy: Focus on patients´ experiences”. PloS One6 (2017): e0180054.
  68. Milne Sarah C., et al. “Rehabilitation for ataxia study: protocol for a randomised controlled trial of an outpatient and supported home-based physiotherapy programme for people with hereditary cerebellar ataxia”. BMJ Open12 (2020): e040230.
  69. Abe Hiroshi., et al. “Potential of Hybrid Assistive Limb Treatment for Ataxic Gait Due to Cerebellar Disorders Including Hemorrhage, Infarction, and Tumor”. Acta Neurochirurgica 129 (2018): 135-140.
  70. Vogel Adam P., et al. “Speech treatment improves dysarthria in multisystemic ataxia: a rather-blinded, controlled pilot-study in ARSACS”. Journal of Neurology5 (2019): 1260-1266.
  71. Heller Karen. “Genetic counseling: DNA testing for the patient”. Proceedings2 (2005): 134-137.
  72. Lowit Anja., et al. “Symptom Burden of People with Progressive Ataxia, and Its Wider Impact on Their Friends and Relatives: A Cross-Sectional Study”. Health Open Research 3 (2023): 28.
  73. Griggs RC., et al. “Hereditary paroxysmal ataxia: response to acetazolamide”. Neurology12 (1978): 1259-1264.
  74. Farzam K and Abdullah M. Acetazolamide. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing (2023).
  75. Orsucci Daniele., et al. “Therapy of episodic ataxias: case report and review of the literature”. Drugs in Context 8 (2019): 212576.
  76. Çekici, Hande and Nilüfer Acar Tek. “Determining energy requirement and evaluating energy expenditure in neurological diseases”. Nutritional Neuroscience7 (2020): 543-553.
  77. Cruz Melissa Mercadante Santana., et al. “Estimation of skeletal muscle mass in patients with spinocerebellar ataxia type 3 and 10”. The International Journal of Neuroscience7 (2019): 698-702.
  78. P Divya and Asha Kishore. “Treatable cerebellar ataxias”. Clinical Parkinsonism3 (2020): 100053.
  79. Ocana-Santero Gabriel., et al. “Future Prospects of Gene Therapy for Friedreich and Ataxia”. International Journal of Molecular Sciences4 (2021): 1815.
  80. Ogawa Masafumi. “Pharmacological treatments of cerebellar ataxia”. Cerebellum2 (2004): 107-111.
  81. Takimoto Kazuhiro., et al. “Case of cerebellar ataxia successfully treated by virtual reality-guided rehabilitation”. BMJ Case Reports5 (2022): e242287.

Ahmad R Bassiouny., et al. “Ataxia: Neurological Condition with Intertwining Multifactorial Mechanisms”. EC Neurology  15.7 (2023): 64-87.