Sign Up for a Free Account
  • Updated 02.17.2024
  • Released 08.23.2019
  • Expires For CME 02.17.2027

Nonparaneoplastic autoimmune cerebellar ataxias



Immune-mediated cerebellar ataxias are divided into paraneoplastic and nonparaneoplastic diseases. The latter include gluten ataxia, postinfectious cerebellitis, opsoclonus myoclonus ataxia syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia (PACA). When autoimmunity is triggered by another condition (eg, gluten sensitivity in gluten ataxia and infection in postinfectious cerebellitis), treatment priority should be given to the removal of the trigger. If this is not possible, or when autoimmunity is not caused by an obvious trigger (eg, primary autoimmune cerebellar ataxia), various combinations of immunotherapies can be used to prevent the progression of the ataxia or stabilize any clinical deficits. Immunotherapy should be introduced as soon as possible, during the period of maintained cerebellar reserve, defined as the capacity for compensation and restoration of neural function. Assuming immunotherapies arrest the progression, the reversibility of the ataxia depends on functional remodeling in the cerebellar circuitry, which is characterized by a high degree of plasticity. Good prognosis is characteristic of nonparaneoplastic immune-mediated cerebellar ataxias, in contrast to the poor prognosis seen in paraneoplastic cerebellar degeneration. For successful intervention, a diagnosis of nonparaneoplastic immune-mediated cerebellar ataxias is necessary at the early stages of the disease before neuronal loss compromises cerebellar reserve.

Key points

• Nonparaneoplastic immune-mediated cerebellar ataxias include diverse etiologies.

• Nonparaneoplastic immune-mediated cerebellar ataxias are characterized by subacute onset, frequent autoimmune disease history in the patient or relatives, and predominant gait ataxia, usually associated with autoantibodies.

• Immunotherapy should be considered when the underlying trigger is not identified or cannot be removed.

• Immunotherapies should be introduced during the period of maintained cerebellar reserve, defined as the capacity for compensation and restoration of cerebellar function.

Historical note and terminology

Various pathologies result in cerebellar insult, leading to the development of cerebellar ataxias and resulting in motor and cognitive incoordination (121; 87; 83). Examples include vascular diseases, tumors, and metabolic, degenerative, and immune-mediated diseases. The documentation of immune-mediated cerebellar ataxias originates from a classical work by Charcot J.M. (15). At a well-known lecture on multiple sclerosis in 1868, he described the development of cerebellar ataxia in patients with multiple sclerosis and the appearance of intention tremor, scanning speech, and nystagmus (Charcot triad) in addition to optic neuritis and paralysis. Another historical milestone was the report by Brouwer in 1919, which described the association of cerebellar ataxias with ovarian tumor and was the first report of paraneoplastic cerebellar degeneration (10). Two further breakthroughs occurred in the 1980s. First, an autoantibody against the Purkinje cells, later named anti-Yo, was described in a patient with ovarian tumor-associated with cerebellar ataxia (37). The identification of other specific autoantibodies followed, including anti-Hu, anti-Tr, anti-CV2, anti-Ri, anti-Ma2, and anti-VGCC, which are shown to be associated with specific types of neoplasms, especially breast, uterine, and ovarian cancers as well as small-cell lung carcinoma and Hodgkin lymphoma (25). At present, there is general agreement that autoimmunity triggered by the neoplasm results in the development of cerebellar ataxias (25).

The association of otherwise idiopathic cerebellar ataxias with autoantibodies against the cerebellum was subsequently reported in patients without evidence of cancer (38; 51; 93; 92; 97; 98; 53; 52; 50). Two main clinical entities have been established based on specific clinical features and type of associated autoantibodies: gluten ataxia (46) and anti-glutamic acid decarboxylase 65 antibodies (GAD 65 antibodies)-associated cerebellar ataxia (anti-GAD ataxia) (61).

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660



ISSN: 2831-9125