International Encyclopedia of Rehabilitation

Autosomal Dominant Cerebellar Ataxias

Michel Delcey
Association des paralysés de France (APF)

Autosomal dominant ataxias are inherited and degenerative in nature, that affects the spinal cord and/or cerebellum (spinocerebellar heredodegeneration) or essentially the cerebellum (atrophies or systemic cerebellar ataxias). There are multiple types of these ataxias which are poorly distinguished to be described in detail in this article. They are different groups of related forms of conditions rather than distinctive entities. They are grouped according to their common name. Knowledge in this area will undoubtedly progress significantly in the near future. Ataxias are divided in two large groups according to their respective model of genetic transmission:

Diseases involving autosomal recessive transmission, includes Friedreich's ataxia and Strumpell-Lorrain disease. The Strumpell-Lorrain disease in its 'pure' form, selectively affects the spinal cord.

Distinction between forms of autosomal dominant cerebellar ataxias are in full-throttle revolution with genetic research. These dominant diseases are called Pierre-Marie's ataxia, olivopontocerebellar atrophy of the Menzel type (OPCA), pure cortical cerebellar atrophy of the Holmes type or Machado-Joseph disease, according to their clinical presentations or level of lesions.

These sets of conditions are classified in four large groups (according to Harding); although genetic knowledge is assisting in refining the distinction between related forms of ataxias; these groups distinguish four clinical pictures based on the disorders associated with cerebellar ataxia:

  1. Ataxia type I (the most frequent): motor impairment (pyramidal), optic atrophy, oculomotor paralysis, intelligence disorders;
  2. Ataxia type II: retinal degeneration;
  3. Ataxia type III: pure cerebellar ataxia;

Dominant cerebellar ataxias affect about 5 out of 100,000 individuals (about 3,000 individuals in France). Genetic research has constantly shown evidence of their complexity; for instance, it is known that type I ataxia may be caused by the alteration of five different genes.

The onset of this disease occurs most frequently between age 25 and 45, but sometimes earlier or later in life. In type I ataxia, equilibrium disorders reveal the presence of the disease. The onset of other signs of cerebellum damage (speech production disorders among others) may occur later. These disorders are most frequently associated with the impairment of proprioception (perception of one's body parts in space). Later, paralysis of specific types of eye muscles, swallowing disorders, and impairment of the sphincter function can be associated to the primary condition.

Signs and symptoms of dominant cerebellar ataxias vary greatly from person to person, including within the same family. These types of diseases progress gradually over a period of 20-30 years, but the signs and symptoms may remain stable over several years.

There is still no treatment available to stop the degeneration of nerve cells involved in the disease. The treatment modalities currently used are symptomatic in nature and aim at removing some signs and symptoms, and preserving the individual's independence.

As a matter of interest, some of the features of the best-known conditions are given below. It is essential to remember that these grouping covers closely related forms of autosomal dominant ataxias; of which knowledge and distinction are constantly changing. Their names are already obsolete, but still in use.

  • Pierre-Marie's cerebellar heredo-ataxia comprises forms of conditions that are different from those of the Friedreich's disease. They often include later onset (by the second or third decade of life, but also as early as childhood), slower progression, absence of deep sensibility and cardiac disorders, as well as deformities (scoliosis, pes cavus), and different genetic transmission that is most often dominant (every carrier is affected). It produces a cerebellar syndrome and affects voluntary motor control via a pyramidal condition. This condition may be linked to a form of dominant autosomal cerebellar ataxia of type I.
  • Roussy-Levy hereditary areflexic dystasia is a lot more mislabeled than the conditions previously mentioned. Some consider it as a peculiar form of Friedreich's ataxia, but others think this is a form of Charcot-Marie-Tooth disease (akin to Dejerine-Sottas neuropathy). It follows an autosomal dominant mode of transmission and has a very early onset, and the clinical signs (deep sensibility disorders, muscle atrophy) are generally moderate.
  • Olivopontocerebellar atrophy (OPCA) is a condition primarily characterized by the combination of lesions at the brainstem (pons and olivary body) and cerebellum. Clinically, it is similar to Pierre-Marie's cerebellar heredo-ataxia and associated with medullar damage similar to the one of Friedreich's ataxia (OPCA of the Menzel type). The age of onset may vary, including within the same family, but generally occurs during childhood. Its rhythm of progression is often slow and extremely variable as well. It follows a heterogeneous mode of genetic transmission (most frequently dominant) proving that the OPCA is related to various similar conditions affecting about one individual out of 30,000 in France, and not to a singular entity.
    Genetic research constantly refines the distinction between the three forms: type I is very heterogeneous (five different genes are involved), type II is more rare and characterized by an associated eye condition (retinitis pigmentosa).
  • Ramsay-Hunt myoclonic cerebellar dyssynergia primarily involves damage to cerebellar pathways descending to the spinal cord. Clinically, the cerebellar syndrome is associated with myoclonia (Brief, involuntary and sudden muscular contractions). This syndrome is also associated with a heterogeneous group of mitochondrial conditions at both clinical and genetic levels.
  • Olivocerebellar atrophy of the Holmes type and atrophy of the granular layer of the cerebellum—rare autosomal recessive disease, the onset of which occurs during the first year of life, with associated ataxia and mental disorder, and is more or less progressive—are two other similar conditions (or group of conditions).
  • Machado-Joseph disease is a variant form of Joseph disease: It is an inherited spinocerebellar ataxia, particularly common in Portugal and Japan, the onset occurs between ages 30 and 40 years (cerebellar ataxia, ocular paralysis, sensory loss, muscle weakness, etc.). This inherited, autosomal dominant disease is classified in the autosomal dominant cerebellar ataxias.
  • Ataxia with a vitamin E deficiency is a rare disease, with a clinical presentation very similar to Friedreich's disease. Vitamin E concentration in blood is the common diagnosis for this condition. Taking supplemental vitamin E slows down its progression and may lead to positive outcomes if diagnosed at an early stage.

For more information on autosomal dominant cerebellar ataxias (for individuals directly concerned by this type of diseases): consultation on appointment: Professor Brice, Dr Durr, Fédération des Neurologues, Hôpital de la Salpêtrière, 47, bd de l'Hôpital, 75013 Paris (1) 42 16 17 94.

Many thanks to Professor A. Brice for his help in the writing of this appendix.

Source

Association des paralysés de France. 1996. Déficiences motrices et handicaps, Aspects sociaux, psychologiques, médicaux, techniques et législatifs, troubles associés. Paris : Association des paralysés de France. 505 p. Used with permission.

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