Definition : An ailment at first characterized by the association of lesions on the level of the cerebellar trunk (pons or protuberance and bulbous olive) and of the cerebellum. It can be associated with a medullar affliction approaching that of Friedreich’s ataxia. It is also a progressive destruction of the nervous tracts which connect several different structures of the encephalon (starting from the nervous system in the skull) each playing a particular role in the nervous system. This degeneration (the anatomical lesions which reach the nervous tracts) is at the origin of the cerebellar syndrome i.e. the symptoms. The cerebellum being affected, this brings about troubles of balance and coordination.

Mode of transmission : autosomic (afflicts both sexes) and dominant ( one single parent can transmit the disease).

Age : affects the adult at a mature age (around 40 years) but precocious forms can affect children and later forms can affect seniors. The age is variable even within the same family. The disease leads to a wheelchair.

Evolution : the evolutive rhythm is often slowly progressive and extremely variable leading to a loss of autonomy.

Cause : many different genes. At least 14 of which several are known. The known mutations consist of a repeated expansion of trinucleotides of which the unstable character is at the origin of the phenomenon of anticipation since its appearance at an earlier age is observed.

Symptoms : cerebellar ataxia, problem of balance, of coordination and of elocution, sensorial losses, muscular weakness, difficulty swallowing and nystagmus.

This ataxia is a part of a group of afflictions, itself classified in 4 large groups, allowing one to better identify it according to the precise criteria of troubles associated with cerebellar ataxia.

Definition : Affliction of the cerebellum which brings about troubles of balance and of the coordination of movements. Affliction characterized by the association of lesions on the level of the cerebellar trunk and the cerebellum and especially the white substance of the cerebellum, the cerebellar peduncle and the bulbous olives. Otherwise stated, OPCA is the progressive destruction of the nervous cells which link several different structures of the encephalon part of the central nervous system. These degenerations go right to the cerebellum. They are at the origin of the cerebellar syndrome, that is to say, the clinical signs which the afflicted person presents.

Cause : several genes. The expansion of trinucleotides is easily tested and confirms the diagnosis in a person belonging to a family which already has cases or even in an isolated case.

Age : variable including in the same family. In general, around 40 years of age (always at an adult age).

Evolution : slowly progressive. Variable from one individual to another. It is sometimes complicated by troubles afflicting the sphincters which are the muscles allowing the closing and the opening of orifices. Some patients present a muscular hypertrophy characterized by a contraction of the muscles.

Frequency : the risk is one child out of two of an afflicted subject.

Symptoms : A cerebellar syndrome characterized thusly :

• excessive muscular slackening (excessive muscular hypotonia)
• an unsure walk (resembles a case of intoxication) and when he is standing he has a tendency to spread his legs to increase his balance.
• an impossibility or difficulty to execute in totality the movements ordered in the brain.
• the gestures go too far (hypermetria). The movements begin somewhat late and most often overreach the goal which the person had intended. The direction is nevertheless kept and there is sometimes trembling. Changing movements is no longer possible.

Definition : it is a hereditary spinocerebellar ataxia especially frequent in the Portuguese and the Japanese population (because of immigration, it is present in Canada). This disease was discovered in 1970 but research began in 1994.

Cause : genetic (a repeated expansion of glutamate).

Mode of transmission : dominant autosomic (afflicts both sexes and one single parent is sufficient in order to transmit the disease and afflict 50% of the children.

Origins : Portuguese, French, Chinese, Japanese, German, American (more frequent in the Portuguese and the Japanese).

Gene : the gene is discovered. SCA3 is due to an expanded CAG repeat in a coding region of the SCA3 gene, encoding ataxin-3, a protein thought to be involved in processing of other proteins. Ataxin-3 is also called MJD protein 1. Like the other dominant polyglutamine diseases, the toxic effect is believed to be primarily due to a gain of function of the mutated protein, rather than a lost function of the wild-type.

Appearance : the disease appears between 30 and 40 years of age and leads to a wheelchair. About 25% of dominant ataxias are SCA3 type.

Symptoms : cerebellar ataxia, ocular paralysis, difficulty swallowing, nystagmus.

Episodic ataxia (EA) designates a group of autosomal dominant channelopathies that manifest as paroxysmal attacks of imbalance and incoordination. EA conditions are clinically and genetically heterogeneous. Seven types of EA have been reported so far but the majority of clinical cases result from two recognized entities.Episodic ataxia (EA) designates a group of autosomal dominant channelopathies that manifest as paroxysmal attacks of imbalance and incoordination. EA conditions are clinically and genetically heterogeneous. Seven types of EA have been reported so far but the majority of clinical cases result from two recognized entities.

Disease characteristics. Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks some individuals may experience vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing. Onset is in childhood or early adolescence. Other findings can include delayed motor development, cognitive disability, choreoathetosis, and carpal spasm. Diagnosis/testing. Diagnosis is based on clinical findings and molecular genetic testing of KCNA1, the only gene known to be associated with EA1.

Management.

Treatment of manifestations: Acetazolamide (ACTZ), a carbonic-anhydrase (CA) inhibitor, may reduce the frequency and severity of the attacks in some but not all affected individuals. Antiepileptic drugs (AEDs) may significantly reduce the frequency of the attacks in some individuals.

Prevention of secondary complications: Joint contractures can be prevented by appropriate physiotherapy.

Surveillance: annual neurologic examination.

Agents/circumstances to avoid: General anesthetics have occasionally been reported to precipitate or aggravate neuromyotonia.

Genetic counseling. EA1 is inherited in an autosomal dominant manner. Most individuals diagnosed with EA1have an affected parent; to date, only one de novo mutation has been reported. Each child of an individual with EA1 has a 50% chance of inheriting the mutation. Prenatal diagnosis for pregnancies at increased risk is possible if the disease-causing mutation has been identified in an affected family member.

Source: Mauro Pessia, Michael G Hanna. Episodic Ataxia Type 1. GeneReviews [Internet].

Disease characteristics. Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia, vertigo, and nausea typically lasting minutes to days in duration. Attacks can be associated with dysarthria, diplopia, tinnitus, dystonia, hemiplegia, and headache. About 50% of individuals with EA2 have migraine headaches. Onset is typically in childhood or early adolescence (age range 2-32 years). Frequency of attacks can range from once or twice a year to three or four times a week. Attacks can be triggered by stress, exertion, caffeine, alcohol, and phenytoin and can be stopped or decreased in frequency and severity by administration of acetazolamide. Between attacks, individuals may initially be asymptomatic but eventually develop interictal findings that can include nystagmus and ataxia.

Diagnosis/testing. The diagnosis of EA2 is most commonly made on clinical grounds. MRI can demonstrate atrophy of the cerebellar vermis. Mutations in CACNA1A can cause EA2. Molecular genetic testing is available on a clinical basis for CACNA1A.

Management.

Treatment of manifestations: Acetazolamide is effective in controlling or reducing the frequency and severity of attacks; although generally well tolerated, the most common side effects are paresthesias of the extremities, rash, and renal calculi; acetazolamide does not appear to prevent the progression of interictal symptoms.

Surveillance: Annual neurologic examination.

Agents/circumstances to avoid: Phenytoin has been reported to exacerbate symptoms.

Genetic counseling. EA2 is inherited in an autosomal dominant manner. Most individuals with a diagnosis of EA2 have an affected parent. The proportion of cases caused by de novo gene mutations is unknown. Offspring of affected individuals have a 50% chance of inheriting the disease-causing gene mutation. Prenatal testing is available for pregnancies at increased risk for EA2 if the mutation has been identified in the family.

Source: Sian Spacey. Episodic Ataxia Type 2. GeneReviews [Internet].