Ataxia-cause Patterns Emerge in Study but Researchers Unable to Establish Any in a Third of Cases

A group of brain diseases known as sporadic late-onset acute cerebellar ataxias have been attributed to lots of causes, so an American research team decided to study 80 patients to try to find patterns.

They identified some patterns, but their two-year study’s findings basically backed up scientists’ long-held contention that there are many, many causes of the diseases, which include Friedreich’s  ataxia.

One pattern was that the leading cause of ataxia in the patients studied was a neurological disorder known as multiple system atrophy. Another pattern was that inherited diseases were the second leading cause of ataxia in the patient population. Still another pattern was that the researchers were unable to identify any cause of ataxia in a third of the patients.

Trying to pinpoint causes required extensive neurological and non-neurological tests, the researchers added.

The study, “Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work,” was published in the Journal of Neurology.

One of the researchers’ goals was to come up with a list of as many potential causes of ataxia as they could, and see if there was a fit between the causes and patients’ symptoms.

The team included in their study patients at their medical center who had developed a cerebellar ataxia after they were 40 years old.

Researchers gave each of the patients comprehensive general-health and neurological examinations. One was a test for assessing the severity of ataxia known as the Scale for the Assessment and Rating of Ataxia, or SARA. Another was a test evaluating patients’ level of disability from one of the diseases, known as the Spinocerebellar Degeneration Functional Score, or SDFS. Other tests dealt with patients’ disease-related cognitive impairment.

The research team also ordered laboratory tests, electrophysiological and imaging tests, and genetic analyses of the patients.

Despite the battery of tests, the team was able to establish a cause for ataxia in only 65 percent of the patients.

The most common cause was multiple system atrophy, or MSA-C, with the C standing for a cerebellar dysfunction subtype.

MSA is a rare neurodegenerative disorder characterized by progressive failure of involuntary movement muscles, ataxia and parkinsonism. Parkinsonism is not the same as Parkinson’s disease. It refers to a group of neurological disorders that cause movement problems similar to those seen in Parkinson’s, such as tremors, slow movement and stiffness.

The cerebellar variation of MSA, or MSA-C, is a subtype of the disease. Its hallmarks include uncoordinated arm and walking movements, slurred or slow speech,  and eye movement problems.

Researchers said the inherited diseases that collectively constituted the second largest cause of ataxia included “spinocerebellar ataxias, late-onset Friedreich’s disease, SLC20A2 mutations, fragile X-associated tremor ataxia syndrome (FXTAS), mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), and other mitochondrial diseases.” Mitochondrial diseases impair the functioning of mitochondria, components of cells that convert food into energy.

The research team was unable to find a cause of ataxia in a third of the patients they diagnosed with the disease, despite exhaustive analysis.

An interesting finding was that these patients’ ataxia progressed slower than the diseases in those where a cause was identified.

The age when patients developed ataxia affected its progression, the team said. It progressed faster in those who developed it later.

Overall, “sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy,” the researchers concluded.