Predictors of diagnosis in Huntington disease

HD Lighthouse Contributing Editor's Comment: The researchers found that

With several promising compounds in the research pipeline, it will not be long before the Huntington's Disease community has its first treatment. At that point, there will be a paradigm shift. Currently most people at risk decide against predictive testing. Once a treatment is available, then interest in testing will grow and a key question will be, "At what point should I start taking the treatment if I test positive for the gene?"

Potential treatments are often tested in the HD mice before symptoms begin. Ideally one would want to start treatments before the disease process gets started to get the best results and there may even be treatments that will only be effective early on. At the same time, every medication has side effects and it would be also be good to avoid starting a drug before it is needed.

Studies like Predict-HD and COHORT are very valuable because they are giving us a natural history of the disease which has been lacking and they will help to answer the question of when a treatment should start.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 05-22-2007

Predictors of diagnosis in Huntington's Disease

Douglas R. Langbehn, MD, PhD, Jane S. Paulsen, PhD and The Huntington Study Group

Objective:

Subtle signs and symptoms of Huntington disease (HD) are often present before impairments reach a point where the neurologic disease is manifest and a diagnosis must be considered. The objective is to examine the prognostic significance of these early clinical signs and symptoms regarding time until unequivocal clinical HD diagnosis.

Methods:

We analyzed longitudinal data from 218 at-risk but healthy participants in the Huntington Study Group database who had either normal motor examination results or minimal soft motor signs at first observation. This group was followed periodically in HD clinics for up to 4.5 years. We used survival analysis to examine predictors of time until HD diagnosis.

Results:

Diagnostic prediction was significantly improved using specific, nonredundant items from the Unified Huntington's Disease Rating Scale. When a movement disorder specialist initially had a global impression of "soft signs" present, cumulative relative risk of diagnosis was 4.68 times greater at 1.5 years of follow-up and 3.58 at 3 years. A neuropsychological test pattern with psychomotor speed 1 SD worse than a semantic knowledge measure increased cumulative risk by 1.99 times at 1.5 years and 1.81 at 3 years. Finally, reports of various subjective HD symptoms increased 3-year relative risk by 2.6 to 3.4.

Conclusions:

Findings demonstrate that neuropsychological performance and both the clinician rating and the patient subjective perception of motor difficulties contribute nonredundantly to a prediction of Huntington disease diagnosis. These findings may have implications for prognostic assessment of persons at risk and eventually assist with early interventions.

Source: Neurology 2007;68:1710-1717