In this week’s The Lancet Neurology, Tabrizi and colleagues summarized their analysis of various outcome measures (some expensive, some not) that may help predict phenotypic progression in people with early stages of Huntington’s disease as well as disease onset in patients with the huntingtin gene mutation. The multicenter, longitudinal, natural history study, called the TRACK-HD study examining patients with early Huntington’s Disease and patients with the huntingtin gene mutation (but without showing symptoms yet). Patients were followed for 36 months and given a battery of tests to determine their prognostic values. The tests included MRIs, clinical, cognitive, quantitative motor, and neuropsychiatric assessments. These parameters along with patient’s age, the CAG repeat length were examined in relation to disease onset and/or progression.
By following patients at the beginning of disease onset as well as before disease onset, the TRACK-HD study hoped to provide valuable insight into which testing pramaters are most valuable. And the results were very interesting. As expected, neuroimaging analysis found that changes in volume of the whole brain volume and various basal ganglia areas had strong predictive value regarding disease progression. Interestingly, some less expensive measures, such as speed tapping or certain motor-cognitive measures such as the symbol digit modality test, indirect circle tracing annulus length, and spot the change in 5 sec test, were also good predictors of disease progression. Not all tests were good predictors however and readers are strongly encouraged to obtain a copy of the study to ascertain the tests that may or may not be helpful in assessing disease progression and onset.
In an interview accompanying the article, Dr. Tabrizi discussed some interesting take home messages from the study. They included:
Huntington’s disease is a rare neurodegenerative disorder due to a CAG repeat expansion in the huntingtin gene. The disease causes rapid deterioration in many cortical areas, most notably in the basal ganglia that lead to progressive decline of motor and cognitive functions, as well as neuropsychiatric disturbances. The disease often begins to present itself in young-middle aged adults (30 – 40 yrs old) and progresses rapidly. Huntington’s disease is an autosomal-dominant disorder and genetic testing is available.
Currently there are limited treatment options for patients with Huntington’s disease but numerous investigative drugs are in development that may benefit from the TRACK-HD study.
In a commentary of the study, Francis Walker from the Department of Neurology at Wake Forest Medical School eloquently wrote “Hippocrates is generally credited with recognising the importance of the timeline of disease evolution epitomised by the objective recording of daily findings and methods and terms such as chronicity, exacerbation, paroxysm, and crisis. Sarah Tabrizi’s team has provided a modernised and extended example of this practice, one that sets the standard for observational studies in other neurodegenerative diseases.”
For more information about Huntington’s disease, visit www.hdsa.org
Tabrizi SJ, Scahill RO, Owen G, et al. Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data. The Lancet Neurol 2013;12(7):637-49.