192 | APRIL 2011 | VOLUME 7 www.nature.com/nrneurol NEWS & VIEWS systems need to be tailored to local circum- stances, and additional data are required to establish their effectiveness, but the call for their establishment should be heeded— prevention of stroke is always preferable to dealing with its consequences. Duke Stroke Center, Duke University Medical Center, Box 3651, Bryan Research Building, Research Drive, Durham, NC 27710, USA. golds004@mc.duke.edu Competing interests The author declares no competing interests. 1. Johnston, S. C. et al. National Stroke Association recommendations for systems of care for TIA. Ann. Neurol. doi:10.1002/ ana.22332. 2. Fussman, C., Rafferty, A. P ., Lyon-Callo, S., Morgenstern, L. B. & Reeves, M. J. Lack of association between stroke symptom knowledge and intent to call 911: a population-based survey. Stroke 41, 1501–1507 (2010). 3. Johnston, S. C. et al. Prevalence and knowledge of transient ischemic attack among US adults. Neurology 60, 1429–1434 (2003). 4. Howard, V. J. et al. Care seeking after stroke symptoms. Ann. Neurol. 63, 466–472 (2008). 5. Goldstein, L. B. et al. New transient ischemic attack and stroke: outpatient management by primary care physicians. Arch. Int. Med. 160, 2941–2946 (2000). 6. Castle, J. et al. Agreement regarding diagnosis of transient ischemic attack fairly low among stroke-trained neurologists. Stroke 41, 1367–1370 (2010). 7. Furie, K. L. et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42, 227–276 (2011). 8. Goldstein, L. B. Statewide hospital-based stroke services in North Carolina: changes over 10 years. Stroke 41, 778–783 (2010). 9. Lichtman, J. H. et al. Stroke patient outcomes in US hospitals before the start of the Joint Commission Primary Stroke Center certification program. Stroke 40, 3574–3579 (2009). 10. Fonarow, G. C. et al. Characteristics, performance measures, and in-hospital outcomes of the first one million stroke and transient ischemic attack admissions in Get With The Guidelines–Stroke. Circ. Cardiovasc. Qual. Outcomes 3, 291–302 (2010). NEURODEGENERATIVE DISEASE Tracking disease progress in Huntington disease Roger A. Barker and Sarah L. Mason One of the main challenges associated with late-onset genetic neurodegenerative diseases is predicting when the condition begins and how it progresses over time. In a new study, Tabrizi et al. have used a range of imaging, clinical and neuropsychiatric measures to assess the progression of Huntington disease. Barker, R. A. & Mason, S. L. Nat. Rev. Neurol. 7, 192–193 (2011); published online 15 March 2011; doi:10.1038/nrneurol.2011.37 Huntington disease (HD) is a rare autosomal dominant disorder that results from abnor- mal CAG expansion in exon 1 of the HTT gene, which encodes huntingtin protein. 1 The resultant mutant protein accumulates in neurons and causes neuronal dysfunction and, ultimately, death. Patients with clini- cally manifest HD typically experience abnormal movements, cognitive deficits and psychiatric disturbances. 2 Other clini- cal features associated with HD include endocrine, sleep 3 and metabolic 4 abnormali- ties. The ability to predict when a patient with the mutant HTT gene will develop the disease represents one of the greatest challenges in the HD field. At present, the examining physician determines HD onset when a patient presents with motor abnormalities in keeping with the disorder. Clearly, documenting manifest HD in this way represents a very crude estimation of disease onset. Subtle motor 5 and nonmotor features 6 of HD may be present before the characteristic motor abnormalities are evident, and these less-obvious features may be preceded or accompanied by changes in CNS structure and function. 7 To address this issue, Tabrizi and colleagues have examined disease progression in 230 patients with either premanifest HD or early HD. 8 In their prospective, observational study, known as TRACK-HD, Tabrizi et al. recruited carriers of the mutant HTT gene (116 patients with premanifest HD and 114 patients with early HD) from four study sites in Canada, France, The Netherlands and the UK, and assessed disease progression in these patients using 3T MRI and clinical, cognitive, motor, oculomotor and neuro- psychiatric tests. The researchers reported that over a 12-month period, changes in brain atrophy, cognition and measures of motor function occurred in cases of both premanifest HD and early HD. In particular, the study showed that annualized rates of whole-brain, caudate and putamen atrophy were greater in patients with premanifest or early HD than in controls. Performance on the circle tracing task (a measure of visuo- motor integration and motor planning); a quantitative motor grasping and lifting task, and a change in the chorea position index (a quantitative measure of involun- tary choreiform movements), were worse in patients with premanifest or early HD than in controls. By contrast, deficits in executive functioning (Stroop and symbol digit modalities tests), psychomotor speed (speeded tapping test), negative emotion recognition, smell recognition (University of Pennsylvania Smell Identification Test) and functional health and well-being (self- reported measures of functional capac- ity [short form 36]) were only evident in patients with early HD compared with con- trols. Deficits in total functional capacity but not total motor score correlated with whole-brain and caudate atrophy and ven- tricular expansion. These findings indicate that novel disease-modifying therapies for HD might, for the first time, be amenable to investigation in cohorts of similar size to those in the TRACK-HD study. The Tabrizi et al. study is the first to sys- tematically evaluate the utility of a range of biomarkers in a large cohort of patients with HD, and paves the way for clinical trials of HD therapies, as we now have the means to accurately track the progression of this disease. The ability to assess HD progres- sion in patients with premanifest HD as well as in patients with manifest HD is impor- tant because the rate of disease progression may change during the disease process. Data from the Tabrizi et al. study support such a scenario, as the rate of atrophy (both ‘‘ …rates of whole-brain, caudate and putamen atrophy were greater in patients with premanifest or early HD… ’’ © 2011 Macmillan Publishers Limited. All rights reserved