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E1 Diagnostic criteria for huntington’s disease based on natural history
  1. Christopher A Ross1,
  2. Ralf Reilmann2
  1. 1Division of Neurobiology, Department of Psychiatry, and Departments of Neurology, Neuroscience, and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  2. 2George-Huntington-Institute, Technology-Park, Muenster, Germany

Abstract

The diagnosis of Huntington’s disease (HD) is currently based on the presence of otherwise unexplained motor signs in someone at risk, indicating 99% “diagnostic confidence” for HD. Recent advances in study of HD neurobiology and natural history indicate that disease-related brain changes begin at least 12 to 15 years before the formal diagnosis based on motor onset. In addition, subtle motor dysfunction, cognitive changes, and behavioural alterations are also often seen before the motor diagnosis can be made according to the current criteria. These changes can cause significant disability, and may be amenable to symptomatic treatment. Furthermore, experimental disease-modifying treatments are rapidly being developed, which would be desirable to begin early in the disease course. As part of a Task Force of the Movement Disorders Society, we therefore suggest that expanded diagnostic criteria for HD should be adapted to better reflect the natural history of the disease, to facilitate the conduct of clinical trials in premanifest subjects targeting prevention of neurodegeneration, and to facilitate earlier symptomatic treatment. We propose a revised set of criteria for HD diagnostic categories in the International Classification of Diseases to reflect our current understanding of HD natural history and pathogenesis. We suggest, as an initial proposal for discussion, that individuals with confirmed CAG expansion in Huntingtin (i.e., “genetically confirmed”) should be categorised as either “presymptomatic” (i.e., no clinical signs of symptoms and no functional disability),” “prodromal” (i.e., some subtle motor or cognitive changes representing a decrement from baseline and causing subtle subjective or objective difficulties) or “manifest” (i.e., clear motor and cognitive changes representing a decrement from baseline and causing significant subjective or objective disability. We suggest that depression be left as a separate diagnosis, since it can occur at any time during an individual’s lifespan, not be clearly related to HD onset, and should itself be the focus of active attention and treatment. However apathy and irritability, and other personality changes characteristic of HD may be considered when diagnosing prodromal and manifest HD. For individuals “not genetically confirmed,” we would propose categories of “clinically at risk,” “clinically prodromal,” and “clinically manifest”. We emphasise that these categories and criteria represent a proposal and we will be looking for feedback during the meeting.

  • diagnostic criteria
  • diagnosis
  • care
  • clinical trials
  • presymptomatic HD
  • premanifest HD
  • prodromal HD
  • manifest HD
  • chorea
  • extrapyramidal
  • depression
  • apathy
  • irritability
  • International Classification of Diseases

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