Rating Scales for Motor Symptoms and Signs in Huntington's Disease: Critique and Recommendations

Abstract

Motor symptoms are a major feature of Huntington's disease (HD). The International Parkinson and Movement Disorder Society (MDS) commissioned the assessment of the clinimetric properties of motor rating scales in HD to make recommendations regarding their use, following previously established standardized criteria. After a systematic literature search, a total of 6 rating scales assessing motor symptoms and signs in HD were included for review. Performance testing (reviewed elsewhere) and quantitative motor rating methods were excluded. Only the Unified Huntington's Disease Rating Scale‐Total Motor Score (UHDRS‐TMS) was classified as “recommended” for assessing the severity of motor signs in HD. The following scales were classified as “suggested”: Abnormal Involuntary Movement Scale, the UHDRS‐TMS4, the Quantified Neurological Examination, and the Marsden and Quinn Chorea Severity Scale. The committee also concluded that further assessment of existing rating scales, including the UHDRS‐TMS, is necessary to determine sensitivity to change and to screening for the presence of motor signs specific to HD. There is also a need to develop a motor rating scale to be used in positive gene carriers with subtle but not definite motor signs.

The use of wearable/portable digital sensors in Huntington's disease: A systematic review

“…We conducted a validity analysis of the included wearable/portable devices/tools. We followed the strategy proposed by the Movement Disorder Society Committee on Rating Scales Development to appraise clinical assessment tools in HD [ 6 , [20] , [21] , [22] , [23] ]. We included seven criteria with a Yes/No/Not Applicable response, namely: 1- used in HD, 2- used in HD by more than one group, 3- test-retest reliability, 4- ability to discriminate cases from controls, 5- ability to capture disease stage/severity, 6- ability to capture changes over time, 7- ability to detect therapeutic response.…”

“…Phenotype variability and the difficulty in consistently detecting subtle early clinical manifestations pose challenges to therapeutic development as well as clinical management. The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS TMS), has been “recommended” by the International Parkinson and Movement Disorder Society (MDS) for the assessment of motor signs in HD [ 6 ] and included by the National Institute for Neurological Disorder and Stroke HD group in a list of recommended sensitive outcome measures to be used as primary or secondary endpoints HD clinical trials [ 7 ]. However, its use in clinical trials has shown limited sensitivity, especially in the pre-manifest stage of HD [ 3 , 8 ].…”

Mutant huntingtin and neurofilament light have distinct longitudinal dynamics in Huntington’s disease

“…This notable success led to the first phase 3 trial of such a drug, whose primary outcomes are the total functional capacity (TFC) score of the Unified Huntington's Disease Rating Scale (UHDRS) in the United States and a composite UHDRS (cUHDRS) measure combining motor, functional, and cognitive scores in Europe (9). Such clinical rating scales quantify overt clinical manifestations but are less sensitive to detect deterio-ration or its therapeutic benefit in preHD (10)(11)(12)(13), making their use as outcomes in prevention trials problematic. Although clinically relevant, they are also far removed from the core disease mechanism: neuronal injury by the huntingtin gene product.…”

The risks of converting post-hoc findings into primary outcomes in subsequent trials

“…, due to several characteristics, including: a precise pathogenic agent (4), a natural history that comprises a long presymptomatic phase (10,11) followed by an extended diseased survival (12), a broad symptomatic spectrum including most of the clinical features present on neurodegenerative diseases (motor, behavioural and cognitive) (1), well-validated assessment tools (13)(14)(15)(16), pioneering imaging and biofluid biomarkers (10,17), and well-organized research and patient networks (18). These factors have encouraged drug developers to invest in HD as shown by the proportionately high number of clinical trials conducted in this rare disease population.…”