Coexistence of Gait Disturbances and Chorea in Experimental Huntington’s Disease

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat. The clinical features are progressive motor dysfunction, cognitive deterioration, and psychiatric disturbances. Unpredictable choreic movements, among the most characteristic hallmarks, may contribute to gait disturbances and loss of balance in HD individuals. In this study, we aimed to investigate and characterize the gait abnormalities and choreic movements in a transgenic rat model of HD (tgHD). TgHD presents typical neuropathological, neurophysiological, and behavioral aspects mimicking some of the key features of human HD and is the only described experimental model for HD that exhibits choreiform movements. We used the Catwalk, with emphasis on static and dynamic gait parameters, to test the hypothesis that at symptomatic age (9 months) the dynamic measures of gait in HD are altered and coexist with choreiform movements. Our results showed that the dynamic parameters seem to be more affected than static parameters at this age in tgHD rats. The number of steps and step cycles and swing speed of the paws were increased in tgHD rat in comparison to wild-type controls. Our study demonstrates that gait abnormalities coexist with chorea rather than being caused by it. These symptoms may originate from distinct networks in the basal ganglia and downstream connections.

Disease‐modifying effects of ganglioside GM1 in Huntington's disease models

“…Gait analysis provides an additional sensitive method to assess motor impairment and basal ganglia deficits (Amende et al , ; Vandeputte et al , ; Abada et al , ). Gait abnormalities are well documented in HD patients (Delval et al , ,b; Kegelmeyer et al , ; Casaca‐Carreira et al , ) and are often resistant to treatments that improve other motor symptoms (Ferrara et al , ; Kegelmeyer et al , ). Q140 mice displayed several gait abnormalities compared to Q7/7 littermates (Fig ).…”

Drug or disease - Differentiating and managing motor symptoms associated with late onset Huntington’s disease from extrapyramidal side-effects of antipsychotics

“…Patients also present with other abnormal movements, difficulty in initiating movements and rigidity. Dystonia leading to abnormal postures tics similar to that seen in Tourette syndrome and cerebellar signs, mainly ataxia, are also seen in patients with Huntington's disease [16].…”

“…It is defined as a rapid, unpredictable, involuntary, non-repetitive movement affecting limbs, trunk and face [16]. Patients also present with other abnormal movements, difficulty in initiating movements and rigidity.…”

Autoregressive modeling to assess stride time pattern stability in individuals with Huntington’s disease

“…Huntington’s disease (HD) is a fatal neurodegenerative disorder for which there is presently no cure [1–4]. This neurodegenerative disorder leads to both cognitive and physical impairments due to the degeneration of nerve cells in the brain [3–5].…”

“…This neurodegenerative disorder leads to both cognitive and physical impairments due to the degeneration of nerve cells in the brain [3–5]. Gait, which is governed by the neuromuscular system, is altered due to these impairments that often manifest as reductions in gait speed, diminished step height and length and increased stride time variability [1, 5–7]. Unfortunately, as the disease progresses, these conditions intensify and significantly alter an individual’s gait stability [5, 6, 8].…”