Tremor in the Degenerative Cerebellum: Towards the Understanding of Brain Circuitry for Tremor

Abstract

Background: Cerebellar degenerative pathology has been identified in tremor patients; however, how the degenerative pathology could contribute to tremor remains unclear. If the cerebellar degenerative pathology can directly drive tremor, one would hypothesize that tremor is likely to occur in the diseases of cerebellar ataxia and follows the disease progression in such disorders. Methods: To further test this hypothesis, we studied the occurrence of tremor in different disease stages of classical cerebellar degenerative disorders: spinocerebellar ataxias (SCAs). We further separately analyzed postural tremor and rest tremor, two forms of tremor that both involve the cerebellum. We also explored tremor in different subtypes of SCAs. Results: We found that 18.1% of SCA patients have tremor. Interestingly, SCA patients with tremor have worse ataxia than those without tremor. When stratifying patients into mild, moderate, and severe disease stages according to the severity of ataxia, moderate and severe SCA patients more commonly have tremor than those with mild ataxia, the effect most prominently observed in postural tremor of SCA3 and SCA6 patients. Finally, tremor can independently contribute to worse functional status in SCA2 patients, even after adjusting for ataxia severity. Conclusions: Tremor is more likely to occur in the severe stage of cerebellar degeneration when compared to mild stages. Our results partially support the cerebellar degenerative model of tremor.

Cerebellar Purkinje cell microcircuits are essential for tremor

“…We note that some studies of human cases of tremor have found Purkinje cell loss as well as Purkinje cell degeneration and abnormal morphology (17). As our model is constitutive and Vgat is removed from Purkinje cells throughout the cerebellum, it does not mimic the progressive loss of Purkinje cells or a localized insult to cerebellar circuitry that has been associated with some manifestations of tremor in humans (36,37). However, Purkinje cell loss is not always necessary for tremor to occur (11,23).…”

Collaborative Efforts for Spinocerebellar Ataxia Research in the United States: CRC-SCA and READISCA

“…As the result of the CRC-SCA natural history study, we found that the rates of disease progression of SCA1, SCA2, SCA3, and SCA6 (annual increase in SARA by 1.61, 0.71, 0.65, and 0.87 points, respectively) ( 12 ) are consistent with those in EUROSCA ( 15 ). In addition, we found that the severity of depressive symptoms also tracks along with ataxia progression ( 16 ), while dystonia and tremor could be prominent features of SCA patients in a subtype-specific manner ( 17 – 19 ). Another important piece of information from this cohort is that we found that the occurrence of cardiovascular risk factors is quite low ( 20 ), which will have implications in assessing the vulnerability to side effects for novel therapies.…”

Phase I randomized single-blinded controlled study investigating the potential benefit of aerobic exercise in degenerative cerebellar disease

“…The stratum variable was disease severity (mild (Scale for the Assessment and Rating of Ataxia score <10) and moderate (Scale for the Assessment and Rating of Ataxia score ⩾10)). 15 Participants in the aerobic group performed four weeks of cycling at home after one baseline assessment. A post-training assessment was performed at the completion of the four weeks.…”