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

• Authors: Ruo-Yan Lai, Vagelos College of Physicians and Surgeons; Darya Tomishon, Vagelos College of Physicians and Surgeons; Karla P. Figueroa, University of Utah; Stefan M. Pulst, University of Utah; Susan Perlman, University of California Los Angeles; George Wilmot, Emory University; Christopher M. Gomez, University of Chicago; Jeremy D. Schmahmann, Massachusetts General Hospital; Henry Paulson, University of Michigan; Vikram G. Shakkottai, University of Michigan; Sarah H. Ying, Johns Hopkins University; Theresa Zesiewicz, University of South Florida; Khalaf Bushara, University of Minnesota Twin Cities; Michael Geschwind, University of California San Francisco; Guangbin Xia, University of New Mexico; S. H. Subramony, University of Florida; Tetsuo Ashizawa, Houston Methodist Research Institute; Sheng-Han Kuo, Vagelos College of Physicians and Surgeons
• Journal Title: Cerebellum
• Volume: Volume 18, Number 3
• Publisher: Springer Link | 2019-06-15, Pages 519-526
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1007/s12311-019-01016-6
• Subjects: Biology, Neuroscience; Health Sciences, Medicine and Surgery; Health Sciences, Rehabilitation and Therapy
• Keywords: Cerebellum; Neurodegeneration; Tremor; Adult; Aged; Cerebellum; Female; Humans; Male; Middle Aged; Spinocerebellar Ataxias; 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.