Tabish A Saifee1, Isabel Pareés2, Panagiotis Kassavetis2, Diego Kaski3, Adolfo M Bronstein3, John C Rothwell2, Anna Sadnicka2, Michael P Lunn4, Hadi Manji4, James T Teo2, Kailash P Bhatia2, Mary M Reilly4, Mark J Edwards2. 1. Sobell Department for Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, 33 Queen Square, London WC1N 3BG, UK. Electronic address: t.saifee@ucl.ac.uk. 2. Sobell Department for Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, 33 Queen Square, London WC1N 3BG, UK. 3. Academic Department of Neuro-otology, Faculty of Medicine, Imperial College London, London, UK. 4. MRC Centre for Neuromuscular Diseases, Department of Molecular Neurosciences, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Abstract
OBJECTIVES: Tremor in Charcot-Marie-Tooth disease (CMT) can be disabling. Cerebellar abnormalities are thought to underpin neuropathic tremor. Here, we aim to clarify the potential role of the cerebellum in CMT tremor. METHODS: We assessed prevalence of tremor by questionnaire in 84 patients with CMT. Of those, 23 patients with CMT with and without arm tremor and healthy controls underwent a clinical assessment, classical eyeblink conditioning, electro-oculography, visuomotor adaptation test, tremor recording with surface EMG and accelerometry, and retrospective correlation with nerve conduction studies to investigate the possible mechanisms of tremor generation. RESULTS: The prevalence study revealed tremor in 21% of patients and in 42% of those it caused impairment of function. Tremor recordings revealed a mild-to-moderate amplitude tremor with a weight load-invariant 7.7 Hz frequency component. Performance on classical eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. CONCLUSIONS: These results argue against a prominent role for an abnormal cerebellum in tremor generation in the patients studied with CMT. Rather, our results suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism for tremor in the patients studied. SIGNIFICANCE: This study is the first to propose differing pathogenic mechanisms for subtypes of neuropathic tremor.
OBJECTIVES: Tremor in Charcot-Marie-Tooth disease (CMT) can be disabling. Cerebellar abnormalities are thought to underpin neuropathic tremor. Here, we aim to clarify the potential role of the cerebellum in CMT tremor. METHODS: We assessed prevalence of tremor by questionnaire in 84 patients with CMT. Of those, 23 patients with CMT with and without arm tremor and healthy controls underwent a clinical assessment, classical eyeblink conditioning, electro-oculography, visuomotor adaptation test, tremor recording with surface EMG and accelerometry, and retrospective correlation with nerve conduction studies to investigate the possible mechanisms of tremor generation. RESULTS: The prevalence study revealed tremor in 21% of patients and in 42% of those it caused impairment of function. Tremor recordings revealed a mild-to-moderate amplitude tremor with a weight load-invariant 7.7 Hz frequency component. Performance on classical eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. CONCLUSIONS: These results argue against a prominent role for an abnormal cerebellum in tremor generation in the patients studied with CMT. Rather, our results suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism for tremor in the patients studied. SIGNIFICANCE: This study is the first to propose differing pathogenic mechanisms for subtypes of neuropathic tremor.
Authors: Anna Sadnicka; Lorenzo Rocchi; Anna Latorre; Elena Antelmi; James Teo; Isabel Pareés; Britt S Hoffland; Kristian Brock; Katja Kornysheva; Mark J Edwards; Kailash P Bhatia; John C Rothwell Journal: Mov Disord Date: 2022-03-21 Impact factor: 9.698