Saifee, TA; (2015) The clinical spectrum and pathophysiology of neuropathic tremor. Doctoral thesis , UCL (University College London).

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Abstract

This thesis describes a series of studies involving patients with neuropathies and healthy controls. In the studies of disease, two groups were recruited: patients with inflammatory neuropathies and those with hereditary neuropathies. Each group was separated into those with and those without tremor and compared with healthy controls. Clinical assessments and neurophysiological tests were employed to correlate cerebellar function with tremor. The final study of healthy participants investigated the effect of transcranial direct current stimulation (TDCS) on the cerebellum during finger tapping. 1) Tremor was most common in IgM paraproteinaemic neuropathies, also occurring in 58% of those with chronic inflammatory demyelinating polyradiculoneuropathy and 56% of those with multifocal motor neuropathy with conduction block (MMNCB). Tremor was generally refractory to treatment and contributed to disability in some patients. Although tremor severity correlated with F wave latency, it was insufficient to distinguish those with, from those without tremor. 2) Impaired eyeblink classical conditioning and paired associative stimulation in patients with inflammatory neuropathy and tremor differentiated them from neuropathy patients without tremor and healthy controls, strongly suggesting impairment of cerebellar function is linked to the production of tremor in these patients. 3) The prevalence study in CMT1A patients revealed tremor in 21% and in 42% of those it caused impairment. Eyeblink conditioning, visuomotor adaptation and electro-oculography were no different between tremulous and non-tremulous patients and healthy controls. This argues against a prominent role for an abnormal cerebellum in tremor generation in the patients studied. Rather, they suggest an enhancement of the central neurogenic component of physiological tremor as a possible mechanism. 4) TDCS of the lateral cerebellum and its effect on paced finger tapping was examined. There was no effect on accuracy or variability of the intertap interval, providing no support for a direct role of the cerebellum in event based timing.

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