Characterisation of Tremor and Imbalance in Demyelinating Polyneuropathies

Abstract

Neuropathic tremor is defined as tremor occurring in the context of neuropathy, in the absence of alternative causes. The pathophysiology of neuropathic tremor remains unclear and very little focus has been given to lower limb tremor. Given the impact tremor can have on balance, the potential combination of lower limb tremor causing imbalance is also of clinical importance.

Neuropathic tremor is most common in demyelinating neuropathies, which was the focus of this thesis. Mild upper limb postural tremor was found in two thirds of patients, irrespective of the underlying neuropathy diagnosis, suggesting a potentially shared mechanism. Upper limb tremor was shown to occur at higher frequencies in proximal compared with distal muscles, forming a gradient along the limb, and the peak tremor frequency correlated with peripheral nerve conduction findings. The peak tremor frequency was unchanged with weight loading and there was no change as the limb fatigued. This thesis also reports the novel finding of an elevated tremor stability index, suggesting an unstable tremor. Overall, the upper limb findings support the hypothesis that distorted peripheral inputs confuse a dominant central generator or network, leading to tremor. Importantly, lower limb tremor was also associated with imbalance in each group. Additionally, the novel finding of a high frequency vertical movement was detected on posturography in those with preserved balance.

In summary, this thesis confirmed the hypothesis that upper limb neuropathic tremor in demyelinating neuropathies is contributed to by both peripheral and central mechanisms. It also provided new insights into the prevalence of lower limb neuropathic tremor, and the role it plays in imbalance in these cohorts. Finally, this thesis reports high frequency movements in those who maintain their balance, suggesting a potentially adaptive mechanism in demyelinating neuropathies, which may allow for targeted management strategies in the future.