Dystonic tremor may be one cause of SWEDDs

Recent large clinical drugs trials in patients with Parkinson`s Disease (PD) have shown that 11-15% of patients entered for these trials with a diagnosis of PD made using established clinical criteria, in fact have normal functional dopaminergic imaging. Although initially it was suspected that the imaging techniques were not sensitive enough to pick up changes in early PD, follow-up imaging has remained normal in these patients after 4 years. The diagnosis in these patients (most of whom have resting tremor) remains unclear, and they have since been classified as SWEDDs (Scans Without Evidence of Dopaminergic Deficit). It is important to understand the underlying pathophysiology of these patients both to characterize the disorder more clearly, and also to help differentiate them from patients with PD (something that is clearly not possible using current clinical criteria). It has recently been suggested that one cause of SWEDDs may be dystonic tremor. This suggestion has arisen from a clinical study of patients with rest tremor diagnosed as PD, but with normal DaTSCANs. Of the twelve patients reported in this study, 8 had clear evidence of dystonic posturing, and all had elements of their tremor that could be compatible with dystonic tremor. Dystonia may be an important cause of SWEDDs, and we therefore hypothesize that the electrophysiological characteristics of tremor and of cortical motor physiology in SWEDDs will be different from PD, and will be similar to that seen in dystonia. Our aims in this study are therefore: 1. To use electrophysiological techniques to examine the characteristics of tremor (frequency, amplitude, coherence, power spectrum analysis, response to loading) in patients with SWEDDs. 2. To use transcranial magnetic stimulation techniques to examine cortical excitability (cortical silent period, intracortical inhibition and facilitation, short and long latency afferent inhibition) in patients with SWEDDs. 3. To examine motor cortical plasticity using the paired associative stimulation technique in patients with SWEDDs. 4. To compare the results of these tests in patients with SWEDDs to the results of similar tests performed in patients with PD, essential tremor (ET), segmental dystonia and healthy controls. We hope that this comprehensive electrophysiological assessment will help to characterize the pathophysiology of SWEDDs, and provide a more rigorous distinction from other disorders that cause tremor, particularly PD.