Distinguishing SWEDDs patients with asymmetric resting tremor from Parkinson's disease: A clinical and electrophysiological study

Abstract

SummaryApproximately 10% of subjects thought clinically to have early Parkinson's disease (PD) have normal dopaminergic functional imaging (SWEDDs -Scans Without Evidence of Dopaminergic Deficit). SWEDDs are a heterogeneous group. Here we aimed to delineate clinical and electrophysiological characteristics of a distinct subgroup of SWEDDs patients from PD and to clarify the underlying pathophysiology of this subgroup as a form of parkinsonism or dystonia. Therefore we compared clinical details of 25 patients referred with a diagnosis of tremor-dominant PD but with normal DaT SPECT scans (SWEDDs) with 12 tremor-dominant PD patients with abnormal DaT SPECT scans. We performed tremor analysis using accelerometry in the following patients with 1) SWEDDs, 2) PD, 3) primary segmental dystonia with dystonic limb tremor and 4) essential tremor (ET). We used transcranial magnetic stimulation with a facilitatory paired associative stimulation (PAS) paradigm to test if sensorimotor plasticity in SWEDDs resembled the pattern seen in PD, dystonia or ET. Although PD and SWEDDs patients shared several clinical features, the lack of true bradykinesia, occurrence of dystonia, and position-and task-specificity of tremor favoured a diagnosis of SWEDDs, whereas re-emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs as well as presence of nonmotor symptoms made PD more likely. Basic tremor parameters overlapped between SWEDDs, PD, segmental dystonia and ET. However, a combination of re-emergent tremor and highest tremor amplitude in the resting condition was characteristic of PD tremor, while SWEDDs, dystonia and ET subjects had the highest tremor amplitude during action. Both SWEDDs and segmental dystonia patients exhibited an exaggerated pattern of sensorimotor plasticity in response to the PAS paradigm, with spread of excitation to an adjacent hand muscle. In contrast, PD patients showed no response to PAS, and the response of ET patients was no different from controls. Taken together, these results may help differentiate these SWEDDs patients from PD and support our hypothesis that adultonset dystonia is the underlying diagnosis in this sub-group of patients with SWEDDs.

Glucocerebrosidase mutations and the pathogenesis of Parkinson disease

“…However, there is debate as to whether these patients have early PD or whether adult-onset dystonia is the underlying diagnosis (Schwingenschuh et al, 2010).…”

The Treatment of Tremor

“…A recent study of 25 patients with dystonic tremor found that only 40 % of patients benefitted from oral therapy. Anticholinergics [i.e., trihexyphenidyl (range, 3-6 mg/day)] produced the best results; propranolol also produced some benefit [91].…”

Neuromodulatory Neurotransmitters Influence LTP-Like Plasticity in Human Cortex: A Pharmaco-TMS Study

“…Impaired PAS-induced LTP-like plasticity is typically observed in disorders associated with a dysfunctional dopaminergic system such as Parkinson's disease (Morgante et al, 2006;Ueki et al, 2006;Schwingenschuh et al, 2010) or schizophrenia (Frantseva et al, 2008), or a deficient central cholinergic system such as Alzheimer's disease (Battaglia et al, 2007), whereas exaggerated PASinduced LTP-like plasticity can be observed in states of increased endogenous central cholinergic tone such as dystonia (Quartarone et al, 2003(Quartarone et al, , 2008Weise et al, 2006;Schwingenschuh et al, 2010).…”