Vascular parkinsonism (VP) is difficult to diagnose with any degree of clinical certainty. We investigated the importance of macroscopic cerebral infarcts and pathological findings associated with microscopic "small vessel disease" (SVD) in the aetiology of VP. The severity of microscopic SVD pathology (perivascular pallor, gliosis, hyaline thickening, and enlargement of perivascular spaces) and the presence of macroscopically visible infarcts were assessed in 17 patients with parkinsonism and no pathological evidence of either Parkinson's disease or any histopathological condition known to be associated with a parkinsonian syndrome, and compared with age-matched controls. Microscopic SVD pathology was significantly more severe in the parkinsonian brains. Most patients presented with bilateral bradykinesia and rigidity together with a gait disorder characterised predominantly by a shuffling gait. Four patients presented acutely with hemiparesis and then progressed to develop a parkinsonian syndrome. They could be distinguished from the remaining VP patients by the presence at autopsy of macroscopically visible lacunar infarcts in regions where contralateral thalamocortical drive might be reduced. The clinical features at presentation varied according to the speed of onset and the underlying vascular pathological state. New clinical criteria for a diagnosis of VP are proposed based on the clinicopathological findings of this study.

Patients with Parkinson's disease experience motor and perceptual timing difficulties, which are ameliorated by dopaminergic medication. We investigated the neural correlates of motor timing in Parkinson's disease, including the effects of dopaminergic medication on patterns of brain activation. Eight patients with Parkinson's disease and eight healthy controls were scanned with H(15)(2)O positron emission tomography while engaged in three tasks: synchronization (right index finger tapping in synchrony with a tone presented at 1 Hz), continuation (tapping at 1 Hz in the absence of a tone), and a control simple reaction time task. During the first 6 scans, the patients were assessed after overnight withdrawal of medication. Scans 7-12 were completed with the patients in the 'ON' state, after injections of apomorphine, a dopamine receptor agonist. For the healthy controls, relative to the control reaction time task, motor timing (synchronization + continuation) was associated with significantly greater activation in left medial prefrontal cortex (Brodmann area 10, 32), right hippocampus, bilateral angular gyrus (Brodmann area 39), left posterior cingulate (Brodmann area 31) and left nucleus accumbens/caudate. This pattern of brain activation during motor timing was not observed for patients, who showed significantly greater activation in bilateral cerebellum, right thalamus and left midbrain/substantia nigra compared to the control participants. Relative to the externally-paced synchronization task, the internally controlled continuation task was associated with greater activation in the dorsolateral prefrontal cortex (Brodmann area 46/9) in both the control and Parkinson's disease groups. Analysis of medication-related effects indicated that cortical activation was significantly more predominant during motor timing when the patients were 'ON' medication, whereas pallidal and cerebellar activations were evident 'OFF' medication. Effective connectivity analysis established that activity in the left caudate nucleus was associated with increased activity in the right lentiform nucleus and cerebellum 'OFF' medication, and with increased activity in the prefrontal cortex 'ON' medication. These results suggest that in Parkinson's disease, in the 'OFF' medication state, excessive inhibitory pallidal outflow is associated with a lack of adequate frontal activation and reliance on the cerebellum for motor timing. In contrast, our results establish for the first time that administration of dopaminergic medication increases striatal-frontal connectivity between the caudate nucleus and prefrontal cortex during motor timing.

This study raises the possibility that there is a neurobiological link between low sensation seeking traits--which might underlie the parkinsonian personality--and the hypothetical protective effect of cigarette smoking and caffeine consumption on PD.

Consecutive and integrated dual-task training led to similar and sustained improvements in dual-task gait velocity without increasing fall risk. These novel findings support adoption of dual-task training in clinical practice. © 2017 International Parkinson and Movement Disorder Society.

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There is substantial evidence to support a role for small vessel disease (SVD) as a cause for vascular parkinsonism (VP). Using [(123)I] FP-CIT SPECT (single photon emission computed tomography), we have tried to determine whether VP patients have pre-synaptic dopaminergic function similar to PD patients, and whether the severity of parkinsonian symptoms as well as the levodopa response in VP patients are correlated with pre-synaptic dopaminergic dysfunction. Thirteen patients fulfilling operational clinical criteria for VP had [(123)I] FP-CIT scans. Mean [(123)I] FP-CIT uptake in the basal ganglia was significantly lower in VP patients than in healthy controls, and the asymmetry index was not significantly different between these groups. In contrast, compared with the PD group, only the mean asymmetry index was significantly lower in VP patients. None of the parameters measured was significantly different between VP patients who had an insidious onset of parkinsonism (VPi) and those who had an acute onset (VPa). There was a significant correlation between the bilateral basal ganglia FP-CIT uptake reduction in the VP patients and UPDRS motor scores, but not with the mean % reduction in motor UPDRS after levodopa. We suggest that in the majority of VP patients, pre-synaptic dopaminergic function is reduced. The presence of a rather symmetrical FP-CIT uptake in the basal ganglia may help to distinguish VP from PD and could therefore be used as a criterion for the clinical diagnosis of VP.

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There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.