Clinical Phenotype-Specific Differences in Cerebral Haemodynamics in Idiopathic Parkinson's Disease

Al-Bachari, S. and Parkes, L. and Vidyasagar, R. and Hanby, M. and Tharaken, V. and Leroi, I. and Emsley, H. (2013) Clinical Phenotype-Specific Differences in Cerebral Haemodynamics in Idiopathic Parkinson's Disease. Journal of Neurology, Neurosurgery and Psychiatry, 84 (11). e2-e2. ISSN 0022-3050

Abstract

INTRODUCTION: Idiopathic Parkinson's disease (IPD) exhibits significant heterogeneity in respect of both motor and non motor clinical features. The 'neurovascular model' implicates neurovascular mechanisms as key players in the neurodegenerative process.(1) We aimed to determine whether magnetic resonance imaging (MRI) physiological and structural measurements of cerebral haemodynamics can reveal cerebrovascular dysfunction in IPD and whether this is specific to certain IPD phenotypes.\n\nMETHODS: 14 IPD patients (mean age 65.1±5.9) and 14 (mean age 64.6±4.2) age and cardiovascular risk matched control subjects underwent a 3T MRI scan protocol. This comprised an arterial spin labeling (ASL) sequence, applied continuously pre, during and after a 6 min hypercapnic challange and a fluid attenuated inversion recovery (FLAIR) sequence with subsequent determination of white matter lesion score (WML).(2) ASL applies a magnetic label to endogenous water, enabling quantitative measures, including cerebral blood flow (CBF) and arrival time (tA-time from labelling to imaging slice). A vasodilator stimulus (hypercapnia) enables measurement of cerebrovascular reactivity (CVR). IPD phenotype was assessed using the unified Parkinson's disease rating scale (UPDRS), including postural instability and gait disorder (PIGD), tremor-dominant and intermediate subtyping. Non motor IPD features were assessed using clinical scales.\n\nRESULTS: Patients showed a significant widespread increase in baseline tA, dominated by the tremor dominant group (p=0.0009 in tremor dominant group vs. p=0.1 in PIGD group). There were no significant differences in global baseline CBF but voxel-based analysis revealed focal regions of thalamic hyperperfusion in the IPD group compared to controls and areas of hypoperfusion in the posterior cortices. CVR_CBF was significantly higher in the tremor dominant group compared to controls, with no difference between the PIGD group and controls. WML score was significantly higher in the PIGD compared to controls, but not in the tremor-dominant group. One control subject and 6 IPD patients displayed at least mild cognitive impairment (MOCA score of ≤25), with 4 of these IPD patients being in the PIGD group (p=0.08). 3 IPD patients (2 PIGD, 1 intermediate) had mild depression compared to no controls. Non motor features did not correlate with ASL or WML measures.\n\nDISCUSSION: This study revealed differences in cerebral haemodynamics between patients and controls. tA was significantly prolonged in the patient group. Interpretation of this measure is challenging and may reflect chronic vascular alterations in order to maintain CBF or increased collateral circulation, chronic vasodilatation and/or increased tortuosity of vessels as demonstrated in other studies.(3) CBF differences were much more localised, with posterior cortical hypoperfusion in the IPD brain in keeping with recent studies.(4) In addition, cerebrovascular reactivity differed between the PIGD and tremor-dominant IPD phenotypes. These findings, and the suggestion that pathophysiology relating to vascular dysfunction differs between IPD phenotypes, merit further study.