Clinical correlates of cerebral white matter abnormalities in patients with Parkinson's disease

This study considers the potential relevance of changes in the white matter of the brain seen on MRI scans in patients with Parkinson's... confluent and scattered white lesions are commonly observed on T2 weighted MRI scans as people get older. By and large these lesions are attributed to small vessel disease (SVD). SVD is different to diseases of the large blood vessels which cause stroke and the accumulating SVD burden largely passes under the clinical radar, unless it causes problems with walking and cognition over time. Control of vascular risk factors is all that can be done to reduce an increasing burden of SVD... controlling blood glucose, hypertension and cholesterol, and stopping smoking.

The authors here set out to see if posturally-related drops in blood pressure (orthostatic hypotension) might explain an increasing burden of these WM lesions. It is plausible for example that transient drops in blood pressure related to standing could temporarily reduce blood flow to the brain and cause WM lesions to accumulate. This is an important research question that the authors raise. However, the design they used (cross-sectional) makes it very difficult to know what comes first... is it the WM lesions or the low blood pressure??

Perhaps more concerning is that whilst they take account of some potential confounding factors such as age, l-dope use and hypertension, they do not adjust for blood glucose or diabetes status. I think this could be important... we are seeing increasing evidence that diabetes may be linked to Parkinson's and evidence that diabetes drugs may be able to treat Parkinson's... it could be that unmeasured blood glucose or undiagnosed diabetes explains at least some of the association between the two given that it is separately associated with orthostatic hypotension and WM lesions, and does not lie on a causal pathway between them... I think the authors should have clarified the number of people that had blood glucose measured and/or a diagnosis of diabetes and indicated whether this affected the results...

It is worth mentioning that what we see on a scan in any case is only the tip of the iceberg and does not identify what is going on at a cellular/microscopic level...

Alastair Noyce

Parkinsonism Relat Disord. 2017 Dec 27. pii: S1353-8020(17)30868-4. doi: 10.1016/j.parkreldis.2017.12.029. [Epub ahead of print]
Ten Harmsen BL, van Rumund A, Aerts MB, Bergkamp MI, Esselink RAJ, Richard E, Meijer FJA, Bloem BR, van Wamelen DJ

https://www-sciencedirect-com.libproxy.ucl.ac.uk/science/article/pii/S1353802017308684

OBJECTIVE: To determine if autonomic dysfunction, cognitive disorders or axial disability are associated with white matter lesions (WML) in Parkinson disease (PD).

METHODS: We performed a retrospective cross-sectional review study on 204 consecutive PD patients who underwent cerebral MRI in our center between January 2012 and July 2016. For each patient, we scored the severity of WML and PV (periventricular) WML using the Fazekas score and using the ARWMC scale for WML and BG (basal ganglia) and clinical characteristics such as neurogenic orthostatic hypotension and cognitive function.

RESULTS: 204 PD patients were included of whom n = 53 (26.0%) had neurogenic orthostatic hypotension (nOH). The presence of nOH was significantly associated with the severity of WML as defined by the Fazekas score and the ARWMC scale. An ordinal regression model confirmed this association with an OR of 0.41 (95% CI 0.18-0.92: p = .03) and an OR of 0.39 (95% CI 0.17-0.88: p = .02). There were no significant associations between WML and other co-variables, including hypertension, dopaminergic medication use, Hoehn and Yahr stage, gender and cognitive decline.

CONCLUSION: The presence of nOH is associated with WML severity in PD patients.