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02-12-2014 | Neurology | Article

Prodromal symptoms precede PD by up to a decade


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medwireNews: Many prodromal symptoms of Parkinson’s disease (PD) appear long before a clinical diagnosis is made, shows a large study of patients in primary care.

Indeed, in the case–control study, tremor and constipation started to appear as much as 10 years before a PD diagnosis. At this point, tremor was 7.59 times more common in patients who later received a PD diagnosis than in those who did not, and constipation was 2.01-fold more common.

“The findings further emphasise the frequency and complexity of the early premotor or prodromal phase of the disorder”, writes Anthony Lang (University of Toronto, Ontario, Canada) in a related commentary in The Lancet Neurology.

He says that although the study mostly confirms previous research, “its size is impressive and the data were collected prospectively in the course of routine primary care, without recall or selection bias towards the diagnosis of Parkinson’s disease.”

The study by Anette Schrag (University College London, UK) and colleagues involved 8166 PD patients and 46,755 controls who did not develop the condition, whose data were obtained from the Health Improvement Network UK primary care database.

Tremor was the most common prodromal symptom to appear during the 2 years preceding PD diagnosis, occurring in 41% of PD patients versus less than 1% of controls, giving an incidence risk ratio (IRR) of 32.54.

The next most frequent symptom was constipation, occurring in 32% of patients and 19% of controls, at an IRR of 2.44. And the highest IRR besides that for tremor was for hypotension, at 3.03, but this only occurred in 2% of PD patients and 1% of controls. In all, 14 symptoms were significantly associated with a PD diagnosis within 2 years; other symptoms included fatigue, dizziness, depression, shoulder pain or stiffness, anxiety, urinary dysfunction and erectile dysfunction.

The team excluded symptoms that occurred in less than 1% of the cohort, such as rapid eye movement sleep behaviour disorder, apathy and hypersalivation.

Ten symptoms were associated with a PD diagnosis 5 years later. Again, tremor was the most common, occurring in 7% of PD patients and less than 1% of controls, and had the highest IRR, at 13.7.

Only tremor and constipation remained associated with a PD diagnosis 10 years later. Tremor occurred in 2% of patients versus less than 1% of controls and constipation occurred in 20% versus 14%.

Lang highlights one important drawback to the study: the reportedly high rates of misdiagnosis of PD in clinical practice, which suggest that many patients in the database might not have had PD. “This possibility emphasises the crucial need for reliable and widely applicable diagnostic biomarkers”, he says.

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2014

By Eleanor McDermid, Senior medwireNews Reporter

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