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Gait difficulties in Parkinson's linked to new blood vessels in brain

Thursday November 05, 2015

Catharine Paddock PhD

Medical News Today - Targeting the formation of unwanted blood vessels in the brain could be a way to help Parkinson's disease patients whose balance and walking difficulties persist despite dopamine-restoring medication.

This is the potential implication of a study published in the journal Neurology that found biomarkers of blood vessel formation in the brain are increased in patients living with Parkinson's disease, and they are linked to gait difficulties.

The study confirms similar findings by other researchers who analyzed brain tissue obtained postmortem from Parkinson's patients.

Study leader Dr. Oskar Hansson, from Lund University in Sweden, says:

"The strength of our study is the number of participants, and the fact that they are alive. Because many suffer from several parallel diseases at the final stage of their lives, it is difficult to analyze samples from deceased persons."

Despite adequate medication, many people with Parkinson's disease eventually develop problems with walking and balance. Also, some cannot tolerate full doses of dopamine-restoring medication because of the side effects.

Parkinson's disease arises from the death of brain cells in a few restricted areas of the brain. The affected brain cells release dopamine, a chemical messenger that is important for the control of movement, emotional responses and other functions.

As the disease progresses, levels of available dopamine fall, and symptoms like tremors, slowness, impaired balance and stiffness get worse. Normal life erodes - at different rates in different people - as walking, talking and looking after oneself become increasingly difficult.

There is no cure for Parkinson's disease, and patients must rely mainly on drug-based treatments to control their symptoms. The drugs are designed to increase dopamine in the affected parts of the brain.

Angiogenesis linked to walking and balance difficulties in Parkinson's

The formation of new blood vessels, or angiogenesis, in the brain is also a feature of Parkinson's disease and other neurodegenerative disorders. The reason for this is not clear, but one theory is that the death of cells triggers it. Angiogenesis can also be triggered by inflammation and damage to tissue.

It is possible to assess the extent of angiogenesis in the brain by measuring biomarkers in cerebrospinal fluid.

In their study, Dr. Hansson and colleagues found clear links between several markers of angiogenesis and walking or balance difficulties in patients with Parkinson's disease.

Dr. Hansson says they also noted "an increased permeability of the blood-brain barrier, which leads to blood components potentially leaking into the brain and causing damage."

The team arrived at these results by comparing the cerebrospinal fluid from 100 Parkinson's patients with that of 38 healthy people (the controls). They measured levels of a number of angiogenesis markers and also, from magnetic resonance imaging (MRI) scans, they assessed any damage to brain tissue (for example, white matter lesions and small bleeds). They then confirmed the results in two further patient groups of approximately the same size.

The results showed that cerebrospinal fluid markers of brain angiogenesis are "upregulated" in Parkinson's disease.

The authors note that the increased angiogenesis was linked with gait difficulties, blood-brain barrier dysfunction, and signs of damage to brain tissue in the Parkinson's patients but not the controls, and write that "these interactions are specific" for Parkinson's disease.

Regarding the study's implications, Dr. Hansson notes:

"Medication for angiogenesis already exists. If we can confirm our results in further studies, these drugs can be tested on Parkinson's patients in the future."

Before embarking on human trials, the team plans to carry out animal studies first, so as to understand more about the underlying mechanisms, and also to screen for the most appropriate candidate drugs.

Angiogenesis has also been implicated in other neurodegenerative diseases. For example, in 2011, Medical News Today reported a study where researchers suggest that a profusion of blood vessels may explain how Alzheimer's disease destroys the brain.