June 23, 2016
Collins, Thomas S.
ARTICLE
IN BRIEF
Two movement disorders specialists
debate whether vascular risk factors contribute to parkinsonism. One cites data
showing comorbid vascular diseases, while the other counters that it is
difficult to make the association because the definition of vascular
parkinsonism is ill-defined.
VANCOUVER—Whether vascular causes
play a major role in parkinsonism is a gray area, said two Parkinson's disease
experts here in a plenary discussion of controversies in neurology at the AAN
Annual Meeting in April. And they said how to answer that question is a matter
of debate.
The lack of a universal rule on
how to define parkinsonism contributes to the controversy, both experts agreed.
Aron S. Buchman, MD, professor of
neurological sciences at the Rush University Alzheimer's Disease Center, said a
review of cases at his center seems to show that vascular diseases, risk
factors, and pathologies in the brain and spinal cord are strongly related to
parkinsonism, while Alberto J. Espay, MD, FAAN, clinical research director of
the James J. and Joan A. Gardner Center for Parkinson's Disease and Movement
Disorders at the University of Cincinnati, countered that it's difficult to
make that claim.
THE CASE FOR VASCULAR ETIOLOGY
 |
| DR. ARON S. Buchman |
Dr. Buchman cited data from the
Religious Order Study, in which more than 1,300 nuns and priests across the US
have been followed up at a 95 percent rate and with a 90 percent autopsy rate,
adding up to more than 600 autopsies, and the Chicago-area Memory & Aging Project,
with 1,800 people followed up at a rate of 90 percent, with 650 autopsies
available.
At Rush, researchers categorized
people as demonstrating parkinsonism using the 26 items in the motor section of
the Unified Parkinson Disease Rating Scale, which is divided into four domains
— parkinsonian gait, rigidity, bradykinesia, and tremor — with several tasks
within each domain. If a person met two or more criteria within a domain, that
domain was considered to be present. The presence of two more domains meant that
a person was considered to have parkinsonism.
Using data from these studies,
they looked at whether vascular diseases and vascular risk factors were related
to parkinsonism. They reported in a 2011 paper in Stroke that
demographics, such as age and education, together with vascular diseases like
myocardial infarction and stroke as well as risk factors such as body-mass
index and diabetes, accounted for approximately 30 percent of the parkinsonism
variance they saw in the cohort. But they also found other vascular factors,
such as claudication and hypertension, were not significant predictors.
What's more, Dr. Buchman said,
researchers have also found that cerebrovascular pathology is associated with
the severity of parkinsonism, with macroinfarcts, microinfarcts, and
arteriolosclerosis predicting the severity of parkinsonism even when
controlling for demographics and Parkinson's disease pathology of the
substantia nigra.
“This finding of the microinfarcts
and arteriolosclerosis is very important,” he said. “About one-third of the
cohort had these. These abnormalities would not be seen with ante-mortem
magnetic resonance imaging [MRI]. You could only see them postmortem. And so it
suggests that it's an unrecognized cause of parkinsonism that you wouldn't be
able to see even if you did an MRI.”
Researchers also closely examined
the microvascular pathology in the brains and spinal cords of 150 people, and
found that arteriolosclerosis of the spinal cord was present to a greater
degree than arteriosclerosis in the brain, and it was the only factor that
explained any of the variance of parkinsonism.
“All the other brain pathologies”
— which included atherosclerosis, Lewy Body, nigral neuronal loss, and
Alzheimer's disease pathology — “fall out and don't explain any of the variance
of parkinsonism,” Dr. Buchman said.
This, he said, “suggests that
there's a tremendous gap in our ability to understand what the basis of
parkinsonism is. It suggests that we need to look at the entire pathway that
probably includes the nerve and muscle and the musculoskeletal element to
really explicate what we're talking about.”
THE CASE AGAINST VASCULAR
INVOLVEMENT
 |
| Dr Alberto Espay |
Dr. Espay countered that it's
difficult to make the claim that vascular etiology is a common cause of
parkinsonism because “vascular parkinsonism” (VaP) is so ill-defined. It's a
diagnosis, he said, without specific clinical, imaging, or pathologic features.
One systematic review, published
in 2010 in the journal Movement Disorders, covered 25 articles on
differentiating vascular parkinsonism from idiopathic Parkinson's disease and
found no abnormal imaging pattern that was specific to vascular parkinsonism.
There also seems to be no
clinical-pathological correlation, Dr. Espay said. In one of only two
post-mortem studies, with vascular parkinsonism defined as the presence of
parkinsonism and pathological evidence of cerebrovascular lesions but no
depigmentation or Lewy bodies at the substantia nigra, researchers found no
difference in the extent of vascular lesions in the basal ganglia between those
with VaP and those with Binswanger's disease, or subcortical vascular dementia.
The term “vascular parkinsonism”
itself is defined very loosely, he said. A study that helped generate the
current criteria for the syndrome showed that the severity of microscopic
small-vessel disease did not differ between the frontal, temporal, parietal,
occipital, and striatal regions. There was also no clinical specificity in its
VaP definition — with VaP criteria met, for instance, with either acute, delayed,
or insidious presentations, either uni- or bi-lateral parkinsonism, with or
without gait impairment, or with focal or diffuse lesions.
He added that data on prevalence
also don't seem to support a causal connection between vascular etiology and parkinsonism.
“If you truly think that there is
a condition called ‘vascular parkinsonism,’” he said, “we could assume that
cerebrovascular disease and parkinsonism are going to increase in prevalence in
parallel. But the data that have accumulated so far show that there really
isn't a correlation between cerebrovascular disease and parkinsonism.”
Both Drs. Buchman and Espay
agreed, however, that if the term is going to be used, it's in the best
interests of the field to begin describing vascular parkinsonism using
objective measures. Dr. Buchman described how his center is beginning to use
body sensors to describe gait in a more thorough, objective fashion.
“I think that moving in the
direction of having objective measures and dispensing with qualitative labels
would be very helpful for moving forward to understand the biology,” he said.
Dr. Espay agreed. “I suspect that
many of the concepts related to parkinsonism and vascular phenotype are really
driven by a poor characterization of the gait and the overall features,” he
said. “And in this I agree that we need to have more sophisticated measurements
and certainly cannot rely purely on imaging.”
Howard I. Hurtig, MD, emeritus professor
of neurology specializing in Parkinson's disease at the University of
Pennsylvania Perelman School of Medicine, who attended the debate, called Dr.
Buchman's view a “plausible hypothesis.”
“I definitely accept that that's a
possibility,” he said. “I don't think he goes overboard and says that strokes
in old people definitely cause Parkinson's or parkinsonism signs. He says they
may contribute, which is reasonable.”
Clinically, insofar as this view
leads to more awareness of vascular health, it is helpful, he said. “Forever
we've struggled with the fact that hypertension is under-treated in society,
and if people were more aware of the risks of stroke-related hypertension, then
individuals would be more vigilant about watching their blood pressure and
having it treated. So I think to the extent that this has a practical
application, it's a good point. If you can prevent cerebrovascular disease by
simply treating high blood pressure, which is one of the most important causes
of stroke and microinfarcts, then at least you've achieved something in the
realm of public policy.”
“It's good to assume that vascular
factors can contribute,” Dr. Hurtig continued. “The big problem of course is
that it's [often] too late for treatment when someone starts to develop these
signs.”
http://journals.lww.com/neurotodayonline/Fulltext/2016/06230/News_from_the_AAN_Annual_Meeting__What_is_the_Role.10.aspx
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