Pauline Anderson
February 08, 2016
Transcutaneous needle biopsy of the submandibular gland may
identify Lewy-type synucleinopathy (LTS) in patients with early Parkinson's disease
(PD).
A new study shows that LTS was present in the submandibular
glands — which play a role in making saliva — of almost three quarters of the
assessable glandular tissue specimens from patients with PD.
Currently, the diagnosis of PD relies on clinical examinations,
so developing a test to determine whether a patient has this disorder would be
helpful in both the research setting and clinically, said lead author Charles
H. Adler, MD, PhD, professor, neurology, Mayo Clinic College of Medicine, Scottsdale,
Arizona.
In PD, α-synuclein proteins are found not only in the brain but
throughout the body, including in the colon, stomach, olfactory bulb, and
esophagus. The best place to biopsy would be the brain, but that, of course, is
impossible. Compared with other potential sites from which to obtain tissue,
the submandibular gland is the easiest to reach and potentially the safest,
posing the fewest risks for side effects, said Dr Adler.
The study was published in
the February issue of Movement Disorders.
The analysis included 25 patients diagnosed with PD within the
previous 5 years (mean age, 69.8 years; 64% male) plus 10 controls (mean age,
64.7 years; 30% male), who had no evidence of a neurodegenerative disorder.
The patients with PD were required to have a dopamine
transporter (DaT) scan. As Dr Adler explained, one marker of PD is a positive
DaT scan, which indicates loss of dopamine nerves, although the test isn't
specific to PD.
Smell Tests
All study participants had olfactory testing with the University
of Pennsylvania Smell Identification Test (UPSIT-40), a kind of
scratch-and-sniff test. Most patients with PD lose some sense of smell, likely
partly because of degeneration of the olfactory bulb, said Dr Adler.
Again, this test isn't specific to PD, "but if you lose
your sense of smell and have a positive DaT scan, the likelihood that you have
PD goes up and up," he said.
For the biopsy, participants underwent local anesthesia, after
which an ear, nose, and throat specialist inserted a needle through the skin,
into the submandibular gland, to obtain three to six needle cores. All biopsies
were performed unilaterally. There was no difference in the mean number of
needle cores taken per participant.
Slides were examined by experts blinded to clinical diagnosis,
DaT scan, and smell test results. The total number of slides reviewed did not
differ between LTS-positive and -negative groups.
Tissues from 7 patients with PD and 1 control were insufficient
for determining whether LTS was present, leaving 18 patients with PD and 9
controls. However, 1 of the 7 PD cases was later found to be LTS positive and
so was included in the LTS-positive group analysis.
Overall, 14 (74%) of the 19 patients with PD had biopsy
specimens positive for LTS. Five patients with PD were negative, probably
because the affected tissue was missed, said Dr Adler.
Another possibility is that these patients don't actually have
PD.
Of the 9 controls with adequate glandular tissue, 2 (22%) had
LTS. "It could mean that these people have PD that we haven't seen signs
of yet," said Dr Adler, although he personally examined them and saw no
signs of PD.
It's also possible that these were false-positive results, he
said.
The PD group had significantly more olfactory dysfunction than
controls (mean UPSIT score of 18.4 vs 35.7; P < .001). But
there was no significant difference in mean UPSIT scores between the
LTS-positive and negative patients with PD (15.4 and 19.6; P =
.27).
"This suggests that those [negative] patients probably have
PD or they certainly have a neurodegenerative disorder that's affected their
sense of smell," said Dr Adler.
These negative patients with PD also had abnormal DaT scans,
indicating that their dopamine levels were low.
"So the 2 things we use as markers to try to figure out if
someone has a neurodegenerative disorder were both abnormal," said Dr.
Adler. "I still believe that most of the 5 [negative PD patients] probably
do have PD; it's just a matter of needle probably missing the tissue."
Dr Adler said he doesn't think it's important that the
percentage of men was lower in the control group, especially considering the
small sample size.
Side effects of the biopsy mostly included swelling and bruising,
which were minor and transient.
Patient Selection
Dr Adler sees this biopsy test being used by researcher who
strive to enroll patients in treatment trials early in the course of the
disease. Now, they have to rely on sometimes inaccurate clinical examinations
for diagnostic information.
"If you were to enroll 100 people in a placebo group and
100 people in an active drug group, and let's say 25% in both groups didn't
have PD, then you probably powered the study wrong," said Dr Adler.
"And so drugs that were noneffective may actually have been effective if
everybody had had PD."
Clinically, the biopsy test could help prevent patients who
don't have PD from being subjected to sometimes invasive treatments, such as
deep-brain stimulation, stem cell transplants, and injections of levodopa gel
into the intestines.
"All the invasive therapies pretty much only work in people
with PD, so if they have another neurodegenerative disease, they won't
work," said Dr Adler. "This would be an opportunity, if the test turns
out to be as accurate as we hope, to be absolutely sure that the person you're
sending for an invasive treatment is someone you should send for an invasive
treatment."
Dr Adler's site is involved in a Michael J. Fox Foundation for
Parkinson's Research–funded initiative, the Systemic Synuclein Sampling (S4)
Study. Researchers will take biopsy samples of the skin, colon, and
submandibular gland as well as samples of saliva, and spinal fluid, in the same
patients with PD and controls, to see which offers the best biomarker.
Medscape Medical News asked Michael S. Okun, MD, professor and
chair, neurology, University of Florida, Gainesville, and national medical
director, National Parkinson Foundation, to comment on the study.
"The idea of developing a simple test to diagnose early
Parkinson's disease is not only appealing, but it will be critically important
to the field," said Dr Okun.
That two of the controls in the study had a positive biopsy
"raises the important question about the diagnostic accuracy of the
test," said Dr Okun. On the other hand, this finding "also raises the
intriguing possibility that the authors may have uncovered prodromal
Parkinson's disease."
Although the results are "intriguing," Dr Okun said
they "don't suggest that in its current form a submandibular biopsy will
become the gold standard for early Parkinson's disease diagnosis."
However, he added that improvements on the technique "may
change this status in the near future."
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