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Biopsy findings link multifocal motor neuropathy to chronic inflammatory demyelinating polyneuropathy.

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Development of Leuodopa Complications among Four Subgroups of Levodopa-treated
DATA TOP Subjects Balanced for Disease Severity
Original Treatment
Adverse effects
35 (51%)
15 (22%)
21 (30%)
38 (55%)
46 (65%)
those not so treated by an average of 9 months in the length
of time before they required levodopa symptomatic treatment, the same as for the whole DATATOP cohort [2].
However, the groups did not differ in their degree of impairment at the final evaluation, nor in their rate of developing
levodopa-related treatment complications (Table). Since
these disease-matched subgroups were very similar to those
of the group as a whole, it seems that differences in disease
severity do not account for our finding that prior deprenyl
therapy did not influence the development of levodopainduced adverse effects.
After our initial findings favoring deprenyl [2], the conversion of all DATATOP subjects to open-label deprenyl
excluded an ongoing placebo-controlled trial. In retrospect,
our follow-up studies would have benefited from a placebo
comparison group. However, the initial results of the DATATOP trial were so dramatic that it was not clinically justifiable to deny deprenyl to our research subjects. We did maintain the investigators’ and subjects’ blindness with regard to
the initial treatment assignment. O u r study had the advantage of having all subjects on deprenyl at the end of the
evaluation period so that its symptomatic effects were the
same across all groups. Thus, we could examine possible neuroprotective effects of prior deprenyl therapy in the presence
of the symptomatic effects of ongoing deprenyl therapy.
These symptomatic effects could well account for the reduced need for levodopa that the correspondents observed
in their studies.
Indeed, a longer study should make subtle differences between groups more apparent. However, the large number of
subjects in our study should have compensated somewhat
for the relatively short 18-month difference between the
groups with respect to initial deprenyl treatment. Somerset
Pharmaceuticals (Tampa, FL) has supported a follow-up
study of the DATATOP cohort involving a second randomization of our subjects to continue on or withdraw from
deprenyl and follow-up for an additional 2 years. This study
should provide longer time differences for exposure to deprenyl.
We are unable to comment on the findings of three cited
but unpublished studies whose design and results have not
been disclosed. We look forward to peer-reviewed reports of
the European studies cited by Orion so that readers may
form their own judgments about whether their results differ
948 Annals of Neurology Vol 40
No 6
December 1996
Deprenyl Plus
29 (44%)
16 (24%)
5 (8%)
15 (23%)
44 (66%)
46 (70%)
from ours. Meanwhile, we stand by our recommendation
that both the initial benefit of deprenyl [I, 21 and the less
encouraging longer term results [3, 41 should be weighed in
the decision to prescribe deprenyl.
Massachusetts General Hospital
Department of Neurology
Warren 408
Boston, MA 02114
University of Rochester Medical Center
Department of Neurology
601 Elmwood Avenue
Rochester, NY 14642
1. Parkinson Study Group. Effect of deprenyl on the progression
of disability in early Parkinson’s disease. N Engl J Med 1989;
321 :1364-1371
2. Parkinson Study Group. Effects of tocopherol and deprenyl on
the progression of disability in early Parkinson’s disease. N Engl
J Med 1993;328:176-183
3. Parkinson Study Group (Shoulson I, primary author). Impact
of deprenyl and tocopherol treatment on Parkinson’s disease in
DATATOP subjects not requiring levodopa. Ann Neurol 1996;
4. Parkinson Study Group (Penney J, primary author). Impact of
deprenyl and tocopherol treatment on Parkinson’s disease in
DATATOP subjects requiring levodopa. Ann Neurol 1996;39:
Biopsy Findings Link Multifocal Motor
Neuropathy to Chronic Inflammatory
Demyelinating Polyneuropathy
D. A. Krendel
I read with interest the article recently published in Annals
of Neurology by Corse and colleagues [l]. My colleague and
I previously questioned their definition of multifocal motor
neuropathy (MMN) as a distinct entity, believing that their
patients fit within the accepted clinical spectrum of chronic
inflammatory demyelinating polyneuropathy (CIDP) [2, 31.
In this more recent article, they describe sensory nerve biopsy
findings in these patients. They found onion bulbs, demyeh a t e d fibers, and active demyelination in sensory nerves, as
expected in CIDP. Yet they concluded that their findings
support the diagnosis of M M N as distinct from CIDP in
their patients. They cite absence of inflammation and subperineurial and endoneurial edema as if these were expected
biopsy findings in CIDP. However, inflammation is usually
absent from nerve biopsy specimens from CIDP patients,
and when present is very mild [4-61. This was reported by
Prineas and McCleod [6], whom Corse and colleagues cite
as supporting their implication that inflammation is an expected biopsy finding in CIDP. Lack of inflammation has
led some investigators to drop the word “inflammatory”
from the name of this disease, and substitute “acquired
chronic demyelinating polyneuropathy” [4]. I find subperineurial and endoneurial edema difficult to assess, and have
not found it to be diagnostically useful. Edema within the
endoneurium should reflect the severity of an active pathological process, and it does not surprise me that it was not
seen in these patients with relatively indolent disease.
Corse and colleagues showed that their patients have
chronic multifocal demyelinating neuropathies involving
both motor and sensory nerves consistent with CIDP. In my
opinion, this argues against rather than for their concept of
M M N as a distinct entity.
AM Corse, MD, V Chaudhry, MD, RW Kuncl, MD,
PhD, DR Cornblath, MD, T Crawford, MD,
and JW Griffin, M D
Our report of mild demyelinating findings in sensory nerve
biopsy specimens from patients with multifocal motor neuropathy (MMN) [l] led Dr Krendel to reiterate his opinion
[2] that patients with M M N “fit within the accepted clinical
spectrum of chronic inflammatory demyelinating polyneuropathy (CIDP).” Unfortunately, he misinterprets our report
as concluding that the biopsy findings alone support the diagnosis of M M N as distinct from CIDP. Certainly, M M N
is a chronic disorder with demyelinating physiology and sensory nerve pathology reflecting very mild demyelination, giving a superficial resemblance to CIDP. However, the highly
selective motor involvement seen clinically and electrophysiologically, the natural history, the uniformly mild sensory
nerve demyelination, and the response to treatment, when
taken together, strongly favor categorizing M M N as a demyelinating neuropathy distinct from CIDP [3].
It was the intent of our report to examine the biopsy
pathology in 11 patients with the distinctive clinical and
physiological features considered by our group and others [4,
51 to be characteristic of MMN. Because the spectrum of
biopsy findings in CIDP is large, ranging from severe demyelinating changes to normal [6-91, one can argue that the
very mild sensory nerve demyelination in M M N is at the
most mild extreme of the spectrum of CIDP. Certainly any
one of the biopsy specimens from our 11 patients with
M M N might be interpreted as consistent with the broad
range of findings in CIDP. We argue that it is not the nature
of the pathological change in M M N that is distinct from
CIDP but the uniformly quantitative and qualitative differences that are striking. For example, the degree of demyelination and minor onion bulb formation seen in all 11 of our
M M N sensory nerve biopsy specimens was extraordinarily
mild compared to the average tissue from CIDP. Inflammation was never seen in our M M N specimens, in contrast to
published series of CIDP pathology [6, 91. Subperineurial
edema was also never present in our M M N specimens; although Krendel finds that unhelpful, both Prineas and
Schmidt found it in a large minority of patients with CIDP,
as do most investigators [6, 8, 91.
This debate would be helped by data. T o provide the closest comparison, we reviewed our own last 15 consecutive
sensory nerve biopsy specimens in patients meeting accepted
Department of Neurohgy
The Emory Clinic
1365 Clzjion Rd, N.E.
Atlanta, GA 30322
V, Crawford TO, et al. Sensory nerve
pathology in multifocal motor neuropathy. Ann Neurol 1996;
2. Chaudhry V, Corse AM, Cornblath DR, et al. Multifocal motor
neuropathy: response to human immunoglobulin. Ann Neurol
3. Krendel DA, Costigan DA. Multifocal motor neuropathy or
CIDP? Ann Neurol 1993;34:750 (Letter)
4. Bouchard C, Said G. Acquired chronic demyelinating polyneuropathy: a retrospective study. J Neurol 1994;241(suppl 1):SlOl
5. Krendel DA, Parks HB, Anthony DC, et al. Sural nerve biopsy
in chronic inflammatory demyelinating polyradiculoneuropathy.
Muscle Nerve 1989;12:265-272
6. Prineas JW, McCleod JG. Chronic relapsing polyneuritis. J
Neurol Sci 1976;27:439
1. Corse AM, Chaudhry
Endoneurial inflammation
Subperineurial edema
Active macrophage-mediated demyelination
Current Series
Prineas and
McLeod [6]
Schmidt et a1 [9]
Corse et a1 111
4/15 (27%)
8/15 (53%)
5 / 15 (33%)
6/26 (23%)
9/26 (35%)
6/26 (23%)
10113 (77%)
6 / 13 (469’0)
Not availablea
0/11 (0%)
o/ 11 (0%)
1/ 11 @yo)
’Endoneurial macrophages were increased in 13/ 13 biopsy specimens, but the relation of these macrophages to fibers undergoing active
demyelination was not reported.
Annals of Neurology
Vol 40
No 6
December 1996 949
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biopsy, multifocal, motor, link, neuropathy, inflammatory, demyelination, findings, chronic, polyneuropathy
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