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Ataxia and paraproteinemic polyneuropathy.

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LETTERS
Ataxia and Paraproteinemic
Poly neuropathy
John J. Kelly, Jr, MD
I enjoyed reading Dr. Dalakas’ extensive report on chronic
idiopathic ataxic neuropathy [I], a disorder referred to by
most neurologists as idiopathic or (if associated with carcinoma) carcinomatous sensory neuropathy (or neuronopathy). In
regard to D r Dalakas’s presentation, I disagree with two
points.
First, although most patients do not respond to aggressive
immunosuppressive therapy, occasional patients do. We recently treated two patients, a 47-year-old woman and a 61yea-old man, with intensive immunosuppression, including
plasmapheresis plus either azathioprine or cyclophosphamide
and prednisone. The woman became asymptomatic and the
man was able to walk again after several months.
The responses of these patients to intensive immunosuppression suggests an inflammatory or autoimmune cause.
Perhaps the rare patient capable of responding to such therapy has reversible disease of the dorsal root ganglia and peripheral nerves, rather than complete destruction of sensory
cytons or peripheral nerves, which would make recovery
impossible. There may be a narrow window of time during
the illness when therapy can be effective, after which the
damage is too extensive to allow recovery. Of course, alternately, the mechanism of the neuropathy may be different in
those patients who are able to recover.
My second point of disagreement with D r Dalakas is the
inclusion of patients who had myelin-associated glycoprotein
(MAG)-reactive IgM serum monoclonal proteins with other
idiopathic sensory neuropathy patients who did not have
gammopathies. Although superficially similar, these conditions differ clinically, electrophysiologically, and pathologically. Clinically, the patients with gammopathy usually
have evidence of motor involvement, which can become
striking as the neuropathy increases in severity [2, 33. These
patients also have striking slowing of motor nerve conduction velocities with dispersed compound muscle action potentials and markedly increased distal latencies, features suggestive of a prominent demyelinating component and never
seen in the sensory neuronopathy syndrome 12, 4). Nerve
biopsy in the anti-MAG-reactive cases, including electron
microscopy and immunofluorescent studies, reveals evidence
of demyelination and axonal loss, adherence to the myelin
sheaths of the IgM-kappa monoclonal protein, and a peculiar
splitting of the intraperiod lines of the outer lamellae of
rnyelin, features seen only in MAG-reactive IgM gammopathies [ 5 ] . In addition, the gammopathy patients often
respond to immunosuppression [3]. They likely suffer from
a rnyelin sheath disorder, not the relatively pure axonopathy
or neuronopathy of the primary sensory neuronopathy syndrome. For these reasons, I think that these disorders should
be regarded as separate until they are better understood.
Department of Neurology
Tubs University-New England Medical Center
Boston, MA
94
References
1. Dalakas MC: Chronic idiopathic ataxic neuropathy. Ann Neurol
1986; 19C545-554
2. Hafler DA, Johnson D, Kelly JJ Jr, et al: Monoclonal gammopathy and neuroparhy myelin-associated glycoprotein reactivity and clinical characteristics. Neurology 1986; 36:75-78
3. Sherman WH, Olarte MR, McKiernan G, et al: Plasma exchange
treatment of peripheral neuropathy associated with plasma cell
dyxrasia. J Neurol Neurosurg Psychiatry 1984; 472313-914
4 . Kaufman MD, Hopkins LC, Hurwitz BJ: Progressive sensory
neuropathy in patients without carcinoma: a disorder with distinctive clinical and electroph-jsiological findings. Ann Neurol 1981;
91237-242
5. Kelly JJ Jr: Peripheral neriropathies associated with monoclonal
proteins: a clinical review. Muscle Nerve 1985; 8:138- 150
Reply
Marinos C. Dalakas, M D
I appreciate Dr Kelly’s comments. H e raises two points: one
that I agree with and is of clinical interest, and a second that
can cause confusion and with which I disagree. In his first
point, Dr Kelly reports that two of his patients with chronic
idiopathic ataxic neuropathy (CIAN) responded to immunosuppressive therapy. This is in contrast to 15 of my
patients who did not respond El]. H e provides a reasonable
explanation. I also believe that rare patients with CIAN,
especially of subacute onset. may have a potentially treatable
neuropathy if treatment is started early in the disease at a
time when some ganglionic neurons are in a transitional state
of nonfunction rather than cell death. Such improvement was
reported in some patients with ataxic neuropathy due to
pyridoxine abuse, when the pyridoxine was discontinued
early after neurological symptoms began [2].
My patients with CIAN did not undergo immunotherapy
early in their illness. It would have been very helpful if Dr
Kelly had provided some pertinent clinical data on his 2
patients, i.e., duration and stage of the disease when therapy
began, or any associated immune abnormalities or an accompanying motor deficit, masked within the clinical picture of
ataxia. In reference to the ataxia, it should be remembered
that some patients with dernyelinating neuropathies may
have, in addition to sensory araxia, a motor deficit caused by
involvement of the ventral roots in a form of chronic sensorimotor radiculoneuropathy with an ataxic component,
rather than pure CIAN; such patients more often respond to
immunotherapy 131.
In reference to the second point raised by Dr Kelly, I
strongly disagree. Ataxic neuropathy can be due to a variety
of different causes, as shown by Table 4 in my paper [I].
One such cause is the association with paraproteinemia of
any class. Paraproteinemic pol yneuropathies (PP) are clinically, electrophysiologically, irrmunologically, and histologically heterogeneous. In a recent review { 4 ] of 14 patients
with PP and monoclonal IgM, we found the following: (1)
in 6 patients who had demyelinating PP, the IgM reacted
with myelin-associated glycoprotein (MAG), but only 4 responded to therapy; (2) in 2 patients with dernyelinating PP,
the IgM reacted only with gangliosides but not MAG [ 5 ] ;
one responded to therapy; (3) in one patient with demyelinating PP who responded to therapy, the IgM did not
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