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Chronic motor neuropathies Diagnosis therapy and pathogenesis.

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Chronic Motor Neuropahes:
Diagnosis, Therapy, and Pathogenesis
Andrew J. Kornberg, MB BS, FRACP, and Alan Pestronk, M D
~~
~~~
Pure motor neuropathy syndromes resemble amyotrophic lateral sclerosis variants with no upper motor neuron signs.
Their identification is important, as, in contrast to amyotrophic lateral sclerosis, they are often immune mediated and
treatable. Typically the immune-mediated motor neuropathy syndromes are distal and asymmetrical and progress
slowly. The clinical features may help alert the clinician to the diagnosis, but other ancillary evidence such as abnormalities on electrophysiological testing and the presence of serum autoantibodies to neural antigens are helpful in making
the diagnosis more secure. Electrophysiological abnormalities include not only motor conduction block but also other
evidence of a demyelinative process such as prolonged distal latencies or F-wave abnormalities. High-titer anti-GM,
antibodies occur frequently but more specific patterns of reactivity may be especially helpful. Treatment of these
motor neuropathy syndromes includes cyclophosphamide, which we use in combination with plasma exchange, and
in some patients, human immune globulin. Clinical responses to therapy may occur within the first 2 to 4 months in
patients with motor neuropathy syndromes with demyelinative features, but only become obvious 6 months or later
after starting treatment in patients with predominantly axonal disorders.
Kornberg AJ, Pestronk A. Chronic motor neuropathies: diagnosis, therapy, and
pathogenesis. Ann Neurol 1995;37(S1):S43-S50
There is increasing evidence that some pure motor
neuropathy syndromes can be distinguished from
amyotrophic lateral sclerosis (ALS). Identification of
these motor neuropathy syndromes is important, as
they are often immune mediated and treatable, in contrast to ALS [l-61. The motor neuropathy syndromes
usually have characteristic, but not unique, patterns of
weakness and no upper motor neuron signs 171. Additional laboratory evaluation, including electrodiagnostic studies and measurement of serum autoantibodies,
is usually needed to clearly diagnose these syndromes
in individual patients. However, the methodology and
reliability of these laboratory tests are subjects of some
controversy. We review the motor neuropathy syndromes, their diagnostic work-up, and methods that
have been employed for their treatment.
Historical Aspects
The original descriptions of pure motor syndromes
without upper motor neuron signs were probably cases
of “progressive muscular atrophy” in the writings of
Duchenne, Aran, and others during the 19th century
[S-lO]. Benign focal motor neuron disorders, such as
monomelic amyotrophy, were subsequently reported
[1 1- 131. These syndromes were usually considered
variants of ALS, as early pathological studies suggested
that the primary focus of the disease was on cell bodies
in the ventral horn [141. The first full report of a paFrom the Department of Neurology, Washington University School
of Medicine, St. Louis, MO.
tient with a pure motor syndrome that was clearly due
to disease along the course of the axon appeared in
1782 1151. Pathological studies of this patient, with a
lower motor neuron (LMN) syndrome and a serum
IgM M protein, showed primary damage to motor axons rather than cell bodies. Descriptions of patients
with motor neuropathies diagnosed during life by electrodiagnostic testing were provided in 1986 and 1988
11, 16, 171. Nerve conduction studies showing blockade of impulses along the course of motor axons provided strong evidence that the primary site of disease
lay in the peripheral nerve rather than the cell body.
The phenomenon of conduction block in patients with
sensory-motor neuropathies (chronic inflammatory demyelinating polyneuropathy [CIDP)) had been described in 1982 [18). Conduction block was related to
focal regions of immune-mediated demyelination along
the course of the nerve. A 1986 report described a
patient with a LMN syndrome without conduction
block, but with a serum IgM M protein that bound to
GM, ganglioside [17]. In this instance the association
of the motor syndrome with an autoantibody directed
against a neural antigen suggested that the disorder
might be immune mediated. However, attempts at immunosuppression had no effect on the progressive disease in that patient. A clinical response to immunotherapy remains a “gold standard,” without which it is
difficult to argue that a syndrome is immune mediated.
Address correspondence to Dr Pestronk, Department of Neurology,
Box 8 111, Washington University School of Medicine, 660 South
Euclid, Sr. Louis, MO 63 110.
Copyright 0 1995 by the American Neurological Association
S43
In 1988, 2 patients with a multifocal motor neuropathy, motor conduction block, and serum IgM anti-GM,
antibodies were reported to improve after treatment
with cyclophosphamide { 11. Subsequent reports suggested that either motor conduction block or serum
anti-GM, antibodies alone could be markers for patients with LMN syndromes with a strong chance of
response to immunomodulating therapy 13, 5, 6).
Clinical Features
Immune-mediated motor neuropathies are usually
characterized by asymmetrical, slowly progressive
weakness, with histories extending 1 to 25 years 17).
The weakness most often begins distally, in the arms.
Males are affected 1.5 to 2 times as often as females.
The average age at onset is in the fifth decade, with a
range of 20 to 70 years. Physical examination reveals
asymmetrical weakness and atrophy. During the early
stages of the disease, weakness can appear focally, variably affecting muscles supplied by a single nerve. Patients may be misdiagnosed during this phase of the
disease as having nerve entrapment syndromes, and
undergo surgery 111. The presence of weakness in
muscles with normal bulk is a useful important clinical
finding that correlates with motor conduction block
without axonal loss 120, 21). With long-standing disease, muscle atrophy occurs along with axonal loss and
the pattern of weakness becomes more symmetrical
and generalized. Fasciculations are not uncommon 11,
161, and can add to the diagnostic confusion between
motor neuropathies and variants of ALS. In regions
with normal strength, tendon reflexes are often preserved. In areas of weakness, reflexes may initially be
normal, but often become reduced with progression of
the disease. Hyperreflexia and spasticity, typical of
ALS, virtually never occur with the motor neuropathies. Sensory symptoms and signs are usually absent
or clinically insignificant. When found they are usually
distal, symmetrical, and in a distribution different from
the motor loss. Rarely, patients have had cranial nerve
signs including external ophthalmoplegia and unilateral
tongue weakness and atrophy 14).
Electrophysiology
The most distinct electrodiagnostic finding in the motor neuropathies is focal blockade of impulse conduction along the course of motor, but not sensory axons
{I, 7, 17, 21-24]. Motor conduction block is probably
the major electrophysiological correlate of weakness
in dernyelinating polyneuropathies when there is no
associated axonal loss {20, 2 1, 257. Patients with a pure
motor disorder, as described already, and localized regions of motor conduction block can be diagnosed as
having the syndrome multifocal motor neuropathy
(MMN). The presence of conduction block, especially
at multiple sites, is often taken as evidence of the pres-
ence of an immune-mediated demyelinating disorder.
Recent pathological studies confirmed the idea that focal demyelination occurs at sites of conduction block
{21, 23, 261. The conduction block in MMN is
chronic, often remaining unchanged at the same site
for years. This suggests that immune processes not
only may cause the focal demyelination, but also may
prevent remyelination 123, 261.
Motor conduction block has been variably defined
as a 15 to 50% reduction in the compound muscle
action potential (CMAP) evoked from proximal compared to distal sites of stimulation {18, 20, 21,27-29}.
Conduction block may go undetected unless multiple
segments of several nerves are tested. Not all reductions of CMAP are attributable to conduction block.
Temporal dispersion and phase cancellation over long
nerve segments should be ruled out {20, 27-30}. The
finding of conduction block is most reliable when a
reduction in CMAP is 50% or more, focal, and present
in a distal segment of nerve other than one commonly
involved in entrapments, Other electrophysiological
signs of demyelination, such as prolonged distal latencies or slow conduction velocities, are less prominent
[7}, but can occur, in addition to the conduction block,
in MMN 124). Sensory conduction studies usually
show remarkably normal results, even when performed
over nerve segments with significant motor conduction
block 11, 7, 23, 24, 31).
In a majority of patients with distal, asymmetrical
LMN syndromes, conduction block cannot be detected. Other electrodiagnostic signs, such as prolonged distal latencies or F waves, may provide clues
to the presence of demyelination 13, 7). However, in
the majority of such patients there is only electrophysiological evidence of axonal loss. Distinction between a
motor neuropathy and an untreatable motor neuron
disorder (i.e., ALS variant) is then especially difficult
and may depend on other testing, such as measurement
of serum autoantibodies 13, 321, pathology evaluation
of nerve 1331, or therapeutic trials of human immune
globulin (HIG) or immunosuppressive medications.
Serum Autoantibodies
Numerous studies support the idea that motor neuropathy syndromes are often associated with high titers of
serum autoantibodies (Table 1) directed against GM,
ganglioside {l, 7, 22, 32, 34, 351. The initial recognition of serum IgM anti-GM, antibodies in patients with
MMN who improved after immunosuppressive therapy raised hopes that their measurement would provide objective diagnostic support for diagnosing treatable motor neuropathy syndromes [11. However,
issues of methodology, specificity, and sensitivity must
be resolved by clinical laboratories for simple quantitative measurements to be useful in any but the minority
of patients with very high titers of anti-GM, antibodies
544 Annals of Neurology Supplement 1 to Volume 37, 1995
Table 1 . Autoantibodies in Motor Neuropatbies
A. Positive enzyme-linked immunosorbent assay
1. High titers of serum IgM binding to GM, ganglioside (2 1:600) and NP-9 antigen (21: 2,500) with
low binding to histone H3 (low cross-reactivity {Cy]
ratio).
2. Very high titers of serum IgM binding to GM, ganglioside (21:6,000) with low binding to histone
H3.
3. Very high titers of serum IgM binding to asialoGM, ganglioside ( 2 1:6,000) with low binding to
histone H3.
4. Very high titers of serum IgG binding to GM,ganglioside (2 1: 1,000)with low binding to sulfatide.
B. Interpretation of positive results
1. Provide strong independent support for immunemediated motor neuropathies.
2. Distinguish these disorders from other polyneuropathies and amyotrophic lateral sclerosis.
3. Indicate that immunomodulating treatment may be
beneficial.
C. Guidelines during cyclophosphamide therapy
1. Aim for reduction of antibody titer to < 30% of initial level.
2. Serial titers help to determine appropriate dose and
likelihood of efficacy of immunosuppressive
treatment.
3. A rise in titer after treatment may be an early indicator of recurrence.
[22, 32, 34-36}. As individual laboratories tend to
develop their own distinctive methodology for measuring anti-GM, antibodies, interpretation must be based
on testing of both normal control subjects and patients
with a variety of disease syndromes. It is not sufficient
to define categories of results based simply on the
mean and standard deviation of titers in a few selected
sera.
In the interpretation of quantitative measurements
of IgM anti-GM, antibodies, results can be divided into
three categories. Titers of selective serum IgM binding
to GM, ganglioside above 1:6,000 have specificity for
distal, asymmetrical motor neuropathy syndromes, including MMN [7, 32, 34, 351. These very high titers
rarely occur in patients with ALS or polyneuropathies.
While titers in this range appear to have specificity,
they are not sensitive markers, as only 20 to 30% of
patients with MMN have titers in this range.
A second group of patients have titers of serum IgM
anti-GM, antibodies that are intermediately high,
above the normal range (2 1:400), but below 1:6,000.
Forty to 50% of patients with MMN have titers in this
range [7, 32, 371. However, these intermediate titers
have poor specificity for MMN as they also occur in
10 to 20% of patients with polyneuropathies, typical
ALS, and other disorders [7, 32, 34, 35, 381. Thus,
intermediately high titers may be helpful in certain
clinical situations [3} but are not diagnostic for MMN
or other potentially treatable motor neuropathies. Re-
sults in sera with titers in this range are also subject
to methodological variability. They are inconsistently
reported as positive or negative by different laboratories {32}.
A final, relatively large, group of patients have measurable serum IgM anti-GM, antibodies that are present only in low titer ( 5 1:400). There is general agreement that low titers of serum IgM anti-GM, antibodies
may occur in other neurological and immune disorders
and in normal subjects 134, 36, 38, 391. They have
little clinical significance.
In our laboratory we have found that testing sera for
IgM binding to two additional antigens, histone H 3
and NP-9, has much greater sensitivity and specificity
compared to quantitative measurement of anti-GM
antibodies alone [32}. Histone H 3 is a nuclear DNAbinding protein [40]. NP-9 is a lipid that copurifies
with myelin-associated glycoprotein during the initial
steps in its isolation [41). Sera with high titers of IgM
binding to both GM, and NP-9 antigen, but low binding to histone H3, have over 90% specificity for two
syndromes, MMN and distal asymmetrical LMN syndromes without conduction block C32). Less than 1%
of patients with other disorders, such as polyneuropathies, and none with classic ALS have had this pattern
of IgM binding. The specificity of this serum IgMbinding pattern in patients with MMN or distal LMN
syndromes without conduction block suggests that
these two syndromes are pathogenetically related motor neuropathies that are distinguishable from other
immune neuropathies and ALS. As a practical matter,
when this pattern of IgM binding is detected, additional electrodiagnostic studies searching for conduction block are indicated.
Other patterns of serum antibody reactivity occur
less frequently but also appear to have a high degree
of specificity for MMN and distal asymmetrical LMN
syndromes (see Table 1). These include selective, very
high titer (21:6,000) IgM binding to (1)GM, ganglioside and (2) asialo-GM, (GA,) ganglioside C6, 42).
High titers (> 1: 1,000)of selective serum IgG binding
to GM, ganglioside (with low binding to sulfatide) have
strong specificity for chronic, asymmetrical, distal LMN
syndromes without conduction block and acute axonal
motor neuropathies 1431. Overall, the finding of hightiter serum antibodies with any one of four specific
patterns of binding (see Table 1) provides strong independent support for the diagnosis of immune-mediated
motor neuropathy syndromes, helps to exclude other
neurological disorders such as polyneuropathies and
ALS, and indicates that immunomodulating treatment
may be beneficial.
,
Differential Diagnosis
The differential diagnosis of the motor neuropathies
includes demyelinating neuropathies on one hand, and
Kornberg and Pestronk: Chronic Motor Neuropathies S45
motor neuron disorders on the other. In some patients
motor neuropathies may appear similar to ALS with
predominantly LMN signs and axonal changes on electrodiagnostic studies [7, 15, 191. Certain features can
aid in the differentiation between these disorders (Table 2). Patients with motor neuropathies may have preserved reflexes in weak muscles, but hyperreflexia is
not noted. Overt spasticity and bulbar features are conspicuously lacking, as opposed to patients with ALS
who often have prominent upper motor neuron and
bulbar findings. The prolonged course that is often
noted in patients with motor neuropathies also helps
to differentiate them from most cases of ALS.
There is still some controversy as to whether MMN
is a motor variant of CIDP [44}. However, the differences in clinical, electrophysiological, and immunological features are more prominent than the similarities
(see Table 2). MMN commonly presents with distal
asymmetrical weakness while in CIDP, proximal symmetrical weakness is a more common finding [45, 461.
The remitting and relapsing course that can occur in
CIDP 145-47) is uncommon in the motor neuropathies. Patients with MMN rarely have significant sensory symptoms while in CIDP, sensory signs are the
rule 145, 461. Electrophysiological testing may show
conduction block in both conditions. However, other
features of demyelination such as prolonged distal latencies and slowed conduction velocities are more
prominent in CIDP {4S]. Abnormalities in sensory
nerve conduction studies are usually seen in CIDP
{45],but not in MMN, unless complicated by another
disease process. The spinal fluid examination shows
markedly increased protein concentration in the majority of patients with CIDP [45-471 while this change
is rare in patients with MMN [ l , 16, 17). High-titer
anti-GM, antibodies as well as more specific patterns
of autoantibody reactivity (see above) are common in
MMN [32l. In CIDP anti-GM, antibodies are unusual.
Serum autoantibody binding to tubulin is more common 1491. Finally, differences in the frequency of therapeutic response to prednisone and plasma exchange
(common in CIDP, but rare in motor neuropathies)
underscore a practical difference in the management
of the two disorders [ l , 2, 7, 50, 511.
Therapy
The decisions concerning whether to treat a patient
with a motor syndrome, and which immunomodulating
therapy to use, require analysis of clinical patterns of
disease and laboratory data, including electrodiagnostic
studies, serum autoantibodies, and response to therapeutic trials (Table 3). A benefit-risk analysis must be
carried out for each patient, as the significant costs or
potential side effects of therapy may weigh against
treatment in mildly affected patients. Recommendations are based on experiences with series of patients.
Because the motor neuropathies are relatively unusual,
controlled studies will be difficult to carry out.
The greatest clinical experience has been obtained
for patients with MMN syndromes that include both
conduction block and high titers of IgM anti-GM, antibodies (with or without testing for additional specificity). Treatment with cyclophosphamide El, 2 ) or HIG
[4-6, 521 is often followed by useful functional im-
Table 2. Motor Syndromes: Diagnostic Summary
Syndrome
Clinical
Electrophysiology
Serum Antibody
Therapy
MMN
Motor
Distal > proximal
Asymmetrical
Slowly progressive
Motor
Distal > proximal
Asymmetrical
Slowly progressive
Motor > sensory
Proximal + distal
weakness
Symmetrical
Progressive, stable, or
relapsing
Upper and lower motor
neuron
Distal + proximal
Asymmetrical
Bulbar findings
Conduction block
Axonal loss
2 Other evidence of
demyelination
Axonal loss
IgM vs GM, and NP-9
Low histone H 3 binding
Cyclophosphamide
HIG
IgM vs GM, and NP-9
Low histone H 3 binding
Cyclophosphamide
Asymmetrical conduction
slowing
Conduction block
Prolonged distal latencies
Abnormal F-wave
responses
Axonal loss
N o conduction block
IgM or IgG vs P-tubulin
Corticosteroids
Other immunosuppressive agents
Plasma exchange
HIG
Distal LMN
syndrome
CIDP
ALS
MMN = multifocal motor neuropathy; LMN = lower motor neuron; CIDP
amyotrophic lateral sclerosis; HIG = human immune globhn.
S46 Annals of Neurology Supplement 1 to Volume 37, 1995
=
chronic inflammatory demyelinating polyneuropathy; ALS
=
Table 3. Motor Syndromes: Likely Response to Treatment
to
Clinical Pattern of Weakness
Motor
Conduction
Block
Autoantibodies
GM,
Ganglioside
Evidence for
Response to
Therapya
Distal, asymmetrical
+
+
Strong
Distal, asymmetrical
-
-t
Moderate
Distal, asymmetrical
+
-
Distal, asymmetrical
Proximal
Distal upper motor neuron signs
-
-
Moderate, rule out
CIDP
None
None
None
Therapyb
CTX
HIG
CTX
??HIG
CTX
?Prednisone
"Evidence based on case reports and patient series.
bThe decision on whether to treat is also based on a benefit-risk ratio, determined in part by clinical severity of weakness and side effects of
medication.
CTX = cyclophosphamide; HIG = human immune globulin; CIDP = chronic inflammatory demyelinating polyneuropathy.
provement. Improvement in strength after treatment
with H I G (a total dose of 2.0-2.5 gmlkg given over
2-5 days) is common (50% of patients), but the length
of benefit is variable, lasting from 2 weeks to 6 months
or longer {4-6, 52). HIG should not be used in patients who are IgA deficient as hypersensitivity reactions to the IgA in H I G may occur 153). Common,
but relatively benign adverse effects include transient
headache and fever {53, 541. The great expense of
H I G mandates objective quantitative documentation
of any benefit to justify continued use. Further studies
are required to document the role of H I G over the
long term. It is unclear whether HIG treats the underlying pathogenic process in MMN. In some patients it
may produce symptomatic benefit while allowing progression of the underlying immune-mediated nerve
damage { 5 5 ] . Repeated doses of H I G may become less
effective with time.
Cyclophosphamide is the only immunosuppressive
medication that has been reported to induce long-term
benefit in many patients (50-80%) with MMN (1, 2).
Effective therapeutic regimens usually include relatively high doses that are necessary to reduce anti-GM,
antibody titers 11, 56). Unfortunately, the toxicity of
cyclophosphamide, especially the increased risk of neoplasia with high cumulative doses, limits its utility {5761). We originally used an initial dose of 3 gm/m2 over
8 days followed by chronic oral medication (100-150
mg/day for 6-12 months) 11, 2). Our more recent
experience suggests that monthly intravenous cyclophosphamide (1 gm/m2), preceded on each occasion
by plasma exchange on two consecutive days, is equally
effective, has fewer adverse effects, and utilizes a 50
to 70% lower cumulative dose of drug 131. We added
plasma exchange to optimize any immunosuppressive
effects of cyclophosphamide, theoretically focusing cytotoxic drug effects at a time when B cells are stimulated by reduction of serum autoantibody levels 154,
62, 63). Treatment is stopped after 8 months, serum
anti-GM, antibodies are reduced to less than 30% of
initial titers for 2 to 3 months, or clear sustained improvement in strength can be documented. Improvement in strength may continue for another 6 to 12
months. Remission usually persists for at least 1 to
2 years, even when patients are off all medications.
Antibody titers may then rise, and weakness recur. Retreatment may then be necessary.
There are relatively few descriptions of effects of
treatment for patients with MMN with conduction
block but without anti-GM, antibodies { S , 643. H I G
infusion was followed by improvement in strength in
some patients E5). Prednisone, which only rarely produces benefit for patients with the full syndrome of
MMN with anti-GM, antibodies 11, 2, 71, is also unlikely to be effective in this group. Two patients improved after treatment with high doses of cyclophosphamide (643.
The decision concerning whether to treat patients
with distal, asymmetrical LMN syndromes without
conduction block is often difficult. The presence of
serum anti-GM, antibodies, especially with the specific
patterns of serum binding outlined here, or some
pathological (3 3) or electrodiagnostic evidence of segmental demyelination are useful indications that a motor syndrome may be immune mediated C71. Measurable improvement after treatment with HIG, although
unusual in this group (521, may provide support for
additional immunotherapy, with agents such as cyclophosphamide, or further periodic H I G infusions. Studies that evaluated the effects of cyclophosphamide
treatment for patients with LMN syndromes over short
periods of time, up to 6 months, failed to find evidence
of benefit 164). We treated 4 patients with progressive,
distal asymmetrical LMN syndromes and high titers
of serum IgM anti-GM, antibodies using the plasma
exchange plus cyclophosphamide protocol outlined for
Kornberg and Pestronk: Chronic Motor Neuropathies S47
MMN. All these patients showed progressive improvement in strength over the 6 to 24 months following
treatment. Initial benefit began as late as 6 to 9 months
after the onset of treatment and persisted for 1 to 2
years, or longer, after treatment was stopped {3).
There is no convincing evidence that immunomodulating therapy of any kind alters the progression of
disability in patients with motor syndromes that include upper motor neuron signs {65-67).
Pathogenesis of Motor Neuropathies
The original descriptions of patients with LMN syndromes and motor neuropathies associated with serum
IgM binding to GM, ganglioside {I, 191led to speculation that these antibodies may play a pathogenic role.
Gangliosides are a family of acidic glycolipids composed of lipid (ceramide) and carbohydrate moieties
with sialic acid {68). The abundance of gangliosides in
neuronal membranes, the extracellular location of their
carbohydrate epitopes, and their role in membrane and
cellular functions {68-70) made it attractive to speculate that they may be targets of pathogenic antibodies
in MMN and other motor syndromes. There is circumstantial evidence supporting the pathogenicity of antiGM, antibodies. This evidence includes a clinical correlation of improvement in strength with falling serum
titers after immunosuppressive treatment { 1, 2). Some
sera containing IgM antibodies against GM, bind to
the nodes of Ranvier 171, 721, nerve [73}, spinal cord,
and motor neurons 174). If the blood-nerve barrier
remains impaired at focal regions along the nerve, demyelination could be induced, and remyelination impaired {75}. When passively transferred to peripheral
nerves in animals in vivo, some of these sera can produce motor conduction block on electrophysiological
testing {76-781. Further elucidation of the fine specificity and cross-reactivity of the anti-GM, antibodies
to other gangliosides has determined that the terminal
disaccharide moiety on GM,, Gal(Pl-3)GalNAc, is the
target for some of the anti-GM, antibodies {79-82).
Other sera recognize different, or larger, carbohydrate
epitopes on GM, [7, 831. The lipid moiety on GM,
also can play a role in its antigenicity 137). Immunization of rabbits with GM, or some of its carbohydrate
moieties produced an autoimmune neuropathy with
similarities to MMN 1841. However, most anti-GM,
antibodies that are induced by immunization do not
appear to be pathogenic [85}. This observation suggests that other factors in serum, possibly with crossreactivity to GM,, may turn out to be pathological
factors {78), or that fine specificities of the antibodies
govern whether they are pathogenic {86}.The interesting predilection for motor axons in MMN may also
depend on fine specificities of anti-GM, antibodies.
Human anti-GM, autoantibodies have been shown to
bind preferentially to motor neurons and motor nerves
S48
and not to sensory neurons {73,74).There are measurable differences in the ganglioside compositions of motor and sensory nerves 187, 881.
summary
Immune-mediated motor neuropathies are most often
disorders manifest clinically by slowly progressive,
asymmetrical, distal weakness, starting in the hands
more often than the legs. In some patients electrophysiological findings show multifocal conduction block
along the length of motor axons. Other patients have
findings consistent with only axonal loss. Laboratory
test results are unremarkable except for high-titer serum autoantibodies to GM, and other neural antigens.
Diagnosis of immune-mediated motor neuropathies
provides an opportunity for effective immunomodulating therapy that can significantly improve quality of
life in affected patients. The identification of antigenic
targets of serum autoantibodies in patients with motor
neuropathies lends hope that immunotherapies to specifically treat the autoimmune disorder can be developed.
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S50 Annals of Neurology Supplement 1 to Volume 37, 1995
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