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Demyelinating Neuropathy in Diabetes Mellitus
Khema R. Sharma, MD;
John Cross, MD;
Oscar Farronay, MD;
D. Ram Ayyar, MD;
Robert T. Shebert, MD;
Walter G. Bradley, DM, FRCP
Arch Neurol. 2002;59:758-765.
ABSTRACT
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Background Recent studies have reported that patients with diabetes mellitus (DM)
have a predisposition to develop chronic inflammatory demyelinating polyneuropathy
(CIDP).
Objectives To determine whether patients with DM have a polyneuropathy fulfilling
electrophysiologic criteria for CIDP, and whether CIDP is more frequent in
patients with type 1 than in patients with type 2 DM.
Methods We prospectively studied the frequency of electrophysiologic changes
meeting the criteria for CIDP in patients with DM seen in our electrophysiology
laboratory during a 51-month period (period 1). To evaluate the relationship
between DM and CIDP, we prospectively determined during a 14-month period
(period 2) the frequency of DM in patients seen in our electrophysiology laboratory
with other neuromuscular diseases, and the frequency of idiopathic CIDP.
Results During period 1, 120 patients with DM met the electrophysiologic criteria
for CIDP (DM-CIDP). The most frequent clinical features of DM-CIDP were those
of a predominantly large-fiber sensorimotor neuropathy, with recent motor
deterioration and a moderately increased cerebrospinal fluid protein concentration.
Twenty-six of the 120 patients were given intravenous immunoglobulin (400
mg/kg per day for 5 days), and 21 patients (80.8%) had significant improvement
in the neurologic deficit at the end of 4 weeks of therapy. The DM-CIDP occurred
equally in type 1 and type 2 DM. During period 2, 1127 patients were seen.
Of these, 189 (16.8%) had DM with various neurologic disorders, including
32 patients (16.9%) with DM-CIDP. Among the remaining 938 patients without
DM, 17 (1.8%) had idiopathic CIDP. The odds of occurrence of DM-CIDP was 11
times higher among diabetic than nondiabetic patients (P<.001).
Conclusions Demyelinating neuropathy meeting the electrophysiologic criteria for
CIDP occurred in both types of DM, and its occurrence was significantly higher
in diabetic than in nondiabetic patients.
INTRODUCTION
PERIPHERAL neuropathies of several types are common in diabetes mellitus
(DM),1 including symmetric sensorimotor polyneuropathy,
single or multiple mononeuropathy, autonomic neuropathy, truncal radiculopathy,
plexopathy, and proximal motor neuropathy. Pathological studies of diabetic
nerves have shown segmental demyelination,2-3
in addition to axonal loss,1 vasculopathy,
and inflammatory infiltrates.4-12
Peripheral sensorimotor demyelinating neuropathy indistinguishable from idiopathic
chronic inflammatory demyelinating polyneuropathy (I-CIDP) has been reported
in patients with both type 1 and type 2 DM by some authors,13-25
but not by others.26-28
We shall apply the term DM-CIDP to patients with
both conditions. Patients with diabetic neuropathies have been reported to
respond to various therapies directed at immunologic disorders.8-9,11, 14, 16-25
Thus, it is unclear whether CIDP occurs more frequently than would be expected
by chance in DM, and whether the clinical characteristics of the neuropathy
in patients with DM-CIDP differ from those in patients with "pure" diabetic
neuropathy. To answer these questions, we have compared the frequency of DM
in CIDP with that in other neuromuscular disorders in a population of patients
seen in our electrophysiology laboratory, and compared the characteristics
of DM-CIDP with those of I-CIDP.
PATIENTS AND METHODS
PATIENT SELECTION
All patients with peripheral sensorimotor neuropathy related to DM,
referred for electrophysiologic (EP) examination to the Neurology Electrophysiology
Laboratory at University of Miami–Jackson Memorial Medical Center, Miami,
Fla, between June 1, 1996, and August 31, 2000 (period 1), were examined prospectively.
Exclusionary criteria were a clinical picture of diabetic amyotrophy or lumbosacral
plexopathy; a typical picture of diabetic chronic distal sensory neuropathy,
unless there were new symptoms of progressive weakness involving proximal
and distal muscles; concomitant disease (paraproteinemia, endocrinopathy other
than diabetes, connective tissue disorder, vitamin B12 and folic
acid deficiency, heavy metal intoxication, human immunodeficiency virus infection,
hepatitis, Lyme disease, cancer, and kidney failure); or a family history
of neuropathy.
To evaluate the relative frequency of I-CIDP and DM-CIDP, and the relative
frequency of DM in other neuromuscular diseases, we prospectively obtained
data to determine the total number of patients with each condition seen in
our electrophysiology laboratory between July 1, 1999, and August 31, 2000,
and whether they had DM (period 2).
DIAGNOSTIC CRITERIA FOR DM-CIDP
Patients underwent EP testing to evaluate whether the peripheral neuropathy
was predominately demyelinating and met the EP criteria for the diagnosis
of CIDP. The criteria were based on those recommended by the American Academy
of Neurology (AAN) Ad Hoc Subcommittee AIDS Task Force 1991,29
except that the criteria for partial conduction block were more stringent,
as recommended by the American Association of Electrodiagnostic Medicine30 and other investigators.24, 31
As recommended by Saperstein et al,32 we did
not require cerebrospinal fluid (CSF) examination and sural nerve biopsy.
We did adopt more stringent diagnostic criteria for CIDP (modified from AAN
199129; see next paragraph).
The diagnosis of diabetic demyelinating peripheral neuropathy was established
by (1) the presence of proved DM33; (2) the
presence of a chronic, progressive or relapsing, motor, sensory, or sensorimotor
polyneuropathy of at least 2 months' duration associated with hyporeflexia
or areflexia; and (3) EP criteria for demyelinating neuropathy as defined
by the AAN Ad Hoc Subcommittee on AIDS29 and
adapted by the American Association of Electrodiagnostic Medicine.30 Partial conduction block
was diagnosed when the amplitude and area of the compound muscle action potential
(CMAP) were decreased by more than 50% on proximal compared with distal stimulation
across a standard peripheral nerve segment, when the distal CMAP amplitude
was greater than 1 mV, and the duration was increased by less than 30% of
the distal CMAP amplitude duration. Abnormal temporal dispersion was diagnosed when the proximal CMAP duration was increased by more
than 30%, but where the proximal CMAP amplitude and area were not decreased
by more than 50% across a standard peripheral nerve segment with a distal
CMAP amplitude of more than 1 mV. For patients without partial conduction
to be diagnosed as having a demyelinating neuropathy, they were required to
have all 3 of the following abnormalities: (1) prolonged distal motor latency
(as defined in the AAN 1991 criteria for CIDP29)
in at least 2 motor nerves; (2) slowed conduction velocity (as defined in
the AAN 1991 criteria for CIDP29) in at least
2 motor nerves; and (3) delayed (as defined in the AAN 1991 criteria for CIDP29) or absent F waves in at least 2 motor nerves.
NEUROLOGIC ASSESSMENT
All patients had quantitative evaluation by means of the Neuropathy
Impairment Score (NIS),34 which summates deficits
in strength, sensation, and reflexes found on neurologic examination. Deficits
in strength were scored from 1 (25% deficit) to 4 (100% deficit); deficits
in sensation and reflexes were scored as 0 (no deficit), 1 (decreased function),
or 2 (absent function). The neuropathy severity was graded as mild with an
NIS score of 15 to 25, moderate with an NIS score of 26 to 50, and severe
with an NIS score of higher than 50.
EP STUDIES
Nerve conduction and electromyographic studies were performed in at
least 3 limbs, which included 1 affected and the contralateral limb, by means
of standard techniques. If 2 limbs were affected, a 4-extremity study was
performed. We measured motor nerve conduction and corresponding F waves in
4 or more of the following nerves: tibial, peroneal, median, and ulnar. The
radial motor nerve was studied in patients in whom the median and ulnar motor
responses could not be obtained, or were less than 1 mV because of associated
compressive neuropathies. The radial nerve was stimulated by the near nerve
needle electrode technique distally in the forearm, at the elbow, and at midarm,
recording over the extensor indicis muscle. Similarly, the sciatic nerve,
stimulated at the popliteal fossa and gluteal fold by near nerve needle stimulation
with recording over the medial gastrocnemius muscle, was studied in patients
in whom the distal tibial motor response could not be obtained or was less
than 1 mV. Needle electromyography was performed in affected limbs. The skin
temperature was maintained above 32°C in the upper extremities and above
31°C in the lower extremities.
LABORATORY EVALUATION
All patients underwent screening laboratory examination, including anti-GM1
and anti–myelin-associated glycoproteins antibody titers and glycosylated
hemoglobin level. A CSF examination, including cell count, glucose level,
protein level, and IgG index, was performed in 49 patients. No patient had
a nerve biopsy (reasons as described in the "Comment" section).
STUDY DESIGN FOR A SUBGROUP OF PATIENTS FOR INTRAVENOUS IMMUNOGLOBULIN
THERAPY
The details of design for this component of the study are reported elsewhere.35 In brief, the study was a 4-week, open-label pilot
study of intravenous immunoglobulin with serial quantitative measures of neurologic
impairment. The primary outcome measure in this study was changes from baseline
to 4 weeks in mean NIS. We defined the criterion indicating improvement as
more than a 5-point decrease in NIS.36-37
STATISTICAL ANALYSIS
StatView II (Abacus Concepts Inc, Berkeley, Calif) was used for data
analysis. We determined the statistical significance of differences between
categorical variables by means of a  2 or Fisher exact test
as appropriate and for differences between continuous variables by means of
2-tailed paired or unpaired t test. All data are
expressed as mean ± SD. The data were adjusted for multiple comparisons
(Bonferroni correction). Statistical significance for all analyses was defined
as P<.05.
RESULTS
PERIOD 1
We identified 120 patients with DM who met the EP criteria for demyelination
during the period from June 1, 1996, to August 31, 2000.
Clinical Features
The main clinical features of these 120 patients (Table 1) were sensory symptoms, limb weakness, pain, and poor balance.
Sensory symptoms were present initially in 112 patients (93.3%). Pain was
a prominent symptom in 49 patients (40.8%); it took the form of aching to
sharp pain in 34 and burning dysesthesia in 15. All the patients had weakness
in both upper and lower limbs, and of those, one third had greater proximal
than distal weakness, typical of CIDP. Poor balance was a predominant symptom
in 6 patients (5.0%). Six patients (5 with type 2 DM) had a preexisting predominantly
sensory peripheral neuropathy of 4 to 7 years' duration before the onset of
the new symptoms of progressive weakness of extremity muscles. The mean motor
deficit score was 22.7 ± 15.3 (range, 10-83). The combined (sensory
and motor deficit) mean NIS score was 41.3 ± 21.2 (range, 20-125).
The motor deficit score was higher than the sensory deficit score in 106 patients,
lower than the sensory score in 10 patients, and equal in 4 patients. Among
the 10 patients with higher sensory deficit scores, 6 patients presented with
poor balance.
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Table 1. Clinical Features and Laboratory Data for 120 Patients*
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The spectrum of neuropathy severity in our patients varied from mild
(45 patients), to moderate (44 patients), to severe (31 patients). Sixty-four
patients (53.3%) were able to walk without aids, 15 (12.5%) required a cane
for walking, 20 (16.7%) needed a walker, and 21 (17.5%) required a wheelchair.
One hundred one patients had adult-onset DM, with disease duration of
10.5 ± 9.2 years (range, 0-40 years), requiring insulin in 6, insulin
plus oral hypoglycemic agent in 25, oral hypoglycemic agent alone in 66, and
diet control alone in 4. Nineteen patients had juvenile-onset DM requiring
insulin, with disease duration of 21.8 ± 9.2 years (range, 4-40 years).
The patients with type 1 DM were younger (45.0 ± 11.9 years [range,
18-63 years]) and had a longer disease duration (21.8 ± 9.2 years [range,
4-40 years]) than those with type 2 DM (age: 61.0 ± 11.3 years [range,
40-90 years], P<.01; duration: 10.5 ± 9.2
years [range, 0-40 years], P<.01). There was no
difference between the patients with type 1 and 2 DM with respect to sex ratio,
glycosylated hemoglobin percentage (8.9% ± 2.5% [range, 5.1%-14.8%;
reference value, <6%] vs 8.2% ± 1.8% [range, 5.8%-13.5%], respectively; P = .11), disability (NIS, 40.2 ± 27.5 [range, 21-92]
vs 33.1 ± 23.6 [range, 20-125]; P = .25),
nerve conduction abnormalities (conduction block: 9 of 19 patients with type
1 DM vs 39 of 101 with type 2; P = .21), and CSF
protein level. The CSF protein level was increased (103 ± 48.2 mg/dL
[range, 40-258 mg/dL]) in all but 1 of the 49 patients who had a CSF examination.
The results of CSF cell count and IgG index were normal in these patients.
EP Studies
Nerve conduction study findings are summarized in Table 2. All patients fulfilled at least 3 of the 4 criteria for
demyelination (conduction block, prolonged distal motor latency, slowed conduction
velocity, delayed or absent F waves), but there was a wide range of EP abnormalities
(Table 3). A total of 630 motor
nerves were examined (Table 2,
which does not include details of 8 facial nerves studied; Table 3). Distal latencies were prolonged in 292 (46.3%) of 630
nerves tested; conduction velocity was slowed in 375 (59.5%) and F waves were
prolonged or absent in 445 (70.6%; Table
3). Partial conduction block was demonstrated in at least 1 nerve
in 48 of the total 120 patients (40.0%; Table 3). Temporal dispersion was observed in at least 1 nerve in
58 patients (48.3%; 46 patients had type 2 DM), and 16 of these patients with
temporal dispersion also had associated partial conduction block (Table 3). The mean summated CMAP amplitude
(normalized for number of nerves studied in a patient) tended to be higher
in patients with conduction block (5.4 ± 2.0 mV) than in patients without
conduction block (4.4 ± 1.6 mV; P = .049).
There was no difference in motor deficit score between those with (43.5 ±
24.1) and those without (40.0 ± 19.4) conduction block (P = .4). Linear regression analysis showed a significant inverse correlation
(r = -0.4, P = .006)
between the summated CMAP amplitude and the motor deficit score in patients
with and without conduction block. Conduction block occurred equally among
patients with mild (21 of 45 patients [46.7%]), moderate (16 of 44 patients
[36.4%]), and severe (11 of 31 patients [35.5%]) neuropathy (P = .51).
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Table 2. Results of Electrodiagnostic Studies*
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Table 3. Summary of Abnormal Nerve Conduction Findings*
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Response to Intravenous Immunoglobulin
The details of the results are reported elsewhere.35
In brief, the average NIS of the 26 patients improved significantly from baseline
(59.6 ± 26.7; range, 25-125) to 4 weeks after the intravenous immunoglobulin
therapy (33.0 ± 29.6; range, 3-119; P<.001).
The improvement in NIS (motor component) was observed on the third day of
the treatment in 3 patients (11.5%), on the fifth day of the treatment in
4 patients (15.4%), and after the completion of the 5-day course in the remainder.
In 21 (80.8%) of the 26 patients, the improvement in NIS was more than 5 points
after 4 weeks. There was significant (P = .01) improvement
in lower limb motor function 4 weeks after the intravenous immunoglobulin
therapy compared with baseline as indicated by the number of patients in the
following groups: able to walk without aid (13 of 26 patients [50.0%] at 4
weeks vs 30.8% at baseline), requiring an aid to walk (10 of 26 patients [38.5%]
vs 19.2% at baseline), and requiring a wheelchair (3 of 26 patients [11.5%]
vs 50% at baseline). A greater proportion of patients with conduction block
(11 of 11) showed an improvement in NIS in response to the intravenous immunoglobulin
therapy than of those without conduction block (10 of 15; P = .03). Similarly, relapses occurred less often in the responders
with conduction block (1/11 [9.1%]) than in responders without conduction
block (5/10 [50.0%]; P = .04). Twenty-one (80.8%)
of the 26 patients who responded to intravenous immunoglobulin treatment were
followed up for a mean duration of 26 ± 10.6 (range, 1-42 months).
Fifteen of the patients had no relapse of the DM-CIDP and required no further
immunotherapy. Six patients had a relapse of the DM-CIDP from 9 to 19 months
after initial intravenous immunoglobulin treatment. Intravenous immunoglobulin
therapy was generally well tolerated. Three patients (11.5%) developed a reversible
decrease in renal function.
PERIOD 2
Relative Frequency of I-CIDP and That Associated With Types 1 and 2
Diabetes
During period 2, 1127 patients were seen in our electrophysiology laboratory.
Of these, 189 (16.8%), 15 with type 1 diabetes and 174 with type 2, had DM
with various neurologic disorders. Of these 189, 32 (16.9%) had DM-CIDP. The
proportion of patients with DM-CIDP was not different in type 1 (4/15 [26.7%])
and type 2 (28/174 [16.1%]; P = .49) diabetes. Among
the 938 patients without DM, 17 (1.8%) had I-CIDP. Looked at another way,
during period 2 a total of 49 patients meeting EP criteria for CIDP were seen,
of whom 32 (65.3%) had associated DM. The odds of the occurrence of CIDP was
11 times higher in patients with DM than in patients without DM (odds ratio,
11.04; 95% confidence interval, 6.1-21.8; P<.001).
Frequency of Diabetes in Various Neuromuscular Diseases
During period 2, 9 (7.5%) of the 120 patients with amyotrophic lateral
sclerosis (ALS) (definite, 85; probable, 35)38
had DM, and 9 (6.6%) of 136 patients with myasthenia gravis (MG) had DM. The
odds of the occurrence of DM in patients with CIDP was more than 20 times
higher than that in patients with MG (odds ratio, 28.2; 95% confidence interval,
10.7-76.9; P<.001) and in those with ALS (odds
ratio, 24.7; 95% confidence interval, 9.3-67.4; P<.001).
There was no age difference among the patients with ALS (63.0 ± 12.5
years; range, 32-86 years), the patients with MG (60.0 ± 18.3 years;
range, 15-90 years), and all the patients (n = 49) with demyelinating peripheral
neuropathy meeting EP criteria for CIDP (56 ± 13.8 years; range, 18-90
years; P = .06). Similarly, there was no difference
among these 3 groups with respect to the sex ratio.
COMMENT
The main focus of this study was on the EP abnormalities and clinical
profile of patients with DM. We did not require CSF examination or sural nerve
biopsy, and we agree with the recommendations of Saperstein et al.32 The CSF protein level is increased in a significant
proportion of patients with other types of diabetic neuropathy (axonal neuropathy
or lumbosacral plexopathy)9, 11-12
and is normal in a significant proportion (10%-21%) of patients with I-CIDP.22, 32, 39-40 Sural
nerve biopsy abnormalities as criteria for demyelination lack sensitivity
and specificity (40%-50%),32, 39-41
and endoneurial inflammatory infiltrates (mononuclear cells) occur infrequently
(7%-18%)22, 39, 42
Dyck et al40 coined the term CIDP for a large cohort of patients (N = 53) with a clinical picture
of a predominantly motor symmetric weakness, proximal and distal, associated
with hyporeflexia or areflexia and a relapsing or a chronic progressive course.
After this initial report, although often considered under the rubric of CIDP,
many subtypes of CIDP have been reported,22, 29, 32, 42
including our recently published review of the atypical cases of CIDP,24 suggesting that the spectrum of CIDP is much broader
than the restrictive one initially proposed from the point of view of the
presence of pain, asymmetry, radicular distribution, etc. In this study, we
have restricted inclusion of cases to those fulfilling the clinical criteria
recommended by the AAN Ad Hoc Committee,29
and we have adopted more stringent EP criteria for the diagnosis of CIDP (see
the "Patients and Methods" section). All patients had motor involvement, 94%
involving proximal muscles to some extent (Table 1). Sensory symptoms were present in 93% of cases, including
pain in feet and hands in 41% of cases. Pain is not a major symptom in patients
with I-CIDP; the occurrence of pain in hands and feet varies from 3% to 42%,22, 39-40 and radicular pain
or truncal numbness varies from 6% to 7.5%.22, 40
We found that 16.9% of patients with DM met the EP criteria for CIDP,
which occurred equally frequently in patients with type 1 and type 2 DM. The
odds of the occurrence of CIDP were 11 times higher in diabetic than nondiabetic
patients. We also found that the odds for the occurrence of DM among patients
with CIDP were more than 20 times higher than in patients with MG and in those
with ALS. Diabetes mellitus (especially type 1) has been associated with MG,43 the reported frequency ranging from 0.6% to 7%,44-47 which
is similar to that found in our study (6.6%). The frequency of DM in patients
with ALS has been reported to be from 2.1% to 28.9%,48-51
which compares with 7.5% in our study.
However, our study has limitations due to the potential bias of patient
referral. Most of the patients referred to our tertiary care center laboratory
had a severe neuropathy. We probably saw few patients with DM and typical
peripheral predominantly sensory polyneuropathy, since most of these patients
probably do not undergo electroneurophysiologic examination. Many of our patients
presented with worsening motor weakness, frequently proximal in distribution,
suggesting the possible diagnosis of CIDP. Nevertheless, the very high frequency
of CIDP in patients with DM, and vice versa, is striking, and we do not believe
that selection bias can explain the observation that DM was much more frequent
in CIDP than in MG and ALS. The frequency of DM in patients with MG and ALS
in our study population was similar to that observed in population-based case-control
epidemiologic studies.44-46,48, 51
We found that DM-CIDP occurred equally in patients with type 1 and type
2 diabetes. While our study is potentially subject to referral bias, the proportion
of cases with type 1 and type 2 diabetes was similar in our study to that
in the US diabetic population.52 Selection
bias may explain to some extent the results of previous reports of a preponderance
of either type 1 DM11, 13-14
or type 2 DM15-18
with demyelinating neuropathies, or the report that demyelinating neuropathy
is rare in DM.27
Miyasaki et al53 studied the specificity
of EP diagnostic criteria for CIDP in 543 patients (307 male; age, 60.4 ±
11.1 years) with diabetic neuropathy. There were 169 patients with moderate
to severe neuropathy. Among these 169 patients, 20 (11.8%) met the EP criteria
for CIDP. They concluded that demyelinating peripheral neuropathy meeting
EP criteria for CIDP is not rare in diabetic patients.
Our data demonstrated that a subgroup of patients (16.9%) with DM have
a predominantly demyelinating peripheral neuropathy. Many of these patients
(40.0%) had conduction block. Previous reports of EP studies in diabetic neuropathy
have varied from no conduction block,28 or
its rare occurrence,27 to the frequent finding
of conduction block.9, 11, 15-17,19, 24, 53
In these studies, conduction block was defined as a greater than 20% decline
in proximal CMAP compared with distal, with less than 15% increase in CMAP
duration in the proximal CMAP.29 We have adopted
the stricter criteria recommended by Cross et al,15
Rotta et al,24 and Notermans et al,54 defining conduction block as at least a 50% decline
in proximal CMAP compared with distal, with less than 30% increase in CMAP
duration with proximal stimulation. Conduction block has been correlated with
segmental demyelination in pathological studies.55
The 2 main pathophysiologic mechanisms proposed for diabetic neuropathy
are nerve ischemia (microangiopathy) and metabolic derangement of nerves.
However, DM is one of the group of autoimmune disorders,43, 56
and there is growing evidence that immune and inflammatory processes play
a role in some of the neuropathies occurring in DM, including demyelinating
polyneuropathy.1, 6-15,57-69
Mitchell et al7 reported finding major histocompatibility
class II antigen expression on Schwann cells, similar to that found in I-CIDP,
in the nerves of patients with diabetic amyotrophy. Younger et al8 found that up to 60% of sural nerve biopsy specimens
from 20 diabetic patients with various types of neuropathy had lymphocytic
microvasculitis or perivasculitis, and endoneurial T-cell infiltrates, with
increased expression of tumor necrosis factor  , cytokines, and components
of the membrane attack complex. Several studies have suggested that autoantibodies
directed against phospholipid,65-66
gangliosides,66 sulphatide,65
nerve growth factor,63 and advanced glycation
end products67-68 may play a role
in the pathogenesis of diabetic neuropathy.
Immunotherapy, including intravenous immune globulin, has been shown
to be effective in some patients with several types of diabetic neuropathy.8-9,11, 14, 16-25
Menkes et al23 reported that 8 (25.8%) of 31
patients with acquired demyelinating polyneuropathy had DM and that, although
these patients were thought to have untreatable "axonal diabetic neuropathy,"
all responded to immunotherapy.23 In our study,
26 patients, all but 1 of them with type 2 DM, were treated with intravenous
immunoglobulin, and 21 of them improved.35
The mechanism of action of intravenous immunoglobulin in treating the autoimmune
disorders is uncertain. Proposed mechanisms include the neutralization of
the pathogenic antibodies by anti-idiotype antibodies,70
attenuation of complement-mediated tissue damage,71
and saturation or functional blockade of Fc receptors on macrophages that
are the major effectors of demyelination.72-74
Other mechanisms may include the functional modulation of T lymphocytes and
their production of proinflammatory cytokines,75
and the binding of anti-idiotypic antibodies to antigen receptors on B cells,
thus decreasing autoantibody production.76
It is likely that several of these mechanisms contribute to the short-term
and long-term effects of intravenous immunoglobulin therapy in many autoimmune
diseases. The results presented in this article support the contention that
DM-CIDP responds as well as I-CIDP to intravenous immunoglobulin therapy,
although a controlled trial will be needed to prove this. While therapeutic
response cannot be used to prove a pathophysiologic mechanism, it provides
further supporting evidence for the autoimmune hypothesis of the occurrence
of DM in CIDP.
AUTHOR INFORMATION
Accepted for publication December 14, 2001.
Author contributions: Study concept and design (Drs Sharma and Farronay); acquisition of data (Drs Sharma, Cross, Farronay, Ayyar, and Shebert); analysis and interpretation
of data (Drs Sharma, Farronay, and Bradley); drafting
of the manuscript (Drs Sharma, Farronay, and Bradley);
critical revision of the manuscript for important intellectual content (Drs Sharma, Cross, Farronay, Ayyar, Shebert, and Bradley);
statistical expertise (Dr Sharma); administrative,
technical, or material support (Drs Sharma, Cross, Farronay,
Ayyar, Shebert, and Bradley); study supervision (Drs Sharma and Bradley).
This study was presented in part at the 51st annual meeting of the American
Academy of Neurology, Toronto, Ontario, April 20, 1999.
We thank Robert C. Duncan, PhD, and Mauricio Concha, MD, who kindly
provided guidance for data analysis, and Regina Menendez-Choy for help in
preparation of the manuscript.
Corresponding author and reprints: Khema R. Sharma, MD, Department
of Neurology, University of Miami School of Medicine (M740), 1150 NW 14th
St, Room 603, Miami, FL 33136 (e-mail: ksharma{at}med.miami.edu).
From the Department of Neurology, University of Miami School of Medicine,
Miami, Fla.
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