Beruflich Dokumente
Kultur Dokumente
Peripheral Neuropathy Research Laboratory, Mayo Clinic, 200 First Street SW,
Rochester, Minnesota 55905, USA
2
Department of Neurology, Mayo Clinic and Mayo Foundation,
Rochester, Minnesota 55905, USA
Accepted 3 December 2001
Distinct clinical and pathological varieties of neuropathy are associated with diabetes mellitus. Although diabetic lumbosacral radiculoplexus neuropathy (DLRPN) is not the most common type of
diabetic neuropathy, it undoubtedly causes major
suffering among those affected. It is a devastating
Abbreviations: CASS, composite autonomic severity score; CSF, cerebrospinal fluid; DLRPN, diabetic lumbosacral radiculoplexus neuropathy;
EMG, electromyography; IVIg, intravenous immunoglobulin; LRPN, nondiabetic lumbosacral radiculoplexus neuropathy; NIS, neuropathy impairment score; RDNS, Rochester Diabetic Neuropathy Study
Key words: diabetic amyotrophy; diabetic lumbosacral radiculoplexus
neuropathy; lumbosacral plexopathy; lumbosacral radiculoplexus neuropathy; microvasculitis; necrotizing vasculitis; peripheral neuropathy
Correspondence to: P.J.B. Dyck; e-mail: dyck.pjames@mayo.edu
2002 Wiley Periodicals, Inc.
Published online 25 February 2002 in Wiley InterScience (www.interscience.
wiley.com). DOI 10.1002/mus.10080
Lumbosacral Plexopathy
condition that usually affects otherwise asymptomatic people. Diabetic lumbosacral radiculoplexus neuropathy causes severe lower-limb pain and weakness,
and, although monophasic, morbidity is prolonged.
It has been known by many names including the
BrunsGarland syndrome,5,11 diabetic myelopathy,26
diabetic amyotrophy,24,25 diabetic mononeuritis
multiplex,40,41 diabetic polyradiculopathy,6 femoral
or femoralsciatic neuropathy of diabetes,9,44 diabetic motor or paralytic neuropathy,8,33,34 proximal
diabetic neuropathy, 2,48 diabetic lumbosacral
plexopathy,7 and, the term we prefer, DLRPN.20 The
many names used for this disorder demonstrate the
diverse opinions concerning anatomical localization
and underlying causes.
In contrast to the diabetic variety, nondiabetic
lumbosacral radiculoplexus neuropathy (LRPN) is a
April 2002
477
HISTORICAL REVIEW
478
Lumbosacral Plexopathy
April 2002
Lumbosacral Plexopathy
April 2002
479
Table 1. Clinical and laboratory characteristics of DLRPN and LRPN patients and a population-based diabetic cohort (RDNS).
P values*
DLRPN
Continuous
Age (y)
Duration of diabetes (y)
Duration of neuropathy
(mo)
Onset to bilateral (mo)
Fasting plasma glucose
(mg/dl)
Glycated hemoglobin (%)
Body mass index (kg/m2)
Weight change (lb)
Creatinine (mg/dl)
Spinal fluid glucose (mg/dl)
Spinal fluid protein (mg/dl)
Spinal fluid cells (cells/l)
ESR (mm/h)
NIS, total
NIS, lower limb
33
33
65.4
4.1
35.875.9
0.035.8
33
32
6.7
3.0
1.442.0
0.060.0
30
30
29
33
30
26
26
26
31
33
33
144.5
7.5
25.7
30.0
0.9
85.0
89.5
1.0
6.0
43.0
37.0
Dichotomous
Sex, male
Diabetes, type II
Insulin use
Retinopathy
Nephropathy
Cardiovascular disease
Rheumatoid factor, reactive
ANA, positive
Median
Range
75.0225.0
5.112.9
17.836.7
120.00.0
0.73.4
56.0130.0
44.0214.0
1.011.5
0.060.5
7.087.0
7.062.0
Yes
No
20
32
13
4
2
3
2
7
13
1
18
13
31
30
25
25
33
33
31
17
33
33
27
32
LRPN
SD
Median
10.4 57
7.9 NA
Range
69.4
27.886.5
0.560.0
0.072.0
8.9
10.6
57
45
7.0
3.0
44.3
2.0
4.9
32.6
0.5
19.4
35.3
2.1
14.6
18.6
14.4
57
34
50
57
53
49
50
49
56
57
57
96.0
5.5
25.1
15.0
1.0
63.0
66.5
1.0
13.5
36.5
33.5
69.0124.0
4.37.1
17.835.4
90.00.0
0.61.9
48.088.0
18.0283.0
0.012.0
0.062.0
6.0106.3
6.077.0
Yes
No
57
NA
NA
29
28
40
50
6
8
34
42
RDNS
SD
12.3 195
195
Median
Range
SD
65.0
15.0
19.088.0
5.974.8
15.1
8.5
12.4
11.6
NA
NA
11.5
0.7
4.6
19.6
0.2
9.3
56.9
2.2
14.4
21.2
17.0
195
195
195
195
195
169.9
9.8
28.6
0.4
1.0
195
195
0.0
0.0
0.018.0
0.014.0
Yes
No
96
148
134
128
20
73
99
46
61
67
175
122
195
194
195
195
195
195
DLRPN DLRPN
vs
vs
LRPN
RDNS
.03
NS
<.001
NS
NS
94.2389.0 41.9
5.516.5
2.0
17.850.8
5.7
8.710.1
2.6
0.52.5
0.2
2.5
2.3
.0001
.0001
NS
.002
NS
.0001
.009
NS
.02
NS
NS
NS
.001
<.001
.002
<.001
.023
.0001
.0001
NS
.005
.007
.001
NS
.001
NS
NS
Abbreviations: ANA, antinuclear antibody; NA, not applicable; NS, not significant (P > 0.05); ESR, erythrocyte sedimentation rate.
*Wilcoxon rank sum test for continuous data and Fishers Exact test for dichotomous data.
For DLRPN and LRPN, weight change is from onset to evaluation; for RDNS, weight change is over 1 year.
Nonproliferative retinopathy.
(Table has been modified and reprinted with permission from Dyck et al.21)
developed new autonomic symptoms with their illness, which included orthostatic intolerance, change
in sexual function, and change in bowel and bladder
function.20 Similarly, most of our patients had sensory loss in both proximal and distal segments, and
all classes of sensory fibers were affected. Some patients had sensory sparing as reported by Garland.24,25
Although improvement occurs in almost all patients, recovery is usually delayed and incomplete.
There is much more long-term morbidity in this disorder than is often appreciated. Of the 33 prospectively studied DLRPN patients, only two believed that
they had completely recovered after a median time
of 2 years. The severity of the neuropathy is also
greater than usually appreciated. The median value
of the neuropathy impairment score (NIS)17 was 43
(Table 1), which is indicative of severe impairment.
Almost half of our patients were in wheelchairs (16
of 33) at the time of initial evaluation. Most patients
had substantial improvement, and few required the
long-term use of wheelchairs (only 3 of 33 were still
in wheelchairs after a median follow-up of 2 years).
Nonetheless, many of the patients with DLRPN had
persistent pain and weakness. Proximal injury usually resolves earlier and more effectively than does
480
Lumbosacral Plexopathy
April 2002
Table 2. Severity of symptoms, anatomic location and use of ambulating aids in DLRPN and LRPN.
DLRPN
Onset
(n = 33)
Mayo
evaluation
(n = 33)
Telephone
follow-up
(n = 31)
27
0
6
0
13
0
20
0
6
2
21
2
Significance*
Most involved site
Foot or leg
Hip or thigh
Buttock or back
None
Significance
Aids in ambulation
Wheelchair
Walker, cane, or brace
None
Significance
LRPN
<.001
12
18
3
0
Onset
(n = 57)
Mayo
evaluation
(n = 57)
Telephone
follow-up
(n = 42)
49
1
7
0
10
0
47
0
12
1
26
3
0.05
14
19
0
0
NS
<.0001
24
5
0
2
<.001
16
14
3
21
33
3
0
0.03
27
30
0
0
NS
3
16
12
<.001
DLRPN vs LRPN
Onset
Mayo
evaluation
Telephone
follow-up
NS
.03
NS
NS
NS
NS
NS
NS
32
7
0
3
<.0001
28
28
1
5
21
16
<.0001
Three LRPN and two DLRPN patients reported they were recovered.
(Table has been modified and reprinted with permission from Dyck et al.21)
Lumbosacral Plexopathy
Bastron and Thomas6 noted that patients with DLRPN frequently had involvement of regions other
than the lower limbs, most notably the thoracic levels. Consequently, the authors called the condition
diabetic polyradiculopathy. In our DLRPN cohort,
4 of 33 patients had additional symptoms and findings consistent with thoracic radiculopathy (chest or
abdominal wall pain or weakness). One third (n =
11) of patients had upper-limb involvementmost
of these were mononeuropathies (ulnar neuropathy
at the elbow or median neuropathy at the wrist), but
about 10% (3 of 33) had a more diffuse disorder
consistent with a cervical radiculoplexus neuropathy.20 Consequently, finding truncal or upper-limb
involvement does not exclude the diagnosis of DLRPN. We have chosen to classify these coexisting
neuropathies as disorders separate from DLRPN, as
they occur in a minority of cases. Nonetheless, we
believe that the truncal radiculopathies and the cervical radiculoplexus neuropathies probably have the
same pathophysiological basis (ischemic injury from
microvasculitis) as DLRPN. It is probable that many
of the upper-limb mononeuropathies in DLRPN are
April 2002
481
As expected, fasting blood glucose levels and glycated hemoglobin levels are elevated in DLRPN as
compared with LRPN (Table 1). However, for a
group of diabetic patients, the metabolic control of
our DLRPN cohort was good. When the DLRPN cohort was compared with the RDNS cohort (a population-based study of diabetic patients living in Rochester, Minnesota),15 their glycated hemoglobin was
significantly lower, their body mass index was significantly lower, and more had type II diabetes mellitus
(Table 1).
In both DLRPN and LRPN, the cerebrospinal
fluid (CSF) protein concentration is significantly elevated (Table 1)evidence that the disease process
extends to the nerve root level. An occasional patient
in both groups had an elevated erythrocyte sedimentation rate, reactive rheumatoid factor, positive antinuclear antibodies, or other markers of immunemediated disorders (Table 1). Although the
subgroup of patients with elevated erythrocyte sedimentation rates has been reported to have a different condition,7 in our experience, the DLRPN and
LRPN patients with elevated erythrocyte sedimentation rates do not differ from the rest of the patients.21
ELECTROPHYSIOLOGIC FINDINGS OF DLRPN
AND LRPN
Bastron and Thomas6 and Subramony and Wilbourn45 have written extensively about nerve conduction and electromyogram (EMG) abnormalities
in DLRPN. Subramony and Wilbourn45 proposed
two electrophysiological subtypes of DLRPN: patients whose electrophysiologic abnormalities are
confined to the affected lower limb and those with
evidence of a more diffuse peripheral neuropathy in
482
Lumbosacral Plexopathy
April 2002
Lumbosacral Plexopathy
flammatory infiltrates in biopsies of patients with DLRPN. Kelker et al.31 found evidence for a polymorphonuclear vasculitis with immune complex and
complement deposition.
We studied the pathologic findings of DLRPN by
prospectively evaluating all static or worsening cases
over a period of 3 years.20 Evaluation included distal
cutaneous nerve biopsy (usually sural) from the
more involved leg in each patient. We found strong
evidence implicating an ischemic disorder (Table 3).
Most nerves (19 of 33) showed multifocal fiber loss
(Fig. 1), perineurial thickening (24 of 33; Fig. 2),
neovascularization (21 of 33), and abortive regeneration of nerve fibers forming microfasciculi (injury
neuroma; 12 of 33). Some fibers from damaged regions showed enlarged dark axons (from accumulation of organelles) that contained light cores (areas
of intact axoplasm). These dark axons with light
cores have been described in experimental models
of ischemic nerve damage.38 Teased-fiber abnormalities consisted of an increased rate of axonal degeneration, empty nerve strands, and segmental demyelination. Frequently, the segmental demyelination
was clustered on individual nerve fibers, suggesting a
demyelinating disorder secondary to axonal pathology.20
Several explanations might account for the high
rate of ischemic damage. The ischemic injury of DLRPN could be caused by a vasculopathy due to the
chronic hyperglycemic state of diabetes mellitus
(metabolic damage). However, when we compared
our DLRPN group with a population-based cohort of
diabetics (RDNS cohort), we found that our DLRPN
patients had better glycemia control, used less insulin, were more likely to have type II than type I diabetes mellitus, had been diabetic for a shorter period
of time, and had less vascular disease (fewer cardiovascular events) than did our population-based diabetic patients (Table 1). Also, the microvasculitis of
DLRPN is unlike the endoneurial microvessel disease (degeneration of pericytes and reduplication of
basement membranes) associated with chronic hyperglycemia.27 Consequently, it seems unlikely that
a diabetes-induced vasculopathy is the cause of
DLRPN.
Our evidence suggests that the primary event in
DLRPN is an immune attack and probably microvasculitis of nerve. We found evidence of inflammation
in association with the ischemic damage.20 All DLRPN nerves sampled had some degree of inflammation, usually surrounding epineurial microvessels.
The degree of inflammation was much greater than
in healthy control nerves or in nerves from patients
April 2002
483
Table 3. Pathologic results of distal cutaneous nerve biopsies from DLRPN compared with LRPN, diabetic polyneuropathy (DPN),
and healthy control nerves.
DLRPN
Variable
Characteristics of patients biopsied
n
Sex, male
Median age, y
Paraffin and epoxy sections
Endoneurial and perineurial abnormality
Fiber degeneration or loss
Multifocal fiber degeneration or loss
Focal perineurial degeneration
Focal perineurial thickening
Injury neuroma
Interstitial abnormality
Perivascular inflammation
Individual cells (<10 cells)
Small collections (1150 cells)
Moderate collections (51100 cells)
Large collections (>100 cells)
Inflammation of vessel wall
Diagnostic of microvasculitis
Hemosiderin in macrophages
Neovascularization
LRPN
DPN
p*
33
20
65.4
47
24
67.2
NS
NS
21
15
57.0
25
19
6
24
12
37
31
7
27
16
NS
NS
NS
NS
NS
15
2
0
2
0
33
0
21
7
5
15
2
19
21
47
5
29
6
7
24
7
25
21
NS
6
5
1
0
0
0
0
0
1
NS
NS
NS
NS
Healthy controls
p*
p*
14
9
61.5
NS
NS
NS
<.001
NS
<.001
.002
0
0
0
2
0
<.001
<.001
NS
<.001
.009
<.001
2
2
0
0
0
0
0
0
1
<.001
NS
.002
<.001
NS
<.001
<.001
<.002
NS
<.001
<.001
484
Lumbosacral Plexopathy
all nerves studied is compelling evidence of an immune mechanism. The segmental demyelination
seen is probably due to ischemic injury from vasculitis and not due to a primary demyelinating condition. The demyelinating changes are typical of those
caused by axonal dystrophy.14,16,38
PATHOPHYSIOLOGY OF LRPN
Little has been written about the underlying pathologic mechanisms of LRPN.7 However, because of
similarities in the clinical, laboratory, and electrophysiologic features of DLRPN and LRPN, it seemed
likely to us that these two conditions are probably
due to the same pathophysiologic mechanisms.
Consequently, we did a retrospective study identifying those LRPN patients who had nerve biopsies.
The purpose was to determine whether the pathologic findings in distal cutaneous nerve in LRPN
are the same as in DLRPN.
The pathologic findings in LRPN are strikingly
similar to those of DLRPN (Table 3).18 We found
multifocal fiber loss (31 of 47; Fig. 1), regions of
abortive regeneration within or beyond the original
perineurium forming microfasciculi (injury neuroma, 16 of 47; Fig. 1), focal degeneration or scarring of the perineurium (33 of 47; Fig. 2), epineurial
April 2002
Lumbosacral Plexopathy
April 2002
485
FIGURE 2. Transverse paraffin sections of sural nerves showing changes seen in DLRPN and LRPN. Upper panel, Massons trichrome
stain, showing inflammation in the wall of an epineurial microvessel (right upper), probably fibrinoid degeneration of the perineurium (long
arrow), and a region of neovascularization (arrowhead). Middle panel, Luxol fast blue-periodic acid Schiff stain, showing several fascicles
surrounded by normal thickness perineurium (right middle, between the arrowheads) and one fascicle with extremely thick perineurium
(left middle, between the arrowheads). We attribute the latter finding to scarring and repair after ischemic injury (note all fascicles are
devoid of myelinated fibers). Lower panel, Turnbull blue stain, showing accumulation of hemosiderin (iron stains bright blue, arrow)
deposited along the inner aspects of the perineurium. All of these pathological features are frequently seen together and are best
explained by ischemic injury. (Reproduced with permission from Dyck et. al. 18)
486
Lumbosacral Plexopathy
April 2002
FIGURE 3. Changes characteristic of microvasculitis in LRPN (left column) and in DLRPN (right column). Upper panels, Mononuclear
cell infiltration of the vessel walls with separation of mural elements (hemotoxylin and eosin stain). Middle panels, Fibrinoid necrosis of
the walls of subperineurial microvessels associated with mononuclear cell infiltration. Although occasionally found, fibrinoid necrosis of
vessel walls is not typical of these conditions, presumably because of the small size of the vessels involved. Lower panels, Mononuclear
cells reacted to leukocyte common antigen (CD45) infiltrate the walls of epineurial microvessels. Note the close similarity of the findings
of the diabetic and the non-diabetic conditions.
Lumbosacral Plexopathy
loss (as seen in both DLRPN and LRPN) is also common in vasculitic disorders. The small size of the
blood vessels involved and their anatomic location
(more prominent in the lumbosacral plexus) probably explains the patchy, widespread, asymmetric
process rather than discrete multiple mononeuropa-
April 2002
487
FIGURE 4. Serial skip paraffin sections of a microvessel above (upper panels), at (middle panels), and below (lower panels) region
of microvasculitis in the sural nerve of a patient with LRPN. The sections in the left column are stained with hematoxylin and eosin, the
sections in the middle column are reacted to antihuman smooth muscle actin (Dako, Carpenteria, California), and the sections in
the right column are reacted with leukocyte common antigen (CD 45). The smooth muscle of the tunica media in the region of the
microvasculitis (middle panels) are separated by mononuclear cells, fragmented, and decreased in amount. The changes are those of
a focal microvasculitis. These changes are seen in both the diabetic and nondiabetic conditions.
488
Lumbosacral Plexopathy
April 2002
There are no proven treatments for DLRPN. Because of the evidence that both DLRPN and LRPN
are probably immune-mediated neuropathies due to
microvasculitis of nerve, immunotherapy might be
useful if employed early, when the disease is still
active. To date, no controlled studies have been
done. Said et al.42 treated with prednisone two patients who had evidence of vasculitis on nerve biopsy
and reported improvement. Krendel et al.32 treated
with immunotherapy 15 patients with DLRPN. Seven
patients were treated with a combination of intravenous immunoglobulin (IVIg) and prednisone, 5
with IVIg alone, 2 with a combination of prednisone
and cyclophosphamide, and 1 with prednisone
alone. All patients were reported to be improved and
5 were markedly better. Pascoe et al.39 compared 12
DLRPN patients who received treatment (prednisone, IVIg, or plasma exchange) with 29 DLRPN patients who received no treatment. The authors concluded that, on average, the group that received
immune-modulating treatment had a greater impairment before treatment than did the nontreated
group but improved to a greater extent and at a
faster rate after treatment was begun. The results
from these studies support the idea that immunemodulating therapies might be helpful in DLRPN.
However, as DLRPN is a monophasic illness and
spontaneous improvement is usual, these reports of
efficacy must be viewed as preliminary.
Consequently, two double-blind, placebocontrolled trials in DLRPN have been initiated; one
with intravenous methylprednisolone and the other
with IVIg. In order to study only patients with active
Lumbosacral Plexopathy
April 2002
489
SYMPTOMATIC TREATMENT
490
Lumbosacral Plexopathy
April 2002
22.
23.
24.
25.
REFERENCES
26.
1. Archer AG, Watkins PJ, Thomas PK, Sharma AK, Payan J. The
natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiatry 1983;46:491499.
2. Asbury AK. Proximal diabetic neuropathy. Ann Neurol 1977;
2:179180.
3. Auche MB. Des alterations des nerfs peripheriques. Arch Med
Exp Anat Pathol 1890;2:635676.
4. Awerbuch GI, Nigro MA, Sandyk R, Levin JR. Relapsing lumbosacral plexus neuropathy. Eur Neurol 1991;31:348351.
5. Barohn RJ, Sahenk Z, Warmolts JR, Mendell JR. The BrunsGarland syndrome (diabetic amyotrophy) revisited 100 years
later. Arch Neurol 1991;48:11301135.
6. Bastron JA, Thomas JE. Diabetic polyradiculopathy: clinical
and electromyographic findings in 105 patients. Mayo Clin
Proc 1981;56:725732.
7. Bradley WG, Chad D, Verghese JP. Painful lumbosacral
plexopathy with elevated erythrocyte sedimentation rate: a
treatable inflammatory syndrome. Ann Neurol 1984;15:
457464.
8. Bruns L. Ueber neuritsche Lahmungen beim diabetes mellitus. Berlin Klin Wochenschr 1890;27:509.
9. Calverley JR, Mulder DW. Femoral neuropathy. Neurology
1960;10:963967.
10. Chokroverty S. Proximal nerve dysfunction in diabetic proximal amyotrophy. Arch Neurol 1982;39:403407.
11. Chokroverty S, Reyes MG, Rubino FA. BrunsGarland syndrome of diabetic amyotrophy. Trans Am Neurol Ass 1977;
102:14.
12. Chokroverty S, Reyes MG, Rubino FA, Tonaki H. The syndrome of diabetic amyotrophy. Ann Neurol 1977;2:181199.
13. Chokroverty S, Sander HW. AAEM Case Report #13: diabetic
amyotrophy. Muscle Nerve 1996;19:939945.
14. Dyck PJ, Johnson WJ, Lambert EH, OBrien PC. Segmental
demyelination secondary to axonal degeneration in uremic
neuropathy. Mayo Clin Proc 1971;46:400431.
15. Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM,
Wilson DM, OBrien PC, Melton LJ, Service FJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology
1993;43:817824.
16. Dyck PJ, Lais A, Karnes J, Sparks M, Dyck PJB. Peripheral
axotomy induces neurofilament decrease, atrophy, demyelination and degeneration of root and fasciculus gracilis fibers.
Brain Res 1985;340:1936.
17. Dyck PJ, Sherman WR, Hallcher LM, Service FJ, OBrien PC,
Grina LA, Palumbo PJ, Swanson CJ. Human diabetic endoneurial sorbital, fructose, and myo-inositol related to sural
nerve morphometry. Ann Neurol 1980;8:590596.
18. Dyck PJB, Engelstad J, Norell J, Dyck PJ. Microvasculitis in
non-diabetic lumbosacral radiculoplexus neuropathy
(LSRPN): similarity to the diabetic variety (DLSRPN). J Neuropathol Exp Neurol 2000;59:525538.
19. Dyck PJB, Norell JE, Dyck PJ. Methylprednisolone may improve lumbosacral radiculoplexus neuropathy. Can J Neurol
Sci 2001;28:224227.
20. Dyck PJB, Norell JE, Dyck PJ. Microvasculitis and ischemia in
diabetic lumbosacral radiculoplexus neuropathy. Neurology
1999;53:21132121.
21. Dyck PJB, Norell JE, Dyck PJ. Non-diabetic lumbosacral ra-
27.
Lumbosacral Plexopathy
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
diculoplexus neuropathy. Natural history, outcome and comparison with the diabetic variety. Brain 2001;124:11971207.
Ellenberg M. Diabetic neuropathic cachexia. Diabetes 1974;
23:418423.
Evans BA, Stevens JC, Dyck PJ. Lumbosacral plexus neuropathy. Neurology 1981;31:13271330.
Garland H. Diabetic amyotrophy. BMJ 1955;2:1287.
Garland H. Diabetic amyotrophy. Br J Clin Pract 1961;15:
913.
Garland HT, Tavernor D. Diabetic myelopathy. BMJ 1953;2:
1405.
Giannini C, Dyck PJ. Pathologic alterations in human diabetic
polyneuropathy. In: Dyck PJ, Thomas PK, editors. Diabetic
neuropathy. Philadelphia: WB Saunders; 1999. p 279295.
Grant IA, OBrien P, Dyck PJ. Neuropathy tests and normative
results. In: Dyck PJ, Thomas PK, editors. Diabetic neuropathy.
Philadelphia: WB Saunders; 1999. p 123141.
Gregersan G. Diabetic amyotrophy: a well defined syndrome?
Acta Med Scand 1969;185:303310.
Hinchey JA, Preston DC, Logigian EL. Idiopathic lumbosacral
neuropathy: a cause of persistent leg pain. Muscle Nerve
1996;19:14841486.
Kelkar PM, Masood M, Parry GJ. Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy).
Neurology 2000;55:8388.
Krendel DA, Costigan DA, Hopkins LC. Successful treatment
of neuropathies in patients with diabetes mellitus. Arch Neurol 1995;52:10531061.
Leyden E. Beitrag zur Klinik des diabetes mellitus. Wien Med
Wochenschr 1893;43:926.
Leyden E. Die Entzundung der peripheren Nerven. Dtsch
Militar Z 1887;17:49100.
Llewelyn JG, Thomas PK, King RHM. Epineurial microvasculitis in proximal diabetic neuropathy. J Neurol 1998;245:
159165.
Low PA. Composite autonomic scoring scale for laboratory
quantification of generalized autonomic failure. Mayo Clin
Proc 1993;68:748752.
Marra TR. The clinical and electrodiagnostic features of idiopathic lumbo-sacral and brachial plexus neuropathy1: a review of 20 cases. Electromyogr Clin Neurophysiol 1987;27:
305315.
Nukada H, Dyck PJ. Acute ischemia causes axonal stasis, swelling, attenuation, and secondary demyelination. Ann Neurol
1987;22:311318.
Pascoe MK, Low PA, Windebank AJ, Litchy WJ. Subacute diabetic proximal neuropathy. Mayo Clin Proc 1997;72:
11231132.
Raff MC, Asbury AK. Ischemic mononeuropathy and mononeuropathy multiplex in diabetes mellitus. N Engl J Med
1968;279:1722.
Raff MC, Sangalang V, Asbury AK. Ischemic mononeuropathy
multiplex associated with diabetes mellitus. Arch Neurol
1968;18:487499.
Said G, Goulen-Goeau C, Lacroix C, Moulonguet A. Nerve
biopsy findings in different patterns of proximal diabetic neuropathy. Ann Neurol 1994;35:559569.
Sander JE, Sharp FR. Lumbosacral plexus neuritis. Neurology
1981;31:470473.
Skanse B, Gydell K. A rare type of femoral-sciatic neuropathy
in diabetes mellitus. Acta Med Scand 1956;155:463468.
Subramony SH, Wilbourn AJ. Diabetic proximal neuropathy.
J Neurol Sci 1982;53:501509.
Triggs WJ, Young MS, Eskin T, Valenstein E. Treatment of
idiopathic lumbosacral plexopathy with intravenous immunoglobulin. Muscle Nerve 1997;20:244246.
Verma A, Bradley WG. High-dose intravenous immunoglobulin therapy in chronic progressive lumbosacral plexopathy.
Neurology 1994;44:248250.
Williams IR, Mayer RF. Subacute proximal diabetic neuropathy. Neurology 1976;26:108116.
April 2002
491