INVITED REVIEW

ABSTRACT: Diabetic lumbosacral radiculoplexus neuropathy (DLRPN)

(also called diabetic amyotrophy) is a well-recognized subacute, painful,
asymmetric lower-limb neuropathy that is associated with weight loss and
type II diabetes mellitus. Nondiabetic lumbosacral radiculoplexus neuropathy (LRPN) has received less attention. Comparison of large cohorts with
DLRPN and LRPN demonstrated that age at onset, course, type and distribution of symptoms and impairments, laboratory findings, and outcomes are
similar. Both conditions are lumbosacral radiculoplexus neuropathies that
are associated with weight loss and begin focally with pain but that evolve
into widespread, bilateral paralytic disorders. Although both are monophasic
illnesses, patients have prolonged morbidity from pain and weakness, and
many patients become wheelchair-dependent. Although motor-predominant, there is unequivocal evidence that autonomic and sensory nerves are
also involved. Cutaneous nerves from patients with DLRPN and LRPN show
pathological evidence of ischemic injury (multifocal fiber loss, perineurial
thickening and degeneration, neovascularization, microfasciculation, and
swollen axons with accumulated organelles) and microvasculitis (mural and
perivascular inflammation, separation and fragmentation of mural smooth
muscle layers of microvessels and hemosiderin-laden macrophages). Controlled trials with immune-modulating therapies in DLRPN are in progress,
and preliminary data suggest that such therapy may be beneficial in LRPN.
It is likely that DLRPN and LRPN are immune-mediated neuropathies that
should be separated from chronic inflammatory demyelinating polyneuropathy and from systemic necrotizing vasculitis.
2002 Wiley Periodicals, Inc. Muscle Nerve 25: 477491, 2002

DIABETIC AND NONDIABETIC LUMBOSACRAL

RADICULOPLEXUS NEUROPATHIES: NEW
INSIGHTS INTO PATHOPHYSIOLOGY
AND TREATMENT
P. JAMES B. DYCK, MD,1,2 and ANTHONY J. WINDEBANK, MD2
1

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

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April 2002

477

more recently recognized condition that has been

studied in less detail.23,43 However, the clinical features of this disorder appear to be very similar to
those of the diabetic variety.21
Here, we review the history of these conditions
(DLRPN and LRPN), describe the clinical and electrophysiologic features, compare the diabetic with
the nondiabetic varieties, and review the underlying
pathophysiological mechanisms of these disorders
and their implication for treatment trials. We find
that DLRPN frequently involves distal as well as
proximal lower limbs. Although it begins focally and
unilaterally, it becomes widespread and bilateral and
has long-term morbidity due to pain and weakness.
The disease process involves root, lumbosacral
plexus, and peripheral nerve (i.e., a lumbosacral radiculoplexus neuropathy). Frequently, there are associated thoracic radiculopathies. The underlying
pathological process is probably altered immunity
and microvasculitis of nerve rather than metabolic
derangement. Nondiabetic lumbosacral radiculoplexus neuropathy has essentially the same clinical
and histopathological features, and both conditions
are underrecognized. These conditions may be improved with immune-modulating therapy, and controlled clinical trials are being conducted. The pattern of lumbosacral plexopathy should be added to
those of polyradiculoneuropathy (such as in chronic
inflammatory demyelinating polyneuropathy) and
multiple mononeuropathies (such as in systemic
necrotizing vasculitis) as suggesting an immunemediated neuropathy.

HISTORICAL REVIEW

Most authors attribute the original description of

DLRPN to a paper written by Bruns in 1890.8 However, the condition was also recognized by Auche3
and Leyden33,34 at about the same time. In 1887,
Leyden reported three types of diabetic neuritis:
(1) hyperesthetic, or neuralgic; (2) paralytic (motor); and (3) ataxic. As examples of the paralytic
subtype (probably DLRPN), the author described
cases with intense lower-limb pain associated with
paralysis that later improved. The syndrome was
largely forgotten until Garland described it again in
1953, first calling it diabetic myelopathy26 and then
diabetic amyotrophy,24 because of uncertainty
about the pathoanatomical localization. Garland
wrote that the condition was one of pain and weakness in proximal lower-limb muscles and was associated with weight loss. The author emphasized that it
had a monophasic course and that it was a motor

478

Lumbosacral Plexopathy

neuropathy because the clinical sensory examination

was normal. Although most of Garlands patients
had thigh and hip symptoms, some also had distal
findings.25
Since Garlands time, there has been much debate about the clinical features and underlying
disease mechanisms: ischemic injury, metabolic derangement (hyperglycemia), or immune mechanisms including vasculitis. There has been debate
about whether DLRPN is one entity or part of a continuum, with rapid onset and asymmetric features
(perhaps from ischemia) being at one extreme and
a slowly evolving symmetric disorder (perhaps from
metabolic derangement) at the other extreme.2,13,29
Raff and Asbury40 and Raff and coworkers41 emphasized the rapid onset and asymmetric course and
referred to the condition as a diabetic mononeuritis
multiplex. The authors detailed study of a case at
postmortem revealed evidence of ischemic injury. In
contrast, Chokroverty and coworkers1012 emphasized the bilateral, symmetric, and insidious development of the condition and the predominance of motor involvement and weight loss. They concluded
that metabolic factors (hyperglycemia) best explained the disease pathophysiology. Both groups
emphasized proximal lower-limb involvement.
Other groups, however, have expressed the belief
that the disease is multifocal and widespread and can
involve distal regions.5,6,29 Bastron and Thomas6
called the condition diabetic polyradiculopathy
and included all asymmetric diabetic truncal and
lower-limb syndromes in this entity. Barohn et al.5
noted that the disorder began focally and unilaterally but evolved into a more widespread process involving proximal and distal lower-limb elements.
The debate about the underlying mechanism has
continued, and many authors have proposed that
different subtypes of the condition are due to different mechanisms. Bradley et al.7 argued for more
than one cause of lumbosacral plexus neuropathy
and wrote that those cases with elevated sedimentation rates had an immune cause, as evidenced by
inflammatory cell cuffing around blood vessels in
nerve biopsy specimens. Said et al.42 found evidence
for two subtypes: in severe cases, ischemic injury and
vasculitis predominated, whereas in mild cases,
metabolic factors and demyelination were believed
to be more important. Others5 wrote that all of their
cases seemed to be due to ischemic injury (multifocal fiber loss) and did not find evidence for different
subtypes. More recent authors have also emphasized
that at least some cases are due to immune causes
including vasculitis.31,35
Another subacute painful neuropathy that occurs
in diabetic patients has been described as diabetic

MUSCLE & NERVE

April 2002

neuropathic cachexia.1,22 It has some features in

common with DLRPN in that they both tend to occur in type II diabetic patients, are not related to
duration of diabetes, are monophasic, and are associated with pain and weight loss. However, unlike
DLRPN, this painful condition does not produce
weakness. Although diabetic neuropathic cachexia
may really be part of the spectrum of DLRPN, at this
time, we believe it should be classified as a different
disorder.
Much less has been written about LRPN than
about DLRPN. Consequently, there has been less debate about the underlying pathophysiological
mechanisms. The condition was first recognized in
1981,23,43 when two groups described a subacute,
painful, paralytic lower-limb neuropathy attributed
to pathological involvement of the lumbosacral
plexus. Evans and colleagues23 reported that the
condition was monophasic but that the morbidity
was prolonged due to pain and weakness. Subsequently, there have been reports of individual or
small groups of patients with an unusual course or
response to treatment.4,30,37,46,47 The only previous
pathological studies described three nondiabetic
cases (along with three diabetic cases) and implicated an immune mechanism and ischemic injury.7
To address the questions of underlying pathophysiology, clinical pattern, and different subtypes of
DLRPN, we chose to prospectively study all DLRPN
patients we evaluated and obtain an ipsilateral nerve
biopsy from them.20 We tried to avoid a priori judgments about whether proximal or distal elements
were primarily involved, whether the condition was
purely motor, or if sensory and autonomic fibers
might also be affected. Rather, we included all diabetic patients who had a subacute onset of pain and
weakness of the lower limbs not attributable to another cause. We then retrospectively identified a cohort of LRPN patients who had nerve biopsies performed and compared the clinical and pathological
features of the two conditions.
CLINICAL FEATURES OF DLRPN

Typically DLRPN develops in patients with type II

diabetes mellitus in middle or old age. Frequently,
there is a large, concomitant weight loss. In our series, 28 of 33 patients lost more than 10 lbs.20 In
general, patients had not been diabetic for a long
period of time and the glycemic dysregulation was
not severe. In some cases, patients did not know that
they were diabetic until the condition was discovered
(in our series, 7 of 33 patients). In DLRPN, the condition begins abruptly and focally and patients often
recall the exact day their symptoms began, whereas
diabetic polyneuropathy begins insidiously and sym-

Lumbosacral Plexopathy

metrically. Patients with DLRPN usually do not have

many of the long-term complications of diabetes
mellitus, such as co-existing retinopathy or nephropathy, that are frequently seen in diabetic polyneuropathy. We compared our DLRPN cohort with the
Rochester Diabetic Neuropathy Study (RDNS) cohort15 (which is representative of local community
diabetic patients) and found that DLRPN patients
had better diabetic control and fewer diabetic complications. They had better glycemia control and
lower body-mass index, took insulin less often, had
been diabetic for a shorter period of time, were
more likely to have type II than type I diabetes mellitus, and had less retinopathy and less cardiovascular disease than did the RDNS cohort (Table 1).
The condition usually starts with pain that may be
described as sharp or lancinating, deep aching,
burning, or contact allodynia (mild tactile stimuli
causing pain). The disorder begins asymmetrically
(usually unilaterally) and focally, involving the hip
and thigh somewhat more frequently than the foot
and leg (Table 2). However, it quickly spreads to
involve the initially unaffected segments and the
contralateral side so that by the time of evaluation
the disorder usually appears more widespread and
symmetric than when it first began. In the prospectively studied series, the syndrome began unilaterally
in 29 of 33 patients but became bilateral in 32 of 33
patients.20 Consequently, early in the disease course,
one segment (thigh or leg) is often primarily involved, and so it is not uncommon to find weak thigh
muscles and absent knee reflexes with intact ankle
reflexes. However, with the passage of time, the
other lower-limb segments usually become involved
and more widespread weakness and reflex changes
are seen. The median time to bilateral disease in
DLRPN was 3 months (Table 1). The disorder involves not only proximal segments but also distal segmentsa point that many investigators have not appreciated. Not uncommonly, the condition begins
with distal symptoms (in our series, 12 of 33). Nonetheless, in most cases, the condition eventually involves both proximal and distal segments and becomes bilateral (Table 2).
Although pain is the most prominent early symptom, weakness soon becomes the major symptom
(Table 2). Patients often complain of both proximal
weakness (difficulty in going up and down stairs or
getting out of low chairs, or one of their legs giving
way beneath them) and distal weakness (footdrop
and tripping). The weakness is severe, and half of
the patients in our series were wheelchair-bound at
some point during their illness; almost all of them
required aids for ambulation (Table 2). In addition
to pain and weakness, about half of DLRPN patients

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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

distal damage. Consequently, footdrop tends to be

the most common long-term problem for DLRPN
patients.
CLINICAL FINDINGS IN LRPN

Nondiabetic lumbosacral radiculoplexus neuropathy is a clinical syndrome that is similar to DLRPN.

Based on large cohorts of LRPN (n = 57) and
DLRPN (n = 33), we believe that the diabetic and
nondiabetic lumbosacral plexopathies are essentially
alike except for the occurrence of diabetes mellitus
in DLRPN.18,20,21 Consequently, the clinical features
of the two conditions are almost indistinguishable.
Like DLRPN, LRPN begins with a subacute, painful
neuropathy with focal involvement of the leg or
thigh. It usually becomes more generalized and bilateral within several months (Table 1). Early in the
course, pain is the predominant symptom, whereas
later, weakness predominates (Table 2). As in
DLRPN, the symptoms often begin on a known date
and progress over weeks or months. Also, like
DLRPN, the proximal segments in LRPN are initially
involved somewhat more frequently (36 of 57) than
are the distal segments (21 of 57). With time, most
patients develop proximal and distal symptoms (52
of 57) and bilateral involvement (51 of 57). The NIS

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April 2002

Table 2. Severity of symptoms, anatomic location and use of ambulating aids in DLRPN and LRPN.
DLRPN

Most severe symptom

Pain
Prickling
Weakness
None

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

NS, not significant (P > .05).

*Fishers Exact test.

Three LRPN and two DLRPN patients reported they were recovered.
(Table has been modified and reprinted with permission from Dyck et al.21)

also shows severe impairment (Table 1). Weight loss

is (as in DLRPN) a characteristic finding in LRPN.21
Of 57 patients in our series of LRPN, 42 had weight
loss exceeding 10 lbs. Because LRPN patients are not
diabetic, their weight loss cannot be attributed to
poorly controlled diabetes mellitus (as it usually is
for DLRPN). In addition to motor and sensory symptoms, about one half of patients have one or more
autonomic symptoms including orthostatic hypotension, urinary dysfunction, change in sexual function,
diarrhea, constipation, or change in sweating.
Long-term morbidity is also severe in LRPN. Only
3 of 42 LRPN patients reported that they had recovered completely after a median follow-up time of 3
years. The rest still had residual pain, weakness, or
numbness (Table 2). Nevertheless, important improvement had occurred: at initial evaluation, 25
used a wheelchair, whereas at later follow-up, only 5
were wheelchair-dependent. The long-term impairment was confined to distal segments (legs and feet)
in 25 of the 39 nonrecovered patients.
The degree of long-term recovery and morbidity
are essentially the same in DLRPN and LRPN. Both
conditions can be recurrent. In our LRPN series,
about 17% of patients (7 of 42) had recurrent episodes of pain and weakness. Patients with LRPN usually do not later develop diabetes mellitus (only 2 of
42 in our cohort eventually became diabetic, one 5

Lumbosacral Plexopathy

years and the other 7 years after the neurologic illness).

OTHER SITES OF NEUROLOGIC INVOLVEMENT

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

MUSCLE & NERVE

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481

related to compression injury secondary to weight

loss and wheelchair dependence.
The findings were similar in the nondiabetic condition. Nine of 57 LRPN patients had symptoms and
signs consistent with thoracic radiculopathies. Almost half of LRPN patients (26 of 57) also had some
upper-limb involvement, but in all cases it was
milder than the lower-limb syndrome. Mononeuropathies, probably from compression (ulnar neuropathy at the elbow and median neuropathy at the
wrist), accounted for most of the upper-limb involvement, but about 10% (6 of 57) had a more widespread disorder affecting multiple upper-limb nerves
consistent with a cervical radiculoplexus neuropathy.21
LABORATORY FINDINGS IN DLRPN AND LRPN

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

addition to the lower-limb syndrome. We did not

divide our patients in this manner. There are no
strong reasons to postulate a separate peripheral
neuropathy due to a different mechanism for most
patients. It is more likely that the subgroup of
DLRPN patients who are reported as having a separate polyneuropathy are the more severely affected
patients and so have more diffuse electrophysiologic
abnormalities. Based on epidemiologic studies of
community diabetic patients (RDNS cohort15), it is
clear that most DLRPN patients have not been diabetic for a long enough period of time or have had
poor enough glycemia control to be expected to
have developed a pre-existing distal diabetic polyneuropathy. The RDNS data15 have also shown that
the occurrence of diabetic polyneuropathy is highly
associated with diabetic retinopathy and nephropathy. Most of our DLRPN patients do not have retinopathy or nephropathy, so few would be expected
to have diabetic polyneuropathy.
In the cohorts of DLRPN and LRPN, there are
marked reductions in amplitude of the compound
muscle action potentials and sensory nerve action
potentials, with only mild slowing of nerve conduction velocities.20,21 Needle electromyography shows
fibrillation potentials; decreased recruitment; and
long-duration, high-amplitude motor unit potentials
in muscles innervated by multiple nerve roots and
different peripheral nerves. Paraspinal muscles are
usually involved. Fibrillation potentials in lumbosacral paraspinal muscles were seen in 29 of 30 DLRPN
patients and in 33 of 48 LRPN patients who had the
paraspinal muscles examined. The electrophysiologic abnormalities tend to be much more widespread than the clinical deficits. The electrophysiologic findings in the two conditions are essentially
the same, with the diabetic group having slightly
worse findings.20,21 These abnormalities are more
suggestive of a process of axonal degeneration than
segmental demyelination.
The finding of low-amplitude compound muscle
action potentials in distal muscles does not necessarily mean that a separate diabetic polyneuropathy is
present. The disease process clearly involves distal as
well as proximal nerves, so that distal nerve conduction abnormalities can easily be explained by the
lumbosacral plexopathies. The electrophysiologic
abnormalities are in keeping with a pathologic process that involves lower-limb roots, plexus, and peripheral nerves (a lumbosacral radiculoplexus neuropathy).

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April 2002

QUANTITATIVE SENSORY AND

AUTONOMIC TESTING

There is now good evidence that DLRPN and LRPN

are not isolated motor neuropathies. They involve
sensory and autonomic as well as motor nerve fibers.
Almost all patients with these neuropathies have
pain, and about half have autonomic symptoms.20,21
We have performed quantitative sensory and autonomic testing on cohorts of both DLRPN and
LRPN.20,21 Results of quantitative sensory tests show
that there are unequivocal sensory abnormalities in
the foot, leg, and thigh and that all fiber classes are
involved. There were no significant differences in
sensory test results between the DLRPN and LRPN
cohorts.20,21 Similarly, for quantitative autonomic
testing, the composite autonomic severity scores
(CASS)36 show a moderate to severe autonomic dysfunction overall for both DLRPN and LRPN patients. The CASS scores of both groups were not
significantly different, and both groups suffered
from generalized autonomic dysfunction.20,21
PATHOPHYSIOLOGY OF DLRPN

Raff and Asbury40 and Raff et al.41 published the first

pathologic report for DLRPN in an autopsy report in
1968. These studies showed multiple areas suggestive
of nerve ischemia within the lumbosacral plexus and
obturator nerve, and an occluded blood vessel was
identified. Inflammatory mononuclear infiltrates
were present around vessels, but clear vasculitis was
not present. The inflammation was judged to be reactive. Barohn et al.5 confirmed ischemic damage by
studying 10 cases with biopsied distal nerves that
showed multifocal fiber loss, but the authors did not
comment on inflammatory lesions. Reporting on patients with elevated sedimentation rates, Bradley et
al.7 described six patients with painful lumbosacral
plexopathies (three with and three without diabetes
mellitus) whose biopsies showed multifocal fiber loss
and perivascular inflammatory cell cuffing.
More recently, Said et al.42 have proposed that
different subtypes of DLRPN are due to different
mechanisms, including ischemic injury from vasculitis and metabolic injury from hyperglycemia. The
authors reported pathologic findings from cutaneous thigh nerves in 10 patients with DLRPN. Biopsies
from the 3 most severe cases showed multifocal fiber
loss (ischemic injury), 2 of which were diagnostic of
vasculitis. The other 7 were believed to be more mild
cases due to metabolic causes. Other authors have
also emphasized immune mechanisms. Llewelyn et
al.35 found vasculitic changes in 3 of 14 biopsies of
cutaneous thigh nerves. Others32,39 have found in-

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

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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

NS, not significant (P >.05).

*Wilcoxon rank sum test for continuous data and Fishers Exact test for dichotomous data.

Injury neuroma = abortive regenerative activity outside of the original perineurium.

(Table has been modified and reprinted with permission from Dyck et al.18,20)

with diabetic polyneuropathy (Table 3). In half of

biopsies, the inflammatory cells disrupted vessel
walls and were suggestive of microvasculitis (Fig. 3).
Large vessels (large arterioles and small arteries)
typically were not involved. Rather, the pathologic
process involved small arterioles, venules, or capillaries (and was, thus, a microvasculitis). Consequently, although fibrinoid degeneration of vessel
walls was seen, it was uncommon (Fig. 3). However,
evidence of previous bleeding due to vessel damage
was common; hemosiderin-laden macrophages were
seen in half of the cases.
Our findings suggest that DLRPN is a uniform
disease due to one underlying mechanism: ischemic
injury from microvasculitis. We do not find evidence
that some cases are due to metabolic injury, whereas
other cases are due to ischemic injury, as has been
postulated.2,42 We are not bothered that all cases do
not show vasculitic changes. One would not expect
to find microvasculitis in all biopsied cases for the
following reasons: (1) vasculitic disorders are, by nature, patchy; (2) these disease processes involve
roots, plexus, and proximal and distal peripheral
nerves; and (3) only a short nerve segment is examined in a biopsy. Finding changes suggestive of vasculitis in half and increased inflammation in almost

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

MUSCLE & NERVE

April 2002

neovascularization (21 of 47; Fig. 2), and changes in

myelinated fibers typical of ischemic injury (enlarged dark axons with light cores). We attribute
these ischemic changes to an immune attack and
microvasculitis. Epineurial perivascular inflammatory collections were seen in all nerves. There were
features suggestive of microvasculitis, with inflammatory cells separating microvessel wall elements in half
of the nerves (24 of 47; Fig. 3). As in DLRPN, fibrinoid degeneration (typical of large-vessel vasculitis)
was rarely seen. This is probably because the vessels
affected tend to be microvessels and so have smaller
amounts of muscle in their walls.
Teased-fiber preparations from LRPN nerves
confirm the impression that fiber loss and axonal
degeneration are the main pathologic abnormalities of myelinated fibers. There are increased numbers of fibers undergoing axonal degeneration, fibers with segmental demyelination, and empty nerve
strands. Although the frequency of segmental demyelination is low, it is significantly increased compared with normal.18 The segmental demyelination
tends to be clustered along the length of individual
nerve fibers, suggesting that it is secondary to axonal
dystrophy.14
MICROVASCULITIS IS MULTIFOCAL IN DLRPN
AND LRPN

FIGURE 1. Transverse semithin epoxy sections of sural nerve

from patients with LRPN stained with methylene blue, showing
multifocal fiber degeneration and loss (A and B) and reactive
repair injury neuroma (microfasciculation; C), which we attribute
to ischemic injury and repair. (A) Low-magnification view showing
that most fascicles are devoid of myelinated fibers, whereas other
fascicles are more intact. (B) Higher-power view of the area
within the inset of (A). The left fascicle shows an admixture of
normal and actively degenerating fibers; the right fascicle is essentially devoid of myelinated fibers and only rare degenerating
profiles remain. (C) Transverse section of part of a fascicle,
showing nerve regeneration. There is a crescent of microfasciculi
(injury neuroma, arrowhead) between the leaflets of thickened
perineurium (edges demonstrated by long, thin arrows). The
short arrow identifies a cluster of regenerated fibers. Most of the
fibers in the large fascicle are small myelinated fibers and are
probably regenerating. These findings are similar in the diabetic
and nondiabetic conditions. (Modified and reproduced with permission from Dyck et al.18)

Lumbosacral Plexopathy

Serial skip sections from 8 nerves (4 from LRPN and

4 from DLRPN) were examined, to follow vascular
inflammation along microvessels. By using immunohistochemical staining, we saw evidence that leukocytes separated and surrounded smooth muscle cells
of microvessel walls. The smooth muscle was separated, fragmented, displaced outward, and diminished in amount (Fig. 4). These serial sections
showed that the inflammatory lesions were localized
only to short segments along the vessels and were
more common than we recognized in routine sections.18
The pathologic findings of DLRPN and LRPN
are strikingly similar. When we compare the findings
from our two cohorts, there are no statistically significant differences except a higher rate of empty
nerve strands in the DLRPN cohort. One explanation for the greater numbers of empty strands in
DLRPN biopsies is that the patients in the diabetic
cohort were more severely affected than were the
nondiabetic patients; another explanation is that a
small minority of the DLRPN patients also had a
coexisting diabetic polyneuropathy (although most
DLRPN patients probably do not, as discussed earlier). Our findings provide strong evidence that the
primary insult to DLRPN and LRPN nerves is isch-

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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

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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.

emic injury and that this ischemic injury is secondary

to a microvasculitis.
We believe that DLRPN and LRPN most likely
are forms of nonsystemic vasculitis of nerve. A vasculitic process could explain the clinical pattern of a
subacute, painful, asymmetric neuropathy. Weight

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-

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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.

thies typical of large-vessel necrotizing vasculitis. It is

unclear why the lumbosacral roots, plexus, and
nerves are particularly susceptible in these conditions, but given the relatively frequent comorbidity
of thoracic radiculopathies and cervical radiculo-

488

Lumbosacral Plexopathy

plexus neuropathies, the lumbosacral level is often

not the only anatomic level involved.
Further evidence supporting the microvasculitis
hypothesis over the metabolic (hyperglycemia) hypotheses is the strong similarity in the clinical and

MUSCLE & NERVE

April 2002

pathological findings between the diabetic and the

nondiabetic lumbosacral plexopathies. As LRPN patients are not diabetic, it is difficult to implicate hyperglycemia as the cause of their neuropathy. It
might be asked whether patients with LRPN really
have undetected mild diabetes mellitus. This seems
unlikely, as only 2 of 42 LRPN patients eventually
developed diabetes mellitus.21 Nonetheless, hyperglycemia is probably a risk factor in developing
DLRPN, if not the direct cause. Based on data from
the RDNS cohort,15 we estimate the frequency of
DLRPN among diabetic patients to be about 1%.
The frequency of LRPN among the general population is not known. However, most investigators believe that lumbosacral radiculoplexus neuropathies
occur much more frequently among diabetic patients. Consequently, the diabetic state (hyperglycemia) probably plays a role in the disease process,
even if it is not the direct cause of the condition.
IMMUNOTHERAPY

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

disease, included cases must be static or worsening

and within the first 6 months of disease onset. The
neuropathy can be unilateral or bilateral, and the
predominant disease manifestation may be confined
to the leg or to the thigh or may be more widespread. However, the symptoms and findings cannot
be confined to one nerve or to one nerve root distribution. Structural causes are excluded with magnetic resonance imaging of the lumbosacral spine
and lumbosacral plexus.
The intravenous methylprednisolone study is a
multicenter study being conducted at six centers in
the USA and Canada. Two thirds of patients receive
active drug, whereas one third receives placebo. The
methylprednisolone is initially given at a dose of 1 g,
3 times weekly and then at lesser frequencies and
lower doses over a 12-week period. Patients are examined, and a neurologic symptom questionnaire is
administered to determine whether symptoms are
worsening or improving (Neuropathy Symptom and
Change)28 on eight separate occasions (baseline and
weeks 1, 6, 12, 24, 36, 52, and 104) over a 2-year
period. The final endpoint of the study is time to
improvement in the NIS by 4 points. The NIS17 is a
global score summating muscle weakness, decrease
in reflexes, and decrease in sensation. Secondary
endpoints include a functional gait scale; isometric
muscle strength testing; Neuropathy Symptom and
Change score; analog pain scale; quantitative sensory
testing performed on the foot, leg and thigh; quantitative autonomic testing (autonomic reflex screen);
and nerve conduction studies (bilateral femoral, peroneal, and tibial motor; sural sensory).
There have been significant concerns about giving diabetic patients intravenous steroids. As noted
above, patients with DLRPN usually have type II diabetes mellitus and have blood glucose under good
control. Most of the patients in our study have not
had marked disruption in their glycemia control after infusion of the study drug, although some patients have had transient fluctuations in their blood
sugars. No patients to date have had major complications related to steroidsone patient had a rectal
abscess, which was surgically treated. Another patient died of pneumonia several months after completing her study treatments, and her death was believed probably to be unrelated to her study drug.
Treating with steroids may theoretically be expected
to be more efficacious than with IVIg if the disease
process is vasculitic.
The IVIg study in DLRPN has a very similar design. There are three arms to the study: a high-dose
IVIg, a low-dose IVIg, and a control (saline) arm. It
is being conducted at a single center. This study has

MUSCLE & NERVE

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489

the same dosing frequency, number of evaluations,

and outcome measures as the methylprednisolone
study.
Little is known about treatment of the nondiabetic condition, LRPN. Bradley et al.7 reported
that 4 of their 6 patients improved with prednisone,
whereas Awerbuch et al.4 reported that their single
patient treated with prednisone did not improve.
Verma and Bradley47 reported 2 patients who responded to high-dose IVIg. Triggs et al.46 reported
that 5 patients improved with IVIg.
We conducted an open trial of weekly intravenous infusions of methylprednisolone in 11 LRPN
patients over 8 to 16 weeks.19 All had marked improvement of pain; in many, pain resolved completely. All patients had some improvement of weakness, and 9 of 11 graded this improvement as
marked. The median NIS was statistically improved
after the treatments, half by at least 50% (Fig. 5).
Before treatment, half of the patients were in wheelchairs and all but 1 used aid in ambulating, whereas
after treatment only 1 patient was still in a wheelchair and 6 walked independently. We believe these
treatment data are preliminary and are not definitive. There were no control patients, and LRPN can
improve spontaneously. However, we believe the
treatment probably was helpful, because the improvement in symptoms began with initiation of
treatment in all cases and the degree of improvement was marked. Prospective placebo-controlled,
double-blind studies (as described above for DLRPN)
will be needed to determine whether immunemodulating therapies are effective in treating LRPN.

FIGURE 5. The NIS of 11 patients with LRPN plotted with time

after a course of intravenous methylprednisolone therapy. Each
line represents a different patient; large dots represent patient
evaluations; solid lines represent the treatment period. Without
exception, the NIS improved (scores decreased) after the treatment period, sometimes dramatically. This improvement in NIS
probably reflects efficacy of therapy, but the study was an open
trial, bias could have influenced results, and improvement may
occur spontaneously. (Reproduced with permission from Dyck et.
al.19)

SYMPTOMATIC TREATMENT

Both DLRPN and LRPN are severe illnesses with

great morbidity. Because they are usually a monophasic illness that improves with time, physicians
may under-appreciate the suffering and disability experienced. Patients frequently are so weak and have
such severe pain that they are unable to work; they
often require hospitalization to achieve adequate
pain control. Most patients require narcotic medication as well as treatment with other chronic neuropathic pain medications (such as tricyclic antidepressants and antiseizure agents). Patients should be
warned that it is often impossible to relieve the pain
completely, and the goal is to make the pain tolerable. Because these conditions begin abruptly and
severely, these conditions are often misdiagnosed,
and many patients get unnecessary operations for
suspected disk disease. Patients often worry that the
disease will be progressive and fatal, and because of
the associated weight loss, they believe they may have

490

Lumbosacral Plexopathy

cancer. Almost invariably, patients with DLRPN and

LRPN become depressed due to protracted pain and
weakness.
Patients should be warned that although the disease may be monophasic, its course tends to be long
and recovery is often incomplete, and they should be
encouraged to stay involved with hobbies and other
interests. Depression should be treated with appropriate antidepressant medication. Physical therapy
should be used. Homes should be made as safe as
possible. Bracing such as anklefoot orthoses should
be fitted and used if needed. Physicians need to be
aggressive in helping patients with pain control and
hospitalization and in obtaining health and disability
insurance when needed. It is very important to encourage patients that although the illness may get
worse before it gets better, essentially all patients
with DLRPN and LRPN do improve to some degree,
if incompletely, over time.

MUSCLE & NERVE

April 2002

The authors gratefully acknowledge the secretarial help of Mary

Lou Hunziker, the data analysis help of Jane E. Norell, and the
editorial help of Peter J. Dyck and Christopher J. Klein in the
preparation of the manuscript. This work was supported in part
from grants received from the National Institute of Neurologic
Disorders and Stroke (NS36797).

22.
23.
24.
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