may improve Lumbosacral Radiculoplexus Neuropathy
James B. Dyck, Jane E. Norell, and Peter James Dyck
Objective: To report on an open trial of intravenous
methylprednisolone (IV MP) in nondiabetic lumbosacral radiculoplexus
neuropathy (LSRPN). Background: Lumbosacral radiculoplexus
neuropathy is a subacute, unilateral or asymmetric syndrome
of pain, weakness, and paresthesia of the lower extremity, which
is attributed to ischemic injury from microvasculitis in lumbosacral
roots, plexus, and nerves. Methods: Eleven nondiabetic
patients with worsening LSRPN were treated - ten with infusions
of IV MP (1 gm/wk) for 8 to 16 weeks and one with an equivalent
dosage of oral prednisone. The main endpoints evaluated were:
1) the Neuropathy Impairment Score (NIS), and 2) the Neuropathy
Symptoms and Change (NSC) scores. Results: The
median age of our patients was 67 years, range 49 to 86 years.
Seven patients were women. All 11 patients reported improvement
during treatment - nine reported marked improvement. The median
NIS improved from 42 points (range 9 to 106 points) before treatment,
to 20 points (range 5 to 57 points) (p = 0.005) after treatment.
Pain was completely resolved in four patients and much improved
in seven. The change subscore and the severity subscore of the
NSC were statistically significantly improved after treatment.
Prior to treatment, all patients had significant weakness with
six confined to wheelchairs and four using mechanical devices
to aid in ambulation. After treatment, the weakness was markedly
improved in nine patients; only one still required a wheelchair
and six walked independently (p = 0.03). Conclusions:
1) In LSRPN, pain and neurological deficits improved (often
dramatically) with IV MP treatment. 2) Although our results
should be interpreted with caution since this trial is uncontrolled,
IV MP may favorably affect the natural history of LSRPN. 3)
The results are sufficiently promising to provide a rationale
for prospective, sham controlled, double blind trials.
La méthyprednisolone peut améliorer la neuropathie
du plexus lombo-sacré. Objectif: De rapporter
une étude ouverte sur l'injection intraveineuse de méthylprednisolone
(MPIV) chez des sujets non diabétiques présentant
une neuropathie du plexus lombo-sacré (NPLS). Introduction:
La neuropathie lombosacrée est un syndrome douloureux
subaigu unilatéral ou asymétrique accompagné
de faiblesse et de paresthésies du membre inférieur
qui est attribué à une lésion ischémique
due à une microvasculite des racines lombosacrées,
du plexus et des nerfs. Méthodes: Onze
patients non diabétiques présentant une NPLS de
plus en plus sévère ont été traités
- dix au moyen d'infusions (1 gm par semaine) de MPIV pendant
8 à 16 semaines et un au moyen d'une dose équivalente
de prednisone orale. Les principaux critères d'évaluation
des résultats étaient: 1) le Neuropathy Impairment
Score (NIS) et 2) les Neuropathy Symptoms and Change (NSC) scores.
Résultats: L'âge médian des
patients était de 67 ans (écart de 49 à
86 ans). Sept des patients étaient des femmes. Tous les
patients ont rapporté une amélioration des symptômes
pendant le traitement et cette amélioration était
importante chez neuf. Le NIS s'est amélioré de
42 points (écart de 9 à 106 points) avant le traitement,
à 20 points (écart de 5 à 57 points) (p
= 0.005) après le traitement. La douleur est disparue
complètement chez quatre et a été très
améliorée chez sept. L'analyse statistique des
scores de changement et de sévérité du
NSC a montré une amélioration significative après
le traitement. Avant le traitement, tous les patients avaient
une faiblesse importante et six étaient confinés
au fauteuil roulant alors que quatre utilisaient un soutien
mécanique pour la marche. Après traitement, la
faiblesse était très améliorée chez
neuf patients; seulement un utilisait un fauteuil roulant et
six marchaient sans aide (p = 0.03). Conclusions: 1)
Dans la NPLS, la douleur et les déficits neurologiques
se sont améliorés, souvent de façon dramatique,
avec le traitement par la MPIV; 2) bien que nos résultats
doivent être interprétés avec prudence étant
donné qu'il s'agit d'une étude ouverte, la MPIV
peut influencer favorablement l'histoire naturelle de la NLS;
3) ces résultats sont assez prometteurs pour justifier
des études prospectives, à double insu, avec placebo.
J. Neurol. Sci. 2001; 28: 224-227
neuropathies, inflammatory varieties are common and include
such disorders as acute inflammatory demyelinating polyneuropathy,
chronic inflammatory demyelinating polyneuropathy, vasculitic
neuropathies, and granulomatous neuropathies among others. Some
of these conditions have been shown to respond favorably to
immune modulating therapy. Response to immunotherapy may be
recognized by amelioration of symptoms and impairments which
persists for a period of time thereafter, (perhaps the typical
response in CIDP) or by lessening the severity and duration
of the disease (as in AIDP and perhaps also in nondiabetic lumbosacral
radiculoplexus neuropathy (LSRPN) as discussed here).
lumbosacral radiculoplexus neuropathy, first recognized in 1981,
is a syndrome of unilateral or asymmetric lower-limb pain, weakness
and paresthesia which occurs in patients without diabetes mellitus.
[1,2] Since then, only a few reports have been published.
[3-7] Bradley et al  reported ischemic injury
and perivascular inflammatory cell cuffing in biopsies from
six cases with increased sedimentation rates, three with and
three without diabetes mellitus. Recently, we studied biopsied
distal nerves from 47 LSRPN cases (some included in this report)
and found evidence of ischemic injury and microvasculitis. 
We also found that although the condition tends to be monophasic,
there is pronounced long-term morbidity in almost all patients.
spite of this long-term morbidity, there is no proven treatment
for LSRPN. There are reports of improvement with prednisone
and intravenous immunoglobulin in a small number of patients.
[5,7,8] Here, we report on an open trial of intravenous
methylprednisolone (IV MP) in 10 patients with LSRPN and the
treatment of one LSRPN patient with an equivalent dose of oral
11 cases had subacute onset of pain, weakness, or paresthesia
of one or both lower extremities and clinical and electromyographic
characteristics in keeping with localization of the disease
process to lumbosacral roots, plexuses, or nerves. For inclusion,
patients had to show electromyographic abnormalities attributable
to lesions in at least two peripheral nerves and in the distribution
of at least two nerve roots. Cases were not included if their
neuropathic disorder was explained by such structural lesions
as tumor or compression, if they were clinically improving,
if they had a history of diabetes mellitus, or their fasting
blood sugars were in the diabetic range by American Diabetes
Association criteria (fasting plasma glucose 126
mg/dl) (7.0 mmol/L). Also excluded were patients with systemic
vasculitis or connective tissue diseases, Lyme disease, sarcoidosis,
inherited tendency to pressure palsies, radiation neuropathy
or other diagnoses that could explain the neurological deficit.
Patients were selected irrespective of whether the clinical
involvement was localized primarily to the buttock, hip, thigh,
or leg. Patients were not excluded if they also developed some
upper extremity symptoms or signs, but the most severely involved
segment had to be in the lower extremities and the pattern had
to be that of an asymmetric disorder, not that of a length-dependent
characteristics and distribution of the neuropathy were quantitated
using the Neuropathy Impairment Score (NIS),  which
provides a single score of neuropathic impairment summating
muscle weakness, decrease of muscle stretch reflexes, and decreased
sensation based on a standard evaluation of a fixed group of
tests and corrected for age, gender, anthropometric features,
and physical fitness. The score is designed to give a higher
score for weakness than for sensory loss or reflex change. Neuropathic
symptoms were evaluated by the Neuropathy Symptoms and Change
(NSC) score.  Included in the NSC are number of
neuropathic symptoms (from 38), summated severity (graded 1
to 3 for each item of NSC) and summated change (symptoms after
treatment compared to symptoms at baseline (or a defined date)
and graded as unchanged (0), better (1 to 3), or worse (-1 to
-3) for each item of NSC). Also assessed were activities of
statistics were used to express results and to compare attributes
between groups. For continuous measurements, we expressed results
as medians and ranges and compared groups using Wilcoxon Rank
Sum Tests. For dichotomous variables, we used Fisher's Exact
of the neuropathy
median age of the eleven LSRPN patients was 67 years, range
49 to 86 years. Four were men and seven were women. The characteristic
symptoms were asymmetric lower limb pain, weakness and atrophy,
and paresthesia. The different types of pain included aching
or hurting, stabbing or electrical shock-like sensations, and
burning. Excessive tenderness to touch (allodynia) was a prominent
feature in many patients. In general, the disorder began with
pain followed by weakness and followed a subacute course that
had been progressive over months.
patients had unilateral disease whereas nine patients had bilateral
disease. All patients' disease began unilaterally or asymmetrically.
One patient had predominant involvement in L2, 3, 4
segments, one in L5,S1 segments and nine
in both. Four patients had mild upper-limb involvement, which
were probably due to compressive neuropathies (three ulnar neuropathies
at the elbow and one median neuropathy at the wrist). At initiation
of this open trial, the symptoms and impairments of all patients
were moderate or severe and static or worsening.
the 11 patients, ten received weekly infusions (1 gram/week)
of IV MP for eight to 16 weeks. The other patient received an
equivalent dosage of oral prednisone therapy. Four patients
received multiple infusions during the first week of treatment.
the initiation of therapy, the neuropathy had been present for
a median of 5.0 months (range 1.0 to 48.0 months). The median
time of follow-up after initial evaluation was 3.8 months (range
1.8 to 10.1 months). Usually, patients were evaluated shortly
after the end of the infusions to grade their response to treatment.
Some patients were seen multiple times in follow-up (see Figure).
eleven patients improved, sometimes dramatically during the
treatment period. Nine of the eleven judged their improvement
as marked. The median NIS before treatment was 42 points (range
9 to 106 points), whereas after treatment, the median NIS was
20 points (range 5 to 57 points) (p = 0.005, paired t test).
In assessing the change in NIS scores of individual patients,
all improved during treatment and five of 11 improved by at
least 50 percent (Figure).
Most of the improvement reflected improved measured weakness
of lower limb muscles. Consequently the NIS lower limb (NIS
(LL)) also improved dramatically. Before treatment, the median
NIS (LL) was 40 points (range 9 to 71 points) whereas after
treatment the median NIS (LL) was 19 points (range 5 to 57 points)
(p = 0.025, paired t test). All patients had severe pain prior
to treatment and most required narcotic medication. After treatment,
the pain was completely resolved in four, much better in the
other seven, and none needed narcotics. Patients noted that
the improvement in pain began shortly after the initiation of
treatment. Patients' symptoms, as graded by the NSC scores,
improved during treatment. The change subscore of the NSC (which
assesses how neurologic symptoms change with time) showed worsening
before treatment (median change -21 points, range -30 to -5
points) and a marked improvement after treatment (median change
11 points, range -1 to 42 points) (p = 0.002). All patients
had improved change subscores following treatment. The severity
subscore of the NSC also showed significant improvement from
before treatment (median 26.5 points, range 9 to 40 points),
to after treatment (median 19 points, range 7 to 30 points)
(p = 0.04) and all severity scores except one showed improvement
with treatment. Before treatment, all patients had severe weakness
with six confined to wheelchairs and four others needing walkers
or canes to ambulate. After treatment, the weakness was markedly
improved in nine of the 11 patients; only one still required
a wheelchair and six could walk independently (p = 0.03). All
of the patients felt they were actively worsening in their pain
and neurological deficits at the beginning of the treatment
period. They all felt that their improvement coincided with
the initiation of IV MP.
patients who had initially had marked improvement with IV MP
treatment later relapsed at varying periods of time following
treatment. Two were retreated with IV MP and again had dramatic
improvement. The third patient is currently being retreated
with IV MP.
the first descriptions of LSRPN, there have been rare case reports
and small series but no large studies of this disorder. [3-8]
In contrast, the diabetic form of this condition, diabetic lumbosacral
radiculoplexus neuropathy (DLSRPN) (diabetic amyotrophy, proximal
diabetic neuropathy) has been extensively studied. [13-18]
We have recently studied large cohorts of both DLSRPN and LSRPN
patients and found that the conditions appear to be alike and
are both caused by a microvasculitis. [9,10,18] We found
that both conditions tend to start unilaterally but become bilateral,
have substantial weight loss and are monophasic disorders. Nevertheless,
patients with both LSRPN and DLSRPN are left with long-term
impairments and morbidity due to pain and weakness and only
a small minority feel that they have recovered years later.
[9,10,18] The main difference is the occurrence of diabetes
mellitus in DLSRPN.
attention has been given to finding effective treatments for
either DLSRPN or LSRPN. It may be that investigators have not
sought treatment since the disorders are reported to have a
favorable outcome and because they are monophasic. However,
both DLSRSN and LSRPN are debilitating, painful, paralytic and
protracted conditions for which efficacious treatment is needed.
Treatment that could reduce the severity and duration of the
symptoms and impairments would undoubtedly decrease the disability,
which is usually severe and prolonged. Although most patients
improve over time, most do not return to their pre-morbid baseline.
Also, in our referral practice, LSRPN is not an uncommon diagnosis
and is probably under recognized by most neurologists.
data on treatment response of LSRPN are limited and variable.
Bradley et al  reported that four of their six patients
improved with prednisone. Awerbuch et al  reported
that their one patient treated with prednisone did not improve.
Verma et al5 reported that two patients responded to high dose
intravenous immunoglobulin. Triggs et al  reported
that five patients improved with intravenous immunoglobulin.
Although these data are encouraging, they are conducted on small
groups of patients, are uncontrolled and the treatment response
is not quantitated.
we report our experience of an open trial of IV MP in treating
LSRPN patients. Our studies were also uncontrolled but they
involved a somewhat larger group of patients than previously
reported and stereotyped treatments and quantitative endpoints
were used. All patients had marked improvement in pain and many
had complete resolution of pain. All had some degree of improvement
of weakness and most had major improvement in weakness. The
NIS score, the change scale of the NSC, and the severity scale
of the NSC were statistically significantly improved after the
treatment trial. More specifically, the NIS score and the change
scale of the NSC improved in every case, and in half of the
patients the improvement in the NIS was marked (see Figure).
Patients were significantly less dependent on wheelchairs and
aids in ambulating after treatment than they were before treatment.
All patients reported deterioration before treatment and felt
their improvement started shortly after initiation of IV MP
we think these results of treatment with IV MP in LSRPN are
strongly suggestive of efficacy, we do believe that they are
preliminary and not definitive. This was an open trial with
no control patients. Furthermore, as mentioned above, LSRPN
may improve spontaneously and so it is difficult to know how
much of the improvement can be attributed to the treatment.
However, the information available about natural history suggests
that spontaneous improvement is usually slow and incomplete.
In our series of long-term follow-up of LSRPN patients, only
three of 42 patients had recovered back to baseline at a median
of 35.5 months (range 5.0 to 198.5 months).  It
seems likely that the degree of improvement seen in our treated
LSRPN patients exceeded spontaneous improvement for the following
reasons: 1) improvement in pain and weakness began with initiation
of treatment in all cases; 2) the improvement was often of a
large magnitude; 3) all patients reported that their symptoms
had been worsening for the preceding months (in a few cases,
years) before treatment; and 4) all patients had improvement
of pain and weakness at follow-up (and none were worse). Nonetheless,
placebo-controlled, double blind, prospective studies will be
needed to answer definitively whether IV MP is efficacious or
not. However, our results are sufficiently promising to provide
a rationale for such trials in LSRPN as we are presently conducting
thank Mary Lou Hunziker and Carol Overland 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).
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the Peripheral Neuropathy Research Laboratory, Mayo Clinic
and Mayo Foundation, Rochester, Minnesota.
Presented at the American Academy of Neurology Meeting,
San Diego, California, 2000.
Received January 24, 2001. Accepted in final form May
Reprint requests to: P. James B. Dyck, Mayo Clinic, 200
First Street SW, Rochester, MN 55905 USA.
J. Neurol. Sci. 2001; 28: 224-227