1602
Outcome of Peroneal Neuropathies in Patients with
Systemic Malignant Disease
Devon I. Rubin, M.D.
David W. Kimmel, M.D.
Terrence L. Cascino, M.D.
Department of Neurology, Mayo Clinic and Mayo
Foundation, Rochester, Minnesota.
Address for reprints: David W. Kimmel, M.D., De-
partment of Neurology, Mayo Clinic, 200 First
Street SW, Rochester, MN 55905.
Received September 22, 1997; revision received
February 19, 1998; accepted March 25, 1998.
© 1998 American Cancer Society
BACKGROUND. Peroneal neuropathies in patients with systemic cancer previously
have been attributed to weight loss, but to the authors’ knowledge other associated
conditions have not been assessed, and the outcome of peroneal neuropathies in
cancer patients has not been studied.
METHODS. A retrospective chart review of patients evaluated at the Mayo Clinic
between 1984 and 1993 with systemic malignant disease and a clinical diagnosis of
peroneal neuropathy was performed to define factors associated with peroneal
neuropathies and to assess outcome. All patients underwent neurologic examina-
tion and electromyography.
RESULTS. Fifty-eight patients with systemic malignant disease were found to have
a peroneal neuropathy. Peroneal neuropathies occurred more often in men (45
patients) than in women (13 patients). The median age of the patients was 70 years.
The most common cancers were hematologic (12 patients) and pulmonary (11
patients), followed by tumors of the prostate (8 patients), gastrointestinal tract (7
patients), transitional cell (5 patients), breast (5 patients), and colon (5 patients), as
well as sarcomas and melanoma (5 patients). The median time to the diagnosis of
peroneal neuropathy after the diagnosis of cancer was 5 months. At the time of
diagnosis, 34 patients had severe deficits, 19 had moderate deficits, and 5 had mild
deficits. Associated factors included weight loss (occurring in 60% of patients), leg
crossing (35% of patients), recent chemotherapy (16% of patients), cutaneous
vasculitis (5% of patients), and local metastatic lesions (3% of patients). In nearly
50% of patients, peroneal neuropathy improved (25.9%) or resolved (22.4%). In
39.7% of patients, follow-up was inadequate because death occurred soon after
diagnosis. Of the patients with adequate follow-up before death, 80% had either
improvement (42.9%) or resolution (37.1%).
CONCLUSIONS. For those patients with systemic malignant disease in whom per-
oneal neuropathy develops, the outcome of the neuropathy is good, with the
majority of patients achieving partial or complete resolution. Cancer 1998;83:
1602– 6. © 1998 American Cancer Society.
KEYWORDS: peroneal neuropathy, footdrop, malignancy, vasculitis, outcome.
N euromuscular disorders are not uncommon in patients with sys-
temic malignant disease.1 Disorders of muscle, neuromuscular
junction, peripheral nerve, and brachial and lumbosacral plexuses
may occur both as a direct result and as a remote effect of an
underlying malignancy. Peroneal neuropathies commonly occur in
older patients with significant weight loss, crossing of the legs, or
traumatic compression of the nerve, such as that occurring with
intraoperative positioning. Peroneal neuropathies previously have
been associated with cancer, although the association has been at-
tributed to severe weight loss from the underlying malignant disease.1
To our knowledge, no previous studies have evaluated causes, con-
 Peroneal Neuropathies in Malignant Disease/Rubin et al.
tributing factors, or outcome in patients with concom-
itant peroneal neuropathy and systemic malignant
disease.
METHODS
A retrospective chart review was performed of patients
evaluated at the Mayo Clinic between 1984 –1993 who
had a diagnosis of “footdrop” or “peroneal neuropa-
thy” and a systemic malignant disease noted in the
dismissal diagnosis. Inclusion criteria was comprised
of peroneal neuropathy diagnosed by a staff neurolo-
gist and by electromyography and documented malig-
nant disease. Patients were excluded if they were not
evaluated by a neurologist, did not have evidence of
an isolated peroneal neuropathy on electromyography
(e.g., those with L5 radiculopathy or sciatic neuropa-
thy), did not have systemic malignant disease or had a
malignant lesion located adjacent to or involving the
peroneal nerve (e.g., osteochondroma of the fibular
head), or were not seen in follow-up after the diagno-
sis of peroneal neuropathy was made.
Charts were reviewed and if the inclusion criteria
were fulfilled patient characteristics were abstracted,
including age and gender, cancer type, documented
metastatic disease, treatment (specifically including
abdominal or pelvic surgery, abdominal or pelvic ra-
diation, and chemotherapy), time from the diagnosis
of malignant disease to the diagnosis of peroneal neu-
ropathy, contributing or causative factors, and out-
come. Outcome was determined according to im-
provement in motor strength on the neurologic
examination when documented, or according to com-
ments made in the medical record on following visits.
Improvement in strength of $ 25% (i.e., improvement
by $ 1 grades on neurologic examination) during
manual muscle testing of the weakest muscle was
considered significant improvement. Patients were
separated into four categories—“worsened,” “no
change,” “improved,” and “resolved”— on the basis of
statements made during follow-up examinations and
documented in the medical records. In addition, the
severity of the neuropathy at the time of diagnosis was
graded according to the severity of weakness of the
most affected muscle as follows: 75–100% loss of
strength: “severe”; 25–75% loss of strength: “moder-
ate”; and 0 –25% loss of strength: “mild.”
RESULTS
One hundred and sixty-eight charts were retrieved in
which diagnoses of “footdrop” or “peroneal neuropa-
thy” and systemic malignant disease and an electro-
myographic study were recorded. One hundred and
ten charts did not fulfill the inclusion criteria and were
excluded from further analysis. The most frequent
1603
reason for exclusion was an alternative neuromuscu-
lar diagnosis (64 patients), including focal or multiple
lumbosacral radiculopathies (40 patients), generalized
peripheral neuropathy (7 patients), upper motor neu-
ron lesion (6 patients), sciatic neuropathy (5 patients),
lumbosacral plexopathy (2 patients), and no clear
neurologic diagnosis (4 patients). Other reasons for
exclusion were no neurologic evaluation (10 patients),
no electromyography performed for the pertinent
problem (18 patients), and no history of or future
development of systemic malignant disease (10 pa-
tients). In four patients, peroneal neuropathy devel-
oped from a clearly defined cause that was unrelated
to malignancy: blunt trauma from a motor vehicle
accident in three patients and a penetrating bullet
injury in one patient. Four patients had a malignant
tumor directly involving or adjacent to the peroneal
nerve. Of these patients, two had fibrous histiocyto-
mas and two had osteochondromas of the fibular
head. They were excluded from further analysis.
During the period 1984 –1993, 115,081 patients
(51% of whom were male) were identified with an
underlying systemic malignant disease, and peroneal
neuropathy was diagnosed clinically and electromyo-
graphically in 58 of these patients (0.05%). The most
common malignancies associated with peroneal neu-
ropathies were hematologic (12 patients) and lung
carcinoma (11 patients), followed by carcinoma of the
prostate (8 patients), gastric and other upper gastro-
intestinal tract (7 patients), transitional cell (5 pa-
tients), breast (5 patients), and colon (5 patients), as
well as sarcomas and melanoma (5 patients). Three
patients had two unrelated malignant lesions. Twenty
of the 58 patients had documented metastatic disease.
The characteristics of and associated features in
patients with cancer and peroneal neuropathies are
listed in Table 1. The median age at the time of diag-
nosis of peroneal neuropathy was 70 years (range,
28 –94 years). Peroneal neuropathies occurred more
frequently in men (45 patients) than in women (13
patients), for a male to female ratio of 3.5:1. Eleven
patients had bilateral peroneal neuropathies. The per-
oneal neuropathy at onset was “severe” in 34 patients
(59%), “moderately severe” in 19 patients (33%), and
“mild” in 5 patients (8%). The median time to the
diagnosis of peroneal neuropathy after the diagnosis
of malignant disease was 5 months (range, 1.6 –59.0
months). Symptoms developed in 8 patients before
the diagnosis of malignant disease, with the earliest
onset occurring 12 months before diagnosis.
The most common factor associated with pero-
neal neuropathy was weight loss, occurring in 35 of
the 58 patients. Other associated features were a his-
tory of leg crossing (20 patients) and chemotherapy
1604 CANCER October 15, 1998 / Volume 83 / Number 8

TABLE 1
Characteristics of and Contributing Factors in Patients with Peroneal Neuropathy and Underlying Malignant Disease

Age (yrs) Gender

No. of Time to Weight Leg Pelvic
Tumor type patients Median Range M F Dxa (mos) loss crossing Postoperative Chemotherapy Vasculitis Metastasis irradiation

Lung 11 67 56–79 9 2 4 7 1 4 4 1 0 0
Prostate 8 72 62–94 8 0 48 4 3 2 0 0 0 1
Bladder 5 71 54–77 3 2 11 1 2 2 0 0 0 0
Colon 5 74 59–81 5 0 5 3 2 0 0 1 0 0
Breast 5 71 43–76 0 5 12 3 2 1 1 0 0 1
Stomach 7 64 49–73 7 0 2 7 4 1 1 0 2 0
Hematologic 12 66.5 28–78 8 4 5 9 4 0 3 1 0 0
Other 5 59 41–72 5 0 12 1 2 2 0 0 0 0
Totalb 58 70 28–94 45 13 5 35 (60) 20 (34) 12 (21) 9 (16) 3 (5) 2 (3) 2 (3)

a
Months after the diagnosis of malignant disease (median).
b
Percentages in parentheses.
M: male; F: female; DX: diagnosis.

TABLE 2
Outcome of Peroneal Neuropathy in Patients with an Underlying Malignant Disease

Died
Resolved Improved No change Worsened (no follow-up)
No. of
Tumor type patients No. % No. % No. % No. % No. %

Lung 11 2 18 4 36 2 18 0 0 3 27
Prostate 8 1 13 2 25 0 0 0 0 5 63
Bladder 5 2 40 2 40 1 20 0 0 0 0
Colon 5 1 20 1 20 0 0 1 20 2 40
Breast 5 3 60 0 0 1 20 0 0 1 20
Stomach 7 0 0 0 0 1 14 0 0 6 86
Hematologic 12 2 17 3 25 1 8 0 0 6 50
Other 5 2 40 3 60 0 0 0 0 0 0
Total 58 13 22.4 15 25.9 6 10.3 1 1.7 23 39.7

within the past year (9 patients). The agents used in thy, which developed between 1 day and 2 weeks after
these patients were cyclophosphamide (five patients), surgery. Eight patients had a concomitant diagnosis of
doxorubicin (two patients), vincristine (two patients), diabetes mellitus. Five patients had none of the fea-
cisplatin (two patients), and etoposide, 5-fluorouracil, tures noted earlier, and no contributing factors were
vinblastine, mitomycin, bleomycin, and cyclosporine identified.
(one patient each). Five patients were in the midst of The outcome of peroneal neuropathy was as-
a chemotherapeutic regimen at the time that peroneal sessed quantitatively when documented and qualita-
neuropathy developed, and the other four patients tively otherwise (Table 2). Peroneal neuropathy re-
had finished chemotherapy between 1 month and 7 solved completely in 22.4% of the patients and
months before peroneal neuropathy occurred. Only partially in 25.9%. The small numbers of patients in
two patients had undergone previous pelvic irradia- each histologic category precluded statistical analysis.
tion. Cutaneous vasculitis recently had been diag- Peroneal neuropathy progressed in only one patient
nosed in three patients, and local metastatic lesions after the diagnosis was confirmed. In 39.7% of pa-
involving the peroneal nerve occurred in two patients, tients, no follow-up preceded death. The median time
both of whom had widespread metastatic gastric car- to death after the diagnosis of peroneal neuropathy in
cinoma and presented with pain in the lateral leg. The the 23 patients without follow-up was 7 months
diagnosis of bony metastasis to the tibia or femur was (range, 1 week-2 years). Excluding these 23 patients,
made with magnetic resonance imaging. Twelve pa- 37.1% of the patients with adequate follow-up had
tients experienced postoperative peroneal neuropa- resolution of the peroneal neuropathy and 42.9% had
 Peroneal Neuropathies in Malignant Disease/Rubin et al.
improvement. The time from the initial diagnosis to
the final recorded evaluation at follow-up in these
patients ranged from 4 days-8 years (median, 6
months).
DISCUSSION
Peroneal neuropathy is a common neuromuscular
condition, accounting for approximately 30% of all
cases of footdrop.2 Most commonly, weakness of the
toe extensors and ankle dorsiflexors and everters oc-
curs as a result of compressive entrapment of the
common peroneal nerve at the level of the fibular
head. Numerous causes have been responsible for or
associated with peroneal neuropathies, including
blunt and penetrating trauma, constrictive devices
such as plaster casts, leg crossing, and intraoperative
positioning of the leg. In addition, peroneal neuropa-
thies and marked weight loss have been closely asso-
ciated, although the mechanism has not been eluci-
dated clearly.3,4
Peroneal neuropathies have been known to occur as
a result of compression by local bony tumors (such as
osteochondromas),5,6 nerve sheath tumors (such as neu-
rofibromas),7 or other local masses (such as ganglion
cysts).8 To our knowledge there has not been any previ-
ously identified association between systemic cancer
and peroneal neuropathies, aside from the association
with weight loss.1 In a combination of two large series of
peroneal neuropathies with a total of 212 patients,2,9 no
mention was made of systemic malignant disease in any
patient. We selectively reviewed patients with known
systemic cancer and peroneal neuropathy to assess
causative or associated factors and to evaluate the out-
come of the neuropathy.
In this series, the median age of patients at the
time of diagnosis of the neuropathy was older than
that previously reported9 and most likely is due to
selection bias of the patient population in this study.
The occurrence of peroneal neuropathies reflects the
relative frequencies of the various malignant diseases
in the population from which this series was drawn.
Peroneal neuropathy developed in eight patients be-
fore the diagnosis of cancer. Although it is unclear
whether there is any relation between peroneal neu-
ropathy and malignant disease in patients whose neu-
ropathy preceded the cancer diagnosis, it is possible
that constitutional symptoms such as weight loss may
have been occurring, contributing to the peroneal
neuropathy. Lymphomatous infiltration of a sural
nerve has been reported in a patient with generalized
peripheral neuropathy 7 years before the development
of systemic B-cell lymphoma,10 supporting the idea
that peripheral nervous system manifestations may
precede the diagnosis of systemic malignant disease
1605
by several months to years. However, there have been
no prior reports of solid tumor infiltration of periph-
eral nerves. In addition, spontaneous improvement of
the neuropathy in the majority of our patients argues
against this mechanism.
The pathophysiology of peroneal neuropathies
has been attributed to focal demyelination with sec-
ondary axonal degeneration or to pure axonal loss
without demyelination,9 which most commonly is due
to focal compression of the common peroneal nerve.
It is likely that patients with systemic malignant dis-
ease also have focal compression from secondary fac-
tors, such as weight loss and leg crossing. However,
other potential mechanisms may be causative or con-
tributory to the development of peroneal neuropathy.
Although 20 of 58 patients in our series had known
metastatic disease, none underwent nerve biopsy or
postmortem examination of peripheral nerves to as-
sess for tumor infiltration. In two patients, metastases
to the distal femur and proximal tibia developed ad-
jacent to the peroneal nerve, most likely causing either
compression or infiltration of the nerve.
Radiation-induced lumbosacral neuropathies have
occurred after irradiation of paraaortic, pelvic, inguinal,
and sacral sites.11,12 Only two patients in the current
series received pelvic radiation, and given the location of
the radiation, it is unlikely that it had any relation to the
development of an isolated peroneal neuropathy. Che-
motherapeutic agents such as cisplatin and Vinca alka-
loids are well known to be neurotoxic, leading to senso-
rimotor or sensory peripheral neuropathies. Isolated
peroneal neuropathy related to vincristine toxicity also
has been reported.13 Nine patients in our series received
chemotherapeutic agents within 1 year before the onset
of neuropathy, although only 5 of them received agents
that would be considered neurotoxic.
It is interesting to note that three patients with
peroneal neuropathy had a previous diagnosis of bi-
opsy-proven cutaneous vasculitis. In none of these
three patients was a nerve biopsy performed to eval-
uate for vasculitic neuropathy. Sensorimotor periph-
eral neuropathy due to vasculitis has been reported,
albeit rarely, in patients with prostate and kidney car-
cinoma and lymphoma.1,14 It is believed to be a re-
mote effect of the malignant disease causing an in-
flammatory response limited to the peripheral nerves,
and this may have occurred in our three patients.14
Although peroneal neuropathy is a common neu-
rologic disorder, limited data are available on out-
come. In an early study of 20 predominantly compres-
sive peroneal neuropathies, 18 had resolved or
improved and only 2 had improved minimally.15 Berry
and Richardson16 assessed 70 patients with peroneal
neuropathies from different causes and monitored
1606 CANCER October 15, 1998 / Volume 83 / Number 8
progress in 34 patients to the point of full recovery or
for 1 year and found “good” to “moderate” outcomes
in 28 patients. There was no mention of malignancy in
any of the patients. In a later study of 14 patients with
spontaneous or compressive peroneal neuropathies,17
6 had clinical resolution and 8 had improvement after
a follow-up period of 1–2 years. Comparing outcome
in our selected group of patients with that in patients
with peroneal neuropathy from other causes was not
the goal of this study. However, the good outcome in
these patients appears consistent with the outcomes
reported in the literature, as previously mentioned.
Because patients with systemic malignant disease
often have marked weight loss, have poor nutritional
status, and are debilitated or bedridden, one might ex-
pect a poor outcome with little or no improvement after
the development of peroneal neuropathy. Surprisingly,
of the 58 patients in the current study, 28 (48.3%) had
either resolution or improvement. Twenty-three patients
died soon after peroneal neuropathy was diagnosed,
most likely as a result of advanced disease. These pa-
tients did not have adequate neurologic follow-up. If
these patients with advanced disease and rapid death
are excluded, 42.9% of the remaining patients with per-
oneal neuropathies had resolution, and 80% of these
patients had either complete or partial resolution at a
median follow-up of 5 months.
The current study has several limitations. The ret-
rospective review may have identified patients with
peroneal neuropathies that in fact were not associated
with systemic malignant disease but occurred in pa-
tients with a separate diagnosis of cancer. In an effort
to minimize this, cases were excluded if a clear cause
of the peroneal neuropathy such as trauma was iden-
tified. In addition, the diagnosis may have been over-
looked in patients with only mild weakness or over-
whelming medical complications. A substantial
number of patients also were excluded because of
inadequate neurologic or electrophysiologic evalua-
tions or follow-up. If all patients had been included,
the results and overall outcome of the study might
have been altered. Follow-up in this study is limited to
clinical and subjective assessment, because few pa-
tients underwent serial electromyographic studies.
Because of the small number of patients with fol-
low-up electromyograms and the good outcome, it
was not possible to evaluate outcome with electro-
myographic findings. It would be of interest to corre-
late clinical and electrophysiologic improvement, be-
cause it is possible that even more patients would
have shown improvement, and electromyography also
may have been useful as a prognostic tool.
Isolated peroneal mononeuropathy is a neuro-
muscular condition of many known causes that occurs
frequently in the general population. Systemic malig-
nant disease should be added to the list of associated
factors. Although the relation between peroneal neu-
ropathy and malignant disease most commonly ap-
peared to be due to constitutional symptoms and local
compression such as weight loss and leg crossing,
other mechanisms, including local or infiltrated met-
astatic lesions or a “paraneoplastic” vasculitis, also
may contribute. Most patients had improvement or
complete recovery.
REFERENCES
1. Stubgen JP. Neuromuscular disorders in systemic malig-
nancy and its treatment. Muscle Nerve 1995;18:636 – 48.
2. Van Langenhove M, Pollefliet A, Vanderstraeten G. A retro-
spective electrodiagnostic evaluation of footdrop in 303 pa-
tients. Electromyogr Clin Neurophysiol 1989;29:145–52.
3. Sotaniemi KA. Slimmer’s paralysis—peroneal neuropathy
during weight reduction. J Neurol Neurosurg Psychiatry
1984;47:564 – 6.
4. Cruz Martinez A. Slimmer’s paralysis: electrophysiological
evidence of compressive lesion. Eur Neurol 1987;26:189 –92.
5. Levin KH, Wilbourn AJ, Jones HR Jr. Childhood peroneal
neuropathy from bone tumors. Pediatr Neurol 1991;7:308 –9.
6. Watson LW, Torch MA. Peroneal nerve palsy secondary to
compression from an osteochondroma. Orthopedics 1993;
16:707–10.
7. Nagel A, Greenebaum E, Singson RD, Rosenwasser MP, McCann
PD. Foot drop in a long-distance runner. An unusual presentation
of neurofibromatosis. Orthop Rev 1994;23:526–30.
8. Antonini G, Bastianello S, Nucci F, Artico M, Bozzao L,
Millefiorini M. Ganglion of deep peroneal nerve: electro-
physiology and CT scan in the diagnosis. Electromyogr Clin
Neurophysiol 1991;31:9 –13.
9. Katirji MB, Wilbourn AJ. Common peroneal mononeuropa-
thy: a clinical and electrophysiologic study of 116 lesions.
Neurology 1988;38:1723– 8.
10. Vital C, Vital A, Julien J, Rivel J, deMascarel A, Vergier B, et al.
Peripheral neuropathies and lymphoma without monoclo-
nal gammopathy: a new classification. J Neurol 1990;237:
177– 85.
11. Thomas PK, Holdorff B. Neuropathy due to physical agents. In:
Dyck PJ, Thomas PK, editors. Peripheral neuropathy. Volume
2, 3rd edition. Philadelphia: W.B. Saunders, 1993:1000 – 6.
12. Thomas JE, Cascino TL, Earle JD. Differential diagnosis be-
tween radiation and tumor plexopathy of the pelvis. Neu-
rology 1985;35:1–7.
13. Levitt LP, Prager D. Mononeuropathy due to vincristine
toxicity. Neurology 1975;25:894 –5.
14. Johnson PC, Rolak LA, Hamilton RH, Laguna JF. Paraneo-
plastic vasculitis of nerve: a remote effect of cancer. Ann
Neurol 1979;5:437– 44.
15. Garland H, Moorhouse D. Compressive lesions of the exter-
nal popliteal (common peroneal) nerve. Br J Med Psychol
1952;2:1373– 8.
16. Berry H, Richardson PM. Common peroneal nerve palsy: a
clinical and electrophysiological review. J Neurol Neurosurg
Psychiatry 1976;39:1162–71.
17. Smith T, Trojaborg W. Clinical and electrophysiological re-
covery from peroneal palsy. Acta Neurol Scand 1986;74:
328 –35.