1
Lewis-Sumner syndrome associated with ulcerative colitis: report of a
patient with complete recovery after colectomy
Dra. M. Fragoso, Hospital de Terrassa, Barcelona
Introduction
Multifocal demyelinating sensory and motor neuropathy, also referred to as Lewis-Sumner
syndrome or multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, is
defined clinically by a multifocal and asymmetrical motor weakness and sensory loss with a
distribution consistent with the involvement of the peripheral nerve trunks, of insidious onset
with predominantly distal involvement affecting the upper extremities, and slowly progressive
course. Exceptionally, the cranial nerves may be involved. The disease is clinically similar to
multiple mononeuritis. Reflexes are usually diminished in a multifocal and asymmetrical pattern
but are rarely absent [1]. Neurophysiological studies reveal conduction blocks related to the
focal demyelinating regions of probable immune-mediated pathogenesis and other features
suggestive of demyelinating in one or more nerves, both in motor and sensory nerve conduction
studies [1]. Other findings include prolonged distal latencies, slowed conduction velocities,
temporal
dispersion,
conduction
blocks,
and
prolonged
F-wave
latencies.
Needle
electromyography (EEG) shows signs of active and chronic denervation. Analysis of the
cerebrospinal fluid (CSF) is usually unrevealing, although there is a high protein content in
many patients.
Retrospective clinical series have shown a favorable response to intravenous
immunoglobulins in a large percentage of patients. In contrast to multifocal motor neuropathy
(MMN), oral corticosteroid treatment is also effective. Some authors have suggested that MMN
and MADSAM are variants of the same disorder, --chronic inflammatory demyelinating
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polyneuropathy (CIDP)--, although they are mostly differentiated by the response to treatment.
Also, the main difference is the absence of sensory neuropathy in patients with MMN.
Acquired or non-hereditary chronic demyelinating neuropathies except for those caused
by drugs, such as amiodarone, are immune-mediated inflammatory disorders of the peripheral
nervous system. It can be associated with autoimmune systemic diseases, particularly
rheumatologic disorders or chronic inflammatory bowel disease. Extraintestinal complications
associated with inflammatory bowel disease are well established in the literature, the incidence
of which ranges between 0.2% and 35.7%. Peripheral neuropathy is one of the neurological
manifestations most frequently reported in patients with ulcerative colitis and Crohn’s disease,
including cases of acute inflammatory demyelinating polyneuropathy (AIDP or Guillain-Barré
syndrome), CIDP, non-demyelinating sensory, motor or mixed polyneuropathy, and even
isolated mononeuropathy [2,3].
Most neuropathies in ulcerative colitis are related with an immunological mechanism,
although other cases have been reported in relation to vitamin deficiency (vitamin B12, folic
acid) due to malabsorption, adverse effects of sulfasalazine that may cause sensory motor
neuropathy, or other drugs used in the treatment of ulcerative colitis, such as metronidazole or
infliximab [4-6].
We here describe the case of a patient with multifocal demyelinating sensory and motor
neuropathy (Lewis-Sumner syndrome) associated with ulcerative colitis, in whom complete
neurological recovery was achieved after total colectomy.
Case Report
A previously healthy 44-year-old was diagnosed of a moderate episode of ulcerative colitis
based on clinical manifestations and colonoscopy findings. He was initially treated with oral
and rectal administration of mesazaline to which oral corticosteroid treatment (1 mg/kg/day)
was added on the 3rd day of treatment. Ten days later, he was admitted to the hospital because
of a diagnosis of severe ulcerative colitis unresponsive to corticoid therapy. A consultation was
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made to the Service of Neurology because of motor weakness in the extremities.
Retrospectively, at the same time of the gastrointestinal episode, he referred a 3 weeks’ history
of progressive weakness for dorsal flexion of the left foot, proximal muscle weakness in the
right leg and difficulty climbing steps, clumsiness and paresthesias of the hands predominantly
in the right hand, and calf cramps.
The neurological examination showed hypoactive (particularly in the right upper
extremity) or abolished (bilateral Achilles reflexes) osteotendinous reflexes. Asymmetrical
muscle weakness with distal weakness in the left leg, impairment of the dorsal flexion of the
foot, and distal weakness of the right hand were noted. The Lassegue’s and Bragard’s tests were
negative. Sensory and cranial nerve examinations were normal. Laboratory data disclosed
anemia, high sedimentation rate, hypoalbuminemia, increased serum C-reactive protein level,
and positive IgM for cytomegalovirus (CMV) infection (IgM negative). Serologic tests for
hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and
toxoplasmosis were negative. Vitamin B12 and folate levels were within normal limits.
Neurophysiological studies showed slowed conduction velocities in the forearm segments of the
median nerves (distal latencies were preserved) and sciatic nerve block in the left popliteal fossa
(with normal distal conduction velocities and latencies). Motor conduction studies for the right
peroneal nerve and both ulnar nerves were normal. Sensory nerve conduction studies showed
preservation of distal potentials and block at mid-forearm of both median nerves. These findings
were compatible with an acquired multifocal demyelinating sensory and motor neuropathy.
Approximately one month after the onset of symptoms and after having being treated with oral
and intravenous corticosteroids for the episode of ulcerative colitis as well as cyclosporine (2.3
mg/kg/day) and rehabilitation therapy, neurological symptoms slowly improved but a marked
weakness of dorsiflexion of the left foot persisted.
Three months later, the patient was readmitted to the hospital because of worsening of
gastrointestinal symptoms. Because of lack of response to treatment with cyclosporine and
azathioprine, he was given infliximab (5 mg/kg). On the 5th day after the first dose of
infliximab, surgical treatment was indicated due to severity of symptoms, progressive anemia
4
requiring packed red cell transfusion and sustained hypoalbuminemia. The neurological
symptoms remained stable with a tendency towards improvement with physical rehabilitation
therapy. The patient underwent laparoscopic total abdominal colectomy with terminal
ileostomy. Histopathological findings of the surgical specimen were compatible with active
ulcerative colitis with extensive inflammatory ulceration and mild to moderate involvement in
the distal resection margins. Postoperatively, a marked neurological improvement was noted
(flexion of the left foot against gravity was possible). Six weeks after surgery, a control
neurophysiological study showed significant improvement of motor conduction studies,
persisting only a block of the left median nerve but of lesser intensity.
Discussion
We here describe the case of a patient who presented simultaneously a first episode of ulcerative
colitis and MADSAM, with resolution of both conditions after total colectomy. There are a few
cases reported in the literature in which a relationship between clinical improvement of
neurological symptoms with definitive surgical treatment of ulcerative colitis had been
established. On the basis of the patient’s clinical history and data of physical examination, a first
tentative diagnosis of multiple mononeuritis was made and a Guillain-Barré syndrome was not
considered due to the marked asymmetry and the absence of clinical signs of involvement of the
nerve roots despite of the well-known association of both diseases [3]. Although neuropathies
appearing as an extraintestinal complication of ulcerative colitis may be independent of the
activity of the inflammatory bowel disease, the parallel clinical course of both diseases in our
patient suggested the presence an immune-mediated neuropathy. Involvement of sensory
conduction studies on neurophysiological examination confirmed the diagnosis of MADSAM
and excluded the diagnosis of MMN; both conditions also show differences in the therapeutic
response. Since neurological symptoms remained stable and given the favorable response to
corticosteroid treatment in cases of MADSAM reported in the literature, an expectant attitude
was considered adequate given that the patient was being treated with oral and intravenous
corticoids at the same doses than those used in the management of immune-mediated
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neuropathies [7,8]. After a few days, intravenous cyclosporine followed by azathioprine was
given because of worsening of gastrointestinal symptoms, and there was a slowly progressive
neurological improvement. Intravenous immunoglobulins or corticosteroids are the treatment of
choice of MADSAM, and there is no evidence of the effect of other immunosuppressant agents
in the literature. Data regarding the usefulness of azathioprine and cyclophosphamide are
inconclusive [8].
Finally, surgical treatment was crucial to achieve digestive and neurological recovery.
The patient was practically asymptomatic at the control visit 6 weeks after surgery.
In summary, we report a case of MADSAM associated with ulcerative colitis both of
new onset and complete resolution after definitive treatment of the underlying disease, in this
case, total surgical colectomy.
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