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Case Report - Hypoesthesia and Paralysis PDF
Case Report - Hypoesthesia and Paralysis PDF
Dr. Daniel B. Rubin (Neurology): A 57-year-old-woman was admitted to this hospital From the Departments of Neurology
because of progressive hypoesthesia, paresthesia, and weakness in the arms and legs. (M.P.B., W.S.D., T.A.C.) and Pathology
(A.S.D.), Massachusetts General Hospi‑
The patient had been in her usual health until 18 months before this admission, tal, and the Departments of Neurology
when paresthesia developed in the feet. Sixteen months before this admission, the (M.P.B., W.S.D., T.A.C.) and Pathology
patient underwent lumbar surgery, including laminectomy and facetectomies at (A.S.D.), Harvard Medical School —
both in Boston.
L3–L4 and bilateral foraminotomies at L4. After surgery, she reported that the
symptoms in the feet had diminished. N Engl J Med 2017;377:1977-84.
DOI: 10.1056/NEJMcpc1710564
Nine months before this admission, hypoesthesia and weakness recurred in the Copyright © 2017 Massachusetts Medical Society.
feet; over a period of several months, they spread to involve the legs and hands.
The patient had several falls at home and began to use a cane and then a wheel-
chair. Eight months before this admission, she was evaluated at an outpatient
neurology clinic, and electromyography and nerve-conduction studies were per-
formed. A presumptive diagnosis of chronic inflammatory demyelinating polyneu-
ropathy (CIDP) was made, and intravenous immune globulin (IVIG) was adminis-
tered; the patient reported transient improvement in sensation and strength in her
legs and hands. During the next 6 months, IVIG was administered every 4 weeks,
but hypoesthesia and weakness progressed to involve both arms. When she was
no longer able to transfer safely into a wheelchair, she presented to the emergency
department of another hospital for evaluation.
In the emergency department of the other hospital, the patient reported incon-
sistent bowel and bladder continence and progressive hypoesthesia and weakness
in her legs and arms. She had a history of chronic low-back pain (which had been
treated with opioids), fibromyalgia, headaches, and depression. Surgeries included
appendectomy, cholecystectomy, and hysterectomy in the distant past, as well as
Roux-en-Y gastric bypass approximately 4 years earlier. Medications included
controlled-release morphine sulfate, hydrocodone with acetaminophen, gabapentin,
diazepam, cyclobenzaprine, valproic acid, citalo- pinprick was absent in the legs and diminished
pram, cyanocobalamin, and cholecalciferol. The in the arms. Sensation to pinprick was impaired
patient was married, lived with her husband in caudal to the T4 level. The plantar reflex was
New England, and did not smoke tobacco, drink absent bilaterally. A blood test for antinuclear
alcohol, or use illicit drugs. There was no family antibodies was positive at a titer of 1:40, with a
history of autoimmune disease; her father had a speckled pattern. Serum protein electrophoresis
history of bladder cancer. revealed a normal pattern, with a moderate, dif-
On examination at the other hospital, the fuse increase in immune globulin. Screening tests
temperature was 36.6°C, the blood pressure for antitreponemal antibodies and for antibodies
138/66 mm Hg, the pulse 64 beats per minute, to Borrelia burgdorferi and human T-lymphotropic
the respiratory rate 18 breaths per minute, and virus (HTLV) types 1 and 2 were negative. Other
the oxygen saturation 100% while the patient was laboratory test results are shown in Table 1.
breathing ambient air. The oropharynx had no Nerve-conduction studies and needle electromy-
erythema or exudate; the patient was edentulous, ography were performed.
with a normal-appearing oral mucosa and tongue. Dr. William S. David: The nerve-conduction stud-
Results of cranial-nerve examinations were nor- ies revealed normal sensory responses, apart from
mal (although the first cranial nerve was not a mildly reduced amplitude of the right ulnar
tested). Strength was 0–1 out of 5 in the legs and nerve. Fibular motor responses could not be
3 out of 5 in the arms. Sensation to pinprick was elicited in the extensor digitorum brevis muscle
decreased in both legs, from the toes to the hips. in either leg; fibular motor responses were se-
Negative inspiratory force at functional residual verely reduced in the tibialis anterior muscle in
capacity and vital capacity were normal. A stage 2 both legs, as were posterior tibial motor respons-
pressure ulcer was present over the sacrum. The es in the abductor hallucis muscle. Distal motor
remainder of the examination was normal. latencies and velocities were normal. Needle elec-
Blood levels of electrolytes, glucose, vitamin B12 tromyography revealed scattered fibrillation po-
(cobalamin), and vitamin B9 (folate) were normal, tentials and positive sharp waves in two muscles
as were results of kidney- and liver-function tests. in the right arm and two muscles in the right
Blood tests for human immunodeficiency virus leg. The patient was unable to activate units in
(HIV) type 1 p24 antigen and antibodies to HIV several muscles in the arms and legs. In other
types 1 and 2 and hepatitis C virus were nega- muscles, there was a reduced number of normal-
tive. The blood level of valproic acid was 15.3 μg appearing motor units and slow firing of those
per milliliter (therapeutic range, 50 to 100). Uri- units, findings suggestive of impaired activation.
nalysis was unremarkable. Other laboratory test Dr. Rubin: MRI of the cervical, thoracic, and
results are shown in Table 1. Magnetic reso- lumbar spine, performed with and without the
nance imaging (MRI) of the head was performed administration of intravenous contrast material,
without the administration of contrast material; revealed mild scattered degenerative changes of
T2-weighted images showed mild abnormalities the spine, with no evidence of cord compression,
in the periventricular white matter, a finding nerve-root impingement, or a demyelinating pro-
consistent with a chronic small-vessel ischemic cess. A lumbar puncture was performed for
process. Valproic acid was stopped, high-dose analysis of the cerebrospinal fluid (CSF); results
methylprednisolone was administered, and the are shown in Table 1. Hypoesthesia and weak-
patient was transferred to the neurology depart- ness in the arms and legs did not improve, and
ment of this hospital for evaluation. the results of a neurologic examination were
On examination at this hospital, results of a unchanged from those obtained on admission.
mental-status examination (including tests of Dr. David: On the fifth hospital day, studies
language, attention, and memory) were normal. for somatosensory evoked potentials were per-
There was no voluntary movement in the legs; formed. The right median somatosensory evoked
there was atrophy of the calf and foot muscles. potential was normal; the left side was not
Weakness was more severe in the hands than in studied. The P37 scalp waveform was absent in
the proximal arms. Deep-tendon reflexes were the right tibial somatosensory evoked potential,
2+ at the ankles, 3+ at the patellas, and 3+ at the a finding that suggested a disruption of central
biceps. Perception of vibration, light touch, and conduction.
* Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at
Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results.
They may therefore not be appropriate for all patients.
Dr. Rubin: A diagnostic test was performed. or to poor effort of the patient during testing.
Finally, the right tibial somatosensory evoked
Differ en t i a l Di agnosis potential with central slowing in combination
with a normal median somatosensory evoked
Dr. Michael P. Bowley: The first step in construct- potential supports dysfunction of the dorsolat-
ing a differential diagnosis in this case is to de- eral columns in the thoracic or lumbar region of
termine the location of the disease process in the spinal cord. After considering these find-
the nervous system. This patient had reduced ings, we can conclude that this patient has a
sensation to pinprick on the trunk below the T4 diffuse myelopathy involving the cervical, thorac-
level. This finding, which indicates disruption of ic, and lumbosacral spinal cord.
the ascending spinothalamic fibers at the ap-
proximate level of the thoracic spinal cord, is a Myelopathy
clinical hallmark of spinal cord dysfunction. In The differential diagnosis of myelopathy is broad
addition, she had weak limbs accompanied by and includes infectious, structural, inflammatory,
hyperreflexia, a finding that indicates dysfunc- autoimmune, vascular, hereditary, and metabolic
tion of upper motor neurons or their descending causes. The chronic and progressive nature of this
projections in the corticospinal tracts. Finally, she patient’s illness rules out many acute or subacute
had a history of bladder incontinence, a symptom causes of myelopathy. The negative HIV test rules
that can be seen with injury of the central ner- out the chronic vacuolar myelopathy seen in ad-
vous system, typically between the pons and vanced HIV infection. The negative test for anti-
sacral spinal cord. Taken together, the sensory bodies to HTLV type 1 and the absence of travel
loss, hyperreflexia, and bladder incontinence in argue against the chronic myelopathy seen in
this patient help to localize the disease process tropical spastic paraparesis. The negative test for
to a central origin. Because the results of her antitreponemal antibodies and the atypical symp-
mental-status and cranial-nerve examinations toms rule out tertiary syphilis (tabes dorsalis),
were normal, it is likely that her neurologic con- and the absence of infectious symptoms and of
dition was caused by primary spinal cord dys- clinically significant abnormalities on CSF analy-
function, also known as myelopathy. sis makes other infectious causes of chronic
The results of electrophysiological investiga- myelopathy (e.g., Tropheryma whipplei infection,
tions further support this localization. First, the brucellosis, and schistosomiasis) unlikely.
patient had marked sensory symptoms, and the Structural spondylosis, autoimmune causes
nerve-conduction studies revealed normal sensory (e.g., primary progressive multiple sclerosis), and
responses but marked attenuation in motor- inflammatory causes (e.g., neurosarcoidosis,
response amplitudes. This pattern is inconsistent Behçet’s disease, or Sjögren’s syndrome) would
with a polyneuropathy (e.g., CIDP) and indicates be expected to result in abnormalities on imag-
a preganglionic localization of neurologic dys- ing studies of the spine. The absence of such
function that affects the dorsal roots or ascend- abnormalities makes these diagnoses unlikely in
ing sensory tracts in the spinal cord or brain. this case.
Second, her arm weakness was out of proportion Could this patient have myelopathy due to a
to the normal motor responses observed on the spinal dural arteriovenous fistula? A spinal dural
nerve-conduction studies; this finding further arteriovenous fistula is a direct communication
suggests dysfunction of upper motor neurons or between a spinal artery and a spinal vein without
their descending projections in the corticospinal an intervening capillary bed, and it leads to ve-
tracts. Third, the reduced number of normal- nous congestion, edema, and ischemia of the
appearing motor units and the slow firing of cord parenchyma. Patients with a spinal dural
those units in most muscles on needle electro- arteriovenous fistula classically present with non-
myography indicate impaired activation of motor specific spinal cord dysfunction, chronic and
units. This pattern of activation indicates a cen- progressive sensory loss, weakness, and inconti-
tral origin; the poor muscle activation may be due nence, typically beginning in the fifth or sixth
to dysfunction of upper motor neurons or their decade of life.1 This patient’s presentation fits
descending projections in the corticospinal tracts with this description, and this diagnosis should
be considered in any middle-aged person who Table 2. Neurologic Disorders and Associated Nutritional Deficiencies That
presents with symptoms or signs of chronic Complicate Bariatric Surgery, According to Time of Onset.
myelopathy. However, several specific features of
her presentation lower the likelihood of a spinal Neurologic Disorder Associated Deficiencies
dural arteriovenous fistula. The most important Early (<1 yr after surgery)
of these features is the extent of the myelopathy, Polyradiculoneuropathy Vitamin B1
which involves the cervical, thoracic, and lumbo-
Encephalopathy Vitamins B1 and B12
sacral spinal cord. In 80% of reported cases of
spinal dural arteriovenous fistulas, the myelopa- Late (≥1 yr after surgery)
thy affects the thoracolumbar segments between Optic neuropathy Vitamins A and B1 and copper
T6 and L2. Cervical involvement (which is seen Myelopathy Vitamins B9, B12, and E and copper
in this patient) is rare.2 In addition, the absence
Polyneuropathy Vitamins B1, B6, B9, B12, and E and copper
of abnormalities in the cord parenchyma on MRI
is possible but atypical in the context of a spinal Myopathy Vitamin D and copper
dural arteriovenous fistula.3
Because the patient had a history of bariatric
surgery, she is at increased risk for the develop-
ment of nutritional deficiencies and associated Vitamin B12 Deficiency
neurologic dysfunction. The patient had under- Does a vitamin B12 deficiency explain the myelopa-
gone Roux-en-Y gastric bypass that resulted in thy in this patient? Vitamin B12 deficiency has
the creation of a small proximal stomach pouch long been associated with subacute combined
that was directly connected to the midjejunum degeneration, which is a myelopathic syndrome
and thus bypassed most of the stomach, duode- characterized by dysfunction of the posterior
num, and proximal jejunum — the portion of and lateral columns of the spine that results in
the digestive tract that is critical for fat and paresthesias, impaired perception of vibration,
mineral absorption. Therefore, the procedure loss of proprioception, ataxia, weakness, and
produced a malabsorptive state that can result in hyperreflexia,10 features consistent with this
numerous nutritional deficiencies, including de- patient’s symptoms. Other signs of vitamin B12
ficiencies in vitamins A, B1, B2, B6, B9, B12, D, and deficiency may include encephalopathy, optic
E, as well as iron, copper, and other micronutri- neuropathy, polyneuropathy, and hematologic
ents. After surgery, patients who have intractable abnormalities, such as macrocytic anemia and
vomiting, cannot tolerate food, use alcohol ex- pancytopenia. Vitamin B12 deficiency is the most
cessively, lose more weight than expected, or do commonly reported nutritional deficiency among
not take vitamin supplementation as instructed patients who undergo bariatric surgery,4 and it is
are at the greatest risk for the development of typically a late complication, since the body has
nutritional deficiencies.4-6 large natural stores of vitamin B12.
Neurologic disorders occur as a complication In this patient, the blood vitamin B12 level was
of bariatric surgery in 5 to 16% of patients5,7 and reported as normal, and this result possibly ar-
are largely attributed to nutritional deficiencies. gues against vitamin B12 deficiency as the prin-
Such disorders are classified according to the cipal cause of myelopathy. However, the exact
time of onset (Table 2).8 Myelopathy is consid- vitamin B12 level was not provided. In patients
ered to be a late complication; it typically occurs with symptoms consistent with vitamin B12 defi-
an average of 9 years after bariatric surgery.9 ciency, a low normal or borderline level of vita-
Nutritional deficiencies that are specifically as- min B12 may lead to further evaluation,11 such as
sociated with myelopathy include deficiencies in tests for methylmalonic acid and homocysteine,
vitamins B9, B12, and E and copper; deficiencies which are sensitive markers of vitamin B12 defi-
in vitamin B12 and copper are reported most ciency. Because the results of these tests are not
often.9 The normal vitamin B9 level in this patient reported in this case and the precise blood vita-
argues against a vitamin B9 deficiency, and there- min B12 level is not available, we are unable to
fore, deficiencies in vitamin B12 and E and cop- rule out vitamin B12 deficiency as the underlying
per are left as possible diagnoses. cause of this patient’s myelopathy.
References
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