in Vitamin B12 Deficiency Myelopathy
R. Locatelli, Robert Laureno, Pamela Ballard and Alexander S.
Background: Little is known about vitamin B12 deficiency
myelopathy's magnetic resonance imaging (MRI) manifestations
and their relationship to the onset, evolution, and resolution
of neurologic signs and symptoms. Methods: We
present a case and review eleven additional reported cases of
subacute combined degeneration of the spinal cord detected by
MRI. Results: Our patient had increased T2-weighted
signal and gadolinium contrast enhancement of the posterior
columns in the cervical and thoracic regions and enhancement
of the lateral columns in the high cervical region. This is
a case with imaging evidence for lateral column lesions. Two
prior reports have shown posterior column enhancement. T1-weighted
images may show decreased signal in the posterior columns and
sometimes demonstrate reversible spinal cord swelling. MRI abnormalities
typically improve after vitamin replacement therapy. However,
clinical signs may persist despite resolution of imaging abnormalities,
and these abnormalities do not always resolve completely. In
addition, symptoms may precede the imaging abnormality. Conclusions:
Vitamin B12 deficiency may produce an increased T2-weighted
signal, decreased T1-weighted signal, and contrast enhancement
of the posterior and lateral columns of the spinal cord, mainly
of the cervical and upper thoracic segments. Because the symptoms
may precede any imaging abnormality, it is clear that spinal
cord MRI may not be a highly sensitive, early test for subacute
RMN dans la myélopathie due à une déficience
en vitamine B12
Introduction: On connaît peu de choses
sur les manifestations de la déficience en vitamine B12
à l'imagerie par résonance magnétique (RMN)
et sur leur relation avec le début, l'évolution
et la résolution des signes et des symptômes neurologiques.
Méthodes: Nous présentons un cas
de dégénérescence combinée subaiguë
de la moelle détecté par RMN et nous revoyons
onze autres cas rapportés dans la littérature.
Résultats: Notre patient avait une augmentation
du signal T2 à l'examen en séquence pondérée
en T2 et une densification par le gadolinium au niveau de la
corne latérale de la moelle à la région
cervicale haute. Ceci constitue un cas avec observation à
la RMN de lésions de la corne latérale. Chez deux
autres cas, on rapportait un rehaussement de la corne postérieure
de la moelle. Les images pondérées en T1 peuvent
montrer un signal diminué dans les cornes postérieures
et parfois un gonflement réversible de la moelle épinière.
Il est typique de voir les anomalies de la RMN s'améliorer
suite au traitement de remplacement vitaminique. Cependant,
les signes cliniques peuvent persister en dépit de la
résolution des anomalies observées à l'imagerie
et ces anomalies ne disparaissent pas toujours complètement.
De plus, les symptômes peuvent précéder
les anomalies observées à l'imagerie. Conclusions:
La déficience en vitamine B12 peut produire une
augmentation du signal pondéré en T2, une diminution
du signal pondéré en T1 et un rehaussement du
contraste des cornes postérieures et latérales
de la moelle, surtout au niveau des segments cervicaux et thoracique
supérieurs. Comme les symptômes peuvent précéder
les anomalies observées à l'imagerie, il est clair
que la RMN de la moelle n'est probablement pas un test hautement
sensible pour détecter précocement la dégénérescence
J. Neurol. Sci. 1999; 26: 60-62
with subacute combined degeneration may show spinal cord signal
abnormalities on MRI.(1-12)
30-year-old African-American woman presented to another hospital
with inability to walk, numbness of her trunk and extremities,
and urinary and bowel incontinence.
months earlier, she had noticed bilateral hand and foot numbness
and tingling, which was followed by progressive leg weakness.
Eventually she had become wheelchair bound. She was alert, oriented,
and depressed. She could move the upper extremities against
some resistance, but she was unable to raise the lower extremities
off the bed. Only with great assistance could she stand. Sensation
was decreased below the T10 level and was absent in the legs.
Tendon reflexes were brisk in the upper extremities and absent
in the lower extremities.
was 7.9 g/dL, hematocrit 22.8%, and WBC 1 100/µL. The mean
corpuscular volume was 123 fL (nl 80-100 fL). Vitamin B12 level
was 60 pg/mL (nl 200-1610 pg/mL) and folic acid was 12.5 ng/mL
(nl 3.0-17 ng/mL). The intrinsic factor blocking antibody was
positive, the anti-parietal cell antibody was negative, and
the Schilling test was consistent with pernicious anemia. Nerve
conduction studies and electromyography showed mild peripheral
neuropathy, manifest by absent sural sensory responses and distal
lower extremity fibrillations. On MRI the brain was normal;
however, the spinal cord had increased T2-weighted signal in
the posterior columns of the cervical and thoracic regions,
mostly at the C3-C8 level. (Figure
1A). In the cervical and upper thoracic spinal cord, the
posterior columns showed gadolinium contrast enhancement, marked
at the C3-C8 level. At the high cervical region the lateral
columns also showed mild enhancement (Figure
been given the diagnosis of pernicious anemia with subacute
combined degeneration of the spinal cord, the patient received
7 daily intramuscular vitamin B12 (1000 µg) injections.
Thereafter she continued to receive the same dose once weekly.
Hypothyroidism was treated with oral levothyroxin (100 mcg/day).
20 days of vitamin B12 therapy, the patient was transferred
to The National Rehabilitation Hospital. Mental status, language,
and cranial nerve examinations were normal, including Humphrey
and Goldmann visual field testing. Motor, sensory, and cerebellar
examinations were normal in the upper extremities. Although,
unable to walk or stand, she could move the right leg against
gravity and the left leg against some resistance. Tendon reflexes
were absent; a Babinski sign was present on the right. In the
lower extremities, vibration sense and proprioception were absent,
and sensation to light touch and to pin-prick were decreased.
42 days of vitamin B12 therapy the spinal cord MRI was normal
(Figure 2). There was improvement
in mood. Standing and walking were possible with much assistance.
Patellar reflexes were present but ankle reflexes were absent.
Light touch and pin-prick sensation were decreased, moderately
up the hips and minimally to midthoracic level. Hypersensitivity
of the feet to light and noxious stimuli interferred with plantar
combined degeneration of the spinal cord was documented by the
clinical features (paresthesias, loss of vibration and position
sense, and paraparesis with Babinski sign), the evidence of
vitamin B12 deficiency, the presence of posterior and lateral
column lesions on MRI, and the improvement with
B12 replacement. This is the first report with imaging documentation
of lateral column lesions and the third case reported with gadolinium
enhancement of the posterior columns.
are twelve prior single case studies reporting MRI spinal cord
signal abnormalities associated with vitamin B12 deficiency.(1-12)
All patients were treated with intramuscular vitamin B12. In
1992, Tracey and Schiffman first reported a 36-year-old woman
with Lhermitte's symptom for one year, bilateral hand and foot
numbness for 2 months, and a C5 sensory level.(1) The posterior
columns at the C3-C6 levels showed increased T2-weighted signal
on the MRI scan. A repeat scan was normal after 4 months of
therapy. Timms et al. next reported a 69-year-old man with unsteady
gait and burning dysesthesias of his hands and feet.(2) After
2 weeks of symptoms, cervical MRI was normal. However, after
3 more months of symptom progression, repeat MRI showed increased
T2-weighted signal in the posterior columns at the cervical
and thoracic levels. The MRI showed no lateral column involvement.
The MRI was improved after 5 and again after 10 months of vitamin
therapy. Murata et al. reported a 66-year-old man with 3 months
of marked sensory ataxia associated with a high T2-weighted
MRI signal at the T9-T11 level in the posterior columns; the
abnormality was absent on a repeat scan performed after 10 weeks
of vitamin replacement. There is no explicit statement indicating
whether the cervical region was scanned.(3) Tajima et al. also
described a B12 deficient patient with high signal in the posterior
columns of the cervical region on T2-weighted images.(4) Wolansky
et al. presented a 10-year-old child with 2 weeks of sensory
ataxia.(5) There was increased T2-weighted signal and decreased
T1-weighted signal in the posterior columns at all spinal cord
levels. With gadolinium injection there was symmetric contrast
enhancement of the posterior columns. This was the first report
of contrast enhancement in this disease. There was no repeat
spinal cord MRI scan. In 1996 Duprez et al. observed a 65-year-old
woman with gradual onset of a spastic tetraparesis, a T8 sensory
level, loss of vibration and position sense, and bladder dysfunction.(6)
There was increased T2-weighted signal in the posterior columns
at the C2-C7 levels and low vertebral bone marrow signal on
both T1- and T2-weighted images. On MRI, 10 weeks after vitamin
replacement, there was incomplete improvement of the spinal
1997 a flurry of case reports appeared. Larner et al. reported
a 38-year-old woman with 3 months of sensory ataxia.(7) The
MRI showed slight but definite swelling of the upper cervical
cord on T1-weighted images and increased T2-weighted signal
of the posterior columns at the C1-C5 levels. Six months after
vitamin replacement, spinal cord MRI was normal. Küker
et al. reported a 50-year-old woman with 5 months of sensory
ataxia.(8) The MRI showed an ill-defined increased T2-weighted
signal in the posterior parts of the thoracic spinal cord. T1-weighted
images showed multifocal, slightly expansive, contrast enhancing
lesions in the posterior columns of the cervical and thoracic
spinal cord. After 18 days of vitamin replacement, the lesions
had disappeared; this case report was the first to document
resolution of contrast enhancing lesions. Ng et al. documented
a 19-year-old vegetarian man, with absent reflexes and sensory
impairment only in the upper extremities.(9) MRI showed a swollen
cervical cord and increased T2-weighted signal of the posterior
aspect of the cord from the cervico-medullary junction to the
C6-C7 level. He had a complete clinical recovery after 6 months
of vitamin replacement. On T2-weighted images, only a faint
diffuse increased signal was seen in the posterior columns.
Imaiso et al. described a 54-year-old man with sensory ataxia
limited to the upper extremities.(10) T2-weighted images showed
increased signal in the posterior columns at the C1-T1 levels,
especially in the fasciculus cuneatus. Finally, Springer and
Key presented a 17-year-old man, who carried the diagnosis of
agammaglobulinemia of Bruton and who then had suffered with
peripheral paresthesias and sensory ataxia for 6 weeks.(11)
He was diagnosed as having vitamin B12 deficiency. MRI images
showed increased T2-weighted signal of the posterior columns
at the C1-C7 levels. The authors did not comment on the post
contrast images. No follow-up imaging was reported. None of
these 11 cases in the previously published literature had lateral
column involvement by MRI criteria.
careful review, we have excluded one case, a 43-year-old patient
with pernicious anemia and Lhermitte's symptom as the only neurologic
abnormality.(12) Axial T2 gradient echo images at the C3-C4
level and sagittal T2-weighted images showed a increased spinal
cord signal centrally. Because these MRI findings were not in
the characteristic distribution of the spinal cord lesions of
vitamin B12 deficiency and because the neurologic exam was normal,
we are not confident that the MRI findings in this case reflect
subacute combined degeneration.
the spinal cord cases discussed above, four had MRI of the brain.
In our patient and in two other cases the brain MRI was normal.(7,11)
In the fourth case, T2-weighted brain images showed non-specific
small high-signal foci within the cerebral hemispheres.(2) The
findings could not be attributed to vitamin deficiency. Haan
described five patients with vitamin B12 deficiency.(13) In
3 of these patients brain MRI showed increased T2-weighted signal
in the periventricular white matter. There is no documentation
of improvement of these lesions with treatment; it is unlikely
that they were related to vitamin B12 deficiency. Chatterjee
et al. and Stojsavljevic et al. each reported a patient with
leukoencephalopathy, who improved clinically and radiographically
after vitamin B12 replacement.(14,15) MRI of the spinal cord
was not performed in any of these reported cases of leukoencephalopathy.
in brain or spinal cord, the abnormal signal detected in advanced
cases of vitamin B12 deficiency, presumably reflects increased
water content of the tissue, similar to that seen in multiple
sclerosis or spinal cord infarction. It is the location and
relative symmetry of the lesions rather than their signal characteristics
which allow differentiation of this disease from other intramedullary
lesions of the spinal cord.(16)
summary, spinal cord lesions of vitamin B12 deficiency may produce
increased signal on T2-weighted images, spinal cord swelling,
decreased signal on T1-weighted images, and gadolinium enhancement.
Symptoms may precede MRI abnormalities. MRI changes appear primarily
in the cervical or cervico-thoracic region, a distribution consistent
with the classical pathological descriptions.(17,18) On MRI,
involvement of the posterior columns is more commonly seen;
similarly on pathological examination posterior column involvement
is earlier in onset and more severe than that of the lateral
columns.(17,18) The multifocal involvement of the posterior
columns reported in one MRI case also has precedent in pathological
studies.(18) Usually, but not always, MRI abnormalities improve
after vitamin replacement therapy. However, neurological signs
may persist despite resolution of the MRI abnormalities. Thus
far there are no convincing cases of combined MRI evidence of
leukoencephalopathy and subacute combined degeneration of the
spinal cord in the same B12 deficient patient.
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the Departments of Neurology (E.R.L., R.L.) and Radiology
(A.S.M.), Washington Hospital Center, the Department
of Neurology (E.R.L., R.L.),The George Washington University,
and the National Rehabilitation Hospital (P.B.), Washington,
June 9, 1998. Accepted in final form October 29, 1998.
requests to: Eduardo R. Locatelli, Department of Neurology,
The George Washington University Medical Center, 2150
Pennsylvania Avenue, #7-404 Washington, DC 20037 U.S.A.
J. Neurol. Sci. 1999; 26: 60-62