Journal of the Neurological Sciences 273 (2008) 152–154

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Journal of the Neurological Sciences
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / j n s

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Serum vitamin B12 deficiency and hyperhomocystinemia: A reversible cause of acute
chorea, cerebellar ataxia in an adult with cerebral ischemia
C. Shyambabu a, S. Sinha a,⁎, A.B. Taly a, J. Vijayan a, J.M.E. Kovoor b
a
b

Department of Neurology, NIMHANS, Hosur Road, Bangalore, 560029, India
Department of Neuroimaging and Interventional Neuroradiology, NIMHANS, Hosur Road, Bangalore, 560029, India

A R T I C L E

I N F O

Article history:
Received 23 April 2008
Received in revised form 20 June 2008
Accepted 25 June 2008
Available online 3 August 2008
Keywords:
Cerebellar ataxia
Chorea
Hyperhomocystinemia
Vitamin B12 deficiency
Wernicke's aphasia

A B S T R A C T
Patients with vitamin B12 deficiency have protean neurological manifestations that are often insidious. Acute
onset of cerebellar dysfunction and extrapyramidal manifestations like dystonia and chorea are rather
uncommon in adults. We describe a patient who manifested with acute onset of language dysfunction,
chorea and ataxia. There was no history of hypertension, diabetes or ischemic heart disease. He had low
serum vitamin B12 and elevated serum homocystine levels. He improved dramatically following B12
replacement therapy. Our patient provides insight into the pathophysiological mechanism of this rare
manifestation. Further the importance of considering vitamin B12 deficiency, in country like India, where
vegetarian food practice is quite common, is being emphasized.
© 2008 Elsevier B.V. All rights reserved.

1. Introduction
Subacute combined degeneration of the spinal cord (SCD) is the most
frequent neurological syndrome of vitamin B12 deficiency[1]. It affects
the dorsal and lateral columns of the spinal cord[2]. The neurological
manifestations are paraesthesia, sensory ataxia, weakness of limbs,
dementia, optic atrophy, and mood disorders and commonly occur in
the 5th to 7th decade. Cerebellar ataxia and extrapyramidal manifestations like dystonia and chorea have been documented infrequently in
adults [2,3].
The present report highlights an unusual and acute presentation of
vitamin B12 deficiency in the form of ischemic stroke, chorea, and
cerebellar ataxia which had improved dramatically following treatment with B12 injections.
2. Case report
A 40-year-old gentleman manifested with 5 weeks history of acute
onset of “irrelevant” speech and inability to comprehend. A week before,
he developed involuntary movements of upper extremities and
unsteadiness of gait. He was noted to have hyperpigmentation of
hands and feet for the last few months, which was confirmed during
evaluation (Fig. 1A, D). There was no history of psychiatric disturbances,
paraesthesia or weakness of limbs or systemic diseases like hyperten-

⁎ Corresponding author. NIMHANS, Hosur Road, Bangalore, 560029, India. Tel.: +91
8026995150; fax: +91 8026564830.
E-mail addresses: sanjib_sinha2004@yahoo.co.in, sanjib_sinha@nimhans.kar.nic.in
(S. Sinha).
0022-510X/$ – see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2008.06.034

sion, diabetes or ischemic heart disease. He was a pure vegetarian and
didn't have any habits like drinking or substance abuse. He had features
of Wernicke's aphasia by western aphasia battery, choreiform movement in upper extremities, wide based gait and truncal and limb ataxia,
requiring support by one person for all activities of daily living. Muscle
strength was normal (MRC: 5/5), the stretch reflexes were normal and
there was no kinesthetic impairment. Romberg's sign was absent.
The investigations revealed hemoglobin of 12.6 g%, TLC—7600 mm3,
PCV—38%, ESR —30 mm/h, MCV—103.8 fl, Platelets—2.9 lakhs/mm3.
Peripheral smear showed hypersegmented neutrophils. The routine
biochemical parameters were in the normal range. Serum and CSF VDRL,
ANA, RA factor, LE cell phenomena, antiphospholipid antibody, anticardiolipin antibody, and lupus anticoagulant were normal. Thyroid
function was normal. Serum homocysteine was elevated −50 µmol/l
(normal: 5–15 µmol/l) while serum vitamin B12 was low — 62.96 pg/ml
(normal: 243–894 pg/ml). Serum folate level estimation was not carried
out. Upper GI endoscopy showed normal mucosa. The cranial MRI and
MRA showed infarct in the left MCA territory involving inferior part of
parietal lobe and anterior part of temporal lobe (Fig. 1B, C, E, F). There
was no lesion in the basal ganglia, brainstem or cerebellum. Carotid and
vertebral Doppler and 2D echo of heart were normal. The motor and
sensory nerve conduction study revealed values within normal limits.
Visual evoked potential study showed mildly increased P100 latency of
113.4 ms in both eyes and somatosensory and brainstem auditory
evoked responses were normal. A diagnosis of vitamin B12 deficiency
related neurological syndrome manifesting as chorea, cerebellar ataxia
and ischemic stroke was considered.
He received parenteral cyanocobalamin 3000 µg daily for a month
followed by 1000 µg/week for a month. After 2 months, he improved

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153

Fig. 1. A,D: Hyperpigmentation of dorsum of hand and knuckles and dorsum of feet and toes. B: axial CT brain showing infarct in the left MCA territory. C: Axial T1W image showing
subacute infarct (with gadolinium enhancement) in the left MCA territory. E: Axial T2W sequence showing infarct in the left MCA territory. F: MR angiography showing left MCA
occlusion.

remarkably in his gait, involuntary movements and language. He was
able to walk independently, the choreoathetotic movements had
reduced markedly in severity and extent, and it was only limited to
fingers. Serial speech and language assessment revealed improvement
in overall comprehension, however writing was still impaired. The
repeat hemoglobin at 2 months was 13 g%, TLC—4800 mm3, ESR—
12 mm/h and MCV—88.3 fl. Following 3 months of treatment, the
serum homocysteine level (7.73 µmol/l) and vitamin B12 (2000 pg/ml)
were normal. Repeat peripheral smear also did not reveal any
hypersegmented neutrophil.
3. Discussion
Our patient, a vegetarian had low serum concentration of vitamin
B12, increased serum level of homocysteine and improved with
treatment. The neurological symptoms of chorea and cerebellar ataxia
improved markedly after 2 months of vitamin B12 replacement and it
could be attributed to the deficiency of vitamin B12. Involuntary
movements like tremors, twitches, chorea, myoclonus or combination
have been reported in about 50% of the infants with infantile cobalamin
deficiency [4–6]. In adults with vitamin B12 deficiency, focal dystonia,
chorea, parkinsonism, myoclonus and even ataxia have been documented as single case reports [3,8–11].
The left middle cerebral artery territory infarction might be due to
hyperhomocysteinemia related thrombo-embolism, secondary to B12
deficiency or mutations in MTHFR gene, which was not carried out in our
patient. Caldera et al. (2003) had reported a 60-year-old woman with
ataxia and pulmonary emboli due to pernicious anemia, hyperhomo-

cysteinemia, and a G20210A prothrombin gene mutation [12]. Leemann
et al. [13] had discussed possible association of high plasma level of
homocysteine in the context of pernicious anemia in 44-year-old
women of frontal ischemic stroke [13]. Moderate hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases,
osteoporotic fractures and complications during pregnancy. Vitamin
deficiency is by far the most common cause of hyperhomocysteinemia.
Retrospective and prospective studies emphasize a causal relationship
between hyperhomocysteinemia and the vascular risk factor [14].
Vitamin B12 induces an increased homocysteine, which is required for
the methylation of methionine. The neurotoxic N-methyl-D-aspartate
(NMDA) agonist action of homocysteine produces excitatory activity
in the basal ganglia by its action on the thalamocortical pathway and
there by causing dystonia and chorea [7,8]. The excess methyl levels
in B12 deficiency increase the levels of methyl tetra hydrofolate,
which acts as agonist of kainic acid. In experimental animals, this
kainate produces damage similar to that in Huntington's disease
[15,16]. Also, the methymalonic acidemia (MMA), an inborn error of
metabolism, usually presents with acute extrapyramidal syndrome
in infants, and some cases respond to vitamin B12 therapy. Brain
imaging and autopsy studies in MMA have shown symmetrical
involvement of basal ganglia [17].
Our patient is unique in view of the presence of a combination of
involuntary movements, ataxia and ischemic stroke. In country like
India, where vegetarianism is common, one needs to consider it as a
possibility. Even though the pathophysiological mechanisms are
speculative, the reversibility of the clinical symptoms with cyanocobalamin therapy is striking.

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