Correspondence

Reversible Chorea and Focal Dystonia in Vitamin B₁₂ Deficiency

N Engl J Med 2002; 347:295July 25, 2002

Article

To the Editor:

A 71-year-old man presented in June 2000 with a two-month history of progressive right hemichorea. His medical history included a resection for gastric cancer at the age of 55 years. Neurologic examination revealed a postural, symmetric, rapid tremor of the hands; choreic movements of the right upper limb and right toes; and moderate hypopallesthesia in the four limbs. The results of laboratory tests showed a macrocytic anemia: erythrocytes, 4.15×10⁶ per microliter (normal range, 4.7 to 6.1); mean corpuscular volume, 102.4 fl (normal range, 80 to 94); a normal hemoglobin level; and vitamin B₁₂, 124 pg per milliliter (normal range, 243 to 894). Tests for tumor markers; serologic tests for borrelia, Treponema pallidum hemagglutination, and human immunodeficiency virus types 1 and 2; and a genetic test for Huntington's disease were negative. Nuclear magnetic resonance imaging of the brain was normal.

A brief trial of amantadine was ineffective, but treatment with 300 g of tiapride daily resulted in an 80 percent reduction in the choreic movements until January 2001, when, over a period of three to four days, disabling, generalized chorea developed with blepharospasm-type focal dystonia and dysarthria in the absence of cognitive symptoms. The rest of the neurologic examination was unchanged. A new laboratory assessment showed 3.19×10⁶ erythrocytes per microliter, a mean corpuscular volume of 106.1 fl, a hemoglobin level of 11.7 g per deciliter (normal range, 14 to 18), a vitamin B₁₂ level of 93 pg per milliliter, and a serum homocysteine level of 40.1 mmol per liter (normal range, <15); the blood copper level, folic acid level, and antistreptolysin ratio were in the normal range. A computed tomographic scan of the brain was normal, and no signal alteration was found on nuclear magnetic resonance imaging of the spinal cord. Electrophysiological investigation revealed a mild sensory neuropathy.

At the end of January, the patient started treatment with high doses of cyanocobalamin (5000 μg daily for four weeks, then twice weekly for an additional month, and once a month thereafter) in association with folic acid once a month and tiapride. A follow-up visit after two months showed residual involuntary movements of the toes, laboratory tests revealed 3.98×10⁶ erythrocytes per microliter, a mean corpuscular volume of 99.3 fl, a vitamin B₁₂ level of 1306 pg per milliliter, and a serum homocysteine level of 17.6 μmol per liter. Tiapride was stopped over a two-week period, and at follow-up visits in November 2001 and February 2002, involuntary movements were absent and the neurologic examination was normal.

Vitamin B₁₂ deficiency induces an increase in homocysteine, which is required for the methylation of the methionine.1 The neurotoxic, N-methyl-D-aspartate–agonist action of homocysteine produces excitatory activity in the basal ganglia by means of the thalamocortical pathway2 and leads to dystonia.3 The excess methyl levels in vitamin B₁₂ deficiency increase the levels of methyltetrahydrofolate, which acts as an agonist of kainic acid. In experiments in animals, this neurotoxin produces a pattern of damage similar to that seen in patients with Huntington's disease.4,5 With respect to our patient, these pathophysiological relations are only speculative, but the reversibility of the syndrome with cyanocobalamin supplementation is striking.

Claudio Pacchetti, M.D.
Silvano Cristina, M.D.
Giuseppe Nappi, M.D.
Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico, 27100 Pavia, Italy
claudio.pacchetti@mondino.it

5 References

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Citing Articles (5)

Citing Articles

1. 1

   B. Edvardsson, S. Persson. (2011) Chorea associated with vitamin B12 deficiency. European Journal of Neurology 18:10, e138-e139
   CrossRef

2. 2

   Ruth H. Walker. (2011) Differential Diagnosis of Chorea. Current Neurology and Neuroscience Reports 11:4, 385-395
   CrossRef

3. 3

   Stanley Fahn, Joseph Jankovic, Mark Hallett. 2011. Chorea, ballism, and athetosis. , 335-349.
   CrossRef

4. 4

   C. Shyambabu, S. Sinha, A.B. Taly, J. Vijayan, J.M.E. Kovoor. (2008) Serum vitamin B12 deficiency and hyperhomocystinemia: A reversible cause of acute chorea, cerebellar ataxia in an adult with cerebral ischemia. Journal of the Neurological Sciences 273:1-2, 152-154
   CrossRef

5. 5

   (2003) Current Awareness: Pharmacoepidemiology and Drug Safety. Pharmacoepidemiology and Drug Safety 12:1, 73-88
   CrossRef