Reversible subacute chorea caused by vitamin B12 deficiency

Dear Editor,

We present the case of a 47-year-old man who worked as a baker and was admitted to hospital due a 4-day history of subacute symptoms of choreoathetosis predominantly affecting the head and left limbs, as well as motor impersistence and dysarthria. The physical, neuropsychological, and psychiatric examinations revealed no other relevant findings, including normal muscle balance and polymodal sensitivity. He had no family history of interest and a personal history of migraine, smoking, and moderate alcohol dependence (3 mixed drinks per day; his alcohol consumption habits had not changed in the past few months).

He underwent a complete blood study (electrolytes; TSH; PTH; copper; ceruloplasmin; folate; and vitamins E, B₁, and B₁₂), autoimmune tests (ANA; ENA; ANCA; TPO; lupus anticoagulants; and cardiolipin, gliadin, and intrinsic factor antibodies), serology tests, blood smear, test for antineuronal antibodies, lumbar puncture, and a urine toxicology test. The only relevant findings were macrocytosis (MCV = 115 fL [normal values: 80–100 fL]) and vitamin B₁₂ deficiency (148 pg/mL [normal values: 200–900 pg/mL]). Our patient displayed no anaemia and no other imbalances. A brain MRI scan revealed a slightly hyperintense area adjacent to the third ventricle and in the mammillary bodies, which may be related to our patient's alcohol consumption habits; no other alterations were found (Fig. 1). A CT scan of the neck, chest, abdomen, and pelvis showed no signs of hidden neoplasm.

Figure 1.

Brain MRI scan (coronal FLAIR sequence) showing hyperintensities adjacent to the third ventricle and in the mammillary bodies.

While waiting for results from the laboratory tests, we initiated empirical treatment with IV immunoglobulins, which did not improve our patient's symptoms. We ruled out toxic, infectious, dysimmune, vascular, neoplastic, and paraneoplastic causes. Since we suspected subacute choreoathetosis due to vitamin B₁₂ deficiency, the patient started IM vitamin B₁₂ (1000 μg/day for 7 days, followed by 1000 μg/week for a month, and 1000 μg/month) plus oral tiapride dosed at 50 mg every 8 hours; symptoms improved steadily and had resolved completely one week after treatment onset. Our patient remained asymptomatic one month later, so tiapride was discontinued. At 3 months, he continued to be asymptomatic and showed normal vitamin B₁₂ levels.

Vitamin B₁₂ deficiency is typically associated with such neurological disorders as subacute combined degeneration, dementia, and polyneuropathy.¹ However, the literature also includes isolated cases of such extrapyramidal disorders as parkinsonism, focal dystonia, ataxia, myoclonus, or even chorea associated with vitamin B₁₂ deficiency.^1–6

From a clinical viewpoint, chorea secondary to vitamin B₁₂ deficiency may be either unilateral or markedly asymmetrical with no associated structural lesions, as with other types of chorea (those linked to deficiencies or metabolic changes).³ Chorea linked to vitamin B₁₂ deficiency is thought to be caused by the glutamatergic activation of the basal ganglia due to excess of homocysteine (an NMDA agonist); in addition, there may be a potential neurotoxic effect resulting from an excess of methyltetrahydrofolate (an agonist of kainic acid which induces Huntington chorea in animal models).^2,7,8 Unfortunately, homocysteine levels in our patient were not tested during the acute phase. If sensory alterations are associated with vitamin B₁₂ deficiency,³ they may contribute to choreoathetosis by a deafferentation mechanism. However, this does not seem to be a necessary condition; in our patient and in other cases, examinations revealed no sensory alterations.^2,6

As in other cases in the literature, our patient's diagnosis of subacute reversible chorea caused by vitamin B₁₂ deficiency was based on the temporal relation between symptoms and vitamin B₁₂ deficiency, the exclusion of other potential causes of chorea, symptom resolution having coincided with stabilisation of vitamin B₁₂ levels, and the lack of recurrence after tiapride was discontinued. Given that not all patients with low vitamin B₁₂ levels develop neurological symptoms, other factors such as long-term alcohol abuse are likely to trigger the syndrome. MRI findings in our patient match those classically associated with Wernicke encephalopathy due to vitamin B₁ deficiency⁹; however, our patient showed normal vitamin B₁ levels.

In conclusion, chorea is a rare manifestation of vitamin B₁₂ deficiency which can be resolved with replacement therapy. We recommend including vitamin B₁₂ tests in the aetiological study of chorea of unknown origin.

Funding

The authors have received no funding for this study.

Conflicts of interest

The authors have received travel grants and/or consulting fees from Biogen-Idec, Sanofi-Genzyme, Teva, Novartis, Almirall, Merck-Serono, and Schering-Bayer. The authors have no conflicts of interest to declare.