Clinically and MRI documented funicular myelosis in a patient with metabolical vitamin B12 deficiency but normal vitamin B12 serum level

Sirs: Funicular myelosis is a subacute degeneration of the dorsal columns of the spinal cord that is associated with vitamin B12 deficiency. Early treatment reverses pathological changes in the spinal cord and prevents long-term disability. However, some assays currently in use have too low a diagnostic sensitivity and specificity to serve as the sole criterion for vitamin B12 deficiency. Therefore, the vitamin B12-dependent decomposition products methylmalonyl acid and homocysteine, which are metabolized in the two vitamin B12dependent reactions in humans, were introduced several years ago as a very sensitive test for vitamin B12 deficiency [1, 2]. Here we describe a 66-year-old woman who had metabolic vitamin B12 deficiency but normal vitamin B12 serum levels and developed clinically and MRI-documented funicular myelosis. The 66-year-old woman was admitted with a 3 months history of ataxia of stance and gait. Neurological examination revealed a lowgrade spastic tetraparesis with no vibration sense or feeling of pain and temperature below the T 6 level, and marked ataxia. The deep tendon reflexes were increased (+ + +) and symmetric; a Babinski sign was elicited in the right foot. The results of heel-to-knee testing were normal. The patient was unable to walk with a tandem gait and had a tendency to veer to the right when walking. In addition, her tongue was smooth (Hunter’s glossitis was suspected), and she reported a burning sensation in her throat of almost 6 months’ duration. There was no apparent cognitive decline. Repeated lumbar puncture revealed normal cerebrospinal fluid without any sign of infection. Blood tests revealed 3.53 μIU erythrocyte count (normal values 3.8–5.8), 12.7 g/dL hemoglobin (12–16), 37 % hematocrit (35–47 %), mean corpuscular volume 107.5 fL (78–98), and mean corpuscular hemoglobin 36.0 (27–34). Mild macrocytemia due to vitamin B12 deficiency was suspected, but her vitamin B12 serum level was 338 ng/L (reference range 160–925 ng/L). Repeated determination of vitamin B12 revealed normal values (312 ng/L and 298 ng/L, respectively). Magnetic resonance imaging (MRI) of the head was normal. However, MRI of the spine showed a hyperintensity on T2-weighted images of the dorsal cervical and thoracic spinal cord (Fig. 1 A, B). T1-weighted images revealed no contrast enhancement of the lesion. This finding further supported the diagnosis of funicular myelosis [1], and therefore homocysteine and methylmalonyl acid were measured in the serum. These metabolites degrade in inverse proportion to the amount of vitamin B12 present. Thus, their increase indicates vitamin B12 deficiency [2]. The serum level of total homocysteine was 120 mcm/L (normal value 5–15 mcm/L) and 15,292 nmol/L for methylmalonyl acid (normal value 73–271 nmol/L). Nutritional status was normal with no restrictive dietary habits. The Schilling test indicated severe impairment of cobalamin resorption, and gastroscopy revealed chronic atrophic gastritis (type A). Antibodies against parietal cells were not detected and the intrinsic factor was normal. The patient was treated intravenously with 1 mg vitamin B12 daily for 12 days and subsequently once a week. Intramuscular application was avoided, because she was on Marcumar therapy for thrombosis of the pelvic veins, and had had a pulmonary embolism, 3 months previously. During therapy, the patient reported a slow improvement of her symptoms, especially the vibration sense. Four weeks after beginning treatment the serum level of total homocysteine (10.5 mcm/L) and methylmalonyl acid (237 nmol/L) normalized, and the vitamin B12 serum level increased (1760 pg/ml). After 6 months, ataxia had disappeared and only a mild dysesthesia of the legs remained. MRI revealed that the cervicothoracic hyperintensity had disappeared (Fig. 1 C). The clinical symptoms, the appearance of the cervicothoracic lesion on MRI [3], Hunter’s glossitis, and the macrocytemia led to the diagnosis of funicular myelosis despite a normal vitamin B12 serum level. The reason for the normal vitamin B12 serum level but metabolic vitamin B12 deficiency in our patient was not investigated. However, some patients with neurological manifestations of vitamin B12 deficiency but normal vitamin B12 serum levels have exhibited “analogues” of vitamin B12 on standard laboratory tests. These analogues are non-functional and not bound effectively by the intrinsic factor [5]. The treatment of elevated free homocysteine levels with folate reduces the risk of thrombosis and other vascular diseases [3]. However, it remains speculative, LETTER TO THE EDITORS