Journal of the Neurological Sciences 216 (2003) 183 – 184 www.elsevier.com/locate/jns Short communication Cerebellar ataxia and leukoencephalopathy associated with cobalamin deficiency Shuhei Morita *, Hideto Miwa, Tameko Kihira, Tomoyoshi Kondo Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8510, Japan Received 31 December 2002; received in revised form 28 May 2003; accepted 18 July 2003 Abstract We report a patient who presented progressive cerebellar ataxia associated with vitamin B12 deficiency. Brain magnetic resonance imaging (MRI) demonstrated a diffuse leukoencephalopathy. Six months after the initiation of methylcobalamin therapy, there were clinical improvement and reduction in the MRI abnormalities. D 2003 Elsevier B.V. All rights reserved. Keywords: Vitamin B12 deficiency; Leukoencephalopathy; Cerebellar ataxia 1. Introduction Various neurological disorders are known to present with leukoencephalopathy. Recently, we encountered a patient with progressive cerebellar ataxia associated with vitamin B12 (B12) deficiency and whose brain magnetic resonance imaging (MRI) demonstrated diffuse leukoencephalopathy. 2. Case report A 48-year-old woman with a history of anemia was admitted because of unsteadiness of gait. Six years before the admission, she experienced difficulty in breathing and was found to have anemia (hemoglobin, 4.9 g/dl). Since her levels of serum iron and B12 were found to be below the normal ranges, she was intravenously injected with saccharated ferric oxide and methylcobalamin for 1 month (detail unknown). Following the treatment, her anemia improved, and she was well for a long time without any treatment. Two weeks before the admission, she developed progressive gait ataxia; she was unable to walk without support at the time of admission. Her medical and family histories were unremarkable. On admission, her general condition was also unremarkable. On neurological examination, she was alert and well * Corresponding author. Tel.: +81-73-441-0655; fax: +81-73-441-0655. 0022-510X/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/S0022-510X(03)00219-3 oriented. She did not have overt dementia. Based on Hasegawa’s dementia scale (HDS), the Japanese version of a convenient clinical scaling of dementia similar to the MiniMental State Examination, the patient’s intelligence level was within the normal range. Her cranial nerve functions were intact, except for a mildly slurred speech. Her gait was ataxic, and she stood with her legs spread widely apart. During performance of the finger-to-nose test, her arms mildly oscillated. There was no weakness of her limbs nor abnormality of deep tendon reflexes. There was no pyramidal sign. Pain, touch, position and vibration sensations were all preserved. Laboratory tests revealed a low level of serum B12 (150 pg/ml; normal, 205 – 700 pg/ml). The following tests revealed normal findings: routine serum chemistries, complete blood count (hemoglobin, 12.0 g/dl; hematocrit, 38.3%; corpuscular volume, 83.6 fl), thyroid function tests and tests for sedimentation rate, C-reactive protein, homocysteine level and antinuclear antibody. She was positive for both the anti-intrinsic factor antibody and anti-gastric parietal cell antibody. Gastroendoscopic examination revealed an atrophic gastritis. CSF analytical finding were normal. T2-weighted brain MRI revealed diffused highsignal-intensity changes of the white matter, which includes the centrum semiovale, the posterior limbs of internal capsule, part of the pontine base where longitudinal fibers pass and the middle cerebellar peduncle (Fig. 1). Several EEG studies were normal. Nerve conduction studies and EMG were normal. 184 S. Morita et al. / Journal of the Neurological Sciences 216 (2003) 183–184 Fig. 1. MRI of the present patient. T2-weighted MR images before methylcobalamin therapy (A) and 6 months after the initiation of methylcobalamin therapy (B). Therefore, we presumed that her symptoms might be caused by B12 deficiency and intensive methylcobalamin therapy was started. During the first 2 months, 500 Ag of methylcobalamin was intramuscularly administered three times a week. After 1 month of therapy, a marked improvement in her ataxic gait was observed. Two months later, her gait became almost normal. From that time, the patient continued to receive methylcobalamin (500 Ag i.m.) once a month. Six months after the initiation of methylcobalamin therapy, the follow-up MRI showed an improvement of the T2 high signal intensities (Fig. 1). 3. Discussion The present patient showed two novel characteristics: cerebellar ataxia and diffuse leukoencephalopathy. The combination of these two findings is quite unusual for cases of B12 deficiency. Representative neurological symptoms generally observed in patients with B12 deficiency are abnormalities in deep sensations, pyramidal tract signs and/or cognitive deficits or neuropsychiatric symptoms [1 –5]. However, all of these were absent in the present patient. The improvement in her ataxia after initiation of methylcobalamin therapy suggests a causal relationship between her cerebellar ataxia and B12 deficiency. The MRI findings in cases of leukoencephalopathy associated with B12 deficiency are generally multiple focal and confluent periventricular white matter lesions [2,5]. On the other hand, the MRI findings of the present patient showed the extensive involvement of the subcortical white matter. It is quite difficult to explain why the present patient showed cerebellar ataxia without cognitive impairments or other symptoms commonly associated with B12 deficiency, in spite of the prominent and extensive distribution of leukoencephalopathy in the brain. Although her intelligence level evaluated by the dementia scale was within the normal range, it may be possible that she had some cognitive impairment. According to a previous report [6], the cerebellum is a region with the lowest protein carboxymethylation activity, indicating that the cerebellum has a smaller requirement for B12 and a higher tolerance to its deficiency than other regions in the brain. On the other hand, it may indicate a smaller pool of B12 stored in the cerebellum. The present patient had a long-standing but mild B12 deficiency that did not cause overt anemia. A lower capacity to store B12 in the cerebellum may be a potential cause of the ataxia of this patient. There has been a previous report on abnormal MRI findings of the cerebellum induced by B 12 deficiency, suggesting that the cerebellum occasionally can be vulnerable to B12 deficiency [7]. Finally, we propose that B12 deficiency should be added to the list of possible causes of leukoencephalopathy, even without anemia or cognitive decline. References [1] Berger JR. Cobalamine deficiency. Neurology 1997;48:295. [2] Chatterjee A, Yapundich R, Palmer CA, Marson DC, Mitchell GW. Leukoencephalopathy associated with cobalamin deficiency. Neurology 1996;46:832 – 4. [3] Gilbert GJ. Cobalamine deficiency. Neurology 1997;48:2959. [4] Katsaros VK, Glocker FX, Hemmer B, Schumacher M. MRI of spinal cord and brain lesions in subacute combined degeneration. Neuroradiology 1998;40:716 – 71. [5] Stojsavljevic N, Levic Z, Drulovic J, Dragutinovic GA. 44-Month clinical-brain MRI follow-up in a patient with B12 deficiency. Neurology 1997;49:878 – 81. [6] Coggins M, Scott JM, Weir DG. Regional differences in protein carboxylation in post-mortem human brain. Clin Sci (Lond) 1998;94: 677 – 85. [7] Katsaros VK, Glocker FX, Hemmer B, Schumacher M. MRI of spinal cord and brain lesions in subacute combined degeneration. Neuroradiology 1998;40:716 – 9.