Article, Neurology

Neurologic disease and vitamin B12 deficiency

Case Report

Neurologic disease and vitamin B12 deficiency

Two cases of severe Vitamin B12 deficiency are presented. Both patients had prolonged and progressive symptoms and had had rather extensive outpatient workups without diagnosis. Diagnosis was considered when routine blood work in the emergency department (ED) showed Severe anemia. Both showed improvement after institution of B12 therapy. B12 deficiency is common especially in the elderly and can present with variable neurologic symptoms. Early diagnosis can limit morbidity and inappropriate workups and should be considered in ED in patients with vague symptoms such as weakness or paresthesias.

Vitamin B12 deficiency is relatively common, especially in the elderly population. Neurologic manifestations can be the initial presenting complaint, most notably peripheral neuropathy. Early diagnosis is important, because a myriad of adverse outcomes can be averted including cognitive decline and progressive, irreversible neurologic abnormalities. We present 2 cases of vitamin B12 deficiency presenting to the ED with progressive neurologic decline. Each had a rather extensive neurologic workup, but the diagnosis was only suggested when hematologic abnormalities were found.

A 50-year-old woman presented to the ED with a 7-week history of progressive numbness of her arms, feet, and legs. She had a history of hypothyroidism. She had seen her own physician. A test to check her thyroid-stimulating hormone (TSH) level was done, which yielded normal results. A magnetic resonance imaging (MRI) of her head and spine revealed nonspecific white matter changes. She came to the ED because of increasing weakness. She had been dieting and lost 20 lb over 6 months. She was taking a multivitamin up until 2 months previously.

Except for decreased sensation to light touch in a stocking glove distribution, results of her neurologic examination were normal. A complete blood count was done, which yielded the following results: white blood cell count, 3.1; hemoglobin level, 8.4; platelets, 103. Her mean corpuscular volume (MCV) was elevated at 118 and her reticulocyte count was 1.5%. Because of her polyneuropathy and pancytopenia, a test to check her B12 level was performed. Her B12 level was 72 pg/mL (normal range, 245-895). Her folate and TSH levels were normal.

She was started on intramuscular B12 injections. She was seen 1 week after beginning her B12 injections, and although her hemoglobin level had not changed, her

reticulocyte count was 14.1%. Her neurologic symptoms were slightly improved. Further follow-up was done with her local physician.

A 25-year-old woman presented to the ED complaining of increasing weakness. She had a 6-month history of functional decline. She first developed some difficulty with sensation in her legs. About 3 months earlier, she had trouble walking independently and began to use a walker. Three weeks earlier, she began to use a wheelchair because of instability even with her walker. On the day of presentation she reported increasing weakness in her arms. She did complain of a bad taste in her mouth, but had no weight loss.

Workup by her own physician included an MRI of her brain and LS spine and except for mild central disk herniation at L5-S1, no abnormalities were observed. Electromyogram was done, which subsequently yielded normal results.

Her neurologic examination revealed decreased sensation in a stocking glove distribution, and decreased vibratory sensation in her lower extremities. Motor strength was 5/5 in the upper extremities, 4+/5 in the hip flexors, and 4/5 distally. She was unable to stand unassisted. A CBC was done, which showed a white blood cell count of 1.7, hemoglobin level of 2.9, platelets of 12, and an MCV of 89. Her reticulocyte count was 1%. A serum B12 was undetectable, and folate level was normal. A bone marrow biopsy revealed megaloblastic changes consistent with severe B12 deficiency.

The patient was admitted and transfused with 4 units of Packed red blood cells (RBCs). She was started on intramuscular B12 injections. When seen 2 months later, her sensory abnormalities had improved, but her motor abnormalities were unchanged and she continued to use a wheelchair.

Vitamin B12 is essential cofactor for the conversion of homocysteine to methionine and methymalonyl CoA to succinyl CoA. Impairment in the conversion of homocys- teine to methionine leads to defects in DNA synthesis and a megaloblastic maturation pattern as well as to defective production of choline and choline containing phospholipids. In addition, increases in tissue levels of methylmalonyl CoA and its precursor leads to formation and incorporation of nonphysiologic fatty acids into neuronal lipids.

Clinical features of B12 deficiency involve the hemato- logic system, the gastrointestinal (GI) tract, and the nervous system. The hematologic manifestations are mainly the

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result of anemia. The GI manifestations reflect the effect on the rapidly proliferating GI epithelium and include sore tongue, anorexia, weight loss, and diarrhea. The neurologic manifestations begin with demyelination, followed by axonal degeneration and eventual irreversible damage due to axonal death. The patient first notices general weakness and paresthesias. This is followed by Unsteady gait and then weakness and ataxic paraplegia. The neurologic disease may occur in a patient with normal hematocrit and RBC indices [1].

In those patients presenting with vitamin B12 and neurologic syndromes, evoked potentials and MRI changes have been found to be consistent with focal demyelination of white matter in the spinal cord and optic nerve [2]. Magnetic resonance imaging of the brain and spinal cord can demonstrate a typical pattern of white matter degener- ation commonly seen in Multiple sclerosis [3]. neurologic complications are found in 75% to 90% of patients with clinically apparent B12 deficiency. In approximately 25% to 33% of patients with neurologic symptoms, neuropathy is the sole clinical manifestation [4]. Neurologic symptoms are often inversely correlated with the degree of anemia [5]. Although the symptoms and imaging manifestations can be similar, there is no clear causal relationship between multiple sclerosis and vitamin B12 deficiency [6].

Both of our patients presented with a peripheral neuropathy and a very extensive neurologic workup had been done without laboratory testing. The etiology of their neuropathy was suggested by their hematologic abnormal- ities. The diagnosis may have been made earlier had a CBC been performed, although as noted earlier, normal RBC indices can be found in those with neurologic disease. Had the diagnosis been made earlier, the neurologic symptoms may have been more reversible. Reversibility of neurologic complications is inversely related to Delay in diagnosis [1]. Although the first patient’s dieting and lack of vitamin supplementation suggested a possible etiology of her deficiency, dietary causes are uncommon except in strict vegetarians [7].

The prevalence of B12 deficiency may be common in the ED population. Prevalence studies show that 3% of the US population has deficient B12 levels, but up to 40% of the population in the Americas have deficient B12 levels [8,9]. Prevalence increases with increasing age. Depending on the definition of deficient levels, prevalence may be anywhere from 10% to 40% in the elderly [10]. Peripheral neuropathy is common in the elderly, and B12 may play a role in its development [11]. The estimated prevalence of peripheral neuropathy is 3%, but may be as high as 15% in the elderly population. Peripheral neuropathy has numerous causes, including hereditary, toxic, metabolic, infectious,

inflammatory, ischemic, and paraneoplastic disorders. Diabetes and alcoholism are the most common etiologies of peripheral neuropathy of adults in the developed world [12]. Etiology can be identified in anywhere from 75% to 90% of cases [13].

B12 deficiency is very common in the general popula- tion. The diagnosis should be considered in patients presenting to the ED with peripheral neuropathy and no clear underlying cause. Simple screening with a CBC may lead to early diagnosis and treatment, limiting the neuro- logic complications.

James Svenson MD Section of Emergency Medicine University of Wisconsin, Madison

WI 53792, USA

E-mail address: [email protected] doi:10.1016/j.ajem.2007.02.036

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