Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with "normal" serum B12 levels

Abstract

Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over the course of 5 years. The patient had progressive, severe leukoencephalopathy on multiple MRI scans over 5 years. Serum B(12) levels ranged from 267 to 447 pg/ml. Homocysteine and methylmalonic acid levels were normal. Testing for antibody to intrinsic factor was positive, consistent with pernicious anaemia. After treatment with intramuscular B(12) injections (1000 μg daily for 1 week, weekly for 6 weeks, then monthly), she made a remarkable clinical recovery but remained amnesic for major events of the last 5 years. Repeat MRI showed partial resolution of white matter changes. Serum B(12), homocysteine and methylmalonic acid levels are unreliable predictors of B(12)-responsive neurologic disorders, and should be thoroughly investigated and presumptively treated in patients with unexplained leukoencephalopathy because even long-standing deficits may be reversible.

Subacute combined degeneration of the spinal cord following recreational nitrous oxide use

“…Oxidation of the cobalt ion by N 2 O inhibits methylcobalamin as a cofactor of methionine synthase in the production of methionine and subsequently S -adenosylmethionine, which is necessary for methylation of myelin sheath phospholipids 1 2. The result is demyelination of the nervous system involving the spinal cord and sometimes peripheral neuropathy and optic atrophy 3. Thus, N 2 O induces subacute combined degeneration through inactivation of the vitamin B 12 metabolism.…”

Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments

“…Conversely, vitamin B12 deficits or resulting hyperhomocysteinemia have also been shown to decrease GSK3 phosphorylation/inhibition (Nicolia et al, 2011; Zhuo et al, 2011) (Figure 3) and could thus impair myelination (Azim and Butt, 2011). This may help explain the epidemiologic (Clarke et al, 1998; Kim et al, 2008) and animal model (Chan and Shea, 2007; Zhuo et al, 2011) studies that report associations between these nutritional deficiencies and increased AD risk as well as white matter deficits (de Lau et al, 2009; Graber et al, 2011) (reviewed in Bartzokis, 2011a). …”

Cobalamin Deficiency: Clinical Picture and Radiological Findings

“…Vitamin B12 status has been associated with the severity of white-matter lesions, especially periventricular ones, in some [68], but not all, studies [69]. The partial reversal of white-matter lesions has been documented with cobalamin treatment [70], emphasizing the importance of early detection and treatment of vitamin B12 deficiency. A correlation of vitamin B12 treatment and a decrease in MMA and homocysteinemia has been shown [71], suggesting a reversal of metabolic abnormalities.…”