Vitamin B-12 Associated Neurological Diseases Publications (119)


Vitamin B-12 Associated Neurological Diseases Publications

Arch. Med. Res.
Arch Med Res 2016 Jul;47(5):388-393
Department of Neurology, and Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases, Tianjin Huanhu Hospital, Tianjin, China.
Am. J. Clin. Nutr.
Am J Clin Nutr 2016 Sep 17;104(3):790-6. Epub 2016 Aug 17.
Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom;

Aging is associated with a progressive decline in vitamin B-12 status. Overt vitamin B-12 deficiency causes neurologic disturbances in peripheral and central motor and sensory systems, but the public health impact for neurologic disease of moderately low vitamin B-12 status in older people is unclear. Evidence from observational studies is limited by heterogeneity in the definition of vitamin B-12 status and imprecise measures of nerve function. Read More

We aimed to determine whether vitamin B-12 status is associated with electrophysiologic indexes of peripheral or central neurologic function in asymptomatic older people with moderately low vitamin B-12 status.
We used a cross-sectional analysis of baseline data from the Older People and Enhanced Neurological Function study conducted in Southeast England. This trial investigated the effectiveness of vitamin B-12 supplementation on electrophysiologic indexes of neurologic function in asymptomatic older people (mean age: 80 y) with moderately low vitamin B-12 status (serum vitamin B-12 concentrations ≥107 and <210 pmol/L without anemia, n = 201). Vitamin B-12 status was assessed with the use of total vitamin B-12, holotranscobalamin, and a composite indicator of vitamin B-12 status (cB-12). Electrophysiologic measures of sensory and motor components of peripheral and central nerve function were assessed in all participants by a single observer.
In multivariate models, there was no evidence of an association of vitamin B-12, holotranscobalamin, or cB-12 with any nerve conduction outcome. There was also no evidence of an association of vitamin B-12 status with clinical markers of neurologic function.
This secondary analysis of high-quality trial data did not show any association of any measure of vitamin B-12 status with either peripheral or central neurologic function or any clinical markers of neurologic function in older people with moderately low vitamin B-12 status. The results of this study are unlikely to be generalizable to a less healthy older population with more severe vitamin B-12 deficiency. This trial was registered at as ISRCTN54195799.

J Clin Neurophysiol
J Clin Neurophysiol 2017 Jan;34(1):84-91
*Department of Clinical Neurophysiology, Hospital Ramón y Cajal, Madrid, Spain; †Department of Clinical Neurophysiology, Hospital General Universitario de Ciudad Real, Madrid, Spain; ‡Department of Clinical Neurophysiology, Hospital Universitario de Torrejón, Madrid, Spain; and Departments of §Neurology & Neurological Sciences and ‖Neurosurgery, Stanford University School of Medicine, Stanford, California, U.S.A.

Although large amplitude evoked potentials (EPs) are typically associated with progressive myoclonic epilepsy patients, giant EPs imply central nervous system (CNS) hyperexcitability and can be seen in various nonepileptic disorders.
We performed a retrospective chart review including history, physical examination, imaging and diagnostic studies of nonepileptic patients with large amplitude somatosensory evoked potentials (SSEPs) and visual evoked potentials (VEPs) during 2007 to 2013. Large amplitude EPs were defined as follows: VEPs (N75-P100) >18 μV; and SSEPs (N20-P25) >6. Read More

4 μV. Recording montage for VEPs was Oz-Cz and SSEPs C3'/C4'-Fz.
Fifty-two patients (33 females, 19 males; age range, 9-90 years) were identified. No CNS pathology was detected in 7 patients. All remaining patients were diagnosed with new CNS disorders including: vascular (37%); myelopathies (13%); demyelinating (11%); space occupying lesions (8.7%); syringomyelia (8.7%); hydrocephalus (6.5%); Vitamin B-12 deficiency (4.3%); multiple system atrophy (4.3%); and toxins (2.2%).
This study supports the notion that large amplitude EP implies CNS hyperexcitability and CNS disease. These results confirm the utility of EP studies in patients with suspected CNS pathology.

Anaesth Intensive Care
Anaesth Intensive Care 2016 Jul;44(4):447-52
Director, General Intensive Care Unit, Hadassah University Hospital, Jerusalem, Israel.
BMJ Case Rep
BMJ Case Rep 2016 Apr 22;2016. Epub 2016 Apr 22.
Department of Medicine, Hospital São Francisco Xavier/CHLO/NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.

Catatonia is a motor and behavioural syndrome with multiple psychiatric, general medical and neurological aetiologies that might be simultaneously present. B12 deficiency is a rare, treatable cause of catatonia, not always easy to rule out. The authors present a case of a woman with catatonia associated with severe cyanocobalamin deficiency, admitted to an internal medicine ward. Read More

The benign course was related to an adequate and early diagnosis.

Encephale 2015 Dec 4;41(6):550-5. Epub 2015 Sep 4.
Service de psychiatrie G, hôpital Razi la Mannouaba, faculté de médecine de Tunis, Tunis, Tunisie.

Biermer disease or pernicious anemia is an autoimmune atrophic gastritis characterized by the lack of secretion of gastric intrinsic factor. This leads to an insufficient absorption of vitamin B12 in the ileum. Clinical manifestations are mainly hematologic. Read More

Neuropsychiatric manifestations are known but are less frequent especially early in the disease. Inaugural neuropsychiatric arrays are rare and various thus making diagnosis difficult. In this article, we report through two clinical cases different neuropsychiatric manifestations revealing pernicious anemia. Mrs. C.O., aged 56, presented after surgery for gallstones, an acute psychiatric array associated with gait disorders. She had no history of neurological or psychiatric problems. The psychiatric interview revealed delirious syndrome, depressive symptoms and anxiety. Neurological examination noted a flaccid paraplegia with peripheral neuropathic syndrome and myoclonus in the upper limbs. At the full blood count, a macrocytosis (VGM: 112.2fl) without anemia was found. The level of vitamin B12 in the blood was low. Cerebro-spinal MRI was suggestive of a neuro-Biermer and showed hyper signal in the cervical cord on T2-weighted sagittal section. In axial section, hyper signal appears at the posterior columns in the form of V. There were no brain abnormalities. A sensorimotor axonal polyneuropathy was diagnosed. The patient received vitamin B12 intramuscularly for ten days associated with neuroleptic treatment. Mrs. R.M., aged 40, was brought to the psychiatry consultation for acute behavioral disorders progressively worsening over a month. An anxiety syndrome, depressive syndrome and delirious syndrome were identified. Neurological examination showed a posterior cordonal syndrome with quadripyramidal syndrome. Full blood count showed a macrocytic anemia. Serum B12 level was collapsed. Cerebro-spinal MRI was normal. She received vitamin B12 with clinical and biological improvement. Features of pernicious anemia vary according to studies and age range. Digestive and hematological manifestations are well known. Neurological and psychiatric manifestations of pernicious anemia were also described in the early literature. They can be the initial symptoms or the only ones. However, inaugural neuropsychiatric features are often unrecognized. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. Neurological involvement includes mainly combined spinal sclerosis, peripheral neuropathy and dementia. Cerebellar ataxia and movement disorders are reported less often. Severity of neuropsychiatric features and therapeutic efficacy depends on the duration of signs and level of B12 deficiency. Macrocytic anemia may lack. Neuropsychiatric manifestations could be isolated or be the first manifestation of vitamin deficiency and occur without any hematological or gastrointestinal context. Pernicious anemia and serum B12 assay should be discussed in all patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. Nevertheless, B12 level could be normal in genuine pernicious anemia diseases and macrocytic anemia may lack. Substitutive vitaminotherapy is required when diagnosis is strongly suspected and etiologic assessment is negative.

Neuroscience 2015 Jul 16;298:293-301. Epub 2015 Apr 16.
Division of Brain Sciences, Imperial College, London W12 0NN, UK.

We have previously demonstrated that multiple sclerosis (MS) patients have abnormal cerebrospinal fluid (CSF) levels of the key myelin-related molecules cobalamin (Cbl), epidermal growth factor (EGF), and normal cellular prions (PrP(C)s), thus confirming that some CSF abnormalities may be co-responsible for remyelination failure. We determined the levels of these three molecules in post-mortem spinal cord (SC) samples taken from MS patients and control patients. The control SC samples, almost all of which came from non-neurological patients, did not show any microscopic lesions of any type. Read More

All of the samples were supplied by the U.K. MS Tissue Bank. The Cbl, EGF, and PrP(C) levels were determined using enzyme-linked immunosorbent assays. The SC total homocysteine level was determined using a competitive immunoenzymatic assay. CSF samples, taken from a further group of MS patients, were used for the assay of holo-transcobalamin (holo-TC) levels. The Cbl, EGF, and PrP(C) levels were significantly decreased in MS SCs in comparison with controls and, paradoxically, the decreased Cbl levels were associated with decreased SC levels of homocysteine, a biochemical marker of Cbl deficiency. The trends of EGF and PrP(C) levels paralleled those previously found in CSF, whereas that of Cbl was the opposite. There was no significant difference in CSF holo-TC levels between the MS patients and the controls. Given that we have previously demonstrated that Cbl positively regulates central nervous system EGF levels, it is conceivable that the low EGF levels in the MS SC may be causally related to a local decrease in Cbl levels. Only PrP(C) levels were invariably decreased in both the SC and CSF regardless of the clinical course of the disease. These findings suggest that the simultaneous lack of Cbl, EGF, and PrP(C)s may greatly hamper the remyelination process in MS patients, because they are key molecules of the machinery for remyelination.

Gen Hosp Psychiatry
Gen Hosp Psychiatry 2015 May-Jun;37(3):273.e5-7. Epub 2015 Feb 23.
Université Lille Nord de France, Lille, France; Department of Psychiatry, CHU Lille, Lille, France. Electronic address:

Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. Psychiatric symptoms can sometimes occur without hematological and neurological abnormalities and can be prodromal of vitamin B12 deficiency. We report a case of autoimmune B12 deficiency presenting as catatonia without signs of anemia or macrocytosis, in which a correlation was found between the patient's B12 blood levels and catatonic symptoms over time. Read More

This catatonic episode was successfully treated with only lorazepam and adequate doses of cyanocobalamin.

Nutr Neurosci
Nutr Neurosci 2016 May 24;19(4):162-8. Epub 2015 Feb 24.
a Section of Palliative Care, Department of Medicine , Yale University School of Medicine and Smilow Cancer Hospital , New Haven , CT , USA.

Neuropathies often accompany vitamin B12 deficiency. Since many neuropathies are linked to oxidative stress and since B12 has both antioxidant and neurotrophic properties, B12 may also be effective treatment in non-deficient subjects. Thus, the characteristics and predictors of B12-responsive neuropathies and their relationship to disorders associated with increased oxidative stress (oxidant risks) were examined. Read More

Retrospective review of 78 subjects with neurological abnormalities treated with B12 and evaluated by the measurement of B12 and the B12-dependent metabolites, methylmalonic acid (MMA), and homocysteine.
Sixty-five subjects had neurological improvement (83%), including 35 with other known causes of neuropathy. Only two responders had B12-responsive macrocytosis. Pretherapy B12, MMA, and homocysteine values were normal in 72, 33 and 54% of responders, with all three normal in 23%. Moreover, B12 therapy did not significantly decrease elevated MMA and homocysteine levels in 20 and 37%, respectively, of responders tested but did decrease both metabolites in 75% of evaluable non-responders. At least one oxidant risk was present in 41 of the 46 responders with normal B12 levels (89%). Oral therapy was effective, but parenteral B12 improved responses in four subjects.
B12-responsive neuropathies are thus (1) common even when confounding disorders are present; (2) dissociated from the presence of hematological abnormalities; (3) dissociated from the presence of B12-responsive metabolical abnormalities; and (4) associated with the presence of oxidant risks when B12 levels are normal. Since no predictors of responses to B12 therapy were identified, empiric trials with parenteral B12 should be considered in appropriate subjects.

To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years.
Open label, randomized, multicenter study.
High-sensitivity C-reactive protein. Read More

Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress.
Blood and stool samples were collected on days 1 and 56.
Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP<3 mg/l, subgroup 1) and 21 participants with low-grade inflammation at baseline (hsCRP≥3 mg/l, subgroup 2). In subgroup 2 addition of VSL#3 increased bifidobacteria (p = 0.005) in more participants and improved both folate (p = 0.015) and vitamin B12 (p = 0.035) levels compared with subgroup 1. The increases were positively correlated to the change in the bifidobacteria concentration for folate (p = 0.023) and vitamin B12 (p = 0.001). As expected change in homocysteine correlated negatively to change in folate (r = -0.629, p = 0.002) and vitamin B12 (r = -0.482, p = 0.026).
Addition of VSL#3 increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low-grade inflammation. Decrease in homocysteine with VSL#3 was clinically relevant. suggesting protective potentials for aging-associated conditions, e.g. cardiovascular or neurological diseases. NCT01069445-NCT01179789.