Reversal of severe neurological abnormalities after vitamin B12 replacement in the Imerslund-Grasbeck syndrome

Summary Vitamin B₁₂ malabsorption in the ileum has been postulated as the underlying cause of the Imerslund-Grasbeck syndrome comprising megaloblastic anemia, proteinuria, and multiple neurological abnormalities. A young Saudi child with spasticity, truncal ataxia, cerebral atrophy, megaloblastic anaemia and proteinuria is described. Replacement therapy with parenteral vitamin B₁₂ resulted in the complete resolution of his neurological findings and brain atrophy.     

Peripheral neuropathy with vitamin B12 deficiency

Summary Seven patients with neuropathy associated with vitamin B₁₂ deficiency are reported. Four of them had other signs of malabsorption aside from the abnormal Schilling test. The neuropathy was diagnosed on the basis of the whole clinical picture and the neurophysiological findings. The pathogenesis of the peripheral nerve disease is discussed in the light of the evidence in the literature.

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Zusammenfassung Es wird über 7 Patienten mit einer Neuropathie bei gesicherter Vitamin B₁₂ Resorptionsstörung berichtet. Bei 4 Patienten wurden andere Anzeichen einer Malabsorption neben dem pathologischen Schilling Test festgestellt. Die Neuropathie wird aus dem gesamten klinischen Bild und den neurophysiologischen Befunden diagnostiziert. Die Pathogenese der peripheren Nervenschädigung wird anhand der Literatur diskutiert.

     

Sensory peripheral neuropathy of vitamin B12 deficiency: A primary demyelinating disease?

Summary In five patients with peripheral neuropathy due to vitamin B₁₂ deficiency, electrodiagnostic studies demonstrated severe reduction in sensory nerve conduction velocities compatible with a demyelinating disorder affecting sensory nerve fibres. It is suggested that in some patients lack of vitamin B₁₂ may cause primary sensory demyelinating neuropathy.     

Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone

Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59,P = 0.0084) between serum vitamin B₁₂ and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of Viamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B₁₂ and folate were below the reference medians. We hypothesize that low or reduced vitamin B₁₂/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low Viamin B₁₂/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B₁₂ and folate metabolism in patients with MS.     

Giant axonal neuropathy: Possibly secondary to vitamin B12 malabsorption

Summary A giant axonal neuropathy is described in an adult with no evidence of a childhood onset of his disease and no history of exposure to toxic hydrocarbons. A causal relation to vitamin B₁₂ malabsorption is proposed. This case suggests the need to expand the spectrum of diagnoses that must be considered when giant axons are encountered in peripheral nerve biopsy specimens.     

Downbeat nystagmus indicates cerebellar or brain-stem lesions in vitamin B12 deficiency

Summary Two cases of vitamin B₁₂ deficiency caused by gastric atrophy are described. Together with the neuropsychiatric features usually associated with this condition, a downbeat nystagmus syndrome was observed. It is concluded that vitamin B₁₂ deficiency may also result in lesions to those cerebellar or brain-stem structures that are generally assumed to cause downbeat nystagmus.     

Role of vitamin B12, folate, and thyroid stimulating hormone in dementia: A hospital-based study in north Indian population

Background:

Vitamin B₁₂ and folate represent modifiable risk factors for dementia. They may increase the risk of Alzheimer′s dementia (AD) and vascular dementia (VaD) as their deficiency can increase the homocysteine level due to slowed methylation reaction. Homocysteine has a neurotoxic effect that could lead to neurologic disturbances. Hence, it is important to explore the status of serum B₁₂ and folate in AD and VaD to evolve the treatment strategies for the same.

Objectives:

A retrospective study was conducted to assess the levels of vitamin B₁₂, folate, and thyroid stimulating hormone (TSH) in serum and the relationship of these factors, including age and sex to cognitive decline in VaD, AD, and dementia due to other causes (DOC).

Materials and Methods:

Serum vitamin B₁₂, folate, TSH, and total cholesterol were studied in 32 AD patients (mean age: 65 years), 12 VaD patients (mean age: 61 years), 83 DOC (mean age: 65 years), and 127 control subjects (mean age: 49 years). Results: In AD, VaD, and DOC, the levels of vitamin B₁₂ and folate were significantly lower (P < 0.002; 0.026; 0.002 for vitamin B₁₂ and P < 0.000 in all the 3 groups for folate) as compared with the controls. Similarly, TSH levels were significantly lower in AD and DOC (P < 0.008; 0.038) as compared with the controls.

Conclusion:

Vitamin B₁₂ and folate were significantly low in both AD and VaD patients. Hence, B vitamin supplementation should be considered as possible targets for the therapeutic intervention in dementia.     

Involuntary movements due to vitamin B12 deficiency

Abstract

Deficiency of vitamin B₁₂ produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B₁₂ may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B₁₂ supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B₁₂ deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B₁₂ supplementation.     

Folate, Vitamin B12, and Homocysteine as Risk Factors for Cognitive Decline in the Elderly

Objective

Cross-sectional studies have shown that the dysregulation of one-carbon metabolism is associated with cognitive impairment. However, the findings of longitudinal studies investigating this association have been inconsistent. This study investigated the prospective associations between cognitive decline and the levels of folate, vitamin B₁₂ and homocysteine both at baseline and over course of the study period.

Methods

A total of 607 (83%) elderly individuals were selected from a group of 732 elderly individuals without dementia at baseline and followed over a 2.4-year study period. The Mini-Mental State Examination (MMSE) was administered to the subjects, and the serum levels of folate, vitamin B₁₂ and homocysteine were assayed both at baseline and at follow-up examinations. Covariates included demographic data, disability, depression, alcohol consumption, physical activity, vascular risk factors, serum creatinine level, vitamin intake, and apolipoprotein E genotype.

Results

Cognitive decline was associated with decreasing quintiles of folate at baseline, a relative decline in folate and an increase in homocysteine across the two examinations after adjustment for relevant covariates.

Conclusion

These results suggest that folate and homocysteine are involved in the etiology of cognitive decline in the elderly.     

Recovery of VEP delay in patients with vitamin B12 deficiency

Two patients with a neurologic syndrome of vitamin B₁₂ deficiency and delayed Visual Evoked Potentials are reported. VEP latencies returned to normal values from 90 to 110 days following parenteral treatment with cyanocobalamin.

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Sommario Sono descritti due pazienti che presentavano una sindrome neurologica da carenza di vitamina B-12 ed un allungamento della latenza del potenziale evocato visivo (VEP). Dopo rispettivamente 90 e 110 giorni dalla istituzione della terapia parenterale con cianocobalamina si è assistito alla rinormalizzazione delle latenze del VEP.

     

Vorkommen von Psychosen bei B12-Avitaminosen ohne Anämie

Zusammenfassung Bei 54 Patienten, die im fortgeschrittenen Lebensalter standen (über 50 Jahre alt), nicht an einer Anämie litten und das klinische Krankheitsbild einer endogenen bzw. endogen mitbedingten Psychose zeigten (überwiegend protahierte Depressionen), wurden Untersuchungen auf eine B₁₂-Avitaminose mit dem Schilling-Test und der Methylmalonsäure-Bestimmung durchgeführt. Eine sichere Vitamin B₁₂-Mangelpsychose konnte in keinem Fall festgestellt werden. Der Schilling-Test fiel bei allen Patienten normal aus; eine erhöhte Methylmalonsäure-Ausscheidung konnte lediglich in drei Fällen nachgewiesen werden. Auch die kritische Durchsicht der Literatur ergab, daß Psychosen infolge Vitamin B₁₂-Mangel ohne Anämie sehr selten sind. Entgegen der Vermutung einiger Autoren ist demnach nicht zu erwarten, daß ein wesentlicher Anteil protrahierter Psychosen im fortgeschrittenen Lebensalter durch einen Vitamin B₁₂-Mangel verursacht wird.Herrn Prof. Schulte zum 60. Geburtstag.     

Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type

Summary The influence of vitamin B₁₂ on the activity of methionine adenosyltransferase (MAT) in postmortem brains of patients with senile dementia of the Alzheimer's type (SDAT) was investigated. In samples of cortex gyrus frontalis from SDAT patients with normal and low levels of serum B₁₂, MAT V_max was significantly increased by 25% and 19%, respectively. MAT V_max from a SDAT group chronically treated with B₁₂ was similar to controls. In contrast to cortex gyrus frontalis, no significant alterations were seen in MAT activity in nucleus caudatus. This study provides evidence that SDAT is associated with significant alterations in transmethylation mechanisms in specific regions of the brain. The relationship between blood levels of B₁₂ and the actual status of this vitamin in the brain influencing the rates of synthesis of both methionine and SAM may, however, be far more complex and cannot be directly clarified on the basis of the present human brain results.     

Maternal micronutrients (folic acid and vitamin B(12)) and omega 3 fatty acids: implications for neurodevelopmental risk in the rat offspring

Altered maternal micronutrients (folic acid, vitamin B₁₂) are suggested to be at the heart of intra-uterine programming of adult diseases. We have recently described interactions of folic acid, vitamin B₁₂ and docosahexaenoic acid in one carbon metabolism that is considered to play a key role in regulation oxidative stress and chromatin methylation. However its impact on fetal oxidative stress and brain fatty acid levels has been relatively unexplored. The present study examined the effect of imbalance in maternal micronutrients (folic acid and vitamin B₁₂) and maternal omega 3 fatty acid supplementation on oxidative stress parameters and brain fatty acids and in the offspring at birth. Pregnant female rats were divided into six groups at two levels of folic acid both in the presence and absence of vitamin B₁₂. Both the vitamin B₁₂ deficient groups were supplemented with omega 3 fatty acid. Oxidative stress marker (malondialdehyde) and polyunsaturated fatty acid profiles in plasma and brain were analyzed in dam and offspring at d20. Our results for the first time indicate that imbalance in maternal micronutrients (excess maternal folic acid supplementation on a B₁₂ deficient diet) increases (p < 0.01) oxidative stress in both mother and pups. This increased maternal oxidative stress resulted in lower (p < 0.01) fetal brain DHA levels. Omega 3 fatty acid supplementation was able to restore (p < 0.05) the levels of brain DHA in both the vitamin B₁₂ deficient groups. Our data has implications for implications for neurodevelopmental disorders since micronutrients and DHA are important modulators for neural functioning.     

Higher vitamin B12 level at Parkinson's disease diagnosis is associated with lower risk of future dementia

IntroductionTo determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.MethodsWe utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.ResultsPD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44–0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60–0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05).ConclusionHigher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.     

Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis

A meta-analysis was conducted to assess the relationship between serum homocysteine, vitamin B₁₂, and folate levels in patients with multiple sclerosis (MS). The DerSimonian and Laird Q test was used to evaluate the degree of heterogeneity between studies and a funnel plot was used to assess publication bias. The pooled effect size (standardized mean difference [SMD]) between patients with MS and control patients) from a random effects model was 0.84 (95% confidence interval: 0.18, 1.49) for homocysteine and -0.25 (-0.45, -0.04) for vitamin B₁₂, and from a fixed effects model was 0.98 (0.80, 1.16) for homocysteine and -0.25 (-0.41, -0.09) for vitamin B₁₂. Both nutrients were statistically significant, but the SMD for folate was not. Patients with MS were found to have raised homocysteine levels but low B₁₂ levels, which might contribute to the pathogenesis of MS.     

Reversibility of neurological deficits in vitamin B12 deficiency

Summary A female patient with subacute neurological deficits secondary to an hereditary vitamin B₁₂ deficiency was repeatedly examined clinically and neurophysiologically. It is concluded that neurological normalization after treatment with vitamin B₁₂ also occurs within the CNS. Such normalization takes place soon after initiating treatment and probably reflects other neuronal mechanisms than remyelination, i.e. recovery from conduction block in fast somatosensory pathways and/or improvement of synaptic transmission.     

血清叶酸、维生素B12水平与脑梗死的关系

目的为探讨血清叶酸、维生素B12水平与脑梗死的关系.方法运用放射免疫分析法检测50例脑梗死患者和44例正常对照组的血清叶酸、维生素B12浓度.结果脑梗死组血清叶酸、维生素B12浓度分别为(5.97±1.96)μg/ml、(511.47±212.06)μg/ml;对照组分别为(8.08±2.25)μg/ml、(806.91±254.60)μg/ml.脑梗死组血清叶酸、维生素B12水平均明显低于对照组,两组有显著性差异(P＜0.01).结论提示血清叶酸、维生素B12水平下降与脑梗死的发生有关,可能是其中又一危险因素.     

Blood levels of homocysteine,cysteine, glutathione,folic acid,and vitamin B<Subscript>12</Subscript> in the acute phase of atherothrombotic stroke

Blood levels of total homocysteine (tHcy), cysteine (Cys), total and reduced glutathione (tGSH and rGSH), folic acid (FA), and vitamin B₁₂ (B₁₂) change during ischemic stroke as accompaniment of the tissue damage. The relationship between these changes remains scantly investigated. We evaluated the variation of these molecules in the 48 h after acute large artery atherothrombotic stroke (LAAS) and searched for the presence of matched variation of them. The study involved 50 subjects affected by acute LAAS and 49 healthy controls. Plasma levels of tHcy and Cys were significantly higher and serum levels of FA and B₁₂ and plasma levels of rGSH were significantly lower in the patients than in the control group. Acute LAAS was associated with increased Hcy—decreased tGSH and decreased FA/tGSH. Pathways involved in cellular stress and in tissue repair are activated during acute LAAS.