Vitamin B12 deficiency neurological syndromes: a clinical,MRI and electrodiagnostic study

BACKGROUND: Vegetarianism is an important cause of vitamin B12 deficiency, especially in countries like India. We managed 17 patients with neurological syndrome due to vitamin B12 deficiency in a tertiary care referral teaching hospital which caters to relatively affluent population. AIM: To evaluate neurophysiological and MRI changes in patients presenting with vitamin B12 deficiency neurological syndrome and interpret these is the light of reported autopsy findings. SETTING: Tertiary care referral teaching hospital. METHODS: Patients with vitamin B12 deficiency neurological syndrome diagnosed by low serum vitamin B12 and/or megaloblastic bone marrow were subjected to clinical evaluation and spinal MRI. The neurophysiological tests included nerve conduction studies, tibial somatosensory evoked potential (SEP), motor evoked potential (MEP) and visual evoked potential (VEP) studies. The recovery was defined on the basis of 6 months Barthel Index score into complete, partial or poor. RESULTS: There were 17 patients with vitamin B12 deficiency neurological syndrome, 3 were females and 12 lactovegetarian. The clinical syndrome was that of myelopathy in 8, myeloneuropathy in 5, dementia myelopathy in 3 and neuropathy in 1 patient. All the patients had impaired joint position and vibration sensation in the lower limbs and 4 had in upper limbs as well. Lower limbs were spastic in 13 and upper limbs in 2 patients. Spinal MRI revealed T2 hyperintensity in cervicodorsal region in 6 and cord atrophy in 3 patients. Sural nerve conduction was abnormal in 8 and peroneal conduction in 5 patients. In one patient all sensory nerve conductions were unrecordable but motor conductions were normal. Tibial SEP was abnormal in 12 out of 15 and lower limb MEP in 8 out of 12 patients. P100 latency of VEP was prolonged in 7 out of 13 patients. Right to left asymmetry was present in tibial SEP in 4 and VEP in 2 patients. At 6 months followup 2 patients improved completely, 7 partially and 3 had poor recovery. Clinical recovery correlated with MEP but not with SEP or MRI changes. CONCLUSION: The evoked potential and MRI changes in vitamin B12 deficiency neurological syndrome are consistent with focal demyelination of white matter in spinal cord and optic nerve. Myelopathic presentation is commoner and SEP is more frequently abnormal. The outcome at 6 months correlated with MEP changes.     

Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin B12).

Two adolescent patients suffering from persistent sleep-wake schedule disorders appear to have responded to treatment with vitamin B12 (methylcobalamin). A 15-year-old girl with delayed sleep phase syndrome (DSPS) and a 17-year-old boy with hypernychthemeral syndrome complained of not being able to attend school despite many trials of medication. The improvement of the sleep-wake rhythm disorders appeared immediately after the administration of high doses (3,000 micrograms/day) of methylcobalamin. Neither patient showed any laboratory or clinical evidence of vitamin B12 deficiency or hypothyroidism (which can cause B12 deficiency). Serum concentrations of vitamin B12 during treatment were in the high range of normal or above normal. The duration of the sleep period of the DSPS patient decreased gradually from 10 hours to 7 hours, and the time of sleep onset advanced from 2 a.m. to midnight. The period of the sleep-wake cycle of the hypernychthemeral patient was 24.6 hours before treatment and 24.0 hours after treatment. The relationship between the circadian basis of these disorders and vitamin B12 and its metabolites is discussed.     

Staphylococcal scalded skin syndrome in an immunocompromised adult

Staphylococcal scalded skin syndrome, a generalized exfoliative dermatitis complicating infections by exfoliative toxin-producing strains ofStaphylococcus aureus, is rarely observed in adults. In contrast to mortality in infants, mortality in adults is usually high. A case of generalized staphylococcal scalded skin syndrome in an immunocompromised woman is reported. Culture of skin biopsy and pleural fluid yielded identical strains ofStaphylococcus aureus belonging to phage group II. Exfoliative toxins A and B were detected in both isolates. As far as can be determined, this is the first reported case of generalized staphylococcal scalded skin syndrome in an adult with detection of exfoliative toxins A and B in which the patient was treated successfully.     

Manifestations neurologiques associées à la carence en vitamine B12 en milieu carcéral en Guinée : étude de 22 observations

Neurological disorders related to vitamin B12 deficiency are common in prisons of tropical Africa. We collected 22 cases (20 men and 2 women). They all showed vitamin B12 deficiency associated with neurological signs that were represented by sclerosis combined with bone marrow (n = 9), peripheral neuropathy (n = 6), cerebellar syndrome (n = 2), a pyramidal syndrome of the lower limbs (n = 4) and optic neuropathy (n = 1). Laboratory tests showed a mean hemoglobin concentration of 7.2 ± 1.5 g/dl, mean 104 ± 28 fl, macrocytic anemia in 10 patients. Biermer’s disease was identified in 9 patients, 3 patients showed the syndrome of non dissociation of vitamin B12, a gastrectomy in 2 patients and no etiology was identified in 8 patients.     

Comparison of serum vitamin B12 estimation by saturation analysis with intrinsic factor and with R-protein as binding agents.

It has been reported that serum vitamin B12 levels assayed by saturation analysis methods may give misleadingly high results, so much so that the diagnosis of vitamin B12 deficiency may be obscured. This defect was ascribed largely to assays using a vitamin B12 binder other than pure intrinsic factor. To test out this hypothesis two assays were set up, one using saliva (non-intrinsic factor R-binder) and the other using human gastric (intrinsic factor) as B12-binding agents. Both assays were able to differentiate sera from patients with pernicious anaemia from those from control subjects. Published results accumulated over the past 10 years indicate that properly designed and performed saturation analysis vitamin B12 assays are as reliable as microbiological assay methods for detecting low serum B12 levels. The failure of some methods to do does not appear to be due to the nature of the B12-binding agent.     

Down syndrome and epilepsy: a nutritional connection?

Non-Asian individuals with Down syndrome are much more likely to develop epileptic seizure disorders than individuals without Down syndrome. Examination of nutrient and metabolite levels in patients with these two seemingly disparate disorders reveals numerous similarities. Compared to individuals without these disorders, individuals with Down syndrome and individuals with seizures may have lower levels of vitamin A, vitamin B1, folate, vitamin B12, vitamin C, magnesium, manganese, selenium, zinc, carnitine, carnosine, choline, and possibly serine. Excesses of copper, cysteine, phenylalanine, and superoxide dismutase are also sometimes encountered in both disorders. In addition to common nutritional lower levels and excesses, disorders of metabolism involving vitamin B6, vitamin D, calcium, and tryptophan may play a common role. This paper hypothesizes that nutritional factors may account for the high joint occurrence of these conditions. Further examination of these data may provide insights into nutritional, metabolic and pharmacological treatments for both conditions.     

Étude des concentrations sériques en vitamines B9 et B12 dans une population de femmes ayant porté un fœtus atteint de malformation du tube neural

Reduction of vitamin intake, especially of vitamin B9 and B12 which take part in remethylation of homocysteine, leads to hyperhomocysteinemia, known to be a risk factor for neural tube defects. We measured the levels of vitamin B9 and B12 in serums from thirty women who had a pregnancy complicated by neural tube defects and from sixty women who had a normal offspring. Serums were those used for the determination of fetal Down’s syndrome. Vitamin levels were determined by using a reaction of immunocompetition with chemiluminescent detection. There is as many women with vitamin deficiencies in the control group as in the pathologic group. Moreover, comparison of the mean values of each vitamin in the two populations, using Student’s t test, does not show lower vitamin levels in the pathologic group than in the control group. In conclusion, vitamin status alone can’t explain the occurrence of neural tube defects.     

Anaphylaxis to riboflavin (vitamin B2).

BACKGROUND: Vitamin supplements are used more commonly in normal healthy subjects than in patients with vitamin deficiency. Thiamine (vitamin B,) is the vitamin that most frequently induces allergic reactions. To the best of our knowledge, no case of anaphylaxis to riboflavin (vitamin B2) has thus far been reported in the literature. OBJECTIVE: We describe a previously healthy 15-year-old boy in whom anaphylaxis developed several times after he drank one soft drink or took a single multivitamin tablet. This study was done to determine which of the many components found in the soft drink and vitamin tablet caused the anaphylactic reaction. METHODS: In an outpatient clinic with the availability of complete resuscitative procedures, we performed single-blind prick skin tests and intradermal skin tests on the patient with various pure vitamin components of the soft drink and the multivitamin tablet. Physiologic saline and histamine were used for negative and positive controls, respectively. RESULTS: Riboflavin, a component of both the soft drink and the vitamin tablet, produced positive reactions on intradermal skin tests in the patient. Positive reactions were not present in the normal control subjects. CONCLUSIONS: Riboflavin is a previously unreported cause of anaphylaxis. Free-form riboflavin may potentially be associated with an anaphylactic reaction. It is a vitamin widely used in many patients with chronic disease and in healthy subjects. Vitamin B2 must be considered as a cause of anaphylaxis.     

Vitamin D receptor and CD86 expression in the skin of vitamin D-deficient swine

The immunomodulatory role of vitamin D in many diseases is well established. However, the relationship between vitamin D status and skin cancers is unclear. In this study, we examined the effect of vitamin D deficiency and sufficiency on VDR, NF-κB, and CD86 in the epidermis of Yucatan microswine tragi. All of these proteins have known roles in the pathogenesis of cutaneous malignancies such as melanoma and non-melanoma skin cancer. There was weaker and less discrete nuclear staining for VDR and weaker CD86 immunoreactivity with patchy membranous expression in the epidermis of vitamin D-deficient compared to vitamin D-sufficient swine. There was no difference in the immunostaining for NF-κB. Since VDR and CD86 expression are decreased in the setting of melanoma and non-melanoma skin cancers, our findings suggest a potential role of vitamin D-deficiency in the progression of skin malignancies.     

Relationship between megadose vitamin supplementation and immunological function in a healthy elderly population.

We studied the immunological effects of 'megadose' vitamin or mineral supplementation by comparing the immunological functions of healthy elderly subjects taking large amounts of specific nutrients to similar subjects not on supplements. There was a non-significant trend for those subjects taking megadoses of vitamin C to have increased cell-mediated immune responses as measured in vivo by skin test reactivity but not by in vitro mitogen responses. In addition, subjects taking megadoses of vitamin E or any of several B vitamins (B1, B2, B6, folate and niacin) had lower absolute circulating lymphocyte counts than did the rest of the population. The relative lack of effect of megadose vitamins on immunological function in this population compared to reports of short term trials of mega nutrients raises the possibility that some of the previously reported immuno-enhancing properties of megadose vitamins may be due to a non-specific adjuvant effect that disappears with time.     

Vitamin B12 and folic acid deficiency in chronic pancreatitis: a relevant disorder?

Summary Vitamin B12 malabsorption was reported earlier to occur in patients with exocrine pancreatic insufficiency, and pancreatic extracts were shown to improve the absorption of vitamin B12. We investigated serum levels of vitamin B12 and serum folate in patients with chronic pancreatitis and different degrees of pancreatic insufficiency.137 patients (84 males, 53 females, age 34–72 years) with chronic pancreatitis (C.P.) were included in the study. 123 of 137 (89.8%) patients had a pathologic pancreatic function test result, classified into mild (n=24), moderate (n=61) or severe (n=38) insufficiency. The normal range of serum vitamin B12 and folic acid was established in 58 healthy controls and was found to be 190–1020 pg/ml for serum vitamin B12 and 2.4–16.1 ng/ml for folic acid. 7 patients (5.7%) with C.P. had vitamin B12 serum levels below 190 pg/ml; 4 of these had severe and 3 had mild or moderate exocrine pancreatic insufficiency. However there was no overall correlation between the degree of pancreatic insufficiency and vitamin B12 values. Serum levels of Vitamin B12 were 512±48 pg/ml in mild, 493±52 pg/ml in moderate and 428±45 pg/ml in severe exocrine insufficiency. Serum folic acid below 2.4 ng/ml were present in 5 patients (3.6%). Folic acid serum levels were 8.34±0.76 ng/ml in mild, 6.34±0.52 ng/ml in moderate and 7.45±0.53 ng/ml in severe exocrine insufficiency. We conclude that vitamin B12 deficiency is a rare finding in chronic pancreatitis and does not strictly depend on the degree of exocrine pancreatic insufficiency. In clinical practice enzyme supplementation in patients with severe pancreatic insufficiency is obviously sufficient for normal vitamin B12 absorption. Folic acid deficiency is also unfrequently found in chronic pancreatitis.     

Haemoglobin A2 levels in vitamin B12 and folate deficiency.

Haemoglobin A2 levels were measured in 50 patients with vitamin B12 deficiency, 50 patients with folate deficiency, and six patients with combined deficiencies of these vitamins. All were normal except for three patients with vitamin B12 deficiency, who had a slightly elevated Hb A2 level; this fell to normal after vitamin B12 therapy. It is concluded that haemoglobin A2 levels are usually normal in vitamin B12 or folate deficiency. However, raised levels of haemoglobin A2 may be found, but these are not as high as is found in beta thalassaemia trait and should not cause difficutly in diagnosis.     

Clinical variability of tetrasomy 12p

We describe five patients with tetrasomy 12p (one previously reported). These patients exhibit a very wide range of phenotypic features from that of classic Pallister-Killian syndrome to only mild learning disabilities with pigmentary skin changes. As such, these cases highlight the fact that tetrasomy 12p [i(12p)] and Pallister-Killian syndrome are not synonymous, although this combination of genotype and phenotype is often seen. This information is especially important in prenatally ascertained i(12p). The full spectrum of phenotypic possibilities associated with this chromosome aneuploidy should be discussed in prenatal counseling.     

B vitamins suppress spinal dorsal horn nociceptive neurons in the cat

To explore the role of vitamin B in neural mechanisms of analgesia, we investigated the effect of a compound of vitamins B1, B6 and B12 (Neurobion, E. Merck) on the nociceptive responses of single neurons in the spinal cord dorsal horn in anesthetized cats. Intrathecal superfusion of Neurobion, using a small pool placed on the spinal surface, produced a significant dose-dependent depression in the responses evoked by noxious skin heating (50 or 52 degrees C, 10 s) of hindfoot skin, but not of spontaneous activity in dorsal horn neurons. These results indicate that the therapeutic effect of vitamin B compounds in the clinical management of pain may involve a suppression of nociceptive transmission at the spinal level.     

FA、VitB12与Hcy检测对老年巨幼细胞性贫血与骨髓增生异常综合征的鉴别诊断价值

目的 分析对比老年巨幼细胞性贫血（MA）和骨髓增生异常综合征（MDS）患者的实验室指标特点,并探讨其临床意义.方法 对121例老年MA患者和81例老年MDS患者的外周血像、血清造血原料水平、总胆红素、间接胆红素、同型半胱氨酸等实验室指标进行回顾分析.结果 MA组的平均红细胞体积、平均血红蛋白含量、平均血红蛋白浓度、胆红素、同型半胱氨酸水平明显高于MDS组（P＜0.05）;MA纽的白细胞计数、红细胞计数、维生素B12铁蛋白明显低于MDS组（P＜0.05）.两组间血红蛋白、血小板计数、红细胞体积分布宽度、叶酸水平差异无统计学意义（P＞0.05）.结论 对于怀疑MA或MDS的老年患者,平均红细胞体积、平均血红蛋白含量、平均血红蛋白浓度、总胆红素、间接胆红素、铁蛋白对于MA和MDS的鉴别诊断价值小,而叶酸、维生素B12联合同型半胱氨酸水平检测可用于两者鉴别,对于基层医院无条件检测叶酸、维生素B12的情况下,同型半胱氨酸水平升高提示叶酸和维生素B12缺乏,同型半胱氨酸水平升高为MA与MDS的鉴别诊断提供重要参考依据.     

The master key effect of vitamin B12 in treatment of malignancy – A potential therapy?

Vitamin B12 plays a functional role in a variety of organs and body systems and the list of these organs and body systems is growing. According to our working hypothesis ("Master Key Effect") vitamin B12 has some unique functions, which are still not accepted; vitamin B12 functions to keep body systems in balance, even under the stress of severe pathology. What is the explanation for elevation of cobalamin level in oncological patients? As yet I have not been able to find another explanation for high level of vitamin B12 in oncology patients other than that it is a compensatory mechanism. Perhaps following this body's "warning sign", we should start treatment with high doses of vitamin B12 to try to help the stabilization of normal function of the organs and systems. Laboratory researches should be continued to substantiate introduction of cobalamin as preliminary treatment of particular diseases.     

中国4城市2—7岁分析人群维生素B12营养状况流行病学调查

目的了解4城市2～7岁分析人群维生素B12的营养状况。方法2007年5～9月和2008年5—10月,对2002名2～7岁分析人群进行体格检查、膳食调查、血常规检查及血清维生素B12水平测定,其中重庆市485名、北京市513名、珠海市503名、武汉市501名。结果①2002名2～7岁分析人群平均维生素B12水平（ng·L^-1）为775±312,市区（835±271）高于郊区（720±338）,P〈0．001;其中重庆市为756±220、北京市为840±414、珠海市为772±245、武汉市为736±317,地区间差异有统计学意义,P〈0．001。②2～7岁分析人群维生素B12水平性别差异不显著,P〉0．05;2—5岁组维生素B12水平随年龄增长呈降低趋势,r=-0．146,P〈0．001;5岁～组和〈7岁组维生素B12水平相近。（3）4城市分析人群维生素B12减少（〈300）检出率为4．7％。其中维生素B12缺乏（〈200）检出率为1．5％,边缘性缺乏（200—300）检出率为3．2％。重庆市、北京市、珠海市和武汉市分析人群血清维生素B12减少检出率分别为2．1％、3．9％、3．2％和9．6％。④分析人群维生素B12水平主要受膳食维生素B12摄入量的影响,P〈0．001。分析人群平均膳食维生素B12摄入量（μg·d^-1）市区（2．4±2．0）高于郊区（2．0±1．4）,P〈0．05;重庆市、北市京、珠海市和武汉市分析人群平均膳食维生素B,2摄入量分别为1．9±1．3、2．8±1．6、2．6±1．8和1．6±1．2,差异有显著统计学意义,P〈0．001。⑤分析人群维生素B12水平与Hb水平呈低度相关,P〈0．001。结论4城市分析人群存在维生素B12减少,以边缘性缺乏为主。儿童维生素B12营养状况受膳食维生素B12摄入量的影响,分析人群血清维生素B12水平何时达到成人水平有待研究。     

Folate and vitamin B12 status of adolescent girls in northern Nigeria

The diets of populations in many developing countries are low in folate and vitamin B12 and a deficiency of either of these vitamins results in increased risk for cardiovascular disease and neural tube defects. The rates of neural tube defects in Nigeria are among the highest reported worldwide. Since many girls marry at an early age in northern Nigeria, we therefore determined the folate and vitamin B12 status of adolescent girls between 12 and 16 years of age in Maiduguri, Nigeria. The mean serum folate concentration for subjects was 15.3 +/- 5.2 nmol/L. Whereas only four subjects (2.4%) had serum folate concentrations lower than 6.8 nmol/L, a level indicative of negative folate balance, 9% of the subjects had serum vitamin B12 concentrations at or below 134 pmol/L, the lower limit of the reference range for their age group. Serum homocysteine was measured in 56 of the 162 subjects and the mean level was 15.9 +/- 5.0 mumol/L. The majority of subjects had serum homocysteine concentrations above the upper limit of the reference range for their age group. We conclude that the adolescent girls we studied were at greater risk for vitamin B12 deficiency than folate deficiency. This conclusion is consistent with the fact that their diet included few foods that contained vitamin B12.     

Vitamin B12 supplement exerts a beneficial effect on the seminiferous epithelium of cimetidine-treated rats

Treatment of gastric ulcer with cimetidine reduces acid secretion and interferes in the vitamin B(12) absorption. Regarding the harmful effect of cimetidine on the seminiferous tubules, the aim of the present study was to verify if prolonged treatment with cimetidine causes vitamin B(12) deficiency and whether the testicular damages are attenuated by vitamin B(12) supplementation. Adult male rats received, for 50 days, cimetidine (CMTG), cimetidine and vitamin B(12) (CMT/B(12)G), vitamin B(12) (B(12)G) and saline solution (CG). Vitamin B(12) and homocysteine plasma levels were evaluated and the testes were embedded in glycol methacrylate for the morphometric analyses of total, epithelial and luminal areas of the seminiferous tubules, number of Sertoli cells and frequencies of tubules according to stages and containing Sertoli and germ cells in the lumen. Terminal deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) method and proliferating cell nuclear antigen (PCNA) immunohistochemistry were carried out. CMTG showed TUNEL-positive Sertoli cells and significant reductions in the epithelial and total tubular areas, number of Sertoli cells and frequency of tubules VII-VIII. In the CMT/B(12)G, the number of Sertoli cells and the epithelial and total tubular areas were similar to CG. The number of Sertoli cells (in B(12)G) and the frequency of tubules at stages VII-VIII (in B(12)G and CMT/B(12)G) increased significantly; PCNA-positive Sertoli cells were found in these groups. Although cimetidine was not able to induce vitamin B(12) deficiency, this drug causes tubular atrophy due to Sertoli cell damage and loss of germ cells. However, vitamin B(12) supplement is able to stimulate spermatogenesis and restore the number of Sertoli cells, softening the harmful effect of cimetidine on spermatogenesis.     

Racial differences in vitamin B12 levels in the United States

Studies from Africa have demonstrated that black people have higher vitamin B12 (cobalamin) levels than do white people. The authors compared healthy white people, black people, and Latin-Americans in the United States. Their study is also the largest in which the effect of race and sex on the cobalamin levels has been examined. Analysis of 233 healthy subjects showed that black people had significantly higher (P less than 0.0001) vitamin B12 levels than did white people. Latin-Americans had levels intermediate between those of white and black people, although their levels were significantly different only in comparison with white people (P = 0.0029). Based on the study of 305 healthy subjects, no sex difference in vitamin B12 levels was noted. Conflicting claims have been made on sex difference in the past. The authors conclude that there is a racial but not a sex difference in vitamin B12 levels in the United States. Like African black people, black people and Latin-Americans in this country have significantly higher vitamin B12 levels than do white people. This finding supports the thesis that genetic factors contribute to the racial differences in vitamin B12 levels.