A study of neurobehavioral, clinical psychometric, and P3 changes in vitamin B12 deficiency neurological syndrome

Kalita, Jayantee; Agarwal, Ritu; Chandra, Satish

doi:10.1179/1476830512y.0000000028

Cited by 26 publications

(35 citation statements)

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“…The neurophysiologic evaluation of our participants also included QST and SSEPs, but no changes were observed in these variables after the vitamin B-12 injection, possibly because an improvement in vitamin B-12 status affects mainly large afferent peripheral nerves rather than the smaller fibers. Similar improvements in peripheral sensory conduction velocity were described in vitamin B-12-deficient patients with clinical symptoms by Kalita et al (30), although they also showed an increase in the amplitude of the motor compound action potential. Tredici et al (31), in an experimental model of vitamin B-12 deficiency in rats, described intramyelinic and interstitial edema without axonal damage associated with a reduction of nerve conduction velocity.…”

Section: Discussionsupporting

confidence: 62%

“…Tredici et al (31), in an experimental model of vitamin B-12 deficiency in rats, described intramyelinic and interstitial edema without axonal damage associated with a reduction of nerve conduction velocity. Only at a more-advanced stage, when the abnormalities are clinically expressed, would the peripheral sensory neuropathy express as axonal (6,16,30). The fact that we detected changes in peripheral but not central nerve conduction suggests that sensory peripheral nerve conductivity is the most-useful method for the assessment of subclinical neurologic effects of vitamin B-12 deficiency and repletion.…”

Section: Discussionmentioning

confidence: 76%

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Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status

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Hertrampf

et al. 2016

The American Journal of Clinical Nutrition

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Background: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. Objective: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid. Design: A pretreatment and posttreatment study was conducted in 51 participants (median 6 SD age: 73 6 3 y; women: 47%) with serum vitamin B-12 concentrations ,120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by measuring cB-12 and neurophysiologic variables at baseline and 4 mo after treatment. Results: Treatment increased serum vitamin B-12, holotranscobalamin, and cB-12 (P , 0.001) and reduced plasma tHcy and serum MMA (P , 0.001). Treatment produced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of both the left and right sural nerves improved on the basis of faster median conduction times of 3.1 and 3.0 ms and 3.3 and 3.4 ms, respectively (P , 0.0001). A total of 10 sensory potentials were newly observed in sural nerves after treatment. Participants with high serum folate at baseline (above the median, $33.9 nmol/L) had less improvement in cB-12 (P , 0.001) than did individuals whose serum folate was less than the median concentration (i.e., with a concentration ,33.9 nmol/L). Conclusion: Asymptomatic Chilean elderly with poor vitamin B-12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatment and an interaction with folate status, which was detected only with the use of cB-12. This trial was registered at www.controlled-trials.com as ISRCTN02694183.Am J Clin Nutr 2016;103:250-7.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 76%

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status

Brito

Verdugo

Hertrampf

et al. 2016

The American Journal of Clinical Nutrition

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“…Other authors have also reported visual-evoked potential abnormality in up to 70% (9) and sensory-evoked potential abnormality up to 100% of patients (10). Cognitiveevoked potential was abnormal in 58% patients with VBDNS and improved after therapy (2). The improvement in evoked potentials suggests an important role of vitamin B-12 in myelin functions.…”

mentioning

confidence: 88%

“…The frequency of neuropsychiatric and cognitive abnormalities in vitamin B-12 deficiency depends on the extent of evaluation. In one study, 42% of patients with vitamin B-12 deficiency neurological syndrome (VBDNS) had abnormalities on neuropsychiatric inventory; these included anxiety, apathy, aggression, irritability, hallucinations, delusions, and disinhibition, in descending order (2). In another study of VBDNS (3), myelopathy was present in 93% of patients, cognitive impairment in 48%, and neuropathy in 44%.…”

mentioning

confidence: 98%

“…Detailed cognitive testing in VBDNS revealed frontal-subcortical neurobehavioral and cognitive abnormalities, which improved after vitamin B-12 therapy. The improvement was reflected by motor speed and precision test, trail-making test, clock-drawing test, category naming, and Mini-Mental State Examination along with improvement in cognitive-evoked potentials (2).…”

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confidence: 99%

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Benefit of vitamin B-12 supplementation in asymptomatic elderly: a matter of endpoints

Kalita

2015

The American Journal of Clinical Nutrition

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The myth and panacea of vitamin B-12 have attracted many scientists in the past century. Six Nobel Prizes have been awarded to the scientists who worked on vitamin B-12: George Hoyt Whipple, George Richards Minot, and William Parry Murphy were awarded the prize in 1934 for the discovery of vitamin B-12; Robert B Woodward received it in 1965 for synthesis of vitamin B-12; and Lord Todd and Dorothy Crowfoot Hodgkin were awarded in 1957 and 1964, respectively, for discovering the structure of vitamin B-12. The journey of vitamin B-12 was started as a panacea for anemia, followed by a definite association with subacute combined degeneration and remarkable improvement with vitamin B-12, and lately a controversial role of vitamin B-12 in prevention of dementia and cardiovascular complications. The prevalence of vitamin B-12 deficiency in industrialized countries ranges between 2% and 20% and may occur in 30% in elderly malnourished sick individuals. In the Framingham study, the prevalence of vitamin B-12 deficiency in the elderly was 12% (1). Vitamin B-12 is an essential cofactor in 2 enzymatic pathways in mammalian cells. It acts as a cofactor with methionine synthase to convert homocysteine to methionine and with L-methylmalonyl-CoA mutase to convert methylmalonyl-CoA to succinyl-CoA. Humans are unable to synthesize cobalamin; hence, an exogenous supply is essential. The daily requirement of vitamin B-12 in adults is 2.4 lg/d, and only 1-5% of crystalline cobalamin is absorbed. In the elderly, the absorption is reduced; hence, the daily requirement is higher than in younger individuals. Vitamin B-12 deficiency can result from pernicious anemia; vegetarianism; poor intake in isolated, elderly, or psychiatric patients; food cobalamin absorption; gastric or ileal resection; malabsorption; alcohol intake; Sjogren syndrome; deficiency in transcobalamin II, intracellular enzymes, or haptocorin; and frequent use of certain drugs (e.g., H2-receptor antagonists, proton-pump inhibitors, biguanids).The clinical manifestations of vitamin B-12 deficiency are diverse and include hematologic, skin, behavioral, and neurologic manifestations. The frequency of neuropsychiatric and cognitive abnormalities in vitamin B-12 deficiency depends on the extent of evaluation. In one study, 42% of patients with vitamin B-12 deficiency neurological syndrome (VBDNS) had abnormalities on neuropsychiatric inventory; these included anxiety, apathy, aggression, irritability, hallucinations, delusions, and disinhibition, in descending order (2). In another study of VBDNS (3), myelopathy was present in 93% of patients, cognitive impairment in 48%, and neuropathy in 44%. Combined syndromes were common, and the isolated syndrome occurred in only 2% of patients. Healton et al. (4) reported myelopathy and encephalopathy in 88% and 15% of patients, respectively. Dementia in VBDNS is mild to moderate, although initial studies reported megaloblastic madness (5). Detailed cognitive testing in VBDNS revealed frontal-subcortical neurobehavioral and cognitive abn...

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Maternal Phenylketonuria: Long-term Outcomes in Offspring and Post-pregnancy Maternal Characteristics

et al. 2014

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Maternal phenylketonuria (MPKU) is a well-recognized complication of PKU and one of the most potent teratogenic syndromes of pregnancy. Virtually all offspring from untreated pregnancies in women with classic PKU have intellectual disabilities and microcephaly. Congenital heart disease and intrauterine growth retardation occur many times more often than expected in the general population. Control of maternal blood phenylalanine during pregnancy prevents most if not all of these complications. Previous studies demonstrated the benefits of treatment in terms of birth parameters and early development. In this study, physical examinations, a medical history, and neuropsychological evaluation were obtained in 47 children from 24 mothers with PKU who received treatment during pregnancy. Mothers were interviewed and administered an abbreviated IQ test. Associations between maternal factors and offspring outcomes were also analyzed.The 21 male and 26 female offspring ranged in age from 1 month to 26 years with 21 (62%) over 6 years. Results indicated mean intercanthal distances above the 70th percentile. Microcephaly was present in 19% of offspring, with head circumference below the third percentile. None of the offspring had cardiac anomalies. Mean offspring IQ was 94 ± 19, with 12% performing in the range of intellectual disability (IQ < 70). Among children >5 years of age, 25% had learning disabilities, 31% had attention deficit hyperactivity disorder (ADHD), 22% were on ADHD medication, and 34% had a diagnosis of anxiety and/or depression. Among the 24 mothers, 12 reported following the diet for PKU. Only one woman on diet had a blood phenylalanine concentration <360 μmol/L (recommended range) and the majority had indications of poor nutritional status. Mean maternal Full Scale IQ was 94 ± 16 (range = 61-117), with 25% performing in the borderline intellectual range (IQ < 85). Verbal IQ was significantly lower than Performance IQ (p = 0.01, CI 2.7, 16.1). On the self-report Beck Depression Inventory, Second Edition, 25% received scores indicating mild to moderate depression, and on the Beck Anxiety Inventory, 46% reported mild to moderate anxiety. Offspring IQ correlated with maternal metabolic control during pregnancy (r = 0.51), maternal IQ (r = -0.62), and socioeconomic position (r = -0.48). Offspring with ADHD, learning disabilities, or emotional disturbances were more likely to have mothers with anxiety and/or depression. To ensure optimal offspring outcomes, healthcare providers need to assess maternal nutrition, blood phenylalanine concentrations, cognitive abilities, and socioeconomic position. Interventions can then be initiated that reduce psychosocial stressors and enhance adherence to diet and positive parenting, which in turn can lead to better cognitive functioning, behavior, and emotional well-being in their children.

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A study of neurobehavioral, clinical psychometric, and P3 changes in vitamin B12 deficiency neurological syndrome

Abstract: VBDNS results in frontal-subcortical neurobehavioral and cognitive abnormalities which may be due to cortical and subcortical dysfunction. The reversibility of these changes is suggestive of metabolic alteration in neuronal or myelin function.

Cited by 26 publications

References 31 publications

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status

Vitamin B-12 treatment of asymptomatic, deficient, elderly Chileans improves conductivity in myelinated peripheral nerves, but high serum folate impairs vitamin B-12 status response assessed by the combined indicator of vitamin B-12 status

Benefit of vitamin B-12 supplementation in asymptomatic elderly: a matter of endpoints

Maternal Phenylketonuria: Long-term Outcomes in Offspring and Post-pregnancy Maternal Characteristics

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