Neuroimaging Findings in Vitamin B12-Deficient Infants With Neurologic Features.

Background:Vitamin B12 deficiency causes serious neurologic problems among infants. However, its neuroradiologic correlate is still largely obscure. Methodology: This prospective study was conducted on patients aged 6 months to 2 years. All children with proven vitamin B12 deficiency were planned to undergo magnetic resonance imaging (MRI) and magnetic resonance spectroscopy of the brain. Results: A total of 35 patients (63% female) were enrolled. Twenty-six (74%) patients had significant findings on brain MRI scan, commonest of which were thinning of corpus callosum and prominence of extra-axial spaces in 28.6% children, cerebral atrophy in 17%, and diffuse symmetrical hyperintensity of white matter in 5.7% patients. Using logistic regression, it was found that odds of abnormal neuroimaging findings were higher in children below 12 months, in females, and in patients with developmental regression, but none of them were statistically significant. Conclusion: Most of the infants with vitamin B12 deficiency have abnormal neuroimaging findings.

Effects of B12 Deficiency Anemia on Radial Peripapillary and Macular Vessel Density: An Optical Coherence Tomography Angiography (OCTA) Study.

BACKGROUND: To evaluate the macular and optic disc vascular changes in vitamin B12 deficiency anemia. METHODS: A total of 24 patients with vitamin B12 deficiency anemia and 24 healthy controls were involved in this study. All participants were evaluated for central macular thickness (CMT), peripapillary retina nerve fiber layer (RNFL) thickness, foveal avascular zone (FAZ) area, macular vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP), choriocapillaris flow area, and optic disc radial peripapillary capillary (RPC) VD using optic coherence tomography (OCT) and optic coherence tomography angiography (OCTA). Metabolic parameters were also noted. RESULTS: Temporal RNFL thickness significantly decreased in the B12 deficiency anemia group (p = 0.04). Choriocapillaris flow area (p = 0.045) and macular vessel density in both SCP (p = 0.022) and DCP (p = 0.018) markedly declined in the study group. Optic disc RPC VD in the B12 deficiency anemia group was lower in all regions compared to that of the control group, but the difference was not statistically significant (p > 0.05). There were significant positive correlations between choriocapillaris flow area, macular VD, vitamin B12, and hemoglobin. CONCLUSION: Retinal vascular alterations were observed in B12 deficiency anemia, and OCTA may be beneficial in the diagnosis and follow-up of ocular complications in these cases.

Structural and Functional Brain Changes Associated with Vitamin B12 Deficiency using Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

AIM: This review was conducted to assess the structural and functional brain changes associated with vitamin B12 deficiency in different age groups using MRI. METHODS: PubMed, Embase, Medline, CINAHL, Scopus, Web of Science, and Google Scholar were searched for magnetic resonance imaging (MRI) studies that explored structural and functional brain changes associated with vitamin B12 deficiency in different age groups. The inclusion criteria were as follows: (1) the population consisted of people and not animals; (2) patients with known B12 deficiency; (3) English publications; (3) at least one of the following brain MRI techniques had been employed: VBM, DWI, DTI, fMRI, or rs-fMRI. However, case reports, systematic reviews and meta-analyses were excluded. RESULTS: Twelve articles met the inclusion criteria. The results of my review show a connection between vitamin B12 deficiency and abnormal structural and functional brain changes in several brain regions. These changes were observed in different age groups ranging from a mean age of seven years to a mean age in the 70s. The results also highlight the association between brain changes and cognitive decline among affected subjects. Improvements in damaged brain regions post-vitamin B12 treatment were also studied. CONCLUSION: Structural and functional brain damage was found to be associated with vitamin B12 deficiency in all age groups. Vitamin B12 treatment may lead to partial or complete structural and/or functional recovery, as well as a cognitive recovery.

A case of subacute combined spinal cord degeneration and suspected leukoencephalopathy associated with vitamin B12 deficiency showing improved imaging findings after vitamin B12 administration.

We report a case of subacute combined spinal cord degeneration (SCD) caused by vegetarianism and autoimmune gastritis, which is rarely reported in Japan, and which showed improvement in symptoms and imaging findings after vitamin B12 administration. As delayed treatment can lead to irreversible damage, we suggest that patients with characteristic abnormal signals in the posterior cervical cord should be examined while considering the possibility that SCD may occur even in the absence of a history of gastrectomy or heavy drinking. We also describe the patient's reversible abnormal signals in the cerebral white matter on magnetic resonance imaging, indicative of an early sign of leukoencephalopathy associated with vitamin B12 deficiency. J. Med. Invest. 69 : 299-301, August, 2022.

Subcortical lesions due to cobalamin deficiency: an unusual MRI lesion pattern.

We present a 44-year-old male patient with new onset of right focal epilepsy and bilateral hand hypesthesia. Cerebral MRI showed bilateral T2w/DWI hyperintense subcortical lesions in the cingulate gyrus, insula, and amygdala, whereas spinal MRI revealed a cervical posterior column lesion, corresponding to subacute combined degeneration. Laboratory workup revealed a cobalamin deficiency due to type A gastritis, and no evidence of antibodies associated with limbic encephalitis. After sufficient cobalamin substitution, the cerebral and spinal lesions gradually regressed. Our case represents a unique cerebral subcortical MRI lesion pattern in a patient with epilepsy and cobalamin deficiency. Thus, the latter represents an important differential diagnosis for autoimmune encephalitis.

Does B12 deficiency lead to change in brain metabolites in pediatric population? A MR spectroscopy study.

OBJECTIVES: The aim of this study is to examine metabolite changes in different brain regions of the children with vitamin B12 deficiency disease using MR spectroscopy. METHODS: Eighteen children with serum vit. B12 deficiency and 12 healthy volunteer children were included in the study. All children were examined with single-voxel spectroscopy examination via 1.5-Tesla MRI. The spectra were obtained from the left frontal periventricular white matter, left lentiform nucleus and left cerebellar hemisphere. The comparisons between patient group and control group were made with ratios calculated as NAA/Cr, Cho/Cr, mI/Cr, and Glx/Cr. All brain images were also examined in terms of brain atrophy, abnormal brain parenchyma intensity changes, or myelination status. RESULTS: The children were between 3 months and 16 years old in the patient group, and between 3 months and 15 years old in the control group. There were no statistical differences in terms of metabolite ratios in the three different brain regions between the patients and control group. In two patients, periventricular white matter hyperintensities were observed. In four patients, brain atrophy was detected. DISCUSSION: MR spectroscopy examination demonstrated that there were no statistical differences in terms of all metabolite ratios in left frontal periventricular white matter, left lentiform nucleus and left cerebellar hemisphere.

Distinct clinical, neuroimaging and genetic profiles of late-onset cobalamin C defects (cb1C): a report of 16 Chinese cases.

OBJECTIVE: The importance of late-onset cobalamin C (cblC) disorder is underestimated in adults. Improved awareness on its clinical and neuroimaging features helps timely diagnosis and appropriate treatment. METHODS: Totally 16 late-onset cblC cases were diagnosed based on clinical, biochemical findings and MMAHC gene mutation analysis. Clinical presentations, neuroimaging features and mutational spectrum were reviewed. RESULTS: The case series included 10 males and 6 females, with average age of 22 (range 13-40) years. All the 16 patients displayed bilateral pyramidal tract signs, and most of the cases (13) had cognitive impairment. Other symptoms included psychiatric symptoms (6), epilepsy (6), peripheral nerve damage (5), ocular symptoms (4) and lower-limb thrombosis (1). The neuroimaging findings were dominated by cerebral atrophy (11/16), followed by white matter lesions (4), cerebellar lesions/atrophy (2) and spinal cord lesions (1). There were also 2 patients with normal imaging. All the MMACHC mutations were compound heterozygous, of which the most and second frequent was c.482G > A (p.R161Q; 15/16 case; allele frequency: 46.88%) and c.609G > A(p.W203X; 6/16 case; allele frequency: 18.75%). In addition, patients carrying frameshift mutations (deletion/duplication) presented more frequently with psychiatric symptoms (57.1%) and optic nerve damages (42.9%) than those carrying point mutations (22.2 and 11.1%, respectively). In contrast, peripheral nerve (44.4%) and white matter lesions (33.3%) were more frequently identified in point mutation- carriers. However, the differences did not achieve statistical significance (all p > 0.05). CONCLUSION: Compared to the early-onset form, late-onset cblC displayed some clinical, neuroimaging and mutational profiles, which warrants particular attention in adult neurologic practice. These findings not only broaden our insights into the genotypes and phenotypes of the disease, but highlight the importance of early diagnosis and initiation of appropriate treatments.

Nitrous oxide myelopathy with functional vitamin B 12 deficiency.

Recreational use of nitrous oxide as a 'legal high' is increasing in the UK. Physicians should be 'street wise' to this increasing prevalence and aware of the potential neurological complications which may result from misuse. We describe a 17-year-old male patient who presented to neurology with a severe myelopathy following prolonged recreational use of nitrous oxide. MRI demonstrated characteristic changes affecting the dorsal columns and blood tests demonstrated a 'functional' B12 deficiency. Clinical and radiological improvement was noted following initiation of vitamin B12 replacement.

Hemiconvulsion-Hemiplegia-Epilepsy in a girl with cobalamin C deficiency.

Hemiconvulsion-Hemiplegia-Epilepsy initially involves an infantile presentation of febrile focal motor status epilepticus, with subsequent hemiplegia of the initially affected side. Months to years later, affected children go on to develop a chronic epilepsy with recurrent focal seizures which are often refractory to treatment. This uncommon paediatric epilepsy syndrome is poorly understood, with only a very small minority of cases associated with an underlying genetic or metabolic abnormality. We present a four-year-old girl with genetic cobalamin C deficiency who had a dramatic presentation with Hemiconvulsion-Hemiplegia-Epilepsy. She had febrile focal status epilepticus, with right hemiconvulsive seizures for nearly 10 hours, ultimately requiring a midazolam infusion. Over subsequent days, she developed progressively worsening cerebral oedema, leading to herniation and requiring a craniectomy to relieve pressure. This girl's presentation is the first association of cobalamin deficiency with hemiconvulsion-hemiplegia-epilepsy; and illustrates the importance of considering this entity when patients with this metabolic disorder present with acute deterioration. More importantly, the case also raises the possibility that derangements of cobalamin metabolism could be a contributing factor in cases of hemiconvulsion-hemiplegia-epilepsy, as well as febrile seizures in general.

Evaluation of diffusion tensor imaging changes and neurocognitive effects of asymptomatic vitamin B12 deficiency.

Vitamin B12 plays an important role in the mechanisms which are responsible for myelinization in the central nervous system. It can particularly lead to hematological and neuropsychiatric symptoms when serum levels fall due to insufficient intake with diet or absorption problems. The purpose of this study was to show the cognitive effects in vitamin B12 deficiency cases that have not reached clinical symptom level using neuropsychological tests, and to show possible cerebral neuronal damage using diffusion tensor imaging (DTI) method. A total of 62 asymptomatic vitamin B12 deficiency patients and 40 healthy subjects were included in the study and both groups were subjected to Standardized Mini-Mental State Examination, Montreal Cognitive Assessment Test, Rey Auditory Verbal Learning Test, forward and backward digit span (WMS-R forward and backward), Visual Reproduction Subtest (WMS-III), Category Fluency Test, Trail Making (Trail A-B) (21) and Similarities (BENZ) tests. DTI examinations were performed on both groups. Patient group was determined to get lower scores in all neuropsychological tests compared to control group. In DTI examination, a significant decrease in FA values of bilateral hippocampus and a prominent increase in apparent diffusion coefficient (ADC) values were determined in the patient group compared to control group. In this study, it was determined that there was microstructural damage in the brain in the presence of vitamin B12 deficiency even in the asymptomatic period, and the patients revealed cognitive decline. In accordance with this result, early treatment of the easily diagnosed and treated vitamin B12 deficiency may prevent possible irreversible damage in the future.

Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric presentations.

The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic acidemia and homocystinuria in plasma, is an inborn error of cobalamin metabolism. The late-onset cblC siblings patients were rarely reported. In this study, we analyzed the clinical presentations and treatment outcomes of late-onset cblC in Chinese sibling patients with neuropsychiatric presentations. The clinical data of four pairs of Chinese patients were retrospectively analyzed. Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene analysis were carried out in all patents. Patients were reevaluated after treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B. The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric disturbances including cognitive decline (3/8), psychiatric disturbances (4/8), gait instability (2/8), lower extremity weakness and numbness (3/8) and thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum homocysteine when patients were diagnosed was 109.4 (range 69.5-138) µM/L. The abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6) and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two siblings showed homozygous mutation with c.452A > G in MMACHC gene. After treatments, the psychiatric symptoms were obviously relieved in all the patients. In Chinese siblings with late-onset cblC, the main clinic manifestation and abnormal radioimaging were cognitive decline and cerebral atrophy respectively. The most common gene mutation was c.482G > A of MMACHC gene. The patients responded well to the treatments.

Tc-99m-ECD SPECT as the measure for therapeutic response in patients with cobalamin deficiency: Two case reports.

BACKGROUND: Cobalamin (Cbl) is an essential vitamin for human health. While an increasing body of evidence supports the negative impact of Cbl deficiency on cognition, the causality has yet to be determined, and the reported therapeutic responses after Cbl supplement therapy have been inconsistent. Besides, few reports have described neuroimaging characteristics associated with the therapeutic response. METHODS: To describe and compare technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc-99m-ECD SPECT) findings in 2 patients with Cbl deficiency with distinct therapeutic responses. RESULTS: Case 1 scored 12/30 in the mini-mental state examination (MMSE) and 34/100 in the cognitive abilities screening instrument (CASI). Profound deficits in mental manipulation, drawing, short-term/long-term memory, and verbal fluency were noted. Case 2 scored 24/30 in the MMSE and 78/100 in the CASI, mainly due to impaired mental manipulation, abstract thinking, and borderline performance in short-term memory and verbal fluency. While both cases showed widespread hypoperfusion within bilateral frontotemporal regions and thalamus on Tc-99m-ECD SPECT, Case 2 demonstrated relatively preserved radio-uptake in the frontal regions, especially the anterior cingulate cortex (ACC) and prefrontal cortex (PFC), consistent with the better therapeutic response (Case 1: 12/30 to 11/30 in the MMSE; Case 2: 24/30 to 28/30 in the MMSE). CONCLUSION: Given that the ACC integrates the limbic system and frontosubcortical circuits and the PFC governs executive function, the extent and severity of hypofrontality may be responsible for the worse prognosis. Our Tc-99m-ECD SPECT observations revealed that the negative impact on cerebral metabolic tone is relevant to the severity of Cbl deficiency, and the functional integrity of the ACC and PFC is highly associated with the preservation of global cognitive function in our cases with Cbl deficiency.