One month of nitrous oxide abuse causing acute vitamin B 12 deficiency with severe neuropsychiatric symptoms.

A 21-year-old university student studying abroad in the USA presented to the emergency department with double vision, lower extremity weakness with difficulty ambulating and other neuropsychiatric symptoms. MRI of the brain and spinal cord were normal. Vitamin B12 was 78 pg/mL (58 pmol/L, reference 211-911 pg/mL). The patient had been using nitrous oxide capsules used for whipped cream recharging, which she obtained from other students, a few times daily for a month for the purpose of anxiety relief. The patient was not a vegan or vegetarian. The patient was treated with intramuscular vitamin B12 repletion with partial resolution of neurologic symptoms and discharged on vitamin B12 supplementation.

Vitamin D status in cervical spondylotic myelopathy: comparison of fusion rates and patient outcome measures.

BACKGROUND: Patients undergoing elective spinal fusion have an alarming rate of vitamin D deficiency, but its impact on bone fusion and patient outcomes is unclear. We investigated the association of perioperative vitamin D levels, fusion rates, and patient-reported outcome in patients undergoing spinal fusion for cervical spondylotic myelopathy. METHODS: In this one-year, prospective, single-center observational study, serum 25-OH vitamin D levels were measured perioperatively in adult patients. Serum vitamin D levels <30 ng/mL were considered abnormal. The primary outcome measures were postoperative patient-reported outcomes (Neck Disability Index, Visual Analog Scale, EuroQol EQ-5D-3L, EQ-VAS). Secondary outcome measures were the presence of and time to solid bony fusion, controlling for Body Mass Index (BMI), age, and number of motion segments. RESULTS: Forty-one of 58 patients (71%) had laboratory-confirmed abnormal vitamin D levels. Patients with low vitamin D were younger (P<0.05) and had a higher BMI (P<0.05) than patients with adequate vitamin D, but the groups were otherwise similar. There were no differences in mean time to fusion between the two groups, but patients with low vitamin D reported more postoperative disability (P<0.05). Multivariate model analysis demonstrated an independent, significant association between normal vitamin D and lower postoperative neck disability index (P=0.05) and EQ-5D-3L (P=0.03). CONCLUSIONS: Vitamin D deficiency (<30 ng/mL) is highly prevalent in patients undergoing elective spinal fusion for cervical myelopathy. Low vitamin D levels were associated with worse patient-reported outcomes and were an independent predictor of greater disability, which suggests vitamin D supplementation may offer some benefit in these patients.

Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations.

Study of micronutrients (copper, zinc and vitamin B12) in posterolateral myelopathies.

BACKGROUND: Vitamin B12 deficiency is a well recognized cause of posterolateral myelopathy. In Indian subcontinent, it may coexist with nutritional copper deficiency producing partial response of patients to B12 supplementation. Hence the study was planned to look for association of hypocupremia and B12 deficiency. METHODS: Twenty-three patients with posterolateral myelopathy (Romberg sign positive) were enrolled and investigated for levels of vitamin B12, copper and zinc and followed up for six months. RESULT: In three patients, copper deficiency alone was found to be the cause. In another three, both copper and vitamin B12 were deficient. In all these six patients, ceruloplasmin and 24h urinary copper were found to be low suggesting dietary copper deficiency. Hyperzincemia was found in four of these patients. Magnetic resonance imaging of spine was normal in lone Cu deficient patients but showed T2 hyperintensity of posterior column in lone B12 or combined B12 and copper deficiency. CONCLUSION: In cases of B12 deficiency myelopathy not responding to supplementation, copper deficiency must be sought at the earliest to avoid and treat persistent neurological disability.

Copper deficiency myelopathy.

Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myelopathy (CDM) was only described within the last decade, and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration due to vitamin B12 deficiency. Here, 55 case reports from the literature are reviewed regarding their demographics, aetiology, haematological and biochemical parameters, spinal imaging, treatment and outcome. The pathophysiology of disorders of copper metabolism is discussed. CDM most frequently presented in the fifth and sixth decades and was more common in women (F:M = 3.6:1). Risk factors included previous upper gastrointestinal surgery, zinc overload and malabsorption syndromes, all of which impair copper absorption in the upper gastrointestinal tract. No aetiology was established in 20% of cases. High zinc levels were detected in some cases not considered to have primary zinc overload, and in this situation the contribution of zinc to the copper deficiency state remained unclear. Cytopenias were found in 78%, particularly anaemia, and a myelodysplastic syndrome may have been falsely diagnosed in the past. Spinal MRI was abnormal in 47% and usually showed high T2 signal in the posterior cervical and thoracic cord. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Low serum copper and caeruloplasmin levels confirmed the diagnosis and, in contrast to Wilson's disease, urinary copper levels were typically low. Treatment comprised copper supplementation and modification of any risk factors, and led to haematological normalisation and neurological improvement or stabilisation. Since any neurological recovery was partial and case numbers of CDM will continue to rise with the growing use of bariatric gastrointestinal surgery, clinical vigilance will remain the key to minimising neurological sequelae. Recommendations for treatment and prevention are made.

[Subacute combined degeneration of the spinal cord: easy diagnosis, effective treatment]. / Gecombineerde strengziekte door vitamine-B12-deficiëntie: eenvoudige diagnose, effectieve therapie.

Four patients, three women aged 49, 47 and 74 years, and a man aged 64 years, presented with progressive sensory deficit, pyramidal tract symptoms and postural instability. Tests revealed megaloblastic anaemia and low vitamin B12 levels. Two of the female patients had undergone gynaecological surgery with nitrous oxide anaesthesia, and the male patient had undergone a gastric resection. Subacute combined degeneration of the spinal cord is a neurological disease based on vitamin B12 deficiency. It involves the posterior and lateral columns of the spinal cord, and sometimes the peripheral nerves, the optic nerve or the brain. An MRI scan of the cervical cord revealed abnormalities for three of the four patients. Following parenteral supplementation of vitamin B12, the symptoms and the MRI abnormalities either disappeared or significantly improved. Vitamin B12 deficiency can cause subacute combined degeneration of the cord by interfering with myelin synthesis. As vitamin B12 deficiency is caused by malabsorption in the gastrointestinal tract, oral supplementation is insufficient. It is essential to recognise this treatable disease at an early stage, and not to reject the possible diagnosis if the MRI findings are abnormal. Simple blood tests can lead to the diagnosis and to effective treatment.

Vitamin E deficiency in dogs does not alter preferential incorporation of RRR-alpha-tocopherol compared with all rac-alpha-tocopherol into plasma.

The plasma and lipoprotein transport of RRR and all rac-alpha-tocopherols, labeled with different amounts of deuterium [2R,4'R,8'R-alpha-[5-C2H3]tocopheryl acetate (d3RRR-alpha-tocopheryl acetate] and 2RS, 4'RS, 8'RS-alpha-[5,7-(C2H3)2]tocopheryl acetate (d6all rac-alpha-tocopheryl acetate), was studied in adult beagle dogs that had been fed a vitamin E-deficient (-E; two dogs) or supplemented (+E; two dogs) diet for two years. We set out to test the hypothesis that the activity of the hepatic tocopherol binding protein (which is thought to preferentially incorporate RRR-alpha-tocopherol into the plasma) is up-regulated by vitamin E deficiency. Labeled alpha-tocopherols increased and decreased similarly in plasma of both -E and +E dogs. Irrespective of diet, d3RRR-alpha-tocopherol was preferentially secreted in plasma. Thus, vitamin E deficiency in dogs does not markedly increase the apparent function of the hepatic tocopherol binding protein. We also studied vitamin E transport in a German Shepherd dog with degenerative myelopathy (DM). Based on the coincident appearance of d3RRR-alpha-tocopherol in plasma and chylomicrons, we suggest that the abnormality in DM may be associated with abnormal vitamin E transport resulting from an impaired function of the hepatic tocopherol binding protein.

Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy.

Extracts of tissue fluids from a patient with subacute necrotizing encephalomyelopathy inhibit thiamine pyrophosphate-adenosine triphosphate phosphotransferase of rat brain. Brain tissue from the patient, in contrast to normal brain tissue, contained essentially no thiamine triphosphate, although thiamine and its other phosphate esters were present in normal concentrations. These findings suggest a relation between this disease and thiamine triphosphate.