Role of vitamin B12 in depressive disorder--a case report

Vitamin B12 deficiency anemia may have psychiatric manifestations preceding the hematological symptoms. Although a variety of symptoms are described, there are only sparse data on the role of vitamin B12 in depression. We report a case of vitamin B12 deficiency presenting with recurrent episodes of depression.     

Vitamin B12 deficiency associated with symptoms of frontotemporal dementia

We report the case of an elderly patient with cobalamin deficiency who progressively developed cognitive and behavioral symptoms associated with neuropsychiatric disturbances. His neuropsychological profile showed many features suggestive for a frontal-dysexecutive syndrome and was related to a predominant asymmetric (right > left) frontal lobe hypoperfusion. He completely recovered after a treatment with vitamin B12 and follow-up of 7 years showed that his improvement remained stable. Along with the other cases reported in the literature, our case also proves that there are some cases of vitamin B12 deficiency that can manifest with the symptoms of frontotemporal dementia and that they are completely reversible after substitution therapy.     

Treatment responsive executive and behavioral dysfunction associated with Vitamin B12 deficiency

Vitamin B12 deficiency can manifest with various neuropsychiatric symptoms. We report a case of an individual with vitamin B12 deficiency presenting with personality, emotional and behavioral changes. Neuropsychological tests revealed disproportionate disturbance of executive functions. Single photon emission tomography (Tc99m HMPAO) showed right fronto-temporo-parietal hypoperfusion. After vitamin B12 injections, the patient's executive and behavioral dysfunction disappeared and performance on neuropsychological tests was once again in the normal range.     

Vitamin B12, folate,and homocysteine in depression: the Rotterdam Study

OBJECTIVE: The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study. METHOD: The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability. RESULTS: Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent. CONCLUSIONS: The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity.     

Catatonia and other psychiatric symptoms with vitamin B12 deficiency

OBJECTIVE: To study unusual psychiatric manifestation of vitamin B12 deficiency and related issues. METHOD: A case study of 52-year-old female and review of relevant literature. RESULTS: Complete remission of psychiatric symptoms without recurrence for the next 4 years with vitamin B12 as the only specific therapy instituted. CONCLUSION: Importance of B12 estimation and replacement in patients with varied psychiatric manifestations.     

Treatment responsive executive and behavioral dysfunction associated with Vitamin B12 deficiency*

Vitamin B12 deficiency can manifest with various neuropsychiatric symptoms. We report a case of an individual with vitamin B12 deficiency presenting with personality, emotional and behavioral changes. Neuropsychological tests revealed disproportionate disturbance of executive functions. Single photon emission tomography (Tc99m HMPAO) showed right fronto-temporo-parietal hypoperfusion. After vitamin B12 injections, the patient's executive and behavioral dysfunction disappeared and performance on neuropsychological tests was once again in the normal range.     

Mood disorder with mixed features due to vitamin B(12) and folate deficiency

Vitamin B(12) and folate deficiency is often associated with affective disorders mainly of the depressive type. We report a case of a 42-year-old woman with a mood disorder with mixed depressed/manic features that was due to vitamin B(12) and folate deficiency. The psychopathology developed over a five-year period without hematologic or other overt clinical characteristics of pernicious anemia. Replacement treatment with vitamin B(12) and folate was rapidly followed by full clinical remission, electroencephalographic normalization and neuropsychological improvement. At a one-year follow-up this condition was stable. Consequently, patients who respond poorly to psychopharmacologic treatment and/or present with atypical mood symptoms would warrant determination of vitamin B(12) and folate serum levels.     

笑气滥用导致神经功能缺损的临床特点

目的 探讨笑气滥用导致神经功能缺损的临床特点.方法 回顾性分析2例笑气滥用导致神经功能缺损患者的临床资料,并对相关文献资料进行复习.结果 1例以模拟格林-巴利综合征的症状发病,表现为四肢对称性的麻木无力,脊椎横断面T2WI显示颈髓后索倒"V"形高信号,EMG呈多发性周围神经脱髓鞘和轴索损伤.另1例以模拟急性脊髓炎症状起...     

Psychiatric manifestations of vitamin B12 deficiency: a case report

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.     

Prostaglandin E1 in conjunction with high doses of vitamin B12 improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve con     

Postoperative dementia: toxicity of nitrous oxide

INTRODUCTION: Post-operative neuropsychiatric manifestations represent a frequent situation and may be due to several aetiologies. The responsibility of vitamin B12 deficiency must be evoked, especially in case of anaesthesia with a currently used substance: nitrous oxide. CASE REPORT: A 65 year-old man with no medical history, presented problems walking and memory loss 16 days after surgery for femoral prosthesis. Neurological examination revealed paraplegia with syndrome of combined degeneration of the spinal cord. The exploration of cognitive functions showed disorientation in time with memory disorders and disturbance of executive functioning. There was no apraxia, aphasia or agnosia. There were neither psychotic symptoms nor mood changes. MMS was at 18/30. Red blood count revealed an anaemia with macrocytosis (MGV=120 3). Vitamin B12 rate was very low (less than 30 g/l). Folate blood level was normal. Brain MRI showed moderate cerebral atrophy. Other investigations led to the diagnosis of Biermer's disease (fundic atrophy at biopsy with presence in the serum of antibodies to intrinsic factor). The diagnosis of neurological attack related to a vitamin B12 deficiency secondary to Biermer's disease was established, but the appearance of disorders in the post-operative period suggested the existence of an added factor. The recovery of informations revealed that anaesthesia was maintained by nitrous oxide during two hours and the patient exhibited pre-operative anaemia with macrocytosis. The hypothesis of decompensation of latent vitamin B12 deficiency by nitrous oxide was evoked. Replacement therapy by vitamin B12 induced real improvement of the cognitive impairment. MMS increased to 25/30. DISCUSSION: Cognitive impairment due to vitamin B12 deficiency is rarely dominated by isolated memory disorders. An authentic dementia is exceptional. Our patient had a dementia diagnosed on the basis of DSM IV criteria including memory disorders, disturbance of executive functioning and significant impairment in social and occupational functioning, associated with a combined degeneration of the spinal cord, common in vitamin B12 deficiency. Furthermore, he had an unknown Biermer's disease responsible for pre-operative deficiency which was clinically latent (there was only macrocytosis anaemia). The appearance of problems in the post-operative period was due to an acute decompensation of the latent deficiency induced undoubtedly by nitrous oxide used in anaesthesia. According to Christensen, nitrous oxide causes irreversible oxidation of vitamin B12 cobalt's atom responsible for its inactivation and the appearance of clinical manifestations. Evolution under vitamin B12 replacement therapy depends on the rapidity of its founding. In our case, it led to an improvement, notably in cognitive functions. CONCLUSION: Through this observation, the authors underline the necessity to search for vitamin B12 deficiency in the case of cognitive features following general anaesthesia.     

Subacute combined degeneration of the spinal cord and the vitamin B12 metabolism, a clinical study.

In 28 patients suffering from subacute combined degeneration of the spinal cord, vitamin B12 metabolism was investigated. Two postulates, proving vitamin B12 deficiency and excluding another cause for the clinical symptoms, have to be fulfilled. Two patients had no disturbance in their vitamin B12 metabolism. Seven patients had a distinct vitamin B12 deficiency. In the remaining 19 patients we found a mild vitamin B12 deficiency. Of these patients, 5 had had a subtotal gastrectomy, one had had a low absorption of vitamin B12, and 13 patients we could not find a distinct cause for the vitamin B12 deficiency. It is not impossible that nutritional habits can be hold responsible for this deficiency. The question whether these 13 patients should be treated with vitamin B12 for the rest of their lives is difficult to answer. It is a conditio sine qua non that in the patients with S.C.D. the vitamin B12 metabolism is examined circumstantially. By so doing, it may be possible to detect, in cases with minor clinical signs and symptoms of S.C.D., the cause of their illness.     

Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report

ABSTRACT: Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were "irritability, regressive behavior, apathy, crying and truancy" which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg's sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5?mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg's sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3?months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6?months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.     

A sequential study of visual evoked potential in patients with vitamin B12 deficiency neurological syndrome.

OBJECTIVE: Visual pathways are vulnerable to vitamin B(12) deficiency but there is paucity of studies evaluating visual evoked potential (VEP) changes following vitamin B(12) supplementation. Our aim was to evaluate the visual evoked potential changes in patients with vitamin B(12) deficiency neurological syndrome and their changes after vitamin B(12) therapy. METHODS: Seventeen patients with vitamin B(12) deficiency neurological syndromes diagnosed on the basis of megaloblastic bone marrow or low serum vitamin B(12) level or both were subjected to testing of visual acuity, field of vision, colour vision and neurological examination. Cranial magnetic resonance imaging was done in 9 patients and pattern reversal VEP was carried out on admission. P(100) latency and amplitude were measured. Visual function and VEP studies were repeated at 3 and 6 months after vitamin B(12) therapy. RESULTS: The patients' age ranged between 17 and 69 years; 7 were females and 16 were lactovegetarians. The duration of symptoms ranged between 10 days and 10 years. Visual acuity, colour vision, field of vision and fundus oculi were normal. VEP revealed prolongation of P(100) latency in 10 patients (17 eyes) which was mild in 2, moderate in 10 and marked in 5 eyes. Six months after treatment, P(100) latency improved to normal in all except 4 eyes. VEP abnormality was related to duration of illness and antiparietal cell antibodies. CONCLUSIONS: VEP is frequently prolonged in patients with vitamin B(12) deficiency neurological syndrome although asymptomatic. It usually returns to normal after treatment.     

Carence en vitamine B12, ataxie cérébelleuse et troubles cognitifs

Introduction

Vitamin B12 deficiency is often associated with neurological disorders of which combined sclerosis of the spinal cord is a common manifestation.

Case report

We report the case of a woman who presented cerebellar ataxia and cognitive deficits associated with leukoencephalopathy on the brain MRI. These symptoms were associated with vitamin B12 deficiency due to Biermer's disease. Vitamin B12 supplementation led to symptom improvement. Later her treatment was discontinued and the patient's clinical status worsened to a bedridden status.

Conclusion

Ataxia cerebellar dementia and leukoencephalopathy can result from vitamin B12 deficiency. To limit the risks of sequelae, vitamin B12 supplementation should be started at an early stage.     

Nitrous oxide-induced vitamin B(12) deficiency

Two patients with asymptomatic vitamin B(12) deficiency developed a peripheral neuropathy 6-7 weeks after exposure to nitrous oxide during general anaesthesia, and 3 and 11 days after receiving cyclophosphamide. The serum B(12) concentration was less than 20 pmol/l and the symptoms resolved after B(12) replacement. We believe that the neurological symptoms were triggered by exposure to nitrous oxide. A possible novel feature in these patients was the close temporal relationship between the onset of the symptoms and cyclophosphamide treatment. It is possible that cyclophosphamide reduced the availability of remaining B(12) stores.     

Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: case report and literature review

A previously healthy 27-year-old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B(12) deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B(12) resulted in dramatic clinical improvement, with near-complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B(12) deficiency.     

West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia

Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.     

Vitamin B12 concentrations in psychiatric patients.

In an attempt to evaluate the possible relationship between vitamin B12 deficiency and mental disease, the blood content of vitamin B12 was investigated in 835 consecutive psychiatric patients. Low serum vitamin B12 values were found in approximately 10% of these patients, due to latent pernicious anaemia in one case, post-gastrectomy in seven cases and small intestinal resection in one case. In the remaining 72 cases vitamin B12 deficiency was probably caused by nutritional insufficiency. After correction of the dietary defect there was a spontaneous increase in serum vitamin B12 in 75% of these patients. No specific psychiatric syndrome was connected with hypovitaminosis B12, but a preponderance of arteriosclerotic dementia suggests that low serum vitamin B12 values are secondary to mental illness leading to apathy and loss of appetite. Most cases will recover without further vitamin B12 supplements. But some patients may need treatment because of severe mental and physical disabilities.     

An investigation of vitamin B12 deficiency in elderly inpatients in neurology department

Objective

To investigate the status of vitamin B12 deficiency in elderly inpatients in the department of neurology.

Methods

A total number of 827 patients in the department of neurology of Shanghai Punan hospital, from March 2007 to July 2008, were employed in the present study. They were 60 years or older, and the average age was 77.1±7.5 years old. All the patients were diagnosed with no severe hepatic or renal dysfunction, without any usage of vitamin B12 during the previous 3 months before the detection. The levels of serum vitamin B12, folate and homocysteine (Hcy) were evaluated. The patients with vitamin B12 deficiency were screened. The resulting symptoms, positive signs of neurological examination, and the neuroelectricphysiological results were compared between patients with or without vitamin B12 deficiency.

Results

Vitamin B12 deficiency was found in 163 patients (19.71% of the total patients), and was more prevalent in female than in male patients, also with increased incidences with aging. Patients with low levels of serum vitamin B12 exhibited higher rate of gastrointestinal diseases, while only 9.82% of the vitamin B12 deficient patients had megaloblastic anemia. Symptoms of vitamin B12 deficiency included unsteadily walking in the darkness and hypopallesthesia, and some chronic diseases such as cerebral ischemia, hypertension, Parkinson’s disease (Parkinsonism), diabetes mellitus and coronary heart disease. Most of the vitamin B12 deficient patients had neuroelectricphysiological abnormalities.

Conclusion

Vitamin B12 deficiency is remarkably common in elderly patients in neurology department, with various and atypical clinical manifestations, and the neurological symptoms are more common than megaloblastic anemia symptoms.