Organic psychosis without anemia or spinal cord symptoms in patients with vitamin B12 deficiency

The authors describe two patients with organic psychosis who had vitamin B12 deficiency and no hematologic or spinal cord abnormalities. They review the literature that supports a causal relationship between B12 deficiency and cerebral dysfunction, as measured by the EEG, and consequent organic mental changes. The authors cite evidence that these EEG and organic mental changes are reversible with B12 replacement. They emphasize that psychiatric manifestations may be the first symptoms of vitamin B12 deficiency and thus antedate anemia and spinal cord disease. They recommend consideration of B12 deficiency and serum B12 determinations in all patients with organic mental symptoms.     

Use of rCBF in diagnosis and follow-up of cerebral vitamin B12 deficiency

Evidence for cerebral B12 deficiency was searched for in 16 patients (age range 54–94 years) with subnormal serum B12 values (<110 pmol/l) with or without anaemia using sequential regional cerebral blood flow measurement (rCBF). Three patterns of responses followed B12 substitution in 11/16 cases: marked increase of the cerebral blood flow after one week (1); complete or partial normalization of regional decreases after one week (2) or after 1–3 months (3). Mental disturbances were observed in 14/16 patients and abnormally slow EEG activity in 11/12 patients before B12 substitution. During substitution a parallel clinical improvement was observed in 5/7 cases, who could cooperate in a follow-up study, and normalization or marked improvement of the abnormal EEG activity was observed in three cases. We propose that rCBF is a valuable tool for diagnosis and follow-up of this deficiency state. In addition, our results indicate that prophylactic B12 substitution should be considered at serum B12 serum values above the lower normal value especially in aged patients with coexisting organic brain disease.     

Vitamin B12 deficiency in infancy as a cause of developmental regression

Vitamin B₁₂ deficiency can cause serious developmental regression, hypotonia and cerebral atrophy in infants. We report a 6-month-old infant, with insidious developmental regression and brain atrophy showed by CT scan, secondarily to vitamin B₁₂ deficiency. His mother was a strict vegetarian and the patient was exclusively breastfed. The clinical symptoms and the brain CT were normalized after vitamin B₁₂ administration.     

Seizures during treatment of Vitamin B12 deficiency.

Epileptic seizures during infancy have a wide variety of clinical presentations and the outcome differs according to the etiology. Among the benign and rare causes of infantile seizures, Vitamin B12 deficiency has been encountered. Common symptoms of Vitamin B12 deficiency in infants include megaloblastic anemia, feeding difficulties, developmental delay, microcephaly, failure to thrive, hypotonia, lethargy, irritability, involuntary movements, seizures and cerebral atrophy. Involuntary movements and seizures may rarely be the initial symptoms of Vitamin B12 deficiency. Involuntary movements have also been reported to appear after initiation of Vitamin B12 supplementation in isolated cases, whereas, no such information exits for seizures. In this paper, three infants with Vitamin B12 deficiency associated with motor and mental retardation are reported because of long-lasting focal/multifocal epileptic seizures following the initiation of intramuscular Vitamin B12 treatment. Antiepileptics were introduced in addition to Vitamin B12. Seizures disappeared within a few days or weeks; electroencephalographic findings were normalized in a few months. No relapses occurred during the follow-up period.     

Stroke after zoster ophthalmicus in a 12-year-old girl with protein C deficiency.

A 12-year-old girl who had zoster ophthalmicus 10 months earlier presented with hemiparesis and corresponding basal ganglionic infarction related to middle cerebral artery branch thrombosis ipsilateral to the zoster. Hematologic evaluation disclosed protein C deficiency. This represents the first zoster-associated stroke reported in childhood associated with protein C deficiency, with extension of the latency period between zoster and infarction, previously reported to be 6 months.     

The induction and reversibility of cerebral acidosis in thiamine deficiency

Regional cerebral pH was determined autoradiographically using carbon 14-labeled dimethyloxazolidinedione in normal rats, following various durations of thiamine deficiency and replenishment with thiamine when the clinical sequelae of the deficiency appeared. In our model the clinical sequelae of thiamine deficiency (opisthotonus) appeared on the average on day 18. Regional cerebral pH on day 12 was comparable to that in controls and ranged between 7.02 +/- 0.03 and 7.09 +/- 0.03 (mean +/- SEM) in gray matter structures. On day 14 the pH in the inferior colliculus was 6.85 +/- 0.08 and relative acidosis also appeared in thalamic structures. At opisthotonus the pH was 6.48 +/- 0.17 in the mamillary body, 6.43 +/- 0.14 in the vestibular nucleus, and 6.36 +/- 0.14 in the medial dorsal nucleus of the thalamus (p less than 0.01). One dose of thiamine replenishment at this stage transiently raised the pH in the inferior colliculus to 7.25 +/- 0.19 and in the medial dorsal nucleus to 7.20 +/- 0.13 (p less than 0.01). Cerebral regions showing significant acidosis during thiamine deficiency coincided largely with those known to be histologically vulnerable and those previously reported to show a focal rise in local cerebral glucose utilization between days 11 and 14 of thiamine deficiency. This focal acidosis shown to occur in thiamine deficiency may be one mechanism contributing to the selective histological vulnerability in this model.     

Cerebral aneurysms in a child with acquired immune deficiency syndrome during rapid immune reconstitution

A 12-year-old boy with perinatally acquired human immunodeficiency virus infection an d Centers for Disease Control and Prevention class C3 disease presented with acute onset of confusion and a right-sided movement disorder 5 months after beginning a new antiretroviral regimen. His CD4 count had been below 50 cells/microL for 4 years but had abruptly risen to more than 250 cells/microL. Computed tomographic and magnetic resonance imaging scans showed cerebral aneurysms and new cerebral lesions consistent with ischemic strokes. The presentation during immune reconstitution suggests that cerebral aneurysms in pediatric patients with acquired immune deficiency syndrome can result from an immune-mediated response to chronic vascular infection.     

Protein S deficiency in middle-aged women with stroke.

We examined the relationship between free protein S deficiency and cerebrovascular disease by reviewing the records of all patients with the diagnoses of cerebral thrombosis, cerebral embolism, and cerebral vascular occlusion who were referred for coagulation studies over a 12-month period. We assayed for free protein S antigen, protein C antigen, and antithrombin III and tested for lupus-like anticoagulant and anticardiolipin antibody. Twenty-two of 267 patients (8.2%) admitted with thrombotic strokes were referred for coagulation studies. Free protein S antigen was significantly lower in women than in men (62 +/- 25% versus 88 +/- 24%, p = 0.03; n = 11 in each group). Six women had free protein S antigen levels below the range recorded for a contemporary group of 24 age-matched normal women (17 to 59% versus 70 to 102%, p less than 0.001); four of these women had cerebral arterial thrombosis and two had venous dural sinus thrombosis. The six women were aged 29 to 55 at the time of their first strokes; two had family members with protein S deficiency, and one of these had died of a stroke at age 52. Other abnormalities in this population included a positive test for lupus-like anticoagulant or anticardiolipin in five patients, a modest decrease in protein S in two men, and one patient with an isolated deficiency of antithrombin III. We conclude that protein S deficiency may be an important risk factor for stroke in middle-aged women but this requires confirmation by prospective studies in unselected patients.     

Infratentorial and supratentorial leukoencephalopathy associated with vitamin B12 deficiency

Background: Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B₁₂ deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. Observation: A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B₁₂ deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B₁₂ supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. Conclusion: Leukoencephalopathy and dementia should raise the suspicion of a vitamin B₁₂ deficiency because vitamin B₁₂ supplementation may result in at least partial clinical improvement.     

Die B-Vitamine aus neurologischer Sicht

Summary Deficiencies of one of the vitamins of the B complex are a pathogenetic factor in some encephalopathies and neuropathies. Wernicke's encephalopathy due to inadequate thiamine uptake in alcoholics, or pellagra encephalopathy due to diets deficient in nicotinic acid and tryptophan are both examples of classical deficiency diseases.Neuropathy due to vitamin B₁₂ deficiency is not only characterized by subacute combined degeneration of the spinal cord, but also by signs of polyneuropathy and diffuse encephalopathy. Psychosis and pathological EEG recordings may be the only manifestations of this neuropathy. Polyneuropathy as a result of a pyridoxine deficiency, a side-effect in patients treated with isonicotinic acid hydrazide, is an example of the action of vitamin antagonists, each vitamin of the B complex having its specific type of known inhibitor.In this context, the folic acid deficiency state after prolonged anticonvulsive treatment of epileptics is also to be considered as is the role of B₁₂ in chronic cyanide poisoning.Pyridoxine-dependent cerebral seizures are another phenomenon of interest, illustrating the action of the vitamin B complex on cerebral metabolism (e.g. amino acids etc.).Compared with B₁, B₂, B₆ and B₁₂ the other vitamins of the B complex are of lesser importance when looked at from the pathogenetic and therapeutic point of view. Methods for detecting vitamin deficiencies also are of practical importance in neurology, including tests for transketolase activity in red cells indicative of thiamine, or the B₁₂ absorption or Schilling test.

Herrn Prof. Dr. Georges Schaltenbrand zum 75. Geburtstag gewidmet.     

Cerebral folate deficiency with developmental delay, autism, and response to folinic acid

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral folate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills.     

NEUROLOGICAL COMPLICATIONS IN AN UNSELECTED GROUP OF PATIENTS PARTIALLY GASTRECTOMIZED FOR GASTRIC ULCER

A clinical neurological follow-up study is submitted, including 128 patients with a history of surgery for benign gastric ulcer an average of 12 years previously. Among these 128 patients, 44 had signs of myelopathy, peripheral neuropathy or severe intellectual impairment, presumably due to vitamin B₁₂ deficiency. Four of these patients were on vitamin B₁₂ therapy. In the remaining 40 the serum vitamin B₁₂ averaged 154 pg/ml. Out of the 44 affected patients 14 were in the serum B₁₂ range 150–200 pg/ml. B₁₂ therapy is recommended also for this group of “questionable reduction” to avoid irreversible cerebral and spinal lesions due to the B₁₂ deficiency.     

Carbamyl phosphate synthetase 1 deficiency: a destructive encephalopathy

Carbamyl phosphate synthetase I is a urea cycle enzyme. Severe deficiency of carbamyl phosphate synthetase I presents in the neonatal period as hyperammonemic encephalopathy with altered consciousness and occasional seizures after feeding begins. Episodes of altered consciousness with or without seizures and focal neurologic deficits are seen later with patients of partial carbamyl phosphate synthetase I deficiency. Fatal cerebral edema with brain herniation may develop on occasion. Three patients presenting with carbamyl phosphate synthetase I deficiency are reported with neuroimaging and pathologic findings illustrating the destructive encephalopathy with acute cerebral edema, followed by diffuse cerebral atrophy and occasional cystic encephalomalacia. The deterioration in carbamyl phosphate synthetase I deficiency occurs during the hyperammonemic crises. This deficiency may be difficult to treat despite the current advances in treatment strategies, especially in neonatal-onset patients with low carbamyl phosphate synthetase I activity.     

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.     

Homocystinemia and stroke in vegetarians

Homocysteine is a sulfurated amino acid with a central role in the metabolism of thiol compounds. Homocystinemia is a recognized independent potentially remediable risk factor for vascular disease. It is associated with both macro and micro vascular ischemic stroke. It can often be normalized by polyvitamin therapy. This inexpensive and well-tolerated treatment is considered effective in decreasing the incidence of stroke. We report 2 young strict vegetarians with no known vascular risk factors. The first suffered a left middle cerebral artery infarct, and the second multiple bilateral small cerebral infarctions. Extensive investigations showed moderately elevated homocysteine and low serum B12 levels, suggesting that these are most probably the underlying etiology. We believe that a high index of suspicion is needed, particularly in younger people with a potential underlying cause for B12 deficiency and no identifiable stroke risk factor.     

高同型半胱氨酸血症及相关因子与脑梗死相关性的研究

目的 :研究高同型半胱氨酸血症及N5N10 亚甲基四氢叶酸还原酶 (methylenetetrahydrofolatereductase ,MTHFR)基因、叶酸和维生素B12 与脑梗死的关系。方法 :PCR RFLP技术检测 5 4例脑梗死患者及 3 0例对照的MTHFR基因型 ;高效液相色谱法测定空腹及蛋氨酸负荷后血浆tHcy水平 ;化学发光法测定血清叶酸和维生素B12 浓度。结果 :患者组中MTHFR基因T/T型及T等位基因频率、空腹及负荷后tHcy水平显著高于对照组 ;而血清叶酸和维生素B12 水平低于对照组。结论 :MTHFR基于突变、高同型半胱氨酸血症及叶酸、维生素B12 缺乏与脑卒中发病有关。     

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.     

The effect of thiamine deficiency on local cerebral glucose utilization

Rats maintained on a thiamine-free diet for two to seven weeks and control animals were studied by the [¹⁴C]deoxyglucose technique prior to the development of histological lesions. This technique permits measurement of local cerebral glucose utilization (LCGU) in discrete nuclei and tracts. Levels of thiamine in brain and blood were also determined. In the 41 central nervous system (CNS) structures in which it was measured, cerebral glucose utilization decreased with diminishing concentration of cerebral thiamine. Thus, the primary metabolic consequence of thiamine deficiency is a widespread reduction in cerebral glucose utilization. Furthermore, with decreasing cerebral thiamine concentrations, glucose utilization declined more rapidly in many of the structures which in humans develop histological lesions with prolonged thiamine deficiency than in structures less susceptible to the development of lesions. One determinant of the specific distribution of histological lesions occurring in human thiamine deficiency may be the variable rate at which the CNS structures lose their metabolic activity with continuing thiamine deficiency.     

Cerebrovascular lesions in acquired immune deficiency syndrome (AIDS)

Summary Cerebrovascular lesions were seen in 28 of 83 cases (34%) of acquired immune deficiency syndrome (AIDS). Cerebral hemorrhage was noted in 4 cases, cerebral infarct in 23 cases and both in 1 case. Cerebral hemorrhage was in various locations such as intraparenchymal, subarachnoid space, subdural space and epidural space. Large, clinically evident hemorrhage was noted in 2 of 5 cases and bleeding tendency was noted in 2 cases. Most of the 24 cases with cerebral infarcts were not clinically evident; they were multiple, small and mainly involved the striatum, cerebral cortex and brain stem. Mural thickening of occasional small blood vessels was seen in 12 of the cases (50%) with infarcts. Other changes in blood vessels included vasculitis in one cases and perivascular lymphocytic infiltration in another. In addition to thrombo-embolism and systemic ischemia/anoxia, these blood vessel changes may have a role in the development of cerebral infarcts in AIDS.     

Cerebral infarction associated with protein C deficiency.

BACKGROUND AND PURPOSE: A deficiency of plasma protein C, both the hereditary and acquired types, is one cause of thromboembolic disease. Several antineoplastic agents have been reported to decrease the production of protein C in the liver by impairing either the absorption or metabolism of vitamin K, leading to acquired protein C deficiency. CASE DESCRIPTION: We treated a young woman with protein C deficiency, who had developed a cerebral infarction of the right parietal cortex of sudden onset. On admission, the antigenic level of plasma protein C was 38%. Serial cerebral angiography revealed occlusion of the right middle cerebral artery, which subsequently recanalized completely. This patient had taken fluorouracil derivatives orally for as long as 3 years following a left mastectomy for stage II breast cancer. Tests revealed that the patient's mother had only one-half the normal activity of plasma protein C despite a normal antigenic level. CONCLUSIONS: We speculate that the etiology of the cerebral infarction in this patient might involve an embolic mechanism associated with protein C deficiency induced by an interaction between inherited and acquired factors.