vitamin-b-12 and Nerve-Degeneration

Subacute combined degeneration (SCD) is a neuropathy due to cobalamin (Cbl) (vitamin B(12)) deficiency acquired in adult age. Hitherto, the theories advanced to explain the pathogenesis of SCD have postulated a causal relationship between SCD lesions and the impairment of either or both of two Cbl-dependent reactions. We have identified a new experimental model, the totally gastrectomized rat, to reproduce the key morphological features of the disease [spongy vacuolation, intramyelinic and interstitial edema of the white matter of the central nervous system (CNS), and astrogliosis], and found new mechanisms responsible for the pathogenesis of SCD: the neuropathological lesions in TGX rats are not only due to mere vitamin withdrawal but also to the overproduction of the myelinolytic tumor necrosis factor (TNF)-alpha and the reduced synthesis of the two neurotrophic agents, epidermal growth factor (EGF) and interleukin-6. This deregulation of the balance between TNF-alpha and EGF synthesis induced by Cbl deficiency has been verified in the sera of patients with pernicious anemia (but not in those with iron-deficient anemia), and in the cerebrospinal fluid (CSF) of SCD patients. These new functions are not linked to the coenzyme functions of the vitamin, but it is still unknown whether they involve genetic or epigenetic mechanisms. Low Cbl levels have also been repeatedly observed in the sera and/or CSF of patients with Alzheimer's disease or multiple sclerosis, but whether Cbl deficit plays a role in the pathogenesis of these diseases is still unclear.

Topics: Animals; Disease Models, Animal; Epidermal Growth Factor; Gastrectomy; Humans; Interleukin-6; Models, Biological; Nerve Degeneration; Rats; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 12 Deficiency

In humans, subacute combined degeneration of the spinal cord and brain, a primary demyelinating disease, is caused by cobalamin or methyltetrahydrofolate deficiency. Experimental studies into its pathogenesis suggest that dysfunction of the methyl-transfer pathway may be the cause. Compelling evidence for this comes from the study of inborn errors of cobalamin metabolism where deficiency of methylcobalamin, but not deoxyadenosylcobalamin, is associated with demyelination. Recent studies have focused upon inborn errors of the methyl-transfer pathway. Cerebrospinal fluid concentrations of metabolites of the methyl-transfer pathway have been measured in humans with sequential errors of the pathway and correlated with demyelination demonstrated on magnetic resonance imaging of the brain. This has provided new data suggesting that deficiency of S-adenosylmethionine is critical to the development of demyelination in cobalamin deficiency.

Topics: Brain Diseases; Demyelinating Diseases; Humans; Metabolism, Inborn Errors; Methylation; Nerve Degeneration; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Analgesics; Clinical Trials as Topic; Cobamides; Coenzymes; Drug Tolerance; Female; Humans; Male; Neoplasms; Nerve Degeneration; Pain; Peripheral Nervous System Diseases; Vitamin B 12

Irradiation of food at 50-55 kGy results in a profound, chronic demyelinating-remyelinating disease of the entire central nervous system (CNS) in cats, named Feline Irradiated Diet-Induced Demyelination (FIDID). This study examines the early stages of demyelination and long-term consequences of demyelination and remyelination on axon survival or loss. Myelin vacuolation is the primary defect leading to myelin breakdown, demyelination then prompt remyelination in the spinal cord and brain. There is no evidence of oligodendrocyte death. The spinal cord dorsal column is initially spared yet eventually becomes severely demyelinated with subsequent loss of axons in the core and then surface of the fasciculus gracilis. However remyelination of the sub-pial axons in the dorsal column results in their protection. While there was a lack of biochemical evidence of Vitamin B12 deficiency, the pathological similarities of FIDID with sub-acute combined degeneration (SCD) led us to explore treatment with Vitamin B12. Treatment led to recovery or improvement in some cats and neurologic relapse on cessation of B12 therapy. While the reason that irradiated food is myelinotoxic in the cat remains unresolved, nonetheless the neuropathological changes match exactly what is seen in SCD and its models and provide an ideal model to study the cellular and molecular basis of remyelination.

Topics: Acute Disease; Animals; Axons; Cats; Chronic Disease; Demyelinating Diseases; Diet; Disease Models, Animal; Female; Macrophages; Male; Metabolome; Microglia; Myelin Sheath; Nerve Degeneration; Neuropathology; Radiation; Remyelination; Spinal Cord; Time Factors; Vitamin B 12

Increased homocysteine has in some cases been linked with an increased incidence of Alzheimer's disease and motor neuron disease. Folate or B12 deficiency increases homocysteine, but controversy exists as to whether their levels also correlate with either disorder. Since their presence within various dietary constituents may confound interpretation, we tested the impact of deprivation of either or both in the closed environment of neuronal cell cultures. Deprivation of either increased cytosolic calcium, reactive oxygen species, intracellular homocysteine, and apoptosis, but deprivation of both fostered substantially larger increases, supporting the notion that both are required for optimal neuroprotection.

Topics: Calcium; Cell Line, Tumor; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Nerve Degeneration; Neuroblastoma; Neurons; Reactive Oxygen Species; Vitamin B 12; Vitamin B 12 Deficiency

In the present work we measured blood levels of total homocysteine ((t)Hcy), vitamin B(12) and folic acid in patients with Parkinson s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma (t)Hcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of (t)Hcy in PD patients was folic acid deficiency, whereas in controls (t)Hcy levels were mainly determined by plasma vitamin B(12) concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma (t)Hcy, folic acid and vitamin B(12) levels in parkinsonians. Furthermore, disease duration was positively associated with (t)Hcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.

Topics: Analysis of Variance; Case-Control Studies; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Levodopa; Male; Matched-Pair Analysis; Middle Aged; Nerve Degeneration; Parkinson Disease; Reference Values; Statistics, Nonparametric; Vitamin B 12

Topics: Aged; Amyloid beta-Peptides; Biomarkers; Chromatography, High Pressure Liquid; Creatinine; Dementia; Enzyme-Linked Immunosorbent Assay; Female; Folic Acid; Germany; Homocysteine; Humans; Immunoassay; Linear Models; Male; Middle Aged; Nephelometry and Turbidimetry; Nerve Degeneration; Peptide Fragments; tau Proteins; Vitamin B 12

The question arises as to whether oxidative stress has a primary role in neurodegeneration or is a secondary end-stage epiphenomenon. The aim of the present study was to determine oxidative stress parameters like malondialdehyde (MDA), carbonyl proteins (CP) and Albumin-disulphide (Alb-SSR) and relate these parameters to the immune parameter neopterin, folic acid and vitamin B12 as vitamins and homocysteine in patients with neuro-degenerative diseases (NDD), namely mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to an aged matched control group. MDA, CP and Alb-SSR were significantly increased in the NDD group compared to controls, but not vitamin B12, folic acid and neopterin. Significant correlations were found between CP and Alb-SSR, CP and MDA and between MDA and Alb-SSR including patients with NDD and the control group. These results support the hypothesis that oxidative damage to lipids and proteins is an important early event in the pathogenesis of neurodegenerative diseases.

Topics: Aged; Alzheimer Disease; Biomarkers; Case-Control Studies; Cognition Disorders; Disulfides; Female; Folic Acid; Homocysteine; Humans; Male; Malondialdehyde; Middle Aged; Neopterin; Nerve Degeneration; Oxidative Stress; Protein Carbonylation; Serum Albumin; Severity of Illness Index; Vitamin B 12

Both in vitro and in vivo studies indicate that homocysteine (Hcy) may be directly involved in the damage of motor neurons and in several pathways implicated in amyotrophic lateral sclerosis (ALS) pathogenesis.. To determine whether plasma Hcy levels were higher in ALS patients than healthy controls and to examine the relationship between Hcy levels and clinical ALS phenotypes.. In a cross-sectional study, we compared Hcy, B(12), and folate levels in 62 patients with ALS and 88 age- and sex-matched controls recruited as outpatients in a tertiary clinical center.. Patients with ALS had higher median plasma Hcy levels (11.2 [range 5.8 to 46] vs 9.7 [range 4.5 to 15.9] micromol/L; p = 0.0004) and lower folate levels (4.4 [range 1.7 to 22.1] vs 5.8 [range 2.3 to 21.1] ng/mL; p = 0.0003), compared with controls. Multivariate logistic regression revealed a strong direct association between plasma Hcy levels and presence of ALS (odds ratios adjusted for age, sex, and B-vitamin levels comparing the top tertile [Hcy levels >or= 11.6 micromol/L] with the bottom tertile [Hcy levels < 9.2 micromol/L]: 6.4; 95% CI 2.2 to 19.1; p for trend = 0.0008). We also found a trend for higher Hcy levels in patients with shorter interval from symptom onset to diagnosis (ODI; <14 months), compared with patients with longer ODI (>14 months; median Hcy levels 11.8 [range 5.8 to 46] vs 10.1 [range 7.2 to 17.6] micromol/L; p = 0.09). In a multivariate model, Hcy levels strongly correlated with shorter interval onset diagnosis (r(2) = 0.18; p = 0.01).. Plasma homocysteine (Hcy) levels were significantly increased in patients with amyotrophic lateral sclerosis (ALS) compared with healthy controls. ALS cases with shorter time to diagnosis presented higher Hcy levels, suggesting that higher Hcy may be linked to faster progression of the disease.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Biomarkers; Central Nervous System; Comorbidity; Cross-Sectional Studies; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Male; Middle Aged; Nerve Degeneration; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Up-Regulation; Vitamin B 12

Cobalamin-deficient (Cbl-D) central neuropathy in the rat is associated with a locally increased expression of neurotoxic tumour necrosis factor-alpha (TNF-alpha) and a locally decreased expression of neurotrophic epidermal growth factor (EGF). These recent findings suggest that cobalamin oppositely regulates the expression of TNF-alpha and EGF, and raise the possibility that these effects might be independent of its coenzyme function. Furthermore, adult Cbl-D patients have high levels of TNF-alpha and low levels of EGF in the serum and cerebrospinal fluid. Serum levels of TNF-alpha and EGF of cobalamin-treated patients normalize concomitantly with haematological disease remission. These observations suggest that cobalamin deficiency induces an imbalance in TNF-alpha and EGF levels in biological fluids that might have a role in the pathogenesis of the damage caused by pernicious anaemia.

Topics: Anemia, Pernicious; Animals; Central Nervous System; Disease Models, Animal; Epidermal Growth Factor; Gastrectomy; Humans; Nerve Degeneration; Nerve Growth Factor; Rats; Tumor Necrosis Factor-alpha; Vitamin B 12; Vitamin B 12 Deficiency

We report a rare case of subacute combined degeneration of the spinal cord concomitant with gastric cancer. A 67-year-old man was admitted because of posterior column symptoms, pyramidal tract sign and peripheral neuropathy with severe hyperchromic anemia. He was treated with mecobalamin 1 mg IM, after which his anemia and neurological signs recovered. He was diagnosed as having subacute combined degeneration with pernicious anemia. Subsequent stomach biopsy revealed gastric cancer, and the patient underwent gastrectomy. It is a well known association that chronic atrophic gastritis is associated with gastric cancer or subacute combined degeneration. Our findings suggest that in this case subacute combined degeneration and gastric cancer are independent of each other; rather, both resulted from chronic atrophic gastritis.

Topics: Aged; Anemia, Hypochromic; Humans; Male; Nerve Degeneration; Peripheral Nervous System Diseases; Spinal Cord; Spinal Cord Diseases; Stomach Neoplasms; Vitamin B 12

A 55 year old male presented 2 years after a jejuno-iliectomy with weakness of all limbs, paraesthesiae, and difficulty in walking. Clinical examination revealed loss of posterior column sensations. Investigations were suggestive of a deficiency of vitamin B12 and folate. MRI showed a band of hyperintensity on T2 image, in the dorsal portion of the spinal cord.

Topics: Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration; Sensation Disorders; Spinal Cord; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Aged; Demyelinating Diseases; Female; Humans; Magnetic Resonance Imaging; Nerve Degeneration; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Cervical Vertebrae; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration; Spinal Cord; Spinal Cord Diseases; Thoracic Vertebrae; Vitamin B 12

Topics: Adolescent; Diet, Vegetarian; Follow-Up Studies; Humans; Male; Nerve Degeneration; Risk Assessment; Severity of Illness Index; Spinal Cord Diseases; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

To observe the presentations and in the patients with subacute combined degeneration (SCD) changes of electrophysiology (EP) and magnetic resonance image (MRI) before and after treatment and to analyze their values in diagnosis.. 10 patients received a series of examinations, including clinical neurological functions, serum vitamin B12 and folic acid concentrations, spinal cord MRI, peripheral nerve conduction velocity, sensory evoked potential (SEP) and visual evoked potential(VEP). They were followed up for 3 to 36 months. The changes of spinal cord MRI and SEP before and after the treatment were studied.. After Vitamin B12 therapy, all the patients improved,but there were still some abnormalities of SEP left. The lesions could be shown sensitively by EP. The changes of SEP and clinical symptoms correlated with each other. The spinal cord MRIs of most patients showed the lesions objectively, demonstrating primarily long-tape abnormal signals in posterior and lateral columns, iso-intense on T1 and hyper-intense on T2 without contrast. Most lesions were seen at the thoracic cord. The lesions constricted or disappeared when the clinical conditions improved.. Spinal cord MRI and EP could objectively show the lesions of SCD and the change before and after the treatment. These examinations and the follow-up of disease could be helpful in the diagnosis of SCD.

Topics: Adult; Aged; Evoked Potentials, Somatosensory; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration; Spinal Cord; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Severe permanent cobalamin (Cbl) deficiency was induced in rats either by total gastrectomy (TG) or through prolonged dietary Cbl deprivation. This paper deals with an ultrastructural investigation of different parts of the central nervous system (CNS) of rats made Cbl-deficient through one of these of two procedures. In both totally gastrectomized (TGX) rats and in rats chronically fed a Cbl-deficient diet, we observed intramyelin edema, with splitting of the lamellae, and interstitial edema affecting the white matter, mainly in the spinal cord (SC). These lesions were also present in the subcortical white matter, although to a lesser degree. In both TGX-rats and in rats chronically fed a Cbl-deficient diet the pyramidal tract and the optic nerve were completely spared. Vascular lesions were never observed. Intramyelin edema and interstitial edema of the white matter account for the patchy myelopathic spongy vacuolation, which is the histological hallmark of human subacute combined degeneration and has been previously seen in SC white matter of TGX-rats. Macro- and micro-glial cells in the white matter were activated, at least as seen ultrastructurally. Interestingly enough, there were activated glial cells even in the gray matter, in which neurons showed absolutely no alterations. Chronic subcutaneous Cbl administration of TGX-rats partially repaired the CNS damage. However, the amelioration produced by this treatment was greater when Cbl was given shortly after TG than when given three and four months after TG, i.e. when the lesions have already been formed.

Topics: Animals; Blood Vessels; Central Nervous System; Gastrectomy; Humans; Male; Microscopy, Electron; Myelin Sheath; Nerve Degeneration; Neuroglia; Rats; Rats, Sprague-Dawley; Spinal Cord; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients.. Clinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients before and after treatment.. The most prominent clinical and electrophysiological findings in all patients were dysfunctions of the posterior column. Corresponding hyperintense lesions in the posterior column of the spinal cord were found in two patients by T2 weighted MRI. Damage to the central motor pathway was identified in four patients. Demyelinating neuropathy was present in one patient and axonal neuropathy in four. All patients showed improvement of their symptoms after treatment with cobalamin. Abnormalities of the spinal cord on MRI disappeared early in recovery. Motor evoked potentials and median somatosensory evoked potentials typically normalised after treatment, whereas tibial somatosensory evoked potentials remained abnormal in most patients.. Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B12 deficiency are diverse. Thus vitamin B12 deficiency should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.

Topics: Acute Disease; Aged; Aged, 80 and over; Axons; Diagnosis, Differential; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Female; Humans; Magnetic Resonance Imaging; Male; Nerve Degeneration; Retrospective Studies; Spinal Cord Diseases; Tibial Nerve; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Acute Disease; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration; Spinal Cord Diseases; Spinal Nerves; Vitamin B 12

The totally gastrectomized (TGX) rat is a new experimental model with which to produce widespread spongy vacuolation in spinal cord (SC) white matter, strongly reminiscent of that observed in subacute combined degeneration (SCD) of human SC.. We did in long-term experiments combined biochemical and histologic studies on SCs from both TGX-rats and rats fed a cobalamin-deficient (Cbl-D) diet. We also investigated the effects of single in vivo administration of some neurotrophic growth factors on the activity of L-ornithine decarboxylase (ODC) (the key-point in the polyamine biosynthetic pathway) in rat SC.. Biochemically, ODC activity was still induced 3 and 6 months after total gastrectomy (TG), while it did not change significantly even after 9 months of feeding a Cbl-D diet. Both TG and feeding the Cbl-D diet greatly decreased the cobalamin level in both serum and SC, although these decreases occurred more slowly in rats fed a Cbl-D diet. Nerve growth factor did not induce ODC in either Cbl-D myeloneuropathy; epidermal growth factor induced ODC in both Cbl-D myeloneuropathies. Basic fibroblast growth factor induced SC ODC only in TGX-rats. Histologically, spongy vacuolation was still widespread 3 and 6 months after TG, while it was spotty even after 9 months of feeding a Cbl-D diet. There was massively increased staining of astrocytes positive for glial fibrillary acidic protein, mainly in the gray matter, in both Cbl-D myeloneuropathies. Finally, repeated in vivo injections of cobalamin to TGX rats only partially reduced ODC induction, the severity of spongy vacuolation, and the increase in glial fibrillary acidic protein-positive astrocytes.. These results suggest: (a) ODC induction is a persistent and inherent feature in the TG-induced SCD of rat SC; (b) an increase in glial fibrillary acidic protein positive astrocytes in rat SC is not mandatorily connected with an increase in polyamine biosynthesis; (c) a mere deficiency of Cbl seems to be not the only key-point in the pathogenesis of the ODC induction and of the SCD-like lesions, both brought about in rat SC by TG.

Topics: Animals; Astrocytes; Enzyme Induction; Gastrectomy; Glial Fibrillary Acidic Protein; Male; Nerve Degeneration; Nerve Growth Factors; Ornithine Decarboxylase; Rats; Rats, Sprague-Dawley; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Humans; Nerve Degeneration; Rats; Vitamin B 12

Totally gastrectomized rats have been used to induce a spongy demyelination in the white matter of the spinal cord (SC) which is strongly reminiscent of that observed in subacute combined degeneration of human SC. Totally gastrectomized rats are deprived of intrinsic factor and thereafter become deficient in cobalamin. Morphologically, the spongy demyelination of the white matter of the rat SC, was evident 2 months after total gastrectomy. Biochemically, we investigated the hypothesis that polyamine biosynthesis might be deranged in the rat SC with experimental subacute combined degeneration, since polyamines are well known to be bound to myelin in the mammalian central nervous system. We measured the levels of both the polyamine biosynthetic decarboxylases, L-ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase, the key points in the polyamine biosynthetic pathway, in these SC. There was a sharp increase in ODC activity in SC 2 months after total gastrectomy, without significant changes in S-adenosyl-L-methionine decarboxylase activity. The increase in ODC activity seems to be organ-specific and was not due to a proliferation of neuroglial cells. Interestingly enough, the same morphologic and biochemical features found in SC of 2-month-totally-gastrectomized rats were present also in SC of newborn rats, which indeed showed incomplete myelination, vacuolated appearance, and an ODC activity level higher than that of adult SC. Therefore, total gastrectomy seems to induce a type of regression in the SC of totally gastrectomized rats toward neonatal life, at least in terms of the degree of myelination and of ODC activity level. Biochemically, no changes in ODC activity were observed in SC of rats fed a cobalamin-deficient diet for 3 months. Morphologically, only a proliferation of neuroglial cells with a moderate demyelination was observed in SC of these rats maintained on a cobalamin-deficient diet for 3 months.

Topics: Animals; Carboxy-Lyases; Enzyme Induction; Folic Acid; Gastrectomy; Male; Nerve Degeneration; Ornithine Decarboxylase; Polyamines; Rats; Rats, Inbred Strains; Spinal Cord; Vitamin B 12

The present study investigates the de- and regenerative changes in the saphenous nerve of the rabbit following systemic treatment with a combination of the vitamins B1, B6 and B12 and a control group that was treated with physiological saline solution. Cold lesion of the nerve, which led to an optimal axonotmesis, was used to cause a secondary degeneration. After 4, 10 and 21 days the nerves were removed and investigated by light and electron microscopy. The morphological results show that the number of regenerating axons is higher and that of degenerating axons lower in the group treated with the given doses of the vitamins than in the comparable control group. Statements as to the metabolic processes and vitamins from which the better regeneration results are due are as yet not possible. Further investigations with the individual vitamins are necessary. Clinical indications of neurotoxicity due to the dose levels used were not observed in any of the cases.

Topics: Animals; Axons; Dose-Response Relationship, Drug; Hindlimb; Microscopy, Electron; Nerve Degeneration; Nerve Fibers, Myelinated; Nerve Regeneration; Peripheral Nerves; Pyridoxine; Rabbits; Thiamine; Vitamin B 12; Wallerian Degeneration

A female patient with subacute neurological deficits secondary to an hereditary vitamin B12 deficiency was repeatedly examined clinically and neurophysiologically. It is concluded that neurological normalization after treatment with vitamin B12 also occurs within the CNS. Such normalization takes place soon after initiating treatment and probably reflects other neuronal mechanisms that remyelination, i.e. recovery from conduction block in fast somatosensory pathways and/or improvement of synaptic transmission.

Topics: Evoked Potentials, Somatosensory; Evoked Potentials, Visual; Female; Humans; Median Nerve; Middle Aged; Motor Neurons; Nerve Degeneration; Nervous System Diseases; Neural Conduction; Sensation; Spinal Cord; Sural Nerve; Vitamin B 12; Vitamin B 12 Deficiency

A 23-year-old woman with pernicious anemia, previously treated with folic acid, demonstrated an unusually rapid and severe course of neurologic deterioration. She was first seen with coma, myelopathy, and peripheral neuropathy. Her EEG showed repetitive nonperiodic suppression bursts, probably related to the severe impairment of consciousness. A sural nerve biopsy specimen revealed prominent axonal degeneration. With cyanocobalamin treatment, she regained normal mentation and the use of the upper limbs. She remains paraplegic, however, with a T10 sensory level.

Topics: Adult; Axons; Biopsy; Coma; Electroencephalography; Female; Folic Acid; Humans; Nerve Degeneration; Sural Nerve; Vitamin B 12; Vitamin B 12 Deficiency

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.

Topics: Adult; Aged; Diagnosis, Differential; Female; Folic Acid; Folic Acid Deficiency; Follow-Up Studies; Humans; Hydroxocobalamin; Intestinal Absorption; Male; Middle Aged; Nerve Degeneration; Recurrence; Spinal Cord; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Experiments were performed to investigate the effects of Vitamin B12, i.e., methylcobalamin and cobamide, on the neural degeneration and regeneration. Male Wistar rats (140 to 150 g) under conditions of experimental unilateral sciatic nerve crushing were treated consecutively with methylcobalamin (50 and 500 mug/kg/day i.p.), cobamide (50 and 500 mug/kg/day i.p.) or saline. EMG recordings were periodically carried out and rats of each group were sacrificed to determine the weight-loss of denervated muscles 1, 2, 3 and 4 weeks after crush. Neither methylcobalamin nor cobamide exerted any significant effect on body-weight gain of the nerve-crushed rats with a daily injection of 50 and 500 mug/kg i.p.. The EMG pattern of the denervated biceps femoris muscle showed a total lack of fibrillation for 2 days after the nerve-crush. Thereafter, the fibrillation appeared and continued for 10 to 14 days until the nerve had regenerated, as evidenced by the appearance of a complex NMU voltage. The occurrence of fibrillation voltage was slightly delayed in methylcobalamin group (500 mug/kg/day) as compared with the saline control group. The re-appearance of normal NMU voltage was more rapid in the methylcobalamin 500 mug/kg group than in controls and other experimental groups. Neither methylcobalamin nor cobamide had any significant effect on the weight-loss of the gastrocnemius and tibialis anterior muscles following crush of the sciatic nerve. However, a daily injection of 500 mug/kg of methylcobalamin produced a significant increase in the weight of the soleus muscle which recovered to the extent of being the same weight of the contralateral 4 weeks after the nerve-crush. These results suggest that methylcobalamin may have an inhibitory effect on Wallerian degeneration and also a facilitatory effect on the neural regeneration of the crushed sciatic nerve of rats.

Topics: Animals; Cobamides; Electromyography; Male; Muscle Denervation; Muscles; Nerve Degeneration; Nerve Regeneration; Organ Size; Rats; Sciatic Nerve; Vitamin B 12

Male Wistar rats (140 to 150 g) in which the unilateral sciatic nerve had been crushed were treated consecutively with methylcobalamin (5, 50 and 500 mug/kg/day i.p.) or saline immediately after the nerve-crush. Thereafter, they were periodically sacrificed for biochemical and histological examinations. At different intervals after the nerve-crush, L-leucine-4,5-T (20 mu Ci/100g, specific activity 15 mCi/m mole) or L-leucine -14C(U) (15 muCi/100g, specific activity 270 mCi/m mole) was given i.p. to some rats of each group and 3 hr later they were sacrificed to determine the rate of leucine incorporation into protein fractions of the crushed nerve and the denervated muscles. The nerve and muscles of the contralateral side served as control. Longitudinal sections of proximal and distal stumps of the sciatic nerve were prepared and stained with hematoxylin and eosin. As compared with saline group, repeated injections of 5, 50 and 500 mug/kg/day of methyl-cobalamin caused a significant increase of the in vivo incorporation of radioactive leucine into the protein fraction of the crushed sciatic nerve 5 to 7 days after the crush. In contrast, a recovery of the increased incorporation of leucine into the crushed nerve was more rapid in methylcobalamin groups than in the saline group. On the other hand, methylcobalamin (5 approximately 500 mug/kg/day i.p.) had no significant effect on the leucine incorporation into the denervated muscles (m. gastrocnemius, m. tibialis anterior and m. soleus). In addition, consecutive injections of methylcobalamin (5 approximately 500 mug/kg/day) did not affect the mitosis of Schwann cells during the period of Wallerian degeneration of the crushed sciatic nerve. These results suggest that methylcobalamin possesses a stimulating effect on proteosynthesis in Schwann cells at the initial stage of axon regeneration and it may facilitate neural regeneration.

Topics: Animals; Leucine; Male; Mitosis; Nerve Degeneration; Nerve Regeneration; Nerve Tissue Proteins; Rats; Schwann Cells; Sciatic Nerve; Vitamin B 12

One case each of pernicious anemia and folic acid deficiency with chronic malabsorption with disease of the cord and histologically demonstrated concomitant disease of the peripheral nerve system in the sense of a polyneuropathy are described. The histological findings of nerve obtained by biopsy show, in both cases, the loss of individual nerve fibers as an expression of a chronic axonal degeneration. The pathogenetic basis to be considered in these cases is presented.

Topics: Aged; Anemia, Pernicious; Axons; Female; Folic Acid Deficiency; Humans; Leg; Malabsorption Syndromes; Male; Middle Aged; Nerve Degeneration; Neurologic Manifestations; Peripheral Nerves; Peripheral Nervous System Diseases; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

This paper describes the clinical history of an adult male who was found to be suffering from subacute combined degeneration of the spinal cord. It is believed that this is the first report of this condition in Papua New Guinea.

Topics: Acute Disease; Humans; Male; Middle Aged; Nerve Degeneration; Neurologic Examination; Spinal Cord Diseases; Vitamin B 12

Topics: Adrenal Glands; Animals; Dose-Response Relationship, Drug; Kidney; Liver; Male; Muscles; Nerve Degeneration; Pancreas; Rats; Sciatic Nerve; Vitamin B 12

Topics: Adolescent; Adult; Anemia, Hypochromic; Bone Marrow Examination; Child; Electroencephalography; Electromyography; Evoked Potentials; Female; Folic Acid; Hemoglobinometry; Humans; Male; Middle Aged; Muscular Diseases; Nerve Degeneration; Neural Conduction; Neurologic Examination; Neurologic Manifestations; Night Blindness; Peripheral Nerves; Peripheral Nervous System Diseases; Potassium; Reflex, Monosynaptic; Serum Albumin; Sprue, Tropical; Vitamin B 12

Topics: Animals; Axons; Carboxylic Acids; Cyclopentanes; Methyltransferases; Mice; Myelin Sheath; Nerve Degeneration; Spinal Cord Diseases; Vitamin B 12

Topics: Adult; Crohn Disease; Folic Acid; Humans; Ileum; Malabsorption Syndromes; Male; Nerve Degeneration; Postoperative Complications; Spinal Cord Diseases; Vitamin B 12; Vitamin B 12 Deficiency

Lhermitte's sign is a common early symptom of subacute combined degeneration of the cord occurring in 11 out of 44 patients admitted to the National Hospitals for Nervous Diseases during the decade 1962-71 with this diagnosis. Two patients, in both of whom it was the presenting complaint, are described in detail. It is concluded that, in these cases, Lhermitte's sign is due to stretching of demyelinated fibres in the posterior columns in the cervical cord, produced by neck flexion. The symptoms disappear after treatment with vitamin B(12). The clinical importance of this symptom is emphasized.

Topics: Adult; Female; Humans; Male; Middle Aged; Nerve Degeneration; Sensation; Spinal Cord Diseases; Vitamin B 12

Topics: Animals; Demyelinating Diseases; Diet; Female; Haplorhini; Macaca; Macrophages; Male; Monkey Diseases; Nerve Degeneration; Neurofibrils; Papio; Peripheral Nervous System Diseases; Pregnancy; Ranvier's Nodes; Sciatic Nerve; Tibial Nerve; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diet, Vegetarian; Female; Humans; Middle Aged; Nerve Degeneration; Neurologic Manifestations; Spinal Cord Diseases; Vitamin B 12

Topics: Animals; Brain; Demyelinating Diseases; Diet; Erythrocyte Count; Haplorhini; Hematocrit; Hemoglobins; Macaca; Monkey Diseases; Nerve Degeneration; Nervous System; Papio; Paralysis; Peripheral Nerves; Spinal Cord; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Animals; Chelating Agents; Chlorothiazide; Copper; Folic Acid; Hydrocephalus; Male; Mice; Nerve Degeneration; Riboflavin; Thiamine; Vitamin A; Vitamin B 12

Topics: Animals; Demyelinating Diseases; Haplorhini; Nerve Degeneration; Paralysis; Vitamin B 12

Topics: Animals; Diet; Haplorhini; Monkey Diseases; Nerve Degeneration; Vitamin B 12; Vitamin B 12 Deficiency