A suspected case of alcoholic pellagra encephalopathy with marked response to niacin showing myoclonus and ataxia as chief complaints]

We report a 47-year-old alcoholic man with alcoholic pellagra encephalopathy (APE) showing myoclonus and ataxia as chief complaints. He had been a heavy drinker for 30 years. He had noticed appetite loss and subsequently showed a subacutely progressive gait disturbance. He had no history of diarrhea, dementia, or dermatitis. On admission, he showed severe alcoholic liver cirrhosis with a large amount of ascites, limbs and truncal ataxia, myoclonus of the limbs and areflexia, although his consciousness was alert and there were no sign of dermatitis. Though the plasma level of ammonia was normal, we started administration of amino acids suspecting hepatic encephalopathy. Symptoms showed no improvement, and subsequent administration of thiamine was also ineffective. A decreased serum level of niacin was demonstrated. After administration of nicotinamide, the symptoms improved gradually. This patient received a diagnosis of APE. Endemic pellagra, characterized by the classical triad of dermatitis, diarrhea and dementia, is known to be caused by a dietary deficiency of the niacin, and has now become very rare in developed countries. At present, pellagra is encountered most often in patients with chronic alcoholism, which is called APE. APE patients often show only disturbance of consciousness. Although several reports has described ataxia and myoclonus in patients with APE, APE patients with myoclonus and ataxia as chief complaints have not previously been reported. On autopsy cases, central chromatolysis of neurons in the dentate nucleus of the cerebellum, gracile and cuneate nuclei, and the Clarke's column has been demonstrated. The APE patients would show myoclonus and ataxia as their first symptoms. In conclusion, we would like to emphasize that administration of niacin should be started for the treatment of chronic alcoholic patients showing myoclonus and ataxia even without the classical triads found in endemic pellagra patients.     

Thiamine deficiency polyneuropathy after gastrectomy associated with high level of serum vascular endothelial growth factor (VEGF). A case report]

We report a 66-year-old man who developed vitamin B1 deficiency polyneuropathy long after a gastrectomy. After a preceding bronchial infection, the patient noticed numbness and weakness in his extremities, followed by generalized edema and exertional dyspnea. He had undergone subtotal gastrectomy due to duodenal ulcer at age 19. His daily oral intake of food was normal without any alcoholic abuse. He was admitted to our hospital with rapidly progressive gait disturbance due to muscle weakness, and sensory disturbance. Neurological examination showed peripheral polyneuropathy with distal dominant muscular weakness and sensory disturbance. Chest X-ray film showed marked cardiomegaly and pleural effusion. Nerve conduction studies showed decreases in the action potentials of both the motor and sensory nerves, with the sensory nerves being more severely affected than the motor nerves. Sural nerve biopsy demonstrated severe axonal degeneration without any inflammatory change. The blood concentration of thiamine (vitamin B1) was slightly decreased below the normal range (19 ng/ml; normal, 20-50), and the serum vascular endothelial growth factor (VEGF) was high (890 pg/ml; normal < 200 pg/ml). Intravenous administration of vitamin B1 (50 mg per day) dramatically improved his symptoms in a few days and the level of VEGF returned to nearly normal. In this gastrectomized patient many years ago, vitamin B1 deficiency neuropathy is warranted in view of a prompt response to thiamine administration. This case suggests that VEGF is involved in the pathogenesis of vitamin B1 deficiency polyneuropathy.     

Acute axonal polyneuropathy in chronic alcoholism and malnutrition.

In contrast to the classic, slowly progressive polyneuropathy in alcoholic patients, acute forms, clinically mimicking Guillain-Barré syndrome, are rare. We present a patient who developed motor weakness and sensory loss in all four limbs within four days. Laboratory data were consistent with long-term alcohol abuse and documented thiamine deficiency. Repeated cerebrospinal fluid examinations were normal. Electrophysiological studies showed an acute sensorimotor polyneuropathy with predominantly axonal involvement. We conclude that acute alcoholic neuropathy has to be distinguished from Guillain-Barré syndrome and other forms of acute polyneuropathy by using clinical, laboratory, and electrophysiological data. Both ethanol toxicity and vitamin deficiency could play a role in the pathogenesis.     

Transient encephalopathy in a postoperative non-alcoholic female with Marchiafava-Bignami disease

Marchiafava-Bignami disease (MBD) is historically reported in middle-aged alcoholic men. We describe the presentation, course and radiological findings of a young non-alcoholic woman who developed encephalopathy and MRI findings consistent with MBD postoperatively. She returned to baseline after vitamin supplementation. We believe it is important to diagnose MBD because it is a potentially reversible encephalopathy.     

Early intervention in alcoholism: confrontational techniques

Abstaining from use of a chemical that has provided a desirable sensation will not occur as long as the pleasure or relief derived from its use exceeds the unpleasant consequences--hence, the popular observation that an alcoholic does not stop drinking until he hits rock bottom. Waiting for rock bottom to occur, however, is fraught with physical and emotional risk both for the alcoholic and for the significant others in his life. The author describes two interventions designed to make the patient realize the gravity of the alcoholism problem. The first is conducted through conventional medical or psychiatric settings. The second consists of a collective, guided effort by significant persons in the patient's environment to confront the patient with specific details of his inebriety and with the changes they are prepared to make in their own lives if he does not enter treatment. The author also describes a treatment plan to be initiated after successful intervention.     

慢性酒精中毒性脑病诊治及分析

目的 探讨慢性酒精中毒性脑病的临床表现及治疗.方法 对12例住院病人临床、CT、MRI、电生理及治疗回顾性分析.结果 所有患者均有长期酗酒史,存在不同程度抑郁症倾向,符合ICD-10抑郁症诊断标准.伴有中枢神经系统症状及肝功能损伤,CT/MRI有不同程度脑萎缩、脑梗死、脑白质脱髓鞘、韦尼克脑病,及胼胝体变性等多病变并存,其中4例患者肌电图MCV、SCV减慢或消失,考虑合并周围神经病（CAPN）.结论 慢性酒精中毒性脑病是多病变并存的临床综合症候群,存在抑郁倾向,戒酒并辅以维生素B族及适度抗抑郁治疗,对本病有效.     

Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study

BACKGROUND: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). OBJECTIVE: To examine the relationship between antioxidant supplement use and risk of AD. DESIGN: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. SETTING: Cache County, Utah. PARTICIPANTS: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. MAIN OUTCOME MEASURE: Diagnosis of AD by means of multistage assessment procedures. RESULTS: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.     

调脂与抗氧化类抗动脉粥样硬化药物研究进展

目前临床常用的调脂类药物包括3-羟-3-甲基戊二酰辅酶A还原酶（HMG CoA还原酶）抑制剂、苯氧乙酸衍生物（贝特类）、烟酸类和胆汁酸结合树脂，各类药物各有其特点，以HMG CoA还原酶抑制剂使用最为广泛；抗氧化类主要有天然抗氧化剂如VitC、VitE和β-胡萝卜素和合成抗氧化剂如普罗布考（又名丙丁酚），而后者的应用得到了大量循证医学证据的支持。因此，选用调脂与抗氧化类抗动脉粥样硬化药物应依据循证医学的结果，遵循安全、有效、经济的原则。     

Delirium associated with vitamin B12 deficiency after pneumonia

A case is presented of a 65-year-old man with chronic schizophrenia who, after four years of remission, developed psychotic symptoms after pneumonia. The patient was found to be deficient in vitamin B12. His psychosis remitted within 5 days of administration of vitamin B12 and folic acid. This case emphasizes the need to measure vitamin B12 in psychogeriatric patients, especially when they present with a severe infection and organic mental symptoms.     

Appearance of EEG abnormalities in two patients during long-term treatment with B vitamins

Two female patients, one treated for epilepsy by phenobarbital (PB) and carbamazepine (CBZ), the other suffering from neurosis and free of any drug therapy, were given group B vitamins (riboflavin and nicotinic acid respectively) and showed during the long-term administration of these vitamins 2-3 Hz generalized electro-encephalographic (EEG) abnormalities. These EEG changes were detected incidentally and were not associated with any clinical manifestation; they disappeared progressively within several weeks after discontinuation of vitamin therapy. In our opinion, it is likely that the treatment with B vitamins was entirely responsible for the EEG changes, as one of the patients did not receive any other drug, while the other did not show any significant change of PB and CBZ plasma levels during vitamin therapy. However, other cases reported will be necessary to confirm our impressions.     

The influence of age and gender on niacin skin test results - implications for the use as a biochemical marker in schizophrenia

Investigation of abnormal skin response to niacin (vitamin B3) stimulation has gained increasing interest in schizophrenia research during last years. However, current efforts to implement niacin tests in routine diagnostics are jeopardised by wide inter-individual variations of skin response. We investigated age and gender as potential factors of influence on niacin sensitivity in 117 healthy subjects (63 male, 54 female). Niacin was applied in three dilution steps (0.1, 0.01, 0.001 M) onto the inner forearm skin. Skin reaction was assessed in three minute intervals over 15 min using optical reflection spectroscopy. Males displayed a significantly weaker flush response than females. The rate of non-responders at the lowest concentration was about twice as high in men than women. Significant negative correlations between age and niacin sensitivity were revealed for both sexes. Age and gender considerably influence niacin sensitivity, possibly due to the effects of sex hormones on vasomotor function and prostaglandin metabolism. Consideration of gender and age is strongly recommended for further clinical niacin studies.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.     

Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease

CONTEXT: It is currently not known whether dietary intakes of folate and vitamins B12 and B6, co-factors in the methylation of homocysteine, protect against Alzheimer's disease. OBJECTIVE: To examine the association between risk of incident Alzheimer's disease and dietary intakes of folate, vitamin B-12, and vitamin B-6. DESIGN: Prospective cohort study. SETTING: Geographically defined biracial Chicago community. PARTICIPANTS: 1,041 residents, aged 65 years and older, initially free of Alzheimer's disease and followed a median 3.9 years for the development of incident disease. MAIN OUTCOME MEASURE: Probable Alzheimer's disease identified through structured clinical neurological evaluation using standardized criteria. RESULTS: A total of 162 persons developed incident Alzheimer's disease during follow-up. In logistic regression models adjusted for age, sex, race, education, cognitive activities, APOE-epsilon4, and dietary intakes of vitamin E in food and total niacin, there was no association between risk of developing Alzheimer's disease and quintiles of folate intake or of vitamin B-12 intake. The adjusted odds ratio was 1.6 (95% confidence interval: 0.5, 5.2) for persons in the highest quintile of total folate intake (median of 752.7 microg/d) compared with persons in the lowest quintile of intake (median, 202.8 microg/d). Compared with persons in the first quintile of total vitamin B-12 intake (median, 3.1 microg/d) the odds ratio was 0.6 (95% confidence interval: 0.2, 1.6) for persons in the fifth quintile of intake (median, 20.6 microg/d). Intake of vitamin B-6 was not associated with incident Alzheimer's disease after control for dietary intakes of vitamin E and total niacin. CONCLUSION: Dietary intakes of folate, vitamin B-12, or vitamin B-6 do not appear to be associated with the development of Alzheimer's disease.     

Neuromyopathy and vitamin E deficiency in man

A 12-year-old boy, born of a consanguineous marriage, had ataxia, sensory neuropathy, generalized muscle hypotrophy and a lower serum vitamin E level. Two of his relatives had died of a clinically similar disorder in their late adolescence. Morphologically, his striated muscle fibers and Schwann cells of his sural nerve contained numerous autofluorescent acid phosphatase-positive lipopigments which, by electron microscopy, consisted of a finely granular matrix surrounded by a trilaminar membrane. These lysosomal lipopigments were similar to those observed in muscle fibers of a patient afflicted with abeta-lipoproteinemia. They probably represent the morphological sequelae of long-standing vitamin E deficiency in this child, the extract origin of which has not been fully elucidated.     

The biochemical pathways of central nervous system neural degeneration in niacin deficiency

Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency. Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemi- cal mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degener- ation. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are： 1） the trypto- phan-kyneurenic acid pathway, 2） the mitochondrial ATP generation related pathways, 3） the poly （ADP-ibose） polymerase （PARP） pathway, 4） the BDNF-TRKB Axis abnormalities, 5） the genetic influences of niacin deficiency.     

Vitamin E deficiency associated with vision loss and bulbar weakness

We describe a 14-year-old boy who was severely debilitated by the neurological syndrome associated with vitamin E deficiency secondary to chronic cholestatic liver disease. In addition to the usual neurological deficits described with this deficiency, the patient had severe bulbar weakness and vision loss which we attribute to the degree and duration of his vitamin E deficiency. Vitamin A deficiency may have contributed to his visual disturbance. Early recognition of vitamin E deficiency is important, as the neurological and visual disorders which result are treatable.     

Vitamin B nutrition in the Nigerian tropical ataxic neuropathy.

Assessment of nutritional status of vitamin B components by plasma or blood levels indicated riboflavin deficiency and possibly thiamine deficiency in Nigerian patients who suffered from tropical ataxic neuropathy and neurologically normal Nigerians who subsisted on predominant cassava diet. Serum levels of folate, niacin, pyridoxine and panthothenic acid were normal. Vitamin deficiencies probably are minor factors, if any, in the pathogenesis of tropical ataxic neuropathy in Nigerians.     

'Catatonia' due to disulfiram toxicity

In an alcoholic patient, catatonia developed while he was receiving disulfiram (Antabuse). Resolution of the question whether his state was classically catatonic required a detailed review of the literature on the subject. The conclusion reached is that the original definition still holds for psychiatric illness, but application of the term to neurological and metabolic states has often been based on imprecise criteria and failure to consider akinetic mutism and extrapyramidal motor disturbances as factors. The action of disulfiram as an inhibitor of dopamine beta hydroxylase provides a possible mechanism for the cerebral toxic effect, but nonetheless the various interpretations remain largely speculative.     

Alcoholic cognitive deterioration and nutritional deficiencies

Chronic alcoholic patients frequently exhibit a mild to moderate cognitive impairment that has been related to Wernicke-Korsakoff encephalopathy and attributed tentatively to nutritional and vitamin deficiencies. To elucidate the posible relation between alcoholic cognitive deterioration (ACD) and nutritional and vitamin deficiencies, several tests of intelligence and memory were administered to 54 chronic alcoholic patients and 30 controls. Serum levels of thiamine, folic acid, vitamins B12, A, and E, and certain nutritional indexes were determined in most of the subjects. The alcoholics scored significantly lower in intellectual and visuospatial tasks but not in verbal memory tasks. They had a lower serum level for thiamine but not of the remaining vitamins. However, the correlations between serum thiamin and cognitive performance scores were low, and according to stepwise regression analysis, duration of alcohol intake and education were the variables with predictive value for intellectual and memory test performance. These results suggest that serum thiamin deficiency is not the main pathogenetic factor related to ACD.