烟酸缺乏症35例临床分析

目的探讨烟酸缺乏症的病因、发病机制、实验室检查、脑电图特点、治疗及预后。方法收集本院2004年至2014年的34例诊断为烟酸缺乏症和1例合并亚急性联合变性的烟酸缺乏症的患者病例资料,对其临床资料进行分析。结果本病男女比例1:2,病因多种多样,主要临床表现为"4D综合征",即皮炎,腹泻,痴呆及死亡,给予补充烟酸等综合处理后,皮肤损害多在15~25d较前明显好转。结论烟酸缺乏严重者可继发周围及中枢神经损害,可合并亚急性脊髓联合变性,早期给予烟酸治疗可改善预后。     

沃勒变性在中枢神经系统的MRI表现

目的 回顾沃勒变性及继发跨神经元退变的病理学改变,分析其在中枢神经系统的MRI表现。方法 根据沃勒变性的影像学标准,选择1995～1999年经MRI确诊的沃勒变性患者20例,年龄16～70岁,平均52岁。其中脑梗死11例,脑出血4例,创伤手术后2例,肿瘤术后1例,脑膜瘤1例,脑白质病1例。回顾性分析其MRI表现。结果 20例患者原发病灶均位于幕上,16例于原发病灶同侧出现条带样连续或不连续长T_1或等T_1、长T_2改变,位于皮质脊髓束通路。FLAIR及DWI扫描均显示高信号病灶。3例仅见原发灶同侧大脑脚萎缩,但未见异常信号。7例见局限性胼胝体萎缩,T_2加权像信号略显增高。2例患者出现交叉性小脑萎缩,示皮质脑桥小脑通路退变。结论 对中枢神经系统的沃勒变性和继发跨神经元退变描述的是分子水平的病理学变化,因变性是沿着已知的神经通路的、且存在特定信号改变,故MRI可在活体中对其进行观察和诊断。     

Peripheral nerve lesion in spongy degeneration of the central nervous system

Summary This report describes a peripheral nerve lesion found in a case of spongy degeneration of the central nervous system. The lesion consisted of abnormal cellular infiltrates in the peri- and endoneurium, axonal changes, and demyelination. Possible relation of the lesion to that of the central nervous system is discussed.Supported by grant NB-02255 from the National Institutes of Health, United States Public Health Service.     

Congenital muscular dystrophy and severe central nervous system atrophy in two siblings

Severe degenerative features of the nervous system of a hitherto unknown kind, associated with a neuromuscular disorder with histopathological features of congenital muscular dystrophy, are reported in two female siblings. The clinical profile was characterized by generalized hypotonia followed by spastic tetraplegia, contractures, polyneuropathy, lack of cognitive development and progressive microcephaly. There was no involvement of the eyes. Neuropathological examination of the brain of one sibling, who died at the age of 30 months, revealed subtotal loss of neurons in the cerebral and cerebellar cortex and in the ventral pons, and secondary loss of myelin in the cerebral and cerebellar subcortical white matter. Sural nerve biopsy in the other sibling, who had a similar neurological affection, showed a lack of large myelinated fibers.This investigation is part of the research program Disorders of the Neuromuscular System of the University of Nijmegen     

Sub-acute cerebellar degeneration with anti-Yo autoantibodies: immunohistochemical analysis of the immune reaction in the central nervous system

B. Giometto, G. C. Marchiori, P. Nicolao, T. Scaravilli, A. Lion, P. G. Bardin and B. Tavolato (1997) Neuropathology and Applied Neurobiology, 23, 468–474 Sub-acute cerebellar degeneration without any anti-Yo autoantibodies: immunomstochemical analysis of the immune reaction in the central nervous system We report the pathological findings of a woman with a sub-acute cerebellar syndrome who had undergone surgery 3 years before for endometrial carcinoma. Both serum and cerebrospinal fluid contained high titres of autoantibodies against the cytoplasm of Purkinje cells that recognized a band of 62 kDa on immunoblotting of neuronal extracted proteins (pattern anti-Yo). No tumour was found despite a full range of gynaecological investigations; the neoplastic marker CA125 was slightly elevated and oligoclonal bands were detected in the cerebrospinal fluid. The patient died from acute myocardial infarction 4 months after developing this syndrome. At autopsy, no macroscopic evidence of tumour was obtained and the brain showed no abnormalities. On microscopic examination of the central nervous system diffuse degeneration of Purkinje cells could be seen throughout the cerebellum. Immunohistochemical analysis showed a CD8 lymphocyte infiltration in the cerebellum and cerebral cortex and diffuse microglial activation throughout the brain. These cells expressed high levels of MHC-II antigens on their cell membranes. The serum autoantibodies reacted with the cytoplasm of the remaining Purkinje cells. The short interval between the onset of symptoms and death of the patient could explain the difference between our findings and those reported in the literature in which no inflammatory infiltrates were detected. The immunohistochemical findings as well as the inflammatory cerebrospinal fluid profile seen in our case seem to support the concept that in paraneoplastic cerebellar degeneration with anti-Yo antibodies, an immune mediated mechanism is responsible for the damage to the cerebellum.     

Ultrastructure of 6-aminonicotinamide (6-AN) —Induced lesions in the central nervous system of rats

Summary Ultrastructure of neuronal chromatolysis and other lesions in the gray matter of the cervical cord due to 6-aminonicotinamide (6-AN) administration, an antinicotinamide, to rats, were followed up during a 35-days period. Neuronal chromatolysis which was prominent in the anterior horn cells in the acute stage, was completely recovered from via the temprary hyperchromasia of their cytoplasm. Their axons, however, which form the anterior nerve roots, did not show any particular changes throughout the whole period of the experiment. This evidence suggests that neuronal chromatolysis induced by 6-AN might not be the result of axonal damage, but was due to the direct action of 6-AN on the soma of the anterior horn cells.In addition, necrosis of the internuncial cells, various reactions of glial and mesenchymal elements and the spongy state of the neuropil in the laminae VI and VII of Rexed of the cervical gray matter were observed in the acute stage. They were later repaired by glia. These lesions are usually absent in the central nervous system of human cases with pellagra.It is considered that the findings with 6-AN simulate the central nervous lesions of pellagra in human, but some minor differences in pathology such as presence of severer lesions in glia and other elements in the experimental rats would probably be caused by additional factors such as drastic mode of action, probable difference in catabolism of nicotinamide and 6-AN, and so forth.     

Spongy degeneration of the central nervous system (Van Bogaert-Bertrand type?) in a newborn infant

Summary Autopsy findings on a 5 day old infant with hypotonia from birth showed extensive spongy changes of the myelinating tracts within the cerebrum, cerebellum and brain stem. The spongy changes, similar to Van Bogaert-Bertrand disease, resulted from intramyelinic edema. However, unlike the typical forms of this disease, swollen astrocytes with abnormal mitochondria were not found. The relationship of this case to typical forms of Van Bogaert-Bertrand disease is discussed. This case may represent a very early from of Van Bogaert-Bertrand disease or a new pathologic entity.     

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.     

Spongy degeneration of the central nervous system in kittens

Summary The paper describes the clinical and morphological features of a congenital neurological disease affecting two in-bred litter-mate kittens. The principal neurological features were ataxia and dysmetria. In one of the kittens light microscopy revealed widespread vacuolation of white and grey matter of the brain and spinal cord. Electron microscopy revealed intra-myelinic vacuolation and some expansion of the extracellular space. Neuronal, axonal and glial changes were not seen, nor was there evidence of myelin breakdown. The entity is compared with congenital brain oedema of calves and spongy degeneration of the CNS in man.     

Comparative effects of alcohol and thiamine deficiency on the developing central nervous system

The present study addresses the still unresolved issue of the character of alcohol-thiamine metabolic interferences in the developing central nervous system (CNS). Investigations compare developmental neurotoxicity evoked by three patterns of maternal thiamine deficiency (pre, peri and postnatal), with two patterns of maternal chronic alcohol intake (alcohol alone and alcohol + thiamine cotreatment), on seven neurodevelopmental abilities in the offspring. The three patterns of thiamine deficiency, pair-compared with controls, highlight four sequences of development: (1) embryonic-perinatal sequence; (2) perinatal-postnatal sequence; (3) “ontogeny in ontogeny out” sequence; (4) “off and on” developing sequence. The results suggest a temporally- and regionally emergence of structures and centers underlying functional maturation during CNS ontogenesis. Furthermore, both developmental thiamine deficiencies and ethanol exposure produce two waves of neurofunctional alterations, peaking at P15 (postnatal day 15) and P25, respectively. The first peak of vulnerability is a prenatal event; it may interfere with the periods of intense cellular proliferation and migration. The second peak represents both perinatal and postnatal events; it may interfere with the periods of cellular differentiation, synaptogenesis, axonogenesis and myelinogenesis. Alcohol + thiamine cotreatment fails to reduce the first peak, but neutralizes essentially the second peak. The results suggest that alcohol interferes with thiamine during cellular differentiation and membrane developmental processes mainly. Indeed, among the three conditions of thiamine-deficient diet, only perinatal thiamine deficiency exhibits a closer relationship with developmental alcohol exposure. Together, these observations suggest that the critical period for alcohol-thiamine antagonism occurs perinatally and affects primarily cellular differentiation.     

Ultrastructure of 6-aminonicotinamide (6-AN)-induced lesions in the central nervous system of rats

Summary Lesions in the CNS induced by 6-aminonicotinamide (6-AN) presented a spongy state of the gray matter and neuronal chromatolysis. With aging of the experimental animals the lesions extended from the phylogenetically early developed structures to those developed later, i.e., from spinal gray matter, dentate nuclei, and brain stem nuclei through limbic structures and striatum to the cerebral cortex. Changes of the neurons were more prominent with aging.Lesions in the CNS of rats at the age, corresponding to the involutional period in the human, were similar to those of Creutzfeldt-Jakob disease (C-J disease) in the presenile age. In recent years, the resemblance between C-J disease and pellagra encephalopathy had been noted by several authors, and they resemble the lesions caused by 6-AN, an antimetabolite of nicotinamide used in our experiment. This evidence, therefore, has led to the hypothesis that dysfunction of NAD(H)- or NADP(H)-dependent enzymes in the CNS of the aged, even if not the primary cause, may be one possible pathogenetic factor of C-J disease.     

神经干细胞及其在中枢神经创伤修复中的应用前景

神经干细胞具有很强的增殖和分化能力,它已在中枢神经组织损伤修复方面展示了不可估量的临床应用前景。但是,目前有关神经干细胞的组织来源、定向诱导分化、移植技术和神经功能修复的功能判定等方面尚存在诸多难题。如何解决这些难题,并建立一个适合于临床中枢神经损伤修复的神经干细胞移植治疗技术平台是非常迫切的问题。本文着重就神经干细胞的来源、分化增殖调控、移植治疗技术及神经干细胞移植修复中枢神经组织损伤的可能机制等提出一些初步看法和展望。     

Spongy degeneration in the central nervous system of domestic animals

Summary Severe spongy degeneration of the central nervous system (CNS) was seen in 11 cattle, 19 sheep, 4 pigs and 1 goat, associated with a variety of hepatic diseases, particularly those caused by hepatotoxic pyrrolizidine alkaloids. It was also seen in a milder form in 2 of 8 horses examined, 1 dog of 5 dogs examined, and in 1 rabbit only of a large number of laboratory animals examined.This paper reports results of experiments which confirmed initially that the CNS disease could be caused by pyrrolizidine alkaloid intoxication. This was done by poisoning sheep and calves withSenecio jacobaea, a plant which contains pyrrolozidine alkaloids, and by poisoning lambs with lasiocarpine.As the disease was seen in hepatoses not caused by pyrrolizidine alkaloids, the hypothesis that CNS spongy degeneration in lambs could follow any hepatic disease irrespective of its cause, was tested by poisoning lambs with allyl formate, an hepatotoxin chemically unrelated to pyrrolizidine alkaloids. Three of 4 lambs poisoned by the allyl formate showed spongy degeneration in their brains.As the CNS spongy degeneration was an apparent form of hepatocerebral disease, an experiment was conducted to show that the neural disease in sheep was caused by hyperammonaemia. CNS spongy degeneration developed in the brains of all sheep infused intravenously with ammonium acetate, and advanced spongy changes developed in the sheep infused for more than 3 days. The cerebral changes were probably temporary, since sheep infused for 5 days and retained for 3 weeks showed marked regression of vacuolation.Hyperammonaemia caused by intravenous ammonium acetate infusion is a simple, rapid model of CNS spongy degeneration. The syndrome, CNS spongy degeneration caused by hepatic failure and hyperammonaemia, is probably one of the morphologic expressions of hepatocerebral disease in domestic animals and could be an analogue of similar congenital and hepatocerebral diseases in man.     

Spongy degeneration in the central nervous system of domestic animals

Spongy degeneration or status spongiosus of the central nervous system (CNS) was described in a number of domestic animal species, notably sheep, cattle, pigs and in one goat. The condition was characterized by diffuse or focal vacuolation, or polymicrocavitation of the CNS, particularly the white matter. The vacuolation showed a well defined pattern of distribution following a number of myelinated tracts in CNS white matter, in isolated fibres crossing grey matter in the brain stem, and along grey and white matter borders in the cerebrum and spinal cord. The vacuoles were not altered by a variety of methods of rapid brain fixation, processing and staining. The appearance of the vacuolation repeatedly favouring the same areas in the CNS in a large number of animals studied, its common origin either by hepatocerebral disease or hyperammonaemia, strongly suggests that CNS spongy degeneration of domestic animals is a distinct disease entity.     

Spongy degeneration in the central nervous system of domestic animals

Two experiments were completed in which brains and spinal cords from lambs affected with spongy degeneration of the central nervous system (CNS) were analysed for water, sodium and potassium, as measures of cerebral oedema. In a third experiment, lambs with CNS spongy degeneration were tested for permeability of cerebral blood vessels by intravenous injections of Evans blue. The CNS spongy degeneration was produced by poisoning with the hepatotoxic pyrrolizidine alkaloid lasiocarpine. In the first experiment, 2 male lambs were poisoned by lasiocarpine and a third injected with saline alone. One lamb injected with lasiocarpine showed widespread spongy changes in the CNS and the other 2 showed normal brains. In the second experiment, 5 males lambs were poisoned by lasiocarpine and 5 were injected with saline. Three of the 5 poisoned lambs showed widespread spongy changes, a fourth showed minor vascuolation and the remaining 6 had normal brains...     

Advances in ontogeny of the enteric nervous system

The neurons and glia that comprise the enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, are derived from vagal and sacral regions of the neural crest. In order to form the ENS, neural crest-derived precursors undergo a number of processes including survival, migration and proliferation, prior to differentiation into neuronal subtypes, some of which form functional connections with the gut smooth muscle. Investigation of the developmental processes that underlie ENS formation has progressed dramatically in recent years, in no small part due to the attention of scientists from a range of disciplines on the genesis of Hirschsprung's disease (aganglionic megacolon), the major congenital abnormality of the ENS. This review summarizes recent advances in the field of early ENS ontogeny and focuses on: (i) the spatiotemporal migratory pathways followed by vagal and sacral neural crest-derived ENS precursors, including recent in vivo imaging of migrating crest cells within the gut, (ii) the roles of the RET and EDNRB signalling pathways and how these pathways interact to control ENS development, and (iii) how perpendicular migrations of neural crest cells within the gut lead to the formation of the myenteric and submucosal plexi located between the smooth muscle layers of the gut wall.     

Ret expression in the central nervous system

The ret proto-oncogene product (Ret) has been shown to be one of the glial cell line-derived neurotrophic factor (GDNF) receptors in dopaminergic, norepinephric and motor neurons. We immunohistochemically examined the expression of Ret in the human central nervous system (CNS). The distribution of Ret was generally identical to that of myclin as stained using the Klüver-Barrera method. We further investigated the expression of Ret in human fetal brains (19, 29 and 39 weeks gestation) and various brain tumors. The Ret positivity was observed to be associated with the myelin sheath of the cerebral white matter in 29-and 39-week-old fetal brains. Ret is known to be expressed in neural crest-derived cells. We could immunohistochemically confirm the Ret expression in the pheochromocytomas and neuroblastomas of retroperitoneal space. As for the brain tumors, no Ret expression was observed in glioblastomas, oligodendrogliomas, and schwannomas examined, although the glial cells surrounding the tumor and the pre-existing myelin sheath revealed positivity for Ret. In the CNS, Ret expression appears to be closely associated with the myelin sheath; therefore, Ret immunostaining may be useful in ascertaining the demyelinating lesions in the CNS.