Central nervous system fungal infections: Observations from a large tertiary hospital in northern India

Objective

To report our observations regarding fungal infections of the brain over two years from a large tertiary hospital in northern India. To identify fungal infections in immunocompetent and immunocompromised patients and to compare the two groups with respect to their age of occurrence, demographic data, clinical profile, radiological findings, response to treatment and outcome.

Methods

All consecutive cases of central nervous system (CNS) fungal infections admitted to the hospital over two years were included in this study. The patients were categorized as immunocompetent and immunocompromised, the predisposing factors, symptoms and clinical presentation were studied in detail and the outcomes of the two groups were compared.

Results

Of the 50 cases, 25(50%) were that of mucormycosis, 17(34%) were cryptococcosis and 8(16%) cases were that of aspergillosis. 14(28%) cases were immunocompetent and 36(72%) were immunocompromised. The outcome studied was as follows: 28% died of which 4% were HIV positive, 12% were diabetics with severe rhinorbital involvement, 2% had idiopathic thrombocytopenic purpura (ITP), 6% had advanced cancer and 4% had no predisposing illness.

Conclusions

We observed fungal infections of the brain in both immunocompetent and immunocompromised patients. In immunocompetent patients, early diagnosis and appropriate treatment frequently leads to recovery from the illness. The mortality and morbidity of fungal infections are less in the immunocompetent group of patients.     

Role of cytokines and chemokines in prion infections of the central nervous system

Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.     

我国人类免疫缺陷病毒和梅毒螺旋体感染中枢神经系统研究进展

获得性免疫缺陷综合征(亦称艾滋病)和梅毒在全球范围内广泛流行,严重危害国家公共卫生安全。我国对人类免疫缺陷病毒(HIV)相关中枢神经系统损害及神经梅毒的研究日益增多。本文检索目前国内学者发表的HIV和梅毒螺旋体感染中枢神经系统的相关文献,总结其流行病学特征、发病机制、临床特点、诊断与治疗策略,以为临床诊断与治疗提供新的思路。     

石家庄地区中枢神经系统感染的住院资料分析

目的探讨中枢神经系统感染性疾病的发病特点。方法对我院1996-2005年间收治的中枢神经系统感染性疾病的住院病例进行回顾性分析。结果10年间我院共收治中枢神经系统感染性疾病的患者3929例，其中病毒性脑（膜）炎2506例（63．8％），脑囊虫病682例（17．4％），结核性脑膜炎（简称结脑）411例（10．4％），化脓性脑膜炎（简称化脑）303例（7．7％），隐球菌性脑膜炎（简称隐脑）27例（0．7％）。2001-2005年，病毒性脑（膜）炎、结脑、化脑、隐脑的病例数较前5年分别增加了53．5％、21．3％、35．3％、77．3％。脑囊虫病病例数较前5年下降了32．4％。病毒性脑（膜）炎主要集中在7～9月份，结脑主要集中在4～6月份。病毒性脑（膜）炎、脑囊虫病、结脑、化脑、隐脑的病死率分别为8．1％、6．9％、22．4％、12．9％、33．3％。结论近5年来，中枢神经系统感染性疾病在河北省石家庄市附近局部有增加的趋势，应该提高警惕，做好防治工作。     

Viral infections of the central nervous system

Viral infections of the central nervous system in the tropical countries of Asia and the Indian subcontinent are different from those of the Western and developed world. Many of the endemic and epidemic encephalitides that are prevalent in these regions, such as Japanese encephalitis, have characteristic findings on imaging, especially on magnetic resonance imaging, allowing a rapid diagnosis and differentiation from clinically similar syndromes. Other emerging viral infections in the region in recent years have posed new challenges. The contribution of neuroimaging to the management of these emerging infections is also discussed.     

中枢神经系统损伤修复与治疗性疫苗

中枢神经系统（central nerve system。CNS）损伤后，受损神经轴突不能自然再生。从而导致个体感觉、运动及认知的永久性缺失。引发严重的社会问题。因只要一部分神经纤维束连接得以再通即可完成显著的功能信号转导，因此探寻新的策略。最大程度上促进CNS损伤后修复再生具有重大意义。     

Central nervous system and renal investigations in patients with Lowe syndrome

We describe three patients with Lowe (oculocerebrorenal) syndrome, emphasizing primarily the central nervous system and renal pathology. Using magnetic resonance imaging, we noted diffuse high T2 signals periventricularly, indicating significant white matter destruction, which may be responsible in part for the mental retardation, seizure disorder, hypotonia, and areflexia observed in the patients. In contrast to previously published reports, there was minimal renal tubular dysfunction; however, proteinuria was significantly increased in all patients. We believe that the observed proteinuria is primarily the result of glomerular pathology rather than renal tubular dysfunction and may represent a net loss of negative charges within the glomerular filter. This loss of charge may be linked to the increased excretion of glycosaminoglycans in the urine.     

Epidemiology of central nervous system neoplasms A regional survey in Central Finland

An epidemiologic survey of central nervous system (CNS) neoplasms in Central Finland revealed a total of 367 neoplasms, 298 of which were diagnosed during 1975-82, the remaining being diagnosed earlier. Histological verification was available in 83% of intracranial and 90% of intraspinal neoplasms. 14% of the intracranial neoplasms diagnosed during 1975-82 were found incidentally at autopsy. Metastases corresponded to 18% of all CNS neoplasms. Age- and sex-adjusted annual incidence rates for primary and metastatic intracranial neoplasms were 12.3 and 3.4/100,000, and for intraspinal neoplasms 1.3 and 0.7/100,000, respectively. The total incidence of all CNS neoplasms was 17.7/100,000/year. Of the different types of intracranial neoplasms, meningiomas were more frequent among women than among men with a ratio of 8:1; metastases were more common among men with a ratio of 2.5:1. For primary intracranial neoplasms, point prevalences (January 1, 1983) were 65.9/100,000 and intraspinal neoplasms 9.1/100,000. The corresponding period prevalences for 1982 were 73.7 and 9.5/100,000.     

Autoimmune maintenance and neuroprotection of the central nervous system

The genesis of immune privilege high in the evolutionary tree suggests that immune privilege is necessary, if not advantageous for the progressive development of the CNS. Upon reaching a certain degree of complexity, it seems as if the CNS was obliged to restrain the immune system from penetrating the blood-brain barrier. CNS autoimmunity against myelin proteins is known to be a contributory factor in the pathophysiology of multiple sclerosis and in the animal model of experimental autoimmune encephalomyelitis (EAE) (Wekerle, 1993). Such autoimmunity has therefore been regarded as detrimental and hence obviously undesirable. However, recent findings in our laboratory suggest that T-cell autoimmunity to CNS self-antigens (Moalem et al., 1999), if expressed at the right time and the right place, can do much good in the CNS. We shall review the experiments briefly, and then discuss their implications for our understanding of immune privilege and CNS maintenance after injury.     

中枢神经系统肿瘤转化医学是理念更是实践

现代医学对中枢神经系统肿瘤的认识和诊治的进步从来就没有离开过基础研究的推动.经过二十余年的研究积累,我们对恶性脑肿瘤的分子生物学和分子遗传学、信号转导通路、细胞起源、恶性进展和生物学特性等方面的认识不断深入:近三十年间,WHO中枢神经系统肿瘤分类相继更新了四版,各肿瘤病种、亚型及其不同组织学表现形式的病理学特点得以精确注释,并附加描述了各类肿瘤的流行病学、临床症状与体征、影像学、结局和预测因素;四十年以来,以CT和MRI为代表(还包括PET-CT、SPECT、脑磁图)的影像学技术的发明与应用,促进了脑肿瘤诊断和治疗的飞跃发展.     

Morphology of demyelination in the human central nervous system

The principles of the neuropathological classification of disorders of central nervous system myelin are recalled. They are illustrated by a few selected examples. Dysmyelination is characterized by the production of an abnormal and unstable myelin sheath; it is often associated with hypomyelination (paucity of myelin formation) and is due to metabolic disorders. It is the main process in leukodystrophies. Storage of different lipids (e.g. sulfatides, long-chain fatty acids) or associated pathology of various cell types (in Alexander's disease, for example) are used for classifying these disorders. Biochemical and genetic characterizations are presently ongoing. Demyelination is the destruction of apparently normal myelin. It is often followed by remyelination. Our present knowledge on the neuropathology of multiple sclerosis, the most common demyelinating disease, is summarized. Cell-mediated demyelination affects the myelin sheaths for an obscure reason. The causes of the multifocal and sharply demarcated plaques, and of the fading of the remyelination process at the edge of some plaques, are not clear. A few examples of demyelinating diseases of known etiology and of various mechanisms are given. The similarities between acute disseminated leukoencephalitis and experimental autoimmune encephalitis are stressed. In progressive multifocal leukoencephalopathy, chronic infection of oligodendrocytes by JC virus induces poorly defined areas of demyelination. In AIDS, the pathogenesis of the myelin change is unclear. Macrophages may be responsible. Toxic and vascular disorders provide also good models for the understanding of mechanisms of demyelination.     

中枢神经系统淋巴瘤MRI表现

目的：探讨中枢神经系统淋巴瘤的影像学特征。方法：对１９例经手术及病理证实的中枢神经系统淋巴瘤的影像学表现，特别是ＭＲ表现进行分析。结果：单发肿瘤１５例，位于幕上１３例，幕下２例。多发肿瘤４例。多数病灶位于深部白质，１４例病灶邻近脑室。肿瘤平均最大径超过３ｃｍ。Ｔ１像１４例信号较低，５例等信号。Ｔ２像５例低信号，余为等信号。肿瘤水肿相对较轻。注射造影剂后，肿瘤多数均匀强化。病理均为ＮＨＬ恶性淋巴瘤。结论：中枢神经系统淋巴瘤的影像学表现与某些中枢神经系统病变有类似及重叠之处。通过认真的影像分析并结合活检结果，有利于治疗方法的选择。     

Distribution of measles virus in the central nervous system of HIV-seropositive children

In an autopsy study the distribution of measles virus (MV) in the central nervous system (CNS) of 18 measles-infected children (13 HIV seropositive, 5 HIV seronegative), in Abidjan, Ivory Coast was examined using immunocytochemistry and in situ hybridization. Of these children 17 died from measles giant cell pneumonia. In 3 of the 13 HIV-seropositive patients MV antigens and genomic RNA was detected in the CNS. One of these positive patients had an MV encephalitis with abundant virus throughout most of the CNS. MV was not detected in the CNS of any of the 5 HIV-seronegative patients. These findings, albeit in a small number of cases, would suggest there may be an increased susceptibility to infection of the CNS with MV in HIV-positive children. In this respect entry and growth of MV in the CNS in HIV-seropositive individuals may be similar to the occurrence of measles inclusion body encephalitis in immunocompromised individuals. Furthermore, comparison of the HIV-MV encephalitis patient with two patients with subacute sclerosing panencephalitis (SSPE) demonstrated a paucity of virus in neuronal processes in the HIV-MV encephalitis. Unlike in SSPE, MV maturation by budding through the plasma membrane may occur, thereby minimizing build up of and intracellular movement of incomplete virus. Received: 6 March 1998 / Revised, accepted: 2 June 1998     

The effects of antimicrobial and antiepileptic treatment on the outcome of epilepsy associated with central nervous system (CNS) infections

The course and outcome of epilepsy following central nervous system (CNS) infections has been poorly characterized. Likewise, the impact of antimicrobial treatment as well as other preventative and therapeutic interventions on the development of epilepsy following neurological infectious disorders has been insufficiently studied. The CNS infections that can cause epilepsy may be either acute or chronic-recurrent. For most acute infections, for example, viral encephalitis and bacterial meningitis, the effect of specific antimicrobial treatment on the development of epilepsy cannot be studied in a controlled manner due to logistic and ethical reasons. In the specific case of neurocysticercosis (NCC), the risk of seizures in the short term is reduced following either anthelminthic or corticosteroid treatment or both. The effect of anthelminthic treatment on seizure outcome in the long term has not been studied. Finally, treatment with antiepileptic drugs (AEDs) needs to be optimally defined in the case of epilepsy associated with neurological infectious disorders.     

Langerhans' cell histiocytosis and the nervous system

Summary We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed.     

Central nervous involvement by chronic lymphocytic leukaemia

Inclusion of the central nervous system (CNS) in the course of chronic lymphocytic leukaemia (CLL) is rare. At the moment no risk factors or proven treatment methods are known. The disease is described both in its early phase and during its acceleration period, thus it has been suggested that there might be independent mechanisms influencing the development of this condition. As there are no unified diagnostic procedure algorithms each patient needs to be assessed individually. CLL can manifest mostly in elderly people, for whom a possibility of development of neurological disorders with their aetiology different from leukaemia, should also be taken into consideration. The thesis presents a group of seven patients with CLL with CNS infiltration. Patients with prolymphocytic leukaemia, Richter's transformation and the original location of leukemic infiltration within the eye socket constitute an especially interesting case.     

Central nervous system imaging in reevaluation of patients with neurofibromatosis type 1

We report the results of the reevaluation of 24 patients with neurofibromatosis type 1 (NF1) using central nervous system (CNS) imaging techniques. The first examination by computed tomography (CT) or magnetic resonance imaging (MRI) indicated the presence of optic glioma in three cases, unidentified bright objects (UBOs) in six, and a suspected right frontal tumor in one. In two patients optic glioma and UBOs were both present and in one of them a bulbar tumor was also suspected. Later imaging examinations revealed the appearance of optic glioma in three more cases and UBOs in nine. In two of these patients both optic glioma and UBOs were present. This study indicates that the likelihood of detecting imaging abnormalities in patients with NF1 increases when systematic follow-up is performed. Optic gliomas are characteristic of pediatric patients; they rarely give rise to clinical manifestations (1/6 cases) and in general progress very slowly. For these reasons, therapeutic strategy must be carefully considered and individually decided. UBOs are very frequent findings in pediatric patients with NF 1 and therefore they must be considered diagnostically relevant. They are not related to clinical manifestations and spontaneous regression has been observed. The nature of these imaging abnormalities is still unknown, but because they do not behave like tumors, useless and dangerous therapeutic procedures should not be employed.     

Central nervous system immunity associated with clinical outcome in acute encephalitis

To search for useful laboratory measures of central nervous system (CNS) immunity that may provide an accurate prognosis or clues regarding treatment choice, cerebrospinal fluid (CSF) samples were obtained from 14 consecutive patients with acute encephalitis during acute as well as convalescent or chronic stages, and then examined for surface antigen expressions by lymphocytes and the presence of antineuronal tissue antibodies as well as the levels of IgG-related parameters and proinflammatory cytokines, including IL-2, IL-6, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha). Seven patients with aseptic viral meningitis served as nonencephalitic controls. Eight of the 14 acute encephalitis patients recovered fully, and reductions in the percentages of CD4(+)CD29(+) helper inducer T cells and IL-2 receptor-positive CD4(+) cells were associated with early recovery and favorable outcome, respectively, whereas a low percentage of CD4(+)CD26(+) memory T cells during an acute stage was associated with an unfavorable outcome following adjunctive intravenous corticosteroid treatment. Further, three of the four encephalitis patients who exhibited autoantibodies had a poor prognosis. These findings suggest that CNS immunity status has an effect on prognosis, while flow cytometric analyses of CSF CD4(+) helper T cell subsets may serve as effective means of assessment.     

中枢神经系统肿瘤相关炎症研究进展

19世纪Rudolf Virchow在肿瘤组织中第一次发现了炎症细胞,肿瘤与炎症免疫之间的关系便成为人们研究肿瘤的一个重要途径[1].炎症在肿瘤的发生、发展过程中的重要作用已逐步为人们所认识[2].