Clinical relevance of polymerase chain reaction (PCR) assays and antigen-driven immunoblots for the diagnosis of neurological infectious diseases

Polymerase chain reaction assays are a powerful tool for detecting the presence of infectious genomes in the cerebrospinal fluid. Positive results always mean a current or pending infection of the central nervous system. Subacute (>7 days) or chronic infections induce an intrathecal humoral immune response and the appearance of oligoclonal IgG antibodies directed against the causal infectious agent. This local synthesis may be observed even in cases of severe systemic immunodeficiency. The use of polymerase chain reactions in combination with the detection of a specific intrathecal immune response should represent the most reliable strategy for the diagnosis of viral and chronic infections of the central nervous system. The authors describe their experience, using this approach, in herpetic encephalitis, acute and recurrent herpetic meningitis, varicella zoster-induced neurological diseases, cytomegalovirus encephalitis, progressive multifocal leukoencephalitis and tuberculous meningitis.     

Neuroepidemiology of acquired immune deficiency syndrome

Neuroepidemiology is that branch of chronic disease epidemiology dealing with disorders that affect the nervous system. The potential for neurological involvement in the diagnosis and pathogenesis of Acquired Immune Deficiency Syndrome (AIDS) has recently been noted. The following review outlines the spectrum of neurological conditions seen in AIDS patients to date. These conditions include: infectious central nervous system complications of viral, bacterial, fungal or protozoan origin; noninfectious central nervous system complications such as neoplasms or cerebral vascular accidents, and cranial and peripheral neuropathy. The incidence of neurological abnormalities among AIDS cases may be seriously underestimated due to a delay in the presentation of an overt neurological syndrome and/or the overlooking of subtle neurological signs and symptoms in such an overwhelming systemic disease.     

Neuroimmunology II: Antigenic specificity of the nervous system

Antigenic specificity of the nervous system refers to a property conveyed by unique cell surface that are present on different classes of nervous system tissue. These structures are a major importance for the study of nervous system structure and function, and can play a central role in determining patterns of nervous system injury. Thus, the major classes of nervous system cell are identified by structures that are unique to them: neurons by the presence of tetanus toxin receptors on their surface and oligodendrocytes by the presence of surface galactocerebroside, for example. With the advent of hybridoma technology, a large number of monoclonal antibodies are being identified which have increased by several orders of magnitude the ability to define subclasses of nervous system tissue according to unique antigens. In addition surface nervous system tissue may determine the specificity of nervous system injruy by (1) functioning as receptors for viruses or (2) being the targets of autoimmune responses. Patterns of viral injury to the nervous system are often extraordinarily selective (e.g., poliiviurs tropism for motor neurons), and nervous system viral tropism is due in some instances to the interaction of a virus with a unique surface antigen on neural cells. The specificity of injury in autoimmune disease (such as that against the acetylcholine receptor in myasthenia gravis) likewise must be explained by an immune response against unique system and other tisseus or between nervous system and infectious agents such as bacteria or viruses. The presence of shared antigenic structures between the nervous system and infectious agents creates the possibility that an immune response generated against a virus may concurrently damage normal nervous system tissue.     

组织细胞坏死性淋巴结炎累及神经系统的临床表现及鉴别诊断的研究进展

组织细胞坏死性淋巴结炎(HNL)又名Kikuchi-Fujimoto病(KFD),是一种全身性疾病,典型临床表现为发热、淋巴结肿大及白细胞减少。KFD累及中枢和周围神经系统者较少见,可表现为无菌性脑膜炎、脑脊髓炎、周围神经病、小脑性共济失调以及震颤等。以神经系统症状为主要临床表现的KFD患者容易被误诊误治,因此笔者现主要围绕KFD累及神经系统的临床表现及相关鉴别诊断的研究进展进行综述,以期进一步指导KFD的临床诊治。     

The spectrum of progressive multifocal leukoencephalopathy: a practical approach

John Cunningham virus (JCV) infection of the central nervous system causes progressive multifocal leukoencephalopathy (PML) in patients with systemic immunosuppression. With the increased application of modern immunotherapy and biologics in various immune‐mediated disorders, the PML risk spectrum has changed. Thus, new tools and strategies for risk assessment and stratification in drug‐associated PML such as the JCV antibody indices have been introduced. Imaging studies have highlighted atypical presentations of cerebral JCV disease such as granule cell neuronopathy. Imaging markers have been developed to differentiate PML from new multiple sclerosis lesions and to facilitate the early identification of pre‐clinical manifestations of PML and its immune reconstitution inflammatory syndrome. PML can be diagnosed either by brain biopsy or by clinical, radiographic and virological criteria. Experimental treatment options including immunization and modulation of interleukin‐mediated immune response are emerging. PML should be considered in any patient with compromised systemic or central nervous system immune surveillance presenting with progressive neurological symptoms.     

急性播散性脑脊髓炎合并多发性神经病的临床研究

目的分析急性播散性脑脊髓炎合并多发性神经病的临床特点,以提高临床医生对本病的认识和诊疗水平。方法对2017-12—2019-04就诊于河南省人民医院的8例急性播散性脑脊髓炎合并多发性神经病患者的临床表现、影像学、神经电生理、脑脊液特点及全身免疫相关指标进行回顾性分析。结果本组8例患者为急性或亚急性起病,起病前多有前驱感染史。首先表现为中枢神经系统受累,其中7例影像学证实脑和(或)脊髓白质受累,1例脑电图证实中枢神经系统受损;迟缓性瘫痪、腱反射减弱或消失等周围神经受损的证据也随后出现,而后肌电图证实多发性神经根受损或神经源性损害。脑脊液检查细胞轻度升高或正常,蛋白升高或正常,只有1例见脑脊液细胞-蛋白分离。治疗上急性期激素冲击或免疫球蛋白治疗,症状和体征明显改善,缓解期辅以免疫抑制剂,随访无复发。结论中枢神经系统和周围神经系统同时或相继出现脱髓鞘性改变,可能是一种不同于单纯中枢神经系统脱髓鞘和周围神经系统脱髓鞘的新疾病体,也可能是一种新的叠加综合征。     

Idiopathic orthostatic hypotension: Shy-Drager's syndrome (author's transl)]

The authors report a clinical case of idiopathic orthostatic hypotension with associated signs of focal cerebrovascular lesion. They discuss aetiopathologic hypotheses which have been proposed to interpret pathological situations of this type. It seems reasonable to attribute an autonomous disease classification to idiopathic orthostatic hypotension as a systemic degenerative disease concerning peripheral and central structures with vegetative functions. The Shy-Drager syndrome (idiopathic orthostatic hypotension associated with diverse signs of involvement of the central nervous system) must not, however, be considered as an independent form of disease. The associated signs are none other than the expression of commonly found cerebral ischemic lesions deriving from abrupt arterial hypotension, or from cerebral dysautoregulation; or the expression of the association of a systemic degenerative disease with another, a not infrequent occurrence well known in the pathology of the nervous system.     

Update on neuroimaging in infectious central nervous system disease

PURPOSE OF REVIEW: Neuroimaging constitutes an important component in the diagnosis of the underlying infectious agents in central nervous system infection. This review summarizes progress in the neuroimaging of infectious central nervous system disease since January 2003. It focuses on imaging of viral encephalitis, including that caused by exotic and emerging viruses, and on imaging in immunodeficient patients. RECENT FINDINGS: Diffusion-weighted imaging has been shown to be superior to conventional magnetic resonance imaging for the detection of early signal abnormalities in herpes simplex virus encephalitis but also in enterovirus 71 encephalitis and in West Nile encephalitis. Several studies defined the pattern of magnetic resonance imaging signal changes in endemic diseases such as West Nile encephalitis, Murray Valley encephalitis, enterovirus 71 encephalitis and Japanese encephalitis, but also in encephalitides due to ubiquitous viruses such as measles virus and Lyssavirus (rabies). In patients with HIV infection, apparent diffusion coefficient ratios obtained by diffusion-weighted imaging were significantly greater in lesions due to Toxoplasma encephalitis than in primary central nervous system lymphomas. SUMMARY: The diagnosis of unclear infectious central nervous system diseases remains a challenge. More recent magnetic resonance imaging techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy, provide additional helpful information. However, the mainstay of diagnosis remains the detection of viral DNA or serological markers of specific infectious agents within the cerebrospinal fluid.     

New directions in multiple sclerosis therapy: matching therapy with pathogenesis

All currently approved therapies for multiple sclerosis (MS) modulate systemic immune components prior to their entry into the central nervous system (CNS). Available data indicate they lack impact on the progressive phases of disease; the more potent systemic immune-directed agents predispose to development of infectious or neoplastic disorders. Development of new agents that enhance disease stage related efficacy and limit systemic toxicity will need to consider the underlying mechanisms related to each phase of the clinical disorder, namely relapses, remission, and progression. This report focuses on disease related mechanisms ongoing within the CNS that contribute to the different phases of MS and how these may serve as potential therapeutic targets. Such mechanisms include CNS compartment specific immunologic properties especially as related to the innate immune system and neural cell-related properties that are determinants of the extent of actual tissue injury and repair (or lack thereof).     

Vasculitis of the nervous system

Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PMS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS. “Primary angiitis of the CNS” is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments.. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.     

Sepsis associated encephalopathy

INTRODUCTION: Alteration of sensorium or an encephalopathy is a common diagnostic dilemma in critically ill patients and can be caused by a number of conditions. Sepsis associated encephalopathy (SAE) is now the most common encephalopathy encountered among intensive care unit (ICU) patients. DEFINITIONS: SAE is an encephalopathy attributed primarily to sepsis or systemic inflammatory response syndrome (SIRS) and has often been a diagnosis of exclusion. CONCLUSION: It is important to recognize SAE for its therapeutic and prognostic aspects. SAE worsens morbidity and mortality among ICU patients. Most therapeutic options center around aggressive treatment of the underlying infection.     

Stroke associated with infections including immunizations

Stroke in children and adolescents can be a complication of a central nervous sytem infection, such as bacterial meningitis, varicella zoster virus infection, human immunodeficiency virus infection, or tuberculous meningoencephalitis, or might complicate pharyngitis, pneumonia, a systemic viral illness, or sepsis. Rarely, stroke might be a complication of the varicella zoster vaccine. The clinical presentation of stroke associated with infection is similar to stroke attributable to other causes, but the diagnostic approach is different. A review of the pathophysiology, diagnostic studies, and treatment of infectious causes of stroke in children and adolescents is presented.     

Angiitis of the central nervous system.

Angiitis of the central nervous system is a rare disease which may result from numerous causes responsible for the presence of inflammatory lesions of the vascular wall. These inflammatory lesions may sometimes be associated with necrosis. Cerebral vessels of all sizes may be involved. The clinical presentation is highly variable, with focal to diffuse manifestations and acute to chronic evolution. Angiography is the cornerstone diagnostic procedure, showing multiple segmental stenoses of the cerebral arteries sometimes separated by fusiform dilatations. Although suggestive, this angiographical pattern is not unequivocal and other causes must be carefully ruled out. Only cerebral and/or leptomeningeal biopsy can provide a definite diagnosis of cerebral angiitis but this invasive diagnostic procedure is not performed in the majority of cases. Among the numerous causes of cerebral angiitis, one can individualize infectious diseases, primary systemic angiitis with cerebral involvement, angiitis secondary to various systemic diseases and other miscellaneous causes such as drug abuse or neoplasm.     

Recurrent stroke as a manifestation of primary angiitis of the central nervous system in a patient infected with human immunodeficiency virus

CONTEXT: Cerebral vasculitis in patients infected with human immunodeficiency virus (HIV) is usually related to additional or secondary infectious agents other than neoplastic diseases or HIV itself. OBJECTIVE: To describe a 31-year-old patient infected with HIV who presented with 2 recurrent, acute episodes of neurologic impairment in a 5-month period. DESIGN: Comparison of clinical and histologic data between the present case and previously published cases. SETTING: Community hospital. PATIENT: A 31-year-old, HIV-infected patient with recurrent strokes and chronic lymphocytic meningitis. INTERVENTION: After ruling out cardiac embolisms and coagulation disorders, the presence of central nervous system vasculitis, probably secondary to an infectious process, was suspected based on the clinical examination and cerebrospinal fluid abnormalities. RESULTS: Necropsy findings suggest the diagnosis of primary angiitis of the central nervous system, and the only infectious agent that could be found was HIV. CONCLUSIONS: Histologic studies were compatible with a diagnosis of primary angiitis of the central nervous system, but the pathogenic role of HIV in the genesis of the vasculitic process cannot be elucidated.     

Post infectious CNS disorders: towards a unified approach

The spectrum of post infectious (PI) central nervous system (CNS) conditions includes a range of grey and white-matter disorders which can occur after viral or bacterial infections or in response to vaccinations. The clinical, radiological and immunological phenomenology raises a number of issues regarding the nature of immune-mediated CNS abnormalities, their etiology, pathogenesis and therapy. Here we focus on crucial issues pertaining to pathogenesis and aim to identify where current knowledge is insufficient in order to suggest future avenues of clinical and experimental research that may help to devise optimal therapy for these conditions.     

Peripheral neuropathy in pediatric systemic lupus erythematosus

Peripheral neuropathy is an uncommon manifestation of systemic lupus erythematosus and has not yet been characterized in pediatric patients. We report the clinical and electrophysiologic features of peripheral neuropathy in one child and three adolescents with lupus erythematosus. There were three females and one male. The peripheral neuropathy followed the onset of lupus erythematosus by a mean of 3 years. The onset of the neuropathy correlated with lupus erythematosus activity and presented with either severe pain or dropfoot. Nerve conduction studies revealed sensory and motor polyneuropathy in all patients and mononeuritis multiplex in two patients. Only one patient had associated central nervous system involvement at that time. All patients were positive for IgM and IgG anticardiolipin antibodies. Patients were treated with steroids, gabapentin, carbamazepine, azathioprine, and cyclophosphamide. Response to treatment was variable: two patients recovered and two had a partial response. Although an unusual manifestation, peripheral neuropathy should be kept in mind as part of the neurologic spectrum in lupus erythematosus. It is not necessarily associated with central nervous system disease. A role for antiphospholipid antibodies in the pathogenesis is suggested.     

270例中枢神经系统结核病患者的临床及病理

目的 分析中枢神经系统结核病的临床表现、病理特征及其误诊的原因。方法 对２７０例中枢系统结核病患者进行回顾性调查,并对其中３２例经尸解理证实的患者进行分析。结果临床表现除脑膜刺激征、颅高压外有中枢神经系统局灶损害症状,死亡６１例（占２２．５９％）,颅高压是其主要的死因,尸检发现以脑膜病变为主,大脑实质、小脑、脑干、脑室及脑血管和脊髓均有病变。误诊４９例,其中生前诊３２例,总误诊率为１８．１５％,结     

脓毒症发生相关脑病的危险因素：284例病例报告

Sepsis-associated encephalopathy(SAE) is a diffuse and acute cerebral dysfunction caused by sepsis.Many sepsis patients exhibit acute deterioration in mental status during the early stage of disease,and central nervous system dysfunction has been shown to increase patient mortality.The present study selected 284 sepsis patients who were admitted to the Intensive Care Unit of Beijing Friendship Hospital,Capital Medical University,from January to December 2009.The patients were assigned to SAE and non-SAE patient groups according to SAE occurrence.SAE incidence was 37.68%,and mortality was significantly greater in SAE patients compared with non-SAE patients(41.12% vs.17.51%,P < 0.01).Univariate analysis and multivariate logistic regression analysis indicated lower arterial partial pressure of oxygen and greater alanine aminotransferase and Acute Physiology and Chronic Health Evaluation II scores in the SAE group compared with the non-SAE group.Arterial partial pressure of oxygen,alanine aminotransferase,and Acute Physiology and Chronic Health Evaluation II scores were determined to be potential risk factors for SAE.     

Central nervous system infections in the systemic vasculitides

PURPOSE OF REVIEW: Central nervous system infections are not uncommon in systemic vasculitides. Being vigilant of central nervous system infections as an alternative consideration, instead of systemic vasculitides per se, could prove to be lifesaving in certain circumstances. RECENT FINDINGS: Common pathogens, such as tuberculosis, Cryptococcus, and Listeria, still occur commonly as the major causes of central nervous system infection in systemic vasculitides. However, rare pathogens could be responsible among those immunocompromised hosts, and they should not be overlooked. The manifestation of central nervous system infection tends to be atypical among systemic vasculitides patients. History, physical, and cerebrospinal fluid analyses are still time-honored approaches to establishing the correct diagnosis. Newer techniques such as interferon-gamma release assay for tuberculosis, cerebrospinal fluid cytokine, or chemokine profiling need further validation and careful interpretation among such a special patient population. Immune disturbance, mainly due to immunosuppressive therapy, and polymorphism of the innate immune pathway (for example, Toll-like receptor) could be susceptibility factors for certain central nervous system infections. The biologic agents (for example, anti-tumor necrosis factor alpha, and B-cell depletion therapy) represent novel methods for treating systemic vasculitides, but they raise a critical issue owing to their increased likelihood for being associated with opportunistic infections. SUMMARY: Despite the recent progress in this special field, the mortality of central nervous system infection in systemic vasculitides is still high, and the prognostic factors are still largely undetermined.     

Systemic and central immunity in Alzheimer's disease: therapeutic implications

Clinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system.