RESUMO
BACKGROUND: Varicella zoster virus (VZV) vasculopathy produces stroke secondary to viral infection of cerebral arteries. Not all patients have rash before cerebral ischemia or stroke. Furthermore, other vasculitides produce similar clinical features and comparable imaging, angiographic, and CSF abnormalities. METHODS: We review our 23 published cases and 7 unpublished cases of VZV vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody and were positive for either or both. RESULTS: Among 30 patients, rash occurred in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%). Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small arteries were involved in 15 (50%), small arteries in 11 (37%), and large arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients, reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. CONCLUSIONS: Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV) vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most patients had mixed large and small artery involvement. Detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit of concurrent steroid therapy awaits studies with larger case numbers.
Assuntos
Transtornos Cerebrovasculares/líquido cefalorraquidiano , Transtornos Cerebrovasculares/virologia , Herpesvirus Humano 3 , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/etiologia , Varicela/líquido cefalorraquidiano , Varicela/complicações , Varicela/virologia , Exantema/líquido cefalorraquidiano , Exantema/diagnóstico , Exantema/virologia , Herpes Zoster/líquido cefalorraquidiano , Herpes Zoster/complicações , Herpes Zoster/virologia , Humanos , Imageamento por Ressonância Magnética/métodosAssuntos
Herpes Zoster/complicações , Isquemia do Cordão Espinal/etiologia , Isquemia do Cordão Espinal/patologia , Vasculite do Sistema Nervoso Central/complicações , Vasculite do Sistema Nervoso Central/virologia , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Artérias/patologia , Artérias/fisiopatologia , Artérias/virologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Paralisia/etiologia , Paralisia/patologia , Paralisia/fisiopatologia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Isquemia do Cordão Espinal/fisiopatologia , Falha de Tratamento , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/patologia , Bexiga Urinaria Neurogênica/fisiopatologia , Vasculite do Sistema Nervoso Central/fisiopatologiaRESUMO
OBJECTIVE: To demonstrate the specificity of expanded CD138(+) plasma cell clones recovered from the CSF of a patient with subacute sclerosing panencephalitis (SSPE) for measles virus (MV). METHODS: IgG variable region sequences of single-antibody-secreting CD138(+) cells sorted from SSPE CSF were amplified by single-cell PCR and analyzed. Human IgG1 recombinant antibodies (rAbs) were produced from four expanded CD138(+) clones and assayed for immunoreactivity against MV proteins. RESULTS: Clonal expansion was a prominent feature of the SSPE plasma cell repertoire, and each of the four rAbs assayed was specific for either the MV fusion or the MV nucleocapsid protein. CONCLUSIONS: Expanded plasma cell clones in the CSF of patients with subacute sclerosing panencephalitis produce disease-relevant antibodies. Recombinant antibodies derived from CSF B cells could provide a tool to identify target antigens in idiopathic inflammatory disorders.
Assuntos
Anticorpos Antivirais/líquido cefalorraquidiano , Vírus do Sarampo/imunologia , Plasmócitos/virologia , Panencefalite Esclerosante Subaguda/líquido cefalorraquidiano , Panencefalite Esclerosante Subaguda/virologia , Proteínas Virais/imunologia , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Separação Celular , Células Cultivadas , Criança , Células Clonais/imunologia , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Masculino , Proteínas do Nucleocapsídeo/imunologia , Plasmócitos/imunologia , Proteínas Recombinantes de Fusão/líquido cefalorraquidiano , Proteínas Recombinantes de Fusão/imunologia , Panencefalite Esclerosante Subaguda/imunologia , Proteínas Virais de Fusão/imunologiaRESUMO
BACKGROUND: Factors that may obscure the diagnosis of varicella zoster virus (VZV) vasculopathy include the absence of rash before TIAs or stroke as well as similar clinical features and imaging, angiographic, and CSF abnormalities to those of other vasculopathies. Diagnosis relies on virologic confirmation that detects VZV DNA, anti-VZV IgG antibody, or both in the CSF. METHODS: We reviewed our current 14 cases of patients diagnosed with VZV vasculopathy based on combined clinical, imaging, angiographic, or CSF abnormalities. All CSFs must have been tested for VZV DNA by PCR and for anti-VZV IgG antibody by enzyme immunoassay and found to be positive for either or both. Of the 14 subjects, 8 had a history of recent zoster, whereas 6 had no history of zoster rash before developing vasculopathy. RESULTS: All 14 subjects (100%) had anti-VZV IgG antibody in their CSF, whereas only 4 (28%) had VZV DNA. The detection of anti-VZV IgG antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection of VZV DNA (p < 0.001). CONCLUSIONS: In varicella zoster virus (VZV) vasculopathy, the diagnostic value of detecting anti-VZV IgG antibody in CSF is greater than that of detecting VZV DNA. Although a positive PCR for VZV DNA in CSF is helpful, a negative PCR does not exclude the diagnosis of VZV vasculopathy. Only when the CSF is negative for both VZV DNA and anti-VZV IgG antibody can the diagnosis of VZV vasculopathy be excluded.
Assuntos
Anticorpos Antivirais/líquido cefalorraquidiano , Varicela/complicações , Herpesvirus Humano 3/imunologia , Imunoglobulina G/líquido cefalorraquidiano , Vasculite do Sistema Nervoso Central/líquido cefalorraquidiano , Vasculite do Sistema Nervoso Central/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias Cerebrais/imunologia , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , DNA Viral/análise , DNA Viral/genética , Feminino , Herpesvirus Humano 3/genética , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Vasculite do Sistema Nervoso Central/diagnósticoAssuntos
Neoplasias da Mama/patologia , Carcinoma/secundário , Gânglios Espinais/patologia , Herpes Zoster/patologia , Neoplasias Meníngeas/secundário , Meningite Asséptica/complicações , Adulto , Anticorpos Antivirais/líquido cefalorraquidiano , Antivirais/administração & dosagem , Neoplasias da Mama/complicações , Carcinoma/complicações , Doença Crônica , Evolução Fatal , Feminino , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/imunologia , Humanos , Hidronefrose/complicações , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/complicações , Meningite Asséptica/patologia , Meningite Asséptica/fisiopatologia , Músculos Psoas/patologia , Insuficiência Renal/etiologia , Raízes Nervosas Espinhais/patologiaRESUMO
Two-dimensional gel electrophoresis and peptide mass fingerprinting were used to identify proteins in cerebrospinal fluid (CSF) pooled from three patients with multiple sclerosis (MS) and in CSF pooled from three patients with non-MS inflammatory central nervous system (CNS) disorders. Resolution of CSF proteins on three pH gradients (3-10, 4-7 and 6-11) enabled identification of a total of 430 spots in the MS CSF proteome that represented 61 distinct proteins. The gels containing MS CSF revealed 103 protein spots that were not seen on control gels. All but four of these 103 spots were proteins known to be present in normal human CSF. The four exceptions were: CRTAC-IB (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC-like protein (a calcium binding cell signalling glycoprotein), and autotaxin t (a phosphodiesterase). It remains unknown whether these four proteins are related to the cause and pathogenesis of MS.
Assuntos
Líquido Cefalorraquidiano/química , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Proteômica , Adulto , Eletroforese em Gel Bidimensional , Feminino , Humanos , Pessoa de Meia-Idade , Mapeamento de Peptídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Proteomics combines two-dimensional gel electrophoresis and peptide mass fingerprinting and can potentially identify a protein(s) unique to disease. Such proteins can be used either for diagnosis or may be relevant to the pathogenesis of disease. Because patients with multiple sclerosis (MS) have increased amounts of immunoglobulin (Ig) G in their cerebrospinal fluid (CSF) that is directed against an as yet unidentified protein, we are applying proteomics to MS CSF, studies that require optimal separation of proteins in human CSF. We found that recovery of proteins from CSF of MS patients was improved using ultrafiltration, rather than dialysis, for desalting. Resolution of these proteins was enhanced by acetone precipitation of desalted CSF before electrophoresis and by fractionation of CSF using Cibacron Blue sepharose affinity chromatography. Improved protein recovery and resolution will facilitate excision from gels for analysis by peptide mass fingerprinting.
Assuntos
Proteínas do Líquido Cefalorraquidiano/análise , Eletroforese em Gel Bidimensional/métodos , Esclerose Múltipla/líquido cefalorraquidiano , Albuminas , Humanos , Focalização Isoelétrica/métodos , SaisRESUMO
After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.
Assuntos
Herpes Zoster/complicações , Herpesvirus Humano 3 , Paresia/etiologia , Doenças da Medula Espinal/etiologia , Zoster Sine Herpete/etiologia , Doença Crônica , Feminino , Anticorpos Anti-HTLV-I/sangue , Anticorpos Anti-HTLV-I/líquido cefalorraquidiano , Anticorpos Anti-HTLV-I/metabolismo , Herpes Zoster/sangue , Herpes Zoster/líquido cefalorraquidiano , Herpes Zoster/virologia , Humanos , Pessoa de Meia-Idade , Paresia/sangue , Paresia/líquido cefalorraquidiano , Paresia/virologia , Doenças da Medula Espinal/sangue , Doenças da Medula Espinal/líquido cefalorraquidiano , Doenças da Medula Espinal/virologia , Fatores de Tempo , Zoster Sine Herpete/sangue , Zoster Sine Herpete/líquido cefalorraquidiano , Zoster Sine Herpete/virologiaRESUMO
Polymerase chain reaction (PCR) revealed herpes simplex virus (HSV) and varicella zoster virus (VZV) DNA in human nodose and celiac ganglia. This is the first detection of VZV DNA in ganglia of the human autonomic nervous system. The ability of reactivated VZV to produce serious, sometimes fatal neurological disease in the absence of rash, raises the possibility that VZV reactivation from autonomic ganglia might be involved in visceral disease.
Assuntos
Gânglios Simpáticos/virologia , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Gânglio Nodoso/virologia , Idoso , Idoso de 80 Anos ou mais , DNA Viral/análise , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Ativação ViralRESUMO
The presence of increased IgG in the brains of humans with infectious and inflammatory CNS diseases of unknown etiology such as multiple sclerosis may be a clue to the cause of disease. For example, the intrathecally synthesized oligoclonal bands in diseases such as subacute sclerosing panencephalitis (SSPE) or cryptococcal meningitis have been shown to represent Ab directed against the causative agents, measles virus (MV), or Cryptococcus neoformans, respectively. Using SSPE as a model system, we developed a strategy to identify the antigenic targets of the intrathecal disease-relevant IgG in chronic human inflammatory and demyelinating diseases of the CNS. Libraries of cDNA Ags were displayed on the surface of T7Select bacteriophage and biopanned on IgG extracted from the brain of an SSPE patient, or on a monospecific recombinant Fab identified from SSPE brain. After three or six rounds of biopanning on either Ab, positive phage-displayed Ags reacting with IgG were enriched to 35-77% of all panned clones. Sequence analysis of the positive clones identified fragments of the nucleocapsid protein of MV, the cause of SSPE. The sensitivity of the system was determined by diluting the positive clones from this SSPE phage-displayed library at a ratio of 10(-6) into another phage-displayed library that did not contain any detectable MV Ags; after six rounds of panning, the positive clones comprised 34% of all phage and were also shown to be MV nucleocapsid specific. This strategy will be useful to identify potentially rare Ags in diseases of unknown cause.
Assuntos
Antígenos Virais/imunologia , Encéfalo/imunologia , Imunoglobulina G/imunologia , Vírus do Sarampo/imunologia , Biblioteca de Peptídeos , Panencefalite Esclerosante Subaguda/imunologia , Adulto , Antígenos Virais/genética , Humanos , Masculino , Proteínas do Nucleocapsídeo/genética , Proteínas do Nucleocapsídeo/imunologia , Sensibilidade e EspecificidadeRESUMO
Herpesviruses cause various acute, subacute, and chronic disorders of the central (CNS) and peripheral (PNS) nervous systems in adults and children. Both immunocompetent and immunocompromised individuals may be affected. Zoster (shingles), a result of reactivation of varicella zoster virus (VZV), is the most frequent neurologic complication. Other neurological complications include encephalitis produced by type I herpes simplex virus (HSV-1), and less frequently HSV-2, as well as by VZV and cytomegalovirus (CMV). Acute meningitis is seen with VZV and HSV-2, and benign recurrent meningitis with HSV-2. Combinations of meningitis/ encephalitis and myelitis/radiculitis are associated with Epstein Barr Virus (EBV); myelitis with VZV, CMV, EBV, and HSV-2; and ventriculitis/encephalitis with VZV and CMV. Brainstem encephalitis due to HSV and VZV, and polymyeloradiculitis due to CMV are well documented. HHV-6 produces childhood exanthem subitum (roseola) and febrile convulsions. Immunocompetent and immunocompromised hosts manifest different incidences and patterns of herpesvirus infections. For example, stroke due to VZV-mediated large vessel disease (herpes zoster ophthalmicus) occurs predominantly in immunocompetent hosts, while small vessel disease (leukoencephalitis) and ventriculitis develop almost exclusively in immunocompromised patients. EBV-associated primary CNS lymphomas also are restricted to immunosuppressed individuals. Recent large CSF PCR studies have shown that VZV, EBV, and CMV more frequently produce meningitis, encephalitis, or encephalopathy in immunocompetent hosts than was formerly realized. We review herpesvirus infections of the nervous system and illustrate the expanding spectrum of disease by including examples of a 75-year-old male on steroid treatment for chronic lung disease with fatal HSV-2 meningitis and an 81-year-old male with myasthenia gravis, long-term azathioprine use, and an EBV-associated primary CNS lymphoma.
Assuntos
Infecções por Herpesviridae/classificação , Sistema Nervoso/virologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Citomegalovirus/genética , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Feminino , Infecções por Herpesviridae/patologia , Infecções por Herpesviridae/fisiopatologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/imunologia , Herpesvirus Humano 2/patogenicidade , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Herpesvirus Humano 3/patogenicidade , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 6/genética , Herpesvirus Humano 6/imunologia , Herpesvirus Humano 6/patogenicidade , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/patologia , Sistema Nervoso/fisiopatologiaRESUMO
Herpesviruses are among the most successful human pathogens. In healthy individuals, primary infection is most often inapparent. After primary infection, the virus becomes latent in ganglia or blood mononuclear cells. Three major subfamilies of herpesviruses have been identified based on similar growth characteristics, genomic structure, and tissue predilection. Each herpesvirus has evolved its own unique ecological niche within the host that allows the maintenance of latency over the life of the individual (e.g. the adaptation to specific cell types in establishing latent infection and the mechanisms, including expression of different sets of genes, by which the virus remains latent). Neurotropic alphaherpesviruses become latent in dorsal root ganglia and reactivate to produce epidermal ulceration, either localized (herpes simplex types 1 and 2) or spread over several dermatomes (varicalla-zoster virus). Human cytomegalovirus, the prototype betaherpesvirus, establishes latency in bone marrow-derived myeloid progenitor cells. Reactivation of latent virus is especially serious in transplant recipients and AIDS patients. Lymphotropic gammaherpesviruses (Epstein-Barr virus) reside latent in resting B cells and reactivate to produce various neurologic complications. This review highlights the alphaherpesvirus, specifically herpes simplex virus type 1 and varicella-zoster virus, and describes the characteristics of latent infection.
Assuntos
Infecções por Herpesviridae/genética , Herpesviridae/genética , Herpesviridae/patogenicidade , Latência Viral/genética , Alphaherpesvirinae/genética , Alphaherpesvirinae/patogenicidade , Animais , DNA Viral/genética , Gânglios Sensitivos/patologia , Gânglios Sensitivos/fisiopatologia , Gânglios Sensitivos/virologia , Regulação Viral da Expressão Gênica/fisiologia , Infecções por Herpesviridae/fisiopatologia , HumanosRESUMO
Varicella-zoster virus (VZV) causes chickenpox in children; establishes latency in cranial nerve, dorsal root, and autonomic ganglia; and reactivates decades later to produce zoster. VZV produces disease only in humans. Although attempts to produce disease and study VZV latency in experimentally infected animals have resulted in virus in trigeminal or dorsal root ganglia, no clinical signs of infection or reactivation developed. In contrast, simian varicella virus (SVV) produces a naturally occurring exanthematous disease in non-human primates that mimics human varicella. Experimental inoculation of non-human primates causes similar, if not identical, clinical and pathological changes observed in monkeys naturally infected with SVV. Like VZV, SVV becomes latent in ganglia and reactivates, often with entire body rash. SVV and VZV encode antigenically related polypeptides. Both virus genomes have been sequenced and shown to be colinear, sharing up to 75% DNA homology. During latency, an SVV homolog of one of the five VZV genes transcribed in latently infected human ganglia has been detected in monkey ganglia. Preliminary studies in which monkeys were inoculated intratracheally with SVV revealed the presence of viral DNA and RNA in multiple tissues, including blood mononuclear cells, months after experimental infection. These findings differed from the expected restricted localization of the virus DNA to ganglia only and the expected limited viral gene expression, and probably reflect the high virus load delivered intratracheally compared to natural SVV infection in monkeys. Nevertheless, clinical, pathological, and molecular similarities between SVV and VZV indicate that SVV infection in non-human primates has considerable potential as an animal model for human varicella.
Assuntos
Varicela/genética , Modelos Animais de Doenças , Haplorrinos/virologia , Herpesvirus Humano 3/patogenicidade , Animais , Varicela/patologia , Varicela/fisiopatologia , DNA Viral/genética , DNA Viral/metabolismo , Herpesvirus Humano 3/genética , Humanos , Sistema Nervoso/patologia , Sistema Nervoso/fisiopatologia , Sistema Nervoso/virologia , Carga ViralRESUMO
The authors report three patients with acute, chronic, and recurrent neuropathy associated with varicella zoster virus (VZV) infection but without zoster rash. CSF of all three patients contained VZV immunoglobulin G antibody, but not herpes simplex virus. In two patients, serum/CSF ratios of VZV immunoglobulin G were reduced compared to normal ratios for immunoglobulin G and albumin, and one patient also had VZV immunoglobulin M in CSF. All three patients received antiviral therapy and improved. The diagnosis of nervous system infection by VZV may be confirmed by the presence of antibody to VZV in CSF even without detectable VZV DNA.
Assuntos
Doenças do Sistema Nervoso Central/patologia , Sistema Nervoso Central/patologia , Herpes Zoster/patologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Central/fisiopatologia , Feminino , Herpes Zoster/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , RecidivaRESUMO
The strict definition of the Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by an erythematous vesicular rash on the ear (zoster oticus) or in the mouth. J Ramsay Hunt, who described various clinical presentations of facial paralysis and rash, also recognised other frequent symptoms and signs such as tinnitus, hearing loss, nausea, vomiting, vertigo, and nystagmus. He explained these eighth nerve features by the close proximity of the geniculate ganglion to the vestibulocochlear nerve within the bony facial canal. Hunt's analysis of clinical variations of the syndrome now bearing his name led to his recognition of the general somatic sensory function of the facial nerve and his defining of the geniculate zone of the ear. It is now known that varicella zoster virus (VZV) causes Ramsay Hunt syndrome. Compared with Bell's palsy (facial paralysis without rash), patients with Ramsay Hunt syndrome often have more severe paralysis at onset and are less likely to recover completely. Studies suggest that treatment with prednisone and acyclovir may improve outcome, although a prospective randomised treatment trial remains to be undertaken. In the only prospective study of patients with Ramsay Hunt syndrome, 14% developed vesicles after the onset of facial weakness. Thus, Ramsay Hunt syndrome may initially be indistinguishable from Bell's palsy. Further, Bell's palsy is significantly associated with herpes simplex virus (HSV) infection. In the light of the known safety and effectiveness of antiviral drugs against VZV or HSV, consideration should be given to early treatment of all patients with Ramsay Hunt syndrome or Bell's palsy with a 7-10 day course of famciclovir (500 mg, three times daily) or acyclovir (800 mg, five times daily), as well as oral prednisone (60 mg daily for 3-5 days). Finally, some patients develop peripheral facial paralysis without ear or mouth rash, associated with either a fourfold rise in antibody to VZV or the presence of VZV DNA in auricular skin, blood mononuclear cells, middle ear fluid, or saliva. This indicates that a proportion of patients with "Bell's palsy" have Ramsay Hunt syndrome zoster sine herpete. Treatment of these patients with acyclovir and prednisone within 7 days of onset has been shown to improve the outcome of recovery from facial palsy.
Assuntos
Transtornos Parkinsonianos , Paralisia de Bell/fisiopatologia , HumanosRESUMO
BACKGROUND: Diseases that present with protean manifestations are the diseases most likely to pose diagnostic challenges for both clinicians and pathologists. Among the most diverse disorders caused by a single known toxic, metabolic, neoplastic, or infectious agent are the central and peripheral nervous system complications of varicella-zoster virus (VZV). METHODS: The pathologic correlates of the neurologic complications of VZV infection, as well as current methods for detecting viral infections, are discussed and presented in pictorial format for the practicing pathologist. RESULTS: Varicella-zoster virus causes chickenpox (varicella), usually in childhood; most children manifest only mild neurologic sequelae. After chickenpox resolves, the virus becomes latent in neurons of cranial and spinal ganglia of nearly all individuals. In elderly and immunocompromised individuals, the virus may reactivate to produce shingles (zoster). After zoster resolves, many elderly patients experience postherpetic neuralgia. Uncommonly, VZV can spread to large cerebral arteries to cause a spectrum of large-vessel vascular damage, ranging from vasculopathy to vasculitis, with stroke. In immunocompromised individuals, especially those with cancer or acquired immunodeficiency syndrome, deeper tissue penetration of the virus may occur (as compared with immunocompetent individuals), with resultant myelitis, small-vessel vasculopathy, ventriculitis, and meningoencephalitis. Detection of the virus in neurons, oligodendrocytes, meningeal cells, ependymal cells, or the blood vessel wall often requires a combination of morphologic, immunohistochemical, in situ hybridization, and polymerase chain reaction (PCR) methods. The PCR analysis of cerebrospinal fluid remains the mainstay for diagnosing the neurologic complications of VZV during life. CONCLUSIONS: Varicella-zoster virus infects a wide variety of cell types in the central and peripheral nervous system, explaining the diversity of clinical disorders associated with the virus.
Assuntos
Varicela/diagnóstico , Herpes Zoster/diagnóstico , Doenças do Sistema Nervoso/diagnóstico , Adulto , Idoso , Anticorpos Antivirais/líquido cefalorraquidiano , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Varicela/patologia , Criança , Diagnóstico Diferencial , Feminino , Herpes Zoster/patologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/imunologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Imunocompetência , Hospedeiro Imunocomprometido , Masculino , Doenças do Sistema Nervoso/patologia , Neuralgia/diagnóstico , Neuralgia/patologia , Nervos Periféricos/patologia , Nervos Periféricos/virologia , Reação em Cadeia da PolimeraseRESUMO
The cause of multiple sclerosis (MS) is unknown. Despite indications from epidemiological and identical-twin studies that MS is infectious, no virus or other infectious agent has been tightly linked to disease. The isolation of Chlamydia pneumoniae from the cerebrospinal fluid (CSF) of MS patients and the detection of both Chlamydia-specific DNA and antibody in MS CSF have been reported. Other analyses of brain and CSF have shown no significant difference in C. pneumoniae-specific DNA or antibody between MS and control subjects. Recent work has revealed intrathecal production of C. pneumoniae-specific IgG in only 24% of MS patients compared with 5% of control patients. More importantly, the major CSF oligoclonal bands from MS patients did not react to C. pneumoniae.