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1226.   Angelini L.  Bugiani M.  Zibordi F.  Cinque P.  Bizzi A. Brainstem encephalitis resulting from Epstein-Barr virus mimicking an infiltrating tumor in a child. Pediatric Neurology.  22(2):130-2, 2000 Feb.


A case of a child with subacute neurologic features and imaging findings   consistent with a brainstem encephalitis that was discovered to be related to a primary central nervous system infection caused by Epstein-Barr virus is presented. A brainstem tumor was initially suspected, but a correct diagnosis was formulated on the basis of the favorable clinical course and the detection of positive Epstein-Barr virus serology. In contrast to a prompt recovery of neurologic signs the neuroimaging alterations persisted for a longer time. The present report emphasizes the possible role of Epstein-Barr virus in the pathogenesis of infectious neurologic disorders in childhood, underlining the unusual presentation of a brainstem encephalitis, and considers the discrepancy between the course of neurologic features and the evolution of imaging alterations.


1227.   Anonymous. WHO Expert Committee on Biological Standardization. World Health Organization Technical Report Series.  889:i-vi, 1-111, 1999.


This report presents the recommendations of a WHO Expert Committee  commissioned to coordinate activities leading to the adoption of international requirements for the production and control of vaccines and other biologicals and the establishment of international biological reference materials. The report starts with a discussion of general issues brought to the Committee's attention and provides information on the status and development of reference materials for various antibodies, antibiotics, antigens, blood products and related substances, cytokines and growth factors and other substances for which the Committee has discerned a need for international reference materials. The second part of the report, of particular relevance of manufacturers and national control authorities, contains guidelines for the production and control of  synthetic peptide vaccines, requirements for tick-borne encephalitis vaccine (inactivated), guidelines for thromboplastins and plasma used to control oral anticoagulant therapy, an amendment to the requirements for hepatitis B vaccine made by recombinant DNA techniques and a report on the standardization and calibration of cytokine immunoassays.


1228.   Carrigan DR. Adenovirus infections in immunocompromised patients. [Review] [05 refs] American Journal of Medicine.  102(3A):71-4, 1997 Mar 17.


Adenovirus infections have been reported in as many as one-fifth of bone  marrow transplant (BMT) recipients and patients with acquired immunodeficiency syndrome (AIDS), and in a lesser, though still prominent, proportion of organ transplant recipients. The relative contributions of primary infections versus reactivations from latency in immunocompromised patients remain unclear. Compared with adult BMT recipients, pediatric BMT recipients appear to be infected by adenovirus more frequently and earlier in the post-transplant period. The diagnosis of adenovirus infection is complicated by the existence of > 40 viral serotypes, although certain subgroups are more likely to be involved in certain patient populations. Adenoviruses are responsible for a broad range of clinical diseases that may be associated with high mortality, including pneumonia, hepatitis, encephalitis, hemorrhagic cystitis, and gastroenteritis. The clinical and histopathologic features of adenovirus disease may resemble those of cytomegalovirus disease, potentially complicating the diagnosis. Risk  factors for clinical adenovirus disease include the number of sites from which the virus is cultured and, in BMT recipients, the presence of moderate to severe acute graft-versus-host disease. [References: 05]


1229.   Chen Z.  Dong Y.  Cui W. Detection and identification of enteroviruses RNA by using polymerase chain reaction. Journal of Tongji Medical University.  18(3):156-60, 1998.


For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay. Primers homologous to the conserved 5' non-coding region were designed by analyzing enteroviral genomes, and then they were used to enzymatically amplify RNA from 31 prototype enteroviral strains and enteroviruses (EV) in cerebrospinal fluid (CSF) of 34 cases of aseptic meningitis and 11 cases of aseptic encephalitis. The RT-PCR products generated with these enteroviral primers were analyzed by agar gel electrophoresis and dot blot hybridization analysis. 31 EV strains showed an obvious monoclonal amplification band, and all dot blot hybridization  results were positive. Four other viruses and cells cultured were all negative. The study of sensitivity of the RT-PCR showed that amplification production were positive to 10(-2)-10(-3) 50% tissue culture infective doses. With this assay, 21 (61.8%) of 34 aseptic meningitis and 8 (72.7%) of 11 aseptic encephalitis contained EV RNA in CSF samples. Two cases of meningitis and one of encephalitis with EV infection were still positive during convalescence. Our results suggest that this RT-PCR method was a fast, sensitive and specific technique for detection of common EV infection.


1230.   Cuzzubbo AJ.  Vaughn DW.  Nisalak A.  Solomon T.  Kalayanarooj S.  Aaskov J.  Dung NM.  Devine PL. Comparison of PanBio Dengue Duo IgM and IgG capture ELISA and venture technologies dengue IgM and IgG dot blot. Journal of Clinical Virology.  16(2):135-44, 2000 Apr.


BACKGROUND: A number of commercial ELISA for dengue diagnosis have recently become available, though direct comparison between these assays have not been published. OBJECTIVES: The Venture Technologies Dengue IgM and IgG Dot Blot assays and the PanBio Dengue Duo IgM and IgG Capture ELISA were compared. STUDY DESIGN: Paired sera from patients with dengue (n=20) and Japanese encephalitis (JE, n=10), and single sera from patients with typhoid (n=10), leptospirosis (n=10) and scrub typhus (n=10) were assayed according to the manufacturer's instructions. RESULTS: The Dot Blot IgM ELISA showed higher sensitivity than the PanBio IgM ELISA (100 vs. 95%), while the PanBio IgM ELISA showed higher specificity in JE (100 vs. 20%) and non-flavivirus infections (100 vs. 97%). Defining elevation of either IgM or IgG as a positive result, the Dot Blot and ELISA tests both showed 100% sensitivity in dengue infection, while the PanBio test showed superior specificity in JE (70 vs. 0%) and non-flavivirus  infections (100 vs. 67%). CONCLUSIONS: Both assays are useful aids to the  serological diagnosis of dengue infection. The clinical setting, user  preference and local conditions will be important in determining which  test is more appropriate.


1231.   Dumpis U.  Crook D.  Oksi J. Tick-borne encephalitis. [Review] [98 refs]  Clinical Infectious Diseases.  28(4):882-90, 1999 Apr.


Tick-borne encephalitis (TBE) is a zoonotic arbovirus infection endemic to  Russia and Eastern and Central Europe. Despite being a common and serious life-threatening disease for which a mass vaccination program was implemented in Austria, there is only limited reference to this disease in the English-language literature. TBE is transmitted to humans usually by the bite of a tick (either Ixodes persulcatus or Ixodes ricinus); occasionally, cases occur following consumption of infected unpasteurized milk. Transmission is seasonal and occurs in spring and summer, particularly in rural areas favored by the vector. TBE is a serious cause of acute central nervous system disease, which may result in death or long-term neurological sequelae. Effective vaccines are available in a few countries. The risk for travelers of acquiring TBE is increasing with the  recent rise in tourism to areas of endemicity during spring and summer.  [References: 98]


1232.   Groen J.  Velzing J.  Copra C.  Balentien E.  Deubel V.  Vorndam V. Osterhaus AD. Diagnostic value of dengue virus-specific IgA and IgM serum antibody  detection. Microbes & Infection.  1(13):1085-90, 1999 Nov.


The diagnostic value of dengue virus (DV)-specific immunoglobulin A (IgA) serum antibody detection, by an indirect immunofluorescence assay (IFA) was evaluated. For this study, the kinetics of DV-specific IgA serum antibodies was analysed in two experimentally immunised macaques, paired samples from 35 patients suspected of a primary or secondary DV infection, paired sera from patients with high levels of IgA specific antibodies against influenza virus (n = 15), sera from patients with other viral infections (n = 40) and healthy blood donors (n = 10), which served as controls. The presence of DV-specific IgA serum antibodies in humans and in monkeys was compared with that of DV-specific IgM demonstrated in a capture enzyme-linked immunosorbent assay (ELISA). The development of DV-specific IgA and IgM antibodies in macaques proved to be similar to that observed in humans with a DV infection. In sera obtained from suspected primary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 1/6 (17%) and 6/6 (100%), whereas IgM was detected in 4/6 (67%) and 5/6 (83%), respectively. In sera from suspected secondary DV patients during the acute phase and convalescent phase, DV-specific IgA was detected in 18/29 (62%) and 28/29 (97%), whereas IgM was detected in 20/29 (69%) and 28/29 (97%), respectively. The control group consisted of five paired serum samples from yellow fever vaccinated individuals and a patient with acute tick-borne encephalitis, 15 paired serum samples from patients with high levels of IgA antibodies specific for influenza virus and 40 serum samples from patients with  specific IgM antibodies against other viruses. Ten serum samples from healthy blood donors were included. Among the control serum samples, in one patient, both DV-specific IgA and IgM antibodies were present, and in three sera DV-specific IgM antibodies could be demonstrated. These data suggest that detection of DV-specific IgA serum antibodies by IFA may have  additional value for the diagnosis of DV infection.



1233. Kalita J.  Misra UK. Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. Journal of the Neurological Sciences.  174(1):3-8, 2000 Mar 1.


Japanese encephalitis (JE) is the commonest endemic encephalitis but there are very few studies on the radiological changes and these are based on relatively small number of patients. The present study aims at comparing the CT scan and MRI findings in JE and correlate these with the reported histopathological findings. Forty two patients with JE were subjected to detailed neurological examination. Cranial CT scan was carried out in 38 and MRI scan in 31 patients. Haemagglutination inhibition test was carried out in the acute and convalescent sera. The CT scan and MRI findings have been compared. Both CT scan and MRI were available in 28 patients. In 21 patients, CT scans were abnormal and changes included thalamic hypodensity in 15, midbrain and basal ganglia hypodensity in 1 patient each, cerebral oedema in 4 and cortical atrophy with ventricular dilatation in 2 patients. MRI however was abnormal in all 31 patients including 17 with normal CT scan. Cranial MRI revealed either mixed intensity or hypointense lesion on T(1) and hyperintense or mixed intensity lesion on T(2) in  thalami in all except two patients. The MRI lesions were also noted in basal ganglia in 11, midbrain in 18, pons in 8, cerebellum and cerebral cortex in 6 patients each and subcortical white matter in 2 patients. MRI was more sensitive than CT scan in revealing thalamic and extrathalamic abnormalities. Thalamic changes may be helpful in the diagnosis of JE especially in endemic area.


1235.  Kamat DV.  Chakravorty BP. Comparative values of CSF-LDH isoenzymes in neurological disorders. Indian Journal of Medical Sciences.  53(1):1-6, 1999 Jan.


The present study was carried out to evaluate the usefulness of Cerebrospinal fluid (CSF) Lactate dehydrogenase (LDH) isoenzymes in the diagnosis in tuberculous meningitis (TBM), pyogenic meningitis (PM), viral encephalitis (VE) and hydrocephalus (HC). A characteristic dominance of isoenzymes in cerebrospinal fluid was observed: LDH4 in TBM while LDH3 in PM. However, in VE and HC, LDH2 and LDH1 were dominant respectively. The control subjects revealed the presence of isoenzymes LDH1 and LDH2 in very low concentrations. Pattern of LDH isoenzymes in CSF may serve as a diagnostic tool to differentiate these neurological disorders.


1236. Kumar R. Viral encephalitis of public health significance in India: current status. Indian Journal of Pediatrics.  66(1):73-83, 1999 Jan-Feb.


Japanese encephalitis (JE) and rabies are 2 viral encephalitis that are of  public health importance in India. JE is a zoonosis with the primary cycle  occurring in arthropods (mosquito vectors) and vertebrate animals (primarily the pig), man being only an incidental 'dead end' host. Out-breaks have been seen in most parts of India except the north west. The disease presents with a prodromal stage, an acute encephalitic stage with coma, convulsions and variable deficits and a convalescent stage. Diagnosis can be made by viral isolation from CSF or brain, or serologic tests such as haemagglutination inhibition test and IgM antibody capture ELISA in CSF and blood. There is no specific treatment. Mortality ranges from 20-50% and almost half the survivors have sequelae. The most effective control measure besides control of mosquitos is vaccination. A   killed mouse brain vaccine is being prepared in India and is safe and   effective but expensive. Rabies is a highly fatal encephalomyelitis  primarily occurring in urban dogs and wild animals especially canines. It is endemic in India and affects an estimated 3 per 100,000 persons annually. The patient initially may display bizarre combative behaviour. The disease can be effectively prevented by post exposure vaccination. The nervous tissue vaccine is no longer recommended because of unacceptable neurotoxicity. Three cell culture vaccines are presently available with about equal efficacy.


1237. Nebuloni M.  Pellegrinelli A.  Ferri A.  Tosoni A.  Bonetto S.  Zerbi P.

Boldorini R.  Vago L.  Costanzi G. Etiology of microglial nodules in brains of patients with acquired immunodeficiency syndrome. Journal of Neurovirology.  6(1):46-50, 2000 Feb.


Microglial nodules associated with opportunistic and HIV-related lesions are frequently found in the brains of AIDS patients. However, in many cases, the causative agent is only presumptively suspected. We reviewed 199 brains of AIDS patients with micronodular lesions to clarify their etiology by immunohistochemistry (to Toxoplasma gondii, cytomegalovirus, herpes simplex virus I/II, varicella zoster virus and HIV-p24 core protein), PCR (for herpetic viruses and Mycobacterium tuberculosis) and electron microscopy. Productive HIV infection was observed in 110 cases (55.1%): 30 cases with Toxoplasma gondii encephalitis, 30 with cytomegalovirus encephalitis, eight with multiple cerebral diseases, while in the remaining 42 cases HIV was the only pathogenetic agent.  Multinucleated giant cells (hallmark of HIV infection) were found in the MGNs of 85/110 cases with HIV-related lesions; the remaining 25 cases had only p24 positive cells but no multinucleated giant cells. In these latter cases the micronodular lesions had been initially attributed to the main opportunistic agent found in the brain, or defined as subacute encephalitis. Individual microglial nodules positive for an opportunistic pathogen were generally negative for HIV antigens. In 13 cases no opportunistic agent or HIV productive infection was found. In these cases, PCR and electron microscopy examination for HIV and other viral infections were negative. Our data suggest that HIV-immunohistochemistry should be used for the etiological diagnosis of micronodular lesions in AIDS brains, even in the presence of other pathogens. After extensive search, the etiology of the microglial nodules remains unknown in only a small percentage of cases.


1238. Reuben R.  Gajanana A. Japanese encephalitis in India. Indian Journal of Pediatrics.  64(2):243-51, 1997 Mar-Apr.


Japanese encephalitis (JE), caused by a mosquito-borne virus was first  recognised in India in 1955 and since then many major out-breaks from different parts of the country have been reported, predominantly in rural areas. Children are mainly affected, with morbidity rate estimated at 0.30 to 1.5 per 100,000 population. Case fatality rate has ranged from 10% to 60%, and up to 50% of those who recover may be left with neurological deficits. Reported incidence has generally been higher in males than in females, but subclinical infections have occurred equally in both sexes. A large number of subclinical infections occur each year during the transmission season. Diagnosis at the primary health centre (PHC) level is based on clinical symptoms only. Therefore, there is a need to develop simple tests for use at the peripheral level both for diagnosis and for  epidemiological surveys. JE is a vaccine preventable disease, but there are many logistic problems for effective implementation of vaccination.


1239. Tardei G.  Ruta S.  Chitu V.  Rossi C.  Tsai TF.  Cernescu C. Evaluation of immunoglobulin M (IgM) and IgG enzyme immunoassays in serologic diagnosis of West Nile Virus infection. Journal of Clinical Microbiology.  38(6):2232-9, 2000 Jun.


A unique urban encephalitis epidemic in Romania signaled the emergence of  neurological infection due to West Nile (WN) virus as a novel public health threat in Eastern Europe and provided an opportunity to evaluate patterns of immunoglobulin G (IgG) and IgM reactivity in IgM capture and IgG enzyme-linked immunosorbent assays (ELISAs). WN virus infection was diagnosed serologically in 236 of 290 patients from whom acute serum or cerebrospinal fluid (CSF) samples were available. In 37% of serum samples and in 25% of CSF samples collected in the first week of illness, anti-WN virus IgM antibody was detected in the absence of virus-specific IgG. The switch to an IgG antibody response occurred after 4 to 5 days of illness and earlier in CSF than in serum. A specific humoral immune response was detected in the CSF before the serum in some patients for whom paired CSF and serum samples from the same day were available. IgM antibody in convalescent serum samples persisted beyond 2 months after the onset of illness in more than 50% of patients. ELISA optical density values and  antibody concentrations were well correlated for both IgM and IgG immunoassays. Anti-WN virus IgM antibody in acute-phase samples did not cross-react significantly with flaviviruses in other antigenic groups.



1240.   Thomas RE. Preparing patients to travel abroad safely. Part 2: Updating vaccinations. Canadian Family Physician.  46:646-52, 655-6, 2000 Mar.


OBJECTIVE: To provide, for family physicians without access to a travel   clinic, evidence-based recommendations on vaccinating infants and children, adults, pregnant women, and immunocompromised patients traveling to non-Western countries. QUALITY OF EVIDENCE: Searches were undertaken of MEDLINE from 1990 to November 1998 (372 articles); the Cochrane Collaboration Library; publications of the National Action Committee on Immunization and the Committee to Advise on Tropical Medicine and Travel in Canada Communicable Disease Reports; the Canadian Immunization Guide; and Laboratory Centre for Disease Control, United States Centres for Disease Control, and World Health Organization websites. Evidence-based statements, randomized controlled trials, systematic reviews, and  meta-analyses were selected. Vaccination recommendations are based on this  evidence. MAIN MESSAGE: Physicians should complete vaccination schedules for children whose primary series is incomplete and vaccinate unvaccinated adults. Hepatitis A is widespread, and travelers to areas where it is endemic should be vaccinated. The elderly should be vaccinated against influenza and pneumococcal disease. Pregnant women should receive vaccines appropriate to their trimester. Immunocompromised patients should be vaccinated, but BCG and live vaccines are contraindicated. Travelers to areas where meningitis, typhoid, cholera, Japanese encephalitis, and rabies are endemic should be vaccinated if they are likely to be exposed. Those traveling to areas where tuberculosis is endemic should take  precautions and should have skin tests before traveling and 2 to 4 months after return. CONCLUSIONS: Family physicians can administer all necessary  vaccinations. They can advise pregnant women and immunocompromised people about the balance of risk of disease and benefits of vaccination.


1241.   Weiler Z.  Nelly P.  Baruchin AM.  Oren S. Diagnosis and treatment of cervical tuberculous lymphadenitis. Journal of Oral & Maxillofacial Surgery.  58(5):477-81, 2000 May.


PURPOSE: This study presents the long-term results of treatment of a series of patients with tuberculous mycobacterial lymphadenitis of the head and neck. PATIENTS: Twenty-one patients were seen in a 10-year period. The median age at onset was of 41.2 years (range, 4 to 79 years), and the male-to-female ratio was 11:10. Sixteen patients were of Ethiopian origin, 3 from the former USSR, and 2 were Israeli women (1 of Indian and 1 of Morrocan origin). Symptoms started between 2 weeks and 6 months before presentation (mean, 5.8 weeks). Most patients had negative chest radiographs, a variable response to the tuberculin skin test, and a negative culture for mycobacterial organisms. RESULTS: Fine-needle aspiration (FNA) of the cervical lymph nodes was the most reliable method  to confirm the bacteriologic agent causing the lymphadenopathy. Acid-fast  bacilli smears of the aspirate were positive in all but 3 patients, whereas histologic examination of the lymph nodes gave diagnostic results in only two thirds of cases examined. All patients were treated with antituberculous chemotherapy. Sixteen patients also underwent surgical excision of their cervical lymph nodes, and all of them showed a complete response to the combined treatment. The remaining patients reacted to chemotherapy alone with complete cure. One patient died of gastric carcinoma, and the only acquired immune deficiency syndrome (AIDS) patient died a year later of cytomegalovirus encephalitis. CONCLUSION: The most reliable indicator of cervical mycobacterial infection is an acid-fast smear from the FNA specimen. Antituberculous chemotherapy, with or without surgical excision of the involved cervical lymph nodes, is the method of choice for treatment of this disease.



1642. Ashok MS.  Rangarajan PN. Evaluation of the potency of BIKEN inactivated Japanese Encephalitis vaccine and DNA vaccines in an intracerebral Japanese Encephalitis virus challenge [letter]. Vaccine.  19(2-3):155-7, 2000 Sep 15.


1643. Borgo F.  Sgaramella TM.  Penello B.  L'Erario R.  Toso V. A componential analysis of visual object recognition deficits in patients with herpes simplex virus encephalitis. Brain & Cognition.  43(1-3):53-6, 2000 Jun-Aug.


  Five patients with a diagnosis of Herpes Simplex Virus Encephalitis (HSVE)  underwent neuropsychological assessment to explore the integrity of their visual perceptual abilities. Selective deficits affecting different levels  of the recognition processing were found; impaired recognition abilities were also influenced by selective task requirements, which resulted either in facilitatory or constraining effects on patients' performance. A theoretical model of object recognition (Humphreys & Riddoch, 1987) was taken into account to explain patients' performance. Further, the role of specific components of visual processing was evidenced in explaining the performance of patients affected by HSVE.


1644. Cherpillod P.  Tipold A.  Griot-Wenk M.  Cardozo C.  Schmid I.  Fatzer R.   Schobesberger M.  Zurbriggen R.  Bruckner L.  Roch F.  Vandevelde M. Wittek R.  Zurbriggen A. DNA vaccine encoding nucleocapsid and surface proteins of wild type canine distemper virus protects its natural host against distemper. Vaccine.  18(26):2927-36, 2000 Jul 1.


  Canine distemper virus (CDV), a member of the genus Morbillivirus induces a highly infectious, frequently lethal disease in dogs and other carnivores. Current vaccines against canine distemper consisting of attenuated viruses have been in use for many years and have greatly reduced the incidence of distemper in the dog population. However, certain strains may not guarantee adequate protection and others can induce post vaccinal encephalitis. We tested a DNA vaccine for its ability to protect dogs, the natural host of CDV, against distemper. We constructed plasmids containing the nucleocapsid, the fusion, and the attachment protein genes of a virulent canine distemper virus strain. Mice inoculated with these plasmids developed humoral and cellular immune responses against CDV antigens. Dogs immunized with the expression plasmids developed  virus-neutralizing antibodies. Significantly, vaccinated dogs were protected against challenge with virulent CDV, whereas unvaccinated animals succumbed to distemper.


1645. Dallasta LM.  Wang G.  Bodnar RJ.  Draviam R.  Wiley CA.  Achim CL. Hamilton RL.

Differential expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in chronic murine retroviral encephalitis. Neuropathology & Applied Neurobiology.  26(4):332-41, 2000 Aug.


  The cell adhesion molecules, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, are important mediators of immune interactions within the central nervous system (CNS). A wide variety of pro-inflammatory insults to the brain, including viral infection, result in upregulation of these molecules on brain endothelial cells, astrocytes, and microglia. This study investigated the expression of ICAM-1 and VCAM-1 in chronic encephalitis induced by infection with a temperature sensitive (ts-1) strain of Moloney murine leukaemia virus (MoMuLV), an ecotropic murine retrovirus. During the late stages of disease, viral antigen was present in both endothelial cells and microglia, but not astrocytes, in regions of spongiform change and gliosis. In these areas, ICAM-1 staining was detected on activated  microglia, but not on endothelial cells or astrocytes. In contrast, no  cells showed increased VCAM-1 expression in the CNS. These findings demonstrate that there is cell-specific, differential expression of these adhesion molecules in ts-1 retroviral encephalitis. The lack of endothelial cell expression correlates with the characteristic lack of lymphocytic infiltrate in this chronic retroviral encephalitis and suggests that increased microglial ICAM-1 expression may play a role in the pathogenesis of MoMuLV (ts-1)-mediated neurodegeneration.


1646. De La Blanchardiere A.  Rozenberg F.  Caumes E.  Picard O.  Lionnet F. Livartowski J.  Coste J.  Sicard D.  Lebon P.  Salmon-Ceron D. Neurological complications of varicella-zoster virus infection in adults with human immunodeficiency virus infection. Scandinavian Journal of Infectious Diseases.  32(3):263-9, 2000.


  This multicentre retrospective study describes the clinical features and  prognostic significance of Varicella-zoster virus (VZV)-associated neurological complications. The study was performed in patients with human immunodeficiency virus (HIV) infection, hospitalized for VZV neurological complications, confirmed in every case by positive VZV polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). Between 1990 and 1995, 34 HIV-infected patients were included in the study. At diagnosis, 59% had AIDS, with a median CD4 count of 11 x 10(9)/l. A past history of zoster was noted in 35% of cases. A concomitant herpes zoster rash and/or acute retinal necrosis were noted in 71% and 12% of patients, respectively. The predominant neurological manifestations were encephalitis (13), myelitis (8), radiculitis (7) and meningitis (6). The mean CSF white blood cell count was 126/mm3 and the mean CSF protein concentration was 2.3 g/l. Interferon-alpha level was increased in 36% of patients. VZV was isolated from CSF cultures in 2/6 cases. Magnetic resonance imaging was abnormal, demonstrating encephalitis lesions. After intravenous antiviral therapy, complete recovery was obtained in 18 cases (53%), serious sequelae were  observed in 10 cases (29%) and 6 patients died (18%). Severe symptoms and  a low CD4 cell count appeared to be associated with death or sequelae. In conclusion, VZV should be considered as a possible cause of encephalitis, myelitis, radiculitis or meningitis in HIV-infected patients, especially in patients with a history of or concomitant herpes zoster or acute retinal necrosis. VZV-PCR in the CSF may allow rapid diagnosis and early specific antiviral treatment.


1647. Derouin F.  Jacqz-Aigrain E.  Thulliez P.  Couvreur J.  Leport C. Cotrimoxazole for prenatal treatment of congenital toxoplasmosis?. Parasitology Today.  16(6):254-6, 2000 Jun.


  Congenital toxoplasmosis is still one of the most frequent causes of fetal  death. Despite a significant improvement in diagnosis, particularly in utero diagnosis, maternal treatment is only partially effective in preventing transmission to the fetus and treating fetal infection. Maternal treatment is based on drugs developed 50 years ago, which may have limited efficacy (spiramycin) or serious side-effects (pyrimethamine). Data on the use of cotrimoxazole in mouse models of toxoplasmosis and for preventing toxoplasmic encephalitis in patients suffering from AIDS have led Francis Derouin and colleagues to consider the potential of cotrimoxazole for prenatal prevention and treatment of toxoplasmic fetal death.


1648. Dobbs SM.  Dobbs RJ.  Weller C.  Charlett A.Link between Helicobacter pylori infection and idiopathic parkinsonism. Medical Hypotheses.  55(2):93-8, 2000 Aug.


  The conventional concept for an environmental cause of idiopathic

  parkinsonism is an insult (e.g. neurotoxin or encephalitis), superimposed

  on age-related attrition of nigral dopaminergic neurons, and temporally

  remote from neurological diagnosis. To the contrary, we describe the fit

  of Helicobacter pylori. This commonest of known bacterial infections,

  usually acquired in childhood, persists, and has been linked with peptic

  ulcer/non-ulcer dyspepsia, immunosuppression and autoimmunity. Acquired

  immunosuppression, predisposing to auto-immunity, is assessed as a model

  for the pathogenesis of parkinsonism and parkinsonian-like attributes of

  ageing. Eradication of a trigger has potential to change the approach to

  parkinsonism, just as it did to peptic ulcer. The tenet of inevitable

  age-related attrition of dopaminergic neurons may also require revision.

  Copyright 2000 Harcourt Publishers Ltd.


1649. Gambhir IS.  Mehta M.  Singh DS.  Khanna HD. Evaluation of CSF-adenosine deaminase activity in tubercular meningitis. Journal of the Association of Physicians of India.  47(2):192-4, 1999 Feb.


  Sixty patients of inflammatory brain disease were diagnosed and classified

  according to clinico-investigational criteria by Ahuja et al into

  tuberculous meningitis group (36 patients) and non-tuberculous meningitis

  group (24 patients). Tuberculous meningitis (TBM) patients were classified

  as probable (9 patients) and possible (27 patients) TBM. Non-TBM group

  comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%),

  cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal

  fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM

  and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10

  IU/L and was significantly elevated as compared to viral encephalitis and

  enteric encephalopathy cases; but difference was insignificant in

  comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral

  malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity

  of 44% and specificity of 75% was observed.


1650. Leach CT.Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes. [Review] [72 refs]Current Opinion in Pediatrics.  12(3):269-74, 2000 Jun.


  Human herpesvirus-6 (HHV-6) and -7 (HHV-7) infections typically are silent

  or manifested as mild febrile illnesses including classic roseola. In

  addition, case reports and epidemiologic data support the rare occurrence

  of HHV-6 encephalitis in immunocompromised as well as immunocompetent

  subjects. Although many other diseases have been putatively associated

  with HHV-6 or HHV-7, these associations are not well documented due to

  small numbers, use of tests incapable of distinguishing latent from

  replicating virus, potential virus cross-reactivity, or contradictory

  results. Further careful studies are needed to confirm these disease

  associations. Laboratory tests for diagnosing active HHV-6 and HHV-7

  infections include virus culture, antigen detection, and polymerase chain

  reaction of cell-free biologic fluid. Although HHV-6 and HHV-7 are

  inhibited by several antiviral drugs in the laboratory, including

  ganciclovir and foscarnet, no clinical trials have assessed their benefit.

  Nevertheless, treatment may be considered for patients with serious HHV-6-

  or HHV-7-associated disease confirmed with accurate virologic tests.  [References: 72]


1651. Mandl CW.  Allison SL.  Holzmann H.  Meixner T.  Heinz FX. Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site. Journal of Virology.  74(20):9601-9, 2000 Oct.


  The impact of a specific region of the envelope protein E of tick-borne

  encephalitis (TBE) virus on the biology of this virus was investigated by

  a site-directed mutagenesis approach. The four amino acid residues that

  were analyzed in detail (E308 to E311) are located on the upper-lateral

  surface of domain III according to the X-ray structure of the TBE virus

  protein E and are part of an area that is considered to be a potential

  receptor binding determinant of flaviviruses. Mutants containing single

  amino acid substitutions, as well as combinations of mutations, were

  constructed and analyzed for their virulence in mice, growth properties in

  cultured cells, and genetic stability. The most significant attenuation in

  mice was achieved by mutagenesis of threonine 310. Combining this mutation

  with deletion mutations in the 3'-noncoding region yielded mutants that

  were highly attenuated. The biological effects of mutation Thr 310 to Lys,

  however, could be reversed to a large degree by a mutation at a

  neighboring position (Lys 311 to Glu) that arose spontaneously during

  infection of a mouse. Mutagenesis of the other positions provided evidence

  for the functional importance of residue 308 (Asp) and its charge

  interaction with residue 311 (Lys), whereas residue 309 could be altered

  or even deleted without any notable consequences. Deletion of residue 309

  was accompanied by a spontaneous second-site mutation (Phe to Tyr) at

  position 332, which in the three-dimensional structure of protein E is

  spatially close to residue 309. The information obtained in this study is

  relevant for the development of specific attenuated flavivirus strains

  that may serve as future live vaccines.


1652. Markert JM.  Medlock MD.  Rabkin SD.  Gillespie GY.  Todo T.  Hunter WD.   Palmer CA.  Feigenbaum F.  Tornatore C.  Tufaro F.  Martuza RL. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial [see comments]. Gene Therapy.  7(10):867-74, 2000 May.


G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both gamma(1)34.5 loci and a lacZ insertion disabling the UL39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score > or = 70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter. Serial magnetic resonance images were obtained for volumetric analysis. The trial commenced at a dose of 10(6) plaque forming units (p.f.u.) inoculated at a single enhancing site and was completed when the  21st patient was inoculated with 3x10(9) p.f.u. at five sites. While adverse events were noted in some patients, no toxicity or serious adverse events could unequivocally be ascribed to G207. No patient developed HSV encephalitis. We found radiographic and neuropathologic evidence suggestive of  anti-tumor activity and long-term presence of viral DNA in some cases.


1653. Maschio M.  Giudiceandrea F.  Contadini P.  Jandolo B. Cytomegalovirus encephalitis: diagnosis with clinical approach, EEG and PCR techniques. Italian Journal of Neurological Sciences.  20(4):255-8, 1999 Aug.


Cytomegalovirus (CMV) encephalitis is particularly evident in immunodepressed patients. Often diagnosis is difficult and time-consuming because of the complex basic clinical picture of these patients. We describe the diagnostic steps taken in a case of cytomegalovirus encephalitis affecting an elderly patient, classified as immunodepressed and deceased on the thirty-fifth day of hospitalisation in the intensive care unit due to acute myocardial infarction. Treatment with ganciclovir, 30 mg/kg per day, begun at the time of diagnosis, appears to have had a positive effect on the neurologic symptoms.


1654. Najioullah F.  Bosshard S.  Thouvenot D.  Boibieux A.  Menager B.  Biron F.  Aymard M.  Lina B. Diagnosis and surveillance of herpes simplex virus infection of the central nervous system. Journal of Medical Virology.  61(4):468-73, 2000 Aug.


Herpes simplex viruses (HSV) are responsible for neurological disorders that require rapid diagnostic methods and specific antiviral therapy.  During 1997, 1431 cerebrospinal fluid samples (CSF) collected from 1339  patients with neurological disorder presentations were processed for HSV  detection. Eleven patients were positive for HSV, seven presenting with  encephalitis (6/7 due to HSV1) and 4 with aseptic meningitis (4/4 due to  HSV2). The incidence of HSV encephalitis was 2.33 cases / 10(6)  inhabitants/year. Among encephalitis (HSV encephalitis) cases, 1 patient  died due to the late implementation of antiviral therapy, and sequelae were observed in 4 cases. No sequelae were observed in aseptic meningitis cases. Four HSV encephalitis cases were monitored by PCR detection in CSF. Despite acyclovir therapy, PCR remained positive in CSF up to 20 days in 2 cases. This result suggest that the antiviral treatment for HSV  encephalitis should be monitored by PCR detection of HSV in CSF. Copyright 2000 Wiley-Liss, Inc.


1655. Pletnev AG.  Karganova GG.  Dzhivanyan TI.  Lashkevich VA.  Bray M. Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus. Virology.  274(1):26-31, 2000 Aug 15.


Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in mosquito cell culture were completely attenuated in SCID mice but still capable of providing protection against LGT. To develop the chimeras into vaccine candidates, we adapted them to replicate efficiently in simian Vero cells, a satisfactory substrate for human vaccines. The adapted chimeras remained completely attenuated for SCID mice and, significantly, provided protection in immunocompetent mice against tick-borne encephalitis virus, the most virulent of the tick-borne flaviviruses. Copyright 2000 Academic Press.


1656. Portegies P.  Corssmit N. Epstein-Barr virus and the nervous system. [Review] [32 refs] Current Opinion in Neurology.  13(3):301-4, 2000 Jun.


The neurological complications of Epstein-Barr virus infection include viral meningitis, encephalitis and neuromuscular complications. The introduction of cerebrospinal fluid polymerase chain reaction for Epstein-Barr virus DNA has improved diagnosis of these conditions and of primary central nervous system lymphoma in acquired immune deficiency syndrome, and has enabled cerebrospinal fluid monitoring of therapy. Prognosis remains good for most Epstein-Barr virus-related neurological complications; for primary central nervous system lymphoma in acquired immune deficiency syndrome the prognosis is still poor. [References: 32]


1657. Pushko P.  Bray M.  Ludwig GV.  Parker M.  Schmaljohn A.  Sanchez A. Jahrling PB.  Smith JF. Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis virus protect guinea pigs and mice from Ebola hemorrhagic  fever virus. Vaccine.  19(1):142-53, 2000 Aug 15.


RNA replicons derived from an attenuated strain of Venezuelan equine   encephalitis virus (VEE), an alphavirus, were configured as candidate vaccines for Ebola hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP) genes were introduced into the VEE RNA downstream from the VEE 26S promoter in place of the VEE structural protein genes. The resulting recombinant replicons, expressing the NP or GP genes, were packaged into VEE replicon particles (NP-VRP and GP-VRP, respectively) using a bipartite helper system that provided the VEE structural proteins in trans and prevented the regeneration of replication-competent VEE during packaging. The immunogenicity of NP-VRP and GP-VRP and their ability to protect against lethal Ebola infection were evaluated in BALB/c  mice and in two strains of guinea pigs. The GP-VRP alone, or in combination with NP-VRP, protected both strains of guinea pigs and BALB/c  mice, while immunization with NP-VRP alone protected BALB/c mice, but neither strain of guinea pig. Passive transfer of sera from VRP-immunized animals did not confer protection against lethal challenge. However, the complete protection achieved with active immunization with VRP, as well as the unique characteristics of the VEE replicon vector, warrant further testing of the safety and efficacy of NP-VRP and GP-VRP in primates as candidate vaccines against Ebola hemorrhagic fever.


1658. Quereda C.  Corral I.  Laguna F.  Valencia ME.  Tenorio A.  Echeverria JE.  Navas E.  Martin-Davila P.  Moreno A.  Moreno V.  Gonzalez-Lahoz JM. Arribas JR.  Guerrero A. Diagnostic utility of a multiplex herpesvirus PCR assay performed with cerebrospinal fluid from human immunodeficiency virus-infected patients  with neurological disorders. Journal of Clinical Microbiology.  38(8):3061-7, 2000 Aug.


We used a multiplex nested-PCR assay for the simultaneous detection in  cerebrospinal fluid (CSF) of five human herpesviruses (HVs) (cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], herpes simplex virus [HSV], and human herpesvirus 6 [HHV-6]) in a clinical evaluation of human immunodeficiency virus (HIV)-infected patients with neurological disorders. This method, which has the advantages of being rapid and economical, would be of particular interest for the diagnosis of neurological syndromes caused by more than one HV. We studied 251 CSF samples from 219 patients. HV DNA was demonstrated in 93 (37%) of the CSF samples (34% of the patients). CMV was the HV most frequently detected in our patients (25%), while EBV, VZV, HSV, and HHV-6 DNAs were present in significantly fewer cases (7, 4, 3, and 1%, respectively). When results were compared with the final etiological diagnoses of the patients, the multiplex HV PCR showed high specificity for the diagnosis of CMV and VZV neurological diseases and for cerebral lymphoma (0.95, 0.97, and 0.99, respectively). The sensitivity of the assay was high for CMV disease (0.87), was low for cerebral lymphoma (0.33), and was not evaluable for VZV disease due to the small number of patients with this diagnosis. Nevertheless, detection of VZV DNA had possible diagnostic value in four of the nine cases, and EBV DNA amplification always predicted the diagnosis of cerebral lymphoma in

  patients with cerebral masses. Detection of HSV DNA was frequently associated with CMV amplification and fatal encephalitis. HHV-6 was not considered to have a pathogenetic role in the three cases in which it was detected. This multiplex HV PCR assay is a specific and clinically useful method for the evaluation of HIV-infected patients with neurological disorders related to HV.


1659. Rajnik M.  Ottolini MG. Serious infections of the central nervous system: encephalitis, meningitis, and brain abscess. [Review] [100 refs] Adolescent Medicine.  11(2):401-25, 2000 Jun.


Central nervous system infections in adolescents range from the diffuse  cerebritis of encephalitis to the regional inflammation of meningitis, and very focal disease of brain abscess. Clinical presentations reflect this wide spectrum, with encephalitis primarily characterized by altered mental status, meningitis by fever, headache, and neck stiffness, and brain abscess manifesting localizing findings. Encephalitis and viral meningitis are frequently caused by the seasonal enteroviruses and arboviruses, while most adolescent bacterial meningitis is due to Neisseria meningitidis and Streptococcus pneumoniae. The microbiology of brain abscess reflects underlying host risk factors. Gram-positive cocci are seen in patients with congenital heart disease, while respiratory flora including anaerobes are associated with sinus or otic disease. Lumbar puncture to characterize and culture the CSF remains the optimal test for the diagnosis and management of encephalitis and meningitis, while CT-guided needle biopsy may be both diagnostic and therapeutic for brain abscesses. New diagnostic tests include the use of PCR. A variety of safe and effective treatment regimens exists for most bacterial infections as well as for some  herpesvirus infections. New vaccines are under study to further control  bacterial meningitis. [References: 100]


1660. Ratho RK.  Sethi S.  Singh S.Role of serology in the diagnosis of herpes simplex encephalitis. Indian Journal of Pathology & Microbiology.  42(3):333-7, 1999 Jul.


Twenty one cerebrospinal fluid (CSF)/brain tissue (16 CSF and 5 brain tissue) from patients clinically suspected of herpes simplex encephalitis (HSE) were collected during one year period and was subjected for the detection of HSV type I and type II antigen by direct Immunofluorescence (DIF). Paired serum and CSF samples obtained from 12 patients were tested for herpes simplex virus antibodies by indirect immunofluorescence test. Of the 21 cases, two were positive for HSV-1 antigen in CSF and one in brain tissue by DIF. Virus specific IgG antibody in paired CSF and serum samples was positive in one case only. In none, virus could be grown in  verocell line. In 2 Patients antemortem diagnosis was possible and parenteral acyclovir could be administered in one case that recovered following treatment. Thus, besides antibody detection, direct  immunofluorescence is an useful and rapid method for the early diagnosis of HSE.



1661. Sauerbrei A.  Eichhorn U.  Hottenrott G.  Wutzler P. Virological diagnosis of herpes simplex encephalitis. Journal of Clinical Virology.  17(1):31-6, 2000 Jun.


BACKGROUND: The herpes simplex encephalitis (HSE) represents one of the most severe infectious diseases of the central nervous system. As effective antiviral drugs are available, rapid and reliable diagnosis has become important. OBJECTIVES: To evaluate retrospectively the usefulness of polymerase chain reaction (PCR) as well as serological procedures for the diagnosis of HSE. STUDY DESIGN: 631 cerebrospinal fluids (CSF) from patients with clinical suspicion of encephalitis were tested for type-specific herpes simplex virus (HSV) DNA using PCR. Virus-specific antibodies including their intrathecal synthesis were measured in 624 CSF and 2409 serum samples of 2711 patients suspected of having encephalitis. RESULTS: Positive results were obtained by PCR in eight patients (1. 3%) for HSV-1 and in seven (1.1%) for HSV-2. Intrathecal antibody synthesis  was estimated in 24 (3.8%) patients. In general, no intrathecal antibodies  could be measured in patients with positive PCR results and vice versa the  intrathecal immune response became positive when CSF was cleared from the  HSV. Results of the antibody detection in serum specimens revealed an active HSV infection in 268 out of 2367 patients (11.3%). CONCLUSIONS: The detection of HSV-DNA by PCR is the method of choice for diagnosis of HSE in the early phase of the disease. During the later stage, it has to be diagnosed by the estimation of intrathecally synthesized antibodies.


1662. Smith MB.  Boyars MC.  Veasey S.  Woods GL. Generalized tuberculosis in the acquired immune deficiency syndrome. Archives of Pathology & Laboratory Medicine.  124(9):1267-74, 2000 Sep.


OBJECTIVE: Generalized, or hematogenously disseminated, tuberculosis (TB) in patients with the acquired immune deficiency syndrome (AIDS) has been associated with a high incidence of cases remaining undiagnosed until postmortem. To better characterize generalized TB in the setting of AIDS, this report describes the clinical, laboratory, radiologic, and pathologic features of 20 fatal cases. DESIGN: The medical records, autopsy protocols, and histologic material from patients with AIDS and concomitant TB were reviewed. All patients were autopsied at a tertiary care medical center during the years 1985-1997. RESULTS: In 50% of our 20 cases, diagnosis was not made until postmortem. Signs and symptoms were few, including the absence of fever (temperature > or = 38 degrees C) in 55% of  patients. Consistent laboratory abnormalities of a nonspecific nature were  limited to hyponatremia (sodium <135 mmol/L) in 60%. Both peripheral and deep (thoracic and abdominal) lymphadenopathy, unusual in adults with TB, occurred in 45% and 95% of cases, respectively. In contrast to previous reports, all of the 6 cases of tuberculous meningitis presented as acute meningitis with a predominance of neutrophils in cerebrospinal fluid. Necrotizing encephalitis with extension of the acute inflammation into the superficial cortex was seen in all cases and tuberculous brain abscesses occurred in 50% of cases, a higher frequency than previously reported. Despite lung involvement in 90% of the cases, 33% of chest radiographs were interpreted as normal and disseminated mycobacterial disease was not suggested in the radiograph report in any of the other cases. Soft tissue abscesses in uncharacteristic locations such as the neck, mediastinum, and perirectal area occurred in these patients. Histologically, 95% of organs sampled showed inflammatory foci characterized by extensive necrosis with numerous neutrophils and/or karyorrhectic debris, numerous acid-fast bacilli, few or no epithelioid histiocytes, and no Langhans giant cells. CONCLUSION: Clinically and pathologically, generalized TB in the setting of AIDS is characterized by either unusual features or a lack of the  typical features described for generalized TB in patients who do not have AIDS. This absence of classic features contributes to the high incidence of cases that remain undiagnosed until postmortem examination.


1663. Smith-Jensen T.  Burgoon MP.  Anthony J.  Kraus H.  Gilden DH.  Owens GP.  Comparison of immunoglobulin G heavy-chain sequences in MS and SSPE brains  reveals an antigen-driven response [see comments]. Neurology.  54(6):1227-32, 2000 Mar 28.


OBJECTIVE: To better understand B-cell activation in MS by analyzing the  immunoglobulin (Ig)G heavy chain variable region (VH) repertoire found in MS brains and comparing it with brain VH sequences in individuals with  subacute sclerosing panencephalitis (SSPE)--a chronic encephalitis

  produced by measles virus (MV)-and characterized by an antigen-driven

  oligoclonal IgG response to MV antigens. BACKGROUND: The specificity of

  oligoclonal IgG in MS CSF and plaques, and their relevance to the

  pathogenesis of MS is unknown. METHODS: Nested PCR was used to amplify and

  sequence the rearranged IgG heavy-chain VH repertoire in plaques of three

  acute MS brains and in three SSPE brains. A representative population of

  VH sequences from each tissue was aligned to the known 51 functional VH

  germline segments. From this the authors determined the closest VH family

  germline segment, and the degree and location of somatic mutations for

  each unique IgG. RESULTS: As expected for an antigen-driven response

  against MV antigens, most VH sequences from the SSPE brains were mutated

  extensively compared with their closest germline segments. Furthermore,

  SSPE VH sequences accumulated replacement mutations preferentially in the

  complementary-determining regions (CDRs) relative to framework

  regions-features normally observed during antigen-driven selection. A

  comparison of VH family and germline usage also demonstrated that each

  SSPE brain had its own unique IgG response. When the authors compared the

  VH response in MS plaques with SSPE, MS VH sequences were also mutated

  extensively, displayed a preferential accumulation of replacement

  mutations in CDRs, and were unique in each MS brain. CONCLUSION: The

  presence of an antigen-driven response in MS, rather than a

  nonconventional mechanism of B-cell activation, warrants additional

  analysis of the specificity of IgG in MS brain and CSF.


1664. Studahl M.  Hagberg L.  Rekabdar E.  Bergstrom T. Herpesvirus DNA detection in cerebral spinal fluid: differences in clinical presentation between alpha-, beta-, and gamma-herpesviruses. Scandinavian Journal of Infectious Diseases.  32(3):237-48, 2000.


  To evaluate the role of 6 human herpesviruses (cytomegalovirus (CMV),

  Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), herpes simplex

  virus (HSV) types 1 and 2 and varicella zoster virus (VZV)) in infections

  of the nervous system, cerebrospinal fluid (CSF) samples from 662 patients

  with suspected viral aetiology to neurological symptoms were investigated

  for presence of herpesviral DNA in a PCR-based study. Of the 69 patients

  (2 patients had 2 herpesvirus DNA detected in CSF) who had herpesvirus DNA

  detected in the CSF, 60 (87%) were non-immunocompromised (CMV 7; HHV-6 6;

  EBV 16; HSV-1 18; HSV-2 9 and VZV 6) and 9 (13%) were immunocompromised

  (CMV 3; HHV-6 0; EBV 5; HSV-1 0; HSV-2 1 and VZV 0). The study was

  performed in a retrospective/prospective manner. The HSV-1, HSV-2, VZV and

  CMV DNA-positive patients usually had typical clinical syndromes, such as

  encephalitis/myelitis and meningitis, but also other neurological

  conditions were associated with findings of these viruses. HHV-6 and EBV

  DNA were detected in patients presenting with a variety of neurological

  symptoms, and in some of the cases, concurrent with diagnosis of other

  infections of the central nervous system. Despite the overall variability

  of clinical conditions seen, a pattern associated with each investigated

  herpesvirus was discernable as regards clinical presentation.


1665. Tsai TF.New initiatives for the control of Japanese encephalitis by vaccination:  minutes of a WHO/CVI meeting, Bangkok, Thailand, 13-15 October 1998. Vaccine.  18 Suppl 2:1-25, 2000 May 26.


  Japanese encephalitis (JE) is a leading cause of viral encephalitis in

  Asia that, in several countries, has been controlled effectively through

  national vaccine programs. However, in recent years, transmission has been

  recognized or has intensified in new locations where the available

  vaccines are either unaffordable or unlicensed. In addition, the

  near-eradication of poliomyelitis from Asia has elevated JE in the public

  health agenda of preventable childhood diseases, and surveillance of acute

  neurological infections to confirm polio eradication, simultaneously, has

  led to a greater awareness of the disease burden attributable to JE. The

  only internationally licensed JE vaccine, an inactivated mouse-brain

  derived vaccine, is efficacious but is problematic from the perspectives

  of reactogenicity, requirement for numerous doses, cost and reliance on a

  neurological tissue substrate. A live-attenuated vaccine distributed only

  in China also is efficacious and requires fewer doses; however, production

  and regulatory standards are unresolved. Several approaches toward

  developing novel JE vaccines that could fill the gap in JE vaccine need

  are under pursuit. The minutes and recommendations of a meeting of experts

  to discuss these issues, jointly sponsored by the World Health

  Organization and the Children's Vaccine Initiative in Bangkok, Thailand,

  13-15 October, 1998, are presented.


1666. Wong KT. Emerging and re-emerging epidemic encephalitis: a tale of two viruses.  Neuropathology & Applied Neurobiology.  26(4):313-8, 2000 Aug.


  Two major epidemics of viral encephalitis occurred in Asia in 1997 and

  1998. The first was a re-emergence of neurovirulent strains of enterovirus

  71, which caused severe encephalomyelitis in children in Malaysia, Taiwan

  and Japan, on a background of hand, foot and mouth disease. Necropsy

  studies of patients who died of enterovirus 71 infection showed severe

  perivascular cuffing, parenchymal inflammation and neuronophagia in the

  spinal cord, brainstem and diencephalon, and in focal areas in the

  cerebellum and cerebrum. Although no viral inclusions were detected,

  immunohistochemistry showed viral antigen in the neuronal cytoplasm.

  Inflammation was often more extensive than neuronal infection, suggesting

  that other factors, in addition to direct viral cytolysis, may be involved

  in tissue damage. The second epidemic of viral encephalitis was the result

  of a novel paramyxovirus called Nipah, which mainly involved pig handlers

  in Malaysia and Singapore. Pathological evidence suggested that the

  endothelium of small blood vessels in the central nervous system was

  particularly susceptible to infection. This led to disseminated

  endothelial damage and syncytium formation, vasculitis, thrombosis,

  ischaemia and microinfarction. However, there was also evidence of

  neuronal infection by the virus and this may also have contributed to the

  neurological dysfunction in Nipah encephalitis. Some patients who seemed

  to recover from the acute symptoms have been re-admitted with clinical

  findings suggestive of relapsing encephalitis. As these two epidemics

  indicate, the emergence and re-emergence of viral encephalitides continue

  to pose considerable challenges to the neuropathologist, in establishing

  the diagnosis and unravelling the pathogenesis of the neurological



1667. Yan JJ.  Wang JR.  Liu CC.  Yang HB.  Su IJ. An outbreak of enterovirus 71 infection in Taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis. Journal of Clinical Virology.  17(1):13-22, 2000 Jun.


  BACKGROUND: In a recent enterovirus outbreak in Taiwan, serotype 71 was

  the culprit of encephalitis causing rapid clinical deterioration and death

  among young children. OBJECTIVES: Since knowledge of enterovirus 71 (EV71)

  infection in the central nervous system is still limited, the purpose of

  the present case study was attempted to uncover the pathogenesis of the

  virus. STUDY DESIGN: We performed a detailed pathological examination,

  virological and molecular studies on a case of EV71 infection with a

  rapidly fatal outcome. In addition, the whole genome of the virus was

  sequenced to determine the genetic relationships to other enteroviruses

  and two other EV71 strains (a prototype BrCr and a neurovirulent MS

  strain), and to provide the genetic basis of its neurovirulence of the new

  isolate, NCKU9822 strain. RESULTS: Characteristic features of acute

  encephalomyelitis were observed, with most prominent lesions in the spinal

  cord and brain stem. Mild myocarditis and pancreatitis were also noticed.

  EV71 antigen was localized to neurons on immunohistochemical staining.

  EV71 was recovered from all organs with inflammatory reaction. Sequence

  analysis showed that overall NCKU9822 and the two EV71 strains shared 80%

  nucleotide identity and 95% amino acid identity. It had only 45% amino

  acid and 52% nucleotide identities with polioviral P1 capsid region.

  CONCLUSION: The spinal cord and brain stem were the main targets of EV71

  in the fatal cases in this outbreak, however, heart and pancreas might

  also be involved. Since the amino acid sequences in the P1 region are

  conserved (97% identity) among the three EV71 strains as compared to other

  enteroviruses and polioviruses, these EV71 neurovirulent strains might

  share the same mechanisms of neurovirulence, and the mechanisms might be

  different from those in polioviruses.




2157.        No abstract


2158. Barnett M.  Prosser J.  Sutton I.  Halmagyi GM.  Davies L.  Harper C. Dalmau J. Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. Journal of Neurology, Neurosurgery & Psychiatry.  70(2):222-5, 2001 Feb.


  A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.


2159. No abstract

2160. No abstract

2161. Fine A.  Layton M. Lessons from the West Nile viral encephalitis outbreak in New York City, 1999: implications for bioterrorism preparedness. [Review] [5 refs] Clinical Infectious Diseases.  32(2):277-82, 2001 Jan 15.


  The involvement and expertise of infectious disease physicians,  microbiologists, and public health practitioners are essential to the early detection and management of epidemics--both those that are naturally occurring, such as the 1999 outbreak of West Nile virus (WN virus) in New York City, and those that might follow covert acts of bioterrorism. The experience with the WN virus outbreak offers practical lessons in outbreak detection, laboratory diagnosis, investigation, and response that might usefully influence planning for future infectious disease outbreaks. Many of the strategies used to detect and respond to the WN virus outbreak resemble those that would be required to confront other serious infectious disease threats, such as pandemic influenza or bioterrorism. We provide an overview of the critical elements needed to manage a large-scale, fast-moving infectious disease outbreak, and we suggest ways that the existing public health capacity might be strengthened to ensure an  effective response to both natural and intentional disease outbreaks. [References: 5]


2162. No abstract


2163.  Kassubek J.  Juengling FD.  Nitzsche EU.  Lucking CH. Limbic encephalitis investigated by 18FDG-PET and 3D MRI. Journal of Neuroimaging.  11(1):55-9, 2001 Jan.


  Two patients with clinically probable or possible limbic encephalitis (LE) are reported, both cases with typical findings in clinical symptoms (severe neuropsychological deficits and complex partial seizures) and in routine magnetic resonance imaging (MRI) (hyperintense mesiotemporal lesions). Underlying malignancy was identified (rectal carcinoma) in one case but could not be detected in the other patient. The 2 patients were investigated by cerebral 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and 3-dimensional (3D) MRI, and abnormalities in metabolic activity were mapped using coregistration of spatially normalized PET and MRI. Highly significant focal hypermetabolism in bilateral hippocampal areas was found in both cases. The authors' findings support FDG-PET coregistered to 3D MRI as a potentially valuable additional tool in the imaging diagnostics of LE. Results are discussed with respect to the clinical symptoms and previously reported imaging findings in the disease.


2164. Kesson AM. Management of neonatal herpes simplex virus infection. [Review] [30 refs]  Paediatric Drugs.  3(2):81-90, 2001.


  Herpes simplex viruses (HSV) are ubiquitous pathogens which can be transmitted vertically causing significant morbidity and mortality in neonates. Neonatal HSV infection is infrequent with an incidence ranging from 1 in 3,500 to 1 in 20,000, depending on the population. Neonatal HSV infection is much more frequent in infants born to mothers experiencing a primary HSV infection with an incidence approaching 50%, while infants born to mothers experiencing recurrent HSV infection have an incidence of less than 3%. Neonatal infections are clinically categorised according to the extent of the disease. They are: (i) skin, eye and mouth (SEM) infections; (ii) central nervous system infection (encephalitis)--neonatal encephalitis can include SEM infections; and (iii) disseminated infection involving several organs, including the liver, lung, skin and/or adrenals. The central nervous system may also be involved in disseminated infections. Caesarean section, where the amniotic membranes are intact or have been ruptured for less than 4 hours, is recommended for those women who have clinical evidence of active herpes lesions on the cervix or vulva at the time of labour. This procedure significantly decreases the risk of transmission to the infant. Diagnosis of neonatal infection requires a very high level of clinical awareness as only a minority of mothers will have a history of genital HSV infection even though they are infected. Careful physical examination and appropriate investigations of the infant should accurately identify the infection in the majority of cases. Treatment is recommended where diagnosis is confirmed or there is a high level of suspicion. The current recommendation for treatment is aciclovir 20 mg/kg 3 times daily by intravenous infusion. Careful monitoring of hydration and renal function as well as meticulous supportive care of a very sick infant is also required. The newer anti-herpes agents, valaciclovir and famciclovir, offer no advantage over aciclovir and are not recommended for neonatal HSV infection. Prognosis is dependent upon the extent of disease and the efficacy of treatment, with highest rates of morbidity and mortality in disseminated infections, followed by central nervous system infection and the least in SEM infection. However, SEM infection is associated with poor developmental outcome even in infants who do not have encephalitis. Studies to improve the outcome of SEM infection are in progress. Neonatal HSV infections, although being relatively uncommon, are associated with significant morbidity and mortality if unrecognised and specific treatment is delayed. Diagnosis relies on a high level of clinical suspicion and appropriate investigation. With early therapy, the prognosis for this infection is considerably improved. [References: 30]



2165. Konishi E.  Fujii A.  Mason PW. Generation and characterization of a mammalian cell line continuously expressing Japanese encephalitis virus subviral particles. Journal of Virology.  75(5):2204-12, 2001 Mar.


  We have generated a cell line (F cells) producing a secreted form of Japanese encephalitis virus (JEV) subviral particle (extracellular particles [EPs]) that contains the JEV envelope glycoprotein (E) and a precursor (prM) of the virion membrane protein (M). The F cells were engineered to synthesize these JEV products from a cDNA encoding a mutated (furin proteinase resistant) form of prM, since stable cell lines expressing E and the authentic form of prM could not be obtained, due (in part) to the cell-fusing ability of EPs containing E and M. Our biochemical alteration of the prM protein was critical for the successful production of EP-producing cell lines. EPs produced by F cells share the biochemical properties of empty viral particles produced by JEV-infected cells, except that the F-cell EPs lack hemagglutinating activity and M. F-cell EPs were recognized by a panel of monoclonal antibodies to E, and EPs were shown to be useful as vaccine candidates in mice and as diagnostic reagents in evaluating human immune responses to JE vaccination. The amounts of E antigen released into the culture fluid of F cells were similar to those found in virion fractions of JEV-infected cell culture fluids or JEV-infected weanling mouse brains (the current source of antigen used to produce human vaccines for JE). Thus, the F-cell line would appear to be a useful source of antigen for JE vaccines and diagnostics.


2166. Limoges J.  Poluektova L.  Ratanasuwan W.  Rasmussen J.  Zelivyanskaya M. McClernon DR.  Lanier ER.  Gendelman HE.  Persidsky Y. The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis. Virology.  281(1):21-34, 2001 Mar 1.


  Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddI/d4T decreased the numbers of infected cells by 75%, while ddI/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by > or = 25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary. Copyright 2001 Academic Press.


2167. No abstract


2168. No abstract


2169. Muench J.  Verdieck A.  Lopez-Vasquez A.  Newell M. Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers. Journal of the American Board of Family Practice.  14(1):46-50, 2001 Jan-Feb.


  BACKGROUND: The patient who complains of vague mental status changes requires extra vigilance in that the underlying condition might itself affect the patient's ability to communicate well and relate a medical history. The differential diagnosis of delirium is broad, ranging from the benign to the potentially fatal. The diagnostic uncertainty inherent in primary care is compounded when language and cultural differences interfere with physician-patient communication. METHODS: We undertook a MEDLINE-assisted review of the medical literature concerning herpes simplex encephalitis. Additionally, we performed an Internet search of several government Web sites to find current legal and federal guidelines concerning the use of medical interpreters. RESULTS AND CONCLUSIONS: We recount the case of a young Eastern European immigrant who complained initially of vague mental status changes and was found to have herpes  simplex encephalitis. Diagnosis could have been made sooner had the physician been familiar with the patient's baseline mental status or had cultural and language barriers not stood between the physician and the patient and his mother. Herpes simplex encephalitis is a rare, but specific, cause of delirium for which prompt diagnosis and treatment with intravenous acyclovir can prevent death or serious sequelae.



2170. Odaka M.  Yuki N.  Hirata K. Anti-GQ1b IgG antibody syndrome: clinical and immunological range. Journal of Neurology, Neurosurgery & Psychiatry.  70(1):50 5, 2001 Jan.


  OBJECTIVES: To clarify the nosological relation among Miller Fisher syndrome (MFS), Guillain-Barre syndrome (GBS) with ophthalmoplegia, Bickerstaff's brain stem encephalitis (BBE), and acute ophthalmoparesis without ataxia. Serum samples from patients with each condition often have anti-GQ1b IgG antibody. METHODS: Information on antecedent illness, initial symptoms, neurological signs during the illness, and CSF findings were reviewed in 194 patients with anti-GQ1b IgG. It was determined whether overlapping MFS and GBS (MFS/GBS), as well as overlapping BBE and GBS (BBE/GBS), is explained by the combined action of anti-GQ1b IgG and anti-GM1 or anti-GD1a IgG, serological markers of GBS. RESULTS: Based on the diagnostic criteria, all the patients with acute ophthalmoparesis, MFS, MFS/GBS, BBE/GBS, and BBE had external ophthalmoplegia; all the patients with MFS, MFS/GBS, or GBS had hyporeflexia or areflexia; and all those with MFS and BBE showed ataxia. Tendon reflexes were decreased or absent in 91% of those with BBE/GBS, 67% of those with BBE, and 53% of those with acute ophthalmoparesis. Ataxia was present in 68% of the patients with MFS/GBS and 45% of those with BBE/GBS. Antecedent illness caused by upper respiratory tract infection had occurred in 60% to 80% of these patients, and CSF albuminocytological dissociation in 25% to 75%. Anti-GM1 or anti-GD1a IgG was present in 50% of those with GBS, 35% of those with MFS/GBS, 27% of those with BBE/GBS, 16% of those with MFS, and 8% of those with BBE. CONCLUSIONS: These findings together with the common autoantibody (anti-GQ1b IgG) suggest that a common autoimmune mechanism functions in the pathogenesis of these illnesses. In a larger study, it was confirmed clinically that MFS, GBS, BBE, and acute ophthalmoparesis are closely related, forming a continuous range. This is supported by the immunological findings. The term "anti-GQ1b IgG antibody syndrome" is not intended to be used as a clinical diagnosis, but recognition of this syndrome is useful for understanding the aetiological relation among the various illnesses and for introducing the established treatments of GBS for use with other conditions.

2171. No abstract

2172. No abstract

2173. Shu PY.  Chen LK.  Chang SF.  Yueh YY.  Chow L.  Chien LJ.  Chin C.  Lin TH.  Huang JH. Dengue NS1-specific antibody responses: isotype distribution and serotyping in patients with Dengue fever and Dengue hemorrhagic fever. Journal of Medical Virology.  62(2):224-32, 2000 Oct.


  To understand the antibody responses to dengue (DEN) nonstructural 1 (NS1)  glycoprotein and their roles in protective immunity or pathogenesis of dengue fever (DF) and dengue hemorrhagic fever (DHF), we have analyzed the NS1-speccific IgM, IgA and IgG antibodies from patients with DF and DHF. An isotype-specific, indirect enzyme-linked immunosorbent assay (ELISA) was established by coating a NS1-specific monoclonal antibody (MAb), D2/8-1, to capture soluble NS1 antigens secreted in the culture supernatants of Vero cells infected with DEN virus. We observed strong anti-NS1 antibody responses in all of the convalescent sera of patients with DF and DHF. Similar NS1-specific isotypic and serotypic antibody responses were found in the sera from DF and DHF patients. The results  showed that all DEN infections induced significant NS1-specific IgG, whereas 75% and 60% of primary DF patients vs. 40% and 90% of secondary DF patients produced IgM and IgA antibodies, respectively. Specificity analysis showed that DEN NS1-specific IgG and IgA antibodies cross-react strongly to Japanese encephalitis (JE) virus NS1 glycoprotein, whereas DEN NS1-specific IgM antibodies do not cross-react to JE virus NS1 glycoprotein at all. The serotype specificity of NS1-specific IgM, IgA and IgG were found to be 80%, 67% and 75% for primary infections, and 50%, 22% and 30% for secondary infections in positive samples of DF patients. Similar pattern was found in DHF patients. The results showed that all of the DF and DHF patients produced significant NS1-specific antibodies. We did not observe direct correlation between the anti-NS1 antibody responses and DHF because sera from patients with DF and DHF showed similar anti-NS1 antibody responses. Copyright 2000 Wiley-Liss, Inc.



2724.    Anonymous. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 12-2001. A 16-year-old boy with an altered mental status and muscle rigidity. New England Journal of Medicine.  344(16):1232-9, 2001 Apr 19.

2725.    Fine A.  Layton M. Lessons from the West Nile viral encephalitis outbreak in New York City, 1999: implications for bioterrorism preparedness. [Review] [5 refs] Clinical Infectious Diseases.  32(2):277-82, 2001 Jan 15.

2726.    Franciotta D.  Martino G.  Zardini E.  Furlan R.  Bergamaschi R.  Andreoni L.  Cosi  V. Serum and CSF levels of MCP-1 and IP-10 in multiple sclerosis patients with acute and stable disease and undergoing immunomodulatory therapies. Journal of Neuroimmunology.  115(1-2):192-8, 2001 Apr 2.

2727.    Garban F.  Attal M.  Rossi JF.  Payen C.  Fegueux N.  Sotto JJ.  Intergroupe Francophone du Myelome. Immunotherapy by non-myeloablative allogeneic stem cell transplantation in multiple myeloma: results of a pilot study as salvage therapy after autologous transplantation. Leukemia.  15(4):642-6, 2001 Apr.

2728.    Hung KL.  Liao HT.  Tsai ML. The spectrum of postinfectious encephalomyelitis. Brain & Development.  23(1):42-5, 2001 Mar.

2729.    Nam H.  Lee SK.  Chung CK.  Hong KS.  Chang KH.  Lee DS. Incidence and clinical profile of extra-medial-temporal epilepsy with hippocampal atrophy.  Journal of Korean Medical Science.  16(1):95-102, 2001 Feb.

2730.    Nash D.  Mostashari F.  Fine A.  Miller J.  O'Leary D.  Murray K.  Huang A.  Rosenberg A.  Greenberg A.  Sherman M.  Wong S.  Layton M.  1999 West Nile Outbreak Response Working Group. The outbreak of West Nile virus infection in the New York City area in 1999. [see comments]. New England Journal of Medicine.  344(24):1807-14, 2001 Jun 14.

2731.    Petignat P.  Vial Y.  Laurini R.  Hohlfeld P. Fetal varicella-herpes zoster syndrome in early pregnancy: ultrasonographic and morphological correlation. Prenatal Diagnosis.  21(2):121-4, 2001 Feb.

2732.    Rantalaiho T.  Farkkila M.  Vaheri A.  Koskiniemi M. Acute encephalitis from 1967 to 1991.  Journal of the Neurological Sciences.  184(2):169-77, 2001 Mar 1.

2733.    Rezaie P.  Lantos PL. Microglia and the pathogenesis of spongiform encephalopathies. [Review] [194 refs] Brain Research - Brain Research Reviews.  35(1):55-72, 2001 Mar.

2734.    Zhao ML.  Kim MO.  Morgello S.  Lee SC. Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis. Journal of Neuroimmunology.  115(1-2):182-91, 2001 Apr 2.



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