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Biomedical subjects

B Sköldenberg

Publications and source records attributed to B Sköldenberg.

At least 19 recordsLinked to original sources

Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid.

With the aim of improving early diagnosis of herpes simplex encephalitis a polymerase chain reaction (PCR) assay with two "nested" primer pairs was developed for the amplification of herpes simplex virus DNA in cerebrospinal fluid (CSF). Southern blotting was used to confirm the specificity of the amplification. The assay was applied to 151 CSF samples from 43 consecutive patients with herpes simplex encephalitis verified by the finding of herpes simplex virus/viral antigen in a brain biopsy sample or at necropsy (13) and/or intrathecal production of IgG antibody to the virus (40). As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be herpes simplex encephalitis but excluded by the absence of intrathecal antibody synthesis) were tested. PCR detected herpes simplex virus DNA in 42 of the 43 patients with proven herpes simplex encephalitis; all but 1 were positive in the first CSF sample taken. The 1 PCR-negative patient had been treated with acyclovir from 20 h after the onset of symptoms. All the control subjects were PCR negative, as were 270 internal contamination controls. The PCR result remained positive in samples drawn up to 27 days after the onset of neurological symptoms. This method is a rapid and non-invasive means to diagnose herpes simplex encephalitis; it is highly sensitive and specific.

Acyclovir

Herpes simplex encephalitis.

Diagnostic and therapeutic advances in the management of herpes simplex encephalitis (HSE) have been significant over the last decade. Serological analysis of simultaneously drawn CSF and serum samples allows reliable diagnostics of HSE, but not until after 3-10 days following the onset of neurological symptoms. Polymerase chain reaction (PCR) assay with two nested primer pairs, being developed for the amplication of HSV DNA in CSF, was applied to 151 CSF samples from 43 consecutive patients with HSE. As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be HSE but excluded by the absence of intrathecal HSV antibody synthesis) were tested. PCR detected HSV DNA in 42/43 patients and remained positive up to 27 days after the onset of neurological symptoms. By a combination of PCR and serological analysis of intrathecal HSV antibody synthesis, aetiological diagnosis of HSE can be made by one or both methods from early disease and up to 15 years after the onset of HSE. In one Swedish and one American trial of acyclovir versus vidarabine in HSE, acyclovir 10 mg/kg 8-hourly for 10 days significantly decreased mortality as well as morbidity in the survivors. Early start of acyclovir treatment is necessary in HSE; the prognosis is correlated to age and stage of consciousness and neurological involvement at start of the therapy. Data has shown the need of neuropsychological assessment in final determination of the level of disability after HSE. The profiles and dynamics of the inflammatory cascade of cytokines from lymphocytes and other brain cells, provoked by the intracerebral HSV infection, needs to be characterized to enable understanding of the pathogenic process in HSE and hence its adequate antiinflammatory treatment.

Antibodies, Viral

Neurovirulence of herpes simplex virus types 1 and 2 isolates in diseases of the central nervous system.

Herpes simplex virus (HSV) isolates derived from the central nervous system of ten patients with HSV-1-induced encephalitis, one patient with multiple sclerosis, and 14 patients with HSV-2-induced meningitis were investigated for neurovirulence by assaying the LD50 after nose and intracerebral (i.c.) inoculation of mice. HSV-1 encephalitis strains were significantly more virulent after nose inoculation (i.e. neuroinvasive) when compared with HSV-1 isolates from patients with oral lesions only, whereas HSV-2 meningitis strains were significantly more virulent after i.c. inoculation when compared with HSV-2 isolates from patients with genital lesions only. No correlation between high neurovirulence (defined as low LD50 for both routes of infection) and replication in cell cultures of neuronal and non-neuronal cell lines was found, but the weakly neurovirulent HSV-1 strain isolated from a patient with multiple sclerosis gave low replication yields. After nose inoculation, a highly neuroinvasive HSV-1 laboratory reference strain replicated to high titers in nose tissue, the trigeminal ganglia and brainstem, while a strain with low neuroinvasiveness but high i.c. virulence replicated less well in the brainstem. Neuroinvasiveness of the virus strain might be one factor of relevance in the pathogenesis of HSV-1 encephalitis in man.

Animals

Clinical manifestations and diagnosis of neuroborreliosis.

Lyme borreliosis has in a few years turned out to be a health problem not only in the United States, but also in many European countries. When it affects the nervous system, Lyme borreliosis acts as the great disease imitator. Because of this characteristic it is often difficult to diagnose on clinical grounds. Patients with neuroborreliosis might appear within all medical disciplines. Clinical markers, such as preceding tick bite and/or ECM, are important clues to the diagnosis. Mononuclear pleocytosis and elevated CSF protein are present in most patients with neuroborreliosis. Final evidence for the diagnosis is the demonstration of specific antibodies in serum and/or CSF. Measurement of antibody titers should be carried out in both serum and CSF, since these methods are complementary when trying to obtain a serological diagnosis of neuroborreliosis.

Adolescent

Treatment of Lyme borreliosis with emphasis on neurological disease.

We have studied 113 patients with neurologic Lyme borreliosis and meningitis who were treated with intravenous high-dose antibiotics (penicillin G, 12 g, mostly for 14 days in 47 patients; penicillin G, 9 g, mostly for 10 days in 58 patients; doxycycline, 200 mg, in 5 patients; and cefuroxime, 4.5-9 g, in 3 patients). Seventy percent of the patients had peripheral nerve symptoms and 13% had central nervous symptoms. Almost half of the patients were treated more than 4 weeks after the onset of symptoms and 15% of the patients had persisting or progressive symptoms between 4 and 11 months. There seemed to be clinical benefit as well as a decrease of spinal fluid pleocytosis and spinal proteins. No significant symptoms of Herxheimer reaction were demonstrated.

Anti-Bacterial Agents

Acyclovir treatment in infectious mononucleosis: a clinical and virological study.

Fifty-six patients with a clinical and laboratory diagnosis of infectious mononucleosis who had not been ill for more than seven days, were randomised for peroral treatment with acyclovir (800 mg five times daily) or placebo for seven days in a double blind trial. Clinical, virological and immunological parameters were monitored in each patient for six months. During treatment, shedding of Epstein-Barr virus' as assessed in 36 patients, was significantly reduced (p less than 0.001). However, virus production in the oropharynx returned to pre-treatment levels one week after the cessation of therapy. Virus was detected in 35 patients at enrollment and in 28 of 36 patients at the six-month control. No effect on the clinical course of the disease was noticed. The virus-specific antibody response was also unaffected. A significant reduction in spontaneous outgrowth of in vivo Epstein-Barr virus-infected B-lymphocytes was found at 180 days after treatment in four acyclovir-treated patients compared to six controls (p less than 0.001). In another three patients with over-whelming clinical symptoms causing airway obstruction and/or disseminated intravascular coagulopathy, treatment with intravenous acyclovir (10 mg/kg three times daily) was combined with prednisolone (0.7 mg/kg daily) for ten days. Virus shedding ceased transiently during treatment, but returned to initial levels within one week. A dramatic clinical effect on the pharyngeal oedema and general health of the two patients with airway obstruction was noticed, but was much less evident in a patient with intravascular coagulopathy.

Acyclovir

Clinical manifestations of Borrelia infections of the nervous system.

Clinical, treatment and laboratory parameters were analyzed in 46 consecutive Swedish patients with Borrelia infections of the nervous system. The importance of age in the clinical symptoms, the wide spectrum of disease, and the chronic behaviour of the Borrelia infection of the nervous system was stressed, as well as the benefit of high-dose intravenous antibiotics, especially penicillin G. Borrelia infection of the nervous system can imitate other diseases. When associated with meningitis it can mimic psychosomatic disorders, when associated with radiculoneuritis it may imitate herniated discs and when central nervous involvement of the Borrelia infection occurs, it can mimic a non-infectious, thrombotic or haemorrhagic cerebro-vascular disease.

Adolescent

Serological diagnosis of Borrelia meningitis.

The antibody response against a Borrelia strain isolated from Swedish Ixodes ricinus ticks was determined by enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) of cerebrospinal fluid (CSF) and serum specimens from 45 patients with chronic meningitis. Probable Borrelia etiology could be demonstrated in 41 of 45 (91%) patients with clinical symptoms of chronic meningitis. Approximately 25% of the patients had significantly elevated titer of antibody to the spirochete in CSF but not in serum. Patients with short duration of disease were especially prone to be antibody negative in serum but positive in CSF. Significant rise in serum antibody titers was seldom demonstrated in patients treated with antibiotics.

Animals

Amantadine for prophylaxis against influenza A.

Amantadine, 200 mg daily, for 5 days was used in an attempt to restrict the spread of influenza A in a hospital ward. After index cases of influenza A amantadine was given to 2 patients with clinical symptoms and to 8/10 patients who were not yet ill. No further case of clinical influenza was seen among the patients, but 3 of those receiving amantadine developed subclinical infection. No side effects of amantadine were noted. Amantadine was not given to any of the 23 hospital staff on duty. In this group 8 cases of influenza A appeared, 3 of them during the week after the introduction of amantadine to patients.

Amantadine

Effect of acyclovir on infectious mononucleosis: a double-blind, placebo-controlled study.

Thirty-one patients with clinical and laboratory diagnoses of infectious mononucleosis who had had symptoms for seven or fewer days were randomized for intravenous treatment with acyclovir (10 mg/kg) or placebo at 8-hr intervals for seven days in a double-blind trial. Clinical signs and symptoms were registered, and excretion of virus in the saliva as well as antibody responses in sera and saliva were assessed before, during, and at regular intervals in the six months after treatment. Acyclovir significantly (P less than .001), but reversibly, inhibited oropharyngeal shedding of Epstein-Barr virus. The humoral and cellular immune responses, however, did not differ between the two groups; nor did the development of viral latency. There were no significant (P greater than .05) differences in individual clinical symptoms or in laboratory parameters between the two groups; however, when data concerning duration of fever, weight loss, tonsillar swelling, pharyngitis, and self-assessment by the patient were combined, a significant (P less than or equal to .01) effect of treatment with acyclovir was evident.

Acyclovir

Erythema chronicum migrans in Sweden: clinical manifestations and antibodies to Ixodes ricinus spirochete measured by indirect immunofluorescence and enzyme-linked immunosorbent assay.

26 Swedish patients with erythema chronicum migrans (ECM) were studied regarding associated clinical symptoms and antibodies to Swedish Ixodes ricinus spirochete. 11/26 (42%) of the patients had associated symptoms, compared to more than 90% of 314 American patients with ECM, as described by Steere et al. Only 2/26 (8%) had multiple skin lesions, compared to 48% of the American patients. Elevated erythrocyte sedimentation rate and circulating immune complexes were demonstrated in 6/25 (24%) and 8/25 patients (32%), respectively, as against in 53% and 84%, respectively, of the American patients. The antibody response to Ixodes ricinus spirochete was measured by indirect immunofluorescence (IFA) and enzyme-linked immunosorbent assay (ELISA). Compared to the 95% percentile of controls, significantly high antibody titers were demonstrated in 3/25 (12%) by IFA, and 7/25 (28%) by ELISA. The ELISA antibody titers differed significantly (p less than 0.05) between ECM-patients and controls. The spirochetal antibody response in ECM was also compared with that in spirochete-associated disease of the central nervous system.

Adolescent

Accuracy of computed tomography in the diagnosis of herpes simplex encephalitis.

The accuracy of computed tomography (CT) in the diagnosis of herpes simplex encephalitis (HSE) was assessed in 121 patients who during a 2 1/2 year period entered a prospective Swedish joint study with participation of six University Centres. The patients presented with symptoms and signs of febrile focal encephalopathy. The age ranged from 1 month to 76 years (mean 37.3 years). Only 6 were infants less than one year old. HSE was diagnosed in 50 patients by the demonstration of intrathecal HSV antibody production and/or by HSV isolation or antigen detection in brain tissue specimens. A total of 308 CT examinations--the majority performed during the first 5 days after onset of CNS symptoms--were evaluated under blind conditions. The correct diagnosis of HSE was usually suggested within 5 days after onset of neurologic symptoms yielding a sensitivity of 0.73 and a specificity of 0.89. Predominant location of the HSE lesions was the temporal lobes (88%), which rarely were involved in the non-HSE group (11%). Haemorrhage was a rare finding (12% ) and enhancement after intravenous contrast administration was insignificant. Repeat examinations further increased accuracy. It is concluded that the good reliability of high resolution CT, further improvement of immunologic techniques and the advent of new atoxic antiviral drugs all are factors which may in the future obviate the need for brain biopsy.

Adolescent