The Role of Antigranulocyte Scintigraphy in Diagnosis of Aortic Graft Infection and Evaluation of Treatment Outcome.

BACKGROUND: The aim of this study was to assess the eventual added benefit of antigranulocyte monoclonal antibodies scintigraphy for the diagnostic imaging of aortic graft infection (AGI) and its role in evaluation of treatment outcome. METHODS: A population-based, retrospective, register-based analysis was carried out of all patients with infected aortic grafts after treatment for aneurysmal or aortoiliac occlusive disease at Karolinska University Hospital, covering the greater Stockholm area during November 2012-December 2020. Cases were based on the definitions in the 2016 Management of Aortic Graft Infection Collaborations consensus. Using the in-hospital electronic patient registry (Take Care®) and the Swedish National Registry for Vascular Surgery (Swedvasc), 835 patients who had been treated for aortic aneurysms or aortoiliac occlusive disease were identified. The diagnostic arsenal of laboratory tests, computed tomography (CT), and clinical signs has been supplemented by antigranulocyte monoclonal antibodies (anti-G mAb) scintigraphy. Data were analyzed using SPSS Statistics. RESULTS: Eighteen cases of AGI out of 835 operations incorporating aortic grafts during the period were identified. Fourteen patients (78%) were categorized as diagnosed AGI (AGI-D), and the remaining 4 (22%) were classified as suspected AGI (AGI-S). In the AGI-D group (n = 14), 10 patients (71%) had positive CTs and 4 (29%) had low-probability CTs. In the group of 10 positive CTs, 9 patients also had positive scintigraphy scans with only one negative scintigraphy scan. There were no negative scintigraphy scans without ongoing antibiotic treatment at the time of investigation. In 15 of 18 cases, a culprit agent was identified, either preoperatively or perioperatively. Thirteen of the 18 patients were treated solely by antibiotics, whereas 5 underwent surgical treatment in addition to antibiotic treatment. The outcome has been divided into 3 groups: infection-free (n = 6; 33%), lifelong antibiotic treatment (n = 7; 39%), and deceased (n = 5; 28%). CONCLUSIONS: The imaging modalities in AGI diagnostics are a cornerstone of the investigative work-up, complemented by clinical signs and laboratory methods. The main advantage conveyed by anti-G mAb scintigraphy is in postoperative imaging and its ability to differentiate between infection and general postoperative changes in the areas of concern. We have identified 6 patients in our cohort in whom antibiotic therapy was discontinued after a negative anti-G mAb scintigraphy scan. Anti-G mAb scintigraphy may fulfill a unique need for diagnosis in suspected cases, evaluation of therapeutic efficacy in patients requiring long-term antibiotic treatment, and aiding in the decision to discontinue antibiotic therapy.

Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences.

OBJECTIVES: During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. METHODS: In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. RESULTS: HSV-specific interleukin(Il)-4 and Il-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. CONCLUSIONS: The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.

Cerebrospinal fluid kynurenine and kynurenic acid concentrations are associated with coma duration and long-term neurocognitive impairment in Ugandan children with cerebral malaria.

BACKGROUND: One-fourth of children with cerebral malaria (CM) retain cognitive sequelae up to 2 years after acute disease. The kynurenine pathway of the brain, forming neuroactive metabolites, e.g. the NMDA-receptor antagonist kynurenic acid (KYNA), has been implicated in long-term cognitive dysfunction in other CNS infections. In the present study, the association between the kynurenine pathway and neurologic/cognitive complications in children with CM was investigated. METHODS: Cerebrospinal fluid (CSF) concentrations of KYNA and its precursor kynurenine in 69 Ugandan children admitted for CM to Mulago Hospital, Kampala, Uganda, between 2008 and 2013 were assessed. CSF kynurenine and KYNA were compared to CSF cytokine levels, acute and long-term neurologic complications, and long-term cognitive impairments. CSF kynurenine and KYNA from eight Swedish children without neurological or infectious disease admitted to Astrid Lindgren's Children's Hospital were quantified and used for comparison. RESULTS: Children with CM had significantly higher CSF concentration of kynurenine and KYNA than Swedish children (P < 0.0001 for both), and CSF kynurenine and KYNA were positively correlated. In children with CM, CSF kynurenine and KYNA concentrations were associated with coma duration in children of all ages (P = 0.003 and 0.04, respectively), and CSF kynurenine concentrations were associated with worse overall cognition (P = 0.056) and attention (P = 0.003) at 12-month follow-up in children ≥5 years old. CONCLUSIONS: CSF KYNA and kynurenine are elevated in children with CM, indicating an inhibition of glutamatergic and cholinergic signaling. This inhibition may lead acutely to prolonged coma and long-term to impairment of attention and cognition.

Lemierre's syndrome caused by Fusobacterium necrophorum complicated with multiple brain abscesses-A case report, literature review, and suggested management.

We present an unusual case of Lemierre´s syndrome complicated by multiple brain abscesses, a literature review and suggested management. A young man with multiple brain abscesses deteriorated despite two weeks of directed antibiotics. A multidisciplinary approach was successful. Hyperbaric oxygen treatment (HBOT) should be considered in refractory or severe cases.

Acute viral infections of the central nervous system in immunocompetent adults: diagnosis and management.

Patients with viral infections of the central nervous system (CNS) may present with a variety of neurological symptoms, most commonly dominated by either encephalitis or meningitis. The aetiological panorama varies in different parts of the world as well as over time. Thus, virological first-line diagnostics must be adapted to the current epidemiological situation and to the individual patient history, including recent travels. This review focuses on the diagnostics and treatment of viral CNS infections in the immunocompetent host from a Northern European perspective. Effective vaccines are available for viruses such as poliovirus and tick-borne encephalitis virus (TBEV) and for the childhood diseases morbilli (measles), rubella (German measles), parotitis (mumps) and varicella (chickenpox). However, cases do appear due to suboptimal immunization rates. In viral CNS infections, epidemiological surveillance is essential for establishing preventive strategies and for detecting emerging viruses. Knowledge of the possibilities and limitations of diagnostic methods for specific viral CNS infections is vital. A positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) finding is usually reliable for aetiological diagnosis. The demonstration of intrathecal antibody synthesis is useful for confirming the aetiology in a later stage of disease, hitherto sufficiently evaluated in herpes simplex encephalitis (HSE) and tick-borne encephalitis (TBE). Despite improved virological and differential diagnostic methods, aetiology remains unknown in about half of the cases with suspected viral encephalitis. Antiviral treatment is available chiefly for infections caused by herpesviruses, and acyclovir (aciclovir) is the drug of choice for empirical therapy in suspected viral encephalitis. However, randomized, controlled antiviral trials have only been conducted for HSE, while such studies are lacking in other viral CNS infections. Viral cytolysis and immune-mediated mechanisms may contribute to varying extents to neurological damage. Although the brain damage is believed to depend, to a varying degree, on the intrathecal host immune response, the use of corticosteroids in viral CNS infections is scarcely studied, as is specific treatment for neuroinflammation. Improved antiviral and immunomodulating treatment is desirable. Since neurological sequelae are still abundant, follow-up after severe viral CNS disease must include a neuropsychological assessment and an individually adapted rehabilitation plan.

Sustained elevation of kynurenic Acid in the cerebrospinal fluid of patients with herpes simplex virus type 1 encephalitis.

Herpes simplex virus (HSV) type 1 encephalitis (HSE) is a viral infectious disease with commonly occurring neurodegeneration and neurological/cognitive long-term sequelae. Kynurenic acid (KYNA) is a neuroactive tryptophan metabolite, which is elevated in the cerebrospinal fluid (CSF) during viral infection as a result of immune activation. The aim of the study was to investigate the role of endogenous brain KYNA for the long-term outcome of the disease. CSF KYNA concentration was analyzed in 25 HSE patients along the course of the disease and compared with that of 25 age-matched healthy volunteers. Within 3 weeks of admission CSF KYNA of HSE patients was markedly elevated (median 33.6 nM) compared to healthy volunteers (median 1.45 nM). Following a decline observed after 1-2 months, levels of CSF KYNA were elevated more than 1 year after admission (median 3.4 nM range: 1-9 years). A negative correlation was found between initial CSF KYNA concentrations and severity of the long-term sequelae. This study show a marked elevation in CSF KYNA from patients with HSE, most pronounced during the acute phase of the disease and slowly declining along the recovery. We propose that brain KYNA might potentially protect against neurodegeneration while causing a long-lasting loss in cognitive function associated with the disease.

Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.

The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.

High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV serology in adults with acute aseptic meningitis in Stockholm.

Acute aseptic meningitis (AAM) affects 10-20/100,000 inhabitants per years in Sweden. Up to the beginning of the 1980s the diagnoses were made by virus isolation and/or determination of viral antibodies in serum. The development of PCR for detection of viruses in CSF samples has increased the sensitivity and diagnostic efficiency considerably. We investigated the aetiology of AAM and the diagnostic efficiency in an adult population in Stockholm, using a limited first-line combination of microbiological assays. CSF and serum samples, consecutively collected in 419 patients with clinical symptoms of AAM in northern Stockholm during 1999-2004, were included. PCR assays for herpes simplex virus (HSV) DNA and enterovirus (EV) RNA in the CSF as well as ELISA for IgM in serum to tick-borne encephalitis virus (TBEV) were performed routinely. A viral diagnosis was obtained in 255 of the 419 cases (62%) with these routinely performed assays. Clinical findings in combination with additional diagnostic tests resulted in an overall aetiological yield of 72%. EV was the major causative agent (27%) followed by TBEV (21%) and HSV-2 (19%). We conclude that consistent use of CSF-PCR for EV and HSV and TBEV serology established a diagnosis in the majority of AAM patients.

Increased detection rate in diagnosis of herpes simplex virus type 2 meningitis by real-time PCR using cerebrospinal fluid samples.

Efficient and sensitive diagnostic methods are needed in the management of virus infections in the central nervous system. There is a demand for an evaluation of the sensitivity of PCR methods for early diagnosis of meningitis due to herpes simplex type 2 (HSV-2) and varicella-zoster virus (VZV). The objective of this study was to evaluate real-time PCR in the detection of HSV-2 and VZV DNA from cerebrospinal fluid (CSF) for etiological diagnoses in clinically well-characterized cases of primary and recurrent aseptic meningitis. Samples from 110 patients, 65 of whom were diagnosed with or were strongly suspected of having HSV-2 meningitis and 45 with acute aseptic meningitis of unknown causes, were analyzed. Results were compared with the outcome of nested PCR for HSV-2 infection. Clinical parameters were analyzed in relation to CSF viral load. With real-time PCR, HSV-2 DNA was found in CSF from 80% (52/65) of patients with clinical HSV-2 meningitis compared to 72% (47/65) found by nested PCR. The sensitivity of real-time HSV-2 PCR was found to be 87% (33/38) in primary and 70% (19/27) in recurrent meningitis. The HSV-2 viral load was significantly higher in primary than in recurrent meningitis and correlated with the degree of inflammation. VZV DNA was detected in 2 of 45 samples (4.4%). Real-time PCR for the diagnosis of HSV-2 meningitis was evaluated in a large, clinically well-characterized sample of material and found to identify more cases than nested PCR in the group of patients with recurrent meningitis. Quantification of DNA enables further research of disease prognosis and treatment.