Browsing by Subject "CEREBROSPINAL-FLUID"

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  • Hayes, A.; Nguyen, D.; Andersson, M.; Anton, A.; Bailly, J-L; Beard, S.; Benschop, K. S. M.; Berginc, N.; Blomqvist, S.; Cunningham, E.; Davis, D.; Dembinski, J. L.; Diedrich, S.; Dudman, S. G.; Dyrdak, R.; Eltringham, G. J. A.; Gonzales-Goggia, S.; Gunson, R.; Howson-Wells, H. C.; Jääskeläinen, A. J.; Lopez-Labrador, F. X.; Maier, M.; Majumdar, M.; Midgley, S.; Mirand, A.; Morley, U.; Nordbo, S. A.; Oikarinen, S.; Osman, H.; Papa, A.; Pellegrinelli, L.; Piralla, A.; Rabella, N.; Richter, J.; Smith, M.; Strand, A. Söderlund; Templeton, K.; Vipond, B.; Vuorinen, T.; Williams, C.; Wollants, E.; Zakikhany, K.; Fischer, T. K.; Harvala, H.; Simmonds, P. (2020)
    Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
  • Jacob, Laurent; Boisserand, Ligia Simoes Braga; Geraldo, Luiz Henrique Medeiros; Neto, Jose de Brito; Mathivet, Thomas; Antila, Salli; Barka, Besma; Xu, Yunling; Thomas, Jean-Mickael; Pestel, Juliette; Aigrot, Marie-Stephane; Song, Eric; Nurmi, Harri; Lee, Seyoung; Alitalo, Kari; Renier, Nicolas; Eichmann, Anne; Thomas, Jean-Leon (2019)
    Cranial lymphatic vessels (LVs) are involved in the transport of fluids, macromolecules and central nervous system (CNS) immune responses. Little information about spinal LVs is available, because these delicate structures are embedded within vertebral tissues and difficult to visualize using traditional histology. Here we show an extended vertebral column LV network using three-dimensional imaging of decalcified iDISCO(+)-clarified spine segments. Vertebral LVs connect to peripheral sensory and sympathetic ganglia and form metameric vertebral circuits connecting to lymph nodes and the thoracic duct. They drain the epidural space and the dura mater around the spinal cord and associate with leukocytes. Vertebral LVs remodel extensively after spinal cord injury and VEGF-C-induced vertebral lymphangiogenesis exacerbates the inflammatory responses, T cell infiltration and demyelination following focal spinal cord lesion. Therefore, vertebral LVs add to skull meningeal LVs as gatekeepers of CNS immunity and may be potential targets to improve the maintenance and repair of spinal tissues.
  • Sillanpaa, Heidi; Skogman, Barbro H.; Sarvas, Heikki; Seppala, Ilkka J. T.; Lahdenne, Pekka (2014)
  • Smura, Teemu; Blomqvist, Soile; Kolehmainen, Pekka; Schuffenecker, Isabelle; Lina, Bruno; Boettcher, Sindy; Diedrich, Sabine; Love, Arthur; Brytting, Mia; Hauzenberger, Elenor; Dudman, Susanne; Ivanova, Olga; Lukasev, Alexander; Fischer, Thea Kolsen; Midgley, Sofie; Susi, Petri; Savolainen-Kopra, Carita; Lappalainen, Maija; Jääskeläinen, Anne J. (2020)
    Picornaviruses (family Picornaviridae) are small, nonenveloped, positive-sense, single-stranded RNA viruses. The members of this family are currently classified into 47 genera and 110 species. Of picornaviruses, entero-and parechoviruses are associated with aseptic meningitis. They are transmitted via fecal-oral and respiratory routes, and occasionally, these viruses may cause a brief viremia and gain access to central nervous system (CNS). During the diagnostic screening of entero-and parechovirus types in Finland in year 2013-14, we detected a cluster of echovirus 4 (E4) infections in young adults and adolescents. As E4 is infrequently detected in Finland, we contacted several Northern and Central European laboratories that conduct routine surveillance for enteroviruses and, for those who have had E4 cases, we send a query for E4 sequences and data. Here we report CNS infections caused by E4 in Finland, Sweden, Norway, Denmark, Iceland and Germany in 2013 and 2014, and show that the E4 detected in these countries form a single lineage. In contrast, E4 strains circulating in these countries preceding the year 2013, and those circulating elsewhere in Europe during 2013-2014, formed several independent clusters.
  • Okuneva, Olesya; Li, Zhilin; Korber, Inken; Tegelberg, Saara; Joensuu, Tarja; Tian, Li; Lehesjoki, Anna-Elina (2016)
    Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.
  • Paavola, Anne; Bernards, Christopher M.; Rosenberg, Per H. (2016)
    In order to avoid the risks of sideeffects of epidural local anesthetics and opioids, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) epidurally would be an interesting option of analgesic therapy. The fairly short duration of action of spinally administered NSAIDs, e.g., ibuprofen, may be prolonged by using controlled release poloxamer gel formulation. Using a microdialysis technique we studied the epidural and intrathecal pharmacokinetics of ibuprofen after its epidural administration as a poloxamer 407 formulation or a solution formulation. In addition, plasma ibuprofen concentrations were analyzed from central venous blood samples. Ibuprofen concentrations in the epidural space were significantly higher and longer lasting after the epidural gel injection compared with the epidural solution injection. The epidural AUC of ibuprofen was over threefold greater after epidural ibuprofen gel injection compared with the ibuprofen solution injection (p <0.001). The systemic absorption of ibuprofen from 25% poloxamer 407 gel was very low. The in situ forming poloxamer gel acted as a reservoir allowing targeted ibuprofen release at the epidural injection site and restricted ibuprofen molecules to a smaller spinal area. Ibuprofen diffusion from the epidural space to the intrathecal space was steady and prolonged. These results demonstrate that the use of epidurally injectable poloxamer gel can increase and prolong ibuprofen delivery from epidural space to the CSF enhancing thus ibuprofen entry into the central neuroaxis for spinal analgesia. Further toxicological and dose-finding studies are justified. (C) 2016 Elsevier B.V. All rights reserved.
  • Reinert, Jochim; Richard, Bernhard C.; Klafki, Hans W.; Friedrich, Beate; Bayer, Thomas A.; Wiltfang, Jens; Kovacs, Gabor G.; Ingelsson, Martin; Lannfelt, Lars; Paetau, Anders; Bergquist, Jonas; Wirths, Oliver (2016)
    In Alzheimer's disease (AD) a variety of amyloid beta-peptides (A beta) are deposited in the form of extracellular diffuse and neuritic plaques (NP), as well as within the vasculature. The generation of A beta from its precursor, the amyloid precursor protein (APP), is a highly complex procedure that involves subsequent proteolysis of APP by beta-and gamma-secretases. Brain accumulation of A beta due to impaired A beta degradation and/or altered ratios between the different A beta species produced is believed to play a pivotal role in AD pathogenesis. While the presence of A beta 40 and A beta 42 in vascular and parenchymal amyloid have been subject of extensive studies, the deposition of carboxyterminal truncated A beta peptides in AD has not received comparable attention. In the current study, we for the first time demonstrate the immunohistochemical localization of A beta 37 and A beta 39 in human sporadic AD (SAD). Our study further included the analysis of familial AD (FAD) cases carrying the APP mutations KM670/671NL, E693G and I716F, as well as a case of the PSEN1 Delta Exon9 mutation. A beta 37 and A beta 39 were found to be widely distributed within the vasculature in the brains of the majority of studied SAD and FAD cases, the latter also presenting considerable amounts of A beta 37 containing NPs. In addition, both peptides were found to be present in extracellular plaques but only scarce within the vasculature in brains of a variety of transgenic AD mouse models. Taken together, our study indicates the importance of C-terminally truncated A beta in sporadic and familial AD and raises questions about how these species are generated and regulated.
  • Chaudhry, Shafqat Rasul; Kahlert, Ulf Dietrich; Kinfe, Thomas Mehari; Lamprecht, Alf; Niemelä, Mika; Hänggi, Daniel; Muhammad, Sajjad (2020)
    Background: Aneurysmal subarachnoid hemorrhage (SAH) is a highly complex disease with very high mortality and morbidity. About one-third of SAH patients suffer from systemic infections, predominantly pneumonia, that can contribute to excess mortality after SAH. Immunodepression is probably the most important mechanism leading to infections. Interleukin-10 (IL-10) is a master regulator of immunodepression, but it is still not clear if systemic IL-10 levels contribute to immunodepression, occurrence of infections and clinical outcome after SAH. Methods: This explorative study included 76 patients with SAH admitted to our neurointensive care unit within 24 h after ictus. A group of 24 patients without any known intracranial pathology were included as controls. Peripheral venous blood was withdrawn on day 1 and day 7 after SAH. Serum was isolated by centrifugation and stored at -80 degrees C until analysis. Serum IL-10 levels were determined by enzyme-linked immunoassay (ELISA). Patient characteristics, post-SAH complications and clinical outcome at discharge were retrieved from patients' record files. Results: Serum IL-10 levels were significantly higher on day 1 and day 7 in SAH patients compared to controls. Serum IL-10 levels were significantly higher on day 7 in patients who developed any kind of infection, cerebral vasospasm (CVS) or chronic hydrocephalus. Serum IL-10 levels were significantly higher in SAH patients discharged with poor clinical outcome (modified Rankin Scale (mRS) 3-6 or Glasgow Outcome Scale (GOS) 1-3). Conclusion: Serum IL-10 might be an additional useful parameter along with other biomarkers to predict post-SAH infections.
  • Puurunen, Jenni; Tiira, Katriina; Vapalahti, Katariina; Lehtonen, Marko; Hanhineva, Kati; Lohi, Hannes (2018)
    Anxiety-related disorders, including fearfulness are common and leading welfare problems among the worldwide dog population. The etiology of anxieties is complex and affected by genetic and environmental factors. Thus, there is a need for more comprehensive approaches, such as metabolomics, to understand the causes of anxiety and to identify anxiety-related biomarkers for more efficient diagnostic and treatment options. To study metabolic alterations related to canine fearfulness, a non-targeted plasma metabolite profiling was performed in a cohort of 20 fearful and 21 non-fearful dogs. The results showed that nine metabolic features were significantly associated with fearfulness. The most prominent change included increased plasma glutamine and gamma-glutamyl glutamine (gamma-Glu Gln) in fearful dogs across breeds. Alterations in glutamine metabolism have previously been associated with several psychiatric disorders, indicating the relevance of this finding also in dogs. In addition, we describe a novel breed-specific association between renal biomarker symmetric dimethylarginine (SDMA) and canine fearfulness. These observed metabolic alterations may result from high levels of prolonged psychological stress in fearful dogs.
  • Tenhu, Elina; Teräsjärvi, Johanna; Cruzeiro, Manuel Leite; Savonius, Okko; Rugemalira, Emilie; Roine, Irmeli; He, Qiushui; Pelkonen, Tuula (2020)
    Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) ofTLR4andTLR9are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPsTLR4rs4986790 (896A > G) andTLR9rs187084 (-1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes inTLR4was significantly higher in patients withHaemophilus influenzaemeningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2-5.4;p= 0.021), whereas the frequency of variant genotypes inTLR9was significantly lower in patients withH. influenzaemeningitis than controls (OR, 0.4; 95% CI, 0.2-0.9;p= 0.036). No such differences were found with other causative pathogens, such asStreptococcus pneumoniaeandNeisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variantTLR4genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52-109.80;p= 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07-131.49;p= 0.044) than those with the wild-typeTLR4genotype. Our study suggests an association betweenH. influenzaemeningitis and genetic variation betweenTLR4andTLR9in Angolan children.
  • Basnyat, Pabitra; Virtanen, Elina; Elovaara, Irina; Hagman, Sanna; Auvinen, Eeva (2017)
    Sensitive biomarkers are needed to better manage multiple sclerosis (MS) patients for natalizumab (NTZ)-associated risk of progressive multifocal leukoencephalopathy (PML). A currently used risk stratification algorithm, mainly based on JC polyomavirus (JCPyV) serology, has not led to a reduction of PML incidence. Therefore, this study was designed to evaluate the presence and prevalence of JCPyV miRNAs in plasma of NTZ-treated MS patients, and to explore their biomarker potential for NTZ-associated PML risk assessment. Altogether, 102 plasma samples from 49 NTZ-treated and 28 interferon-beta (IFN-beta)-treated relapsing-remitting MS patients, and 25 healthy controls (HCs) were analyzed for jcv-miR-J1-5p (5p miRNA) and jcv-miR-J1-3p (3p miRNA) expression. The overall detection rate of 5p miRNA was 84% (41/49) among NTZ-treated patients, 75% (21/28) among IFN-beta-treated patients, and 92% (23/25) in HCs. Relative 5p miRNA expression levels were lower in NTZ-treated patients as compared to patients treated with IFN-beta (p = 0.027) but not to HCs. Moreover, 5p miRNA expression inversely correlated with anti-JCPyV antibody index among JCPyV seropositive long-term NTZ-treated patients (r = -0.756; p = 0.002). The overall detection rate of 3p miRNA was low. Our results suggest that JCPyV miRNA in plasma may be linked to the reactivation of persistent JCPyV, to enhanced virus replication, and eventually to the risk of developing PML among NTZ-treated MS patients. However, further study is warranted in a larger data set including samples from PML patients to confirm the clinical relevance of JCPyV miRNA as a sign of/in viral reactivation, and to identify its potential to predict developing PML risk.
  • Sonninen, Tuuli-Maria; Hämäläinen, Riikka H.; Koskuvi, Marja; Oksanen, Minna; Shakirzyanova, Anastasia; Wojciechowski, Sara; Puttonen, Katja; Naumenko, Nikolay; Goldsteins, Gundars; Laham-Karam, Nihay; Lehtonen, Marko; Tavi, Pasi; Koistinaho, Jari; Lehtonen, Sarka (2020)
    In Parkinson's disease (PD), the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta is associated with Lewy bodies arising from the accumulation of alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a disease of the DA neurons, a glial contribution, in particular that of astrocytes, in PD pathogenesis is starting to be uncovered. Here, we report findings from astrocytes derived from induced pluripotent stem cells of LRRK2 G2019S mutant patients, with one patient also carrying a GBA N370S mutation, as well as healthy individuals. The PD patient astrocytes manifest the hallmarks of the disease pathology including increased expression of alpha-synuclein. This has detrimental consequences, resulting in altered metabolism, disturbed Ca2+ homeostasis and increased release of cytokines upon inflammatory stimulation. Furthermore, PD astroglial cells manifest increased levels of polyamines and polyamine precursors while lysophosphatidylethanolamine levels are decreased, both of these changes have been reported also in PD brain. Collectively, these data reveal an important role for astrocytes in PD pathology and highlight the potential of iPSC-derived cells in disease modeling and drug discovery.
  • Outinen, Tuula K.; Tervo, Laura; Makela, Satu; Huttunen, Reetta; Maenpaa, Niina; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka; Aittoniemi, Janne (2013)
  • Peltola, Heikki; Pelkonen, Tuula; Roine, Irmeli; Cruzeiro, Manuel Leite; Bernardino, Luis; Latin Amer Meningitis Study Grp (2016)
    Introduction: C-reactive protein (CRP), a marker of inflammation, shows high serum levels in invasive bacterial infections. We investigated the potential of a single CRP measurement at different phases of acute childhood bacterial meningitis to predict outcomes. Methods: Using whole-blood finger-prick samples with no centrifugation, CRP was measured quantitatively on arrival and on day 3 or 4 in children participating in 2 prospective, randomized, double-blind treatment studies conducted in Latin America or Angola. The results were compared with patient outcomes. Results: Although initial CRP values from 669 children gave useful prognostic information, the 3rd or 4th day measurements taken from 275 children associated significantly with seizures, slow recovery and low scores on the Glasgow Outcome Scale, with odds ratios for CRP values above the median (62 mg/L) ranging from 2 to 6, 2 to 5, and 3 to 5 (Latin America-Angola), respectively. Hearing impairment, although not full deafness, was 3 to 7 times more likely if CRP was above the median soon after hospitalization. Conclusions: Especially in resource-poor settings, clinicians have few simple-enough tools to identify the child with meningitis who requires maximum attention. CRP is a worthy addition.
  • Tenorio-Laranga, Jofre; Coret-Ferrer, Francisco; Casanova-Estruch, Buenaventura; Burgal, Maria; García-Horsman, JA (2010)
  • Chaudhry, Shafqat Rasul; Hafez, Ahmad; Rezai Jahromi, Behnam; Kinfe, Thomas Mehari; Lamprecht, Alf; Niemelä, Mika; Muhammad, Sajjad (2018)
    Aneurysmal subarachnoid hemorrhage (aSAH) represents only a small portion of all strokes, but accounts for almost half of the deaths caused by stroke worldwide. Neurosurgical clipping and endovascular coiling can successfully obliterate the bleeding aneurysms, but ensuing complications such as cerebral vasospasm, acute and chronic hydrocephalus, seizures, cortical spreading depression, delayed ischemic neurological deficits, and delayed cerebral ischemia lead to poor clinical outcomes. The mechanisms leading to these complications are complex and poorly understood. Early brain injury resulting from transient global ischemia can release molecules that may be critical to initiate and sustain inflammatory response. Hence, the events during early brain injury can influence the occurrence of delayed brain injury. Since the damage associated molecular pattern molecules (DAMPs) might be the initiators of inflammation in the pathophysiology of aSAH, so the aim of this review is to highlight their role in the context of aSAH from diagnostic, prognostic, therapeutic, and drug therapy monitoring perspectives. DAMPs represent a diverse and a heterogenous group of molecules derived from different compartments of cells upon injury. Here, we have reviewed the most important DAMPs molecules including high mobility group box-1 (HMGB1), S100B, hemoglobin and its derivatives, extracellular matrix components, IL-1α, IL-33, and mitochondrial DNA in the context of aSAH and their role in post-aSAH complications and clinical outcome after aSAH.
  • Saarinen, Aino; Lieslehto, Johannes; Kiviniemi, Vesa; Häkli, Jani; Tuovinen, Timo; Hintsanen, Mirka; Veijola, Juha (2020)
    Background: Physiological brain pulsations have been shown to play a critical role in maintaining interstitial homeostasis in the glymphatic brain clearance mechanism. We investigated whether psychotic symptomatology is related to the physiological variation of the human brain using fMRI. Methods: The participants (N= 277) were from the Northern Finland Birth Cohort 1986. Psychotic symptoms were evaluated with the Positive Symptoms Scale of the Structured Interview for Prodromal Syndromes(SIPS). We used the coefficient of variation of BOLD signal (CVBOLD) as a proxy for physiological brain pulsatility.The CVBOLD-analyses were controlled for motion, age, sex, and educational level. The results were also compared with fMRI and voxel-based morphometry (VBM) meta-analyses of schizophrenia patients (data from theBrainmap database). Results: At the global level, participants with psychotic-like symptoms had higher CVBOLDin cerebrospinal fluid(CSF) and white matter (WM), when compared to participants with no psychotic symptoms. Voxel-wise analy-ses revealed that CVBOLDwas increased, especially in periventricular white matter, basal ganglia, cerebellum and parts of the cortical structures. Those brain regions, which included alterations of physiological fluctuation in symptomatic psychosis risk, overlappedb6% with the regions that were found to be affected in the meta-analyses of previous fMRI and VBM studies in schizophrenia patients. Motion did not vary as a function of SIPS. Conclusions: Psychotic-like symptoms were associated with elevated CVBOLDin a variety of brain regions. The CVBOLD findings may produce new information about cerebral physiological fluctuations that have been out of reach in previous fMRI and VBM studies.
  • Chaudhry, Shafqat Rasul; Frede, Stilla; Seifert, Gerald; Kinfe, Thomas Mehari; Niemelä, Mika; Lamprecht, Alf; Muhammad, Sajjad (2019)
    Aneurysmal subarachnoid hemorrhage (aSAH) is a highly complex disease. Majority of aSAH survivors confront post-SAH complications including cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) that mainly influence the clinical outcome. Tissue damage during early brain injury may lead to release of damage associated molecular pattern molecules (DAMPs) that may initiate and sustain inflammation during the course of aSAH through activation of pattern recognition receptors. Mitochondrial DNA (mtDNA) due to unmethylated CpG motifs acts as a DAMP via binding to toll-like receptor-9. The aim of this study was to investigate the cell free circulating mtDNA in the systemic circulation of aSAH patients and its association with post-SAH complications and clinical outcome. The DNA was extracted from the serum of 80 aSAH patients at days 1, 3, 5, 7, 9, 11, 13 and from 18 healthy controls. Three representative mitochondrial gene fragments including Cytochrome B (CytB), D-Loop and Cytochrome c oxidase subunit-1 (COX-1) were quantified using a Taqman-probes based qPCR. Levels of mtDNA were quantified from standard curves generated using mtDNA extracted from HepG2 cell mitochondria. Clinical outcome of the patients was assessed by Glasgow outcome scale (GOS) and modified Rankin scale (mRS). Clinical data and post-SAH complications were recorded from patient's record file. Serum D-Loop and COX-1 were significantly elevated early after aSAH and remained high over first 2 weeks. CytB levels were however, initially unchanged but elevated later at day 7 as compared to healthy controls. Cumulative levels measured over two weeks showed significant correlations with post-SAH complications including a negative correlation of D-Loop with pneumonia infection, hydrocephalus and occurrence of epilepsy, a positive correlation of Cyt B with occurrence of CVS and a negative correlation of COX-1 with occurrence of systemic infections and seizures. Cumulative D-Loop values negatively correlated with clinical outcome. Our data suggest that mtDNA may directly or indirectly influence post-SAH complications and clinical outcome.
  • Savonius, Okko; Roine, Irmeli; Alassiri, Saeed; Tervahartiala, Taina; Helve, Otto; Fernandez, Josefina; Peltola, Heikki; Sorsa, Timo; Pelkonen, Tuula (2019)
    Background. Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods. Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996-2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results. MPO correlated positively with MMP-8 (rho 0.496, P
  • Heikinheimo-Connell, T.; Poutiainen, E.; Salonen, O.; Elovaara, I.; Ristola, Matti A (2015)
    Objectives: Is it possible to live without neurocognitive or neurological symptoms after being infected with HIV for a very long time? These study patients with decades-long HIV infection in Finland were observed in this follow-up study during three time periods: 1986-1990, in 1997 and in 2013. Setting: Patients from greater Helsinki area were selected from outpatient's unit of infectious diseases. Participants: The study included 80 HIV patients. Patients with heavy alcohol consumption, central nervous system disorder or psychiatric disease were excluded. Primary and secondary outcome measures: The patients underwent neurological and neuropsychological examinations, MRI of the brain and laboratory tests, including blood CD4 cells and plasma HIV-1 RNA. Neuropsychological examination included several measures: subtests of Wechsler Adult Intelligence Scale, Wechsler Memory Scale-Revised, list learning, Stroop and Trail-Making-B test. The Beck Depression Inventory and Fatigue Severity Scale were also carried out. The obtained data from the three time periods were compared with each other. Results: Owing to high mortality among the original 80 patients, eventually, 17 participated in all three examinations performed between 1986 and 2013. The time from the HIV diagnosis was 27 (23-30) years. Blood CD4 cells at the diagnosis were 610 (29-870) cells/mm(3), and the nadir CD4 168 (4-408) cells/mm(3). The time on combined antiretroviral treatment was 13 (5-17) years. 9 patients suffered from fatigue, 5 had polyneuropathy and 3 had lacunar cerebral infarcts. There was a subtle increase of brain atrophy in 2 patients. Mild depressive symptoms were common. The neuropsychological follow-up showed typical age-related cognitive changes. No HIV-associated dementia features were detected. Conclusions: Polyneuropathy, fatigue and mild depression were common, but more severe neurological abnormalities were absent. These long-term surviving HIV-seropositive patients, while on best-available treatment, showed no evidence of HIV-associated neurocognitive disorder in neuropsychological and neuroradiological evaluations.