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Background: Attempts to determine the prognostic factors that affect the survival time of canine patients with meningoencephalitis of unknown origin (MUO) have produced highly variable results. Scaled complex ratings to predict general outcomes are required. Scaled rating was recently proven to help predicting prognosis in general MUO population of dogs. However, Yorkshire Terriers (YST) are predisposed to necrotizing meningoencephalitis, especially necrotizing leukoencephalitis, which more frequently manifests itself with forebrain lesions and may exhibit a distinct disease course compared to granulomatous meningoencephalitis. This study aimed to determine the usefulness of neurological assessment scales in the prognosis of YST with MUO. The study population comprised 127 YST which met inclusion criteria for a highly probable diagnosis of MUO. This multicentre, cohort study was designed as a retrospective review of medical records. Based on documented neurological examinations, animals were scored on three scales: the Modified Glasgow Coma Scale, Neuro Disability Scale 1 (Smith et al.), and Neuro Disability Scale 2 (Gonçalves et al.). The association between the scores and survival time was investigated over three periods of time - 7 days, 100, and 365 days (1 year) after onset of clinical signs., Results: All scales were significantly associated (p < 0.001) with MUO-specific survival and death of MUO within the first 7 days and had high prognostic accuracy in terms of short-term prognosis. None of the scales was significantly associated with the probability of survival after 100 or 365 days. Dogs with unilateral lesions on magnetic resonance images (MRI) had approximately 12- and threefold higher odds of surviving up to 100 and 365 days, respectively, than dogs with bilateral lesions on MRI. Dogs heavier than 3.2 kg at presentation had approximately sixfold higher odds of survival up to day 365., Conclusions: The study provides strong evidence for a high short-term prognostic accuracy of the three neurological assessment scales in YST with MUO - the scales seem to be very useful in predicting death within the first week of the onset of MUO. However, the scales do not appear to have prognostic value in the longer time frame. However, the presence of unilateral MRI changes and dog's body weight may assist with medium- and long-term prognosis., Competing Interests: Declarations. Ethics approval and consent to participate: This study has been granted an exemption from requiring ethics approval, according to the decision (9/2024) of the Animal Welfare Advisory Team Supervisor of Wroclaw University of Environmental and Life Sciences. In accordance with the Experiments on Animals Act from January 15th, 2015 (Journal of Laws of the Republic of Poland, 2015, item. 266), concerning the welfare of the animals used for research or teaching purposes, the restrictions defined in the law shall not apply to clinical veterinary studies carried out according to Article 37ah-37ak of the Act from September 6th, 2001 – Pharmaceutical Law (Journal of Laws from 2008, No. 45, item 271 as amended in item 4). Hence, ethical review and approval was not required for this animal study as the study was retrospective. Additionally, MRI and CSF examinations are standard diagnostic procedures performed in diagnosis of central nervous system diseases in companion animals. Informed written consent for all medical procedures was obtained from all owners. The animals were handled according to high ethical standards and national legislation. Decision to euthanise was made by the animal's owner in consultation with the veterinarian and performed in accordance with the national law. The medicament used (pentobarbital) is registered for euthanasia reasons and was administered IV as the second step after sedation or general anaesthesia. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cryptococcosis, caused by fungi of the genus Cryptococcus , manifests in a broad range of clinical presentations, including severe pneumonia and disease of the central nervous system (CNS) and other tissues (bone and skin). Immune deficiency or development of overexuberant inflammatory responses can result in increased susceptibility or host damage, respectively, during fungal encounters. Leukotrienes help regulate inflammatory responses against fungal infections. Nevertheless, studies showed that Cryptococcus exploits host 5-lipoxygenase (5-LO), an enzyme central to the metabolism of arachidonic acid into leukotrienes, to facilitate transmigration across the brain-blood barrier. To investigate the impact of host 5-LO on the development of protective host immune responses and mortality during cryptococcosis, wild-type (C57BL/6) and 5-lipoxygenase-deficient (5-LO -/- ) mice were given experimental pulmonary and systemic Cryptococcus sp., infections. Our results showed that 5-LO -/- mice exhibited reduced pathology and better disease outcomes (i.e., no mortality or signs associated with cryptococcal meningoencephalitis) following pulmonary infection with C. deneoformans, despite having detectable yeast in the brain tissues. In contrast, C57BL/6 mice exhibited classical signs associated with cryptococcal meningoencephalitis. Additionally, brain tissues of 5-LO -/- mice exhibited lower levels of cytokines (CCL2 and CCL3) clinically associated with Cryptococcus -related immune reconstitution inflammatory syndrome (C-IRIS). In a systemic mouse model of cryptococcosis, 5-LO -/- mice and those treated with a Federal Drug Administration (FDA)-approved 5-LO synthesis inhibitor, zileuton, displayed significantly reduced mortality compared to C57BL/6 infected mice. These results suggest that therapeutics designed to inhibit host 5-LO signaling could reduce disease pathology and mortality associated with cryptococcal meningoencephalitis., Importance: Cryptococcosis is a mycosis with worldwide distribution and has a broad range of clinical manifestations, including diseases of the CNS. Globally, there is an estimated 179,000 cases of cryptococcal meningitis, resulting in approximately 112,000 fatalities per annum and 19% of AIDS-related deaths. Understanding how host immune responses are modulated during cryptococcosis is central to mitigating the morbidity and mortality associated with cryptococcosis. Leukotrienes (LTs) have been shown to modulate inflammatory responses during infection. In this study, we show that mice deficient in 5-lipoxygenase (5-LO), an enzyme central to the metabolism of arachidonic acid into leukotrienes, exhibit reduced pathology, disease, and neurological signs associated with cryptococcal meningitis. Additionally, mice given an experimental cryptococcal infection and subsequently treated with an FDA-approved 5-LO synthesis inhibitor exhibited significantly reduced mortality rates. These results suggest that therapeutics designed to inhibit host 5-LO activity could significantly reduce pathology and mortality rates associated with cryptococcal meningitis., Competing Interests: The authors declare no conflict of interest.

Background: The prognosis of individual dogs with meningoencephalomyelitis of unknown etiology (MUE) remains difficult to predict. MUE cases with no lesions detected by magnetic resonance imaging (MRI) occur, but it is unknown whether this finding is associated with prognosis., Hypothesis: MUE cases without detectable lesions on MRI have a better outcome than cases with detectable lesions., Animals: Study included 73 client-owned dogs with MUE presenting to Purdue University Veterinary Hospital from 2010 to 2020., Methods: Retrospective study. Dogs with a clinical diagnosis of MUE were identified by medical record search. MRI reports were reviewed for presence or absence of lesions consistent with MUE. Clinical findings at presentation, treatment, disease-specific survival, and outcomes including rates of remission and relapse were compared between cases with normal MRI or abnormal MRI., Results: Overall, 54 dogs (74%) were classified as abnormal MRI, and 19 dogs (26%) were classified as normal MRI cases. Death caused by MUE occurred in 1/19 (5%) normal MRI dogs and 18/54 (33%) abnormal MRI dogs (P = .016). Median survival was >107 months in both groups, but survival was significantly longer in the normal MRI group (P = .019). On multivariate analysis, abnormal MRI was significantly related to death (hazard ratio, 7.71; 95% confidence interval 1.03-58.00, P = .0470), whereas significant relationships with death were not identified for either the use of secondary immunosuppressive medications or cerebrospinal fluid nucleated cell count., Conclusions: MUE dogs with no detectable lesions on MRI have reduced disease-related death compared with dogs with abnormal MRI. The presence or absence of MRI lesions in MUE dogs is prognostically relevant., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking., Objectives: To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE <52 weeks old., Animals: Thirty-four client-owned dogs., Methods: Multicenter retrospective case series. Records from 5 referral centers were searched. Data was extracted from the medical records and referring veterinarians were contacted for survival data if this was not available from the record., Results: The mean age was 31 weeks; the youngest dog was 11 weeks and 3 dogs were <16 weeks old. Altered mentation (71%), ataxia (44%), seizures (29%), and circling (26%) were the most common presenting complaints. Neuroanatomical localization was to the forebrain (38%), multifocal (35%), brainstem (18%), and cerebellum (12%). Corticosteroid monotherapy (n = 15) and corticosteroid plus cytosine arabinoside (n = 15) were used in equal proportions. Outcome data was available for 26 dogs, 8 (31%) were alive at the time of data collection with a follow-up range of 135 to 2944 days. Death or euthanasia was related to MUE in 17/18 dogs that died during the study period. Kaplan-Meier survival analysis demonstrated a median survival time for all-cause death of 84 days., Conclusion: The prognosis for MUE in this subset of dogs was considered poor., (© 2024 Davies Veterinary Specialists part of Linnaeus Veterinary Ltd. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To describe the long-term outcomes, overall survival, progression-free survival, and prognostic factors in dogs with necrotizing encephalitis (NE)., Animals: 37 client-owned dogs clinically diagnosed with NE., Methods: All dogs underwent MRI and CSF analysis. Cox proportional hazards regression was used to examine factors related to the risk of relapse and death, including signalment, history, diagnostic investigation results, and treatments before the first relapse., Results: The medians of the overall and progression-free survival times were 639 days (IQR, 342 to 1,482 days) and 233 days (IQR, 111 to 775 days), respectively. Overall survival was highly correlated with progression-free survival. Four dogs (11%) died or were euthanized within 3 months of diagnosis. Relapse within 6 months was associated with a shorter overall survival. However, no prognostic factors for overall survival were found. The category of patients with presenting clinical signs that lasted 29 days to 6 months (OR, 3.26; 95% CI, 1.35 to 7.90) was associated with a higher risk of relapse. Seizures were presented in 75.7% of dogs, with a recurrence rate of 100%., Clinical Relevance: This report provides comprehensive follow-up information for dogs with NE, revealing a fair prognosis and low early mortality rate. Seizure is a very common clinical sign with a high recurrence rate.

Background: Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging., Objectives: Identify clinical prognostic variables in dogs with MUO., Animals: A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO., Methods: Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse., Results: Eighty-two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P = .03), epileptic seizures (P < .001), paresis (P < .001), and higher neurodisability scale (NDS) score (P < .001) at presentation were negatively associated with survival to 6 months. Dogs with persistent deficits had higher NDS scores on presentation (P = .001). Median follow-up time was 11 months (interquartile range [IQR], 1-24) and 50.6% (160/316) relapsed during treatment (median time to relapse, 7 months; IQR, 2-15). Incomplete resolution of the clinical signs during the 6 months after diagnosis (P < .001), higher NDS score (P < .001), and longer duration of the clinical signs (P < .001) were associated with relapse., Conclusions and Clinical Importance: Knowledge of risk factors associated with survival, incomplete recovery and clinical relapse in MUO can help guide monitoring and treatment and improve owner communications regarding prognosis for this debilitating disease., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Neurological diseases in cattle can be caused by several infectious agents. Astroviruses are increasingly recognized as the causative agent of encephalitis in various animals, including humans. In this study, a neuroinvasive astrovirus (BoAstV 20B05) was discovered in the brain tissues of an 81-month-old Korean native cattle with neurological symptoms. Lymphocyte infiltration and multifocal perivascular cuffing were observed in the cerebrum and brain stem, and viral antigens were also detected in the meninges. In particular, the concentration of the astroviral genome was high in the brain tissues. Korean BoAstV 20B05 was classified into the CH13/NeuroS1 clade and was closely related to the Neuro-Uy and KagoshimaSR28-462 strains. Our evolutionary analysis showed that Korean BoAstV 20B05 belongs to the sub-lineage NeuroS1 and evolved independently of BoAstV KagoshimaSR28-462. These results suggest that neuroinvasive astroviruses were first introduced in Korea. However, analysis is limited by the lack of reference astrovirus sequences reported in various countries within Asia, and further analysis should be performed using more strains. In this study, we identified a neuroinvasive astrovirus infection with neurological symptoms for the first time in South Korea and confirmed that BoAstV 20B05 may have been introduced in South Korea a long time ago.

Cryptococcal meningoencephalitis was first described over a century ago. This fungal infection is preventable and treatable yet continues to be associated with excessive morbidity and mortality. The largest burden of disease resides in people living with HIV in low-income and middle-income countries. In this group, mortality with the best antifungal induction regimen (7 days of amphotericin B deoxycholate [1·0 mg/kg per day] and flucytosine [100·0 mg/kg per day]) in a clinical trial setting was 24% at 10 weeks. The world is now at an inflection point in terms of recognition, research, and action to address the burden of morbidity and mortality from cryptococcal meningoencephalitis. However, the scope of interventional programmes needs to increase, with particular attention to implementation science that is specific to individual countries. This Review summarises causes of excessive mortality, interventions with proven survival benefit, and gaps in knowledge and practice that contribute to the ongoing high death toll from cryptococcal meningoencephalitis. TRANSLATIONS: For the Vietnamese and Chichewa translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests KES, AL, MA, TSH, HCM, and DGL declare no competing interests. TB has received research funding from Gilead Sciences and speaker fees from Gilead Sciences and Pfizer. JND has received fees for scientific consulting for Viamet Pharmaceuticals. JRP has research grants from, and does consultations for, Astellas, Pfizer, Merck, F2G, Amplyx, Matinas, Scynexis, Appili, and Minnetronix. WH holds, or has recently held, research grants with F2G, Astellas Pharma, Spero Therapeutics, Antabio, Allecra, Bugworks, and NAEJA-RGM. WH has received personal fees in his capacity as a consultant for F2G, Amplyx, Ausperix, Spero Therapeutics, VenatoRx, Pfizer, and BLC/TAZ. JNJ declares no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In Cryptococcus neoformans meningoencephalitis, brain MRI findings might reflect the phathomechanism of disease progression that is fungal accumulation in the peri-venular space and consequent invasion into the parenchyma. This study analyzed serial brain MRI findings of 76 patients with cryptococcus meningoencephalitis in association with the disease progression and outcomes. MRI parameters included the enlarged periventricular space (ePVS) score (range 0-8), periventricular lesion extension, cryptococcoma, and hydrocephalus. Clinical outcomes at 2-week, 10-week, and 6-month were evaluated using modified Rankin scale (mRS). At 6 months, 15 (19.7%) patients died and 34 (44.1%) had poor neurological outcomes (mRS scores > 2). At baseline, an ePVS score of ≥ 5 (Odds-ratio [OR]: 94.173, 95% confidence-interval [95%CI]: 7.507-1181.295, P < .001), periventricular lesion extension (OR: 51.965, 95%CI: 2.592-1041.673, P = .010), and presence of encephalitis feature (OR: 44.487, 95%CI: 1.689-1172.082, P = .023) were associated with 6-month poor outcomes. Presence of two or more risk factors among encephalitis feature, ePVS score ≥ 5, and periventricular lesion extension at baseline, was associated with 6-month poor outcomes (area under the curve [AUC]: 0.978, P < .001) and mortality (AUC: 0.836, P < .001). Disease progression was associated with interval development of cryptococcoma and hydrocephalus. Brain MRI findings might be useful in predicting outcomes and monitoring the progression of cryptococcus meningoencephalitis.

Background: Combination therapy with glucocorticoids and adjunctive immunomodulating drugs has been generally accepted as a standard treatment regimen for meningoencephalomyelitis of unknown etiology (MUE). We hypothesized that treatment with MMF as an adjunctive agent along with glucocorticoids would be effective and well-tolerated protocol in dogs with MUE. Eighty-six dogs with MUE between May 2009 and June 2017 were included (59 females and 27 males; mean age of 5.93 years; mean body weight of 3.83 kg). The medical records of dogs with MUE treated with prednisolone and MMF were retrospectively evaluated to determine the therapeutic response, survival time, and treatment-related adverse effects., Results: A partial or complete response (CR) was recorded for 75 dogs. The overall median survival time from the initiation of treatment was 558 days. Dogs that showed CR with no relapse over the treatment period (from diagnosis to death) had significantly longer median survival times. A significantly higher mortality hazard ratio of 4.546 was recorded in dogs that failed to achieve CR. The interval between the onset of clinical signs and the clinical presentation was not significantly associated with CR, relapse rate, and survival time. Adverse effects included gastrointestinal upsets in 26 dogs (30.23%), sporadic infections in 17 dogs (19.77%), and pancreatitis in seven dogs (8.14%)., Conclusions: The results suggest that adjunctive MMF treatment for MUE is safe and comparable to other immunosuppressive protocols. The treatment should focus on the achievement of CR and preventing relapse for successful management.

Background: Rickettsia felis has recently emerged worldwide as a cause of human illness. Typically causing mild, undifferentiated fever, it has been implicated in several cases of non-fatal neurological disease in Mexico and Sweden. Its distribution and pathogenicity in Southeast Asia is poorly understood., Methodology/principal Findings: We retroactively tested cerebrospinal fluid (CSF) or sera from 64 adult patients admitted to hospital in North Sulawesi, Indonesia with acute neurological disease. Rickettsia felis DNA was identified in the CSF of two fatal cases of meningoencephalitis using multi-locus sequence typing semi-nested PCR followed by Sanger sequencing. DNA from both cases had 100% sequence homologies to the R. felis reference strain URRWXCal2 for the 17-kDa and ompB genes, and 99.91% to gltA., Conclusion/significance: The identification of R. felis in the CSF of two fatal cases of meningoencephalitis in Indonesia suggests the distribution and pathogenicity of this emerging vector-borne bacteria might be greater than generally recognized. Typically Rickettsia are susceptible to the tetracyclines and greater knowledge of R. felis endemicity in Indonesia should lead to better management of some acute neurological cases., Competing Interests: The authors have declared that no competing interests exist.

Encephalitis causes high morbidity and mortality. An incidence of 4.3 cases of encephalitis/100 000 population has been reported in the UK. We performed a retrospective evaluation of the diagnosis and management of adults admitted to hospital with a clinical diagnosis of encephalitis/meningoencephalitis. Clinical, laboratory and radiological data were collated from electronic records. Thirty-six patients, median age 55 years and 24 (67%) male were included. The aetiology was confirmed over nine months in 25 (69%) of whom 16 were infections (six viral, seven bacterial, two parasitic and one viral and parasitic co-infection); 7 autoimmune; 1 metabolic and 1 neoplastic. Of 24 patients with fever, 15 (63%) had an infection. The median time to computed topography, magnetic resonance imaging and electroencephalography (EEG) was 1, 8 and 3 days respectively. Neuroimaging was abnormal in 25 (69%) and 17 (89%) had abnormal EEGs. Only 19 (53%) received aciclovir treatment. Six (17%) made good recoveries, 16 (44%) had moderate disability, 8 (22%) severe disability and 6 (17%) died. Outcomes were worse for those with an infectious cause. In summary, a diagnosis was made in 69.4% of patients admitted with encephalitis/meningoencephalitis. Autoimmune causes are important to consider at an early stage due to a successful response to treatment. Only 53% of patients received aciclovir on admission. Neuroimaging and EEG studies were delayed. The results of this work resulted in further developing the clinical algorithm for managing these patients.

Suppurative meningitis-meningoencephalitis (M-ME) is a sporadic disease in neonatal ungulates and only a few studies have reported the involvement of Streptococcus bovis/Streptococcus equinus complex (SBSEC) members in bovine neonatal M-ME. The SBSEC taxonomy was recent revised and previous biotype II/2 was reclassified as S. gallolyticus subsp. pasteurianus (SGP). The aim of this study was to describe a case of fatal neonatal neurological syndrome associated with SGP in calves. Ten calves were monitored because of neurological hyperacute symptoms associate with bilateral hypopyon and death. They were not fed with maternal colostrum; two of them died and were subjected to bacteriological, histopathological and biomolecular analysis as well as antibiotic susceptibility test. Both animals presented lesions mostly concentrated to meninges and brain and had bilateral hypopyon. Nine strains isolated in purity from brain, ocular humors and colon were identified as S. bovis group by using the API Strep system and as S. gallolyticus by using the 16S rRNA sequence. Two of these strains where subjected to WGS analysis that confirmed the sub-species identification and the clonality of the two SGP strains. The strains were found resistant to OT, SXT, MTZ and EN and susceptible to AMP, AMC, KZ and CN. We hypothesized that the syndrome observed could be due to the lack of maternal colostrum feeding. A timely and precise diagnosis could have likely prevented the death of the calves and, since the zoonotic potential of SBSECs members is known, accurate and rapid identification is required., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Primary amebic encephalitis (PAM) is a devastating central nervous system infection caused by Naegleria fowleri, a free-living amoeba, which can survive in soil and warm fresh water. Here, a 43-year-old healthy male was exposed to warm freshwater 5 days before the symptom onset. He rapidly developed severe cerebral edema before the diagnosis of PAM and was treated with intravenous conventional amphotericin B while died of terminal cerebral hernia finally. Comparing the patients with PAM who has similar clinical symptoms to those with other common types of meningoencephalitis, this infection is probably curable if treated early and aggressively. PAM should be considered in the differential diagnosis of purulent meningoencephalitis, especially in patients with recent freshwater-related activities during the hot season.

The aim of our study was to describe the clinical features, the etiologies, and the factors associated with poor outcome of encephalitis in French Guiana. Our study was retrospective, including all cases of encephalitis hospitalized in the Cayenne General Hospital, from January 2007 to July 2017. Patients were included through the 2013 encephalitis consortium criteria and the outcome was evaluated using the Glasgow outcome scale at 3 months from the diagnosis of encephalitis. We included 108 patients, giving an approximate incidence rate of four cases/100,000 inhabitants/year. The origin of the encephalitis was diagnosed in 81 cases (75%), and 72 of them (66.7%) were from an infectious origin. The most common infectious causes were Cryptococcus sp. (18.5%) independently of the immune status, Toxoplasma gondii (13.9%), and Streptococcus pneumoniae (5.5%). In the follow-up, 48 patients (46.6%) had poor outcome. Independent risk factors associated with poor outcome at 3 months were "coming from inside area of the region" ( P = 0.036, odds ratio [OR] = 4.19; CI 95% = 1.09-16.06), need for mechanical ventilation ( P = 0.002, OR = 5.92; CI 95% = 1.95-17.95), and age ≥ 65 years ( P = 0.049, OR = 3.99; CI 95% = 1.01-15.89). The most identified cause of encephalitis in French Guiana was Cryptococcus . The shape of the local epidemiology highlights the original infectious situation with some local specific pathogens.

The efficacy of recombinant interferon γ (rIFN-γ) for cryptococcal meningoencephalitis has been poorly understood. Compared to Cryptococcus gattii, rIFN-γ significantly improved the survival in experimental meningoencephalitis due to Cryptococcus neoformans. The number of phagocytic macrophages and the levels of inflammatory cytokines production for ex vivo co-incubation with C. neoformans were increased after rIFN-γ stimulation but not C. gattii. Intraspecies differences of phagocytosis by the rIFN-γ-activated macrophages might be associated to the severity of cryptococcal infection.

Cryptococcus neoformans is a major fungal pathogen that disseminates to the central nervous system (CNS) to cause fatal meningoencephalitis, but little is known about immune responses within this immune-privileged site. CD4 + T cells have demonstrated roles in anticryptococcal defenses, but increasing evidence suggests that they may contribute to clinical deterioration and pathology in both HIV-positive (HIV+) and non-HIV patients who develop immune reconstitution inflammatory syndrome (IRIS) and post-infectious inflammatory response syndrome (PIIRS), respectively. Here we report a novel murine model of cryptococcal meningoencephalitis and a potential damaging role of T cells in disseminated cryptococcal CNS infection. In this model, fungal burdens plateaued in the infected brain by day 7 postinfection, but activation of microglia and accumulation of CD45 hi leukocytes was significantly delayed relative to fungal growth and did not peak until day 21. The inflammatory leukocyte infiltrate consisted predominantly of gamma interferon (IFN-γ)-producing CD4 + T cells, conventionally believed to promote fungal clearance and recovery. However, more than 50% of mice succumbed to infection and neurological dysfunction between days 21 and 35 despite a 100-fold reduction in fungal burdens. Depletion of CD4 + cells significantly impaired IFN-γ production, CD8 + T cell and myeloid cell accumulation, and fungal clearance from the CNS but prevented the development of clinical symptoms and mortality. These findings conclusively demonstrate that although CD4 + T cells are necessary to control fungal growth, they can also promote significant immunopathology and mortality during CNS infection. The results from this model may provide important guidance for development and use of anti-inflammatory therapies to minimize CNS injury in patients with severe cryptococcal infections. IMPORTANCE CNS infection with the fungal pathogen Cryptococcus neoformans often results in debilitating brain injury and has a high mortality rate despite antifungal treatment. Treatment is complicated by the fact that immune responses needed to eliminate infection are also thought to drive CNS damage in a subset of both HIV+ and non-HIV patients. Thus, physicians need to balance efforts to enhance patients' immune responses and promote microbiological control with anti-inflammatory therapy to protect the CNS. Here we report a novel model of cryptococcal meningoencephalitis demonstrating that fungal growth within the CNS does not immediately cause symptomatic disease. Rather, accumulation of antifungal immune cells critically mediates CNS injury and mortality. This model demonstrates that antifungal immune responses in the CNS can cause detrimental pathology and addresses the urgent need for animal models to investigate the specific cellular and molecular mechanisms underlying cryptococcal disease in order to better treat treat patients with CNS infections.

Background: Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors., Methods: MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597., Findings: We enrolled 818 cases from 372 centres, including 107 maternal-neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41-0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01-8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32-14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79-6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82-7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60-8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50-13·98], p=0·008)., Interpretation: The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis., Funding: Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although several studies indicate that meningoencephalitis of unknown aetiology (MUA) might affect every dog breed at every age, little is known about clinical presentation, diagnostic findings and long-term survival in large breed dogs. The aim of this study was therefore to compare the clinical presentation, diagnostic findings and long-term survival between large and small/medium breed dogs diagnosed with MUA. One hundred and eleven dogs met the inclusion criteria. 28 (25 per cent) dogs were considered large breed dogs compared with 83 (75 per cent) small/medium breed dogs. Large breed dogs presented significantly more often with a decreased mentation. Age, gender, duration of clinical signs prior to diagnosis, presence of seizures or cluster seizures, variables on complete blood count and cerebrospinal fluid analysis, and all variables on MRI were not significantly different between small/medium and large breed dogs. Median survival time was 281 and 106 days for the large and small/medium breed dogs, respectively, with no significant difference in survival curves for both groups. Although considered not typically affected by MUA, 25 per cent of dogs included in this study were considered large breed dogs. Therefore, MUA should be included in the differential diagnosis for large breed dogs presenting with intracranial neurological signs. If diagnosed with MUA, large breed dogs also carried a guarded prognosis., (British Veterinary Association.)

Background: Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management., Methods: We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia between February 2012 and March 2013. Cerebrospinal fluid was sent for microscopy, biochemistry, bacterial and mycobacterial cultures, Mycobacterium tuberculosis polymerase chain reaction (PCR), and multiplex and MassCode PCR for various viral and bacterial pathogens., Results: A total of 84 patients with clinically suspected meningitis and encephalitis were enrolled. An aetiological agent was confirmed in 37/84 (44 %) of the patients. The most common diagnoses were tuberculous meningitis (TBM) (41/84, 48.8 %) and cryptococcal meningoencephalitis (14/84, 16.6 %). Mycobacterium tuberculosis was confirmed in 13/41 (31.7 %) clinically diagnosed TBM patients by cerebrospinal fluid PCR or culture. The acute case fatality rate during hospital admission was 16/84 (19 %) in all patients, 4/43 (9 %) in non-TBM, and 12/41 (29 %) in TBM patients respectively (p = 0.02)., Conclusion: TBM is the most common cause of CNS infection in patients aged 12 years or older in Kota Kinabalu, Sabah, Malaysia and is associated with high mortality and morbidity. Further studies are required to improve the management and outcome of TBM.

Background: Bacterial meningitis is a life-threatening emergency that is still associated with high mortality and poor outcome., Objective: The purpose of this article is to provide a review of clinical presentation, diagnostic procedure, therapy, and prognosis in bacterial meningitis. Prognostic factors which could be influenced positively are identified and a focused procedure in the emergency setting and for the treatment of complications are provided., Material and Methods: This work is based on a literature search (PubMed, guidelines) and personal experience (standard operating procedures, SOP)., Results: Despite improved health care, bacterial meningitis is still associated with high mortality and poor neurological outcome, which has remained largely unaltered during recent decades. Diagnosis and, more importantly, effective therapy of bacterial meningitis are often delayed, having an immediate negative influence on clinical outcome. Neurological and nonneurological complications often necessitate intensive care and may occur rapidly or in the further course of the disease., Conclusion: Immediate initiation of effective therapy is crucial to positively influence mortality and neurological outcome. Antibiotics should be administered within 30 min after admission. To achieve this, a focused and well-organized procedure in the emergency setting is necessary. Because of intra- and extracranial complications, patients need to be treated on intensive care units including neurological expertise and interdisciplinary support.

Cryptococcal meningoencephalitis (CM) may present as an acute, subacute, or chronic infection. It manifests as a chronic process in over 75 % of cases, but, sometimes, it presents with a more acute onset, mostly in HIV-associated patients. Until now, there has been no study performed on the clinical features of HIV-negative CM patients with acute/subacute onset. We collected 106 HIV-negative patients diagnosed with CM in our hospital during a 15-year period, analyzed their epidemiological and clinical features, as well as the outcomes, and explored the independent prognosis factors and the factors related to the survival time among them. We found that impaired consciousness (23.4 % vs. 3.4 %, p = 0.017) was more common in CM patients with acute/subacute onset, while decreased cerebrospinal fluid (CSF) glucose (51.9 % vs. 75.9 %, p = 0.026) was less common. The ratio of CSF glucose/blood glucose [odds ratio (OR) 0.04, 95 % confidence interval (CI) 0.004-0.262, p = 0.02], impaired consciousness (OR 5.09, 95 % CI 1.477-17.522, p = 0.01), and hospitalization length (OR 0.98, 95 % CI 0.977-0.999, p = 0.04) were indicated to be not only independent prognosis factors in HIV-negative CM patients with acute/subacute onset, but also factors significantly related to the survival time. The results of our study demonstrated that the contact history and potential history risk factors would not affect the onset process of HIV-negative CM patients, and the mortality, hospitalization length, and survival time has not been related to the onset process. However, the ratio of CSF glucose/blood glucose, consciousness level, and hospitalization length of the HIV-negative CM patients with acute/subacute onset should be of greater focus in the clinical work.

Background: Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D., Methods: In vivo, we studied the effects of vitamin D3 on survival and the host's immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured., Results: Mice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation., Conclusion: Our observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

The objective of the present study was to elucidate the specific clinical features of otogenic intracranial complications (ICC) encountered in the current otorhinolaryngological practice. The work is based on the results of the retrospective analysis of 106 adult patients presenting with otogenic intracranial complications admitted for the treatment to multidisciplinary clinics of Sankt-Peterburg and Krasnoyarsk. Forty six (42.5%) patients presented with acute otitis media. 90% of them had suppurative destructive mastoiditis. In sixty (56.6%) patients, chronic suppurative otitis media (epitympanophonia) was associated with the extensive destructive process spreading toward dura mater of the medial and posterior cranial fossae and onto the sigmoid sinus. The prevalence of intracranial complications among the adult patients suffering from suppurative otitis media and treated in the otorhinolaryngological clinics amounted to 3.17%. The overall structure of otogenic intracranial complications was as follows: meningitis 42.5%, brain and cerebellum abscess 24.5%, suppurative meningoencephalitis 19.8%, sinus thrombosis 5.7%, epidural and subdural empyemas 4.7%, the combined suppurative brain lesions 2.8%. Systemic inflammatory response syndrome (sepsis) was diagnosed in 33 (31%) patients with otogenic ICC. The high intrahospital mortality rate among the patients with this condition (20.8%) is emphasized. The main causes of the fatal outcome in the patients with otogenic intracranial complications are supposed to be brain oedema with the concomitant development of dyslocation syndrome and sepsis.

Cryptococcus neoformans is a human fungal pathogen that causes lethal infections of the lung and central nervous system in immunocompromised individuals. C. neoformans has a defined bipolar sexual life cycle with a and α mating types. During the sexual cycle, which can occur between cells of opposite mating types (bisexual reproduction) or cells of one mating type (unisexual reproduction), a dimorphic transition from yeast to hyphal growth occurs. Hyphal development and meiosis generate abundant spores that, following inhalation, penetrate deep into the lung to enter the alveoli, germinate, and establish a pulmonary infection growing as budding yeast cells. Unisexual reproduction has been directly observed only in the Cryptococcus var. neoformans (serotype D) lineage under laboratory conditions. However, hyphal development has been previously associated with reduced virulence and the serotype D lineage exhibits limited pathogenicity in the murine model. In this study we show that the serotype D hyperfilamentous strain XL280α is hypervirulent in an animal model. It can grow inside the lung of the host, establish a pulmonary infection, and then disseminate to the brain to cause cryptococcal meningoencephalitis. Surprisingly, this hyperfilamentous strain triggers an immune response polarized towards Th2-type immunity, which is usually observed in the highly virulent sibling species C. gattii, responsible for the Pacific Northwest outbreak. These studies provide a technological advance that will facilitate analysis of virulence genes and attributes in C. neoformans var. neoformans, and reveal the virulence potential of serotype D as broader and more dynamic than previously appreciated.

Objectives: Infective native valve endocarditis (NVE) complicated by a preoperative neurological event still remains a surgical challenge. Particularly, great uncertainty exists with regard to the optimal timing of surgery. We call for a multidisciplinary team approach for individualized risk estimation and analysed our experience obtained over the past decade., Methods: Between 1997 and 2012, a total of 495 patients underwent valve surgery for the treatment of NVE. Of these, 70 (14.1%) patients suffered from NVE complicated by an acute neurological event and formed the study group. The remaining 425 (85.9%) patients served as the control group. The mean age of the predominantly male (80.0%) study population was 54 ± 14 years. EuroSCORE and EuroSCORE II predicted a high surgical risk (24.9 ± 6.8 and 10.8 ± 8.1%, respectively). The mean follow-up time was 4.0 ± 3.1 years, ranging up to 15.6 years with an interquartile range from 1.7 to 5.4 years. An interdisciplinary team consisting of a cardiac surgeon, a cardiologist and a neurologist made the decision for surgery., Results: Observed neurological deficits mainly consisted of ischaemic stroke (75.7%), meningoencephalitis (12.9%) and intracerebral haemorrhage (8.6%). The mean time interval between the neurological event and surgery was 8.7 ± 10.3 days for all patients, 8.0 ± 7.0 days for ischaemic stroke and 17 ± 24 days for intracerebral haemorrhage. Postoperatively, most of the patients experienced no change (22.9%) or even improvement (67.1%) of their neurological symptoms. Only 10.0% showed further deterioration of their neurological status. This was particularly true for patients suffering from intracerebral haemorrhage, with 33.3% experiencing further neurological impairment. The presence of a preoperative neurological event was identified as an independent risk factor for in-hospital mortality (OR 2.66; 95% CI: 1.02-6.78; P = 0.046) but not for mortality during further follow-up (P = 0.257). The hospital mortality rate was 17.2%; and the 1-, 5- and 10-year survival rates were 74.3, 68 ± 5.0 and 67.1 ± 9.0%, respectively., Conclusions: NVE complicated by neurological events remains a challenging disease with high mortality and morbidity. Cardiac surgery seemed to be safe in the observed time interval, particularly for patients suffering from ischaemic stroke. A multidisciplinary approach is advocated for very individualized risk estimation., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Cryptococcosis is a potentially lethal opportunistic infection among human immunodeficiency virus (HIV)-infected individuals. The mortality rate of patient with cryptococcal meningoencephalitis (CM) in Thailand is high. Studying the factors associated with treatment failure is important to improve outcome., Material and Method: A retrospective study of patients with cryptococcosis in Siriraj Hospital, Thailand, during 2005-2008 was conducted. Treatment options, outcomes, survival and factors associated with outcomes and mortality were analyzed., Results: A total of 143 patients with cryptococcosis were enrolled. Mean age was 39 years old and 58.7% were male. There were 124 HIV-infected patients (86.7%) and 116 of those had CM. Favorable clinical response in HIV-associated CM was 55.2% and 6-month survival was 67.2%. Relapse was found in 21 patients (18.1%). Factors associated with favorable clinical response included lower opening and closing pressures and a higher white blood cell in cerebrospinal fluid (CSF). Favorable mycological response was 56.8% and factors associated with favorable mycological response were a lower CD4+ T-lymphocyte count and a longer amphotericin B treatment. The median time to achieve CSF sterilization was 30 days. Factors associated with survival were a longer course of amphotericin B, a lower CSF opening pressure and a higher white blood cell in CSF., Conclusion: High mortality rate of HIV-associated CM was demonstrated and most likely linked to inadequate induction antifungal therapy resulting in inability to sterilize CSF. New strategies and/or guidelines are suggested to improve survival.

We report the first identified transmission of Balamuthia mandrillaris through solid organ transplantation. Kidneys were transplanted from a donor with presumptive diagnosis of autoimmune encephalitis. Shortly after, the recipients developed neurologic symptoms. Magnetic Resonance Imaging of the brain from the donor and both kidney recipients demonstrated multiple ring enhancing lesions with surrounding edema and adjacent leptomeningeal extension. In addition most of the lesions demonstrated signal changes suggesting central hemorrhagic foci. Specimens were tested locally and at the Centers for Disease Control and Prevention. Histopathology revealed B. mandrillaris in either brain tissue and/or cerebral spinal fluid in the donor and recipients.

Meningoencephalitis of unknown origin (MUO) is a common inflammatory CNS disease in dogs, with a variable and unpredictable outcome. MRI and cerebrospinal fluid (CSF) features were prospectively evaluated to establish their utility as prognostic markers for predicting mortality, relapse and long-term outcome in 39 dogs with MUO. MRI and CSF analysis were performed at initial diagnosis and three months into treatment with prednisolone and cytosine arabinoside. When possible, MRI was repeated every 12 months thereafter. Median survival time was 26 days. All deaths occurred within 52 days of diagnosis (22/39; 56 per cent). One-third (13/39) died within 72 hours of diagnosis. Outcome was good or excellent in 12/17 surviving dogs. Loss of the cerebral sulci and foramen magnum herniation on MRI were associated with increased risk of mortality. An abnormal CSF analysis at the three-month re-examination was associated with increased risk of relapse (P=0.04). The combination of MRI and CSF analysis provided a greater sensitivity for predicting relapse than one modality alone. Discontinuing treatment before MRI lesions resolved always resulted in relapse. The presence of certain MRI characteristics may indicate an increased risk of mortality. Dogs alive three months following diagnosis have a very low risk of death due to MUO.

Based on the examination and treatment of 120 patients with tuberculous meningoencephalitis (TM) in the later stages of HIV infection, the differences between these patients and patients without HIV infection were found. HIV-infected patients with TM had a more acute disease onset, more clinical symptoms of encephalitis confirmed by magnetic resonance imaging of the brain, more frequent presence of mycobacterium tuberculosis in the cerebrospinal fluid and higher level of resistance to tuberculosis drugs. The morphologic study demonstrated the domination of necrotic and exudative reactions over productive inflammation with destructive abscess-type lesions in the brain matter. The mortality was more than 2 times higher than that in the control group.

Invasive candidiasis (IC) is a leading cause of morbidity and mortality in preterm infants. Even if successfully treated, IC can cause significant neurodevelopmental impairment. Preterm infants are at increased risk for hematogenous Candida meningoencephalitis owing to increased permeability of the blood-brain barrier, so antifungal treatment should have adequate central nervous system penetration. Amphotericin B deoxycholate, lipid preparations of amphotericin B, fluconazole, and micafungin are first-line treatments of IC. Fluconazole prophylaxis reduces the incidence of IC in extremely premature infants, but its safety has not been established for this indication, and as yet, the product has not been shown to reduce mortality in neonates. Targeted prophylaxis may have a role in reducing the burden of disease in this vulnerable population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To describe clinical and clinicopathologic findings and outcome of horses with meningitis and meningoencephalomyelitis., Design: Retrospective case series., Animals: 28 horses., Procedures: Medical records of horses admitted to the hospital during a 25-year period were reviewed. Horses with a definitive diagnosis of meningitis or meningoencephalomyelitis were included in this study. Information extracted from the medical records included signalment, history, reason for admission, clinical signs, results of clinicopathologic testing and diagnostic procedures, treatment, outcome, and necropsy findings., Results: 22 horses had confirmed infectious disease (19 bacterial, 2 parasitic, and 1 fungal), 4 had suspected infectious disease on the basis of CSF cytologic examination findings, and 2 had noninfectious meningitis or meningoencephalomyelitis. Trauma of the head and vertebral column with disruption of the blood-brain barrier and local ascending or hematogenous spread were the most common routes of infection. Common neurologic signs included abnormal mental status, cranial nerve deficits, vestibular dysfunction, ataxia, tetraparesis, and apparent neck pain. Common hematologic abnormalities included leukocytosis, neutrophilia, lymphopenia, and hyperfibrinogenemia. Cytologic examination of CSF samples revealed moderate to marked suppurative inflammation. Mortality rate was 96.4%. Microbial culture of CSF yielded bacterial growth in 15 of 23 horses (before death [2 horses], after death [11], and both [2])., Conclusions and Clinical Relevance: Results suggested that meningitis and meningoencephalomyelitis are uncommon disorders in horses. Infectious disease was more common than noninfectious disease. Local trauma, ascending infection, or hematogenous spread of infection were the most common causes of meningitis or meningoencephalomyelitis. Neurologic deficits, neutrophilia, lymphopenia, hyperfibrinogenemia, and CSF with neutrophilic pleocytosis were common findings in affected horses.

Background: Despite the advances in critical care, severe viral meningoencephalitis continues to impose high rates of morbidity and mortality. Consequently, new treatment strategies are needed and we present therapeutic hypothermia (TH) as one of the possible efficacious treatment tools., Methods: We present the case series in an adult intensive care unit of a tertiary care hospital. Eleven patients suffering from severe viral meningoencephalitis were treated with hypothermia. The major indication for TH was severely impaired consciousness associated with carbon dioxide reactivity loss assessed by Transcranial Doppler. Besides from the established treatment, all the patients underwent TH. Mild hypothermia (rectal temperature of 32-34°C) was maintained with continuous veno-venous hemofiltration., Results: Median Glasgow coma scale score in our patients at admission was 8 (3-10) and median Acute Physiology and Chronic Health Evaluation score was 24 (12-32). The overall mortality rate was 9% (1/11). Among survivors, the outcome was favorable in five patients [Glasgow Outcome Scale score (GOS) 4-5]. Remaining five patients had severe residual neurological deficit (GOS 3). Median GCS at discharge was 15 (8-15). With respect to disease severity, the outcome in presented patients was generally satisfactory., Conclusions: Our results suggest that use of mild hypothermia in selected adult patients with viral meningoencephalitis could be a promising treatment tool.

Introduction: To compare the effectiveness and safety of short term 6 month-treatment and long term 12 month-treatment schedules for meningoencephalitis due to tuberculosis in two hospitals from Lima-Peru., Methods: Comparative, retrospective and observational study. The patients were divided in two groups: Group 1: long term 12 month-treatment with isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months; then isoniazid and rifampin for 10 months. Group 2: short term 6 month-treatment with isoniazid and rifampin, pyrazinamide and ethambutol for the first 2 months; then isoniazid and rifampin for 4 months. Clinical records, effectiveness, treatment failure, treatment side effects, mortality and late consequences after treatment were reviewed., Results: Twenty-six patients with meningoencephalitis level I were included, 10 received the long term schedule and 16 the short term schedule treatment. From 51 patients with meningoencephalitis level II, 27 received the long term schedule and 24 the short term schedule treatment and of 31 patients with meningoencephalitis level III, 18 received the long term schedule treatment and 13 the short term schedule treatment. There was no statistically significant differences among levels I, II and III when effectiveness of short and long term schedule was evaluated. Moreover, there was no statistically significant difference in the frequency of treatment failure, treatment side effects, mortality and late consequences among groups., Conclusions: Long term 12 month-treatment and short term 6 month-treatment had similar effectiveness and safety in the treatment of meningoenchephalitis due to tuberculosis in HIV negative patients., (Copyright © 2009 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.)

Background: Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I., Methods: C57BL/6 mice received 4×10(3) PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue., Results: All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4+ and CD8+ T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain., Conclusion: Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.

Introduction: There are only limited data on the long-term outcome of patients receiving specialized neurocritical care. In this study we analyzed survival, long-term mortality and functional outcome after neurocritical care and determined predictors for good functional outcome., Methods: We retrospectively investigated 796 consecutive patients admitted to a non-surgical neurologic intensive care unit over a period of two years (2006 and 2007). Demographic and clinical parameters were analyzed. Depending on the diagnosis, we grouped patients according to their diseases (cerebral ischemia, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), meningitis/encephalitis, epilepsy, Guillain-Barré syndrome (GBS) and myasthenia gravis (MG), neurodegenerative diseases and encephalopathy, cerebral neoplasm and intoxication). Clinical parameters, mortality and functional outcome of all treated patients were analyzed. Functional outcome (using the modified Rankin Scale, mRS) one year after discharge was assessed by a mailed questionnaire or telephone interview. Outcome was dichotomized into good (mRS ≤ 2) and poor (mRS ≥ 3). Logistic regression analyses were calculated to determine independent predictors for good functional outcome., Results: Overall in-hospital mortality amounted to 22.5% of all patients, and a good long-term functional outcome was achieved in 28.4%. The parameters age, length of ventilation (LOV), admission diagnosis of ICH, GBS/MG, and inoperable cerebral neoplasm as well as Therapeutic Intervention Scoring System (TISS)-28 on Day 1 were independently associated with functional outcome after one year., Conclusions: This investigation revealed that age, LOV and TISS-28 on Day 1 were strongly predictive for the outcome. The diagnoses of hemorrhagic stroke and cerebral neoplasm leading to neurocritical care predispose for functional dependence or death, whereas patients with GBS and MG are more likely to recover after neurocritical care.

Introduction: Anthrax, a cattle-born zoonosis has been a serious infectious disease and its meningoencephalitic form remains a rapidly fatal illness even now., Aim: The aim of this paper is to evaluate the incidence and clinical profile of anthrax meningoencephalitis admitted to a teaching hospital predominantly serving a rural population in South India., Materials and Methods: We made a systematic study of the case records of patients with microbiologically confirmed diagnosis of anthrax meningoencephalitis admitted over a 20-year period. We searched the internet and office records for the anthrax outbreaks and the preventive strategies in place in India., Results: The admissions occurred in two clusters, four during 1992-1994 and six in 1998-2000; with no further detection unto August 2008. All patients were adult males with agriculture related occupation. Three of the 10 patients had no evidence of primary focus of infection. Majority were in coma at admission and had documented evidence of septicemia. CSF was haemorrhagic and death was the uniform outcome despite high dose intravenous penicillin G; maximum duration of hospital survival being 48 h., Comment: Anthrax is a rare, but catastrophic cause of meningoencephalitis. Improvement in education and life styles as well as livestock vaccination in rural areas appear to have effectively decreased the incidence of this dreaded acute zoonosis in the South Indian states of Tamilnadu and Puducherry.

Necrotizing meningoencephalitis (NME) in the Pug is an invariably fatal disease with an early age of onset whose cause remains unknown. Breed predilection strongly suggests genetic component(s), and viral etiology proves negative in studied cases. The current study was undertaken as the first analysis of the heritable component(s) involved in NME in the Pug. Complete medical records, individual characteristics, and pedigree information were collected for 58 affected dogs with data pertaining to 4698 dogs analyzed. A high inbreeding coefficient with differences across gender and significant differences across coat color classes and variable expression was evident. Median onset age was 19months and median survival time 23days. Screening for herpes-, adeno-, and parvoviruses was negative. The data demonstrate a strong familial inheritance of NME in the Pug. This investigation provides parameters of disease from the largest Pug NME cohort analyzed to date and offers evidence of previously unrecognized familial inheritance.

In April 2005, an outbreak of Chikungunya fever occurred on the island of Réunion in the Indian Ocean. During winter 2005, six patients developed meningoencephalitis and acute hepatitis due to Chikungunya virus. Our objectives were to determine the incidence and mortality of atypical Chikungunya viral infections and to identify risk factors for severe disease. A hospital-based surveillance system was established to collect data on atypical Chikungunya cases. Case reports, medical records and laboratory results were reviewed and analysed. We defined an atypical case as one in which a patient with laboratory-confirmed Chikungunya virus infection developed symptoms other than fever and arthralgia. We defined a severe atypical case as one which required maintenance of at least one vital function. We recorded 610 atypical cases of Chikungunya fever: 222 were severe cases, 65 affected patients died. Five hundred and forty-six cases had underlying medical conditions (of which 226 suffered from cardiovascular, 147 from neurological and 150 from respiratory disorders). Clinical features that had never been associated with Chikungunya fever were recorded, such as bullous dermatosis, pneumonia, and diabetes mellitus. Hypertension, and underlying respiratory or cardiological conditions were independent risk factors for disease severity. The overall mortality rate was 10.6% and it increased with age. This is the first time that severe cases and deaths due to Chikungunya fever have been documented. The information presented in this article may assist clinicians in identifying the disease, selecting the treatment strategy, and anticipating the course of illness.

Naegleria fowleri is a free-living amoeba and the etiologic agent of primary amoebic meningoencephalitis (PAM). Trophozoites reach the brain by penetrating the olfactory epithelium, and invasion of the olfactory bulbs results in an intense inflammatory reaction. The contribution of the inflammatory response to brain damage in experimental PAM has not been delineated. Using both optical and electron microscopy, we analyzed the morphologic changes in the brain parenchyma due to inflammation during experimental PAM. Several N. fowleri trophozoites were observed in the olfactory bulbs 72 h post-inoculation, and the number of amoebae increased rapidly over the next 24 h. Eosinophils and neutrophils surrounding the amoebae were then noted at later times during infection. Electron microscopic examination of the increased numbers of neutrophils and the interactions with trophozoites indicated an active attempt to eliminate the amoebae. The extent of inflammation increased over time, with a predominant neutrophil response indicating important signs of damage and necrosis of the parenchyma. These data suggest a probable role of inflammation in tissue damage. To test the former hypothesis, we used CD38-/- knockout mice with deficiencies in chemotaxis to compare the rate of mortality with the parental strain, C57BL/6J. The results showed that inflammation and mortality were delayed in the knockout mice. Based on these results, we suggest that the host inflammatory response and polymorphonuclear cell lysis contribute to a great extent to the central nervous system tissue damage.

Viral encephalitides are life-threatening diseases in neonates partly due to the irreversible damage inflammation causes to the CNS. This study explored the role of proinflammatory cytokines in the balance between controlling viral replication and eliciting pathologic immune responses in nonlytic viral encephalitis. We show that neonatal mice challenged with arenavirus Tacaribe (TCRV) develop a meningoencephalitis characterized by high IFN-gamma and TNF-alpha levels and mild T cell infiltration. Neutralization of the TNF-alpha using mAb was associated with lower chemokine expression, reduced T cell infiltration, and lower levels of IFN-gamma, and TNF-alpha in the CNS and led to 100% survival. Moreover, treatment with Abs to TNF-alpha improved mobility and increased survival even after the mice developed bilateral hind limb paralysis. Of note, animals treated with anti-TNF-alpha Abs alone did not clear the virus despite generating Abs to TCRV. Direct activation of the innate immune response using CpG oligodeoxynucleotides in combination with anti-TNF-alpha Abs resulted in 100% survival and complete viral clearance. To our knowledge, this is the first demonstration of the use of innate immune modulators plus Abs to TNF-alpha as therapeutics for a lethal neurotropic viral infection.

The records of 11 dogs with evidence of meningoencephalomyelitis of unknown origin were reviewed. Two of them had had a focal form of the disease and the other nine a disseminated form. The forebrain was involved in five of the nine dogs with disseminated disease, the brainstem in all nine and the cerebellum in one. They had been treated with courses of cytosine arabinoside every three weeks and immunosuppressive doses of prednisolone. Their response to the treatment, in terms of quality of life, was judged by their owners and referring veterinarians to have been excellent in five, good in five and poor in one; their survival times ranged from 78 days to more than 603 days. The cumulative probability of survival at two years was 58.4 per cent. No signs of myelosuppression or other side effects associated with cytosine arabinoside were observed.

This study was conducted to evaluate the feasibility of cerebral perfusion pressure-targeted therapy in children with raised intracranial pressure caused by central nervous system infection. A prospective observational pilot study was conducted in the pediatric intensive care unit of a tertiary care teaching hospital. Twenty children (ages 6 months to 12 years) with a clinical diagnosis of meningitis or meningoencephalitis were included. Intracranial pressure and blood pressure monitoring were initiated soon after enrollment. Interventions to reduce intracranial pressure and elevate blood pressure were used to achieve a target cerebral perfusion pressure of greater than 70 mm Hg in children 2 years of age or older and greater than 60 mm Hg in children less than 2 years. Therapies used to achieve target cerebral perfusion pressure were initial fluid boluses (in 14 patients), vasopressors (in 8), and mannitol (in 10). The target cerebral perfusion pressure was achieved in 6 patients, whereas a cerebral perfusion pressure greater than 50 mm Hg was achieved in 16 patients. All 4 patients with mean cerebral perfusion pressure less than 50 mm Hg died of intractable, raised intracranial pressure. In contrast, only 3 of 16 patients with mean cerebral perfusion pressure more than 50 mm Hg died. In children with raised intracranial pressure caused by central nervous system infection, it was feasible to achieve a cerebral perfusion pressure greater than 50 mm Hg, mainly by increasing the blood pressure within the first 24 hours and by reducing intracranial pressure after the first 24 hours.

Unlabelled: Results of treatment and outcomes of 89 adults with purulent encephalomeningitis, treated in years 1996-2002 in the Department of Infectious Diseases and Hepatology, Medical University of Lodz, were analyzed. Eighty nine patients were retrospectively included into the study. Results of treatment were evaluated at the last day of patient's hospitalization, and classified as: cure, disability or death. Results of treatment were analyzed in relation to etiology of purulent encephalomeningitis, age and gender of patients, course of the disease, and time from the onset of symptoms to admission to the Department. No statistically significant correlations between age, gender and prognosis were found. Thirty seven out of 89 patients were cured (41.6%); 29 of 89 patients died (32.6%); in 18 patients (19/89; 20.2) disability was diagnosed. In remaining 5 cases (5.6%), the result of treatment remained unknown. These patients were transferred to Intensive Care Units, outside our Hospital. In the studied group, etiologic factor was identified in 40 out of 89 cases (44.9%). In 40 patients, positive results of bacterial examination of cerebrospinal fluid were achieved. In 22 out of these 40 cases (55.0%), Streptococcus pneumoniae was identified as the etiologic factor. Higher percentage of patients died in subgroup with known etiology than in in subgroup of unknown etiology (p = 0.02). Higher percentage of cases with unconsciousness and higher percentage of cases with respiratory insufficiency were diagnosed in patients who died, than in patients who were cured (p = 0.00001)., Conclusion: 1. Purulent meningoencephalitis in adults, despite progress in antibiotic treatment, is still a serious condition, with poor prognosis. 2. Diagnostics and treatment modalities of purulent meningo-encephalitis should be urgently extended in order to achieve better outcomes in these group of patients.

The main and immediate causes of death, pathogenetic mechanisms of postoperative cerebral inflammatory-purulent complications (CIPC) in patients, suffering the brain tumour, were analyzed. The main pathogenetic patterns of the postoperative period course in the CIPC occurrence were studied, basing on the data of analysis of 30 patients, who died after the operation. There was proved, that the sepsis occurrence on the background of postoperative meningoencephalitis means the lethal ending of the disease. There was established, that in occurrence of septic complications, connected with postoperative meningoencephalitis, the most frequently the affection of respiratory and urinary systems occurs.