Meningoencephalitis Of Unknown Etiology Research Articles

Monotherapie met prednisolone bij honden met meningo-encefalitis van onbekende oorsprong

Meningo-encefalitis van onbekende oorsprong is een vaak gediagnosticeerde neurologische aandoening die meestal fataal afloopt. Het doel van deze retrospectieve studie was het evalueren van drie behandelingsschema’s enkel bestaande uit prednisolone, gedoseerd in een afbouwend schema van drie, acht of achttien weken. De diagnose werd gesteld aan de hand van in de literatuur beschreven klinische criteria. Zevenendertig honden werden in de studie opgenomen, waarvan er zeventien, vijftien en zes respectievelijk het gedurende drie-, acht- en achttien-weken afbouwend schema toegediend kregen. Er werd een significant verschil waargenomen in overlevingstijd tussen de drie schema’s. Zevenendertig % van de honden in de studie stierf of werd geëuthanaseerd wegens de aandoening. Verrassend genoeg werd de hoogste mortaliteit vastgesteld in de groep die behandeld werd met het acht weken afbouwend schema (56%), gevolgd door het drie weken (26%) en het achttien weken afbouwend schema (0%). Gebaseerd op deze resultaten kunnen er geen definitieve conclusies getrokken worden voor wat betreft het ideale cortisonebehandelingsschema voor honden met meningo-encefalitis van onbekende oorsprong, maar een meer agressief en immunosuppressief schema zou kunnen leiden tot een lagere mortaliteit.

Acute Progress of Necrotizing Meningoencephalitis in a Dog; Serial Clinical Observation, Magnetic Resonance Imaging, and Histopathological Findings

A 13-month-old intact female poodle dog presented with an acute history of circling and seizure episodes. On the basis of the results of neurologic examination combined with magnetic resonance imaging and cerebrospinal fluid analysis (CSF), meningoencephalitis of unknown etiology (MUE) was suspected. Therapy with mycophenolate mofetil plus prednisolone was initiated, following which the clinical signs showed improvement for only one month before gradually worsening again. Acute progression of the clinical disease was observed, and the patient was euthanized 91 days after initial presentation. This case was definitively diagnosed as necrotizing meningoencephalitis (NME) according to the results of post-mortem histopathological examination. This report describes the clinical findings, serial magnetic resonance imaging (MRI) characteristics, and histopathological changes in a case of acute NME.

RETROSPECTIVE STUDY EVALUATING ASSOCIATIONS BETWEEN MIDLINE BRAIN SHIFT ON MAGNETIC RESONANCE IMAGING AND SURVIVAL IN DOGS DIAGNOSED WITH MENINGOENCEPHALITIS OF UNKNOWN ETIOLOGY.

Difficulty has been encountered when trying to identify ante mortem prognostic indicators for dogs with meningoencephalitis of unknown etiology (MUE). Identifying MRI imaging parameters associated with prognosis may impact treatment decision-making for clinician and owner. Our hypotheses for this retrospective cohort study are that dogs diagnosed with MUE that had midline shift on brain MRI would have a poorer survival compared to dogs without midline shift; and that younger age, lower weight, and low cerebrospinal fluid (CSF) cell count would be correlated with improved survival. Medical records were reviewed from two institutions. Inclusion criteria included: clinical signs referable to intracranial disease, brain MRI at presentation, abnormal CSF analysis, and negative infectious disease testing. Magnetic resonance imaging scans were evaluated for midline shift using the T2-weighted transverse image at the interthalamic adhesion and at the site of maximal deviation. Fifty-two dogs met the inclusion criteria. Median midline deviation was 0.12 cm. Median survival for dogs with no shift was 906 days and with shift was 84 days. Survival was not significantly different between groups (P = 0.11). This remained true when correcting for age (P = 0.22) and CSF TNCC (total nucleated cell count) (P = 0.12). Age at the time of diagnosis (P = 0.02) and CSF TNCC (P = 0.03) were significantly associated with survival. Cerebrospinal fluid protein value (P = 0.84) and weight (P = 0.82) were not significantly associated with survival. In this study of 52 dogs with MUE, MRI evidence of midline brain shift between 0.04 and 0.3 cm at the level of the interthalamic adhesion was not associated with shorter survival.

Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

BackgroundSteroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease affecting young adult dogs and a potential large animal model for neutrophilic meningitis. Similarities between SRMA and infectious central nervous system (CNS) diseases in lymphocyte subsets suggest an infectious origin.Toll-like receptors (TLRs) are pattern recognition receptors playing an important role in innate immunity. Due to their ability to recognize both self and non-self antigens, we hypothesize that TLRs are among the key factors for the induction of the inflammatory process in SRMA and provide an indirect hint on the etiology of the disease.MethodsThe expression profile of cell surface TLRs (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR3 and TLR9) of canine leukocytes was analyzed by immunophenotyping and subsequent flow cytometric measurements. Experiments were performed on cerebrospinal fluid (CSF) and peripheral blood (PB) samples of dogs affected with SRMA during the acute phase (n = 14) as well as during treatment (n = 23) and compared with those of dogs with bacterial meningitis (n = 3), meningoencephalitis of unknown etiology (n = 6), neoplasia of the central nervous system (n = 6) and a group of dogs with miscellaneous neurological diseases (n = 9). Two additional control groups consisted of dogs with pyogenic infections (n = 13) and of healthy dogs (n = 6).ResultsAll examined groups showed a high percentage of TLR2, TLR4 and TLR5 positive PB polymorphonuclear cells (PMNs) in comparison to healthy dogs. Very high values of TLR9 positive PB PMNs were detected in acute SRMA. Only a few similarities were found between SRMA patients and dogs with pyogenic infections, both groups were characterized by high expression of TLR4 positive PB monocytes. Glucocorticosteroid therapy reduced TLR2, TLR4 and TLR9 expression in PB monocytes.ConclusionsA relatively high expression of TLR4 and TLR9 in acute SRMA suggests that these two receptors might be involved in the inflammatory process in SRMA, enhancing the autoimmune reaction. Systematic CSF cell analysis for TLRs can be performed in future treatment studies in larger animals, such as dogs.

Proteome Analysis of Cerebrospinal Fluid in Healthy Beagles and Canine Encephalitis

We performed proteomics analysis of the cerebrospinal fluid (CSF) of healthy dogs and dogs with meningoencephalitis of unknown etiology (MUE). By comparing two-dimensional electrophoreses (2DE), an upregulated spot was found in MUE dogs. This protein was identified as a neuron-specific enolase (NSE) by analysis with MALDI-TOF mass spectrometry. In comparing dot blots using an antibody against NSE, the NSE levels in the CSF of MUE dogs was significantly higher than that of the controls. NSE is a diagnostic marker of neuroendocrine tumors, brain injury and spinal cord trauma in humans. It seems that the NSE concentration in the CSF is increased by cellular destruction in canine encephalitis. Though elevation of NSE may not be specific in canine encephalitis because the NSE level was increased in other CNS diseases, further study including measurement with serum is necessary.

Long-Term Immunosuppressive Therapy with Cyclosporine plus Prednisolone for Necrotizing Meningoencephalitis in a Pekingese Dog

A 4-year-old intact female Pekingese dog was presented with ataxia and seizure episodes. Based on magnetic resonance imaging and cerebrospinal fluid analysis results, meningoencephalitis of unknown etiology was suspected. The present case survived for 1,096 days under cyclosporine plus prednisolone therapy and was definitively diagnosed with necrotizing meningoencephalitis. This report describes the clinical findings, serial magnetic resonance imaging characteristics and pathologic features of a necrotizing meningoencephalitis and long-term survival after cyclosporine with prednisolone therapy.

Evaluation of Brain Tissue or Cerebrospinal Fluid with Broadly Reactive Polymerase Chain Reaction forEhrlichia, Anaplasma, Spotted Fever GroupRickettsia, Bartonella, andBorreliaSpecies in Canine Neurological Diseases (109 Cases)

Vector-transmitted microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, Bartonella, and Borrelia are commonly suspected in dogs with meningoencephalomyelitis (MEM), but the prevalence of these pathogens in brain tissue and cerebrospinal fluid (CSF) of dogs with MEM is unknown. To determine if DNA from these genera is present in brain tissue and CSF of dogs with MEM, including those with meningoencephalitis of unknown etiology (MUE) and histopathologically confirmed cases of granulomatous (GME) and necrotizing meningoencephalomyelitis (NME). Hundred and nine dogs examined for neurological signs at 3 university referral hospitals. Brain tissue and CSF were collected prospectively from dogs with neurological disease and evaluated by broadly reactive polymerase chain reaction (PCR) for Ehrlichia, Anaplasma, Spotted Fever Group Rickettsia, Bartonella, and Borrelia species. Medical records were evaluated retrospectively to identify MEM and control cases. Seventy-five cases of MUE, GME, or NME, including brain tissue from 31 and CSF from 44 cases, were evaluated. Brain tissue from 4 cases and inflammatory CSF from 30 cases with infectious, neoplastic, compressive, vascular, or malformative disease were evaluated as controls. Pathogen nucleic acids were detected in 1 of 109 cases evaluated. Specifically, Bartonella vinsonii subsp. berkhoffii DNA was amplified from 1/6 dogs with histopathologically confirmed GME. The results of this investigation suggest that microorganisms in the genera Ehrlichia, Anaplasma, Rickettsia, and Borrelia are unlikely to be directly associated with canine MEM in the geographic regions evaluated. The role of Bartonella in the pathogenesis of GME warrants further investigation.

Broadly Reactive Pan-Paramyxovirus Reverse Transcription Polymerase Chain Reaction and Sequence Analysis for the Detection of Canine Distemper Virus in a Case of Canine Meningoencephalitis of Unknown Etiology

Despite the immunologic protection associated with routine vaccination protocols, Canine distemper virus (CDV) remains an important pathogen of dogs. Antemortem diagnosis of systemic CDV infection may be made by reverse transcription polymerase chain reaction (RT-PCR) and/or immunohistochemical testing for CDV antigen; central nervous system infection often requires postmortem confirmation via histopathology and immunohistochemistry. An 8-month-old intact male French Bulldog previously vaccinated for CDV presented with multifocal neurologic signs. Based on clinical and postmortem findings, the dog's disease was categorized as a meningoencephalitis of unknown etiology. Broadly reactive, pan-paramyxovirus RT-PCR using consensus-degenerate hybrid oligonucleotide primers, combined with sequence analysis, identified CDV amplicons in the dog's brain. Immunohistochemistry confirmed the presence of CDV antigens, and a specific CDV RT-PCR based on the phosphoprotein gene identified a wild-type versus vaccinal virus strain. This case illustrates the utility of broadly reactive PCR and sequence analysis for the identification of pathogens in diseases with unknown etiology.