Post-infectious inflammatory response syndrome in an HIV-negative patient after Cryptococcus gattii meningoencephalitis: a case report and review of the literature.

BACKGROUND: Cryptococcal meningitis (CM) is an inflammatory mycosis of the central nervous system caused by meninge infection or brain parenchyma with Cryptococcus species. It is associated with high morbidity and mortality, and patients with acquired immune deficiency syndrome are particularly susceptible. There have been increasing reports of CM in HIV-negative patients in China over the last few years. CASE PRESENTATION: A 31-year-old healthy Chinese male presented with fever and gradually developed headache, projectile vomiting, and other manifestations that were later confirmed as Cryptococcus gattii meningoencephalitis. However, multiple disease changes occurred during the course of treatment, and the regimen was accordingly modified after the diagnosis of post-infectious inflammatory response syndrome (PIIRS). The patient eventually recovered. CONCLUSION: There has been a growing trend in the incidence of C. gattii meningoencephalitis in HIV-negative patients. It shows rapid onset and severe prognosis. This case report can provide a reference to treat PIIRS following CM in HIV-negative patients.

Meningoencephalitis following Le Fort I osteotomy: a case report.

Le Fort I osteotomies, although they are common procedures, carry a degree of risk of injury to the surrounding structures. Skull base fractures and cerebrospinal fluid rhinorrhoea are amongst the most serious on the list of complications. This is the first reported case of meningoencephalitis post Le Fort I osteotomy, shedding some light on its identification, causes, and management.

Biomarkers of non-infectious inflammatory CNS diseases in dogs - Where are we now? Part I: Meningoencephalitis of unknown origin.

Meningoencephalitides of Unknown Origin (MUO) comprises a group of non-infectious inflammatory brain conditions, which frequently cause severe neurological disease and death in dogs. Although multiple diagnostic markers have been investigated, a conclusive diagnosis, at present, essentially relies on postmortem histopathology. However, different groups of biomarkers, e.g. acute phase proteins, antibodies, cytokines, and neuro-imaging markers may prove useful in the diagnostic investigation of dogs with MUO. It appears from the current literature that acute phase proteins such as C-reactive protein are often normal in MUO, but may be useful to rule out steroid responsive meningitis-arteritis as well as other systemic inflammatory conditions. In antibody research, anti-glial fibrillary acidic protein (GFAP) may play a role, but further research is needed to establish this as a consistent marker of particularly Pug dog encephalitis. The proposed diagnostic markers often lack specificity to distinguish between the subtypes of MUO, but an increased expression of interferon-γ (IFN-γ) in necrotizing meningoencephalitis (NME) and interleukin-17 (IL-17) in granulomatous meningoencephalitis (GME) in tissue biopsies may indicate their potential as specific markers of NME and GME, respectively, suggesting further investigations of these in serum and CSF. While neuro-imaging is already an important part of the diagnostic work-up in MUO, further promising results have been shown with Positron Emission Tomography (PET) as well as proton resonance spectroscopy (1H MRS), which may be able to detect areas of necrosis and granulomas, respectively, with relatively high specificity. This review presents different groups of established and potential diagnostic markers of MUO assessing current results and future potential.

Classification of neoplastic and inflammatory brain disease using MRI texture analysis in 119 dogs.

Magnetic resonance imaging is the primary method used to diagnose canine glial cell neoplasia and noninfectious inflammatory meningoencephalitis. Subjective differentiation of these diseases can be difficult due to overlapping imaging characteristics. This study utilizes texture analysis (TA) of intra-axial lesions both as a means to quantitatively differentiate these broad categories of disease and to help identify glial tumor grade/cell type and specific meningoencephalitis subtype in a group of 119 dogs with histologically confirmed diagnoses. Fifty-nine dogs with gliomas and 60 dogs with noninfectious inflammatory meningoencephalitis were retrospectively recruited and randomly split into training (n = 80) and test (n = 39) cohorts. Forty-five of 120 texture metrics differed significantly between cohorts after correcting for multiple testing (false discovery rate < 0.05). After training the random forest algorithm, the classification accuracy for the test set was 85% (sensitivity 89%, specificity 81%). TA was only partially able to differentiate the inflammatory subtypes (granulomatous meningoencephalitis [GME], necrotizing meningoencephalitis [NME], and necrotizing leukoencephalitis [NLE]) (out-of-bag error rate of 35.0%) and was unable to identify metrics that could correctly classify glioma grade or cell type (out-of-bag error rate of 59.6% and 47.5%, respectively). Multiple demographic differences, such as patient age, sex, weight, and breed were identified between disease cohorts and subtypes which may be useful in prioritizing differential diagnoses. TA of MR images with a random forest algorithm provided classification accuracy of inflammatory and neoplastic brain disease approaching the accuracy of previously reported subjective radiologist evaluation.

18F-FDG PET Imaging Predicts the Epileptogenic Zone Prospectively in Recurrent Cryptogenic Meningoencephalitis with Subsequent Simple Partial Visual Seizures.

18F-FDG PET scans have proven to be useful in the diagnosis and management of encephalitis patients. 18F-FDG PET scans are also the standard of care in the evaluation of epilepsy patients before surgery. Encephalitis patients who later develop epilepsy may have useful imaging findings at the time of diagnosis. We present a case of 18F-FDG PET imaging in a patient with recurrent cryptogenic meningoencephalitis. 18F-FDG PET imaging after resolution of the encephalitis revealed hypometabolism in previously hypermetabolic areas. Hence, the initial 18F-FDG PET scan prospectively predicted the epileptogenic zone and seizure-onset zone.

Aseptic meningitis as an initial presentation of Sjögren syndrome: a report of two cases and literature review.

Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.

Unusual Presentation of Severe Endobronchial Obstruction Caused by Cryptococcus gattii in a Child.

Disease caused by Cryptococcus gattii typically manifests as meningoencephalitis or pulmonary nodules. Endobronchial lesions are rare, and most cases are caused by Cryptococcus neoformans. We describe here a case of endobronchial disease in a child caused by C gattii. The disease spectrum in this patient was notable for the discovery of anti-granulocyte macrophage colony-stimulating factor autoantibodies.

Atypical presentations of intracranial dysgerminoma mimicking central nervous system inflammatory or demyelinating disease.

OBJECTIVES: The aim of this study is to report a case series of atypical presentations of intracranial dysgerminoma in which the diagnosis was delayed due to clinical and radiographic findings initially suggestive of CNS inflammatory or demyelinating diseases, such as MS. METHODS: This study is a case series detailing the history, clinical presentations, radiographic and laboratory results, and management of three patients with biopsy-proven intracranial dysgerminoma. RESULTS: All three patients demonstrated hyperintense lesions on MRI that were more suggestive of demyelinating or inflammatory diseases, including lesions involving the midbrain and corpus callosum. All three patients were serum positive for oligoclonal bands and negative for both AFP and beta-hCG (these two markers are commonly seen in dysgerminoma cases). One case involved a steroid-responsive tumor whereas the other two cases either did not respond to steroids or steroids were withheld due to uncertainty of etiology. Following biopsy, all three results were consistent with dysgerminoma. CONCLUSION: Clinicians should be aware that dysgerminoma may mimic the clinical and radiographic presentations of demyelinating diseases such as MS. These lesions can cause acute visual loss or diplopia, have MRI and CSF findings that might mimic MS, and have been shown to respond to steroids. Atypical clinical (e.g., headache, dorsal midbrain syndrome, bilateral optic neuropathy) or atypical radiographic features (e.g., mass effect, hydrocephalus) should prompt consideration for repeat imaging and possible biopsy even if serum or CSF tumor markers (beta-hCG and AFP) are negative for dysgerminoma.

Rare cause of Hemophagocytic Lymphohistiocytosis due to mutation in PRF1 and SH2D1A genes in two children - a case report with a review.

BACKGROUND: Hemophagocytic Lymphohistiocytosis (HLH) is a rare, complex, life-threatening hyper-inflammatory condition due to over activation of lymphocytes mediated secretory cytokines in the body. It occurs as a primary HLH due to genetic defect that mostly occurs in the childhood and associated with early neonatal death. Secondary HLH is triggered by secondary to infection and can occur at any age. CASE PRESENTATION: The current report presents two cases of HLH. Case 1, three-months-old boy born to second degree consanguineous parents was clinically suspected with HLH. A pathogenic variant in exon 2 of PRF1 gene [c.386G > C (p.Trp129Ser); FLH-type2] was detected. The parents and the fetus under investigation were shown to be heterozygous carriers, while Case-1 was homozygous for the said variant. Case 2, a one and half-year old male child referred for work-up was born to non-consanguineous young parents. His HLH suspicion was in accordance with HLH-2004 Revised diagnostic guidelines (fulfilling 5/8 criteria). Molecular study revealed hemizygous likely pathogenic variant c.138-3C > G in intron 1 of SH2D1A gene. Both the mother and younger sister were confirmed to be the carrier of the same variant. CONCLUSION: This study has represented two rare cases of HLH carrying missense variant in PRF1 and splice site variant in SH2D1A gene. Detailed molecular analysis has helped the families with precise genetic counselling and prenatal diagnosis during subsequent pregnancy. It is advocated that male patients presenting with EBV-associated HLH may be screened for XLP that may lead to early diagnosis and therapeutic implication if any.

Autoimmune inflammatory meningoencephalitis in a patient negative for glial fibrillary acidic protein-specific immunoglobulin G.

BACKGROUND: In this study, we describe clinical findings in a patient with autoimmune inflammatory meningoencephalitis who was negative for antibodies against glial fibrillary acidic protein (GFAP-IgG). METHODS: Serum and cerebral spinal fluid (CSF) samples were collected from the patient as part of a study of 520 patients with neurological syndromes. Antibodies against GFAP and other proteins associated with neurological disorders were measured by rat brain- and cell-based indirect immunofluorescence assays. RESULTS: A 42-year-old female was diagnosed with autoimmune inflammatory meningoencephalitis. She experienced a subacute and relapsing course with decreased vision, fever, headache, ataxia, hemiplegia, and disturbance of consciousness. Brain magnetic resonance imaging showed extensive lesions in the white matter along the ventricle, brainstem, right internal capsule, and meninges. The patient responded well to steroid treatment. Examination of CSF revealed a normal white blood cell count and protein level. Serum and CSF were negative for GFAP-specific antibodies and all other autoantibodies tested. Immunohistochemical staining of a brain biopsy collected during relapse revealed chronic inflammation and severe edema. Extensive and strong staining of CD163+ macrophages were evident throughout the lesions; however, CD3+ cells were rare and CD138+ and CD20+ cells were absent. CONCLUSION: We describe a case of subacute corticosteroid-responsive nonvasculitic autoimmune inflammatory meningoencephalitis in the absence of GFAP-IgG. The pathological features were distinct from those of patients with GFAP-IgG-positive meningoencephalitis, suggesting that nonvasculitic autoimmune inflammatory meningoencephalitis is a heterogeneous neurological syndrome.

Central Nervous System Tuberculosis : Etiology, Clinical Manifestations and Neuroradiological Features.

PURPOSE: As a result of multilateral migration and globalization in times of humanitarian crises, western countries face a possible increase in the incidence of central nervous system tuberculosis (CNS TB). The diagnosis of CNS TB is challenging and often delayed due to the manifold and often non-specific presentation of the disease. The aim of this review is to analyze and summarize imaging features and correlated clinical findings of CNS TB. METHODS: The different manifestations of CNS TB are explained and illustrated by characteristic neuroradiological as well as neuropathological findings. An overview on diagnostic and therapeutic approaches is provided. For clarity, tables summarizing the lesion patterns, differential diagnoses and diagnostic hints are added. RESULTS: The CNS TB can be manifested (1) diffuse as tuberculous meningitis (TBM), (2) localized as tuberculoma or (3) tuberculous abscess or (4) in extradural and intradural spinal infections. Information on clinical presentation, underlying pathology and the distinguishing features is demonstrated. The TBM is further described, which may lead to cranial nerve palsy, hydrocephalus and infarction due to associated arteritis of the basal perforators. The differential diagnoses are vast and include other infections, such as bacterial, viral or fungal meningoencephalitis, malignant causes or systemic inflammation with CNS. Complicating factors of diagnosis and treatment are HIV coinfection, multi-drug resistance and TB-associated immune reconstitution inflammatory syndrome (IRIS). CONCLUSIONS: Neurologists and (neuro-)radiologists should be familiar with the neuroradiological presentation and the clinical course of CNS TB to ensure timely diagnosis and treatment.

Hypertrophic pachymeningoencephalitis associated with temporal giant cell arteritis.

We report the rare case of an 80-year-old male patient with hypertrophic pachymeningoencephalitis that may be associated with temporal arteritis. The patient presented to our neurological department with a 2-week history of latent paresis and ataxia affecting his right hand. He had been diagnosed with temporal arteritis 12 years earlier. Brain MRI showed an enhancement of the left-sided frontoparietal meninges with oedema of the adjacent tissue of the precentral and postcentral cortex. A leptomeningeal biopsy was performed. An autoimmune-mediated immunoglobulin G4-associated hypertrophic pachymeningoencephalitis was diagnosed. The patient received a high-dose corticosteroid therapy and his symptoms gradually improved. Our results suggest that hypertrophic pachymeningoencephalitis may occur as a complication of giant cell arteritis and may cause central neurological deficits by cerebral perifocal oedema.

A case of anti-MOG antibody-positive unilaterally dominant meningoencephalitis followed by longitudinally extensive transverse myelitis.

BACKGROUND: There are few reports of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive, unilaterally dominant cerebral cortical encephalitis onset with epilepsy. We present such a case in a young female patient with myelitis. CASE PRESENTATION: A 19-year-old female developed generalized tonic seizures lasting several minutes. She had a low-grade fever and headache without other clinical neurological abnormalities while at our hospital. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Other laboratory tests indicated no apparent abnormalities. Unilateral meningeal hyperintensity was seen on T2 fluid-attenuated inversion recovery MRI with associated cortical swelling and gadolinium enhancement of the cortical layer. One thousand mg/day of levetiracetam and a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered. Dysuria appeared on the twentieth day of illness, and spinal MRI revealed a longitudinally extensive cord lesion from C5 to L1 consistent with myelitis. Two cycles of a 3-day course of intravenous methylprednisolone at 1000 mg/day were administered, and all symptoms disappeared. We found the patient to be anti-MOG antibody-positive using serum and CSF (titer: serum 1:256; CSF 1:128). CONCLUSION: Our report illustrates a unique case of anti-MOG presenting as new onset epilepsy secondary to unilaterally dominant meningoencephalitis preceding the onset of longitudinally extensive transverse myelitis.

Calvarial osteomyelitis and intracranial extension post-Mohs micrographic surgery.

Mohs micrographic surgery (MMS) is a specialised micrographic technique used for the treatment of locally invasive skin cancers. Despite being a relatively low risk surgery, the overall complication rates range between 1.6% and 3%. Common complications include postoperative haemorrhage, haematoma formation, wound infection, wound dehiscence and flap/graft necrosis. Osteomyelitis after dermatological cancer surgery is exceedingly rare. There have only been two cases of osteomyelitis in association with Mohs surgery reported in the literature to date. Here, we describe an epidemiologically atypical patient who initially presented with fever and altered mental status and later found to have calvarial osteomyelitis, intracranial abscess (empyema) and meningoencephalitis as a result of Mohs surgery. Although rare, it is a predictable side effect postsurgery, and prevention of such complications are critical to decrease morbidity and mortality in patients undergoing MMS.

Brain Immunohistopathology in a Patient with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel meningoencephalomyelitis. However, the pathogenesis of this disease is unclear. We therefore examined a brain biopsy from a patient with autoimmune GFAP astrocytopathy by immunohistopathology. METHODS: We examined brain biopsy sections from a patient with autoimmune GFAP astrocytopathy using hematoxylin and eosin (HE) and Luxol fast blue (LFB) staining, and immunostaining with antibodies for CD4, CD8, CD3, CD20, CD68, CD138, Neu-N, GFAP, myelin oligodendrocyte glycoprotein (MOG), and aquaporin-4 (AQP4). RESULTS: HE staining revealed extensive inflammatory cells (marked lymphocytes) around brain vessels, and LFB showed no signs of demyelination or axon loss. Immunohistochemical analysis showed CD3+ and CD4+ T cells cuffing around brain vessels, accompanied by CD8+ T cells, CD20+ B cells, and CD138+ plasma cells, while some macrophages (CD68+) were scattered throughout the brain parenchyma. There was no loss of AQP4 or MOG expression in this patient, while GFAP was abundantly expressed. CONCLUSIONS: These findings suggest that inflammatory cells, including T cells, B cells, plasma cells, and macrophages, are involved in autoimmune GFAP astrocytopathy. Demyelination and astrocyte loss may not necessarily occur in this disease.