Case report: Chronic Candida albicans meningitis: a rare entity diagnosed by metagenomic next-generation sequencing.

The aetiology of chronic aseptic meningitis is difficult to establish. Candida meningitis in particular is often diagnosed late, as cerebrospinal fluid (CSF) work-up and imaging findings are nonspecific. A 35-year-old patient with chronic aseptic meningitis, for which repeated microbiological testing of CSF was unrevealing, was finally diagnosed with Candida albicans (C. albicans) meningitis with cauda equina involvement using metagenomic next-generation sequencing (mNGS). This report highlights the diagnostic challenges and the difficulties of treating shunt-associated fungal meningitis.

[Cryopyrin-associated periodic fever syndrome (CAPS) presenting as early-onset dementia, lacking typical recurrent fever or skin rash: a case report].

A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/µl and 307 |pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

BACKGROUND: In regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM. METHODS: Adult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed. RESULTS: Seventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001). CONCLUSIONS: Our study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

Primary diffuse leptomeningeal primitive neuroectodermal tumor presenting as chronic meningitis.

Primary diffuse leptomeningeal primitive neuroectodermal tumor is a rare meningeal neoplasm which can masquerade as chronic meningitis. While the clinical presentation and radiological features may provide a clue to this condition, meningeal biopsy is essential to clinch the diagnosis. A high index of suspicion and a low threshold for re-evaluating cases of neuroinfection that do not respond to empirical therapy are essential in this scenario. We present the case of a nine year old boy who was initiated on antituberculous treatment for chronic meningitis with hydrocephalus. Meningeal biopsy revealed a primary diffuse leptomeningeal primitive neuroectodermal tumor.

Candida dubliniensis chronic meningitis in an immunocompetent patient: Case report and literature review.

Chronic meningitis due to Candida species is a rare presentation generally associated with immunocompromise. We present a case of chronic meningitis due to Candida dubliniensis in an immunocompetent systemically well man who presented with 32 months of headache and visual changes. This is the fourth reported case in an immunocompetent patient. Injecting drug use was identified as a risk factor in all cases which presented similarly, with prolonged headache and papilloedema. A significant delay to diagnosis is common to all the reported cases. Candidal chronic meningitis in immunocompetent patients may be underdiagnosed due to lack recognition of risk factors, timely cerebrospinal fluid sampling and appropriate culture.

When time is short, and we are late!: A story of chronic meningitis.

We often face situations when the exact etiological diagnosis of meningitis is difficult. The reason behind this is that many pathogens have similar clinical, radiological, and laboratory pictures. The low yield of the pathogen in cerebrospinal fluid (CSF), non-availability of detail tests in all corners of the world, delay in availability of reliable results (like cultures), and difficulty in performing confirmatory tests like brain biopsy (in inconclusive cases) make the job of a clinician challenging. We report here a case where a late diagnosis of a disease owing to inconclusive results leads to dissemination. The complications following the introduction of the treatment based on presumption lead to further difficulty. We remained inclined to our diagnosis based on clinical judgement, acknowledged and managed the inflammatory changes secondary to the infection, and finally won the long battle. So, sometimes we need to make decisions based on clinical grounds. We need to depend on the fact that uncommon presentations of common diseases are commoner than a common presentation of uncommon diseases.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Diagnostic and Prognostic Value of Cerebrospinal Fluid Lactate and Glucose in HIV-Associated Tuberculosis Meningitis.

The role of cerebrospinal fluid (CSF) lactate in tuberculosis meningitis (TBM) diagnosis and prognosis is unclear. The aim of this study was to evaluate the performance of CSF lactate alone and in combination with CSF glucose in predicting a diagnosis of TBM and 14-day survival. HIV-positive Ugandan adults were investigated for suspected meningitis. The baseline CSF tests included smear microscopy; Gram stain; cell count; protein; and point-of-care glucose, lactate, and cryptococcal antigen (CrAg) assays. Where CrAg was negative or there was suspicion of TBM, a CSF Xpert MTB/RIF Ultra (Xpert Ultra) test was performed. We recorded baseline demographic and clinical data and 2-week outcomes. Of 667 patients, 25% (n = 166) had TBM, and of these, 49 had definite, 47 probable, and 70 possible TBM. CSF lactate was higher in patients with definite TBM (8.0 mmol/L; interquartile ratio [IQR], 6.1 to 9.8 mmol/L) than in those with probable TBM (3.4 [IQR, 2.5 to 7.0] mmol/L), possible TBM (2.6 [IQR 2.1 to 3.8] mmol/L), and non-TBM disease (3.5 [IQR 2.5 to 5.0] mmol/L). A 2-fold increase in CSF lactate was associated with 8-fold increased odds of definite TBM (odds ratio, 8.3; 95% confidence interval [CI], 3.6 to 19.1; P < 0.01) and 2-fold increased odds of definite/probable TBM (odds ratio, 2.3; 95% CI, 1.4 to 3.7; P < 0.001). At a cut point of >5.5 mmol/L, CSF lactate could be used to diagnose definite TBM with a sensitivity of 87.7%, specificity of 80.7%, and a negative predictive value of 98.8%. CSF lactate was not predictive of 2-week mortality. IMPORTANCE Tuberculosis meningitis (TBM) is the most severe form of tuberculosis, and its fatality is largely due to delays in diagnosis. The role of CSF lactate has not been evaluated in patients with HIV presenting with signs and symptoms of meningitis. In this study, using a point-of-care handheld lactate machine in patients with HIV-associated meningitis, we showed that high baseline CSF lactate (>5.5 mmol) may be used to rapidly identify patients with TBM and shorten the time to initiate treatment with a similar performance to the Xpert Ultra assay for definite TBM. Elevated CSF lactate levels, however, were not associated with increased 2-week mortality in patients with HIV-associated TBM. Due to moderate specificity, other etiologies of meningitis should be investigated.

Meningitis tuberculosa: un desafío diagnóstico en pediatría / Tuberculous meningitis: diagnostic challenge in pediatrics

Resumen La meningitis por Mycobacterium tuberculosis es infrecuente en pediatría y su diagnóstico definitivo representa un desafío clínico. Presentamos el caso de un lactante de dos años, que presentó un cuadro de meningitis crónica. Se logró el diagnóstico tras la sospecha imagenológica y la confirmación tras la búsqueda seriada del complejo M. tuberculosis por RPC en LCR y en biopsia de tejido cerebral. A pesar de sus complicaciones, el paciente respondió favorablemente al tratamiento antituberculoso. En Chile, la tuberculosis es infrecuente en niños y los síntomas son generalmente inespecíficos. Los hallazgos en RM cerebral asociados a alteraciones del LCR permiten sospechar el compromiso meníngeo precozmente. Se recomienda iniciar el tratamiento antituberculoso empírico ante la sospecha, ya que mejora el pronóstico. A pesar de los avances diagnósticos y terapéuticos, la meningitis tuberculosa sigue teniendo una alta tasa de complicaciones y un pronóstico ominoso.

Abstract Mycobacterium tuberculosis meningitis is rare in the pediatric population and its definitive diagnosis represents a clinical challenge. We present the case of a 2-year-old infant with chronic meningitis. Diagnosis was accomplished by suggestive radiological findings and serial search for M. tuberculosis complex by real-time polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF) and in brain tissue. Despite the complications, the patient evolved favorably with the tuberculosis treatment. In Chile, tuberculosis is a rare disease in children and symptoms are generally nonspecific. Brain MRI findings associated with CSF alterations allow early suspicion of MTBC. Start of empirical antituberculosis treatment upon suspicion is recommended given it is associated with better prognosis. Despite diagnostic and therapeutic advances, MTBC continues to have a high complication rate and an ominous prognosis.

Neurotuberculosis: an update.

Tuberculous (TB) meningitis (TBM), accounting for 70-80% of cases of neurotuberculosis, is one of the most severe forms of extrapulmonary tuberculosis. Two-thirds of new TB cases come from eight countries. Polymorphisms in toll-interleukin-1 receptor domain and in leukotriene A4 hydrolase (LTA4H) gene, affect the risk of inflammation in TBM. The common site of tuberculoma in children is cerebellum, and they may rarely develop tuberculous encephalopathy which has a high mortality. Young females with a high cerebrospinal fluid (CSF) protein have an increased predisposition to develop optochiasmatic arachnoiditis. Spinal TB meningitis may mimic transverse myelitis or Guillain-Barre syndrome. An extra-neural focus of TB should be sought clinically and radiologically as it may indicate safer and more accessible sites for diagnostic samplings. Cartridge-based nucleic acid amplification test (CBNAAT), also known as Genexpert test, is a polymerase chain reaction (PCR)-based method for detection of TB which also detects rifampicin resistance as it targets the rpob gene of mycobacteria. Line probe assays, based on PCR and reverse hybridization methods, identify mutations associated with drug resistance within a week. TBM being a paucibacillary disease, often evades a definite diagnosis and empirical treatment for a minimum of 9 months is warranted based on clinical judgement. All TBM patients should receive adjunctive corticosteroids, even those with HIV infection. Drug resistance is strongly associated with previous treatment and bedaquiline as well as delamanid have received approvals for multidrug resistant (MDR) TB. The key principle of managing MDR TB is never to add a single drug to a failing regimen. Correct combination and duration of most effective second line drugs in MDR TB require further modifications. Early shunting should be considered in those with hydrocephalus failing medical management. The single most important determinant of outcome is the stage of TBM at which treatment has been started.

Brucellosis.

Brucellosis is a common Zoonosis affecting half a million people annually. The most common mode of infection is by consuming unpasteurized milk or milk products. The general manifestations are those of fever with generalized symptoms. The nervous system is affected in 4-7% of cases. The manifestations are protean and include meningo-encephalitis as well as peripheral nervous system involvement. The diagnosis relies on culture, which is cumbersome and can be falsely negative. Agglutination tests for the various species of the organism are the mainstay for diagnosis. Treatment is for 3-6 months with combination therapy including Doxycycline, Rifampicin and ceftriaxone. The main issue is prevention and better animal husbandry.

Case Report: Candida dubliniensis as a Cause of Chronic Meningitis.

Background: Candida dubliniensis is closely related to Candida albicans and rarely isolated in clinical specimens. C. dubliniensis is increasingly recognized as a pathogen in immunocompromised hosts. We present the third known case of Candida dubliniensis meningitis in a young immunocompetent host. Case Presentation: A 27-year-old female with a history of intravenous heroin use and chronic hepatitis C presented with a 10-month history of headaches and progressive bilateral vision loss. On physical examination, visual acuity was 20/20 in her right eye and grade II papilledema was noted. Examination of her left eye revealed complete loss of vision and grade IV papilledema. An MRI with and without contrast revealed increased leptomeningeal enhancement involving the posterior fossa and spinal cord. After multiple lumbar punctures, cerebrospinal fluid fungal cultures grew Candida dubliniensis. The patient was successfully treated with a combination of liposomal amphotericin and fluconazole for 6 weeks with complete resolution of her CNS symptoms, with the exception of irreversible vision loss. Conclusion: We report a case of chronic meningitis due to Candida dubliniensis in an immunocompetent woman with hepatitis C and a history of intravenous heroin use. Additional studies are needed to confirm risk factors for Candida dubliniensis colonization, which likely predisposes individuals to invasive candidiasis.

Additional considerations for "checklists to guide the supportive and critical care of tuberculous meningitis".

Checklists are pivotal in the systematic assessment of critically ill patients, pre-operative assessments and for patients with multisystem involvements. Management of tuberculous meningitis is challenging due to prolonged hospital stay, multiple neurological complications like seizures, stroke, raised intracranial tension, stroke, neurosurgical interventions, multiple invasive procedures, health-care-associated sepsis, and ventilation. All these complications are managed by separate checklists to avoid treatment-related errors. The current manuscript aims to ensure completeness of inpatient care addressing issues addressing diagnostic issues, supportive care, and intensive care related issues.

Meningitis as the initial manifestation of systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is an idiopathic chronic autoimmune disease that can affect multiple organs including the Central Nervous System (CNS). CNS involvement is seen in many SLE patients; however, usually it is preceded by/or in conjunction with other organ-system involvement. The spectrum of CNS involvement is wide and includes numerous neuro-psychiatric syndromes but rarely meningitis. Even when meningitis occurs it is almost never the presenting manifestation of SLE. Our case had chronic aseptic meningitis as the initial and seemingly sole manifestation of SLE, which was erroneously, treated as tuberculous (TB) meningitis.

Comparative evaluation of IS6110 and protein antigen b PCR in cerebrospinal fluid for rapid diagnosis of tuberculous meningitis in children.

Introduction. Childhood tuberculosis meningitis is a severe form of tuberculosis with high morbidity and mortality. The diagnosis is frequently missed and delayed due to lack of sensitive tests like acid-fast bacilli (AFB) smear and delayed results by culture.Aims. To compare the role of IS6110 and protein antigen b PCR in cerebrospinal fluid (CSF) for rapid diagnosis of tuberculous meningitis (TBM) in children.Methodology. Forty-five cases of TBM and 20 controls were enrolled in this prospective study.Results. The mean ages of cases and controls were 4.2±0.5 years and 4.5±0.7 years, respectively. In the TBM group, two-thirds of the children were <4 years of age, and 62 % were males. Sensitivities of AFB smear examination, Löwenstein-Jensen (LJ) medium and bactenecin (BACTEC) culture in cases were 4.4, 0 and 2.2%, respectively. The protein antigen b PCR was most sensitive as it was positive in 35 (77.8 %) of TBM patients; IS6110 PCR was positive in 27 (60 %) patients. Both PCR-based tests had higher positivity than conventional tests and BACTEC culture. No significant difference was seen between the PCR tests. Excellent agreement was observed between both PCR-based tests as they were concordant for 26 positive samples and 35 negative samples.Conclusion. Protein b PCR is a sensitive and rapid method for the diagnosis of TBM (sensitivity 77.8 %). Both PCRs were more sensitive than smear, LJ and BACTEC. The specificity of both PCR was 100 %.

Discrepancy between ventricular and lumbar CSF in chronic meningitis.

Meningitis patient can present with various manifestation including hydrocephalus due to multiple reason. Diagnosis of meningitis mainly rely on CSF analysis which is usually obtained from lumbar puncture. In case of hydrocephalus CSF can be obtain from ventricles during VP shunt operation. Sometimes ventricular CSF can be normal in meningitis patient while lumbar CSF shows abnormality. Possible mechanisms behind this phenomenon are discussed here. Patients who present with hydrocephalus and have normal Ventricular CSF should investigated with lumbar CSF analysis in a view of delay in diagnosis and treatment.

Neurobrucellosis: A neglected entity? An update from tertiary care Neurocentre of South East Asia.

Neurobrucellosis is the most serious complication of brucellosis with neither a typical clinical manifestations nor a specific cerebrospinal fluid (CSF) picture and mimics other neurological disorders leading to diagnostic dilemma. The prevalence of Neurobrucellosis ranges from 1.7 to 10% of brucellosis worldwide. This present study highlights the integrated diagnostic and clinical approaches in the diagnosis of neurobrucellosis. Cases with neurological abnormalities associated with abnormal CSF findings were included in the study. Serum and CSF samples were subjected to Rose Bengal Plate Test (RBPT), standard tube agglutination test (STAT), indirect Enzyme linked immunosorbent assay (iELISA) for IgM & IgG antibodies and polymerase chain reaction (PCR) to detect BCSP31 gene. Out of 473 cases, 278 (58.8%) were positive in serum and/or CSF by any of the methods. Out of 278, Only IgM anti-brucella antibody was positive in 105 (22.19%) cases. 122 (25.79%) cases were positive by any of the diagnostic methods in serum and not in CSF whereas 51(10.78%) cases were positive in serum and CSF and these 51 cases were considered as Neurobrucellosis among patients presenting with neurological illness. Chronic meningitis was the most common form of presentation. Multimodal differential diagnostic approaches are crucial for accurate diagnosis, effective treatment and to prevent morbidity and mortality associated with neurobrucellosis.

Fatal chronic meningitis caused by Candida dubliniensis after liver transplantation.

We report a case of fatal chronic Candida dubliniensis meningitis complicated by severe hydrocephalus secondary to liver transplantation, in which diagnosis was considerably delayed.

Advances in the Diagnosis and Management of Tubercular Meningitis in Children.

Tubercular meningitis (TBM) continues to be a common cause of neuromorbidity in children. There is no single diagnostic method that can rapidly detect Mycobacterium tuberculosis (M.tb) in TBM patients with high sensitivity and specificity. Newer diagnostic modalities like Xpert/RIF assay and Loop mediated isothermal amplification assay (LAMP) have gained an essential stand in molecular diagnostics due to their high specificity, modest sensitivity in cerebrospinal fluid (CSF) and quick availability of results. Intensified drug regimens using high dose rifampicin, fluoroquinolone and aspirin appear to be useful adjunct therapy but more pediatric clinical trials on large scale are needed to determine their appropriate place in pediatric TBM. The emergence of multi and extreme drug resistant M.tb strains further challenges the standard therapy. In this review authors summarize challenges of the currently used diagnostic methods and treatment for TBM and discuss the recent advances.