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.

Central nervous system reactivation of herpesviridae family in patients with COVID-19.

The objective of this study is to describe our COVID-19 patients with herpesviridae reactivation in the central nervous system (CNS). Four patients were described including two with acute encephalitis and two with acute encephalomyelitis. Three of four patients had abnormal findings on neuroimaging studies. One of four patients died, one survived with major neurological sequelae, and two others fully recovered. Herpesviridae reactivation in the CNS in patients with COVID-19 is a rare but serious coincidence. The optimal therapeutic management has not been investigated and until more information is available, it is prudent to treat these patients with appropriate antivirals with or without anti-inflammatory agents.

Neurobrucellosis: report of 54 cases.

BACKGROUND: Brucellosis is among the most widespread zoonotic diseases worldwide. Although rare, nervous system involvement due to Brucella infection is a major diagnostic challenge in endemic regions. PATIENTS AND METHODS: This study was a cross-sectional investigation of hospitalized adults with neurobrucellosis from March 2007 to February 2017. We described the clinical characteristics, radiographical and laboratory features, and clinical outcomes of patients with neurobrucellosis. RESULTS: Fifty-four patients with neurobrucellosis were included. The median age was 35 (interquartile range, 25-50) years, and 32 (59%) cases were male. Thirty-four (63%) patients were stockmen or shepherds. The most common clinical manifestations were fever in 49 (91%) cases, headache in 47 (87%), decreased consciousness in 12 (22%), and seizures in 6 (11%). Meningeal signs were detected in 36 (67%) cases. Brucella species were isolated in five cases from blood or cerebrospinal fluid (CSF). The median of CSF leukocytes was 75 per µL, CSF protein 83 mg/dL, and CSF glucose 39 mg/dL. Only two cases had severe hypoglycorrhachia and one CSF protein ≥ 500 mg/dL. No patient died during hospitalization. CONCLUSIONS: The symptoms of neurobrucellosis could be mild and nonspecific and the classic triad of meningitis is uncommon. Mild CSF pleocytosis of fewer than 50 leukocytes per microliter of CSF was common but severe hyperproteinorrhachia and severe hypoglycorrhachia were rare in neurobrucellosis. Differentiation between neurobrucellosis and systemic brucellosis is important, because more prolonged treatment is indicated for neurobrucellosis, and it could be associated with a broad spectrum of complications that require close follow-up.

Bacterial meningitis in patients with multiple myeloma: a prospective nationwide cohort study and review of the literature.

OBJECTIVES: To study the clinical features of bacterial meningitis in patients with myeloma. METHODS: We analyzed patients with myeloma who were included in a nationwide cohort of patients >16 years old with community-acquired bacterial meningitis in the Netherlands from 2006 to 2018. Subsequently, we reviewed the literature for articles reporting patients with myeloma with bacterial meningitis. RESULTS: A total of 27 of 2306 episodes (1.6%) of bacterial meningitis occurred in patients with myeloma. Six of 27 patients (22%) underwent stem cell transplantation. Median cerebrospinal fluid (CSF) leukocyte count was 172/µl, and 12 of 26 patients (46%) had a CSF leukocyte count <100/µl. Streptococcus pneumoniae was the causative pathogen in 25 patients (93%). Fourteen patients (52%) had unfavorable outcomes, of whom 10 (37%) died. Ninety-one patients with myeloma with bacterial meningitis were described in the literature. The most common pathogen in these patients was S. pneumoniae (35 of 48; 73%) and four (20%) of 20 patients died. CONCLUSION: Bacterial meningitis in patients with multiple myeloma is a severe disease with high rates of unfavorable outcome. Patients often present with a lower CSF leukocyte count than patients with bacterial meningitis without multiple myeloma. Physicians should set a low threshold to perform lumbar puncture in patients with myeloma and start antibiotic treatment pending CSF chemistry and culture results.

Infective Endocarditis: Clinical Characteristics and Echocardiographic Findings.

Purpose: Infective endocarditis (IE) remains a disease with high morbidity and mortality. The aim of this study was to determine the clinical characteristics and echocardiographic features of patients with IE. Methods: We analyzed patients with either definitive or probable diagnosis of IE who were hospitalized in a teaching hospital in Mashhad, Iran between June 2011 and January 2020. Patients who survived were followed up by echocardiography for at least 6-month after hospital discharge. Results: A total of 82 cases with IE were included of which 62 (75.6%) received definitive diagnosis. The mean age was 39.7 ± 18.7 years and 52 (63.4%) were male. The most common preexisting structural cardiac abnormality that predispose patients to IE were congenital heart diseases (28 %) of which bicuspid aortic valve was more common (n = 12, 14.6%), followed by ventricular septal defect (n = 9, 11%) and Tetralogy of Fallot (TOF) (n = 2, 2.4%). Three (3.6 %) cases had rheumatic heart disease and 12 (14.6 %) were injecting drug users. The most common causative pathogen was Staphylococcus aureus, detected in 7 (19.4%) cases. Follow-up echocardiography revealed right or left ventricular failure in 10 (12.1%) cases. Cardiac complications occurred in 41 (50%) cases and systemic complications in 63 (76.8%). All-cause mortality was 41.5% (n = 34) and 6 (18.1%) patients died due to cardiovascular complications. Conclusions: The short- and long-term prognosis in IE was poor and the predictors for in-hospital and 1-year mortality were defined as heart failure and septic shock. Congenital heart disease and intravenous illicit drug using (IVDU) were the most common predisposing condition which may necessitate a revision in the IE prophylaxis recommendations.

Management of granulomatous lobular mastitis: an international multidisciplinary consensus (2021 edition).

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

Central nervous system infections in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical and microbiological characteristics, and outcomes. A systematic search of PubMed/Medline and Embase electronic databases was performed (March 2021) to identify all published studies on CNS infections and their characteristics in patients with SLE. A random-effects model was adopted and findings were reported with 95% CI. Overall, 6 studies involving 17 751 patients with SLE and 209 SLE cases with CNS infection were included in our meta-analysis. The frequency rate of CNS infections in patients with SLE was 0.012 (95% CI: 0.008 to 0.018). Meningitis was the most common clinical syndrome (93.5%, n=109/114, 95% CI: 82.6% to 97.8%) and Cryptococcus neoformans (35.9%, n=55, 95% CI: 27.2% to 45.7%) and Mycobacterium tuberculosis (27.1%, n=43, 95% CI: 14.6% to 44.8%) were the most common causative pathogens. Our patient-pool showed a mean SLE Disease Activity Index (SLEDAI) score of 7.9 (95% CI: 6.1 to 9.6), while 92.4% (n=72/76, 95% CI: 83.0% to 96.8%) of cases were on oral systemic corticosteroids, with a prednisone equivalent mean daily dose of 30.9 mg/day (95% CI: 18.0 to 43.7). Our meta-analysis revealed a mortality rate of 29.0% (95% CI: 15.0% to 48.6%). Clinicians should maintain a high index of suspicion for cryptococcal and tuberculosis (TB) meningitis in patients with SLE with suspected CNS infection, particularly in those with higher SLEDAI and on higher doses of systemic corticosteroids. In conclusion, initiation of empiric antituberculous treatment for patients with SLE who are highly suspected to have CNS TB is warranted while awaiting the results of diagnostic tests. Antifungals might also be potentially useful empirically in patients with SLE who are suspected to have fungal CNS infections. However, with respect to side effects such as toxicity and high cost of antifungals, decision regarding early antifungal therapy should be guided by early and less time-consuming fungal diagnostic tests.

Steroid-Responsive Post-Traumatic Persistent Neutrophilic Meningitis.

Post-traumatic meningitis is a potentially fatal condition that presents as a diagnostic and therapeutic challenge. The vast majority of post-traumatic meningitides are caused by infectious pathogens, most commonly multi-drug-resistant (MDR) bacterial pathogens. However, aseptic meningitis occurs less frequently due to tissue response to injury or stimulation by noninfectious agents, such as blood breakdown products or chemicals. Here, we present a case of post-traumatic persistent neutrophilic meningitis who was found to be steroid responsive. Diagnostic evaluation in our patient did not reveal any infectious pathogen, and the patient did not respond to broad-spectrum antimicrobial treatment. We suggest that physicians who treat patients with post-traumatic meningitis should consider steroid-responsive post-traumatic persistent neutrophilic meningitis (SPNM) in the list of differential diagnosis particularly when no infectious etiology is found and the patient does not respond to empirical antimicrobial treatment. Brain injury-induced immune dysregulation causing exaggerated inflammatory reaction might play a role in the pathogenesis of SPNM; however, further neuropathological studies are absolutely necessary to evaluate and characterize trauma-induced immune dysregulation.

Errors in Diagnosing Infectious Diseases: A Physician Survey.

Background: Infectious diseases are commonly missed or misdiagnosed. Errors in diagnosing infectious diseases not only affect the patient but also the community health. Objectives: To describe our investigation on the most common errors in diagnosing infectious diseases and their causes according to the physicians' reports. Methods: Between August 2018 and February 2019, specialist physicians and residents across Mashhad, Iran were invited to participate in a survey to report errors they had made or witnessed regarding the diagnosis of infectious diseases. Results: Overall, 465 cases were reported by 315 participants. The most common infectious diseases affected by diagnostic errors were upper respiratory tract infections (URTIs) (n = 69, 14.8%), tuberculosis (TB) (n = 66, 14.1%), pleuro-pulmonary infections (n = 54, 11.6%), central nervous system (CNS) infections (n = 51, 10.9%), and urinary tract infections (n = 45, 9.6%). Errors occurred most frequently in generating a diagnostic hypothesis (n = 259, 55/7%), followed by history taking (n = 200, 43%), and physical examination (n = 191, 41/1%). Errors related to the diagnosis of TB (odds ratio [OR]: 2.4, 95% confidence interval [CI]:0.9-5.7; P value: 0.047) and intra-abdominal infections (OR: 7.2, 95% CI: 0.9-53.8; P value: 0.02) were associated with more-serious outcomes. Conclusion: A substantial proportion of errors in diagnosing infectious diseases moderately or seriously affect patients' outcomes. URTIs, TB, and pleuropulmonary infections were the most frequently reported infectious diseases involved in diagnostic error while errors related to the diagnosis of TB and intraabdominal infections were more frequently associated with poor outcomes. Therefore, contagious and potentially life-threatening infectious diseases should always be considered in the differential diagnosis of patients who present with compatible clinical syndromes.

Suspected Central Nervous System Infections in HIV-Infected Adults.

Objectives: To study the differential diagnosis of HIV-infected patients with suspected central nervous system (CNS) infections and the association of CD4 counts with the final diagnosis. Methods: We analyzed HIV-infected patients from a prospective cohort study on the diagnostic accuracy of clinical and laboratory characteristics in adults with suspected CNS infections in an academic hospital in Amsterdam, the Netherlands, who underwent cerebrospinal fluid (CSF) examination. Results: Thirty-four (9.4%) out of 363 patients with suspected CNS infections were HIV-positive of whom 18 (53%) were diagnosed to have CNS infection, with median CD4 counts of 255 cells/µl. The spectrum of CNS infections consisted of progressive multifocal leukoencephalopathy in three patients (17%); cryptococcal meningoencephalitis, toxoplasma encephalitis, angiostrongylus eosinophilic meningitis, and HIV encephalitis each in two (11%); and cytomegalovirus encephalitis, neurosyphilis, tuberculous meningoencephalitis, histoplasma encephalitis, and varicella-zoster virus meningitis each in one (6%). Clinical characteristics and blood parameters did not differ between HIV-infected patients with CNS infections and other diagnoses. The best predictor for CNS infections was the CSF leukocyte count (AUC = 0.77, 95 CI% 0.61-0.94). The diagnosis of CNS infection was not associated with the CD4 count (median 205 vs. 370, p = 0.21). Two patients (11%) with CNS infections died and two (11%) had neurological sequelae. Conclusions: Half of the patients with suspected CNS infections are diagnosed with a CNS infection, and this was not related to CD4 counts. The best predictor for CNS infections was the CSF leukocyte count.

Vertebral osteomyelitis in bacterial meningitis patients.

OBJECTIVE: To analyze the clinical and laboratory characteristics of vertebral osteomyelitis in community-acquired bacterial meningitis patients. METHODS: All episodes of vertebral osteomyelitis in a cohort study of adult patients with community-acquired bacterial meningitis in the Netherlands were analyzed. Subsequently, a systematic review of published cases was performed. RESULTS: Between March 2006 and August 2018, 10 of 1974 (0.5%) meningitis patients were diagnosed with vertebral osteomyelitis. The median age was 70 years (interquartile range (IQR) 54-74 years); six (60%) were male and four (40%) were female. The median time between diagnosis of bacterial meningitis and vertebral osteomyelitis was 6 days (IQR 1-13 days). The most common presenting symptoms were back or neck pain, occurring in seven patients (70%); one patient presented with neurological deficits due to cauda equina compression. Streptococcus pneumoniae was the causative pathogen in five patients and Staphylococcus aureus in three. The literature review identified 32 additional cases, showing a similar distribution by age, sex, and pathogen. Seven (18%) of 40 patients from the series presented here and those reported in the literature died. CONCLUSIONS: Concomitant vertebral osteomyelitis is rare in community-acquired bacterial meningitis patients. Persisting back pain is a clue to the diagnosis and should prompt magnetic resonance imaging of the spine, because prolonged antibiotic treatment or surgical treatment may be indicated.

Antimicrobial Resistance among Community-Acquired Uropathogens in Mashhad, Iran.

Background: Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the appropriateness of recommended empiric antimicrobial regimens for treatment of urinary tract infections (UTIs). Aims: To describe the microbial spectrum and resistance profile of community-acquired uropathogens and predictors of isolation of resistant strains. Methods: Between October 2017 and June 2019, individuals who visited the outpatient clinics for diagnosis of UTIs or screening of asymptomatic bacteriuria were included in the study if they were tested for urine culture in one of the three main medical diagnostic laboratories of Mashhad, Iran. The standard disk diffusion antimicrobial susceptibility testing was used, with the Clinical and Laboratory Standards Institute (CLSI) threshold cutoffs for susceptibility of isolated uropathogens. Results: Three hundred thirty cases were included with a median age of 47 years. Two hundred seventy-six (83.6%) were female. The most common isolated uropathogens were Escherichia coli in 201 (60.9%) cases and Klebsiella species in 46 (13.9%) cases. E. coli isolates showed the highest rates of susceptibility to nitrofurantoin (89.3%), cefixime (75%), and gentamicin (72.4%). Exposure to antibiotics in the past 3 months was a predictor of resistance to ciprofloxacin (OR: 2.8, 95% CI: 1.33-6.28), and older age was a predictor of resistance to TMP-SMX (OR: 2.1, 95% CI: 1.07-3.97) among E. coli isolates. Conclusion. E. coli and Klebsiella species accounted for about two-thirds of community-acquired uropathogens. In regard to the high susceptibility rates, nitrofurantoin was identified as the first-choice agent for empiric treatment of community-acquired cystitis, while cefixime and gentamicin might be the second-choice alternatives. Ciprofloxacin and TMP-SMX, on the other hand, cannot be considered appropriate agents for empiric therapy of community-acquired UTIs, particularly in those who had exposure to antibiotics in the past 3 months and the elderly.

Diagnostic Errors in Tuberculous Patients: A Multicenter Study from a Developing Country.

Although there is still much to learn about the types of errors committed in health care and why they occur, enough is known today to recognize that a serious concern exists for patients. Tuberculosis (TB) is an infectious disease that is frequently subject to diagnostic errors. Missed or delayed diagnosis of TB can affect patients and community adversely. Our aim in the present study was at evaluating the type of diagnostic errors in TB patients from symptom onset to diagnosis. This was a multicenter cross-sectional study conducted in three university hospitals in Mashhad, Iran. We showed a long delay in diagnosing TB that is mostly related to the time from first medical visit to diagnosis. Errors in the diagnostic process were identified in 97.5% of patients. The most common type of error in diagnosing TB was failure in hypothesis generation (72%), followed by history taking and physical examination. In conclusion, it seems likely that efforts to improve public awareness of and health literacy for TB, to coordinate the referral and follow-up systems of patients, and to improve physicians' skills in history taking and physical examination and clinical reasoning will result in reduced delay in diagnosis of TB and, perhaps, improved patient safety and community health.

Frequency of Different Types of Diagnostic Errors in Patients with Central Nervous System Infections: A Cross-Sectional Observational Study.

OBJECTIVES: To assess the frequency of different types of diagnostic errors in patients with central nervous system (CNS) infection from the onset of symptoms to admission to the hospital, where the correct diagnosis was made. METHODS: A cross-sectional observational design was used, and the information was collected by interviewing patients and/or their knowledgeable relatives as well as reviewing the accompanying medical record documents and hospital records. RESULTS: Of 169 adult patients with CNS infection, 129 (76.33%) were subject to diagnostic errors. Failure in ordering tests and hypothesis generation were the most common types of diagnostic errors that accounted for more than 70% of errors. Several contributing factors that were associated with incorrect diagnostic hypotheses included failure in taking a patient's comprehensive history such as detecting relevant epidemiological clues, conducting a full clinical examination, and interpreting diagnostic evidence. The relationship between poor clinical outcome and longer delay from the onset of illness to diagnosis, inappropriate empirical antibiotic therapy, and lower level of consciousness on admission were found to be statistically significant. CONCLUSIONS: Although diagnosis and management of CNS infection in some patients are straightforward, clinical decision making in facing patients with complex scenarios often requires clinical reasoning instead of relying only on intuitive diagnosis. Justification in requesting diagnostic measures and interpretation of their results based on clinical findings and patient information could be a critical factor in preventing a substantial number of diagnostic errors in patients with CNS infection.

The Etiological Spectrum of Febrile Encephalopathy in Adult Patients: A Cross-Sectional Study from a Developing Country.

The profile of febrile encephalopathy varies based on different demographic and geographical characteristics of the study population. This retrospective, cross-sectional study was conducted to evaluate the etiological spectrum of febrile encephalopathy in hospitalized adult patients. A total of 293 patients with the mean age of 49.7 ± 23 were evaluated of whom 77.1% presented with encephalopathy syndrome. The most common diagnosis in patients with clinical syndromes suggestive of central nervous system (CNS) infection was sepsis associated encephalopathy (SAE) (22.9%), followed by bacterial meningitis (14%) and neurotuberculosis (9.9%). The comparison between the elderly and young adults showed that, in the young adults, bacterial meningitis and neurotuberculosis, and in the elderly SAE, are among the most common causes of clinical syndromes suggestive of CNS infection including febrile encephalopathy in our region. Moreover, we illustrated an upward trend for the proportion of diagnosing CNS infections among those who underwent diagnostic LP, from 40.4% in 2011 to 70% in 2015, that could be indicative of an increasing threshold for performing LP at least in our center in recent years. Whether these changes have been associated with increasing the rate of diagnostic errors or not needs to be evaluated in future studies.

The mask of acute bacterial pneumonia may disguise the face of tuberculosis.

INTRODUCTION: Pulmonary tuberculosis (TB) can present as acute pneumonia. Differentiation of tuberculous from non-tuberculous community-acquired pneumonia (CAP) is an important challenge in endemic areas. The purpose of this study was the comparison between characteristics of tuberculous and non-tuberculous CAP patients. METHODS: In this prospective and observational study, all adult patients (aged ≥16 years) who were admitted to Imam Reza Hospital in Mashhad (Iran) with the diagnosis of CAP, between February 2013 and January 2014, were enrolled. Clinical, radiological, and microbiological data of the patients were collected and reviewed. Statistical analyses were performed using SPSS 14 software and R programming language. RESULTS: We studied 120 patients with diagnosis of acute CAP including 21 (17.5%) tuberculous and 99 (82.5%) non-tuberculous CAP. The etiologies of CAP in the latter group were as follow: S. pneumoniae 29 (29.3%), followed by S. aureus, polymicrobial including anaerobes, and other agents. The diagnosis of pneumonia remained unknown in 49 (40%) patients. We found approximately equal gender distribution among two study groups (14/21 vs. 61/99, 63.6% vs. 62.9%, p=0.948). Fifty percent of patients with tuberculous CAP had opioid addiction that was more frequent compared with non-tuberculous group (p=0.240). 52.4%, 63.2%, 30%, and 90% of patients with tuberculous CAP had severe presentation based on PSI, IDSA/ATS, CURB-65, and SMART-COP, respectively. CONCLUSIONS: The diagnosis of TB should be considered in all patients who presented with CAP in endemic regions. It could not be differentiated from other causes of pneumonia on clinical and radiological grounds.

A Healthy Young Woman with Acute Respiratory Distress Syndrome: an unfamiliar face of a familiar disease.

The presented case features a rare manifestation of pulmonary tuberculosis in a previously healthy young woman who had acute presentation of tuberculous pneumonia complicated by acute respiratory distress syndrome. In developing countries, mycobacterium tuberculosis is an important cause of community-acquired pneumonia (CAP). TB can present as an acute process and should be included in the differential diagnosis of CAP. This case is special in its manifestation from several clinical perspectives, including the lack of an underlying medical condition or immune defect and the development of acute respiratory distress syndrome (ARDS) in non-miliary and non-disseminated tuberculosis. In conclusion, the diagnosis of TB should be considered in all patients who present with CAP in endemic regions.