The clinical characteristics and outcome of cryptococcal meningitis with AIDS in a tertiary hospital in China: an observational cohort study.

BACKGROUND: Despite the profound impact of antiretroviral therapy in the control of AIDS mortality, central nervous system opportunistic infections remains a significant burden in AIDS patients. This retrospective study aims to elucidate the clinical characteristics, outcome and risk factors of cryptococcal meningitis (CM) poor prognosis in AIDS patients from a tertiary hospital in China. METHODS: Clinical data from 128 patients admitted in Beijing Ditan Hospital, Capital Medical University from November 2008 to November 2017 was collected. The cohort was stratified based on treatment outcome (effective 79%, and ineffective 21%), and Multivariate Logistic regression analysis used to identify risk factors of poor disease prognosis. RESULTS: Age, incidence of cerebral infarction, the proportion of consciousness disorder, and fasting plasma glucose was higher in the ineffective treatment group than the effective treatment group. The duration of treatment in the induction period of the ineffective group was significantly shorter than that of the effective group. Multivariate Logistic regression analysis indicated that the occurrence of cerebral hernia and consciousness disorder were risk factors for the prognosis of AIDS patients with CM infection, while the duration of treatment in the induction period was a indicative of a better prognosis in AIDS with CM infection complications. Finally, shunt decompression therapy correlated with a better disease outcome. CONCLUSIONS: This retrospective study exposes the main risk factors associated with worse disease prognosis in AIDS patients with CM infection complications.

[Predictive value of serum procalcitonin and hypersensitive C-reactive protein levels in patients with acute cerebral infarction complicated with infection].

OBJECTIVE: To analyze the changes of early procalcitonin (PCT) and hypersensitive C-reactive protein (hs-CRP) in patients with acute cerebral infarction, and to explore the predictive value of both for acute cerebral infarction with infection. METHODS: 206 acute cerebral infarction patients admitted to the department of neurology of Feicheng Mining Center Hospital from May 2014 to May 2019 were enrolled. Clinical data of patients and serum PCT and hs-CRP levels at 24, 48 and 72 hours after onset were collected. Patients were divided into infected group (n = 69) and non-infected group (n = 137) according to whether infection occurred within 5 days after onset. And 60 healthy people in the same period were selected as the healthy control group. The trends of serum PCT and hs-CRP levels in each group were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the values of serum PCT and hs-CRP levels in identifying acute cerebral infarction with infection. RESULTS: The serum level of PCT at 24, 48 and 72 hours in the infected group and the non-infected group were significantly higher than those in the healthy control group, and the serum level of PCT at 48 hours and 72 hours in the infected group were significantly higher than those in the non-infected group (µg/L: 0.28±0.08 vs. 0.19±0.03, 0.31±0.07 vs. 0.15±0.06, both P < 0.05). Compared with 24 hours, the serum PCT level in the infected group at 48 hours and 72 hours were significantly increased, but decreased in the non-infected group. The serum hs-CRP level in the infected group at 24, 48 and 72 hours were significantly higher than those in the non-infected group and the healthy control group (mg/L: 5.86±1.73 vs. 5.45±1.08, 5.25±1.33; 8.01±2.41 vs. 5.67±2.13, 5.25±1.33; 14.25±2.19 vs. 12.30±1.87, 5.25±1.33; all P < 0.05). And the serum hs-CRP level in the non-infected group at 72 hours was significantly higher than that in the healthy control group. Compared with 24 hours, the serum hs-CRP level in the infected group and non-infected group at 48 hours and 72 hours were significantly increased. It was shown by ROC curve analysis that serum PCT and hs-CRP levels at 24 hours had no predictive value for infection in patients with acute cerebral infarction [area under ROC curve (AUC) was 0.440, 0.576 respectively, both P > 0.05]. At 48 hours, the AUC of serum PCT in diagnosis of acute cerebral infarction with infection was 0.850 [95% confidence interval (95%CI) = 0.784-0.916], the sensitivity and specificity were 66.7% and 97.8% when the cut-off of PCT was 0.25 µg/L; the AUC of serum hs-CRP was 0.759 (95%CI = 0.689-0.830), the sensitivity and specificity were 66.7% and 76.6% when the cut-off of hs-CRP was 6.80 mg/L; the AUC of PCT combined with hs-CRP was 0.911 (95%CI = 0.859-0.964), the sensitivity was 90.5%, the specificity was 86.9%. At 72 hours, the AUC of serum PCT in diagnosis of acute cerebral infarction with infection was 0.952 (95%CI = 0.916-0.989), the sensitivity and specificity were 89.9% and 93.4% when the cut-off of PCT was 0.23 µg/L; the AUC of serum hs-CRP was 0.753 (95%CI = 0.678-0.828), the sensitivity and specificity were 60.9% and 83.2% when the cut-off of hs-CRP was 14.01 mg/L; the AUC of PCT combined with hs-CRP was 0.954 (95%CI = 0.918-0.991), the sensitivity was 97.1%, and the specificity was 89.8%. The results showed that the diagnostic value of serum PCT at 48 hours and 72 hours were higher than those of hs-CRP, and the predictive value of PCT combined with hs-CRP was higher than those of single index. CONCLUSIONS: Acute cerebral infarction itself has an effect on serum PCT level; serum PCT level above 0.23 µg/L at 72 hours after onset and reference to serum hs-CRP level have a high predictive value for the diagnosis of infection in patients with acute cerebral infarction.

Biomarkers of Cerebral Injury and Inflammation in Pediatric Tuberculous Meningitis.

Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neurospecific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analyzed for the neuromarkers S100B, neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP), in addition to multiple inflammatory markers. Results were compared with 2 control groups: patients with (1) a fatty filum (abnormal filum terminale of the spinal cord); and (2) pulmonary tuberculosis (PTB). Imaging was conducted on admission and at 3 weeks. Outcome was assessed at 6 months. Results: Data were collected from 44 patients with TBM (cases; median age, 3.3 [min-max 0.3-13.1] years), 11 fatty filum controls (median age, 2.8 [min-max 0.8-8] years) and 9 PTB controls (median age, 3.7 [min-max 1.3-11.8] years). Seven cases (16%) died and 16 (36%) had disabilities. Neuromarkers and inflammatory markers were elevated in CSF on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and NSE were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE, and GFAP. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased. Cerebral infarcts were associated with highest overall neuromarker concentrations and an increasing profile over time. Tuberculomas were associated with elevated interleukin (IL) 12p40, interferon-inducible protein 10, and monocyte chemoattractant protein 1 concentrations, whereas infarcts were associated with elevated tumor necrosis factor α, macrophage inflammatory protein 1α, IL-6, and IL-8. Conclusions: CSF neuromarkers are promising biomarkers of injury severity and are predictive of mortality. An increasing trend suggested ongoing brain injury, even though markers of inflammation declined with treatment. These findings could offer novel insight into the pathophysiology of TBM.

Successful repair of a syphilitic aortic arch aneurysm accompanied by serious cerebral infarction.

We present a 52-year-old male with a syphilitic aortic arch aneurysm accompanied by relevant extensive cerebral infarction. He was admitted to a local hospital for sudden loss of consciousness, where he was diagnosed with serious cerebral infarction. During his treatment, a multilocular aortic arch aneurysm involving the arch vessels was found incidentally. He was transferred to our hospital for surgical treatment. A preoperative routine laboratory test for syphilis was highly positive, which suggested that the aneurysm was likely caused by syphilis and the cerebral infarction was also induced by the involvement of syphilitic aortitis or arteritis. After 2 weeks of antibiotic therapy for syphilis, total arch replacement was performed successfully using meticulous brain protection with antegrade selective cerebral perfusion and deep hypothermia. He recovered without any further cerebral deficits. The pathological examination of the surgical specimen showed some characteristic changes of syphilitic aortitis.

Management of infective endocarditis with cerebral complications.

PURPOSE: Management of patients with infective endocarditis complicated by neurological deficits is challenging. No clear management guidelines have been defined, and the timing of surgery remains controversial. The purpose of this study was to evaluate our management algorithm. METHODS: Thirty-eight adult patients with left-sided infective endocarditis undergoing valve surgery were analyzed. Before the operation, enhanced brain computed tomography (CT) was performed to rule out a cerebral complication. Pre and postoperative data were retrospectively reviewed to clarify whether our algorithm was effective. Sixteen patients having neurological complication (CVC group) were compared with 22 patients without neurological complication. RESULTS: Age, sex, New York Heart Association (NYHA) functional class, affected valve and pathogens were not different between two groups. Mean interval from the onset of neurological dysfunction to cardiac operation was 27.8 ± 27.8 days (median 23 days). Of the 16 CVC group patients, 12 experienced cerebral infarction. Mass effects were seen in 3 patients, with 1 of these 3 patients died following aneurysm rupture. Mycotic aneurysm was detected in 4 patients, with 3 undergoing successful staged operations. Mortality and postoperative neurological exacerbation in CVC group was 6.3% (1 patient). Most patients who fulfilled the algorithm showed good outcomes. CONCLUSIONS: Our suggested management algorithm for infective endocarditis appears effective.

Mucormycosis-associated intracranial hemorrhage.

Rhinoorbitocerebral mucormycosis is a devastating infection being increasingly recognized in immunocompromised hosts and carries poor prognosis. Early recognition and treatment are critical in order to improve clinical outcomes and decrease the development of complications. Fatal cerebral infarctions have been described in patients with rhinoorbitocerebral mucormycosis, likely due to the thrombotic occlusion of the affected blood vessels directly invaded by this aggressive mycotic infection. We report a patient that presented with aplastic anemia, subsequently complicated by systemic mucormycosis, which generated reactive plasmacytosis, and developed intracranial infarction and hemorrhage.

Aggregatibacter aphrophilus endocarditis: a case report.

We present a case of endocarditis with embolic stroke and digital infarction due to the recently renamed Aggregatibacter aphrophilus. The isolation and identification of this organism can be problematic but was achieved in this case using both older phenotypic and newer genotypic methods. A benign tongue lesion is suggested as the likely portal of entry for this oropharyngeal organism. The patient made a good recovery with six weeks of intravenous ceftriaxone but will need cardiac valvular surgery at some point in the future.

Mitral valve repair during acute phase infective endocarditis with extensive destruction of the anterior leaflet rough zone and cerebral infarction.

Some reports suggest that mitral valve repair has good outcomes and may, therefore, be the preferred surgical approach in patients with active infective endocarditis (Doukas et al. in Heart 92(3):361-363, 2006); Ruttmann et al. in J Thorac Cardiovasc Surg 130(3):765-771, 2005; Sternik et al. in J Heart Valve Dis 11(1):91-97, 2002). However, in cases of active infective endocarditis of the mitral valve, extensive destruction of valvular tissue may make reliable valve repair difficult. Moreover, the timing of valve repair for active infective endocarditis remains controversial, especially in patients having cerebral complications. We present a case of a 34-year-old woman who had active infective endocarditis of the mitral valve complicated by multiple acute cerebral infarctions from septic embolisation. We could successfully carry out mitral valve repair 36 h after the diagnosis of active infective endocarditis and cerebral infarction was made. Her postoperative course was uneventful, and the patient remained in good health without recurrence of infective endocarditis and neurological complications.

[Infective endocarditis appearing with meningeal signs]. / Meningealis izgalmi tünetekkel jelentkezo infektív endocarditis.

The authors present the case of a 12-year old girl with infective endocarditis. Following an initial three-day period of malaise, she was admitted to the hospital with meningeal signs. The clinical symptoms and the results of the laboratory examinations, lumbar puncture and hemoculture supported the diagnosis of Staphylococcus sepsis and meningitis. The initiation of antimicrobial therapy resulted in temporary improvement while a systolic cardiac murmur appeared. Transthoracal echocardiogram raised the diagnosis of mitral valve endocarditis. Due to the subsequent deterioration in her condition, the patient was referred to the Pediatric Heart Center of the Gottsegen György National Institute of Cardiology where transoesophageal echocardiogram confirmed the diagnosis. The vegetations were removed by extracorporeal cardiac surgery including mitral valve plasty. Retrospectively, septic embolisation caused multiplex brain infarcts were identified by cranial MRI scan as the underlying cause of the initial clinical symptoms and liquor results. Following her recovery, patient remained well with some mild residual mitral regurgitation and without any residual neurological symptoms.

[Effects of voriconazole and vascular lesions in invasion of aspergillosis into the central nerve system].

We report 2 patients showing invasion of aspergillosis into the central nerve system (CNS). Patient 1, an 81-year-old woman, underwent surgery for sphenoidal sinusitis. She developed cerebral infarction with unconsciousness on 12th postoperative day. CSF examination demonstrated pleocytosis with increased protein and aspergillus antigen. She was diagnosed as having invasion of aspergillosis into the CNS, and was treated with voriconazole. Her clinical manifestations and CSF findings markedly improved. However, the effects of voriconazole gradually attenuated and she demonstrated recurrence of the cerebral infarction. After 2 months, she died of systemic aspergillosis and sepsis. Autopsy studies. Severe atherosclerotic changes with calcification were demonstrated in the bilateral carotid and basilar arteries, and many aspergillus were clustered in the vessel walls. Granulomatous inflammatory lesions with aspergillus were also demonstrated in the area surrounding the chiasm. There were no massive infarcts or bleeding in the brain, but multiple small infarcts were present. Patinet 2, a 64-year-old man, showing bilateral visual loss, was receiving treatment with corticosteroids under a diagnosis of optic neuritis. Two weeks later, he developed cerebral infarction. CSF examination showed pleocytosis with increased protein and aspergillus antigen. He was diagnosed as having invasive aspergillosis from the sphenoidal sinusitis into the CNS. He was treated with voriconazole, and unconsciousness and CSF findings improved transiently. However, he developed a recurrence of the brain infarction and pneumonia and finally died 6 months later. Treatment by voriconazole was definitely effective in both patients, but both patients died of recurrent cerebral infarction, possibly due to resistance for voriconazole, or developing multicellular filamentous biofilms. Voriconazole is recommended as the first choice of antifungal agents for aspergillosis. Aspergillus infection is strongly invasive into arterial vessels. It is important to consider the possible occurrence of cerebrovascular disease when treating invasion of aspergillosis into the CNS.

[Manifestations of systemic mycoses and related infections in the central nervous system]. / Szisztémás mycosisok és hasonló infekciók központi idegrendszeri manifesztációi.

UNLABELLED: In daily practice mycotic infections of the CNS have become more and more frequent. The main causes are the wide-ranging use of corticosteroids, immunosuppressive, cytostatic drugs and antibiotics, the spreading of AIDS, the increasing number of surviving immature newborns. To illustrate the diagnostic difficulties, the authors report several cases. CASE REPORTS: 1. Multifocal hemorrhagic infarcts of the brain, caused by generalized aspergillosis in mantle cell malignant lymphoma. 2. Cerebral microabscesses, caused by systemic candidiasis in a premature infant. 3. Fatal actinomycosis, mimicking a space occupying tumour in the thigh and with an abscess in the brain, radiologically indicated as a metastasis. The cause of death was actinomycotic pneumonia. 4. A successfully treated and recovered patient with recurrent pneumonia and multiplex brain abscesses, caused by filamentous microorganism of a Nocardia species revealed by histological examination of the neurosurgical specimen. DISCUSSION AND CONCLUSIONS: We have to be aware for the development of the mycotic and related infections of endangered patients. Aspergillosis and candidiasis play the most significant role in the involvement of the central nervous system. Actinomycosis and nocardiosis are more sensitive to treatment, so their diagnosis is of life-saving importance. The therapeutic chances of high risk patients with aspergillosis and candidiasis will be definitively better, if the infection is recognized and appropriately treated before the involvement of the CNS.

Cerebral fungal infection with mycotic aneurysm of basilar artery and subarachnoid haemorrhage.

A 28-year-old Pakistani man was admitted with unresolved severe headaches for the past four weeks. Magnetic resonance (MR) imaging and MR angiography showed an enhancing mass in the sphenoid sinus, bilateral cerebellar infarcts and aneurysmal dilatation of the basilar artery. The differential diagnosis included fungal infection versus neoplastic lesion. The scrappings taken through the endoscope from the sphenoid sinus were initially negative for fungal infection. However, the second biopsy, done after putting him on antifungal, itraconazole 200 mg twice daily, revealed the presence of a fungal infection (aspergillosis). MR imaging revealed extension of the fungal infection from the sphenoid sinus into the clivus, and then intracranially. Imaging also revealed aneurysmal dilatation of the basilar artery and infarctions in the cerebellum and subarachnoid haemorrhage. Despite aggressive antifungal treatment, the patient died after 29 days. This case report describes the probable mechanism of fungal mycotic aneurysmal vascular dilatation and growth. It also points to the need for a rapid diagnosis of potential cases and an aggressive treatment approach of confirmed cases of fungal infections of the central nervous system.

An aspergillotic aneurysm of the internal carotid artery following allogeneic bone marrow transplantation: successful management with catheter coil embolization and long-term antifungal agents.

We report a case of a mycotic aneurysm of the internal carotid artery and cerebral hemorrhagic infarction resulting from Aspergillus middle ear infection in a patient with severe aplastic anemia who received unrelated bone marrow transplantation. Although a mycotic aneurysm is a rare complication, and most often fatal, the patient was successfully treated with catheter coil embolization of the internal carotid artery and long-term systemic antifungal therapy. This case emphasizes the need for the rapid diagnosis of potential fungal involvement of the vascular system and suggests the necessity for aggressive treatment, such as with the modality illustrated in this case.

Relevant imaging findings of cerebral aspergillosis on MRI: a retrospective case-based study in immunocompromised patients.

The aim of the study was to assess neuroimaging patterns of cerebral aspergillosis with magnetic resonance imaging (1.5 T). The clinical and imaging data of nine patients were reviewed. Patients were included in the study if the diagnosis of aspergillosis was confirmed by either biopsy, autopsy, aspergillus antigen determination and/or neuroradiological and clinical response to specific treatment. Four patients had single or multiple abscesses presenting as ring-enhancing lesions on T1-weighted images, hypointensity of the ring on T2-weighted MR images and low to high signal intensity on diffusion-weighted imaging. Four patients had single or multiple infarctions affecting all compartments of the brain with hyperintensities on T2-weighted images in three of four patients, irregular parenchymal contrast enhancement in all patients and hemorrhagic transformation of the infarcted parenchyma in one patient. Diffusion-weighted images were positive in all ischemic areas. One patient with paranasal sinusitis developed a mycotic aneurysm of the internal carotid artery. Cerebral aspergillosis presents three principal neuroimaging findings: areas consistent with infarction; ring lesions consistent with abscess formation following infarction; and dural or vascular infiltration originating from paranasal sinusitis or orbital infiltration. Recognition of these patterns in cerebral aspergillosis may lead to more timely and effective diagnosis and treatment.

PCR typing of genetic determinants for metallo-beta-lactamases and integrases carried by gram-negative bacteria isolated in Japan, with focus on the class 3 integron.

From January 2001 to December 2002, 587 strains of gram-negative bacterial isolates demonstrating resistance to ceftazidime and a combination of sulbactam and cefoperazone were subjected to a disk diffusion screening test using sodium mercaptoacetic acid; 431 strains (73.4%) appeared to produce metallo-beta-lactamase (MBL). Of these 431 strains, 357 were found by PCR to carry genes for IMP-1 type MBL (bla(IMP-1)), while only 7 and 67 strains carried the IMP-2 gene (bla(IMP-2)) and the VIM-2 gene (bla(VIM-2)), respectively. Neither VIM-1 nor SPM-1 type MBL genes were found among the strains tested. Of 431 strains, 427 carried the intI1 gene, and 4 strains carrying both the intI1 and intI3 genes were reidentified as Pseudomonas putida harboring bla(IMP-1). Of these four P. putida strains, three strains and one strain, respectively, were separately isolated from two hospitals located in the same prefecture, and the three strains showed very similar pulsed-field gel electrophoresis patterns. Of 357 bla(IMP-1) carriers, 116, 53, 51, 47, and 30 strains were identified as Pseudomonas aeruginosa, Alcaligenes xylosoxidans, P. putida/fluorescens, Serratia marcescens, and Acinetobacter baumannii, respectively. Four strains carrying bla(IMP-2) were reidentified as P. putida. Sixty-three P. aeruginosa strains and four P. putida strains carried bla(VIM-2). Of 427 intI1-positive strains, 180, 53, 51, 47, and 35 were identified as P. aeruginosa, A. xylosoxidans, P. putida/fluorescens, S. marcescens, and A. baumannii, respectively. In the present study, it was confirmed that strains carrying bla(IMP-1) with a class 1 integron are the most prevalent type in Japan, although several intI3 carriers have also been identified sporadically in this country.

Fatal subarachnoid hemorrhage, with brainstem and cerebellar infarction, caused by Aspergillus infection after cerebral aneurysm surgery: case report.

OBJECTIVE AND IMPORTANCE: Intracranial aspergillosis has been reported to cause subarachnoid hemorrhage (SAH) attributable to ruptured mycotic aneurysms. We describe a case of Aspergillus arteritis that caused SAH without aneurysm formation, followed by successive brainstem and cerebellar infarction. CLINICAL PRESENTATION: A 50-year-old woman experienced a sudden onset of headache. Computed tomography demonstrated SAH. After angiography revealed an aneurysm of the anterior communicating artery, a complete neck-clipping operation was performed, without neurological deterioration. However, the patient experienced another episode of SAH on the 26th postoperative day. INTERVENTION: We repeated the craniotomy and confirmed that the clip was still intact. A second angiographic evaluation did not reveal an aneurysm or any other cause of hemorrhage. On the 30th postoperative day, magnetic resonance imaging demonstrated cerebellar infarction in the territory of the anteroinferior cerebellar artery. The patient died on the 40th postoperative day, after another episode of SAH and progressive cerebellar and brainstem infarction. The postmortem examination revealed destruction of the basilar artery and occlusion of the basilar and vertebral arteries attributable to Aspergillus arteritis. CONCLUSION: When a patient presents with SAH of unknown origin followed by cerebral infarction, Aspergillus arteritis should be included in the differential diagnosis. Earlier recognition of this fungal infection improves the prognosis.

Cerebral and spinal cord involvement resulting from invasive aspergillosis.

Although central nervous system involvement in disseminated aspergillosis is known to occur in immunocompromised patients, particularly after bone marrow transplantation, localized involvement of the spinal cord is exceedingly rare. In this report we present and illustrate detailed imaging findings of central nervous system invasion by Aspergillus fumigatus in a 30-year-old woman, with emphasis on the spinal cord involvement.

Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma.

A 57-year-old female in complete remission of grade IV non-Hodgkin lymphoma whilst on intensive chemotherapy, suddenly developed unilateral hemispheric stroke with a fatal outcome in 3 days. She was apyrexial and had received antifungal prophylaxis during her treatment. Post-mortem examination showed complete thrombosis of the internal carotid artery leading to infarction in the territory of the middle and anterior cerebral arteries. Microscopic examination of the brain showed involvement of intra-cranial vessel walls and brain parenchyma by mucormyces, with no evidence of systemic mucormycosis. Isolated cerebral mucormycosis is a rare occurrence, more commonly found in intravenous drug abusers, but can occur in patients with haematological malignancy.