Cryptococcal Meningitis in Patient with Chronic Myeloid Leukemia

Objective: This study aimed to report the case of a female patient with chronic myeloid leukemia affected by cryptococcal meningitis. Case report: ML, white, 48 years old, female sex, previously diagnosed with chronic myeloid leukemia that has been refractive to the use of imatinib and who has recently begun using nilotinib, was admitted complaining of sudden and disabling migraine in the last 1 month associated with asthenia, adinamia, anorexia, disinterest for daily activities, dizziness, nausea, and vomiting. She evolved with ataxia, and started to stroll with help and showed decrease of muscular strength in her upper limbs. She also presented episodes of decrease of consciousness, with look fixation, no respond to sound stimulation, and short-term hearing loss. The cerebrospinal fluid showed presence of Cryptococcus sp. and, therefore, we began treatment with intravenous liposomal amphotericin B in the dose of 3 mg/kg/day, for 6 weeks. A new cerebrospinal fluid analysis, at the end of treatment, also showed rare structures that are compatible with Cryptococcus sp. As sequelae, she continued with hearing loss in her right ear and enhancement in her right auditory canal, seen in the magnetic resonance imaging. After stabilization and clinical improvement, she was discharged. After 3 weeks, she was hospitalized again with degeneration of the condition, and died due to intracranial hypertension secondary to cryptococcal infection. Final Considerations: This report reinforces the need of reflecting on fungi pathologies, especially in immunosuppressant patients, as well as the importance of early diagnosing and making a fast intervention, with the aims of providing quality of life and comfort to the patient and of minimizing neurological sequelae to the patient.

Cryptococcal Meningitis of the HIV-Infected Person in Lomé: About 102 Cases over 10 Years

Objective: To describe the clinical, epidemiological and evolutionary aspects of cryptococcal meningitis. Methods: This was a retrospective descriptive study on all HIV-infected patients who had been hospitalized for cryptococcal meningitis between 2006 and 2016 in the principal structures for the care of HIV infected person in Lomé. The diagnosis of meningitis was clinical and confirmed by the presence of cryptococci on Chinese ink or the detection of CSFsoluble antigens. All patients have made the CD4 rate assay and received an antifungal treatment based on fluconazole or Amphotericin B, followed later by antiretroviral triple therapy. Results: A total of 102 patients infected with cryptococcal meningitis (62 men for 40 women) were found. The sex ratio was 1.55. The median age was 34 years with extremes of 15 to 49 years. Clinically, headache was the symptomatic symptom in 100% of cases, prone to long runs and weight loss respectively in the proportions of 45% and 65%. The mean CD4 cell count was 65 ± 22 cells per mm3. The duration of hospital stay was short (less than 7 days) for the deceased. A total of 62 patients were able to receive treatment, 40 of them with fluconazole and 22 with Amphotericin B. The mortality was very high (65%), 25% were lost to follow-up, and 9.5% still in live 3 months after admission to the hospital. Conclusion: Cryptococcal meningitis has a very reserved prognosis. It is to be feared in cases of severe immunosuppression, hence the early detection of HIV for optimal management is important.

Successful Treatment with Triple Therapy of Amphotericin B, Voriconazole and Flucytosine on an AIDS Patients with Severe Cryptococcal Meningitis

A 35-year-old man(body weight=63 kg)with AIDS complaining fever and headache after having commenced anti-retroviral therapy(ART)for a week was admitted to our hospital.Five lumbar punctures performed during38 days could not confirm a cryptococcal meningitis(CM)based on staining or culture methods for cerebrospinal fluid(CSF).The disease quickly progressed with serious hearing/vision impairment and frequent onset of seizure and coma after being treated with corticosteroids for five days,and then CM was confirmed.Subsequent lumbar puncture showed elevated intracranial pressure as high as 870 mm H2O,even though treated with standard antifungal regimens for CM.His disease was finally controlled by a new triple therapy with amphotericin B(0.7mg?kg-1?day-1,intravenously),flucytosine(100 mg/kg perday,orally in four divided doses),and voriconazole(200mg every 12 hours)and ART containing lamivudine(300 mg/day),stavuding(30 mg,twice a day)and efavirenz(300 mg,orally every night).Although it is rare,negative CSF stain or culture for cryptococci in AIDS patients with CM can persist for a long time.Corticosteroids should be used cautiously when an effective anti-fungal therapy is not administered.Triple therapy with amphotericin B,flucytosine and voriconazole may be selectively applied in severe CM.Voriconazole can be co-administered with efavirenz with modified dosing.

Characteristic analysis of diffuse leptomeningeal glioneuronal tumor misdiagnosed as cryptococcal meningitis in adolescent female

Diffuse leptomeningeal glioneuronal tumor(DLGNT)in adolescent female is rare and easy to be misdiagnosed due to its nonspecificity.This article described the characteristics of an adolescent female DLGNT patient with no history of tumor whose first symptoms are headache and vision loss,and analyzed the causes why DLGNT is easy to be misdiagnosed as cryptococcal meningitis.Treatment remedies:the adolescent female presented with progressive exacerbations of headache,vomiting and vision loss after general treatment.Dynamic monitoring of routine biochemical changes in cerebrospinal fluid(CSF)found abnormal high CSF pressure and protein,repeated examination of antibodies and acid-fast bacilli were negative,and high-throughput pathogen gene examination excluded viral meningitis,tuberculous meningitis and other diseases.To save the optic nerve,the Ommaya capsule was implanted to reduce the intracranial pressure.After diagnostic antifungal treatment,the patient’s condition did not improve.To identify the etiology,extensive meningeal enhancement was eventually detected by enhanced magnetic resonance imaging(MRI),and highly atypical tumor cells were identified by repeated examination of fresh CSF cytology.Post treatment evaluating:for DLGNT,consult oncology.Meningeal biopsy and PET-CT(positron emission tomographycomputed tomography)examination were recommended,and intrathecal chemotherapy and whole-brain radiotherapy were performed according to the examination results.But the patient’s family refused to have a meningeal biopsy and asked to be released from the hospital.Conclusions:the adolescent female without a history of tumor can not rule out the disease,and cryptococcal meningitis also has meningeal enhancement.The gold standard for the diagnosis of DLGNT is to find cancer cells.There is no effective cure for DLGNT,the timely placement of Ommaya sac can significantly improve the quality of the patient’s life,and the active adoption of targeted therapy is expected to extend the patient’s survival.

Treatment of cryptococcal meningitis with low-dose amphotericin B and flucytosine

Background Amphotericin B （0.7 mg/kg） with flucytosine is the standard treatment for cryptococcal meningitis.However,the long treatment course can induce adverse reactions in patients; therefore,reducing the dose may decrease such reactions.We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B （0.4 mg/kg or 0.7 mg/kg per day） and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.Methods Retrospective analysis was conducted on inpatients at the First Affiliated Hospital,College of Medicine,Zhejiang University （January 2005 to December 2009）.Low- or high-dose amphotericin B （0.4 or 0.7 mg/kg per day,respectively） plus flucytosine was used.The negative conversion rate of Cryptococcus in the cerebrospinal fluid （CSF）,patient mortality,and the incidence of side effects for the two groups （low- vs.high-dose） were compared immediately after treatment and 2 and 10 weeks later.Data were analyzed by the Student＇s t test,chi-square tests using SPSS 12.0 statistical soitware.Results Two weeks post-treatment,Cryptococcus negative CSF rates were 78% （18/23） in the low-dose group and 87% （13/15） in the high-dose group （P=0.28）.Ten weeks post-treatment,both groups were negative.The mortality rate was 8% （2/25） in the low-dose group and 17% （3/18） in the high-dose group （P=-0.25）.There was a statistically significant difference in the incidence of adverse events between the groups,48% （12/25） and 78% （14/18） in the low- and high-dose groups,respectively （P=0.04）.Adverse events that required a change in treatment program in the low-dose group were 12% （3/25） compared to 39% （7/18） in the high-dose group （P=-0.04）.Conclusion Low-dose treatment regimens were better tolerated

Voriconazole in an infant with cryptococcal meningitis

Cryptococcus neoformans （C. neoformans） is the most common cause of fungal meningitis worldwide.1 Cryptococcal meningitis is an opportunistic infection commonly found in immunocompromised hosts, especially HIV-infected adults. It also occurs in apparently immunocompetent individuals. Rarely has it been reported in children, and it is almost nonexistent in infants. Voriconazole is a member of a second generation of antifungal triazoles with broad spectrum antifungal activity, oral and parenteral bioavailability and a favorable safety profile in adults.3 This patient shows improved in vitro activity against C. neoformans when compared to fluconazole and it has been used successfully in about half the patients with refractory cryptococcosis.4 However, the efficacy and safety of voriconazole as a antifungal agent in children with cryptococcal meningitis have not been well assessed, This report described cryptococcal meningitis in a 13-day-old premature neonate who recovered without overt toxicity after voriconazole was added to an antifungal regimen that included amphotericin B and flucytosine. We focused on the response of this child with cryptococcal meningitis to voriconazole.

Antifungal therapy for treatment of cryptococcal meningitis

Objective To compare the curative effects of three different antifungal regimens in the treatment of cryptococcal meningitis Methods Twenty two patients were divided into 3 groups: Group Ⅰ was given intravenous amphotericin B alone or combination with flucytosine therapy Group Ⅱ received intravenous fluconazole alone or combination with flucytosine The treatment of Group Ⅲ was divided into two steps, where the patients received intrathecal amphotericin B plus intravenous amphotericin B with or without intravenous fluconazole until the mycological culture of cerebrospinal fluid (CSF) turned negative, followed by oral fluconazole or itraconazole as maintenance therapy until direct microscopic examination of CSF showed negative once a week for three consecutive weeks Results Of the twenty two patients, 17 (77 3%) were cured, 2 (9 1%) improved, 3 (13 6%) died, and one (4 5%) relapsed Of the 8 patients in Group Ⅰ, 5 were cured, 2 improved, one died and one relapsed; Of the 4 patients in Group Ⅱ, 2 were cured, and 2 died; All the 10 patients in Group Ⅲ were cured without any recurrence Conclusion The two step therapeutic regimen may be suited to the treatment of cryptococcal meningitis

A Mimic of Hepatic Encephalopathy: Two Cases of Cryptococcal Meningitis in North America

In the non-human immunodeficiency virus infected population,cryptococcosis occurs primarily in people who are functionally immunosuppressed,including patients who have undergone solid organ transplantation requiring immunosuppressive medications,are on corticosteroids,or have renal failure or cirrhosis.Cryptococcal meningitis poses a particular challenge in the setting of cirrhosis because its clinical presentation can mimic hepatic encephalopathy.Here,we describe two patients with decompensated cirrhosis,both with a known history of hepatic encephalopathy who had lumbar punctures and were found to have cryptococcal meningitis.The first patient had a subacute fluctuating change in mental status,while the second patient had progressive subacute headaches,gait disturbance,and hearing loss.Both patients were treated with amphotericin B and flucytosine induction,but only the second survived to maintenance therapy.These cases demonstrate the importance of having a high index of suspicion for cryptococcal meningitis in cirrhosis and having a low threshold for performing a lumbar puncture when altered mental status or other neurologic complaints are not fully explained by hepatic encephalopathy.We also provide a brief review of the pathobiology of cryptococcal infection in cirrhosis and highlight the challenges in therapy.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis:a 2-year retrospective analysis

Background:Cryptococcal meningitis(CM)is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus(HIV)-infected patients,and is complicated with significant morbidity and mortality.This study retrospectively analyzed the clinical features,characteristics,treatment,and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up.Methods:Data from all patients(n=101)of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality.Results:Of the 101 patients,86/99(86.9%)of patients had CD4 count<50 cells/mm^3,57/101(56.4%)were diagnosed at≥14 days from the onset to diagnosis,42/99(42.4%)had normal cerebrospinal fluid(CSF)cell counts and biochemical examination,30/101(29.7%)had concomitant Pneumocystis(carinii)jiroveci pneumonia(PCP)on admission and 37/92(40.2%)were complicated with cryptococcal pneumonia,50/74(67.6%)had abnormalities shown on intracranial imaging,amongst whom 24/50(48.0%)had more than one lesion.The median time to negative CSF Indian ink staining was 8.50 months(interquartile range,3.25-12.00 months).Patients who initiated antiretroviral therapy(ART)before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients(7 vs.12 months,χ^2=15.53,P<0.001).All-cause mortality at 2 weeks,8 weeks,and 2 years was 10.1%(10/99),18.9%(18/95),and 20.7%(19/92),respectively.Coinfection with PCP on admission(adjusted odds ratio[AOR],3.933;95%confidence interval[CI],1.166-13.269,P=0.027)and altered mental status(AOR,9.574;95%CI,2.548-35.974,P=0.001)were associated with higher mortality at 8 weeks.Conclusion:This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data.Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Metataxonomics of Internal Transcribed Spacer amplicons in cerebrospinal fluid for diagnosing and genotyping of cryptococcal meningitis

Background:Cryptococcal meningitis is a severe infectious disease associated with high morbidity and mortality.Rapidity and accuracy of diagnosis contribute to better prognosis,but readily available tools,such as microscopy,culture,and antigens do not perform well all the time.Our study attempted to diagnose and genotype cryptococcus in the cerebrospinal fluid(CSF)samples from patients with cryptococcal meningitis using the approach of metataxonomics of Internal Transcribed Spacer(ITS)amplicons.Methods:The CSF samples were collected from 11 clinically suspected cryptococcal meningitis patients and four non-infectious controls.Samples were recruited from the First Affiliated Hospital of Fujian Medical University Hospital,Fuzhou Fourth Hospital and the 476th Hospital of Chinese People's Liberation Army from December 2017 to December 2018.ITS1 ribosomal deoxyribonucleic acid(rDNA)genes of 15 whole samples were amplified by universal forward primer ITS1(CTTGGTCATTTAGAGGAAGTAA)and reverse primer ITS2(GCTGCGTTCTTCATCGATGC),sequenced by Illumina MiSeq Benchtop Sequencer.The results were confirmed by sanger sequencing of ITS1 region and partial CAP59 gene of microbial isolates from 11 meningitic samples.Pair-wise comparison between infectious group and control group was conducted through permutational multivariate analysis(PERMANOVA)in R software.Results:The 30,000 to 340,000 high-quality clean reads were obtained from each of the positively stained or cultured CSF samples and 8 to 60 reads from each control.The samples from 11 infected patients yielded detectable cryptococcal-specific ITS1 DNA with top abundance(from 95.90%to 99.97%),followed by many other fungal groups(each<1.41%).ITS genotype was defined in 11 CSF samples,corresponding to ITS type 1,and confirmed by Sanger sequencing.A statistically significant difference(r2=0.65869,P=0.0014)between infectious group and control group was observed.Conclusions:The metataxonomics of ITS amplicons facilitates the diagnosis and genotype of cryptococcus in CSF samples,which may provide a better diagnostic approach of cryptococcal infection.

Current diagnosis and treatment of cryptococcal meningitis without acquired immunodeficiency syndrome

Cryptococcal meningitis(CM)is a central nervous system infectious disease caused by Cryptococcus.It is the most common fungal infection in the central nervous system,accounting for about 48%of fungal infection.The disease occurs mainly in acquired immunodeficiency syndrome(AIDS)patients and concentrates in the immunocompromised people without AIDS.There are nearly one million new cases of CM each year,and about 70%of them died.In China,CM occurs mainly in people without AIDS and there is an increasing trend in recent years.Early diagnosis and treatment is the key to reducing morbidity and mortality associated with CM.The diagnosis mainly depends on laboratory examination such as morphological examination,fungal culture and antigen detection.History,clinical manifestation and imaging examination are the important parts of auxiliary examination.The initial combined antifungal treatment is emphasized,and the principle of fractional treatment including induction,consolidation and maintenance therapy should be followed.The high intracranial pressure must be reduced actively at the same time.In addition,it is proved that the novel immunotherapy combined with antifungal agents can improve the curative effect and limit the chance of antimicrobial resistance.Large-scale clinical trials are needed for further study.

HIV相关隐球菌脑膜炎免疫重建综合征研究进展

免疫重建综合征是HIV相关隐球菌脑膜炎常见的并发症,该并发症的发生增加了HIV相关隐球菌脑膜炎的死亡率。目前,对于HIV相关隐球菌脑膜炎免疫重建综合征的发病机制尚不清楚,给该病的防治带来了困难。本文综述了HIV相关隐球菌脑膜炎免疫重建综合征发病机制、危险因素及诊疗新进展。

宿主免疫与HIV相关隐球菌性脑膜炎预后研究进展

即使在全球开展抗逆转录病毒治疗和抗真菌药物治疗背景下,HIV相关隐球菌性脑膜炎仍然是艾滋病患者死亡的重要原因。宿主免疫状态是决定HIV相关隐球菌性脑膜炎预后的关键因素,近年来宿主免疫与HIV相关隐球菌性脑膜炎预后相关性的研究取得一些进展,本文就宿主先天免疫、适应性免疫、中枢神经系统免疫及免疫重建综合征对HIV相关隐球菌性脑膜炎预后的影响进行综述。

138例非HIV隐球菌性脑膜炎患者临床特征及药敏结果分析

目的 分析非HIV隐球菌性脑膜炎患者的临床特征及体外药物敏感情况。方法 回顾性分析医院2018-2021年收治的138例隐球菌性脑膜炎患者的临床资料,对患者临床表现、基础病情和实验室检查等数据进行分析。结果 138例非HIV隐球菌性脑膜炎患者墨汁染色检测阳性率为73.9%,CrAg检测阳性率为100%,42例患者存在免疫功能抑制疾病,49例伴有其他基础疾病,另外47名患者无基础疾病。患者多伴有头痛、发热、呕吐、四肢乏力和意识障碍等症状。脑脊液生化检查显示糖和氯化物减低,脑脊液蛋白升高。138株隐球菌对5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑、伏立康唑的MIC范围分别为≤4~≥16μg/mL、≤0.5~1μg/mL、1~16μg/mL、≤0.125~0.5μg/mL、≤0.06~0.5μg/mL。5种抗真菌药物中5-氟胞嘧啶敏感性为95.60%,氟康唑敏感性为94.93%,伊曲康唑敏感性65.22%,两性霉素B和伏立康唑的敏感性均为100%。结论 隐球菌性脑膜炎患者多伴有基础疾病(含免疫功能抑制疾病);CrAg检测阳性率明显高于墨汁染色检测;非HIV隐球菌性脑膜炎患者分离菌株对不同抗真菌药物敏感性有差异,为临床用药提供参考。

艾滋病合并隐球菌脑膜炎患者CD4^(+)、CD8^(+)淋巴细胞计数变化及与预后的关系

[目的]探讨艾滋病(AIDS)合并隐球菌脑膜炎患者外周血CD4^(+)淋巴细胞计数、CD4^(+)/CD8^(+)比例变化及与预后的关系.[方法]选择自2019年1月至2023年5月间就诊于郑州市第六人民医院的AIDS合并隐球菌脑膜炎患者86例纳入研究组,并选择同时期30名体格检查健康者纳入对照组.采用流式细胞术检测两组外周血CD4^(+)淋巴细胞及CD4^(+)/CD8^(+)比例,并进行比较;分析研究组患者预后情况.[结果]研究组外周血CD4^(+)淋巴细胞计数及CD4^(+)/CD8^(+)比例均明显低于对照组(P<0.05);自患者入院至出院后3个月无失访情况,其中存活74例,死亡12例;死亡组外周血CD4^(+)淋巴细胞计数<50个/μL、意识障碍占比、HIV RNA数、颅内压情况、存在其他合并症占比均明显高于生存组(P<0.05);意识障碍、低外周血CD4^(+)计数、高HIV RNA、高颅内压、存在其他合并症均是影响AIDS合并隐球菌脑膜炎患者预后不良的危险因素(P<0.05).[结论]AIDS合并隐球菌脑膜炎患者CD4^(+)淋巴细胞计数明显下降,低水平CD4^(+)与患者预后不良有关.

隐球菌脑膜炎患者的抗真菌治疗分析与药学监护

目的对1例隐球菌脑膜炎患者的抗真菌治疗及药学监护进行分析,为临床用药提供参考。方法临床药师全程参与1例免疫功能正常且无其他基础疾病的青年男性隐球菌脑膜炎患者的临床治疗过程,协助医生为患者制定个体化抗真菌治疗方案,同时对患者进行药学监护,包括疗效监护和药物不良反应监测。结果在临床药师的协助和药学监护下,医生接受临床药师的建议,进行了有效的抗真菌治疗,同时治疗期间药物相关不良反应得到积极处理,未出现严重不良反应,得到了较好的治疗效果。结论临床药师参与1例隐球菌脑膜炎患者的抗真菌治疗并进行药学监护,提高了患者用药的有效性和安全性。

有无隐球菌脑膜炎的隐球菌肺炎的临床及CT特征比较

目的:探讨有无隐球菌脑膜炎(CM)的隐球菌肺炎(PC)患者的临床及CT特征差异,旨在为CM的早期诊断提供更多的预警指标。方法:回顾性分析2014年1月-2022年6月于本院经肺部穿刺活检或手术病理证实的87例PC患者的临床及CT资料,其中38例合并CM(脑膜炎组),49例不合并CM(对照组),比较两组临床及CT特征的差异。结果:脑膜炎组免疫功能受损病史、CD4^(+)T细胞比例降低及CD4^(+)/CD8^(+)T细胞比值降低的发生率均显著高于对照组,差异均有统计学意义(P均<0.05)。两组患者的年龄、性别构成比、吸烟史、CD3^(+)及CD8^(+)T细胞比例降低的发生率差异均无统计学意义(P均>0.05)。脑膜炎组空洞、胸内淋巴结肿大的发生率均显著高于对照组,而晕征、充气支气管征的发生率显著低于对照组,差异均有统计学意义(P均<0.05);两组病灶分布、CT分型、病灶数目、毛刺征、分叶征、胸膜牵拉征及胸腔积液的发生率差异均无统计学意义(P均>0.05)。结论:有无合并CM的PC患者的临床及CT特征存在差异,当PC患者有免疫功能受损病史、细胞免疫功能异常、肺内病灶出现空洞且无晕征及充气支气管征、伴胸内淋巴结肿大时需高度警惕CM的发生,尽早筛查并及时调整治疗方案,从而改善患者预后。

非人类免疫缺陷病毒相关隐球菌性脑膜炎患者55例临床特征分析

目的分析55例非人类免疫缺陷病毒(human immunodeficiency virus,HIV)相关隐球菌性脑膜炎(cryptococcal meningitis,CM)患者的临床特征,为该病早期临床诊断提供科学依据。方法回顾性分析2004年1月至2023年10月广西医科大学附属武鸣医院及其他五家基层医院实验室诊断为非HIV相关CM患者的电子病历资料,分析其既往史、首发临床特征、实验室检查、影像学检查等。结果55例非HIV相关CM患者中,男性27例(49.1%),中位年龄为57岁(43,67),40例(72.73%)居住在乡村,32例(58.18%)有基础疾病。头痛为最典型的首发临床症状(76.36%),其次为恶心呕吐(50.91%)、头晕(45.45%)、脑膜刺激征阳性(43.64%)、发热(41.82%)。颅内压升高、脑脊液(cerebrospinal fluid,CSF)白细胞计数升高、CSF蛋白定量检测增高、CSF糖定量检测降低和CSF氯化物定量检测降低分别占73.33%、94.34%、86.00%、68.52%和64.81%。白细胞计数升高占50.91%,中性粒细胞百分比升高占67.27%。影像学检查异常占50.91%,以梗死、异常信号病变和脱髓鞘病变为主。结论非HIV相关CM发病以中老年患者为主,居住环境多在乡村,首发临床特征以头痛、恶心呕吐、头晕、脑膜刺激征阳性和发热为主,颅内压和CSF相关指标大多异常,提高医生对非HIV相关CM的认识有助于患者的早期诊疗。

隐球菌脑炎和(或)脑膜炎三例及文献复习

回顾性分析3例经病原学确诊为隐球菌脑炎和(或)脑膜炎患者的临床及影像资料。3例患者临床症状均以头痛为主,其中1例患者表现为孤立性头痛,查体无颈强直、无神经系统局灶性定位体征,既往糖尿病史;其他2例患者表现为头痛伴颅高压。经脑脊液培养均确诊为隐球菌脑炎和(或)脑膜炎。对于孤立性头痛的患者,临床医师很少把隐球菌脑炎和(或)脑膜炎作为首要考虑。然而,头痛是隐球菌脑炎和(或)脑膜炎最典型的临床表现,并且隐球菌感染越来越多见于免疫功能正常的非艾滋病人群,可导致急性脑梗死。因此,本文作者总结分析3例隐球菌脑炎和(或)脑膜炎患者的诊疗过程,旨在提高临床医师对该病的早期识别和诊疗。

隐球菌性脑膜炎预后不良危险因素分析及列线图预测模型构建

目的筛查隐球菌性脑膜炎预后不良危险因素,并基于危险因素构建风险预测列线图(Nomogram)模型。方法纳入2010年1月至2022年8月遵义医科大学附属医院收治的100例隐球菌性脑膜炎患者,均予以抗隐球菌治疗,根据住院期间脑脊液隐球菌培养结果以及出院时临床症状与体征分为预后良好组(19例)和预后不良组(81例),单因素和多因素逐步法Logistic回归分析筛查隐球菌性脑膜炎患者预后不良危险因素,并基于危险因素构建Nomogram模型,绘制受试者工作特征(ROC)曲线和校准曲线并行Hosmer-Lemeshow拟合优度检验。结果预后不良组患者入院时营养风险筛查2002(NRS 2002)评分(Z=-3.898,P=0.000)、脑脊液压力>250 mm H_(2)O比例(χ^(2)=9.512,P=0.002)、抗真菌治疗时间<14 d比例(χ^(2)=17.847,P=0.000)高于预后良好组,血常规红细胞计数(t=-2.802,P=0.006)和淋巴细胞计数(Z=-2.878,P=0.004)、血浆白蛋白(t=-4.332,P=0.000)、应用两性霉素B比例(χ^(2)=4.597,P=0.032)低于预后良好组。Logistic回归分析显示,入院时NRS 2002评分高(OR=3.258,95%CI:1.337~7.940;P=0.009)、脑脊液压力>250 mm H_(2)O(OR=0.108,95%CI:0.018~0.659;P=0.016)、抗真菌治疗时间<14 d(OR=0.092,95%CI:0.011~0.742;P=0.025)是隐球菌性脑膜炎预后不良的危险因素。根据上述3项危险因素构建Nomogram模型,ROC曲线下面积为0.927(95%CI:0.873~0.980,P=0.000),该模型预测隐球菌性脑膜炎预后不良的截断值为53.50分;校准曲线(一致性良好)、Hosmer-Lemeshow拟合优度检验(χ^(2)=2.694,P=0.912)表明该模型具有良好的区分度、校准度和稳定性。结论入院时NRS 2002评分高、颅内压>250 mm H_(2)O、抗真菌治疗<14 d的隐球菌性脑膜炎患者预后较差,据此构建的Nomogram模型具有较高的预后不良风险预测价值。