miliary

milsiary
  • 文章类型: Case Reports
    一名79岁的II型糖尿病患者,最近被诊断为特发性血小板减少性紫癜,在两周内出现进行性呼吸困难。他被发现有弥漫性的粟粒性结节,致密的空洞固结,胸部影像学上广泛的囊性改变,并在入院后48小时内死亡。他的血清球虫抗体和尿液组织胞浆抗原均为阳性。他后来从血液中生长出球虫,支持组织胞浆阳性可能是抗原测试交叉反应性的结果的理论。球孢子菌病通常表现为轻度,自我限制的症状,但也可能迅速传播,导致暴发性,危及生命的疾病.及时识别暴发性球孢子菌病的危险因素并了解血清学检测的缺陷对于正确诊断和治疗该疾病至关重要。
    A 79-year-old man with type II diabetes mellitus and recently diagnosed idiopathic thrombocytopenic purpura presented to the Emergency Department with progressive dyspnea over the course of two weeks. He was found to have diffuse miliary nodules, dense cavitary consolidation, and widespread cystic changes on chest imaging and died within 48 hours of admission to the hospital. His serum Coccidioides antibody and urine Histoplasma antigen were both positive. He later grew Coccidioides immitis from the blood, supporting the theory that Histoplasma positivity was likely the result of antigen test cross-reactivity. Coccidioidomycosis typically presents with mild, self-limited symptoms, but may also disseminate rapidly, causing fulminant, life-threatening disease. Prompt recognition of risk factors for fulminant coccidioidomycosis and understanding flaws in serologic testing are essential to the appropriate diagnosis and management of this disease.
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  • 文章类型: Case Reports
    背景:睫状结核(TB)是结核分枝杆菌的致死性血行传播形式,儿童死亡率约为15-20%。本报告重点介绍了一名12岁女孩异常表现的粟粒性结核病的临床表现。
    方法:在这种情况下,尽管没有呼吸道症状,但仍有广泛的肺部受累.此外,在脑桥中检测到一些具有高强度边缘结节的中枢低强度,右脑花梗和扁形核。
    结论:这项研究的结果表明,即使在接受卡介苗(BCG)疫苗的人中,也可能发生严重的粟粒性结核病。
    BACKGROUND: Miliary tuberculosis (TB) is a lethal hematogenous spread form of mycobacterium tuberculosis with approximately 15-20% mortality rate in children. The present report highlights the clinical manifestations of an unusual presentation of miliary tuberculosis in a 12-year-old girl.
    METHODS: In this case, extensive lung involvement was presented despite the absence of respiratory symptoms. Also, some central hypo-intense with hyper-intense rim nodules were detected in the brain\'s pons, right cerebral peduncles and lentiform nucleus.
    CONCLUSIONS: The results of this study showed that severe miliary TB may occur even in a person who received the Bacille Calmette-Guérin (BCG) vaccine.
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  • 文章类型: Journal Article
    背景:胸部影像学上的网状图案通常归因于结核病(TB)感染。然而,无数的条件可能会导致一个milsiary模式,其中许多威胁生命。研究问题:我们研究的主要目的是阐明立体胸部成像模式的潜在原因,以改善检查和经验性治疗选择。次要目的是辨别粟粒病病因的预测因素,并确定是否给予适当的经验性抗微生物疗法。研究设计和方法:在这项回顾性队列研究中,我们在放射学数据库中搜索了用"milsiary"一词描述的胸部影像学研究患者.如果受试者年龄在18岁以下,并且没有足够的客观数据来支持杂性疾病的病因,则将其排除在外。放射科医生独立检查了所有的影像学检查,和研究似乎没有一个真正的milsiary模式被排除。收集的数据包括患者的人口统计,免疫受损的危险因素,与粟粒性疾病相关的条件,β-D-葡聚糖水平,血清嗜酸性粒细胞计数,和经验性治疗。结果:从我们的41名患者队列中,22例(53.7%)临床诊断为球孢子菌病,8(19.5%)与TB,7例(17.1%)转移性实体癌,1例(2.4%)患有淋巴瘤,1(2.4%)与其他(猿类分枝杆菌),3例(7.3%)患有未知疾病(总和等于42例患者,因为一名患者被诊断患有球孢子菌病和TB)。所有6例嗜酸性粒细胞大于500/μL的患者均被诊断为球孢子菌病。在被诊断为球孢子菌病的22例患者中,20例(90.91%)采用抗真菌方案进行经验性治疗。在8名结核病患者中,6例接受了结核病的经验性治疗.解释:根据我们的数据,该数据来自靠近结核病流行区的球虫流行区,菌丝病的主要原因是球孢子菌病,虽然结核病和癌症也是常见的病因。在我们的患者队列中,血清嗜酸性粒细胞增多和β-D-葡聚糖水平升高是球孢子菌病的强烈预测因素,并具有绒状胸部成像模式。
    Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential causes of miliary chest imaging patterns to improve workup and empiric therapy selection. The secondary aims are to discern the predictors of miliary disease etiology and to determine whether appropriate empiric antimicrobial therapies were given. Study Design and Methods: In this retrospective cohort study, we searched a radiology database for patients with chest imaging studies described by the word \"miliary\". Subjects were excluded if they were under 18 years of age and if there were insufficient objective data to support a miliary disease etiology. A radiologist independently reviewed all imaging studies, and studies that did not appear to have a true miliary pattern were excluded. The collected data include patient demographics, immunocompromising risk factors, conditions associated with miliary disease, β-D-glucan levels, serum eosinophil count, and empiric therapies received. Results: From our 41-patient cohort, 22 patients (53.7%) were clinically diagnosed with coccidioidomycosis, 8 (19.5%) with TB, 7 (17.1%) with metastatic solid cancer, 1 (2.4%) with lymphoma, 1 (2.4%) with other (Mycobacterium simiae), and 3 (7.3%) with unknown diseases (the sum equals 42 patients because one individual was diagnosed with both coccidioidomycosis and TB). All six patients with greater than 500 eosinophils/μL were diagnosed with coccidioidomycosis. Of the 22 patients diagnosed with coccidioidomycosis, 20 (90.91%) were empirically treated with an antifungal regimen. Of the eight patients with TB, six were empirically treated for TB. Interpretation: Based on our data from a Coccidioides-endemic region with close proximity to tuberculosis-endemic areas, the leading cause of miliary disease is coccidioidomycosis, although TB and cancer are also common etiologies. Serum eosinophilia and elevated β-D-glucan levels were strongly predictive of coccidioidomycosis in our patient cohort with a miliary chest imaging pattern.
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  • 文章类型: Journal Article
    结核病(TB)是全球死亡的主要传染性原因。尽管结核病发病率和患病率正在下降,免疫抑制药物的使用和免疫功能低下疾病如合并症的日益普遍,恶性肿瘤,免疫抑制剂的使用是播散性结核病(DTB)的危险因素。本研究旨在确定相关的临床,实验室,放射学,DTB的组织病理学特征,以及评估在阿卜杜勒阿齐兹国王医疗城(KAMC)诊断为该疾病的患者的典型解剖分布和治疗结果。
    进行了回顾性图表审查,包括所有在KAMC诊断为milsiary或DTB的患者,并提供可检索的医疗文件。
    该研究包括55名患者,其中35人(63.6%)为男性,中位年龄为64岁。35例(63.6%)感染患者得到及时诊断并最终治愈。最常见的合并症是糖尿病,慢性肾病,和免疫受损的条件,其中37人中存在(67.2%),12(21.8%),和11名患者(20%),分别。最常见的症状是发烧和咳嗽,在31例(56.3%)和26例(47.2%)患者中,分别,其次是25(45.4%)的体重减轻,15人中有盗汗(27.2%),和呼吸急促14例(25.4%)。大约三分之二的患者患有肺部沙粒性结核(MTB)(38;69.1%),其次是结核性淋巴结炎(21;38.2%),中枢神经系统受累(13;23.6%),骨骼受累(11;20%),胃肠道受累(5;9.1%),胸膜受累(3;5.5%),和泌尿生殖系统结核(2;3.6%)。死亡率为14例(25.5%)。
    由于非特异性临床,MTB的诊断具有挑战性,实验室,和成像发现。与有发展DTB风险的患者打交道的临床医生应了解典型的表现和异常的临床发现。他们还应该有一个较低的门槛来启动对这种疾病的具体调查,早期诊断和有效治疗对于降低发病率和死亡率至关重要。
    UNASSIGNED: Tuberculosis (TB) is the primary infectious cause of mortality worldwide. Although TB incidence and prevalence are declining, the use of immunosuppressive drugs and the growing prevalence of immunocompromising conditions such as comorbidities, malignancies, and the use of immunosuppressive agents are risk factors for disseminated TB (DTB). This study aims to identify the relevant clinical, laboratory, radiological, and histopathological features of DTB, as well as to assess the typical anatomical distributions and treatment outcomes of patients diagnosed with the disease at King Abdulaziz Medical City (KAMC).
    UNASSIGNED: A retrospective chart review was conducted, including all patients diagnosed with miliary or DTB at KAMC with retrievable medical files.
    UNASSIGNED: The study included 55 patients, of whom 35 (63.6%) were male and the median age was 64 years old. 35 (63.6%) of the infected patients were timely diagnosed and eventually cured from the illness. The most common comorbid conditions were diabetes, chronic kidney disease, and immunocompromising conditions, which were present in 37 (67.2%), 12 (21.8%), and 11 (20%) of the patients, respectively. The most common presenting symptoms were fever and cough, present in 31 (56.3%) and 26 (47.2%) of the patients, respectively, followed by weight loss in 25 (45.4%), night sweats in 15 (27.2%), and shortness of breath in 14 (25.4%). Approximately two-thirds of the patients had pulmonary miliary TB (MTB) (38; 69.1%), followed by TB lymphadenitis (21; 38.2%), central nervous system involvement (13; 23.6%), skeletal involvement (11; 20%), gastrointestinal involvement (5; 9.1%), pleural involvement (3; 5.5%), and urogenital TB (2; 3.6%). The mortality rate was 14 (25.5%) patients.
    UNASSIGNED: MTB is challenging to diagnose due to nonspecific clinical, laboratory, and imaging findings. Clinicians dealing with patients who are at risk of developing DTB should be aware of the typical presentations and abnormal clinical findings. They should also have a low threshold to initiate specific investigations for the disease, as early diagnosis and effective treatment is critical in reducing morbidity and mortality rates.
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  • 文章类型: Case Reports
    一名76岁的男子因咳嗽被转诊到我们医院。胸部计算机断层扫描(CT)显示左上叶舌段有45毫米的肿块。经支气管肿瘤活检显示腺癌。增强CT和骨闪烁显像显示肺,胸膜,和骨转移。患者诊断为左上叶腺癌cT2bN3M1cIVB期。使用OncomineDxTargetTestMulti-CDx系统对原发性肿瘤进行的遗传分析显示,表皮生长因子受体(EGFR)(L858R)和CTNNB1突变呈阳性。基于这些发现,患者接受奥希替尼(80mg/d)作为一线治疗.六个月后,肿瘤增大了,表明疾病进展。停止奥希替尼,并开始使用卡铂(曲线5下面积)和培美曲塞(500mg/m2)进行二线治疗。化疗三个周期后,患者出现痴呆和定向障碍。头部的对比增强磁共振成像显示了粟粒性脑转移。睫状体播散是一种罕见的脑转移。肺转移的纤毛模式与EGFR外显子19缺失密切相关。已报道了外显子19缺失的非小细胞肺癌的粟粒性脑转移的放射学特征。据我们所知,这是首例肺癌伴粒性脑转移和EGFR(L858R)和CTNNB1共突变的病例报告.总之,EGFR(L858R)和CTNNB1的共突变以及EGFR-酪氨酸激酶抑制剂的停药可能有助于粟粒性脑转移的发展。需要进一步的案例研究。
    A 76-year-old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45-mm mass in the lingular segment of the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. Contrast-enhanced CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi-CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first-line therapy. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped and second-line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast-enhanced magnetic resonance imaging of the head showed miliary brain metastases. Miliary dissemination is a rare form of brain metastasis. Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. The radiological features of miliary brain metastases of non-small cell lung cancer with the exon 19 deletion have been reported. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co-mutations of EGFR (L858R) and CTNNB1. In conclusion, co-mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR-tyrosine kinase inhibitor may contribute to the development of miliary brain metastases. Further case studies are warranted.
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  • 文章类型: Case Reports
    背景:干扰素γ释放测定(IGRA)用于在怀疑炎症性风湿病的情况下进行生物治疗之前检测潜伏性结核病。
    方法:我们报告了一例50岁女性,在阿达木单抗用于推测的轴性脊柱关节炎之前,IGRA试验阴性。
    结果:治疗中症状的恶化导致了进一步的研究,并且播散性结核病(TB)的诊断后来被确定为多骨性和多骨性部位,例如脊柱炎和骶髂关节炎。患者病史显示既往接触过肺结核。该观察结果说明了IGRA在这种情况下的局限性,这是由于其用于主动TB诊断的可变性能。
    结论:由于非特异性征象,骨结核经常被误诊。我们提请注意在对可疑的慢性炎症性风湿病进行生物治疗之前进行全球风险评估的重要性,并回顾了IGRA假阴性的危险因素。暴露于抗TNF-α后可能需要延长疗程。
    BACKGROUND: Interferon gamma release assay (IGRA) is used to detect latent tuberculosis prior to biological treatments in the context of suspected inflammatory rheumatism.
    METHODS: We report the case of a 50-year-old woman with negative IGRA test before adalimumab introduction for presumed axial spondyloarthritis.
    RESULTS: The worsening of symptoms under treatment led to further investigations and the diagnostic of disseminated tuberculosis (TB) was later established with miliary and multiple bone locations such as spondylitis and sacroilitis. The patient\'s history revealed past exposure to tuberculosis. This observation illustrates the limitations of IGRA in such situation due to its variable performance for active TB diagnosis.
    CONCLUSIONS: Misdiagnosis is frequent in bone tuberculosis due to non-specific signs. We draw the attention to the importance of a global risk assessment prior to the introduction of biological treatment for suspected chronic inflammatory rheumatism and recall the risk factors for false-negative IGRA. An extended treatment course may be necessary after exposure to anti-TNF-alpha.
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  • 文章类型: Journal Article
    背景:组织胞浆菌病主要被描述为HIV感染者(PLHIV)中的一种传播疾病。与免疫能力个体的历史描述相比,对肺组织胞浆菌病(PH)的详细临床和放射学发现以及结局缺乏了解。忽视或误诊为其他定义艾滋病的疾病,由于治疗不当,PLHIV的预后可能存在风险.
    方法:1988年1月至2019年10月在法属圭亚那的PLHIV中进行了一项回顾性多中心研究。通过真菌学直接检查证实了PH,文化,或组织学。合并呼吸道感染的患者被排除在外。
    结果:在65名患者中,性别比M:F为2.4,中位年龄为39岁[IQR25-75%:34-44].中位CD4计数为24细胞/mm3[11-71],88%的人以组织胞浆菌病为艾滋病定义条件,29%的人同时患有艾滋病定义条件。临床表现为发热(89%),咳嗽(58%),呼吸困难(35%),咳痰(14%),咯血(5%)。进行了61次X射线和24次CT扫描。在X射线上,主要发现间质性肺病(77%)。在CT扫描中,结节型占主导地位(83%):主要是粟粒性疾病(63%),但也挖出了结核(35%)。合并占46%,21%的人与粟粒性疾病相关。58%的人发现胸部淋巴结肿大,主要是肺门和对称(33%)。尽管有抗真菌治疗,一个月的病死率为22%。
    结论:在晚期PLHIV患者中,当面对X线片显示的间质性肺病或CT扫描显示的网状模式时,流行地区的医生,除了肺结核或肺孢子虫病,应包括组织胞浆菌病作为其鉴别诊断的一部分。
    BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care.
    METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded.
    RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%.
    CONCLUSIONS: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.
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  • 文章类型: Case Reports
    与痛风相关的关节症状,主要以关节爆发为特征,众所周知。Tophi代表痛风的主要皮肤表现,最常与慢性和未充分控制的疾病相关。在极少数情况下,可能出现不典型的皮肤表现。我们介绍了一名已知患有高尿酸血症的36岁男子的橘红色痛风形式。皮肤材料的显微直接分析表明存在尿酸单钠(MSU)晶体。皮质类固醇治疗后皮疹消失,关节症状恢复。了解这种不寻常的痛风相关皮肤病对于诊断痛风的罕见表现至关重要,有时发生在关节症状之前。这个案例突出了对任何疑似痛风的皮肤病变进行采样的重要性,用于MSU晶体识别,并提供了明确的诊断。
    Joint symptoms associated with gout, mostly characterized by joint flare-ups, are well known. Tophi represent the main cutaneous manifestation of gout, most often associated with a chronic and inadequately controlled disease. On rare occasions, atypical skin manifestations may occur. We present the case of a miliary form of gout in a 36-year-old man known to have hyperuricemia. Microscopic direct analysis of the skin material revealed the presence of monosodium urate (MSU) crystals. Rash disappeared with corticosteroid therapy in parallel with joint symptoms recovery. Knowledge of this unusual gout-related skin disease is essential to diagnosing uncommon presentations of gout, which sometimes occur before joint symptoms. This case highlights the importance of sampling any skin lesion suspected of being tophus, for MSU crystal identification, and provides a definitive diagnosis.
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  • 文章类型: Case Reports
    结核病(TB)在发展中国家非常普遍,肺外病例的发病率不断上升。骨骼和关节的结核病诊断是相当具有挑战性的。大多数脊柱结核病变位于胸部和腰部;宫颈病变很少见。因此,大多数颈部疼痛被标记为颈椎病,因为颈椎结核(CTB)的症状尚不清楚。一名38岁的男性颈部长期疼痛六个月,与任何局灶性神经功能缺损无关,恶心,呕吐,或者视力模糊.经过当地从业者的初步评估,疼痛是,像往常一样,归于颈椎病并保守治疗。然而,他的疼痛加重了,他最终带着改变的精神状态来找我们。在现实中,他有CTB,后来并发危及生命的播散性结核病,颅内和肺部受累,他只有在长期ICU护理后才能存活.即使是轻度的颈椎疼痛也不容忽视,必须进行适当的评估。慢性颈痛的鉴别诊断应考虑CTB,特别是在结核病流行的国家。
    Tuberculosis (TB) is quite prevalent in developing countries, with an ever-rising incidence of extrapulmonary cases. TB of bones and joints is quite challenging to diagnose. Most spinal TB lesions localize at the thoracic and lumbar levels; cervical lesions are a rarity. Hence, most neck pains are labelled cervical spondylosis as the symptomatology of cervical spine tuberculosis (CTB) remains unclear. A 38-year-old male had long-standing neck pain for six months, not associated with any focal neurological deficit, nausea, vomiting, or blurred vision. After the initial evaluation by local practitioners, the pain was, as usual, attributed to cervical spondylosis and conservatively managed. However, his pain worsened, and he ultimately came to us with altered mental status. In reality, he had CTB, which later complicated to life-threatening disseminated TB with intracranial and pulmonary involvement, and he could only survive after prolonged ICU care. Even mild cervical pain should not be neglected and must undergo proper evaluation. We should consider CTB in the differential diagnosis of chronic neck pain, especially in countries where TB is endemic.
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  • 文章类型: Journal Article
    背景:睫状结核(TB)是结核病最严重的表现之一,当伴有中枢神经系统(CNS)受累时可能致命。细菌学,在这项研究中,我们评估了生化和放射学方法,以发现在沙粒性TB中的CNS合并症.
    方法:回顾性地从中国两家指定的结核病医院中纳入连续的恶性结核病成年人。脑脊液(CSF)的检查能力,评估了诊断中枢神经系统受累的脑计算机断层扫描(CT)和磁共振成像(MRI).
    结果:在392例急性粟粒性结核病中,有282例进行了腰椎穿刺和/或神经影像学检查的中枢神经系统受累评估。在这282名患者中,87.59%(247/282)有中枢神经系统受累。脑增强MRI(96.05%,170/177)和MRI(93.15%,204/219)的敏感度明显高于脑脊液检查(71.92%,146/203,P<0.001)和CT(34.69%,17/49,P<0.001)。脑脊液检查的敏感性优于CT扫描(P<0.001)。尽管59.65%(134/225)的粟粒性结核病患者通过痰液检查获得了细菌学证据,常规和分子检测脑脊液检查阳性率仅为8.82%(21/238)。
    结论:几乎所有的粟粒性结核都有中枢神经系统受累,MRI表现出优于其他方法的潜力。因此,应强烈建议在具类结核中常规筛查CNSTB,在资源丰富的环境中,MRI可作为初始方法.
    BACKGROUND: Miliary tuberculosis (TB) is one of the severest manifestations of TB that can be lethal when concomitant with the central nervous system (CNS) involvement. Bacteriological, biochemical and radiological methods for find CNS comorbidity in miliary TB was evaluated in this study.
    METHODS: Consecutive miliary TB adults were retrospectively enrolled from two designated TB hospitals in China. The capacities of examinations of cerebrospinal fluid (CSF), cerebral computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis of CNS involvement were assessed.
    RESULTS: Assessment of CNS involvement with a lumbar puncture and/or neuroimaging was undertaken in 282 out of 392 of acute miliary TB. Of these 282 patients, 87.59% (247/282) had CNS involvement. Cerebral contrast-enhanced MRI (96.05%, 170/177) and MRI (93.15%, 204/219) yielded significantly higher sensitivities over CSF examination (71.92%, 146/203, P < 0.001) and CT (34.69%, 17/49, P < 0.001). The sensitivity of CSF examination was superior to CT scan (P < 0.001). Although 59.65% (134/225) miliary TB patients acquired bacteriological evidence with sputum examination, the positivity was only 8.82% (21/238) for CSF examination by conventional and molecular tests.
    CONCLUSIONS: Almost all miliary TB had CNS involvement and MRI demonstrated outstanding potential over other methods. Therefore, a routinely screening of CNS TB should be strongly suggested in miliary TB and MRI could be used as the initial approach in resources rich settings.
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