A renal transplant recipient in her 60s presented with a history of chronic headaches and progressive encephalopathy. Serial cerebrospinal fluid examinations were consistent with chronic lymphocytic meningitis, but no definitive cause was identified. Imaging studies showed the development of an enhancing suprasellar mass lesion and hydrocephalus. Symptoms progressed despite empiric antimicrobial therapy, and the patient died after an acute large-volume subarachnoid hemorrhage. A complete autopsy was performed. The differential diagnosis, pathologic findings, and diagnosis are discussed.
一名60多岁的肾移植受体患者,有慢性头痛和进行性脑病病史。系列脑脊液检查符合慢性淋巴细胞性脑膜炎,但是没有明确病因。影像学检查显示一个增强的鞍上病灶和脑积水,且进行性加重。尽管给予经验性的抗生素治疗,症状仍然进展,患者死于急性重型蛛网膜下腔出血,随后对患者进行了完整的尸检。本文对鉴别诊断,病理结果和诊断进行了讨论。
A woman in her 60s with hypertension and a prior cadaveric renal transplant treated with chronic immunosuppression (mycophenolate mofetil, tacrolimus, and prednisone) was referred for management of chronic lymphocytic meningitis. Nine months prior to transfer to our institution, she was bitten by a pet cat and over several weeks developed a slowly progressive headache associated with generalized weakness, fatigue, and myalgias. She was treated with analgesics but never had complete resolution of her symptoms. Six months after symptom onset, her head magnetic resonance imaging (MRI) was normal. A cerebrospinal fluid (CSF) analysis revealed an elevated white blood cell count and low glucose level, but no infectious agent was found. She was treated empirically with rifampin and doxycycline for 3 weeks and showed minimal improvement. She was then treated with ciprofloxacin, but her symptoms continued to worsen. Follow-up imaging showed an interval development and progression of a new suprasellar lesion, as well as mild communicating hydrocephalus. After 2 months of ciprofloxacin, she developed worse headaches associated with nausea and vomiting, gait ataxia, and altered mental status. This progressed for 2 weeks before she transferred to our hospital.
一名60多岁的女性,既往高血压和尸体肾移植病史,应用慢性免疫抑制剂(霉酚酸酯,他克莫司,强的松),转诊来治疗慢性淋巴细胞性脑膜炎。转到我们医院前的9个月,她被宠物猫咬过,在几个星期内出现缓慢进展的头痛,伴有全身乏力、疲劳和肌痛。她用了止痛药,但症状未完全缓解。起病后六个月,头部磁共振成像(MRI)正常。脑脊液分析显示白细胞计数升高,血糖降低,但未发现感染源。给予利福平和多西环素经验性治疗3周,症状稍微有所好转。患者随后接受了环丙沙星治疗,但她的症状持续恶化。随访影像显示新的鞍上病变出现并进展,以及轻度交通性脑积水。经过2个月的环丙沙星治疗之后,她头痛加重,伴有恶心,呕吐,共济失调步态,精神状态改变。2周后转到我们医院。
On arrival, she was afebrile and hemodynamically stable but drowsy and only oriented to person. She had significant ataxia, but her cranial nerve examination, strength testing, and reflexes were normal. Empiric treatment started with rifampin, ampicillin, vancomycin, erythromycin, ceftriaxone, and amphotericin. The head MRI showed enlargement of the suprasellar mass with involvement of the sphenoid sinus and worsening hydrocephalus. The neurosurgery department was consulted for a biopsy, but before any additional diagnostic tests could be performed, she acutely declined and became unresponsive. Emergent head computed tomography demonstrated a large subarachnoid hemorrhage with intraventricular extension and a marked increase in hydrocephalus. An external ventricular drain was placed, but ultimately her family opted to pursue palliative measures and she died. A complete autopsy was performed.
入院后,患者的体温正常,血流动力学稳定,但昏睡,仅能认识人。她有明显的共济失调,但她的颅神经检查,肌力检查和反射均正常。开始给予利福平、氨苄西林、万古霉素、红霉素、头孢曲松和两性霉素等经验性治疗。头部MRI显示鞍上肿物增大累及蝶窦,脑积水较前加重。神经外科会诊打算进行活检,但在其他的辅助诊断检查进行之前,她病情急剧进展,出现反应迟钝。急诊头颅CT显示为大量蛛网膜下腔出血,脑室扩大,脑积水明显增加。放置脑室外引流,但最终她的家人选择了姑息治疗,患者死亡,死后进行了完整的尸检。
Laboratory and Imaging Studies
实验室和影像学检查
An initial head MRI 6 months after symptom onset showed leukoaraiosis, but otherwise was unremarkable. Laboratory studies showed an elevated erythrocyte sedimentation rate of 43mm/h but normal C-reactive protein, complete blood cell count, electrolytes, and liver function test results. Blood cultures were negative. A CSF analysis revealed a white blood cell count of 100/μL (65%lymphocytes, 27% neutrophils, and 8%monocytes) (to convert to ×109 per liter, multiply by0.001), albumin count of 0.047g/dL(to convert to gramsper liter, multiply by 10), glucose count of 40mg/dL (to convert to millimoles per liter, multiply by 0.0555), and red blood cell count of 5×106/μL (to convert to ×1012 per liter, multiply by 1). The CSF opening pressure and corresponding serum glucose were not available. Her cytology was negative for malignancy. An extensive workup on CSF identified no infectious cause and included a negative gramstain, an acid-fast bacilli culture, and a fungal culture. Polymerase chain reaction test results for herpes simplex virus, varicella-zoster virus, cytomegalovirus, enterovirus, Epstein-Barr virus, Bartonella, Mycobacterium tuberculosis, and Borrelia burgdorferi were all negative. Serology results for syphilis,Toxoplasma, Cryptococcus, Coccidioides, and Histoplasma were also negative.
起病后6个月时,初始头部MRI显示脑白质疏松,其他无明显异常。实验室检查发现,红细胞沉降率升高,43mm/h,但C反应蛋白、全血细胞计数、电解质、肝功能检查结果正常。血培养阴性。脑脊液分析显示:白细胞计数100 /μL(淋巴细胞65%,中性粒细胞27%,单核细胞8%)(转换为×109/L,乘以0.001)、白蛋白计数0.047g /dL(转换为g /L,乘以10),葡萄糖40mg/dl(转换为mmol/L,乘以0.0555),红细胞计数5×106 /μL(转换为×1012/L,乘以1)。CSF初始压力和相应的血糖结果不详。细胞学检查未见肿瘤细胞。多种脑脊液检查没有发现感染原因,包括革兰氏染色,抗酸杆菌培养、真菌培养阴性。单纯疱疹病毒、水痘-带状疱疹病毒、巨细胞病毒、肠道病毒、EB病毒、结核分枝杆菌、巴尔通体和伯氏疏螺旋体聚合酶链反应检测结果均为阴性。梅毒、弓形虫、隐球菌、球孢子菌属和组织包浆菌血清学结果也均为阴性。
Owing to worsening symptoms, MRI was repeated at 8 months after symptom onset. There was a new enhancing suprasellar mass extending over the meninges of the planum sphenoidale and invading the pituitary gland. There was also mild communicating hydrocephalus. Additional CSF analysis at the time of the second MRI showed a white blood cell count of 149/μL (64% lymphocytes, 22% neutrophils, and 14%monocytes), an albumin count of 0.046g/dL, and a red blood cell count of 1×106/μL. The CSF opening pressure and glucosewere not available. Because of continuing decline, MRI was repeated 1 month later, showing progression of the enhancing suprasellar mass, now with involvement of the sphenoid and cavernous sinuses (Figure 1). There was also a new enhancing leptomeningeal lesion adjacent to the right pons and abnormal meningeal enhancement over the tentorium and falx. The magnetic resonance angiogram and magnetic resonance venogram were unremarkable.
由于症状逐渐加重,症状出现后8个月重新复查了MRI。有一个新的鞍上增强占位延伸到蝶骨平台脑膜并侵犯到垂体,同时有轻度交通性脑积水。在第二次MRI时再次行脑脊液分析显示白细胞计数149 /μL(淋巴细胞64%,中性粒细胞22%,单核细胞14%),蛋白0.046 g/dl,红细胞计数1×106 /μL。脑脊液初始压力和血糖不详。因为病情持续恶化,1个月后重复进行MRI检查,鞍上增强的占位病灶又有进展,蝶窦、海绵窦也受累(图1)。右侧桥脑相邻的柔脑膜也有一个新的强化病灶以及在小脑幕和大脑镰脑膜有异常强化。MRA和MRV未见明显异常。
图1 MRI图像
A,矢状T1增强图像显示鞍上增强占位延伸到蝶骨平台脑膜并侵及垂体和蝶窦(箭头)。B,在右侧脑桥表面第五颅神经进入区可见一个基于软脑膜的增强结节(箭头)。有继发性交通性脑积水。
The CSF analysis performed on arrival to our hospital (9 months after symptom onset) showed a white blood cell count of 286/μL (90% neutrophils,5% lymphocytes,and 5%monocytes),a red blood cell count of 13×106/μL, an albumin count of 0.083 g/dL, and a glucose count of 27 mg/dL with a simultaneous serum glucose count of 105 mg/dL. She had an acute decompensation 1week after transfer, and emergent head computed tomography showed a large volume subarachnoid hemorrhage with an intraventricular extension and marked increase in hydrocephalus.
我们医院的CSF分析(发病后9个月):白细胞计数286 /μL(中性粒细胞90%,淋巴细胞5%,单核细胞5%),血红细胞计数13×106 /μL、白蛋白计数0.083 g/dL,葡萄糖27 mg/dL,同期血糖105 mg/dL。入院后1周,她出现急性的呼吸困难,急诊头部CT显示大量蛛网膜下腔出血伴脑室扩大,脑积水明显增加。
Clinical Discussion (Dr Pichler)
临床讨论
The differential diagnosis for chronic meningitis is vast. Broad categories include autoimmune or inflammatory conditions, neoplasia, and infection. The CSF profile may be used to narrow the differential, but it is imperfect. Hypoglycorrhachia, or low CSF glucose level, is likely influenced by many factors including decreased glucose delivery to the choroid plexus because of reduced blood flow, dysfunctioning glucose transport across the blood-brain barrier, and increased cerebral metabolism. It was previously thought that glucose consumption by bacteria or immune cells was responsible for hypoglycorrhachia. However, hypoglycorrhachia is now understood as a nonspecific finding and can be seen in cases of stroke, infection, sarcoidosis, chemical meningitis, and neoplasia. The CSF cell count and differential diagnosis may help distinguish between different classes of infection, but this is also imperfect and there can be overlap among viral, bacterial, and fungal infections.
慢性脑膜炎的鉴别诊断非常多。大的分类包括自身免疫或炎性疾病,肿瘤和感染。脑脊液分析可以用来缩小鉴别诊断,但它并不完美。脑脊液葡萄糖水平降低,可能会受到多种因素的影响,包括由于血流量减少导致的运送到脉络丛的葡萄糖减少,血脑屏障葡萄糖转运功能障碍,以及脑代谢增加。先前认为葡萄糖消耗是细菌引起的,免疫细胞和脑脊液葡萄糖水平降低有关。然而,葡萄糖水平降低现在被认为是一种非特异性的表现,可以出现在中风、感染、结节病、化学性脑膜炎和肿瘤的患者中。脑脊液细胞计数和鉴别诊断可能有助于区分不同类别的感染,但这也并不绝对,也可以是病毒、细菌和真菌感染的重叠。
Neurosarcoidosis is an inflammatory disorder of unknown etiology that most commonly involves the cranial nerves, hypothalamus, and pituitary gland. Subacute or chronic meningitis are common resulting manifestations, and obstructive hydrocephalus may occur.However, isolated neurosarcoidosis without systemic involvement is rare (fewer than 1% of cases).4 Other inflammatory conditions that could produce similar clinical and radiographic findings include Beh?et disease, systemic lupus erythematosus, and granulomatosis with polyangiitis. However, the lack of systemic involvement, continued worsening despite immunosuppression, and ultimate subarachnoid hemorrhage make the occurrence of an autoimmune or inflammatory process less likely in this patient.
神经系统结节病是一种病因不明,最常累及颅神经、下丘脑和腺垂体的炎症性疾病。亚急性或慢性脑膜炎是常见的表现,梗阻性脑积水也可以发生。然而,没有全身系统受累的孤立的神经系统结节病是罕见的(少于1%)。其他炎性疾病可产生类似的临床和影像学表现包括Beh?et病、系统性红斑狼疮,和血管炎性肉芽肿,然而,没有全身受累的证据,尽管给予免疫抑制剂治疗,病情仍持续恶化,最终出现蛛网膜下腔出血不大支持该患者为自身免疫性或炎性疾患。
Neoplasia must be considered as an outcome for an immunosuppressed patient with chronic meningitis and a new mass lesion. Neoplastic meningitis can be seen in up to 5% of patients with solid tumors, with an even higher incidence in cases of hematologic malignancy.6 Neoplastic meningitis could account for the leptomeningeal enhancement on MRI and can show similar cell counts and hypoglycorrhachia in the CSF. However, neoplastic meningitis would be unlikely to cause the subarachnoid hemorrhage and atypical cells are often seen in CSF.
应用免疫抑制剂的慢性脑膜炎患者,出现了新的占位性病变,一定要考虑到肿瘤。肿瘤性脑膜炎见于高达5%的实体肿瘤患者,在血液系统恶性肿瘤中,肿瘤性脑膜炎有更高的发病率。肿瘤性脑膜炎可以解释MRI上的软脑膜增强并且脑脊液可有类似的细胞计数和脑脊液葡萄糖水平降低。然而,肿瘤性脑膜炎不太可能引起蛛网膜下腔出血,脑脊液中常可见非典型细胞。
Viral, bacterial, and fungal infections can cause chronic meningitis.Many of the common viruses affecting the central nervous system(CNS) (arboviruses, herpes, cytomegalovius, and Epstein-Barr virus) are easily detected by polymerase chain reaction testing or serologies and would not be expected to cause enhancing mass lesions or a hemorrhage. Most bacterial CNS infections cause fulminantmeningitis with rapid deterioration and death if untreated. Causes of bacterial meningitis with a more prolonged course include syphilis,Bartonella,and Mycobacterium. Repeatedly negative results for syphilis with the Venereal Disease Research Laboratory test and rapid plasma reagin makes this diagnosis unlikely. Bartonella infection is often associated with a cat bite or scratch, and up to 10% of patients may develop disseminated disease. Bacillary angiomatosis is a rare complicationof Bartonella infection, which may be seen in cases of human immunodeficiency virus or an organ transplant. The disorder is characterized by vascular lesions, which typically involve the skin but have also been reported in other organs. Central nervous system involvement is rare and would be unlikely to lead to subarachnoid hemorrhage. Mycobacterium tuberculosis affects the CNS in up to 5% of cases, most often as meningitis. Focal caseating granulomas may occur, and strokes are also well described. The lack of pulmonary involvement and negative CSF and serum testing results would not indicate a tuberculosis diagnosis for this patient.
病毒、细菌、真菌感染可引起慢性脑膜炎。许多常见的影响中枢神经系统(CNS)病毒(虫媒病毒、疱疹病毒、巨细胞病毒,和EB病毒)很容易通过聚合酶链反应检测或血清学检测到,一般不会导致占位性病灶的增强或出血。大多数细菌性CNS感染引起迅速恶化的暴发型脑膜炎,如果不治疗就会死亡。广义的细菌性脑膜炎的原因包括梅毒、巴尔通体、结核分枝杆菌。梅毒的性病实验室检查和快速血浆反应素试验多次结果阴性,故不大考虑该诊断。巴尔通体感染常与猫的抓咬有关,高达10%的患者可能发展为播散性感染。杆菌型血管瘤病是巴尔通体感染一个罕见的并发症,可见于人类免疫缺陷病毒或器官移植患者。此疾病的特征是血管病变,通常涉及皮肤,但也有其他器官的报道。中枢神经系统受累罕见,不太可能导致蛛网膜下腔出血。5%的结核杆菌感染患者可有中枢神经系统受累,最常见的是脑膜炎。可以发生局灶性干酪样肉芽肿,卒中也经常见到。本患者缺乏肺部受累的证据,CSF检查阴性和血清学测试也不支持患者结核的诊断。
图2 病理发现
基底池大量出血(A)蛛网膜下腔出血聚集在鞍旁周围(B)。脑室增大铸型。C,在右脑桥前方第五颅神经出口区附近有一个出血性软化灶,延伸到延髓区域。D,显微镜下,垂体相对保存,明显纤维化的鞍膈含有大量的坏死性炎症灶多发脓肿(箭头)其中一些延伸到硬膜下表面(星号)(原始放大×12.5)。微脓肿(E-G)含有辐射状的隔膜菌丝,可见含真菌(星号)以及相关坏死(F)的坏死灶,(原放大倍数×200 [E ],×100 [F],和×200 [G])。H、众多的分枝隔膜菌丝六胺银染色阳性(原始放大×200)。
Fungal infections are a common cause of meningitis in immunocompromised patients and can be difficult to diagnose. Yeasts, such as Candida and Cryptococcus, are unicellular organisms that typically spread hematogenously. Their small size allows them to enter the subarachnoid space, leading to dissemination and meningitis. Although less common, both Candida and Cryptococcus can also form local granulomas or abscesses. Hydrocephalus is a frequent and potentially deadly complication, but subarachnoid hemorrhage would not be expected. Hyphae, such as Aspergillus and Mucormycosis (referring to any fungi within the family Mucoraceae), grow in branchlike colonies. Their larger morphology prevents access to the meningeal microcirculation. Sinus involvement is commonly seen, with direct extension through CNS barriers if untreated. The angioinvasion of cerebral vessels may result in vasculitis, sinus thrombosis, infarcts, or a hemorrhage. Most rhinocerebral Mucormycosis infections occur among patients with diabetes in ketoacidosis, which was not present in this patient. Additionally, rhinocerebral Mucormycosis is a rapidly progressive disorder that would not be expected to linger for months. Aspergillus, on the other hand, may present with chronic sinusitis before neurologic involvement is apparent. Thus, the most likely etiology of chronic meningitis and subarachnoid hemorrhage in this immunocompromised patient is an unidentified fungal infection.
真菌感染是免疫功能低下患者脑膜炎的常见原因,一般难以诊断。酵母菌,像念珠菌和隐球菌是单细胞生物,通常是血源性传播。其体积小,能够进入蛛网膜下腔,导致微生物的传播和脑膜炎。虽然不太常见,念珠菌和隐球菌可以形成局部肉芽肿或脓肿。脑积水是常见的和致命的并发症,但蛛网膜下腔出血少见。菌丝,如曲霉菌和毛霉菌(指任何毛霉菌家族的真菌),以分枝状菌落生长。其较大的形态无法进入脑膜微循环。窦受累常见,如果未经治疗,通过中枢神经系统屏障直接延伸,在血管内入侵可导致血管炎、静脉窦血栓形成、脑梗死或脑出血。大多数鼻脑毛霉菌病感染常发生于糖尿病酮症酸中毒的患者中,而本患者没有糖尿病酮症酸中毒。此外,鼻脑毛霉菌病是一个快速进展型疾病,不会迁延几个月。另一方面,曲霉菌病可以在神经系统受累前表现为慢性鼻窦炎。因此,在免疫功能低下的患者中,慢性脑膜炎、蛛网膜下腔出血最可能的病因是一个原因不明的真菌感染。
Neuropathological Discussion
(Dr Parisi) 神经病理讨论
During the patient’s autopsy, extensive blood was present in the basilar cisterns of the skull base (Figure 2A). The brain showed mild generalized cerebral edema and subarachnoid blood that was most marked at the base and centered around the sella (Figure 2B). The diaphragm sellae was thickened and covered by a shaggy purulent exudate (Figure 2A). Coronal sections through the cerebral hemispheres showed hydrocephalus and massive intraventricular casts of blood. Transverse sections through the cerebellum and brainstem disclosed the hemorrhagic softening of the right anterior pons near the region of the fifth cranial nerve exit zone that extended caudally to the rostral medulla (Figure 2C). On removal of the pituitary gland, there was apparent erosion of the sellar floor into the sphenoid sinus that contained purulent material.
患者的尸检发现,颅底基底池存在大量的血液(图2a)。大脑表现为轻度广泛性脑水肿,以鞍区为中心的蛛网膜下腔出血,在基底最明显(图2B)。鞍隔膜增厚,被粗糙的脓性渗出物覆盖(图2A)。通过大脑半球的冠状面显示脑积水和大量脑室内出血铸型。通过小脑和脑干横断面显示脑桥右前方靠近第五对颅神经出口区域有出血性软化向下延伸到延髓头端(图2C)。在切除垂体时,蝶鞍底有明显的侵蚀到蝶窦,其内含有化脓性物质。
Microscopically, the pituitary gland was relatively preserved. The thickened diaphragm sellae contained numerous necroinflammatory foci with multiple microabscesses (Figure 2D). Some of these were contiguous with the leptomeningeal surface of the adjacent optic chiasm and hypothalamus (Figure 2D-E), which showed chronic nonspecific leptomeningitis. Intermingled with the necrotic debris were numerous fungal forms with branching septate hyphae often arranged in a starburst pattern (Figure 2F-G), highlighted with a Grocott Methenamine Silver stain (Figure 2H) and morphologically consistent with the Aspergillosis species. A foci of fungal vasculitis also was present. The hemorrhagic lesions of the right pons and medulla corresponded microscopically to areas of hemorrhagic necrosis.
显微镜下,垂体相对保存。增厚的鞍膈含有大量的坏死性炎症灶伴多发微脓肿(图2D)。其中一些与相邻的视交叉和下丘脑的软脑膜表面相邻(图2D-E),表明有慢性非特异性的脑膜炎。大量的星爆样排列的分枝隔膜菌丝与坏死碎片混合在一起(图2F-G),在六胺银染色时很明显(图2H)与曲霉菌病菌株形态一致。真菌性血管炎的病灶也存在。右侧脑桥和延髓出血性病变在显微镜下与出血坏死区相对应。
In this case, Aspergillus was the cause of chronic meningitis, hydrocephalus, and an ultimately fatal subarachnoid hemorrhage. Aspergillus is a ubiquitous organism foundin soil, water, and decaying vegetation. Aspergillus fumigatus is, to our knowledge, the most common species to affect humans. Fungal spores are released into the atmosphere, and inhalation is the typical route of entry for infection. It is estimated that humans inhale hundreds of spores daily.Alveolar macrophages and neutrophils are important defense mechanisms, and immunocompetent patients typically have no adverse effects despite continuous exposure.
在本患者中,曲霉菌是慢性脑膜炎,脑积水,最终致命性蛛网膜下腔出血的原因。曲霉菌是一种在土壤,水,和腐烂的植物中普遍存在的微生物。据我们所知,烟曲霉是人类感染最常见的一种。真菌孢子释放到大气中,吸入是感染的典型途径。据估计,人类每日吸入数以百记的孢子。肺泡巨噬细胞和中性粒细胞是重要的防御机制,尽管连续暴露,免疫功能正常的患者通常没有不良影响。
From the respiratory tract, disease can spread hematogenously to any organ system, referred to as invasive aspergillosis. Disease spreading to the gastrointestinal tract, liver, and CNS is most common. Invasive aspergillosis occurs almost exclusively in cases of humanimmunodeficiency virus or immunosuppression. Factors that may play a role in aspergillosis include the type of transplant and immunosuppressive medications, neutropenia, and coinfections. The incidence is as high as 4% among renal transplant recipients and higher (up to 25%)in other conditions, such as hematopoietic stem cell or heart and lung transplants.11
侵袭性曲霉菌病可以从呼吸道血源性传播至任何器官。该病最常见的是传播到胃肠道、肝脏和中枢神经系统。侵袭性曲霉菌病几乎只发生在感染人类免疫缺陷病毒或免疫抑制的情况下,在曲霉菌感染中可能发挥作用的因素有:移植类型、免疫抑制药物、中性粒细胞减少和混合感染。肾移植受体患者的发病率高达4%,在其他情况下更高(高达25%),如造血干细胞细胞或心肺移植。
In addition to hematogenous spread from the lungs, Aspergillus may also enter the CNS via direct invasion from the paranasal sinuses. Acute Aspergillus rhinosinusitis is frequently seen in bone marrow transplant or neutropenic patients. In contrast, chronic invasive sinusitis is more typical in solid organ transplant recipients. As the disease progresses, usually over months, signs and symptomsof local involvement become apparent. Imaging findings can help identify fungal sinus infection.
除了肺源性血行播散,曲霉菌也可以通过直接侵犯鼻窦进入中枢神经系统。急性曲霉菌鼻窦炎常见于骨髓移植或中性粒细胞减少的患者。相比之下,慢性侵袭性鼻窦炎在实体器官移植受体患者中更为常见。随着疾病的进展,通常在几个月后,局部受累的体征和症状开始出现。影像学检查可以帮助识别真菌性鼻窦感染。
Noncontrast head computed tomography may show nonspecific hyperattenuation, thought to be secondary to high concentration of metal ions and calcium salts in fungal masses. Magnetic resonance imaging is useful in providing additional support. Decreased signal intensity on T1-weighted MRI and very decreased signal intensity on T2-weighted MRI is suggestive of fungal sinusitis, as opposed to bacterial infections and neoplasia, which are typically hyperintense. Dural enhancementis usually seen in lesions adjacent to infected paranasal sinuses and indicates the direct extension of the disease. However, this finding is typically absent or subtle early in the course of an infection.
平扫CT可显示非特异性的高密度,认为是继发于真菌菌群中高浓度的金属离子和钙盐。磁共振成像有助于提供额外的信息。MRI T1加权信号强度降低,和T2加权信号强度明显降低提示真菌性鼻窦炎,相对的细菌感染和肿瘤是典型的高信号。硬脑膜强化通常发生在感染病变相邻的鼻窦,提示疾病的直接延伸。然而,这一发现在感染过程的早期通常不可见或者不典型。
A predilection for angioinvasion and hemorrhage is also characteristic of Aspergillus. This occurs because of the production of the enzyme elastase, which compromises the elastin component present in the walls of blood vessels. Digesting elastin subsequently elicits an inflammatory reaction, resulting in vasculitis, infarction, mycotic aneurysms, or intracranial hemorrhage. This patient likely had chronic Aspergillus sinus involvement, ultimately leading to invasion through the sphenoid sinus, causing meningitis and a suprasellar mass lesion. The local extension of the fungal mass and angioinvasion were likely responsible for the hemorrhage. While Aspergillus is a rare cause of chronic meningitis, this must be considered for immunocompromised patients, especially When focal parenchymal disease or vascular involvement is present. An aggressive diagnosis with a biopsy should be pursued early, as there can be devastating consequences if treatment is delayed. For chronic invasive Aspergillus sinusitis, surgical debridement and prolonged antifungal therapy with amphotericin is required.
容易侵袭血管和出血也是曲霉菌的特征。这是弹性蛋白酶的作用,其构成了血管壁上的弹性蛋白。弹性蛋白的吸收随后引发炎症反应,导致血管炎,脑梗死,霉菌性动脉瘤,或颅内出血。该患者可能患有慢性曲霉菌鼻窦炎,最终通过蝶窦入侵,引起脑膜炎和鞍上病变。出血的原因可能是真菌性肿物的局部扩张和侵犯血管。虽然曲霉菌是一种罕见的慢性脑膜炎的原因,但是对于免疫功能低下的患者,特别是出现局灶性实质性疾病或血管受累时必须考虑到该病。应该早期活检,积极明确诊断,因为如果治疗延迟,可能出现灾难性的后果。对于慢性侵袭性曲霉菌性鼻窦炎,需要手术清创和延长两性霉素的抗真菌治疗。
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