Surgical treatment for fungal infections in the central nervous system

The hospital records of 78 patients who underwent surgical therapy for fungal infections of the central nervous system (CNS) between 1964 and 1984 are summarized. Nine different fungal types were identified, but Coccidioides immitis and Cryptococcus neoformans accounted for most (67.1%) of the infections. A variety of clinical syndromes were seen, including chronic basal meningitis (45 patients), intracranial mass lesions (12 patients), and communicating hydrocephalus (six patients). Thirteen patients had rhinocerebral forms of fungal infection, and two presented with spinal involvement. Delays in diagnosis were frequent and ranged from 2 months to 11 years. In 31 patients the CNS lesion was the first indication of a fungal infection, and lesion biopsy or cerebrospinal fluid (CSF) examination confirmed the diagnosis. A total of 144 surgical procedures were carried out, including lesion biopsy or excision in 13 patients, primary CSF shunting in 22, and placement of an Ommaya reservoir for administration of intraventricular or intracisternal antifungal agents in 48. All patients received parenteral and, in some cases, intrathecal or oral antifungal chemotherapy in addition to surgical therapy. Overall mortality was 43.6% (34 deaths). With prompt diagnosis and treatment, the mortality rate was 39% whereas, when appropriate treatment was delayed, the mortality rate was 64%. An additional 14 surviving patients (17.9%) exhibited permanent morbidity due to neurological deficits, seizure disorders, or renal toxicity following treatment with amphotericin B. The combined mortality and morbidity rate was 62.8%. Clinical symptoms were resolved completely in 29 patients, although in 10 evidence of disease persisted and chemotherapy was continued. Fungal infections of the CNS are being recognized with increased frequency. It is suggested that a high index of suspicion, aggressive attempts to obtain a diagnosis, and early and vigorous therapy may reduce the unfortunate outcome seen in a relatively high proportion of patients with CNS fungal infections.     

Cryptococcal meningitis in an immunocompetent patient with obstructive hydrocephalus: A case report

Background

Cryptococcal infections of the central nervous system are very rare in immunocompetent patients. They usually present as meningitis or as fungal cysts with or without hydrocephalus. Rapid diagnosis and treatment is crucial to the prognosis.

Intraventricular cryptococcal cysts masquerading as racemose neurocysticercosis

BACKGROUND: Cryptococcal infections of the CNS are infrequent in immunocompetent hosts. When present, they usually present as meningitis and hydrocephalus or as fungal masses called cryptococcomas. We report a case in which intraventricular cryptococcal cysts clinically and radiologically simulated the racemose form of neurocysticercosis. CASE DESCRIPTION: A 23-year-old man presented to the emergency department with a 1-week history of severe headache, dizziness, nausea, vomiting, and some lethargy. A computed tomography scan revealed significant hydrocephalus. The patient was admitted to the hospital and immediately underwent a right ventriculostomy tube placement. CSF examination showed a meningitic pattern. Magnetic resonance imaging, including FLAIR images, showed multiple large cysts in the temporal horns of both lateral ventricles in addition to hydrocephalus. When an endoscopic left temporal cyst fenestration failed to decompress his trapped right temporal horn, he underwent placement of a left lateral ventricle to peritoneal shunt and a right temporal cyst to peritoneal shunt. ELISA test results for HIV-1 and -2 antibodies in the patient's serum were negative. His CD4 and CD8 counts were within normal limits. Multiple tests for CSF anticysticercal antibody using IgG ELISA gave unequivocally negative results. Latex agglutination tests detected Cryptococcus neoformans antigen in his CSF in titers of 1:1024, which progressively decreased in response to antifungal therapy. The patient underwent treatment with IV amphotericin B for 7 weeks, IV 5-FC for 2 weeks, and oral fluconazole for 5 weeks. At discharge, 3 consecutive CSF cultures were negative for bacteria and fungi. His neurologic status returned to baseline. CONCLUSIONS: Cryptococcal CNS infections in immunocompetent hosts can mimic the intraventricular form of racemose neurocysticercosis. Distinguishing between the two is essential because the medical management of the 2 conditions is distinct from each other.     

Spinal seeding of anaplastic ependymoma mimicking fungal meningitis. A case report and review of the literature

BACKGROUND: The spinal seeding from brain tumors sometimes mimicks fungal meningitis on examination of cerebrospinal fluid. METHODS AND RESULTS: A 19-year-old woman gradually developed increased intracranial hypertension. MRI identified a mass in the right parieto-occipital area. It was totally removed and histologically diagnosed as an anaplastic ependymoma. Radiation- and chemotherapy were administered postoperatively. The patient reported low back pain 5 months after the surgical treatment. MRI disclosed neither spinal dissemination nor tumor recurrence at the primary site. Lumbar puncture was performed and the cerebrospinal fluid (CSF) was found to have an extremely low glucose level (5 mg/dl); no tumor cells were identified. Blood samples were obtained and a relative increase of WBC and CRP was noted. A slight degree of inflammation and low-grade fever were recorded. A tentative diagnosis of fungal meningitis was made and anti-fungal therapy was administered transventricularly and transvenously. However, her neurological condition continued to deteriorate gradually. Sequential CSF studies showed that the glucose level remained extremely low, it even decreased to 0 mg/dl Eight months after the surgical treatment, MRI with Gd-DTPA revealed marked subarachnoid enhancement in both intracranial and spinal areas. An open biopsy was performed and a histological diagnosis of intracranial and spinal seeding of the anaplastic ependymoma was returned. CONCLUSIONS: We report a patient with intracranial and spinal seeding of an anaplastic ependymoma that mimicked fungal meningitis. We discuss the difficulty of obtaining a differential diagnosis in this case and describe the mechanism of the decreased CSF glucose level.     

A case of cryptococcal meningitis with nephrotic syndrome and renal insufficiency under immunosuppressive therapy

A 76 year-old woman was admitted to our hospital because of pyrexia and fatigue. One year earlier, she was diagnosed as nephrotic syndrome(NS) caused by focal segmental glomerulosclerosis and immunosuppressive therapy was started with marked amelioration of proteinuria. Thereafter, her renal function worsened, but only supportive treatment was continued. After admission, a cerebrospinal fluid (CSF) examination revealed Cryptococcus neoformans (C. neoformans) by india ink staining and a subsequent CSF culture confirmed C. neoformans infection. Accordingly, we made the diagnosis of cryptococcal meningitis and immediately started multiple anti fungal drugs with dosage modification according to her impaired renal function. Immunosuppressive therapy for NS was temporarily terminated. The inflammatory signs and symptoms soon were markedly improved, but the anti cryptococcal antibody titer in the serum and CSF remained high. Immunosuppressive therapy was started again at a low dosage because urinary protein had increased again. One hundred and eight days from admission, she was discharged with a regimen of multiple anti fungal drugs. Proteinuria and renal insufficiency was almost stable during hospitalization. Most fungal infection develops in patients in an immunosuppressive state induced by immunosuppressive drugs, HIV infection and so on. Patients with NS are frequently in an immunosuppressive state because of urinary loss of immunoglobulins and the use of immunosuppressive drugs. Therefore, it should be remembered that patients with NS are at a high risk of suffering from fungal infection.     

Central nervous system cryptococcoma in immunocompetent patients: a short review illustrated by a new case

Objective  

Cryptococcal infection in CNS is frequently seen in HIV patients and those with other immunosuppressed conditions. However, cryptococcal granuloma in CNS in immunocompetent patient is rare. We present one new case of cryptococcoma and review literature to illustrate diagnosis and treatment of these lesions.     

获得性免疫缺陷综合征合并新型隐球菌性脑膜炎及结核性脑膜炎一例并相关文献复习

目的提升对获得性免疫缺陷综合征（AIDS）合并中枢神经系统新型隐球菌及结核分枝杆菌混合感染的认知。 方法分析1例AIDS合并新型隐球菌性脑膜炎及结核性脑膜炎患者的诊疗过程，并结合相关文献进行复习。 结果1例38岁男性患者因AIDS合并新型隐球菌性脑膜炎于2015年3月17日于武汉大学中南医院住院诊治，完善检查后确诊为新型隐球菌及结核分枝杆菌颅内混合感染，给予抗感染及对症综合治疗后，病情缓解，预后较好。 结论AIDS合并隐球菌性脑膜炎及结核性脑膜炎患者应及时诊断，予以抗隐球菌、抗结核综合治疗并适时启动抗逆转录病毒治疗，可改善预后。     

Sensitivity and specificity of a latex agglutination test for detection of cryptococcal antigen in meningitis

A cryptococcal latex agglutination test (Crypto-La; International Biological Laboratories, Canbury, New Jersey, USA) was evaluated for its ability to detect cryptococcal antigen in cerebrospinal fluid (CSF) specimens obtained from black patients with a clinical diagnosis of meningitis. Of the 445 Gram-stained and bacterial culture-negative CSF specimens routinely tested for cryptococcal antigen, 34 (7,6%) were positive. With the exception of 1 false-positive result, the remaining 33 specimens were obtained from 12 patients in whom the diagnosis of cryptococcal meningitis was confirmed by the isolation of Cryptococcus neoformans. The Crypto-La test gave false-positive results on 1% (4/384) of control CSF specimens tested. Nonspecific agglutination reactions were observed with 1,6% (13/829) of all CSF specimens and 22% (10) of sera tested. The ethylenediaminetetra-acetic heat-extraction method proved reliable in eliminating false-positives and nonspecific agglutination reactions in CSF and serum specimens.     

Cerebral cysticercosis: A case report

A case of cerebral cysticercosis is reported in a 49-year-old female who presented with headache, nausea, and vomiting. Lumbar CSF showed the findings of mild aseptic meningitis. CT scan revealed an enlargement of the left ambient cistern and a small cystic lesion in the left frontal cortex. MRI demonstrated multilobular cysts in the left ambient cistern with enhancement of their capsules, which compressed and distorted the midbrain. The cysts were surgically excised, and histological examination of the specimen disclosed characteristic features of cysticercus with viable larva. An excellent value of MRI in the diagnosis of intracisternal cysticercosis is emphasized.     

Late Manifestations of Traumatic Lesions of the Anterior Skull Base

The authors review their experience in detecting occult traumatic dural lesions. In a retrospective study covering the period from January 1, 1984 to December 31, 1996, 23 patients were evaluated for occult traumatic dural lesions. Clinical presentation, diagnostic work-up, and management of the dural lesions were analyzed.

The clinical presentations of the previously undetected dural lesions of the anterior skull base were meningitis in eight cases, cerebrospinal fluid (CSF) rhinorrhea in eight cases, both meningitis and CSF rhinorrhea in five cases, and a pulsating swelling in the region of the right upper eyelid in one case. In another case a fracture of the posterior frontal wall was detected incidentally on the preoperative CT scan performed prior to surgery for chronic sinusitis. One patient had a CSF fistula of the lateral skull base in addition to the frontobasal fistula. The interval between trauma and diagnosis varied from 1 to 48 years. Dural lesions were localized by high-resolution CT, fluorescein nasal endoscopy, CT cisternography, and MRI. Intraoperative exposure of the dural lesions and duraplasty were possible in all cases. During the first attempt successful repair of the dural lesions was accomplished in 22 (95.7%) of the 23 patiants. Two interventions were necessary to close a CSF leak of the cribriform plate.

Modern clinical and radiologic diagnostic methods should be employed to search for an occult dural lesion in patients with recurrent meningitis, meningitis caused by upper airway pathogens, or CSF rhinorrhea. The patient will remain at risk of potentially fatal meningitis until the lesion is appropriately repaired by duraplasty.

     

Late manifestations of traumatic lesions of the anterior skull base

The authors review their experience in detecting occult traumatic dural lesions. In a retrospective study covering the period from January 1, 1984 to December 31, 1996, 23 patients were evaluated for occult traumatic dural lesions. Clinical presentation, diagnostic work-up, and management of the dural lesions were analyzed.The clinical presentations of the previously undetected dural lesions of the anterior skull base were meningitis in eight cases, cerebrospinal fluid (CSF) rhinorrhea in eight cases, both meningitis and CSF rhinorrhea in five cases, and a pulsating swelling in the region of the right upper eyelid in one case. In another case a fracture of the posterior frontal wall was detected incidentally on the preoperative CT scan performed prior to surgery for chronic sinusitis. One patient had a CSF fistula of the lateral skull base in addition to the frontobasal fistula. The interval between trauma and diagnosis varied from 1 to 48 years. Dural lesions were localized by high-resolution CT, fluorescein nasal endoscopy, CT cisternography, and MRI. Intraoperative exposure of the dural lesions and duraplasty were possible in all cases. During the first attempt successful repair of the dural lesions was accomplished in 22 (95.7%) of the 23 patiants. Two interventions were necessary to close a CSF leak of the cribriform plate.Modern clinical and radiologic diagnostic methods should be employed to search for an occult dural lesion in patients with recurrent meningitis, meningitis caused by upper airway pathogens, or CSF rhinorrhea. The patient will remain at risk of potentially fatal meningitis until the lesion is appropriately repaired by duraplasty.     

Intracranial tuberculomas mimicking a malignant disease in an immunocompetent patient

We present the unusual occurrence of multiple systemic and two central nervous system tuberculomas in an immunocompetent young patient. A large left frontal epidural tuberculoma with transcalvarian extension was removed surgically and chemotherapy was initiated. The patient remained on a chemotherapy with INH, RMP, and EMB and was followed clinically and with MRI scans for 24 months. Findings. The clinical presentation and neuroimaging studies initially suggested malignant disease. Surgical resection of the left frontal lesion was required to relieve the mass effect. The histological evaluation showed a granulomatous inflammation with epithelial and Langhans giant cells, but no acid-fast bacilli. Cultures of the specimens yielded a mixed infection with Corynebacterium species and Staphylococcus epidermidis. Based on the histological findings, chemotherapy for tuberculosis was initiated. Subsequently, Mycobacterium tuberculosis was cultured from the surgical specimen and sputum. Interpretation. Parenchymal CNS tuberculosis with or without extracerebral manifestations may present as a space-occupying lesion. Because a tuberculoma is rarely suspected especially if there is atypical morphology, biopsy is required to establish the diagnosis and expedite specific treatment.     

Atypical pseudotumoral neuromeningeal cryptococcosis in an immunocompromised patient treated for pontine glioma. Case report and literature review

Background and purpose

We report an atypical feature of neuromeningeal cryptococcosis presenting as spinal cystic arachnoiditis and cerebellar cryptococcoma in a child treated for pontine glioma.

Case report

In November 2003, we diagnosed a pontine glioma in a six-year-old female child. She was initially treated with radiotherapy (54 Gy for six weeks) and dexamethasone until July 2006. From January 2004 to September 2006, the patient received 30 cycles of chemotherapy including vincristine 1.5 mg/m² Day 1, carboplatin 150 mg/m² Day 1, and temozolomide 150 mg/m² Days 2-6 every 28 days. In October 2006, the patient suffered spontaneous acute low back pain radiating into both lower limbs revealing lumbar cystic arachnoiditis and cerebellar cryptococcoma. The cerebrospinal fluid (CSF) sample showed lymphocytic pleocytosis and Cryptococcus neoformans; glucose and protein levels were low. First-line medical treatment including liposomal amphotericin B, then fluconazole effectively decreased the pain. However, in February 2007, she presented with cauda equina syndrome and the spinal MRI showed that the lumbar cyst had increased in size. The patient underwent a lumbar laminectomy and cyst removal. Histology confirmed the arachnoiditis with no cancer cells or pathogenic agents.

Conclusions

Arachnoiditis and cryptococcoma are rare. They can appear to be a brain neoplasm because of their pseudotumoral aspect. Often, the diagnosis can be made from the CSF sample.     

Liver cryptococcosis manifesting as obstructive jaundice in a young immunocompetent man: Report of a case

A 25-year-old immunocompetent Japanese man was referred to us for investigation and treatment of obstructive jaundice. Computed tomography (CT) showed dilatation of the bilateral intrahepatic bile ducts and a low-attenuated mass extending along the portal tract, from the hepatic hilum to the periphery, suggestive of cholangiocellular carcinoma (CCC) with periductal infiltration. However, the culture of bile obtained by percutaneous transhepatic biliary drainage revealed Cryptococcus neoformans. Microscopic examination of a biopsy specimen of the mass-like lesion in the liver revealed fungal organisms encapsulated in multinucleated giant cells. A small area of infiltration in the left lung was also detected on chest CT, and a diagnosis of liver and lung cryptococcosis was made. After 8 months of antifungal therapy, both the liver and lung lesions had vanished and the biliary stricture resolved. Unnecessary surgical intervention was avoided by an early and accurate diagnosis and effective antifungal therapy. The bile culture was the key to the definitive diagnosis in this case.     

Systemic and cerebrospinal fluid T-helper cytokine responses in organ transplant recipients with Cryptococcus neoformans infection

BACKGROUND: The role of Th1 and Th2 mediated cytokine responses in the pathogenesis of Cryptococcus neoformans infection in organ transplant recipients has not been defined. METHODS: We assessed cytokine levels in the sera and CSF collected prospectively at the time of diagnosis of infection in 25 transplant recipients with cryptococcosis. Serum levels were compared with those in healthy individuals and transplant recipients without cryptococcosis. IFN-gamma or IL-12 (Th1)/IL-10 (Th2) ratio < 1.0 was considered a dominant Th2 response. RESULTS: Cases had lower ratios of IFN-gamma/IL-10 (p = 0.03) and IL-12/IL-10 (p = 0.03) compared to healthy individuals. Cytokine responses, however, did not differ significantly for cases vs. transplant controls. Cases with fungemia compared to those without fungemia tended to have higher serum IL-10 levels (p = 0.07) and lower IL-12/IL-10 ratios (p = 0.06). CSF ratios of IFN-gamma/IL-10 (p = 0.04) and IL-12/IL-10 (p = 0.04) were lower in cases with cryptococcal meningitis compared to those without meningitis; 80% (8/10) of the cases with cryptococcal meningitis vs. 0% (4/4) of those without meningitis had CSF IFN-gamma/IL-10 ratio of < 1.0 (p = 0.015). The levels of IL-10 (p = 0.04) and IFN-gamma (p = 0.04) in the CSF in cases with cryptococcal meningitis were significantly higher than those in their serum, respectively. CONCLUSIONS: High expression of Th2 phenotype in cryptococcal meningitis and in fungemia suggests that Th dysregulation may contribute to the pathogenesis of cryptococcosis in organ transplant recipients.     

An endoscopically proven ventriculitis-type, cyst-like intraventricular primary lymphoma of the central nervous system

Summary Primary ventriculitis form of primary CNS lymphoma (PCNSL) is very rare and difficult to diagnose from radiological findings. A 55-year-woman presented with a cystic mass in the lateral ventricle without evidence of demonstrable malignant cells in the cerebrospinal fluid (CSF). The endoscopic biopsy showed a ventriculitis-like thin web on the surface of the ventricular wall around the foramen of Monro, resulting in obstruction. Pathological diagnosis was non-Hodgkin’s lymphoma, B cell type. This case suggests that PCNSL should be considered as a differential diagnosis for a cystic ventricular lesion even with no malignant cells in the CSF.     

Isolated cerebral cryptococcosis

Summary A case of cerebral infection with cryptococcus neoformans whose symptoms simulated those of an intracranial space-occupying lesion is described. Differential diagnosis is a problem because of the aspecificity of the clinical and neuroradiological features of this grave fungal infection.     

利用环介导等温扩增技术检测新型隐球菌

目的：建立一种快速检测新型隐球菌的方法。方法根据新型隐球菌的18 S rRNA基因序列设计内外引物各一对,在不同温度下对新型隐球菌进行环介导等温扩增,以探明环介导等温扩增法检测新型隐球菌最适宜的温度。对新型隐球菌、其他几种常见引起脑膜炎的病原菌以及部分种类的念珠菌进行扩增,以研究环介导等温扩增技术检测隐球菌的特异性。将新鲜培养的新型隐球菌稀释后加入非隐球菌感染患者的脑脊液中,模拟脑膜炎感染后的脑脊液环境,以研究环介导等温扩增技术检测新型隐球菌的敏感性。结果环介导等温扩增法检测新型隐球菌在60℃～65℃条件下均能实现良好扩增。环介导等温扩增法对其他病原菌的检测结果均为阴性,仅新型隐球菌的检测结果为阳性,特异性达到100%。用环介导等温扩增法从脑脊液中检测新型隐球菌的最低检出限为102 CFU/ml。用环介导等温扩增技术检测新型隐球菌性脑膜炎,能节省培养及传统鉴定的时间,从DNA的提取至反应结束在2～3h内即可完成,大大减少了诊断所需时间。结论环介导等温扩增是一种灵敏度高,特异性强,耗时短,且操作简便的检测新型隐球菌感染的方法。     

Expanding mature pineal teratoma syndrome. Case report

We present a case of growing teratoma syndrome of the pineal region. To our knowledge, this is the fourth case reported in the literature. A 13-year-old boy was referred for intracranial hypertension and bilateral papillary edema. CT scan showed a pineal region tumor with obstructive hydrocephalus. After CSF (cerebrospinal fluid) shunting, MRI showed that the tumor had a heterogenous signal enhancement. The tumor marker HCG (human chorionic gonadotrophin) was elevated in CSF and serum. After three cycles of chemotherapy, MRI showed an important increase in tumor size with morphologic modifications. However, HCG in CSF and serum returned to normal. Surgical resection was performed and histological examination of the whole specimen showed mature teratoma. On postoperative MRI, there was a small area of signal enhancement of the left thalamus. Radiotherapy was given. The child was in complete remission 15 months after the diagnosis. Growing teratoma syndrome is a mixed germ cell tumor with a secreting portion that responds to chemotherapy and a non secreting portion of mature teratoma that continues to grow under chemotherapy. The treatment should include chemotherapy for the malignant secreting portion and surgery for the mature teratoma.     

Intérêt du dosage du D(-) lactate pour le diagnostic rapide de méningite après craniotomie. Etude préliminaire

The early diagnosis of postoperative bacterial meningitis (BM) may be difficult. CSF cultures may remain sterile. Clinical features and routine laboratory data often fail to give an evidence. As early antibiotic therapy is essential in such patients, a rapid diagnosis is required. Different authors proposed the D(-) isomer of lactic acid as an early and effective marker of infection in the body fluids (including CSF). D(-) lactate is produced by bacteriae and fungi ; L(+) lactate may be produced also by human tissues in anaerobic situations. We conducted a prospective study in a neurosurgical intensive care unit to evaluate this technique for the diagnosis of meningitis following craniotomy. Fifty-four patients were included, 40 in group A (not infected or infected out of the CNS), 4 in group B (suspected BM), 10 in group C (BM with positive CSF cultures). No patient suffered from septicemia, haemodynamic or ventilatory instability, nor metabolic disorder. Clinical data, CSF and blood samples (cytology, conventional biochemistry, D(-) and L(+) lactate, bacteriology) were collected at inclusion and, in group B and C patients, at day 2, 5 and at clinical recovery. D(-) lactate measurements were performed with an enzymatic method adaptated from a Boehringer Mannheim kit (for determination in foodstuff). Statistics were based on the comparison of group A vs C patients. D(-) and L(+) lactate concentrations in the CSF were significantly higher in group C patients, and blood concentrations were similar. With a cut off value in the CSF of 100 μmol · L⁻¹, the sensitivity, specificity, positive and negative predictive values for the D(-) lactate assay were respectively : 100, 97.5, 90.9, 100 %. This test was equally sensitive and more specific than the L(+) lactate measurement. D(-) lactate seems to be a good marker of meningitis in neurosurgical patients, and helful for the rapid (< 2 h) diagnosis. These data are consistent with the literature concerning in-community-acquired BM. Further studies are required to distinguish between and bacterial meningitis.