Multifocal Pseudotumorous Form of Neuroparacoccidioidomycosis in an Immunocompetent Patient: A Clinicopathological Review Based on a Case Report

Neuroparacoccidiodimycosis (NPDM) is an uncommon granulomatous disease, which more frequently affects immunocompromised male patients over 30 years of age in the course of chronic lung disease. Paracoccidioides brasiliensis (PB) is an endemic fungus in Brazil, and grows as thick-walled yeast (with round to oval bodies) measuring 10 µm to 60 µm in diameter. Neuroparacoccidiodimycosi may develop many years after transmission and/or primary lung involvement. The authors describe a case of NPDM affecting a male patient, 52 years of age, farmer, heavy smoker, with clinical complaint of headache, asthenia, seizures, and prostration in the previous nine months. Upon physical examination, the patient presented regular general condition, without other relevant physical alterations. Computed tomography (CT) showed multiple bilateral pulmonary nodules associated to enlargement of the mediastinal lymph node. Magnetic resonance imaging (MRI) and CTscans of the central nervous system showed six heterogeneous nodular lesions compromising the frontal and parietal lobes, the largest one measuring 3.8 3.2 3.2 cm. The hypothesis of a neoplastic process compromising the lung and brain was considered. A biopsy of the mediastinal lymph node showed epithelioid granulomas, which exhibited round, thin-walled fungal structures in Grocott silver stain. The stereotactic biopsy of the frontal lesion was constituted by necrotic tissue admixed with some round to oval, thin-walled fungi measuring 10 µm to 60 µm, compatible with PB (identified on Grocott silver stain/confirmed in culture). The diagnosis of NPDM was then established. The employed therapeutic regimen was intravenous amphotericin B, itraconazole, and sulfamethoxazole-trimetropin. After ninety days of clinical follow-up, no episodes of seizures/neurological deficits were identified, and a marked decrease in the number and size of the lung and brain lesions were found.

Solitary Intracerebral Phaeoid Fungal Granuloma: A Case Report.

Fungal granuloma in the brain parenchyma caused by pheohyphomycosis is extremely rare. Antifungal drugs are not very effective. The present report is a case of solitary pheohyphomycosis granuloma, which underwent surgical excision followed by antifungal drug treatment with excellent result.

Pre-operative Voriconazole in patients undergoing surgery for Central Nervous System fungal infections: Special Report.

Fungal infections of the central nervous system (CNS) are uncommon. Despite several advancements in diagnosis and treatment of these infections, the mortality rates remain high. The current retrospective study was planned to define the demographic and clinical features of patients with CNS fungal infections. Conducted at Aga Khan University Hospital, Karachi, and comprising CNS fungal infections operated between January 2000 and December 2015. The study analysed whether a short course of pre-operative anti-fungal therapy may improve outcomes in these patients. There were 47 cases confirmed on histopathology and/or microbiology. Outcome measures used were Glasgow coma score (GCS), Glasgow outcome score (GOS) and Karnofsky performance score (KPS). The overall 30-day mortality was 20(42.5%). Fungal infections of the CNS can occur in both immune-compromised and immune-competent patients. Early diagnosis, radical surgery, pre-operative anti-fungal therapy for at least 2 weeks, pre- and postoperative Voriconazole therapy results in more favourable outcomes.

Cavernous sinus fungal infection: a rare case.

Intracranial fungal infection of the cavernous sinus is a condition that usually affects immunocompromised individuals and is rarely seen in immunocompetent individuals. It is a potentially life threatening condition which requires prompt treatment. Here we present a case of an immunocompetent patient with a fungal infection of the cavernous sinus.

Fungal infections in pediatric neurosurgery.

INTRODUCTION: Invasive mycosis of the central nervous system represent a diverse group of diseases that have gradually emerged as not only opportunistic infections in patients with immune susceptibility due to congenital and acquired deficiency, immunomodulation, solid organ and stem cell transplantation, hematological malignancies, and chronic steroid use but also in selected risk populations such as low weight preterm infants, patients with shunted hydrocephalus and external ventricular drainages, skull base surgery, and head injury. OBJECTIVES: The purpose of this review is to familiarize the pediatric neurosurgeon with the most common mycosis and their clinical scenarios which can be encountered in the clinical practice, with special emphasis on clinical, radiological, and laboratory diagnosis beyond classical microorganism cultures as well as options in medical and surgical treatment given the high incidence of morbidity and mortality associated with these challenging entities. METHODS: We conducted an online database review (Ovid, PubMed) gathering relevant English language literature published in the last 20 years with special emphasis on recent breakthroughs in the diagnosis and treatment of invasive mycosis of the CNS as well as reported cases within the pediatric neurosurgical literature and their surgical management. RESULTS: Fungal agents capable of invading the CNS can behave as aggressive entities with rapid progression manifesting as overwhelming meningoencephalitis with vascular compromise or can lead to space-occupying lesions with abscess formation which require prompt diagnosis by either laboratory identification of the components of these biological agents and their host response or by obtaining tissue specimens for microbiological identification which may not be straightforward due to prolonged culture time. CONCLUSION: Following a high degree of suspicion with prompt initiation of antifungal agents and reversal of potential immunosuppressant therapies along with neurosurgical evacuation of intracranial collections or removal of infected hardware (CSF shunts) can lead to more optimistic outcomes of these complex clinical scenarios.

Cryptococcus gattii genotype VGIIa infection imported from Vancouver Island to Japan.

A 71-year-old Japanese man with travel history to the Vancouver Island, Canada was diagnosed the pulmonary and central nervous system infections caused by Cryptococcus gattii genotype VGIIa. This is the first imported case of Cryptococcus gattii genotype VGIIa infection from endemic area of North America to Japan. He was recovery with no residual neurological dysfunction by early resection of brain mass and antifungal therapy. Early surgical resection of cerebellar cryptococcoma may shorten the length of induction therapy with antifungal drugs.

Multiple brain abscesses caused by Rhinocladiella mackenziei in an immunocompetent patient: a case report and literature review.

Primary cerebral phaeohyphomycosis due to Rhinocladiella mackenziei is an extremely rare infection carrying more than 80% mortality, with most cases reported from the Middle East region. This darkly pigmented black yeast is highly neurotropic, aggressive and refractory to most antifungal agents. Here we present an immunocompetent elderly male, presenting with multiple brain abscesses, with R. mackenziei confirmed by nuclear ribosomal repeat region sequencing, who was successfully treated by surgical debridement and intravenous voriconazole. To our knowledge this is the first case reported from the United Kingdom. We also present a review of all such cases so far reported in the English literature world-wide, which we believe is a step further to understanding the pathogenesis and establishing effective treatment of this rare, yet often fatal disease.

Combined medico-surgical strategy for invasive sino-orbito-cerebral breakthrough fungal infection with Hormographiella aspergillata in an acute leukaemia patient.

Hormographiella aspergillata is a rare causative agent of invasive filamentous breakthrough infection, mostly arising after echinocandin exposure. We report a neutropenic patient who developed a severe sino-orbito-cerebral H. aspergillata infection while receiving empirical caspofungin, successfully controlled by an aggressive strategy associating surgical debridement and combined high-dose regimen of antifungal drugs.

Intracranial Fungal Granulomas: A Single Institutional Clinicopathologic Study of 66 Patients and Review of the Literature.

INTRODUCTION: Fungal granulomas of the central nervous system are rare and have a high rate of mortality and morbidity, irrespective of treatment. The authors report their experience of managing 66 patients during 15 years and discuss the clinical, radiological, surgical, and pathologic findings. This series is among the largest reported. MATERIAL AND METHODS: A retrospective analysis was performed on patients with intracranial fungal granulomas (ICFGs), treated in the authors' institution, between January 1997 and May 2011. Only mass-forming histopathologically proven ICFGs were included in this study. RESULTS: The age of the patients ranged from 7 years to 67 years (mean = 32.3 years), and most patients were in the third and fourth decades of life. The study population comprised 47 male and 19 female patients. The most common symptom was headache (41 patients), followed by vomiting (16 patients) and blurring of vision (16 patients). Only 3 patients presented with fever. The duration of symptoms was less than 6 months in all cases and less than 3 months in 39 cases. Anterior cranial fossa and frontal lobe was involved in 35 cases (54.5%), followed by middle cranial fossa in 20 cases (30.3%). Three cases had granulomas in the cerebellopontine angle. Three cases had multicompartmental involvement, and 4 had multilobar involvement. Nine patients had predisposing factors for fungal infection Based on clinical and imaging data, preoperative diagnosis of a possible fungal lesion was made in 44 (some had only computed tomography imaging) patients. All the patients were treated surgically, followed by antifungal treatment with amphotericin-B and/fluconazole/itraconazole for a period of 6 weeks. Eight patients had symptomatic recurrence of lesions 3-12 weeks after treatment and underwent reoperation. Six patients were lost to follow-up. Nine patients died in the postoperative period (within 30 days postoperatively). Fifteen patients died during follow-up because of recurrent lesions, repeat surgery, renal failure, and unrelated causes. Overall mortality was 24 (36.3%). Poor neurologic status before surgery, emergency craniotomy, severe brain edema with mass effect, and opening of ventricles during surgery were associated with poor outcome. Aspergillus species were the causative organism in an overwhelming majority of patients (n = 52) followed by Mucor in 7 cases, Cladosporium in 3 cases, eumycetoma in 2 cases, and maduramycosis and blastomycosis in 1 case each. CONCLUSION: ICFGs have high rates of morbidity and mortality. Early diagnosis, radical surgery, and antifungal treatment for 6 weeks may improve outcome. Poor neurologic status of patients at the time of presentation, immunocompromised state, contamination of ventricular cerebrospinal during surgery, and renal failure (attributable to amphotericin-B) are associated with poor outcome.

Curvularia abscess of the brainstem.

OBJECTIVE: To present a unique case of a brainstem Curvularia fungal infection and review the diagnosis and management of this rare phenomenon. METHODS: A 33-year-old immunocompetent African American male presented with 2 weeks of headache, nausea, and vomiting in a setting of a recent 20-lb weight loss. Neurological examination was positive for multiple cranial nerve palsies, hemisensory loss, and gait instability. Magnetic resonance imaging demonstrated an enhancing medullary lesion. RESULTS: Metastatic and infectious workup revealed a left lung lesion, which on subsequent biopsy was positive for a granuloma yielding no further clues to the etiology of the brainstem lesion. On surgical exploration of the cranial lesion, a puss-filed, encapsulated lesion was encountered that was tightly adherent to the brainstem. Intraoperative biopsy of the lesion capsule was initially negative but on postoperative day 9, fungal hyphae were encountered identified on morphology as Curvularia species. The patient was started on triple antifungal therapy but necessitated a second surgery for lesion debulking and drainage. The patient was discharged home 10 weeks after initial presentation. At the 13-months follow-up the patient is doing very well and his neurological examination continues to improve. CONCLUSIONS: This is the first reported case of a brainstem Curvularia infection. This case highlights the importance of an aggressive surgical and antibiotic therapy in the treatment of central nervous system Curvularia infections. There appears to be a strong relationship between heavy marijuana use and Curvularia infection, producing lung granulomas that may extend to other organs such as the central nervous system of immunocompetent patients.

Endoscopic coagulation of choroid plexus hyperplasia.

Hydrocephalus is a clinical disorder resulting from an imbalance between the production of CSF and its resorption, of which the latter is mostly a disadvantage. In rare cases of choroid plexus papilloma or carcinoma, hydrocephalus is due to an overproduction of CSF. Choroid plexus hyperplasia (CPH) is a distinct clinicopathological entity in which the enlarged choroid plexus produces large amounts of CSF. Historically, patients with CPH were treated by shunt procedures or by microsurgical removal of the choroid plexus, which is associated with a high complication rate. In this paper the authors show that endoscopic plexus coagulation can result in restoring the equilibrium of the intracranial fluid volumes, resulting in shunt independency. In this way, both the shunt-related complications and the bleeding risks of microsurgical plexectomy are avoided. In instances of hydrocephalus, thorough efforts should be made to demonstrate the underlying pathophysiology to choose the optimal treatment, of which shunt procedures should receive the least priority.

Neuroendoscopic diagnosis of central nervous system histoplasmosis with basilar arachnoiditis.

OBJECTIVE: Histoplasmosis of the central nervous system (CNS) is seen in 10% to 20% of patients with disseminated histoplasmosis and/or in association with immunocompromised patients. Meningitis, arachnoiditis, and hydrocephalus are the most common clinical manifestations of CNS histoplasmosis. Patients with CNS histoplasmosis present similarly to other infectious etiologies, and confirmatory diagnosis is important in the management of these patients. However, diagnosis of CNS histoplasmosis can be difficult, and sometimes performing a parenchymal biopsy is necessary to confirm the diagnosis. METHODS AND RESULTS: We describe the case of a 41-year-old man with HIV/AIDS who presented with the signs, symptoms, and radiologic evidence of basal meningitis and hydrocephalus. Cerebrospinal fluid (CSF) analysis from multiple lumbar punctures was negative. The patient underwent a neuroendoscopic procedure with diagnostic and therapeutic goals. Internal CSF diversion (endoscopic third ventriculostomy) and biopsy of the floor of the third ventricle and subarachnoid space were performed; surgical biopsies identified noncaseating granulomas, and ventricular CSF was positive for Histoplasmosis antibodies. The patient was treated with liposomal amphotericin B and itraconazole. The patient had resolution of his symptoms immediately after surgery, and 1-month follow-up computed tomography of the head demonstrated resolution of the hydrocephalus. At the last follow-up 12 months postoperatively, the patient has not required insertion of a ventriculoperitoneal shunt. CONCLUSION: Clinicians should maintain a high index of suspicion for fungal basal meningitis in patients with AIDS and hydrocephalus. With nondiagnostic lumbar CSF sampling, neuroendoscopy can be considered as an alternative for diagnosis and treatment of basal meningitis and hydrocephalus.

Allergic fungal sinusitis with massive intracranial extension presenting with tearing.

A 24-year-old male presented with tearing, and subsequent workup and imaging showed a mass with fluid involving the nasopharynx, the paranasal sinuses, and the posterior dehiscence of the left frontal sinus intracranially compressing the frontal lobe significantly. Microscopic examination confirmed the diagnosis of allergic fungal sinusitis. Endoscopic drainage and sinostomy was performed by the otolaryngology (ear-nose-throat) service. The patient was followed 9 months postoperatively and did well with resolution of the epiphora. Although epiphora alone is an unusual presentation of allergic fungal sinusitis, ophthalmologists need to be aware of this entity, as it may invade the orbit through the sinus cavities or compress on the nasolacrimal duct before it causes other mass-related symptoms. Radiology and the characteristic histopathologic findings are the most useful in establishing the correct diagnosis.

Invasive rhino-cerebral fungal granuloma.

BACKGROUND: Increased incidence of fungal infection has been reported globally in the recent years. Fungal infection of the central nervous system remains one of the most difficult diseases to treat and requires multi-modality intensive therapeutic strategies. MATERIALS AND METHODS: Retrospective analysis of case records of patients with confirmed skull base fungal granuloma treated at a tertiary hospital between 1988-2008. An attempt was made to stage the extent of skull base fungal granuloma based on neuroimaging, operative findings and course of the disease on serial follow-up. RESULTS: Thirty-three patients with skull base fungal granuloma were treated surgically during the study period. The mean age at presentation was 33.2 years and diabetes was a major predisposing factor. Eight patients expired in the first two months following surgical intervention due to flare-up of the disease. Eighteen patients who underwent grossly total excision had a mean progression-free survival (PFS) of 43 months and seven patients with subtotal excision had a mean PFS of 23 months. Better survival probability was noted in those patients who underwent total excision at surgery and received complete course of amphotericin. CONCLUSION: Total surgical excision with complete course of antimycotic drug therapy increases PFS. A better antimycotic drug with less toxicity and high efficacy with fungicidal property can make a difference in the outcomes of the disease.

Simplified aqueductal stenting for isolated fourth ventricle using a small-caliber flexible endoscope in a patient with neurococcidiomycosis: technical case report.

OBJECTIVE: Endoscopic aqueductoplasty and stenting are a preferred treatment for isolated fourth ventricle syndrome related to membranous aqueductal obstruction. We describe a technique using a small-caliber flexible endoscope that may address some limitations of current strategies. CLINICAL PRESENTATION: A 39-year-old woman with hydrocephalus caused by neurococcidiomycosis and a functional right frontal ventriculoperitoneal shunt presented with vomiting and an isolated fourth ventricle. Magnetic resonance imaging showed an enlarged fourth ventricle and exuberant basilar arachnoiditis obstructing the outlet foramina of the fourth ventricle. Ventriculography indicated aqueductal obstruction. INTERVENTION: Aqueductoplasty was planned to allow spinal fluid to flow from the fourth ventricle to the ventriculoperitoneal shunt. A stent-endoscope construct was prepared by feeding a flexible endoscope through a ventricular catheter cut 4 cm from the tip. The flexible endoscope was contoured to fit the anatomy of the aqueduct. Uncomplicated aqueductoplasty was performed through a single left frontal burr hole using the stent-endoscope construct to perforate a membranous veil and inspect the fourth ventricle. The stent was deployed over the endoscope using the proximal end of the catheter to deliver and secure the stent as the endoscope was withdrawn. CONCLUSION: Aqueductoplasty and stenting using a small-caliber flexible endoscope is feasible. The endoscope can be contoured to suit the anatomy of the aqueduct and improves visualization of the leading edge of the stent during deployment. Furthermore, when the endoscope is used to create the perforation, the target is not obscured by the shaft of the device used to make the perforation.

Fonsecaea monophora cerebral phaeohyphomycosis: case report of successful surgical excision and voriconazole treatment and review.

We report a case of Fonsecaea monophora cerebral phaeohyphomycosis successfully treated with surgical excision and voriconazole monotherapy in a patient receiving maintenance immunosuppression therapy for 8 years after cadaveric renal transplantation. She presented with a severe frontal headache in the absence of any constitutional or neurologic symptoms. Brain magnetic resonance imaging showed an irregular 3.1 x 3.4 cm ring-enhancing lesion in her left frontal lobe. The patient underwent craniotomy and resection of her mass, with intraoperative spillage of some of her abscess contents into her lateral ventricle. Histopathology of her resected mass showed necrotic fragments of brain parenchyma with granulomatous inflammation and numerous pigmented fungal forms. A mold, recovered from cultures inoculated with portions of her brain resection specimen, was later definitively identified as Fonsecaea monophora. Initial serum (1-->3) beta-D-glucan (BG) levels exceeded 500 pg/ml. The patient received voriconazole, which she tolerated well, without recurrent headaches or abscess formation noted on serial brain imaging. Her BG declined to <31 pg/ml one year following her abscess resection. She discontinued antifungal therapy after an 18-month treatment course, and has remained free of any clinical or radiographic evidence of recurrent abscess formation three years later.