Case Report
Aqueductal Stenosis Has a New Dimension—Aspergillosis: A Rare Case Report and Review of the Literature Soubhagya Ranjan Tripathy1, Sudhanshu Sekhar Mishra1, Rama Chandra Deo1, Itibrata Mohanta1, Kalpalata Tripathy2
Key words Aqueductal stenosis - Aspergillosis - Hydrocephalus - Voriconazole
- BACKGROUND:
Abbreviations and Acronyms CNS: Central nervous system CSF: Cerebrospinal fluid ETV: Endoscopic third ventriculostomy
- CASE
-
From the Departments of 1Neurosurgery and 2Pathology, SCB Medical College, Cuttack, Odisha, India To whom correspondence should be addressed: Soubhagya Ranjan Tripathy, M.S., M.Ch.(std) [E-mail: [email protected]] Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2015.05.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION Invasive cerebral aspergillosis, often encountered in immunocompromised patients, is almost always fatal despite radical surgical and medical management and frequently is a finding at autopsy (1). Although occurring most commonly in the immunosuppressed patient, cerebral aspergillosis infection has been reported after trauma or neurosurgical procedures (2). Attempts at fungal isolation often are unsuccessful, and a high index of radiologic suspicion is warranted (3).The clinical and laboratory diagnosis of cerebral aspergillosis is problematic, and mortality is quite high, even in cases that receive appropriate treatment (4). Aspergillus is a fungal organism that comprises many species, a few of which are pathogenic (14). Aspergilli are opportunistic pathogens that are ubiquitous fungi found in soil and organic materials and can establish saprophytic growth within the respiratory tract after inhalation of the airborne spores. Host factors are important in preventing disease. Invasive aspergillosis in patients with granulocyte dysfunction
Cerebral aspergillosis, often encountered in immunocompromised patients, is almost always fatal despite radical surgical and medical management and frequently is a finding at autopsy. Attempts at fungal isolation often are unsuccessful, and a high index of radiologic suspicion is necessary.
DESCRIPTION: A premature, 5-month-old female infant, born via normal vaginal delivery, presented with a progressive increase in head size since birth, delayed developmental milestones, and intermittent vomiting for 1 month. There was no history of trauma and no evidence of diabetes mellitus or hypertension, family history of tuberculosis, gestational diabetes, jaundice, or febrile eruptions. Neonatal jaundice was present after day 1, remained for 2 days, and was treated with phototherapy. Findings of the general and systemic examinations were unremarkable. Findings of a neurologic examination revealed a hypoactive infant with papilledema and extensor plantar bilaterally. Computed tomography scan of brain showed hydrocephalus attributable to aqueductal stenosis. On endoscopic third ventriculostomy, dense, friable, whitish yellow, nonvascular masses were encountered in the third ventricle, obstructing it. Her endoscopic third ventriculostomy success score was 10 D 0 D 10 [ 20%. Histopathologic examination and culture revealed Aspergillus flavus. A week later, a mediumpressure ventriculoperitoneal shunt was done, and voriconazole was added.
- RESULTS:
At discharge on the 7th postoperative day, 4 weeks and 12 weeks later (ie, first and second follow-up) the child was active, playful, and feeding normally. The first reported case of an aqueductal stenosis due to aspergillosis was in 2000 by van Landeghem FK et al. (Clin Neuropathol 19:26L29, 2000). To the best of our knowledge, this may only be the second reported case of hydrocephalus attributable to aqueductal stenosis caused by Aspergillosis. In conclusion, aspergillosis should not be ruled out as a differential diagnosis in aqueductal stenosis, even when the patient seems to be immunocompetent.
and after corticosteroid, antibiotic, or cancer chemotherapy is well documented. Both neutrophils and macrophages are important in host defense: macrophages are effective against conidia and neutrophils against hyphae (6). Most patients with invasive aspergillosis have dysfunction of one or both of these systems. The organism can become pathogenic in the presence of immune suppression, granulocytopenia, diabetes mellitus, or prolonged hospitalization. Aspergillosis of the central nervous system (CNS) presents as meningitis, encephalitis, brain abscesses, subdural abscesses, mycotic arteritis, or sellar abscess (7).
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
Aspergillus can reach the CNS via 3 different routes. The first is by hematogenous spread from a remote extracranial focus, usually the lung. The second is by extension from a contiguous extracranial location that is often the paranasal sinus or the nasal cavity. The third is direct introduction of aspergillus by a neurosurgical procedure iatrogenically (8). The antifungal armamentarium available to clinicians has increased in the last several years to include new formulations of amphotericin B, antifungal triazoles, and the echinocandins. In recent studies voriconazole has been shown to be more effective and well tolerated in CNS
www.WORLDNEUROSURGERY.org
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CASE REPORT SOUBHAGYA RANJAN TRIPATHY ET AL.
aspergillosis and may be considered as a first-line treatment (13). The first reported case of an aqueductal stenosis caused by an aspergillosis was in 2000 by van Landeghem et al. (15). To the best of our knowledge, our patient may only be the second reported case of hydrocephalus attributable to aqueductal stenosis caused by aspergillosis. The earlier case had aplasia cutis congenita at the scalp vertex and hypoplastic left heart syndrome (15); however, our patient did not present with any such congenital defects clinically. Hence, aspergillosis should not be ruled out as a differential diagnosis in aqueductal stenosis, even when the patient seems to be immunocompetent. CASE DESCRIPTION S.S.S., a 5-month-old female infant, presented with progressive increase in head size since birth, i.e., a head circumference of 55 cm (Figure 1A); with delayed developmental milestones and intermittent vomiting for 1 month. There was no history of trauma, diabetes mellitus, or family/contact history of tuberculosis. In perinatal history, the mother had taken adequate iron and folic acid (IFA) tablets and 2 doses of tetanus toxoid. No gestational diabetes, jaundice, or febrile eruptions were present, and the mother did not take any medications during her pregnancy except for iron and folic acid tablets. The child was born prematurely to a primigravida mother via normal vaginal delivery and weighed 1.3 kg at birth. She cried immediately at
ASPERGILLOSIS AND AQUEDUCTAL STENOSIS
birth and had no asphyxia. Neonatal jaundice presented after day 1, remained, for 2 days, and was treated with phototherapy accordingly. The findings of general and systemic examinations, including the ear, nose, and paranasal sinuses, were unremarkable. Findings of the neurologic examination revealed a hypoactive infant who moved all limbs equally, with both pupils of equal size that reacted normally to light, and with bilateral papilledema and plantar extensor bilaterally. A clinical diagnosis of congenital hydrocephalus was made. Noncontrast computed tomography scan of brain showed both lateral and IIIrd ventricular enlargement, with periventricular lucency, thin cortical mantle, and a normal-sized IVth ventricle (Figure 1B). From this clinical history and imaging findings, a diagnosis of congenital hydrocephalus due to aqueductal stenosis was reached. Endoscopic third ventriculostomy (ETV) was planned. An endoscope was inserted through the right Kocher’s point to the lateral and third ventricles. Cerebrospinal fluid (CSF) with high protein content and a whitish yellow material were cleared after repeated irrigation with normal saline. Bleeding points were cauterized. However, we could not continue with the ETV procedure because of dense, friable, whitish yellow, nonvascular masses we encountered in the third ventricle (Figure 2A), obstructing it. The patient’s ETV success score was 10 þ 0 þ 10 ¼ 20%; therefore, there was 20% probability of ETV success, preoperatively (9), which explains the failure of ETV.
Figure 1. Pre- and Postoperative imaging. (A) The head circumference was 55 cm with engorged scalp veins present. (B) Noncontrast computed
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A biopsy was taken and sent for histopathologic study. CSF samples also were sent for cytology and biochemical study. Histopathologic examination revealed a lesion composed of confluent granulomata. Smears from the tissue revealed dichotomously branching, Gram stain negative, periodic acideSchiff -positive hyphae suggestive of Aspergillus spp (Figure 2B), a finding also supported by results of a silver stain (Figure 2D). The fungal culture with SDA, chloramphenicol, and cycloheximide agar grew Aspergillus flavus (Figure 2C). A week later, a medium-pressure ventriculoperitoneal shunt was inserted at the right posterior parietal area. CSF was yellowish and clear and under high pressure sent for cytology and biochemical study. On both the occasions, results of the CSF study revealed a predominance of mononuclear cells; the findings were turbid the first and clear on second study. Similarly, protein concentrations were 691 mg% at CSF study after first surgery and 418 mg% in the second. At discharge from the hospital on the seventh postoperative day (Figure 1C), the child was active, playful, and feeding normally; vomiting had subsided, and she moving all limbs equally. Her head circumference was 48 cm. The mother was advised to breastfeed the infant exclusively, with bottle feeding as and when necessary; voriconazole in tablet form (200 mg) was prescribed in a dose of 6 mg/kg/dose once daily for 3 days then 4 mg/kg/dose twice daily for 25 days, to be taken with sips of water.
tomography shows aqueductal stenosis. (C) At discharge from the hospital. (D) At 1-month follow-up. (E) At 3-month follow-up.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.05.005
CASE REPORT SOUBHAGYA RANJAN TRIPATHY ET AL.
ASPERGILLOSIS AND AQUEDUCTAL STENOSIS
Figure 2. Operation, biopsy, and culture. (A) Endoscopic third ventriculostomy. (B) Filamentous septate hyphae (at 40, 100, and 400 magnification; with acute angle branching), with dense acute and chronic
At 4 weeks after discharge (Figure 1D), the patient’s head circumference was 47.5 cm and she was active and feeding well. At second follow-up (Figure 1E), her head circumference had increased a little to 48.5 cm, but she was active and feeding well. The limitations in this case were unavailability of immunoglobulin M enzyme-linked immunosorbent assay for aspergillus antigens (because of financial reasons), even though differential and absolute eosinophil and total leukocyte count in both blood and repeated CSF studies were within the normal limits. Other investigations, like fasting blood sugar, erythrocyte sedimentation rate, chest radiograph, paranasal sinus radiograph, blood tests for HIV, and hepatitis C and hepatitis B, also were within normal limits.
DISCUSSION Aqueductal stenosis is a common cause of hydrocephalus during infancy (5). The first reported case was an infant born with aplasia cutis congenita (15) at the scalp vertex and hypoplastic left heart syndrome developing systemic aspergillosis after cardiac surgery. The infant died at 76 days of age despite systemic antimycotic therapy with a combination of flucytosine and amphotericin B. Postmortem examination revealed meningitis, multiple brain aspergillomas and microabscesses with focal ependymitis, focal bronchopneumonia, and necrotizing enterocolitis. One of the brain aspergillomas was located close to the aqueduct, causing an aqueductal stenosis and an obstructive hydrocephalus.
inflammatory cells suggestive of cerebral aspergillosis. (C). SDA, chloramphenicol, and cycloheximide culture. (D) Silver staining.
Histologically, aspergillus hyphae could only be detected in the aspergilloma of the aqueduct (15). There are only 2 previous reports of immunocompetent patients with an isolated nondural-based Aspergilloma of the cerebellum (9). Of the 2 reported immunocompetent patients with an isolated cerebellar aspergilloma, one was an adult (10), and the other was an infant (his immune status was unknown) (11). The source of infection in our patient is unclear. Although Aspergillus is known to reside in tuberculous cavities, chest radiographs did not reveal cavitatory lesions or a fungal ball. In fact, in our patient, differential count, total leukocyte count, erythrocyte sedimentation rate, serum immunoglobulin E level, chest radiographs, and paranasal sinus radiographs all were within normal limits. Enzyme-linked immunosorbent assay findings for hepatitis B surface antigen, HIV, and hepatitis C virus also were negative. Further cultures of blood and CSF could not be performed because of financial restraints, as was a postoperative computed tomography scan. Patients with isolated fungal granulomas of the brain may be subjected to prolonged antituberculous therapy empirically in this part of the world where tuberculosis is endemic, leading to a delay in diagnosis and administration of antifungal treatment and resulting in a poor outcome (12). In our case, the diagnosis of aspergillosis was made as a result of histopathologic examination because clinical and radiologic findings were nonspecific. A high index of suspicion is required to order fungal culture studies. Total
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
excision of the mass followed by adequate antifungal therapy, as was undertaken in our case, is likely to result in a cure. CONCLUSION Surgery followed by aggressive systemic antifungal therapy offers the best outcomes in patients with intracranial mass lesions (13). Whenever feasible, safe radical excision along with normal nervous tissue around it should be performed. Sinocranial aspergillosis is a rare entity and the mass lesions can be intracranial extracerebral (mostly in anterior cranial fossa), intracerebral, or both. The clinical and laboratory diagnosis of cerebral aspergillosis is problematic and mortality is quite high, even in cases receiving appropriate antifungal treatment (4). Hence, a high index of suspicion is necessary in children with appropriate clinical features, even in immunocompetent patients. The timing of therapeutic intervention seems to have a significant impact on survival. To the best of our knowledge, this is the second reported case of an aqueductal stenosis caused by aspergillosis. Hence, aspergillosis should not be discarded as a potential differential diagnosis in aqueductal stenosis in all those infants who have with presumed immunocompetence, as the timely administration of voriconazole can alter the course of this dreaded disease rather dramatically. REFERENCES 1. Antony AK, Hong RW: Free latissimus dorsi flap used in treatment of cerebral aspergillosis: a case
www.WORLDNEUROSURGERY.org
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CASE REPORT SOUBHAGYA RANJAN TRIPATHY ET AL.
report and review of the literature. Microsurgery 23:313-316, 2003. 2. Endo T, Numagami Y, Jokura H, Ikeda H, Shirane R, Yoshimoto T: Aspergillus parasellar abscess mimicking radiation-induced neuropathy: case report. Surg Neurol 56:195-200, 2001. 3. Endo T, Tominaga T, Konno H, Yoshimoto T: Fatal subarachnoid hemorrhage, with brainstem and cerebellar infarction, caused by Aspergillus infection after cerebral aneurysm surgery: case report. Neurosurg 50:1147-1151, 2002. 4. Kan VL, Bennett JE: Lectin-like attachment sites on murine pulmonary alveolar macrophages bind Aspergillus fumigatus conidia. J Infect Dis 158: 407-414, 1988. 5. Kulkarni AV, Drake JM, Malluci CL, Sgouros S, Roth J, Constantini S: Canadian Pediatric Neurosurgery Study Group: Endoscopic third ventriculostomy in the treatment of childhood hydrocephalus. J Pediatr 155:254-259.e1, 2009. 6. Kulkarni V, Rajshekhar V, Mathews MS: An isolated non-dural-based cerebellar aspergilloma in an immunocompetent patient. Neurol India 55: 310-311, 2007.
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ASPERGILLOSIS AND AQUEDUCTAL STENOSIS
7. Mohindra S, Gupta R, Mohindra S, Gupta SK, Vaipehi K: Cerebellar aspergillosis in an infant. Neurosurgery 58:E587, 2006. 8. Parker KM, Nicholson JK, Cezayirli RC, Biggs PJ: Aspergillosis of the sphenoid sinus: presentation as a pituitary mass and postoperative Gallium-67 imaging. Surg Neurol 45:354-358, 1996. 9. Salmon MA: Aspergillus of cerebellum. J Roy Soc Med 76:611-613, 1983. 10. Sav H, Atalay MA, Demir G: Early diagnosis of cerebral aspergillosis with various methods: a case report. Infez Med 21:134-138, 2013. 11. Schwartz S, Ruhuke M, Riband P, Corey L, Driscoll T, Cornely OA, Driscoll T, Cornely OA, Schuler U, Lutsar I, Troke P, Thiel E: Improved outcome in central nervous system aspergillosis using variconazole treatment. Blood 106: 2641-2645, 2005. 12. Sharma BS, Khosla VK, Kak VK, Banerjee AK, Vasishtha RK, Prasad KS, Sharma SC, Mathuriya SN, Tewari MK, Pathak A: Intracranial fungal granuloma. Surg Neurol 47:489-497, 1997. 13. Thakar S, Chickabasaviah YT: Spontaneous resolution of invasive cerebral aspergillosis following
partial resection in a medically untreated infant. J Neurosurg Pediatr 10:71-74, 2012. 14. Thomas KE, Owens CM, Veys PA, Novelli V, Costoli V: The radiological spectrum of invasive aspergillosis in children: a 10-year review. Pediatr Radiol 33:453-460, 2003. 15. van Landeghem FK, Stiller B, Lehmann TN, Sarioglu N, Sander B, Lange PE, StoltenburgDidinger G: Aqueductal stenosis and hydrocephalus in an infant due to aspergillus infection. Clin Neuropathol 19:26-29, 2000.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 21 March 2015; accepted 4 May 2015 Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2015.05.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.05.005
Aqueductal Stenosis Has a New Dimension—Aspergillosis: A Rare Case Report and Review of the Literature Soubhagya Ranjan Tripathy1, Sudhanshu Sekhar Mishra1, Rama Chandra Deo1, Itibrata Mohanta1, Kalpalata Tripathy2
Key words Aqueductal stenosis - Aspergillosis - Hydrocephalus - Voriconazole
- BACKGROUND:
Abbreviations and Acronyms CNS: Central nervous system CSF: Cerebrospinal fluid ETV: Endoscopic third ventriculostomy
- CASE
-
From the Departments of 1Neurosurgery and 2Pathology, SCB Medical College, Cuttack, Odisha, India To whom correspondence should be addressed: Soubhagya Ranjan Tripathy, M.S., M.Ch.(std) [E-mail: [email protected]] Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2015.05.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
INTRODUCTION Invasive cerebral aspergillosis, often encountered in immunocompromised patients, is almost always fatal despite radical surgical and medical management and frequently is a finding at autopsy (1). Although occurring most commonly in the immunosuppressed patient, cerebral aspergillosis infection has been reported after trauma or neurosurgical procedures (2). Attempts at fungal isolation often are unsuccessful, and a high index of radiologic suspicion is warranted (3).The clinical and laboratory diagnosis of cerebral aspergillosis is problematic, and mortality is quite high, even in cases that receive appropriate treatment (4). Aspergillus is a fungal organism that comprises many species, a few of which are pathogenic (14). Aspergilli are opportunistic pathogens that are ubiquitous fungi found in soil and organic materials and can establish saprophytic growth within the respiratory tract after inhalation of the airborne spores. Host factors are important in preventing disease. Invasive aspergillosis in patients with granulocyte dysfunction
Cerebral aspergillosis, often encountered in immunocompromised patients, is almost always fatal despite radical surgical and medical management and frequently is a finding at autopsy. Attempts at fungal isolation often are unsuccessful, and a high index of radiologic suspicion is necessary.
DESCRIPTION: A premature, 5-month-old female infant, born via normal vaginal delivery, presented with a progressive increase in head size since birth, delayed developmental milestones, and intermittent vomiting for 1 month. There was no history of trauma and no evidence of diabetes mellitus or hypertension, family history of tuberculosis, gestational diabetes, jaundice, or febrile eruptions. Neonatal jaundice was present after day 1, remained for 2 days, and was treated with phototherapy. Findings of the general and systemic examinations were unremarkable. Findings of a neurologic examination revealed a hypoactive infant with papilledema and extensor plantar bilaterally. Computed tomography scan of brain showed hydrocephalus attributable to aqueductal stenosis. On endoscopic third ventriculostomy, dense, friable, whitish yellow, nonvascular masses were encountered in the third ventricle, obstructing it. Her endoscopic third ventriculostomy success score was 10 D 0 D 10 [ 20%. Histopathologic examination and culture revealed Aspergillus flavus. A week later, a mediumpressure ventriculoperitoneal shunt was done, and voriconazole was added.
- RESULTS:
At discharge on the 7th postoperative day, 4 weeks and 12 weeks later (ie, first and second follow-up) the child was active, playful, and feeding normally. The first reported case of an aqueductal stenosis due to aspergillosis was in 2000 by van Landeghem FK et al. (Clin Neuropathol 19:26L29, 2000). To the best of our knowledge, this may only be the second reported case of hydrocephalus attributable to aqueductal stenosis caused by Aspergillosis. In conclusion, aspergillosis should not be ruled out as a differential diagnosis in aqueductal stenosis, even when the patient seems to be immunocompetent.
and after corticosteroid, antibiotic, or cancer chemotherapy is well documented. Both neutrophils and macrophages are important in host defense: macrophages are effective against conidia and neutrophils against hyphae (6). Most patients with invasive aspergillosis have dysfunction of one or both of these systems. The organism can become pathogenic in the presence of immune suppression, granulocytopenia, diabetes mellitus, or prolonged hospitalization. Aspergillosis of the central nervous system (CNS) presents as meningitis, encephalitis, brain abscesses, subdural abscesses, mycotic arteritis, or sellar abscess (7).
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
Aspergillus can reach the CNS via 3 different routes. The first is by hematogenous spread from a remote extracranial focus, usually the lung. The second is by extension from a contiguous extracranial location that is often the paranasal sinus or the nasal cavity. The third is direct introduction of aspergillus by a neurosurgical procedure iatrogenically (8). The antifungal armamentarium available to clinicians has increased in the last several years to include new formulations of amphotericin B, antifungal triazoles, and the echinocandins. In recent studies voriconazole has been shown to be more effective and well tolerated in CNS
www.WORLDNEUROSURGERY.org
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CASE REPORT SOUBHAGYA RANJAN TRIPATHY ET AL.
aspergillosis and may be considered as a first-line treatment (13). The first reported case of an aqueductal stenosis caused by an aspergillosis was in 2000 by van Landeghem et al. (15). To the best of our knowledge, our patient may only be the second reported case of hydrocephalus attributable to aqueductal stenosis caused by aspergillosis. The earlier case had aplasia cutis congenita at the scalp vertex and hypoplastic left heart syndrome (15); however, our patient did not present with any such congenital defects clinically. Hence, aspergillosis should not be ruled out as a differential diagnosis in aqueductal stenosis, even when the patient seems to be immunocompetent. CASE DESCRIPTION S.S.S., a 5-month-old female infant, presented with progressive increase in head size since birth, i.e., a head circumference of 55 cm (Figure 1A); with delayed developmental milestones and intermittent vomiting for 1 month. There was no history of trauma, diabetes mellitus, or family/contact history of tuberculosis. In perinatal history, the mother had taken adequate iron and folic acid (IFA) tablets and 2 doses of tetanus toxoid. No gestational diabetes, jaundice, or febrile eruptions were present, and the mother did not take any medications during her pregnancy except for iron and folic acid tablets. The child was born prematurely to a primigravida mother via normal vaginal delivery and weighed 1.3 kg at birth. She cried immediately at
ASPERGILLOSIS AND AQUEDUCTAL STENOSIS
birth and had no asphyxia. Neonatal jaundice presented after day 1, remained, for 2 days, and was treated with phototherapy accordingly. The findings of general and systemic examinations, including the ear, nose, and paranasal sinuses, were unremarkable. Findings of the neurologic examination revealed a hypoactive infant who moved all limbs equally, with both pupils of equal size that reacted normally to light, and with bilateral papilledema and plantar extensor bilaterally. A clinical diagnosis of congenital hydrocephalus was made. Noncontrast computed tomography scan of brain showed both lateral and IIIrd ventricular enlargement, with periventricular lucency, thin cortical mantle, and a normal-sized IVth ventricle (Figure 1B). From this clinical history and imaging findings, a diagnosis of congenital hydrocephalus due to aqueductal stenosis was reached. Endoscopic third ventriculostomy (ETV) was planned. An endoscope was inserted through the right Kocher’s point to the lateral and third ventricles. Cerebrospinal fluid (CSF) with high protein content and a whitish yellow material were cleared after repeated irrigation with normal saline. Bleeding points were cauterized. However, we could not continue with the ETV procedure because of dense, friable, whitish yellow, nonvascular masses we encountered in the third ventricle (Figure 2A), obstructing it. The patient’s ETV success score was 10 þ 0 þ 10 ¼ 20%; therefore, there was 20% probability of ETV success, preoperatively (9), which explains the failure of ETV.
Figure 1. Pre- and Postoperative imaging. (A) The head circumference was 55 cm with engorged scalp veins present. (B) Noncontrast computed
1.E2
www.SCIENCEDIRECT.com
A biopsy was taken and sent for histopathologic study. CSF samples also were sent for cytology and biochemical study. Histopathologic examination revealed a lesion composed of confluent granulomata. Smears from the tissue revealed dichotomously branching, Gram stain negative, periodic acideSchiff -positive hyphae suggestive of Aspergillus spp (Figure 2B), a finding also supported by results of a silver stain (Figure 2D). The fungal culture with SDA, chloramphenicol, and cycloheximide agar grew Aspergillus flavus (Figure 2C). A week later, a medium-pressure ventriculoperitoneal shunt was inserted at the right posterior parietal area. CSF was yellowish and clear and under high pressure sent for cytology and biochemical study. On both the occasions, results of the CSF study revealed a predominance of mononuclear cells; the findings were turbid the first and clear on second study. Similarly, protein concentrations were 691 mg% at CSF study after first surgery and 418 mg% in the second. At discharge from the hospital on the seventh postoperative day (Figure 1C), the child was active, playful, and feeding normally; vomiting had subsided, and she moving all limbs equally. Her head circumference was 48 cm. The mother was advised to breastfeed the infant exclusively, with bottle feeding as and when necessary; voriconazole in tablet form (200 mg) was prescribed in a dose of 6 mg/kg/dose once daily for 3 days then 4 mg/kg/dose twice daily for 25 days, to be taken with sips of water.
tomography shows aqueductal stenosis. (C) At discharge from the hospital. (D) At 1-month follow-up. (E) At 3-month follow-up.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.05.005
CASE REPORT SOUBHAGYA RANJAN TRIPATHY ET AL.
ASPERGILLOSIS AND AQUEDUCTAL STENOSIS
Figure 2. Operation, biopsy, and culture. (A) Endoscopic third ventriculostomy. (B) Filamentous septate hyphae (at 40, 100, and 400 magnification; with acute angle branching), with dense acute and chronic
At 4 weeks after discharge (Figure 1D), the patient’s head circumference was 47.5 cm and she was active and feeding well. At second follow-up (Figure 1E), her head circumference had increased a little to 48.5 cm, but she was active and feeding well. The limitations in this case were unavailability of immunoglobulin M enzyme-linked immunosorbent assay for aspergillus antigens (because of financial reasons), even though differential and absolute eosinophil and total leukocyte count in both blood and repeated CSF studies were within the normal limits. Other investigations, like fasting blood sugar, erythrocyte sedimentation rate, chest radiograph, paranasal sinus radiograph, blood tests for HIV, and hepatitis C and hepatitis B, also were within normal limits.
DISCUSSION Aqueductal stenosis is a common cause of hydrocephalus during infancy (5). The first reported case was an infant born with aplasia cutis congenita (15) at the scalp vertex and hypoplastic left heart syndrome developing systemic aspergillosis after cardiac surgery. The infant died at 76 days of age despite systemic antimycotic therapy with a combination of flucytosine and amphotericin B. Postmortem examination revealed meningitis, multiple brain aspergillomas and microabscesses with focal ependymitis, focal bronchopneumonia, and necrotizing enterocolitis. One of the brain aspergillomas was located close to the aqueduct, causing an aqueductal stenosis and an obstructive hydrocephalus.
inflammatory cells suggestive of cerebral aspergillosis. (C). SDA, chloramphenicol, and cycloheximide culture. (D) Silver staining.
Histologically, aspergillus hyphae could only be detected in the aspergilloma of the aqueduct (15). There are only 2 previous reports of immunocompetent patients with an isolated nondural-based Aspergilloma of the cerebellum (9). Of the 2 reported immunocompetent patients with an isolated cerebellar aspergilloma, one was an adult (10), and the other was an infant (his immune status was unknown) (11). The source of infection in our patient is unclear. Although Aspergillus is known to reside in tuberculous cavities, chest radiographs did not reveal cavitatory lesions or a fungal ball. In fact, in our patient, differential count, total leukocyte count, erythrocyte sedimentation rate, serum immunoglobulin E level, chest radiographs, and paranasal sinus radiographs all were within normal limits. Enzyme-linked immunosorbent assay findings for hepatitis B surface antigen, HIV, and hepatitis C virus also were negative. Further cultures of blood and CSF could not be performed because of financial restraints, as was a postoperative computed tomography scan. Patients with isolated fungal granulomas of the brain may be subjected to prolonged antituberculous therapy empirically in this part of the world where tuberculosis is endemic, leading to a delay in diagnosis and administration of antifungal treatment and resulting in a poor outcome (12). In our case, the diagnosis of aspergillosis was made as a result of histopathologic examination because clinical and radiologic findings were nonspecific. A high index of suspicion is required to order fungal culture studies. Total
WORLD NEUROSURGERY - [-]: ---, MONTH 2015
excision of the mass followed by adequate antifungal therapy, as was undertaken in our case, is likely to result in a cure. CONCLUSION Surgery followed by aggressive systemic antifungal therapy offers the best outcomes in patients with intracranial mass lesions (13). Whenever feasible, safe radical excision along with normal nervous tissue around it should be performed. Sinocranial aspergillosis is a rare entity and the mass lesions can be intracranial extracerebral (mostly in anterior cranial fossa), intracerebral, or both. The clinical and laboratory diagnosis of cerebral aspergillosis is problematic and mortality is quite high, even in cases receiving appropriate antifungal treatment (4). Hence, a high index of suspicion is necessary in children with appropriate clinical features, even in immunocompetent patients. The timing of therapeutic intervention seems to have a significant impact on survival. To the best of our knowledge, this is the second reported case of an aqueductal stenosis caused by aspergillosis. Hence, aspergillosis should not be discarded as a potential differential diagnosis in aqueductal stenosis in all those infants who have with presumed immunocompetence, as the timely administration of voriconazole can alter the course of this dreaded disease rather dramatically. REFERENCES 1. Antony AK, Hong RW: Free latissimus dorsi flap used in treatment of cerebral aspergillosis: a case
www.WORLDNEUROSURGERY.org
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 21 March 2015; accepted 4 May 2015 Citation: World Neurosurg. (2015). http://dx.doi.org/10.1016/j.wneu.2015.05.005 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.05.005
