- Email: [email protected]
Isolated Intraventricular Chronic Mucormycosis in an Immunocompetent Infant: A Rare Case with Review of the Literature
Case Report
Isolated Intraventricular Chronic Mucormycosis in an Immunocompetent Infant: A Rare Case with Review of the Literature Shruti Gupta1, Anant Mehrotra1, Gagandeep Attri1, Lily Pal2, Awadhesh Kumar Jaiswal1, Raj Kumar1
Key words Immunocompetent - Intraventricular - Mucormycosis -
Abbreviations and Acronyms CNS: Central nervous system CSF: Cerebrospinal fluid CT: Computed tomography MRI: Magnetic resonance imaging
- BACKGROUND:
Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases.
- CASE
To whom correspondence should be addressed: Anant Mehrotra, M.Ch. [E-mail: [email protected]]
DESCRIPTION: We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature.
Citation: World Neurosurg. (2019) 130:206-210. https://doi.org/10.1016/j.wneu.2019.06.190
- CONCLUSIONS:
From the Departments of 1Neurosurgery and 2Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.
1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
INTRODUCTION Mucormycosis was first described in humans by Paultaff in 1885.1 Mucormycosis of the central nervous system (CNS) is an uncommon infection.2-5 Isolated, chronic involvement of the CNS is a rare occurrence, and only 6 cases have been reported in immunocompetent patients.2,4,6-8 Isolated, chronic, involvement of the CNS in an immunocompetent infant, presenting only as hydrocephalus, has not been reported previously. We present the case of an immunocompetent infant who presented with features of increased intracranial pressure underwent cerebrospinal fluid (CSF) diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris.
progressively increasing head size since birth and downward gaze for the previous 2 months. There was history suggestive of global developmental delay. The child was born at term by a caesarean delivery due to fetal distress, and there was a delayed cry. There was history of neonatal sepsis with end-organ failure, for which the child was admitted and treated in neonatal intensive care unit for 2 weeks. On examination, the child weighed 7 kg, had sun-setting eyes, and tense anterior fontanelle. Sutural diastasis with Macewen sign was seen, and there were dilated veins over the scalp. The orbitofrontal circumference was 52 cm. There was developmental delay in all 4 fields. The child was unable to hold up his neck, unable to reach for objects, social smile was absent, and he spoke no monosyllables.
CASE REPORT History and Examination A 9-month-old, first-born, male child from a nonconsanguineous marriage presented to our outpatient department with
206
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Evaluation The child was referred to us with a noncontrast computed tomography (CT) scan and a magnetic resonance imaging (MRI) scan of the head, which showed evidence
of communicating hydrocephalus (Figure 1). The bifrontal diameter was 70 mm and the Evan’s ratio was 0.68. The temporal horns measured 17 mm and the third ventricle was 15 mm in diameter. Cortical mantle thickness was 15 mm. There was evidence of a septation in the atrium in the right lateral ventricle pointing toward old infection (Figure 1A, D, and F). Corpus callosal agenesis was seen. Intervention We performed an endoscopic third ventriculostomy on the patient (Figure 2). A curvilinear incision was made, and a burr hole was created at Kocher’s point on the right side. On hitting the ventricle (at w1 cm), CSF came out under pressure indicating raised intracranial pressure. CSF was clear and not xanthochromic or purulent or blood stained. The right foramen of Monro was identified and entered to reach the third ventricle (Figure 2A). The third ventricle floor was identified and the premamillary membrane perforated (Figure 2F). A
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.190
CASE REPORT SHRUTI GUPTA ET AL.
CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 1. (A, B) Noncontrast axial computed tomography (CT) images show dilatation of the bilateral lateral ventricles and bilateral temporal horns. A septation is seen in the right lateral ventricle pointing to postinfective origin of hydrocephalus. The fourth ventricle is open and dilated, as is the prepontine cistern, suggestive of communicating hydrocephalus. (C, D) T1-weighted axial magnetic resonance imaging (MRI) shows
naturally perforated septum pellucidum was appreciated (Figure 2A). There was evidence of debris in the dependent part of the occipital horn of lateral ventricle, and a biopsy was taken (Figure 2D, E). The ventricular wall was studded with nodular debris, and multiple septations were seen as well. There was obstruction of the aqueduct due to formation of a membrane. The membrane itself was studded with multiple nodular debris (Figure 2G). Histology The biopsy sent from the ventricular debris was suggestive of a fungal ball of mucormycosis with granulomatous reaction (Figure 3). The histologic section showed bits of brain parenchyma with inflammatory infiltrate comprising of histiocytes, plasma cells, and lymphocytes (Figure 3A). A few granulomas and multinucleated giant cells also were seen. Sheets of fungal profiles having broad aseptate hyphae with right-angle branching were
identified, (Figure 3B, degenerated parenchyma
dilated lateral ventricles with patent foramen of Monro bilaterally and bilateral subdural hygroma. (E) T2-weighted sagittal MRI showing patent aqueduct of Sylvius. (F, G) Contrast axial and sagittal MRI show no evidence of active infection or mass lesion. (H) Postoperative noncontrast CT showing resolution of subdural hygroma.
confirming mucormycosis C). Two foci of calcified fungal elements within the were seen (Figure 3D).
Hospital Course and Follow-Up The child was evaluated vigorously after the surgery in view of postinfective hydrocephalus. No other source of mucor was found, neither clinically nor on imaging. CSF workup was sent, and fluid protein was 4 mg% with nil cells. CSF bacterial, fungal, and tubercular cultures were negative. The child was discharged in stable condition on postoperative day 7. The child was then managed in consultation with a neurophysician with antifungal therapy. Immunodeficiency workup (including Ig A, G, M, E, HIV workup) was normal. At 1-month follow-up, the child presented with irritability and inability to feed. A noncontrast CT showed increased hydrocephalus, which was managed with CSF diversion in the form of a ventriculoperitoneal shunt. At 12 months
WORLD NEUROSURGERY 130: 206-210, OCTOBER 2019
follow-up, the child was gaining milestones, he was able to stand with support, had pincer grasp, spoke monosyllables, and enjoyed peek-a-boo game. On imaging, a contrast-enhanced MRI head was done, which showed asymmetrical reduction in hydrocephalus.
DISCUSSION Mucormycosis of the CNS is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor (in decreasing order of frequency).1-7,9,10 Spores of these fungi may harbor in the upper respiratory tract of normal individuals and are nonpathogenic in the immunocompetent host.1,3,11,12 They may reach the brain via the hematogenous route, contiguous involvement of areas like the orbit, or the paranasal sinuses or by direct inoculation as in cases of trauma or postsurgical cases.1,3,4,6,7,12
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CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 2. (A) Endoscopic panoramic view on entering the right lateral ventricle shows septum pellucidum replaced by streaks of tissue, bilateral thalamostriate veins in the floor. Two separate foramen of Monro were not identifiable; rather, there was a large opening in the floor of the lateral ventricle leading to the third ventricle. The floor of third ventricle was also seen with premammillary membrane anteriorly and aqueduct of sylvius posteriorly. (B) Debris seen in the atrium of the lateral ventricle on the same side. (C) The wall of the lateral ventricle
Mucormycosis is a disease of the immunocompromised patient, occurring commonly in those with primary immunodeficiency as well as those with secondary risk factors such as diabetes mellitus, intravenous drug abuse, HIV seropositivity, chronic renal failure, immune-suppressive drugs, steroid intake, chronic alcoholism, organ transplant recipients, malnutrition, and hematologic malignancies.1,2,4-7,9-11,13 Of all these risk factors, although diabetes mellitus is overall the most commonly occurring risk factor, intravenous drug abuse is deemed to be the most important for isolated intracerebral mucormycosis.3,4,11,13 Mucormycosis has been rarely reported in immunocompetent patients, with only 6 cases described in the literature so far, contributing to the uniqueness of our case.2,4,6-8 To the best of our knowledge, only 2 of these have been in the pediatric population, further highlighting the rarity of our case (Table 1). In 2010, Tsung et al.6 described the case of a 3-year-old Chinese boy who presented
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was studded with multiple nodular debris (suspicion of granulomas). (D, E) A biopsy was taken from the whitish debris in the atrium. (F) The premammillary membrane was perforated with a 4-Fr Fogarty catheter. (G) A thin membrane covered the aqueduct of sylvius; this membrane also was perforated with a 4-Fr Fogarty catheter. (H) Final endoscopic view after endoscopic third ventriculostomy; perforation of membrane at the aqueduct and biopsy of the intraventricular debris is shown.
with history of watery diarrhea followed by hypotension and epilepsy due to a left parietal abscess and diffuse meningeal involvement. In 2015, Al Barbarawi and Allouh2 described a right-sided cerebellopontine angle lesion in a 4-year-old girl presenting with facial asymmetry and unsteady gait. Mucormycosis usually manifests as an acute fulminant sporadic infection in either of its more common forms viz. rhino-orbito-cerebral, gastro-intestinal, cutaneous, pulmonary, or disseminated forms.2-4,10,12,13 Isolated CNS infections, in the absence of rhino-orbital involvement, are rare. In 2006, Verma et al.7 reported a case of isolated cerebral mucormycosis in an immunocompetent patient presenting with seizure and suggested the use of the term “focal isolated cerebral mucormycosis.” Isolated chronic involvement of the CNS is a rare occurrence, with no case of isolated chronic involvement of the ventricles having been reported to date.4,12,13 In 2002, Rumboldt and Castillo12 first
described a case of indolent intracranial mucormycosis in an immunocompromised young adult that remained silent for nearly a year; however, this infection was found to have spread from the sphenoid sinus. The chronicity of the infection is thought to be related to the immune capacity of the patient, although the virility of the fungus as well as the size and route of inoculum are deemed equally important. Pathologically, mucormycosis may manifest as granulomas, abscess, vasculitis, or infarcts.3,6,9,11-13 Acute infections usually manifest as fungal vasculitis and abscess in contrast to chronic, which manifest as granuloma.3 Presentation of mucormycosis with hydrocephalus alone, in the absence of active meningitis, such as our patient, is extremely rare. There has been only 1 such case report by Bichile et al.,8 in 1985, who reported a case of chronic meningitis with hydrocephalus in a 22-year-old immunocompetent patient. Common radiologic differentials include lymphoma, granulomatous infections like
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.190
CASE REPORT SHRUTI GUPTA ET AL.
CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 3. (A and C) Low-power view of hematoxylin and eosinstained section shows granulomas composed of mixed inflammatory cells including lymphocytes, plasma cells, and multinucleate giant cells along with multiple fungal profiles
tuberculosis, sarcoidosis, and neurocysticercosis.1,12 Histologically, these fungi appear as non-septate broad hyphae with right-angled branching.4,12 In chronic cases, there may be granuloma formation with presence of multinucleate giant cells and even a nonspecific inflammatory infiltrate. Early diagnosis is a critical key to successful management.3,11 CSF studies and radiologic studies such as MRI or CT of
(magnification 20). (B) Periodic acid Schiff stain showing multiple broad aseptate fungal profiles with right angle branching confirming mucormycosis (magnification 40). (D) GMS silver stain shows argyrophilic broad fungal hyphae (magnification 40).
the head and paranasal sinuses are often nonspecific.9,11 Definitive diagnosis is usually by sampling of the tissue, histology, or by a positive fungal culture.3,11 Surgical debridement and intravenous antifungals are the cornerstones of treatment.1,3,4,10,13 Intravenous liposomal amphotericin is the antifungal of choice, although other antifungals include voriconazole and posaconazole.1,3,4,10,13 With amphotericin, side effects such as
headache, vomiting, nephrotoxicity, cranial nerve paresis, and paraparesis should monitored.6 Optimization of the predisposing risk factor and hyperbaric oxygen are adjuncts in treatment.10 Acute fulminant mucormycosis has a grave prognosis despite therapy, with mortality rates >60% (up to 100% in untreated cases).1-4,6,9,11 Prognosis not only depends on the extent and aggressiveness of infection but also on the overall
Table 1. Reported Cases of Isolated Intracranial Mucormycosis in Immunocompetent Children
Patient Age/Sex
Immune Status
Established Risk Factor
Medical History
Isolated Intracerebral Involvement
Treatment
Tsung et al., 20106
3 years/Boy
Immunocompetent
None
Admission for watery diarrhea
Yes
Surgery þ IV amphotericin
Al Barbarawi and Allouh, 20152
4 years/Girl
Immunocompetent
None
Untreated nasal polyp
Yes
9 months/Boy
Immunocompetent
None
NICU stay 2 weeks
Yes
Study
Present case
Outcome/ Follow-Up Duration Recovered, few years
Debulking þ IV amphotericin Recovered, 12 weeks ETV þ IV amphotericin
Recovered, 18 months
IV, intravenous; NICU, neonatal intensive care unit; ETV, endoscopic third ventriculostomy.
WORLD NEUROSURGERY 130: 206-210, OCTOBER 2019
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condition of the patient, including the immune status, and initial response to treatment.6,7,10 Among the 6 immunocompetent patients reported, only 1 mortality has been described, by Verma et al.6 in 2006. No mortality is known in the pediatric subset. CONCLUSIONS Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted. REFERENCES 1. Herrera DA, Dublin AB, Ormsby EL, Aminpour S, Howell LP. Imaging findings of rhinocerebral mucormycosis. Skull Base. 2009;19:117-125. 2. Al Barbarawi MM, Allouh MZ. Successful management of a unique condition of isolated intracranial mucormycosis in an immunocompetent child. Pediatr Neurosurg. 2015;50:165-167.
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3. Ma J, Jia R, Li J, et al. Retrospective clinical study of eighty-one cases of intracranial mucormycosis. J Glob Infect Dis. 2015;7:143-150. 4. Air EL, Vagal AA, Kendler A, McPherson CM. Isolated cerebellar mucormycosis, slowly progressive over 1 year in an immunocompetent patient. Surg Neurol Int. 2010;13:81. 5. Ginsberg F, Peyster RG, Hoover ED, Finkelstein SD. Isolated cerebral mucormycosis: case report with CT and pathologic correlation. Am J Neuroradiol. 1987;8:558-560. 6. Tsung LL, Zhu XL, Chu WC, Sun DT, Cheung KL, Leung TF. Intraventricular amphotericin for absidiomycosis in an immunocompetent child. Hong Kong Med J. 2010;16:137-140. 7. Verma A, Brozman B, Petito CK. Isolated cerebral mucormycosis: report of a case and review of the literature. J Neurol Sci. 2006;240:65-69.
of infective rhinocerebral mucormycosis. J Laryngol Otol. 2010;124:1314-1317. 11. Malik AN, Bi WL, McCray B, Abedalthagafi M, Vaitkevicius H, Dunn IF. Isolated cerebral mucormycosis of the basal ganglia. Clin Neurol Neurosurg. 2014;124:102-105. 12. Rumboldt Z, Castillo M. Indolent intracranial mucormycosis: case report. AJNR Am J Neuroradiol. 2002;23:932-934. 13. Han SR, Choi CY, Joo M, Whang CJ. Isolated cerebral mucormycosis. J Korean Neurosurg Soc. 2007; 42:400-402.
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.
8. Bichile LS, Abhyankar SC, Hase NK. Chronic mucormycosis manifesting as hydrocephalus. J Neurol Neurosurg Psychiatry. 1985;48:1188.
Received 15 March 2019; accepted 25 June 2019
9. Dhakar MB, Rayes M, Kupsky W, Tselis A, Norris G. A cryptic case: isolated cerebral mucormycosis. Am J Med. 2015;128:1296-1299.
Journal homepage: www.journals.elsevier.com/worldneurosurgery
10. Kulendra K, Habibi M, Butler C, Clarke P, Howard D. Use of posaconazole in the treatment
Citation: World Neurosurg. (2019) 130:206-210. https://doi.org/10.1016/j.wneu.2019.06.190
Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.190
Isolated Intraventricular Chronic Mucormycosis in an Immunocompetent Infant: A Rare Case with Review of the Literature Shruti Gupta1, Anant Mehrotra1, Gagandeep Attri1, Lily Pal2, Awadhesh Kumar Jaiswal1, Raj Kumar1
Key words Immunocompetent - Intraventricular - Mucormycosis -
Abbreviations and Acronyms CNS: Central nervous system CSF: Cerebrospinal fluid CT: Computed tomography MRI: Magnetic resonance imaging
- BACKGROUND:
Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases.
- CASE
To whom correspondence should be addressed: Anant Mehrotra, M.Ch. [E-mail: [email protected]]
DESCRIPTION: We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature.
Citation: World Neurosurg. (2019) 130:206-210. https://doi.org/10.1016/j.wneu.2019.06.190
- CONCLUSIONS:
From the Departments of 1Neurosurgery and 2Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.
1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.
INTRODUCTION Mucormycosis was first described in humans by Paultaff in 1885.1 Mucormycosis of the central nervous system (CNS) is an uncommon infection.2-5 Isolated, chronic involvement of the CNS is a rare occurrence, and only 6 cases have been reported in immunocompetent patients.2,4,6-8 Isolated, chronic, involvement of the CNS in an immunocompetent infant, presenting only as hydrocephalus, has not been reported previously. We present the case of an immunocompetent infant who presented with features of increased intracranial pressure underwent cerebrospinal fluid (CSF) diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris.
progressively increasing head size since birth and downward gaze for the previous 2 months. There was history suggestive of global developmental delay. The child was born at term by a caesarean delivery due to fetal distress, and there was a delayed cry. There was history of neonatal sepsis with end-organ failure, for which the child was admitted and treated in neonatal intensive care unit for 2 weeks. On examination, the child weighed 7 kg, had sun-setting eyes, and tense anterior fontanelle. Sutural diastasis with Macewen sign was seen, and there were dilated veins over the scalp. The orbitofrontal circumference was 52 cm. There was developmental delay in all 4 fields. The child was unable to hold up his neck, unable to reach for objects, social smile was absent, and he spoke no monosyllables.
CASE REPORT History and Examination A 9-month-old, first-born, male child from a nonconsanguineous marriage presented to our outpatient department with
206
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Evaluation The child was referred to us with a noncontrast computed tomography (CT) scan and a magnetic resonance imaging (MRI) scan of the head, which showed evidence
of communicating hydrocephalus (Figure 1). The bifrontal diameter was 70 mm and the Evan’s ratio was 0.68. The temporal horns measured 17 mm and the third ventricle was 15 mm in diameter. Cortical mantle thickness was 15 mm. There was evidence of a septation in the atrium in the right lateral ventricle pointing toward old infection (Figure 1A, D, and F). Corpus callosal agenesis was seen. Intervention We performed an endoscopic third ventriculostomy on the patient (Figure 2). A curvilinear incision was made, and a burr hole was created at Kocher’s point on the right side. On hitting the ventricle (at w1 cm), CSF came out under pressure indicating raised intracranial pressure. CSF was clear and not xanthochromic or purulent or blood stained. The right foramen of Monro was identified and entered to reach the third ventricle (Figure 2A). The third ventricle floor was identified and the premamillary membrane perforated (Figure 2F). A
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.190
CASE REPORT SHRUTI GUPTA ET AL.
CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 1. (A, B) Noncontrast axial computed tomography (CT) images show dilatation of the bilateral lateral ventricles and bilateral temporal horns. A septation is seen in the right lateral ventricle pointing to postinfective origin of hydrocephalus. The fourth ventricle is open and dilated, as is the prepontine cistern, suggestive of communicating hydrocephalus. (C, D) T1-weighted axial magnetic resonance imaging (MRI) shows
naturally perforated septum pellucidum was appreciated (Figure 2A). There was evidence of debris in the dependent part of the occipital horn of lateral ventricle, and a biopsy was taken (Figure 2D, E). The ventricular wall was studded with nodular debris, and multiple septations were seen as well. There was obstruction of the aqueduct due to formation of a membrane. The membrane itself was studded with multiple nodular debris (Figure 2G). Histology The biopsy sent from the ventricular debris was suggestive of a fungal ball of mucormycosis with granulomatous reaction (Figure 3). The histologic section showed bits of brain parenchyma with inflammatory infiltrate comprising of histiocytes, plasma cells, and lymphocytes (Figure 3A). A few granulomas and multinucleated giant cells also were seen. Sheets of fungal profiles having broad aseptate hyphae with right-angle branching were
identified, (Figure 3B, degenerated parenchyma
dilated lateral ventricles with patent foramen of Monro bilaterally and bilateral subdural hygroma. (E) T2-weighted sagittal MRI showing patent aqueduct of Sylvius. (F, G) Contrast axial and sagittal MRI show no evidence of active infection or mass lesion. (H) Postoperative noncontrast CT showing resolution of subdural hygroma.
confirming mucormycosis C). Two foci of calcified fungal elements within the were seen (Figure 3D).
Hospital Course and Follow-Up The child was evaluated vigorously after the surgery in view of postinfective hydrocephalus. No other source of mucor was found, neither clinically nor on imaging. CSF workup was sent, and fluid protein was 4 mg% with nil cells. CSF bacterial, fungal, and tubercular cultures were negative. The child was discharged in stable condition on postoperative day 7. The child was then managed in consultation with a neurophysician with antifungal therapy. Immunodeficiency workup (including Ig A, G, M, E, HIV workup) was normal. At 1-month follow-up, the child presented with irritability and inability to feed. A noncontrast CT showed increased hydrocephalus, which was managed with CSF diversion in the form of a ventriculoperitoneal shunt. At 12 months
WORLD NEUROSURGERY 130: 206-210, OCTOBER 2019
follow-up, the child was gaining milestones, he was able to stand with support, had pincer grasp, spoke monosyllables, and enjoyed peek-a-boo game. On imaging, a contrast-enhanced MRI head was done, which showed asymmetrical reduction in hydrocephalus.
DISCUSSION Mucormycosis of the CNS is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor (in decreasing order of frequency).1-7,9,10 Spores of these fungi may harbor in the upper respiratory tract of normal individuals and are nonpathogenic in the immunocompetent host.1,3,11,12 They may reach the brain via the hematogenous route, contiguous involvement of areas like the orbit, or the paranasal sinuses or by direct inoculation as in cases of trauma or postsurgical cases.1,3,4,6,7,12
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CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 2. (A) Endoscopic panoramic view on entering the right lateral ventricle shows septum pellucidum replaced by streaks of tissue, bilateral thalamostriate veins in the floor. Two separate foramen of Monro were not identifiable; rather, there was a large opening in the floor of the lateral ventricle leading to the third ventricle. The floor of third ventricle was also seen with premammillary membrane anteriorly and aqueduct of sylvius posteriorly. (B) Debris seen in the atrium of the lateral ventricle on the same side. (C) The wall of the lateral ventricle
Mucormycosis is a disease of the immunocompromised patient, occurring commonly in those with primary immunodeficiency as well as those with secondary risk factors such as diabetes mellitus, intravenous drug abuse, HIV seropositivity, chronic renal failure, immune-suppressive drugs, steroid intake, chronic alcoholism, organ transplant recipients, malnutrition, and hematologic malignancies.1,2,4-7,9-11,13 Of all these risk factors, although diabetes mellitus is overall the most commonly occurring risk factor, intravenous drug abuse is deemed to be the most important for isolated intracerebral mucormycosis.3,4,11,13 Mucormycosis has been rarely reported in immunocompetent patients, with only 6 cases described in the literature so far, contributing to the uniqueness of our case.2,4,6-8 To the best of our knowledge, only 2 of these have been in the pediatric population, further highlighting the rarity of our case (Table 1). In 2010, Tsung et al.6 described the case of a 3-year-old Chinese boy who presented
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was studded with multiple nodular debris (suspicion of granulomas). (D, E) A biopsy was taken from the whitish debris in the atrium. (F) The premammillary membrane was perforated with a 4-Fr Fogarty catheter. (G) A thin membrane covered the aqueduct of sylvius; this membrane also was perforated with a 4-Fr Fogarty catheter. (H) Final endoscopic view after endoscopic third ventriculostomy; perforation of membrane at the aqueduct and biopsy of the intraventricular debris is shown.
with history of watery diarrhea followed by hypotension and epilepsy due to a left parietal abscess and diffuse meningeal involvement. In 2015, Al Barbarawi and Allouh2 described a right-sided cerebellopontine angle lesion in a 4-year-old girl presenting with facial asymmetry and unsteady gait. Mucormycosis usually manifests as an acute fulminant sporadic infection in either of its more common forms viz. rhino-orbito-cerebral, gastro-intestinal, cutaneous, pulmonary, or disseminated forms.2-4,10,12,13 Isolated CNS infections, in the absence of rhino-orbital involvement, are rare. In 2006, Verma et al.7 reported a case of isolated cerebral mucormycosis in an immunocompetent patient presenting with seizure and suggested the use of the term “focal isolated cerebral mucormycosis.” Isolated chronic involvement of the CNS is a rare occurrence, with no case of isolated chronic involvement of the ventricles having been reported to date.4,12,13 In 2002, Rumboldt and Castillo12 first
described a case of indolent intracranial mucormycosis in an immunocompromised young adult that remained silent for nearly a year; however, this infection was found to have spread from the sphenoid sinus. The chronicity of the infection is thought to be related to the immune capacity of the patient, although the virility of the fungus as well as the size and route of inoculum are deemed equally important. Pathologically, mucormycosis may manifest as granulomas, abscess, vasculitis, or infarcts.3,6,9,11-13 Acute infections usually manifest as fungal vasculitis and abscess in contrast to chronic, which manifest as granuloma.3 Presentation of mucormycosis with hydrocephalus alone, in the absence of active meningitis, such as our patient, is extremely rare. There has been only 1 such case report by Bichile et al.,8 in 1985, who reported a case of chronic meningitis with hydrocephalus in a 22-year-old immunocompetent patient. Common radiologic differentials include lymphoma, granulomatous infections like
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.06.190
CASE REPORT SHRUTI GUPTA ET AL.
CHRONIC INTRAVENTRICULAR MUCORMYCOSIS
Figure 3. (A and C) Low-power view of hematoxylin and eosinstained section shows granulomas composed of mixed inflammatory cells including lymphocytes, plasma cells, and multinucleate giant cells along with multiple fungal profiles
tuberculosis, sarcoidosis, and neurocysticercosis.1,12 Histologically, these fungi appear as non-septate broad hyphae with right-angled branching.4,12 In chronic cases, there may be granuloma formation with presence of multinucleate giant cells and even a nonspecific inflammatory infiltrate. Early diagnosis is a critical key to successful management.3,11 CSF studies and radiologic studies such as MRI or CT of
(magnification 20). (B) Periodic acid Schiff stain showing multiple broad aseptate fungal profiles with right angle branching confirming mucormycosis (magnification 40). (D) GMS silver stain shows argyrophilic broad fungal hyphae (magnification 40).
the head and paranasal sinuses are often nonspecific.9,11 Definitive diagnosis is usually by sampling of the tissue, histology, or by a positive fungal culture.3,11 Surgical debridement and intravenous antifungals are the cornerstones of treatment.1,3,4,10,13 Intravenous liposomal amphotericin is the antifungal of choice, although other antifungals include voriconazole and posaconazole.1,3,4,10,13 With amphotericin, side effects such as
headache, vomiting, nephrotoxicity, cranial nerve paresis, and paraparesis should monitored.6 Optimization of the predisposing risk factor and hyperbaric oxygen are adjuncts in treatment.10 Acute fulminant mucormycosis has a grave prognosis despite therapy, with mortality rates >60% (up to 100% in untreated cases).1-4,6,9,11 Prognosis not only depends on the extent and aggressiveness of infection but also on the overall
Table 1. Reported Cases of Isolated Intracranial Mucormycosis in Immunocompetent Children
Patient Age/Sex
Immune Status
Established Risk Factor
Medical History
Isolated Intracerebral Involvement
Treatment
Tsung et al., 20106
3 years/Boy
Immunocompetent
None
Admission for watery diarrhea
Yes
Surgery þ IV amphotericin
Al Barbarawi and Allouh, 20152
4 years/Girl
Immunocompetent
None
Untreated nasal polyp
Yes
9 months/Boy
Immunocompetent
None
NICU stay 2 weeks
Yes
Study
Present case
Outcome/ Follow-Up Duration Recovered, few years
Debulking þ IV amphotericin Recovered, 12 weeks ETV þ IV amphotericin
Recovered, 18 months
IV, intravenous; NICU, neonatal intensive care unit; ETV, endoscopic third ventriculostomy.
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CASE REPORT SHRUTI GUPTA ET AL.
condition of the patient, including the immune status, and initial response to treatment.6,7,10 Among the 6 immunocompetent patients reported, only 1 mortality has been described, by Verma et al.6 in 2006. No mortality is known in the pediatric subset. CONCLUSIONS Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted. REFERENCES 1. Herrera DA, Dublin AB, Ormsby EL, Aminpour S, Howell LP. Imaging findings of rhinocerebral mucormycosis. Skull Base. 2009;19:117-125. 2. Al Barbarawi MM, Allouh MZ. Successful management of a unique condition of isolated intracranial mucormycosis in an immunocompetent child. Pediatr Neurosurg. 2015;50:165-167.
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3. Ma J, Jia R, Li J, et al. Retrospective clinical study of eighty-one cases of intracranial mucormycosis. J Glob Infect Dis. 2015;7:143-150. 4. Air EL, Vagal AA, Kendler A, McPherson CM. Isolated cerebellar mucormycosis, slowly progressive over 1 year in an immunocompetent patient. Surg Neurol Int. 2010;13:81. 5. Ginsberg F, Peyster RG, Hoover ED, Finkelstein SD. Isolated cerebral mucormycosis: case report with CT and pathologic correlation. Am J Neuroradiol. 1987;8:558-560. 6. Tsung LL, Zhu XL, Chu WC, Sun DT, Cheung KL, Leung TF. Intraventricular amphotericin for absidiomycosis in an immunocompetent child. Hong Kong Med J. 2010;16:137-140. 7. Verma A, Brozman B, Petito CK. Isolated cerebral mucormycosis: report of a case and review of the literature. J Neurol Sci. 2006;240:65-69.
of infective rhinocerebral mucormycosis. J Laryngol Otol. 2010;124:1314-1317. 11. Malik AN, Bi WL, McCray B, Abedalthagafi M, Vaitkevicius H, Dunn IF. Isolated cerebral mucormycosis of the basal ganglia. Clin Neurol Neurosurg. 2014;124:102-105. 12. Rumboldt Z, Castillo M. Indolent intracranial mucormycosis: case report. AJNR Am J Neuroradiol. 2002;23:932-934. 13. Han SR, Choi CY, Joo M, Whang CJ. Isolated cerebral mucormycosis. J Korean Neurosurg Soc. 2007; 42:400-402.
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.
8. Bichile LS, Abhyankar SC, Hase NK. Chronic mucormycosis manifesting as hydrocephalus. J Neurol Neurosurg Psychiatry. 1985;48:1188.
Received 15 March 2019; accepted 25 June 2019
9. Dhakar MB, Rayes M, Kupsky W, Tselis A, Norris G. A cryptic case: isolated cerebral mucormycosis. Am J Med. 2015;128:1296-1299.
Journal homepage: www.journals.elsevier.com/worldneurosurgery
10. Kulendra K, Habibi M, Butler C, Clarke P, Howard D. Use of posaconazole in the treatment
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