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“Fungimitosis”: Invasive fulminant Aspergillus brain infection mimicking gliomatosis cerebri Sir, Fungi are commensals in humans.[1] However, whenever host defenses are at stake, fungi can lead to opportunistic infections, some of which can be lethal. Aspergillosis is an infection caused by fungi of the Aspergillus fumigatus family. Commonly, maxillary sinusitis of dental origin and pulmonary aspergillosis act as primary sources of the infection.[2] Central nervous system (CNS) aspergillosis can affect the cerebral parenchyma, the meninges or the vascular system. Rarely, the infection may also be air‑borne, contaminating the operative field during a neurosurgical procedure.[3] A 50‑year‑old male patient presented with gradually progressive, holocranial, and dull aching headache for 4 months, associated with memory deficits over a period of 3 months. He had mild clumsiness in using his right hand. There was neither any history of co‑morbid conditions nor any evident features suggestive of an immunocompromised state. On examination, the patient had a mini‑mental state examination score of 24/30. His motor system examination was unremarkable except for positive pronator drift on the right side along with ipsilateral upgoing plantars. His hematological investigations were normal including nonreactivity for human immunodeficiency virus (HIV). Cranial magnetic resonance imaging showed a diffuse lesion, hypointense on T1WI and hyperintense on T2WI, involving the left frontal, parietal and temporal lobes with patchy contrast enhancement. There was diffuse hemispheric edema of the same lobes with mass effect and midline shift [Figure 1a‑f]. These features were suggestive of gliomatosis cerebri. Hence, the patient underwent a left fronto‑temporo‑parietal (FTP) craniotomy, left temporal lobectomy with decompression, and biopsy of the lesion from the frontal lobe via the middle frontal gyrus approach.
At surgery, the lesion was found to be grayish white, minimally vascular, firm to hard (gritty) in consistency, which raised the suspicion of an infective etiology. Hence, microbiological staining (Gram’s, KOH preparation, acid‑fast bacillus staining) and cultures (aerobic, tubercular, and fungal) of the sample were sought, apart from its histopathogical examination. In the immediate postoperative period, the patient developed aphasia and right hemiplegia although this improved gradually over a period of 4 days. The histopathological examination showed fungal hyphae in the excised tissue and culture of the tissue suggested the diagnosis of aspergillus infection. The patient was started on intravenous amphotericin‑B on postoperative day 2 (dose 1.5 mg/kg wt/daily). During the course in the hospital, the patient deteriorated in sensorium, and a repeat computed tomography (CT) of the brain showed diffuse cerebral edema with mass effect for which a left FTP decompressive craniectomy was performed. Over the next 2 days, the patient did not show any improvement in the neurological status, prompting us to repeat his CT head. The CT scan showed dilated ventricles for which an external ventricular drainage was instituted. The patient, however, continued to deteriorate and finally succumbed to the illness on the 8th postoperative day. Invasive fungal infection involving the central nervous system (CNS) is often fulminant and fatal with a reported mortality of nearly 100% in the older literature. This disease was described as “almost always a clinical surprise” by Nadkarni and Goel.[4] These cases present an interesting diagnostic dilemma for the neurosurgeons and neuroradiologists, as neither the clinical nor the imaging features of CNS fungal infections are truly diagnostic of the disease and with the patient being immuno‑competent, the possibility of fungal infection is seldom considered in the list of clinical differentials.[5] Cerebral parenchymal lesions can range from fungal granuloma, diffuse cerebritis to frank abscess formation. A sinonasal disease with intracranial extension is the most frequent presentation although isolated parenchymal lesions without evidence of any sinonasal involvement are not infrequent. They usually present as an heterogenous signal intensity lesion on T1WI and T2WI images, often showing areas of diffusion restriction within. Because of rarity of the lesion and its non‑specific imaging findings, most cases are often confused with tumors and infarcts. In our case, involvement of one whole hemisphere mimicked gliomatosis cerebri; hence, we named it as “fungimitosis.” Impaired/poor nutritional status, injudicious use of steroids or antituberculous drugs, and parasitic infections are all considered as predisposing factors for fungal infections.[6,7]
Neurology India / May 2015 / Volume 63 / Issue 3
439
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Letters to Editor
a
d
c
b
e
f
Figure 1: Magnetic resonance imaging of the brain showing a lesion which is hypointense on T1W images (a) and hyperintense on T2W and fluid attenuation inversion recovery images (b and c) involving the left frontal, temporal, and parietal regions with patchy enhancement on contrast imaging (d, e, f)
Though no specific guidelines are available, early aggressive surgery followed by aggressive empirical antifungal therapy appears to be a reasonable approach considering the remarkable invasiveness of Aspergillus and its potential complications.[8] The patients with CNS Aspergillosis often show a peculiar response to surgery characterized by a disease flare up which may at times be fulminant and refractory to the medical management. The reason for this unique stormy postoperative course is incompletely understood but immunocompromise secondary to surgery and/or the stimulation of previously quiescent fungi due to surgical tissue handling have been proposed as the offending factors.[9,10] Aspergillus infection may uncommonly cause cerebral vasculitis leading to thrombosis of vessels and large infarcts which may contribute to the poor outcome after surgery.[6] Hence, it is not surprising that the prognosis of CNS aspergillosis is mostly unfavourable To conclude, CNS Aspergillus infection, although rare, can affect immunocompetent individuals. The protean clinical manifestations as well as diffuse brain parenchymal involvement may lead to a diagnostic dilemma. Although the prognosis remains largely poor, an early diagnosis and radical surgical management followed by aggressive antifungal chemotherapy may help to improve the outcome.
Alugolu Rajesh, Srikant Reddy, Malladi Venkat Surya Subbalaxmi1, Megha Shantveer Uppin2 440
Departments of Neurosurgery, 1Medicine and 2Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India E‑mail: [email protected]
References 1.
Kothari M, Goel A. Fungi: Too evolved to be condemned. Neurol India 2007;55:189‑90. 2. Saravia‑Gomez J. Aspergillosis of the central nervous system. In: Vinken PJ, Bruyn GW, editors. Handbook of Clinical Neurology. Vol. 35. Holland: North‑Holland Publishing Company; 1978. p. 395‑400. 3. Sharma RR, Gurusinghe NT, Lynch PG. Cerebral infarction due to Aspergillus arteritis following glioma surgery. Br J Neurosurg 1992;6:485‑90. 4. Nadkarni T, Goel A. Aspergilloma of the brain: An overview. J Postgrad Med 2005;51 Suppl 1:S37‑41. 5. Saini J, Gupta AK, Jolapara MB, Chatterjee S, Pendharkar HS, Kesavadas C, et al. Imaging findings in intracranial Aspergillus infection in immunocompetent patients. World Neurosurg 2010;74:661‑70. 6. Murthy JM. Fungal infections of the central nervous system: The clinical syndromes. Neurol India 2007;55:221‑5. 7. Kim DG, Hong SC, Kim HJ, Chi JG, Han MH, Choi KS, et al. Cerebral aspergillosis in immunologically competent patients. Surg Neurol 1993;40:326‑31. 8. Murthy J. Central nervous system mycoses: The challenges. Neurol India 2007;55:187‑8. 9. Nadkarni TD, Desai KI, Muzumdar D, Goel A, Shenoy A. Ischaemic complications after surgical resection of intracranial aspergilloma. J Clin Neurosci 2003;10:500‑2. 10. Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Pathology of fungal infections of the central nervous system: 17 years’ experience from Southern India. Histopathology 2006;49:396‑405.
Neurology India / May 2015 / Volume 63 / Issue 3
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Letters to Editor
systemic examination did not reveal any abnormality. A noncontrast cranial CT showed a sharply delineated fat attenuation lesion within the quadrigeminal plate and extending into the cistern on the right side with focal cisternal widening [Figure 2a and b]. An MRI study confirmed the presence of a focal lesion within the quadrigeminal cistern. The lesion demonstrated marked hyperintensity on T1‑weighted (T1W) images with relatively less hyperintensity on T2‑weighted (T2W) images with suppression of signal on short T1 inversion recovery (STIR) sequence confirming the fatty nature of the lesion [Figure 2c‑f]. No other intracranial abnormality was noted.
Access this article online Quick Response Code
Website: www.neurologyindia.com DOI: 10.4103/0028-3886.158250 PMID: xxxxx
Quadrigeminal cistern lipoma revisited
The third case, a 42‑year‑old female, presented with recurrent episodes of severe headache of 4 months duration and being previously treated with the clinical diagnosis of migraine. Her general and neurological examination was normal. An MRI of the brain was performed which showed a small focus of fat signal intensity within the quadrigeminal cistern. The lesion was hyperintense on T1W images, with relatively less hyperintensity on T2W and fluid‑attenuated inversion recovery images, with no mass effect or ventricular dilatation [Figure 3a‑c]. No other abnormal findings were noted.
Sir, We wish to share our experience with three cases of quadrigeminal cistern lipomas, all of whom were discovered incidentally during computed tomography/magnetic resonance imaging (CT/MRI) examination of patients for related or unrelated conditions. The first case, a 31‑year‑old male, presented with a history of minor head injury with no loss of consciousness, convulsions or vomiting. A noncontrast cranial CT study was performed which revealed a fat attenuation lesion on the left side of the quadrigeminal cistern [Figure 1]. No other intracranial pathology was detected.
All the three patients did not require any surgical intervention and were managed conservatively. They are on a regular follow‑up. Intracranial lipomas are neither tumors nor hamartomas. They represent developmental anomalies resulting from abnormal
The second case, a 36‑year‑old male, presented with recurrent headache and dizziness. His neurological and
a
b
Figure 1: (a and b) Axial computed tomography scan shows a fat attenuation lesion in the left quadrigeminal cistern suggestive of a lipoma
Neurology India / May 2015 / Volume 63 / Issue 3
441
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Letters to Editor
Access this article online Website:
Quick Response Code
www.neurologyindia.com DOI: 10.4103/0028-3886.158247 PMID: xxxxx
“Fungimitosis”: Invasive fulminant Aspergillus brain infection mimicking gliomatosis cerebri Sir, Fungi are commensals in humans.[1] However, whenever host defenses are at stake, fungi can lead to opportunistic infections, some of which can be lethal. Aspergillosis is an infection caused by fungi of the Aspergillus fumigatus family. Commonly, maxillary sinusitis of dental origin and pulmonary aspergillosis act as primary sources of the infection.[2] Central nervous system (CNS) aspergillosis can affect the cerebral parenchyma, the meninges or the vascular system. Rarely, the infection may also be air‑borne, contaminating the operative field during a neurosurgical procedure.[3] A 50‑year‑old male patient presented with gradually progressive, holocranial, and dull aching headache for 4 months, associated with memory deficits over a period of 3 months. He had mild clumsiness in using his right hand. There was neither any history of co‑morbid conditions nor any evident features suggestive of an immunocompromised state. On examination, the patient had a mini‑mental state examination score of 24/30. His motor system examination was unremarkable except for positive pronator drift on the right side along with ipsilateral upgoing plantars. His hematological investigations were normal including nonreactivity for human immunodeficiency virus (HIV). Cranial magnetic resonance imaging showed a diffuse lesion, hypointense on T1WI and hyperintense on T2WI, involving the left frontal, parietal and temporal lobes with patchy contrast enhancement. There was diffuse hemispheric edema of the same lobes with mass effect and midline shift [Figure 1a‑f]. These features were suggestive of gliomatosis cerebri. Hence, the patient underwent a left fronto‑temporo‑parietal (FTP) craniotomy, left temporal lobectomy with decompression, and biopsy of the lesion from the frontal lobe via the middle frontal gyrus approach.
At surgery, the lesion was found to be grayish white, minimally vascular, firm to hard (gritty) in consistency, which raised the suspicion of an infective etiology. Hence, microbiological staining (Gram’s, KOH preparation, acid‑fast bacillus staining) and cultures (aerobic, tubercular, and fungal) of the sample were sought, apart from its histopathogical examination. In the immediate postoperative period, the patient developed aphasia and right hemiplegia although this improved gradually over a period of 4 days. The histopathological examination showed fungal hyphae in the excised tissue and culture of the tissue suggested the diagnosis of aspergillus infection. The patient was started on intravenous amphotericin‑B on postoperative day 2 (dose 1.5 mg/kg wt/daily). During the course in the hospital, the patient deteriorated in sensorium, and a repeat computed tomography (CT) of the brain showed diffuse cerebral edema with mass effect for which a left FTP decompressive craniectomy was performed. Over the next 2 days, the patient did not show any improvement in the neurological status, prompting us to repeat his CT head. The CT scan showed dilated ventricles for which an external ventricular drainage was instituted. The patient, however, continued to deteriorate and finally succumbed to the illness on the 8th postoperative day. Invasive fungal infection involving the central nervous system (CNS) is often fulminant and fatal with a reported mortality of nearly 100% in the older literature. This disease was described as “almost always a clinical surprise” by Nadkarni and Goel.[4] These cases present an interesting diagnostic dilemma for the neurosurgeons and neuroradiologists, as neither the clinical nor the imaging features of CNS fungal infections are truly diagnostic of the disease and with the patient being immuno‑competent, the possibility of fungal infection is seldom considered in the list of clinical differentials.[5] Cerebral parenchymal lesions can range from fungal granuloma, diffuse cerebritis to frank abscess formation. A sinonasal disease with intracranial extension is the most frequent presentation although isolated parenchymal lesions without evidence of any sinonasal involvement are not infrequent. They usually present as an heterogenous signal intensity lesion on T1WI and T2WI images, often showing areas of diffusion restriction within. Because of rarity of the lesion and its non‑specific imaging findings, most cases are often confused with tumors and infarcts. In our case, involvement of one whole hemisphere mimicked gliomatosis cerebri; hence, we named it as “fungimitosis.” Impaired/poor nutritional status, injudicious use of steroids or antituberculous drugs, and parasitic infections are all considered as predisposing factors for fungal infections.[6,7]
Neurology India / May 2015 / Volume 63 / Issue 3
439
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Letters to Editor
a
d
c
b
e
f
Figure 1: Magnetic resonance imaging of the brain showing a lesion which is hypointense on T1W images (a) and hyperintense on T2W and fluid attenuation inversion recovery images (b and c) involving the left frontal, temporal, and parietal regions with patchy enhancement on contrast imaging (d, e, f)
Though no specific guidelines are available, early aggressive surgery followed by aggressive empirical antifungal therapy appears to be a reasonable approach considering the remarkable invasiveness of Aspergillus and its potential complications.[8] The patients with CNS Aspergillosis often show a peculiar response to surgery characterized by a disease flare up which may at times be fulminant and refractory to the medical management. The reason for this unique stormy postoperative course is incompletely understood but immunocompromise secondary to surgery and/or the stimulation of previously quiescent fungi due to surgical tissue handling have been proposed as the offending factors.[9,10] Aspergillus infection may uncommonly cause cerebral vasculitis leading to thrombosis of vessels and large infarcts which may contribute to the poor outcome after surgery.[6] Hence, it is not surprising that the prognosis of CNS aspergillosis is mostly unfavourable To conclude, CNS Aspergillus infection, although rare, can affect immunocompetent individuals. The protean clinical manifestations as well as diffuse brain parenchymal involvement may lead to a diagnostic dilemma. Although the prognosis remains largely poor, an early diagnosis and radical surgical management followed by aggressive antifungal chemotherapy may help to improve the outcome.
Alugolu Rajesh, Srikant Reddy, Malladi Venkat Surya Subbalaxmi1, Megha Shantveer Uppin2 440
Departments of Neurosurgery, 1Medicine and 2Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Telangana, India E‑mail: [email protected]
References 1.
Kothari M, Goel A. Fungi: Too evolved to be condemned. Neurol India 2007;55:189‑90. 2. Saravia‑Gomez J. Aspergillosis of the central nervous system. In: Vinken PJ, Bruyn GW, editors. Handbook of Clinical Neurology. Vol. 35. Holland: North‑Holland Publishing Company; 1978. p. 395‑400. 3. Sharma RR, Gurusinghe NT, Lynch PG. Cerebral infarction due to Aspergillus arteritis following glioma surgery. Br J Neurosurg 1992;6:485‑90. 4. Nadkarni T, Goel A. Aspergilloma of the brain: An overview. J Postgrad Med 2005;51 Suppl 1:S37‑41. 5. Saini J, Gupta AK, Jolapara MB, Chatterjee S, Pendharkar HS, Kesavadas C, et al. Imaging findings in intracranial Aspergillus infection in immunocompetent patients. World Neurosurg 2010;74:661‑70. 6. Murthy JM. Fungal infections of the central nervous system: The clinical syndromes. Neurol India 2007;55:221‑5. 7. Kim DG, Hong SC, Kim HJ, Chi JG, Han MH, Choi KS, et al. Cerebral aspergillosis in immunologically competent patients. Surg Neurol 1993;40:326‑31. 8. Murthy J. Central nervous system mycoses: The challenges. Neurol India 2007;55:187‑8. 9. Nadkarni TD, Desai KI, Muzumdar D, Goel A, Shenoy A. Ischaemic complications after surgical resection of intracranial aspergilloma. J Clin Neurosci 2003;10:500‑2. 10. Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VS, Panigrahi M, et al. Pathology of fungal infections of the central nervous system: 17 years’ experience from Southern India. Histopathology 2006;49:396‑405.
Neurology India / May 2015 / Volume 63 / Issue 3
[Downloaded free from http://www.neurologyindia.com on Tuesday, June 09, 2015, IP: 61.16.135.116]
Letters to Editor
systemic examination did not reveal any abnormality. A noncontrast cranial CT showed a sharply delineated fat attenuation lesion within the quadrigeminal plate and extending into the cistern on the right side with focal cisternal widening [Figure 2a and b]. An MRI study confirmed the presence of a focal lesion within the quadrigeminal cistern. The lesion demonstrated marked hyperintensity on T1‑weighted (T1W) images with relatively less hyperintensity on T2‑weighted (T2W) images with suppression of signal on short T1 inversion recovery (STIR) sequence confirming the fatty nature of the lesion [Figure 2c‑f]. No other intracranial abnormality was noted.
Access this article online Quick Response Code
Website: www.neurologyindia.com DOI: 10.4103/0028-3886.158250 PMID: xxxxx
Quadrigeminal cistern lipoma revisited
The third case, a 42‑year‑old female, presented with recurrent episodes of severe headache of 4 months duration and being previously treated with the clinical diagnosis of migraine. Her general and neurological examination was normal. An MRI of the brain was performed which showed a small focus of fat signal intensity within the quadrigeminal cistern. The lesion was hyperintense on T1W images, with relatively less hyperintensity on T2W and fluid‑attenuated inversion recovery images, with no mass effect or ventricular dilatation [Figure 3a‑c]. No other abnormal findings were noted.
Sir, We wish to share our experience with three cases of quadrigeminal cistern lipomas, all of whom were discovered incidentally during computed tomography/magnetic resonance imaging (CT/MRI) examination of patients for related or unrelated conditions. The first case, a 31‑year‑old male, presented with a history of minor head injury with no loss of consciousness, convulsions or vomiting. A noncontrast cranial CT study was performed which revealed a fat attenuation lesion on the left side of the quadrigeminal cistern [Figure 1]. No other intracranial pathology was detected.
All the three patients did not require any surgical intervention and were managed conservatively. They are on a regular follow‑up. Intracranial lipomas are neither tumors nor hamartomas. They represent developmental anomalies resulting from abnormal
The second case, a 36‑year‑old male, presented with recurrent headache and dizziness. His neurological and
a
b
Figure 1: (a and b) Axial computed tomography scan shows a fat attenuation lesion in the left quadrigeminal cistern suggestive of a lipoma
Neurology India / May 2015 / Volume 63 / Issue 3
441
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
