The Neuroradiology Journal 20: 525-530, 2007
www. centauro. it
Imaging of Isolated Cerebral Mucormycosis. A Report of Three Cases
H. CUELLAR*, R. RIASCOS**, E. PALACIOS***, R. ROJAS****, P. MOLINA***** * Department of Endovascular Therapy , Interventional Neuroradiology Fellow, Clinica Nuestra Señora del Rosario; Madrid, España ** Department of Radiology, The University of Texas Medical Branch; Galveston, TX, USA *** Department of Neuroradiology, Tulane University; New Orleans, LA, USA **** Department Neuroradiology, Beth Israel Deaconess Medical Center, Boston, MA, USA ***** Internal Medicine Resident, Geisinger Medical Center; Danville, PA, USA
Key words: mucormycosis, cerebral mycosis, isolated mucormycosys, MR imaging
SUMMARY – Mucormycosis is a rare infection in immunosupressed patients caused by fungi from the family Mucoraceae. Three types of disease spread have been described: rhinocerebral, systemic and isolated. Isolated spread is the most uncommon form, usually resulting in death. It has been described in diabetics, immunosupressed patients and intravenous drug abusers. Neuroimaging can aid the diagnosis of this entity, but biopsy remains the only reliable method. Imaging findings of Mucormycosis include abscesses and hemorrhagic or ischemic infarcts, usually in the basal ganglia and frontal lobes. Single or multiple lesions have been described as well as meningoencephalitis. Understanding these findings can help to detect the infection in an early stage. We describe three cases of isolated cerebral mucormycosis; all of them were intravenous drug abusers with one patient also being HIV positive.
Introduction Mucormycosis is the term used to describe infections caused by several genera of the family Mucoraceae. The genera Absidia sp., Rhizopus sp., Mortierella sp. and Mucor sp., are the predominant pathogens 1,2, Rhizopus being the most commonly identified 3. These ubiquitous organisms are found in bread, fruits, soil and as a normal human nasal flora 4. Mucormycosis usually occurs in patients with predisposing factors such as diabetes mellitus, ketoacidosis, hematological malignancies and immunosuppressive entities like leukemia, lymphoma and glucocorticoid or chemotherapeutic treatments. Infection in otherwise healthy persons is extremely rare 2,5. Mucormycosis has two described inoculation pathways: a) inhalation of spores which is followed by colonization of the nasal and oral mucosa or passed into the lungs producing the rhinocerebral or systemic presentation, and b) hematogenous spread to different organs in the body.
The brain can be affected in either form 6. These fungi are very invasive and have a predilection for blood vessels where they produce a fibrin reaction that can result in vascular occlusion, ischemia, infarction, rapid spread and tissue necrosis 7,8. One case of nosocomial mucormycosis in a newborn secondary to an indwelling jugular canula has also been reported 9. We describe three cases of isolated cerebral mucormycosis in intravenous drug abusers. All presented with acute neurological deficit and progressed rapidly to death, only one patient was diagnosed pre-mortem with cerebral mucormycosis. Case 1
A 25-year-old male with history of intravenous drug abuse presented with acute neurological deficit. At admission a CT showed a hypodense lesion on the right basal ganglia with a small central high density zone on the putamen and slight mass effect (figure 1A). Initial diagnosis was acute infarction versus cerebritis probably secondary to meningitis or 525
Imaging of Isolated Cerebral Mucormycosis
A
H. Cuellar
B
C
Figure 1 A) CT axial image showing loss of gray-white matter differentiation with edema in the right basal ganglia, a hyper dense lesion is seen in the external capsule and lateral margin of the lenticular nucleus. B,C) Axial MR. FLAIR and T2WI respectively. Hyperintense lesion with heterogeneous signal and peripheral edema demonstrated as a higher signal zone in the lateral margin of the lesion on the right. Also hyperintensity of the caudate nucleus on the left demonstrating that it is also involved.
vasculitis. Subsequently an MR was performed (figure 1B and 1C). The patient evolved rapidly into a severe neurological deficit and cardiorespiratory failure and died within a week of admission. 526
Case 2
A 31-year-old female intravenous drug abuser and HIV positive also presented with acute neurological deficit.
www. centauro. it
A
The Neuroradiology Journal 20: 525-530, 2007
B
C
Figure 2 A,B) Axial MR T2WI and FLAIR. Bilateral hyperintensity of the basal ganglia, corresponding to edema. Also note the important mass effect. C) Post- contrast T1WI showing multiple rim enhancing lesions bilaterally more prominent on the left basal ganglia.
An MR was performed at admission, showing bilateral heterogeneous lesions on the basal ganglia more prominent on the left side (figure 2). These findings were considered nonspecific
with the diagnosis of a necrotic and hemorrhagic process of inflammatory origin. Lumbar puncture was negative for cultures of bacteria, virus, fungi and acid-alcohol resistant bacilli. Medical treatment was initiated immedi527
Imaging of Isolated Cerebral Mucormycosis
A
H. Cuellar
B
C
Figure 4 Coronal cut of the autopsy specimen of case 3 showing bilateral inflammatory lesions more prominent on the left side. Bilateral septic hemorrhagic infarcts were demonstrated with the presence of necrosis, hemorrhagic encephalitis and abscess formation, secondary to inflammatory vasculopathy in the presence of primary cerebral mucormycosis. p Figure 3 A) Coronal MR image. T1W1. Bilateral hypointense lesions are seen more prominent on the left side with hyperintense foci of petechial hemorrhage. B) Coronal MR image. T1WI after contrast administration. Same lesions as (A) showing rim enhancement. C) Coronal MR image. T2WI. Hyperintense bilateral lesions in the same patient with important mass effect on the left side.
ately with cloramfenicol and penicillin and because of the probable autoimmune origin of the disease steroids were also given. This patient presented transtentorial herniation and died shortly afterwards. 528
Case 3
A 22-year-old female intravenous drug abuser presented at admission with fever and neurological deficit. Clinical suspicion for a cerebral
www. centauro. it
The Neuroradiology Journal 20: 525-530, 2007
abscess led us to perform an MR which showed multiple lesions on the basal ganglia bilaterally with peripheral enhancement more prominent on the left (figure 3). Medical treatment was initiated with cefotaxime, dexamethasone, metronidazol and mannitol. Later, acyclovir was also added in the suspicion that findings could correspond to herpetic encephalitis. The patient continued to deteriorate and in the absence of a clear diagnosis a stereotactic cerebral biopsy was performed. Microscopic study showed nonseptated hyphae that corresponded to a zygomycete. This led to initiate treatment with amphotericin B and dexamethasone. Despite all efforts the patient continued to deteriorate and died. In all three cases the anatomopathologic study of the brain showed extensive areas of hemorrhagic encephalitis on the basal ganglia and inflammatory thrombosis with non-septated hyphae of mucormycosis in the necrotic zone (figure 4).
20
Discussion
The diagnosis of this aggressive fungal infection is difficult in the immunocompromised patient. Imaging and laboratory findings are not specific and there are no available serological or PCR-based diagnostic tests for the diagnosis of mucormycosis 13. Biopsy remains the only reliable method for the diagnosis of this disease. Findings include large non-septated hyphae which are observed using specific staining techniques in samples taken from necrotic tissue or the borders of necrotic and viable tissue 4,5. Growing the organism in culture is very difficult: usually, specimen samples obtained from paranasal tissues grow more easilt than those obtained directly from the brain lesions 3. Imaging findings of mucormycosis include abscesses and hemorrhagic or ischemic infarcts usually in the basal ganglia and frontal lobes and probably due to thrombosis secondary to a vasculitic process 1,2,5,20,22,23. Single or multiple lesions have been described as well as meningoencephalitis 2. CNS involvement can be evident on head CT as a low density mass with or without peripheral enhancement as it has been seen in severely neutropenic patients [13]. MR images can demonstrate hypointense confluent lesions on T1 and T2-weighted images with peripheral enhancement and a predilection for the basal ganglia, thalamus and midbrain. These findings are nonspecific and may be related to coagulative necrosis and accumulation of paramagnetic materials from hemoglobin. Proton MR spectroscopy, although nonspecific, demonstrates
Cerebral involvement has been described in three forms, rhinocerebral, systemic and isolated mucormycosis. Rhinocerebral mucormycosis is by far the most common form. The brain and meninges are secondarily affected by direct extension through the cribiform plate, superior orbital fissure or basal foramina. Penetration of the cavernous sinus and the internal carotid artery may also occur 4,10. The systemic form of mucormycosis usually starts in the lungs and progresses hematogenously to other organs 2. Isolated cerebral mucormycosis is a rare and frequently fatal entity that does not affect the sinuses, but results from hematogenous dissemination of fungi. It has been described in intravenous drug abusers, penetrating head trauma and surgical patients 2,5. In 1970, Hameroff et Al described the association between mucormycosis and IV drug use 11. Due to the rising number of IV drug abusers, there has been an increased prevalence of this presentation of disease 2,5,12-19. Isolated cerebral mucormycosis is an uncommon presentation of this fungal infection, having a high mortality rate 18 and a predilection for diabetics, immunocompromised patients and IV drug abusers. IV drug abuse is the most important of these risk factors, as the vasoconstrictor effect of illicit drugs sensitizes the vasculature to damage. The cerebral presentation could be facilitated by the synergic effect of the association between amphetamines and Mucor
. The hypothesized causes of infection include previous contamination of the needle by the organism or direct inoculation in a patient with a cutaneous infection, added to the use of drugs that have a vasoconstrictor effect 20,21. There are no gender, age or associated conditions associated with this condition, but a higher incidence has been described in patients under steroid therapy. HIV infection is not considered a risk factor by itself 18. Cerebral involvement is secondary to hematogenous spread and is associated with suppurative lesions 21. These patients can present with altered mental status, seizures and focal neurologic signs secondary to vascular occlusion and infarction or abscess formation 6. Alternatively, symptoms may be related to meningitis or meningoencephalitis including headache, ophthalmoplegia, gait abnormalities, hemiparesis or psychiatric symptoms 2,3. Diagnosis
529
Imaging of Isolated Cerebral Mucormycosis
elevation of the lactate peak and resonances compatible with succinate, acetate and alanine, and the depletion of N-acetyl aspartate, creatine and myo-inositol, findings resembling those of bacterial abscesses 24. Siegal et Al described cerebral mucormycosis to have the classical spectroscopic findings of bacterial lesion although without the commonly found aminoacid resonance 24. The rapid progression of this entity and its difficult early diagnosis leads to an increased number of post-mortem diagnoses. Management The treatment of cerebral mucormycosis includes early diagnosis, early and radical surgical debridement and antifungal therapy mainly based on the use of amphotericin B 2,7. Lipid formulations of amphotericin B have been investigated in the treatment of mucormycosis without conclusive results 2,7. Intrathecal amphoter-
H. Cuellar
icin B has also been used with contradictory results. In patients with resistance to amphotericin B, ketoconazol has been used with good results. Hyperbaric oxygen and immunostimulating medications have been used with varying success 6. Mortality is as high as 70% for the rhinocerebral form of mucormycosis and near 100% for the disseminated form 7,25. Conclusions Early diagnosis of isolated cerebral mucomycosis is difficult. Biopsy remains as the only reliable diagnostic tool, but neuroimaging can aid in early detection and management of this condition which can lead to a non-fatal prognosis. Isolated cerebral mucormycosis is seen in intravenous drug users secondary to vascular inoculation of the pathogen possibly acting in synergy with the vasoconstrictive effects of the substance of abuse.
References 1 Bauer H et Al: Cerebral mucormycosis: pathogenesis of the disease; description of the fungus, Rhizopus oryzae, isolated from a fatal case. Am J Med 18: 822-31, 1955. 2 Zarei M et Al: Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma. Eur J Neurol 7: 443-7, 2000. 3 Fong KM, Seneviratne EM, McCormack JG: Mucor cerebral abscess associated with intravenous drug abuse. Aust N Z J Med 20: 74-7, 1990. 4 Hendrickson RG, Olshaker J, Duckett O: Rhinocerebral mucormycosis: a case of a rare, but deadly disease. J Emerg Med 17: 641-5, 1999. 5 Cook BA et Al: Survival after isolated cerebral mucormycosis. Am J Pediatr Hematol Oncol 11: 330-3, 1989. 6 Nussbaum ES, Hall WA: Rhinocerebral mucormycosis: changing patterns of disease. Surg Neurol 41: 152-6, 1994. 7 Al-Abdely HM: Management of rare fungal infections. Curr Opin Infect Dis 17: 527-32, 2004. 8 Gonzalez CE, Rinaldi MG, Sugar AM: Zygomycosis. Infect Dis Clin North Am 16: 895-914, 2002. 9 Marchevsky AM, et Al: The changing spectrum of disease, etiology, and diagnosis of mucormycosis. Hum Pathol 11: 457-64, 1980. 10 Calli C et Al: Isolated pontine infarction due to rhinocerebral mucormycosis. Neuroradiology 41: 179-81, 1999. 11 Hameroff SB, Eckholdt JW, Lindenberg R: Cerebral phycomycosis in a heroin addict. Neurology 20: 261-5, 1970. 12 Birchall D, Leong WK, McAuliffe W: Cerebral mucormycosis. J Neurol Neurosurg Psychiatry 66: 404-5, 1999. 13 Eucker J et Al: Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis. Infection 28: 246-50, 2000. 14 Gollard R et Al: Isolated cerebral mucormycosis: case report and therapeutic considerations. Neurosurgery 34: 174-7, 1994. 15 Inamasu J et Al: Basilar artery occlusion due to mu-
530
16 17 18 19 20 21 22 23 24 25
cormycotic emboli, preceded by acute hydrocephalus. Clin Neurol Neurosurg 102: 18-22, 2000. Kasantikul V, Shuangshoti S, Taecholarn C: Primary phycomycosis of the brain in heroin addicts. Surg Neurol 28: 468-72, 1987. Ostrow TD, Hudgins PA: Magnetic resonance imaging of intracranial fungal infections. Top Magn Reson Imaging 6: 22-31, 1994. Siddiqi SU, Freedman JD: Isolated central nervous system mucormycosis. South Med J 87: 997-1000, 1994. Smirniotopoulos JG et Al: Neuroimaging--autopsy correlations in AIDS. Neuroimaging Clin N Am 7: 615-37, 1997. Micozzi MS, Wetli CV: Intravenous amphetamine abuse, primary cerebral mucormycosis, and acquired immunodeficiency. J Forensic Sci 30: 504-10, 1985. Escobar A, Del Brutto OH: Multiple brain abscesses from isolated cerebral mucormycosis. J Neurol Neurosurg Psychiatry 53: 431-3, 1990. Masucci EF et Al: Cerebral mucormycosis (Phycomycosis) in a heroin addict. Arch Neurol 39: 304-6, 1982. Whelan MA, Stern J, deNapoli RA: The computed tomographic spectrum of intracranial mycosis: correlation with histopathology. Radiology 141: 703-7, 1981. Siegal JA et Al: Cerebral mucormycosis: proton MR spectroscopy and MR imaging. Magn Reson Imaging 18: 915-20, 2000. Adam RD et Al: Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 19: 67-76, 1994.
H. Cuellar, MD Department of Endovascular and Percutaneous Treatment Clinica Nuestra Señora del Rosario Principe de Vergara 53 28006 Madrid, Spain Tel.: +34 918 374411 Fax: +34 918 374411 E-mail: [email protected]
www. centauro. it
Imaging of Isolated Cerebral Mucormycosis. A Report of Three Cases
H. CUELLAR*, R. RIASCOS**, E. PALACIOS***, R. ROJAS****, P. MOLINA***** * Department of Endovascular Therapy , Interventional Neuroradiology Fellow, Clinica Nuestra Señora del Rosario; Madrid, España ** Department of Radiology, The University of Texas Medical Branch; Galveston, TX, USA *** Department of Neuroradiology, Tulane University; New Orleans, LA, USA **** Department Neuroradiology, Beth Israel Deaconess Medical Center, Boston, MA, USA ***** Internal Medicine Resident, Geisinger Medical Center; Danville, PA, USA
Key words: mucormycosis, cerebral mycosis, isolated mucormycosys, MR imaging
SUMMARY – Mucormycosis is a rare infection in immunosupressed patients caused by fungi from the family Mucoraceae. Three types of disease spread have been described: rhinocerebral, systemic and isolated. Isolated spread is the most uncommon form, usually resulting in death. It has been described in diabetics, immunosupressed patients and intravenous drug abusers. Neuroimaging can aid the diagnosis of this entity, but biopsy remains the only reliable method. Imaging findings of Mucormycosis include abscesses and hemorrhagic or ischemic infarcts, usually in the basal ganglia and frontal lobes. Single or multiple lesions have been described as well as meningoencephalitis. Understanding these findings can help to detect the infection in an early stage. We describe three cases of isolated cerebral mucormycosis; all of them were intravenous drug abusers with one patient also being HIV positive.
Introduction Mucormycosis is the term used to describe infections caused by several genera of the family Mucoraceae. The genera Absidia sp., Rhizopus sp., Mortierella sp. and Mucor sp., are the predominant pathogens 1,2, Rhizopus being the most commonly identified 3. These ubiquitous organisms are found in bread, fruits, soil and as a normal human nasal flora 4. Mucormycosis usually occurs in patients with predisposing factors such as diabetes mellitus, ketoacidosis, hematological malignancies and immunosuppressive entities like leukemia, lymphoma and glucocorticoid or chemotherapeutic treatments. Infection in otherwise healthy persons is extremely rare 2,5. Mucormycosis has two described inoculation pathways: a) inhalation of spores which is followed by colonization of the nasal and oral mucosa or passed into the lungs producing the rhinocerebral or systemic presentation, and b) hematogenous spread to different organs in the body.
The brain can be affected in either form 6. These fungi are very invasive and have a predilection for blood vessels where they produce a fibrin reaction that can result in vascular occlusion, ischemia, infarction, rapid spread and tissue necrosis 7,8. One case of nosocomial mucormycosis in a newborn secondary to an indwelling jugular canula has also been reported 9. We describe three cases of isolated cerebral mucormycosis in intravenous drug abusers. All presented with acute neurological deficit and progressed rapidly to death, only one patient was diagnosed pre-mortem with cerebral mucormycosis. Case 1
A 25-year-old male with history of intravenous drug abuse presented with acute neurological deficit. At admission a CT showed a hypodense lesion on the right basal ganglia with a small central high density zone on the putamen and slight mass effect (figure 1A). Initial diagnosis was acute infarction versus cerebritis probably secondary to meningitis or 525
Imaging of Isolated Cerebral Mucormycosis
A
H. Cuellar
B
C
Figure 1 A) CT axial image showing loss of gray-white matter differentiation with edema in the right basal ganglia, a hyper dense lesion is seen in the external capsule and lateral margin of the lenticular nucleus. B,C) Axial MR. FLAIR and T2WI respectively. Hyperintense lesion with heterogeneous signal and peripheral edema demonstrated as a higher signal zone in the lateral margin of the lesion on the right. Also hyperintensity of the caudate nucleus on the left demonstrating that it is also involved.
vasculitis. Subsequently an MR was performed (figure 1B and 1C). The patient evolved rapidly into a severe neurological deficit and cardiorespiratory failure and died within a week of admission. 526
Case 2
A 31-year-old female intravenous drug abuser and HIV positive also presented with acute neurological deficit.
www. centauro. it
A
The Neuroradiology Journal 20: 525-530, 2007
B
C
Figure 2 A,B) Axial MR T2WI and FLAIR. Bilateral hyperintensity of the basal ganglia, corresponding to edema. Also note the important mass effect. C) Post- contrast T1WI showing multiple rim enhancing lesions bilaterally more prominent on the left basal ganglia.
An MR was performed at admission, showing bilateral heterogeneous lesions on the basal ganglia more prominent on the left side (figure 2). These findings were considered nonspecific
with the diagnosis of a necrotic and hemorrhagic process of inflammatory origin. Lumbar puncture was negative for cultures of bacteria, virus, fungi and acid-alcohol resistant bacilli. Medical treatment was initiated immedi527
Imaging of Isolated Cerebral Mucormycosis
A
H. Cuellar
B
C
Figure 4 Coronal cut of the autopsy specimen of case 3 showing bilateral inflammatory lesions more prominent on the left side. Bilateral septic hemorrhagic infarcts were demonstrated with the presence of necrosis, hemorrhagic encephalitis and abscess formation, secondary to inflammatory vasculopathy in the presence of primary cerebral mucormycosis. p Figure 3 A) Coronal MR image. T1W1. Bilateral hypointense lesions are seen more prominent on the left side with hyperintense foci of petechial hemorrhage. B) Coronal MR image. T1WI after contrast administration. Same lesions as (A) showing rim enhancement. C) Coronal MR image. T2WI. Hyperintense bilateral lesions in the same patient with important mass effect on the left side.
ately with cloramfenicol and penicillin and because of the probable autoimmune origin of the disease steroids were also given. This patient presented transtentorial herniation and died shortly afterwards. 528
Case 3
A 22-year-old female intravenous drug abuser presented at admission with fever and neurological deficit. Clinical suspicion for a cerebral
www. centauro. it
The Neuroradiology Journal 20: 525-530, 2007
abscess led us to perform an MR which showed multiple lesions on the basal ganglia bilaterally with peripheral enhancement more prominent on the left (figure 3). Medical treatment was initiated with cefotaxime, dexamethasone, metronidazol and mannitol. Later, acyclovir was also added in the suspicion that findings could correspond to herpetic encephalitis. The patient continued to deteriorate and in the absence of a clear diagnosis a stereotactic cerebral biopsy was performed. Microscopic study showed nonseptated hyphae that corresponded to a zygomycete. This led to initiate treatment with amphotericin B and dexamethasone. Despite all efforts the patient continued to deteriorate and died. In all three cases the anatomopathologic study of the brain showed extensive areas of hemorrhagic encephalitis on the basal ganglia and inflammatory thrombosis with non-septated hyphae of mucormycosis in the necrotic zone (figure 4).
20
Discussion
The diagnosis of this aggressive fungal infection is difficult in the immunocompromised patient. Imaging and laboratory findings are not specific and there are no available serological or PCR-based diagnostic tests for the diagnosis of mucormycosis 13. Biopsy remains the only reliable method for the diagnosis of this disease. Findings include large non-septated hyphae which are observed using specific staining techniques in samples taken from necrotic tissue or the borders of necrotic and viable tissue 4,5. Growing the organism in culture is very difficult: usually, specimen samples obtained from paranasal tissues grow more easilt than those obtained directly from the brain lesions 3. Imaging findings of mucormycosis include abscesses and hemorrhagic or ischemic infarcts usually in the basal ganglia and frontal lobes and probably due to thrombosis secondary to a vasculitic process 1,2,5,20,22,23. Single or multiple lesions have been described as well as meningoencephalitis 2. CNS involvement can be evident on head CT as a low density mass with or without peripheral enhancement as it has been seen in severely neutropenic patients [13]. MR images can demonstrate hypointense confluent lesions on T1 and T2-weighted images with peripheral enhancement and a predilection for the basal ganglia, thalamus and midbrain. These findings are nonspecific and may be related to coagulative necrosis and accumulation of paramagnetic materials from hemoglobin. Proton MR spectroscopy, although nonspecific, demonstrates
Cerebral involvement has been described in three forms, rhinocerebral, systemic and isolated mucormycosis. Rhinocerebral mucormycosis is by far the most common form. The brain and meninges are secondarily affected by direct extension through the cribiform plate, superior orbital fissure or basal foramina. Penetration of the cavernous sinus and the internal carotid artery may also occur 4,10. The systemic form of mucormycosis usually starts in the lungs and progresses hematogenously to other organs 2. Isolated cerebral mucormycosis is a rare and frequently fatal entity that does not affect the sinuses, but results from hematogenous dissemination of fungi. It has been described in intravenous drug abusers, penetrating head trauma and surgical patients 2,5. In 1970, Hameroff et Al described the association between mucormycosis and IV drug use 11. Due to the rising number of IV drug abusers, there has been an increased prevalence of this presentation of disease 2,5,12-19. Isolated cerebral mucormycosis is an uncommon presentation of this fungal infection, having a high mortality rate 18 and a predilection for diabetics, immunocompromised patients and IV drug abusers. IV drug abuse is the most important of these risk factors, as the vasoconstrictor effect of illicit drugs sensitizes the vasculature to damage. The cerebral presentation could be facilitated by the synergic effect of the association between amphetamines and Mucor
. The hypothesized causes of infection include previous contamination of the needle by the organism or direct inoculation in a patient with a cutaneous infection, added to the use of drugs that have a vasoconstrictor effect 20,21. There are no gender, age or associated conditions associated with this condition, but a higher incidence has been described in patients under steroid therapy. HIV infection is not considered a risk factor by itself 18. Cerebral involvement is secondary to hematogenous spread and is associated with suppurative lesions 21. These patients can present with altered mental status, seizures and focal neurologic signs secondary to vascular occlusion and infarction or abscess formation 6. Alternatively, symptoms may be related to meningitis or meningoencephalitis including headache, ophthalmoplegia, gait abnormalities, hemiparesis or psychiatric symptoms 2,3. Diagnosis
529
Imaging of Isolated Cerebral Mucormycosis
elevation of the lactate peak and resonances compatible with succinate, acetate and alanine, and the depletion of N-acetyl aspartate, creatine and myo-inositol, findings resembling those of bacterial abscesses 24. Siegal et Al described cerebral mucormycosis to have the classical spectroscopic findings of bacterial lesion although without the commonly found aminoacid resonance 24. The rapid progression of this entity and its difficult early diagnosis leads to an increased number of post-mortem diagnoses. Management The treatment of cerebral mucormycosis includes early diagnosis, early and radical surgical debridement and antifungal therapy mainly based on the use of amphotericin B 2,7. Lipid formulations of amphotericin B have been investigated in the treatment of mucormycosis without conclusive results 2,7. Intrathecal amphoter-
H. Cuellar
icin B has also been used with contradictory results. In patients with resistance to amphotericin B, ketoconazol has been used with good results. Hyperbaric oxygen and immunostimulating medications have been used with varying success 6. Mortality is as high as 70% for the rhinocerebral form of mucormycosis and near 100% for the disseminated form 7,25. Conclusions Early diagnosis of isolated cerebral mucomycosis is difficult. Biopsy remains as the only reliable diagnostic tool, but neuroimaging can aid in early detection and management of this condition which can lead to a non-fatal prognosis. Isolated cerebral mucormycosis is seen in intravenous drug users secondary to vascular inoculation of the pathogen possibly acting in synergy with the vasoconstrictive effects of the substance of abuse.
References 1 Bauer H et Al: Cerebral mucormycosis: pathogenesis of the disease; description of the fungus, Rhizopus oryzae, isolated from a fatal case. Am J Med 18: 822-31, 1955. 2 Zarei M et Al: Acute isolated cerebral mucormycosis in a patient with high grade non-Hodgkins lymphoma. Eur J Neurol 7: 443-7, 2000. 3 Fong KM, Seneviratne EM, McCormack JG: Mucor cerebral abscess associated with intravenous drug abuse. Aust N Z J Med 20: 74-7, 1990. 4 Hendrickson RG, Olshaker J, Duckett O: Rhinocerebral mucormycosis: a case of a rare, but deadly disease. J Emerg Med 17: 641-5, 1999. 5 Cook BA et Al: Survival after isolated cerebral mucormycosis. Am J Pediatr Hematol Oncol 11: 330-3, 1989. 6 Nussbaum ES, Hall WA: Rhinocerebral mucormycosis: changing patterns of disease. Surg Neurol 41: 152-6, 1994. 7 Al-Abdely HM: Management of rare fungal infections. Curr Opin Infect Dis 17: 527-32, 2004. 8 Gonzalez CE, Rinaldi MG, Sugar AM: Zygomycosis. Infect Dis Clin North Am 16: 895-914, 2002. 9 Marchevsky AM, et Al: The changing spectrum of disease, etiology, and diagnosis of mucormycosis. Hum Pathol 11: 457-64, 1980. 10 Calli C et Al: Isolated pontine infarction due to rhinocerebral mucormycosis. Neuroradiology 41: 179-81, 1999. 11 Hameroff SB, Eckholdt JW, Lindenberg R: Cerebral phycomycosis in a heroin addict. Neurology 20: 261-5, 1970. 12 Birchall D, Leong WK, McAuliffe W: Cerebral mucormycosis. J Neurol Neurosurg Psychiatry 66: 404-5, 1999. 13 Eucker J et Al: Disseminated mucormycosis caused by Absidia corymbifera leading to cerebral vasculitis. Infection 28: 246-50, 2000. 14 Gollard R et Al: Isolated cerebral mucormycosis: case report and therapeutic considerations. Neurosurgery 34: 174-7, 1994. 15 Inamasu J et Al: Basilar artery occlusion due to mu-
530
16 17 18 19 20 21 22 23 24 25
cormycotic emboli, preceded by acute hydrocephalus. Clin Neurol Neurosurg 102: 18-22, 2000. Kasantikul V, Shuangshoti S, Taecholarn C: Primary phycomycosis of the brain in heroin addicts. Surg Neurol 28: 468-72, 1987. Ostrow TD, Hudgins PA: Magnetic resonance imaging of intracranial fungal infections. Top Magn Reson Imaging 6: 22-31, 1994. Siddiqi SU, Freedman JD: Isolated central nervous system mucormycosis. South Med J 87: 997-1000, 1994. Smirniotopoulos JG et Al: Neuroimaging--autopsy correlations in AIDS. Neuroimaging Clin N Am 7: 615-37, 1997. Micozzi MS, Wetli CV: Intravenous amphetamine abuse, primary cerebral mucormycosis, and acquired immunodeficiency. J Forensic Sci 30: 504-10, 1985. Escobar A, Del Brutto OH: Multiple brain abscesses from isolated cerebral mucormycosis. J Neurol Neurosurg Psychiatry 53: 431-3, 1990. Masucci EF et Al: Cerebral mucormycosis (Phycomycosis) in a heroin addict. Arch Neurol 39: 304-6, 1982. Whelan MA, Stern J, deNapoli RA: The computed tomographic spectrum of intracranial mycosis: correlation with histopathology. Radiology 141: 703-7, 1981. Siegal JA et Al: Cerebral mucormycosis: proton MR spectroscopy and MR imaging. Magn Reson Imaging 18: 915-20, 2000. Adam RD et Al: Mucormycosis: emerging prominence of cutaneous infections. Clin Infect Dis 19: 67-76, 1994.
H. Cuellar, MD Department of Endovascular and Percutaneous Treatment Clinica Nuestra Señora del Rosario Principe de Vergara 53 28006 Madrid, Spain Tel.: +34 918 374411 Fax: +34 918 374411 E-mail: [email protected]
