A 44-year-old man who had suffered from chest pain and persistent hemoptysis for about 2 months before being admitted to 103 Mliltary Hospital. During hospitalization, he developed symptoms of nervous injuries (disturbance of consciousness and right-sided paralysis) as well as imaging of a tumor in the left lateral ventricle on megnetic resonance imaging.
Journal of military pharmaco-medicine no6-2019 CASE REPORT: A PATIENT SUSPECTED OF HAVING CEREBRAL MUCORMYCOSIS AT 103 MILITARY HOSPITAL Tran Ngoc Dung1; Le Tran Anh2 Nguyen Thanh Bac1; Nguyen Van Ngoc1 SUMMARY A 44-year-old man who had suffered from chest pain and persistent hemoptysis for about months before being admitted to 103 Mliltary Hospital During hospitalization, he developed symptoms of nervous injuries (disturbance of consciousness and right-sided paralysis) as well as imaging of a tumor in the left lateral ventricle on megnetic resonance imaging He was diagnosed of fungal brain tumor, suspected of mucorales by discovering irregular non-septate hyphae on staining histological specimen after surgical debridement The patient died due to postoperative bleeding complication before taking antifungal drugs Cerebral mucormycosis is a rare disease and it is challenging to diagnose without tissue biopsy There is in need of adding fungal etiology in differential diagnosis in those patients to perform interventional procedures to collect specimens for accurate diagnosis and early treatment * Keywords: Cerebral mucormycosis; Fungi; Mucorales INTRODUCTION Mucorales is an order of Kingdom fungi, diviso Mucoromycota, class Mucoromycetes Mucorales are saprophytes, distributes widely in outdoor environment, but they can cause human diseases [11], the most popular are the spices of genus Rhizopus, Mucor, Absidia and Cunninghamella, in there, Phizopus oryzae spp is account for 70% of mucormycosis cases [13] Fungi can penetrate into body through respiratory or gastrointestinal tract or skin, causing the injuries in brain, lungs, stomach, skin or disseminated form [13] The incidence tends to increase, from 0.7 cases per million inhabitants in France in 1997 to that of 1.2 cases per million in 2006 [2] This was estimated about 910,000 cases per year worldwide [3] The highest incidence was recorded in India with 0.14 cases per 1,000 inhabitants, 80 times as many as these in developed countries [4] Mucormycosis is an opportunistic infection, commonly occurs in diabetes mellitus, burned, trauma and severely immunocompromised patients [13] Mucormycosis has high mortality rate, especially when creating brain injuries In 1980s, motarlity rate of cerebral mucormycosis was 100% [7] Nowadays, early diagnosis combination with surgery and amphoterian B treatment make this rate decrease to 50% [13] (Riley et al, 2016) 103 Military Hospital Vietnam Military Medical University Corresponding author: Nguyen Thanh Bac (bacnt103@gmail.com) Date received: 05/06/2019 Date accepted: 05/08/2019 208 Journal of military pharmaco-medicine no6-2019 Because of rare occurrence, atypical symptoms and challenging diagnosis Up to now, Vietnam had not had any reports of mucormycosis Herein, we would like to report a case of cerebral mucormycosis diagnosed and treated at 103 Military Hospital as a reference source for clinicians and epidemiologists CASE REPORT A 44-year-old-man, living in Dacnong province admitted to 103 Military Hospital on March 18th, 2019, discharged (requested by his own family) on April 19th, 2019 Discharge diagnosis: Deep coma due to ventricle bleeding and brainstem/left lateral ventricular cyst, performed microsurgical debridement in the 3rd day, chronic hepatitis B, atypical pneumonia in stabilized stage The patient had the medical history of alcoholism (200 mL/day in years) and irregularly controlled chronic hepatitis B In January 2019, he had symptoms of fever in the afternoon, night sweat, weight loss, accompanied with chest pain, persistent cough, sometimes coughing up small amount of dark blood He had had some examination in some southern hospitals (Choray Hospital, Hochiminh City Medicine and Pharmacy University Hospital) but they could not detect the diagnosis He was admitted to 103 Military Hospital on March 18th, 2019 in the state of wakefulness, dull chest pain, hemoptysis X-rays and CT-scan showed many disseminated bright spots in lungs The treatment with antibiotics, hemostasis and expectorants were made A next CT-scan on March 28th revealed pulmonary injuries mostly disappeared (few spots remained) However, he developed symptoms of nervous injuries: clouding of consciousness, disorientation of person, time and space Cerebrospinal fluid test (March 28th) showed slightly opaque fluid, cell count 20 cell/mL with 93% lymphocytes Antibodies against toxocara were detected by ELISA blood test (OD = 0.814) The patient was diagnosed of multiple brain and lung injuries, suspected by metastasis/hepatitis B virus cirrhosis, differentially diagnosed of parasitic brain and lung injuries Albendazole (800 mg/day) was indicated CT-scan (April 1st) detected a cyst in the left lateral ventricle (Fig 1) After that, the patient was transferred to Department of Neurological Surgery in the state of difficult contact (Glasgow 12 - 13 points), right-sided paralysis, anemia, coagulation disorder (blood test on April 16th) showed the following values: Red blood cell count 3.67 x 1012/L, hemoglobin: 122 g/L, hematocrit: 0.355 l/L, white blood cell count 107 x 109/L, PT (%): 56%, PT(s): 18.3) On April 17th, 2019, the microsurgical debridement was presented by anterior interhemispheric craniotomy throughout corpus callosum into the left lateral ventricle, revealing a fluffy white tumor (like cotton candy), no feeding arteries, 2.0 x 1.5 cm in size That tumor had thin wall and stuck to the anterior wall of the left lateral ventricle and spread to the foramen of Monro Next, the tumor was removed and a ventricular drain was setup On April 18th, 2019, he woke up and obeyed commands well, breathed on his own The tracheostomy tube was removed then On April 19th, 2019, he was in coma (Glasgow points) CT-scan showed the imaging of bleeding fourth ventricle and 209 Journal of military pharmaco-medicine no6-2019 cyst Regardless of intensive treatment with hemostatic drugs, anti-cerebral edema measures, he could not recover and die on April 20th, 2019 Figure 1: Magnetic resonance imaging of the tumor in the left lateral ventricle Histopathology report showed many non-septate hyphae with irregular diameter, suspected of mucorales (Fig 2) Nevertheless, the culture technique was not done to identify accurately fungal species Figure 2: Imaging of hyphae on histological specimen 210 DISCUSSION Rhino-orbital-cerebral is the most common type of mucormycosis [6] In the cases without nose and sinus injury, fungi can move from a primary infection (lungs mostly) through the bloodstream into brain [8] Spores of mucorales have small size (average of 6.6 µm), low sedimentation rate so that they can spread easily in spite of light movement of air [12] Although there was no confirming evidence of pulmonary mucormycosis, initial respiratory symptoms suggested that These could explain why the definitive diagnosis had not been made by some big hospitals Also, we had difficulties in determining risk factors because he had no medical history of diabetes mellitus, drug injecting, immunocompromised state neither the risk factors of mucormycosis [6, 12] Bala K et al (2015) found that 24% of mucormycosis patients had no risk factors Diagnosis Diagnosis of mucormycosis is challenging due to the fact that mucorales are seldom isolated from blood or cerebrospinal fluid, as well as there is no reliable serum test to determine So, most of reports were based on results of issue biopsy [5] The typical imaging of mucorales on histological specimens is irregular hyphae (5 - 10 µm in diameter), having some septa or no septa at all The branch angle changes from 45 - 90o [10] These were suitable for the patient’s histological report, however, culture or molecular biology techniques must be done to identify precisely species [5] Journal of military pharmaco-medicine no6-2019 Treatment Fungal species of the order mucorales regularly respond weakly to antifungal drugs, excepting amphotericin B has the greatest in vitro activity against them [10] The current recommended treatment is the combination of antifungal drugs with surgery and risk factor treatment The preferred drug is amphotericin B, the alternative is posaconazole or isavuconazole in case of amphotericin B intolerance [13] Mucorales infection is specifically characterized by the invasion and issue necrosis, reducing the penetration of antifungal substances into infected issues Therefore, early surgical debridement can enhance survival rate [9] This patient was performed such surgery but did not take antifungal drugs timely and died due to surgical complications In general, invasive mucormycosis has poor prognosis and high mortality rate (50%) regardless of intensive treatment CONCLUSIONS We reported the case of the 44-yearsold patient having a brain fungal tumor, suspected of causative mucormycosis The patient had no specific risk factors and initiated with respiratory symptoms, following by nervous injury (disturbance of consciousness and right-sided paralysis) Magnetic resonance imaging revealed a tumor in a lateral ventricle The diagnosis of fungal infection was made only if the surgical debridement was performed to collect specimen to stain The histological report showed the irregular and nonseptate hyphae, considering mucorales The patient died as a consequence of postoperative bleeding complication before taking antifungal drugs Cerebral mucormycosis is a rare infection with difficult diagnosis without biopsy By presenting this case report, we would like to point out that causative fungi should be included in the patients having brain tumors to present interventional procedures to collect specimen in order to make precise diagnosis and early treatment REFERENCES Bala K, Chander J, Handa U, Punia R, Attri A A prospective study of mucormycosis in north India: Experience from a tertiary care hospital Med Mycol 2015, 53, pp.248-257 Bitar D, Cauteren, D Van, Lanternier F, Dannaoui E, Che D, Dromer F, Lortholary O Increasing incidence of zygomycosis (mucormycosis), France, 1997 - 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