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Primary amebic meningoencephalitis diagnosed in the emergency department
0ASE REPORT amebic meningoencephalitis; meningoencephalitis, amebic
Primary Amebic Meningoencephalitis Diagnosed in the Emergency Department Reported is a case of primary amebic meningoencephalitis diagnosed in the emergency department. The patient, a previously healthy teenager, developed Naegleria meningoencephalitis after swimming in a freshwater public pool. The Naegleria caused acute fulminating infection culminating in the death of the patient 36 hours after admission. Results of a spinal tap, together with the history of swimming in warm fresh water, led to the emergency department diagnosis. [McCool JA, Spudis EV, McLean W, White J, Visvesvara GS: Primary amebic meningoencephalitis diagnosed in the emergency department. Ann Emerg Med 12:35-37, January 1983.]
INTRODUCTION More than 145 cases of primary amebic meningoencephalitis (PAME) due to small, pathogenic, free-living amebae of the genera Naegleria and Acanthamoeba have been described in the world literature. Naegleria organisms cause acute, fulminating infection often affecting the olfactory neuroepithelium and brain undersurface, culminating in the death of the host within five to eight days. 1 We describe this case because the diagnosis was recorded in the emergency department prior to spinal tap, because the few survivors of this infection have been treated early in the course of their i~ness, and because it is unlikely that we will be able to collect many additional cases in this region.1
James A. McCool, MD* Edward V. Spudis, MDt William McLean, MD~ Janice White, MD{ Winston-Salem, North Carolina Govinda S. Visvesvara, PhD** Atlanta, Georgia From the Department of Pathology* and the Section of Neurology,t Forsyth Memorial Hospital, Winston-Salem, North Carolina; the Departments of Neurology~ and Pathology,{ Bowman Gray School of Medicine, Winston-Salem, North Carolina; and the Center for Disease Control,** Atlanta, Georgia. Address for reprints: Edward V. Spudis, MD, Section of Neurology, Forsyth Memorial Hospital, 3333 Silas Creek Parkway, Winston-Salem, North Carolina 27103.
CASE REPORT A 14-year-old girl was brought to the Forsyth Memorial Hospital Emergency Department. The patient had arrived without symptoms in WinstonSalem, NC, from Hepzabah, GA, three days prior. She was alert until she awakened at 2 AM on the day after her arrival with headache, vomiting, and lethargy. The next day she was anorexic and sleepy. At 3 AM on the third day, her sister heard her collapse to the floor. The patient was well developed, well nourished, and lethargic. Blood pressure was 19.0/68 m m Hg; temperature, 39.6 C (rectal); respirations, 18; and pulse, 94. She made several brief sentences that were appropriate, complained of headache, and demanded to go home. Ocular flmdi, pupils, and eye movements were normal. Her tongue was midline and moist, and the pharynx was normal. There were no enlarged cervical lymph nodes. Her neck was moderately stiff. Heart, lungs, and abdomen were normal. Reflexes were hypoactive in the upper extremities and absent at the knees and ankles. Straight leg raising was negative. Prior to attempting a spinal tap, 2 the physician quizzed the sister about swimming. She described a two-acre pool with a sandy bottom, cement retaming walls, dirty water, and no chlorination. She estimated that 100 or more people had been swimming in the same pool each day, and that temperatures were above 32 C each day. Spinal fluid pressure was elevated to 501 m m H20. Four grams of ampicillin in 50 ml of 5% dextrose in water was started when the fluid was seen to be pearly white. The spinal fluid contained 190 RBC/~I and 172 WBC/~I. Spinal fluid protein was 299 mg/dl, and glucose, 47 mg/dl. There were 177 12:1 January 1983
Annals of Emergency Medicine
35/77
PAME Spudis et al
Fig. 1. Oil immersion view of phosphotu.ngstic acid hematoxylin-stained amebae in spinal fluid. (Magnification 1000 X.) Fig. 2. Grossphotograph, brain, showing hemorrhagic meninges in area of olfactory tract. motile amebae per microliter varying from 10 to 20 microns in size on the unstained w e t p r e p a r a t i o n . T h e trophozoites contained a single nucleus with a large karyosome, and were vigorously motile (Figure 1). After consultation the ampicillin was stopped and amphotericin-B was started at a rate of 50 mg every six hours. Six hours after admission she was delirious but moving all extremities. Her temperature rose to 40.5 C, and over a period of approximately one hour she became comatose. At 2 PM, tachyeardia varied from 130 to 150 beats per minute. She became apneic with nonreactive pupils. She was g i v e n 100% o x y g e n , 3.75 g sodium bicarbonate, 20% mannitol, and 8 mg d e x a m e t h a s o n e sodium phosphate. She began spontaneous respiratory movements at 16/min, but her pupils remained dilated. Respiratory ffmction again ceased at 3 AM on the day after admission. Computerized cranial tomography was normal. Her intracranial pressure readings could not be brought below systemic blood pressure. She died 36 hours after admission. PATHOLOGY The spinal fluid was inoculated into non-nutrient agar plates and into Nelson's and Chang's axenic culture media. The amebae that grew were designated as HBWS-1, and are still alive at the Center for Disease Control. Studies of suckling mice inoculated intracerebrally, and monkey kidney cell and human embryonic cell c u l t u r e s and a m e b a e f l a g e l l a t e transformation tests all confirmed the presence of Naegleria. Antigens from sonicated amebae showed precipitin lines indicating antigenic homogeneity with N fowleri. The autopsy performed two hours after the patient's death showed the brain to be severely swollen (1,333 g), with bilateral tonsillar herniation. A thick, yellow-gray exudate covered the base of the brain and olfactory bulbs (Figure 2). There were similar areas scattered over the pons and cerebel78/36
lum. The spinal cord contained no gross lesions, but microscopically the leptomeninges, throughout all areas of the brain and spinal cord, were infiltrated w i t h a p o l y m o r p h o n u c l e a r leukocytic exudate and focal extravasated red blood cells. In the deeper regions, the perivascular parenchyma contained amebae without polymorphonuclear reaction. Parts of the cerebellum, especially the vermis around the fourth ventricle and inferior cortex, were infiltrated with amebae.
DISCUSSION The extreme rarity of PAME, especially in the areas in which millions of swimmers and countless Naegleria Annals of Emergency Medicine
share the same water, is perplexing. Approximately half the freshwater lakes in the Orlando, FL, area harbor easily cultured pathogenic Naegleria, which seem to have a coastal distribution in the United States. 3,4 Water temperature is likely to be a critical factor in the establishment of the pathogenic process, s Because olfactory bulbs and frontal areas of the brain are more commonly involved, it seems prudent to avoid swimming in freshwater areas during hot days, or in heated indoor pools, especially if one has an upper respiratory infection or k n o w n reasons to be immunosuppressed. There is no guarantee, however, that normally healthy people will 12:1 January 1983
not be affected, for m o s t reported Naegleria infections have been in previously healthy people. This p a t i e n t died q u i c k l y even though the diagnosis was made in the emergency department. One recently reported California survivor was treated early with miconazole and amphotericin-B. In vitro drug sensitivity studies suggested that this combination, intravenously and intrathecally, may be most effective. 1 We suspect that most severe PAME episodes are correctly identified because of the startling motility of the organisms in the fresh spinal fluid. Milder infections, however, may be mislabeled as aseptic meningitis with perhaps some spontaneous recoveries. Fatal cases may have been considered untreatable viral encephalitis. 6 In the microscopic examination of the brain,
12:1 January 1983
the meningitis and encephalitis are obvious, but the amebae, because of their lack of intense staining, may be mistaken for degenerated cells of the e x u d a t e , ie, m a c r o p h a g e s . (These slides were shown as unknowns to a large group of pathologists, and many did not detect the amebae.) In those mild or early infections, a history of swimming in warm fresh water might be a fruitful stimulus to the emergency physician. The authors thank Timothy Horton, ASCP, and Patricia Spelman, ASCP, for their enthusiastic assistance.
REFERENCES 1. Seidel JS, Hormatz P, Visvesvara GS, et al: Successful treatment of primary amebic
Annals of Emergency Medicine
meningoencephalitis. N Engi J Med 306: 346-348, 1982. 2. Duma RJ, Ferrell HW, Nelson EC, et al: Primary amebic meningoencephalitis. N EngI J Med 281:1315, 1969. 3. Wellings FM, Amuso PT, Chang SL, et al: Isolation and identification of pathogenic Naegleria from Florida. Applied and Environmental Microbiology 34:661-667, 1977. 4. Visvesvara GS: The public health importance and disease potential of small free-living amebae. Read before the Second International Conference on the Biology and Pathogenicity of Small Free-Living Amoebae, March 23-25, 1980. 5. Willaert E, Stevens AR: Isolation of pathogenic amebae from thermal-discharge water. Lancet 2:746, 1976. 6. Apley J, Clarke SKR, Roone APCH, et ah Primary amoebic meningoencephalitis in Britain. Br Med J 1:596-599, 1970.
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Primary Amebic Meningoencephalitis Diagnosed in the Emergency Department Reported is a case of primary amebic meningoencephalitis diagnosed in the emergency department. The patient, a previously healthy teenager, developed Naegleria meningoencephalitis after swimming in a freshwater public pool. The Naegleria caused acute fulminating infection culminating in the death of the patient 36 hours after admission. Results of a spinal tap, together with the history of swimming in warm fresh water, led to the emergency department diagnosis. [McCool JA, Spudis EV, McLean W, White J, Visvesvara GS: Primary amebic meningoencephalitis diagnosed in the emergency department. Ann Emerg Med 12:35-37, January 1983.]
INTRODUCTION More than 145 cases of primary amebic meningoencephalitis (PAME) due to small, pathogenic, free-living amebae of the genera Naegleria and Acanthamoeba have been described in the world literature. Naegleria organisms cause acute, fulminating infection often affecting the olfactory neuroepithelium and brain undersurface, culminating in the death of the host within five to eight days. 1 We describe this case because the diagnosis was recorded in the emergency department prior to spinal tap, because the few survivors of this infection have been treated early in the course of their i~ness, and because it is unlikely that we will be able to collect many additional cases in this region.1
James A. McCool, MD* Edward V. Spudis, MDt William McLean, MD~ Janice White, MD{ Winston-Salem, North Carolina Govinda S. Visvesvara, PhD** Atlanta, Georgia From the Department of Pathology* and the Section of Neurology,t Forsyth Memorial Hospital, Winston-Salem, North Carolina; the Departments of Neurology~ and Pathology,{ Bowman Gray School of Medicine, Winston-Salem, North Carolina; and the Center for Disease Control,** Atlanta, Georgia. Address for reprints: Edward V. Spudis, MD, Section of Neurology, Forsyth Memorial Hospital, 3333 Silas Creek Parkway, Winston-Salem, North Carolina 27103.
CASE REPORT A 14-year-old girl was brought to the Forsyth Memorial Hospital Emergency Department. The patient had arrived without symptoms in WinstonSalem, NC, from Hepzabah, GA, three days prior. She was alert until she awakened at 2 AM on the day after her arrival with headache, vomiting, and lethargy. The next day she was anorexic and sleepy. At 3 AM on the third day, her sister heard her collapse to the floor. The patient was well developed, well nourished, and lethargic. Blood pressure was 19.0/68 m m Hg; temperature, 39.6 C (rectal); respirations, 18; and pulse, 94. She made several brief sentences that were appropriate, complained of headache, and demanded to go home. Ocular flmdi, pupils, and eye movements were normal. Her tongue was midline and moist, and the pharynx was normal. There were no enlarged cervical lymph nodes. Her neck was moderately stiff. Heart, lungs, and abdomen were normal. Reflexes were hypoactive in the upper extremities and absent at the knees and ankles. Straight leg raising was negative. Prior to attempting a spinal tap, 2 the physician quizzed the sister about swimming. She described a two-acre pool with a sandy bottom, cement retaming walls, dirty water, and no chlorination. She estimated that 100 or more people had been swimming in the same pool each day, and that temperatures were above 32 C each day. Spinal fluid pressure was elevated to 501 m m H20. Four grams of ampicillin in 50 ml of 5% dextrose in water was started when the fluid was seen to be pearly white. The spinal fluid contained 190 RBC/~I and 172 WBC/~I. Spinal fluid protein was 299 mg/dl, and glucose, 47 mg/dl. There were 177 12:1 January 1983
Annals of Emergency Medicine
35/77
PAME Spudis et al
Fig. 1. Oil immersion view of phosphotu.ngstic acid hematoxylin-stained amebae in spinal fluid. (Magnification 1000 X.) Fig. 2. Grossphotograph, brain, showing hemorrhagic meninges in area of olfactory tract. motile amebae per microliter varying from 10 to 20 microns in size on the unstained w e t p r e p a r a t i o n . T h e trophozoites contained a single nucleus with a large karyosome, and were vigorously motile (Figure 1). After consultation the ampicillin was stopped and amphotericin-B was started at a rate of 50 mg every six hours. Six hours after admission she was delirious but moving all extremities. Her temperature rose to 40.5 C, and over a period of approximately one hour she became comatose. At 2 PM, tachyeardia varied from 130 to 150 beats per minute. She became apneic with nonreactive pupils. She was g i v e n 100% o x y g e n , 3.75 g sodium bicarbonate, 20% mannitol, and 8 mg d e x a m e t h a s o n e sodium phosphate. She began spontaneous respiratory movements at 16/min, but her pupils remained dilated. Respiratory ffmction again ceased at 3 AM on the day after admission. Computerized cranial tomography was normal. Her intracranial pressure readings could not be brought below systemic blood pressure. She died 36 hours after admission. PATHOLOGY The spinal fluid was inoculated into non-nutrient agar plates and into Nelson's and Chang's axenic culture media. The amebae that grew were designated as HBWS-1, and are still alive at the Center for Disease Control. Studies of suckling mice inoculated intracerebrally, and monkey kidney cell and human embryonic cell c u l t u r e s and a m e b a e f l a g e l l a t e transformation tests all confirmed the presence of Naegleria. Antigens from sonicated amebae showed precipitin lines indicating antigenic homogeneity with N fowleri. The autopsy performed two hours after the patient's death showed the brain to be severely swollen (1,333 g), with bilateral tonsillar herniation. A thick, yellow-gray exudate covered the base of the brain and olfactory bulbs (Figure 2). There were similar areas scattered over the pons and cerebel78/36
lum. The spinal cord contained no gross lesions, but microscopically the leptomeninges, throughout all areas of the brain and spinal cord, were infiltrated w i t h a p o l y m o r p h o n u c l e a r leukocytic exudate and focal extravasated red blood cells. In the deeper regions, the perivascular parenchyma contained amebae without polymorphonuclear reaction. Parts of the cerebellum, especially the vermis around the fourth ventricle and inferior cortex, were infiltrated with amebae.
DISCUSSION The extreme rarity of PAME, especially in the areas in which millions of swimmers and countless Naegleria Annals of Emergency Medicine
share the same water, is perplexing. Approximately half the freshwater lakes in the Orlando, FL, area harbor easily cultured pathogenic Naegleria, which seem to have a coastal distribution in the United States. 3,4 Water temperature is likely to be a critical factor in the establishment of the pathogenic process, s Because olfactory bulbs and frontal areas of the brain are more commonly involved, it seems prudent to avoid swimming in freshwater areas during hot days, or in heated indoor pools, especially if one has an upper respiratory infection or k n o w n reasons to be immunosuppressed. There is no guarantee, however, that normally healthy people will 12:1 January 1983
not be affected, for m o s t reported Naegleria infections have been in previously healthy people. This p a t i e n t died q u i c k l y even though the diagnosis was made in the emergency department. One recently reported California survivor was treated early with miconazole and amphotericin-B. In vitro drug sensitivity studies suggested that this combination, intravenously and intrathecally, may be most effective. 1 We suspect that most severe PAME episodes are correctly identified because of the startling motility of the organisms in the fresh spinal fluid. Milder infections, however, may be mislabeled as aseptic meningitis with perhaps some spontaneous recoveries. Fatal cases may have been considered untreatable viral encephalitis. 6 In the microscopic examination of the brain,
12:1 January 1983
the meningitis and encephalitis are obvious, but the amebae, because of their lack of intense staining, may be mistaken for degenerated cells of the e x u d a t e , ie, m a c r o p h a g e s . (These slides were shown as unknowns to a large group of pathologists, and many did not detect the amebae.) In those mild or early infections, a history of swimming in warm fresh water might be a fruitful stimulus to the emergency physician. The authors thank Timothy Horton, ASCP, and Patricia Spelman, ASCP, for their enthusiastic assistance.
REFERENCES 1. Seidel JS, Hormatz P, Visvesvara GS, et al: Successful treatment of primary amebic
Annals of Emergency Medicine
meningoencephalitis. N Engi J Med 306: 346-348, 1982. 2. Duma RJ, Ferrell HW, Nelson EC, et al: Primary amebic meningoencephalitis. N EngI J Med 281:1315, 1969. 3. Wellings FM, Amuso PT, Chang SL, et al: Isolation and identification of pathogenic Naegleria from Florida. Applied and Environmental Microbiology 34:661-667, 1977. 4. Visvesvara GS: The public health importance and disease potential of small free-living amebae. Read before the Second International Conference on the Biology and Pathogenicity of Small Free-Living Amoebae, March 23-25, 1980. 5. Willaert E, Stevens AR: Isolation of pathogenic amebae from thermal-discharge water. Lancet 2:746, 1976. 6. Apley J, Clarke SKR, Roone APCH, et ah Primary amoebic meningoencephalitis in Britain. Br Med J 1:596-599, 1970.
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