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Group A streptococcal meningitis: Report of two cases
116
Case Reports
Group A Streptococcal Meningitis: Report of Two Cases A. E. Moses *~, M. Beeri 2 and D. Engelhard 2 ~Department of Clinical Microbiology and Infectious Diseases and 2Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel Group A streptococcus (GAS) is a very uncommon cause of bacterial meningitis, with less than 30 cases reported in the last quarter of a century. A recent worldwide increase in the incidence and severity of disease due to Streptococcus pyogenes has been observed. Although a rise of incidence of cases of GAS meningitis has not been shown, severe and fulminant cases have been reported in the literature in the last few years. We performed a retrospective analysis of the computer data of cerebrospinal fluid cultures from luly 1987 to December 1995 at the Hadassah University Medical Center in Jerusalem, and report two cases of GAS meninigitis: one with a primary infection acquired through bacteraemia, in a 2-month-old child, and another with meninigitis secondary to cranial surgery in a 75-year-old patient. The cases are discussed and a literature review is presented.
Introduction A recent increase in the incidence and severity of disease due to Streptococcus pyo~enes has been observed by us 1 as well as by others. 2'3 Streptococcus pyogenes rarely causes bacterial meningitis, and less than 30 cases have been reported in the last quarter of a decade, 4 some of whom had a severe and fulminant course. Although a rise of incidence of cases of group A streptococcal (GAS) meningitis has not been reported, severe and fulminant cases have been reported in the last few years. 4 ~n a retrospective analysis of the computer data of cerebrospinal fluid (CSF) cultures from July 1987 to December 1995, we found three positive cultures for GAS. The medical charts of these patients were reviewed. One was a patient with a positive culture without meningitis. This was secondary to a GAS wound infection following cranial surgery. The other two patients had frank meningitis: one primary meningitis in a 2-month-old child, the other a 75-year-old patient with GAS meningitis following cranial surgery.
Case Reports Case 1 A 2-month-old male infant presented with a history of fever and apathy of I day's duration. The child was born weighing 3300 g after a normal pregnancy and delivery. He was breast fed. His past medical history was unremarkable except for 1 day's fever at the age of 6 weeks. One week prior to admission his mother was diagnosed by throat culture with streptococcal tonsillitis and was treated with oral penicillin. On the day before his admission the parents noted sleepiness, poor sucking and apathy, and a temperature of 40 ° C was measured. On admission he was in poor condition with grey skin, poor muscle tone, and a temperature of 37.8 °C. He was tachycardic - 200 beats/minute, tachypneic - 68 breaths/minute and
* To whom correspondence should be addressed. Accepted for publication 13 February 1997.
grunting. The weight and head circumference were appropriate for his age. The blood pressure was 85/39 mmHg. Skin turgor was normal. The anterior fontanelle was bulging. Pupils were equal and reactive to light and accommodation, but no eye contact could be made and he could not follow objects. Tympanic membranes were unremarkable. Thrush was found in the oral cavity. Examination of the lungs, heart abdomen and extremities were within normal limits. No rash was observed. Neurological examination revealed diminished consciousness, hypotonicity and decreased deep tendon reflexes. Moro and sucking reflexes were absent. Laboratory evaluation showed a haematocrit of 26%, leucocytes 6.1 x 109/1 (differential not done), platelets 283 x 109/1. Serum electrolytes, kidney and liver function tests, arterial blood gases and urinalysis were within normal limits. Cerebrospinal fluid was cloudy and contained 5600/ml polymorphonuclear cells and 900/ml red blood cells. Glucose was 0.6 retool/1 (serum glucose was 4.4 mmol/1). Total protein was 6772 mg/1 (normal range 200-650). Gram-positive cocci were seen in Gram stain and CSF cultures yielded Streptococcus pyogenes. Typing of the isolate revealed it to be M-41, T-3. Polymerase chain reaction (PCR) amplification was used to search for the presence of speA or speC, the genes coding for the production of exotoxins A and C, respectively. Both genes were absent in this isolate. Treatment with dexamethasone, cefotaxime and ampicillin was initiated followed by penicillin G as single therapy after culture results were known. A single dose of intravenous gammaglobulin was administered. Shortly after admission, general and focal seizures and decerebrate posturing developed. Endotracheal intubation was performed, and hyperventilation and mannitol were used to reduce intracranial pressure. Treatment with anti-convulsive agents failed to control the seizures. The EEG pattern was compatible with cerebral oedema or subdural effusion. Computed tomograph (CT) scans of the brain disclosed atrophy of the left frontal lobe with a prominent extra axial low density collection consistent with hygroma. There was a small right frontal low density extra axial collection with focal encephalomalacia. After 72 h the seizures ceased and the child was gradually
Case Reports
117
strain, in which the patient succumbed to a fulminant infection within 7 h of presentation. 7 In the two patients we describe, one had spontaneous meningitis without any predisposing condition and one had meningitis secondary to a neurosurgical procedure. Our second case was clearly due to local extension of a skin infection around the site of head surgery. In contrast to Haemophilus influenzae and Streptococcus pneumoniae where meningitis is considered to be secondary to bacteraemia, and Neisseriae meningitidis where meningitis may be secondary to invasion of oropharyngeal mucosa and direct invasion of the cerebrospinal fluid, 9 the pathogenesis of primary GAS meningitis is unclear. In cases reviewed by Chow 4 the most common associated condition was otitis media. This is such a frequent infection in children that direct invasion to the meninges is questionable. Four of the cases described in the literature have been associated with either head injury or surgery. The scarcity of reported cases emphasizes the fact that although infections caused by GAS have been on the increase in the last years, meningitis has not been part of the epidemic. This may be due to a low affinity of the bacterium to the meninges. Although meningitis caused by GAS seems to be an extremely uncommon illness, we found that during 1994, when we treated case 1, three of seven isolates from children with Case 2 bacteraemia belonged to the same serological type M-41, T-3, which caused the meningitis. ~ The cases were not related A 75-year-old man was admitted 2 weeks after temporal craniepidemiologically, but during 1993 this same serotype caused otomy for excision of meningioma. The patient had a past an infection in another three of ten isolates from children with history of hypertension and non-insulin-dependent diabetes GAS bacteraemia. mellitus. He was known to be allergic to penicillin. Several days In the literature review of GAS meningitis reported by Chow, 4 before admission the patient noted swelling, erythema and three of 21 patients had symptoms consistent with pharyngitis. tenderness over the excisional scar. On admission his temThe source of GAS meningitis in the infant we describe was perature was 38 °C and there was marked erythema over the not identified, but the history of the mother who had GAS scar. The patient's neurological examination was normal. CSF tonsillitis 2 weeks prior to the onset of meningitis in her child examination disclosed Gram-positive cocci, 2560/ml polysuggests that this may have been the source. This could not morphonuclear cells. Culture of CSF was positive for group A be confirmed, as the mother's isolate was not available for streptococcus. Blood cultures were negative. The patient was comparison. GAS meningitis has been associated with neurotreated with vancomycin because of the history of penicillin logical sequelae in six of thirteen children. 4' r. * This is somewhat allergy. His temperature subsided, but after 10 days of vanmore than the approximately 30% neurological sequelae decomycin therapy he developed a hypersensitivity rash and scribed for children following bacterial meningitis due to H. medication was changed to oral chloramphenicol which was influenzae and S. pneumonia< but higher than that of N. mencontinued for 3 weeks until his discharge. Three days after ingitides, z° The child we describe with meningitis appeared to discharge he was readmitted complaining of a fever of 37.6 °C have normal developmental milestones at 18 months, but the and increasing swelling and tenderness over the surgical scar. brain CT scan disclosed abnormalities. On examination he was febrile with moderate swelling and Although the incidence of GAS meningitis seems to be pererythema over the scar, with suspected pus under the skin. The sistently low, one must be aware that sporadic cases may have patient was taken to the operating room and 30 cc of purulent a fulminant course with possible neurological sequelae. fluid were evacuated with removal of an acrylic mesh covering the surgical area. Gram stain of the pus was negative and culture was sterile. The patient gradually recovered completely. He died 11 months later from complications of the meningioma. References
weaned from anti-convulsants and mechanical ventilation. Within days, decerebrate posturing disappeared and consciousness was regained. Normal eye movement, good sucking, symmetric four-extremity-movement and response to noise and grimaces returned. A transcranial ultrasound revealed no abnormality and repeat EEG was within normal limits. The child was discharged 16 days after admission. Long-term phenobarbital treatment was recommended. At follow-up 6 months later he was well, with developmental milestones borderline for his age. There was a decreased abdominal muscle tone, mild adductor spasm and a relative weakness of the left arm. His hearing was normal. At 12 months' follow-up an audiogram was normal. At 18 months' follow-up a head CT scan disclosed a right fronto-parietal subdural collection and encephalomalacic changes of the right frontal lobe consistent with hygroma. The left-sided collection resolved and the right subdural collection enlarged significantly. The Denver developmental score was normal at this time and thus there was no further intervention with this subdural collection.
Discussion Group A streptococcal meningitis is uncommon and is described in several reports as comprising less than 0"2% 5 and less than 0.6% ~ of all cases of meningitis. Our two cases represent the two types of meningitis seen with GAS: primary meningitis acquired through bacteraemia, and meningitis secondary to head trauma or surgery. Since the review of Group A streptococcal meningitis by Chow and Muder 4 there have been two new cases of this illness reported in the literature. 78 One was a case of streptococcal toxic shock syndrome with meningitis, caused by a streptococcal pyrogenic exotoxin A-producing
1 Moses AE, Amita~ Z, Harari M, Rahav G, Shapiro M, Engelhard D. Increased incidence and severity of Group A Streptococcal infection in young children. Pediatr InfDis ] 1995; 14: 767-770. 2 Stevens DL. Invasive group A streptococus infections. Clin Infect Dis 1992; 14: 2-13. 3 Begovac J, Marion E, Listc M, Beus I, Bozinovic D, Kuzmanovic N. Group A beta-hemolytic streptococcal toxic shock-like syndrome. Pediatr lnfeet Dis J 1990; 9: 369-370. 4 Chow )W, Muder RR. Group A streptococcal meningitis. Clin Inf Dis 1992; 14: 418-4:21. 5 Schlech WF III, Ward JI, Band JD, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States, 1978 through 1981: The National Bacterial Meningitis SurveilIance Study. lAMA 1985; 253: 6 Qadri SM, Berotte JM, Wende RD. Incidence and etiology of septic
118
Case Reports
meningitis in a metropolitan county hospital. Am ] Clin Pathol 1976; 54: 550-556. 7 Jevon GP, Dunne WM, Hawkins HK, Armstrong DL, Musser JM. Fatal group A streptococcal meningitis and toxic shock-like syndrome: case report. Clin InfDis 1994; 18: 91-93. 8 WalshM, Chodock R, Quinn R, Peglow S. Group A beta-hemolytic streptococcal meningitis associated with uncomplicated varicella (letter). Am ] Emerg Med 1994 12: 602-603.
9 Tunkel AR, Scheld WM, Acute meningitis, In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principlesand practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995: 831-865. 10 Kabani A, ladavji T. Sequelae of acute bacterial meningitis in children. In: SchonfeldH, HelwigH, eds. Bacterial meningitis. Basel: Karger. 1992: 209-217.
A Child Case of Haemophagocytic Syndrome Associated with Cryptococcal IVleningoencephalitis K. Numata, H. Tsutsumi, S. Wakai, N. Tachi and S. Chiba Department of Pediatrics, Sapporo Medical University School of Medicine, Chuo-ku S-I, W-16, Sapporo 060, Japan A previously healthy 12-year-old Japanese girl developed meningoencephalitis due to Cryptococcus neoformans. During the course of her illness she suffered persistent high fever, severe pancytopenia, hypercytokinemia and liver dysfunction. Laboratory findings, including results of a bone marrow examination, strongly indicated complication by haemophagocytic syndrome (HPS). The preceding cryptococcal infection was thought to be a cause of the HPS because no other viral or bacterial infection could be confirmed. The girl died of acute respiratory failure during the progressive course of HPS. This may be the first reported case of HPS due to cryptococcal infection in an otherwise healthy child.
Introduction Infection-associated haemophagocytic syndrome was originally described by Risdall et al.l: histiocytic hyperplasia, haemophagocytosis, blood count depression and liver dysfunction occur in a setting ofimmunosuppression and viral infection and frequently have a rapidly progressive, fatal course. Subsequent reports have broadened the spectrum of this syndrome to include non-viral infections such as bacteria, mycobacteria and fungi.Z 3 There has only been one report of this syndrome with cryptococcosis, in AIDS patients. 3 This present case may be the first report of haemophagocytic syndrome (HPS) associated with cryptococcal meningoencephalitis in an otherwise normal child.
Case Report A 12-year-old, previously healthy Japanese girl experienced headaches, vomiting and temperature of 38 °C for several days, followed by intention tremor, gait and speech disturbance. Following admission to another hospital, the girl's CSF examination showed a white blood cell count of 210/mm 3 (80% Iymphocytes and 20% polymorphonuclear leucocytes), a lower glucose of 39 mg/dl and a higher protein of 58 mg/dl. A Gramstained smear, a stain for acid-fast bacilli, and bacterial and fungal cultures of the CSF were all negative. The complete blood count and serum chemistry were normal. Serum antibodies to Epstein-Barr virus (EBV), herpes simplex virus (HSV) and cytomegalovirus (CMV), including IgM antibody class, were
* Address correspondence to: H. Tsutsumi. Accepted for publication 28 February 1997.
negative. Antinuclear antibodies were negative, A chest radiograph showed no particular findings. A brain computed tomographic (CT) scan showed diffuse brain oedema. The patient was diagnosed with meningoencephalitis of unknown origin and treated conservatively with glycerol and dexamethazone for relief of brain oedema. Her fever fell and her neurological symptoms improved gradually during the following month; however, her headache and slight fever were repeated and slight pleocytosis (30-60/ram 3) continued after that. Two months later she developed high fever, disturbance of consciousness, a stiff neck and right hemiparesis. CSF examination again revealed sIight pleocytosis (23/mm3), Iower sugar (34 mg/dl) and higher protein (69 mg/dl) concentrations. A brain CT scan revealed diffuse cerebral oedema and many small cortical microbleedings. She was rehospitalized and retreated with glycerol and dexamethazone. Despite treatment, the fever and neruological signs continued, and she was transferred to Sapporo Medical University Hospital. Upon admission, her complete blood count showed light leucopenia of 2800/mm 3 (70% polymorphonuclear leucocyte, 18% of lymphocyte), thrombocytopenia of 34 O00/mm 3 and slight anaemia (red blood cell 3.82 x 106/mm 3, Hb 10.2 g/ dl). Serum chemistry was normal range. Bacterial and fungal cultures of the CSF and blood were negative; however, Cryptococcus neoformans was detected in the CSF sediment using an India Ink stain, and an antigen titre of Cryptococcus neoformans with the latex agglutination assay was 1:64. Cryptococcal meningoencephalitis was diagnosed. Dexamethazone had been decreased gradually and was stopped. Intravenous fluconazole injections were initiated. After 1 week of treatment, the patient's neurological symptoms appeared to show slight improvement; however, her high fever continued and her pancytopenia advanced. In addition, severe hepatosplenomegaly appeared. On the 12th day of hospitalization her white blood ceil was
Case Reports
Group A Streptococcal Meningitis: Report of Two Cases A. E. Moses *~, M. Beeri 2 and D. Engelhard 2 ~Department of Clinical Microbiology and Infectious Diseases and 2Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel Group A streptococcus (GAS) is a very uncommon cause of bacterial meningitis, with less than 30 cases reported in the last quarter of a century. A recent worldwide increase in the incidence and severity of disease due to Streptococcus pyogenes has been observed. Although a rise of incidence of cases of GAS meningitis has not been shown, severe and fulminant cases have been reported in the literature in the last few years. We performed a retrospective analysis of the computer data of cerebrospinal fluid cultures from luly 1987 to December 1995 at the Hadassah University Medical Center in Jerusalem, and report two cases of GAS meninigitis: one with a primary infection acquired through bacteraemia, in a 2-month-old child, and another with meninigitis secondary to cranial surgery in a 75-year-old patient. The cases are discussed and a literature review is presented.
Introduction A recent increase in the incidence and severity of disease due to Streptococcus pyo~enes has been observed by us 1 as well as by others. 2'3 Streptococcus pyogenes rarely causes bacterial meningitis, and less than 30 cases have been reported in the last quarter of a decade, 4 some of whom had a severe and fulminant course. Although a rise of incidence of cases of group A streptococcal (GAS) meningitis has not been reported, severe and fulminant cases have been reported in the last few years. 4 ~n a retrospective analysis of the computer data of cerebrospinal fluid (CSF) cultures from July 1987 to December 1995, we found three positive cultures for GAS. The medical charts of these patients were reviewed. One was a patient with a positive culture without meningitis. This was secondary to a GAS wound infection following cranial surgery. The other two patients had frank meningitis: one primary meningitis in a 2-month-old child, the other a 75-year-old patient with GAS meningitis following cranial surgery.
Case Reports Case 1 A 2-month-old male infant presented with a history of fever and apathy of I day's duration. The child was born weighing 3300 g after a normal pregnancy and delivery. He was breast fed. His past medical history was unremarkable except for 1 day's fever at the age of 6 weeks. One week prior to admission his mother was diagnosed by throat culture with streptococcal tonsillitis and was treated with oral penicillin. On the day before his admission the parents noted sleepiness, poor sucking and apathy, and a temperature of 40 ° C was measured. On admission he was in poor condition with grey skin, poor muscle tone, and a temperature of 37.8 °C. He was tachycardic - 200 beats/minute, tachypneic - 68 breaths/minute and
* To whom correspondence should be addressed. Accepted for publication 13 February 1997.
grunting. The weight and head circumference were appropriate for his age. The blood pressure was 85/39 mmHg. Skin turgor was normal. The anterior fontanelle was bulging. Pupils were equal and reactive to light and accommodation, but no eye contact could be made and he could not follow objects. Tympanic membranes were unremarkable. Thrush was found in the oral cavity. Examination of the lungs, heart abdomen and extremities were within normal limits. No rash was observed. Neurological examination revealed diminished consciousness, hypotonicity and decreased deep tendon reflexes. Moro and sucking reflexes were absent. Laboratory evaluation showed a haematocrit of 26%, leucocytes 6.1 x 109/1 (differential not done), platelets 283 x 109/1. Serum electrolytes, kidney and liver function tests, arterial blood gases and urinalysis were within normal limits. Cerebrospinal fluid was cloudy and contained 5600/ml polymorphonuclear cells and 900/ml red blood cells. Glucose was 0.6 retool/1 (serum glucose was 4.4 mmol/1). Total protein was 6772 mg/1 (normal range 200-650). Gram-positive cocci were seen in Gram stain and CSF cultures yielded Streptococcus pyogenes. Typing of the isolate revealed it to be M-41, T-3. Polymerase chain reaction (PCR) amplification was used to search for the presence of speA or speC, the genes coding for the production of exotoxins A and C, respectively. Both genes were absent in this isolate. Treatment with dexamethasone, cefotaxime and ampicillin was initiated followed by penicillin G as single therapy after culture results were known. A single dose of intravenous gammaglobulin was administered. Shortly after admission, general and focal seizures and decerebrate posturing developed. Endotracheal intubation was performed, and hyperventilation and mannitol were used to reduce intracranial pressure. Treatment with anti-convulsive agents failed to control the seizures. The EEG pattern was compatible with cerebral oedema or subdural effusion. Computed tomograph (CT) scans of the brain disclosed atrophy of the left frontal lobe with a prominent extra axial low density collection consistent with hygroma. There was a small right frontal low density extra axial collection with focal encephalomalacia. After 72 h the seizures ceased and the child was gradually
Case Reports
117
strain, in which the patient succumbed to a fulminant infection within 7 h of presentation. 7 In the two patients we describe, one had spontaneous meningitis without any predisposing condition and one had meningitis secondary to a neurosurgical procedure. Our second case was clearly due to local extension of a skin infection around the site of head surgery. In contrast to Haemophilus influenzae and Streptococcus pneumoniae where meningitis is considered to be secondary to bacteraemia, and Neisseriae meningitidis where meningitis may be secondary to invasion of oropharyngeal mucosa and direct invasion of the cerebrospinal fluid, 9 the pathogenesis of primary GAS meningitis is unclear. In cases reviewed by Chow 4 the most common associated condition was otitis media. This is such a frequent infection in children that direct invasion to the meninges is questionable. Four of the cases described in the literature have been associated with either head injury or surgery. The scarcity of reported cases emphasizes the fact that although infections caused by GAS have been on the increase in the last years, meningitis has not been part of the epidemic. This may be due to a low affinity of the bacterium to the meninges. Although meningitis caused by GAS seems to be an extremely uncommon illness, we found that during 1994, when we treated case 1, three of seven isolates from children with Case 2 bacteraemia belonged to the same serological type M-41, T-3, which caused the meningitis. ~ The cases were not related A 75-year-old man was admitted 2 weeks after temporal craniepidemiologically, but during 1993 this same serotype caused otomy for excision of meningioma. The patient had a past an infection in another three of ten isolates from children with history of hypertension and non-insulin-dependent diabetes GAS bacteraemia. mellitus. He was known to be allergic to penicillin. Several days In the literature review of GAS meningitis reported by Chow, 4 before admission the patient noted swelling, erythema and three of 21 patients had symptoms consistent with pharyngitis. tenderness over the excisional scar. On admission his temThe source of GAS meningitis in the infant we describe was perature was 38 °C and there was marked erythema over the not identified, but the history of the mother who had GAS scar. The patient's neurological examination was normal. CSF tonsillitis 2 weeks prior to the onset of meningitis in her child examination disclosed Gram-positive cocci, 2560/ml polysuggests that this may have been the source. This could not morphonuclear cells. Culture of CSF was positive for group A be confirmed, as the mother's isolate was not available for streptococcus. Blood cultures were negative. The patient was comparison. GAS meningitis has been associated with neurotreated with vancomycin because of the history of penicillin logical sequelae in six of thirteen children. 4' r. * This is somewhat allergy. His temperature subsided, but after 10 days of vanmore than the approximately 30% neurological sequelae decomycin therapy he developed a hypersensitivity rash and scribed for children following bacterial meningitis due to H. medication was changed to oral chloramphenicol which was influenzae and S. pneumonia< but higher than that of N. mencontinued for 3 weeks until his discharge. Three days after ingitides, z° The child we describe with meningitis appeared to discharge he was readmitted complaining of a fever of 37.6 °C have normal developmental milestones at 18 months, but the and increasing swelling and tenderness over the surgical scar. brain CT scan disclosed abnormalities. On examination he was febrile with moderate swelling and Although the incidence of GAS meningitis seems to be pererythema over the scar, with suspected pus under the skin. The sistently low, one must be aware that sporadic cases may have patient was taken to the operating room and 30 cc of purulent a fulminant course with possible neurological sequelae. fluid were evacuated with removal of an acrylic mesh covering the surgical area. Gram stain of the pus was negative and culture was sterile. The patient gradually recovered completely. He died 11 months later from complications of the meningioma. References
weaned from anti-convulsants and mechanical ventilation. Within days, decerebrate posturing disappeared and consciousness was regained. Normal eye movement, good sucking, symmetric four-extremity-movement and response to noise and grimaces returned. A transcranial ultrasound revealed no abnormality and repeat EEG was within normal limits. The child was discharged 16 days after admission. Long-term phenobarbital treatment was recommended. At follow-up 6 months later he was well, with developmental milestones borderline for his age. There was a decreased abdominal muscle tone, mild adductor spasm and a relative weakness of the left arm. His hearing was normal. At 12 months' follow-up an audiogram was normal. At 18 months' follow-up a head CT scan disclosed a right fronto-parietal subdural collection and encephalomalacic changes of the right frontal lobe consistent with hygroma. The left-sided collection resolved and the right subdural collection enlarged significantly. The Denver developmental score was normal at this time and thus there was no further intervention with this subdural collection.
Discussion Group A streptococcal meningitis is uncommon and is described in several reports as comprising less than 0"2% 5 and less than 0.6% ~ of all cases of meningitis. Our two cases represent the two types of meningitis seen with GAS: primary meningitis acquired through bacteraemia, and meningitis secondary to head trauma or surgery. Since the review of Group A streptococcal meningitis by Chow and Muder 4 there have been two new cases of this illness reported in the literature. 78 One was a case of streptococcal toxic shock syndrome with meningitis, caused by a streptococcal pyrogenic exotoxin A-producing
1 Moses AE, Amita~ Z, Harari M, Rahav G, Shapiro M, Engelhard D. Increased incidence and severity of Group A Streptococcal infection in young children. Pediatr InfDis ] 1995; 14: 767-770. 2 Stevens DL. Invasive group A streptococus infections. Clin Infect Dis 1992; 14: 2-13. 3 Begovac J, Marion E, Listc M, Beus I, Bozinovic D, Kuzmanovic N. Group A beta-hemolytic streptococcal toxic shock-like syndrome. Pediatr lnfeet Dis J 1990; 9: 369-370. 4 Chow )W, Muder RR. Group A streptococcal meningitis. Clin Inf Dis 1992; 14: 418-4:21. 5 Schlech WF III, Ward JI, Band JD, Hightower A, Fraser DW, Broome CV. Bacterial meningitis in the United States, 1978 through 1981: The National Bacterial Meningitis SurveilIance Study. lAMA 1985; 253: 6 Qadri SM, Berotte JM, Wende RD. Incidence and etiology of septic
118
Case Reports
meningitis in a metropolitan county hospital. Am ] Clin Pathol 1976; 54: 550-556. 7 Jevon GP, Dunne WM, Hawkins HK, Armstrong DL, Musser JM. Fatal group A streptococcal meningitis and toxic shock-like syndrome: case report. Clin InfDis 1994; 18: 91-93. 8 WalshM, Chodock R, Quinn R, Peglow S. Group A beta-hemolytic streptococcal meningitis associated with uncomplicated varicella (letter). Am ] Emerg Med 1994 12: 602-603.
9 Tunkel AR, Scheld WM, Acute meningitis, In: Mandell GL, Douglas RG Jr, Bennett JE, eds. Principlesand practice of infectious diseases. 4th ed. New York: Churchill Livingstone, 1995: 831-865. 10 Kabani A, ladavji T. Sequelae of acute bacterial meningitis in children. In: SchonfeldH, HelwigH, eds. Bacterial meningitis. Basel: Karger. 1992: 209-217.
A Child Case of Haemophagocytic Syndrome Associated with Cryptococcal IVleningoencephalitis K. Numata, H. Tsutsumi, S. Wakai, N. Tachi and S. Chiba Department of Pediatrics, Sapporo Medical University School of Medicine, Chuo-ku S-I, W-16, Sapporo 060, Japan A previously healthy 12-year-old Japanese girl developed meningoencephalitis due to Cryptococcus neoformans. During the course of her illness she suffered persistent high fever, severe pancytopenia, hypercytokinemia and liver dysfunction. Laboratory findings, including results of a bone marrow examination, strongly indicated complication by haemophagocytic syndrome (HPS). The preceding cryptococcal infection was thought to be a cause of the HPS because no other viral or bacterial infection could be confirmed. The girl died of acute respiratory failure during the progressive course of HPS. This may be the first reported case of HPS due to cryptococcal infection in an otherwise healthy child.
Introduction Infection-associated haemophagocytic syndrome was originally described by Risdall et al.l: histiocytic hyperplasia, haemophagocytosis, blood count depression and liver dysfunction occur in a setting ofimmunosuppression and viral infection and frequently have a rapidly progressive, fatal course. Subsequent reports have broadened the spectrum of this syndrome to include non-viral infections such as bacteria, mycobacteria and fungi.Z 3 There has only been one report of this syndrome with cryptococcosis, in AIDS patients. 3 This present case may be the first report of haemophagocytic syndrome (HPS) associated with cryptococcal meningoencephalitis in an otherwise normal child.
Case Report A 12-year-old, previously healthy Japanese girl experienced headaches, vomiting and temperature of 38 °C for several days, followed by intention tremor, gait and speech disturbance. Following admission to another hospital, the girl's CSF examination showed a white blood cell count of 210/mm 3 (80% Iymphocytes and 20% polymorphonuclear leucocytes), a lower glucose of 39 mg/dl and a higher protein of 58 mg/dl. A Gramstained smear, a stain for acid-fast bacilli, and bacterial and fungal cultures of the CSF were all negative. The complete blood count and serum chemistry were normal. Serum antibodies to Epstein-Barr virus (EBV), herpes simplex virus (HSV) and cytomegalovirus (CMV), including IgM antibody class, were
* Address correspondence to: H. Tsutsumi. Accepted for publication 28 February 1997.
negative. Antinuclear antibodies were negative, A chest radiograph showed no particular findings. A brain computed tomographic (CT) scan showed diffuse brain oedema. The patient was diagnosed with meningoencephalitis of unknown origin and treated conservatively with glycerol and dexamethazone for relief of brain oedema. Her fever fell and her neurological symptoms improved gradually during the following month; however, her headache and slight fever were repeated and slight pleocytosis (30-60/ram 3) continued after that. Two months later she developed high fever, disturbance of consciousness, a stiff neck and right hemiparesis. CSF examination again revealed sIight pleocytosis (23/mm3), Iower sugar (34 mg/dl) and higher protein (69 mg/dl) concentrations. A brain CT scan revealed diffuse cerebral oedema and many small cortical microbleedings. She was rehospitalized and retreated with glycerol and dexamethazone. Despite treatment, the fever and neruological signs continued, and she was transferred to Sapporo Medical University Hospital. Upon admission, her complete blood count showed light leucopenia of 2800/mm 3 (70% polymorphonuclear leucocyte, 18% of lymphocyte), thrombocytopenia of 34 O00/mm 3 and slight anaemia (red blood cell 3.82 x 106/mm 3, Hb 10.2 g/ dl). Serum chemistry was normal range. Bacterial and fungal cultures of the CSF and blood were negative; however, Cryptococcus neoformans was detected in the CSF sediment using an India Ink stain, and an antigen titre of Cryptococcus neoformans with the latex agglutination assay was 1:64. Cryptococcal meningoencephalitis was diagnosed. Dexamethazone had been decreased gradually and was stopped. Intravenous fluconazole injections were initiated. After 1 week of treatment, the patient's neurological symptoms appeared to show slight improvement; however, her high fever continued and her pancytopenia advanced. In addition, severe hepatosplenomegaly appeared. On the 12th day of hospitalization her white blood ceil was