Tick-borne Borrelia-Meningitis in Children An Outbreak in the Kalmar Area during the Summer of 1984

ABSTRACT. Nine children, aged 5 to 11 years, with subacute or chronic meningitis were studied. Symptoms started during the summer season in all patients and in eight of the patients the disease began with a localized erythematous lesion (ECM), mostly in the face. In one patient only there was a history of an insect bite at the site of the erythema. The neurological abnormalities included aseptic meningitis, peripheral facial nerve palsy (5/9) and oculomotor nerve palsy (1/9). Most children complained of headache, fatigue, loss of appetite and had a low grade fever. High antibody titers to Borrelia spirochetes in serum and/or cerebrospinal fluid (CSF) were demonstrated by ELISA in eight of the nine patients and by indirect immunofluorescence assay (IFA) in three patients. All patients had a dramatic improvement in their general condition and became afebrile within three days of institution of i.v. penicillin G treatment (i.v. cefuroxime in one patient).     

Clinical manifestation of Lyme borreliosis in childhood

We report on 4 children with different clinical manifestations of Lyme-Borreliosis. One patient presented with a stage 2 typical aseptic meningitis and 2 others with symptoms of Sch?nlein-Henoch purpura and rheumatic disease respectively. A further case had bilateral palsy of abducens nerve and unilateral palsy of trochlearis nerve which are described for the first time in Lyme-Borreliosis. Diagnosis was established by detection of specific antibodies to Borrelia in all patients. Differential diagnosis of these symptoms should include Lyme-Borreliosis.     

Herpes zoster meningitis in immunocompetent children: Two case reports and a literature review

We encountered two cases of Herpes zoster (HZ) meningitis, a rarely occurring complication of HZ, in previously healthy children. One patient treated with i.v. acyclovir (ACV, 31 mg/kg/day) did not recover. His symptoms were relieved somewhat by increased ACV dosage, but it caused transient renal dysfunction. Another patient treated with i.v. ACV (30 mg/kg/day) recovered. Treatment for HZ meningitis in immunocompetent children has not been established. In a literature review, 80% of 20 patients were treated with the usual dose of ACV 15–30 mg/kg/day. The present cases suggest that a high dosage of ACV up to 60 mg/kg/day should be considered (while monitoring for side‐effects) unless symptoms improve. In the review, one of every three vaccine‐strain Varicella zoster virus (VZV) cases was severe, whereas the present cases resulted from wild type. Further investigations must examine different clinical characteristics of HZ meningitis caused by wild‐type and vaccine‐strain VZV.     

Late Ophthalmological Sequelae of Tuberculous Meningitis

One hundred and three patients who had recovered from tuberculous meningitis in 1949—54 were thoroughly re-examined ophthalmologically an average of 8 1/2 years (range 6—12 1/2 years) after recovery. One blind patient and one with severe visual impairment were found. In addition to these, a number of cases with ophthalmological sequelae of minor importance were found; partial structural and functional lesions of the optic nerve were found in 17 cases (including 1 case with associated abducens nerve palsy), nystagmus was found in 2, pupillary disturbances in 6 and scars of choroidal tubercles in 16 cases. Thus 36 cases (35 per cent) showed ophthalmological sequelae of the past illness. Permanent visual disability was found in the 2 cases mentioned above, both of them being late cases with a high block treated with trephination. Of the other sequelae of the disease only intracranial calcification showed some degree of correlation with the ophthalmological sequelae.     

Borrelia infection in children

All children (less than or equal to 15 years) admitted during 1986 to Sachs Children's Hospital and presenting signs of facial palsy and/or meningitis, or with a history of known tick bite followed by headache, fatigue and muscle pain, were investigated for antibodies to Borrelia in serum and cerebrospinal fluid. (The hospital's catchment area has a high incidence of tick-borne Borrelia infections.) Significantly elevated antibody titre was found in 15 of the 33 patients, in three cases only in cerebrospinal fluid. Eight of the 15 children had facial palsy, which was concomitant with meningitis in six cases. Intravenous penicillin was given to all 15 patients with positive antibody titre, and additionally to three severely ill small children with facial palsy and meningitis. Furthermore, two cases of erythema chronicum migrans, which is considered pathognomonic for Borrelia infection, were treated with penicillin perorally. Cases of Borrelia infection occurred throughout the year, but with a peak in August. To emphasize the variety of symptoms, three cases are presented in some detail.     

Borrelia Infection in Children

ABSTRACT. All children (15 years) admitted during 1986 to Sachs Children's Hospital and presenting signs of facial palsy and/or meningitis, or with a history of known tick bite followed by headache, fatigue and muscle pain, were investigated for antibodies to Borrelia in serum and cerebrospinal fluid. (The hospital's catchment area has a high incidence of tick-borne Borrelia infections.) Significantly elevated antibody titre was found in 15 of the 33 patients, in three cases only in cerebrospinal fluid. Eight of the 15 children had facial palsy, which was concomitant with meningitis in six cases. Intravenous penicillin was given to all 15 patients with positive antibody titre, and additionally to three severely ill small children with facial palsy and meningitis. Furthermore, two cases of erythema chronicum migrans, which is considered pathognomonic for Borrelia infection, were treated with penicillin perorally. Cases of Borrelia infection occurred throughout the year, but with a peak in August. To emphasize the variety of symptoms, three cases are presented in some detail.     

Predictors of long term neurological outcome in bacterial meningitis

Objective To study the long-term neurological and developmental outcome and the clinical and laboratory predictors of sequelae in children with acute bacterial meningitis (ABM). Methods Detailed clinical and demographic data was retrieved from the medical records of study children. Subsequently they were followed up for a minimum of 12 months after discharge for development, neurological and hearing assessment. All sequelae were identified and divided into minor or major. For analysis data was divided into 2 groups those with sequelae and without sequelae at follow-up. Statistical analysis was done using SPSS version 10.00 and Epi Info version 2000. Results 61 boys and 19 girls, a mean age of 31.4±41.9 months at the time of ABM, were included in the study. Of these 62.5% children were infants. Mean age at follow-up was 58.6 ± 47.2 months. Sequelae were observed in 32 (40%) children (8 (10%) minor and 24 (30%) major). Mean social quotient at follow-up was 92.8 ± 32.6. Developmentally 22 (37.9%) children were normal and 20 (34.5%) had global delay. Seizures (P=0.015), cranial nerve palsy (P=0.0065), abnormal deep tendon reflexes (P=0.002), Glasgow coma scale score (GCS) < 8 (P = 0.044) at admission, a CSF culture positive for bacteria and abnormal findings on ultrasonography or computed tomography of head at admission had significant association with sequelae at follow-up. All children (7/7) who had infarct on CT scan (P=0.001) and 12 (80%) of 15 patients who had hydrocephalus (OR-9.0, 95% Cl-2.03-45.6, P=0.001) diagnosed on CT scan developed severe sequelae. On multiple regressions GCS score <8, presence of cranial nerve palsy and abnormal deep tendon reflexes were independent predictors of sequelae. Conclusion Neurological and audiological sequelae and global developmental delay may be seen in about one third of survivors of bacterial meningitis. GCS score <8, presence of infarct or cranial nerve palsy, or hydrocephalous on CT/ultrasound at admission may help in identification of children most likely to need long term follow up and rehabilitation.     

Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children

17 cases of purulent meningitis in 15 children, aged 1 day to 5 years (median 8 months) were treated with continuous i.v. infusion of chloramphenicol succinate. Free chloramphenicol in serum and cerebrospinal fluid (C.F.) was assayed by high performance liquid chromatography (HPLC). CF chloramphenicol levels averaged 45 +/- 14% of the serum level. Out of 16 patients only five received the usually recommended dosage. In three others because of initially or progressively high serum levels the dose had to be diminished. In eight others because of subtherapeutic levels the dose had to be raised. The highest dose (390 mg/kg body weight/d) was required in a 2 month old boy. He was shown to have a clearance rate for free chloramphenicol considerably higher than has been reported so far. Maturation of the metabolism could be observed in a small-for-date newborn who acquired a grey baby syndrome during the treatment of his first meningitis. Several weeks later he required exactly the recommended dose to reach therapeutic chloramphenicol levels. As a consequence of these observations we strongly recommend meticulous drug monitoring of chloramphenicol in order to meet the large biological variations seen particularly in neonates and young infants in their capacity to reach and maintain therapeutic serum levels.     

Peripheral Facial Palsy in Children: A Cerebrospinal Fluid Study

Seven children and five adults with acute, peripheral facial palsy were investigated by clinical, blood and cerebrospinal fluid (CSF) examinations. Routine blood examinations and blood and CSF serological tests were normal. In all children studied the CSF showed an increased number of mononuclear white cells despite the absence of clinical signs of meningitis in all but one. Two of the twelve patients studied had normal CSF. Contrary to that in adults the outcome in children was excellent, all recovered totally within three months. The present study indicates that acute, peripheral facial palsy is a manifestation of a generalized disorder with subclinical pathology of the central nervous system, and that in children a lumbar puncture should be done, even if there are no signs of meningitis.     

Peripheral facial palsy in children. A cerebrospinal fluid study

Seven children and five adults with acute, peripheral facial palsy were investigated by clinical, blood and cerebrospinal fluid (CSF) examinations. Routine blood examinations and blood and CSF serological tests were normal. In all children studied the CSF showed an increased number of mononuclear white cells despite the absence of clinical signs of meningitis in all but one. Two of the twelve patients studied had normal CSF. Contrary to that in adults the outcome in children was excellent, all recovered totally within three months. The present study indicates that acute, peripheral facial palsy is a manifestation of a generalized disorder with subclinical pathology of the central nervous system, and that in children a lumbar puncture should be done, even if there are no signs of meningitis.     

Recurrent facial nerve palsy in paediatric patients

The aim of the study was to investigate the clinical presentation and prognosis of recurrent facial nerve palsy (RFNP) in children. The files of 182 patients referred to the Schneider Children's Medical Centre of Israel for neurological evaluation of isolated peripheral facial nerve palsy between October 1992 and December 1998 were reviewed. RFNP was found in 11 patients (9 females, 2 males), with an incidence of 6%. In two males, the aetiology was traced to Melkersson-Rosenthal syndrome and these patients were separated from the rest of the group. Three children had two episodes of facial nerve paresis which completely resolved clinically within several weeks. Six other children underwent electrophysiological studies. Two of the latter with residual neurological damage, and one child with abnormal blink reflex only, showed decreased facial nerve conduction velocity and abnormal blink reflex. Three children with complete recovery had disturbed blink reflex only with normal nerve conduction. Brain imaging studies as well as laboratory work-up were non-contributory in all cases. CONCLUSION: The frequency of recurrent facial nerve palsy in children was similar to that in adults. The most significant factors in the evaluation of recurrent facial nerve palsy are medical history and physical findings at diagnosis and after short follow-up. In our patients, electrophysiological studies did not have either clinical or prognostic significance. The rate of full clinical recovery is about 70%, lower than in Bell palsy.     

Diagnostic utility of Borrelia burgdorferi cerebrospinal fluid polymerase chain reaction in children with Lyme meningitis

BACKGROUND: Cerebrospinal fluid (CSF) laboratory tests are frequently collected to help differentiate Lyme meningitis from other causes of aseptic meningitis. Previous studies using Lyme CSF polymerase chain reaction (PCR) have yielded varied results (sensitivity between 10 and 90%). No studies have specifically examined the diagnostic utility of Lyme CSF-PCR in North American children with Lyme meningitis. METHODS: Retrospective chart review of children presenting to a children's hospital in a Lyme-endemic region between October 1999 and September 2004. Patients were included if they had both Lyme serology and Lyme CSF-PCR performed during the same hospital encounter and had documented meningitis. Patients were considered to have Lyme meningitis if they had meningitis and met CDC criteria for Lyme disease. The Lyme CSF-PCR assay amplified a Borrelia burgdorferi DNA flagellin gene sequence. RESULTS: Of 108 patients with meningitis who qualified for the study, 20 patients met criteria for Lyme meningitis and 88 were classified as aseptic meningitis. Positive Lyme CSF-PCR was found in 1 patient (1 of 20, 5%) with Lyme meningitis and one patient classified as aseptic meningitis (1 of 88, 1%). Lyme CSF-PCR had a sensitivity of 5% and a specificity of 99%. The only Lyme meningitis patient with positive Lyme CSF-PCR had the highest CSF white blood cell count and CSF protein values compared with the other Lyme meningitis patients. CONCLUSIONS: This is the first study to evaluate Lyme CSF-PCR exclusively in North American children. This commercially available laboratory test is not generally helpful for identifying Lyme meningitis because of its low sensitivity.     

Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.     

Outcome in infants of birth weight 500 to 999 g: a continuing regional study of 5-year-old survivors

During 1979 and 1980, 351 infants of birth weight 500 to 999 g were born in the State of Victoria: 89 (25.4%) survived to the age of 2 years corrected for prematurity, and 83 were fully assessed by a multidisciplinary team; partial data were obtained on the remainder. At the age of 5 years, corrected for prematurity, 85/89 (96%) were evaluated by a multidisciplinary team, although not all children could be fully evaluated by the psychologists. Reports were available for another three children; one child was untraced. Of the survivors able to be classified at 5 years, 59/82 (72%) had no functional handicap. Functional handicaps was severe in 16 (19%), moderate in four (5%), and mild in three (4%). Functional handicaps were present in 50% (8/16) of outborn survivors compared with the 23% (15/66) for the inborn survivors (P = 0.02). Cerebral palsy was diagnosed in eight children at 5 years and in 12 children at 2 years. The diagnosis was stable for the children not ambulant at 2 years; five of seven 2-year-old children with mild cerebral palsy had "outgrown" the diagnosis by 5 years, but ataxic cerebral palsy was not identified in one child until 5 years. Six children were blind; four had severe sensorineural or mixed deafness, one more than at 2 years. Of 82 children assessed according to identical criteria for functional handicap at both 2 and 5 years, 52 (63%) remained in the same category at 5 years, three (4%) were judged to be more severely handicapped, and 27 (33%) were less severely handicapped. The 2-year evaluation of extremely low birth weight children often proved to be unduly pessimistic, for many showed improvement or recovery from functional handicaps and impairments by 5 years of age.     

Borreliosis in children - clinical manifestation, diagnosis and treatment

Lyme Disease (Borreliosis) is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi, transmitted by the bite of ixodes infected ticks. We would like to present our experience with the treatment of borreliosis in collaboration with the Warsaw Medical Academy's Department of Infectious Disease. Fifty-nine children (aged between 14 months to 16 years) were hospitalized or ambulatory treated due to borreliosis during 5 years between 1997 and 2001. Erythema migrans was observed in 50 cases. The main localisations of erythema were: face, neck and chest. One patient showed erythema in several other localisations. Erythema migrans returned in two cases after therapy with Amoxicillin in one case at 6 months, in the other one 12 months later. The incubation period of erythema migrans in children varied from 4 to 30 days. Seven cases from the 59 occurred with central nervous system manifestations. These were children between 6 and 16 years of age. The most frequent (65.5%) clinical manifestations of the central nervous system were meningitis and facial nerve palsy, depression and headaches were observed in 6% of cases. In one case admission to hospital was the result of leucopaenia (2800/mm3), bradycardia, headache and fatigue. The positive serologic test results (Elisa assay) were confirmed in two independent laboratories. We had one patient (5 years old boy) with arthritic manifestations. The diagnosis of Lyme disease was based on clinical manifestations and positive serologic test results (Elisa assay). In the acute stage Elisa assay was positive in 33% only. The erythema migrans cases received treatment with Amoxicillin for two weeks, whilst patients with neuroborreliosis were treated for 4 weeks with Ceftriaxon.     

幼年粒单细胞白血病造血干细胞移植疗效初探

目的探讨造血干细胞移植治疗幼年粒单细胞白血病(JMML)的疗效。方法 5例JMML患儿接受无关供者脐血造血干细胞移植治疗。预处理均采用Bu/Cy+Mel+ATG方案:马利兰(0.8～1.0)mg/kg,每6小时1次共用16次(-8d～-5d);环磷酰胺60mg/(kg·d)用2d(-4～-3d);马法兰140mg/m2用1次(-2d):抗胸腺细胞球蛋白2.5mg/(kg·d)连用4d(-4～-1d)。GVHD预防采用CsA+MP±MMF。结果 5例成功植入,3例复发,1例复发后死于卡氏肺囊虫肺炎,1例死于CMV感染相关间质性肺炎,1例长期无病存活。结论 5例JMML移植初步治疗结果不满意,移植失败主要原因为白血病复发。为减少复发,今后需进一步改进移植方法 ,包括选择其他供体、改进GVHD预防方案。     

Cerebral infarction in Hemophilus influenzae type B meningitis

Over a 5-year period, 8 (4.7%) of the 170 children diagnosed at Milwaukee Children's Hospital as having Hemophilus influenzae type b (HITB) meningitis developed cerebral infarction. Compared with children who did not develop infarcts or with children who developed other neurologic complications, such as subdural effusion, empyema, or meningoencephalitis, these children had significantly higher cerebrospinal fluid (CSF) leukocyte counts on initial lumbar puncture and had a greater likelihood of seizure activity. In seven of eight patients with cerebral infarction, a focal or generalized seizure heralded neurologic findings associated with abnormal radiographic studies. Two of the eight patients died, and two were permanently severely damaged. In the other four patients, there was eventual recovery from gross neurologic deficits. The mortality in patients with HITB meningitis complicated by cerebral infarction (25%) was significantly greater than that in other patients with HITB meningitis (0.6%). The pathophysiology of infarction in patients with bacterial meningitis is uncertain but may in part relate to arteriospasm. Cerebral infarction is a serious, and in the present experience, not uncommon complication of H. influenzae meningitis.     

Cefuroxime in bacterial meningitis.

In order to find an alternative antimicrobial treatment for childhood bacterial meningitis 30 infants and children with meningitis, due to Haemophilus influenzae (n = 13), Neisseria meningitis (n = 9), Streptococcus pneumoniae (n = 5), or meningitis of unknown aetiology (n = 3), were treated with cefuroxime, 200 mg/kg a day, as the only antibiotic. Prompt clinical and bacteriological responses were noted and every patient was cured. Cefuroxime concentrations in cerebrospinal fluid ranged from 1.1 to 18.8 (mean 7.0) mg/l at the beginning and from 0.5 to 4.1 (mean 1.6) mg/l at the end of treatment. Three infants developed symptomatic sterile subdural effusions which were managed by repeated subdural aspirations while still on antibiotics. Cefuroxime concentrations in the subdural fluid ranged from 17.4 to 32.4 mg/l. At follow-up 2 patients had moderate unilateral hearing loss and one had mild ataxia. We conclude that cefuroxime is effective and safe for the treatment of childhood bacterial meningitis caused by any of these common organisms.     

Invasive Haemophilus influenzae type b infections in Singapore children: a hospital-based study

OBJECTIVE: A 6-year (1990-95) hospital-based retrospective study was carried out to investigate the pattern of invasive Haemophilus influenzae type b (Hib) disease. METHODOLOGY: Cases with Hib isolated from sterile sites (blood, cerebrospinal fluid, or joint aspirate) were identified from the hospital's microbiological records, and their reviewed case records. Patients with pyogenic meningitis in the same study period were also identified to estimate the incidence of Hib meningitis. RESULTS: Twelve patients had positive cultures from sterile sites, of whom nine children were less than 5 years of age. These included seven cases of meningitis, one patient with acute epiglottitis, and one case of pneumonia. Three of the seven patients with meningitis had significant long-term sequelae. Our data also suggests a relatively low proportion of ethnic Chinese children with invasive disease. It was estimated that 18.4% to 41.1% of pyogenic meningitis in children admitted to the National University Hospital were due to Hib. The estimated annual attack rate of invasive Hib disease was at most 3.3 per 100 000 children aged less than 5 years (95% confidence interval: 2.6-3.5/100 000). CONCLUSION:: Invasive Hib infections are relatively uncommon in our community. This justifies the need for a cost effectiveness study before a universal Hib vaccination program is implemented.     

Meningitis in Hong Kong children, with special reference to the infrequency of haemophilus and meningococcal infection

Objective: To study the epidemiologic and aetiologic features of meningitis in children in Hong Kong.
Methodology: A retrospective study of 85 children resident in the New Territory East region of Hong Kong admitted to a teaching Hospital because of meningitis during a 9 year period.
Results: Mycobacterium tuberculosis was the most common aetiological agent accounting for 13 cases (15.3%). Other bacteria accounted for 41 cases (48%); among these one fifth were caused by Haemophilus influenzae type b. The overall admission rates for tuberculous meningitis in Chinese children were 0.76/100 000 (95% CI 0.25-1.78) and 0.42/100 000 (CI 0.19-0.8) per year, respectively, for under 5 year olds and under 15 year olds. The overall annual incidence rates of bacterial meningitis other than tuberculous were 5.2/100 000 (CI 3.72-7.43) and 1.6/100 000 (CI 1.14-2.29) for Chinese children under 5 years and under 15 years, respectively. The annual incidence of H. influenzae meningitis in Chinese children under 5 years old was low at 1.1/100 000 (0.43-2.2). All five cases of meningococcal meningitis were in Vietnamese children (under 5 years of age incidence: 13.0/100 000 per year, CI 4.2-30.3). There were no cases of meningococcal meningitis in Chinese children during the 9 year period.
Conclusion: M. tuberculosis was the most common aetiological agent of meningitis in Hong Kong children. The incidence of haemophilus or meningococcal meningitis was very low.