Lyme neuroborreliosis in children: Report of nine cases and a review of the literature

Lyme neuroborreliosis is a bacterial infection caused by the dissemination and proliferation of a Borrelia species in the central nervous system. Neuroborreliosis occurs after transmission of the pathogen from an infected tick to a human host during a tick bite. We report nine cases of pediatric neuroborreliosis collected by the National Observatory of Pediatric Bacterial Meningitis in France between 2001 and 2012. The nine children, aged 4–13 years, were identified in northern and eastern France and had the following clinical features: meningeal irritation alone or with facial palsy, or isolated facial palsy. All cases showed anti-Borrelia antibodies in cerebrospinal fluid or serum, or with a positive Borrelia PCR in the CSF. The outcome was favorable in all cases after a 2- to 3-week course of third-generation cephalosporin. On the basis of these nine pediatric cases, this study provides an update on the epidemiology, pathophysiology, diagnostic strategy, and treatment of neuroborreliosis, with insight into the specific features of pediatric neuroborreliosis and the difficulties encountered in the diagnosis of this infection.     

Lyme borreliosis--the most frequent cause of acute peripheral facial paralysis in childhood

A prospective hospital-based multicentre study in Lower Saxony allowed to investigate the frequency of acute peripheral facial palsy due to Lyme borreliosis and its clinical and laboratory characteristics. Diagnosis of Lyme Borreliosis was based on detection of IgM antibodies against Borrelia burgdorferi in serum and CSF as well, using an IgM capture ELISA. Between June 1986 and October 1987 27 consecutive cases with acute peripheral facial palsy were studied. Lyme borreliosis is the main cause of peripheral facial palsy in childhood. It was verified serologically in two thirds of the cases. All cases with a positive history for a tick bite and/or an erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi. Peripheral facial palsy due to Lyme borreliosis represents a monosymptomatic meningoradiculitis. All children with Lyme borreliosis revealed a lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF findings usually were normal. Therefore, in any case of facial palsy with an inflammatory CSF syndrome Lyme borreliosis has to be suspected unless proven otherwise.     

Peripheral facial palsy in childhood--Lyme borreliosis to be suspected unless proven otherwise

27 consecutive cases with acute peripheral facial palsy were studied for Lyme borreliosis. In 16 out of 27 children Lyme borreliosis could be diagnosed by detection of specific IgM antibodies in CSF. CSF findings allow a clear distinction according to etiology. All children with facial palsy due to Lyme borreliosis revealed lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF was usually normal. Bilateral facial palsy occurred only in children with Lyme borreliosis. All cases with a positive history of tick bite and/or erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi.     

Peripheral Facial Palsy in Childhood-Lyme Borreliosis to be Suspected Unless Proven Otherwise

ABSTRACT. 27 consecutive cases with acute peripheral facial palsy were studied for Lyme borreliosis. In 16 out of 27 children Lyme borreliosis could be diagnosed by detection of specific IgM antibodies in CSF. CSF findings allow a clear distinction according to etiology. All children with facial palsy due to Lyme borreliosis revealed lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF was usually normal. Bilateral facial palsy occurred only in children with Lyme borreliosis. All cases with a positive history of tick bite and/or erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi.     

Uncommon manifestations of neuroborreliosis in children

Lyme borreliosis is a tick-borne spirochetal infection which affects the skin, joints, heart and nervous system. Children with a neuroborreliosis usually present with a facial nerve palsy or aseptic meningitis, but the spectrum also includes other rare manifestations. We report four unusual cases of childhood neuroborreliosis and show that seizures with regional leptomeningeal enhancement, acute transverse myelitis, meningoradiculitis with pain and paraesthesia and cranial nerve palsies other than facial nerve palsy can be the leading symptoms of children with neuroborreliosis. All children had serological evidence of an acute infection with Borrelia burgdorferi, a pleocytosis in the cerebrospinal fluid and a complete response to antibiotic treatment. An intrathecal synthesis of IgG antibodies was detected in three children. Thus, diagnostic work up in children with unusual neurological symptoms should include cerebrospinal fluid studies with determination of the white blood cell count and calculation of the antibody index against B. burgdorferi.     

Detection ofBorrelia burgdorferi by nested polymerase chain reaction in cerebrospinal fluid and urine of children with neuroborreliosis

Diagnosis of neuroborreliosis is often difficult since history and clinical presentation may be non-specific and serological tests may initially be negative. We therefore tested the polymerase chain reaction (PCR) for the detection of borrelial sequences in CSF and urine samples of consecutive children with neuroborreliosis seen in a single summer season. Four of eight children were negative in serum for antibodies toBorrelia burgdorferi. Two of eight children were PCR-positive in CSF and one other child was positive in urine. In two out of four children PCR was the only laboratory test confirming the clinical diagnosis. All children recovered after treatment with third generation cephalosporins. When seven of eight children were re-examined 6 months later all were healthy and antibodies toB. burgdorferi were detected in their serum. PCR may assist the paediatrician in establishing a diagnosis of neuroborreliosis; however, a negative result does not rule out neuroborreliosis. PCR is an adjunct, but no substitute for clinical judgement and serology.     

Lyme borreliosis in children

A total of 27 children with clinical symptoms indicative of Lyme borreliosis are described, 21 of which were seropositive. CNS symptoms were found in 17 of the seropositive childen (81%). Of these 21, 7 were CSF negative. Another 3 (with Bell's palsy and/or aseptic meningitis) were initially CSF negative but developed specific CSF titres 80, 65 and 120 days after the first lumbar puncture, respectively. Thus, seropositive children with aseptic meningitis and without initial signs of an infectious aetiology should be checked for a neuroborreliosis even when CSF negative in the first lumbar puncture. Antibiotic therapy undertaken in 26 children showed clinical recovery (Sodium penicillin, 300,000–500,000 units/kg per day for 14 days). One developed residual hypoacusis. Comparison of enzyme-linked immunosorbent assay (ELISA) IgG values from 27 cases with those of 30 healthy controls showed that elevated ELISA titres are a good indication of the disease. However, Lyme borreliosis can only be diagnosed correctly if the clinical symptoms conform with specific titres.Abbreviations Bb Borrelia burgdorferi - CNS central nervous system - CSF cerebrospinal fluid - EBV Epstein-Barr virus - ECM erythema chronicum migrans - ELISA enzyme-linked immunosorbent assay - Ig immunoglobulin - Lb Lyme borreliosis     

快速诊断单纯疱疹病毒脑炎

目的探讨快速诊断单纯疱疹病毒脑炎（ＨＳＥ），比较不同病毒学试验的诊断价值。方法用聚合酶链反应技术检测１７７例急性脑炎患儿的脑脊液（ＣＳＦ）标本中单纯疱疹病毒（ＨＳＶ）特异性ＤＮＡ；用酶联免疫吸附方法检测ＣＳＦ和血清标本中ＨＳＶ特异性ＩｇＭ和ＩｇＧ抗体。结果ＣＳＦ中ＨＳＶ特异性ＤＮＡ、ＩｇＭ和ＩｇＧ抗体阳性率分别为１．７％（３／１７７）、１０％（１／１００）和４７０％（４７／１００），血清ＨＳＶＩｇＭ、ＩｇＧ抗体阳性率分别为１２．５％（６／４８）、７２．９％（５１／７０）（因为标本量不足或缺如，未能对全部病例进行抗体检测）；３例患儿确诊为ＨＳＥ。结论用套式ＰＣＲ检测ＣＳＦ诊断ＨＳＥ较敏感、特异。     

Lyme disease with lymphocytic meningitis, trigeminal palsy and silent thalamic lesion

We describe a follow-up in a 15-year-old boy with neuroborreliosis diagnosed by clinical symptoms, CSF and serum analysis. MRI revealed a thalamic lesion and an enhancement of the right trigeminal nerve clinically associated with mild hypasthesia in the right maxillary region. Both, clinical symptoms and radiological findings disappeared within 2 months after treatment. Borrelia burgdorferi specific IgM and IgG in CSF and IgG in serum became negative between 6 and 12 months after diagnosis. We show that neuroborreliosis at an early stage may present only with moderate neurological deficits and that at this stage MRI reveals distinct cerebral lesions which might even precede clinical manifestation. Thus, early diagnosis and treatment of neuroborreliosis may prevent persistent neurologic lesions.     

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.     

Lyme neuroborreliosis in pediatrics: A retrospective,descriptive study in southwest France

BackgroundThe neurological effects of Lyme borreliosis in children are varied and their clinical progression is not widely reported in the French literature. We carried out a retrospective study to describe the clinical characteristics of Lyme neuroborreliosis in children in southwest France and their clinical progression at 6 months.MethodsThis study was carried out at Toulouse University Hospital during the period 2006–2017 using patient records. Case definition was based on the combined French clinical and laboratory diagnostic criteria.ResultsIn total, 26 children were included. The median age was 8 years (4–14 years). The different neurological symptoms reported were: meningoradiculitis (62%), which was usually associated with facial palsy (54%); isolated facial palsy (15%); isolated meningitis (8%); polyradiculoneuritis (4%); benign intracranial hypertension (4%) and myelomeningoradiculitis (4%). The most common functional symptoms were headaches (54%), the perception of asthenia (42%), neck pain (27%), and a loss of appetite (19%). Patients with laboratory meningitis (84%) often had no signs of meningism or headaches (38%).ConclusionThe majority of the cases involved meningoradiculitis but other, less common, neurological conditions have been described. The clinical signs suggestive of meningitis are not very marked and might delay the diagnosis.     

病毒性脑炎患儿肠道病毒特异性IgM抗体快速检测

目的　为了证实固相反向免疫吸附试验（ＳＰＲＩＳＴ）是肠道病毒特异性ＩｇＭ 抗体的快速检测方法。方法　用ＳＰＲＩＳＴ检测６２ 例临床拟诊为病毒性脑炎患儿脑脊液（ＣＳＦ） 或ＣＳＦ 与血清中肠道病毒ＥＣＨＯ３ 、ＥＣＨＯ５、ＥＣＨＯ７ 、Ｃｏｘ Ｂ３ 特异性ＩｇＭ 抗体。结果　１７ 例（２７－４ ％ ）ＣＳＦ阳性,ＥＣＨＯ３ 、ＥＣＨＯ５、ＥＣＨＯ７ 和ＣＯＸＢ３ 的阳性数分别为５ 例、７ 例、１ 例和４ 例。结论　ＳＰＲＩＳＴ 快速检测肠道病毒特异性ＩｇＭ 抗体可用于中枢神经系统病毒感染的早期诊断,能够指导临床治疗,避免了滥用抗生素。     

Opsoclonus in a child with neuroborreliosis: Case report and review of the literature

Opsoclonus consists of massive erratic rapid eye jerks. They may occur in isolation or in association with myoclonus and ataxia, i.e., opsoclonus-myoclonus syndrome (OMS). We report the case of a 9-year-old girl who suffered from headaches for several days and was shown to have opsoclonus and left peripheral facial palsy. Work-up excluded the diagnosis of neuroblastoma, but CSF analysis showed aseptic meningitis, and serology for Borrelia burgdorferi (Lyme) was positive. The outcome was favorable with complete regression of symptoms after treatment with ceftriaxone 2 g/day for 3 weeks. Although rare, the diagnosis of Lyme neuroborreliosis must be raised in the presence of isolated opsoclonus, particularly if the clinical picture is incomplete and if other features, such as peripheral facial palsy and pleocytosis in the CSF, are present.     

Neurobrucellosis in children

Neurobrucellosis is an uncommon disease in children. The authors present two cases of brucellar meningo-encephalitis. Headache and vomiting were the main complaints and one child had also some behavioural disturbance as well as papilloedema and sixth cranial nerve palsy. The clinical diagnosis was suggested by epidemiological data in both cases. Blood and CSF cultures confirmed brucellar aetiology in one of the cases and positive serum and CSF specific antibodies in both. Clinical course was favourable after treatment with doxycycline, rifampicin and streptomycin. No relapse occurred and there were no sequelae.     

Diagnosis and therapy of Lyme borreliosis in children. Practice guideline of the German Society for Pediatric Infectious Diseases]

Lyme borreliosis is the most frequent tickborne++ disease of man in the Northern hemisphere. A variety of systems may be involved. The most frequent manifestations in childhood include erythema migrans, meningitis, cranial nerve palsy and arthritis. Erythema migrans usually is easily recognised and determination of antibodies to Borrelia burgdorferi should not be performed. Childhood neuroborreliosis is characterised mostly by aseptic meningitis with or without cranial nerve palsy, in most cases facial palsy. Basic CSF findings often show a combined evidence of lymphocytic pleocytosis, IgM-class dominance in intrathecal humoral immune++ response, and blood-CSF barrier dysfunction. Calculation of the Borrelia burgdorferi specific antibody index (according to Reiber) proved to be the most sensitive method for detecting intrathecal synthesis of specific antibodies. Lyme arthritis presents initially as episodic oligoarthritis, mostly involving the knee joint, and may turn into chronic monoarthritis of the knee; usually high titers of IgG antibodies to Borrelia burgdorferi are found. The rarer manifestations encephalomyelitis, chronic arthritis, carditis and inflammatory eye disease may be difficult to diagnosis due to clinical ambiguity and problems in the interpretation of serological results. Antibodies to Borrelia burgdorferi found by sensitive Elisa must always be confirmed by immunoblot analysis, but sometimes immunoblot analysis is more sensitive than Elisa. Treatment is by antibiotics, amoxicillin or doxyciclin for erythema migrans, and i.v. third generation cephalosporins for all other manifestations. Even after successful antibiotic therapy, antibodies may persist for months and years and no further antibiotic treatment is necessary in the absence of attributable clinical manifestations. The differentiation between a persisting immune response and a persisting infection therefore has to be based upon the clinical symptoms, non-specific laboratory data and the development of the antibody titers.     

Canalicular magnetic stimulation lacks specificity to differentiate idiopathic facial palsy from borreliosis in children.

OBJECTIVE: To investigate the role of transcranial magnetic stimulation (TMS) to differentiate between idiopathic facial nerve palsy (iFNP) and facial nerve palsy due to borreliosis (bFNP). PATIENTS AND METHODS: Transcranial and intracanalicular magnetic and peripheral electrical stimulation of the facial nerve together with clinical grading according to the House and Brackmann scale were performed in 14 children and adolescents with facial palsy (median age 11.5yr, range 4.6-16.5yr). Serum and cerebrospinal fluid (CSF) were evaluated for antibodies against Borrelia burgdorferi and CSF cell count, glucose and protein content were screened with methods of routine laboratory testing. Data of patients were compared with normal values established in 10 healthy subjects (median age 10.2yr, range 5.1-15.3yr). RESULTS: Patients with iFNP showed a significant decrease in MEP amplitude to canalicular magnetic stimulation compared with healthy controls (p=0.03). However, MEP amplitude did not discriminate sufficiently between the two groups, because the ranges of dispersion of MEP amplitudes overlapped. Patients with bFNP had normal MEP amplitudes to canalicular magnetic stimulation compared with normal subjects. CONCLUSION: Diagnostic assessment by TMS failed to provide a reliable diagnostic criterion for distinguishing between iFNP and bFNP in children and adolescents.     

Diagnostik und Therapie der Lyme-Borreliose im Kindesalter Empfehlung der Deutschen Gesellschaft für Pädiatrische Infektiologie

Lyme borreliosis is the most frequent tick-borne disease of man in the Northern Hemisphere. A variety of systems may be involved. The most frequent manifestations in childhood include erythema migrans, meningitis, cranial nerve palsy and arthritis. Erythema migrans is usually easily recognized and determination of antibodies to Borrelia burgdorferi should not be performed. Childhood neuroborreliosis is characterized mostly by aseptic meningitis with or without cranial nerve palsy, in most cases facial palsy. Basic CSF findings often show combined evidence of lymphocytic pleocytosis, IgM-class dominance in intrathecal humoral immune response, and blood-CSF barrier dysfunction. Calculation of the B. burgdorferi-specific antibody index (according to Reiber) has proved to be the most sensitive method for detecting intrathecal synthesis of specific antibodies. Lyme arthritis presents initially as episodic oligoarthritis, mostly involving the knee joint, and may turn into chronic monoarthritis of the knee; usually high titers of IgG antibodies to B. burgdorferi are found. Rarer manifestations such as encephalomyelitis, chronic arthritis, carditis and inflammatory eye disease may be difficult to diagnose due to clinical ambiguity and problems in the interpretation of serological results. Antibodies to B. burgdorferi found by the sensitive Elisa test must always be confirmed by immunoblot analysis, but sometimes immunoblot analysis is more sensitive than the Elisa. Treatment is by antibiotics, amoxicillin for erythema migrans, and i. v. third-generation cephalosporins for all other manifestations. Discussion: Even after successful antibiotic therapy, antibodies may persist for months and years, and no further antibiotic treatment is necessary in the absence of attributable clinical manifestations. The differentiation between a persisting immune response and a persisting infection therefore has to be based upon the clinical symptoms, non-specific laboratory data and the development of antibody titers.     

Evaluation of polymerase chain reaction (PCR) for diagnosing Haemophilus influenzae b meningitis

A polymerase chain reaction (PCR) for detecting Hib in cerebrospinal fluid (CSF) was evaluated and compared with culture and a latex agglutination test (LAT) in a hospital-based prospective surveillance. We studied 107 children aged from 1 month to 12 years with a clinical and CSF profile suggestive of acute bacterial meningitis. CSF culture was performed on blood-chocolate agar by standard technique, LAT by a commercially available kit (Wellcogen) and PCR using total DNA extracted from CSF samples. Of 107 children, 79% had received one or more doses of injectable antibiotics. Hib was detected by culture in 14 cases, by LAT in 23 and by PCR in 37. All CSF samples that reveal Hib by culture or LAT had a PCR positive for Hib (sensitivity 100%). PCR also detected 14 additional cases of Hib meningitis which were not detected by culture or LAT. We conclude that PCR is a sensitive and specific diagnostic tool that may be valuable in a population with high pre-hospital antibiotic usage.     

腮腺炎脑膜脑炎患儿血清及脑脊液特异性IgM抗体检测及其临床意义

目的探讨腮腺炎脑膜脑炎患儿血清及脑脊液特异性IgM抗体检测的临床意义。方法对97例临床诊断为腮腺炎脑膜脑炎患儿，应用酶联免疫吸附试验(ELISA)方法检测血清及脑脊液特异性IgM抗体。结果血清IgM抗体阳性率为94.44％(85/90)，脑脊就座IgM抗体阳性率为86.90％(73/84)。结论采用ELISA方法检测脑脊液腮腺炎病毒特异性IgM抗体是早期诊断腮腺炎脑膜脑炎的有效方法之一。