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.     

An early-onset case of multiple sclerosis with thalamic lesions on MRI

We present here an early-onset case of multiple sclerosis (MS) with thalamic lesions. The patient first experienced an episode of ataxic gait at 2 years 3 months of age, with spontaneous remission within 1 month. At 5 years 4 months, she was admitted because of cerebellar ataxia, oculomotor restriction and feeding difficulty. Magnetic resonance imaging (MRI) showed multiple well-defined lesions in the white matter of the cerebellum, mid-brain, periventricle and right frontal lobe. Cerebrospinal fluid (CSF) showed a mild elevation of both immunoglobulin G (IgG) and myelin basic protein (MBP). Serum anti-myelin antibody was also positive, although leukocytosis and elevation of C-reactive protein were not found. Methylprednisolone pulse therapy relieved symptoms within 2 weeks and the abnormal MRI and CSF findings gradually improved. At 6 years 6 months of age, she incurred a third episode of cerebellar ataxia and disturbance of consciousness. Magnetic resonance imaging revealed recurrence and extension of the previous lesions as well as new lesions in the thalamus and internal capsule. CSF IgG and MBP level showed a higher elevation than in the second episode. The combination of the cerebellar, brain-stem, cerebral and thalamic lesions with remission and exacerbation, supported by MRI and CSF findings, allowed the diagnosis of clinically definite MS to be made. This is one of the youngest cases of MS yet described, with the first attack occurring at 27 months of age. In addition, this case is unique for the involvement of the gray matter in the thalamus.     

Evaluation of the polymerase chain reaction for the detection ofBorrelia burgdorferi in cerebrospinal fluid of children with acute peripheral facial palsy

Neuroborreliosis occasionally represents a diagnostic problem, especially in the early stage of the infection. The polymerase chain reaction (PCR) offers an attractive alternative to antibody testing. The aim of our study was to investigate the diagnostic potential of PCR in comparison to antibody tests in CSF of children with facial palsy. In contrast to other manifestations of neuroborreliosis, facial palsy is a welldefined clinical entity in which CSF findings allow an early distinction according to aetiology. The study included 17 children with neuroborreliosis, defined by the detection of specific IgM antibodies in CSF, and 20 children with facial palsy of unknown cause. Primers used for the nested PCR were generated from conserved sequences of the OspA-gene. Most of the cases in both subgroups have been examined within a few days after the onset of the paresis. Only in 2 out of 17 cases with neuroborreliosis could specific DNA be amplified. The PCR gave negative results in all cases of the control group.Conclusion The IgM capture ELISA is superior to PCR to support the clinical diagnosis of neuroborreliosis.     

Acute disseminated encephalomyelitis after allogeneic bone marrow transplantation for pure red cell aplasia – A case report and review of the literature

ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15‐yr‐old boy who was diagnosed with ADEM after an HLA‐identical sibling allogeneic BMT for transfusion‐dependent PRCA. His course was complicated with GVHD affecting the skin and lungs. Five months post‐BMT, he developed neurological symptoms including sudden mental status alteration, dysarthria, facial nerve palsy, and acute paraplegia. The MRI revealed multifocal hyperintense lesions mainly in the subcortical white matter of the cerebrum, the brainstem, the basal ganglia, and the thalami. CSF examination was normal. There was no laboratory evidence of infection. The typical MRI findings and an acute monophasic clinical course were consistent with the diagnosis of ADEM. Clinical and radiological improvement was observed after treatment with high‐dose steroids and IVIG. Complete neurologic recovery was achieved six months after the onset of symptoms. We present a rare case of ADEM post‐BMT and review of the literature.     

Subacute sclerosing panencephalitis (SSPE) associated with congenital measles infection

A 13-month-old male presented with repetitive episodes of myoclonic jerks of the head and extremities for two months. His past medical history revealed that his non-immunized mother had measles at the time of delivery. Measles antibody titers in serum and cerebrospinal fluid (CSF) were 1/512 (hemagglutinin inhibition [HI]) and 1/128 HI, respectively. Immunofixation electrophoresis of CSF revealed an oligoclonal IgG band. The magnetic resonance imaging (MRI) of the brain on T2-weighted images showed lesions of high signal intensity in the subcortical white matter. Electroencephalography (EEG) revealed periodic high-amplitude slow waves. Diagnosis of subacute sclerosing panencephalitis (SSPE) was based upon clinical presentation, a characteristic EEG, and abnormal CSF studies. MRI findings supported the diagnosis. To the best of our knowledge, this is only the 3rd case to date, of SSPE-associated congenital measles in the literature.     

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     

Neuroborreliosis and isolated trochlear palsy.

We report here for the first time a child with isolated trochlear palsy and neuroborreliosis. IgG and IgM antibodies against Borrelia burgdorferi were highly positive in serum and cerebrospinal fluid respectively. The symptoms resolved completely after initiation of antibiotic treatment with ceftriaxone.     

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.     

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.     

Human herpes virus type 6, etiology of an acute encephalitis in childhood: case report]

Primary infection with human herpesvirus-6 (HHV-6) causes the classical roseola infantum. Otherwise the infection is clinically silent but it may sometimes be responsible for central nervous system involvement. In order to illustrate such a type of lesions, we report on a 16-month-old girl with acute leucoencephalitis. The disease started with pyrexia 40 degrees C, followed by an episode of seizure, erythematous rash on the trunk and then coma. Brain MRI showed wide lesions on white matter. HHV-6 DNA was detected by PCR in the CSF and serum at the acute stage, and tests for HHV-6 antibody showed a significant increase of IgG antibody titre between acute and convalescent sera. One month later complete clinical recovery was observed while the MRI showed a partial disappearance of the lesions. The sero-conversion associated with the detection of the viral DNA in the serum identified a primary HHV-6 infection and the detection of viral nucleic acid in CSF gives arguments for the responsibility of the virus in the pathogenesis. When facing an acute leuco-encephalitis in infants, it is important to perform exhaustive virology investigations to rule out the implication of HHV-6 as well as other commonly incriminated pathogens (EBV, CMV, mycoplasma, enterovirus) to avoid accusing wrongly the vaccines.     

Evolution of MRI abnormalities in paediatric acute disseminated encephalomyelitis

Objective

Acute disseminating encephalomyelitis (ADEM) is an inflammatory demyelinating disease affecting the central nervous system and mainly occurs in young children. Children who initially presented with ADEM can be diagnosed with multiple sclerosis (MS) in case new non-encephalopathic clinical symptoms occur with new lesions on MRI at least three months after onset of ADEM. We aim to study the timing of MRI abnormalities related to the evolution of clinical symptoms in our Dutch paediatric ADEM cohort.

Encephalopathy associated with haemophagocytic lymphohistiocytosis following rotavirus infection

A 2-year-old Japanese boy with a haemophagocytic lymphohistiocytosis (HLH) associated encephalopathy which developed after rotavirus infection is described. The neurological symptoms consisted of coma, seizures and spastic quadriplegia. On therapy with steroids, etoposide and cyclosporin A, the patient recovered without any neurological deficits. The interferon-gamma levels in serum and CSF were elevated at onset of the disease but had returned to normal at the time of clinical remission. Brain MRI revealed diffuse white matter abnormalities and parenchymal volume loss. Proton magnetic resonance spectroscopy revealed elevated lactate in the abnormal lesions observed on MRI, indicating that macrophages not exhibiting aerobic metabolism had infiltrated the CNS. At the time of clinical remission, the white matter abnormalities and brain lactate had disappeared. These findings suggested that the neurological symptoms resulted from the overproduction of cytokines by activated T-cells and macrophages. The pathophysiology of a HLH associated encephalopathy was considered to be a local immune response within the CNS, because interferon-gamma can induce the expression of major histocompatibility complex class I and II antigens on glial cells in the CNS. Conclusion Haemophagocytic lymphohistiocytosis associated encephalopathy should be considered early in the differential diagnosis of cases with acute onset neuropathy. Received: 17 March 1998 / Accepted in revised form: 16 July 1998     

Subacute sclerosing panencephalitis presenting as acute disseminated encephalomyelitis

Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood and young adolescence due to persistant measles virus infection of the central nervous system. In majority of cases onset occurs from 5–15 years of age.¹ In a nonimmunized population the average onset is 8 years. Children with SSPE had experienced natural infection with the rubeola virus at an early age, half before age 2 years.² SSPE generally occurs 5–10 years after measles infection. In the early stages of the disease behavioral and personality changes is followed by myoclonic jerks and convulsions. In late stages dementia, stupor and coma develops. Diagnosis is achieved by typical clinical findings, meales antibody titer increase in cerebrospinal fluid (CSF) and serum, high amplitude, slow, sharp waves in EEG. Prognosis is poor and death ensues in about 3 yr after the diagnosis. Here it is presented a 7-years-old boy with involuntary movements in both hands, drop attacks while walking, ataxia and stupor. Due to suggestive radiological and clinical findings and a history of recent mumps infection he was thought to have acute disseminated encephalomyelitis initially and given treatment. But due to clinical deterioration and detection of anti measles IgG in serum, and CSF, SSPE diagnosis was confirmed. With this SSPE case presenting initially as ADEM, the authors tried to emphasize that presentation of SSPE may clinically and radiologically beddiverse and a thorough differential diagnosis is mandatory for a definite diagnosis.     

Measles encephalomyelitis in a patient with a history of vaccination

Secondary vaccine failure (SVF) of measles is generally believed to run a milder course of illness than an ordinary course of infection. Severe complications such as central nervous system involvement have rarely been reported. A 12 year old girl, who had received a live attenuated measles vaccine 10 years earlier, developed an encephalomyelitis in the absence of symptoms indicative of ordinary measles such as Koplik spots. Anti-measles hemagglutination inhibition (HI) titer and measles IgM and IgG anitbody titers were measured in a commercial laboratory. Measles virus genomic sequence was detected by polymerase chain reaction. Both serum and cerebrospinal fluid (CSF) samples obtained at acute phase already showed extremely high titers of HI (x 8192 in serum and x 1024 in CSF, respectively) and IgG antibody along with the presence of IgM antibody. Polymerase chain reaction detected the measles virus genomic sequence in the acute phase CSF. The patient's definite history of measles vaccination, high titers of HI and IgG antibodies observed at the very early stage of illness and the clinical course indicated that this patient had an encephalomyelitis due to SVF of measles. It is suggested that measles virus can be a pathogen of encephalitis without symptoms indicative of ordinary measles in individuals who received live attenuated measles vaccines.     

Progressive multifocal leukoencephalopathy revealing AIDS in a 13-year-old girl]

CASE REPORT: A 13-year-old girl with an immunosuppression developed a right hemiparesis and a cerebellar syndrome. She was seropositive for HIV. A progressive multifocal leukoencephalopathy (PML) was suspected because of white matter lesions (MRI) and established on detection of JC virus in CSF by polymerase chain reaction (PCR). In spite of highly active antiretroviral treatment (HAART) and cidofovir, she died three months later. CONCLUSION: Late AIDS diagnosis was established during a neurological complication, 13 years after a neonatal transmission. PML caused by JC opportunistic virus still has a poor prognosis.     

Lyme borreliosis in childhood]

Ten years after detection of Borrelia burgdorferi as the etiologic agent of Lyme borreliosis and after introduction of serological methods an overview of the disease in children is given and compared with own observations. In view of the wide clinical spectrum and the difficulties in interpreting serological results the early diagnosis of Lyme borreliosis is still problematic at present. On the other hand, in case of late diagnosis therapeutic failure and/or partial recovery may result. Data of 138 children with clinically suspected recent Lyme borreliosis demonstrate that the early diagnosis particularly of neuroborreliosis can only be ameliorated when a careful synopsis of all specific and nonspecific laboratory parameters available is done. Additionally, the results of a prospective randomized study of the treatment of acute neuroborreliosis (penicillin G sodium versus ceftriaxone) and results of liquor patency and half-life of ceftriaxone are presented.     

Serum immunoglobulin E,IgA, and IgG antibodies to different cow's milk proteins in children with cow's milk allergy: Association with prognosis and clinical manifestations

Diverse pathogenic mechanisms elicit different clinical manifestations in cow's milk allergy (CMA). Our aim was to determine the concentration of serum immunoglobulin levels to different cow's milk proteins in patients with CMA and to determine how these values were related to clinical symptoms and prognosis. Fifty children (mean age 10.9 months, range: 1–34 months) with previously confirmed CMA were enrolled in this study. All had various clinical manifestations of CMA, including gastrointestinal, skin, and respiratory symptoms. At the diagnosis of CMA the serum total and the milk‐specific immunoglobulin (Ig)E values were measured by enzyme immunoassay and fluoroimmunoassay, respectively, while the relative levels of serum IgA and IgG antibodies against different cow's milk proteins were determined by a sensitive enzyme‐linked immunosorbent assay (ELISA). The results were compared to those of 30 non‐atopic age‐matched control children. On average, after 9.2 months (range 2–31 months) on a milk‐free diet, a repeated challenge was performed in 38 children. At the re‐challenge, 12 patients had clinical symptoms while the remaining 26 children were symptom‐free. The IgG antibody level to bovine serum albumin (BSA) was significantly lower in the patients than in the controls (median: 0.36 vs. 2.94, p < 0.01). There was a close correlation among all individual IgA and IgG antibodies to different cow's milk proteins. The anti‐α‐casein IgG level (of 2.10) in children with a positive reaction at the re‐challenge was significantly higher than in those with a negative reaction (0.89) (p < 0.05). The total IgE serum concentration was also significantly higher in those who had symptoms at the re‐challenge compared to those who did not have any reaction at this time (22.9 vs. 6.8 kU/l, geometric mean, p < 0.02). There was no association between the clinical manifestations and the IgG and IgA antibody levels to the cow's milk proteins studied, except for the anti‐BSA IgA level, which was higher in patients with gastrointestinal symptoms. The serum total IgE and anti‐α‐casein IgG levels could have prognostic values; their increase at the beginning of the disease may indicate the development of tolerance to cow's milk only at a later age and after a longer duration of CMA. However, as there is considerable overlap among the values observed in different groups of patients, there is a limitation of these tests for predicting the prognosis.     

小儿脑型肺吸虫病的诊治

目的 探讨小儿脑型肺吸虫病的临床特点和诊治.方法 59例患儿中生食淡水蟹或饮用疫水52例,高颅压症状49例,肢体偏瘫19例,偏盲10例,癫痫发作19例,合并肺部症状6例;外周血嗜酸性粒细胞升高45例,白细胞升高36例;肺吸虫抗原皮试阳性55例,ELISA试验阳性15例.CT或MRI检查均发现脑内病灶.结果 所有病例均口服吡喹酮治疗,其中14例手术开颅切除病灶.痊愈41例,好转18例.43例患儿随访6～12个月预后良好.结论 小儿脑型肺吸虫病临床表现多样,早期易误诊.流行病学资料、外周血嗜酸性粒细胞升高、肺吸虫免疫学检查和MRI有助于早期诊断.根据病情采用药物及手术治疗效果满意.     

儿童自身免疫性胶质纤维酸性蛋白星形胶质细胞病1例报告并文献复习

目的分析儿童自身免疫性胶质纤维酸性蛋白胶质细胞病(GFAP-A)的诊断及治疗。方法回顾分析1例自身免疫性GFAP-A患儿的临床资料,并复习相关文献。结果女性患儿,10岁2个月。以发热起病,病程早期出现呼吸困难、尿储留,其后出现进行性意识障碍及惊厥。脑脊液及血液胶质纤维酸性蛋白抗体阳性。头颅磁共振成像(MRI)示双侧丘脑及基底节病变。脊髓平扫加增强示胸段部分脊膜及部分神经根线状强化。患儿最终确诊为GFAP-A,予以丙种球蛋白及激素治疗后病情好转。结论GFAP-A可以脑膜脑炎伴或不伴脊髓炎起病,MRI示脑膜脊膜强化、多发高信号病灶、血管样放射强化,抗体检测有助诊断。     

Successful treatment of neuroborreliosis with ten day regimens

BACKGROUND: There have been few large reports of the treatment and outcome of neuroborreliosis in children. METHODS: All 203 children with symptoms, cerebrospinal fluid and serologic findings compatible with neuroborreliosis and treated at one of the four pediatric hospitals in Stockholm from 1994 through 1996 were included. Children were treated with intravenous beta-lactam antibiotics or oral doxycycline for 10 days and followed until the resolution of symptoms. RESULTS: At the end of treatment 58% and after 2 months 92% of the children had no symptoms. Cerebrospinal fluid findings had no statistically significant influence on the outcome. Facial paralysis persisted longer than other symptoms. CONCLUSIONS: The prognosis of neuroborreliosis in children 2 months after treatment seems to be excellent with 10-day treatment regimens.