Neuroborreliosis in children: Epidemiological and clinical aspects

Abstract

Background: Lyme borreliosis (LB) caused by the bacteria Borrelia burgdorferi sensu lato (Bbsl) is the most common tick transmitted infection in Europe. LB is a multi systemic infection that develops when the bacteria disseminate from the local tick bite to different organs and tissues. Neuroborreliosis (NB) is the neurological manifestation of LB and may affect both the peripheral and the central nervous system. A variety of neurological symptoms are observed; aseptic meningitis (AM) and facial nerve palsy (FNP) are the major manifestations in children. The incidence of FNP and AM in children, as well as the rate of FNP and AM caused by LB is not well described and may vary between areas. Furthermore, it is not well documented how often FNP caused by LB is associated with AM. Finally, the clinical presentation of NB and the result of diagnostic tests may differ between areas and even between children and adults. All these issues have been scarcely addressed in a population based setting in children. Aim: The aim of this thesis was to study the epidemiology of childhood NB, FNP and infectious meningitis in an endemic area of LB in south western Norway. Further, to evaluate demographical, clinical and laboratory aspects of NB, FNP and infectious meningitis in children, and to study the interplay between these conditions. Methods: In a population based study performed during 1996-2009, children up to 14 years old referred to Stavanger University Hospital with suspected NB, including acute FNP, were investigated by a standard procedure including a lumbar puncture. Except when bacterial meningitis (BM) was confirmed, Bbsl serological tests were performed in serum and CSF in all children with CSF pleocytosis. In paper I-III, NB was diagnosed in children with neurological symptoms compatible with NB and with positive Bbsl antibodies or recently EM. In paper IV, Lyme meningitis (LM) was diagnosed in children with CSF pleocytosis and symptoms suggestive of NB in combination with Bbsl antibody index (AI) (confirmed LM) or Bbsl antibodies in serum or CSF (probable LM). 7 Results: The annual incidence of NB in children up to 14 years of age was 21/100.000. A seasonal distribution was observed, all children with NB were diagnosed from April to December. The highest incidence of NB was found in the age group 6-7 years. Near all (98%) of children with NB had CSF pleocytosis, and FNP was observed in 69% of children with NB. The level of CSF inflammation, the proportion of children with positive Bbsl antibodies in serum and CSF, and Bbsl AI, all increased with the duration of symptoms before lumbar puncture. In addition, the level of CSF inflammation differed between clinical groups. The incidence of FNP was 21/100.000, and NB was diagnosed in 65% of children with FNP. Tree quarters of children with FNP had CSF pleocytosis. No other cause than NB was diagnosed in children with both FNP and CSF pleocytosis. Children with FNP without NB were diagnosed through the whole year and were evenly distributed in all age groups, and differed from the age distribution of children with FNP and NB. The incidence of infectious meningitis in children was 38/100.000 and 67% of these were caused by LM. Age, month of admission and clinical and laboratorial characteristics differed between children with LM, NLAM and BM. The positive predictive value for having LM if the child had FNP or meningism as the only symptom was 97% for both variables. The negative predictive value for not having LM if the child did not have a history of EM, or cranial nerve involvement or meningism as the only symptom was 95%. Conclusion: In this population based study, the incidence of NB, incidence of FNP and proportion of FNP caused of NB were among the highest reported in children worldwide. Furthermore, nearly all children with NB had CSF pleocytosis. Our results suggest that in children with possible NB, the duration of symptoms and clinical characteristics must be included in the interpretation of laboratory results. Finally we found LM to be the major cause of infectious meningitis. In children with CSF pleocytosis, distinct clinical characteristics distinguished the majority of children with LM from NLAM.