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.     

Early differentiation of Lyme from enteroviral meningitis

BACKGROUND: Differentiating Lyme meningitis from enteroviral meningitis remains difficult because both occur mostly in the summer and early fall. This distinction is clinically important because pathogen-specific diagnostic test results are not available immediately and only patients with Lyme meningitis require parenteral antibiotic therapy. OBJECTIVES: The objective of this study was to identify clinical and laboratory features that might help clinicians distinguish patients with Lyme meningitis from those with enteroviral meningitis. METHODS: This cross-sectional study compared patients diagnosed with Lyme or enteroviral meningitis evaluated at a large children's hospital between January 1, 1999 and September 20, 2002. RESULTS: Twenty-four patients with Lyme meningitis and 151 patients with enteroviral meningitis had median ages of 10.5 and 5.5 years, respectively (P < 0.0001). There was an equal proportion of boys with Lyme (63%) and enteroviral meningitis (62%; P = 1.0). The duration of symptoms before evaluation was longer for patients with Lyme meningitis (12 days) than with enteroviral meningitis (1 day; P < 0.0001). Cranial neuropathy was a presenting feature in 71% of children with Lyme meningitis. Cranial neuropathy, erythema migrans rash or papilledema occurred in 88% of patients with Lyme meningitis; no patients with enteroviral meningitis exhibited any of these findings (P < 0.0001). Lyme meningitis was unlikely when cerebrospinal fluid neutrophils exceeded 10% (negative predictive value, 99%). CONCLUSIONS: We identified several clinical and laboratory features that may permit early differentiation of Lyme from enteroviral meningitis. These results may assist clinicians with decisions regarding additional testing and empiric antibiotic therapy.     

Clinical data and cerebrospinal fluid findings in Lyme meningitis versus aseptic meningitis

The purpose of this study was to characterise Lyme meningitis (LM) in a Belgian paediatric population and to suggest findings that could allow early distinction from aseptic meningitis (AM). The medical records of patients hospitalised between 1993 and 2000 and with a discharge diagnosis of LM (n=14) or AM (n=16) were retrospectively reviewed. The Kruskal-Wallis test was used to compare data. Of the patients, 16 were identified with AM and 14 with LM, amongst which 7 presented with isolated LM and 7 with associated peripheral facial palsy (PFP). Patients with AM, when compared with LM, complained of more pronounced signs and symptoms of meningitis (fever, headaches, and neck stiffness); they statistically displayed a shorter period of symptoms before admission (1.6 vs 15 days), higher neutrophilic component (mean 56% vs 2.4%), and lower protein levels (mean 0.39 vs 1.12 g/l) on cerebrospinal fluid analysis. In the neuroborreliosis group, the duration of symptoms was shorter and the cerebrospinal protein level was lower in cases of LM associated with PFP compared to isolated LM (mean 1.3 vs 15 days; mean 0.55 g/l vs 1.12 g/l). Conclusions.Our results suggest that some clinical data and laboratory findings may help the physician to diagnose aseptic or Lyme meningitis before completion of serologic testing. LM should be suspected in cases of meningitis with very low CSF neutrophilic counts and high protein levels associated with prolonged duration of symptoms, low grade fever, and absence of pronounced signs of meningitis.     

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     

Anamnesis, clinical aspects and laboratory findings in juvenile "aseptic meningitis" in Lyme borreliosis--a meta-analysis

Lyme borreliosis is currently suspected to be capable of mimicking nearly all known neurologic symptoms and disease entities. The goal of our study is to define the associated anamnestic, clinical and laboratory findings in aseptic meningitis and Lyme borreliosis in childhood by a meta-analysis of recent literature and of our own data. We defined by means of 63 cases derived of 10 publications and own data a list of mainly rather unspecific parameters like insidious onset, fever, mild meningism, encephalitic symptoms and cranial nerve involvement. Mere neurologic presentation without ECM, arthritis or even an anamnestic insect-bite seems to be most frequent. Retrospective studies, however, can not sufficiently characterize the clinical picture of aseptic meningitis in Lyme borreliosis.     

Treatment Complications in Children With Lyme Meningitis

BACKGROUND:: The rate and type of treatment complications in children treated for Lyme meningitis have not been described. METHODS:: We performed a retrospective cohort study of children with Lyme meningitis who presented to 1 of 3 emergency departments located in Lyme disease endemic areas between 1997 and 2010. We defined a case of Lyme meningitis as a child with cerebrospinal fluid pleocytosis and either positive Lyme serology or an erythema migrans rash. We identified prescribed treatment and reasons for all return visits. Our primary outcome was the presence of any treatment complication within 30 days of diagnosis. RESULTS:: We identified 157 patients with Lyme meningitis with a median age of 10 years (interquartile range: 7-13 years). Of the 149 children with Lyme meningitis and available follow-up records, 39 (26%) had 1 or more complications, and 21 (14%) required a change in prescribed antibiotic therapy. The median time for developing the first complication was 11 days (interquartile range: 9-14 days). Ten percent of the patients had an adverse drug reaction. Of the 144 children who had a peripherally inserted central catheter placed, 25 (17%) had at least 1 peripherally inserted central catheter-associated complication: 14 (10%) had a mechanical problem, 11 (8%) had an infectious complication and 1 (1%) had a venous thromboembolism. CONCLUSIONS:: As current Lyme meningitis treatment regimens have substantial associated morbidity, future research should investigate the efficacy of alternate regimens.     

Meningitis due toBorrelia burgdorferi in the initial stage of Lyme disease

Borrelia burgdorferi (B. b.) was isolated from cerebrospinal fluid from two children with aseptic meningitis. Serology forB. b. was initially negative or borderline and became positive during the subsequent course. Children with aseptic meningitis of unknown origin should be re-evaluated within 1 month to detect possible increasing antibody titres toB. b. Aseptic meningitis may be a stage 1 manifestation of Lyme disease.Abbreviations B. b. Borrelia burgdorferi - CSF cerebrospinal fluid - CNS central nervous system - ESR erythrocyte sedimentation rate - IFA immunofluorscence assay     

Overdiagnosis and overtreatment of Lyme disease in children.

AIM: To determine the incidence of overdiagnosis and overtreatment of Lyme disease in children residing in endemic areas using standardized CDC diagnostic criteria. METHODS: Case series, using data collected prospectively from patients referred for Lyme disease to a tertiary care center located in an area endemic for Lyme disease. Data were collected on all referred cases during a 30-month period from August, 1995, to February, 1998. RESULTS: We evaluated 216 patients with ages from birth to 18 years. Results of Lyme enzyme-linked immunosorbent assay and Western blot studies were available for all patients evaluated. Of these, 68 (31%) fulfilled the criteria for active Lyme disease, most commonly having arthritis, facial nerve palsy, aseptic meningitis or erythema migrans; 39 (18%) had a prior history of Lyme disease and were referred with an acute intercurrent illness or lower school grades attributed to the previous Lyme disease; 77% of these were receiving therapy at the time of referral; 109 (50%) of 216 had no past or current evidence of Lyme disease, yet 79% were receiving therapy at the time of referral. CONCLUSIONS: Overdiagnosis and overtreatment of Lyme disease is a major concern in areas endemic for Lyme disease, even after 1995 when standard criteria for diagnosis were published. The most common problem in diagnosis was misinterpretation of Western immunoblot results.     

Lyme disease update

PURPOSE OF REVIEW: Lyme disease is endemic to areas in both Europe and the United States and the incidence is increasing. Despite published guidelines, controversy persists about its diagnosis and management in patients who do not meet strict diagnostic criteria. This review summarizes important recently published studies and recommendations for the diagnosis and management of Lyme disease. RECENT FINDINGS: Recent comprehensive guidelines have been published for the diagnosis and management of pediatric Lyme disease. In addition, recent studies may help physicians differentiate between Lyme and aseptic meningitis, as well as show the poor sensitivity of cerebrospinal fluid polymerase chain reaction. Controversy continues about the diagnosis and management of "chronic Lyme disease", despite the current medical literature. Recently published studies in the US have also better described southern tick-associated rash illness, an entity that may present a similar clinical picture to Lyme disease. Guidelines have also been published on the management and diagnosis of other tick-borne illnesses often seen as co-infections with Lyme disease. Finally, case reports have been published describing new cardiac manifestations associated with Lyme disease. SUMMARY: Controversies persist about the diagnosis and management of Lyme disease. Recently published guidelines and primary research can aid clinicians in diagnosing Lyme properly.     

Lyme Disease in a 12-year-old Girl

ABSTRACT. We report the case of a 12-year-old girl with erythema chronicum migrans, aseptic meningitis and knee arthralgia. Rise of specific antibody titre against an Ixodes ricinus spirochaete was demonstrated. Circulating immune complexes and high levels of Clr-Cis-CIIA complexes indicating activation of the complement system via the classical pathway were found. The clinical features and the laboratory findings warranted a diagnosis of Lyme disease.     

Lyme disease in a 12-year-old girl

We report the case of a 12-year-old girl with erythema chronicum migrans, aseptic meningitis and knee arthralgia. Rise of specific antibody titre against an Ixodes ricinus spirochaete was demonstrated. Circulating immune complexes and high levels of C1r-C1s-C1IA complexes indicating activation of the complement system via the classical pathway were found. The clinical features and the laboratory findings warranted a diagnosis of Lyme disease.     

Outbreak of aseptic meningitis associated with echovirus 13

BACKGROUND: Before 2001, echovirus 13 accounted for only 65 of approximately 45,000 reported enteroviral isolates in the United States. During spring 2001, several outbreaks of echovirus 13 meningitis occurred, primarily affecting children. We investigated a large outbreak in Shelby County, TN, to determine the characteristics and clinical manifestations of echovirus 13 meningitis. METHODS: We identified cases of aseptic meningitis at a children's hospital from April through August 2001 by reviewing discharge records. For patients with laboratory-confirmed echovirus 13 meningitis, we reviewed charts and interviewed parents. RESULTS: We identified 303 hospitalizations caused by aseptic meningitis at the children's hospital from April through August. Hospitalizations peaked in May. Twenty-six percent of hospitalized patients were infants age <4 months; 63% were male. Hospitalization rates were 3 times greater among black children than among white children (140 vs. 47 per 100,000). Echovirus 13 was isolated from specimens from 37 (80%) of 46 patients with positive viral cultures. Of those with laboratory-confirmed echovirus 13, 35 (95%) had fever, 26 (70%) had vomiting, 20 (54%) had headache, 16 (43%) had stiff neck and 16 (43%) had irritability. No sequelae or deaths were identified. CONCLUSIONS: Echovirus 13 emerged as a predominant strain of enterovirus associated with aseptic meningitis in the United States in 2001. In this outbreak echovirus 13 meningitis appeared to be clinically indistinguishable from aseptic meningitis caused by other enteroviruses.     

Herpetic meningitis in the child]

In children, viral meningitis is usually caused by Enteroviruses. Herpes simplex viruses (HSV) are known to be a cause of meningo-encephalitis. HSV-2 has been reported to cause recurrent meningitis (Mollaret's meningitis) in adults. CASE REPORT: We report the case of a three-year-old girl with HSV-1 meningitis, whose evolution with treatment by aciclovir was good. CONCLUSION: HSV-1 has rarely been reported as a cause of isolated aseptic meningitis in children. Primary phase of herpes simplex virus infection is not usually associated with neurologic complications.     

Anti-interleukin-8 auto-antibodies in cerebrospinal fluid of children with purulent meningitis

BACKGROUND: Cerebrospinal fluid (CSF) of patients with purulent meningitis contains a high concentration of interleukin (IL)-8. Recently, the presence of anti-IL-8 auto-antibodies was noted in blood and alveolar fluid. Therefore, measurement of the concentration of anti-IL-8 auto-antibodies was attempted in CSF of children with and without meningitis. METHODS AND RESULTS: We measured the concentration of anti-IL-8 auto-antibodies in CSF of children with purulent or aseptic meningitis and those without meningitis. The CSF obtained on admission showed a significantly higher concentration of anti-IL-8 IgG and IgM auto-antibodies in children with purulent meningitis, compared with those with aseptic meningitis or without meningitis. Among the three groups of children, the concentration of IL-8 was also significantly higher in CSF of children with purulent meningitis. CONCLUSION: Because the anti-IL-8 IgG auto-antibody binds to IL-8 and inhibits IL-8 interaction with specific receptors on neutrophils, the presence of anti-IL-8 auto-antibodies seems to provide a mechanism that limits the bioavailability of free IL-8 in CSF.     

A prefecture-wide survey of mumps meningitis associated with measles, mumps and rubella vaccine

A survey of untoward reactions, especially central nervous system reactions, after the administration of a newly introduced measles, mumps and rubella (MMR) vaccine in Gunma Prefecture, Japan, was initiated soon after 4 patients were hospitalized for aseptic meningitis. Thirty-five, 6 and 2 children developed meningitis, convulsive disorders and parotitis, respectively, within 2 months after MMR vaccination during the 8-month period extending from April to November, 1989. The time lag between MMR vaccination and meningitis ranged from 14 to 28 days in the 35 cases of meningitis. Mumps virus, isolated from the cerebrospinal fluid in 13 patients with aseptic meningitis, was characterized by determination of the nucleotide sequences of the P gene as mumps vaccine strain. The incidence of aseptic meningitis with positive mumps vaccine virus was estimated to be 0.11% (0.3% as a whole) during the 8 months from April to November and increased to 0.3% (0.7% as a whole) in September and October. We conclude that the incidence of aseptic meningitis after MMR vaccination seems to be higher than that reported previously.     

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.     

Cerebrospinal fluid concentrations of alpha-melanocyte-stimulating hormone in bacterial and aseptic meningitis

-Melanocyte-stimulating hormone (-MSH) has potent anti-inflammatory effects in several experimental models of inflammation. It inhibits both the actions and production of proinflammatory cytokines and neutrophil migration. We investigated whether -MSH in cerebrospinal fluid (CSF) increases during the acute stage in patients with bacterial and aseptic meningitis by measuring -MSH in CSF via radioimmunoassay. The -MSH concentrations in CSF from the children with bacterial meningitis who survived (n = 8), those with aseptic meningitis (n = 16), and the control subjects (n = 23) were all below the detection limit. However, CSF -MSH was elevated in four of the five children with bacterial meningitis who had neurological sequelae. We speculate that elevated -MSH levels in CSF during acute bacterial meningitis reflect negative feedback in response to severe inflammation associated with neurological sequelae induced by proinflammatory cytokines. Conclusion: CSF -MSH is elevated in children with severe bacterial meningitis who had neurological sequelae.     

Management of children with aseptic meningitis in the emergency department.

OBJECTIVE: To review the emergency department management of children with aseptic meningitis and compare the clinical features, laboratory findings, and short-term follow-up of those who were hospitalized or discharged to determine guidelines for discharge. DESIGN: Retrospective chart review study. SETTING: Emergency department of an inner-city teaching, level III, children's hospital during an outbreak of aseptic meningitis from, March through December 1993. METHODS: The medical records of children < or = 18 years of age diagnosed in the emergency department with aseptic meningitis after lumbar puncture were retrospectively reviewed and analyzed. Thirty-four parameters were recorded for each child including demographic (2), epidemiologic (5), clinical (2), laboratory (10), and short-term follow-up data (5). RESULTS: Of the 158 eligible patients, 99 (62.7%) were hospitalized, and 59 (37.3%) were discharged. Compared to the hospitalized group, children who were discharged were significantly older (5.7 years vs. 4.7 years, P < 0.05) and experienced a more benign course, with lower rates of headache (54.7 vs. 85.7%, P < 0.05), vomiting (38.2 vs. 69.7%, P < 0.05), and irritability (1.8 vs. 8.1%, P < 0.05). They also had significantly (P < 0.05) lower mean peripheral and cerebrospinal fluid leukocyte counts (13,233 vs. 11,498/mm3 and 293.91 vs. 105.29/mm3, respectively). Interestingly, 30 (50.8%) of children in the discharged group had over 50% polymorphonuclears in their cerebrospinal fluid (CSF) cell count. The hospitalization rate during the day was significantly (P < 0.05) lower than that for the evening and night shifts (51.5 vs. 66.7%, respectively). In the discharged group, symptoms of headache, fever, and vomiting resolved after an average of 3.05 days, 2.25 days, and 1.3 days, respectively. The average hospitalization time was 3.5 days. There were no significant complications in either group. More important, in neither group were there any misdiagnoses of bacterial meningitis as aseptic meningitis. During the study period, the ambulatory management of the 59 patients cost $51,625 less than the hospitalization of an equal number of children. CONCLUSION: It is feasible, clinically safe and less costly to treat a subgroup of children with aseptic meningitis in an ambulatory setting. Although absolute criteria for ambulatory follow-up could not be defined, age >1 year, a nontoxic clinical appearance, normal white blood cell count, mild cerebrospinal fluid pleocytosis (even with a high percentage of polymorphonuclear cells), negative CSF Gram stain, and a reliable family setting could serve as guidelines for decision-making regarding emergency department discharge. Further prospective research is needed to better specify these criteria.     

Optic neuropathy in children with Lyme disease

Involvement of the optic nerve, either because of inflammation or increased intracranial pressure, is a rare manifestation of Lyme disease. Of the 4 children reported here with optic nerve abnormalities, 2 had decreased vision months after disease onset attributable to optic neuritis, and 1 had headache and diplopia early in the infection because of increased intracranial pressure associated with Lyme meningitis. In these 3 children, optic nerve involvement responded well to intravenous ceftriaxone therapy. The fourth child had headache and visual loss attributable to increased intracranial pressure and perhaps also to optic neuritis. Despite treatment with ceftriaxone and steroids, he had persistent increased intracranial pressure leading to permanent bilateral blindness. Clinicians should be aware that neuro-ophthalmologic involvement of Lyme disease may have significant consequences. If increased intracranial pressure persists despite antibiotic therapy, measures must be taken quickly to reduce the pressure.     

Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis

Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process.