Faculty Bibliography

Tick-transmitted infectious agents have assumed increased importance as causes of human disease in the United States. During the past two decades, Lyme borreliosis, ehrlichiosis, and babesiosis have emerged as newly described tick-borne infectious diseases of significance for pediatricians and pediatric neurologists. In fact, the highest rates of infection for Lyme disease and Rocky Mountain spotted fever (RMSF), by decade of age, are in childhood. As such, tick-borne infectious disease are of considerable public health concern, particularly for children residing in endemic regions. RMSF and human ehrlichioses can be life-threatening but are also eminently treatable when recognized early. Delays in diagnosis and treatment can lead to adverse outcomes. This article reviews the clinical and epidemiological features of Lyme borreliosis, RMSF, and ehrlichiosis, important causes of neurological illness among children, and summarizes current therapeutic and preventive strategies.

OBJECTIVE: To determine the relative frequency of abnormal cerebrospinal fluid (CSF) findings in children with Lyme disease-associated facial nerve palsy. DESIGN: A clinical series. A prospective evaluation was undertaken of the condition of children seen between 1988 and 1996 at a single medical center in a Lyme disease endemic area. PATIENTS: Forty children (24 boys and 16 girls, aged 3-19 years) with new onset facial nerve palsy who met the Centers for Disease Control and Prevention case definition of Lyme disease. INTERVENTIONS: Neurologic examinations. Cerebrospinal fluid analysis. MAIN OUTCOME MEASURES: Rates of abnormal CSF findings: white blood cell count, protein level, and Borrelia burgdorferi-specific CSF assays. RESULTS: Cerebrospinal fluid white blood cell count, protein level, or both were abnormal in 27 (68%) of the children. Thirty-six (90%) of the 40 children had a CSF abnormality consistent with central nervous system infection or immune involvement by B burgdorferi. Of the 22 children with CSF pleocytosis, only 7 (32%) had headache and none had meningeal signs. CONCLUSIONS: Most children with Lyme disease-associated facial nerve palsy have CSF abnormalities. Our studies indicate that, in endemic areas, facial nerve palsy in children may be a marker of Lyme disease and occult meningitis. When Lyme disease is suspected, CSF should be examined; in some cases, it may be helpful to expand beyond routine CSF studies to look at a battery of B burgdorferi-specific assays.

Lyme disease is the major tick-borne disease, caused by Borrelia burgdorferi (Bb). Neurological involvement is common in all stages. In vivo expression of Bb antigens (Ags) and the immune response to them has not been well investigated in the cerebrospinal fluid (CSF). Upregulation of outer surface protein (Osp) C and concomitant downregulation of OspA before tick inoculation of the spirochete has been reported in skin and blood in animals. CSF OspA Ag in early disease suggests otherwise in CSF. Early Ag expression and IgM response in human CSF was investigated here. Paired CSF and serum was collected from 16 early, predominantly erythema migrans Lyme disease patients with neurologic problems, 13 late Lyme disease patients, and 19 other neurologic disease (OND) controls. Samples were examined for IgM reactivity to recombinant Bb-specific Osps using ELISA and immunoblot. Of 12 early Lyme disease patients with neurologic involvement with both CSF and serum IgM against OspC, 7 (58%) had IgM to OspA (n = 5) or OspB (n = 2) that was restricted to the CSF, not serum. Overall, 12 of 16 (75%) of these early Lyme disease patients with neurologic involvement had CSF and serum IgM against OspC. Only 3 of 13 (23%) late Lyme disease patients and none of 19 OND controls had CSF IgM directed against OspC. In conclusion, in CSF, OspC and OspA can be coexpressed, and IgM response to them occurs in early Lyme disease patients with neurologic involvement. This biologic finding may also provide a discriminating marker for CNS infection in Lyme disease.

Vertically transmitted HIV-1 infection occurs in an immature developing organism. The maturational stage of the nervous and immune system when exposed to the direct or indirect effects of the virus is likely to be of utmost importance. Innumerable dynamic interactions occur between these two systems during development, and these undoubtedly interact in complex ways with HIV-1 variables. To care for these children and to design rational approaches for treatment and prevention, it is now critical to develop a better understanding of how HIV-1 affects the developing nervous system.