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Biomedical subjects

P K Coyle

Publications and source records attributed to P K Coyle.

At least 19 recordsLinked to original sources

Borrelia burgdorferi-specific immune complexes in acute Lyme disease.

CONTEXT: Diagnosis of infection with Borrelia burgdorferi, the cause of Lyme disease (LD), has been impeded by the lack of effective assays to detect active infection. OBJECTIVE: To determine whether B. burgdorferi-specific immune complexes are detectable during active infection in LD. DESIGN, SETTING, AND PATIENTS: Cross-sectional analysis of serum samples from 168 patients fulfilling Centers for Disease Control and Prevention surveillance criteria for LD and 145 healthy and other disease controls conducted over 8 years. Tests were performed blinded. MAIN OUTCOME MEASURE: Detection of B. burgdorferi immune complexes by enzyme-linked immunosorbent assay and Western blot. RESULTS: The B. burgdorferi immune complexes were found in 25 of 26 patients with early seronegative erythema migrans (EM) LD; 105 of 107 patients with seropositive EM LD; 6 of 10 samples that were seronegative [corrected] with culture-positive EM; 0 of 12 patients who were treated and recovered from LD; and 13 of 13 patients with neurologic LD without EM. Among 147 controls, B. burgdorferi immune complex was found in 0 of 50 healthy individuals; 0 of 40 patients with persistent fatigue; 0 of 7 individuals with frequent tick exposure; and 2 of 50 patients with other diseases. CONCLUSION: These data suggest that B. burgdorferi immune complex formation is a common process in active LD. Analysis of the B. burgdorferi immune complexes by a simple technique has the potential to support or exclude a diagnosis of early as well as active LD infection.

Acute Disease

Glucocorticoids in central nervous system bacterial infection.

OBJECTIVE: To evaluate evidence-based data on adjunctive glucocorticoid therapy in central nervous system bacterial infections. DESIGN: A literature review of studies, particularly controlled trials, that have evaluated dexamethasone therapy for acute bacterial meningitis and glucocorticoid therapy for tuberculous meningitis. MAIN OUTCOME MEASURES: Clinical outcomes were mortality and morbidity rates. Morbidity involved sensorineural hearing loss and other neurologic deficits (motor or behavioral disturbances, epilepsy, cranial nerve palsy, hydrocephalus, and psychomotor retardation). RESULTS: The evidence-based data support adjunctive dexamethasone therapy for children with Haemophilus influenzae meningitis. However, the optimal duration of therapy is not defined. Data are supportive but not conclusive that dexamethasone benefits meningitis caused by other bacterial agents and meningitis in adults. The evidence-based data are supportive but not conclusive that adjunctive glucocorticoid therapy benefits patients with tuberculous meningitis, particularly those with more severe infection. CONCLUSIONS: Although adjunctive glucocorticoid therapy may be beneficial in both acute bacterial meningitis and more severe tuberculous meningitis, there are conclusive data only for H influenzae meningitis in children. For acute bacterial meningitis, further studies are needed to clarify the optimal duration of dexamethasone therapy (2 vs 4 days), whether this therapy should be used routinely for adults with meningitis, and whether it should be used for pathogens other than H influenzae. For tuberculous meningitis, further studies are needed to provide conclusive evidence of benefit.

Acute Disease

Overview of acute and chronic meningitis.

Meningitis can be subdivided based on time course of onset and duration, cerebrospinal fluid (CSF) profile, and underlying origins into acute aseptic and septic meningitis, recurrent meningitis, and chronic meningitis. These are distinct syndromes that require different management strategies. Most cases of meningitis are caused by infection. The causal agent is generally predictable based on the type of meningitis, host factors, and clues from the history and examination. CSF examination remains the critical diagnostic test.

Acute Disease

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Adult

Free light chains in multiple sclerosis urine.

We measured free kappa (kappa) and lambda (lambda) light chains in urine from patients with definite multiple sclerosis (MS), other neurologic diseases (OND), and normal controls by using an enzyme linked immunosorbent assay. Both kappa and lambda light chains were higher in MS than OND or controls. In seven of eight relapsing-remitting (R-R) MS patients serial studies showed that urinary kappa chains were elevated during periods of worsening, and decreased during clinical recovery. In contrast, the levels of kappa chains did not correlate with clinical activity in 10 progressive (P) MS patients. Further correlation of urinary light chains with neurologic evaluations in R-R and P MS patients over a longer period are needed to determine their clinical and biological relevance.

Biomarkers

Simultaneous expression of Borrelia OspA and OspC and IgM response in cerebrospinal fluid in early neurologic Lyme disease.

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.

Adolescent

Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) and post-Lyme syndrome (PLS) share many features, including symptoms of severe fatigue and cognitive difficulty. OBJECTIVE: To examine the neuropsychiatric differences in these disorders to enhance understanding of how mood, fatigue, and cognitive performance interrelate in chronic illness. METHODS: Twenty-five patients with CFS, 38 patients with PLS, and 56 healthy controls participated in the study. Patients with CFS met 1994 criteria for CFS and lacked histories suggestive of Lyme disease. Patients with PLS were seropositive for Lyme disease, had met the Centers for Disease Control and Prevention criteria, or had histories strongly suggestive of Lyme disease and were experiencing severe fatigue that continued 6 months or more following completion of antibiotic treatment for Lyme disease. All subjects completed self-report measures of somatic symptoms and mood disturbance and underwent neuropsychological testing. All patients also underwent a structured psychiatric interview. RESULTS: Patients with CFS and PLS were similar in several somatic symptoms and in psychiatric profile. Patients with CFS reported more flulike symptoms than patients with PLS. Patients with PLS but not patients with CFS performed significantly worse than controls on tests of attention, verbal memory, verbal fluency, and motor speed. Patients with PLS without a premorbid history of psychiatric illness did relatively worse on cognitive tests than patients with PLS with premorbid psychiatric illness compared with healthy controls. CONCLUSIONS: Despite symptom overlap, patients with PLS show greater cognitive deficits than patients with CFS compared with healthy controls. This is particularly apparent among patients with PLS who lack premorbid psychiatric illness.

Adult

Cerebrospinal fluid findings in children with Lyme disease-associated facial nerve palsy.

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.

Adolescent

Vasculitis owing to infection.

Infections are a recognized cause of secondary vasculitis. A variety of pathogens have a propensity to involve blood vessels. Vasculitis, non-vasculitic vasculopathy, and mycotic aneurysms lead to infarction and hemorrhage of nervous system tissue. Treatment of infection-related vasculitis should include appropriate antimicrobial therapy directed against the offending pathogen, and appropriate management of cerebrovascular complications.

Bacterial Infections

Increased levels of interleukin-1beta and soluble intercellular adhesion molecule-1 in cerebrospinal fluid of patients with subacute sclerosing panencephalitis.

Proinflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor [TNF]-alpha, and IL-6) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured in paired cerebrospinal fluid (CSF) and serum samples from patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), or other neurologic diseases (OND) by ELISA. IL-1beta was significantly increased in CSF of the SSPE group compared with levels in the MS or OND group. IL-1beta CSF/serum ratios were higher in the SSPE than in the MS or OND group. TNF-alpha and IL-6 levels were similar in the 3 groups. CSF sICAM-1 was higher in the SSPE group than in the MS or OND group. sICAM-1 CSF/serum ratios were higher in the SSPE than the OND group. The increased CSF/serum ratios of IL-1beta and sICAM-1 in SSPE indicate synthesis of IL-1beta and sICAM-1 in the central nervous system and may be important in the pathogenesis of disease.

Adolescent

Intrathecal production of measles-specific IgA in subacute sclerosing panencephalitis.

OBJECTIVE: We measured measles-specific IgA in matched pairs of cerebrospinal fluid (CSF) and sera of patients with subacute sclerosing panencephalitis (SSPE), multiple sclerosis (MS), other central nervous system (CNS) infectious diseases (INF) and other neurological diseases (OND) by using enzyme linked immunosorbent assay. MATERIALS AND METHODS: CSF and sera from 23 patients with SSPE, 15 with MS, 14 with INF, and 15 with OND were included in the study. RESULTS: The ratios of measles-specific IgA in CSF to serum were increased in SSPE patients compared to patients with MS, INF or OND. CONCLUSION: The data indicate a local production of measles-specific IgA in the CNS of SSPE patients.

Adolescent

A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis.

We determined the effect of influenza vaccine in patients with relapsing/remitting MS. Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients. Prevention of a febrile viral illness is clearly desirable in MS, and previous studies suggest that immunization is safe. Despite this, many clinicians avoid vaccination because they fear precipitating an MS exacerbation. We conducted a multicenter, prospective, randomized, double-blind trial of influenza immunization in patients with relapsing/remitting MS. In the autumn of 1993, 104 patients at five MS centers received either standard influenza vaccine or placebo. Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza. Influenza was operationally defined as fever > or = 38 degrees C in the presence of coryza, cough, or sore throat at a time when the disease was present in the community. Attacks were defined in the standard manner, requiring objective change in the examination. Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months. They were also examined at times of possible attacks but not when they were sick with flu-like illness. Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine (no significant difference). Exacerbation rates in the first month for both groups were equal to or less than expected from published series. The two groups showed no difference in attack rate or disease progression over 6 months. Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months.

Double-Blind Method

Facial nerve palsy in Lyme disease: evaluation of clinical diagnostic criteria.

OBJECTIVE: Lyme disease must be included in the differential diagnosis of acute facial paralysis in endemic areas. When facial nerve palsy occurs as an isolated finding, the diagnosis of Lyme disease may not be readily apparent. The goal of the present study was to evaluate the frequency with which Lyme disease could be diagnosed based on clinical symptoms alone. STUDY DESIGN AND SETTING: This was a retrospective chart review conducted at a tertiary hospital on Long Island, New York, an area endemic for Lyme disease. PATIENTS: The study population was composed of 50 patients with facial nerve palsy who were seropositive for Lyme disease (or had Lyme disease otherwise clinically proven). MAIN OUTCOME MEASURES: Clinical data were initially used to classify patients as having definite, probable, or possible Lyme disease, using the surveillance criteria of the Centers for Disease Control and Prevention. RESULTS: In the majority of cases, the diagnosis of Lyme disease could not be made from clinical data alone. Specific findings, such as erythema migrans and meningoencephalitis, occurred only inconsistently, and serologic or cerebrospinal fluid tests were usually necessary to establish the diagnosis. Intrathecal antibody production was found in a high proportion of patients. CONCLUSIONS: In endemic areas, Lyme disease should be suspected as a cause of acute facial nerve palsy even in the absence of other clinical symptoms. Cerebrospinal fluid serology is helpful in confirming the diagnosis and planning therapy. Central nervous system infection may be common in Lyme disease facial nerve palsy.

Adolescent

The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis.

BACKGROUND: Amantadine hydrochloride and pemoline, both frequently used to treat the fatigue of multiple sclerosis (MS), may also improve attention and other cognitive functions in MS. To our knowledge, these agents have never been compared in a placebo-controlled trial of patients with MS. OBJECTIVE: To evaluate the effects of amantadine and pemoline on cognitive functioning in MS. METHODS: A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine, pemoline, or placebo using a parallel group design. They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning. Primary outcome measures were tests of attention (Digit Span, Trail Making Test, and Symbol Digit Modalities Test), verbal memory (Selective Reminding Test), nonverbal memory (Benton Visual Retention Test), and motor speed (Finger Tapping Test). RESULTS: Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment. All three treatment groups improved on tests of attention (P < .003), verbal memory (P < .001), and motor speed (P < .002). There were no significant differences between amantadine, pemoline, and placebo. CONCLUSIONS: Cognitive functioning in MS is independent of fatigue. Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo.

Adolescent

The neuroimmunology of multiple sclerosis.

The aim of this clinical review is to highlight recent advances in immunology, as well as new information from selected other areas, which have led to a better appreciation of the neuroimmunologic mechanisms involved in Multiple sclerosis (MS). New data on immunopathology, the cytokine network, and the role of oligodendrocytes, lymphocytes, and endothelial cells in this disease, have produced novel therapeutic approaches. New information on clinical course and neuroimaging disease features, as well as the role of genetic factors and infectious agents, have also improved our understanding of the immune basis for MS.

Adult