12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders
Day 1 - April 9, 1999
Day 2 - April 10, 1999 (Valid for CME until October 10, 1999)
|This activity has been planned and implemented in accordance with Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Medical Education Collaborative and Medscape, Inc. Medical Education Collaborative (MEC), a non-profit education organization, is accredited by the ACCME to provide continuing medical education for physicians and takes responsibility for the content, quality and scientific integrity of this CME activity.|
|This activity has also been planned and implemented in accordance with the Quality Criteria of the American Council on Pharmaceutical Education (ACPE) through the cosponsorship of Medical Education Collaborative, Inc. and Medscape.|
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GoalTo define the "state-of-the-art" treatment protocols and clinical strategies for the diagnosis, treatment, and management of Lyme disease and other spirochetal and tick-borne disorders.
Learning ObjectivesThese daily summaries from the 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders are intended for frontline infectious diseases, internal medicine, family practice, pediatric, other primary care physicians, and pharmacists who are likely to treat patients with Lyme disease.
Upon completion of this self-study activity, participants will be able to:
1. determine the challenges involved in confirming a clinical diagnosis of Lyme disease. 2. identify which ticks are the primary vectors for human disease. 3. discuss issues related to the differential diagnosis of Lyme disease and a number of similar multi-symptom disorders.
(CME valid until October 10, 1999)
(not required for CME)
Julie Rawlings, MPH
Human granulocytic ehrlichiosis (HGE), an acute febrile tick-borne illness, is an emerging disease in the United States. It is caused by Ehrlichia phagocytophyla or an E phagocytophyla-like organism and is an obligate intracellular bacterium that infects cells of myeloid derivation in mammalian hosts. Closely related organisms include E equi, which causes disease in horses, and E bovis, which effects cattle. Somewhat more distantly related ehrlichiae include the canine pathogens E canis and E ewingii and another human pathogen, E chaffeensis. HGE is a newly recognized disease; there is still much to learn about its epidemiologic and clinical aspects. Dr. J. Steven Dumler, a microbiologist and pathologist at the Johns Hopkins University School of Medicine, discussed recent advances in the understanding of bacterial and host components involved in HGE.
Age and male gender appear to be risks associated with HGE. The disease occurs primarily in the northeastern and northwestern US; its prevalence in those areas is similar to or exceeds that of Lyme disease. As with Lyme disease, the primary vectors and reservoir for HGE are Ixodes sp. ticks and Peromyscus leucopus, the white-footed mouse. Peak incidence of cases is in the summer (associated with nymphal ticks) and again in the fall (associated with adult tick activity).
Most infections are asymptomatic or subclinical. Dr. Dumler estimated that one in 10 patients develops apparent disease. Even then, symptoms are nonspecific -- fever, headache, myalgias, and malaise characterize HGE in most patients. There may be involvement of the gastrointestinal and respiratory systems and skin, but definite central nervous system involvement has not been documented. Clinical laboratory test results can be extremely helpful to clinicians considering a diagnosis of HGE; abnormalities include thrombocytopenia, leukopenia, and elevations in serum hepatic aminotransferase activities. Treatment with doxycycline provides complete cure.
In severe cases, a sepsis-like syndrome, adult respiratory distress syndrome (similar to hantavirus pulmonary syndrome), rhabdomyolysis, hemorrhage, peripheral neuropathies, severe opportunistic and nosocomial infections, and even death may occur. Severity appears to be related to initial burden of the infectious agent and delays in diagnosis and treatment.
A chronic or persistent phase of HGE has not been documented, and co-infection with other tick-borne agents has not been proven to adversely affect outcome. Most patients recover rapidly in association with a TH1 response and high titers of antibodies. Studies in horses indicate that infection with the HGE agent usually induces life-long immunity, but this has not been proven in humans. Dr. Dumler noted that there have been a couple of human cases in which there appears to have been two sequential disease episodes separated by approximately one year. It is not known whether these cases represented recrudescence of the causative agent or reinfection.
Collaborative studies with Dr. John Madigan at the University of California, Davis, have shown that horses are good mimics of HGE disease in humans. In contrast, mice do not develop any clinical signs of disease and have TH2 responses. They do, however, develop pathologic lesions similar to those observed in humans and other animal models.
In vitro and experimental infections in horses and mice indicate that HGE infection is established in myeloid precursors of bone marrow or other hematopoietic tissues and is mediated via ehrlichial MSP adhesions and leukocyte CD15-associated receptors. After this, bacterial infection may control some host cell functions and responses. Later, infected neutrophils are released into the peripheral circulation and adhere to endothelial surfaces, particularly in the spleen, liver, and lung.
In vitro, infected neutrophils secrete high levels of chemokines, but not proinflammatory cytokines. Thus, the localized secretion of chemokines allows recruitment and activation of mononuclear inflammatory cells that in turn release proinflammatory cytokines and induce localized tissue injury. In mice, a kinetic relationship between ehrlichial burden, IFNK release, and pathologic index is observed, suggesting that E phagocytophila bacteria drive a potentially deleterious inflammatory response but do not directly mediate substantial cell injury. Although not proven, it is suspected that poorly controlled proinflammatory cytokine release may be related to systemic manifestations and increased severity of disease.
Dr. Dumler called for continued study of the ehrlichiae and infected hosts. Such research will contribute greatly to the understanding of HGE and help to devise better management and treatment strategies.
Sam Donta, MD
The confirmation of the diagnosis of Lyme disease can be challenging for a number of reasons. The clinical presentations and course of Lyme disease may vary depending on the different borrelial species involved. The diagnostic tests now available also can vary in their clinical utility.
Borrelia burgdorferi, sensu strictu, is the species most common in North America, and may be more associated with arthritis, Dr. Anthony Lionetti noted in a review of diagnostic issues. B afzeli may be more associated with skin manifestations, and B garinii may be more associated with neurologic manifestations. However, neurologic disease is very common in North America, which may limit the validity of any such association.
Also, new borrelial species are being recognized. For example, B lonestari has been found to be associated with Lyme disease in the lower Midwest and is transmitted by the Lone Star tick, in contrast to the usual, smaller Ixodes vector responsible for most Lyme disease throughout the world.
Another direct detection tool is the Lyme Urinary Antigen Test (LUAT). Because of its great variability, however, it needs further validation before it can be endorsed as a reliable indication of active disease. The indirect detection tests are primarily antibody tests, ie, ELISA and Western blots.
The two-tiered system advised by a Centers for Disease Control and Prevention committee in 1994 screen with ELISA, confirm with Western blot is probably unreliable, as ELISA tests appear to be insensitive and proficiency testing has shown much interlaboratory variability. Western blots are more sensitive and specific but are more difficult to standardize.
The CDC criteria for positivity appear to be outdated and do not give the appropriate attention to the importance of IgM reactivity in chronic disease. Also, the numbers of reactions required for a positive test (5 or more) need to be revised and greater weight placed on the specificity of the reactions.
Psychiatric disturbances, such as mood changes, anxiety, paranoia, mania, and psychosis, also may be seen in Lyme disease. Sometimes these symptoms are a reaction to having a serious disabling illness while other times they stem from an organically induced disorder that improves with appropriate antibiotic therapy.
With regard to neuropsychiatric problems seen in children, Dr. Fallon noted a recent controlled of 22 children with Lyme disease and 27 healthy age- and sex-matched controls aged 8 to 18. The children with Lyme disease were ill for more than 3 years; nearly two-thirds had received intravenous antibiotics in addition to oral antibiotic treatment.
The majority of the ongoing symptoms reported in the infected children were neuropsychiatric, including irritability, rage reactions, mood swings, depression, headache, poor concentration, memory loss, and systemic, including fatigue, arthralgias and insomnia. Each symptom was reported significantly more frequently by the Lyme sample than the controls. The majority of the parents of these children reported that the neuropsychiatric problems seen appeared after the children contracted the disease. The frequency rates of neuropsychiatric disorders seen in this study are not generalizable to all children with chronic Lyme disease given the likelihood of referral bias, Dr. Fallon noted. Still, he said, the findings suggest that clinicians and educators should consider Lyme disease when faced with a child from an endemic area who shows new onset neuropsychiatric and systemic symptoms.
Brian A. Fallon, MD
Two presentations today addressed the overlap that exists between similar disorders one talk focused on diagnostic distinctions between fibromyalgia, Lyme disease, and Gulf War syndrome; the other was devoted to Chronic Fatigue Syndrome and Post-Lyme Disease.
Dr. Sam T. Donta of the Boston University Medical Center discussed fibromyalgia and Lyme disease, noting the increasing awareness of the similarities and differences between chronic Lyme disease and other chronic multi-symptom disorders (CMSDs) such as fibromyalgia, chronic fatigue, and Persian Gulf War illness. Still, since all are characterized by fatigue, musculoskeletal pain, and neurocognitive dysfunction, discriminating one from the others is often difficult.
Descriptions of patients plagued by prominent fatigue states first appear in the 1850s, Dr. Donta said. These early references describe patients' symptoms as "bed cases" or "sofa cases," and physicians characterized such cases as neuromyasthenia. Following both World War I and World War II, epidemics of fatigue were reported and in 1988, the term "chronic fatigue syndrome" was first used. In Europe, the term "myalgic encephalomyelitis" is more commonly used than "chronic fatigue."
It is estimated that the incidence of chronic fatigue is approximately 0.1% -0.2% in the overall population, while in primary care settings the incidence is higher. A recent study indicated an incidence of 11.3% in a primary care sample of 2,376 patients. Following flu-like illness, 15% of patients developed post-infection chronic fatigue. A recent study from England demonstrated that after Q-fever, 42% of patients developed chronic fatigue.
Dr. Donta pointed out that Chronic Fatigue Syndrome shares a number of symptoms with Lyme disease. Symptoms of Lyme disease include fatigue, arthalgias, myalgias, headaches, cognitive problems, mood swings, and paresthesias. Similarly, Chronic Fatigue Syndrome is characterized by a fatigue for 6 months, associated with at least 4 of 8 associated symptoms such as impaired memory, sore throat, tender or swollen lymph nodes, muscle pain, multi-joint pain, unrefreshing sleep, new onset headaches, and post-exertion malaise.
Chronic Lyme disease etiology may be multifactorial, Dr. Donta said. It may stem from a persistent relapsing infection, be an autoimmune-triggered disorder, or result from release of toxin during reactivation of infection.
The persistent infection hypothesis has also been applied to some of the other CMSDs. In recent studies of chronic fatigue syndrome, tests showed evidence of mycoplasma DNA in the WBC buffy coat in 50% of subjects. In another study -- this one of patients with Gulf War Syndrome -- similar findings were seen: mycoplasma fermentens in the blood of half the subjects.
In Lyme disease, Western blot testing appears superior to the ELISA in detecting the illness, Dr. Donta said. In one of Dr. Donta's studies, conducted in a large cohort of patients with Western blot-positive serum results, only 35% (72/205) of the cohort had correspondingly positive ELISA results. These findings, Dr. Donta pointed out, are contrary to the recommendations of the CDC for a two-tiered approach to the serologic testing. The CDC recommendations say patients should not be tested by Western blot unless their screening ELISA results are either positive or equivocal.
Dr. Donta said that in formulating the standardized criteria for the interpretation of a Western blot, the CDC relied upon the number of bands that were most frequently seen rather than the specificity of the bands themselves. For this reason, he says, some of the most specific bands for Lyme disease (eg, the 31 and 34Kd bands) were excluded. Dr. Donta emphasized that a new set of criteria needs to be established for the interpretation of Western blot results, and that those criteria should include the specificity of the bands for Lyme disease.
Further, he said, the CDC case criteria for the diagnosis of Lyme disease do not include one of the more common late manifestations of neurologic Lyme disease: encephalopathy. SPECT imaging can be helpful in the differential diagnosis, demonstrating a pattern of heterogeneity, he said. DNA PCR studies may also be helpful, but Dr. Donta says that in his experience fewer than 5% of patients with chronic Lyme disease have positive PCR results.
Dr. Donta stressed that spinal fluid analysis is an important tool in the differential diagnosis of Lyme disease -- ruling out other disorders before the diagnosis of Lyme disease is firmly established.
Prior studies have demonstrated that risk factors for the development of sequelae from Lyme disease include lengthy duration of disease (>1 year) prior to treatment, high specific IgG antibody titers, and multiple bands on the Western blot (which have been correlated with poor verbal memory performance).
The term "Post-Lyme Syndrome" encompasses chronic or intermittent problems that begin at the time of clinical Lyme disease and persist for months to years despite adequate antibiotic therapy. Synonymous terms include "post treatment Lyme disease" and "chronic Lyme disease". Similar in symptomology to other disorders, Post-Lyme Syndrome (PLS) may produce cognitive disturbances (encephalopathy), fatigue/malaise (Chronic Fatigue Syndrome), joint and muscle pain (fibromyalgia), headache, and other features such as hearing loss, vertigo, mood disturbances, paresthesias, sleep disturbances, and stiff neck.
Dr. Krupp said estimates of the frequency of PLS range from 13% (in a 1993 study of 788 patients), to 53% (in a 1993 study of 215 patients). In a population-based study by Shadick in 1994 comparing Lyme disease patients to community controls, the significantly more common and distinguishing clinical symptoms between the two groups respectively were severe fatigue (26% vs 9%), concentration problems (47% vs 16%), emotional lability (18% vs 5%), difficulty sleeping (47% vs 16%), and objective cognitive impairment (12% vs 5%).
Dr. Krupp said that in addition to persistent infection, reinfection, or a post-infectious immune or inflammatory process, other causes of Post-Lyme Syndrome need to be considered. These include incorrect diagnosis, slow resolution of symptoms, residual damage, and unmasked prior pathology.
In one post-treatment Lyme disease study, Dr. Krupp compared patients with PLS to patients with Chronic Fatigue Syndrome (CFS). The PLS patients had a history of seropositivity, a compatible clinical syndrome, severe fatigue persisting for 6 months or more, and no other explanation for fatigue. The CFS patients had no history of Lyme disease. Although all of the CFS patients met the 1994 CFS criteria, as many as 84% of the PLS patients also met the same criteria. The clinical symptoms that significantly distinguished the two groups, comparing CFS and PLS respectively, were: fever (72% vs 28%), sore throat (76% vs 28%), unrefreshing sleep (96% vs 36%) and tender cervical or axillary lymph nodes (60% vs 26%). In the CSF analyses of these two patient groups, 21-40% of the PLS patients were Borrelia antigen positive vs 0% of the CFS patients. In regards to cognitive performance, both groups had more deficits than the controls, with the PLS patients having more deficits on verbal fluency, verbal memory, and digit span than the CFS patients.
All patients met the CDC case definition of Lyme disease. This placebo-controlled study has 3 primary endpoints: fatigue, cognitive speed, and CSF infection markers. Neurologic, CSF, psychiatric, fatigue, and cognitive measures were applied at baseline and at 6 month follow-up. Of 45 enrolled subjects, 27 have completed treatment and the 6-month follow-up, 13 are in phase, 3 had allergic reactions and 2 have dropped out of the study. Most patients are working full time (77%) and there are slightly more women (55%) than men (45%). About 25% of the patients had only an initial EM rash on presentation, while 55% had an EM and late manifestations, and 20% had only late manifestations (such as arthritis).
At baseline, 100% of the PLS patients had severe fatigue, 63% had objective cognitive impairment, 22% were OspA CSF-antigen postive, and 32% had a current psychiatric disorder. Dr. Krupp said the treatment results thus far from the study could not be divulged because the trial is ongoing.
Dr. Krupp noted that there is considerable overlap between PLS and CFS and that cognitive deficits and psychiatric comorbidity are common.
Julie Rawlings, MPH
To better understand Lyme disease and other tick-borne disorders, it is helpful to understand the biology of ticks. Dr. John Anderson, director of the Connecticut Agricultural Experiment Station, provided this overview, noting that the rise and fall of tick populations is related to land use patterns.
In the eastern portion of the United States prior to colonization, both white-tailed deer (a crucial host for maintaining ticks that transmit Lyme disease) and ticks were exceedingly abundant. While this same land was under cultivation, the deer population was decimated and ticks all but disappeared. Today, this area has come nearly full circle with reforestation and effective hunting regulations.
Ticks are non-permanent obligate bloodsucking arthropods. They are best known as disease vectors. There are more than 800 different types of ticks, but relatively few species feed on humans. Some of those that do feed on humans include species in the genera Amblyomma, Dermacentor, and Ixodes. Ixodes scapularis (the black-legged tick) is the primary vector of Borrelia burgdorferi (the Lyme disease agent) in eastern United States; I pacificus (the western black-legged tick) is the primary vector in the western United States. The closely related Ixodes tick species are the main vectors in Europe.
These ticks take no more than three blood meals during their lifetime. Larvae, tiny ticks that have just emerged from eggs, feed for about three days before dropping from their host and eventually molting. Nymphs also feed for three days and molt. Adult females will feed for seven to nine days. Mating occurs on the host animal before the engorged female drops off and lays eggs. Black-legged ticks feed on many different types of host (lizards, birds, and mammals), including humans. In the eastern United States, most people acquire B burgdorferi from bites of nymphal I scapularis. Nymphs normally need to be attached for 40 or more hours before Borrelia is transferred from the tick to its host. Most humans acquire their infections in late spring and early summer when nymphs actively seek hosts.
Staff at the Connecticut Agricultural Experiment Station have been identifying ticks submitted by citizens and testing them for the presence of spirochetes since 1990. The most common species received have been I scapularis, Dermacentor variabilis (the American dog tick) and Amblyomma americanum (the lone star tick). Of 25,463 I. scapularis cultured or analyzed using indirect fluorescent antibody (IFA) or polymerase chain reaction (PCR) procedures, 5,226 or 22% were infected with B burgdorferi.
Dr. Anderson reminded the audience that ticks feed on humans of all ages; they will attach from head to toe. Therefore it is imperative that people who have ventured into tick habitats examine themselves thoroughly and remove attached ticks promptly. Diligence is required or nymphs may be missed they are small and not easily seen.
Dr. Stafford has been studying the use of acaricides, vegetative management, deer exclusion, and acaricidal treatment of deer for the control of the tick, I scapularis, at residential landscapes in Lyme and Old Lyme, Conn. In 1994 and 1995, he conducted surveys to determine tick control practices by licensed pesticide applicators and found that carbaryl, chlorpyrifos, and cyfluthrin were the most widely used materials for tick control.
Dr. Stafford also tested various combinations of landscape modifications and pesticides at residential home sites. Clearing leaf litter and placing wood chip barriers at the lawn perimeter can reduce nymphal abundance by an average of 42% - 88%. Synthetic pyrethroid insecticides generally reduced nymphal tick abundance by over 90%. Certain combinations of natural pyrethrin, piperonyl butoxide, and insecticidal soap or silicon dioxide can reduce tick abundance by 71% - 97%, although some combinations of these materials were less effective and produced more variable results.
In 1997, Dr. Stafford began assessing USDA-patented pesticide self-application deer feeders (æ4-postersÆ). After monitoring corn consumption and usage of the devices by deer, he found that over 90% of the local deer population utilized the æ4-postersÆ during the first year of the study. Usage declined in fall 1998 with the availability of competing food sources (ie, acorns).
According to Dr. Stafford, acaricides are extremely effective for the control of I scapularis and some less toxic materials may offer an alternative to synthetic chemicals for tick control at individual homes. Moreover, the acaricidal treatment of at least 90% of the local deer population could potentially reduce tick abundance community-wide.
Sam Donta, MD
Researchers are investigating a number of antibiotic compounds as potential therapies for Borrelia burgdorferi. Several show promise, although additional work remains to be done before these new approaches are ready for clinical use. Two presentations at Saturday's session addressed this issue.
The fluroquinolone antibiotics bind to the A subunit to prevent the resealing reaction. The coumerin antibiotics bind to the B subunit to prevent ATP binding and enzyme activity.
B burgdorferi is highly susceptible to coumermycin A1, causing a loss of supercoiling and inhibition of growth of the Borrelia. For several reasons, primarily toxicity, coumermycins are not clinically useful antibiotics. They are helpful, however, in developing a genetic classification system for B burgdorferi.
The fluroquinolone antibiotics have some antimicrobial activity against B burgdorferi, although they are not as active as other antibiotics. Perhaps some of the newer quinolones will have greater activity and eventually be tested in clinical settings.
Dr. Samuels has used the various fluroquinolone antibiotics to map the sites on DNA where gyrase and related topoisomerase enzymes prefer to bind. Using this information, it may be possible to design new quinolones and other antibiotics to be more effective inhibitors of the growth of B burgdorferi.
If multiplication of B burgdorferi is an important part of the development of infection in humans or in the reaction or persistence of infection, this type of antibiotic may find clinical utility. If B burgdorferi does not multiply to any significant degree in human disease, but persists as sometimes dormant, sometimes metabolically active organisms, then other antibiotics (eg, protein synthesis inhibitors such as tetracylines or macrolides) will likely be needed to disrupt their activity.
Dr. Pavia tested the antibiotic for its ability to inhibit growth of B burgdorferi in vitro and to cure mice of an acute Bb infection. For the in vitro experiments, the effect of Ziracin was compared with that of penicillin and ceftriaxone; its effectiveness in against Bb was greater than that of either of the other two drugs. It also showed effectiveness in the infected mice.
These data suggest that Ziracin may be a therapy for Lyme disease since it has better or nearly equal in vitro and in vivo inhibitory activity against Bb compared with two other antibiotics that are frequently used for the treatment of the disease. Some factors might limit this drug's clinically utility, however, including administration by intramuscular injection, limited number of days of use (eg, 4 days), and inability to penetrate cells.
Brian A. Fallon, MD
Cognitive remediation (CR) is a therapeutic method designed to improve patients' impaired neurocognitive and neurobehavioral abilities following brain injury or illness. CR utilizes a systematic program of exercises that address the patient's impaired cognitive domains.
CR's clinical applications could include a role in patients with chronic Lyme disease encephalopathy, according to a presentation by Dr. Leo Shea, III, of the Rusk Institute of Rehabilitation Medicine at New York University.
Cognitive remediation is distinct from cognitive behavioral therapy, the latter being a form of psychotherapy geared to teaching patients how thoughts affect emotions. Cognitive behavioral therapy is typically performed by psychologists, not neuropsychologists.
Cognitive remediation, on the other hand, has several purposes, Dr. Shea explained. First, it is used to improve patients' capacity and ability to process, assimilate and utilize incoming information. Second, it can help patients ameliorate neurocognitive and neurobehavioral deficits by learning compensatory strategies. Third, it can aid patients in using repetitive exercises to restore impaired neurocognitive and neurobehavioral functions to their maximum potential. And fourth, CR can help patients access residual cognitive strengths and use them to support techniques learned in CR.
Dr. Shea reviewed several studies that showed CR was associated with overall improved attention, self-regulation, and memory performance, including a study by Levin in the Archives of Neurology in 1990.
Dr. Shea pointed out that since the findings in these studies demonstrate improvement in many of the domains most involved in Lyme disease. Studies of CR in chronic Lyme Disease need to be undertaken, he noted.
Dr. Shea presented two theoretical models for CR. One, referred to as the "Restorative Model," postulates that deficits within specific cognitive areas can be directly addressed by repetitive, saturation training (eg, list learning, paragraph recall, etc.) and thus can help restore cognition to a pre-injury status.
The "Compensation Model," on the other hand, supposes that specific cognitive deficits cannot be addressed directly and it is only through the use of compensatory strategies that one can circumvent the cognitive difficulties. It is via this "mental detour" process, the Compensation Model postulates, that alternative pathways to improve functioning are formed.
The Compensation Method makes use of external aids (memory notebook systems, alarms, calendars, buzzers, post-it notes, labeled shelving, etc) and internal aids (eg, rehearsing information, mnemonic devices, visual imagery, verbal pegs, etc.).
Dr. Shea emphasized the CR may be helpful at any stage of illness. In fact, studies of head injury rehabilitation have suggested that improvement can occur many years following injury.
Dr. Shea compared many of the clinical features of patients with head injury with the clinical features of patients with Lyme disease. He noted that both groups of patients often have similar cognitive deficits: attention, concentration, short-term memory, visual processing, verbal processing, speed of processing, higher level reasoning, adynamia syndrome (neurofatigue, lack of initiation, poor generation, anhedonia, apathy), disinhibition syndrome (impulsivity, mania, intermittent explosive disorder, irritability, aggressiveness, and low frustration tolerance), depression, and anxiety.
Dr. Shea emphasized that physicians need to make sure that patients with cognitive deficits are referred to therapists adequately trained in cognitive remediation. He said the program at his institution requires a minimum of 1 year of training, but that most psychologists remain for 3 years of training. Many neuropsychologists in the field, he said, have not undergone training of this intensity and thus would be less qualified to conduct cognitive remediation.
Dr. Shea said that at the Rusk Institute, cognitive remediation encompasses a wide variety of modalities, including individual psychotherapy, individual cognitive remediation, group cognitive remediation, and group psychotherapy. Patients typically are in therapy 3-4 days/week, and are assigned homework to complete between sessions. The process is not a rapid treatment, he emphasized, but involves many months of commitment.
Anthony Lionetti, MD
The National Institutes of Health provides most of the funding for Lyme disease research in the United States, with much of that effort supported through the National Institute of Allergy and Infectious Diseases (NIAID).
Dennis Dixon, PhD, Chief of Bacteriology and Mycology at the NIAID, reviewed the basic structure of the NIH and how it relates to government-funded Lyme disease research.
The Institute is divided into the Divisions of Intramural and Extramural research. The Intramural program is advised by a Board of Scientific Councilors and comprised of two sites, one in Bethesda, Md., and the other at the Rocky Mountain Laboratories in Montana. The program is further divided into laboratory studies and clinical studies. Abstracts for these projects can be accessed on the World Wide Web via the institute's Web site, www.niaid.nih.gov. Dr. Dixon also noted that NIH provides access to specific biomedical grant information through a searchable database on its Computer Retrieval of Information on Scientific Projects (CRISP) Web site www.commons.cit.nih.gov/crisp.
The Extramural Lyme disease project, directed by Philip Baker, PhD, oversees the large-scale double-blind Lyme disease treatment trial. This trial is advised by a Data and Safety Monitoring Board as well as a panel of scientists, practicing clinicians and citizen advocates who assist in the design and modification of the clinical protocol.
The study is focused on treatments issues in chronic Lyme disease (CLD), a term that has been used to describe a subset of individuals who have developed Lyme disease and have persistent symptoms of arthralgia, fatigue, and other symptoms that remit or recur despite antibiotic therapy. Dr. Weinstein was unable to share any study data since none of the investigators has access to information aside from screening tests due to the project's double-blind design. He noted, however, that investigators have been concerned with the low enrollment levels in the study, which has only 57 patients so far. Intensive efforts are under way to publicize the study.
Dr. Weinstein reviewed his past research and current concepts of the possible pathogenesis of CLD. He noted that the study's conclusions would be based on evaluation of the results derived from serial administration of the Rand SF-36 physical/mental evaluation profile. A positive response to antibiotic therapy would be represented by a 1 standard deviation improvement in those patients who did receive antibiotics over the patients who did receive placebo.
Researchers will not be making subjective determinations of the level of improvement in any patients, indicating attention to any concerns about potential bias against the general concept of persistence of infection in Lyme disease.
Dr. Weinstein did discuss an interesting finding in a study of cerebrospinal fluid from patients with Lyme disease. In more than 60% of the patients evaluated, researchers found the presence of a 130 kda matrix metalloprotein (MMP-9). A previous study found MMP-9 present in the CSF of 79% of patients studied with acute neuroborreliosis and only in 6% of controls. Despite these results, the significance of this protein as a marker of central nervous system Lyme disease is unknown.
To date, the study has enrolled 45 patients and controls whose sera has been the basis for the described evaluations. It appears that the basic thrust of studies in this area is in immunological investigations of basic mechanisms of pathogenesis. However, Dr. Adriana R. Marques of the NIAID noted that investigators are working on the development of a 16S RNA polymerase chain reaction, which may have improved sensitivity over the currently used primers for OspA.
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|1.||A diagnosis of human granulocytic ehrlichiosis (HGE) should be considered:|
|a.||if a patient who resides or travels in the northeastern United States presents with fever, headache, myalgias, and malaise following a tick bite.|
|b.||for a patient with thrombocytopenia, leukopenia, and elevated liver function test results.|
|c.||for a park ranger with adult respiratory distress syndrome.|
|d.||all of the above.|
|2.||Which of the following statements is true?|
|a.||HGE is an immunologically driven disease.|
|b.||High levels of antibody to the HGE agent indicate persistant infection.|
|c.||Most children bitten by a tick that is infected with the HGE agent will develop severe illness.|
|d.||none of the above.|
|3.||The diagnosis of Lyme disease is best made by:|
|d.||Brain SPECT scan|
|e.||Spinal fluid analysis|
|4.||The most reliable laboratory test (% positive) for Lyme disease is:|
|5.||Which of the following antibiotics interferes with DNA gyrase?|
|6.||Which of the following antibiotics has the least activity against B burgdorferi in vitro?|
|7.||The black-legged tick can transmit the agents of:|
|d.||all of the above|
|8.||The clinical differences between Chronic Fatigue Syndrome and Post-Lyme Syndrome can best be described by the following:|
|a.||patients with CFS have far more fatigue than patients with PLS.|
|b.||patients with CFS more often suffer from fevers and tender lymphadenopathy.|
|c.||patients with CFS more commonly have cognitive deficits in verbal memory, verbal fluency, and digit span.|
|d.||patients with CFS more often have unrefreshing sleep.|
|e.||b and d.|
|9.||Problems with the CDC criteria for the laboratory diagnosis of chronic Lyme disease include the following:|
|a.||encephalopathy is not included in the case definition, although it is one of the more common late manifestations of chronic neurologic Lyme disease.|
|b.||the CDC Western blot criteria were randomly chosen without use of data.|
|c.||the CDC criteria for the interpretation of the Western blot do not include some of the more Lyme-specific bands, such as the 31 and 34 Kd bands.|
|d.||the CDC clinical criteria are over-inclusive.|
|e.||a and c are true.|
|10.||Symptoms shared by patients with head injury and patients with chronic Lyme Disease include:|
|a.||deficits in attention, concentration, short-term memory.|
|b.||deficits in visual processing, verbal processing, speed of processing.|
|c.||adynamia syndrome (neurofatigue, lack of initiation, poor generation, anhedonia, apathy).|
|d.||depression and anxiety.|
|e.||all of the above.|
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|5 4 3 2 1|
|4.||How would you rate the content?|
Will definitely change the way you practice
Challenged you to think about the topics
Applicable to your practice; a good review
Of limited use in your practice
Not applicable to your practice
|5.||How well did this activity meet the goal of summarizing new findings and discussing their practice and research implications?|
|5 4 3 2 1|
|6.||Were your personal objectives for taking this activity met?|
|5 4 3 2 1|
|7.||How long did this session actually take you to complete?|
.25 - .50 hrs
.50 - 1.0 hrs
1.0 - 1.5 hrs
1.5 - 2.0 hrs
More than 2.0 hrs
|8.||What other continuing education topics would be of value to you? Please offer any additional comments.|
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Version: 22Jan. 2004