LymeNet Newsletter Volume 8 Issue 04

Volume: 8
Issue: 04
Date: 28-Apr-00

Table of Contents:

I. LYMENET: Researchers Present New Approaches to Persistent LD II. LYMENET: NIH Offers Resistant Bacterial Infection and Chronic Lyme Disease Grant III. OPTHAMOLOGY: The expanding clinical spectrum of ocular lyme borreliosis. IV. WIEN KLIN WOCHENSCHR: Lyme meningitis: a one-year follow up controlled study. V. HEMATOL ONCOL: Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding? VI. ABOUT THE LYMENET NEWSLETTER

Newsletter:

*********************************************************************** * The National Lyme Disease Network * * http://www.LymeNet.org/ * * LymeNet Newsletter * *********************************************************************** Publishing Lyme disease information on the Internet since 1993

Volume 8 / Number 04 / 28-APR-2000 INDEX

I. LYMENET: Researchers Present New Approaches to Persistent LD II. LYMENET: NIH Offers Resistant Bacterial Infection and Chronic Lyme Disease Grant III. OPTHAMOLOGY: The expanding clinical spectrum of ocular lyme borreliosis. IV. WIEN KLIN WOCHENSCHR: Lyme meningitis: a one-year follow up controlled study. V. HEMATOL ONCOL: Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding? VI. ABOUT THE LYMENET NEWSLETTER

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I. LYMENET: Researchers Present New Approaches to Persistent LD ------------------------------------------------------------------ Sender: The Lyme Disease Research Project <[email protected]> Date: April 17, 2000

Editors's Note: The following is an excerpt from "Lyme in the 21st Century: New Multi-Disciplinary Management Approaches for Late-Stage and Persistent Lyme Borreliosis Patients," originally presented in the technical poster session at the Lyme Disease Foundation's 12th International Scientific Conference on Lyme Disease and Other Spirochetal & Tick-Borne Disorders, April 9 & 10, 1999, New York City.

Author(s) of excerpt: Courtney N. Ganz, MA, Independent Researcher, Member of the Berkshire Brain Injury Support Group* in collaboration with Sarah Rosenthal Ward, MS., C.C.C.\SLP, Massachusetts General Hospital, Boston, MA and Center for Neurologic Recovery, Newton Center, MA and Suzanne D.K. Doswell, Massachusetts Brain Injury Association (Copyright © 1999. All rights reserved.)

Lyme borreliosis is a tick-borne transmitted infection, presenting at times in patients, a wide spectrum of neurologic and non-neurologic manifestations. When it reaches systemic stages, the clinical diversity of Lyme disease [1] and the sometime vagueness of certain complaints overlapping with everyday issues, make it difficult to unfasten all of its troublesome components. [2]

Cognitive functioning and its identification when impaired is still a relatively new field, and is little understood even among health professionals. Specialists who typically have the most expertise, are those who deal with traumatic or acquired brain injury patients, and have developed protocols for testing, managing and addressing cognitive-generated issues for those purposes.

Most physicians treating lyme disease, listen, and patients share, many anecdotal accounts of "vague" complaints, generating interference with their functioning and/or tasks of daily living. They are so numerous and typical among patients, including children [3], in the later stages, they are often reported as an unascertained, yet standard characteristic of the illness.

As science searches to grasp the implications of the disease, newer and more diagnostic testing and studies, aside from serology-based, are being developed to chronicle the disease in other ways and identify, and quantify, in particular, the anecdotal set of vague daily-task oriented complaints. [4]

PET/SPECT scanning, specifically, has led the way to identifying and classifying patterns in the cerebral blood flow typical for the disease, and potentially targeting new means to pinpoint objectively and scientifically the origin of these complaints. [5]

Neuropyschological testing is becoming more experienced in discerning patterns, and saavier at ruling out differential diagnosis, as more patients are evaluated and tested. [6]

Slowly, science is creating new mechanisms to study this disease not only from a serology perspective for pathology purposes, but from an objective stance of clinical documentation and quantification of symptoms. [7]

We are on a new frontier for lyme disease research. We now have some minimal tools to identify the vague, side components of late-stage and/or persistent disease, but what do we do with this data? What means can we address these issues for patients?

How can physicians be perceptive enough to know in a patient, what all the psycho-social-emotional issues mean and translate into, and be able to interpret it for them? [6] What is our next direction, aside from attempting to understand the microbiology of the disease process itself?

"Lyme in the 21st Century: New Multi-Disciplinary Management Approaches for Late-State and Persistent Lyme Borreliosis Patients," hopes to alert researchers to recognize and investigate new areas of study, and to better identify, address, and ultimately optimize the functional capacity of the patient whether during, in-between, or after treatment. Recommendations should not preclude, or supersede treatment, and are for the purposes of enhancement only, in the interest for overall improved patient well-being.

The use of standard protocols for another patient population, such as traumatic or acquired brain injury victims can not only yield fascinating comparison symptomatology, but offer modalities to address, and perhaps, finally put a name, and acknowledgement to what lyme patients complain of, but can't quite communicate.

This research is in its infancy, and hopes for a more formal study through this proposal summary is high. The rich potential application to lyme patients can be rewarding.

And, once patients' neurocognitive symptoms begin to be legitimized and addressed, coping with lyme disease, not identified in time, may be just one step easier to bear, until recovery.

[Please contact the author(s) for permission to include this material in publication form, or research.]

Text Boxes of the Poster and other Resource Material are available through writing the Lyme Disease Research Project c/o United Cerebral Palsy Association of Berkshire County, 141 North St., Pittsfield, MA, 01201 for a postage and handling fee. Write to: [email protected] for more information.

An Extensive Bibliography of References on Neurocognitive Impairments in Lyme Borreliosis Patients and Related References is being compiled and will shortly be available upon request.

* The Author would like to acknowledge and thank the following people for their tutelage, input, and support of her research: Dr. Brian Fallon for the privilege of reviewing his research on the neuropsychiatric manifestations of lyme disease with the author in the fall of 1995, Center for Rehabilitation, Berkshire Medical Center, Pittsfield, MA where the initial research was formulated and conducted, Dr. David Corwin for editorial feedback, Dr. Sam Donta, and Dr. Leo Shea III, whom the author met after this writing at the conference; Suzanne and Bill Doswell, Sarah R. Ward, the Massachusetts Brain Injury Association and Dr. Joan Gold for information on acquired and traumatic brain injury, J.P. for technical assistance, Christine DiMaggio for her administrative and financial coordination, the Lyme Disease Foundation, and others who are not named but were undoubtedly so very helpful, and supportive of this research, technical poster and presentation. Partial funding was provided by United Cerebral Palsy Association of Berkshire County, and
contributions by private donors.

Lastly, the author must include an acknowledgement and thanks to those who were helpful and instructive in the past, but could not go the distance to see the possibilities of the author's progressive work and were sadly resistant to the research concepts and findings. It has to be expected with any new venture, which challenges established standards. May these people find, one day, that the new tools offered through this project will be helpful to them, their support group members, or their patients and open up avenues of understandings and opportunities previously not available to Lyme Disease sufferers and their families.

REFERENCES:

1] Bingham, Galetta, Athreya and Sladsky, Neurologic Manifestations in Children with Lyme Disease. Pediatrics 1995 Dec, v96, n6, p1053(4).

2] such as in this example: Stephens PJ, Carpenter FE, Cases From The Aerospace Medicine Residents' Teaching File. Case #42. An Aviator with Concentration Deficit, Lyme Disease Organic Diagnostic Evaluation, and a Somatoform Disorder (Clinical Conference). Aviat Space Environ Med 1991 Apr; 62(4): 363-5.

3] Bloom BJ, Wyckoff PM, Meissner HC, Steere AC, Neurocognitive Abnormalities In Children after Classic Manifestations of Lyme Disease. Pediatr Infect Dis J 1998 Mar; 17(3):189-96.

4] see: Shadick NA, Phillips CB, Logigian EL, Steere AC, Kaplan RF, Berardi VP, Duray PH, Larson MG, Wright EA, Ginsburg KS, et al, The Long-Term Clinical Outcomes of Lyme Disease. A Population-Based Retrospective Cohort Study. Ann Intern Med, 1994 Oct 15; 121 (8): 560-7; Benke T, Gasse T, Hittmair-Delazer M, Shmutzhard E, Lyme Encephalopathy: Long-Term Neuropsychological Deficits Years After Acute Neuroborreliosis. Acta Neurol Scand 1995 May; 91(5):353-7; Guadino EA, Coyle PK, Krupp LB, Post-Lyme Syndrome and Chronic Fatigue Syndrome: Neuropsychiatric Similarities and Differences. Arch Neurol 1997 Nov; 54 (11): 1372-6.

5] Fallon BA, Keilp J, Prohovnik I, Mann J, Lyme Disease vs. Depression vs. Somatization: Cognitive Tests & Functional Imaging. 9th Annual International Scientific Conference on Lyme Disease & Other Tick-Borne Disorders, Boston, April 1996; Fallon BA, Das S, Plutchok JJ, Tager F, Liegner K, and Heertum R, Functional Brain Imaging and Neuropsychological Testing in Lyme Disease. Clin Infect Dis 1997 Jul; 25 Suppl 1:S57-63; Logigian EL, Johnson, Kijewski, Kaplan RF, Holman, Steere AC, Cerebral Hypoperfusion in Lyme Encephalopathy: A Quantitative SPECT study. Program and Abstracts of the 6th International Congress on Lyme Borreliosis, Bologna, Italy, 1994, etc.

6] ibid.

7] Some of the new research on the electrophysiology (the study of neuron activity) processes at work include: Halperin JJ, Heys MP, Neuroactive Kynurenines in Lyme Borreliosis.Neurology 1992 Jan; 42(1)43-50; Benach JL, Subtle Injury to Transformed Neural Cell Lines by Bb. Presented at the 10th Annual International Scientific Conference on Lyme Disease and Other Tick-Borne Disorders, NIH, Bethesda, MD, April 28-30, 1997.

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II. LYMENET: NIH Offers Resistant Bacterial Infection and Chronic Lyme Disease Grant ------------------------------------------------------------------- Contact: Dawn Caracci, NIH Contract Specialist <[email protected]> Due: July 28, 2000

The Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), has a requirement to support multicenter clinical studies of interventions for serious fungal and healthcare- associated resistant bacterial infections and chronic Lyme disease.

The Bacteriology and Mycology Biostatistical and Operations Unit (BAMBU) is being created as a biostatistical and operations coordinating unit to support present and future clinical studies sponsored by the Bacteriology and Mycology Branch, DMID, NIAID, NIH. Key aspects of the effort will be to provide:

1) statistical leadership, 2) data management and system development, 3) clinical trial operations and support, 4) regulatory support, 5) clinical site monitoring, and 6) data analysis and reporting for the Bacteriology and Mycology Study Group (BAMSG) and the Clinical Studies of Chronic Lyme Disease.

THIS IS A 100% SMALL BUSINESS SET-ASIDE, Standard Industrial Classification (SIC) Code 7379 with a size standard of $18.0 million. Offerors responding to this RFP should also refer to the RFP for the BAMSG (RFP NIH-NIAID-DMID-01-11), a solicitation for proposals to establish a clinical studies collaborative group to conduct clinical studies of serious fungal and healthcare-associated resistant bacterial infections. These RFPs are being released simultaneously. It is anticipated that one (1) cost-reimbursement, completion type contract will be awarded for a period of five (5) years, beginning approximately March 1, 2001. RFP NIH-NIAID-DMID-01-10 will be available electronically on or about April 24, 2000, and may be accessed through the NIAID Contract Management Branch (CMB) Home Page by using the following electronic address and instructions: NIAID/CMB Home Page (via the WWW): Use http://www.niaid.nih.gov/contract to access the NIAID/CMB Home Page. Once at the NIAID/CMB Home Page, click on the "RFPs" link and
then click on "RFP NIH-NIAID-DMID-01-10." Please note that the RFP for this acquisition has been revised to include only the Statement of Work, Deliverable and Reporting Requirements, if any, the Technical Evaluation Criteria, and the Specific RFP Instructions and Provisions. All information required for the submission of an offer will be contained in the electronic RFP package. Following proposal submission and the initial review process, Offerors comprising the competitive range may be requested to provide additional documentation to the Contracting Officer. Responses to this RFP will be due on or about July 28, 2000. All responsible SMALL BUSINESSES may submit a proposal, which will be considered by the Government. This advertisement does not commit the Government to award a contract.

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III. OPTHAMOLOGY: The expanding clinical spectrum of ocular lyme borreliosis. ------------------------------------------------------------------ AUTHORS: Mikkila HO, Seppala IJ, Viljanen MK, Peltomaa MP, Karma A ORGANIZATION: Department of Ophthalmology, Helsinki University Central Hospital, Finland. REFERENCE: Ophthalmology 2000 Mar;107(3):581-7 ABSTRACT:

OBJECTIVE: To delineate the clinical manifestations of ocular Lyme borreliosis, while concentrating on new symptoms and findings and the phase of appearance of ophthalmologic disorders. DESIGN: Observational case series. PARTICIPANTS: Ten patients with Lyme borreliosis-associated ophthalmologic findings previously reported from the Helsinki University Central Hospital in addition to 10 new cases that have since been diagnosed. INTERVENTION/TESTING: The patients underwent medical and ophthalmologic evaluation. The diagnosis of Lyme borreliosis was based on medical history, clinical ocular and systemic findings, determinations of antibodies to Borrelia burgdorferi by enzyme-linked immunosorbent assay and immunoblot analysis, the detection of DNA of B. burgdorferi by polymerase chain reaction, and exclusion of other infectious and inflammatory causes. MAIN OUTCOME MEASURES: Ocular complaints, presenting ophthalmologic findings, and the stage of Lyme borreliosis were recorded. RESULTS: Four patients presented with a neuro-ophthalmologic disorder,
five had external ocular inflammation, 10 patients had uveitis, and one had branch retinal vein occlusion. One patient developed episcleritis and one patient developed abducens palsy within 2 months of the infection incident. In the remaining 14 patients in whom the time of infection was traced, the ocular manifestations appeared in the late stage of Lyme borreliosis. Two patients with a neuro- ophthalmologic disorder and one with external ocular inflammation experienced severe photophobia, whereas the main reported symptom of the patients with uveitis was decreased visual acuity. Four patients with external ocular disease and one with a neuro-ophthalmologic disorder experienced severe periodic ocular or facial pain. Retinal vasculitis developed in seven patients with uveitis. CONCLUSIONS: Lyme borreliosis can cause a variety of ocular manifestations, which develop mainly in the late stage of the disease. Photophobia and severe periodic ocular pain can be characteristic symptoms of Lyme borreliosis. In the differential diagnosis of retinal
vasculitis, Lyme borreliosis should be taken into account, especially in endemic areas.

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IV. WIEN KLIN WOCHENSCHR: Lyme meningitis: a one-year follow up controlled study. ----------------------------------------------------------------- AUTHORS: Cimperman J, Maraspin V, Lotric-Furlan S, Ruzic-Sabljic E, Strle F ORGANIZATION: Department of Infectious Diseases, University Medical Centre, Ljubljana, Slovenia. REFERENCE: Wien Klin Wochenschr 1999 Dec 10;111(22-23):961-3 ABSTRACT:

Thirty-six patients with Lyme meningitis diagnosed at the Department of Infectious Diseases, University Medical Centre, Ljubljana in 1993 and 1994 were enrolled in a prospective study. All patients had lymphocytic meningitis, negative serum IgM antibody titres to tick-borne encephalitis virus and met at least one of the following four criteria: i) isolation of Borrelia burgdorferi sensu lato from cerebrospinal fluid (2 patients), ii) intrathecal borrelial antibody production (22 patients) iii) seroconversion to borrelial antigens (3 patients) and/or iv) erythema migrans in the period of four months prior to the onset of neurological involvement (21 patients). All patients underwent antibiotic treatment and were followed up for one year. The results of our study revealed that Lyme meningitis frequently occurs without meningeal signs and is often accompanied by additional neurological and/or other manifestations of Lyme borreliosis. During the first year after antibiotic treatment, minor and major
manifestations of Lyme borreliosis persisted or occurred for the first time in several patients. They were not infrequent even at the examination performed one year after therapy.

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V. HEMATOL ONCOL: Positive serology for Lyme disease borrelias in primary cutaneous B-cell lymphoma: a study in 22 patients; is it a fortuitous finding? ---------------------------------------------------------------------- AUTHORS: Jelic S, Filipovic-Ljeskovic I ORGANIZATION: Institut za Onkologiju i Radiologiju Srbije, Belgrade, Yugoslavia. REFERENCE: Hematol Oncol 1999 Sep;17(3):107-16 ABSTRACT:

BACKGROUND: The historical association of acrodermatitis chronica atrophicans (ACA), now known to be a late manifestation of Lyme disease caused by Borrelia afzelii, with cutaneous lymphoma, and several small series of PCBCL with positive Lyme disease borrelial serology initiated a study of this association. Material and methods In the last 9 years, 30 patients with PCBCL have been observed and followed, 22 of them were tested for borrelial serology. The control group consisted of 85 patients with NHL (10 cutaneous T-cell, 25 extranodal B-cell non-PCBCL, 50 nodal B-cell), 30 patients with breast cancer and 60 blood donors. The screening tests were two different ELISA tests for B. burgdorferi sensu lato and sensu stricto, and reactive sera were further tested with the ELISA test for B. garinii, a Western blot (WB) test for Swiss Borrelia strains and a WB test for Bavarian Borrelia strains, since an immunoblot made with local strains was not available. Studies with a differential WB test for B. burgdorferi sensu stricto, B. garinii and B. afzelii was performed
afterwards, as well as serological studies ruling out cross-reactions with Leptospiras and Treponema. RESULTS: Fifteen of 22 patients with PCBCL were positive on the screening tests, three of them falsely. Thus, the incidence of positive borrelial serology was 12/22 (55 per cent) in the PCBCL group. No positives were detected in the cutaneous T-cell lymphoma group; 2/25 patients (8 per cent) were positive in the extranodal B-cell NHL group (the localizations being vestibulum nasi and oral cavity), 2/50 (4 per cent) were positive in the nodal B-cell NHL group, 2/30 (7 per cent) in the breast cancer group and 2/60 (3 per cent) in the blood donor group. The cumulative incidence in the control groups was 8/175 (4,6 per cent). The incidence was significantly higher in PCBCL patients as compared to each of the control groups, p value ranging from 0.004 to <0.0001. Two positive patients had ACA, one arthritis. Borrelia afzelii was most often implied for positive serology in the differential WB. No cross-reactions with Treponema
and the Leptospiras were documented. CONCLUSION: In conclusion there appears to be a clustering of positive serology for Lyme disease Borrelias in PCBCL patients possibly related to an ethiopathogenic relationship. Mechanisms of Borrelia escape from immunosurveillance mechanisms, persistence of both their mitogenic and antigenic stimuli for B-cells, and SALT formation may be involved in the pathogenesis of a subset of PCBCL.

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VI. ABOUT THE LYMENET NEWSLETTER ----------------------------------------------------------------------- For the most current information on LymeNet subscriptions, contributions, and other sources of information on Lyme disease, please refer to: http://newsletter.lymenet.org ----------------------------------------------------------------------- To unsubscribe from the LymeNet newsletter, send a message to: [email protected] On the first line of the message, write: unsub lymenet-l ----------------------------------------------------------------------- LymeNet - The Internet Lyme Disease Information Source ----------------------------------------------------------------------- Editor-in-Chief: Marc C. Gabriel <[email protected]> Contributing Editors: Carl Brenner <[email protected]> John Setel O'Donnell <[email protected]> Frank Demarest <[email protected]> Advisors: Carol-Jane Stolow, Director <[email protected]>
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