Lymenet Newsletter April 2000

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* LymeNet Newsletter *

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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

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Sender: The Lyme Disease Research Project <UCP@...>

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: N. Ganz, MA, Independent Researcher,

Member of the Berkshire Brain Injury Support Group* in collaboration

with 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: UCP@...

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.

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. 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, R. Ward, the

Massachusetts Brain Injury Association and Dr. Joan Gold for

information on acquired and traumatic brain injury, J.P. for technical

assistance, 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: s 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, CB, Logigian EL, Steere AC, Kaplan RF,

Berardi VP, Duray PH, Larson MG, 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, , 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

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Contact: Dawn Caracci, NIH Contract Specialist <dk28a@...>

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.

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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.

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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?

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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

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For the most current information on LymeNet subscriptions,

contributions, and other sources of information on Lyme disease,

please refer to:

http://newsletter.lymenet.org

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