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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
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?


*                  The National Lyme Disease Network                  *
*                                    *
*                         LymeNet Newsletter                          *
   Publishing Lyme disease information on the Internet since 1993

                  Volume 8 / Number 04 / 28-APR-2000

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
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?


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

"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.


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.


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 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.


III.  OPTHAMOLOGY: The expanding clinical spectrum of ocular lyme
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

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.


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

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.


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,
REFERENCE: Hematol Oncol 1999 Sep;17(3):107-16

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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