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Volume: 4
Issue: 10
Date: 19-Jul-96


Table of Contents:

I.    LDF: Notes from the IXth Annual LDF Scientific Conference  
      (Part 3 of 3)
II.   About The LymeNet Newsletter


Newsletter:

***********************************************************************
*                  The National Lyme Disease Network                  *
*                         LymeNet Newsletter                          *
***********************************************************************


IDX#                Volume 4 - Number 10 - 7/19/96
IDX#                            INDEX
IDX#
IDX#  I.    LDF: Notes from the IXth Annual LDF Scientific Conference  
IDX#        (Part 3 of 3)
IDX#  II.   About The LymeNet Newsletter
IDX#



I.    LDF: Notes from the IXth Annual LDF Scientific Conference
     (Part 3 of 3)
-----------------------------------------------------------------------
Sender: Lloyd E. Miller, DVM <LloydEM@aol.com>


   Notes from the Ninth Annual Scientific Conference Lyme Disease      
    Foundation -- April 19-20, 1996 -- Westin Copley Plaza Hotel,
                     Boston, Massachusetts, USA

                  Prepared by Lloyd E. Miller, DVM
-----------------------------------------------------------------------
Every effort has been made to report the speaker's statements and to
report suggested drug doses accurately. However, typos do occur and
as information gets passed around or edited mistakes can occur.
The reader is cautioned to not take any medication before checking
the accuracy of name and dose recommendations with the speaker.


Selected abstract statements have been included in the notes.

The notes themselves are from statements made by the speakers.

My editorial comments will be found in brackets like this [COMMENT].

Full abstracts are available electronically from the Lyme/Other
Zoonoses section in the Public Health Forum on Compuserve.


***
Lyme Disease and the Clinical Spectrum of Antibiotic-Responsive
Chronic Meningoencephalomyelitides  -  Kenneth B. Liegner, M.D.


FROM DR. LIEGNERS NOTES:
*  Background: During the past 10 years numerous individuals with
  Lyme disease having neurologic illness have been evaluated in
  depth.  Four representative cases which have been worked up in
  detail illustrate the clinical spectrum, diagnostic conundrum,
  and therapeutic principles applicable in neurologic Lyme disease.


FALSE TEACHINGS IN LYME DISEASE:

1) Patients with late Lyme disease are almost invariably seropositive.

2) 28 days of intravenous antibiotic therapy is virtually always
  curative; continued symptoms following such treatment means that
  the diagnosis was wrong.


3) Neurologic Lyme disease is established by selective intrathecal
  antibody synthesis; in its absence one can feel confident there is
  no central nervous system infection by Bb.


4) It is easy to distinguish neurologic Lyme disease from multiple
  sclerosis.


CONCLUSIONS:

1) Borrelia burgdorferi produces chronic infection of the central
  nervous system.


2) Current therapeutic approaches, including intensive application of
  the most potent antibiotics known to man may be unable to cure the
  infection in some patients.


3) Seronegative Lyme disease may not be rare and seronegativity may
  predispose patients to the development of more serious neurologic
  sequelae of Lyme disease.


4) Adequate evaluation of patients to determine whether or not Lyme
  disease is present requires application of not only standard
  serologic methods, but also "cutting edge" direct antigen detection
  methods.  One cannot depend on a single laboratory in serologic
  testing for Lyme disease.


5) Lyme immunoblots should be performed when Lyme disease is  
  clinically suspected regardless of whether or not Lyme ELISAs are
  positive because Western blots can be positive or suspicious when
  ELISAs are negative.  Perversely, a negative Western blot does not
  negate a positive ELISA since diagnostic Western blots can be very
  slow to evolve.  ELISA and Western blot results can fluctuate over
  time and in response to application of treatment.  It may take more
  than a decade for conclusive serologic proof of Lyme disease to
  develop in patients having clear clinical histories indicative of
  Lyme disease.  Expansion of bands on Western blots over time is
  indirect evidence of chronic persisting infection.


6) In addition to allowing for observation for evidence of clinical
  improvement under empiric therapy (e.g. therapeuticus ex
  euvantibus), intensive treatment of patients who may possibly have
  neurologic Lyme disease may allow uncovering of serologic and/or
  direct antigen evidence of Lyme disease when "cutting-edge" methods
  are used serially.


7) Lyme disease may produce a neurologic illness virtually clinically
  indistinguishable from multiple sclerosis; CSF parameters thought
  to be pathognomonic for M.S. have been shown, at least in one case,
  to resolve and virtually normalize with intensive intravenous
  antibiotic therapy, and to reoccur with cessation of such therapy,
  along with relapse. Lyme disease may be one definable and treatable
  cause of multiple sclerosis, at least for some patients.


8) Systematic controlled prospective studies of "standard" versus
  intravenous antibiotic therapy should be considered for patients
  with multiple sclerosis.


9) Patients diagnosed with multiple sclerosis deserve to be fully
  re-evaluated using modern methods of study in serum and CSF to
  determine whether they might have neurologic Lyme disease.  When
  clinically indicated, empiric trials of treatment along with
  intensive scientific study of clinical response, CSF parameters,
  standard and research assays for Lyme disease, and neuroimaging
  should be considered in individual cases of neurologic illness
  which may be either CNS Lyme disease or multiple sclerosis.


10) Lyme disease should be considered in the differential diagnosis of
   a wide range of neurologic syndromes.  Other neurologic illnesses
   besides M.S. might similarly be studied using modern methods to
   determine if there may be an underlying borrelial etiology.
   Acknowledgment of the possibility of chronic persistent CNS
   infection by Bb opens the door to fruitful consideration of
   pathogenetic mechanisms and therapeutic interventions a variety
   of neurologic illnesses.


11) For some patients, prolonged antibiotic therapy, including
   intravenous therapy, is absolutely essential to permit neurologic
   recovery from chronic CNS Lyme disease, and to avert progressive
   neurologic deterioration.


12) Improved therapeutic approaches are desperately needed for Lyme
   disease in general and particularly for chronic neurologic Lyme
   disease.  Treatment aimed at "sterilizing" the body of borrelia
   needs to be designed and trialed.


13) As long as there continues to be chronic persistent denial of the
   problem of chronic persistent infection in Lyme disease, necessary
   resources will not be allocated to permit improved solutions.


[ COMMENT: Dr. Liegner presented four very difficult cases of Lyme
disease that demonstrated the difficulties of diagnosing and treating
Lyme disease.  The diversity of the disease regarding symptom
presentation and the diversity of response to various therapies is
also quite dramatic.  The diagnosis of Lyme disease still must be made
on clinical grounds with a high degree of suspicion by the doctor and
confirmation of the diagnosis can take a very long time requiring
investigational methods not currently available to the general medical
profession.  There can be no doubt that chronic persistent Lyme
disease is due to chronic persistent infection based on the evidence
presented with each of these cases.  The cases demonstrated quite
succinctly the truth of all the above statements. ]


***
Neurologic Complications of Late and Chronic Lyme Disease  -  
Patricia K. Coyle, M.D.


FROM THE ABSTRACT:
*  Both the central and peripheral nervous systems are major target
  organs in this infection [B. burgdorferi].
*  Late Lyme disease can be operationally defined as the symptomatic
  abnormalities associated with untreated B. burgdorferi infection or
  greater than three months duration.
*  Chronic Lyme disease can be operationally defined as the symptomatic
  abnormalities which are temporally related to B. burgdorferi
  infection, and which continue as persistent problems for months to
  years following antibiotic treatment.
*  Three characteristic syndromes have been reported in late Lyme
  disease. These are mild encephalopathy, characterized by problems
  in attention, memory, word retrieval, and processing; a chronic
  polyradiculoneuropathy; and encephalomyelitis with parenchymal
  involvement
*  Chronic Lyme disease is characterized by major cognitive, pain, and
  fatigue complaints.


FROM THE NOTES:
*  Major symptoms of chronic Lyme disease: cognitive, fatigue /
  malaise, generalized pain and headache.
*  Minor symptoms of chronic Lyme disease: dizziness, paresthesias,
  mood changes, and sleep disturbance.
*  Antibody findings in late and chronic Lyme disease:
  1. IgM response (free and complexed) which is unusual finding
     because IgM is not generally found late in the course of an
     infectious disease.  No current explanation.
  2. IgG2 subclass of immunoglobins predominate - usually it is IgG1.
  3. Antibodies to both OspA and B can be found. OspA reemerges in
     late disease.
  4. Loss of antibodies resulting in seronegative status.
  5. Autoantibodies - maybe anticardiolepin can be found.
*  Preliminary studies correlate cognitive defects with immune and CNS
  findings.
*  Quantitatively brain SPECT cerebral blood flow hypoperfusion deficit
  can be demonstrated.
*  Possible pathologic mechanisms of chronic Lyme disease :
  1. Persistent CNS infection.
  2. Persistent immune / inflammatory process.

  3. A combination of 1 and 2.
*  Chronic Lyme disease clinically: Seropositive documented prior Lyme
  disease with appropriate antibiotic treatment with continued fatigue
  lasting > 6 months with no other documentable reason.
*  Clinical studies - illness duration 4 years - major problems: fatigue
  (81%), arthralgia (68%), myalgias (57%), headache (55%), and memory
  problems (53%).  81% of patients were still seropositive; 75% met
  CDC definition; 60% from hyperendemic areas.


[ COMMENT: This was an excellent presentation.  Unfortunately not
enough time was allotted.  Therefore the notes only report a fraction
of the information.  I hope that Dr. Coyle will continue to publish
the results of her very important studies.  Of significance is that
Dr. Coyle and others are beginning to change their opinions about
chronic Lyme disease.  Now recognizing that not only is there such an
entity as chronic Lyme disease but also that its main involvement is
the nervous system and that it indeed probably involves chronic
persistent infection in at least some cases.  To quote Dr. Coyle "true
chronic Lyme disease is a neurologic disorder." ]


***
Lyme Disease vs. Depression vs. Somatization:  Cognitive Tests &
Functional Imaging  -  Brian A. Fallon, M.D.


FROM THE ABSTRACT:
*  Not infrequently physicians are faced with the task of
  differentiating persistent Lyme disease (LD) from Somatization
  and Depression.
*  The use of neuropsychological tests to differentiate Lyme-related
  vs. depression-related cognitive problems will be discussed.
*  The application of SPECT imaging to neuropsychiatry and to Lyme
  disease in particular will be addressed, emphasizing patterns
  typical of depression vs. Lyme encephalopathy.


FROM THE NOTES:
*  In a study of hypochondria involving 10 patients 5 did not have the
  condition.  Of these 5 two had Lyme.
*  Lyme symptoms described: major depression; compulsive disorders;
  panic attacks; depersonalization ("spaced out"); anorexia nervosa
  (rare); disorientation (lose the way - lasts 3-5 minutes); violent
  outbursts; irritability; personality change; dementia; paranoia
  (fairly common); thought disorders; delusions; auditory / olfactory
  hallucinations.
*  Major depression 3 times more common in Lyme disease versus lupus or
  rheumatoid arthritis.
*  Clues to differentiate psychologic disorder from Lyme:
  1. Atypical features of psychologic disorder in LD.
  2. Atypical response to psycotropic medications  in LD.
  3. Failure to respond to previously effective psycotropic
     medications.
  4. Prior history of psychologic disorder?
  5. Family history of psychologic disorder?
  6. History of exposure to Lyme disease?
  7. Markers of Lyme disease - EM?
*  Common symptoms of late neuroborreliosis: *Intense* fatigue;

  headache; light / sound sensitivity; cognitive tracking
  difficulties; dyslexia; disorientation; ; tingling / burning /
  numbness; shooting pains; insomnia / sleep disturbances; memory
  deficits (esp. retrieval and verbal fluency).
*  Fatigue has positive correlation in memory performance - depression
  does not.
*  SPECT scan of brain provides information about blood flow and
  metabolism: Increased blood flow = increased metabolism.
  1. Scan results different in depression, Alzheimer's, Huntington's,
     stimulant intoxication, and obsessive-compulsive disorder.
  2. Lyme scan has some similarities to Alzheimer's scan - more
     research is needed to determine the significance.
  3. Swiss cheese pattern seen in Lyme disease SPECT scan.  Definitely
     not normal.  Appears to be reversible.  This is not a subtle  
     change.
  4. Lyme disease scan differs from lupus, drug abuse (cocaine);
     multiple infarct dementia, chronic fatigue syndrome, and AIDS.
*  Possible pathogenic mechanisms of Lyme disease may involve

  hypoperfusion of the brain and cellular dysfunction.

***
The Antimicrobial Agent, Melittin, Exhibits powerful in vitro
Inhibitory Effects on the Lyme Disease Spirochete  -  
Claude F. Garon, Ph.D.


FROM THE ABSTRACT:
*  Borrelia burgdorferi has demonstrated an extraordinary capacity to
  resist the effects of powerful eukaryotic and prokaryotic
  replication inhibitors.
*  In contrast, however, the antimicrobial agent, melittin, a 26 amino
  acid, cationic, amphipathic, peptide contained in honeybee venom,
  showed almost immediate and profound inhibitory effects.
*  The extraordinary sensitivity of Borrelia burgdorferi to this small
  peptide may provide both a useful research reagent and important
  clues to the development of effective drugs against Lyme disease.


FROM THE NOTES:
*  Melittin effectively interrupted Bb motility by 90 to 100% within
  seconds.
*  Melittin caused increased bleb formation.
*  Melittin affects inner surface membrane and permeability of the
  outer membrane.
*  Melittin is highly toxic to cells and not usable as a treatment
  option for Lyme disease in the form used in this study.
*  It is hoped that the compound can be used in some way to improve the
  efficacy of drugs that are poorly or totally ineffective to treat
  the disease.


[ COMMENT: I have seen mentioned since the meeting speculation that
bee pollen might be of use in Lyme disease based on the presentation.
It was emphasized that Melittin is in bee *venom* not pollen. ]


***
Tetracycline Therapy of Chronic Lyme Disease  -  Sam T. Donta, M.D.


FROM THE ABSTRACT:
*  Patients with clinical symptoms compatible with chronic Lyme
  disease. In the absence of a reasonable alternative diagnosis, both
  seropositive and seronegative patients were given a trial of oral
  tetracycline, 500mg tid, for 3 months.  If symptoms improved,
  therapy was continued for up to 8 months.  The results were:
  1) 75% of patients with specific reactions by Western blot are
     negative by ELISA,
  2) tetracycline therapy led to cure or significant improvement in
     75% of patients; improvement did not usually begin until after
     4-6 weeks had elapsed (range: 2-10 weeks),
  3) there were no obvious differences in therapeutic responses
     between seropositive and seronegative patients,
  4) 30% of improved patients had relapsing symptoms 1-6 weeks after
     stopping therapy; these symptoms improved either spontaneously
     over several weeks to months or with another 1-3 month course
     of tetracycline,
  5) treatment failures seldom responded to alternative regimes,

     including IV cephalosporins.

FROM THE NOTES:
*  Study involved 277 patients. The study was uncontrolled.
*  Major symptoms reported: fatigue (90%); Musculoskeletal (80%);
  cognitive disorders (50%); cardiac (10%); ocular (10%).
*  Only 29% were positive on both ELISA and Western blot tests.
*  Both tests were negative in 18.5 % of the patients.
*  Test results were discordant in 52% of the patients.
*  Cure was defined as no symptoms 1 year or more after trial.
*  Improvement was defined as >75% improvement as accessed by the
  patient.
*  Failure was defined as no sign of improvement.
*  Cure rate overall was 16%.
*  Failure rate was higher in female patients.
*  Age of patient didn't appear to influence outcome.
*  Presence of rash was not a factor in outcome.
*  The longer the duration of symptoms prior to treatment the higher
  the failure rate.
  1. Less than 1 year:  28% cure; 67% improvement; 5% failure
  2. 1 to 3 years:  15% cure; 75% improvement; 10% failure
  3. Greater than 3 years: 11% cure; 70% improvement; 18% failure

*  Symptom duration related to time of first improvement:
  1. Less than 1 year improvement began in about 2 weeks;
  2. One to 3 years improvement began in about 3 weeks;
  3. Greater than 3 years improvement began in about 4-6 weeks;
  4. Overall it took 1 - 1.5 months to improvement;
  5. By 2 months 50 to 75 % improved;
  6. By 3 months > 75 % improved.
*  Study resulted in improvement or cure in 82% of patients.
*  Mean course of treatment was 4 months.
*  Beyond 5 months of treatment more failures which reflects the
  duration of disease.
*  Untreated patients did much better than previously treated patients.
*  Question whether partial treatment or unsuccessful treatment changes
  the organism so it is less susceptible to subsequent treatment.
*  Serology proved to be nearly irrelevant to what was happening with
  the patients.
*  Repeated rounds of treatment are ineffective.
*  Reasons for choosing tetracycline for trial included the many poor
  responses reported for betalactam antibiotics

*  Twice daily treatment with tetracycline failed often. Three times a
  day treatment did better if treated long enough.
*  Doxycycline is better absorbed but doesn't produce any better
  results.


***
Intramuscular Bicillin For Persistent Pediatric Lyme Disease  -  
Louis Corsaro, M.D.


FROM THE ABSTRACT:
*  We conducted a chart review and follow-up of all patients with
  seropositive Lyme disease treated with IM Bicillin in a private
  pediatric out-patient office in a Lyme endemic area between 1993
  and 1995.
*  Methods:  The diagnosis of Lyme disease was based on at least one
  seropositive test and typical articular or neurological symptoms.  
  Treatment consisted of either Bicillin LA or CR 1.2-2.4 million
  units administered weekly.  Relapse was defined as the return of
  any symptoms which required greater than two weeks of Abx treatment.  
  To assess efficacy, the longest period without symptoms prior to IM
  Bicillin was compared to the symptom free interval after bicillin.
*  61 charts were reviewed of which 25 met study criteria for
  seropositive Lyme disease.  Mean age at time of chart review
  11.9 +/- 4.4 years.  Mean age at time of Lyme disease onset was
  9.4 +/- 4.3 years.  Mean duration of symptoms prior to the
  administration of antibiotics was 16 +/- 32 weeks.

*  All patients failed to sustain improvement after courses of oral
  antibiotics.  Five children received IV antibiotics and all failed
  to sustain improvement.  Of the twenty-five patients given IM PCN
  (Intramuscular Penicillin), the mean duration of IM treatment was
  4-38 weeks (mean 14.5 +/- 8.9 wks; median 10.5 wks).
*  Of the 23 children available to assess relapse after treatment, 19
  were symptom free, 3 had mild symptoms that did not require
  treatment, and 1 relapsed and was being retreated.
*  Conclusion: A chart review and follow-up studies suggest that
  intramuscular Bicillin may be a particularly effective treatment for
  children with antibiotic refractory persistent Lyme disease whether
  previously treated orally or with intravenous antibiotics.


FROM THE NOTES:
*  If the patient was going to relapse it generally occurred the
  second week following cessation of treatment.
*  If relapse occurred treatment was reinstituted for another 4 weeks
  before trying to stop again.  This cycle continued until the patient
  was symptom free for two weeks beyond ending of therapy.


***
Use of Vancomycin in Chronic Persistent Lyme Disease  -  
Joseph Burrascano, Jr., M.D.


FROM THE ABSTRACT:
*  Vancomycin has been shown to be effective in killing Borrelia
  burgdorferi in vitro, and a case report demonstrated the efficacy
  of this agent in a patient with ongoing symptoms unresponsive to
  other treatments.  An expansion of that trial is now reported.


FROM THE NOTES:
*  Why Vancomycin?
  1. Bb may be resistant to Beta Lactam antibiotics.
  2. Bb persists despite long term aggressive antibiotics therapy.
  3. No antibiotic is universally effective.
*  Vancomycin is antibiotic of last resort. Use in advanced LD
  treatment failure cases.  It can have serious side effects.  Other
  organisms can develop resistance to it.
*  Vancomycin can produce "red man syndrome": caused by histamine
  release if given too rapidly - LD patients are especially sensitive
  to this.  Use antihistamine and give slowly.  Drug was better
  tolerated as treatment progressed.
*  Ototoxic and nephrotoxic - especially earlier formulations - seems
  to be less so today.
*  Must use central line -Vancomycin is caustic.
*  Pulse therapy; Standard dose based on blood levels - start low and
  work up - given two days in a row per week - duration of therapy
  based on response.
*  Monitor peak and trough levels.
*  Study statistics. ( Dr. B. stated that the statistics in the printed

  abstract were in error)
  1. Nineteen patients were in study.
  2. The average duration of therapy was 17 weeks (34 doses).
  3. There were no major adverse reactions.
  4. Two of 19 had no response.  (probably not treated long enough.)
  5. Six of 19 had partial response.  (Rx stopped before medically
     should have - insurance ran out and other reasons.)
  6. Eight of 19 had good response.  (Some of these had had 43 weeks
     of IV therapy previously.)
  7. Three of 19 were cured. (Possibly less ill to start with.)
*  Cures in patients treated earlier in the course of the disease.
*  Longer duration of treatment correlated with better outcomes.
*  Vancomycin effectiveness is enhanced with penicillin.
*  Dosage range of Vancomycin used was 500 to 1500mg every 12 hours
  based on blood levels.



=====*=====


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