Lyme disease, caused by the tick-borne pathogen, Borrelia burgdorferi (Bb), is the major human spirochetal infection in the United States and Europe. Neurologic involvement occurs in up to 40% of symptomatic infections.
Two presentations today outlined some of the complexities of this illness and described new tools to assist in diagnosing cases of central nervous system (CNS) Lyme Disease.
Dr. Patricia Coyle, of the State University of New York at Stony Brook, described the typical neurologic presentations in Lyme disease, as well as some of the atypical ones.[1]
Lyme disease may be categorized into three stages: early localized infection, early disseminated infection, and late disseminated infection.
Early localized infection is characterized by the erythema migrans (EM) rash, although in some cases the infection is no longer localized as a result of CNS seeding that may occur even before the EM rash appears.
Early disseminated infection may result in meningitis, cranial nerve palsy, or acute radiculoneuritis.
Late disseminated infection may result in encephalopathy (the most common manifestation of chronic neurologic Lyme disease), encephalomyelitis (which at times may appear similar to multiple sclerosis but most often without the cerebrospinal fluid production of oligoclonal bands), and polyradiculoneuropathy.
The pathology of CNS Lyme disease is most notable for a lack of tissue destruction, signifying that the pathophysiology has less to do with direct damage and more to do with a provoked immune or inflammatory response.
Immunomodulatory therapies, therefore, may have a role in the treatment of neurologic Lyme disease. Steroid treatment, however, should be avoided as it may exacerbate the illness.
Why CNS Lyme Disease is Poorly Understood The gaps in our understanding of CNS Lyme disease stem from several factors.
First, we lack a definitive assay to demonstrate active infection.
Second, Bb infection can be occult, resulting in long periods of latency before symptoms are manifest.
Third, Bb can disseminate to sequestered compartments where antibiotic penetration is difficult and immune surveillance is lacking.
Fourth, Bb is known to have considerable strain heterogeneity. This strain heterogeneity may result in different levels of virulence and different organotropism.
For example, some strains may be more likely to result in arthritic or skin disease whereas others may target the nervous system.
Fifth, the antigenic variability of Bb is known to result in different antigen expression in different locales.
In the tick, outer surface protein (Osp) A is expressed, whereas in the human it is upregulated to Osp C (prior to transfer to the host by the tick).
However, Osp A may be preferentially expressed in the CSF compartment, as the studies at Stony Brook have demonstrated.
CSF studies at Stony Brook also have demonstrated a strong immunoglobulin M response, the presence of immune complexes, and a prominent TH1 proinflammatory cytokine response.
Sixth, the significance of coinfection with other tick-borne organisms such as Babesia is not fully understood. [/b]Such co-infection may be misdiagnosed as being only Lyme disease and result in more severe and refractory cases of Lyme disease.[/b]
Finally, although there are well-characterized neurologic syndromes associated with early and late stage infection, the full spectrum of neurologic Lyme Disease has not yet been fully described.
Patients with new onset Bb infection may develop an acute CNS demyelinated disease that looks much like multiple sclerosis; although rare, these cases do occur and do respond well to intravenous antibiotic therapy.
Stroke-like syndromes and CNS vasculitis have also been induced by CNS infection with Bb.
The optimal treatment of neurologic Lyme disease is not yet known. Intravenous antibiotic therapy with Ceftriaxone or Cefotaxime is the accepted standard because these drugs more effectively penetrate the blood-brain-barrier.
In studies of Lyme arthritis in which patients were treated with oral antibiotics, the treatment failures often showed signs of neurologic involvement, suggesting that oral antibiotics may be insufficient to eradicate infection that may already be sequestered in the CNS compartment.
Dr. Coyle presented preliminary results from a study of children and adults being conducted at the University Hospital at Stony Brook.
Of the adult patients, the sample was primarily early Lyme disease: 40% had EM; 22% had a Bell's Palsy; and 17% had multifocal EM. Of this sample of 18 adults, although 47% had evidence of Bb antibody in the CSF, only 12% had evidence of intrathecal antibody production.
In the 12 children with early-disseminated Lyme disease, 67% had a facial nerve palsy and 25% had multiple EM; of these, only 17% had evidence of intrathecal antibody production.
These findings were reinforced by earlier work done by the SUNY group in collaboration with Dr. Steven Schutzer and others in which immune complex dissociation enabled the disentangling of immune complexes and therefore the detection of Osp antigen and Bb antibodies.[2,3]
Dr. Coyle emphasized that, unlike European Lyme disease, North American neurologic Lyme disease does not commonly demonstrate intrathecal antibody production.
Therefore, the absence of intrathecal antibody production cannot rule out the presence of active neurologic Lyme disease, as in most cases such intrathecal production does not occur.
The most common symptoms in the adults were fatigue, stiff neck, headache, and cognitive problems, whereas the most common symptoms in the children were headaches, sleep problems, fatigue and mood disturbances -- but not memory problems.
Dr. Coyle concluded by noting that adults with neurologic Lyme disease appear to be more symptomatic than children.
New Diagnostic Tools Needed Dr. Ronald Van Heertum, of the Columbia University College of Physicians and Surgeons, addressed the role of functional brain imaging in the diagnosis of chronic CNS Lyme disease.[4]
The need for such adjunctive diagnostic tools stems from the often nonspecific neurobehavioral symptoms presented by patients with chronic Lyme disease.
CT and MRI scans often may not reveal abnormalities in these patients. But functional brain imaging, particularly SPECT imaging, shows promise as a contributory adjunctive diagnostic technique, based on the assumption that brain blood and metabolism are tightly coupled.[5]
The most up-to-date SPECT scans use a triple-headed machine, but Dr. Van Heertum suggested that dual-headed machines also may produce useful images.
In about 70% of chronic Lyme disease patients with cogntive symptoms, brain SPECT scans typically reveal a pattern of global hypoperfusion in a heterogeneous distribution through the white matter.[6]
This pattern is not specific for Lyme disease; it can also be seen in other CNS syndromes such as HIV encephalopathy, viral encephalopathy, chronic cocaine use, and vasculitides.
However, this pattern is different from what one would see with normal controls, patients with primary depression, patients with Alzheimer's disease, and patients with focal brain damage as in stroke.
Dr. Van Heertum presented a recent study from Columbia University, conducted with Drs. Lestor Johnson and Vitale Furman, of 20 patients with chronic Lyme disease and 7 normal controls whose brain SPECT scans were subjected to an SPM analysis.
This quantitative approach to the evaluation of a SPECT image allows comparison of the blood flow in small areas or pixels of brain. Remarkably, the Lyme patients as a group (and each Lyme patient individually) had significantly reduced uptake of radioactive tracer (perfusion), primarily in the white matter.
These results suggest that the primary pathology in Lyme disease is related to white matter dysfunction.
In conclusion, Dr. Van Heertum emphasized that SPECT imaging can have a role in Lyme disease by helping to demonstrate diffuse CNS involvement, differentiating Lyme disease from other syndromes that do not cause a diffuse process, and in monitoring the course of treatment.
References
1. Coyle PK: Neurologic Lyme disease update. 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY, 1999. 2. Coyle PK, Schutzer SE, Deng Z, et al: Detection of Bb-specific antigen in antibody-negative cerebrospinal fluid in neurologic Lyme disease. Neurology 45:2010-2015, 1995. 3. Coyle PK, Deng Z, ,Schutzer SE, et al: Detection of Bb antigens in cerebrospinal fluid. Neurology 43:1093-97, 1993. 4. Heertum RV: Functional brain imaging in the diagnosis of chronic CNS Lyme disaese. 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY, 1999. 5. Logigian EL, Johnson KA, Kijewski MF, et al: Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology 49:1661-1670, 1997. 6. Fallon BA, Das S, Plutchok JJ, et al: Functional brain imaging and neuropsychological testing in Lyme Disease. Clin Infectious Disease 25(s):57-63, 1997.
[ 24. January 2008, 07:45 AM: Message edited by: AliG ]
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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posted
Thanks. I was actually able to understand this!
otm
Posts: 314 | From east coast | Registered: Oct 2007
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AliG
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You're both very welcome!
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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Is this recent? Sounds like it is, but didn't see a date.
Thanks for posting! Great info.
MommaK
Posts: 242 | From Mississippi | Registered: Oct 2006
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AliG
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posted
Actually, I think it is the Medscape coverage from the 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders, New York, NY, 1999.
Not really very recent, but I thought it was very interesting when I read it.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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JRWagner
Frequent Contributor (1K+ posts)
Member # 3229
posted
Thangsnfouothr....webbbunatcjl;?
Neurologic Lyme Symptom Number 3 Inability to speak or spell.
Thanks Ali...this is exactly my issue. NECK AND HEAD pain. Besides this, all is just peachy!
I think I will sleep outside tonight...freeze the little buggers!
Peace, Love and Wellness, JRW
Posts: 1414 | From Ny, Ny | Registered: Oct 2002
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bettyg
Unregistered
posted
quoting article above...I don't understand this; can someone explain in plain English to me??
----North American neurologic Lyme disease does not commonly demonstrate "intrathecal" antibody production.
Therefore, the absence of intrathecal antibody production cannot rule out the presence of active neurologic Lyme disease, as in most cases such intrathecal production does not occur
Thank Ali; informative; I too would like to see a date in the actual article!
I was going to add this to my newbie package....thanks my friend, Ali!
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lymebytes
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posted
Thank you for info - I want my LLMD to see this. It angers me and heres why.
quote:In studies of Lyme arthritis in which patients were treated with oral antibiotics, the treatment failures often showed signs of neurologic involvement, suggesting that oral antibiotics may be insufficient to eradicate infection that may already be sequestered in the CNS compartment.
Proves IV is needed to get well. I have needed IV for 2 years, yet they continue to push orals on me as I continue to ream with nerve pain, numbness and tingling and no reflex response.
quote:The pathology of CNS Lyme disease is most notable for a lack of tissue destruction, signifying that the pathophysiology has less to do with direct damage and more to do with a provoked immune or inflammatory response.
The most interesting word here is "provoked" - what are we doing everytime we herx, we are provoking inflammatory response. Herxing makes things worse, pain is never good.
AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Betty-
The best I can determine, after researching "intrathecal antibodies" is that the intrathecal antibodies would be those detected in the Cerebrospinal fluid via spinal tap or lumbar puncture.
They are in the "subarachnoid space". I think they may be responsible for protecting the blood-brain barrier, but don't quote me on that. Maybe someone else can give a better explanation. ???
As for the date, all I can get for the article is: 12th International Conference on Lyme Disease and Other Spirochetal and Tick-Borne Disorders | Day 1 - Friday, April 9. The conference was in 1999.
It was from a Medscape Continuing Medical Education exam & not a Pubmed or ScienceDirect article as I usually post. Sorry I can't come up with the exact date it was written. I DID try.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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AliG
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posted
Lymebytes,
This info was from 1999. I know that the guidelines of both camps seem to recommend IV for CNS. I too was put through the oral to exhaustion route and wondered about it myself.
I'm not sure but I believe that some of the newer ABX have been found to be better able to cross the BBB & MAY be comparable to IV for SOME people. I unfortunately WAS NOT one of those people.
I think many Drs are now trying to go the oral route first because there are greater Tx risks involved with IV. I think they want to make sure that it's absolutely necessary before they Rx it.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
Another thought Lymebytes,
"Provoked" means it is not without cause & therefore NOT just an autoimmune overactive inflammatory response as IDSA may have a tendency to lead people to believe.
The "provoked" immune/inflammatory response IS caused by the spirochetes.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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