Updated Aug 2014
Distinct Pattern of Cognitive Impairment Noted in Study of Lyme Patients
Marian Rissenberg PhD & Susan Chambers MD, The Lyme Times, Vol. 20, Jan-Mar 1998, pp. 29-32
Contents include:
I. Cognitive Characteristics of Chronic Lyme Encephalopathy
II. Neuropsychological deficits in chronic Lyme disease
III. Possible Pathophysiologic Mechanisms of Cognitive Impairment in Lyme Disease
IV. Clinical Impressions and Implications for Diagnosis and Treatment in Chronic Lyme Disease
V. Cognitive impairment in Lyme disease: specific functions and the impact of deficits
http://www.anapsid.org/cnd/diffdx/rissenberg.html
Course – Missing The Diagnosis: The Hidden Medical Causes of Mental Disorders
by William Matteson, Ph.D.
8 CE credits – $199
Last revised: 09/10/2010
Course content © copyright 2010 by William Matteson, Ph.D. All rights reserved.
Includes a section on Lyme Disease….
ContinuingEdCourses.Net is approved by the American Psychological Association (APA) to sponsor continuing education for psychologists. ContinuingEdCourses.Net maintains responsibility for this program and its content.
https://www.continuingedcourses.net/active/courses/course067.php
ADHD, Depression, Anxiety? Or Is It Lyme Disease?
Posted on November 24, 2010 by Debra Burdick
A study by Hajek et al, published in American Journal of Psychiatry(February 2002; 159:297-31) found that one third of psychiatric inpatients showed signs of past infection with the Lyme spirochete. ILADS found that even severe neuropsychiatric symptoms can be reversed or eliminated when antibiotics are added to the indicated psychiatric treatment.
One of my patients had been treated for unremitting depression with no relief from antidepressant medication. His extreme fatigue and lack of motivation due to tiredness had been diagnosed as symptoms of depression – which they are. His ability to concentrate was severely affected and his job performance was suffering. He spent much of his day sleeping which brought no energy. After he sought out a physician who specializes in Lyme disease and was put on an intensive round of antibiotics, the fatigue and all symptoms of depression completely went away and the ineffective antidepressant was discontinued. His symptoms had been misdiagnosed as depression but were actually caused by Lyme disease.
Lyme disease is difficult to diagnose for several important reasons. First, less than 50% of all Lyme patients recall a tick bite. Secondly, Lyme disease often causes a bull’s eye rash which if present requires no further verification before starting treatment. But less that 50% of patients with Lyme disease recall ever having the rash. Thirdly, to add to the difficulty, many of the standard blood tests developed to detect Lyme disease have a high incidence of false negative results. Some of them show negative results even in the presence of the classic bull’s eye rash.
Consider Lyme disease if there are cognitive changes, extreme fatigue, weight changes, intense headaches, fibromyalgia, multiple sclerosis, explosive rages, sudden mood swings, or ‘spider bites’. For children, think about Lyme disease if there are behavioral changes, fatigue, academic problems, learning disabilities, headaches, sore throats, migrating pains. The key here is to notice changes from prior functioning even if the change was gradual.
For full article go to: http://thebrainlady.com/articles/adhd-depression-anxiety-or-is-it-lyme-disease/
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Updated Jan 2014
The Pillaging Of Personalities: Our Lost Kids Are Being Highjacked By Spirochetes
by Virginia T. Sherr, MD
The Lyme Times
Volume 32
http://www.thehumansideoflyme.net/viewarticle.php?aid=5
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Updated Nov 2013
Why psychologists need to know about Lyme disease
Sarah L. Marzillier, Clinical Psychologist, UK (PDF)
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Links between Lyme and Psychiatric problems:
Up to 40% of patients with Lyme disease develop neurologic involvement of either the peripheral or central nervous system. Dissemination to the CNS can occur within the first few weeks after skin infection. Like syphilis, Lyme disease may have a latency period of months to years before symptoms of late infection emerge. Early signs include meningitis, encephalitis, cranial neuritis, and radiculoneuropathies. Later, encephalomyelitis and encephalopathy may occur. A broad range of psychiatric reactions have been associated with Lyme disease, including paranoia, dementia, schizophrenia, bipolar disorder, panic attacks, major depression, anorexia nervosa, and obsessive-compulsive disorder. Depressive states among patients with late Lyme disease are fairly common, ranging across studies from 26% to 66%. The microbiology of Borrelia burgdorferi sheds light on why Lyme disease can be relapsing and remitting and why it can be refractory to normal immune surveillance and standard antibiotic regimens.
Conclusions: Psychiatrists who work in endemic areas need to include Lyme disease in the differential diagnosis of any atypical psychiatric disorder. Further research is needed to identify better laboratory tests and to determine the appropriate manner (intravenous or oral) and length (weeks or months) of treatment among patients with neuropsychiatric involvement. (Am J Psychiatry 1994; 151:1571-1583)
Source: http://www.ncbi.nlm.nih.gov/pubmed/7943444?dopt=Abstract
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Check out this useful guide available for download at ILADS regarding Psychiatric Lyme Disease!
http://www.ilads.org/lyme/lyme-brochure-psych-2014.pdf
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A new paper on Neuro Lyme disease by Brain Fallon MD:
(PDF) http://www.lymenet.de/literatur/Fallon_Inflammation-and-central-nervous-system-Lyme-disease_2009.pdf
Check out this very comprehensive article on Neuro Lyme assessments by Robert Bransfield MD at:
http://www.mentalhealthandillness.com/tnaold.html
Both are very interesting reads!
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Absolutely brilliant list of neuro psychiatric Lyme papers:
References for Psychiatry and Lyme/Tick-Borne Diseases
This is a list of references in the medical/scientific literature on psychiatry and Lyme/tick-borne disease. Dr Brian Fallon has published more than any other single author in the peer reviewed literature. Below are some of his articles and some other peer reviewed articles:
http://www.lymeinfo.net/psychbiblio.html
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Lyme and Tick-Borne Diseases Research Centre
http://columbia-lyme.org/index.html
Lots of useful information on research studies headed by Brian Fallon MD (Associate Professor of Clinical Psychiatry), assisted by many research scientists and members of a scientific research board. Fallon who was one of the speakers at the IDSA public hearing in July has produced some excellent research in the area of brain imaging, cognitive and psychiatric problems for Lyme patients and risks verses benefits of long term treatment.
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‘Lyme Rage’: Can Lyme Disease Affect Your Personality?
“I’m convinced that Lyme in a chronic form can affect psychiatric issues, neurological issues and you can have neurological problems,” New York epidemiologist Dr. Daniel Cameron said
By ELISABETH LEAMY, JOSH GAYNOR and LEE FERRAN
They’re tiny insects that can cause big problems. A rise in the number of ticks this year has infectious disease experts focused on the best way to treat the Lyme disease that the little buggers can spread.
Some believe the disease can rewire the brain when left untreated.
Some 20,000 Americans are infected and treated every year, but countless others go undiagnosed. The illness has symptoms that include fever, fatigue and headaches, but if left untreated, Lyme disease can be more serious.
While there are physical symptoms of the disease that can include severe headaches, severe joint pain and even numbness in the hands or feet, many experts believe Lyme disease can rewire the human brain and affect personality. “I’m convinced that Lyme in a chronic form can affect psychiatric issues, neurological issues and you can have neurological problems,” New York epidemiologist Dr. Daniel Cameron said.
The Center for Disease Control and Prevention notes that up to 5 percent of patients “may develop chronic neurological complaints months to years after infection.”
Lyme disease patient Kelly Kulesz told “Good Morning America” she saw herself change overnight because of her infection.
“They put me on stage fright medications,” Kulesz said. “Doctors thought it was obsessive compulsive disorder, but it’s just not.”
When Terry Jo Sedlacek went to trial for allegedly gunning down the Rev. Fred Winters in March, the defense cited his Lyme disease infection and it’s contribution to what many call “lyme rage.”
But not all experts believe Lyme disease causes such radical changes in personality. “The example I like to cite is if I have Lyme disease and I get run over by a truck, the Lyme disease didn’t cause my broken leg,” Halperin, said Dr. John Halperin, lead author on the new American Academy of Neurology Guideline on Lyme Disease Treatment.
ABC News medical contributor Dr. Marie Savard, who had lyme disease, said that the possibility of personality changes should at least be taken into consideration. “It does affect the central nervous system. You can have behavior changes, personality changes,” she said. “We have to listen and pay attention.”
http://abcnews.go.com/GMA/MindMoodNews/story?id=8205087
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The psychological effects of Lyme disease
Can a tick bite drive you crazy?
Doctors warn that Lyme disease may cause personality changes
By Valerie Andrews, January 2004
Excerpts below – full text available at:
http://www.igenex.com/psychological_effects.htm
“Most people come to see me because they’ve got something wrong that nobody else can figure out,” says Debra Solomon, MD, a psychiatrist who practices in North Kingston, RI. Fifteen years ago Solomon was confronted with a medical mystery. More and more patients were coming in with the same group of symptoms—fatigue, headaches, migrating joint and muscle pain, accompanied by anxiety, depression, and memory problems. When one of her patients turned out to have Lyme disease, she tested the others, and found that nearly all were positive.
Recent studies show that certain areas of Rhode Island have the highest tick population in the world. Today many of Solomon’s patients come from the island Jamestown, a small farming community where ticks are abundant. Among her cases are:
* A college student in her early twenties who started hearing voices. “She came from a good family and had no previous emotional problems,” says Solomon.
* A businesswoman who suddenly became manic-depressive. “In periods of high energy, she wouldn’t sleep and felt all-powerful. She’d start a new business and begin spending lots of money, then she’d crash.”
* A high school athlete had to drop basketball because he didn’t have the stamina and couldn’t get through his classes without falling sleep. “The teachers accused him of not paying attention, but he didn’t have the concentration to do the work.”
* A 40-year-old book editor who was gaining weight and getting lame in her left leg. “She couldn’t think or process information, and was worried about her job.”
“Lyme affects nearly every person on this island,” says Solomon, “yet each person responds to it in very different ways.”
How can a physician tell the difference between true mental illness and symptoms linked to Lyme disease? With Lyme disease, a patient’s psychiatric symptoms don’t quite fit the textbook definition. There is usually no previous history of psychiatric illness. Symptoms often come in cycles. Patients usually do not respond well to psychiatric medication. And they often describe their problems in very physical terms.
Lyme patients often say, “There’s a wall in my brain and I can’t seem to move my thoughts from the back to the front.” “This arises from encephalopathy, an inflammation in the brain that affects cognitive function,” Solomon explains.
Symptoms often worsen as the Lyme bacteria grow active and begin to reproduce. At the same time, a patient may experience physical symptoms, such as fatigue, muscle pain or headaches. Flare-ups are often triggered by stress, as in the case of Bob C. who ran a shipping department for a manufacturing company. Bob had dozens of people answering to him, but Lyme disease made him anxious and unable to concentrate. Because he couldn’t think, he lost his job, and his symptoms grew more intense.
Family problems, economic changes, job loss, surgery, an auto accident, or a bad case of the flu, can send Lyme patients into a sudden tailspin. Along with antibiotics, these people need to rest—and do anything they can to lessen their emotional load.
The catch-22 is that chronic Lyme disease makes it hard to think and perform one’s daily tasks. This inevitably causes financial hardship and puts a strain on family relationships.
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Death plunge of the wealthy woman turned paranoid by a tick bite
Last updated at 08:40 11 April 2008
Up to one in three ticks carries Lyme disease
A woman plunged to her death from her bedroom window after suffering paranoid delusions caused by a tick bite, an inquest heard.
Jan Linton, 56, was bitten when she stayed on a friend’s nine-acre estate in France.
Within six months she was acting “very strangely” and claimed the police were “out to get her”, Westminster Coroner’s Court was told.
It is believed she had contracted Lyme disease, a tick-borne illness which is notoriously hard to diagnose in its later stages and can cause psychosis and delusions.
She died instantaneously from multiple injuries after falling three storeys from a window in her flat in West Brompton, South-West London, in January.
Six months earlier she was bitten by a tick while working on land around a house owned by her friend of 20 years, Rhian Bradley.
Miss Linton, described as a “very active and independent lady” of private means, stayed on in France until late December when she returned to London to seek medical help for debilitating joint pains that left her walking on crutches, which she thought could be related to the bite.
Miss Linton, whose father was a surgeon, knew of the risk of Lyme disease.
Her private GP suspected the disease and sent her for tests. But her mental state rapidly deteriorated, the inquest heard.
Miss Bradley, who lived with Miss Linton, said her friend became exhausted from a lack of sleep and started suffering from delusions.
“Jan began to have doubts and questioned the whole meaning of her life,” she said.
“She was a person of high integrity and high moral character so it was absolute mental torture to her to think that everything she had thought and believed she was about as a person was an illusion.”
Miss Linton, originally from Perth in Australia, said she feared people would think she was “a nutter”.
At one point she believed police were in the house and were “out to get her”.
Miss Bradley was so concerned about her friend’s health that she installed baby monitors to link their bedrooms so she would be on hand if her friend needed help.
In the early hours of January 16 Miss Bradley said she heard what appeared to be Miss Linton talking to herself, saying something like: “I have put something against the door.”
At around 6am Miss Bradley heard a thudding noise which sounded like Miss Linton falling out of bed.
She added: “I called out ‘Jan, are you all right?’ I heard nothing and that’s when I raced into her room. She wasn’t there.
“I knew what must have happened because the window was wide open.”
Coroner Dr Paul Knapman said Miss Linton was “clearly not herself” at the time of her death and her behaviour was “totally out of character”.
He added: “This before then had been a perfectly rational person.”
He recorded a verdict of death by misadventure.
The life and times of a tick
•Ticks are arthropods. Small black relatives of spiders, they feed only on liquids.
•They have acute senses which can detect the odour of a large mammal.
•They wait in grass, heather, bracken and trees for a host to brush past then attach themselves by burying a probe into the skin to suck blood.
•After gorging, they swell to the size of a pea before turning grey and dropping off their victim.
•Up to one in three ticks carries Lyme disease. Early symptoms include a “bull’s-eye” rash and aching joints, which can be treated with antibiotics.
•Untreated, it can cause arthritis, meningitis, paralysis, blindness, psychotic episodes and death.
•The disease is on the increase in the UK due to warmer, wetter weather. In 2006, there were 768 reported cases, compared with 292 in 2003.
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Role of chronic bacterial & viral infections in Neurodegenerative, Neurobehavioural, Psychiatric, Autoimmune & Fatiguing Illnesses Part 2:
British Jnl Medical Practioners March 2010, Volume 3, Number1
http://www.bjmp.org/files/2010-3-1/bjmp-2010-3-1-301.pdf
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Lyme, Depression, and Suicide
By Robert C. Bransfield, MD
http://www.mentalhealthandillness.com/Articles/LymeDepressionAndSuicide.htm
Extract below (full text available at link above)
In my database, depression is the most common psychiatric syndrome associated with late stage Lyme dis¬ease. Although depression is common in any chronic illness, it is more preva¬lent with Lyme patients than in most other chronic illnesses. There appears to be multiple causes, including a num¬ber of psychological and physical fac¬tors.
From a psychological standpoint, many Lyme patients are psychologically overwhelmed by the large multitude of symptoms associated with this disease. Most medical conditions primarily affect only one part of the body, or only one organ system. As a result, patients singularly afflicted can do activities which allow them to take a vacation from their dis¬ease. In contrast, multi-system diseases such as Lyme, depression, chronic Lyme disease can penetrate into multiple as¬pects of a person’s life. It is difficult to escape for periodic recovery. In many cases, this results in a vi-cious cycle of disappointment, grief; chronic stress, and demoralization.
It should be noted that depression is not only caused by psychological factors. Physical dysfunction can directly cause depression. Endo¬crine disorders such as hypothyroidism, which cause depression, are sometimes associated with Lyme disease and further strengthen the link be¬tween Lyme disease and depression.
The most complex link is the association between Lyme disease and central nervous system functioning. Lyme encephalopathy results in the dysfunction of a number of different mental func¬tions. This in turn results in cognitive, emotional, vegetative, and/or neurological pathology. Although all Lyme disease patients demonstrate many similar symptoms, no two patients present with the exact same symptom profile.
Other mental syndromes associated with late state Lyme disease, such as attention deficit disorder, panic disorder, obsessive-compulsive disorder, etc., may also contribute to the develop¬ment of depression. Dysfunction of other specific pathways may more directly cause depression. The link between encephalopathy and depression has been more thoroughly studied in other illnesses, such as stroke. The neura1 injury from a stroke causes neural dysfunction that causes depression. Injury to specific brain regions has different statisti¬cal correlation with the development of depression. Once depression or other psychiatric syndromes occur with Lyme disease, treating them effectively improves other Lyme disease symptoms as well and prevents the development of more severe conse¬quences, such as suicide.
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Lyme disease presenting as Tourette’s syndrome
Michael Riedel, Andreas Straube, Markus J. Schwarz, Betina Wilske, Norbert Müller
Lyme borreliosis is often misdiagnosed, both in adults and children.1
Central-nervous-system manifestations of Lyme disease include neurological and psychiatric symptoms.2
Although abnormal movements have been observed in Lyme disease,3 a Tourette’s syndrome has not been reported.
A boy at the age of 4 years developed a simple motor tic (blinking) that resolved within a year without treatment. At the age of 9 years, he developed multiple orofacial tics including shaking of the head, and several weeks later a vocal tic occurred. The tics became exacerbated under stress, as typically seen in Tourette’s syndrome. Social disabilities such as loss of impulse control, social withdrawal, and worsened performance at school followed. He came to hospital 11 months after onset of symptoms.
Serum IgM antibody titres against Borrelia burgdorferi measured by ELISA were not increased, although IgG antibody titres (ELISA) were increased at 58 U/mL (normal ≤ 10 U/mL) and 100 U/mL at another examination 2 weeks later. Immunofluorescence absorption test (IFT) was also increased (1:128 [normal: ≤ 1:16]). IgG immunoblot4 was positive. All results indicated an infection with B burgdorferi. Examination of the cerebral spinal fluid showed a slight lymphocytic pleocytosis. (16 cells per µL), which suggested an inflammatory reaction. The CSF:serum igG ratio for IgG antibodies was 2∙0, indicating intrathecal production of B burgdorferi-specific IgG antibodies, as occurs in neuroborreliosis.4
The boy was treated with intravenous ceftriaxone 2 g daily for 14 days. The tics improved after the sixth dose, and after the tenth dose the tics resolved completely. His social skills returned to normal. Follow-up examinations showed no recurrence of tics or other neurological or psychiatric disorder. Serum IgG antibody titres and IFT tests against B burgdorferi were 11 U/mL and 1:32 after 1 year.
Rapid efficacy of antibiotic treatment followed by a decrease in Borrelia-specific antibody titres suggests that the multiple motor and vocal tics were at least partially caused by the tertiary stage of borreliosis.5 Persistence of the tics and increasing severity of the social disabilities over several months suggest that the first signs of a Tourette-like syndrome 11 months previously were an expression of an early Lyme infection. Infection with B burgdorferi should be considered in cases of Tourette’s syndrome in endemic areas.
http://www.tourette-gesellschaft.de/rbk2/012b_bts_lymediseasepresenting.htm
Shapiro ED, Selzter EG. Lyme disease in children. Semin Neurol 1997; 17: 39-44.
Kaplan RF, Jones-Woodward L. Lyme encephalopathy: a neuropsychological perspective.
Semin Neurol 1997; 17: 31-37
Fallon BA, Nields JA, Parsons B, Liebowitz MR, Klein DF. Psychiatric manifestations of Lyme Borreliosis.
J Clin Psychiatry 1997; 54: 263-68.
Wilske B, Fingerle V, Herzer P, et al. Recombinant immunoblot in the serodiagnosis of Lyme Borreliosis.
Med Mikrobiol Immunol 1993; 182: 255-70.
Pfister HW, Wilske B, Weber K. Lyme borreliosis: basic science and clinical aspects.
Lancet 1994; 363: 1013-16.
Psychiatric Hospital (N. Müller), Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, 81377 Munich, Germany and Max-von-Pettenkofer Institute, Munich
© 1998 The Lancet ∙ 42 Bedford Square London WC1B 3SL UK
Publication by courtesy of Prof. Dr. Norbert Müller, Munich, Germany
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Chronic Infection May Spawn Depression
By Rick Nauert PhD Senior News Editor
Reviewed by John M. Grohol, Psy.D. on April 1, 2009
Researchers report an enzyme found throughout the body and long suspected of playing a role in depression, is in fact essential to the onset of depressive symptoms sparked by chronic inflammation.
University of Illinois researchers document their study online in the Journal of Immunology. The investigation is the first to identify the enzyme IDO (indoleamine 2,3 dioxygenase) as a molecular switch that induces depressive symptoms in some cases of chronic inflammation.
For more details go to:
http://psychcentral.com/news/2009/04/01/chronic-infection-may-spawn-depression/5079.html
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Psychiatric impact of Lyme Disease
Untreated or delayed treatment of Lyme disease or coinfections can lead to spirochete involvement in the brain. Some researchers believe that bacteria may migrate to the brain even early on in the infection.
Many psychiatric and neurological conditions can manifest in degrees ranging from mild to severe. It is critical that treating professionals and patients themselves understand that this medical condition may be at the bottom of clinical manifestations of conditions such as depression, anxiety, panic attacks, mood swings that may mimic bi-polar disorder, sleep disorders, Attention Deficit Disorder, Autism-like disorder, rage and impulse disorders, psychosis, seizures and cognitive losses.
More at: http://www.cynthiachasetherapy.com/psychiatric-implication.html
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Borreliosis (Lyme Disease) and its known involvement in Mental Health
By Denise Longman
Scientists and physicians across the world have discovered that the growing numbers of people with mental illness and diseases of the nervous system are being cured or improved by treatment with antibiotics. In other words, it is now known that bacteria can make you mentally ill as well as physically ill!
From Croatia to California, from Sweden to Sicily, conditions such as Schizophrenia and Multiple Sclerosis, even Alzheimer’s disease and Stroke, are being found to have common to all one of the most insidiously infective bacteria on the planet, namely Borrelia.
We present here several medical studies published in recent literature, which link mental illness and brain disease to known Borreliosis infection. There were few to be found that had been carried out in Britain; those quoted here are from the rest of Europe and the United States….
http://lookingatlyme.blogspot.com/2011/06/lyme-disease-and-mental-health.html
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Lyme Disease and Cognitive Impairments
by Robert Bransfield, M.D.
Laboratory tests such as SPECT scans, MRI’s, PET scans, and psychological testing have demonstrated physiological and anatomical findings associated with dysfunction of the cerebral cortex in patients with Lyme and tick-borne diseases. The examination of human and animal brains have further supported these findings.
The cognitive impairments from Lyme disease are very different than we see in Alzheimer’s disease. Lyme disease is predominately a disease of the white matter, while Alzheimer’s is predominately a disease of the gray matter. Memory association occurs in the white matter, while memory is stored in the gray matter. White matter dysfunction is a difficulty with slowness of recall, and incorrect associations. In contrast, gray matter dysfunction is a loss of the information which has previously been stored. For example, and Alzheimer’s patient may not recall the word “pen”, while an LE patient may have a slowness of recall or retrieval of a closely related word. Some of the symptoms I will describe are also found in encephalopathies associated with other illnesses, such as chronic fatigue syndrome, lupus stroke, AIDS, or other diseases which affect the brain. Although no single sign or symptom may be diagnostic of Lyme disease in a mental status exam, we instead look for a cluster and a pattern of signs and symptoms that are commonly associated with Lyme disease.
More at: http://www.mentalhealthandillness.com/Articles/LymeDiseaseAndCognitiveImpairments.htm
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Lyme Disease: A Neuropsychiatric Illness
Brian A. Fallon, M.D., M.P.H., Jenifer A. Nields, M.D.
Special Article, The American Journal of Psychiatry 1994, 151:11, 1571-1583.
Microbiology of Borrelia burgdorferi
http://www.lymenet.de/literatur/microbiology.htm
The microbiology of B. burgdorferi sheds light on why Lyme disease is an illness that at times can be relapsing and remitting and that can be refractory to normal immune surveillance and standard antibiotic regimens.
• The causative agent of Lyme disease -the spirochete B. burgdorferi- has a long replication time, comparable in this respect to Mycobacterium tuberculosis.
• Rapidly transmitted throughout the body, B. burgdorferi is known to invade the central nervous system (CNS) within the first few weeks after infection (20 – 22).
• B. burgdorferi is known to be neurotropic, leaving the cerebrospinal fluid (CSF) to adhere to glial cells or other brain tissue (75).
• Once in the CNS, B. burgdorferi, like Treponema pallidum, may remain latent, only to cause illness months later (23).
Much of the genetic material in B. burgdorferi is contained in plasmids (76), resulting in the possibility of significant variability. This includes
• marked variability in the expression of surface antigens, with consequent alterations in immunogenicity. Such changes could lead to
o resistance to normal immunologic functions -for example, through a failure of the B. burgdorferi-specific antibody to induce phagocytosis- as well as to
o evasion of routine laboratory detection.
Recent animal research (77) has found that the spirochete may undergo genetic alteration once it is sequestered in the CNS, thus resulting in a new strain of spirochete that is different from the infecting peripheral spirochete. The remarkable strain variation of B. burgdorferi may account for the differences between the presentation of Lyme disease in Europe and in the United States (78, 80). For example,
• in Continental Europe, arthritic involvement is less common, and most cases of neurologic Lyme disease have prominent CSF abnormalities.
• Late-stage neurologic Lyme disease in the United States, on the other hand, is less likely to show CSF abnormalities on routine testing (81).
During growth, Bb appears to shed membranous material (blebs) from its surface. These blebs coat the spirochete and have been found free in the CSF, serum, and urine (21, 82, 83).
• The blebs appear to interact specifically with IgM molecules. It is hypothesized that in some cases, the blebs may bind all of the free circulating B. burgdorferi-specific IgM antibodies (Schutzer et al. 1994), thereby enabling the organism itself to escape immune surveillance (Lawrence et al. 1995).
• In addition, the blebs possess potent, nonspecific mitogenic activity that may cause an inappropriate and ineffective stimultation of the immune system (Ma et al. 1993). This could initiate autoimmune disease processes (84).
B. burgdorferi has been shown to be capable of persisting in human hosts despite extensive antibiotic treatment (17, 85 – 88). Because in vitro studies demonstrate that B. burgdorferi
• can be recovered from antibiotic-treated fibroblast monolayers (89) and because B. burgdorferi has been shown to
• lodge inside
o human fibroblasts (89),
o mouse macrophages (90), and
o human endothelial cells (91),
researchers conclude that the intracellular location may enable the spirochete to remain inaccessible to (such) antibiotics (that do not enter into cells, see Brouqui et al. 1996, parenthesis by J. Gruber) and normal immune surveillance. Sequestration in other antibiotic- and immunologically priviledged sites
(e.g.
• CNS,
• joints,
• anterior chamber of the eye)
may also account for persistent illness despite antibiotic treatment (20).
Several features are known to contribute to an organism’s resistance to standard lengths of antibiotic treatment. These features include
• an intracellular location (92),
• long replication time,
• genetic variablity, and
• the ability to become sequestered in difficult-to-penetrate sites.
B. burgdorferi appears to possess all of these characteristics.
References
17. Liegner KB: Lyme disease: the sensible pursuit of answers. J Clin Microbiol 1993; 31: 1961-1963.
20. Luft BJ, Steinman CR, Neimark HC, Muralidhar B, Rush T, Finkel MF, Kunkel M, Dattwyler RJ: Invasion of the CNS by Bb in acute disseminated infection. JAMA 1992; 267:1364-1367.
21. Coyle PK, Deng Z, Schutzer SF, Belman AL, Benach J, Krupp LB, Luft B: Detection of Bb antigens in cerebrospinal fluid. Neurology 1993, 43: 1093-1097.
22. Garcia-Monco JC, Villar BF, Alen JC, Benach JL: Borrelia burgdorferi in the central nervous system: experimental and clinical evidence for early invasion. J Infect Dis 1990; 161:1187-1193.
23. Loggian EL, Kaplan RF, Steere AC: Chronic neurologic manifestation of Lyme disease. N Engl J Med 1990; 323:1483-1444.
75. Garcia-Monco JC, Fernandez-Villar B, Benach JL: Adherence of the Lyme disease spirochete to glial cells and cells of glial origin. J Infect Dis 1989; 160: 497-506.
76. Barbour AG, Garon CF: Linear plasmids of the bacterium Borrelia burgdorferi have covalently closed ends. Science 1987; 237: 409-411.
77. Pachner AR, Itano A: Borrelia burgdorferi infection of the brain: characterization of the organism and response to antibiotics and immune sera in the mouse model. Neurology 1990; 40: 1535-1540.
78. Hanrahan JP, Benach JL, Coleman JL, Bosler EM, Morse DL, Cameron DJ, Edelman R, Kaslow RA: J Infect Dis 1984; 150: 489-596.
79. Steere AC, Taylor E, Wilson ML, Levine JL, Spielman A: Longitudinal assessmentr of the clinical and epidemiological features of Lyme disease in a defined population. J Infect Dis 1986; 154: 295-300.
80. Schwan TG, Burgdorfer W, Garon CF: Changes in infectivity and plasmid profile of the Lyme disease spirochete, Borrelia burgdorferi, as a result of in vitro cultivation. Infect Immun 1988; 56: 1831-1836.
81. Coyle PK: Antigen detection and cerebrospinal fluid studies, in: “Lyme Disease”, Coyle PK (ed.), Philadelphia, Mosby Year Book, 1992.
82. Garon CF, Dorward DW, Corwin MD: Structural features of Bb – the Lyme disease spirochete silver staining for nucleic acids, Scanning Microsc. Suppl 1989, 3: 109-115.
83. Dorward DW, Schwan TG, Garon CF: Immune capture and detection of Bb antigens in urine, blood, or tissues from infected ticks, mice, dogs, and humans, J Clin Microbiol 1991; 29: 1162-1170.
84. Whitmire WM, Garon CF: Specific and nonspecific responses of murine B cells to membrane blebs of Borrelia burgdorferi. Infect Immun 1993; 61: 1460-1467.
85. Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J: Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 1989; 17: 355-359.
86. Haupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schonherr U, Kalden JR, Burmester GR: Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum 1993;, 36: 1621-1626.
87. Hassler D, Riedel K, Zorn J, Preac-Mursic V: Pulsed high-dose cefotaxime therapy in refractory Lyme borreliosis (letter). Lancet 1991; 338: 193.
88. Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L: Recurrence erythema migrans despite extended antibiotic treatment with monocycline in a patient with persisting Borrelia burgdorferi infection. J Am Acad Dermatol 1993; 28: 312-314.
89. Georgilis K, Peacocke M, Klempner MS: Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. J Infect Dis 1992: 166: 440-444.
90. Montgomery RR, Nathanson MH, Malawista SE: The fate of Borrelia burgdorferi in mouse macrophages: destruction, survival, recovery. J Immunol 1993; 150: 909-915.
91. Ma Y, Sturrock A, Weis JJ: Intracellular localization of Borrelia burgdorferi within human endothelial cells. Infect Immun 1991; 59: 671-678.
92. Mahmoud AA: The challenge of intracellular pathogens (editorial) N Engl J Med 1992; 326: 761-762.
The following references, cited by name rather than by numbers, have been added by Dr. J. Gruber.
P. Brouqui, S. Badiaga, D. Raoult: Eucaryotic Cells Protect Borrelia burgdorferi from the Action of Penicillin and Ceftriaxone but Not from the Action of Doxycycline and Erythromycin: NOTES.Antimicrobial Agents and Chemotherapy 1996:1552Ð1554.
Lawrence C, Lipton RB, Lowy FD, Coyle PK: Seronegative chronic relapsing neuroborreliosis. Eur Neurol 1995;35(2):113-117.
Ma Y, Weis JJ: Borrelia burgdorferi outer surface lipoproteins OspA and OspB possess B-cell mitogenic and cytokine-stimulatory properties. Infect Immun 1993 Sep;61(9):3843-53.
Schutzer SE, Coyle PK, Dunn JJ, Luft BJ, Brunner M: Early and specific antibody response to OspA in Lyme Disease. J Clin Invest 1994 Jul;94(1):454-457.
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Version: October 21, 2008.
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In Defense Of Zebras
Spotlight On Lyme Disease By Virginia Sherr
Sometimes, when physicians hear that there may be a tick-borne cause for the mental symptoms of one of their patients, it prompts a lecture – perhaps an attempt to be helpful. A favorite strategy is the recounting of amusing old medical proverbs: “You know, when you hear hoof beats, you should look first for horses, not zebras,” or, “Remember, if you hear barking it usually turns out to be dogs and not foxes.”
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