LYME BORRELIOSIS: Clinical Picture ; Symptoms
Lyme Disease / Borreliosis
Lyme disease is a multi-systemic inflammatory disease resulting from an infection from spirochete bacteria of the Borrelia family. Spirochetes are long, thin, spiral-shaped bacteria that have flagella (tails), which aids their movement throughout the body. The periplasmic flagellum of the spirochete underlies the highly invasive abilities of this bacterium as it allows them to move through semisolid environments, such as the body’s connective tissue, which inhibits the movement of most other bacteria (1, 2). Bacteria of the spirochete family include those responsible for diseases such as syphilis (Treponema pallidum), Leptospirosis (Leptospira) and Relapsing Fever (eg: B. hermsii, B. recurrentis). In the initial stages Lyme disease may simply present as a flu like illness, however as the length of time of infection increases Lyme disease “appears as a chronic progressive disease that involves multiple organs, including the heart, the liver, the kidneys, the musculoskeletal system, the skin, and the central and peripheral nervous systems (3: pge 1711)”. When the infection is detected and treated early, the prognosis for a full recovery is excellent. Unfortunately, due to the various ways the illness can manifest, the lack of definitive laboratory tests for diagnosis and more importantly the overall lack of awareness surrounding Lyme disease, many people may go undiagnosed for long periods of time, rendering the treatment and recovery process more complicated due to the chronic disease process.
To account for the numerous species that can underlie Lyme disease (see Lyme History and Borrelia Species) it may also be called Lyme Borreliosis, or neuroborreliosis, due to the more neurological manifestations associated with some Borrelia species, such as B. garinii and B. valaisiania.
The following uses these terms interchangeably.
The following uses these terms interchangeably.
Clinical Picture
The clinical picture can vary depending on the species of Borrelia underlying the infection, the strength of a person’s immune system and any co-infections that may be acquired at the same time. The most prevalent species originally found to cause human disease are B. burgdorferi sensu stricto (ss), B. garinii, and B. afzelii. The B. burgdorferi ss species is associated with an arthritic clinical picture, whilst the first two species identified in Europe have more dermatological (B. afzelii) and neurological (B. garinii) manifestations (1).
Initial symptoms may be an Erythma Migrans (EM), a bulls-eye rash (though the number of patients that get this is reported as being anywhere between 30 to 70%) or other type of rash, followed by flu like symptoms. After a short period of localised infection, the bacteria begin to spread throughout the blood to the lymph nodes, joints, heart and the nervous system. Some people may develop worsening symptoms within a month or two of initial infection, whilst in others, once the bacteria has moved out of the blood stream (to avoid detection by the immune system), it may lay dormant for an extended period of time before symptoms become noticeable. This is very much like the bacteria responsible for tuberculosis, in which initial symptoms of the primary infection may be minor, and it is not until months or years later that the disease becomes “re-activated”. This may be due to a person’s immune system being compromised or weakened (2) by events such as: an accident; an operation; severe trauma or stress; pregnancy; heavy metal toxicity; mould exposure, vaccinations and immunosuppressant drugs such as steroids.
Initial symptoms may be an Erythma Migrans (EM), a bulls-eye rash (though the number of patients that get this is reported as being anywhere between 30 to 70%) or other type of rash, followed by flu like symptoms. After a short period of localised infection, the bacteria begin to spread throughout the blood to the lymph nodes, joints, heart and the nervous system. Some people may develop worsening symptoms within a month or two of initial infection, whilst in others, once the bacteria has moved out of the blood stream (to avoid detection by the immune system), it may lay dormant for an extended period of time before symptoms become noticeable. This is very much like the bacteria responsible for tuberculosis, in which initial symptoms of the primary infection may be minor, and it is not until months or years later that the disease becomes “re-activated”. This may be due to a person’s immune system being compromised or weakened (2) by events such as: an accident; an operation; severe trauma or stress; pregnancy; heavy metal toxicity; mould exposure, vaccinations and immunosuppressant drugs such as steroids.
Symptoms
Early symptoms:
Include: “flu-like” feeling, headaches, fevers, muscle soreness, fatigue. Initial symptoms may also include (the number of patients that get this is reported as being anywhere between 30 to 70%) the development of Erythma Migrans (EM), a bulls-eye rash or other type of rash.
“Within days to weeks after disease onset, B. burgdorferi often disseminates widely. During this period, the spirochete has been recovered from blood and cerebrospinal fluid, and it has been seen in small numbers in specimens of myocardium, retina, muscle, bone, spleen, liver, meninges, and brain (9:pg 1096)”.
Disseminated symptoms:
Once the bacteria start to spread throughout the body, symptoms broaden to include: persistent swollen glands; sore throat; joint pain/swelling/stiffness; muscle pain, cramps or weakness; bone pain; numbness, tingling, burning; twitching of the face or other muscles; jaw pain, stiffness, or temporomandibular joint disorder (TMJ); constant headaches; hearing loss; sound and light sensitivity; eye pain, vision problems such as floaters, blurry vision, vision loss; difficulty thinking/concentrating; poor short term memory; mood swings, irritability, depression; anxiety, panic attacks; psychosis (hallucinations, delusions, paranoia); tremors; seizures; Bells Palsy (may be early or latent symptom); chronic fatigue (2).
Include: “flu-like” feeling, headaches, fevers, muscle soreness, fatigue. Initial symptoms may also include (the number of patients that get this is reported as being anywhere between 30 to 70%) the development of Erythma Migrans (EM), a bulls-eye rash or other type of rash.
“Within days to weeks after disease onset, B. burgdorferi often disseminates widely. During this period, the spirochete has been recovered from blood and cerebrospinal fluid, and it has been seen in small numbers in specimens of myocardium, retina, muscle, bone, spleen, liver, meninges, and brain (9:pg 1096)”.
Disseminated symptoms:
Once the bacteria start to spread throughout the body, symptoms broaden to include: persistent swollen glands; sore throat; joint pain/swelling/stiffness; muscle pain, cramps or weakness; bone pain; numbness, tingling, burning; twitching of the face or other muscles; jaw pain, stiffness, or temporomandibular joint disorder (TMJ); constant headaches; hearing loss; sound and light sensitivity; eye pain, vision problems such as floaters, blurry vision, vision loss; difficulty thinking/concentrating; poor short term memory; mood swings, irritability, depression; anxiety, panic attacks; psychosis (hallucinations, delusions, paranoia); tremors; seizures; Bells Palsy (may be early or latent symptom); chronic fatigue (2).
Full symptom checklists can be seen at: Canadian Lyme Disease Foundation or Lyme Disease Action UK
For Rash images associated to Lyme and Vector Borne Diseases Click Here
For Rash images associated to Lyme and Vector Borne Diseases Click Here
As can be seen by the length the symptom list, the symptoms associated with Lyme disease are wide and varied. A few basic reasons as to why this is so:
A) The spirochete can cause damage to a person’s tissue, organs and bones: The specialised flagella (tail) of the spirochete allow it to move away from macrophages (A white blood cell of the immune system) whose role is to “ingest” infectious bacteria (3). Their axil filaments (endoflagella) also mean they move in a corkscrew like fashion and are able to “screw” their way into bone, tissue, muscles and organs (4).
B) The immune system’s response to the spirochetes’ presence in the body and their bacterial lipoproteins:
Bacterial Lipoproteins have strong stimulatory properties and whilst most other bacteria only have 3 genes for coding lipoproteins, Borrelia has over 105 (5). Basically, the bacterial lipoproteins - which play a role in adhesion to host cells (resulting in vasculitis), modulation of inflammatory processes and virulence factors - of Borrelia “cause a dysfunction in the immune system by triggering a complex imbalance of chemical immune mediators (cytokines). These cytokines regulate the immune system and when they are over stimulated, they produce harmful reactions from the immune system, such as pain, inflammation, and even apoptosis (cell death)” (6: pge 9).
Constant inflammation within the body is associated to many problems: it can increase the risk of cancer (7) and is associated with many autoimmune diseases such as rheumatoid arthritis, endocrine disorders, celiac disease and those that affect the brain such as multiple sclerosis (8, 9). Tom Grier gives one explanation as to how inflammation can affect the brain “When the human brain becomes inflamed, cells called macrophages respond by releasing a neuro-toxin called quinolinic acid. This toxin is also elevated in Parkinson's disease, MS, ALS, and is responsible for the dementia that occurs in AIDS patients. What quinolinic acid does is stimulate neurons to repeatedly depolarize. This eventually causes the neurons to demyelinate and die. People with elevated quinolinic acid have short-term memory problems” (10: pge 7).
(C) Stimulation of inflammatory and anti-inflammatory cytokines: In many patients, symptoms seem to migrate from one area of the body to another, or be worse from one day to the next: As well as the stimulatory properties of the bacterial lipoproteins, they are also able to induce anti-inflammatory cytokines, which may “explain the focal and transient nature of inflammatory episodes in Lyme disease” (5).
A) The spirochete can cause damage to a person’s tissue, organs and bones: The specialised flagella (tail) of the spirochete allow it to move away from macrophages (A white blood cell of the immune system) whose role is to “ingest” infectious bacteria (3). Their axil filaments (endoflagella) also mean they move in a corkscrew like fashion and are able to “screw” their way into bone, tissue, muscles and organs (4).
B) The immune system’s response to the spirochetes’ presence in the body and their bacterial lipoproteins:
Bacterial Lipoproteins have strong stimulatory properties and whilst most other bacteria only have 3 genes for coding lipoproteins, Borrelia has over 105 (5). Basically, the bacterial lipoproteins - which play a role in adhesion to host cells (resulting in vasculitis), modulation of inflammatory processes and virulence factors - of Borrelia “cause a dysfunction in the immune system by triggering a complex imbalance of chemical immune mediators (cytokines). These cytokines regulate the immune system and when they are over stimulated, they produce harmful reactions from the immune system, such as pain, inflammation, and even apoptosis (cell death)” (6: pge 9).
Constant inflammation within the body is associated to many problems: it can increase the risk of cancer (7) and is associated with many autoimmune diseases such as rheumatoid arthritis, endocrine disorders, celiac disease and those that affect the brain such as multiple sclerosis (8, 9). Tom Grier gives one explanation as to how inflammation can affect the brain “When the human brain becomes inflamed, cells called macrophages respond by releasing a neuro-toxin called quinolinic acid. This toxin is also elevated in Parkinson's disease, MS, ALS, and is responsible for the dementia that occurs in AIDS patients. What quinolinic acid does is stimulate neurons to repeatedly depolarize. This eventually causes the neurons to demyelinate and die. People with elevated quinolinic acid have short-term memory problems” (10: pge 7).
(C) Stimulation of inflammatory and anti-inflammatory cytokines: In many patients, symptoms seem to migrate from one area of the body to another, or be worse from one day to the next: As well as the stimulatory properties of the bacterial lipoproteins, they are also able to induce anti-inflammatory cytokines, which may “explain the focal and transient nature of inflammatory episodes in Lyme disease” (5).
Associations / Misdiagnosis of Lyme as other Diseases
Due to the protean (variable and versatile in their ability to change frequently) manifestations of the disease, and the fact they are both due to infections of a spirochete bacteria, Lyme is often likened to Syphilis: “Lyme disease is like syphilis in its multisystem involvement, occurrence in stages, and mimicry of other diseases (1:pge 2378 ).” The ability of Borrelia to invade every organ in the body and the widespread inflammation that they induce is an underlying reason that Lyme disease has been misdiagnosed as multiple disorders/diseases including:
Those that effect the Brain / Nerves – Brain tumour, Meningitis, Encephalitis, Stroke, Bells Palsy, Seizures/Epilepsy (2-8) ;
Cognitive/ Psychiatric disorders - Alzheimer’s, Psychosis (9-11) ;
Demyelinating and degenerative diseases - Multiple Sclerosis, Parkinson's Disease, Motor Neurone Disease (MND) known as Lou Gehrig’s disease or Amyotrophic Lateral Sclerosis (ALS) in some countries (12-18);
Heart problems - including Myocarditis and Transient atrioventricular blocks (19-22) ;
Musculoskeletal disorders - Bone erosion, Osteomyelitis (23-24) ;
Systemic Inflammatory diseases - Rheumatoid arthritis, Juvenile arthritis, Sarcoidosis (25-27);
Skin / Hair disorders - Pityriasis rosea, Hair loss/ alopecia (28-30).
Those that effect the Brain / Nerves – Brain tumour, Meningitis, Encephalitis, Stroke, Bells Palsy, Seizures/Epilepsy (2-8) ;
Cognitive/ Psychiatric disorders - Alzheimer’s, Psychosis (9-11) ;
Demyelinating and degenerative diseases - Multiple Sclerosis, Parkinson's Disease, Motor Neurone Disease (MND) known as Lou Gehrig’s disease or Amyotrophic Lateral Sclerosis (ALS) in some countries (12-18);
Heart problems - including Myocarditis and Transient atrioventricular blocks (19-22) ;
Musculoskeletal disorders - Bone erosion, Osteomyelitis (23-24) ;
Systemic Inflammatory diseases - Rheumatoid arthritis, Juvenile arthritis, Sarcoidosis (25-27);
Skin / Hair disorders - Pityriasis rosea, Hair loss/ alopecia (28-30).
Of course, a diagnosis of any of the above conditions may simply be what they are, however, if someone has received many of these, or they don’t “fit” the clinical picture of a particular disease (ie: MND for example. It is not “typical” for someone in their early 30’s or 40’s to be diagnosed with MND, as the average age of onset is 50-60), investigating underlying reasons would be very appropriate.
Co-Infections
As Lyme is a vector borne disease (see: Lyme Disease Transmission and Maintenance), there is the possibility of acquiring co-infections that may be transmitted at the same time. These include: parasitic infections such as Babesia/Theileria and bacterial infections such as Bartonella and the Rickettsial diseases – Rickettsia (either: typhus group, spotted fever group or scrub typhus), Ehrlichia, Anaplasma and Coxiella (Q fever). Immuno-compromised individuals may also be more susceptible to acquiring bacterial infections such as Mycoplasma and Chlamydophila (Chlamydia) pneumoniae (CpN) and viral infections such as Epstein - Barr virus (EBV), and ParvoB19.
Co-infections are mentioned briefly here to note that acquisition of one or more of these infections at the same time may alter the severity/course of Lyme disease. It is also noteworthy that whilst other countries recognise that infections due to pathogens such as Babesia, can cause severe illness in humans as well as animals (and can be transmitted via blood transfusions), Australia is yet to acknowledge the potential risks for human disease, even after the death of a NSW male in 2011.
Co-infections are mentioned briefly here to note that acquisition of one or more of these infections at the same time may alter the severity/course of Lyme disease. It is also noteworthy that whilst other countries recognise that infections due to pathogens such as Babesia, can cause severe illness in humans as well as animals (and can be transmitted via blood transfusions), Australia is yet to acknowledge the potential risks for human disease, even after the death of a NSW male in 2011.
Further information on Co-infections can be seen on the following websites:
Lyme Disease Organisation
What is Lyme: Lisa Hilton's Blog
A Chart of numerous co-infections compiled by Louise Jenner, Lyme literate Coach
Lyme Disease Organisation
What is Lyme: Lisa Hilton's Blog
A Chart of numerous co-infections compiled by Louise Jenner, Lyme literate Coach
Additional readings on Lyme Disease:
“When to Suspect Lyme” is an essay written by John D Bleiweiss (MD). It explains the various symptoms associated with Lyme and how they affect the person’s life very well.
“Lyme Disease (Borreliosis): A Plague of Ignorance Regarding the Ignorance of a Plague” by James Scott Taylor (DVM). A good “laymans” explanation. I found this reading very helpful when first looking into how the bacteria responsible for Lyme disease affects the body.
“Advanced Topics in Lyme Disease. Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne Illnesses. Sixteenth Edition”.
Dr J Burrascano’s 2008 guidelines: This is more of a technical read, though good for understanding the overall treatment of the infections, co-infections and the necessity of supporting the immune system.
“When to Suspect Lyme” is an essay written by John D Bleiweiss (MD). It explains the various symptoms associated with Lyme and how they affect the person’s life very well.
“Lyme Disease (Borreliosis): A Plague of Ignorance Regarding the Ignorance of a Plague” by James Scott Taylor (DVM). A good “laymans” explanation. I found this reading very helpful when first looking into how the bacteria responsible for Lyme disease affects the body.
“Advanced Topics in Lyme Disease. Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne Illnesses. Sixteenth Edition”.
Dr J Burrascano’s 2008 guidelines: This is more of a technical read, though good for understanding the overall treatment of the infections, co-infections and the necessity of supporting the immune system.
References: LYME BORRELIOSIS: Clinical Picture ; Symptoms
Please note: Any information with regards to Lyme disease that is freely available at numerous locations on the internet has not been referenced. For specific facts/arguments, see the reference list.
NB: Reference section is separated into segments for ease of updating information
NB: Reference section is separated into segments for ease of updating information
Lyme Disease / Borreliosis
(1) Sellek RE, Escudero R, Gil H, Rodriguez I, Chaparro E, Perez-Pastrana E, Vivo A and Anda P (2002) In vitro culture of Borrelia garinii results in loss of flagella and decreased invasiveness. Infect Immun;70(9):4851-8. http://www.ncbi.nlm.nih.gov/pubmed/12183529
(2) Li C, Motaleb A, Sal M, Goldstein SF and Charon NW (2000) Spirochete periplasmic flagella and motility. J Mol Microbiol Biotechnol;2(4):345-54. http://www.ncbi.nlm.nih.gov/pubmed/11075905
(3) Wallich R, Moter SE, Simon MM, Ebnet K, Heiberger A and Kramer MD (1990) The Borrelia burgdorferi flagellum-associated 41-kilodalton antigen (flagellin): molecular cloning, expression, and amplification of the gene. Infect Immun;58(6):1711-9. http://www.ncbi.nlm.nih.gov/pubmed/2341173
Clinical Picture
(1) Dressler F, Ackermann R and Steere AC (1994). Antibody Responses to the Three Genomic Groups of Borrelia burgdorferi in European Lyme Borreliosis. The Journal of Infectious Diseases;169(2):313-8. http://www.ncbi.nlm.nih.gov/pubmed/8106763
(2) Cedars Sinal, Tuberculosis: http://www.cedars-sinai.edu/Patients/Health-Conditions/Tuberculosis-TB.aspx
Symptoms/Diagnosis
(1) Steere AC, Coburn J and Glickstein L (2004) The emergence of Lyme disease. J Clin Invest;113(8):1093-101. www.ncbi.nlm.nih.gov/pubmed/15085185
(2) Symptoms, Canadian Lyme Disease Foundation: http://canlyme.com/lyme-basics/symptoms/
(3) Macrophage From Wikipedia http://en.wikipedia.org/wiki/Macrophage Accessed 21st Feb 2012
(4) Borrelia burgdorferi and Lyme Disease Todar’s Online Textbook of Bacteriology. By Kenneth Todar, PhD http://textbookofbacteriology.net/Lyme.html
(5) Giambartolomei GH, Dennis VA, Lasater BL and Philipp MT (1999) Induction of pro- and anti-inflammatory cytokines by Borrelia burgdorferi lipoproteins in monocytes is mediated by CD14. Infect Immun; 67(1):140-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96289/
(6) “Lyme Disease (Borreliosis): A Plague of Ignorance Regarding the Ignorance of a Plague” by James Scott Taylor (DVM), 2004. http://www.ra-infection-connection.com/Scott%20Taylor%202004%20CHRONIC%20LYME%20DISEASE.html
(7) The Role of Inflammation in Cancer. SA Biosciences. http://www.sabiosciences.com/pathwaymagazine/minireview/cancerinflammation.php
(8) Inflammation. From Wikipedia, http://en.wikipedia.org/wiki/Inflammation Accessed 21st Feb 2012
(9) Autoimmune Disorders. Medline Plus http://www.nlm.nih.gov/medlineplus/ency/article/000816.htm Accessed 21st Feb 2012
(10) The Complexities of Lyme Disease A Microbiology Tutorial: Part 1 By Thomas M. Grier, MS
http://www.lymeneteurope.org/info/the-complexities-of-lyme-disease
Associations/Misdiagnosis of other diseases
(1) Steere AC (1994) Lyme disease: A growing threat to urban populations. Proc Natl Acad Sci; 91(7): 2378-2383. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43375/
(2) Curless RG, Schatz NJ, Bowen BC, Rodriguez Z, Ruiz A. (1996) Lyme neuroborreliosis masquerading as a brainstem tumor in a 15-year-old. Pediatr Neurol ;15(3):258-60. http://www.ncbi.nlm.nih.gov/pubmed/8916168
(3) Oksi J1, Kalimo H, Marttila RJ, Marjamäki M, Sonninen P, Nikoskelainen J, Viljanen MK (1996) Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain; 119 (6) : 2143-54. http://www.ncbi.nlm.nih.gov/pubmed/9010017
(4) Reik, L Jr (1993) Stroke due to Lyme disease. Neurology, 43(12):2705-7. http://www.ncbi.nlm.nih.gov/pubmed/8255484
(5) Defer G; Levy R; Brugieres P; Postic D; Degos JD (1993). Lyme disease presenting as a stroke in the vertebrobasilar territory: MRI. Neuroradiology, 35(7):529-31. http://www.ncbi.nlm.nih.gov/pubmed/8232882
(6) Halperin JJ; Golightly M (1992) Lyme borreliosis in Bell’s palsy. Long Island neuroborreliosis collaborative study group. Neurology, 42(7):1268-70 . http://www.ncbi.nlm.nih.gov/pubmed/1620330
(7) Bloom BJ; Wyckoff PM; Meissner HC; Steere AC. (1998) Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infectious Disease Journal, 17(3):189-96. http://www.ncbi.nlm.nih.gov/pubmed/9535244
(8) Mourin S; Bonnier C; Bigaignon G; Lyon G (1993) Epilepsy disclosing neuroborreliosis. Rev Neurol (Paris), 149(8-9):489-91. http://www.ncbi.nlm.nih.gov/pubmed/8009148
(9) Miklossy, J (2011) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. Journal of Neuroinflammation; 8:90 http://www.jneuroinflammation.com/content/8/1/90
(10) Roelcke U, Barnett W, Wilder-Smith E, Sigmund D, Hacke W (1992) Untreated neuroborreliosis: Bannwarth's syndrome evolving into acute schizophrenia-like psychosis. A case report. J Neurol, Mar; 239(3):129-31. http://www.ncbi.nlm.nih.gov/pubmed/1573415
(11) Fallon BA; Kochevar JM; Gaito A; Nields J (1998) The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatric Clinics of North America, 21(3):693-703. 1998. http://www.ncbi.nlm.nih.gov/pubmed/9774805
(12) Chmielewska-Badora J, Cisak E, Dutkiewicz J. (2007) Lyme borreliosis and multiple sclerosis: any connection? A seroepidemic study. Ann Agric Environ Med ;7(2):141-3. http://www.ncbi.nlm.nih.gov/pubmed/11153045
(13) Fritzsche M (2005) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable? Med Hypotheses ; 64(3):438-48. http://www.ncbi.nlm.nih.gov/pubmed/15617845
(14) Reik L Jr; Smith L; Khan A; Nelson W (1985) Demyelinating encephalopathy in Lyme disease.
Neurology, 35(2):267-9. http://www.ncbi.nlm.nih.gov/pubmed/3969220
(15) Cassarino DS; Quezado MM; Ghatak NR; Duray PH (2003) Lyme-associated parkinsonism: a neuropathologic case study and review of the literature. Arch Pathol Lab Med, 127(9):1204-6. http://www.ncbi.nlm.nih.gov/pubmed/12946221
(16) Halperin JJ, Kaplan GP, Brazinsky S, Tsai TF, Cheng T, Ironside A, Wu P, Delfiner J, Golightly M, Brown RH, Dattwlyer RJ, Luft, BJ (1990) Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch Neurol ; 47 (5) 586-94. http://www.ncbi.nlm.nih.gov/pubmed/2334308#
(17) De Cauwer H, Declerck S, De Smet J, Matthyssen P, Pelzers E, Eykens L, Lagrou K. (2009) Motor neuron disease features in a patient with neuroborreliosis and a cervical anterior horn lesion. Act Clin Belg; 64 (3) : 225-7. http://www.ncbi.nlm.nih.gov/pubmed/19670562#
(18) Hansel Y; Ackerl M; Stanek G (1995) ALS-like sequelae in chronic neuroborreliosis. Wien Med Wochenschr, 145(7-8):186-8. http://www.ncbi.nlm.nih.gov/pubmed/7610670
(19) Lo R; Menzies DJ; Archer H; Cohen TJ (2003) Complete heart block due to Lyme carditis. Journal of Invasive Cardiology, 15(6):367-9. http://www.ncbi.nlm.nih.gov/pubmed/12777681
(20) Steere AC; Batsford WP; Weinberg M; Alexander J; Berger HJ; Wolfson S; Malawista SE (1980). Lyme carditis: cardiac abnormalities of Lyme disease. Annals of Internal Medicine, 93(1):8-16. http://www.ncbi.nlm.nih.gov/pubmed/6967274
(21) Nagi KS; Joshi R; Thakur RK (1996) Cardiac manifestations of Lyme disease: a review. Can J Cardiol, 12(5):503-6. http://www.ncbi.nlm.nih.gov/pubmed/8640597
(22) Bacino L; Gazzarata M; Siri G; Cordone S; Bellotti P (2011) Complete atrioventricular block as the first clinical manifestation of a tick bite (Lyme disease). G Ital Cardiol (Rome), 12(3):214-6. http://www.ncbi.nlm.nih.gov/pubmed/21560478
(23) Steere AC (1989) Lyme disease. New England Journal of Medicine, 321(9):586-96. http://www.ncbi.nlm.nih.gov/pubmed/2668764
(24) Oksi J; Mertsola J; Reunanen M; Marjamaki M; Viljanen MK (1994) Subacute multiple-site osteomyelitis caused by Borrelia burgdorferi. Clin Infect Dis, 19(5):891-6. http://www.ncbi.nlm.nih.gov/pubmed/7893875
(25) Steere AC (1988) Pathogenesis of Lyme arthritis Annals NY Academy of Sciences, 539:87-92.
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1988.tb31841.x/abstract
(26) Willis AA; Widmann RF; Flynn JM; Green DW; Onel KB (2003) Lyme arthritis presenting as acute septic arthritis in children. J Pediatr Orthop, 23(1):114-8. 2003 http://www.ncbi.nlm.nih.gov/pubmed/12499956
(27) Hua B, Li QD, Wang FM, Ai CX, Luo WC (1992) Borrelia burgdorferi infection may be the cause of sarcoidosis. Chin Med J (Engl) Jul;105(7):560-3. http://www.ncbi.nlm.nih.gov/pubmed/1333393
(28) Stinco G, Ruscio M, Proscia D Piccirillo F (2009) Borrelia Infection and Pityriasis Rosea. Acta Derm Venereol ; 89(1):97-8. http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-0544&html=1
(29) BE, Stonehouse A and Studdiford J (2008). Late Diagnosis of Early Disseminated Lyme Disease: Perplexing Symptoms in a Gardner. J Am Board Fam Med. May-Jun;21(3):234-6. http://www.jabfm.org/content/21/3/234.long
(30) Cimperman J; Maraspin V; Lotric-Furlan S; Ruzic-Sabljic E; Avsic-Zupanc T; Strle F (1999) Diffuse reversible alopecia in patients with Lyme meningitis and tick-borne encephalitis. Wien Klin Wochenschr, 111(22-23):976-7. http://www.ncbi.nlm.nih.gov/pubmed/10666812
(1) Sellek RE, Escudero R, Gil H, Rodriguez I, Chaparro E, Perez-Pastrana E, Vivo A and Anda P (2002) In vitro culture of Borrelia garinii results in loss of flagella and decreased invasiveness. Infect Immun;70(9):4851-8. http://www.ncbi.nlm.nih.gov/pubmed/12183529
(2) Li C, Motaleb A, Sal M, Goldstein SF and Charon NW (2000) Spirochete periplasmic flagella and motility. J Mol Microbiol Biotechnol;2(4):345-54. http://www.ncbi.nlm.nih.gov/pubmed/11075905
(3) Wallich R, Moter SE, Simon MM, Ebnet K, Heiberger A and Kramer MD (1990) The Borrelia burgdorferi flagellum-associated 41-kilodalton antigen (flagellin): molecular cloning, expression, and amplification of the gene. Infect Immun;58(6):1711-9. http://www.ncbi.nlm.nih.gov/pubmed/2341173
Clinical Picture
(1) Dressler F, Ackermann R and Steere AC (1994). Antibody Responses to the Three Genomic Groups of Borrelia burgdorferi in European Lyme Borreliosis. The Journal of Infectious Diseases;169(2):313-8. http://www.ncbi.nlm.nih.gov/pubmed/8106763
(2) Cedars Sinal, Tuberculosis: http://www.cedars-sinai.edu/Patients/Health-Conditions/Tuberculosis-TB.aspx
Symptoms/Diagnosis
(1) Steere AC, Coburn J and Glickstein L (2004) The emergence of Lyme disease. J Clin Invest;113(8):1093-101. www.ncbi.nlm.nih.gov/pubmed/15085185
(2) Symptoms, Canadian Lyme Disease Foundation: http://canlyme.com/lyme-basics/symptoms/
(3) Macrophage From Wikipedia http://en.wikipedia.org/wiki/Macrophage Accessed 21st Feb 2012
(4) Borrelia burgdorferi and Lyme Disease Todar’s Online Textbook of Bacteriology. By Kenneth Todar, PhD http://textbookofbacteriology.net/Lyme.html
(5) Giambartolomei GH, Dennis VA, Lasater BL and Philipp MT (1999) Induction of pro- and anti-inflammatory cytokines by Borrelia burgdorferi lipoproteins in monocytes is mediated by CD14. Infect Immun; 67(1):140-7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96289/
(6) “Lyme Disease (Borreliosis): A Plague of Ignorance Regarding the Ignorance of a Plague” by James Scott Taylor (DVM), 2004. http://www.ra-infection-connection.com/Scott%20Taylor%202004%20CHRONIC%20LYME%20DISEASE.html
(7) The Role of Inflammation in Cancer. SA Biosciences. http://www.sabiosciences.com/pathwaymagazine/minireview/cancerinflammation.php
(8) Inflammation. From Wikipedia, http://en.wikipedia.org/wiki/Inflammation Accessed 21st Feb 2012
(9) Autoimmune Disorders. Medline Plus http://www.nlm.nih.gov/medlineplus/ency/article/000816.htm Accessed 21st Feb 2012
(10) The Complexities of Lyme Disease A Microbiology Tutorial: Part 1 By Thomas M. Grier, MS
http://www.lymeneteurope.org/info/the-complexities-of-lyme-disease
Associations/Misdiagnosis of other diseases
(1) Steere AC (1994) Lyme disease: A growing threat to urban populations. Proc Natl Acad Sci; 91(7): 2378-2383. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43375/
(2) Curless RG, Schatz NJ, Bowen BC, Rodriguez Z, Ruiz A. (1996) Lyme neuroborreliosis masquerading as a brainstem tumor in a 15-year-old. Pediatr Neurol ;15(3):258-60. http://www.ncbi.nlm.nih.gov/pubmed/8916168
(3) Oksi J1, Kalimo H, Marttila RJ, Marjamäki M, Sonninen P, Nikoskelainen J, Viljanen MK (1996) Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Brain; 119 (6) : 2143-54. http://www.ncbi.nlm.nih.gov/pubmed/9010017
(4) Reik, L Jr (1993) Stroke due to Lyme disease. Neurology, 43(12):2705-7. http://www.ncbi.nlm.nih.gov/pubmed/8255484
(5) Defer G; Levy R; Brugieres P; Postic D; Degos JD (1993). Lyme disease presenting as a stroke in the vertebrobasilar territory: MRI. Neuroradiology, 35(7):529-31. http://www.ncbi.nlm.nih.gov/pubmed/8232882
(6) Halperin JJ; Golightly M (1992) Lyme borreliosis in Bell’s palsy. Long Island neuroborreliosis collaborative study group. Neurology, 42(7):1268-70 . http://www.ncbi.nlm.nih.gov/pubmed/1620330
(7) Bloom BJ; Wyckoff PM; Meissner HC; Steere AC. (1998) Neurocognitive abnormalities in children after classic manifestations of Lyme disease. Pediatric Infectious Disease Journal, 17(3):189-96. http://www.ncbi.nlm.nih.gov/pubmed/9535244
(8) Mourin S; Bonnier C; Bigaignon G; Lyon G (1993) Epilepsy disclosing neuroborreliosis. Rev Neurol (Paris), 149(8-9):489-91. http://www.ncbi.nlm.nih.gov/pubmed/8009148
(9) Miklossy, J (2011) Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. Journal of Neuroinflammation; 8:90 http://www.jneuroinflammation.com/content/8/1/90
(10) Roelcke U, Barnett W, Wilder-Smith E, Sigmund D, Hacke W (1992) Untreated neuroborreliosis: Bannwarth's syndrome evolving into acute schizophrenia-like psychosis. A case report. J Neurol, Mar; 239(3):129-31. http://www.ncbi.nlm.nih.gov/pubmed/1573415
(11) Fallon BA; Kochevar JM; Gaito A; Nields J (1998) The underdiagnosis of neuropsychiatric Lyme disease in children and adults. Psychiatric Clinics of North America, 21(3):693-703. 1998. http://www.ncbi.nlm.nih.gov/pubmed/9774805
(12) Chmielewska-Badora J, Cisak E, Dutkiewicz J. (2007) Lyme borreliosis and multiple sclerosis: any connection? A seroepidemic study. Ann Agric Environ Med ;7(2):141-3. http://www.ncbi.nlm.nih.gov/pubmed/11153045
(13) Fritzsche M (2005) Chronic Lyme borreliosis at the root of multiple sclerosis--is a cure with antibiotics attainable? Med Hypotheses ; 64(3):438-48. http://www.ncbi.nlm.nih.gov/pubmed/15617845
(14) Reik L Jr; Smith L; Khan A; Nelson W (1985) Demyelinating encephalopathy in Lyme disease.
Neurology, 35(2):267-9. http://www.ncbi.nlm.nih.gov/pubmed/3969220
(15) Cassarino DS; Quezado MM; Ghatak NR; Duray PH (2003) Lyme-associated parkinsonism: a neuropathologic case study and review of the literature. Arch Pathol Lab Med, 127(9):1204-6. http://www.ncbi.nlm.nih.gov/pubmed/12946221
(16) Halperin JJ, Kaplan GP, Brazinsky S, Tsai TF, Cheng T, Ironside A, Wu P, Delfiner J, Golightly M, Brown RH, Dattwlyer RJ, Luft, BJ (1990) Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch Neurol ; 47 (5) 586-94. http://www.ncbi.nlm.nih.gov/pubmed/2334308#
(17) De Cauwer H, Declerck S, De Smet J, Matthyssen P, Pelzers E, Eykens L, Lagrou K. (2009) Motor neuron disease features in a patient with neuroborreliosis and a cervical anterior horn lesion. Act Clin Belg; 64 (3) : 225-7. http://www.ncbi.nlm.nih.gov/pubmed/19670562#
(18) Hansel Y; Ackerl M; Stanek G (1995) ALS-like sequelae in chronic neuroborreliosis. Wien Med Wochenschr, 145(7-8):186-8. http://www.ncbi.nlm.nih.gov/pubmed/7610670
(19) Lo R; Menzies DJ; Archer H; Cohen TJ (2003) Complete heart block due to Lyme carditis. Journal of Invasive Cardiology, 15(6):367-9. http://www.ncbi.nlm.nih.gov/pubmed/12777681
(20) Steere AC; Batsford WP; Weinberg M; Alexander J; Berger HJ; Wolfson S; Malawista SE (1980). Lyme carditis: cardiac abnormalities of Lyme disease. Annals of Internal Medicine, 93(1):8-16. http://www.ncbi.nlm.nih.gov/pubmed/6967274
(21) Nagi KS; Joshi R; Thakur RK (1996) Cardiac manifestations of Lyme disease: a review. Can J Cardiol, 12(5):503-6. http://www.ncbi.nlm.nih.gov/pubmed/8640597
(22) Bacino L; Gazzarata M; Siri G; Cordone S; Bellotti P (2011) Complete atrioventricular block as the first clinical manifestation of a tick bite (Lyme disease). G Ital Cardiol (Rome), 12(3):214-6. http://www.ncbi.nlm.nih.gov/pubmed/21560478
(23) Steere AC (1989) Lyme disease. New England Journal of Medicine, 321(9):586-96. http://www.ncbi.nlm.nih.gov/pubmed/2668764
(24) Oksi J; Mertsola J; Reunanen M; Marjamaki M; Viljanen MK (1994) Subacute multiple-site osteomyelitis caused by Borrelia burgdorferi. Clin Infect Dis, 19(5):891-6. http://www.ncbi.nlm.nih.gov/pubmed/7893875
(25) Steere AC (1988) Pathogenesis of Lyme arthritis Annals NY Academy of Sciences, 539:87-92.
http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1988.tb31841.x/abstract
(26) Willis AA; Widmann RF; Flynn JM; Green DW; Onel KB (2003) Lyme arthritis presenting as acute septic arthritis in children. J Pediatr Orthop, 23(1):114-8. 2003 http://www.ncbi.nlm.nih.gov/pubmed/12499956
(27) Hua B, Li QD, Wang FM, Ai CX, Luo WC (1992) Borrelia burgdorferi infection may be the cause of sarcoidosis. Chin Med J (Engl) Jul;105(7):560-3. http://www.ncbi.nlm.nih.gov/pubmed/1333393
(28) Stinco G, Ruscio M, Proscia D Piccirillo F (2009) Borrelia Infection and Pityriasis Rosea. Acta Derm Venereol ; 89(1):97-8. http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-0544&html=1
(29) BE, Stonehouse A and Studdiford J (2008). Late Diagnosis of Early Disseminated Lyme Disease: Perplexing Symptoms in a Gardner. J Am Board Fam Med. May-Jun;21(3):234-6. http://www.jabfm.org/content/21/3/234.long
(30) Cimperman J; Maraspin V; Lotric-Furlan S; Ruzic-Sabljic E; Avsic-Zupanc T; Strle F (1999) Diffuse reversible alopecia in patients with Lyme meningitis and tick-borne encephalitis. Wien Klin Wochenschr, 111(22-23):976-7. http://www.ncbi.nlm.nih.gov/pubmed/10666812