Neurologic syndromes in Lyme disease.
Chronic fatigue syndrome in patients with Lyme borreliosis.
Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome.
The Fibromyalgia Impact Questionnaire: a useful tool in evaluating patients with post-Lyme disease syndrome.
Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences.
Clinical and neurocognitive features of the post Lyme syndrome.
Sleep quality in Lyme disease.
Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.  1995
Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome. 1994
Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic.
The measurement of fatigue: a new instrument.
Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis.
The overdiagnosis of Lyme disease.
Rheumatic fever and disorders of the musculoskeletal system.
Non-Lyme disease.

Pol Merkuriusz Lek 2000 Aug;9(50):584-8
[Neurologic syndromes in Lyme disease].
Zajkowska JM, Hermanowska-Szpakowicz T, Kondrusik M, Pancewicz SA. Kliniki Chorob Pasozytniczych i Neuroinfekcji AM w Bialymstoku.

Lyme borreliosis, multisystem disease, when involve neurologic system is named neuroborrelosis. Symptomatology of neuroborreliosis is rich and various. Difficulties in recognition are connected usually with long period from tick bite to late neurological signs. Any headache and psychiatric disorder in the course of Lyme disease could be an early manifestation of invasion of the CNS by the spirochaetes. Each part of neurologic system could be involved. The most common clinical picture of neuroborreliosis is meningitis with cranial or peripheral neuropathies connected with radiculalgia, less common are encephalitis and myelitis, neuropathies and polyneuropathies, encephalopathies. Encephalomyelitis is the most serious form of neuroborreliosis. From the pathophysiologic point of view all cranial and peripheral neuropathies are forms of mononeuritis multiplex. Vasculitis and autoimmunology processes are present. Encephalopathy is due to neuroimmunomodulators, like lymphokines and by toxico-metabolic effect could be connected with each form of systemic borreliosis. Spheroplast L-form of borrelia could be responsible for difficulties with their eradication. Diagnosis of neuroborreliosis is based on culturing of B. burgdorferi from CSF, detection of specific antispirochaetal antibodies produced in subarachnoid space, detection of activated lymphocytes, other antigens detection in CSF (also after dissociation of complexes) or borrelial DNA sequences.
Publication Types:

Review

Review, tutorial

PMID: 11081332

Eur Neurol 2000;43(2):107-9
Chronic fatigue syndrome in patients with Lyme borreliosis.
Treib J, Grauer MT, Haass A, Langenbach J, Holzer G, Woessner R. Department of Neurology, University Hospital of the Saarland, Homburg, Germany.

Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme borreliosis in the past. To further investigate this suspicion of an association without sample bias, we carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies. Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in patients with chronic fatigue syndrome and positive Borrelia serology. Copyright 2000 S. Karger AG, Basel.
Publication Types:

Clinical trial

Randomized controlled trial

PMID: 10686469

Neurology 1999 Oct 12;53(6):1340-1
Absence of Borrelia burgdorferi-specific immune complexes in chronic fatigue syndrome.
Schutzer SE, Natelson BH. Department of Medicine, University of Medicine and Dentistry, New Jersey Medical School, Newark 07103, USA. schutzer@umdnj.edu

Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue, contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients and controls were nonreactive. Centers for Disease Control and Prevention-defined CFS patients lacking antecedent signs of Lyme disease--erythema migrans, Bell's palsy, or large joint arthritis--are not likely to have laboratory evidence of Bb infection.
PMID: 10522896

Arthritis Care Res 1999 Feb;12(1):42-7
The Fibromyalgia Impact Questionnaire: a useful tool in evaluating patients with post-Lyme disease syndrome.
Fallon J, Bujak DI, Guardino S, Weinstein A. Leinhard School of Nursing, Pace University, Pleasantville, New York, USA.

OBJECTIVE: To determine the reliability and validity of a modified version of the Fibromyalgia Impact Questionnaire (FIQ) in evaluating patients with post-Lyme disease syndrome (PLDS). METHODS: In this cross-sectional analysis 13 PLDS, 18 fibromyalgia (FM), and 16 healthy controls (n = 47) completed a modified FIQ containing items to evaluate physical impairment, symptom severity, and global well-being. Comparisons between groups were done using analysis of variance with a significance level set at 0.05. RESULTS: PLDS patients demonstrated statistically significantly greater levels of impairment than controls in physical functioning, FIQ total score, global well-being, joint pain, fatigue, depression, ability to perform activities of daily living, and memory/concentration. FM patients demonstrated a statistically significantly greater level of impairment than the control group in all categories, and the scores were significantly higher than the PLDS group in the measurement of physical impairment, FIQ total score, muscle pain, and joint pain. Overall, the instrument possesses good reliability and validity, although adequacy of this instrument to measure impairment in the male PLDS population needs further elucidation. CONCLUSION: The results of this study suggest that the modified FIQ may be a useful tool in evaluating PLDS patients. The findings suggest that there may be some differences in the etiopathology of the symptoms experienced by PLDS and FM patients.
PMID: 10513489

Arch Neurol 1997 Nov;54(11):1372-6
Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences.
Gaudino EA, Coyle PK, Krupp LB. Department of Neurology, State University of New York at Stony Brook, USA.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) and post-Lyme syndrome (PLS) share many features, including symptoms of severe fatigue and cognitive difficulty. OBJECTIVE: To examine the neuropsychiatric differences in these disorders to enhance understanding of how mood, fatigue, and cognitive performance interrelate in chronic illness. METHODS: Twenty-five patients with CFS, 38 patients with PLS, and 56 healthy controls participated in the study. Patients with CFS met 1994 criteria for CFS and lacked histories suggestive of Lyme disease. Patients with PLS were seropositive for Lyme disease, had met the Centers for Disease Control and Prevention criteria, or had histories strongly suggestive of Lyme disease and were experiencing severe fatigue that continued 6 months or more following completion of antibiotic treatment for Lyme disease. All subjects completed self-report measures of somatic symptoms and mood disturbance and underwent neuropsychological testing. All patients also underwent a structured psychiatric interview. RESULTS: Patients with CFS and PLS were similar in several somatic symptoms and in psychiatric profile. Patients with CFS reported more flulike symptoms than patients with PLS. Patients with PLS but not patients with CFS performed significantly worse than controls on tests of attention, verbal memory, verbal fluency, and motor speed. Patients with PLS without a premorbid history of psychiatric illness did relatively worse on cognitive tests than patients with PLS with premorbid psychiatric illness compared with healthy controls. CONCLUSIONS: Despite symptom overlap, patients with PLS show greater cognitive deficits than patients with CFS compared with healthy controls. This is particularly apparent among patients with PLS who lack premorbid psychiatric illness.
PMID: 9362985

J Rheumatol 1996 Aug;23(8):1392-7
Clinical and neurocognitive features of the post Lyme syndrome.
Bujak DI, Weinstein A, Dornbush RL. Department of Medicine, New York Medical College, Valhalla 10595, USA.

OBJECTIVE: To evaluate neurocognitive impairment in patients with persistent arthralgia, fatigue, and subjective memory loss in patients after Lyme disease (post-Lyme syndrome, PLS). METHODS: We compared the clinical, neurocognitive, and psychological features of 23 patients with PLS to 23 age, sex, and education matched recovered patients (REC). All met Centers for Disease Control criteria for Lyme disease, were ELISA positive at onset of Lyme disease and were previously treated with standard antibiotic regimens. RESULTS: Of the patients with PLS, 7 (30%) had fibromyalgia (FM), 3 (13%) had chronic fatigue syndrome, and 10 (43%) had similar but milder symptoms but did not meet the criteria for either. 22 of 23 patients with PLS complained of decreased memory or concentration problems. Patients with PLS had significantly lower scores on the attention/concentration scale (p = 0.012) of the Wechsler Memory Scale-Revised (WMS-R), indicating lowered attention/concentration. 52% of patients with PLS and 35% in the REC group had significantly lower (p < 0.05) WMS-R verbal memory scores than visual memory scores. The PLS group had subjectively more problems with sleep and mood changes and higher scores on several scales of Symptom Check List 90-R (p < 0.01), indicating greater physical distress. Beck Depression Inventory scores were also higher for the PLS than the REC group (p < 0.005), but were within the normal range. CONCLUSION: Despite antibiotic treatment, a sequelae of Lyme disease may be a PLS characterized by persistent arthralgia, fatigue, and neurocognitive impairment that is probably induced by Lyme disease.
PMID: 8856619

Sleep 1995 Dec;18(10):912-6
Sleep quality in Lyme disease.
Greenberg HE, Ney G, Scharf SM, Ravdin L, Hilton E. Sleep-Wake Disorders Center, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York, USA.

Complaints of chronic fatigue as well as sleep disturbances are prevalent in Lyme disease. We compared polysomnographic measures of sleep in patients with documented Lyme disease with those of a group of age-matched normal control subjects. Eleven patients meeting Centers for Disease Control criteria for late Lyme disease with serologic confirmation by enzyme-linked immunosorbent assay and Western blot without a history of other medical or psychiatric illness and 10 age-matched control subjects were studied. Lyme disease patients and controls underwent 2 nights of polysomnography. Multiple sleep latency testing (MSLT) was performed in the patients. Sleep was staged by standard criteria, and continuity of sleep was assessed for each stage of frequency analysis of consecutive epochs. All patients studied reported sleep-related complaints, including difficulty initiating sleep (27%), frequent nocturnal awakenings (27%), excessive daytime somnolence (73%) and restless legs/nocturnal leg jerking (9%). Greater sleep latency, decreased sleep efficiency and a greater arousal index were noted in Lyme patients. The median length of uninterrupted occurrences of stage 2 and stage 4 non-rapid eye movement (NREM) sleep was less in Lyme patients (6.3 +/- 3.0 epochs in patients vs. 11.4 +/- 4.4 epochs in controls for stage 2, p < 0.01, and 4.3 +/- 4.4 epochs in patients vs. 11.2 +/- 6.3 epochs in controls for stage 4, p < 0.01), indicating greater sleep fragmentation. Mean sleep onset latency during the MSLT was normal (12.7 +/- 5.6 minutes). Three patients demonstrated alpha-wave intrusion into NREM sleep. These sleep abnormalities may contribute to the fatigue and sleep complaints common in this disease.
PMID: 8746401

Curr Opin Rheumatol 1995 Mar;7(2):127-35
Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.
Goldenberg DL. Newton-Wellesley and Tufts University School of Medicine, Massachusetts, USA.

Two important studies in which nuclear magnetic resonance spectroscopy was used convincingly demonstrated that muscle is not the primary pathologic factor in fibromyalgia. There were further studies reporting that fibromyalgia-chronic fatigue syndrome may follow well treated Lyme disease or mimic Lyme disease. The longest therapeutic trial to date in fibromyalgia demonstrated an initial modest effect of tricyclic medications, but at 6 months that efficacy was no longer evident. Investigation in both fibromyalgia and chronic fatigue syndrome now focuses on the central nervous system. The use of new technology, eg, neurohormonal assays and imaging such as single-photon emission computed tomography scan, may be important in understanding these elusive conditions.
Publication Types:

Review

Review, tutorial

PMID: 7766493

Curr Opin Rheumatol 1994 Mar;6(2):223-33
Fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome.
Goldenberg DL. Newton-Wellesley Hospital, Massachusetts.

No major pathophysiologic or therapeutic findings have appeared over the past year regarding fibromyalgia, chronic fatigue syndrome, and myofascial pain syndrome, three poorly understood, controversial, and overlapping syndromes. The frequent prevalence of these disorders in association with Lyme disease and other medical and psychiatric illness was emphasized. New studies demonstrated the potential role for central nervous system activation in fibromyalgia and chronic fatigue syndrome.
Publication Types:

Review

Review, tutorial

PMID: 8024971

Clin Infect Dis 1994 Jan;18 Suppl 1:S24-7
Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic.
Coyle PK, Krupp LB, Doscher C, Amin K. Department of Neurology, Health Sciences Center, SUNY, Stony Brook 11794.

Borrelia burgdorferi is the pathogen that causes Lyme disease. Patients frequently experience fatigue and malaise that can persist after antibiotic treatment. This study examined serological reactivity to B. burgdorferi in patients with chronic fatigue who were from a region in which Lyme disease is endemic. Blood and CSF were collected from patients without a history of infection due to B. burgdorferi (n = 12) and patients with persistent fatigue after antibiotic treatment of Lyme disease (n = 13). Serum and CSF were examined by ELISA for antibodies to B. burgdorferi, and routine studies of CSF were done. In the first group, one patient (8%) was seropositive; no patients had detectable antibodies in CSF. In the second group, nine patients (69%) were seropositive or borderline seropositive; seven (54%) had detectable antibodies in CSF. Unexplained abnormalities in CSF were noted in 42% and 31% of patients in each group, respectively. In this study positive serologies for Lyme disease were not found at a higher than expected rate for patients from a region of Lyme disease endemicity who had idiopathic chronic fatigue. Fatigued patients did show a surprisingly high rate of unexplained minor CSF abnormalities suggestive of CNS or meningeal dysfunction.
PMID: 8148448

J Psychosom Res 1993 Oct;37(7):753-62
The measurement of fatigue: a new instrument.
Schwartz JE, Jandorf L, Krupp LB. Department of Psychiatry and Behavioral Science, SUNY-Stony Brook 11794-8121.

Fatigue is a frequent medical symptom which has not been routinely measured. We present a 29-item fatigue assessment instrument, describe its psychometric properties, and use it to differentiate normal fatigue from fatigue related medical disorders. Differences in fatigue across a variety of medical disorders, the reproducibility of the fatigue instrument, and its convergent validity with other fatigue measures are also described.
PMID: 8229906

Ann Intern Med 1993 Sep 15;119(6):503-9

Comment in:

Ann Intern Med. 1993 Sep 15;119(6):518

Ann Intern Med. 1993 Sep 15;119(6):528-9

Empiric parenteral antibiotic treatment of patients with fibromyalgia and fatigue and a positive serologic result for Lyme disease. A cost-effectiveness analysis.
Lightfoot RW Jr, Luft BJ, Rahn DW, Steere AC, Sigal LH, Zoschke DC, Gardner P, Britton MC, Kaufman RL. Division of Rheumatology, Kentucky Clinic J515, University of Kentucky Medical Center, Lexington 40536-0284.

PURPOSE: To examine the cost-effectiveness of empirical, parenteral antibiotic treatment of patients with chronic fatigue and myalgia and a positive serologic result for Lyme disease who lack classic manifestations. DATA SOURCES: Peer-reviewed journals, opinion of experts in the field, and published epidemiologic reports. STUDY SELECTION: Consensus by authors on articles that indicated methods for patient selection; on criteria used for diagnosis; on immunologic methods used for classifying patients; on the dose and duration of therapy; and on criteria by which responses to therapy were ascertained. DATA EXTRACTION: In a cost-effectiveness model, the costs and benefits of empirical parenteral therapy for patients seropositive for Lyme disease were compared with a strategy in which only patients having classical symptoms of Lyme disease were treated. DATA SYNTHESIS: In areas endemic for Lyme disease, the incidence of false-positive serologic results in patients with nonspecific myalgia or fatigue exceeds by four to one the incidence of true-positive results in patients with nonclassical infections. Treatment of the former group of patients costs $86,221 for each true-positive patient treated. The empirical strategy causes 29 cases of drug toxicity for every case in the more conservative strategy. If patients were willing to pay $3485 to eliminate anxiety about not treating possible true Lyme disease, the empirical strategy would break even. CONCLUSION: For most patients with a positive Lyme antibody titer whose only symptoms are nonspecific myalgia or fatigue the risks and costs of empirical parenteral antibiotic therapy exceed the benefits. Only when the value of patient anxiety about leaving a positive test untreated exceeds the cost of such therapy is the empirical treatment cost-effective.
Publication Types:

Meta-analysis

PMID: 8357117

JAMA 1993 Apr 14;269(14):1812-6

Comment in:

JAMA. 1993 Dec 8;270(22):2682-3

JAMA. 1993 Dec 8;270(22):2682; discussion 2683

JAMA. 1993 Dec 8;270(22):2683

The overdiagnosis of Lyme disease.
Steere AC, Taylor E, McHugh GL, Logigian EL. Division of Rheumatology/Immunology, New England Medical Center, Boston, MA 02111.

OBJECTIVE--To analyze the diagnoses, serological test results, and treatment results of the patients evaluated in a Lyme disease clinic, both prior to referral and from current evaluation. DESIGN--Retrospective case survey of prescreened patients. SETTING--Research and diagnostic Lyme disease clinic in a university hospital. PATIENTS--All 788 patients referred to the clinic during a 4.5-year period who were thought by the referring physician or the patient to have a diagnosis of Lyme disease. MAIN OUTCOME MEASUREMENTS--Symptoms and signs of disease, immunodiagnostic tests of Lyme disease, and tests of neurological function. RESULTS--Of the 788 patients, 180 (23%) had active Lyme disease, usually arthritis, encephalopathy, or polyneuropathy. One hundred fifty-six patients (20%) had previous Lyme disease and another current illness, most commonly chronic fatigue syndrome or fibromyalgia; and in 49 patients, these symptoms began soon after objective manifestations of Lyme disease. The remaining 452 patients (57%) did not have Lyme disease. The majority of these patients also had the chronic fatigue syndrome or fibromyalgia; the others usually had rheumatic or neurological diseases. Of the patients who did not have Lyme disease, 45% had had positive serological test results for Lyme disease in other laboratories, but all were seronegative in our laboratory. Prior to referral, 409 of the 788 patients had been treated with antibiotic therapy. In 322 (79%) of these patients, the reason for lack of response was incorrect diagnosis. CONCLUSIONS--Only a minority of the patients referred to the clinic met diagnostic criteria for Lyme disease. The most common reason for lack of response to antibiotic therapy was misdiagnosis.
PMID: 8459513

Curr Opin Rheumatol 1992 Oct;4(5):718-24
Rheumatic fever and disorders of the musculoskeletal system.
Coovadia HM. University of Natal Medical School, Durban, Congella, South Africa.

New information provided on the pathogenesis and management of rheumatic fever is of current interest. Invasive disease by group A streptococci has been shown to be due to production of toxin A. The natural history and immunopathologic basis for chronic Lyme arthritis are reported. Attention is drawn to pyomyositis and clinical presentation of chronic fatigue syndrome in children. Patients with Sweet's syndrome often have antineutrophil cytoplasmic autoantibodies. Biopsy specimens of panniculitis should be taken to aid treatment. Long-term outcome in chronic osteomyelitis is favorable; recommendations on the rational use of imaging have been reported.
Publication Types:

Review

Review, tutorial

PMID: 1419508

J S C Med Assoc 1991 Aug;87(8):433-6

Non-Lyme disease.
Bryan CS.

Four syndromes of non-Lyme disease are described on the basis of the history and serologic test result. Recognition of non-Lyme disease enables the physician to avoid unnecessary treatment and to keep considering the possibility of alternative diagnoses.
PMID: 1943031