minocycline and Fatigue-Syndrome--Chronic

Topics: Fatigue; Fatigue Syndrome, Chronic; Humans; Minocycline

Objective Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been suggested to be the main cause of chronic fatigue syndrome. In animal models of chronic fatigue, minocycline was reported to act as a suppressor of neural inflammation. Minocycline may thus exert favorable therapeutic effects in patients with ME. Methods Oral minocycline (100 mg×2 on the first day, followed by 100 mg/day for 41 days) was administered to 100 patients with ME. The performance status score (0-9), orthostatic intolerance during the 10-min standing test, neurologic disequilibrium, and neuropathic pain were compared before and after treatment. Results After therapy completion, favorable effects were observed with a decrease in the performance status score of ≥2 points in 27 patients (27%). Before treatment, 6 of the 27 patients had orthostatic intolerance with an inability to complete the 10-min standing test; after treatment, this symptom resolved in 4 and improved in 2 patients. In addition, after treatment, postural orthostatic tachycardia resolved in five of eight patients, disequilibrium resolved in five of eight patients, and fibromyalgia or neuropathic pain was attenuated in four of five patients. The favorable effects appeared dependent on a shorter disease duration, primarily for a duration of less than three years and most frequently within six months of the disease onset. However, acute adverse effects with nausea and/or dizziness caused 38 patients (38%) to discontinue treatment in the first few days. Conclusion Oral minocycline therapy may be an effective treatment option for patients with ME, especially in the initial stage of the disease.

Topics: Dizziness; Fatigue Syndrome, Chronic; Humans; Minocycline; Orthostatic Intolerance; Sensation Disorders

Patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) display multiple symptoms, such as chronic widespread pain, fatigue, sleep disturbance, and cognitive dysfunction. Abnormal pain sensation may be the most serious of these symptoms; however, its pathophysiology remains unknown. To provide insights into the molecular basis underlying abnormal pain in CFS and FMS, we used a multiple continuous stress (CS) model in rats, which were housed in a cage with a low level of water (1.5 cm in depth). The von Frey and Randall-Seritto tests were used to evaluate pain levels. Results showed that mechanical allodynia at plantar skin and mechanical hyperalgesia at the anterior tibialis (i.e., muscle pain) were induced by CS loading. Moreover, no signs of inflammation and injury incidents were observed in both the plantar skin and leg muscles. However, microglial accumulation and activation were observed in L4-L6 dorsal horn of CS rats. Quantification analysis revealed a higher accumulation of microglia in the medial part of Layers I-IV of the dorsal horn. To evaluate an implication of microglia in pain, minocycline was intrathecally administrated (via an osmotic pump). Minocycline significantly attenuated CS-induced mechanical hyperalgesia and allodynia. These results indicated that activated microglia were involved in the development of abnormal pain in CS animals, suggesting that the pain observed in CFS and FMS patients may be partly caused by a mechanism in which microglial activation is involved.

Topics: Animals; Central Nervous System Agents; Disease Models, Animal; Fatigue Syndrome, Chronic; Hyperalgesia; Immunohistochemistry; Male; Microglia; Minocycline; Muscle, Skeletal; Neuroimmunomodulation; Pain Measurement; Random Allocation; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord Dorsal Horn; Stress, Psychological; Touch

To examine whether Coxiella burnetii (C. burnetii) is involved in chronic fatigue syndrome (CFS), we administered tetracycline antibiotics to subjects with CFS, and followed changes in clinical symptoms, PCR findings, and C. burnetii antibody titers.. The subjects were 8 patients with CFS and 213 with nonspecific complaints such as chronic fatigue and low-grade fever for several months or longer but not meeting the diagnostic criteria for CFS. All were examined for C. burnetii infection by nested PCR and the indirect immunofluorescence test (IF).. Four CFS patients (the CFS group) and 54 controls [the post-Q fever fatigue syndrome (QFS) group] positive for C. burnetii were treated mainly with minocycline or doxycycline (100 mg/day) for 3 months. After treatment, all 58 patients tested negative for C. burnetii infection. In the CFS group, no significant difference was noted between the mean pre- and post-treatment temperatures or headache scores. Similarly, there was no significant improvement in performance status (PS) scores. In the QFS group, however, mean temperatures and headache scores were significantly decreased after treatment (p<0.001). PS scores were also improved.. These results suggest the possibility of direct involvement of C. burnetii in the pathological state of CFS to be low, despite the C. burnetii infection rate being high in CFS patients. This is a pilot study and further larger investigations are necessary to confirm our preliminary results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibodies, Bacterial; Child; Coxiella burnetii; DNA, Bacterial; Doxycycline; Fatigue Syndrome, Chronic; Female; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Humans; Male; Middle Aged; Minocycline; Ofloxacin; Pilot Projects; Polymerase Chain Reaction; Q Fever; Retrospective Studies; Treatment Outcome

Topics: Adult; Coxiella burnetii; Fatigue Syndrome, Chronic; Female; Humans; Incidence; Middle Aged; Minocycline; Pregnancy; Prognosis; Q Fever; Risk Assessment

To address the presence of post-Q fever fatigue syndrome (post-QFS) in Japan, and to evaluate the efficacy of minocycline for this condition.. In 20 Coxiella burnetii (C. burnetii) seropositive patients with persistent nonspecific symptoms including general fatigue, low-grade fever, myalgia and arthralgia, changes in subjective symptoms, C. burnetii antibody titers and C. burnetii DNA were evaluated after antibiotic treatment.. After treatment mainly with minocycline (100 mg/day for 3 months), the clinical picture improved in all 20 patients as evidenced by decreases in body temperature (13/17), general fatigue (20/20) and headache (9/12). The mean performance status (PS) score improved from 5.0 to 1.8 (p<0.01). All 7 who had been positive for C. burnetii DNA, became negative together with an improvement in subjective symptoms. Indirect immunofluorescence tests demonstrated 6 of the 20 patients to be positive for C. burnetii IgM antibody to phase II antigen (1:32), and 18 to be positive for IgG antibody (1:128, 1:256). Antibody titers of both IgM (6/6, 1:16) and IgG (18/18, 1:16) decreased markedly after treatment.. These results of an open label study in Japan suggest that minocycline administration is useful for improving chronic nonspecific symptoms considered to be post-Q fever fatigue syndrome caused by C. burnetii infection.

Topics: Adult; Antibodies, Bacterial; Coxiella burnetii; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue Syndrome, Chronic; Female; Follow-Up Studies; Humans; Japan; Long-Term Care; Male; Minocycline; Polymerase Chain Reaction; Probability; Q Fever; Risk Assessment; Statistics, Nonparametric; Treatment Outcome