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Electron micrograph of muscle tissue from a healthy control (A) and from a subject with FM (B) showing zig-zagging of the Z bands. L shows a lipid droplet. M and the white arrow shows a mitochondrion (A). There are no mitochondria in the selected anatomical region of the subject with FM (B). (Original magnification 6 8400.)
Source publication
To determine whether there is evidence of increased DNA fragmentation and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM) compared with healthy controls.
Muscle tissues from 10 community residents with FM and 10 age and sex matched healthy controls were examined "blindly" for the presence of DNA fragmentation by two diff...
Context in source publication
Context 1
... by Gavrieli et al was used to perform this procedure. 31 Snap frozen muscle tissue sections (6 m m) were fixed in 10% buffered formalin (Fisher Scientific, Norcross, GA) for 30 minutes. The slides were washed six times with double distilled water (Fisher Scientific, Norcross, GA), then subjected to proteinase K digestion (10 m g/ml; Boehringer, Germany) at room temperature for 5 minutes. The slides were washed again with double distilled water and incubated with freshly prepared deoxynucleotidyl transferase (TdT) reaction mix (0.3 m l TdT (20 U/ m l), 4.0 m l 5 6 TdT buffer (both from Promega, Madison, WI), and digoxigenin-1 1-dUTP (Boehringer, Germany)) at 37 ̊ C for 1 hour. After washing with Dulbecco’s phosphate buffered salt solution (1 6 phosphate buffered saline), non-specific binding was blocked with 2% horse serum at room temperature for 30 minutes. Next, the incorporated digoxigenin-dUTP was detected by incubation with anti-digoxigenin-AP, Fab fragments (Boehringer, Germany) 1:100 in phosphate buffered saline at room temperature for 45 minutes. Visualisation of the reaction product was performed with Sigma FAST BCIP/ NBT buffered substrate tablet (Sigma BioSciences, St Louis, MO). Each tissue section was analysed for DNA fragmentation in the nuclei of muscle cells in at least 20 areas by two ‘‘blinded’’ investigators (HS, SS). The original magnification for nuclei counting was 6 200. The mean number of counted cells with stained DNA fragments was then calculated. This procedure was performed to confirm the data from the Klenow kit. Immediately after surgical removal of the muscle tissue specimens, they were fixed in 3% glutaraldehyde in 0.1 M cacodylate buffer, pH 7.35, at 4 ̊ C for 1 hour. The tissue was washed in the same buffer at 4 ̊ C, cut into slices 0.5 mm thick, post-fixed in 1% osmium tetroxide in 0.1 M cacodylate buffer at room temperature for 1 hour, dehydrated in graded ethanol and propylene oxide, and embedded in Spurr resin. 32 Ten non-numbered embedding procedures were performed with each tissue specimen. The slides were cured overnight in a 60 ̊ C oven and afterwards the capsules were snapped off. The examiner randomly chose three of 10 possible sections for cutting. Semithin sections were stained with 1% toluidine blue, longitudinal sections were identified, and the blocks were randomly trimmed for ultrathin sectioning. Ultrathin sections were made with a diamond knife on an LKB ultratome and then stained with uranyl acetate and lead citrate. Ten sections of each tissue were examined at 75 kV in a Hitachi H7000 electron microscope. A final magnification of 2.2 6 14 000 was used for determining the number of mitochondria and structural features in all samples. Two investigators independently counted the mitochondria without knowing the origin of the samples, and the average of the two readings was used to calculate group means. The counts for mitochondria of the subjects with FM and the healthy controls then were compared using the non- parametric Mann-Whitney test for independent samples (SPSS for Windows version 7.5.2G, SPSS Inc, Chicago, IL). All other statistical comparisons were performed using Student’s t test. An a level of 0.05 was used for all comparisons. The subjects with FM exhibited significantly lower mean (SEM) pressure pain thresholds (2.47 (0.23) kg/1.54 cm 2 ) at the ACR tender points than the controls (4.13 (0.45) kg/ 1.54 cm 2 ) (p = 0.009). In addition, the subjects with FM produced a mean (SEM) total score on the McGill Pain Questionnaire (25.02 (4.52)) and displayed a significantly higher mean score on the Fatigue Severity Scale (5.09 ¡ 0.35) than the controls (2.51 ¡ 0.32; p = 0.001). Light microscopy showed no histological features indicative of myopathy, polymyositis, or denervation processes in any of the subjects. Succinate dehydrogenase and NADH stainings showed no abnormal findings except type II fibre atrophy in one of the subjects of each group. However, our primary finding was produced by the enzymatic detection method, which showed increased DNA fragmentation in the muscle tissue of the subjects with FM compared with the muscle tissue of healthy subjects (fig 1). Among the subjects with FM, 55% of the muscle cell nuclei were positive for DNA fragmentation as compared with 16% in the controls (table 3). Contrary to our expectation, electron microscopy did not reveal the typical features of apoptosis. There was no evidence of chromatin condensation, nuclear fragmentation, plasma membrane blebbing, or cell shrinkage in any of the muscle specimens. However, because the enzymatic DNA fragmentation assays both showed positive results it must be concluded that the positive DNA fragmentation in nuclei of FM muscle cells does not reflect apoptosis. Nevertheless, electron microscopy did find several abnormalities in the muscle tissue of the subjects with FM. The myofibres and actin filaments were disorganised in all samples from these 10 subjects (fig 2). Interfibrillar lipid and lipofuscin deposits were also seen in the tissue of all subjects with FM. Interfibrillar glycogen was found in the tissue of five of the subjects with FM, and moth-eaten destruction of muscle fibres appeared in the tissue of three of these subjects. In contrast, no myofibre disorganisation was seen in the tissue of any of the healthy controls. Only 2 of the 10 controls showed glycogen in their tissue and only one showed an accumulation of lipid or other tissue abnormalities (fig 3). Electron microscopy also disclosed substantial differences in the number and shape of the mitochondria seen in the muscle tissue specimens between the subjects with FM and the controls. Specifically, the mean (SEM) number of mitochondria found in the muscle tissue of the subjects with FM (7.0 (1.2)) was significantly lower than that found in the muscle tissue of the healthy controls (11.9 (1.0); p = 0.019) (figs 2, 3 and table 4). Moreover, the mitochondria found in the tissue of the subjects with FM (for example, fig 3D) were substantially larger than those in the tissue of the controls (for example, fig 3A). As far as we know this is the first study to show evidence of abnormal DNA fragmentation in the muscle tissue of subjects with FM. Given that FM is associated with enhanced NO levels in circulating blood 19 33 and cerebrospinal fluid, 18 we expected to find evidence of apoptosis in the muscle tissue of our subjects with FM. However, electron microscopy did not identify any of the hallmarks of apoptosis. It must be concluded, then, that increased DNA fragmentation in FM muscle tissues does not reflect apoptosis. Persistent focal contractions in muscle may contribute to ultrastructural tissue abnormalities as ...
Citations
... 8 A drop in pH is probably one of the main activators of peripheral nociceptors, as many painful disturbances of muscle are associated with low pH in muscle tissue. 9 These receptor molecules are channel proteins that span the membrane of the nerve ending and mainly permit Na+ ions to enter the neuron. These Na+ ions then induce neural excitation. ...
Paraspinal spasm is a cramp or "knots," or a finding of splinting, tightness, or decreased range of motion on physical examination. In advancing year of life, paraspinal muscle spasms are becoming a significant source of discomfort, pain and disabiling conditions. Katigraha is a condition which is characterized by Shoola and Stabdhata in Kati Pradesha due to vitiated Vata. It is one of the Nanatmaja vatavyadhi mentioned by Acharya Sharangadhara. It is a common health problem among adults of working age population, and its prevalence or incidence increases with increasing age. 50-80% of adults experience at some point in their life. Lower back spasms can stem from various causes such as poor posture, back injury, lumbar sprains/strains, disc protrusion or rupture, anxiety, and dehydration. They can be sensitized and activated by strong mechanical stimuli, such as trauma or mechanical overloading, as well as by endogenous inflammatory mediators including bradykinin (BK), serotonin, and prostaglandin E2 (PGE2). Vata is gets aggravated by the Avarana or depletion of the Dhatus. So, the treatment like Abhyanga, Swedana, Mridu Virechana, Basti Karma, Upanaha, Bandhan, Lepa, Raktamokshsna and Agnikarma helps in the alleviating the Vata. The present article is an attempt to understand the causes, pathophysiology, symptoms and treatment of Lumber Para Spinal Muscles Spasm W.S.R. Katigraha.
... Mitochondrial pathology, also suggested to be a part of the pathophysiology of FM [12][13][14][15][16], would be an intriguing explanation tying together exercise intolerance and the muscle symptoms of FM. The reason for these putative mitochondrial alterations is not known, and most of the studies do not account for physical activity. ...
Background:
Patients with fibromyalgia (FM) exhibit low peak oxygen uptake ([Formula: see text]O2peak). We aimed to detect the contribution of cardiac output to ([Formula: see text]) and arteriovenous oxygen difference [Formula: see text] to [Formula: see text] from rest to peak exercise in patients with FM.
Methods:
Thirty-five women with FM, aged 23 to 65 years, and 23 healthy controls performed a step incremental cycle ergometer test until volitional fatigue. Alveolar gas exchange and pulmonary ventilation were measured breath-by-breath and adjusted for fat-free body mass (FFM) where appropriate. [Formula: see text] (impedance cardiography) was monitored. [Formula: see text] was calculated using Fick's equation. Linear regression slopes for oxygen cost (∆[Formula: see text]O2/∆work rate) and [Formula: see text] to [Formula: see text]O2 (∆[Formula: see text]/∆[Formula: see text]O2) were calculated. Normally distributed data were reported as mean ± SD and non-normal data as median [interquartile range].
Results:
[Formula: see text]O2peak was lower in FM patients than in controls (22.2 ± 5.1 vs. 31.1 ± 7.9 mL∙min-1∙kg-1, P < 0.001; 35.7 ± 7.1 vs. 44.0 ± 8.6 mL∙min-1∙kg FFM-1, P < 0.001). [Formula: see text] and C(a-v)O2 were similar between groups at submaximal work rates, but peak [Formula: see text] (14.17 [13.34-16.03] vs. 16.06 [15.24-16.99] L∙min-1, P = 0.005) and C(a-v)O2 (11.6 ± 2.7 vs. 13.3 ± 3.1 mL O2∙100 mL blood-1, P = 0.031) were lower in the FM group. No significant group differences emerged in ∆[Formula: see text]O2/∆work rate (11.1 vs. 10.8 mL∙min-1∙W-1, P = 0.248) or ∆[Formula: see text]/∆[Formula: see text]O2 (6.58 vs. 5.75, P = 0.122) slopes.
Conclusions:
Both [Formula: see text] and C(a-v)O2 contribute to lower [Formula: see text]O2peak in FM. The exercise responses were normal and not suggestive of a muscle metabolism pathology.
Trial registration:
ClinicalTrials.gov, NCT03300635. Registered 3 October 2017-Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03300635 .
... MiR-374b-5p is also predicted to target CCL2 gene that codes for MCP-1 which has also been reported to be elevated in FM 41 (Fig. 6). It was proposed that the elevation of MCP-1 may be related to abnormalities in energy metabolism found in biopsy specimens of tender areas of FM patients because MCP-1 was shown to reduce insulin-stimulated glucose uptake in skeletal muscles 41,43 . www.nature.com/scientificreports/ ...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and fibromyalgia (FM) are two chronic complex diseases with overlapping symptoms affecting multiple systems and organs over time. Due to the absence of validated biomarkers and similarity in symptoms, both disorders are misdiagnosed, and the comorbidity of the two is often unrecognized. Our study aimed to investigate the expression profiles of 11 circulating miRNAs previously associated with ME/CFS pathogenesis in FM patients and individuals with a comorbid diagnosis of FM associated with ME/CFS (ME/CFS + FM), and matched sedentary healthy controls. Whether these 11 circulating miRNAs expression can differentiate between the two disorders was also examined. Our results highlight differential circulating miRNAs expression signatures between ME/CFS, FM and ME/CFS + FM, which also correlate to symptom severity between ME/CFS and ME/CFS + FM groups. We provided a prediction model, by using a machine-learning approach based on 11 circulating miRNAs levels, which can be used to discriminate between patients suffering from ME/CFS, FM and ME/CFS + FM. These 11 miRNAs are proposed as potential biomarkers for discriminating ME/CFS from FM. The results of this study demonstrate that ME/CFS and FM are two distinct illnesses, and we highlight the comorbidity between the two conditions. Proper diagnosis of patients suffering from ME/CFS, FM or ME/CFS + FM is crucial to elucidate the pathophysiology of both diseases, determine preventive measures, and establish more effective treatments.
... 3) Decreased peripheral blood flow in fibromyalgia patients was found, which suggests there are functional disturbances in their cardiovascular system (19). 4) In muscles of fibromyalgia patients, increased DNA fragmentation and ultrastructural changes are suggested to be secondary to chronic muscle contraction (20). 5) In a biopsy study of fibromyalgia patients, peripheral fibroblast transforming growth factor-β gene expression is significantly higher compared to controls (21). ...
Acupuncture is a minimally invasive therapeutic method that uses small caliber needles while inserting them through the skin into various areas of the body. Some empirical studies find evidence to support the use of acupuncture as a treatment for certain medical conditions, however, this peculiar practice is widely considered as the domain of alternative and non-evidence-based medicine. Several mechanisms have been suggested in an attempt to explain the therapeutic action of acupuncture, but the way in which acupuncture alleviates chronic non-cancer pain or psychosomatic and psychiatric disorders is not fully understood. A recent study suggested a theoretical model (coined “Fascial Armoring”) with a cellular pathway to help explain the pathogenesis of myofascial pain/fibromyalgia syndrome and functional psychosomatic syndromes. It proposes that these syndromes are a spectrum of a single medical entity that involves myofibroblasts with contractile activity in fascia and aberrant extracellular matrix (ECM) remodeling, which may lead to widespread mechanical tension and compression. This can help explain diverse psycho-somatic manifestations of fibromyalgia-like syndromes. Fascia is a continuous interconnected tissue network that extends throughout the body and has qualities of bio-tensegrity. Previous studies show that a mechanical action by needling induces soft tissue changes and lowers the shear modulus and stiffness in myofascial tissue. This hypothesis and theory paper offers a new mechanism for acupuncture therapy as a global percutaneous needle fasciotomy that respects tensegrity principles (tensegrity-based needling), in light of the theoretical model of “Fascial Armoring.” The translation of this model to other medical conditions carries potential to advance therapies. These days opioid overuse and over-prescription are ubiquitous, as well as chronic pain and suffering.
... However, many recent studies showed consistent changes in skin and muscles in patients with FM. Those changes included elevated levels of substance P, DNA fragmentation of muscle fibers, increase levels of interleukins-1 in cutaneous tissues, and perfusion abnormalities in muscles [9][10][11][12][13]. Those changes may provide a possible link between peripheral tissues and pain in patients with FM. ...
Background
This study aimed to test the changes in the conduction properties of peripheral nerves in patients with primary fibromyalgia (FM). Thirty patients with FM and sixteen healthy controls participated in this study. Visual analogue scale (VAS) for pain severity, pain duration, Widespread Pain Index (WPI), Symptom Severity (SS) scale, Hamilton depression rating scale, Taylor’s manifest anxiety scale, and Fibromyalgia Impact Questionnaire (FIQR) were used for measurement of psychiatric comorbidities and quality of life for each patient. Routine motor and sensory nerve conduction studies of both median, ulnar, common peroneal, posterior tibial, and sural nerves were measured for all study participants.
Results
We found statistically significant increase in Sensory Conduction Velocity (SCV), Sensory Nerve Action Potential (SNAP) amplitude, and decrease in Sensory Latency (SL) in patients with FM compared to controls. There were no significant changes in motor nerve conduction between patients and controls. Regression analysis showed a significant relation between WPI and both SCV and SL especially in nerves of upper limbs. However, no significant relation between SCV and SL and other presumed predictors including VAS for pain severity, pain duration, SS scale, FIQR, and psychiatric comorbidities. Patients with FM suffered more depression and anxiety than controls.
Conclusions
We found enhanced conductivity of the sensory rather than the motor nerves in patients with FM. To our knowledge, this is the first study to describe these sensory changes which may add further evidence of peripheral sensitization in patients with FM.
... Many recent studies have found consistent cutaneous and muscular changes in patients with FM, including elevated levels of substance P and other biochemical changes in their muscles. [32][33][34][35][36] Those changes may provide a link between peripheral tissues and pain in patients with FM. Various forms of peripheral sensitization (PS) in patients with FM including hypersensitivity of polymodal pain receptors and increased responses to mechanical nociceptive stimuli have been described. ...
Background and purpose:
Abnormal excitability of the central nervous system, both spinal and supraspinal, has previously been described as a pathophysiological plastic mechanism for chronic pain syndromes. Primary fibromyalgia (FM) as one extreme of this spectrum of diseases. This case-control study aimed to determine the changes in the spinal excitability by investigating the Hoffman reflex (H-reflex) in patients with FM.
Methods:
Thirty-eight patients with FM and 30 healthy controls participated in this case-control study. We measured the H-reflex bilaterally in the upper limbs (flexor carpi radialis) and the lower limbs (gastrocnemius and soleus). Moreover, pain-related variables were measured, including pain severity (using a visual analogue scale), pain duration, Widespread Pain Index, and the score on the Symptom Severity Scale. Various psychiatric comorbidities and quality-of-life parameters were measured for each patient, including scores on the Hamilton Depression Rating Scale, Taylor's Manifest Anxiety Scale, and the Revised Fibromyalgia Impact Questionnaire.
Results:
A significant increase in the ratio of the maximum baseline-to-peak amplitudes of H and M waves (Hmax/Mmax) but not in the H-wave minimum latency was found in patients with FM compared with healthy controls. There were no significant correlations between this ratio in both muscles and the various pain-related measures, psychiatric comorbidity, and quality of life in patients with FM. Patients with FM suffered more depression and anxiety than did the controls.
Conclusions:
We found increased spinal excitability in patients with FM, which was not confined to the site of maximum pain. This information may help in the diagnosis of FM and supports the hypothesis of central sensitization.
... Although there have been many studies investigating the impact of FMS on muscle fibers, no definitive results have been obtained. Some of these studies have shown specific alterations in muscle fibers caused by local hypoxia due to vasomotor dysregulation, chronic inflammation, and oxidative damage using microscopy, histochemistry, electron microscopy, magnetic resonance imaging (MRI), electrophysiologic tests, and ultrastructural techniques, and others showed no difference between patients and controls [8][9][10][11][12][13][14][15][16][17]. ...
... Studies using histochemistry, electrophysiology, and ultrastructural techniques have assessed deltoid, trapezius, brachioradialis, BB, tibialis anterior, and quadriceps muscles. Minor mitochondrial anomalies, capillary deficiency, impaired capillary microcirculation, and specific and non-specific muscle fiber changes in quadriceps and trapezius muscles were reported in some of these pathophysiology studies [8][9][10][11][12][13][14][15][16], and there was no difference between healthy sedentary controls in others [21][22][23][24]. Some studies noticed that muscles with tender points were affected [25], but asymptomatic muscles were not affected in other studies [26,27]. ...
Background
The main somatic symptoms of fibromyalgia syndrome (FMS) are chronic musculoskeletal pain, stiffness, and fatigue, all of which are related to the muscle system and its functioning.
Aims
The aim of this study was to evaluate whether the asymptomatic upper and lower extremity muscles evaluated using ultrasonography (US) were different from healthy controls in both newly diagnosed and established FMS and to assess whether muscle measurements were related to fatigue and disease severity, as well as quality of life.
Methods
This study was conducted on 152 subjects (102 patients and 50 healthy controls) as a cross-sectional controlled trial. Real-time imaging of cross-sectional thickness (CST) (for deltoid, biceps brachii, triceps brachii, forearm flexor, tibialis anterior, and gastrocnemius medialis), and cross-sectional areas (CSAs) (quadriceps femoris (QF)) measurements were performed using US. Fatigue and disease severity as well as quality of life scales were given to all participants.
Results
In both patient groups, decreased QF muscle CSA was significantly correlated with increased fatigue severity and decreased overall quality of life and energy levels. Moreover, in patients with established disease, there was a significant correlation between the decrease in QF muscle CSA and increased social isolation and between the decrease in biceps brachii muscle CST and increased fatigue severity.
Conclusions
Whether in newly diagnosed or established disease, muscle measurement values and quality of life parameters were significantly decreased in patients with FMS compared with healthy controls.
... In fibromyalgia (FM), various muscular abnormalities have been associated with chronic widespread pain and generalized tenderness, accompanied by fatigue, disturbed sleep and cognitive difficulties that characterize this condition [1]. Among these, we can mention: low levels of ATP (adenosine triphosphate) [2], increased levels of lactate and pyruvate [3], reduced blood flow [4], increased cytokines [5], DNA fragmentation [6], mitochondrial dysfunction, decrease in mitochondrial membrane potential and increased mitophagy, that could contribute to cell-bioenergetic imbalance [7], functional abnormalities of the muscle membrane, with higher muscle fiber conduction, maybe related to fast/hyper-excitable muscle membrane [8]. A possible link between some of these abnormalities could be: reduced blood flow hypoxia mitochondrial dysfunction diminution of ATP production increased lactate and pyruvate concentration as well as low Na + -K + -ATPase activity pain, inflammation and leaky membrane. ...
Introduction: Fibromyalgia (FM) is a condition characterized by chronic widespread pain and generalized tenderness accompanied by fatigue, disturbed sleep and cognitive difficulties. Several types of muscle abnormalities have been reported in FM at tissue, cellular and subcellular level, which could eventually alter the passive electrical response of the muscle. Methods: We evaluated the brachial musculature of 41 women, 21 with FM and 20 without, using multi-frequency electrical impedance myography and the characteristic parameters of the Cole-Cole model were obtained ( R 0 , R ∞, τ and α ). Results: The alpha parameter of the FM group was statistically different (0.21 ± 0.05 against 0.17 ± 0.05 p = 0.008). Discussion: The higher values of alpha parameter in the FM group may suggest that the behaviour of the cell membrane in FM is more permeable to the ions than in the non FM group and, therefore, less resistive.
... Besides this, the local tissue hypoxia may lead to a decreased pH, activating specific pain receptors. It can be hypothesized that due to the local hypoxia, the aerobic energy metabolism is impaired in this patient population, causing a shift to a more anaerobic energy metabolism dysfunction have already been found in muscle tissue of fibromyalgia patients (11,12) . As mitochondria also play an important role in lipid oxidation, the morphology of lipid droplets can also provide relevant information about the aerobic energy metabolism (13) . ...
Objective:
Trapezius myalgia, or more specific, myofascial dysfunction of the upper trapezius mainly affects women performing jobs requiring prolonged low level activation of the muscle. This continuous low muscle load can be accompanied by a shift to a more anaerobic energy metabolism, causing pain. To investigate whether morphological signs of an impaired aerobic metabolism are present in female office workers with trapezius myalgia.
Design:
Muscle biopsy analysis, using electron and light microscopy, was performed to compare mitochondrial and fat droplet morphology, and irregular muscle fibers, between female office workers with (n=17) and without (n= 15) work-related trapezius myalgia.
Results:
The patient group showed a significantly higher mean area (P=0.023) and proportion (P=0.029) for the subsarcolemmal and intermyofibrillar mitochondria respectively, compared to the control group. A significantly lower mean area of subsarcolemmal lipid droplets was found in the patient group (P=0.015), which also displayed a significantly higher proportion of lipid droplets touching the mitochondria (P=0.035). A significantly higher amount of muscle fibers with COX deficient areas were found in the patient group (P=0.030).
Conclusion:
The results of the present study may be indicatve for an impaired oxidative metabolism in work-related trapezius myalgia. However, additional research is necessary to confirm this hypothesis.
... Oxidative stress markers are also proposed as related event in its pathogenesis 2 . Decreased coenzyme Q 10 (CoQ 10 ) levels and increased reactive oxygen species (ROS) production in blood mononuclear cells of FMS patients are a direct evidence of increased oxidative stress at the cellular level; therefore, the therapeutic role of CoQ 10 has been studied 4,5 . A study done on 30 patients and controls of FMS implied mitochondrial dysfunction as cause of inflammation 6 . ...
... The common mutation A3243G and large deletions were not detected in germline mtDNA in these patients including the one with elevated CPK. DNA fragmentation and ultrastructural changes in mitochondria were detected by Sprott et al 4 . ...
Background & objectives: Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS.
Methods: Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at.
Results: None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients.
Interpretation & conclusions: Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.
