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Pain Practice : the Official Journal of... Jul 2024Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While...
BACKGROUND
Gabapentin, a widely prescribed medication for various neuropathic pain conditions, has demonstrated efficacy in managing diverse neurological disorders. While conventional side effects are well-documented, a growing body of evidence suggests the existence of atypical side effects, necessitating comprehensive exploration. This paper aims to systematically review and summarize the literature on the atypical side effects of gabapentin, shedding light on manifestations beyond the conventional spectrum.
METHODS
A systematic review was conducted, encompassing peer-reviewed articles published up to the knowledge cutoff date in November 2023. Databases, specifically PubMed, were searched for relevant studies, focusing on atypical side effects such as myoclonus, ataxia, pediatric aggression, respiratory depression, pneumonia, pregnancy complications, sleep interference, encephalopathy, peripheral edema, suicidal ideation, dyskinesia, anorgasmia, and myopathy. Inclusion criteria comprised studies with a focus on gabapentin-related atypical side effects, published in recognized journals and involving human subjects.
RESULTS
The review identified a spectrum of atypical side effects associated with gabapentin use, ranging from neurological manifestations like myoclonus and ataxia to behavioral changes such as pediatric aggression and suicidal ideation. Additionally, respiratory complications, pregnancy-related issues, sleep disturbances, and rare complications like encephalopathy and myopathy were observed. Literature synthesis provided insights into the incidence, clinical presentation, and potential mechanisms underlying these atypical side effects.
CONCLUSION
This comprehensive review highlights the diverse range of atypical side effects associated with gabapentin use, expanding beyond conventional knowledge. Healthcare practitioners must be cognizant of these manifestations, recognizing their potential impact on patient well-being. As clinical decision-making relies on a thorough understanding of a medication's side effect profile, this review contributes to enhancing awareness and fostering informed practices in the prescription and management of gabapentin. Further research is warranted to elucidate the mechanisms and risk factors associated with these atypical side effects, refining our understanding of gabapentin's safety profile.
PubMed: 38949515
DOI: 10.1111/papr.13400 -
Journal of Visualized Experiments : JoVE Jun 2024Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop...
Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.
Topics: Animals; Sepsis; Mice; Disease Models, Animal; Male; Mice, Inbred C57BL; Muscular Diseases; Muscular Atrophy; Muscle, Skeletal; Hindlimb Suspension
PubMed: 38949310
DOI: 10.3791/66685 -
JPMA. the Journal of the Pakistan... Jun 2024Musculoskeletal (MSK) disorders encompass various conditions impacting bones, muscles, tendons, ligaments, and nerves. An estimated 1.71 billion individuals globally... (Review)
Review
Musculoskeletal (MSK) disorders encompass various conditions impacting bones, muscles, tendons, ligaments, and nerves. An estimated 1.71 billion individuals globally have MSK disorders, causing disability and reduced quality of life. Literature contradicts the notion that musculoskeletal pain and disability solely arise from physical impairments; psychological, behavioural, and social factors contribute significantly. These facets influence pain perception and chronic impairment development. Common interventions-medication, exercise, manual and hydrotherapy, electro-thermal modalities, behavioural and alternative therapies-address pain individually, yet lack the comprehensive response required. In contrast, a multimodal approach combines diverse therapies tailored to individual needs. It ensures lasting symptom relief, prevents recurrence, and improves function. Although proven effective, clinical implementation of this approach remains limited. This mini-review discusses the reasons behind this gap, underscores multimodal approach importance, and enlightens rehabilitation professionals on its potential for managing chronic musculoskeletal issues.
Topics: Humans; Musculoskeletal Diseases; Combined Modality Therapy; Musculoskeletal Pain; Chronic Disease; Exercise Therapy
PubMed: 38949004
DOI: 10.47391/JPMA.24-44 -
PeerJ 2024Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with systemic implications, potentially affecting musculoskeletal health. This study aimed to assess shoulder muscle strength and joint repositioning accuracy in individuals with T2DM, exploring potential correlations and shedding light on the musculoskeletal consequences of the condition. The objectives were two-fold: (1) to assess and compare shoulder strength and joint repositioning accuracy between individuals with T2DM and asymptomatic counterparts, and (2) to examine the correlation between shoulder strength and joint repositioning accuracy in individuals with T2DM.
METHODS
A cross-sectional study enrolled 172 participants using the convenience sampling method, including 86 individuals with T2DM and an age-matched asymptomatic group ( = 86). Shoulder strength was assessed using a handheld dynamometer, while joint repositioning accuracy was evaluated with an electronic digital inclinometer.
RESULTS
Individuals with T2DM exhibited reduced shoulder muscle strength compared to asymptomatic individuals ( < 0.001). Additionally, joint repositioning accuracy was significantly lower in the T2DM group ( < 0.001). Negative correlations were observed between shoulder strength and joint repositioning accuracy in various directions (ranging from -0.29 to -0.46, < 0.001), indicating that higher muscle strength was associated with improved joint repositioning accuracy in individuals with T2DM.
CONCLUSION
This study highlights the significant impact of T2DM on shoulder muscle strength and joint repositioning accuracy. Reduced strength and impaired accuracy are evident in individuals with T2DM, emphasizing the importance of addressing musculoskeletal aspects in diabetes management. The negative correlations suggest that enhancing shoulder muscle strength may lead to improved joint repositioning accuracy, potentially contributing to enhanced physical functioning in this population.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Cross-Sectional Studies; Female; Middle Aged; Muscle Weakness; Muscle Strength; Shoulder; Proprioception; Shoulder Joint; Aged; Adult; Range of Motion, Articular
PubMed: 38948217
DOI: 10.7717/peerj.17630 -
International Journal of Public Health 2024
Topics: Humans; Child; Neuromuscular Diseases; Mental Health
PubMed: 38948087
DOI: 10.3389/ijph.2024.1607460 -
MedRxiv : the Preprint Server For... Jun 2024Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined....
BACKGROUND
Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. Inflammation and mitochondrial dysfunction are the most common histopathological findings. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM patients, highlighting sex differences.
METHODS
We included 38 IBM patients and 22 age- and sex-matched controls without myopathy. Bulk RNA sequencing, Meso Scale Discovery ELISA, western blotting, histochemistry and immunohistochemistry were performed on frozen muscle samples from the study participants.
RESULTS
We demonstrated activation of the NLRP3 inflammasome in IBM muscle samples, with the NLRP3 inflammasome pathway being the most upregulated. On muscle histopathology, there is increased NRLP3 immunoreactivity in both inflammatory cells and muscle fibers. Mitophagy is critical for removing damaged mitochondria and preventing the formation of a vicious cycle of mitochondrial dysfunction-NLRP3 activation. In the IBM muscle samples, we showed altered mitophagy, most significantly in males, with elevated levels of p-S65-Ubiquitin, a mitophagy marker. Furthermore, p-S65-Ubiquitin aggregates accumulated in muscle fibers that were mostly type 2 and devoid of cytochrome-c-oxidase reactivity. Type 2 muscle fibers are known to be more prone to mitochondrial dysfunction. levels correlated with p-S65-Ubiquitin levels in both sexes but with loss of in muscle strength only in males. Finally, we identified sex-specific molecular pathways in IBM, with females having activation of pathways that could offset some of the pathomechanisms of IBM.
CONCLUSIONS
NLRP3 inflammasome is activated in IBM, along with altered mitophagy particularly in males, which is of potential therapeutic significance. These findings suggest sex-specific mechanisms in IBM that warrant further investigation.
PubMed: 38947067
DOI: 10.1101/2024.06.15.24308845 -
Circulation Research Jul 2024Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise...
BACKGROUND
Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism.
OBJECTIVE
To determine whether this mechanism broadly impacts diabetic complications, we investigated the role of ARRDC4 in the pathogenesis of diabetic cardiac and skeletal myopathy.
METHODS AND RESULTS
High glucose promoted translocation of MondoA into the nucleus, which upregulated transcriptional expression, increased lysosomal GLUT1 trafficking, and blocked glucose transport in cardiomyocytes, forming a feedback mechanism. This role of was confirmed in human muscular cells from type 2 diabetic patients. Prolonged hyperglycemia upregulated myocardial expression in multiple types of mouse models of diabetes. We then analyzed hyperglycemia-induced cardiac and skeletal muscle abnormalities in insulin-deficient mice. Hyperglycemia increased advanced glycation end-products and elicited oxidative and endoplasmic reticulum stress leading to apoptosis in the heart and peripheral muscle. However, deletion of augmented tissue glucose transport and mitochondrial respiration, protecting the heart and muscle from tissue damage. Stress hemodynamic analysis and treadmill exhaustion test uncovered that -knockout mice had greater cardiac inotropic/chronotropic reserve with higher exercise endurance than wild-type (WT) animals under diabetes. While multiple organs were involved in the mechanism, cardiac-specific overexpression (beyond levels observed during diabetes) using adenoassociated virus suggests that high levels of myocardial have the potential to contribute to exercise intolerance by interfering with cardiac metabolism through its interaction with GLUT1 in diabetes. Importantly, the mutation mouse line exhibited greater exercise tolerance, showing the potential therapeutic impact on diabetic cardiomyopathy by disrupting the interaction between ARRDC4 and GLUT1.
CONCLUSIONS
ARRDC4 serves as a regulator of hyperglycemia-induced toxicities toward cardiac and skeletal muscle, revealing a new molecular framework that connects hyperglycemia to cardiac/skeletal myopathy to exercise intolerance.
PubMed: 38946541
DOI: 10.1161/CIRCRESAHA.123.323158 -
Journal of Indian Prosthodontic Society Jul 2024Temporomandibular disorders (TMD) comprise ailments involving the jaw joint (temporomandibular joint) and its associated anatomical structures. The complexity involved... (Review)
Review
AIM
Temporomandibular disorders (TMD) comprise ailments involving the jaw joint (temporomandibular joint) and its associated anatomical structures. The complexity involved in TMD is primarily due to its broad spectrum of conditions, clinical signs and symptoms variability, and multifactorial etiology. Considering the above, the present study was performed to help understand the prevailing knowledge and awareness of TMD among Indian dentists in the context of the new specialty "orofacial pain".
SETTINGS AND DESIGN
Questinnaire study and review.
MATERIALS AND METHODS
The questionnaire was distributed using a web-based portal nationwide among Indian dentists. Dentists were invited to participate, clearly stating that the intent and purpose of the questionnaire was to record the existing knowledge and awareness concerning temporomandibular disorders among Indian dentists. The questionnaire was segregated into three sections: pathogenesis, diagnosis, and management of TMDs. The questions were recorded using a Likert three-point scale (1=agree; 2=disagree; 3=not aware). 310 dentists participated in the survey, among which 105 were general dentists (BDS [Bachelor of Dental Surgery] graduates), and 205 were dentists with specialist training (MDS [Masters of Dental Surgery] graduates).
STATISTICAL ANALYSIS USED
The results obtained from the study participants was used to calculate the percentage and frequency, following which tabulations were made based on graduate type and clinical experience. The values obtained from all three sections were recorded, and the responses were analysed using Pearson's Chi-Square test with statistical significance kept at P < 0.05.
RESULTS
Results of the study disclosed that only 58.1% of general dentists and 46.8% of specialists were confident in handling temporomandibular disorder patients. Splint therapy was the preferred treatment modality for general dentists, whereas dentists with specialist training preferred occlusal rehabilitation.
CONCLUSION
The results of the current survey indicate that Indian dentists lack sufficient training in dental schools on all three sections and face difficulty diagnosing and treating TMDs.
Topics: Humans; India; Surveys and Questionnaires; Temporomandibular Joint Disorders; Dentists; Health Knowledge, Attitudes, Practice; Male; Female; Practice Patterns, Dentists'
PubMed: 38946513
DOI: 10.4103/jips.jips_573_23 -
Journal of Medical Case Reports Jul 2024Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
BACKGROUND
Necrotizing myopathies and muscle necrosis can be caused by immune-mediated mechanisms, drugs, ischemia, and infections, and differential diagnosis may be challenging.
CASE PRESENTATION
We describe a case of diabetic myonecrosis complicated by pyomyositis and abscess caused by Escherichia coli. A white woman in her late forties was admitted to the hospital with a 1.5 week history of bilateral swelling, weakness, and mild pain of the lower extremities and inability to walk. She had a history of type 1 diabetes complicated by diabetic retinopathy, neuropathy, nephropathy, and end-stage renal disease. C-reactive protein was 203 mg/l, while creatinine kinase was only mildly elevated to 700 IU/l. Magnetic resonance imaging of her lower limb muscles showed extensive edema, and muscle biopsy was suggestive of necrotizing myopathy with mild inflammation. No myositis-associated or myositis-specific antibodies were detected. Initially, she was suspected to have seronegative immune-mediated necrotizing myopathy, but later her condition was considered to be explained better by diabetic myonecrosis with multifocal involvement. Her symptoms alleviated without any immunosuppressive treatment. After a month, she developed new-onset and more severe symptoms in her right posterior thigh. She was diagnosed with emphysematous urinary tract infection and emphysematous myositis and abscess of the right hamstring muscle. Bacterial cultures of drained pus from abscess and urine were positive for Escherichia coli. In addition to abscess drainage, she received two 3-4-week courses of intravenous antibiotics. In the discussion, we compare the symptoms and findings typically found in pyomyositis, immune-mediated necrotizing myopathy, and diabetic myonecrosis (spontaneous ischemic necrosis of skeletal muscle among people with diabetes). All of these diseases may cause muscle weakness and pain, muscle edema in imaging, and muscle necrosis. However, many differences exist in their clinical presentation, imaging, histology, and extramuscular symptoms, which can be useful in determining diagnosis. As pyomyositis often occurs in muscles with pre-existing pathologies, the ischemic muscle has likely served as a favorable breeding ground for the E. coli in our case.
CONCLUSIONS
Identifying the etiology of necrotizing myopathy is a diagnostic challenge and often requires a multidisciplinary assessment of internists, pathologists, and radiologists. Moreover, the presence of two rare conditions concomitantly is possible in cases with atypical features.
Topics: Humans; Pyomyositis; Female; Abscess; Escherichia coli Infections; Necrosis; Magnetic Resonance Imaging; Anti-Bacterial Agents; Escherichia coli; Diabetes Mellitus, Type 1; Urinary Tract Infections
PubMed: 38946001
DOI: 10.1186/s13256-024-04614-z -
Clinical Radiology Jun 2024Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA... (Review)
Review
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease caused by the degeneration of the α-motor neurons in the anterior horn of the spinal cord. SMA is clinically characterized by progressive and symmetrical muscle weakness and muscle atrophy and ends up with systemic multisystem abnormalities. Quantitative MRI (qMRI) has the advantages of non-invasiveness, objective sensitivity, and high reproducibility, and has important clinical value in evaluating the severity of neuromuscular diseases and monitoring the efficacy of treatment. This article summarizes the clinical use of muscular MRI and magnetic resonance neurography in assessing the progress of SMA.
PubMed: 38945793
DOI: 10.1016/j.crad.2024.06.004