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European Journal of Neurology Dec 2017Amyloid myopathy frequently occurs in the setting of systemic amyloidosis and less commonly in isolation (isolated amyloid myopathy). Anoctaminopathy-5 and...
BACKGROUND AND PURPOSE
Amyloid myopathy frequently occurs in the setting of systemic amyloidosis and less commonly in isolation (isolated amyloid myopathy). Anoctaminopathy-5 and dysferlinopathy were recently recognized as causes of isolated amyloid myopathy. The present study aimed to characterize the isolated amyloid myopathy and to compare it with amyloid myopathy associated with systemic amyloidosis.
METHODS
We searched the Muscle Laboratory database to identify patients with pathologically confirmed amyloid myopathy seen in neurology clinics between January 1998 and September 2016. Patients with monoclonal gammopathy, peripheral neuropathy, organomegaly or symptoms or pathologic evidence of amyloid deposition outside skeletal muscle were classified as having systemic amyloidosis-associated myopathy.
RESULTS
Fifty-two patients were identified, including 14 with isolated amyloid myopathy (eight anoctaminopathy-5, two dysferlinopathy and four genetically unknown) and 38 with systemic amyloidosis (32 immunoglobulin light-chain amyloidosis, four familial amyloid polyneuropathy and two senile systemic amyloidosis). Compared with patients with systemic amyloidosis, patients with isolated amyloid myopathy had a younger age of onset (median, 41.5 vs. 65 years), no dysphagia (0% vs. 26%) or weight loss (0% vs. 26%), but more frequent calf atrophy (57% vs. 0%), small collections of inflammatory cells on muscle biopsy (43% vs. 0%) and asymptomatic hyperCKemia at onset (21% vs. 0%). All patients with isolated amyloid myopathy had creatine kinase (CK) values >2.5 times the upper limit of normal.
CONCLUSIONS
Isolated amyloid myopathy accounts for 27% of patients with amyloid myopathy, mostly due to anoctaminopathy-5. There are various clinical and laboratory parameters that can help to differentiate isolated amyloid myopathy from systemic amyloidosis.
Topics: Adult; Age Factors; Aged; Amyloidosis; Creatine Kinase; Databases, Factual; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases
PubMed: 28888072
DOI: 10.1111/ene.13448 -
Journal of the Neurological Sciences Apr 2015Statin induced necrotizing autoimmune myopathy (SINAM) is a recently characterized entity belonging to the spectrum of statin myotoxicity. It is a more severe form, and... (Review)
Review
Statin induced necrotizing autoimmune myopathy (SINAM) is a recently characterized entity belonging to the spectrum of statin myotoxicity. It is a more severe form, and is usually associated with significant proximal muscle weakness, strikingly elevated creatine kinase levels and persistent symptoms despite statin discontinuation. The characteristic pathological finding is a marked muscle fiber necrosis with minimal or no inflammation on muscle biopsy. SINAM is an autoimmune disorder associated with an antibody against 3-hydroxy-3-methyglutaryl-coenzyme A reductase (HMGCR), and the antibody titer is a useful marker for assessing treatment response. However, anti-HMGCR positive myopathies are also caused by unknown etiologies other than statin exposure, especially in the younger population. SINAM should be promptly recognized as immunosuppressive therapy can improve its clinical outcome significantly. Further research is needed to elucidate its pathogenesis and provide evidence based guidelines for management.
Topics: Autoimmune Diseases; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Muscular Diseases; Necrosis
PubMed: 25765229
DOI: 10.1016/j.jns.2015.02.042 -
Rheumatology (Oxford, England) Jul 2023Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus... (Review)
Review
OBJECTIVES
Symptomatic myopathy in sarcoidosis patients is not always due to sarcoid myopathy (ScM). We investigated the clinical and pathological spectrum including myxovirus resistance protein A (MxA) expression among sarcoidosis patients.
METHODS
We reviewed the Mayo Clinic database (May 1980-December 2020) to identify sarcoidosis patients with myopathic symptoms and pathological evidence of myopathy.
RESULTS
Among 5885 sarcoidosis patients, 21 had symptomatic myopathy. Eight carried a diagnosis of sarcoidosis 5.5 years (median) prior to myopathy onset. Eleven patients had ScM. The remaining had non-sarcoid myopathies (five IBM, one immune-mediated necrotizing myopathy, one non-specific myositis, two non-specific myopathy and one steroid myopathy). Estimated frequency of IBM is 85 per 100 000 sarcoidosis patients. The following features were associated with non-sarcoid myopathies (P < 0.05): (i) predominant finger flexor and quadriceps weakness, (ii) modified Rankin scale (mRS) >2 at time of diagnosis, (iii) creatine kinase >500 U/l, and (iv) absence of intramuscular granulomas. Sarcoplasmic MxA expression was observed in scattered myofibres in three patients, two of whom were tested for DM-specific autoantibodies and were negative. Immunosuppressive therapy led to improvement in mRS ≥1 in 5/10 ScM, none of the five IBM, and 3/3 remaining patients with non-sarcoid myopathies.
DISCUSSION
Symptomatic myopathy occurred in 0.36% of sarcoidosis. IBM was the second most common cause of myopathies after ScM. Frequency of IBM in sarcoidosis is higher than in the general population. Recognition of features suggestive of alternative aetiologies can guide proper treatment. Our findings of abnormal MxA expression warrant a larger study.
Topics: Humans; Muscular Diseases; Myositis; Sarcoidosis; Granuloma; Autoimmune Diseases
PubMed: 36440911
DOI: 10.1093/rheumatology/keac668 -
Continuum (Minneapolis, Minn.) Dec 2019This article provides an overview of mitochondrial and metabolic biology, the genetic mechanisms causing mitochondrial diseases, the clinical features of mitochondrial... (Review)
Review
PURPOSE OF REVIEW
This article provides an overview of mitochondrial and metabolic biology, the genetic mechanisms causing mitochondrial diseases, the clinical features of mitochondrial diseases, lipid myopathies, and glycogen storage diseases, all with a focus on those syndromes and diseases associated with myopathy. Over the past decade, advances in genetic testing have revolutionized patient evaluation. The main goal of this review is to give the clinician the basic understanding to recognize patients at risk of these diseases using the standard history and physical examination.
RECENT FINDINGS
Primary mitochondrial disease is the current designation for the illnesses resulting from genetic mutations in genes whose protein products are necessary for mitochondrial structure or function. In most circumstances, more than one organ system is involved in mitochondrial disease, and the value of the classic clinical features as originally described early in the history of mitochondrial diseases has reemerged as being important to identifying patients who may have a primary mitochondrial disease. The use of the genetic laboratory has become the most powerful tool for confirming a diagnosis, and nuances of using genetic results will be discussed in this article. Treatment for mitochondrial disease is symptomatic, with less emphasis on vitamin and supplement therapy than in the past. Clinical trials using pharmacologic agents are in progress, with the field attempting to define proper goals of treatment. Several standard accepted therapies exist for many of the metabolic myopathies.
SUMMARY
Mitochondrial, lipid, and glycogen diseases are not uncommon causes of multisystem organ dysfunction, with the neurologic features, especially myopathy, occurring as a predominant feature. Early recognition requires basic knowledge of the varied clinical phenotypes before moving forward with a screening evaluation and possibly a genetic evaluation. Aside from a few specific diseases for which there are recommended interventions, treatment for the majority of these disorders remains symptomatic, with clinical trials currently in progress that will hopefully result in standard treatments.
Topics: Adolescent; Aged; Female; Glycogen Storage Disease; Humans; Lipid Metabolism Disorders; Mitochondrial Diseases; Muscular Diseases
PubMed: 31794469
DOI: 10.1212/CON.0000000000000805 -
Brain : a Journal of Neurology Jan 2016Classically, myopathies are categorized according to limb or cranial nerve muscle affection, but with the growing use of magnetic resonance imaging it has become evident... (Review)
Review
Classically, myopathies are categorized according to limb or cranial nerve muscle affection, but with the growing use of magnetic resonance imaging it has become evident that many well-known myopathies have significant involvement of the axial musculature. New disease entities with selective axial muscle involvement have also been described recently, but overall the axial myopathy is unexplored. We performed a PubMed search using the search terms 'myopathy', 'paraspinal', 'axial' and 'erector'. Axial myopathy was defined as involvement of paraspinal musculature. We found evidence of axial musculature involvement in the majority of myopathies in which paraspinal musculature was examined. Even in diseases named after a certain pattern of non-axial muscle affection, such as facioscapulohumeral and limb girdle muscular dystrophies, affection of the axial musculature was often severe and early, compared to other muscle groups. Very sparse literature evaluating the validity of clinical assessment methods, electromyography, muscle biopsy and magnetic resonance imaging was identified and reference material is generally missing. This article provides an overview of the present knowledge on axial myopathy with the aim to increase awareness and spur interest among clinicians and researchers in the field.
Topics: Humans; Muscle, Skeletal; Muscular Diseases; Paraspinal Muscles
PubMed: 26667281
DOI: 10.1093/brain/awv332 -
Journal of Pharmacy Practice Dec 2020To report a case of statin-induced bilateral foot myopathy that resulted from 2 different statins. A 44-year-old Caucasian male with a history of ventricular...
OBJECTIVE
To report a case of statin-induced bilateral foot myopathy that resulted from 2 different statins. A 44-year-old Caucasian male with a history of ventricular fibrillation cardiac arrest, hyperlipidemia, and coronary artery disease experienced bilateral foot pain, weakness, and soreness while taking atorvastatin 20 mg daily. The pain subsided within weeks of discontinuing atorvastatin but returned years later after the initiation of rosuvastatin. The Naranjo probability scale indicates that this is a definite association between bilateral foot myopathy and statin use.
DISCUSSION
There is an association with statin use and lowering cardiovascular risk in patients with dyslipidemia and cardiovascular disease. However, statin metabolites can accumulate in the myocytes of muscle groups to cause a common side effect of myopathy. Statin myopathy typically occurs in large, bilateral, or proximal muscle groups, such as the thighs, back, calves, or buttocks. This patient was unusual in that his muscle symptoms only occurred in his feet and was severe enough to affect his ambulation.
CONCLUSION
Stain-associated muscle symptoms have been reported to lessen medication adherence. There is also a risk with muscle symptoms that the patient could develop rhabdomyolysis, a rare but serious condition. Recognizing statin-associated muscle symptoms even in uncommon locations is important, so that alternative lipid-lowering strategies can be implemented to lower cardiovascular risk.
Topics: Adult; Atorvastatin; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Muscular Diseases; Rhabdomyolysis
PubMed: 31248326
DOI: 10.1177/0897190019857851 -
Arthritis & Rheumatology (Hoboken, N.J.) Aug 2021The idiopathic inflammatory myopathies (IIMs) are chronic disorders characterized by inflammation in skeletal muscle but also in other organs such as the skin, lungs,... (Review)
Review
The idiopathic inflammatory myopathies (IIMs) are chronic disorders characterized by inflammation in skeletal muscle but also in other organs such as the skin, lungs, joints, gastrointestinal tract, and heart. The effect of immunosuppressive treatment varies between individual patients and between organ manifestations within the same individual. Many patients respond poorly to first-line treatment with glucocorticoids and other immunosuppressive agents such as methotrexate or azathioprine, with symptoms persisting in the muscles, skin, and lungs, leading to refractory disease. Management of refractory IIM is a clinical challenge, and a systematic approach is proposed to better understand the lack of treatment response, in order to guide disease management. The first step in the management of refractory IIM is to recognize whether remaining symptoms are caused by persistent inflammation in the affected tissue or whether the symptoms may be attributable to damage preceding inflammation. Thus, a second diagnostic examination is recommended. Second, in particular for patients with remaining muscle weakness, it is important to ascertain whether the diagnosis of myositis is correct or whether another underlying muscle disorder could explain the symptoms. Third, with confirmation of remaining inflammation in the tissues, a strategy to change treatment needs to be undertaken. Few controlled trials are available to guide our treatment strategies. Furthermore, different subgroups of patients may benefit from different therapies, and different organ manifestations may respond to different therapies. In this context, subgrouping of patients with IIM based on autoantibody profile may be helpful, as there are emerging data from open studies and case series to support the notion of a varying treatment response in different autoantibody-defined subgroups of IIM patients.
Topics: Autoantibodies; Diagnosis, Differential; Disease Management; Humans; Immunosuppressive Agents; Muscle Weakness; Muscle, Skeletal; Muscular Diseases; Myositis; Practice Guidelines as Topic; Symptom Assessment
PubMed: 33844450
DOI: 10.1002/art.41762 -
Hormone and Metabolic Research =... May 2024Glucocorticoid-induced myopathy is a non-inflammatory toxic myopathy typified by proximal muscle weakness, muscle atrophy, fatigue, and easy fatigability. These vague... (Review)
Review
Glucocorticoid-induced myopathy is a non-inflammatory toxic myopathy typified by proximal muscle weakness, muscle atrophy, fatigue, and easy fatigability. These vague symptoms coupled with underlying disorders may mask the signs of glucocorticoid-induced myopathy, leading to an underestimation of the disease's impact. This review briefly summarizes the classification, pathogenesis, and treatment options for glucocorticoid-induced muscle wasting. Additionally, we discuss current diagnostic measures in clinical research and routine care used for diagnosing and monitoring glucocorticoid-induced myopathy, which includes gait speed tests, muscle strength tests, hematologic tests, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), electromyography, quantitative muscle ultrasound, histological examination, and genetic analysis. Continuous monitoring of patients receiving glucocorticoid therapy plays an important role in enabling early detection of glucocorticoid-induced myopathy, allowing physicians to modify treatment plans before significant clinical weakness arises.
Topics: Humans; Glucocorticoids; Muscular Diseases
PubMed: 38224966
DOI: 10.1055/a-2246-2900 -
Current Opinion in Neurology Oct 2017This review aims to highlight the most relevant clinical and laboratory findings, regarding acute and progressive metabolic myopathies, and to develop an algorithm... (Review)
Review
PURPOSE OF REVIEW
This review aims to highlight the most relevant clinical and laboratory findings, regarding acute and progressive metabolic myopathies, and to develop an algorithm addressing clinicians to clinical practice.
RECENT FINDINGS
Although diagnosis of metabolic myopathies remains still challenging, the recent identification of new disorders has increased the number of patients requiring specific investigations. Nowadays, a more detailed characterization of the clinical spectrum of metabolic myopathies improved awareness as well as a deeper knowledge on their natural history or multisystem involvement. Diagnostic procedures, as first-line screening tests are necessary for an earlier and more accurate diagnostic work up, not only in infantile cases, but also in adults with suspected metabolic myopathies. New generation diagnostic techniques such as NGS (Next Generation Sequencing) and whole exome/genome sequencing have emerged as innovative tools to extensively evaluate either known genes variants or new candidate genes as possible causes of metabolic myopathies.
SUMMARY
Diagnosis of metabolic myopathies is still challenging for clinicians because of rarity and clinical heterogeneity which is often overlapping with other neuromuscular disorders. Detailed algorithms supported by advanced laboratory investigations may be helpful to timely reach a diagnosis, so allowing an earlier therapeutic decision.
Topics: Humans; Metabolic Diseases; Muscular Diseases
PubMed: 28763305
DOI: 10.1097/WCO.0000000000000483 -
The International Journal of... Oct 2016Neuromyelitis optica spectrum disorders (NMOSD) were generally thought to affect only central nervous system and spare peripheral aquaporin-4 (AQP4)-expressing organs.... (Review)
Review
Neuromyelitis optica spectrum disorders (NMOSD) were generally thought to affect only central nervous system and spare peripheral aquaporin-4 (AQP4)-expressing organs. In recent years, however, increasing evidence has shown that skeletal muscle is involved in NMOSD. We provided a comprehensive review of the relevant literature and summarized the clinical and pathological characteristics of myopathy associated with NMOSD. NMOSD-associated myopathy seems to be characterized by mild muscle symptoms with prominent hyperCKemia and minimal changes on conventional pathological staining. Loss of AQP4 and deposition of IgG and activated complement products on sarcolemma of type II fibers are diagnostic features on immunohistochemical examinations. Creatine kinase leakage as a result of AQP4-IgG-induced, complement-mediated sarcolemmal injury may be a potential mechanism for hyperCKemia. Myopathy should be considered a component of NMOSD unified by AQP4-IgG seropositivity.
Topics: Humans; Muscular Diseases; Neuromyelitis Optica
PubMed: 26514543
DOI: 10.3109/00207454.2015.1113175