Просмотр кода страницы Английская Википедия:Acquired non-inflammatory myopathy

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| caption         = Condition affects skeletal muscle
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| specialty       = neurology
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'''Acquired non-inflammatory myopathy (ANIM)''' is a neuromuscular disorder primarily affecting skeletal muscle, most commonly in the limbs of humans, resulting in a weakness or dysfunction in the muscle.<ref name="Baer 457–479"/> A [[myopathy]] refers to a problem or abnormality with the [[myofibrils]], which compose muscle tissue. In general, non-inflammatory myopathies are a grouping of muscular diseases not induced by an [[autoimmune]]-mediated [[Inflammation|inflammatory]] pathway. These muscular diseases usually arise from a [[pathology]] within the muscle tissue itself rather than the nerves innervating that tissue. ANIM has a wide spectrum of causes which include drugs and toxins, nutritional imbalances, acquired metabolic dysfunctions such as an acquired defect in protein structure, and infections.<ref name="Baer 457–479">{{cite journal | vauthors = Baer AN, Wortmann RL | title = Noninflammatory myopathies | journal = Rheumatic Disease Clinics of North America | volume = 39 | issue = 2 | pages = 457–479 | date = May 2013 | pmid = 23597974 | doi = 10.1016/j.rdc.2013.02.006 }}</ref>

Acquired non-inflammatory myopathy is a different diagnosis than [[inflammatory myopathy]]. Inflammatory myopathies are a direct result of some type of autoimmune mediated pathway whereas ANIM is not the result of a dysfunction of the immune system.<ref name="Castro 111–120"/> In addition, the cause of inflammatory myopathy is relatively unknown, whereas many causal agents for ANIM have been discovered which typically affect the structural integrity and function of the muscle fibers.<ref name="Castro 111–120"/>

Most myopathies are typically first diagnosed and classified as an [[idiopathic]] inflammatory myopathy.<ref name="Castro 111–120"/><ref>{{cite journal | vauthors = Bhai SF, Dimachkie MM, de Visser M | title = Is it really myositis? Mimics and pitfalls | journal = Best Practice & Research. Clinical Rheumatology | volume = 36 | issue = 2 | pages = 101764 | date = June 2022 | pmid = 35752578 | doi = 10.1016/j.berh.2022.101764 | s2cid = 250012951 }}</ref><ref>{{cite journal | vauthors = Szczęsny P, Świerkocka K, Olesińska M | title = Differential diagnosis of idiopathic inflammatory myopathies in adults - the first step when approaching a patient with muscle weakness | journal = Reumatologia | volume = 56 | issue = 5 | pages = 307–315 | date = 2018 | pmid = 30505013 | pmc = 6263305 | doi = 10.5114/reum.2018.79502 }}</ref><ref>{{cite journal | vauthors = Tarnopolsky MA, Hatcher E, Shupak R | title = Genetic Myopathies Initially Diagnosed and Treated as Inflammatory Myopathy | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 43 | issue = 3 | pages = 381–384 | date = May 2016 | pmid = 26911292 | doi = 10.1017/cjn.2015.386 | s2cid = 25515951 | doi-access = free }}</ref> However, a diagnosis of ANIM occurs when the cause of the myopathy is found to not arise from an autoimmune mechanism.<ref name="Baer 457–479"/>

==Symptoms and signs==
Patients with acquired non-inflammatory myopathy typically experience weakness, cramping, stiffness, and [[tetany]], most commonly in skeletal muscle surrounding the limbs and upper shoulder girdle.<ref name="Baer 457–479"/>

The most commonly reported symptoms are:
* [[Muscle fatigue]]<ref name="Baer 457–479"/>
* Pain<ref name="Baer 457–479"/>
* [[Muscle spasms]] and cramps
* Tingling
* Numbness
* [[Tetany]]<ref name="Baer 457–479"/>
* Loss of coordination and balance<ref name="Baer 457–479"/>
* Lack of fine and gross motor control<ref name="Baer 457–479"/>
* Muscular wasting and [[atrophy]]<ref name="Baer 457–479"/>

==Cause==
Acquired non-inflammatory myopathy can be caused by a variety of factors including metabolic abnormalities, drugs, nutritional deficiency, trauma, and upstream abnormalities resulting in decreased function.  Two of the most common causes of ANIM are [[hyperthyroidism]] and excessive steroid use, while many drugs used to treat [[Rheumatoid arthritis|rheumatism]] are known to be inducing agents.  Most cases of ANIM can be linked to drugs or dietary abnormalities.{{citation needed|date=October 2020}}

===Drug-induced myopathy===
It is not uncommon for drugs to damage muscle fibers. Particular families of drugs are known to induce myopathies on the molecular level, thus altering organelle function such as the mitochondria. Use of multiple drugs from these families in conjunction with one another can increase the risk of developing a myopathy.<ref name="Owczarek 2005 23–34"/> Many of the drugs associated with inducing myopathies in patients are found in rheumatology practice.{{citation needed|date=October 2020}}

====Statins====
* Prescribed [[statins]] (HMG-CoA reductase inhibitors) for [[dyslipidemia]] are associated with muscle toxicity. Symptoms of this muscle toxicity include combinations of cramping, weakness, aching or tenderness; and are often experienced in the quadriceps, pectoral, biceps, low back, or abdominal region. Symptoms tend to worsen with muscle exercise, and often continue after a patient is removed from statin therapy.<ref name="Baer 457–479"/> Common types of myopathy due to statins include myalgia, [[myositis]], and [[rhabdomyolysis]]. Statins induce myopathy by inhibiting protein synthesis within the muscle.<ref name="Owczarek 2005 23–34">{{cite journal | vauthors = Owczarek J, Jasińska M, Orszulak-Michalak D | title = Drug-induced myopathies. An overview of the possible mechanisms | journal = Pharmacological Reports | volume = 57 | issue = 1 | pages = 23–34 | year = 2005 | pmid = 15849374 }}</ref> Statin therapy tends to not show any [[histopathological]] differences, and thus a biopsy does not reveal too much about the damage. Often, the damage is found within the mitochondria.<ref name="Baer 457–479"/>
[[File:Colchicine.svg|200px|thumbnail|right|Colchicine is commonly prescribed for gout treatment.]]

====Corticosteroids====
* [[Corticosteroids]] often cause muscle weakness to some degree in patients. Symptoms are usually weakness of the proximal muscles, neck flexor, and in extreme cases, [[respiratory]] muscle weakness can also occur.<ref name="Baer 457–479"/> Corticosteroids have not only been found to cause some degree of muscle atrophy, but also a local or diffuse cell death. These side effects are more common in women than in men, for reasons that are unknown.<ref name="Owczarek 2005 23–34"/> [[Electromyography|EMGs]] illicit a low amplitude motor potentials, and lack spontaneous electrical activity.<ref name="Baer 457–479"/>

====Colchicine====
* Patients who start taking [[colchicine]], and who have compromised renal function, develop a myopathy that shows symptoms in proximal muscle weakness, distal sensory loss and areflexia. A muscle biopsy shows a [[Vacuole|vacuolar]] myopathy without significant cell death or inflammation.<ref name="Baer 457–479"/>

====Chloroquine/Hydroxychloroquine====
* [[Chloroquine]]/[[hydroxychloroquine]] prescriptions can cause a development of a progressively slow muscle weakness that begins in the low extremities, and moves to the upper limbs. Muscle enzymes are increased, commonly lactate dehydrogenase (LDH).<ref name="Baer 457–479"/>

===Diet and Trauma Induced Myopathy===
Many dietary factors and aberrations can induce ANIM.  Chemical imbalances brought on by abnormal diets may either affect the muscle directly or induce abnormal functionality in upstream pathways.
[[File:Obstruction ventilation apnée sommeil.svg|200x192px|thumbnail|left|Muscular Weakness brought on by ANIM can induce sleep apnea]]
* Excess [[Iodine]] consumption, especially in the form of [[kelp]], can induce Hyperthyroidism.  Hyperthyroidism is one of the most common ways to acquire ANIM.<ref name="Essential Neurology, 2005" >{{cite book | vauthors = Wilkinson I, Lennox G |year=2005 |title=Essential Neurology |edition=4th |publisher=Wiley-Blackwell |page=171 |isbn=978-1-4051-1867-5}}</ref>  A hyperactive [[thyroid gland]] produces excessive amounts of hormones T3 and T4 leading to increased metabolism and increased [[sympathetic nervous system]] effects.  The muscles exhibit a pathology similar to an overdose of [[epinephrine]] (commonly known as adrenaline).  Patients with hyperthyroidism show weakness of shoulder girdle muscles in particular with this condition often being asymptomatic. More serious weakness of core and limb muscles may present.<ref name="Essential Neurology, 2005"/>
* A dietary [[Vitamin D deficiency|deficiency of vitamin D]] is most commonly associated with osteoporosis, but can cause ANIM as well.  Vitamin D induced ANIM is most commonly associated with [[sleep deprivation]] as it induces tonsillar and adenotonsillar hypertrophy, as well as weakens the airway muscles.<ref name="McCarthy">{{cite journal | vauthors = McCarty DE, Chesson AL, Jain SK, Marino AA | title = The link between vitamin D metabolism and sleep medicine | journal = Sleep Medicine Reviews | volume = 18 | issue = 4 | pages = 311–319 | date = August 2014 | doi = 10.1016/j.smrv.2013.07.001 | pmid = 24075129 }}</ref>  These changes induce [[sleep apnea]] and sleep disruption.  Vitamin D induced ANM can also be associated with daytime impairment through this pathway.<ref name="McCarthy"/>

[[Injury|Trauma]] to any muscle is also a common cause for acute ANIM.  This is due to muscular contusions and partial or complete loss of function for affected muscle groups.<ref name="Castro 111–120">{{cite journal | vauthors = Castro C, Gourley M | title = Diagnosis and treatment of inflammatory myopathy: issues and management | journal = Therapeutic Advances in Musculoskeletal Disease | volume = 4 | issue = 2 | pages = 111–120 | date = April 2012 | pmid = 22870499 | pmc = 3383519 | doi = 10.1177/1759720x11425092 }}</ref>

==Diagnosis==
[[File:EMG - SIMI.jpg|80x60px|thumbnail|right|EMG is often used as a diagnostic tool for ANIM]]
A patient's history is one of the key factors in diagnosing acquired non-inflammatory myopathy. The history is used not only to analyze the time frame with which the patient began to express symptoms, but to also see if the disease is within the patient's family history, to check medication or drug use history, and to see if the patient has had any trauma due to illness or infection. Basic exams will test for where the muscle weakness is and how weak it is. This is performed by testing for proximal and distal muscle strength, as well as testing for any signs of [[neurogenic]] symptoms such as impaired sensation, deep tendon reflexes, and atrophy.<ref name="Baer 457–479"/>

If needed, more advanced equipment can be used to help determine whether a patient has ANIM. This includes:
* Measurement of [[Serum (blood)|serum]] levels of muscle enzymes<ref name="Baer 457–479"/>
* [[Electromyography]] (EMG)<ref name="Baer 457–479"/>
* [[Magnetic Resonance Imaging]] (MRI)<ref name="Baer 457–479"/>
* [[Muscle biopsy]]<ref name="Baer 457–479"/>

When examining the serum levels of muscle enzymes, the relative levels of [[creatine kinase]], [[aldolase]], [[aspartate aminotransferase]], [[alanine aminotransferase]], and [[lactate dehydrogenase]] are closely examined. Abnormal levels of these proteins are indicative of both [[inflammatory myopathy]] and ANIM.<ref name="Baer 457–479"/>

EMGs are particularly useful in locating the affected muscle groups, as well as determining the distribution of the myopathy throughout the cell. EMGs measure several indicators of myopathies such as:<ref name="Baer 457–479" />
* The spontaneous electrical movement from a single muscle fibre at rest,
* Measurement of a polyphasic, shorter amplitude, [[motor unit]] action potential during muscle stimulation,
* Determining that the muscle group cannot differentiate large motor plate stimulation from small motor plate stimulation involved in recruitment of muscle fibers.<ref name="Baer 457–479"/>

Magnetic Resonance Imaging will elicit edema in inflammatory patients, but it will most likely show nothing in patients with ANIM and if it does, it will show some [[atrophy]].<ref name="Baer 457–479"/>

If an individual's ANIM is a result of a metabolite defect, then additional tests are required. These tests are directed at enzyme function at rest and during exercise, and enzyme intermediates. Molecular [[genetic testing]] is often used to determine if there was any predisposition to the expressed symptoms.<ref name="Baer 457–479"/>

==Screening==
During vigorous [[Ischemia|ischemic]] exercise, skeletal muscle functions anaerobically, generating lactate and ammonia a coproduct of muscle myoadenylate deaminase (AMPD) activity. The forearm ischemic exercise test takes advantage of this physiology and has been standardized to screen for disorders of glycogen metabolism and AMPD deficiency. Patients with a glycogen storage disease manifest a normal increase in ammonia but no change from baseline of lactate, whereas in those with AMPD deficiency, lactate levels increase but ammonia levels do not. If ischemic exercise testing gives an abnormal result, enzyme analysis must be performed on muscle to confirm the putative deficiency state because false-positive results can occur.{{citation needed|date=October 2020}}

==Treatment==
[[File:US Navy 111102-N-IZ292-050 Operations Specialist 1st Class Jennifer Funderburk, right, lifts weights during physical therapy in the Physical Therap.jpg|250x150px|thumbnail|right|Physical Therapy can be used to alleviate atrophy and soreness from ANIM]]
Treatment for acquired noninflammatory myopathy is directed towards resolution of the underlying condition, pain management, and muscle rehabilitation.
Drug induced ANIMs can be reversed or improved by tapering off of the drugs and finding alternative care.<ref name="Owczarek 2005 23–34"/>  Hyperthyroidism induced ANIM can be treated through anti-thyroid drugs, surgery, and not eating foods high in Iodine such as kelp.  Treatment of the hyperthyroidism results in complete recovery of the myopathy.<ref name="Essential Neurology, 2005"/>   ANIM caused by [[Hypovitaminosis D|vitamin D deficiency]] can easily be resolved by taking vitamin supplements and increasing one's exposure to direct sunlight.<ref name="McCarthy" />

Pain can be managed through massaging affected areas and the use of [[NSAID|nonsteroidal anti-inflammatory drugs]] (NSAIDs).
Exercise, physical therapy, and occupational therapy can be used to rehabilitate affected muscle areas and resist the [[atrophy]] process.<ref name="Castro 111–120"/> The use of walkers, canes, and braces may assist with the mobility of the affected individual.

==Research direction==
A diagnostic test for statin-associated auto-immune necrotizing myopathy will be available soon in order to differentiate between different types of myopathies during diagnosis. The presence of abnormal spontaneous electrical activity in the resting muscles indicates an irritable myopathy and is postulated to reflect the presence of an active necrotising myopathic process or unstable muscle membrane potential. However, this finding has poor sensitivity and specificity for predicting the presence of an [[inflammatory myopathy]] on biopsy. Further research into this spontaneous electrical activity will allow for a more accurate differential diagnosis between the different myopathies.<ref name="Baer 457–479"/>

Currently a muscle biopsy remains a critical test, unless the diagnosis can be secured by genetic testing. Genetic testing is a less invasive test and if it can be improved upon that would be ideal. Molecular genetic testing is now available for many of the more common metabolic myopathies and muscular dystrophies. These tests are costly and are thus best used to confirm rather than screen for a diagnosis of a specific myopathy. It is the hope of researchers that as these testing methods improve in function, both costs and access will become more manageable<ref name="Owczarek 2005 23–34"/>

The increased study of muscle pathophysiology is of importance to researchers as it helps to better differentiate inflammatory versus non-inflammatory and to aim treatment as part of the differential diagnosis. Certainly classification schemes that better define the wide range of myopathies will help clinicians to gain a better understanding of how to think about these patients. Continued research efforts to help appreciate the pathophysiology will improve clinicians ability to administer the most appropriate therapy based on the particular variety of myopathy.<ref name="Castro 111–120"/>

The mechanism for myopathy in individuals with low vitamin D is not completely understood. A decreased availability of 250HD leads to mishandling of cellular calcium transport to the sarcoplasmic reticulum and mitochondria, and is associated with reduced actomyosin content of myofibrils.<ref name="McCarthy"/>

== See also ==
* [[Inflammatory myopathy]]
* [[Skeletal striated muscle]]
* [[Motor unit]]
* [[Metabolic myopathy]]

== References ==

{{Reflist}}

[[Category:Neurological disorders]]
[[Category:Muscular disorders]]
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[[Категория:Английская Википедия]]
[[Категория:Википедия]]
[[Категория:Статья из Википедии]]
[[Категория:Статья из Английской Википедии]]