| Synonym: | ANIM |
| Specialty: | neurology |
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. 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 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.[1]
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. 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.
Most myopathies are typically first diagnosed and classified as an idiopathic inflammatory myopathy.[2] [3] [4] However, a diagnosis of ANIM occurs when the cause of the myopathy is found to not arise from an autoimmune mechanism.[1]
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.[1]
The most commonly reported symptoms are:
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 rheumatism are known to be inducing agents. Most cases of ANIM can be linked to drugs or dietary abnormalities.
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. Many of the drugs associated with inducing myopathies in patients are found in rheumatology practice.
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.
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.[8]
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.[1]
If needed, more advanced equipment can be used to help determine whether a patient has ANIM. This includes:
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.[1]
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:
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.[1]
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.[1]
During vigorous 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.
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.[5] 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. ANIM caused by vitamin D deficiency can easily be resolved by taking vitamin supplements and increasing one's exposure to direct sunlight.
Pain can be managed through massaging affected areas and the use of nonsteroidal anti-inflammatory drugs (NSAIDs).Exercise, physical therapy, and occupational therapy can be used to rehabilitate affected muscle areas and resist the atrophy process.[8] The use of walkers, canes, and braces may assist with the mobility of the affected individual.
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.[1]
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[5]
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.[8]
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.[7]