Horses also develop malignant hyperthermia. A causative mutated  allele , ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. [ 20 ]  has been identified in the  American Quarter Horse  and breeds with Quarter Horse ancestry, inherited as an  autosomal dominant . [ 21 ] [ 22 ]  It can be caused by overwork, anesthesia, or stress. [ 23 ]   In dogs, its inheritance is  autosomal recessive . [ 5 ]


An MH mouse has been constructed, bearing the R163C mutation prevalent in humans. These mice display signs similar to human MH patients, including sensitivity to halothane (increased respiration, body temperature, and death). Blockade of RYR1 by  dantrolene  prevents adverse reaction to halothane in these mice, as with humans. Muscle from these mice also shows increased  K + -induced depolarization and an increased caffeine sensitivity. [ 24 ]


The earliest signs may include:  masseter muscle  contracture following administration of succinylcholine, a rise in  end-tidal carbon dioxide concentration  (despite increased minute ventilation), unexplained tachycardia, and muscle rigidity. [ 5 ]   Despite the name, elevation of body temperature is often a late sign, but may appear early in severe cases. Respiratory acidosis is universally present and many patients have developed metabolic acidosis at the time of diagnosis. A  fast rate of breathing  (in a spontaneously breathing patient),  cyanosis , hypertension,  abnormal heart rhythms , and  high blood potassium  may also be seen. Core body temperatures should be measured in any patient undergoing general anesthesia longer than 30 minutes. [ citation needed ]


Malignant hyperthermia is diagnosed on clinical grounds, but various laboratory investigations may prove confirmatory. These include a raised creatine kinase level, elevated potassium, increased phosphate (leading to decreased calcium) and—if determined—raised myoglobin; this is the result of damage to muscle cells. Severe rhabdomyolysis may lead to  acute kidney failure , so  kidney function  is generally measured on a frequent basis.  Patients may also experience  premature ventricular contractions  due to the increased levels of potassium released from the muscles during episodes. [ citation needed ]


The main candidates for testing are those with a close relative who has had an episode of MH or have been shown to be susceptible. The standard procedure is the "caffeine-halothane contracture test", CHCT. A muscle  biopsy  is carried out at an approved research center, under local anesthesia. The fresh biopsy is bathed in solutions containing caffeine or halothane and observed for contraction; under good conditions, the  sensitivity  is 97% and the  specificity  78%. [ 25 ]  Negative biopsies are  not  definitive, so any patient who is suspected of MH by their medical history or that of blood relatives is generally treated with non-triggering anesthetics, even if the biopsy was negative. Some researchers advocate the use of the "calcium-induced calcium release" test in addition to the CHCT to make the test more specific. [ citation needed ]


Less invasive diagnostic techniques have been proposed. Intramuscular injection of halothane 6 vol% has been shown to result in higher than normal increases in local  pCO 2  among patients with known malignant hyperthermia susceptibility. The sensitivity was 100% and specificity was 75%. For patients at similar risk to those in this study, this leads to a  positive predictive value  of 80% and  negative predictive value  of 100%. This method may provide a suitable alternative to more invasive techniques. [ 26 ]
A 2002 study examined another possible metabolic test. In this test, intramuscular injection of caffeine was followed by local measurement of the  pCO 2 ; those with known MH susceptibility had a significantly higher  pCO 2  (63 versus 44 mmHg). The authors propose larger studies to assess the test's suitability for determining MH risk. [ 27 ]


Genetic testing  is being performed in a limited fashion to determine susceptibility to MH. [ 5 ]  In people with a family history of MH, analysis for  RYR1  mutations may be useful. [ 18 ]


A 1994 consensus conference led to the formulation of a set of diagnostic criteria. The higher the score (above 6), the more likely a reaction constituted MH: [ 28 ]


In the past, the  prophylactic  use of dantrolene was recommended for MH-susceptible patients undergoing general anesthesia. [ 29 ]  However, multiple retrospective studies have demonstrated the safety of trigger-free general anesthesia in these patients in the absence of prophylactic dantrolene administration. The largest of these studies looked at the charts of 2214 patients who underwent general or  regional anesthesia  for an elective muscle biopsy. About half (1082) of the patients were muscle biopsy positive for MH. Only five of these patients exhibited signs consistent with MH, four of which were treated successfully with  parenteral  dantrolene, and the remaining one recovered with only symptomatic therapy. [ 30 ]  After weighing its questionable benefits against its possible adverse effects (including nausea, vomiting, muscle weakness and prolonged duration of action of nondepolarizing neuromuscular blocking agents [ 31 ] ), experts no longer recommend the use of prophylactic dantrolene prior to trigger-free general anesthesia in MH-susceptible patients. [ 29 ]


Anesthesia for people with known MH susceptible requires avoidance of triggering agent concentrations above 5 parts per million (all volatile anesthetic agents and succinylcholine). Most other drugs are safe (including nitrous oxide), as are regional anesthetic techniques. Where general anesthesia is planned, it can be provided safely by either flushing the machine or using charcoal filters. [ citation needed ]


To flush the machine, first remove or disable the vaporizers and then flush the machine with 10 L/min or greater fresh gas flow rate for at least 20 minutes. While flushing the machine the ventilator should be set to periodically ventilate a new breathing circuit. The  soda lime  should also be replaced. After machine preparation, anesthesia should be induced and maintained with non-triggering agents. [ 31 ]  The time required to flush a machine varies for different machines and volatile anesthetics. This prevention technique was optimized to prepare older generation anesthesia machines. Modern anesthetic machines have more rubber and plastic components which provide a reservoir for volatile anesthetics, and should be flushed for 60 minutes. [ 32 ]


Charcoal filters can be used to prepare an anesthesia machine in less than 60 seconds for people at risk of malignant hyperthermia. These filters prevent residual anesthetic from triggering malignant hyperthermia for up to 12 hours, even at low fresh gas flows. [ 33 ]  Prior to placing the charcoal filters, the machine should be flushed with fresh gas flows greater than 10 L/min for 90 seconds. [ 34 ]


The current treatment of choice is the intravenous administration of  dantrolene , the only known antidote, discontinuation of triggering agents, and supportive therapy directed at correcting hyperthermia, acidosis, and organ dysfunction. Treatment must be instituted rapidly on clinical suspicion of the onset of malignant hyperthermia. [ 31 ]


Dantrolene is a muscle relaxant that appears to work directly on the ryanodine receptor to prevent the release of calcium. After the widespread introduction of treatment with dantrolene, the mortality of malignant hyperthermia fell from 80% in the 1960s to less than 5%. [ 5 ]  Dantrolene remains the only drug known to be effective in the treatment of MH. [ 29 ]  The recommended dose of dantrolene is 2.5 mg/kg, repeated as necessary. [ 5 ]  It is recommended that each hospital keeps a minimum stock of 36 dantrolene vials (720 mg), sufficient for four doses in a 70-kg person. [ 35 ]


Fast recognition and treatment of MH utilizes skills and procedures that are utilized with a low-frequency and high-risk. [ 36 ]  Conducting MH crisis training for  perioperative  teams can identify system failures as well as improve response to these events. [ 37 ]   Simulation  techniques to include the use of cognitive aids have also been shown to improve communication in clinical treatment of MH. [ 38 ] [ 39 ]


Prognosis is poor if this condition is not aggressively treated. [ 5 ]  In the 1970s, mortality was greater than 80%; however,  with the current management mortality is now less than 5%. [ 5 ]


It occurs in between 1:5,000 and 1:100,000 in procedures involving general anaesthesia. [ 5 ]  This disorder occurs worldwide and affects all racial groups.


In the  Manawatu  region of New Zealand, up to 1 in 200 people are at high risk of the condition. [ 40 ]


The syndrome was first recognized in  Royal Melbourne Hospital , Australia in an affected family by Denborough  et al.  in 1962. [ 41 ] [ 42 ]  Denborough did much of his subsequent work on the condition at the  Royal Canberra Hospital . [ 43 ]  Similar reactions were found in pigs. [ 44 ]  The efficacy of dantrolene as a treatment was discovered by South African anesthesiologist  Gaisford Harrison  and reported in a 1975 article published in the  British Journal of Anaesthesia . [ 45 ]  After further animal studies corroborated the possible benefit from dantrolene, a 1982 study confirmed its usefulness in humans. [ 46 ]


In 1981, the Malignant Hyperthermia Association of the United States (MHAUS)  hotline  was established to provide telephone support to clinical teams treating patients with suspected malignant hyperthermia. The hotline became active in 1982 and since that time MHAUS has provided continuous access to board-certified anesthesiologists to assist teams in treatment. [ 47 ]


Other animals, including certain pig breeds, dogs, and horses, are susceptible to malignant hyperthermia. [ 5 ]


In dogs its inheritance is  autosomal dominant . [ 48 ]  The syndrome has been reported in  Pointers, Greyhounds, Labrador Retrievers, Saint Bernards, Springer Spaniels, Bichon Frises, Golden Retrievers, and Border Collies. [ 49 ]


In pigs its inheritance is  autosomal recessive . [ 5 ]


In horses its inheritance is  autosomal dominant , and most associated with the  American Quarter Horse  although it can occur in other breeds. [ 50 ]


Azumolene  is a 30-fold more water-soluble  analog  of dantrolene that also works to decrease the release of intracellular calcium by its action on the ryanodine receptor. In MH-susceptible swine, azumolene was as potent as dantrolene. [ 51 ]  It has yet to be studied  in vivo  in humans, but may present a suitable alternative to dantrolene in the treatment of MH. [ citation needed ]


Metabolic myopathies  are  myopathies  that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects ( inborn errors of metabolism ) that interfere with the ability to create energy, causing a low ATP reservoir within the muscle cell. [ 1 ] [ 2 ]


Metabolic myopathies are generally caused by an inherited genetic mutation, an inborn error of metabolism. (In livestock, an acquired environmental GSD is caused by intoxication with the alkaloid  castanospermine .) [ 3 ]  Metabolic myopathies cause the underproduction of adenosine triphosphate (ATP) within the muscle cell. [ 4 ]


The genetic mutation typically has an autosomal recessive  hereditary  pattern making it fairly rare to inherit, and even more rarely it can be caused by a random  de novo  genetic mutation, or autosomal dominant, X-linked, or mitochondrial. [ 1 ]  Metabolic myopathies are categorized by the metabolic pathway to which the deficient enzyme or transport protein belongs. The main categories of metabolic myopathies are listed below: [ 5 ]


In the event more ATP is needed from the affected pathway, the lack of it becomes an issue and symptoms develop. People with a metabolic myopathy often experience symptoms such as:


The degree of symptoms varies greatly from person to person and is dependent on the severity of enzymatic or transport protein defect. In extreme cases it can lead to rhabdomyolysis. [ 19 ]  The symptoms experienced also depend on which metabolic pathway is impaired, as different metabolic pathways produce ATP at different time periods during activity and rest, as well as the type of activity ( anaerobic  or  aerobic ) and its  intensity  (level of ATP consumption).  [ citation needed ]


A majority of patients with metabolic myopathies have  dynamic  rather than  static  findings, typically experiencing exercise intolerance, muscle pain, and cramps with exercise rather than fixed muscle weakness. [ 1 ] [ 20 ]  However, a minority of metabolic myopathies have fixed muscular weakness rather than exercise intolerance, imitating an inflammatory myopathy or limb girdle muscular dystrophy. It is uncommon that both static and dynamic signs predominate. [ 1 ] [ 20 ]


At the cellular level, metabolic myopathies lack some kind of  enzyme  or  transport protein  that prevents the chemical reactions necessary to create  adenosine triphosphate (ATP) . [ 1 ] [ 17 ]  ATP is often referred to as the "molecular unit of currency" of intracellular  energy transfer . The lack of ATP prevents the muscle cells from being able to function properly. Some people with a metabolic myopathy never develop symptoms due to the body's ability to produce enough ATP through alternative pathways (e.g. the majority of those with  AMP-deaminase deficiency  are asymptomatic [ 1 ] [ 21 ] ).


H 2 O + ATP → H +  + ADP + P i  + energy → muscle contraction [ 22 ]


ATP is needed for  muscle contraction  by two processes:


ATP is consumed at a high rate by contracting muscles. The need for ATP in muscle cells is illustrated by the phenomenon of  Rigor mortis , which is the muscle rigidity that occurs in dead bodies for a short time after death. In these muscles, all the ATP has been used up and in the absence of further ATP being generated, the calcium transport proteins stop pumping calcium ions into the sarcoplasmic reticulum and the calcium ions gradually leak out. This causes the myosin proteins to grab the actin and pull once, but without further supply of ATP, cannot release and pull again. The muscles therefore remain rigid in the position at death until the binding of myosin to actin begins to break down and they become loose again. [ 23 ]


The symptoms of a metabolic myopathy can be easily confused with the symptoms of another disease. As genetic sequencing research progresses, a non-invasive neuromuscular panel DNA test can help make a diagnosis. Whole genome sequencing is required in more complex cases. [ 1 ]  If the DNA test is inconclusive (negative or  VUS ), then a  muscle biopsy  is necessary for an accurate diagnosis. In mitochondrial myopathies involving a single mtDNA deletion, DNA would have to be tested from affected muscle tissue rather than saliva or blood as unaffected tissues would show normal or near normal levels of mtDNA. [ 1 ] [ 24 ] [ 25 ]


A  blood test  for  creatine kinase  (CK) can be done under normal circumstances to test for signs of tissue breakdown, or with an added cardio portion that can indicate if muscle breakdown is occurring. In metabolic myopathies, baseline CK is either normal or elevated. [ 8 ]  An  electromyography  (EMG) test is sometimes taken in order to rule out other disorders if the cause of fatigue is unknown. [ 4 ]  In metabolic myopathies, the EMG is either normal or myopathic, but spontaneous activity is usually absent. [ 8 ]


An  exercise stress test  can be used to determine an inappropriate rapid heart rate ( sinus tachycardia ) response to exercise, which is seen in  GSD-V , other glycogenoses, and mitochondrial myopathies. [ 7 ] [ 9 ]  A 12 Minutes Walk Test (12MWT) can also be used to determine " second wind " which is also seen in McArdle disease (GSD-V) and  phosphoglucomutase deficiency  (PGM1-CDG/CDG1T/GSD-XIV). [ 7 ] [ 26 ]


A  cardiopulmonary exercise test  can measure both heart rate and breathing, to evaluate the oxygen cost (∆V'O 2 /∆Work-Rate) during incremental exercise. In both glycogenoses and mitochondrial myopathies, patients displayed an increased oxygen cost during exercise compared to control subjects; and therefore, can perform less work for a given  V̇O 2  consumption during submaximal daily life exercises. [ 9 ] [ 10 ]


In fatty acid oxidation disorders (FAOD), while at rest, some exhibit cardiac arrhythmia (commonly various forms of tachycardia, but more rarely, conduction disorders or acute bradycardia); while others have a normal heart rhythm. [ 27 ]


Some GSDs and a mitochondrial myopathy are known to have a  pseudoathletic appearance . McArdle disease (GSD-V) and late-onset Pompe disease (GSD-II) are known to have hypertrophy, particularly of the calf muscles. [ 14 ] [ 15 ]  Cori/Forbes disease (GSD-III) is known to have hypertrophy of the sternocleidomastoid, trapezius, quadriceps, and thigh muscles. [ 13 ] [ 28 ] [ 29 ] [ 30 ]  Muscular dystrophy, limb-girdle, type 1H  (which as of 2017 was excluded from LGMD for showing signs on muscle biopsy as being a mitochondrial myopathy, but not yet assigned new nomenclature) [ 31 ]  is also known to have hypertrophy of the calf muscles. [ 32 ]   Hereditary myopathy with lactic acidosis  (HML), another mitochondrial myopathy, also has hypertrophy of the calf muscles in some. [ 16 ] [ 33 ]


Blood test may show a disturbance in pH, with  lactic acidosis  (low pH) in mitochondrial myopathies either at rest or exercise-induced. [ 34 ]  Glycogen storage diseases may show transient exercise-induced  alkalosis  (high pH),  hyperammonemia , and myogenic  hyperuricemia . [ 35 ] [ 36 ] [ 37 ] [ 38 ] [ 39 ]  During a non-ischemic forearm exercise test, in GSDs the plasma lactate typically fails to rise (and may fall below resting levels); except for a few GSDs such as phosphoglucomutase deficiency (GSD-XIV), [ 39 ]  deficiency of functioning myophosphorylase-a (autosomal dominant PYGM), [ 40 ]  phosphorylase-b kinase deficiency (GSD-IXd), and Pompe disease (GSD-II) where lactate production is normal. [ 2 ]  In myoadenylate deaminase deficiency (AMPD1 deficiency), there is no rise in ammonia. [ 2 ]  Some fatty acid oxidation disorders show lactic acidosis, hypoketotic  hypoglycaemia  and hyperammonemia, while others are asymptomatic. [ 2 ] [ 41 ] [ 42 ]


Differentiating between different types of metabolic myopathies can be difficult due to the similar symptoms of each type such as  myoglobinuria  and  exercise intolerance . It has to be determined whether the patient has fixed (static) or exercise-induced (dynamic) manifestations; and if exercise-related, what kind of exercise, before extensive exercise-related lab testing is done to determine the underlying cause. [ 5 ]


Adequate knowledge is required of the body's  bioenergetic systems , [ 8 ] [ 43 ]  including:


For example, leisurely-paced walking and fast-paced walking on level ground (no incline) are both aerobic, but fast-paced walking relies on more muscle glycogen because of the higher intensity (which would cause  exercise intolerance  symptoms in those with muscle  glycogenoses  that hadn't yet achieved " second wind "). [ 11 ] [ 7 ] [ 18 ] [ 44 ]


When walking at a leisurely pace on level ground (no incline), but there is loose gravel or sand, long grass, snow, mud, or walking into a headwind, that added resistance (requiring more effort) makes the activity more reliant on muscle glycogen also. [ 7 ] [ 18 ]  These and other surfaces, such as ice, can make you tense your muscles (which is anearobic requiring muscle glycogen) as you protect yourself from slipping or falling. [ 7 ] [ 18 ]


Those with muscle glycogenoses can maintain a healthy life of exercise by learning activity adaptations, utilizing the bioenergetic systems that are available to them. Depending on the type of activity and whether they are in second wind, they slow their pace or rest briefly when need be, to make sure not to empty their "ATP reservoir." [ 7 ] [ 18 ]


signs and symptoms


and  low-intensity aerobic  activity


(within seconds to minutes),
by  high-intensity aerobic  activity


and all  anaerobic  activity


Metabolic myopathies have varying levels of symptoms, being most severe when developed during infancy. Those who do not develop a form of a metabolic myopathy until they are in their young adult or adult life tend to have more treatable symptoms that can be helped with a change in diet and exercise. [ 19 ]  It might be more accurate to say that metabolic myopathies described as adult-onset, it isn't necessarily that they didn't develop in infancy (they are inborn—from birth—errors of metabolism) but that they didn't display severe enough symptoms to warrant the attention of medical professionals until their adult years (severe symptoms such as rhabdomyolysis, fixed muscle weakness due to years of repetitive injury, or the de-conditioning of muscles from a more sedentary adult lifestyle which exacerbated symptoms). [ citation needed ]


Due to the rare nature of these diseases, it is very common to be misdiagnosed, even misdiagnosed multiple times. [ 11 ] [ 47 ] [ 43 ] [ 48 ]  Once a correct diagnosis has been made, in adult years, looking back symptoms were present since childhood, but either brushed-off as growing pains, laziness, or told that they just needed to exercise more. [ 43 ] [ 47 ] [ 11 ]  It is especially difficult to get a diagnosis when symptoms are  dynamic  (exercise-induced), such as in muscle  glycogenoses . [ 11 ] [ 20 ] [ 43 ]  Sitting in a doctor's office (at rest) or doing movements that only last a few seconds (within the time limit of the phosphagen system) the patient wouldn't display any noticeable abnormalities (such as  muscle fatigue , cramping, or breathlessness). [ citation needed ]


A brief or only mildly  elevated heart rate  (heart rate taken while sitting down after recently walking across the room or getting up on the examination table) might be assumed to be due to anxiety or illness rather than exercise-induced inappropriate rapid heart rate due to an ATP shortage in the muscle cells. In the absence of severe symptoms (such as hepatomegaly, cardiomyopathy, hypoglycemia, lactic acidosis, myoglobinuria, rhabdomyolysis, acute compartment syndrome or renal failure), it is understandable that a disease would not be noticed by medical professionals for years, when at rest the patient appears completely normal. [ citation needed ]


Depending on what enzyme is affected, a high-protein or low-fat diet may be recommended along with mild exercise. It is important for people with metabolic myopathies to consult with their doctors for a treatment plan in order to prevent acute muscle breakdowns while exercising that lead to the release of muscle proteins into the bloodstream that can cause kidney damage. [ 4 ]


A ketogenic diet has a remarkable effect on CNS-symptoms in  PDH-deficiency  and has also been tried in  complex I deficiency . [ 49 ]  A ketogenic diet has demonstrated beneficial for McArdle disease ( GSD-V ) as ketones readily convert to acetyl CoA for oxidative phosphorylation, whereas free fatty acids take a few minutes to convert into acetyl CoA. [ 46 ]  As of 2022, another study on a ketogenic diet and McArdle disease (GSD-V) is underway. [ 50 ]


For McArdle disease (GSD-V), regular aerobic exercise utilizing " second wind " to enable the muscles to become aerobically conditioned, as well as anaerobic exercise that follows the activity adaptations so as not to cause muscle injury, helps to improve exercise intolerance symptoms and maintain overall health. [ 7 ] [ 11 ] [ 51 ] [ 52 ]  Studies have shown that regular low-moderate aerobic exercise increases peak power output, increases peak oxygen uptake ( VO 2 peak ), lowers heart rate, and lowers serum CK in individuals with McArdle disease. [ 51 ] [ 52 ]


Regardless of whether the patient experiences  symptoms  of muscle pain, muscle fatigue, or cramping, the phenomenon of second wind having been achieved is demonstrable by the  sign  of an increased heart rate dropping while maintaining the same speed on the treadmill. [ 52 ] [ 43 ]  Inactive patients experienced second wind, demonstrated through relief of typical symptoms and the sign of an increased heart rate dropping, while performing low-moderate aerobic exercise (walking or brisk walking). [ 52 ] [ 43 ]  Conversely, patients that were regularly active did not experience the typical symptoms during low-moderate aerobic exercise (walking or brisk walking), but still demonstrated second wind by the sign of an increased heart rate dropping. [ 52 ] [ 43 ]  For the regularly active patients, it took more strenuous exercise (very brisk walking/jogging or bicycling) for them to experience both the typical symptoms and relief thereof, along with the sign of an increased heart rate dropping, demonstrating second wind. [ 52 ] [ 43 ]


Muscle atrophy  is the loss of  skeletal muscle  mass. It can be caused by  immobility , aging,  malnutrition , medications, or a wide range of injuries or diseases that impact the musculoskeletal or  nervous system . Muscle atrophy leads to muscle weakness and causes disability.


Disuse causes rapid muscle atrophy and often occurs during injury or illness that requires immobilization of a limb or bed rest. Depending on the duration of disuse and the health of the individual, this may be fully reversed with activity. Malnutrition first causes fat loss but may progress to muscle atrophy in prolonged starvation and can be reversed with nutritional therapy. In contrast,  cachexia  is a wasting syndrome caused by an underlying disease such as cancer that causes dramatic muscle atrophy and cannot be completely reversed with nutritional therapy.  Sarcopenia  is  age-related  muscle atrophy and can be slowed by exercise. Finally, diseases of the muscles such as  muscular dystrophy  or  myopathies  can cause atrophy, as well as damage to the nervous system such as in  spinal cord injury  or  stroke . Thus, muscle atrophy is usually a finding ( sign or symptom ) in a disease rather than being a disease by itself. However, some  syndromes  of muscular atrophy are classified as disease spectrums or disease entities rather than as clinical syndromes alone, such as the various  spinal muscular atrophies .


Muscle atrophy results from an imbalance between protein synthesis and protein degradation, although the mechanisms are incompletely understood and are variable depending on the cause. Muscle loss can be quantified with advanced imaging studies but this is not frequently pursued. Treatment depends on the underlying cause but will often include exercise and adequate nutrition.  Anabolic agents  may have some efficacy but are not often used due to side effects. There are multiple treatments and supplements under investigation but there are currently limited treatment options in clinical practice. Given the implications of muscle atrophy and limited treatment options, minimizing immobility is critical in injury or illness.


The hallmark sign of muscle atrophy is loss of lean muscle mass. This change may be difficult to detect due to obesity, changes in fat mass or edema. Changes in weight, limb or waist circumference are not reliable indicators of muscle mass changes. [ 1 ]


The predominant symptom is increased weakness which may result in difficulty or inability in performing physical tasks depending on what muscles are affected. Atrophy of the core or leg muscles may cause difficulty standing from a seated position, walking or climbing stairs and can cause increased falls. Atrophy of the throat muscles may cause difficulty swallowing and diaphragm atrophy can cause difficulty breathing. Muscle atrophy can be asymptomatic and may go undetected until a significant amount of muscle is lost. [ 2 ]


Skeletal muscle serves as a storage site for  amino acids ,  creatine ,  myoglobin , and  adenosine triphosphate , which can be used for energy production when demands are high or supplies are low. If metabolic demands remain greater than protein synthesis, muscle mass is lost. [ 3 ]  Many diseases and conditions can lead to this imbalance, either through the disease itself or disease associated appetite-changes, such as loss of taste due to  Covid-19 . Causes of muscle  atrophy , include immobility, aging,  malnutrition , certain systemic diseases ( cancer ,  congestive heart failure ;  chronic obstructive pulmonary disease ;  AIDS ,  liver disease , etc.), deinnervation, intrinsic muscle disease or medications (such as  glucocorticoids ). [ 4 ]


Disuse is a common cause of muscle atrophy and can be local (due to injury or casting) or general (bed-rest). The rate of muscle atrophy from disuse (10–42 days) is  approximately 0.5–0.6% of total muscle mass per day although there is considerable variation between people. [ 5 ]  The elderly are the most vulnerable to dramatic muscle loss with immobility. Much of the established research has investigated prolonged disuse (>10 days), in which the muscle is compromised primarily by declines in muscle protein synthesis rates rather than changes in muscle protein breakdown. There is evidence to suggest that there may be more active protein breakdown during short term immobility (<10 days). [ 5 ]


Certain diseases can cause a complex muscle wasting syndrome known as  cachexia . It is commonly seen in cancer,  congestive heart failure ,  chronic obstructive pulmonary disease ,  chronic kidney disease  and  AIDS  although it is associated with many disease processes, usually with a significant inflammatory component. Cachexia causes ongoing muscle loss that is not entirely reversed with nutritional therapy. [ 6 ]  The pathophysiology is incompletely understood but inflammatory  cytokines  are considered to play a central role. In contrast to weight loss from inadequate caloric intake,  cachexia  causes predominantly muscle loss instead of fat loss and it is not as responsive to nutritional intervention. Cachexia can significantly compromise quality of life and functional status and is associated with poor outcomes. [ 7 ] [ 8 ]


Sarcopenia  is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging. This involves muscle atrophy, reduction in number of muscle fibers and a shift towards "slow twitch" or  type I skeletal muscle fibers  over "fast twitch" or  type II fibers . [ 3 ]  The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. There are many proposed mechanisms of sarcopenia, such as a decreased capacity for oxidative phosphorylation, cellular senescence or an altered signaling of pathways regulating protein synthesis, [ 9 ]  and is considered to be the result of changes in muscle synthesis signalling pathways and gradual failure in the  satellite cells  which help to regenerate skeletal muscle fibers, specifically in "fast twitch" myofibers. [ 10 ]


Sarcopenia can lead to reduction in functional status and cause significant disability but is a distinct condition from  cachexia  although they may co-exist. [ 8 ] [ 11 ]  In 2016 an  ICD code  for sarcopenia was released, contributing to its acceptance as a disease entity. [ 12 ]


Muscle diseases, such as  muscular dystrophy ,  amyotrophic lateral sclerosis  (ALS), or  myositis  such as  inclusion body myositis  can cause muscle atrophy. [ 13 ]


Damage to neurons in the brain or spinal cord can cause prominent muscle atrophy. This can be localized muscle atrophy and weakness or paralysis such as in  stroke  or  spinal cord injury . [ 14 ]  More widespread damage such as in  traumatic brain injury  or  cerebral palsy  can cause generalized muscle atrophy. [ 15 ]


Injuries or diseases of peripheral nerves supplying specific muscles can also cause muscle atrophy. This is seen in nerve injury due to trauma or surgical complication, nerve entrapment, or inherited diseases such as  Charcot-Marie-Tooth disease . [ 16 ]


Some medications are known to cause muscle atrophy, usually due to direct effect on muscles. This includes glucocorticoids causing glucocorticoid myopathy [ 4 ]  or medications toxic to muscle such as  doxorubicin . [ 17 ]


Disorders of the endocrine system such as  Cushing's disease  or  hypothyroidism  are known to cause muscle atrophy. [ 18 ]


Muscle atrophy occurs due to an imbalance between the normal balance between protein synthesis and protein degradation. This involves complex cell signalling that is incompletely understood and muscle atrophy is likely the result of multiple contributing mechanisms. [ 19 ]


Mitochondrial function is crucial to skeletal muscle health and detrimental changes at the level of the mitochondria may contribute to muscle atrophy. [ 20 ]  A decline in mitochondrial density as well as quality is consistently seen in muscle atrophy due to disuse. [ 20 ]


The  ATP -dependent  ubiquitin / proteasome  pathway is one mechanism by which proteins are degraded in muscle. This involves specific proteins being tagged for destruction by a small peptide called  ubiquitin  which allows recognition by the  proteasome  to degrade the protein. [ 21 ]


Screening for muscle atrophy is limited by a lack of established diagnostic criteria, although many have been proposed. Diagnostic criteria for other conditions such as  sarcopenia  or  cachexia  can be used. [ 3 ]  These syndromes can also be identified with screening questionnaires. [ citation needed ]


Muscle mass and changes can be quantified on imaging studies such as  CT scans  or  Magnetic resonance imaging (MRI) . Biomarkers such as urine  urea  can be used to roughly estimate muscle loss during circumstances of rapid muscle loss. [ 22 ]  Other biomarkers are currently under investigation but are not used in clinical practice. [ 3 ]


Muscle atrophy can be delayed, prevented and sometimes reversed with treatment. Treatment approaches include impacting the signaling pathways that induce  muscle hypertrophy  or slow muscle breakdown as well as optimizing nutritional status. [ citation needed ]


Physical activity provides a significant anabolic muscle stimulus and is a crucial component to slowing or reversing muscle atrophy. [ 3 ]  It is still unknown regarding the ideal exercise "dosing." Resistance exercise has been shown to be beneficial in reducing muscle atrophy in older adults. [ 23 ] [ 24 ]  In patients who cannot exercise due to physical limitations such as paraplegia,  functional electrical stimulation  can be used to externally stimulate the muscles. [ 25 ]


Adequate calories and protein is crucial to prevent muscle atrophy. Protein needs may vary dramatically depending on metabolic factors and disease state, so high-protein supplementation may be beneficial. [ 3 ]  Supplementation of protein or  branched-chain amino acids , especially leucine, can provide a stimulus for muscle synthesis and inhibit protein breakdown and has been studied for muscle atrophy for sarcopenia and cachexia. [ 3 ] [ 26 ]   β-Hydroxy β-methylbutyrate  (HMB), a metabolite of  leucine  which is sold as a  dietary supplement , has demonstrated efficacy in preventing the loss of muscle mass in several muscle wasting conditions in humans, particularly  sarcopenia . [ 26 ] [ 27 ] [ 28 ]  Based upon a  meta-analysis  of seven  randomized controlled trials  that was published in 2015, HMB supplementation has efficacy as a treatment for preserving lean muscle mass in older adults. [ 29 ]  More research is needed to determine the precise effects of HMB on muscle strength and function in various populations. [ 29 ]


In severe cases of muscular atrophy, the use of an  anabolic steroid  such as  methandrostenolone  may be administered to patients as a potential treatment although use is limited by side effects. A novel class of drugs, called  selective androgen receptor modulators , is being investigated with promising results. They would have fewer  side effects , while still promoting muscle and bone tissue growth and regeneration. These effects have yet to be confirmed in larger clinical trials. [ 30 ]


Outcomes of muscle atrophy depend on the underlying cause and the health of the patient. Immobility or bed rest in populations predisposed to muscle atrophy, such as the elderly or those with disease states that commonly cause  cachexia , can cause dramatic muscle atrophy and impact on functional outcomes. In the elderly, this often leads to decreased biological reserve and increased vulnerability to stressors known as the " frailty syndrome ." [ 3 ]  Loss of lean body mass is also associated with increased risk of infection, decreased immunity, and poor wound healing. The weakness that accompanies muscle atrophy leads to higher risk of falls, fractures, physical disability, need for institutional care, reduced quality of life, increased mortality, and increased healthcare costs. [ 3 ]


Inactivity and starvation in mammals lead to atrophy of skeletal muscle, accompanied by a smaller number and size of the muscle cells as well as lower protein content. [ 31 ]  In humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts flying in space, are known to result in muscle weakening and atrophy. Such consequences are also noted in small hibernating mammals like the golden-mantled ground squirrels and brown bats. [ 32 ]


Bears  are an exception to this rule; species in the family Ursidae are famous for their ability to survive unfavorable environmental conditions of low temperatures and limited nutrition availability during winter by means of  hibernation . During that time, bears go through a series of physiological, morphological, and behavioral changes. [ 33 ]   Their ability to maintain skeletal muscle number and size during disuse is of significant importance. [ citation needed ]


During hibernation, bears spend 4–7 months of inactivity and anorexia without undergoing muscle atrophy and protein loss. [ 32 ]  A few known factors contribute to the sustaining of muscle tissue. During the summer, bears take advantage of the nutrition availability and accumulate muscle protein. The protein balance at time of dormancy is also maintained by lower levels of protein breakdown during the winter. [ 32 ]   At times of immobility, muscle wasting in bears is also suppressed by a proteolytic inhibitor that is released in circulation. [ 31 ]   Another factor that contributes to the sustaining of muscle strength in hibernating bears is the occurrence of periodic voluntary contractions and involuntary contractions from shivering during  torpor . [ 34 ]   The three to four daily episodes of muscle activity are responsible for the maintenance of muscle strength and responsiveness in bears during hibernation. [ 34 ]


Muscle-atrophy can be induced in pre-clinical models (e.g. mice) to study the effects of therapeutic interventions against muscle-atrophy. Restriction of the diet, i.e. caloric restriction, leads to a significant loss of muscle mass within two weeks, and loss of muscle-mass can be rescued by a nutritional intervention. [ 35 ]  Immobilization of one of the hindlegs of mice leads to muscle-atrophy as well, and is hallmarked by loss of both muscle mass and strength. Food restriction and immobilization may be used in mouse models and have been shown to overlap with mechanisms associated to sarcopenia in humans. [ 36 ]


Muscle fatigue  is when muscles that were initially generating a normal amount of  force , then experience a declining ability to generate force. It can be a result of vigorous  exercise , but abnormal fatigue may be caused by barriers to or interference with the different stages of  muscle contraction . There are two main causes of muscle fatigue: the limitations of a  nerve ’s ability to generate a sustained  signal  (neural fatigue); and the reduced ability of the  muscle fiber  to contract (metabolic fatigue).


Muscle fatigue is not the same as muscle weakness, though weakness is an initial symptom. Despite a normal amount of force being generated at the start of activity, once muscle fatigue has set in and progressively worsens, if the individual persists in the exercise they will eventually lose their hand grip, or become unable to lift or push with their arms or legs, or become unable to maintain an isometric position (such as  plank ). Other symptoms may accompany such as myalgia (muscle pain), shortness of breath, fasciculations (muscle twitching), myokymia (muscle trembling), and muscle cramps during exercise; muscle soreness may occur afterwards. [ 1 ]  An inappropriate rapid heart rate response to exercise may be seen, such as in the metabolic myopathy of McArdle disease (GSD-V), where the heart tries to compensate for the deficit of ATP in the  skeletal muscle  cells (metabolic fatigue) by increasing heart rate to maximize delivery of oxygen and blood borne fuels to the muscles for oxidative phosphorylation. [ 2 ]  The combination of an inappropriate rapid heart rate response to exercise with heavy or rapid breathing is known as an exaggerated cardiorespiratory response to exercise. [ 3 ]


Due to the confusion between muscle fatigue and muscle weakness, there have been instances of abnormal muscle fatigue being described as exercise-induced muscle weakness. [ 4 ] [ 5 ] [ 6 ]


Muscle cells work by detecting a  flow  of electrical impulses from the  brain  which signals them to  contract  through the release of  calcium  by the  sarcoplasmic reticulum .  Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. [ citation needed ]


Nerves  are responsible for controlling the contraction of muscles, determining the number, sequence and force of muscular contraction.  Most movements require a force far below what a muscle could potentially generate, and nervous fatigue is seldom an issue. But, during extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, nervous fatigue (enervation) — in which the nerve signal weakens — can be a limiting factor in untrained individuals. [ citation needed ]


In novice  strength trainers , the muscle's ability to generate force is most strongly limited by nerve’s ability to sustain a high-frequency signal.  After a period of maximum contraction, the nerve’s signal reduces in frequency and the force generated by the contraction diminishes.  There is no sensation of pain or discomfort, the muscle appears to simply ‘stop listening’ and gradually cease to contract, often  going backwards .  Often there is insufficient stress on the muscles and tendons to cause  delayed onset muscle soreness  following the workout. [ citation needed ]


Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with its greatest force.  This neural training can cause several weeks of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit.  Past this point, training effects increase muscular strength through myofibrillar or sarcoplasmic  hypertrophy  and metabolic fatigue becomes the factor limiting contractile force. [ citation needed ]


Though not universally used, ‘metabolic fatigue’ is a common term for the reduction in contractile force due to the direct or indirect effects of two main factors:


Substrates  within the muscle serve to power muscular contractions. They include molecules such as  adenosine triphosphate  (ATP),  glycogen  and  creatine phosphate . ATP binds to the  myosin  head and causes the ‘ratchetting’ that results in contraction according to the  sliding filament model . Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from  adenosine diphosphate  (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of  glucose , used to generate energy quickly as intramuscular phosphocreatine stores become exhausted, producing  lactic acid  as a metabolic byproduct.


Substrate shortage is one of the causes of metabolic fatigue. Substrates are depleted during exercise or are unable to be metabolized (e.g.  metabolic myopathies ), resulting in a lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so.


Metabolites are the substances (generally waste products) produced as a result of muscular contraction.  They include  chloride ,  potassium ,  lactic acid ,  ADP ,  magnesium  (Mg 2+ ),  reactive oxygen species , and  inorganic phosphate .  Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium (Ca 2+ ) from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules  actin  and  myosin  to calcium.


Intracellular  chloride  partially inhibits the contraction of muscles. Namely, it prevents muscles from contracting due to "false alarms", small stimuli which may cause them to contract (akin to  myoclonus ).


High concentrations of  potassium  (K + ) also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the  t-tubule  system and around the muscle fiber as a result of  action potentials . The shift in K +  changes the membrane potential around the muscle fiber. The change in membrane potential causes a decrease in the release of  calcium  (Ca 2+ ) from the  sarcoplasmic reticulum . [ 7 ]


It was once believed that  lactic acid  build-up was the cause of muscle fatigue. [ 8 ]   The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract.  Though the impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.


Produced as a by-product of  fermentation , lactic acid can increase intracellular acidity of muscles.  This can lower the sensitivity of contractile apparatus to Ca 2+  but also has the effect of increasing  cytoplasmic  Ca 2+  concentration through an inhibition of the  chemical pump  that  actively transports  calcium out of the cell.  This counters inhibiting effects of potassium on muscular action potentials.  Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions.  Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca 2+ .


Lactic acid is now used as a measure of endurance training effectiveness and  VO 2  max . [ 9 ]


Muscle fatigue may be due to problems with the  nerve supply ,  neuromuscular disease  (such as  myasthenia gravis ),  inborn errors of metabolism  (such as  metabolic myopathies ), or problems with muscle itself. The latter category includes  polymyositis  and other  muscle disorders .


Muscle fatigue may be due to precise molecular changes that occur  in vivo  with sustained exercise. It has been found that the  ryanodine receptor  present in skeletal muscle undergoes a  conformational change  during exercise, resulting in "leaky" channels that are deficient in  calcium  release. These "leaky" channels may be a contributor to muscle fatigue and decreased exercise capacity. [ 10 ]


Fatigue has been found to play a big role in limiting performance in just about every individual in every sport.  In research studies, participants were found to show reduced voluntary force production in fatigued muscles (measured with concentric, eccentric, and isometric contractions), vertical jump heights, other field tests of lower body power, reduced throwing velocities, reduced kicking power and velocity, less accuracy in throwing and shooting activities, endurance capacity, anaerobic capacity, anaerobic power, mental concentration, and many other performance parameters when sport specific skills are examined. [ 11 ] [ 12 ] [ 13 ] [ 14 ] [ 15 ]


Electromyography  is a research technique that allows researchers to look at muscle recruitment in various conditions, by quantifying electrical signals sent to muscle fibers through motor neurons.  In general, fatigue protocols have shown increases in EMG data over the course of a fatiguing protocol, but reduced recruitment of muscle fibers in tests of power in fatigued individuals.  In most studies, this increase in recruitment during exercise correlated with a decrease in performance (as would be expected in a fatiguing individual). [ 16 ] [ 17 ] [ 18 ] [ 19 ]


Median power frequency is often used as a way to track fatigue using EMG. Using the median power frequency, raw EMG data is filtered to reduce noise and then relevant time windows are Fourier Transformed. In the case of fatigue in a 30-second isometric contraction, the first window may be the first second, the second window might be at second 15, and the third window could be the last second of contraction (at second 30). Each window of data is analyzed and the median power frequency is found. Generally, the median power frequency decreases over time, demonstrating fatigue. Some reasons why fatigue is found are due to action potentials of motor units having a similar pattern of repolarization, fast motor units activating and then quickly deactivating while slower motor units remain, and conduction velocities of the nervous system decreasing over time. [ 20 ] [ 21 ] [ 22 ] [ 23 ]


Muscle balance is necessary for muscles to perform their customary roles and move normally;  muscle imbalance  occurs when there is a lack of parity between corresponding  agonist and antagonist  muscles. [ 1 ]  Muscular imbalance can also arise when a muscle performs outside of its normal physiological muscle function. [ 2 ] [ 3 ]


Muscles are considered balanced when the muscles that surround a joint work together harmoniously, i.e. with appropriate opposing force, to keep the bones aligned where they meet at the joint. This permits normal  human movement . [ 3 ]


Muscles can be categorized as either functional or pathological. Muscle imbalance can be caused either by adaptation of a functional muscle or by dysfunction in a muscle suffering a pathology.


Classic symptoms of muscle imbalances are usually pain associated with the affected joint. [ 1 ]  Symptoms can vary depending on what stage their muscular imbalance is, functional or pathological, but commonly exhibit small tissue damage or lesions accompanied by a change in muscle movement patterns. [ 1 ]  Symptoms may occur after injury or surgery, where the recuperation of the joint affected is left untreated causing either tension or restriction to flexibility and strength of the prime movers. [ 2 ]


Tennis elbow  is the most common elbow problem among athletes, highly associated with world class tennis players, it is a condition that involves the common wrist extensor origin, in particular the origin of extensor carpi radialis. [ 4 ]   The causes for tennis elbow includes any activity, not only tennis, where the repetitive use of the extensor muscles of the forearm may cause acute or chronic tendonitis of the tensinous insertion of these muscles at the lateral epicondyle of the elbow. [ 5 ]  The condition itself is most common with painters, plumbers, and carpenters. Further studied have shown that auto-workers, butchers and cooks also get tennis elbow more often than the rest of the population. [ 5 ]


Lazy eye , in particular  strabismus  may be the result of coordination between the  extraocular muscles , which prevents a person on directing both eyes in unison towards the same fixation point. [ 6 ]  The main cause of strabismus is usually the muscular imbalance of the six surrounding muscles that allow both eyes to focus on the same object. [ 7 ]  As each eye does not have the same focus, different images are sent to the brain, confusing it, resulting in the brain ignoring the image from the weaker eye and if left untreated will cause a loss of vision in the ignored eye called  amblyopia . [ 7 ]  Further symptoms of strabismus include decreased vision,  double vision ,  headaches ,  asthenopia  and  eye fatigue . [ 6 ]


Scoliosis , is a medical condition where a person's spine has several irregular curves that are located between the neck and the pelvis. [ 8 ]  Symptoms of scoliosis in mild cases usually exhibit abnormal posture, back pain, tingling or numbness in the legs and in worse cases can exhibit breathing problems, fatigue, permanent deformities and in rare cases heart problems. [ 8 ]


Functional Imbalances are when the muscles adapt in response for detailed muscle movement patterns, including unequal values in strength or flexibility of antagonistic muscle groups, usually apparent in athletes of different sports ranging from soccer to baseball. [ 1 ]  This type of imbalance is the first stage, it is painless, atraumatic (causes minimal tissue injury [ 9 ] ), adaptive to change and activity specific. [ 1 ]  Studies confirm this as they find the link between muscle imbalance and athletes who perform at elite levels, this also relates to injury occurrence is not treated to muscle specific rehabilitation. [ 10 ]


Pathological muscle imbalance occurs when the imbalance of the muscles begin to inhibit function. [ 1 ]  This pathological muscle imbalance may or may not result from a traumatic event, it is usually associated with pain and dysfunction, although there are cases where pain is not apparent, however pathological muscle imbalances ultimately lead to joint dysfunction and changes in normative muscle movement patterns. [ 1 ]  It would be good to note that this imbalance can progress to either tissue damage and pain or altered movement pattern, with the constant being tightness or weakness. [ 1 ]  A study has shown that athletes that exhibit shoulder pain have been linked to have decreased  rotator cuff  muscle strength and have concluded that they are more susceptible to  rotator cuff tears  and type II superior  labrum  anterior and posterior  lesions . [ 11 ]


Muscle imbalance can be characterized by different factors, namely where the muscle imbalance is on the body, diagnosis varies for these specific areas as each area needs to be handled differently. Other signs include joint pain or muscular pain, abnormal joint movement patterns or in some cases, muscle tears and lesions. [ 11 ]  It can be diagnosed by demonstrating any one of the following:


Although treatment for tennis elbow prior 2010 was unknown because the etiology remained unclear, tests confirmed that the cause was an imbalance with the agonist-antagonist functional relationship. [ 4 ] [ 13 ]  Treatment now includes anti-inflammatory medicines, rest, equipment check, physical therapy, braces, steroid injections, shock wave therapy and if symptoms persist after 6 to 12 months, doctors may recommend surgery. [ 5 ]


Although treatment varies depending on how bad eye alignment is and also the underlying causes of strabismus. [ 14 ]  Treatment for strabismus may include  orthoptics  a term used for eye muscle training, this treatment can be provided by  orthoptists  and also  optometrists . [ 15 ]  Other treatment may include wearing eye patches aimed at strengthening the weaker eye while inhibiting the stronger eye, an alternative to eye patches is the use of an opaque lens, other treatments may include eye drops to temporarily inhibit the stronger eye and at any age eye muscle surgery can be done to correct the muscular balance of the ocular muscles. [ 7 ] [ 14 ] [ 16 ]


Although the cause of scoliosis can sometimes remain unknown ( idiopathic scoliosis ) there is treatment available that targets at strengthening the back muscles, for milder cases usually do not require medical attention, more severe cases require either muscle strengthening exercises aimed at the back muscles and even special back braces or surgery can be recommended if the case is extreme. [ 8 ]  Studies have shown that treatment with a special back brace among children ranging from 10–16 years can be successful and using this method of muscle training scoliosis can be cured with non-surgical treatment. [ 17 ]


In terms of selective muscle weakness or poor flexibility muscular imbalance is frequently regarded as an  etiological  factor in the onset of  musculoskeletal disorders . [ 2 ]  There are a variety of areas that can be affected, each causing different symptoms hence there are also different treatments available, but in general cases muscle strengthening techniques were developed for the use on the weak or tight muscles. [ 18 ]


For a long time muscular imbalance had many different theories that revolved around it. It wasn't until 1949 when there was a first manual on muscle testing appeared, written by therapists Henry and  Florence Kendall , [ 19 ]  which discusses muscle weakness in polio patients and treatments approaching tight and weak muscles. [ 18 ]


In the 1960s  Dr. George Goodheart  and  Dr. Vladimir Janda  each took their own paths in treating patients with muscular imbalance, Goodheart focusing on muscle weakness being the primary cause of muscle imbalance, whilst Janda took on the muscle tightness approach, both developed a large following that continues on today. [ 1 ]


There is evidence to support two different approaches to muscular imbalance, the first is a biomechanical approach that believed the cause was due from repeated movements in one direction or sustained postures, this was widespread by Kendall. The second is a neuromuscular imbalance due to certain muscle groups being tight or weak, popularized by Janda this approach is based on movement patterns that evolve from birth. [ 3 ]  Today there are many different types of therapists who treat muscle imbalance, these include chiropractors, osteopaths, physical therapists, medical doctors and massage therapists each assessing tightness or weakness as the primary cause of muscular imbalance. [ 18 ]


Muscle weakness  is a lack of  muscle  strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness.  True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including  muscular dystrophy  and  inflammatory myopathy . It occurs in  neuromuscular junction  disorders, such as  myasthenia gravis . Muscle weakness can also be caused by low levels of  potassium  and other  electrolytes  within muscle cells. It can be temporary or long-lasting (from seconds or minutes to months or years). The term myasthenia is from my- from Greek μυο meaning "muscle" + -asthenia  ἀσθένεια meaning " weakness ".


Neuromuscular fatigue can be classified as either "central" or "peripheral" depending on its cause. Central muscle fatigue manifests as an overall sense of energy deprivation, while peripheral muscle fatigue manifests as a local, muscle-specific inability to do work. [ 1 ] [ 2 ]


Nerves  control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences  synaptic fatigue  it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring  pathology , neuromuscular fatigue is seldom an issue. [ citation needed ]


For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice  strength trainers , the muscle's ability to generate force is most strongly limited by nerve's ability to sustain a  high-frequency signal . After an extended period of maximum contraction, the nerve's signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply ‘stop listening’ and gradually cease to move, often  lengthening . As there is insufficient stress on the muscles and tendons, there will often be no  delayed onset muscle soreness  following the workout.  Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force.  It is this "neural training" that causes several weeks worth of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit. Past this point, training effects increase muscular strength through myofibrillar or sarcoplasmic  hypertrophy  and metabolic fatigue becomes the factor limiting contractile force. [ citation needed ]


Central fatigue  is a reduction in the  neural  drive or nerve-based motor command to working muscles that results in a decline in the force output. [ 3 ] [ 4 ] [ 5 ]   It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity. [ 6 ] [ 7 ]  There has been a great deal of interest in the role of  serotonergic  pathways for several years because its concentration in the brain increases with motor activity. [ 8 ] [ 9 ] [ 10 ]  During motor activity, serotonin released in synapses that contact  motoneurons  promotes muscle contraction. [ 11 ]  During high level of motor activity, the amount of  serotonin  released increases and a spillover occurs. Serotonin binds to extrasynaptic receptors located on the  axon  initial segment of  motoneurons  with the result that nerve impulse initiation and thereby muscle contraction are inhibited. [ 12 ]


Peripheral muscle fatigue during physical work is an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigue—affecting a national [ where? ]  average of 72% of adults in the work force in 2002. This causes contractile dysfunction that manifests in the eventual reduction or lack of ability of a single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-optimal  aerobic metabolism , generally results in the accumulation of  lactic acid  and other  acidic  anaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue, though recent studies have indicated otherwise, actually finding that lactic acid is a source of energy. [ 13 ]


The fundamental difference between the peripheral and central theories of muscle fatigue is that the peripheral model of muscle fatigue assumes failure at one or more sites in the chain that initiates muscle contraction. Peripheral regulation  therefore depends on the localized metabolic chemical conditions of the local muscle affected, whereas the central model of muscle fatigue is an integrated mechanism that works to preserve the integrity of the system by initiating muscle fatigue through muscle derecruitment, based on collective feedback from the periphery, before cellular or organ failure occurs. Therefore, the feedback that is read by this central regulator could include chemical and mechanical as well as cognitive cues. The significance of each of these factors will depend on the nature of the fatigue-inducing work that is being performed. [ citation needed ]


Though not universally used, "metabolic fatigue" is a common alternative term for peripheral muscle weakness, because of the reduction in contractile force due to the direct or indirect effects of the reduction of substrates or accumulation of metabolites within the  muscle fiber . This can occur through a simple lack of energy to fuel contraction, or through interference with the ability of Ca 2+  to stimulate  actin  and  myosin  to contract. [ citation needed ]


It was once believed that  lactic acid  build-up was the cause of muscle fatigue. [ 14 ]   The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract.  The impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue. [ citation needed ]


Produced as a by-product of  fermentation , lactic acid can increase intracellular acidity of muscles.  This can lower the sensitivity of contractile apparatus to  calcium ions  (Ca 2+ ) but also has the effect of increasing  cytoplasmic  Ca 2+  concentration through an inhibition of the  chemical pump  that  actively transports  calcium out of the cell.  This counters inhibiting effects of  potassium ions  (K + ) on muscular action potentials.  Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving K +  as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions.  Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca 2+ . [ citation needed ]


Muscle cells work by detecting a  flow  of electrical impulses from the  brain  which signals them to  contract  through the release of  calcium  by the  sarcoplasmic reticulum .  Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This causes there to be less calcium available for the muscle cell. In addition an enzyme is proposed to be activated by this released calcium which eats away at muscle fibers. [ 15 ]


Substrates  within the muscle generally serve to power muscular contractions.  They include molecules such as  adenosine triphosphate  (ATP),  glycogen  and  creatine phosphate .  ATP binds to the  myosin  head and causes the ‘ratchetting’ that results in contraction according to the  sliding filament model .  Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from  adenosine diphosphate  (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds.  Glycogen is the intramuscular storage form of  glucose , used to generate energy quickly once intramuscular creatine stores are exhausted, producing  lactic acid  as a metabolic byproduct. Contrary to common belief, lactic acid accumulation does not actually cause the burning sensation we feel when we exhaust our oxygen and oxidative metabolism, but in actuality, lactic acid in presence of oxygen recycles to produce pyruvate in the liver which is known as the Cori cycle. [ citation needed ]


Substrates produce metabolic fatigue by being depleted during exercise, resulting in a lack of intracellular energy sources to fuel contractions.  In essence, the muscle stops contracting because it lacks the energy to do so. [ citation needed ]


The severity of muscle weakness can be classified into different "grades" based on the following criteria: [ 16 ] [ 17 ]


Muscle weakness can also be classified as either " proximal " or " distal " based on the location of the muscles that it affects. Proximal muscle weakness affects muscles closest to the body's midline, while distal muscle weakness affects muscles further out on the  limbs .  Proximal muscle weakness can be seen in  Cushing's syndrome [ 18 ]  and  hyperthyroidism . [ citation needed ]


Muscle weakness can be classified as either "true" or "perceived" based on its cause. [ 19 ]


In some conditions, such as  myasthenia gravis , muscle strength is normal when resting, but  true  weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of chronic fatigue syndrome, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions. [ 21 ] [ 22 ] [ 23 ] [ 24 ] [ 25 ] [ 26 ] [ excessive citations ]


In  medicine ,  myopathy  is a  disease  of the  muscle [ 1 ]  in which the  muscle fibers  do not function properly.  Myopathy  means  muscle disease  ( Greek  : myo-  muscle  + patheia  -pathy  :  suffering ). This meaning implies that the primary defect is within the muscle, as opposed to the nerves (" neuropathies " or " neurogenic " disorders) or elsewhere (e.g., the brain).


This muscular defect typically results in  myalgia  (muscle pain),  muscle weakness  (reduced muscle force), or premature  muscle fatigue  (initially normal, but declining muscle force).  Muscle cramps ,  stiffness ,  spasm , and  contracture  can also be associated with myopathy. Myopathy experienced over a long period (chronic) may result in the muscle becoming an abnormal size, such as  muscle atrophy  (abnormally small) or a  pseudoathletic appearance  (abnormally large).


Capture myopathy can occur in wild or captive animals, such as deer and  kangaroos , and leads to morbidity and mortality. [ 2 ]  It usually occurs as a result of stress and physical exertion during capture and restraint.


Muscular disease can be classified as  neuromuscular  or  musculoskeletal  in nature. Different myopathies may be inherited, infectious, non-communicable, or idiopathic (cause unknown). The disease may be isolated to affecting only muscle (pure myopathy), or may be part of a systemic disease as is typical in  mitochondrial myopathies .


Common symptoms include muscle weakness, cramps, stiffness, and  tetany . [ citation needed ]


Myopathies in systemic disease results from several different disease processes including  endocrine ,  inflammatory ,  paraneoplastic , infectious, drug- and toxin-induced, critical illness myopathy, metabolic,  collagen  related, [ 3 ]  and myopathies with other systemic disorders. Patients with systemic myopathies often present  acutely  or sub acutely. On the other hand,  familial myopathies  or  dystrophies  generally present in a  chronic  fashion with exceptions of  metabolic myopathies  where symptoms on occasion can be precipitated acutely. Metabolic myopathies, which affect the production of ATP within the muscle cell, typically present with  dynamic  (exercise-induced) rather than static symptoms. [ 4 ]  Most of the  inflammatory myopathies  can have a chance association with malignant lesion; the incidence appears to be specifically increased only in patients with dermatomyositis. [ 5 ]


There are many types of myopathy.  ICD-10  codes are provided here where available.


The Food and Drug Administration is recommending that physicians restrict prescribing high-dose  Simvastatin  (Zocor, Merck) to patients, given an increased risk of muscle damage. The FDA drug safety communication stated that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.
"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.


At birth


Onset in childhood


Onset in adulthood [ 5 ]


Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments.  Drug therapy ,  physical therapy , bracing for support,  surgery , and massage are all current treatments for a variety of myopathies. [ citation needed ]


X-linked myopathy with excessive autophagy  (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement.


The incidence of this disease is not precisely known but it is considered to be rare (< 1/10 6  population). It has been reported in 15 families to date mostly from  Canada ,  Finland  and  France . [ citation needed ]


This disease usually presents between the ages of 5 and 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood. [ citation needed ]


This disorder is inherited in a recessive X linked fashion. As a result, males are much more commonly affected than females. It is due to a mutation in  VMA21  gene - the human  homolog  of the  yeast  Vma21p protein. This gene is located on the long arm of  chromosome X  (Xq28). It is an essential assembly  chaperone  of the vacuolar  ATPase  - the principal mammalian proton pump complex. Mutations in this gene increase lysosomal pH. This in turn reduces lysosomal degradative ability and blocks  autophagy . [ citation needed ]


The muscle fibers are rarely necrotic but have evidence of excessive autophagic activity and exocytosis of the phagocytosed material. They have increased variation in size and are predominantly composed of round small and hypertrophic fibers. The vacuoles are strongly reactive for  dystrophin  and lysosome associated membrane protein 2 ( LAMP2 ). Membrane bound vacuoles and balls of dense material under the  basal lamina  are present. Deposition of the C5b-9  complement  attack complex, sub sarcolemmal  deposition of calcium and expression of MHC1 complex also occur. [ citation needed ]


On  electron microscopy  characteristic balls of dense material are commonly seen. The vacuoles may contain remains of  mitochondria , membrane whorls and  calcium apatite  crystals. [ citation needed ]


The diagnosis can be established by muscle biopsy. [ citation needed ]


The serum  creatinine  is raised. [ vague ]


This disorder was described in 1988 by Kalimo  et al  in Finland in three brothers. The same condition affected their maternal grandfather and great-uncle. [ 1 ]


Myositis  is a rarely-encountered  medical condition  characterized by  inflammation  affecting the  muscles . [ 2 ]  The manifestations of this condition may include  skin  issues,  muscle weakness , and the potential involvement of other organs. [ 3 ]  Additionally,  systemic symptoms  like weight loss,  fatigue , and  low-grade fever  can manifest in individuals with myositis.


Myositis can arise from various causes, including  injury , certain  medications ,  infections , inherited muscle disorders, or  autoimmune conditions . In some instances, the origins of myositis remain  idiopathic , without a discernible cause.


There are various tools that can be used to help diagnose myositis. The most common methods are physical examination,  electromyography  (EMG),  magnetic resonance imaging  (MRI),  muscle biopsy , and  blood tests . The first course of action a doctor will likely take is perform a physical exam. [ 2 ]  The doctor assesses for muscle weakness or rashes.


Another possible test is  electromyography. This test involves the insertion of small needles into the patient's muscles. [ 4 ]  This allows a physician to look at the muscles' responses to various electrical  nerve stimuli  and evaluate which muscles potentially have myositis. [ 4 ]   Magnetic resonance imaging  can be useful in diagnosis, [ 9 ]  allowing painless,  non-invasive  visualisation of any  muscle wastage . [ 4 ]


Muscle biopsies, however, are the most reliable tests for diagnosing myositis. [ 4 ]


There are also a variety of blood tests available that help in the diagnosis of myositis. The doctor may look for an elevation of  creatine kinase  in the blood, which is indicative of muscle inflammation. [ 4 ]  Certain  autoantibodies  (antibodies that target muscle cells) can also be found in the blood, which can indicate that myositis is caused by an autoimmune disease. [ 3 ]  Some specific examples of autoantibodies are  Anti-Jo-1 , Anti-HMGCR, Anti-TIF1, etc. [ 3 ]


Treatment for myositis depends on the underlying cause. [ 4 ]  For myositis, which is caused by a viral infection, no treatment is typically needed. [ 4 ]  For myositis caused by a bacterial infection, antibiotics can be used. [ 4 ]  For myositis caused by a medication, it is important to stop using that medication. [ 4 ]


There are a variety of treatment options available if myositis is caused by an autoimmune disease.  Glucocorticoids  are often the first choice for treatment. [ 10 ]  This drug works to weaken the immune system so that it is not able to attack the muscles. It is a type of  steroid  and can cause a wide array of side effects, such as mood changes, increased hunger, trouble sleeping, etc. Another treatment option is a steroid-sparing  immunosuppressive  agent. [ 10 ]  This also works to weaken the immune system but does not cause the side effects that  steroids do. Another treatment option is a class of drugs called  biologics . [ 10 ]  Also, intravenous  immunoglobulins  (IVIg) have  been shown to be effective in the treatment of myositis caused by an  autoimmune disease . [ 11 ]


Myositis Association  https://www.myositis.org


Myositis ossificans  comprises two syndromes characterized by  heterotopic ossification  (calcification) of muscle. In 2020, the World Health Organization classified myositis ossificans together with fibro-osseous pseudotumor of digits as a single specific entity in the category of  fibroblastic and myofibroblastic tumors . [ 1 ]


Most (i.e. 80%) ossifications arise in the thigh or arm, and are caused by a premature return to activity after an injury. Other sites include  intercostal spaces ,  erector spinae ,  pectoralis muscles ,  glutei , and the  chest . On planar x-ray, hazy densities are sometimes noted approximately one month after injury, while the denser opacities eventually seen may not be apparent until two months have passed. [ citation needed ]


The exact mechanism of myositis ossificans is not clear. Inappropriate response of stem cells in the bone against the injury or inflammation causes inappropriate differentiation of  fibroblasts  into  osteogenic  cells. When a  skeletal muscle  is injured, inflammatory cytokines ( Bone morphogenetic protein 2 ,  Bone morphogenetic protein 4 , and  Transforming growth factor ) are released. These cytokines stimulate the  endothelial  cells of the blood vessels to transform into  mesenchymal stem cells . These mesenchymal stem cells then differentiate into  chondrocytes , and  osteoblasts , resulting in bone formation in soft tissues. [ 5 ]


The process of myositis ossificans can be divided into three stages: early, intermediate, and mature. The early phase occurs in the first four weeks of injury with inflammatory phase of bone formation. This is followed by intermediate phase of bone formation (four to eight weeks following injury) where calcification started to occur and is visible on X-rays. During the maturation phase, mature bone started to form. As the maturation continues, the bone will consolidate in the coming months and subsequently bone regression occurs. [ 5 ]


Calcification is typically depicted 2 weeks earlier by ultrasound (US) when compared to radiographs. [ 6 ]  The lesion develops in two distinct stages with different presentations at US. [ 7 ]  In the early stage, termed immature, it  depicts a non-specific soft tissue mass that ranges from a hypoechoic area with an outer sheet-like hyperechoic peripheral rim to a highly echogenic area with variable shadowing. In the late stage, termed mature, myositis ossificans is depicted as an elongated calcific deposit that is aligned with the long-axis of the muscle, exhibits acoustic shadowing, and has no soft tissue mass associated. US may suggest the diagnosis at early stage, but imaging features need to evolve with successive maturation of the lesion and formation of the characteristic late stage changes before they become pathognomonic. [ 8 ]


The differential diagnosis includes many tumoral and nontumoral pathologies. A main concern is to differentiate early myositis ossificans from malignant soft-tissue tumors, and the latter is suggested by a fast-growing process. If clinical or sonographic findings are dubious and extraosseous sarcoma is suspected, biopsy should be performed. At histology, detection of the typical zonal phenomenon is diagnostic of myositis ossificans, though microscopic findings may be misleading during the early stage. [ 9 ]


The radiological features of myositis ossificans are ‘faint soft tissue calcification within 2–6 weeks, (may have well-defined
bony margins by 8 weeks) separated from periosteum by lucent zone and on CT, the characteristic feature is peripheral ossification’. [ 10 ] [ 11 ] [ 12 ]


Since myositis ossificians is more common in those with bleeding disorders, the formation of bone in soft tissue is thought to be associated with  haematoma  formation. As the calcifications will typically resolve after a period of time, non-surgical treatment is encouraged to minimize the unpleasant symptoms and maximize the function of the affected limb. [ 5 ]


Following a skeletal muscle injury, the affected limb should be immobilized with bed rest, ice therapy, compression, and elevation of the affected limb. Crutches can be used for ambulation while providing adequate rest for the affected limb and minimizing the haematoma formation. Ice therapy for 15 to 20 minutes every 30 to 60 minutes is useful to reduce the skeletal muscle blood flow by 50%. Aggressive limb physiotherapy is not recommended at this stage to prevent the worsening of symptoms. After 48 to 72 hours, range of motion exercise can be introduced as long as the range of motion is not painful. If the lesion becomes more mature, active range of motion and resistance strengthening exercises are useful in maintaining joint function. [ 5 ]


Surgical excision is reserved for those who failed the non-surgical treatment, those with intolerable pain, compression of the neurovascular structures, or limitation of the range of motion of the joint which affects the activities of daily living. Surgery is only performed after 6 to 18 months following injury because surgery does not alter the bone maturation process. If a surgery is performed too early, it may predispose to recurrence. However, the optimum timing for surgery and the rate of recurrence following early surgery is controversial because some studies have shown that early surgery does reduce the rate of recurrence. [ 5 ]


For those who had  total hip replacement  or  total hip arthroplasty , postoperative single low-dose radiation with three weeks of oral  indomethacin  regimen will be preventive  for  heterotopic ossification . [ 13 ] [ 14 ]  Radiation therapy is also effective in preventing recurrence in those who had done operative excision of heterotopic ossification of the elbow. [ 15 ]


Myostatin-related muscle hypertrophy  is a rare  genetic condition  characterized by reduced  body fat  and increased  skeletal muscle  size. [ 1 ]  Affected individuals have up to twice the usual amount of muscle mass in their bodies, but increases in muscle strength are not usually congruent. [ 2 ]  Myostatin-related muscle hypertrophy is not known to cause medical problems, and affected individuals are intellectually normal. The prevalence of this condition is unknown.


Mutations  in the  MSTN   gene  cause myostatin-related muscle hypertrophy. The  MSTN  gene provides instructions for making a  protein  called  myostatin , which is active in muscles used for movement ( skeletal muscles ) both before and after  birth . A 2010 research paper in the Journal of Musculoskeletal & Neuronal Interactions, which was discussed outside of academic circles, [ 3 ]  linked Myostatin to muscle mass and bone structure. [ 4 ]  This protein normally restrains muscle growth, ensuring that muscles do not grow too large. Mutations that reduce the production of functional myostatin lead to an overgrowth of muscle tissue. Myostatin-related muscle hypertrophy has a pattern of inheritance known as incomplete autosomal dominance. People with a mutation in both copies of the gene in each  cell  ( homozygotes ) have significantly increased muscle mass. People with a mutation in one copy of the  MSTN  gene in each cell ( heterozygotes ) also have increased muscle bulk but to a lesser degree.


The effect of this growth factor was first described in cattle as “bovine muscular hypertrophy” by the British farmer H. Culley in 1807. Cattle that have a myostatin gene deletion look unusually and excessively muscular.


Researchers at Guangzhou Institutes of Biomedicine and Health in  China  have edited the genome of  beagles  to create double the amount of muscle. [ 5 ]  Of the two beagles that were genetically modified, only one had increased muscle mass. [ 6 ]  The ultimate aim of this project is to be able to better treat genetic neuromuscular diseases (such as  Parkinson's disease ).


Besides beagles, genetic modification has also been done in pigs [ 7 ]  and fish. [ 8 ] [ 9 ]


Orofacial myofunctional disorders  (OMD) (sometimes called “oral myofunctional disorder", and “tongue thrust”) are muscle disorders of the face, mouth, lips, or jaw due to chronic  mouth breathing . [ 1 ]


Recent [ timeframe? ]  studies on the incidence and prevalence of  tongue thrust  behaviors are not available. However, according to previous research, 38% of various populations have OMD. The incidence is as high as 81% in children exhibiting speech/articulation problems (Kellum, 1992).


OMD refers to the abnormal resting posture of the orofacial musculature, atypical chewing, and swallowing patterns, dental malocclusions, blocked nasal airways, and speech problems. [ 2 ]   OMD are patterns involving oral and/or orofacial musculature that interferes with normal growth, development, or function of structures, or calls attention to itself. OMD are found in both children and adults. OMD that are commonly seen in children include  tongue thrust  that is also known as swallowing with an anterior  tongue posture . OMD also refers to factors such as nonnutritive sucking behaviors, such as thumb sucking, clenching, bruxing, etc. that led to abnormal development of dentition and oral cavity. OMD in adult and geriatric populations are due to various neurological impairments,  oral hygiene , altered functioning of muscles due to aging, systemic diseases, etc.


Tongue thrusting  is a type of orofacial myofunctional disorder, which is defined as habitual resting or thrusting the tongue forward and/or sideways against or between the teeth while swallowing, chewing, resting, or speaking. Abnormal swallowing patterns push the upper teeth forward and away from the upper alveolar processes and cause open bites. In children, tongue thrusting is common due to immature oral behavior, narrow dental arch, prolonged upper respiratory tract infections, spaces between the teeth (diastema), muscle weakness, malocclusion, abnormal sucking habits, and open mouth posture due to structural abnormalities of genetic origin. Large tonsils and adenoids also contribute to  tongue thrust swallowing .


From the dental perspective, teeth move in relation to the balance of the soft tissue; the normal relationship of teeth lies in occlusion; and any deviation from the normal occlusion can lead to dental distress. [ 3 ]  Tongue posture plays an important role in swallowing and dentofacial growth.  In case of  tongue thrust  swallowing, the tip of the tongue can come against or between the dentition; the midpoint may be collapsed or extended unilaterally or bilaterally; or the posterior part of the hard palate. In these conditions, there are chances of abnormal dentofacial growth and other concerns regarding the development of the craniofacial complex.


There are pertinent symptomatic questions that can be considered for the diagnosis of tongue thrust swallow. Some of these questions are geared toward tongue protrusion and an opening of lips when the client is in repose; habitual  mouth breathing ; digit sucking; existence of high and narrow palatal arch;  ankyloglossia  (tongue-tie);  malocclusions , (Class II, III); weak chewing muscles (masseter); weak lip muscles (orbicularis oris); overdeveloped chin muscles (mentalis); muscular imbalance; abnormal dentition.


Tongue thrusting and speech problems may co-occur. Due to unconventional postures of the tongue and other articulators, interdental and frontal lisping are very common. The alveolar sounds /s/ and /z/ are produced more anteriorly thus leading to interdental fricative like sounds, /th/. [ 4 ]


While identifying the causes of tongue thrust, it is important to remember that the resting posture of the tongue, jaw, and lips are crucial to the normal development of the mouth and its structures. If the tongue rests against the upper front teeth, the teeth may protrude forward, and adverse tongue pressure can restrict the development of the oral cavity. The tongue lies low in the mouth or oral cavity and is typically forwarded between upper and lower teeth. If tongue thrust behavior is not corrected, it may affect the normal dental development. The teeth may be pushed around in different directions during the growth of permanent teeth.


The adaptation from nasal to mouth breathing takes place when changes such as chronic middle ear infections, sinusitis, allergic rhinitis, upper airway infections, and sleep disturbances (e.g., snoring) take place. In addition, mouth breathing is often associated with a decrease in oxygen intake into the lungs. Mouth breathing can particularly affect the growing face, as the abnormal pull of these muscle groups on facial bones slowly deforms these bones, causing misalignment. The earlier in life these changes take place, the greater the alterations in facial growth, and ultimately an open mouth posture is created where the upper lip is raised and the lower jaw is maintained in an open posture. The tongue, which is normally tucked under the roof of the mouth, drops to the floor of the mouth and protrudes to allow a greater volume of air intake. Consequently, an open mouth posture can lead to malocclusions and problems in swallowing. Other causes of open-mouth posture are the weakness of lip muscles, overall lack of tone in the body or hypotonia, and prolonged/chronic allergies of the respiratory tract.


An orofacial myofunctional therapist reeducates the movement of muscles including teaching the client how to breathe properly, restore correct swallowing patterns, and establish adequate labial-lingual postures. [ 3 ] [ 5 ] [ 6 ]  An interdisciplinary nature of treatment is always desirable to reach functional goals in terms of swallowing, speech, and other aesthetic factors. A team approach has been shown to be effective in correcting orofacial myofunctional disorders. The teams include an orthodontist, dental hygienist, certified orofacial myologist, general dentist, otorhinolaryngologist, and a speech-language pathologist.


Perimyositis  is  inflammation  of the connective tissue around a  muscle . [ 1 ]


Pseudohypertrophy , or  false enlargement,  is an increase in the size of an organ due to  infiltration  of a tissue not normally found in that organ. [ 1 ]  It is commonly applied to enlargement of a muscle due to infiltration of fat or connective tissue, [ 2 ]  famously in  Duchenne muscular dystrophy . This is in contrast with typical  muscle hypertrophy , in which the muscle tissue itself increases in size. [ 2 ]  Because pseudohypertrophy is not a result of increased muscle tissue, the muscles look bigger but are actually atrophied and thus weaker. [ 2 ] [ 3 ]  Pseudohypertrophy is typically the result of a disease, which can be a disease of muscle or a disease of the nerve supplying the muscle. [ 2 ]


Causes of pseudohypertrophy include muscle diseases:  dystrophinopathies ,  limb-girdle muscular dystrophies ,  metabolic myopathy ,  Dystrophic myotonias , Non-dystrophic myotonias,  endocrine disorders , parasitic muscle conditions,  amyloid  and  sarcoid myopathy , and granulomatous myositis. [ 2 ]


Neurological causes include  radiculopathy ,  poliomyelitis ,  Charcot-Marie-Tooth disease ,  spinal muscular atrophy . [ 2 ]


In pseudohypertrophy where the atrophied muscle tissue has been infiltrated by fat tissue, upon palpitation the seemingly large muscles feel doughy. [ 3 ]


Not all muscles infiltrated by fat or other tissue are pseudohypertrophic. In muscular  steatosis , sometimes the muscles may appear a normal or a slender size, even though the atrophied muscle has been infiltrated with fat tissue, such as the calf muscles in  Bethlem myopathy 1 . [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]  In  myosclerosis , the muscle is infiltrated with connective tissue and fibrosis, having a firm, "woody" feel upon palpitation, with the muscles appearing slender. [ 9 ] [ 10 ]


Pseudohypertrophy can be broken up into the following  roots, suffixes, and prefixes :


The term was used by  Duchenne de Boulogne  in his description of  Duchenne muscular dystrophy  in one of his works "paralysie musculaire pseudo-hypertrophique." [ 11 ]


As well as being known as 'false enlargement,' when the muscle has been infiltrated by fat tissue, historically it has also been called muscular  steatosis , pseudohypertrophic atrophy,  lipomatous  pseudohypertrophy, interstitial  lipomatosis , lipomatous muscular dystrophy, or atrophia lipomatosa. [ 12 ]  It is also known as  fatty atrophy  of muscle (not to be confused with fat atrophy, which is atrophy of adipose tissue), as muscle tissue is replaced by fat tissue, the actual muscle atrophies while the fat tissue replaces the bulk. [ 13 ]


Psoas abscess  is a collection of  pus  ( abscess ) in the  iliopsoas muscle  compartment. [ 1 ] [ 2 ]  It can be classified into  primary psoas abscess  (caused by  hematogenous  or lymphatic spread of a  pathogen ) and  secondary psoas abscess  (resulting from contiguous spread from an adjacent infectious focus). [ 2 ]


Psoas abscess may be caused by  lumbar tuberculosis . Owing to the  proximal  attachments of the iliopsoas, such an abscess may drain  inferiorly  into the upper  medial  thigh and present as a swelling in the region. The sheath of the muscle arises from the  lumbar vertebrae  and the  intervertebral discs  between the vertebrae. The disc is more susceptible to infection, from  tuberculosis  and  Salmonella  discitis . The infection can spread into the  psoas muscle  sheath. [ 3 ]


Treatment may involve drainage and  antibiotics . [ 4 ]


Pyomyositis  is a  bacterial   infection  of the  skeletal muscles  which results in an  abscess . Pyomyositis is most common in  tropical  areas but can also occur in  temperate zones .


Pyomyositis can be classified as primary or secondary. Primary pyomyositis is a skeletal muscle infection arising from hematogenous infection, whereas secondary pyomyositis arises from localized penetrating trauma or contiguous spread to the muscle. [ 1 ]


Diagnosis is done via the following manner: [ citation needed ]


The abscesses within the muscle must be drained  surgically  (not all patients require surgery if there is no abscess).  Antibiotics  are given for a minimum of three weeks to clear the infection. [ 2 ]


Pyomyositis is most often caused by the bacterium  Staphylococcus aureus . [ 3 ]  The infection can affect any skeletal muscle, but most often infects the large muscle groups such as the  quadriceps  or  gluteal muscles . [ 2 ] [ 4 ] [ 5 ]


Pyomyositis is mainly a disease of children and was first described by Scriba in 1885. Most patients are aged 2 to 5 years, but infection may occur in any age group. [ 6 ] [ 7 ]  Infection often follows minor trauma and is more common in the tropics, where it accounts for 4% of all hospital admissions. In temperate countries such as the US, pyomyositis was a rare condition (accounting for 1 in 3000 pediatric admissions), but has become more common since the appearance of the  USA300  strain of  MRSA . [ 2 ] [ 4 ] [ 5 ]


Gonococcal pyomyositis is a rare infection caused by  Neisseria gonorrhoeae . [ 8 ]


Rigid spine syndrome , also known as congenital muscular dystrophy with rigidity of the spine (CMARS), is a rare and often debilitating  neuromuscular disorder . It is characterized by progressive  muscle stiffness  and rigidity, particularly in the spine, which can severely limit mobility and impact quality of life. This condition is typically present from birth or early childhood and tends to worsen over time. [ 1 ] [ 2 ]


Despite its rarity, rigid spine syndrome represents a significant challenge for those affected, as well as for their families and healthcare providers.


Rigid spine syndrome is characterized by a range of symptoms that can vary in severity and presentation. Common symptoms of the condition include:


Individuals with rigid spine syndrome often experience tightness and inflexibility in their muscles, particularly in the spine. This rigidity can make movement difficult and may progress over time. [ 3 ]


One of the hallmark features of rigid spine syndrome is the development of spinal deformities, such as  kyphosis  (forward curvature of the spine) and  scoliosis  (sideways curvature of the spine). These deformities can cause pain and further restrict movement. [ 2 ] [ 3 ] [ 4 ]


Contractures , or permanent tightening of the muscles and tendons around a joint, are common in rigid spine syndrome. This can lead to reduced range of motion and joint deformities. [ 4 ] [ 3 ]


While muscle stiffness is a primary symptom, individuals with rigid spine syndrome may also experience  muscle weakness , particularly in the limbs.


In severe cases, rigid spine syndrome can lead to respiratory complications due to the restriction of chest movement caused by spinal deformities and muscle rigidity. [ 2 ] [ 5 ]


The combination of muscle stiffness, joint contractures, and spinal deformities can make walking and other forms of mobility challenging for individuals with rigid spine syndrome. [ 2 ] [ 5 ]


Depending on the severity of the condition, individuals with rigid spine syndrome may also experience  fatigue ,  pain , and difficulty with activities of daily living. [ 6 ]


Rigid spine syndrome is a genetic disorder, primarily caused by mutations in the  SEPN1 gene . [ 7 ] [ 8 ]  This gene provides instructions for making a protein called selenoprotein N, which plays a role in muscle function and development. Mutations in the SEPN1 gene can lead to abnormal muscle stiffness and rigidity, as well as other characteristic features of rigid spine syndrome. [ 9 ]


The inheritance pattern of rigid spine syndrome is  autosomal recessive , which means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. Individuals who inherit only one copy of the mutated gene are known as carriers and typically do not show any symptoms of the condition. [ 10 ]