Cachexia is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and AIDS. Systemic inflammation from these conditions can cause detrimental changes to metabolism and body composition. In contrast to weight loss from inadequate caloric intake, cachexia causes mostly muscle loss instead of fat loss. Diagnosis of cachexia can be difficult due to the lack of well-established diagnostic criteria. Cachexia can improve with treatment of the underlying illness but other treatment approaches have limited benefit. Cachexia is associated with increased mortality and poor quality of life.
Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation of the skeletal muscles after voluntary contraction or electrical stimulation.
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have 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.
Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cells that help build bone, cartilage, tendons, corneas, skin and connective tissue. GAGs are also found in the fluids that lubricate joints.
Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. The presence of sarcomeres manifests as a series of bands visible along the muscle fibers, which is responsible for the striated appearance observed in microscopic images of this tissue. There are two types of striated muscle:
A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.
Myostatin is a protein that in humans is encoded by the MSTN gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle growth. Myostatin is a secreted growth differentiation factor that is a member of the TGF beta protein family.
Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary glands are neuroendocrine organs.
Hyperplasia, or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferation. It may lead to the gross enlargement of an organ, and the term is sometimes confused with benign neoplasia or benign tumor.
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not predisposed to cancer or infection. Cockayne syndrome is a rare but destructive disease usually resulting in death within the first or second decade of life. The mutation of specific genes in Cockayne syndrome is known, but the widespread effects and its relationship with DNA repair is yet to be well understood.
Sarcopenia is a type of muscle loss that occurs with aging and/or immobility. It is characterized by the degenerative loss of skeletal muscle mass, quality, and strength. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. The muscle loss is related to changes in muscle synthesis signalling pathways. It is distinct from cachexia, in which muscle is degraded through cytokine-mediated degradation, although both conditions may co-exist. Sarcopenia is considered a component of frailty syndrome. Sarcopenia can lead to reduced quality of life, falls, fracture, and disability.
Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.
A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur.
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.
Starvation response in animals is a set of adaptive biochemical and physiological changes, triggered by lack of food or extreme weight loss, in which the body seeks to conserve energy by reducing the amount of calories it burns.
Orthopedic pathology, also known as bone pathology is a subspecialty of surgical pathology which deals with the diagnosis and feature of many bone diseases, specifically studying the cause and effects of disorders of the musculoskeletal system. It uses gross and microscopic findings along with the findings of in vivo radiological studies, and occasionally, specimen radiographs to diagnose diseases of the bones.
In cell biology and pathophysiology, cellular adaptation refers to changes made by a cell in response to adverse or varying environmental changes. The adaptation may be physiologic (normal) or pathologic (abnormal). Four types of morphological adaptations include atrophy, hypertrophy, hyperplasia, and metaplasia.
Denervation is any loss of nerve supply regardless of the cause. If the nerves lost to denervation are part of the neuronal communication to a specific function in the body then altered or a loss of physiological functioning can occur. Denervation can be caused by injury or be a symptom of a disorder like ALS, post-polio syndrome, or POTS. Additionally, it can be a useful surgical technique to alleviate major negative symptoms, such as in renal denervation. Denervation can have many harmful side effects such as increased risk of infection and tissue dysfunction.
Electrical impedance myography, or EIM, is a non-invasive technique for the assessment of muscle health that is based on the measurement of the electrical impedance characteristics of individual muscles or groups of muscles. The technique has been used for the purpose of evaluating neuromuscular diseases both for their diagnosis and for their ongoing assessment of progression or with therapeutic intervention. Muscle composition and microscopic structure change with disease, and EIM measures alterations in impedance that occur as a result of disease pathology. EIM has been specifically recognized for its potential as an ALS biomarker by Prize4Life, a 501(c)(3) nonprofit organization dedicated to accelerating the discovery of treatments and cures for ALS. The $1M ALS Biomarker Challenge focused on identifying a biomarker precise and reliable enough to cut Phase II drug trials in half. The prize was awarded to Dr. Seward Rutkove, chief, Division of Neuromuscular Disease, in the Department of Neurology at Beth Israel Deaconess Medical Center and Professor of Neurology at Harvard Medical School, for his work in developing the technique of EIM and its specific application to ALS. It is hoped that EIM as a biomarker will result in the more rapid and efficient identification of new treatments for ALS. EIM has shown sensitivity to disease status in a variety of neuromuscular conditions, including radiculopathy, inflammatory myopathy, Duchenne muscular dystrophy, and spinal muscular atrophy.
Acquired non-inflammatory myopathy (ANIM) is a neurological disorder primarily affecting skeletal muscle, most commonly in the limbs of humans, resulting in a weakness or dysfunction in the muscle. A myopathy refers to a problem or abnormality with the myofibrils, which compose muscle tissue. In general, non-inflammatory myopathies are a grouping of muscular diseases not induced by an autoimmune-mediated inflammatory pathway. These muscular diseases usually arise from a pathology within the muscle tissue itself rather than the nerves innervating that tissue. ANIM has a wide spectrum of causes which include drugs and toxins, nutritional imbalances, acquired metabolic dysfunctions such as an acquired defect in protein structure, and infections.
