NationMaster - Encyclopedia: Myasthenia gravis

Myasthenia gravis (sometimes abbreviated MG; from the Greek myastheneia, lit. 'condition of no strength in the muscle', and Latin gravis, 'serious') is a neuromuscular disease leading to fluctuating muscle weakness and fatiguability. At 20 cases per 100,000 (in the U.S.),^[1] it is one of the lesser known autoimmune disorders. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction,^[2] inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy. Image File history File links Synapse_diag3. ... An axon or nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neurons cell body or soma. ... A simplified, global view of a neuromuscular junction: 1. ... A diagram of the structure of a Myofybril Myofibrils (obsolete term: sarcostyles) are cylindrical organelles, found within muscle cells. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // G00-G99 - Diseases of the nervous system (G00-G09) Inflammatory diseases of the central nervous system (G00) Bacterial meningitis, not elsewhere classified (G01) Meningitis in bacterial diseases classified elsewhere (G02) Meningitis in other infectious and parasitic diseases classified elsewhere (G03) Meningitis due to other and unspecified causes (G04) Encephalitis, myelitis... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... For other uses, see Latin (disambiguation). ... Neuromuscular disease is a very broad term that encompasses many diseases and ailments that either directly (via intrinsic muscle pathology) or indirectly (via nerve pathology) impair the functioning of muscle. ... The word fatigue is used in everyday living to describe a range of afflictions, varying from a general state of lethargy to a specific work induced burning sensation within muscle. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine. ... A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscles surface. ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Immunosuppressive drugs or immunosuppressants are drugs that are used in immunosuppressive therapy to inhibit or prevent activity of the immune system. ... A cholinesterase inhibitor or anticholinesterase is a chemical that inhibits a cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter acetylcholine. ... A thymectomy is an operation to remove the thymus gland. ...

Classification

==of the muscles that control eye movements, unstable or waddling gait, weakness in arms,

Pathophysiology

Myasthenia gravis is an autoimmune disease: it features antibodies directed against the body's own proteins. While in various similar diseases the disease has been linked to a cross-reaction with an infective agent, there is no known causative pathogen that could account for myasthenia. There is a slight genetic predisposition: particular HLA types seem to predispose for MG (B8 and DR3 with DR1 more specific for ocular myasthenia). Up to 25% have a concurrent thymoma, a tumor (either benign or malignant) of the thymus, and other abnormalities are frequently found. The disease process generally remains stationary after thymectomy (removal of the thymus). Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... A pathogen or infectious agent is a biological agent that causes disease or illness to its host. ... HLA region of Chromosome 6 The human leukocyte antigen system (HLA) is the name of the human major histocompatibility complex (MHC). ... In medicine (oncology), thymoma is a neoplasm of the thymus. ... Thymus, see Thyme. ...

In MG, the autoantibodies are directed most commonly against the acetylcholine receptor (nicotinic type), the receptor in the motor end plate for the neurotransmitter acetylcholine that stimulates muscular contraction. Some forms of the antibody impair the ability of acetylcholine to bind to receptors. Others lead to the destruction of receptors, either by complement fixation or by inducing the muscle cell to eliminate the receptors through endocytosis. An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine. ... Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ion channels in cells plasma membranes. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... A motor end plate is the innervation of a muscle fiber which causes muscle contraction. ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... A complement protein attacking an invader. ... It has been suggested that Endocytic cycle be merged into this article or section. ...

The antibodies are produced by plasma cells, that have been derived from B cells. These plasma cells are activated by T-helper cells, which in turn are activated by binding to acetylcholine receptor antigenic peptide sequences (epitopes) that rest within the histocompatibility antigens of antigen presenting cells. The thymus plays an important role in the development of T-cells, which is why myasthenia gravis is associated with thymoma. The exact mechanisms are however not convincingly clarified.

In normal muscle contraction, cumulative activation of the ACh receptor leads to influx of sodium and calcium. Only when the levels of these electrolytes inside the muscle cell is high enough will it contract. Decreased numbers of functioning receptors therefore impairs muscular contraction. A top-down view of skeletal muscle A muscle contraction (also known as a muscle twitch or simply twitch) occurs when a muscle cell (called a muscle fiber) lengthens or shortens. ... For sodium in the diet, see Edible salt. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Standard atomic weight 40. ...

It has recently been realized that a second category of gravis is due to auto-antibodies against the MuSK receptor (Muscle Specific Kinase), a tyrosine kinase receptor which is required for the formation of the neuromuscular junction. Antibodies against MuSK inhibit the signaling of MuSK normally induced by its nerve-derived ligand, agrin. The result is a decrease in patency of the neuromuscular junction, and the consequent symptoms of MG. MuSK (for Muscle Specific Kinase) is a receptor tyrosine kinase important in neuromuscular development. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscles surface. ... Large proteoglycan that is required for the formation of the neuromuscular junction Agrins mechanism of action During development, the growing end of motor neuron axons secrete a protein called agrin. ...

People treated with penicillamine can develop MG symptoms. Their antibody titer is usually similar to that of MG, but both the symptoms and the titer disappear when drug administration is discontinued.

MG is more common in families with other autoimmune diseases. A familial predisposition is found in 5% of the cases. This is associated with certain genetic variations such as an increased frequency of HLA-B8 and DR3. People with MG also have an increased risk of developing another autoimmune disease.

Diagnosis

Myasthenia can be a difficult diagnosis, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.^[3] A patient may have visited the ENT doctor, the ophthalmologist and even the psychiatrist and waited for years for the right diagnosis. Otolaryngology is the branch of medicine that specializes in the diagnosis and treatment of ear, nose, throat, and head & neck disorders. ... This article is about the branch of medicine. ... Psychiatry is a branch of medicine dealing with the prevention, assessment, diagnosis, treatment, and rehabilitation of the mind and mental illness. ...

A thorough physical examination can reveal easy fatiguability, with the weakness improving after rest and worsening again on repeat of the exertion testing. Though this is not often performed, applying ice to the weak muscle groups characteristically improves the weakness. Additional tests are often performed, as mentioned below. Furthermore, a good response to medication can also be considered a sign of autoimmune pathology. In medicine, the physical examination or clinical examination is the process by which the physician investigates the body of a patient for signs of disease. ... Snowflakes by Wilson Bentley, 1902 Ice is the name given to any one of the 14 known solid phases of water. ...

Physical examination

Muscle fatigability can be tested for many muscles. A thorough investigation includes

In ophthalmology, ptosis is an abnormally low position (drooping) of the upper eyelid which may grow more or less severe during the day. ... Diplopia, commonly known as double vision, is the perception of two images from a single object. ...

Blood tests

If the diagnosis is suspected, serology can be performed in a blood test to identify antibodies against the acetylcholine receptor. The test has a reasonable sensitivity of 80–96%, but in MG limited to the eye muscles (ocular myasthenia) the test may be negative in up to 50% of the cases. About half of the patients without antibodies against the acetylcholine receptor have antibodies against the MuSK protein. Often, parallel testing is performed for Lambert-Eaton syndrome, in which other antibodies (against a voltage-gated calcium channel) can be found. Also the thyroid function should be tested. Serology is the scientific study of blood serum. ... Blood tests are laboratory tests done on blood to gain an appreciation of disease states and the function of organs. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine. ... The sensitivity of a binary classification test or algorithm, such as a blood test to determine if a person has a certain disease, or an automated system to detect faulty products in a factory, is a parameter that expresses something about the tests performance. ... // MuSK is required for formation of the Neuromuscular Junction During development, the growing end of motor neuron axons secrete a protein called agrin. ... Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of nerve-muscle (neuromuscular) junction. ... Ion channels are present in the membranes that surround all biological cells. ...

Single-fiber electromyography and repetitive nerve stimulation

Muscle fibers of patients with MG are easily fatigued, and thus do not respond as well as muscles in healthy individuals to repeated stimulation. By repeatedly stimulating a muscle with electrical impulses, the fatiguability of the muscle can be measured. This is called the repetitive nerve stimulation test. In single fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG, a thin needle electrode is inserted into a muscle to record the electric potentials of individual muscle fibers. By finding two muscle fibers belonging to the same motor unit and measuring the temporal variability in their firing patterns (i.e. their 'jitter'), the diagnosis can be made.

Edrophonium test

The "edrophonium test" is infrequently performed to identify MG; its application is limited to the situation when other investigations do not yield a conclusive diagnosis. This test requires the intravenous administration of edrophonium chloride (Tensilon®, Reversol®), a drug that blocks the breakdown of acetylcholine by cholinesterase and temporarily increases the levels of acetylcholine at the neuromuscular junction. In people with myasthenia gravis involving the eye muscles, edrophonium chloride will briefly relieve weakness. An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Sources Brenner, G. M. (2000). ... Acetylcholinesterase In biochemistry, cholinesterase is a term which refers to one of the two enzymes: Acetylcholinesterase (EC 3. ... A neuromuscular junction is the junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscles surface. ...

Imaging

A chest X-ray is frequently performed; it may point towards alternative diagnoses (e.g. Lambert-Eaton due to a lung tumor) and comorbidity. It may also identify widening of the mediastinum suggestive of thymoma, but computed tomography (CT) or magnetic resonance imaging (MRI) are more sensitive ways to identify thymomas, and are generally done for this reason. Frontal chest X-ray. ... FIG. 967â€“ Transverse section through the upper margin of the second thoracic vertebra The mediastinum is a non-delineated group of structures in the thorax (chest), surrounded by loose connective tissue. ... In medicine (oncology), thymoma is a neoplasm of the thymus. ... It has been suggested that Synchrotron X-ray tomographic microscopy, X-ray tomography be merged into this article or section. ... â€œMRIâ€ redirects here. ...

Pulmonary function test

Spirometry (lung function testing) may be performed to assess respiratory function if there are concerns about a patient's ability to breathe adequately. The FEV1 (forced expired volume in one second) or the PEFR (peak expiratory flow rate) may be monitored at intervals in order not to miss a gradual worsening of muscular weakness. Severe myasthenia may cause respiratory failure due to exhaustion of the respiratory muscles. Spirometry (meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs), measuring lung function, specifically the measurement of the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. ... Respiratory failure is a medical term for inadequate gas exchange by the respiratory system. ...

Pathological findings

Immunofluoresence shows IgG antibodies on the neuromuscular junction. (Note that it is not the antibody which causes myasthenia gravis that fluoresces, but rather a secondary antibody directed against it.) Muscle electron microscopy shows receptor infolding and loss of the tips of the folds, together with widening of the synaptic clefts. Both these techniques are currently used for research rather than diagnostically. The primary antibody (in purple) binds to an antigen (in green). ...

Treatment

Myasthenia gravis can usually be controlled with medication. Medication is used for two different endpoints:

Muscle function is improved by cholinesterase inhibitors, such as neostigmine and pyridostigmine. These slow the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor. Usually doctors will start with a low dose, eg 3x20mg pyridostigmine, and increase until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating. Side effects, like perspiration and diarrhea can be countered by adding atropine. Pyridostigmine is a short-lived drug with a half-life of about 4 hours. Immunosuppressive drugs such as prednisone, cyclosporine, mycophenolate mofetil and azathioprine may be used. It is common for patients to be treated with a combination of these drugs with a cholinesterase inhibitor. Treatments with some immunosuppressives take weeks to months before effects are noticed. If the myasthenia is serious (myasthenic crisis), plasmapheresis is used to remove the putative antibody from the circulation. Similarly, intravenous immunoglobulins (IVIg) is used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks. Thymectomy, the surgical removal of the thymus gland (which is abnormal in myasthenia gravis patients), improves symptoms in more than 50 percent of patients. Some patients are cured by thymectomy, suggesting that the thymus plays a significant role in the pathogenesis of myasthenia, but it is not considered a definitive cure for the disease. The positive effects from a thymectomy may be seen within weeks to as much as 3–5 years after surgery. Thymoma is relatively rare in younger (<40) patients, but paradoxically especially younger patients with generalized MG without thymoma benefit from thymectomy. Of course resection is also indicated for those with a thymoma, but it is less likely to improve the MG symptoms.

Prognosis

With treatment, patients have a normal life expectancy, except for those with a malignant thymoma (whose lesser life expectancy is on account of the thymoma itself and is otherwise unrelated to the myasthenia). Quality of life can vary depending on the severity and the cause. The drugs used to control MG either diminish in effectiveness over time (cholinesterase inhibitors) or cause severe side effects of their own (immunosupressants). A small percentage (around 10%) of MG patients are found to have tumors in their Thymus, in which case Thymectomy is a very effective treatment with long term remission. However, most patients need treatment for the remainder of their lives, and their abilities vary greatly. It should be noted that MG is not a progressive disease. The symptoms may come and go, but the symptoms usually don't get worse as the patient ages. For some, the symptoms decrease after 3–5 years. Acetylcholinesterase In biochemistry, cholinesterase is a term which refers to one of the two enzymes: Acetylcholinesterase (EC 3. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Thymus, see Thyme. ... A thymectomy is an operation to remove the thymus gland. ...

Epidemiology

Myasthenia gravis occurs in all ethnic groups and both genders. It most commonly affects women under 40 and people from 50 to 70 years old of both sexes, but it can occur at any age. Younger patients rarely have thymoma. The prevalence in the United States is estimated at 20 cases per 100,000 in the USA. ^[1] Risk factors are female gender, age 20–40, familial myasthenia gravis, D-penicillamine ingestion (drug induced myasthenia) and other autoimmune disease.

The congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The symptoms of CMS usually begin within the first two years of life, although in a few forms patients can develop their first symptoms as late as the seventh decade of life. A diagnosis of CMS is suggested by the following: The placenta is an ephemeral (temporary) organ present in female placental vertebrates during gestation (pregnancy), but a placenta has evolved independently also in other animals as well, for instance scorpions and velvet worms. ... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... It has been suggested that this article or section be merged into Dominance relationship. ...

The symptoms of CMS vary from mild to severe, depending on the form. It's also common for patients with the same form, even members of the same family, to be affected to differing degrees. In most forms of CMS weakness does not progress, and in some forms symptoms may diminish as the patient gets older. Only rarely do symptoms of CMS become worse with time.

Notes

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... JAMA is the acronym for the Journal of the American Medical Association, a leading medical journal. ...

References

External links

Categories: Autoimmune diseases | Neurology Mononeuropathy (or mononeuritis) is a type of neuropathy that only affects a single peripheral or cranial nerve. ... This article is about the medical condition. ... Ulnar nerve entrapment is a condition where the ulnar nerve becomes trapped or pinched due to some physiological abnormalities // Commonly, this causes pain, numbness, or paralysis of the ring and little fingers which may extend up the arm. ... Radial neuropathy (or radial mononeuropathy) is a type of mononeuropathy which results from acute trauma to the radial nerve that runs the length of the arm. ... Complex regional pain syndrome (CRPS) is a chronic condition characterized by severe pain following injury to bone and soft tissue. ... Meralgia paraesthetica or meralgia paresthetica (see spelling differences) (me-ral-gee-a par-es-thet-i-ka) is numbness or pain in the outer thigh not caused by injury to the thigh, but by injury to a nerve that extends from the thigh to the spinal column. ... Tarsal tunnel syndrome is a painful foot condition in which the tibial nerve is impinged and compressed as it travels though the tarsal tunnel. ... Mortons Neuroma. ... Mononeuritis multiplex is the clinical picture that arises from problems with multiple individual nerves serially or almost simultaneously. ... Polyneuropathy is a neurological disorder that occurs when many peripheral nerves throughout the body malfunction simultaneously. ... Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. ... Charcot-Marie-Tooth disease (CMT), known also as Hereditary Motor and Sensory Neuropathy (HMSN) or Peroneal Muscular Atrophy, is a heterogeneous inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms... Dejerine-Sottas Syndrome/Neuropathy (hereditary motor and sensory polyneuropathy type III; sometimes also described as a subtype III of Charcot-Marie-Tooth disease) is an autosomal dominant or autosomal recessive neuropathy. ... Refsums disease (Refsum-ThiÃ©baut disease, Refsum-ThiÃ©baut-Klenk-Kahlke disease), named after Norwegian neurologist Sigvald Bernhard Refsum (1907-1991), is an autosomal recessive (Chromosome 10) neurological disease that results in the malformation of myelin sheaths around nerve cells. ... Morvans syndrome (or fibrillary chorea) is a rare disease named after nineteenth century French physician Augustin Marie Morvan (1819-1897). ... Guillain-BarrÃ© syndrome (GBS) or acute inflammatory demyelinating polyradiculoneuropathy is an acute, autoimmune disease that affects the peripheral nervous system and is usually triggered by an acute infectious process. ... Alcoholic polyneuropathy is a neurological disorder in which many peripheral nerves throughout the body malfunction simultaneously (a polyneuropathy). ... Neuropathy is usually short for peripheral neuropathy, meaning a disease of the peripheral nervous system. ... Electron micrograph showing a cross section through the neuromuscular junction. ... A top-down view of skeletal muscle Muscle (from Latin musculus little mouse [1]) is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. ... Muscular dystrophy refers to a group of genetic, hereditary muscle diseases that cause progressive muscle weakness. ... Myotonic dystrophy (DM) is a chronic, slowly progressing, highly variable inherited multisystemic disease that can manifest at any age from birth to old age. ... Myotonia congenita is a genetic, neuromuscular disorder characterized by the slow relaxation of the muscles. ... Thomsen disease, a form of Myotonia congenita, is a muscular genetic disorder characterized by muscle stiffness (cramp) and an inability of the muscle to relax after a voluntary contraction. ... Neuromyotonia is spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. ... Paramyotonia congenita is a rare congenital neuromuscular disorder which is characterized by a condition in which the muscles do not relax after contracting (myotonia). ... Centronuclear myopathies (CNM) are a group of congenital myopathies where cell nuclei are abnormally located in skeletal muscle cells. ... Nemaline myopathy (NM; also called rod myopathy or nemaline rod myopathy) is a group of congenital, hereditary neuromuscular disorders that cause muscle weakness, generally nonprogressive, of varying severity. ... Mitochondrial myopathy is typically caused by defects in part of the mitochondrion (the power plant of the cell) known as the respiratory chain. ... In medicine, a myopathy is a neuromuscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. ... Periodic paralysis is a rare group of genetic diseases that lead to weakness or paralysis (rarely death) from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. ... Hypokalemic periodic paralysis is characterized by a fall in potassium levels in the blood. ... Hyperkalemic periodic paralysis (HYPP), also known as Impressive Syndrome, is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood of horses. ... Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of nerve-muscle (neuromuscular) junction. ... This article or section is in need of attention from an expert on the subject. ... Familial dysautonomia, or FD, is a disorder of the autonomic nervous system which affects the development and survival of sensory, sympathetic and some parasympathetic neurons in the autonomic and sensory nervous system resulting in variable symptoms including: insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure... Horners syndrome is a clinical syndrome caused by damage to the sympathetic nervous system. ... Multiple system atrophy (MSA) is a degenerative neurological disorder. ... Shy-Drager syndrome is a rare, progressively degenerative disease of the autonomic nervous system. ... These are a group of diseases characterized by neuronal degeneration in the cerebellum, pontine nuclei, and inferior olive. ...

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