Devic's disease, also known as Devic's syndrome, neuromyelitis optica (NMO), or optic-spinal MS, is an autoimmune, inflammatory disorder in which a person's own immune system attacks myelin of the neurons of the optic nerves and spinal cord. This produces an inflammation of the optic nerve (optic neuritis) and the spinal cord (myelitis). Normally, brain neurons are spared but optic nerve lesions cause temporary blindness, occasionally permanent, in one or both eyes. Spinal cord lesions lead to varying degrees of weakness or paralysis in the legs or arms, loss of sensation, and/or bladder and bowel dysfunction.^[1] 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 codes are used with International Statistical Classification of Diseases and Related Health Problems. ... 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. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the Innate immune system and as healthy nor unhealthy on its own: Inflammation helps fight disease, but it comes at the cost of suspending the bodys normal immune and catabolic... A scanning electron microscope image of a single lymphocyte, a component of the human immune system A poop system is a collection of mechanisms within an organism that protect against infection by identifying and killing pathogens. ... In neuroscience, myelin is an electrically insulating phospholipid layer that surrounds the axons of many neurons. ... MRI scan of human eye showing optic nerve. ... The Spinal cord nested in the vertebral column. ... Optic [[neuritis](or retrobulbar neuritis) is the inflammation of the optic nerve that may cause a complete or partial loss of vision. ... Myelitis is a human disease involving swelling of the spinal cord, which disrupts central nervous system functions linking brain and limbs. ... Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. ... Blindness is the condition of lacking visual perception due to physiological or psychological factors. ... Muscle weakness (or lack of strength) is a general term used during a diagnosis before the etiology can be identified. ... Paralysis is the complete loss of muscle function for one or more muscle groups. ... It has been suggested that this article or section be merged with Sensation and perception psychology. ... In anatomy, the urinary bladder is a hollow, muscular, and distensible (or elastic) organ that sits on the pelvic floor in mammals. ... The intestine is the portion of the alimentary canal extending from the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine. ...

Devic's disease is a rare disorder which resembles multiple sclerosis (MS) in several ways, but requires a different course of treatment for optimal results.^[1]. Unlike standard MS, the target of the autoimmune attack has been identified, leaving no doubts about the autoimmune nature of the disease. The target is a protein of the nervous system cells called aquaporin 4.^[2] A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... The Human Nervous System The nervous system of an animal coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. ... Sideview of Aquaporin 1 (AQP1) Channel Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. ...

Symptoms

The main symptoms of Devic's disease are loss of vision and spinal cord function. The visual impairment can consist of a reduced visual field, diminished light sensitivity, or loss of color vision. Spinal cord dysfunction can be muscle weakness and lack of coordination, reduced sensation, or loss of bladder and bowel control.^[3] The typical patient has an acute and severe spastic weakness of the legs (paraparesis) or all four limbs (tetraparesis) with sensory signs, often accompanied by loss of bladder control. This weakness is preceded or succeeded by an acute unilateral or bilateral optic neuropathy with impaired visual acuity and colour vision and central hazy or opaque patches of loss of vision. The symptoms are usually limited to the spinal cord and optic nerves. Look up vision in Wiktionary, the free dictionary. ... The Spinal cord nested in the vertebral column. ... The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. ... Color vision is the capacity of an organism or machine to distinguish objects based on the wavelengths (or frequencies) of the light they reflect or emit. ... It has been suggested that this article or section be merged with Sensation and perception psychology. ... In anatomy, the urinary bladder is a hollow, muscular, and distensible (or elastic) organ that sits on the pelvic floor in mammals. ... Look up acute in Wiktionary, the free dictionary. ... Spasticity is a disorder of the bodys motor system in which certain muscles are continuously contracted. ... Muscle weakness (or lack of strength) is a general term used during a diagnosis before the etiology can be identified. ... Paraplegia is a condition in which the lower part of a persons body is paralyzed and cannot willfully function. ... Quadriplegia, also known as tetraplegia, is a symptom in which a human experiences paralysis of all four limbs, although not necessarily total paralysis. ... A bladder is a pouch or other flexible enclosure with waterproof or gasproof walls. ... Neuropathy, strictly speaking, is any disease that affects the nervous system. ... Traditional Snellen chart used for visual acuity testing. ... Color vision is a psychophysical phenomenon that exists only in our minds. ...

Mechanism

Devic's disease is similar to MS in that the body's immune system attacks the myelin surrounding nerve cells. Unlike standard MS, the attacks are not believed to be mediated by the immune system's T cells but rather by antibodies called NMO-IgG. These antibodies target a protein called aquaporin 4 in the cell membranes of astrocytes which acts as a channel for the transport of water across the cell membrane. ^[1] Aquaporin 4 is found in the processes of the astrocytes that surround the blood-brain barrier, a system responsible for preventing substances in the blood from crossing into the brain. The blood-brain barrier is weakened in Devic's disease, but it is currently unknown how the NMO-IgG immune response leads to demyelination. Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory disease that affects the central nervous system (CNS). ... A scanning electron microscope image of a single lymphocyte, a component of the human immune system A poop system is a collection of mechanisms within an organism that protect against infection by identifying and killing pathogens. ... In neuroscience, myelin is an electrically insulating phospholipid layer that surrounds the axons of many neurons. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Sideview of Aquaporin 1 (AQP1) Channel Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. ... The cell membrane (also called the plasma membrane or plasmalemma) is a semipermeable lipid bilayer common to all living cells. ... Astrocytes, also known as astroglia, are characteristic star-shaped glial cells in the brain. ... Freeze-fracture morphology of the blood-brain barrier of a rat The blood-brain barrier (abbreviated BBB, not to be confused with the blood-cerebrospinal fluid barrier, a function of the choroid plexus) is a membrane that controls the passage of substances from the blood into the central nervous system. ...

Most research into the pathology of Devic's disease has focused on the spinal cord. The damage in the spinal cord can range from inflammatory demyelination to necrotic damage of the white and grey matter. The inflammatory lesions in Devic's disease have been classified as type II lesions (complement mediated demyelinization),^[4] but they differ from MS pattern II lesions in their prominent perivascular distribution. Therefore, the pattern of inflammation is often quite distinct from that seen in MS. ^[1][5] The Spinal cord nested in the vertebral column. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the Innate immune system and as healthy nor unhealthy on its own: Inflammation helps fight disease, but it comes at the cost of suspending the bodys normal immune and catabolic... Necrosis (in Greek Νεκρός = Death) is the name given to accidental death of cells and living tissue. ... White matter is one of the two main solid components of the central nervous system. ... Grey matter is a major component of the central nervous system, consisting of nerve cell bodies and short nerve cell extensions/processes (axons and dendrites). ... Since long time ago, it was noticed that some forms of MS were special. ... A complement protein attacking an invader. ...

Diagnosis

The Mayo Clinic proposed a revised set of criteria for diagnosis of Devic's disease in 2006. The new guidelines for diagnosis require two absolute criteria plus at least two of three supportive criteria being: Main campus in downtown Rochester, Minnesota. ...

Absolute criteria:

1. Optic neuritis
2. Acute myelitis

Supportive criteria: Optic [[neuritis](or retrobulbar neuritis) is the inflammation of the optic nerve that may cause a complete or partial loss of vision. ... Myelitis is a human disease involving swelling of the spinal cord, which disrupts central nervous system functions linking brain and limbs. ...

1. Brain MRI not meeting criteria for MS at disease onset
2. Spinal cord MRI with contiguous T2-weighted signal abnormality extending over 3 or more vertebral segments, indicating a relatively large lesion in the spinal cord
3. NMO-IgG seropositive status. The NMO-IgG test checks the existence of antibodies against the aquaporin 4 antigen.^[6]

After the development of the NMO-IgG test, the spectrum of disorders that comprise Devic's disease was expanded. The Devic's disease spectrum is now believed to consist of: In animals, the brain, or encephalon (Greek for in the head), is the control center of the central nervous system. ... For the scientific journal entitled Magnetic Resonance Imaging, see Magnetic Resonance Imaging (journal). ... The Spinal cord nested in the vertebral column. ... A diagram of a thoracic vertebra. ... A lesion is a non-specific term referring to abnormal tissue in the body. ... Molecular surface of an IgG molecule IgG is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. ... Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Sideview of Aquaporin 1 (AQP1) Channel Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. ... An antigen is a substance that stimulates an immune response, especially the production of antibodies. ...

• Standard Devic's disease, according to the diagnostic criteria described above
• Limited forms of Devic's disease, such as single or recurrent events of longitudinally extensive myelitis, and bilateral simultaneous or recurrent optic neuritis
• Asian optic-spinal MS
• Longitudinally extensive myelitis or optic neuritis associated with systemic auto-immune disease
• Optic neuritis or myelitis associated with lesions in specific brain areas such as the hypothalamus, periventricular nucleus, and brainstem^[7]

Whether Devic's disease is a distinct disease or part of the wide spectrum of multiple sclerosis is debated. Devic's disease differs in that it usually has more severe sequelae after an acute episode than in MS, MS infrequently presents as transverse myelitis, and oligoclonal bands in the CSF, as well as white matter lesions on brain MRI, are uncommon in Devic's disease but occur in over 90% of MS patients. ^[8] Myelitis is a human disease involving swelling of the spinal cord, which disrupts central nervous system functions linking brain and limbs. ... Optic [[neuritis](or retrobulbar neuritis) is the inflammation of the optic nerve that may cause a complete or partial loss of vision. ... Myelitis is a human disease involving swelling of the spinal cord, which disrupts central nervous system functions linking brain and limbs. ... Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. ... A lesion is a non-specific term referring to abnormal tissue in the body. ... The hypothalamus (from Greek ὑποθαλαμος = under the thalamus) is a region of the mammalian brain located below the thalamus, forming the major portion of the ventral region of the diencephalon and functioning to regulate certain metabolic processes and other autonomic activities. ... The Periventricular nucleus is a composite structure of the hypothalamus. ... The brain stem is the stalk of the brain below the cerebral hemispheres. ... A sequela (plural sequelae) is a pathological condition resulting from a disease. ... Transverse myelitis is a neurological disorder caused by a loss of the myelin encasing the spinal cord, also known as demyelination. ... Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space in the brain (the space between the skull and the cerebral cortex—more specifically, between the arachnoid and pia layers of the meninges). ... White matter is one of the two main solid components of the central nervous system. ...

Devic's disease has been associated with many systemic diseases, based on anecdoctal evidence of some Devic's disease patients with a comorbid condition. Such conditions include: collagen vascular diseases, autoantibody syndromes, infections with varicella-zoster virus, Epstein-Barr virus, and HIV, and exposure to Clioquinol and antituberculosis drugs. ^[9] In medicine and in psychiatry, comorbidity is either The presence of one or more disorders (or diseases) in addition to a primary disease or disorder; or The effect of such additional disorders or diseases. ... An infection is the detrimental colonization of a host organism by a foreign species. ... The varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3), is one of the eight herpesviruses known to affect humans (and other vertebrates). ... The Epstein-Barr virus (EBV), also called Human herpesvirus 4 (HHV-4), is a virus of the herpes family (which includes Herpes simplex virus and Cytomegalovirus), and is one of the most common viruses in humans. ... Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. ... Clioquinol is a powerful anti-infective drug available for topical (Vioform) and internal (Enterovioform) use. ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ...

Treatment

Currently, there is no cure for Devic's disease, but symptoms can be treated. Some patients recover, but many are left with impairment of vision and limbs, which can be severe.

Attacks are treated with short courses of high dosage intravenous corticosteroids such as methylprednisolone IV. When attacks progress or do not respond to corticosteroid treatment, plasmapheresis can be an effective treatment.^[7] Clinical trials for these treatments contain very small numbers, and most are uncontrolled. An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Methylprednisolone (molecular weight 374. ... Plasmapheresis is the removal of (components of) blood plasma from the circulation. ...

Prevention of new attacks

No controlled trials have established the effectiveness of treatments for the prevention of attacks. Most clinicians agree that long term immunosuppression is required to reduce the frequency and severity of attacks. Commonly used immunosuppresant treatments include azathioprine (Imuran) plus prednisone, mycophenolate mofetil plus prednisone, Rituximab, Mitoxantrone, intravenous immunoglobulin (IVIG), and Cyclophosphamide.^[10][7] Immunosuppression is the medical suppression of the immune system. ... Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ... Prednisone is a synthetic corticosteroid drug which is usually taken orally and can be used for a large number of different conditions. ... Mycophenolate mofetil (MMF, trade name Cellcept®) is an immunosuppresant drug used to prevent rejection in organ transplantation. ... Rituximab, sold under the trade names Rituxan® and MabThera®, is a monoclonal antibody used in the treatment of B cell non-Hodgkins lymphoma, B cell leukemia, and some autoimmune disorders. ... Mitoxantrone belongs to the general group of medicines known as antineoplastics, specifically the anthracycline class. ... Intravenous immunoglobulin (IVIG) is a blood product administered Intravenously. ... Cyclophosphamide (the generic name for Cytoxan, Neosar) is a nitrogen mustard alkylating agent, used to treat various types of cancer and some autoimmune disorders. ...

Prognosis

Normally, there is some measure of improvement in a few weeks, but residual signs and disability may persist, sometimes severely. Look up disability in Wiktionary, the free dictionary. ...

The disease can be monophasic, i.e. a single episode with permanent remission. However, at least 85% of patients have a relapsing form of the disease with repeated attacks of transverse myelitis and/or optic neuritis. In patients with the monophasic form the transverse myelitis and optic neuritis occur simultaneously or within days of each other. On the other hand, patients with the relapsing form are more likely to have weeks or months between the initial attacks and to have better motor recovery after the initial transverse myelitis event. Relapses usually occur early with about 55% of patients having a relapse in the first year and 90% in the first 5 years.^[1] Unlike MS, Devic's disease rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission. Instead, disabilities arise from the acute attacks.^[11] Remission is the state of absence of disease activity in patients with known chronic illness. ... Transverse myelitis is a neurological disorder caused by a loss of the myelin encasing the spinal cord, also known as demyelination. ... Optic [[neuritis](or retrobulbar neuritis) is the inflammation of the optic nerve that may cause a complete or partial loss of vision. ... Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory disease that affects the central nervous system (CNS). ...

Approximately 20% of patients with monophasic Devic's disease have permanent visual loss and 30% have permanent paralysis in one or more legs. Among patients with relapsing Devic's disease, 50% have paralysis or blindness within 5 years. In some patients (33% in one study), transverse myelitis in the cervical spinal cord resulted in respiratory failure and subsequent death. However, the spectrum of Devic's disease has widened due to improved diagnostic criteria, and the options for treatment have improved; as a result, researchers believe that these estimates will be lowered.^[1] The Spinal cord nested in the vertebral column. ...

Epidemiology

The prevalence and incidence of Devic's disease has not been established partly because the disease is underrecognized and often confused with MS.^[1] Devic's disease is more common in women than men, with women comprising over 2/3 of patients and more than 80% of those with the relapsing form of the disease. ^[1][12] Devic's disease is more common in Asiatic people than Caucasians. In fact, Asian optic-spinal MS (which constitutes 30% of the cases of MS in Japan) has been suggested to be identical to Devic's disease.^[13] In the indigenous populations of tropical and subtropical regions, MS is rare, but when it appears it often takes the form of optic-spinal MS.^[14][15] In epidemiology, the prevalence of a disease in a statistical population is defined as the ratio of the number of cases of a disease present in a statistical population at a specified time and the number of individuals in the population at that specified time. ... In optics one considers angles of incidence. ... Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory disease that affects the central nervous system (CNS). ... Japanese American James Iha, the guitarist in the band The Smashing Pumpkins. ... The 4th edition of Meyers Konversationslexikon (1885-1890) shows the Caucasian race (in blue) as comprising Aryans, Semites and Hamites. The Caucasian race (sometimes called the Caucasoid race) is defined by the Oxford English Dictionary as, relating to a broad division of humankind covering peoples from Europe, western Asia, Middle... The term indigenous peoples has no universal, standard or fixed definition, but can be used about any ethnic group who inhabit the geographic region with which they have the earliest historical connection. ... The tropics are the geographic region of the Earth centered on the equator and limited in latitude by the two tropics: the Tropic of Cancer in the northern hemisphere and the Tropic of Capricorn in the southern hemisphere. ... The subtropics refers to the zones of the Earth immediately north and south of the two tropic zones, which are bounded by the Tropic of Cancer and the Tropic of Capricorn, at latitude 23. ...

The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a non-familial condition.^[1]

History

In 1870, Sir Thomas Clifford Allbutt first reported an association between myelitis and an optic nerve disorder. In 1894, Eugène Devic and his PhD. student Fernand Gault described 16 patients who had lost vision in one or both eyes and within weeks developed severe spastic weakness of the limbs, loss of sensation and often bladder control. They recognized that these symptoms were the result of inflammation of the optic nerve and spinal cord, respectively.^[16] 1870 (MDCCCLXX) was a common year starting on Saturday (see link for calendar) of the Gregorian calendar or a common year starting on Monday of the 12-day-slower Julian calendar. ... Sir Thomas Clifford Allbutt was born in Dewsbury, Yorkshire, the son of Thomas Allbutt, Vicar of Dewsbury and Susan Wooler. ... Myelitis is a human disease involving swelling of the spinal cord, which disrupts central nervous system functions linking brain and limbs. ... MRI scan of human eye showing optic nerve. ... 1894 (MDCCCXCIV) was a common year starting on Monday (see link for calendar). ... Doctor of Philosophy, abbreviated Ph. ... This article or section does not cite its references or sources. ... A human eye. ... Spasticity is a disorder of the bodys motor system in which certain muscles are continuously contracted. ... Muscle weakness (or lack of strength) is a general term used during a diagnosis before the etiology can be identified. ... It has been suggested that this article or section be merged with Sensation and perception psychology. ... In anatomy, the urinary bladder is a hollow, muscular, and distensible (or elastic) organ that sits on the pelvic floor in mammals. ... Inflammation is the first response of the immune system to infection or irritation and may be referred to as the Innate immune system and as healthy nor unhealthy on its own: Inflammation helps fight disease, but it comes at the cost of suspending the bodys normal immune and catabolic... The Spinal cord nested in the vertebral column. ...

Similar instances of optic neuritis and myelitis were reported, and many believed it constituted a distinct clinical entity. However, some patients had pathology in other parts of the brain, a feature which was more suggestive of acute disseminated encephalomyelitis (ADEM) or MS. Optic [[neuritis](or retrobulbar neuritis) is the inflammation of the optic nerve that may cause a complete or partial loss of vision. ... Pathology (from Greek pathos, feeling, pain, suffering; and logos, study of; see also -ology) is the study of the processes underlying disease and other forms of illness, harmful abnormality, or dysfunction. ... In animals, the brain, or encephalon (Greek for in the head), is the control center of the central nervous system. ... Acute disseminated encephalomyelitis (ADEM) is an immune mediated disease of brain. ... Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory disease that affects the central nervous system (CNS). ...

In 2004 the Mayo Clinic identified the aquaporin 4 protein as the target of the disease and developed a test to diagnose Devic's disease by the presence of an antibody, NMO-IgG, in the blood. According to the Mayo Clinic report, this was the first time that a molecular target had been identified for a type of MS.^[17] 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... Main campus in downtown Rochester, Minnesota. ... Sideview of Aquaporin 1 (AQP1) Channel Aquaporins are a class of integral membrane proteins or more commonly referred to as a class of major intrinsic proteins (MIP) that form pores in the membrane of biological cells. ... Molecular surface of an IgG molecule IgG is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. ... Main campus in downtown Rochester, Minnesota. ... Multiple Sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory disease that affects the central nervous system (CNS). ...

See also

• Multiple sclerosis
• Multiple sclerosis borderline

This is the name given to special cases of Multiple sclerosis [1]. These diseases are now called the MS-borderline, because some authors consider them different diseases and others MS variants. ...

References

2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the Anno Domini (common) era. ... January 5 is the 5th day of the year in the Gregorian calendar. ...

External links

• Devic's Disease (Neuromyelitis Optica)
• Mayo Clinic: Devics Disease - Information and treatment options
• Gayle's Place: Worldwide Devic's and Neuromyelitis Optica Support
• EDUMS, European Database for Multiple Sclerosis
• [11]survey written by doctors to study NMO]
• Devic on Frappr, map on which users with Devic's disease mark their location
• Devic's on-line support group