Devic's disease
Encyclopedia
Neuromyelitis optica, also known as Devic's disease or Devic's syndrome, is an autoimmune
, inflammatory
disorder in which a person's own immune system
attacks the optic nerve
s and spinal cord
. This produces an inflammation of the optic nerve (optic neuritis
) and the spinal cord (myelitis
). Although inflammation may also affect the brain, the lesions are different from those observed in the related condition multiple sclerosis
(MS). Spinal cord lesions lead to varying degrees of weakness
or paralysis
in the legs or arms, loss of sensation (including blindness
), and/or bladder
and bowel dysfunction.
Devic's disease is a rare disorder which resembles MS in several ways, but requires a different course of treatment for optimal results. NMO has also been suggested to be a variant form of acute disseminated encephalomyelitis
.. The likely target of the autoimmune attack at least in some patients with NMO has been identified; it is a protein
of the nervous system
cells called aquaporin 4
.
and spinal cord
function. As for other etiologies of optic neuritis
, the visual impairment usually manifests as decreased visual acuity
, although visual field
defects, or loss of color vision
may occur in isolation or prior to formal loss of acuity. Spinal cord dysfunction can lead to muscle weakness, reduced sensation, or loss of bladder
and bowel control. 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.
attacks the myelin
surrounding nerve cells. Unlike standard MS, the attacks are not believed to be mediated by the immune system's T cell
s but rather by antibodies
called NMO-IgG
, or simply NMO antibodies. These antibodies target a protein
called aquaporin 4
in the cell membrane
s of astrocyte
s which acts as a channel for the transport of water across the cell membrane. 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.
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), 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.
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:
Absolute criteria:
Supportive criteria:
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 standard 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.
Recently it has been found that antiviral immune response distinguishes standard multiple sclerosis and neuromyelitis optica, but being MS an heterogeneous condition, as hepatitis
or diabetes are, it is still possible to consider NMO part of the MS spectrum.
condition. Such conditions include: collagen vascular diseases, autoantibody syndromes, infection
s with varicella-zoster virus, Epstein-Barr virus
, and HIV
, and exposure to clioquinol
and antituberculosis drugs
.
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.
s such as methylprednisolone
IV. When attacks progress or do not respond to corticosteroid treatment, plasmapheresis
can be an effective treatment. Clinical trials for these treatments contain very small numbers, and most are uncontrolled.
is required to reduce the frequency and severity of attacks, while others argue the exact opposite. Commonly used immunosuppressant treatments include azathioprine
(Imuran) plus prednisone
, mycophenolate mofetil
plus prednisone, Rituximab
, Mitoxantrone
, intravenous immunoglobulin
(IVIG), and Cyclophosphamide
. The monoclonal antibody rituximab
is under study. In 2007, Devic's disease was reported to be responsive to glatiramer acetate
and to low-dose corticosteroids.
may persist, sometimes severely.
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. Unlike multiple sclerosis, 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.
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.
and incidence
of Devic's disease has not been established partly because the disease is underrecognized and often confused with MS. 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.
According to the Walton Centre in England, "NMO seems to be present across the world unlike MS, which has a higher incidence in temperate climates and white races. Africans and Asians especially in Far East may have a higher risk of NMO, although the exact incidence of this disease is unknown, making specific conclusions difficult". Although many people who have Devic's Disease were initially mis-diagnosed with MS, 35% of African Americans are often mis-diagnosed with MS when they really have Devic's Disease/NMO.
Devic's disease is more common in Asiatic people
than Caucasian
s. 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(Differences between optic-spinal and classic MS in Japanese patients). 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.
The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a non-familial condition.
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 eye
s 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.
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.
In 2004, Mayo Clinic
researchers identified the aquaporin 4
protein as the target of the disease and developed a test to aid in the diagnosis of Devic's disease by detection of an antibody, NMO-IgG
, in the blood. Some patients with NMO may be seronegative
for NMO-IgG whilst some patients with NMO-IgG may still not fulfill clinical criteria for NMO thus serological testing is now an important part of the diagnostic procedure and seropositive and seronegative cases are described in a manner similar to myasthenia gravis
. According to the Mayo Clinic
report, this was the first time that a molecular target had been identified for a type of demyelinating inflammatory disease.
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
, inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
disorder in which a person's own immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
s and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
. This produces an inflammation of the optic nerve (optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
) and the spinal cord (myelitis
Myelitis
Myelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
). Although inflammation may also affect the brain, the lesions are different from those observed in the related condition multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
(MS). Spinal cord lesions lead to varying degrees of weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
or paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
in the legs or arms, loss of sensation (including blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
), and/or bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
and bowel dysfunction.
Devic's disease is a rare disorder which resembles MS in several ways, but requires a different course of treatment for optimal results. NMO has also been suggested to be a variant form of acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis is an immune mediated disease of the brain. It usually occurs following a viral infection but may appear following vaccination, bacterial or parasitic infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple...
.. The likely target of the autoimmune attack at least in some patients with NMO has been identified; it is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
cells called aquaporin 4
Aquaporin 4
Aquaporin 4 also known as AQP4 is protein which in humans is encoded by the AQP4 gene. AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane.- Function :...
.
Symptoms
The main symptoms of Devic's disease are loss of visionVisual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
function. As for other etiologies of optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
, the visual impairment usually manifests as decreased visual acuity
Visual acuity
Visual acuity is acuteness or clearness of vision, which is dependent on the sharpness of the retinal focus within the eye and the sensitivity of the interpretative faculty of the brain....
, although visual field
Visual field
The term visual field is sometimes used as a synonym to field of view, though they do not designate the same thing. The visual field is the "spatial array of visual sensations available to observation in introspectionist psychological experiments", while 'field of view' "refers to the physical...
defects, or loss of color vision
Color vision
Color vision is the capacity of an organism or machine to distinguish objects based on the wavelengths of the light they reflect, emit, or transmit...
may occur in isolation or prior to formal loss of acuity. Spinal cord dysfunction can lead to muscle weakness, reduced sensation, or loss of bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
and bowel control. The typical patient has an acute and severe spastic
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
of the legs (paraparesis) or all four limbs (tetraparesis) with sensory signs, often accompanied by loss of bladder control.
Mechanism
Devic's disease is similar to MS in that the body's immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
attacks the myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
surrounding nerve cells. Unlike standard MS, the attacks are not believed to be mediated by the immune system's T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s but rather by antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
called NMO-IgG
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
, or simply NMO antibodies. These antibodies target a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
called aquaporin 4
Aquaporin 4
Aquaporin 4 also known as AQP4 is protein which in humans is encoded by the AQP4 gene. AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane.- Function :...
in the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s of astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s which acts as a channel for the transport of water across the cell membrane. Aquaporin 4 is found in the processes of the astrocytes that surround the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
, 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.
Most research into the pathology of Devic's disease has focused on the spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
. The damage in the spinal cord can range from inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
demyelination to necrotic
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
damage of the white
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
and grey matter
Grey matter
Grey matter is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil , glial cells and capillaries. Grey matter contains neural cell bodies, in contrast to white matter, which does not and mostly contains myelinated axon tracts...
. The inflammatory lesions in Devic's disease have been classified as type II lesions (complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
mediated demyelinization), 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.
Diagnosis
The Mayo ClinicMayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
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:
Absolute criteria:
- Optic neuritisOptic neuritisOptic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
- Acute myelitisMyelitisMyelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
Supportive criteria:
- BrainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
MRIMagnetic resonance imagingMagnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
not meeting criteria for MS at disease onset - Spinal cordSpinal cordThe spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
MRI with contiguous T2-weighted signal abnormality extending over 3 or more vertebral segments, indicating a relatively large lesionLesionA lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
in the spinal cord - NMO-IgGImmunoglobulin GImmunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
seropositive status. The NMO-IgG test checks the existence of antibodiesAntibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against the aquaporin 4Aquaporin 4Aquaporin 4 also known as AQP4 is protein which in humans is encoded by the AQP4 gene. AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane.- Function :...
antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
.
Variants
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:- 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 myelitisMyelitisMyelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
, and bilateral simultaneous or recurrent optic neuritisOptic neuritisOptic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the... - Asian optic-spinal MS. This variant can present CNS involvement like MS
- Longitudinally extensive myelitisMyelitisMyelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
or optic neuritis associated with systemic auto-immune disease - Optic neuritis or myelitis associated with lesionLesionA lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
s in specific brain areas such as the hypothalamusHypothalamusThe Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, periventricular nucleusPeriventricular nucleusThe Periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. Functions in analgesia....
, and brainstem
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 standard MS, MS infrequently presents as transverse myelitis
Transverse myelitis
Transverse myelitis is a neurological disorder caused by an inflammatory process of the spinal cord, and can cause axonal demyelination. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation...
, and oligoclonal bands in the CSF
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
, as well as white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
lesions on brain MRI, are uncommon in Devic's disease but occur in over 90% of MS patients.
Recently it has been found that antiviral immune response distinguishes standard multiple sclerosis and neuromyelitis optica, but being MS an heterogeneous condition, as hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
or diabetes are, it is still possible to consider NMO part of the MS spectrum.
Causes
Devic's disease has been associated with many systemic diseases, based on anecdoctal evidence of some Devic's disease patients with a comorbidComorbidity
In medicine, comorbidity is either the presence of one or more disorders in addition to a primary disease or disorder, or the effect of such additional disorders or diseases.- In medicine :...
condition. Such conditions include: collagen vascular diseases, autoantibody syndromes, infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s with varicella-zoster virus, Epstein-Barr virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
, and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, and exposure to clioquinol
Clioquinol
Clioquinol is an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication...
and antituberculosis drugs
Tuberculosis treatment
Tuberculosis treatment refers to the medical treatment of the infectious disease tuberculosis .The standard "short" course treatment for TB is isoniazid, rifampicin , pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months...
.
Treatment
Attacks
Attacks are treated with short courses of high dosage intravenous corticosteroidCorticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s such as methylprednisolone
Methylprednisolone
Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....
IV. When attacks progress or do not respond to corticosteroid treatment, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
can be an effective treatment. Clinical trials for these treatments contain very small numbers, and most are uncontrolled.
Secondary prevention
No controlled trials have established the effectiveness of treatments for the prevention of attacks. Many clinicians agree that long term immunosuppressionImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
is required to reduce the frequency and severity of attacks, while others argue the exact opposite. Commonly used immunosuppressant treatments include azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
(Imuran) plus prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
, mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
plus prednisone, Rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, Mitoxantrone
Mitoxantrone
Mitoxantrone is an anthracenedione antineoplastic agent.-Uses:It is used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma...
, intravenous immunoglobulin
Intravenous immunoglobulin
Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...
(IVIG), and Cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
. The monoclonal antibody rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
is under study. In 2007, Devic's disease was reported to be responsive to glatiramer acetate
Glatiramer acetate
Glatiramer acetate is an immunomodulator drug currently used to treat multiple sclerosis...
and to low-dose corticosteroids.
Prognosis
Normally, there is some measure of improvement in a few weeks, but residual signs and disabilityDisability
A disability may be physical, cognitive, mental, sensory, emotional, developmental or some combination of these.Many people would rather be referred to as a person with a disability instead of handicapped...
may persist, sometimes severely.
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
Transverse myelitis
Transverse myelitis is a neurological disorder caused by an inflammatory process of the spinal cord, and can cause axonal demyelination. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation...
and/or optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
. 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. Unlike multiple sclerosis, 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.
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
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
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.
Epidemiology
The prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
and incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of Devic's disease has not been established partly because the disease is underrecognized and often confused with MS. 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.
According to the Walton Centre in England, "NMO seems to be present across the world unlike MS, which has a higher incidence in temperate climates and white races. Africans and Asians especially in Far East may have a higher risk of NMO, although the exact incidence of this disease is unknown, making specific conclusions difficult". Although many people who have Devic's Disease were initially mis-diagnosed with MS, 35% of African Americans are often mis-diagnosed with MS when they really have Devic's Disease/NMO.
Devic's disease is more common in Asiatic people
Asian people
Asian people or Asiatic people is a term with multiple meanings that refers to people who descend from a portion of Asia's population.- Central Asia :...
than Caucasian
Caucasian race
The term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...
s. In fact, Asian optic-spinal MS (which constitutes 30% of the cases of MS in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
) has been suggested to be identical to Devic's disease(Differences between optic-spinal and classic MS in Japanese patients). In the indigenous populations
Indigenous peoples
Indigenous peoples are ethnic groups that are defined as indigenous according to one of the various definitions of the term, there is no universally accepted definition but most of which carry connotations of being the "original inhabitants" of a territory....
of tropical
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately N and the Tropic of Capricorn in the southern hemisphere at S; these latitudes correspond to the axial tilt of the Earth...
and subtropical regions
Subtropics
The subtropics are the geographical and climatical zone of the Earth immediately north and south of the tropical zone, which is bounded by the Tropic of Cancer and the Tropic of Capricorn, at latitudes 23.5°N and 23.5°S...
, MS is rare, but when it appears it often takes the form of optic-spinal MS.
The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a non-familial condition.
History
In 1870, Sir Thomas Clifford Allbutt first reported an association between myelitisMyelitis
Myelitis is a disease involving inflammation of the spinal cord, which disrupts central nervous system functions linking the brain and limbs. The name is derived from Greek referring to the "spinal cord", and the suffix -itis, which denotes inflammation....
and an optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
disorder. In 1894, Eugène Devic
Eugène Devic
Eugène Devic was a French neurologist who was a native of Lyon. He studied medicine in Lyon under internist Léon Bouveret...
and his PhD.
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
student Fernand Gault described 16 patients who had lost vision
Visual perception
Visual perception is the ability to interpret information and surroundings from the effects of visible light reaching the eye. The resulting perception is also known as eyesight, sight, or vision...
in one or both eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
s and within weeks developed severe spastic
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
of the limbs, loss of sensation and often bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
control. They recognized that these symptoms were the result of inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
of the optic nerve and spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, respectively.
Similar instances of optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...
and myelitis were reported, and many believed it constituted a distinct clinical entity. However, some patients had pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
in other parts of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, a feature which was more suggestive of acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis is an immune mediated disease of the brain. It usually occurs following a viral infection but may appear following vaccination, bacterial or parasitic infection, or even appear spontaneously. As it involves autoimmune demyelination, it is similar to multiple...
(ADEM) or MS.
In 2004, Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
researchers identified the aquaporin 4
Aquaporin 4
Aquaporin 4 also known as AQP4 is protein which in humans is encoded by the AQP4 gene. AQP4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane.- Function :...
protein as the target of the disease and developed a test to aid in the diagnosis of Devic's disease by detection of an antibody, NMO-IgG
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
, in the blood. Some patients with NMO may be seronegative
Serostatus
Serostatus is a term used to refer to the presence or absence of specific substances in the blood serum. Most commonly, this medical test is looking for specific antibodies in an effort to diagnose a particular disease....
for NMO-IgG whilst some patients with NMO-IgG may still not fulfill clinical criteria for NMO thus serological testing is now an important part of the diagnostic procedure and seropositive and seronegative cases are described in a manner similar to myasthenia gravis
Myasthenia gravis
Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
. According to the Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
report, this was the first time that a molecular target had been identified for a type of demyelinating inflammatory disease.
External links
- Devic's Disease (Neuromyelitis Optica) at myelitis.org
- Devics Disease – Information and treatment options at Mayo ClinicMayo ClinicMayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
- NMO / Devic's NHSDirect – Documentation on the UK National Health Service Database
- The Guthy-Jackson Charitable Foundation – for NMO Research
- The SistaMoon Foundation For Devic's Disease Information on Research as it relates to Devic's/NMO and Resources
- Specialist NMO information from the UK NHS NMO diagnostic and advisory service