A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency in sensation, movement, cognition, or other functions depending on which nerves are involved.
|Photomicrograph of a demyelinating MS-lesion: Immunohistochemical staining for CD68 highlights numerous macrophages (brown). Original magnification 10×.|
Some demyelinating diseases are caused by genetics, some by infectious agents, some by autoimmune reactions, and some by unknown factors. Organophosphates, a class of chemicals which are the active ingredients in commercial insecticides such as sheep dip, weed killers, and flea treatment preparations for pets, etc., also demyelinate nerves. Neuroleptics can also cause demyelination.
Demyelinating diseases are traditionally classified in two kinds: demyelinating myelinoclastic diseases and demyelinating leukodystrophic diseases. In the first group, a normal and healthy myelin is destroyed by a toxic, chemical, or autoimmune substance. In the second group, myelin is abnormal and degenerates. The second group was denominated dysmyelinating diseases by Poser.
In the most known example, multiple sclerosis, good evidence shows that the body's own immune system is at least partially responsible. Acquired immune system cells called T-cells are known to be present at the site of lesions. Other immune-system cells called macrophages (and possibly mast cells) also contribute to the damage.
Vitamin B12 deficiency can cause demyelination.
Signs and symptomsEdit
Symptoms and signs that present in demyelinating diseases are different for each condition.These symptoms and signs can present in a person with a demyelinating disease:
The role of prolonged cortical myelination in human evolution has been implicated as a contributing factor in some cases of demyelinating disease. Unlike other primates, humans exhibit a unique pattern of postpubertal myelination, which may contribute to the development of psychiatric disorders and neurodegenerative diseases that present in early adulthood and beyond. The extended period of cortical myelination in humans may allow greater opportunity for disruption in myelination, resulting in the onset of demyelinating disease. Furthermore, humans have significantly greater prefrontal white matter volume than other primate species, which implies greater myelin density. Increased myelin density in humans as a result of a prolonged myelination may, therefore, structure risk for myelin degeneration and dysfunction. Evolutionary considerations for the role of prolonged cortical myelination as a risk factor for demyelinating disease are particularly pertinent given that genetics and autoimmune deficiency hypotheses fail to explain many cases of demyelinating disease. As has been argued, diseases such as multiple sclerosis cannot be accounted for by autoimmune deficiency alone, but strongly imply the influence of flawed developmental processes in disease pathogenesis. Therefore, the role of the human-specific prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.
Various methods/techniques are used to diagnose demyelinating diseases:
- Exclusion of other conditions that have overlapping symptoms
- Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to visualize internal structures of the body in detail. MRI makes use of the property of nuclear magnetic resonance (NMR) to image nuclei of atoms inside the body. This method is reliable because MRIs assess changes in proton density. "Spots" can occur as a result of changes in brain water content.:113
- Evoked potential is an electrical potential recorded from the nervous system following the presentation of a stimulus as detected by electroencephalography (EEG), electromyography (EMG), or other electrophysiological recording method.:117
- Cerebrospinal fluid analysis (CSF) can be extremely beneficial in the diagnosis of central nervous system infections. A CSF culture examination may yield the microorganism that caused the infection.
- Quantitative proton magnetic resonance spectroscopy (MRS) is a noninvasive analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders, Alzheimer's disease, depression, and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as muscles.:309
- Diagnostic criteria refers to a specific combination of signs, symptoms, and test results that the clinician uses in an attempt to determine the correct diagnosis.:320
- Fluid-attenuated inversion recovery (FLAIR) uses a pulse sequence to suppress cerebrospinal fluid and show lesions more clearly, and is used for example in multiple sclerosis evaluation.
Demyelinating diseases can be divided in those affecting the central nervous system and those presents in the peripheral nervous system, presenting different demyelination conditions. They can also be divided by other criteria in inflammatory and noninflammatory, according to the presence or lack of inflammation, and finally, a division can also be made depending on the underlying reason for demyelination in myelinoclastic (myelin is attacked by an external substance) and leukodystrophic (myelin degenerates without attacks)
Demyelinating disorders of the CNSEdit
The demyelinating disorders of the central nervous system include:
- Myelinoclastic disorders, in which myelin is attacked by external substances
- Leukodystrophic disorders, in which myelin is not properly produced:
These disorders are normally associated also with the conditions optic neuritis and transverse myelitis, which are inflammatory conditions, because inflammation and demyelination are frequently associated. Some of them are idiopathic and for some others the cause has been found, like some cases of neuromyelitis optica.
Demyelinating diseases of the peripheral nervous systemEdit
The demyelinating diseases of the peripheral nervous system include:
- Guillain–Barré syndrome and its chronic counterpart, chronic inflammatory demyelinating polyneuropathy
- Anti-MAG peripheral neuropathy
- Charcot–Marie–Tooth disease and its counterpart Hereditary neuropathy with liability to pressure palsy
- Copper deficiency-associated conditions (peripheral neuropathy, myelopathy, and rarely optic neuropathy)
- Progressive inflammatory neuropathy
Treatment typically involves improving the patient's quality of life. This is accomplished through the management of symptoms or slowing the rate of demyelination. Treatment can include medication, lifestyle changes (i.e. quit smoking, adjusting daily schedules to include rest periods and dietary changes), counselling, relaxation, physical exercise, patient education, and in some cases, deep brain thalamic stimulation (in the case of tremors).:227–248 The progressive phase of MS appears driven by the innate immune system, which directly contributes to the neurodegenerative changes that occur in progressive MS. Until now, no therapies specifically target innate immune cells in MS. As the role of innate immunity in MS becomes better defined, better treatment of MS by targeting the innate immune system may be possible.
Treatments are patient-specific and depend on the symptoms that present with the disorder, as well as the progression of the condition.
Prognosis depends on the condition itself. Some conditions such as MS depend on the subtype of the disease and various attributes of the patient such as age, sex, initial symptoms, and the degree of disability the patient experiences. Life expectancy in MS patients is 5 to 10 years lower than unaffected people. MS is an inflammatory demyelinating disease of the central nervous system (CNS) that develops in genetically susceptible individuals after exposure to unknown environmental trigger(s). The bases for MS are unknown but are strongly suspected to involve immune reactions against autoantigens, particularly myelin proteins. The most accepted hypothesis is that dialogue between T-cell receptors and myelin antigens leads to an immune attack on the myelin-oligodendrocyte complex. These interactions between active T cells and myelin antigens provoke a massive destructive inflammatory response and promote continuing proliferation of T and B cells and macrophage activation, which sustains secretion of inflammatory mediators. Other conditions such as central pontine myelinolysis have about a third of patients recover and the other two-thirds experience varying degrees of disability. In some cases, such as transverse myelitis, the patient can begin recovery as early as 2 to 12 weeks after the onset of the condition.
Incidence of demyelinating diseases varies by disorder. Some conditions, such as tabes dorsalis appear predominantly in males and begin in midlife. Optic neuritis, though, occurs preferentially in females typically between the ages of 30 and 35. Other conditions such as multiple sclerosis vary in prevalence depending on the country and population. This condition can appear in children and adults.
Research is being conducted in a variety of specific areas. The focus of this research is aimed at gaining more insight into how demyelinating disorders affect the central and peripheral nervous systems, how they develop and how these disorders are affected by various external inputs
Much of the research is targeted towards learning about the mechanisms by which these disorders function in an attempt to develop therapies and treatments for individuals affected by these conditions.
Currently, N-cadherin is believed to play a role in the myelination process. Experimentation has shown that N-cadherin plays an important role in producing a remyelination-facilitating environment. In animal models, a direct correlation exists between the amount of myelin debris present and the degree of inflammation observed.
Effects of environmental inputsEdit
Manipulating the levels of thyroid hormone can be considered as a strategy to promote remyelination and prevent irreversible damage in MS patients. N-cadherin agonists have been identified and observed to stimulate neurite growth and cell migration, key aspects of promoting axon growth and remyelination after injury or disease. It has been shown that intranasal administration of aTf (apotransferrin) can protect myelin and induce remyelination.
In other animalsEdit
Demyelinating diseases/disorders have been found worldwide in various animals. Some of these animals include mice, pigs, cattle, hamsters, rats, sheep, Siamese kittens, and a number of dog breeds (including Chow Chow, Springer Spaniel, Dalmatian, Samoyed, Golden Retriever, Lurcher, Bernese Mountain Dog, Vizsla, Weimaraner, Australian Silky Terrier, and mixed breeds).
Another notable animal found able to contract a demyelinating disease is the northern fur seal. Ziggy Star, a female northern fur seal, was treated at the Marine Mammal Center beginning in March 2014  and was noted as the first reported case of such disease in a marine mammal. She was later transported to Mystic Aquarium & Institute for Exploration for lifelong care as an ambassador to the public.
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