Demyelinating disease

A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged.[1]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.

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., will also demyelinate nerves. Neuroleptics can also cause demyelination.[2]

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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.[3] The second group was denominated dysmyelinating diseases by Poser.[4]

In the most known example, multiple sclerosis, there is good evidence 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.[5]

Vitamin B12 deficiency can cause demyelination.

Symptoms and signs that present in demyelinating diseases are different for each condition. Below is a list of symptoms and signs that can present in a person with a demyelinating disease.:[6]

  • Blurred double vision (Diplopia)
  • Ataxia
  • Clonus
  • Dysarthria
  • Fatigue
  • Clumsiness
  • Hand paralysis
  • Hemiparesis
  • Genital anaesthesia
  • Incoordination
  • Paresthesias
  • Ocular paralysis (Cranial Nerve Palsy)
  • Impaired muscle coordination
  • Weakness (muscle)
  • Loss of sensation
  • Impaired vision
  • Neurological symptoms
  • Unsteady gait
  • Spastic paraparesis
  • Incontinence
  • Hearing problems
  • Speech problems

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.[7] Furthermore, it has been noted that humans have significantly greater prefrontal white matter volume than other primate species, which implies greater myelin density.[8] 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.[9] Therefore, the role of the human-specific prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.

Below are various methods/techniques used to diagnose demyelinating diseases.

  • Exclusion of other conditions that have overlapping symptoms[10]
  • 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.[10]: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.[10]: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.[10]
  • Quantitative proton magnetic resonance spectroscopy (MRS) is a non-invasive 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.[10]: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.[10]: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 non-inflammatory, 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)

The demyelinating disorders of the central nervous system include:

  • Myelinoclastic disorders, in which myelin is attacked by external substances
    • standard multiple sclerosis, Devic’s disease and other disorders with immune system involvement called inflammatory demyelinating diseases.
  • Leukodystrophic disorders, in which myelin is not properly produced:
    • CNS neuropathies like those produced by vitamin B12 deficiency
    • Central pontine myelinolysis
    • Myelopathies like tabes dorsalis (syphilitic myelopathy)
    • leukoencephalopathies like progressive multifocal leukoencephalopathy
    • Leukodystrophies

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.

Guillain–Barré syndrome – demyelination

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).[10]:227–248 The progressive phase of MS appears driven by the innate immune system, which will directly contribute to the neurodegenerative changes that occur in progressive MS. Until now, there are no therapies that specifically target innate immune cells in MS. As the role of innate immunity in MS becomes better defined, it may be possible to better treat MS by targeting the innate immune system.[11]

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 multiple sclerosis 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.[12] Life expectancy in Multiple sclerosis patients is 5 to 10 years lower than unaffected people.[13] 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 promotes continuing proliferation of T and B cells and macrophage activation, which sustains secretion of inflammatory mediators.[14] Other conditions such as central pontine myelinolysis have about a third of patients recover and the other two thirds experience varying degrees of disability.[15] There are cases, such as transverse myelitis where the patient can begin recovery as early as 2 to 12 weeks after the onset of the condition.

Incidence of demyelinating diseases vary from disorder to disorder. Some conditions, such as Tabes dorsalis appear predominantly in males and begins in mid-life. Optic neuritis on the other hand, occurs preferentially in females typically between the ages of 30 and 35.[16] Other conditions such as multiple sclerosis vary in prevalence depending on the country and population.[17] This condition can appear in children as well as adults.[13]

Research is being conducted in a variety of very specific areas. The focus of this research is aimed at gaining more insight into how demyelinating disorders affect the central nervous system and peripheral nervous system,[18][19][20][21][22] how they develop and how these disorders are affected by various external inputs[23][24][25][26][27] . 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 it is believed that N-cadherin plays a role in the myelination process. Experimentation has shown that N-cadherin plays an important role in producing a remyelination-facilitating environment.[18] It has been shown in animal models that there is a direct correlation between the amount of myelin debris present and the degree of Inflammation observed.[19]

Experimentation has shown that manipulating the levels of thyroid hormone can be considered as a strategy to promote remyelination and prevent irreversible damage in Multiple sclerosis patients.[21] 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.[23] It has been shown that intranasal administration of aTf (apotransferrin) can protect myelin and induce remyelination.[25]

Much of the research referenced in this section has been conducted in 2012 and represents very new information about demyelinating diseases and potential therapies for them.

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).[28][29]

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 [30] 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.[31]


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