A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged.
Such damage impairs the conduction of signals in the affected nerves.
The reduction in conduction ability causes deficiency in sensation, movement, cognition, or other functions depending on which nerves are involved.
Demyelinating diseases can be caused by genetics, infectious agents, autoimmune reactions, and other factors, such as being triggered by a viral infection or chemical exposure.
Organophosphate poisoning by commercial insecticides can also result in nerve demyelination.
Chronic neuroleptic exposure may cause demyelination.
Vitamin B12 deficiency may also result in dysmyelination.
Demyelinating diseases are traditionally classified in two kinds: demyelinating myelinoclastic diseases and demyelinating leukodystrophic diseases.
In Demyelinating myelinoclastic disease
There is a normal and healthy myelin that is destroyed by a toxic, chemical, or autoimmune substance.
In demyelinating leukodystrophic diseases myelin is abnormal and degenerates.
In,multiple sclerosis, evidence has shown that the body’s own immune system is at least partially responsible.
T-cells are known to be present at the site of lesions.
Other immune-system cells, macrophages possibly mast cells, also contribute to the damage.
Symptoms and signs that can present in a person with a demyelinating disease:
Diplopia
Ataxia
Clonus
Dysarthria
Fatigue
Clumsiness
Hand paralysis
Hemiparesis
Genital anaesthesia
Incoordination
Paresthesias
Cranial nerve palsy
Impaired muscle coordination
Weakness
Loss of sensation
Impaired vision
Unsteady gait
Spastic paraparesis
Incontinence
Hearing problems
Speech problems
Humans exhibit a 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 may allow greater opportunities for disruption in myelination, resulting in the onset of demyelinating disease.
Humans have significantly greater prefrontal white matter volume than other primate species, implying a greater myelin density.
Increased myelin density in humans may increase risk for myelin degeneration and dysfunction.
Genetics and autoimmune deficiency often fail to explain many cases of demyelinating disease.
Multiple sclerosis cannot be accounted for by autoimmune deficiency alone, but suggests the influence of flawed developmental processes in its disease pathogenesis.
The prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.
MRI makes use of the property of nuclear magnetic resonance (NMR) to image nuclei of atoms inside the body. assessing changes in proton density.
Findings can occur as a result of changes in brain water content.
An 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.
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.
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 (CNS) and those affecting the peripheral nervous system (PNS).
Demyelinating diseases can also be classified by the presence or absence of inflammation.
Demyelinating diseases division may be made based on the underlying cause of demyelination: the disease process can be demyelinating myelinoclastic, myelin is destroyed, or dysmyelinating leukodystrophic, wherein myelin is abnormal and degenerative.
The demyelinating disorders of the central nervous system include:
Myelinoclastic or demyelinating disorders:
Typical forms of multiple sclerosis
Neuromyelitis optica, or Devic’s disease
Idiopathic inflammatory demyelinating diseases
Leukodystrophic or dysmyelinating disorders:
CNS neuropathies such as those produced by vitamin B12 deficiency
Central pontine myelinolysis
Myelopathies such as tabes dorsalis (syphilitic myelopathy)
Leukoencephalopathies such as progressive multifocal leukoencephalopathy
Leukodystrophies
The myelinoclastic disorders are typically associated with symptoms such as optic neuritis and transverse myelitis, because the demyelinating inflammation can affect the optic nerve or spinal cord.
Both myelinoclastic and leukodystrophic modes of disease may result in lesional demyelinations of the central nervous system.
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
Treatments are patient-specific and depend on the symptoms present as well as the progression of the condition.
Treatment can include medication, lifestyle changes, counselling, relaxation, physical exercise, patient education, and in some cases, deep brain thalamic stimulation.
Prognosis:
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.
With 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.
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.
N-cadherin is expressed in regions of active remyelination and may play an important role in generating a local environment conducive to remyelination.
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.
Immunomodulatory drugs such as fingolimod have been shown to reduce immune-mediated damage to the CNS, preventing further damage in patients with MS.
The drug targets the role of macrophages in disease progression.