Demyelinating disease

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:"Symptoms of Demyelinating Disorders - Right Diagnosis." Right Diagnosis. Right Diagnosis, 01 Feb 2012. Web. 24 Sep 2012

{{div col}}

• 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
• Unsteady gait
• Spastic paraparesis
• Incontinence
• Hearing problems
• Speech problems

{{div col end}}

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 opportunities for disruption in myelination, resulting in the onset of demyelinating disease.{{cite journal |vauthors=Miller DJ, Duka T, Stimpson CD, Schapiro SJ, Baze WB, McArthur MJ, Fobbs AJ, Sousa AM, Sestan N, Wildman DE, Lipovich L, Kuzawa CW, Hof PR, Sherwood CC |title=Prolonged myelination in human neocortical evolution |journal=Proc Natl Acad Sci U S A |volume=109 |issue=41 |pages=16480–5 |date=October 2012 |pmid=23012402 |pmc=3478650 |doi=10.1073/pnas.1117943109 |bibcode=2012PNAS..10916480M |doi-access=free}} Furthermore, humans have significantly greater prefrontal white matter volume than other primate species, which implies greater myelin density.{{cite journal |vauthors=Schoenemann PT, Sheehan MJ, Glotzer LD |title=Prefrontal white matter volume is disproportionately larger in humans than in other primates |journal=Nat Neurosci |volume=8 |issue=2 |pages=242–52 |date=February 2005 |pmid=15665874 |doi=10.1038/nn1394 |s2cid=205430527}} 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.{{cite journal |vauthors=Chaudhuri A |title=Multiple sclerosis is primarily a neurodegenerative disease |journal=J Neural Transm (Vienna) |volume=120 |issue=10 |pages=1463–6 |date=October 2013 |pmid=23982272 |doi=10.1007/s00702-013-1080-3 |s2cid=8575687}} Therefore, the role of the human-specific prolonged period of cortical myelination is an important evolutionary consideration in the pathogenesis of demyelinating disease.{{citation needed|date=December 2021}}

Various methods/techniques are used to diagnose demyelinating diseases:

• Exclusion of other conditions that have overlapping symptoms{{cite book |vauthors=Freedman MS |title=Advances in Neurology Volume 98: Multiple Sclerosis and Demyelinating Diseases |year=2005 |publisher=Lippincott Williams & Wilkins |location=Philadelphia |isbn=0781751705 |page=112}}
• 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.{{rp|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.{{rp|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.{{rp|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.{{rp|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 (CNS) and those affecting the peripheral nervous system (PNS). They can also be classified by the presence or absence of inflammation. Finally, a division may be made based on the underlying cause of demyelination: the disease process can be demyelinating myelinoclastic, wherein myelin is destroyed; or dysmyelinating leukodystrophic, wherein myelin is abnormal and degenerative.

The demyelinating disorders of the central nervous system include:{{citation needed|date=August 2021}}

• 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. Many are idiopathic. Both myelinoclastic and leukodystrophic modes of disease may result in lesional demyelinations of the central nervous system.

File:Guillain-barré syndrome - Nerve Damage.gif

The demyelinating diseases of the peripheral nervous system include:{{citation needed|date=August 2021}}

• 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

{{See also|Multiple sclerosis#Medications|Management of multiple sclerosis}}

Treatments are patient-specific and depend on the symptoms that present with the disorder, as well as the progression of the condition. Improvements to the patient's life may be accomplished through the management of symptoms or slowing of the rate of demyelination. Treatment can include medication, lifestyle changes (i.e. smoking cessation, increased rest, and dietary changes), counselling, relaxation, physical exercise, patient education, and in some cases, deep brain thalamic stimulation (to ameliorate tremors).{{rp|227–248}}

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.{{cite journal |vauthors=Weinshenker BG |title=Natural history of multiple sclerosis |journal=Ann Neurol |volume=36 Suppl |issue= |pages=S6–11 |date=1994 |pmid=8017890 |doi=10.1002/ana.410360704 |s2cid=7140070}} Life expectancy in MS patients is 5 to 10 years lower than unaffected people.{{cite journal |vauthors=Compston A, Coles A |title=Multiple sclerosis |journal=Lancet |volume=372 |issue=9648 |pages=1502–17 |date=October 2008 |doi=10.1016/S0140-6736(08)61620-7 |pmid=18970977 |s2cid=195686659}} 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.{{cite journal |vauthors=Minagar A, Alexander JS |title=Blood-brain barrier disruption in multiple sclerosis |journal=Mult Scler |volume=9 |issue=6 |pages=540–9 |date=December 2003 |pmid=14664465 |doi=10.1191/1352458503ms965oa |s2cid=10189144}} Other conditions such as central pontine myelinolysis have about a third of patients recover and the other two-thirds experience varying degrees of disability.{{cite journal |vauthors=Abbott R, Silber E, Felber J, Ekpo E |title=Osmotic demyelination syndrome |journal=BMJ |volume=331 |issue=7520 |pages=829–30 |date=October 2005 |pmid=16210283 |pmc=1246086 |doi=10.1136/bmj.331.7520.829}} 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.{{citation needed|date=August 2021}}

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.{{cite journal |vauthors=Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT |title=Optic neuritis: a population-based study in Olmsted County, Minnesota |journal=Neurology |volume=45 |issue=2 |pages=244–50 |date=February 1995 |pmid=7854520 |doi=10.1212/wnl.45.2.244 |s2cid=25800388}} Other conditions such as multiple sclerosis vary in prevalence depending on the country and population.{{cite journal |vauthors=Rosati G |title=The prevalence of multiple sclerosis in the world: an update |journal=Neurol Sci |volume=22 |issue=2 |pages=117–39 |date=April 2001 |pmid=11603614 |doi=10.1007/s100720170011 |s2cid=207051545}} This condition can appear in children and adults.

Much of the research conducted on demyelinating diseases is targeted towards discovering the mechanisms by which these disorders function in an attempt to develop therapies and treatments for individuals affected by these conditions. For example, proteomics has revealed several proteins which contribute to the pathophysiology of demyelinating diseases.{{cite journal |vauthors=Newcombe J, Eriksson B, Ottervald J, Yang Y, Franzén B |title=Extraction and proteomic analysis of proteins from normal and multiple sclerosis postmortem brain |journal=J Chromatogr B |volume=815 |issue=1–2 |pages=191–202 |date=February 2005 |pmid=15652809 |doi=10.1016/j.jchromb.2004.10.073}}

For example, COX-2 has been implicated in oligodendrocyte death in animal models of demyelination.{{cite journal |vauthors=Palumbo S, Toscano CD, Parente L, Weigert R, Bosetti F |title=The cyclooxygenase-2 pathway via the PGE₂ EP2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced demyelination |journal=J Neurochem |volume=121 |issue=3 |pages=418–27 |date=May 2012 |pmid=21699540 |pmc=3220805 |doi=10.1111/j.1471-4159.2011.07363.x}}

The presence of myelin debris has been correlated with damaging inflammation as well as poor regeneration, due to the presence of inhibitory myelin components.{{cite journal |vauthors=Clarner T, Diederichs F, Berger K, Denecke B, Gan L, van der Valk P, Beyer C, Amor S, Kipp M |title=Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions |journal=Glia |volume=60 |issue=10 |pages=1468–80 |date=October 2012 |pmid=22689449 |doi=10.1002/glia.22367 |s2cid=205834726}}{{cite journal |vauthors=Podbielska M, Banik NL, Kurowska E, Hogan EL |title=Myelin recovery in multiple sclerosis: the challenge of remyelination |journal=Brain Sci |volume=3 |issue=4 |pages=1282–324 |date=August 2013 |pmid=24961530 |pmc=4061877 |doi=10.3390/brainsci3031282 |doi-access=free}}

N-cadherin is expressed in regions of active remyelination and may play an important role in generating a local environment conducive to remyelination.{{cite journal |vauthors=Hochmeister S, Romauch M, Bauer J, Seifert-Held T, Weissert R, Linington C, Hartung HP, Fazekas F, Storch MK |title=Re-expression of N-cadherin in remyelinating lesions of experimental inflammatory demyelination |journal=Exp Neurol |volume=237 |issue=1 |pages=70–7 |date=September 2012 |pmid=22735489 |doi=10.1016/j.expneurol.2012.06.010 |s2cid=33883037}} 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.{{cite journal |vauthors=Burden-Gulley SM, Gates TJ, Craig SE, Gupta M, Brady-Kalnay SM |title=Stimulation of N-cadherin-dependent neurite outgrowth by small molecule peptide mimetic agonists of the N-cadherin HAV motif |journal=Peptides |volume=31 |issue=5 |pages=842–9 |date=May 2010 |pmid=20153391 |doi=10.1016/j.peptides.2010.02.002 |s2cid=207357858}}

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.{{cite journal |vauthors=Gasperini C, Ruggieri S |title=Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, fingolimod will change therapeutic paradigm approach |journal=Drug Des Devel Ther |volume=6 |issue= |pages=175–86 |date=2012 |pmid=22888218 |pmc=3414371 |doi=10.2147/DDDT.S8927 |doi-access=free }}{{cite journal |vauthors=Ransohoff RM, Howe CL, Rodriguez M |title=Growth factor treatment of demyelinating disease: at last, a leap into the light |journal=Trends Immunol |volume=23 |issue=11 |pages=512–6 |date=November 2002 |pmid=12401395 |doi=10.1016/s1471-4906(02)02321-9}}

Manipulating thyroid hormone levels may become a viable strategy to promote remyelination and prevent irreversible damage in MS patients.{{cite journal |vauthors=Silvestroff L, Bartucci S, Pasquini J, Franco P |title=Cuprizone-induced demyelination in the rat cerebral cortex and thyroid hormone effects on cortical remyelination |journal=Exp Neurol |volume=235 |issue=1 |pages=357–67 |date=May 2012 |pmid=22421533 |doi=10.1016/j.expneurol.2012.02.018 |s2cid=1534460}}

It has also been shown that intranasal administration of apotransferrin (aTf) can protect myelin and induce remyelination.{{cite journal |vauthors=Guardia Clausi M, Paez PM, Campagnoni AT, Pasquini LA, Pasquini JM |title=Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event |journal=Glia |volume=60 |issue=10 |pages=1540–54 |date=October 2012 |pmid=22736466 |doi=10.1002/glia.22374 |s2cid=28658807|hdl=11336/67318 |hdl-access=free }}

Finally, electrical stimulation which activates neural stem cells may provide a method by which regions of demyelination can be repaired.{{cite journal |vauthors=Sherafat MA, Heibatollahi M, Mongabadi S, Moradi F, Javan M, Ahmadiani A |title=Electromagnetic field stimulation potentiates endogenous myelin repair by recruiting subventricular neural stem cells in an experimental model of white matter demyelination |journal=J Mol Neurosci |volume=48 |issue=1 |pages=144–53 |date=September 2012 |pmid=22588976 |doi=10.1007/s12031-012-9791-8 |s2cid=15779187}}

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).{{cite web |url=http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/100500.htm |title=Merck Veterinary Manual – Demyelinating Disorders: Introduction |author= |date= |website= |publisher= |access-date=2012-10-30 |archive-url=https://web.archive.org/web/20101219083714if_/http://merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/100500.htm |archive-date=2010-12-19}}{{cite book |vauthors=Johnson RT |title=The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary. |chapter=Demyelinating Diseases |year=2004 |url=https://www.ncbi.nlm.nih.gov/books/NBK83700/ |publisher=NIH}}

• Degenerative disease
• Multiple sclerosis borderline
• The Lesion Project (multiple sclerosis)
• The Myelin Project
• Myelin Repair Foundation

{{Reflist}}

{{Medical resources

| DiseasesDB =17472

| ICD10 = {{ICD10|G|35||g|35}}-{{ICD10|G|37||g|35}}, {{ICD10|G|61|0|g|60}}

| ICD9 = {{ICD9|340}}-{{ICD9|341}}, {{ICD9|357.0}}

| ICDO =

| OMIM =

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D003711

}}

{{CNS diseases of the nervous system}}

{{Demyelinating diseases of CNS}}

{{PNS diseases of the nervous system}}

{{Authority control}}

Category:Neurological disorders

Category:Myelin disorders