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→Amyotrophic lateral sclerosis: update
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==Amyotrophic lateral sclerosis== | ==Amyotrophic lateral sclerosis== | ||
*Abbreviated ''ALS''. | *Abbreviated ''ALS''. | ||
===General=== | ===General=== | ||
*[[AKA]] Lou Gehrig's disease. | *[[AKA]] Lou Gehrig's disease. | ||
*Characterized by motor neuron death. | *Characterized by motor neuron death. | ||
*May be familial and associated with ''SOD1'' | *May be familial and associated with ''C9orf72 expansion'', or ''SOD1'', ''FUS'' and ''TARDBP'' mutations.<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref><ref>{{Cite journal | last1 = Guerrero | first1 = EN. | last2 = Wang | first2 = H. | last3 = Mitra | first3 = J. | last4 = Hegde | first4 = PM. | last5 = Stowell | first5 = SE. | last6 = Liachko | first6 = NF. | last7 = Kraemer | first7 = BC. | last8 = Garruto | first8 = RM. | last9 = Rao | first9 = KS. | title = TDP-43/FUS in motor neuron disease: Complexity and challenges. | journal = Prog Neurobiol | volume = 145-146 | issue = | pages = 78-97 | month = | year = | doi = 10.1016/j.pneurobio.2016.09.004 | PMID = 27693252 }}</ref> | ||
*Pathological protein aggregates cause dysfunction of RNA-binding proteins. | |||
Clinical: | ===Clinical=== | ||
*Weakness. | *Peak incidence: 50-60yrs. | ||
*2-5 per 100,000 individuals worldwide. | |||
*Dead after disease onset: Usu. 2-5yrs. | |||
*Weakness (Progressive bulbar, limb, thoracic, and abdominal muscle atrophy). | |||
*About 20% of ALS cases develop frontotemporal lobar degeneration (FTLD). | |||
*Environmental toxins are discussed (Guam ALS).<ref>{{Cite journal | last1 = Chernoff | first1 = N. | last2 = Hill | first2 = DJ. | last3 = Diggs | first3 = DL. | last4 = Faison | first4 = BD. | last5 = Francis | first5 = BM. | last6 = Lang | first6 = JR. | last7 = Larue | first7 = MM. | last8 = Le | first8 = TT. | last9 = Loftin | first9 = KA. | title = A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans. | journal = J Toxicol Environ Health B Crit Rev | volume = 20 | issue = 4 | pages = 1-47 | month = | year = 2017 | doi = 10.1080/10937404.2017.1297592 | PMID = 28598725 }}</ref> | |||
===Microscopic=== | ===Microscopic=== | ||
Features:<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref> | Features:<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref><ref>{{Cite journal | last1 = Saberi | first1 = S. | last2 = Stauffer | first2 = JE. | last3 = Schulte | first3 = DJ. | last4 = Ravits | first4 = J. | title = Neuropathology of Amyotrophic Lateral Sclerosis and Its Variants. | journal = Neurol Clin | volume = 33 | issue = 4 | pages = 855-76 | month = Nov | year = 2015 | doi = 10.1016/j.ncl.2015.07.012 | PMID = 26515626 }}</ref> | ||
*Motor neurons with ''Bunina bodies''. | *Loss of the giant cells of Betz. | ||
*Motor neurons with eosinophilic inclusions (''Bunina bodies''). | |||
**PAS positive cytoplasmic inclusions. | **PAS positive cytoplasmic inclusions. | ||
*Motor neuron loss + reactive gliosis + neurogenic muscular atrophy. | *Motor neuron loss + reactive gliosis + neurogenic muscular atrophy. | ||
**Loss of myelinated axons in the lateral and anterior columns of the spinal cord. | |||
*Ubiquitinated cytoplasmic inclusions.<ref>{{Cite journal | last1 = Leigh | first1 = PN. | last2 = Anderton | first2 = BH. | last3 = Dodson | first3 = A. | last4 = Gallo | first4 = JM. | last5 = Swash | first5 = M. | last6 = Power | first6 = DM. | title = Ubiquitin deposits in anterior horn cells in motor neurone disease. | journal = Neurosci Lett | volume = 93 | issue = 2-3 | pages = 197-203 | month = Nov | year = 1988 | doi = | PMID = 2853844 }}</ref> | |||
*TDP-43 proteinopathy in motor neurons (90% of all sporadic ALS cases). | |||
*C9orf72 expansion cases: p62+ve, TDP-43-ve inclusions in the dentate gyrus, neocortex, and cerebellum.<ref>{{Cite journal | last1 = Al-Sarraj | first1 = S. | last2 = King | first2 = A. | last3 = Troakes | first3 = C. | last4 = Smith | first4 = B. | last5 = Maekawa | first5 = S. | last6 = Bodi | first6 = I. | last7 = Rogelj | first7 = B. | last8 = Al-Chalabi | first8 = A. | last9 = Hortobágyi | first9 = T. | title = p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS. | journal = Acta Neuropathol | volume = 122 | issue = 6 | pages = 691-702 | month = Dec | year = 2011 | doi = 10.1007/s00401-011-0911-2 | PMID = 22101323 }}</ref> | |||
Images: | Images: | ||
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*[http://pathology.mc.duke.edu/neuropath/CNSlecture4/alsbunina.jpg Bunina body (duke.edu)].<ref>URL: [http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm]. Accessed on: 30 August 2011.</ref> | *[http://pathology.mc.duke.edu/neuropath/CNSlecture4/alsbunina.jpg Bunina body (duke.edu)].<ref>URL: [http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm http://pathology.mc.duke.edu/neuropath/CNSlecture4/CNSlecture4.htm]. Accessed on: 30 August 2011.</ref> | ||
*[http://path.upmc.edu/cases/case291.html ALS - several images (upmc.edu)]. | *[http://path.upmc.edu/cases/case291.html ALS - several images (upmc.edu)]. | ||
DDx: | |||
*Spinal muscular atrophy. | |||
*Primary Lateral Sclerosis. | |||
*Hereditary Spastic Paraparesis (HSP). | |||
==Hallervorden-Spatz disease== | ==Hallervorden-Spatz disease== | ||