Difference between revisions of "Neurodegenerative diseases"

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==Amyotrophic lateral sclerosis==

*Abbreviated ''ALS''.

===General===

*[[AKA]] Lou Gehrig's disease.

*TDP-43 proteinopathy.

*Characterized by motor neuron death.

*May be familial and associated with ''SOD1'' ~~gene~~.<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref>

*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===

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.

*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:

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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://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==

Difference between revisions of "Neurodegenerative diseases"

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@@ Line 677: / Line 677: @@
 ==Amyotrophic lateral sclerosis==
 *Abbreviated ''ALS''.
 ===General===
 *[[AKA]] Lou Gehrig's disease.
-*TDP-43 proteinopathy.
 *Characterized by motor neuron death.
-*May be familial and associated with ''SOD1'' gene.<ref name=Ref_PCPBoD8_679>{{Ref PCPBoD8|679}}</ref>
+*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===
-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.
 *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:
@@ Line 696: / Line 707: @@
 *[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)].
+DDx:
+*Spinal muscular atrophy.
+*Primary Lateral Sclerosis.
+*Hereditary Spastic Paraparesis (HSP).
 ==Hallervorden-Spatz disease==