Altered mental status pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(4 intermediate revisions by the same user not shown)
Line 3: Line 3:
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo, M.D.]], {{PB}}
{{CMG}}; {{AE}}[[User:MoisesRomo|Moises Romo, M.D.]], {{PB}}
==Overview==
==Overview==
[[Altered mental status|'''Altered mental status''']] is a state of a variety of [[diseases]]. Although the [[neural]] science behind [[alertness]], [[wakefulness]], and [[arousal]] are not fully understood, it is known that the [[reticular formation]] plays an important role in these.
[[Altered mental status|'''Altered mental status''']] is a state of a variety of [[diseases]], hence, there is no single [[pathophysiology]] mechanism. Although, the [[neural]] science behind [[alertness]], [[wakefulness]], and [[arousal]] are not fully understood, it is known that the [[reticular formation]] plays an important role in these.


== Pathogenesis ==
==Pathogenesis==
[[Altered mental status|Altered mental status]] is a state of a variety of [[diseases]], hence, there is no single [[pathophysiology]] mechanism. It is known that the [[reticular formation]] plays an important role in the state of alertness. We explain the most important subtypes of [[altered mental status]]:


=== Dementia ===
===Dementia===


==== Alzheimer's disease ====
====Alzheimer's disease====
While the pathogenesis of AD remains unclear, It is thought that dementia is the result of:
While the [[pathogenesis]] of [[Alzheimer's disease|AD]] remains unclear, It is thought that [[dementia]] is the result of:


* Overproduction and/or decreased clearance of amyloid beta peptides.
*[[Neuronal]] loss.<ref name="pmid2531723">{{cite journal |vauthors=Beach TG, Walker R, McGeer EG |title=Patterns of gliosis in Alzheimer's disease and aging cerebrum |journal=Glia |volume=2 |issue=6 |pages=420–36 |year=1989 |pmid=2531723 |doi=10.1002/glia.440020605 |url=}}</ref><ref name="pmid2360787">{{cite journal |vauthors=DeKosky ST, Scheff SW |title=Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity |journal=Ann. Neurol. |volume=27 |issue=5 |pages=457–64 |year=1990 |pmid=2360787 |doi=10.1002/ana.410270502 |url=}}</ref><ref name="pmid1789684">{{cite journal |vauthors=Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R |title=Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment |journal=Ann. Neurol. |volume=30 |issue=4 |pages=572–80 |year=1991 |pmid=1789684 |doi=10.1002/ana.410300410 |url=}}</ref>
* Accumulation of tau proteins.
*Overproduction and/or decreased clearance of [[amyloid beta]] [[peptides]].<ref name="pmid2504495">{{cite journal |vauthors=Selkoe DJ |title=Amyloid beta protein precursor and the pathogenesis of Alzheimer's disease |journal=Cell |volume=58 |issue=4 |pages=611–2 |year=1989 |pmid=2504495 |doi= |url=}}</ref><ref name="pmid2949367">{{cite journal |vauthors=Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL |title=Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus |journal=Science |volume=235 |issue=4791 |pages=880–4 |year=1987 |pmid=2949367 |doi= |url=}}</ref><ref name="pmid15182223">{{cite journal |vauthors=Walsh DM, Selkoe DJ |title=Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration |journal=Protein Pept. Lett. |volume=11 |issue=3 |pages=213–28 |year=2004 |pmid=15182223 |doi= |url=}}</ref>
* Accumulation of neurofibrillary tangles.
*Accumulation of [[neurofibrillary tangles]] ([[Tau protein|tau proteins]]).<ref name="pmid20655099">{{cite journal |vauthors=Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J |title=Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models |journal=Cell |volume=142 |issue=3 |pages=387–97 |year=2010 |pmid=20655099 |doi=10.1016/j.cell.2010.06.036 |url=}}</ref><ref name="pmid2117840">{{cite journal |vauthors=Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Shérrer V, Défossez A |title=Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins |journal=Acta Neuropathol. |volume=80 |issue=2 |pages=111–7 |year=1990 |pmid=2117840 |doi= |url=}}</ref>
* Production of oxygen radicals and nitric oxide, and inflammatory processes.
*Production of [[oxygen radicals]] and [[nitric oxide]], and [[inflammatory]] processes.<ref name="pmid16814555">{{cite journal |vauthors=Boekhoorn K, Joels M, Lucassen PJ |title=Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus |journal=Neurobiol. Dis. |volume=24 |issue=1 |pages=1–14 |year=2006 |pmid=16814555 |doi=10.1016/j.nbd.2006.04.017 |url=}}</ref>
* Decreased levels of cholinergic neurotransmission.
*Decreased levels of [[cholinergic]] [[neurotransmission]].


* Over-excitation of the glutamate neurotransmitter system via N-methyl-D-aspartate  
*Over-excitation of the [[glutamate]] [[neurotransmitter]] system via [[N-methyl-D-aspartate]].


==== Parkinson's disease ====
====Parkinson's disease====
The pathogenesis of Parkinson's disease is a depletion of dopamine due to the following mechanisms:
The [[pathogenesis]] of [[Parkinson's disease]] is a depletion of [[dopamine]] due to the following mechanisms:


Protein misfolding with decreased function and plasticity.
*[[Protein]] misfolding with decreased function and [[plasticity]].<ref name="pmid12951565">{{cite journal |vauthors=Maries E, Dass B, Collier TJ, Kordower JH, Steece-Collier K |title=The role of alpha-synuclein in Parkinson's disease: insights from animal models |journal=Nat. Rev. Neurosci. |volume=4 |issue=9 |pages=727–38 |date=September 2003 |pmid=12951565 |doi=10.1038/nrn1199 |url=}}</ref><ref name="pmid9278044">{{cite journal |vauthors=Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M |title=Alpha-synuclein in Lewy bodies |journal=Nature |volume=388 |issue=6645 |pages=839–40 |date=August 1997 |pmid=9278044 |doi=10.1038/42166 |url=}}</ref><ref name="pmid26790375">{{cite journal |vauthors=Calo L, Wegrzynowicz M, Santivañez-Perez J, Grazia Spillantini M |title=Synaptic failure and α-synuclein |journal=Mov. Disord. |volume=31 |issue=2 |pages=169–77 |date=February 2016 |pmid=26790375 |doi=10.1002/mds.26479 |url=}}</ref>
*Defective [[proteolysis]] with aggregation of this [[protein]] and [[neuronal]] death.<ref name="pmid23580245">{{cite journal |vauthors=Lim KL, Zhang CW |title=Molecular events underlying Parkinson's disease - an interwoven tapestry |journal=Front Neurol |volume=4 |issue= |pages=33 |date=2013 |pmid=23580245 |pmc=3619247 |doi=10.3389/fneur.2013.00033 |url=}}</ref><ref name="pmid23580333">{{cite journal |vauthors=Dehay B, Martinez-Vicente M, Caldwell GA, Caldwell KA, Yue Z, Cookson MR, Klein C, Vila M, Bezard E |title=Lysosomal impairment in Parkinson's disease |journal=Mov. Disord. |volume=28 |issue=6 |pages=725–32 |date=June 2013 |pmid=23580333 |pmc=5131721 |doi=10.1002/mds.25462 |url=}}</ref><ref name="pmid24211851">{{cite journal |vauthors=Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Łos MJ |title=Autophagy and apoptosis dysfunction in neurodegenerative disorders |journal=Prog. Neurobiol. |volume=112 |issue= |pages=24–49 |date=January 2014 |pmid=24211851 |doi=10.1016/j.pneurobio.2013.10.004 |url=}}</ref>
*[[Mitochondrial]] dysfunction with the following [[cell]] damage.<ref name="pmid15377875">{{cite journal |vauthors=Przedborski S, Tieu K, Perier C, Vila M |title=MPTP as a mitochondrial neurotoxic model of Parkinson's disease |journal=J. Bioenerg. Biomembr. |volume=36 |issue=4 |pages=375–9 |date=August 2004 |pmid=15377875 |doi=10.1023/B:JOBB.0000041771.66775.d5 |url=}}</ref><ref name="pmid22446186">{{cite journal |vauthors=Selvaraj S, Sun Y, Watt JA, Wang S, Lei S, Birnbaumer L, Singh BB |title=Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling |journal=J. Clin. Invest. |volume=122 |issue=4 |pages=1354–67 |date=April 2012 |pmid=22446186 |pmc=3314472 |doi=10.1172/JCI61332 |url=}}</ref><ref name="pmid2566813">{{cite journal |vauthors=Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD |title=Mitochondrial complex I deficiency in Parkinson's disease |journal=Lancet |volume=1 |issue=8649 |pages=1269 |date=June 1989 |pmid=2566813 |doi= |url=}}</ref>
*[[Oxidative stress]] with the following [[neuronal]] damage.<ref name="pmid15155938">{{cite journal |vauthors=Greenamyre JT, Hastings TG |title=Biomedicine. Parkinson's--divergent causes, convergent mechanisms |journal=Science |volume=304 |issue=5674 |pages=1120–2 |date=May 2004 |pmid=15155938 |doi=10.1126/science.1098966 |url=}}</ref><ref name="pmid14645467">{{cite journal |vauthors=Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT |title=Mechanism of toxicity in rotenone models of Parkinson's disease |journal=J. Neurosci. |volume=23 |issue=34 |pages=10756–64 |date=November 2003 |pmid=14645467 |doi= |url=}}</ref>
*[[Iron metabolism]] with following increase of storage in the [[substantia nigra]].<ref name="pmid17515544">{{cite journal |vauthors=Oakley AE, Collingwood JF, Dobson J, Love G, Perrott HR, Edwardson JA, Elstner M, Morris CM |title=Individual dopaminergic neurons show raised iron levels in Parkinson disease |journal=Neurology |volume=68 |issue=21 |pages=1820–5 |date=May 2007 |pmid=17515544 |doi=10.1212/01.wnl.0000262033.01945.9a |url=}}</ref><ref name="pmid22266337">{{cite journal |vauthors=Dusek P, Jankovic J, Le W |title=Iron dysregulation in movement disorders |journal=Neurobiol. Dis. |volume=46 |issue=1 |pages=1–18 |date=April 2012 |pmid=22266337 |doi=10.1016/j.nbd.2011.12.054 |url=}}</ref><ref name="pmid22286308">{{cite journal |vauthors=Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI |title=Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export |journal=Nat. Med. |volume=18 |issue=2 |pages=291–5 |date=January 2012 |pmid=22286308 |doi=10.1038/nm.2613 |url=}}</ref>
*[[Immunological|Immunologic]] and [[Inflammation|inflammatory]] mechanisms due to infiltration of [[CD4+ T cells]].<ref name="pmid19296921">{{cite journal |vauthors=Hirsch EC, Hunot S |title=Neuroinflammation in Parkinson's disease: a target for neuroprotection? |journal=Lancet Neurol |volume=8 |issue=4 |pages=382–97 |date=April 2009 |pmid=19296921 |doi=10.1016/S1474-4422(09)70062-6 |url=}}</ref><ref name="pmid19104149">{{cite journal |vauthors=Brochard V, Combadière B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S |title=Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease |journal=J. Clin. Invest. |volume=119 |issue=1 |pages=182–92 |date=January 2009 |pmid=19104149 |pmc=2613467 |doi=10.1172/JCI36470 |url=}}</ref>


Defective proteolysis with aggregation of this protein and neuronal death.
===Delirium===
[[Delirium]] is caused by a broad [[spectrum]] of [[diseases]] and [[clinical]] problems. Among the [[hypothesis]] of [[delirium]] developement are:


Mitochondrial dysfunction with the following cell damage.
*[[Neurotransmitter]] [[hypothesis]]. A decreased [[oxidative metabolism]] in the [[brain]] may cause a reduced [[cholinergic]] function, excess release of [[dopamine]], [[norepinephrine]], and [[glutamate]], and both decreased and increased [[serotonergic]] and [[γ-aminobutyric acid]] activity may underlie the different symptoms and clinical presentations of [[delirium]].<ref name="van der Mast1998">{{cite journal|last1=van der Mast|first1=Rose C.|title=Pathophysiology of Delirium|journal=Journal of Geriatric Psychiatry and Neurology|volume=11|issue=3|year=1998|pages=138–145|issn=0891-9887|doi=10.1177/089198879801100304}}</ref><ref name="Felicetta2016">{{cite journal|last1=Felicetta|first1=James V.|title=Effects of illness on thyroid function tests|journal=Postgraduate Medicine|volume=85|issue=8|year=2016|pages=213–220|issn=0032-5481|doi=10.1080/00325481.1989.11700751}}</ref><ref name="Trzepacz1994">{{cite journal|last1=Trzepacz|first1=Paula T.|title=The Neuropathogenesis of Delirium|journal=Psychosomatics|volume=35|issue=4|year=1994|pages=374–391|issn=00333182|doi=10.1016/S0033-3182(94)71759-X}}</ref>
*[[Inflammatory]] [[hypothesis]]. [[Stress (medicine)|Stress]] causes the release of [[cytokines]] which may directly damage the [[brain]] or affect [[Neurotransmitters|neurotransmitter]] [[synthesis]].<ref name="pmid7537419">{{cite journal |vauthors=Hopkins SJ, Rothwell NJ |title=Cytokines and the nervous system. I: Expression and recognition |journal=Trends Neurosci |volume=18 |issue=2 |pages=83–8 |date=February 1995 |pmid=7537419 |doi= |url=}}</ref><ref name="RenaultHoofnagle2008">{{cite journal|last1=Renault|first1=Pierre|last2=Hoofnagle|first2=Jay|title=Side Effects of Alpha Interferon|journal=Seminars in Liver Disease|volume=9|issue=04|year=2008|pages=273–277|issn=0272-8087|doi=10.1055/s-2008-1040523}}</ref><ref name="Müller1997">{{cite journal|last1=Müller|first1=N.|title=Die Rolle des Zytokinnetzwerks im ZNS und psychische Störungen|journal=Der Nervenarzt|volume=68|issue=1|year=1997|pages=11–20|issn=0028-2804|doi=10.1007/s001150050092}}</ref>


Oxidative stress
==Genetics==


Iron metabolism
===Dementia===


Immunologic and inflammatory mechanisms
====Alzheimer's disease====


======Early onset (Alzheimer's dementia-AD 1, 3 and 4)======
30-50 percent of early-onset Alzheimer's dementia (AD) is associated with an [https://www.wikidoc.org/index.php/Autosomal_dominant_inheritance autosomal dominant inheritance] and consists of mutations in the following [https://www.wikidoc.org/index.php/Genes genes]:<ref name="pmid10441572">{{cite journal |vauthors=Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T |title=Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum |journal=Am. J. Hum. Genet. |volume=65 |issue=3 |pages=664–70 |year=1999 |pmid=10441572 |pmc=1377972 |doi=10.1086/302553 |url=}}</ref><ref name="pmid10593304">{{cite journal |vauthors=Tsuang D, Larson EB, Bowen J, McCormick W, Teri L, Nochlin D, Leverenz JB, Peskind ER, Lim A, Raskind MA, Thompson ML, Mirra SS, Gearing M, Schellenberg GD, Kukull W |title=The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series |journal=Arch. Neurol. |volume=56 |issue=12 |pages=1489–95 |year=1999 |pmid=10593304 |doi= |url=}}</ref>


*[https://www.wikidoc.org/index.php/Presenilin_1 Presenilin1] (''[https://www.wikidoc.org/index.php/Presenilin_1 PS1]'') [https://www.wikidoc.org/index.php/Gene gene], also called [https://www.wikidoc.org/index.php/PSEN1 PSEN1] gene on [https://www.wikidoc.org/index.php/Chromosome_14_(human) chromosome 14]  (20-30% cases)
*[https://www.wikidoc.org/index.php/Presenilin Presenilin 2] (''[https://www.wikidoc.org/index.php/Presenilin PS2]'') [https://www.wikidoc.org/index.php/Gene gene], also called [https://www.wikidoc.org/index.php/PSEN2 PSEN2] gene on [https://www.wikidoc.org/index.php/Chromosome_1_(human) chromosome 1] ( rare)


Pathogenesis is the mechanism by which a certain factor causes disease (''pathos'' = disease, ''genesis'' = development). The term can also be used to describe the development of the disease, whether it is acute, chronic, or recurrent. It can also be used to describe whether the disease causes inflammation, malignancy, necrosis etc.
*[https://www.wikidoc.org/index.php/Point_mutations Point mutations] in [https://www.wikidoc.org/index.php/Amyloid_beta amyloid beta A4] [https://www.wikidoc.org/index.php/Protein protein] [https://www.wikidoc.org/index.php/Gene gene], also called [https://www.wikidoc.org/index.php/Amyloid_precursor_protein amyloid precursor protein] (APP) [https://www.wikidoc.org/index.php/Gene gene] on [https://www.wikidoc.org/index.php/Chromosome_21_(human) chromosome 21] are associated in some cases of early onset (< 65 yr) [https://www.wikidoc.org/index.php/Familial familial] AD cases


==== Template Sentences[edit | edit source] ====
'''Late onset (Alzheimer's dementia -AD2)'''
IF the pathogenesis of the disease is unclear:


* The exact pathogenesis of [disease name] is not fully understood.
*[https://www.wikidoc.org/index.php/APOE Apolipoprotein 4] [https://www.wikidoc.org/index.php/Gene gene] ([https://www.wikidoc.org/index.php/APOE APOE4]) [https://www.wikidoc.org/index.php/Mutation mutation] is associated with late onset (>60 years) Alzheimer's dementia (AD)<ref name="pmid15123497">{{cite journal |vauthors=Khachaturian AS, Corcoran CD, Mayer LS, Zandi PP, Breitner JC |title=Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study |journal=Arch. Gen. Psychiatry |volume=61 |issue=5 |pages=518–24 |year=2004 |pmid=15123497 |doi=10.1001/archpsyc.61.5.518 |url=}}</ref>
* It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*p.Arg47His [https://www.wikidoc.org/index.php/Allele allelic] variant in TREM2 [https://www.wikidoc.org/index.php/Gene gene]<ref name="pmid23150908">{{cite journal |vauthors=Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K |title=Variant of TREM2 associated with the risk of Alzheimer's disease |journal=N. Engl. J. Med. |volume=368 |issue=2 |pages=107–16 |year=2013 |pmid=23150908 |pmc=3677583 |doi=10.1056/NEJMoa1211103 |url=}}</ref>


IF the disease is infectious…
====Parkinson's disease====
Some of specific genes involving in [https://www.wikidoc.org/index.php/Parkinson's_disease PD] are:


* …and the route of transmission is known:
*[https://www.wikidoc.org/index.php/Glucocerebrosidase Glucocerebrosidase gene] <ref name="pmid19846850">{{cite journal |vauthors=Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG |title=Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease |journal=N. Engl. J. Med. |volume=361 |issue=17 |pages=1651–61 |date=October 2009 |pmid=19846850 |pmc=2856322 |doi=10.1056/NEJMoa0901281 |url=}}</ref>
** [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*[https://www.wikidoc.org/index.php/SNCA SNCA]-associated PD <ref name="pmid17761553">{{cite journal |vauthors=Klein C, Schlossmacher MG |title=Parkinson disease, 10 years after its genetic revolution: multiple clues to a complex disorder |journal=Neurology |volume=69 |issue=22 |pages=2093–104 |date=November 2007 |pmid=17761553 |doi=10.1212/01.wnl.0000271880.27321.a7 |url=}}</ref>
** Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[https://www.wikidoc.org/index.php/LRRK2 LRRK2]-associated PD <ref name="pmid11891824">{{cite journal |vauthors=Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F |title=A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1 |journal=Ann. Neurol. |volume=51 |issue=3 |pages=296–301 |date=March 2002 |pmid=11891824 |doi= |url=}}</ref>
*[https://www.wikidoc.org/index.php/Parkin Parkin]-associated PD <ref name="pmid10824074">{{cite journal |vauthors=Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denèfle P, Wood NW, Agid Y, Brice A |title=Association between early-onset Parkinson's disease and mutations in the parkin gene |journal=N. Engl. J. Med. |volume=342 |issue=21 |pages=1560–7 |date=May 2000 |pmid=10824074 |doi=10.1056/NEJM200005253422103 |url=}}</ref>
*[https://www.wikidoc.org/index.php/PINK1 PINK1]-associated PD <ref name="pmid15087508">{{cite journal |vauthors=Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW |title=Hereditary early-onset Parkinson's disease caused by mutations in PINK1 |journal=Science |volume=304 |issue=5674 |pages=1158–60 |date=May 2004 |pmid=15087508 |doi=10.1126/science.1096284 |url=}}</ref>
*[https://www.wikidoc.org/index.php/DJ-1 DJ-1]-associated PD <ref name="pmid12446870">{{cite journal |vauthors=Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P |title=Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism |journal=Science |volume=299 |issue=5604 |pages=256–9 |date=January 2003 |pmid=12446870 |doi=10.1126/science.1077209 |url=}}</ref>


IF the disease has a known genetic component:
===Delirium===
The [[genes]] that may be used as [[RiskMetrics|risk]] [[biomarkers]] for the developement of [[delirium]] are the following:


* [Disease name] is transmitted in [mode of genetic transmission] pattern.
* [[Polymorphisms]] in the [[receptor]] DRD2 and [[dopamine]] [[transporter]] [[genes]] (rs6276, rs6277, and rs2734839)<ref name="van MunsterAronica2011">{{cite journal|last1=van Munster|first1=Barbara C.|last2=Aronica|first2=Eleonora|last3=Zwinderman|first3=Aeilko H.|last4=Eikelenboom|first4=Piet|last5=Cunningham|first5=Colm|last6=de Rooij|first6=Sophia E.J.A|title=Neuroinflammation in Delirium: A Postmortem Case-Control Study|journal=Rejuvenation Research|volume=14|issue=6|year=2011|pages=615–622|issn=1549-1684|doi=10.1089/rej.2011.1185}}</ref>
* Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
* [[Homozygous]] AA [[genotype]] of rs393795 in the SLC6A3 [[gene]]<ref name="van MunsterAronica20112">{{cite journal|last1=van Munster|first1=Barbara C.|last2=Aronica|first2=Eleonora|last3=Zwinderman|first3=Aeilko H.|last4=Eikelenboom|first4=Piet|last5=Cunningham|first5=Colm|last6=de Rooij|first6=Sophia E.J.A|title=Neuroinflammation in Delirium: A Postmortem Case-Control Study|journal=Rejuvenation Research|volume=14|issue=6|year=2011|pages=615–622|issn=1549-1684|doi=10.1089/rej.2011.1185}}</ref>
* APOE4 [[polymorphism]]<ref name="ElyGirard2007">{{cite journal|last1=Ely|first1=Wesley E|last2=Girard|first2=Timothy D.|last3=Shintani|first3=Ayumi K.|last4=Jackson|first4=James C.|last5=Gordon|first5=Sharon M.|last6=Thomason|first6=Jason W. W.|last7=Pun|first7=Brenda T.|last8=Canonico|first8=Angelo E.|last9=Light|first9=Richard W.|last10=Pandharipande|first10=Pratik|last11=Laskowitz|first11=Daniel T.|title=Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*|journal=Critical Care Medicine|volume=35|issue=1|year=2007|pages=112–117|issn=0090-3493|doi=10.1097/01.CCM.0000251925.18961.CA}}</ref>
* Reduced [[Gene expression|expression]] of mi[[RNA]]-124 which results in decreased [[Ku70]]<ref name="ZhuLiu2013">{{cite journal|last1=Zhu|first1=Fei|last2=Liu|first2=Jing-Li|last3=Li|first3=Jing-Pin|last4=Xiao|first4=Fang|last5=Zhang|first5=Zhao-Xia|last6=Zhang|first6=Lei|title=MicroRNA-124 (miR-124) Regulates Ku70 Expression and is Correlated with Neuronal Death Induced by Ischemia/Reperfusion|journal=Journal of Molecular Neuroscience|volume=52|issue=1|year=2013|pages=148–155|issn=0895-8696|doi=10.1007/s12031-013-0155-9}}</ref>


IF certain pathology findings are characteristic of the disease:
==Associated Conditions==
The most important [[conditions]]/[[diseases]] associated with [[altered mental status]] include:


* On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* [[Stroke]]
* On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* [[Metabolic syndrome|Metabolic imbalances]]
* [[Traumatic brain injury]]
* [[Fever]]
* [[Infections]]
* [[Lung diseases]] (e.g. [[cancer]])
* [[Chronic (medical)|Chronic]] or [[Terminal illness|terminal illnesses]]
* [[MI|Miocardial infarction]]


Other relevant information may include the action of the pathogen on a molecular level, the body’s response, whether or not mutations play a role in the disease development, whether the pathophysiology of the disease is different among subgroups of the disease, etc. Additional template sentences are listed below. Due to the highly variable nature of pathophysiology among various diseases, this list is not comprehensive.
==Gross Pathology==


* [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
=== Dementia ===
* The development of [disease name] is the result of multiple genetic mutations.
* The progression to [disease name] usually involves the [molecular pathway].
* The pathophysiology of [disease/malignancy] depends on the histological subtype.


* For an example of a pathogenesis section within a pathophysiology page, click here
==== Alzheimer's disease ====
The most important characteristics of [[Alzheimer's disease]] on [[gross pathology]] are:


== Genetics[edit | edit source] ==
* [[Temporal]] [[atrophy]] (especially in the [[hippocampus]])
* [[Dilation]] of [[ventricles]]


* Some diseases are genetic, and have particular inheritance patterns, and express different phenotypes.
==== Parkinson's disease ====
* The effect that genetics may have on the pathophysiology of a disease can be described in this section.
The most important characteristics of [[Parkinson's disease]] on [[gross pathology]] are:


==== Template sentences[edit | edit source] ====
=== Delirium ===
There are no characteristic [[gross pathology]] findings in [[dementia]].


* [Disease name] is transmitted in [mode of genetic transmission] pattern.
==Microscopic Pathology==
* Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].


== Associated Conditions[edit | edit source] ==
=== Dementia ===


* Conditions associated with the disease can be detailed in this section.
==== Alzheimer's disease ====
The most important [[histopathological]] characteristics of [[Alzheimer's disease]] are:


==== Template sentences[edit | edit source] ====
* [https://www.wikidoc.org/index.php/Neurofibrillary_tangles Neurofibrillary tangles]: Consists of [https://www.wikidoc.org/index.php/Tau_protein tau], location in the [https://www.wikidoc.org/index.php/Hippocampus hippocampus], [https://www.wikidoc.org/index.php/Cerebral_cortex cerebral cortex], [https://www.wikidoc.org/index.php/Hypothalamus hypothalamus]. Dementia severity correlates better with [https://www.wikidoc.org/index.php/Neurofibrillary_tangles neurofibrillary tangles] number rather than [https://www.wikidoc.org/index.php/Senile_plaques senile plaque] number
* [https://www.wikidoc.org/index.php/Senile_plaques Senile plaques] or the neuritic plaques consists of two components which are [https://www.wikidoc.org/index.php/Beta_amyloid A-beta amyloid] which [[Radiation|radiate]] from the center and the neurites with [[Swelling|swollen]] [https://www.wikidoc.org/index.php/Axons axons]. [https://www.wikidoc.org/index.php/Senile_plaques Senile plaques] are considered to be more specific for alzheimer's than [https://www.wikidoc.org/index.php/Neurofibrillary_tangles neurofibrillary tangles]
* Loss of [https://www.wikidoc.org/index.php/Neurons neurons]
* With or without [https://www.wikidoc.org/index.php/Cerebral_amyloid_angiopathy cerebral amyloid angiopathy]


* The most important conditions/diseases associated with [disease name] include:
==== Parkinson's disease ====
** Condition 1: A brief explanation of the condition and its association with the disease
The most important [[histopathological]] characteristics of [[Parkinson's disease]] are:
** Condition 2: A brief explanation of the condition and its association with the disease
 
For an example of an associated conditions sub-section of pathophysiology, click here.
 
== Gross Pathology[edit | edit source] ==
 
* Gross pathology refers to macroscopic or larger scale manifestations of disease in organs, tissues and body cavities. The term is commonly used by pathologist to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.
 
====== Template Sentences[edit | edit source] ======
 
* Template Sentences 1: On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* Template Sentence 2: The most important characteristics of [disease name] on gross pathology are:
** Organ 1: List of characteristics + image
** Organ 2: List of characteristics + image
** Organ 3: List of characteristics + image
* This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [3] and Ask Dr. Wiki [4].
* For an example of this section, click here.
 
== Microscopic Pathology[edit | edit source] ==
 
* Microscopic pathology is the disease process as it occurs at the microscopic level.
* Template Sentence 1: On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
* Template Sentence 2: The most important histopathological characteristics of [disease name] are summarized in the table below:
 
{| class="wikitable"
!Organs
!Light microscope
!Electron microscope
!Images
|-
|Organ 1
|Characteristic 1a
|Characterstic 1b
|Image 1
|-
|Organ 2
|Characteristic 2a
|Characterstic 2b
|Image 2
|-
|Organ 3
|Characterstic 3a
|Characterstic 3b
|Image 3
|}
 
* This section is a good place to include pictures. Search for copyleft images on The Pathology Wiki [5] and Ask Dr. Wiki [6].
* For an example of this section, click here.


==Pathophysiology==
*The [[Pathological|pathologic]] [https://www.wikidoc.org/index.php/Hallmark hallmark] of [https://www.wikidoc.org/index.php/Parkinson's_disease PD] is the presence of [https://www.wikidoc.org/index.php/Lewy_body lewy bodies], which are round [https://www.wikidoc.org/index.php/Cytoplasmic cytoplasmic] [https://www.wikidoc.org/index.php/Eosinophilic eosinophilic] inclusions. The content of these bodies are mostly [https://www.wikidoc.org/index.php/Alpha-synuclein alpha synuclein] and [https://www.wikidoc.org/index.php/Ubiquitin ubiquitin], but we can also find [https://www.wikidoc.org/index.php/Complement complement proteins], microflament subunits, and parkin substrate protein.<ref name="pmid14991825">{{cite journal |vauthors=Murakami T, Shoji M, Imai Y, Inoue H, Kawarabayashi T, Matsubara E, Harigaya Y, Sasaki A, Takahashi R, Abe K |title=Pael-R is accumulated in Lewy bodies of Parkinson's disease |journal=Ann. Neurol. |volume=55 |issue=3 |pages=439–42 |date=March 2004 |pmid=14991825 |doi=10.1002/ana.20064 |url=}}</ref>
Dementia is a symptom


Although the neural science behind alertness, wakefulness, and arousal are not fully known, the [[reticular formation]] is known to play a role in these. The [[ascending reticular activating system]] is a postulated group of neural connections that receives sensory input and projects to the [[cerebral cortex]] through the [[midbrain]] and [[thalamus]] from the retucular formation. Since this system is thought to modulate wakefulness and sleep, interference with it, such as injury, illness, or metabolic disturbances, could alter the level of consciousness.
*The [[Pathological|pathologic]] manifestations of [https://www.wikidoc.org/index.php/Apoptosis apoptosis] include condensation of [https://www.wikidoc.org/index.php/Chromatin chromatin] and [https://www.wikidoc.org/index.php/Cytoplasm cytoplasm], fragmentation of cell and [[lysosome]]-mediated [[phagocytosis]].<ref name="pmid18187492">{{cite journal |vauthors=Pan T, Kondo S, Le W, Jankovic J |title=The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease |journal=Brain |volume=131 |issue=Pt 8 |pages=1969–78 |date=August 2008 |pmid=18187492 |doi=10.1093/brain/awm318 |url=}}</ref> [[Neuronal]] [https://www.wikidoc.org/index.php/Apoptosis apoptosis] occurs in normal individuals (0.5 percent of [https://www.wikidoc.org/index.php/Substantia_nigra substantia nigra] [https://www.wikidoc.org/index.php/Neurons neurons]) but in [https://www.wikidoc.org/index.php/Parkinson's_disease PD] patients this can be as high as 2 percent.<ref name="pmid10809400">{{cite journal |vauthors=Jellinger KA |title=Cell death mechanisms in Parkinson's disease |journal=J Neural Transm (Vienna) |volume=107 |issue=1 |pages=1–29 |date=2000 |pmid=10809400 |doi=10.1007/s007020050001 |url=}}</ref><ref name="pmid12666099">{{cite journal |vauthors=Tatton WG, Chalmers-Redman R, Brown D, Tatton N |title=Apoptosis in Parkinson's disease: signals for neuronal degradation |journal=Ann. Neurol. |volume=53 Suppl 3 |issue= |pages=S61–70; discussion S70–2 |date=2003 |pmid=12666099 |doi=10.1002/ana.10489 |url=}}</ref>


Normally, stupor and coma are produced by interference with the [[brain stem]], such as can be caused by a [[lesion]] or indirect effects, such as [[brain herniation]].  Mass lesions in the brain stem normally cause coma due to their effects on the reticular formation.<ref name="Tindall901">
=== Delirium ===
{{cite book |quote=Mass lesions within the brainstem produce coma by virtue of direct effects on the reticular formation |author=Tindall SC |editor=Walker HK, Hall WD, Hurst JW |chapter= Level of consciousness |title= Clinical Methods: The History, Physical, and Laboratory Examinations
There are no characteristic [[histopathological]] findings in [[delirium]].
|publisher=Butterworth Publishers |location=|year=1990 |pages= |isbn= |oclc= |doi= |accessdate=2008-07-04 |url= http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cm&partid=380
<br />
}}
</ref> Mass [[lesion]]s that occur [[supratentorial|above]] the [[tentorium cerebelli]] (pictured) normally do not significantly alter the level of consciousness unless they are very large or affect both [[cerebral hemisphere]]s.
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 21:38, 24 February 2021

Altered mental status Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Altered mental status from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

CT

MRI

Other Diagnostic Studies

Treatment

Medical Therapy

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case #1

Altered mental status On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Altered mental status

All Images
X-rays
Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Altered mental status

CDC on Altered mental status

Altered mental status in the news

Blogs on Altered mental status

Directions to Hospitals Treating Altered mental status

Risk calculators and risk factors for Altered mental status

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D., Pratik Bahekar, MBBS [2]

Overview

Altered mental status is a state of a variety of diseases, hence, there is no single pathophysiology mechanism. Although, the neural science behind alertness, wakefulness, and arousal are not fully understood, it is known that the reticular formation plays an important role in these.

Pathogenesis

Altered mental status is a state of a variety of diseases, hence, there is no single pathophysiology mechanism. It is known that the reticular formation plays an important role in the state of alertness. We explain the most important subtypes of altered mental status:

Dementia

Alzheimer's disease

While the pathogenesis of AD remains unclear, It is thought that dementia is the result of:

Parkinson's disease

The pathogenesis of Parkinson's disease is a depletion of dopamine due to the following mechanisms:

Delirium

Delirium is caused by a broad spectrum of diseases and clinical problems. Among the hypothesis of delirium developement are:

Genetics

Dementia

Alzheimer's disease

Early onset (Alzheimer's dementia-AD 1, 3 and 4)

30-50 percent of early-onset Alzheimer's dementia (AD) is associated with an autosomal dominant inheritance and consists of mutations in the following genes:[32][33]

Late onset (Alzheimer's dementia -AD2)

Parkinson's disease

Some of specific genes involving in PD are:

Delirium

The genes that may be used as risk biomarkers for the developement of delirium are the following:

Associated Conditions

The most important conditions/diseases associated with altered mental status include:

Gross Pathology

Dementia

Alzheimer's disease

The most important characteristics of Alzheimer's disease on gross pathology are:

Parkinson's disease

The most important characteristics of Parkinson's disease on gross pathology are:

Delirium

There are no characteristic gross pathology findings in dementia.

Microscopic Pathology

Dementia

Alzheimer's disease

The most important histopathological characteristics of Alzheimer's disease are:

Parkinson's disease

The most important histopathological characteristics of Parkinson's disease are:

Delirium

There are no characteristic histopathological findings in delirium.

References

  1. ↑ Beach TG, Walker R, McGeer EG (1989). "Patterns of gliosis in Alzheimer's disease and aging cerebrum". Glia. 2 (6): 420–36. doi:10.1002/glia.440020605. PMID 2531723.
  2. ↑ DeKosky ST, Scheff SW (1990). "Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity". Ann. Neurol. 27 (5): 457–64. doi:10.1002/ana.410270502. PMID 2360787.
  3. ↑ Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991). "Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment". Ann. Neurol. 30 (4): 572–80. doi:10.1002/ana.410300410. PMID 1789684.
  4. ↑ Selkoe DJ (1989). "Amyloid beta protein precursor and the pathogenesis of Alzheimer's disease". Cell. 58 (4): 611–2. PMID 2504495.
  5. ↑ Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987). "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus". Science. 235 (4791): 880–4. PMID 2949367.
  6. ↑ Walsh DM, Selkoe DJ (2004). "Oligomers on the brain: the emerging role of soluble protein aggregates in neurodegeneration". Protein Pept. Lett. 11 (3): 213–28. PMID 15182223.
  7. ↑ Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010). "Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models". Cell. 142 (3): 387–97. doi:10.1016/j.cell.2010.06.036. PMID 20655099.
  8. ↑ Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Shérrer V, Défossez A (1990). "Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins". Acta Neuropathol. 80 (2): 111–7. PMID 2117840.
  9. ↑ Boekhoorn K, Joels M, Lucassen PJ (2006). "Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus". Neurobiol. Dis. 24 (1): 1–14. doi:10.1016/j.nbd.2006.04.017. PMID 16814555.
  10. ↑ Maries E, Dass B, Collier TJ, Kordower JH, Steece-Collier K (September 2003). "The role of alpha-synuclein in Parkinson's disease: insights from animal models". Nat. Rev. Neurosci. 4 (9): 727–38. doi:10.1038/nrn1199. PMID 12951565.
  11. ↑ Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature. 388 (6645): 839–40. doi:10.1038/42166. PMID 9278044.
  12. ↑ Calo L, Wegrzynowicz M, Santivañez-Perez J, Grazia Spillantini M (February 2016). "Synaptic failure and α-synuclein". Mov. Disord. 31 (2): 169–77. doi:10.1002/mds.26479. PMID 26790375.
  13. ↑ Lim KL, Zhang CW (2013). "Molecular events underlying Parkinson's disease - an interwoven tapestry". Front Neurol. 4: 33. doi:10.3389/fneur.2013.00033. PMC 3619247. PMID 23580245.
  14. ↑ Dehay B, Martinez-Vicente M, Caldwell GA, Caldwell KA, Yue Z, Cookson MR, Klein C, Vila M, Bezard E (June 2013). "Lysosomal impairment in Parkinson's disease". Mov. Disord. 28 (6): 725–32. doi:10.1002/mds.25462. PMC 5131721. PMID 23580333.
  15. ↑ Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, Christoffersson J, Chaabane W, Moghadam AR, Kashani HH, Hashemi M, Owji AA, Łos MJ (January 2014). "Autophagy and apoptosis dysfunction in neurodegenerative disorders". Prog. Neurobiol. 112: 24–49. doi:10.1016/j.pneurobio.2013.10.004. PMID 24211851.
  16. ↑ Przedborski S, Tieu K, Perier C, Vila M (August 2004). "MPTP as a mitochondrial neurotoxic model of Parkinson's disease". J. Bioenerg. Biomembr. 36 (4): 375–9. doi:10.1023/B:JOBB.0000041771.66775.d5. PMID 15377875.
  17. ↑ Selvaraj S, Sun Y, Watt JA, Wang S, Lei S, Birnbaumer L, Singh BB (April 2012). "Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling". J. Clin. Invest. 122 (4): 1354–67. doi:10.1172/JCI61332. PMC 3314472. PMID 22446186.
  18. ↑ Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (June 1989). "Mitochondrial complex I deficiency in Parkinson's disease". Lancet. 1 (8649): 1269. PMID 2566813.
  19. ↑ Greenamyre JT, Hastings TG (May 2004). "Biomedicine. Parkinson's--divergent causes, convergent mechanisms". Science. 304 (5674): 1120–2. doi:10.1126/science.1098966. PMID 15155938.
  20. ↑ Sherer TB, Betarbet R, Testa CM, Seo BB, Richardson JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT (November 2003). "Mechanism of toxicity in rotenone models of Parkinson's disease". J. Neurosci. 23 (34): 10756–64. PMID 14645467.
  21. ↑ Oakley AE, Collingwood JF, Dobson J, Love G, Perrott HR, Edwardson JA, Elstner M, Morris CM (May 2007). "Individual dopaminergic neurons show raised iron levels in Parkinson disease". Neurology. 68 (21): 1820–5. doi:10.1212/01.wnl.0000262033.01945.9a. PMID 17515544.
  22. ↑ Dusek P, Jankovic J, Le W (April 2012). "Iron dysregulation in movement disorders". Neurobiol. Dis. 46 (1): 1–18. doi:10.1016/j.nbd.2011.12.054. PMID 22266337.
  23. ↑ Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI (January 2012). "Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export". Nat. Med. 18 (2): 291–5. doi:10.1038/nm.2613. PMID 22286308.
  24. ↑ Hirsch EC, Hunot S (April 2009). "Neuroinflammation in Parkinson's disease: a target for neuroprotection?". Lancet Neurol. 8 (4): 382–97. doi:10.1016/S1474-4422(09)70062-6. PMID 19296921.
  25. ↑ Brochard V, Combadière B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, Bonduelle O, Alvarez-Fischer D, Callebert J, Launay JM, Duyckaerts C, Flavell RA, Hirsch EC, Hunot S (January 2009). "Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease". J. Clin. Invest. 119 (1): 182–92. doi:10.1172/JCI36470. PMC 2613467. PMID 19104149.
  26. ↑ van der Mast, Rose C. (1998). "Pathophysiology of Delirium". Journal of Geriatric Psychiatry and Neurology. 11 (3): 138–145. doi:10.1177/089198879801100304. ISSN 0891-9887.
  27. ↑ Felicetta, James V. (2016). "Effects of illness on thyroid function tests". Postgraduate Medicine. 85 (8): 213–220. doi:10.1080/00325481.1989.11700751. ISSN 0032-5481.
  28. ↑ Trzepacz, Paula T. (1994). "The Neuropathogenesis of Delirium". Psychosomatics. 35 (4): 374–391. doi:10.1016/S0033-3182(94)71759-X. ISSN 0033-3182.
  29. ↑ Hopkins SJ, Rothwell NJ (February 1995). "Cytokines and the nervous system. I: Expression and recognition". Trends Neurosci. 18 (2): 83–8. PMID 7537419.
  30. ↑ Renault, Pierre; Hoofnagle, Jay (2008). "Side Effects of Alpha Interferon". Seminars in Liver Disease. 9 (04): 273–277. doi:10.1055/s-2008-1040523. ISSN 0272-8087.
  31. ↑ Müller, N. (1997). "Die Rolle des Zytokinnetzwerks im ZNS und psychische Störungen". Der Nervenarzt. 68 (1): 11–20. doi:10.1007/s001150050092. ISSN 0028-2804.
  32. ↑ Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, Thomas-Anterion C, Michon A, Martin C, Charbonnier F, Raux G, Camuzat A, Penet C, Mesnage V, Martinez M, Clerget-Darpoux F, Brice A, Frebourg T (1999). "Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum". Am. J. Hum. Genet. 65 (3): 664–70. doi:10.1086/302553. PMC 1377972. PMID 10441572.
  33. ↑ Tsuang D, Larson EB, Bowen J, McCormick W, Teri L, Nochlin D, Leverenz JB, Peskind ER, Lim A, Raskind MA, Thompson ML, Mirra SS, Gearing M, Schellenberg GD, Kukull W (1999). "The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series". Arch. Neurol. 56 (12): 1489–95. PMID 10593304.
  34. ↑ Khachaturian AS, Corcoran CD, Mayer LS, Zandi PP, Breitner JC (2004). "Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study". Arch. Gen. Psychiatry. 61 (5): 518–24. doi:10.1001/archpsyc.61.5.518. PMID 15123497.
  35. ↑ Jonsson T, Stefansson H, Steinberg S, Jonsdottir I, Jonsson PV, Snaedal J, Bjornsson S, Huttenlocher J, Levey AI, Lah JJ, Rujescu D, Hampel H, Giegling I, Andreassen OA, Engedal K, Ulstein I, Djurovic S, Ibrahim-Verbaas C, Hofman A, Ikram MA, van Duijn CM, Thorsteinsdottir U, Kong A, Stefansson K (2013). "Variant of TREM2 associated with the risk of Alzheimer's disease". N. Engl. J. Med. 368 (2): 107–16. doi:10.1056/NEJMoa1211103. PMC 3677583. PMID 23150908.
  36. ↑ Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG (October 2009). "Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease". N. Engl. J. Med. 361 (17): 1651–61. doi:10.1056/NEJMoa0901281. PMC 2856322. PMID 19846850.
  37. ↑ Klein C, Schlossmacher MG (November 2007). "Parkinson disease, 10 years after its genetic revolution: multiple clues to a complex disorder". Neurology. 69 (22): 2093–104. doi:10.1212/01.wnl.0000271880.27321.a7. PMID 17761553.
  38. ↑ Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F (March 2002). "A new locus for Parkinson's disease (PARK8) maps to chromosome 12p11.2-q13.1". Ann. Neurol. 51 (3): 296–301. PMID 11891824.
  39. ↑ Lücking CB, Dürr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denèfle P, Wood NW, Agid Y, Brice A (May 2000). "Association between early-onset Parkinson's disease and mutations in the parkin gene". N. Engl. J. Med. 342 (21): 1560–7. doi:10.1056/NEJM200005253422103. PMID 10824074.
  40. ↑ Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, González-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW (May 2004). "Hereditary early-onset Parkinson's disease caused by mutations in PINK1". Science. 304 (5674): 1158–60. doi:10.1126/science.1096284. PMID 15087508.
  41. ↑ Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (January 2003). "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism". Science. 299 (5604): 256–9. doi:10.1126/science.1077209. PMID 12446870.
  42. ↑ van Munster, Barbara C.; Aronica, Eleonora; Zwinderman, Aeilko H.; Eikelenboom, Piet; Cunningham, Colm; de Rooij, Sophia E.J.A (2011). "Neuroinflammation in Delirium: A Postmortem Case-Control Study". Rejuvenation Research. 14 (6): 615–622. doi:10.1089/rej.2011.1185. ISSN 1549-1684.
  43. ↑ van Munster, Barbara C.; Aronica, Eleonora; Zwinderman, Aeilko H.; Eikelenboom, Piet; Cunningham, Colm; de Rooij, Sophia E.J.A (2011). "Neuroinflammation in Delirium: A Postmortem Case-Control Study". Rejuvenation Research. 14 (6): 615–622. doi:10.1089/rej.2011.1185. ISSN 1549-1684.
  44. ↑ Ely, Wesley E; Girard, Timothy D.; Shintani, Ayumi K.; Jackson, James C.; Gordon, Sharon M.; Thomason, Jason W. W.; Pun, Brenda T.; Canonico, Angelo E.; Light, Richard W.; Pandharipande, Pratik; Laskowitz, Daniel T. (2007). "Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*". Critical Care Medicine. 35 (1): 112–117. doi:10.1097/01.CCM.0000251925.18961.CA. ISSN 0090-3493.
  45. ↑ Zhu, Fei; Liu, Jing-Li; Li, Jing-Pin; Xiao, Fang; Zhang, Zhao-Xia; Zhang, Lei (2013). "MicroRNA-124 (miR-124) Regulates Ku70 Expression and is Correlated with Neuronal Death Induced by Ischemia/Reperfusion". Journal of Molecular Neuroscience. 52 (1): 148–155. doi:10.1007/s12031-013-0155-9. ISSN 0895-8696.
  46. ↑ Murakami T, Shoji M, Imai Y, Inoue H, Kawarabayashi T, Matsubara E, Harigaya Y, Sasaki A, Takahashi R, Abe K (March 2004). "Pael-R is accumulated in Lewy bodies of Parkinson's disease". Ann. Neurol. 55 (3): 439–42. doi:10.1002/ana.20064. PMID 14991825.
  47. ↑ Pan T, Kondo S, Le W, Jankovic J (August 2008). "The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease". Brain. 131 (Pt 8): 1969–78. doi:10.1093/brain/awm318. PMID 18187492.
  48. ↑ Jellinger KA (2000). "Cell death mechanisms in Parkinson's disease". J Neural Transm (Vienna). 107 (1): 1–29. doi:10.1007/s007020050001. PMID 10809400.
  49. ↑ Tatton WG, Chalmers-Redman R, Brown D, Tatton N (2003). "Apoptosis in Parkinson's disease: signals for neuronal degradation". Ann. Neurol. 53 Suppl 3: S61–70, discussion S70–2. doi:10.1002/ana.10489. PMID 12666099.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Altered_mental_status_pathophysiology&oldid=1691884"