Delirium pathophysiology: Difference between revisions

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==Overview==
==Overview==
Exact [[pathophysiology]] of [[delirium]] is still being investigated.  The roles of [[neurotransmitters]] like [[acetylcholine]] and [[dopamine]] seem to be important. It involves disrupted connectivity between [[cortical]] and [[subcortical]] areas of the [[brain]], especially areas concerned with [[sleep]] and [[awakening]].
The exact [[pathophysiology]] of [[delirium]] is still being investigated.  The roles of [[neurotransmitters]] like [[acetylcholine]] and [[dopamine]] seem to be important. It involves disrupted connectivity between [[cortical]] and [[subcortical]] areas of the [[brain]], especially areas concerned with [[sleep]] and [[awakening]]. The role of increased inflammatory [[cytokines]] has been shown in [[delirious ]] [[patients]].


==Pathophysiology==
==Pathophysiology==
* [[Acetylcholine]] has a crucial role in [[sleep]], [[attention]], [[arousal]], and [[memory]].
* [[Acetylcholine]] has a crucial role in [[sleep]], [[attention]], [[arousal]], and [[memory]].
* [[Dopamine]] is involved in the regulation of [[acetylcholine]].   
* [[Dopamine]] is involved in the regulation of [[acetylcholine]].   
* Reduced [[acetylcholine]] and [[histamine]] activity and increased [[dopamine]] and [[glutamate]] activity are observed in [[delirium]].
* Reduced [[acetylcholine]] and [[histamine]] activity and increased [[dopamine]] and [[glutamate]] activity are observed in [[delirium]].<ref name="AdamHaas2020">{{cite journal|last1=Adam|first1=Elisabeth Hannah|last2=Haas|first2=Victoria|last3=Lindau|first3=Simone|last4=Zacharowski|first4=Kai|last5=Scheller|first5=Bertram|title=Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study|journal=BMJ Open|volume=10|issue=1|year=2020|pages=e031212|issn=2044-6055|doi=10.1136/bmjopen-2019-031212}}</ref>
* Roles of [[GABA]] and [[serotonin]] are uncertain.<ref name="Markowitz-2008">{{Cite journal  | last1 = Markowitz | first1 = JD. | last2 = Narasimhan | first2 = M. | title = Delirium and antipsychotics: a systematic review of epidemiology and somatic treatment options. | journal = Psychiatry (Edgmont) | volume = 5 | issue = 10 | pages = 29-36 | month = Oct | year = 2008 | doi =  | PMID = 19724721 }}</ref>   
* Roles of [[GABA]] and [[serotonin]] are uncertain.<ref name="Markowitz-2008">{{Cite journal  | last1 = Markowitz | first1 = JD. | last2 = Narasimhan | first2 = M. | title = Delirium and antipsychotics: a systematic review of epidemiology and somatic treatment options. | journal = Psychiatry (Edgmont) | volume = 5 | issue = 10 | pages = 29-36 | month = Oct | year = 2008 | doi =  | PMID = 19724721 }}</ref>   
* [[Anticholinergics]] are known to predispose to [[delirium]] and at the same time, anti dopaminergics are known to curtail [[delirium]].  
* [[Anticholinergics]] are known to predispose to [[delirium]] and at the same time, anti dopaminergics are known to curtail [[delirium]].  
* [[Cortical]] and [[subcortical]] dysfunctions are behind the development of [[delirium]].  
* [[Cortical]] and [[subcortical]] dysfunctions are behind the development of [[delirium]].  
* Disrupted connectivity is a key feature in [[delirium]] and it is observed in the following [[neuronal]] connections:
* Disrupted connectivity is a key feature in [[delirium]] and it is observed in the following [[neuronal]] connections:
:* The [[dorsal]] lateral [[prefrontal cortex]] and the posterior cingulate cortex.
:* The [[dorsal]] lateral [[prefrontal cortex]] and the posterior cingulate [[cortex]]
:* Intralaminar [[thalamus]] from [[brainstem]] and [[midbrain]] nuclei.
:* Intralaminar [[thalamus]] from [[brainstem]] and [[midbrain]] [[nuclei]]
* [[Midbrain]] nucleus basalis is a source of [[cholinergic]] activation, whereas the [[midbrain]] ventral tegmental area is a source of [[dopaminergic]] innervation.
* [[Midbrain]] nucleus basalis is a source of [[cholinergic]] activation, whereas the [[midbrain]] ventral tegmental area is a source of [[dopaminergic]] innervation.
* [[Mesencephalic]] tegmentum and the [[thalamus]] are linked to the early [[restoration]] of [[alertness]].
* [[Mesencephalic]] tegmentum and the [[thalamus]] are linked to the early [[restoration]] of [[alertness]].
* [[Subcortical]] connections tend to recover sooner than the [[cortical]] connection.
* [[Subcortical]] connections tend to recover sooner than the [[cortical]] connection.<ref name="Gaudreau-2012">{{Cite journal  | last1 = Gaudreau | first1 = JD. | title = Insights into the neural mechanisms underlying delirium. | journal = Am J Psychiatry | volume = 169 | issue = 5 | pages = 450-1 | month = May | year = 2012 | doi = 10.1176/appi.ajp.2012.12020256 | PMID = 22549202 }}</ref>  
* It may be  due to the temporary pharmacological influence of the [[anticholinergic]] used in [[anesthesia]] and the [[antidopaminergic]] drugs administered to obtain [[behavioral]] control.<ref name="Gaudreau-2012">{{Cite journal  | last1 = Gaudreau | first1 = JD. | title = Insights into the neural mechanisms underlying delirium. | journal = Am J Psychiatry | volume = 169 | issue = 5 | pages = 450-1 | month = May | year = 2012 | doi = 10.1176/appi.ajp.2012.12020256 | PMID = 22549202 }}</ref>  
* [[Individuals]] with [[brain]] abnormalities like [[cortical]]  atrophy, [[ventricular]]  enlargement, and increased [[white matter]] lesions are more likely to develop [[delirium]].<ref name="Choi-2012">{{Cite journal  | last1 = Choi | first1 = SH. | last2 = Lee | first2 = H. | last3 = Chung | first3 = TS. | last4 = Park | first4 = KM. | last5 = Jung | first5 = YC. | last6 = Kim | first6 = SI. | last7 = Kim | first7 = JJ. | title = Neural network functional connectivity during and after an episode of delirium. | journal = Am J Psychiatry | volume = 169 | issue = 5 | pages = 498-507 | month = May | year = 2012 | doi = 10.1176/appi.ajp.2012.11060976 | PMID = 22549209 }}</ref>
* [[Individuals]] with [[brain]] abnormalities like [[cortical]]  atrophy, [[ventricular]]  enlargement, and increased [[white matter]] lesions are more likely to develop [[delirium]].<ref name="Choi-2012">{{Cite journal  | last1 = Choi | first1 = SH. | last2 = Lee | first2 = H. | last3 = Chung | first3 = TS. | last4 = Park | first4 = KM. | last5 = Jung | first5 = YC. | last6 = Kim | first6 = SI. | last7 = Kim | first7 = JJ. | title = Neural network functional connectivity during and after an episode of delirium. | journal = Am J Psychiatry | volume = 169 | issue = 5 | pages = 498-507 | month = May | year = 2012 | doi = 10.1176/appi.ajp.2012.11060976 | PMID = 22549209 }}</ref>
* [[Anticholinergic]] drugs such as [[biperiden]] and [[scopolamine]] may have [[hypocholinergic]]  [[delirium]]-like effects.<ref>{{cite journal|last=Hshieh|first=TT|coauthors=Fong, TG; Marcantonio, ER; Inouye, SK|title=Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.|journal=The journals of gerontology. Series A, Biological sciences and medical sciences|date=July 2008|volume=63|issue=7|pages=764–72|pmid=18693233|pmc=2917793}}</ref>
* [[Anticholinergic]] drugs such as [[biperiden]] and [[scopolamine]] may have [[hypocholinergic]]  [[delirium]]-like effects.<ref>{{cite journal|last=Hshieh|first=TT|coauthors=Fong, TG; Marcantonio, ER; Inouye, SK|title=Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence.|journal=The journals of gerontology. Series A, Biological sciences and medical sciences|date=July 2008|volume=63|issue=7|pages=764–72|pmid=18693233|pmc=2917793}}</ref>

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Pratik Bahekar, MBBS [3]; Vishal Khurana, MBBS, MD [4]

Overview

The exact pathophysiology of delirium is still being investigated. The roles of neurotransmitters like acetylcholine and dopamine seem to be important. It involves disrupted connectivity between cortical and subcortical areas of the brain, especially areas concerned with sleep and awakening. The role of increased inflammatory cytokines has been shown in delirious patients.

Pathophysiology

Cerebrospinal fluid biomarkers

Neuroimaging

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References

  1. Adam, Elisabeth Hannah; Haas, Victoria; Lindau, Simone; Zacharowski, Kai; Scheller, Bertram (2020). "Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study". BMJ Open. 10 (1): e031212. doi:10.1136/bmjopen-2019-031212. ISSN 2044-6055.
  2. Markowitz, JD.; Narasimhan, M. (2008). "Delirium and antipsychotics: a systematic review of epidemiology and somatic treatment options". Psychiatry (Edgmont). 5 (10): 29–36. PMID 19724721. Unknown parameter |month= ignored (help)
  3. Gaudreau, JD. (2012). "Insights into the neural mechanisms underlying delirium". Am J Psychiatry. 169 (5): 450–1. doi:10.1176/appi.ajp.2012.12020256. PMID 22549202. Unknown parameter |month= ignored (help)
  4. Choi, SH.; Lee, H.; Chung, TS.; Park, KM.; Jung, YC.; Kim, SI.; Kim, JJ. (2012). "Neural network functional connectivity during and after an episode of delirium". Am J Psychiatry. 169 (5): 498–507. doi:10.1176/appi.ajp.2012.11060976. PMID 22549209. Unknown parameter |month= ignored (help)
  5. Hshieh, TT (July 2008). "Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence". The journals of gerontology. Series A, Biological sciences and medical sciences. 63 (7): 764–72. PMC 2917793. PMID 18693233. Unknown parameter |coauthors= ignored (help)
  6. Cunningham, C (Aug 3, 2012). "At the extreme end of the psychoneuroimmunological spectrum: Delirium as a maladaptive sickness behaviour response". Brain, behavior, and immunity. 28: 1–13. doi:10.1016/j.bbi.2012.07.012. PMID 22884900. Unknown parameter |coauthors= ignored (help)
  7. Hall, RJ (2011). "A systematic literature review of cerebrospinal fluid biomarkers in delirium". Dementia and geriatric cognitive disorders. 32 (2): 79–93. doi:10.1159/000330757. PMID 21876357. Unknown parameter |coauthors= ignored (help)
  8. Witlox, J (July 2011). "Cerebrospinal fluid β-amyloid and tau are not associated with risk of delirium: a prospective cohort study in older adults with hip fracture". Journal of the American Geriatrics Society. 59 (7): 1260–7. doi:10.1111/j.1532-5415.2011.03482.x. PMID 21718268. Unknown parameter |coauthors= ignored (help)
  9. Soiza, RL (September 2008). "Neuroimaging studies of delirium: a systematic review". Journal of psychosomatic research. 65 (3): 239–48. doi:10.1016/j.jpsychores.2008.05.021. PMID 18707946. Unknown parameter |coauthors= ignored (help)
  10. Morandi, A (July 2012). "The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*". Critical Care Medicine. 40 (7): 2182–9. doi:10.1097/CCM.0b013e318250acdc. PMID 22584766. Unknown parameter |coauthors= ignored (help)
  11. Hatano, Y (Sep 21, 2012). "White-Matter Hyperintensities Predict Delirium After Cardiac Surgery". The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. doi:10.1097/JGP.0b013e31826d6b10. PMID 23000936. Unknown parameter |coauthors= ignored (help)
  12. Shioiri, A (August 2010). "White matter abnormalities as a risk factor for postoperative delirium revealed by diffusion tensor imaging". The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 18 (8): 743–53. doi:10.1097/JGP.0b013e3181d145c5. PMID 20220599. Unknown parameter |coauthors= ignored (help)
  13. Kalvas LB, Monroe TB (July 2019). "Structural Brain Changes in Delirium: An Integrative Review". Biol Res Nurs. 21 (4): 355–365. doi:10.1177/1099800419849489. PMC 6794667 Check |pmc= value (help). PMID 31067980.
  14. Choi, SH (May 2012). "Neural network functional connectivity during and after an episode of delirium". The American Journal of Psychiatry. 169 (5): 498–507. doi:10.1176/appi.ajp.2012.11060976. PMID 22549209. Unknown parameter |coauthors= ignored (help)
  15. Janz, DR (September 2010). "Brain autopsy findings in intensive care unit patients previously suffering from delirium: a pilot study". Journal of critical care. 25 (3): 538.e7–12. doi:10.1016/j.jcrc.2010.05.004. PMID 20580199. Unknown parameter |coauthors= ignored (help)
  16. Munster, BC (December 2011). "Neuroinflammation in delirium: a postmortem case-control study". Rejuvenation research. 14 (6): 615–22. doi:10.1089/rej.2011.1185. PMID 21978081. Unknown parameter |coauthors= ignored (help)

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