Editing Polio (section)

== Pathophysiology ==
[[File:Polio spine.png|thumb|left|A photomicrograph of the lumbar spinal cord depicting an [[infarct]] due to Polio Type III surrounding the anterior spinal artery]]

Poliovirus enters the body through the mouth, infecting the first cells with which it comes in contact&nbsp;– the [[human pharynx|pharynx]] and [[intestinal mucosa]]. It gains entry by binding to an [[Immunoglobulin|immunoglobulin-like]] receptor, known as the poliovirus receptor or [[CD155]], on the cell membrane.<ref name=He>{{cite journal | vauthors = He Y, Mueller S, Chipman PR, et al | title = Complexes of poliovirus serotypes with their common cellular receptor, CD155 | journal = Journal of Virology | volume = 77 | issue = 8 | pages = 4827–35 | date = April 2003 | pmid = 12663789 | pmc = 152153 | doi = 10.1128/JVI.77.8.4827-4835.2003 }}</ref> The virus then hijacks the [[Host (biology)|host cell's]] own machinery, and begins to [[viral replication|replicate]]. Poliovirus divides within gastrointestinal cells for about a week, from where it spreads to the [[tonsils]] (specifically the [[follicular dendritic cell]]s residing within the tonsilar [[germinal center]]s), the intestinal [[lymphoid tissue]] including the [[Microfold cell|M cells]] of [[Peyer's patches]], and the deep [[Cervical lymph nodes|cervical]] and [[Inferior mesenteric lymph nodes|mesenteric lymph nodes]], where it multiplies abundantly. The virus is subsequently absorbed into the bloodstream.<ref name=Baron>{{cite book| vauthors = Yin-Murphy M, Almond JW| chapter = Picornaviruses: The Enteroviruses: Polioviruses| title = Baron's Medical Microbiology| veditors = Baron S, etal | edition = 4th| publisher = Univ of Texas Medical Branch| year = 1996| pmid = 21413259| chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.2862| isbn = 978-0-9631172-1-2| url-status = live| archive-url = https://web.archive.org/web/20081207154734/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.2862| archive-date = 7 December 2008}}</ref>

Known as [[viremia]], the presence of a virus in the bloodstream enables it to be widely distributed throughout the body. Poliovirus can survive and multiply within the blood and lymphatics for long periods of time, sometimes as long as 17 weeks.<ref>{{cite web | author = Todar K | title = Polio | work = Ken Todar's Microbial World | publisher = University of Wisconsin – Madison | year = 2006 | url = http://textbookofbacteriology.net/themicrobialworld/Polio.html | access-date = 23 April 2007 | archive-url = https://web.archive.org/web/20100427041918/http://textbookofbacteriology.net/themicrobialworld/Polio.html | archive-date = 27 April 2010 }}</ref> In a small percentage of cases, it can spread and replicate in other sites, such as [[brown fat]], the [[reticuloendothelial]] tissues, and muscle.<ref>{{cite journal | vauthors = Sabin AB | title = Pathogenesis of poliomyelitis; reappraisal in the light of new data | journal = Science | volume = 123 | issue = 3209 | pages = 1151–57 | date = June 1956 | pmid = 13337331 | doi = 10.1126/science.123.3209.1151 | bibcode = 1956Sci...123.1151S }}</ref> This sustained replication causes a major viremia, and leads to the development of minor influenza-like symptoms. Rarely, this may progress and the virus may invade the central nervous system, provoking a local [[inflammatory response]]. In most cases, this causes a self-limiting inflammation of the [[meninges]], the layers of tissue surrounding the [[Human brain|brain]], which is known as nonparalytic aseptic meningitis.<ref name=Chamberlin_2005 /> Penetration of the CNS provides no known benefit to the virus, and is quite possibly an incidental deviation of a normal gastrointestinal infection.<ref name= Mueller>{{cite journal | vauthors = Mueller S, Wimmer E, Cello J | title = Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event | journal = Virus Research | volume = 111 | issue = 2 | pages = 175–93 | date = August 2005 | pmid = 15885840 | doi = 10.1016/j.virusres.2005.04.008 }}</ref> The mechanisms by which poliovirus spreads to the CNS are poorly understood, but it appears to be primarily a chance event&nbsp;– largely independent of the age, gender, or [[Socioeconomics|socioeconomic]] position of the individual.<ref name=Mueller />

=== Paralytic polio ===
[[File:PHIL 2767 Poliovirus Myotonic dystrophic changes.jpg|thumb|right|Denervation of [[skeletal muscle]] tissue secondary to poliovirus infection can lead to paralysis.]]
In around one percent of infections, poliovirus spreads along certain nerve fiber pathways, preferentially replicating in and destroying [[motor neuron]]s within the [[spinal cord]], [[brain stem]], or [[motor cortex]]. This leads to the development of paralytic poliomyelitis, the various forms of which (spinal, bulbar, and bulbospinal) vary only with the amount of neuronal damage and inflammation that occurs, and the region of the CNS affected.<ref>{{cite journal |last1=Punsoni |first1=Michael |last2=Lakis |first2=Nelli S. |last3=Mellion |first3=Michelle |last4=de la Monte |first4=Suzanne M. |date=June 2023 |title=Post-Polio Syndrome Revisited |journal=Neurology International |volume=15 |issue=2 |pages=569–579 |doi=10.3390/neurolint15020035 |doi-access=free |issn=2035-8377 |pmc=10123742 |pmid=37092507}}</ref>

The destruction of neuronal cells produces [[lesion]]s within the [[Dorsal root ganglion|spinal ganglia]]; these may also occur in the [[reticular formation]], [[vestibular nuclei]], [[cerebellar vermis]], and deep [[cerebellar nuclei]].<ref name=Mueller /> Inflammation associated with [[Neuron|nerve cell]] destruction often alters the color and appearance of the gray matter in the [[spinal column]], causing it to appear reddish and swollen.<ref name=Chamberlin_2005/> Other destructive changes associated with paralytic disease occur in the [[forebrain]] region, specifically the [[hypothalamus]] and [[thalamus]].<ref name=Mueller />

Early symptoms of paralytic polio include high fever, headache, stiffness in the back and neck, asymmetrical weakness of various muscles, sensitivity to touch, [[Dysphagia|difficulty swallowing]], [[Myalgia|muscle pain]], loss of superficial and deep [[reflex]]es, [[paresthesia]] (pins and needles), irritability, constipation, or difficulty urinating. Paralysis generally develops one to ten days after early symptoms begin, progresses for two to three days, and is usually complete by the time the fever breaks.<ref name= Silverstein>{{cite book |vauthors=Silverstein A, Silverstein V, Nunn LS |title=Polio |series=Diseases and People |publisher=Enslow Publishers |location=Berkeley Heights, NJ |year=2001 |isbn=978-0-7660-1592-0 |page=[https://archive.org/details/poliodiseasespeo00alvi/page/12 12] |url=https://archive.org/details/poliodiseasespeo00alvi/page/12 }}</ref>

The likelihood of developing paralytic polio increases with age, as does the extent of paralysis. In children, nonparalytic meningitis is the most likely consequence of CNS involvement, and paralysis occurs in only one in 1000 cases. In adults, paralysis occurs in one in 75 cases.<ref name="Gawne_1995">{{cite journal|year=1995|title=Post-polio syndrome: pathophysiology and clinical management|url=http://www.poliosurvivorsnetwork.org.uk/archive/lincolnshire/library/gawne/ppspandcm.html|journal=Critical Review in Physical Medicine and Rehabilitation|volume=7|issue=2|pages=147–88|vauthors=Gawne AC, Halstead LS|archive-url=https://web.archive.org/web/20160630225919/http://www.poliosurvivorsnetwork.org.uk/archive/lincolnshire/library/gawne/ppspandcm.html|archive-date=30 June 2016|access-date=30 June 2016|doi=10.1615/CritRevPhysRehabilMed.v7.i2.40}} Reproduced online with permission by Lincolnshire Post-Polio Library; retrieved on 10 November 2007.</ref> In children under five years of age, paralysis of one leg is most common; in adults, extensive paralysis of the [[chest]] and [[abdomen]] also affecting all four limbs&nbsp;– [[quadriplegia]]&nbsp;– is more likely.<ref name=Young>{{cite journal | vauthors = Young GR | title = Occupational therapy and the postpolio syndrome | journal = The American Journal of Occupational Therapy | volume = 43 | issue = 2 | pages = 97–103 | date = February 1989 | pmid = 2522741 | doi = 10.5014/ajot.43.2.97 | doi-access =  }}</ref> Paralysis rates also vary depending on the serotype of the infecting poliovirus; the highest rates of paralysis (one in 200) are associated with poliovirus type 1, the lowest rates (one in 2,000) are associated with type 2.<ref name=Nathanson>{{cite journal | vauthors = Nathanson N, Martin JR | title = The epidemiology of poliomyelitis: enigmas surrounding its appearance, epidemicity, and disappearance | journal = American Journal of Epidemiology | volume = 110 | issue = 6 | pages = 672–92 | date = December 1979 | pmid = 400274 | doi = 10.1093/oxfordjournals.aje.a112848 }}</ref>

==== Spinal polio ====
[[File:Polio spinal diagram-en.svg|thumb|left|The location of [[motor neuron]]s in the [[Anterior horn (spinal cord)|anterior horn cells]] of the [[spinal column]]]]

Spinal polio, the most common form of paralytic poliomyelitis, results from viral invasion of the motor neurons of the [[Anterior horn (spinal cord)|anterior horn cells]], or the [[ventral]] (front) [[grey matter]] section in the [[spinal column]], which are responsible for movement of the muscles, including those of the [[torso|trunk]], [[limb (anatomy)|limbs]], and the [[intercostal muscle]]s.<ref name= Henry1>{{cite book |vauthors=Frauenthal HW, Manning JV | title = Manual of infantile paralysis, with modern methods of treatment.| publisher = Philadelphia Davis | year = 1914| pages= [https://archive.org/details/amanualinfantil00fraugoog/page/n103 79]–101 |url= https://archive.org/details/amanualinfantil00fraugoog | oclc= 2078290}}</ref> Virus invasion causes inflammation of the nerve cells, leading to damage or destruction of motor neuron [[ganglion|ganglia]]. When spinal neurons die, [[Wallerian degeneration]] takes place, leading to weakness of those muscles formerly [[innervate]]d by the now-dead neurons.<ref>{{Cite web|url = http://phil.cdc.gov/phil/details.asp?pid=2760|title = A photomicrograph of the thoracic spinal cord depicting degenerative changes due to Polio Type III.|date = 18 March 2005|access-date = 24 January 2014|website = Public Health Image Library (PHIL)|publisher = Centers for Disease Control and Prevention| vauthors = Karp H |url-status = live|archive-url = https://web.archive.org/web/20140202193927/http://phil.cdc.gov/phil/details.asp?pid=2760|archive-date = 2 February 2014}}</ref> With the destruction of nerve cells, the muscles no longer receive signals from the brain or spinal cord; without nerve stimulation, the muscles [[atrophy]], becoming weak, floppy and poorly controlled, and finally completely paralyzed.<ref name=Henry1 /> Maximum paralysis progresses rapidly (two to four days), and usually involves fever and muscle pain. Deep [[tendon reflex]]es are also affected, and are typically absent or diminished; [[Sense|sensation]] (the ability to feel) in the paralyzed limbs, however, is not affected.<ref>{{cite web|url = https://www.cdc.gov/vaccines/pubs/surv-manual/chpt12-polio.html|title = Chapter 12: Poliomyelitis|date = 13 April 2013|access-date = 24 January 2014|website = Manual for the Surveillance of Vaccine-Preventable Diseases (5th Edition, 2012)|publisher = Centers for Disease Control and Prevention| vauthors = Wallace GS, Oberste SM |url-status = live|archive-url = https://web.archive.org/web/20140128113623/http://www.cdc.gov/vaccines/pubs/surv-manual/chpt12-polio.html|archive-date = 28 January 2014}}</ref>

The extent of spinal paralysis depends on the region of the cord affected, which may be [[neck|cervical]], [[human thorax|thoracic]], or [[lumbar]].<ref name=Guide>{{cite book |title=Professional Guide to Diseases (Professional Guide Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2005 |pages=[https://archive.org/details/professionalguid0000unse_o7n1/page/243 243–45] |isbn=978-1-58255-370-2 |url=https://archive.org/details/professionalguid0000unse_o7n1/page/243 }}</ref> The virus may affect muscles on both sides of the body, but more often the paralysis is [[Asymmetry|asymmetrical]].<ref name=Baron /> Any [[Limb (anatomy)|limb]] or combination of limbs may be affected&nbsp;– one leg, one arm, or both legs and both arms.  Paralysis is often more severe [[Anatomical terms of location#Proximal distal|proximally]] (where the limb joins the body) than [[Anatomical terms of location#Proximal distalDistally|distally]] (the [[fingertip]]s and [[toe]]s).<ref name=Baron />

==== Bulbar polio ====
[[File:Brain bulbar region.svg|thumb|right|The location and anatomy of the bulbar region (in orange)]]
Making up about two percent of cases of paralytic polio, bulbar polio occurs when poliovirus invades and destroys nerves within the [[bulbar]] region of the [[brain stem]].<ref name = PinkBook2021 /> The bulbar region is a [[white matter]] pathway that connects the [[cerebral cortex]] to the brain stem. The destruction of these nerves weakens the muscles supplied by the [[cranial nerve]]s, producing symptoms of [[encephalitis]], and causes [[Dyspnea|difficulty breathing]], speaking and swallowing.<ref name=Late /> Critical nerves affected are the [[glossopharyngeal nerve]] (which partially controls swallowing and functions in the throat, tongue movement, and taste), the [[vagus nerve]] (which sends signals to the heart, intestines, and lungs), and the [[accessory nerve]] (which controls upper neck movement). Due to the effect on swallowing, secretions of [[mucus]] may build up in the airway, causing suffocation.<ref name = Silverstein /> Other signs and symptoms include [[facial weakness]] (caused by destruction of the [[trigeminal nerve]] and [[facial nerve]], which innervate the cheeks, [[tear duct]]s, gums, and muscles of the face, among other structures), [[diplopia|double vision]], difficulty in chewing, and abnormal [[respiratory rate]], depth, and rhythm (which may lead to [[respiratory arrest]]). [[Pulmonary edema]] and [[shock (circulatory)|shock]] are also possible and may be fatal.<ref name=Guide/>

==== Bulbospinal polio ====
Approximately 19 percent of all paralytic polio cases have both bulbar and spinal symptoms; this subtype is called respiratory or bulbospinal polio.<ref name=PinkBook2021 /> Here, the virus affects the upper part of the cervical spinal cord ([[cervical vertebrae]] C3 through C5), and paralysis of the [[Thoracic diaphragm|diaphragm]] occurs. The critical nerves affected are the [[phrenic nerve]] (which drives the diaphragm to inflate the [[human lung|lungs]]) and those that drive the muscles needed for swallowing. By destroying these nerves, this form of polio affects breathing, making it difficult or impossible for the patient to breathe without the support of a [[medical ventilator|ventilator]]. It can lead to paralysis of the arms and legs and may also affect swallowing and heart functions.<ref name= Hoyt/>