Zespół post-polio – Patofizjologia i mechanizm

Zespół post-polio
Patofizjologia i mechanizm

Zespół post-polio (PPS) to późne powikłanie ostrego porażennego poliomyelitis, manifestujące się po 15-40 latach od pierwotnego zakażenia i dotykające 25-40%, a według nowszych danych nawet ponad 80% osób po przebytym polio. Charakterystyczne objawy to postępujące osłabienie i zanik mięśni, ból mięśniowo-stawowy oraz znaczne zmęczenie. Patogeneza PPS jest wieloczynnikowa, z dominującą teorią zmęczenia neuronalnego, która opisuje nadmierne obciążenie metaboliczne powiększonych jednostek ruchowych powstałych w wyniku sprouting aksonalnego po uszkodzeniu neuronów ruchowych w ostrej fazie choroby. Elektrofizjologiczne badania, takie jak EMG i SFEMG, potwierdzają niestabilność tych jednostek, objawiającą się zwiększonym jitteringiem i blokadami przewodzenia w obrębie połączeń nerwowo-mięśniowych. Inne mechanizmy obejmują przyspieszone starzenie się neuronów ruchowych, procesy zapalne i autoimmunologiczne z podwyższonym poziomem cytokin prozapalnych (TNF-alfa, IFN-gamma, IL-4, IL-10) w płynie mózgowo-rdzeniowym oraz zaburzenia metaboliczne mięśni o podłożu mitochondrialnym, które mogą tłumaczyć objawy zmęczenia i kognitywne („mgła mózgowa”).

Wprowadzenie do zespołu post-polio
Patogeneza zespołu post-polio

Teoria zmęczenia neuronalnego
Wpływ procesów starzenia
Rola procesów zapalnych i immunologicznych
Hipoteza przetrwałego zakażenia wirusem polio
Zaburzenia metaboliczne i mitochondrialne

Mechanizmy komórkowe w zespole post-polio

Zmiany w jednostkach motorycznych

Czynniki ryzyka i predyktory zespołu post-polio
Implikacje kliniczne patogenezy zespołu post-polio
Podsumowanie obecnego stanu wiedzy

Kolejne rozdziały

Wprowadzenie do zespołu post-polio

Zespół post-polio (ang. Post-polio syndrome, PPS) to zaburzenie neurologiczne charakteryzujące się nawrotem lub pogorszeniem objawów choroby neuronu ruchowego, pojawiające się po dekadach od przebycia ostrego porażennego zakażenia wirusem polio (poliomyelitis). Objawy zespołu post-polio zazwyczaj rozwijają się 15-40 lat po przebytym zakażeniu pierwotnym.¹²³ Według danych epidemiologicznych, zespół post-polio dotyka około 25-40% osób, które przeżyły ostre porażenne poliomyelitis, choć nowsze badania wskazują, że objawy zespołu post-polio mogą występować nawet u ponad 80% osób po przebytym polio.⁴⁵

Zespół post-polio charakteryzuje się szeregiem objawów, w tym postępującym osłabieniem mięśni, zanikiem mięśni, bólem mięśni i stawów, a także znacznym zmęczeniem. Unikatową cechą odróżniającą zespół post-polio od innych chorób neuronu ruchowego jest jego historia naturalna, odpowiadająca klinicznemu nawrotowi objawów po zakażeniu wirusem polio przebytym w dzieciństwie.⁶⁷

Patogeneza zespołu post-polio

Dokładny mechanizm powstawania zespołu post-polio pozostaje nieznany, pomimo wielu lat badań. Istnieje kilka wiodących teorii próbujących wyjaśnić patogenezę tego schorzenia, z których najszerzej akceptowaną jest teoria „zmęczenia neuronalnego”.⁸^1″>9

Teoria zmęczenia neuronalnego

Teoria zmęczenia neuronalnego zakłada, że podczas ostrej infekcji wirusem polio dochodzi do zniszczenia znacznej części neuronów ruchowych w rogach przednich rdzenia kręgowego i jądrach ruchowych pnia mózgu. W odpowiedzi na to uszkodzenie, przetrwałe neurony ruchowe tworzą nowe rozgałęzienia aksonalne (sprouting aksonalny), aby przejąć funkcję utraconych neuronów i reinnerwować zdenerwowane włókna mięśniowe.¹⁰¹¹

Ten proces przebudowy prowadzi do zwiększenia rozmiaru jednostek ruchowych – pojedynczy neuron ruchowy zaopatruje większą liczbę włókien mięśniowych niż fizjologicznie. Rozrost jednostek ruchowych powoduje zwiększenie obciążenia metabolicznego ciała komórki nerwowej, która musi odżywiać rozgałęzione włókna. Po latach tego nadmiernego obciążenia, neurony ruchowe nie są w stanie utrzymać wszystkich swoich rozgałęzień aksonalnych, co prowadzi do ich degeneracji, a ostatecznie do śmierci samego neuronu.¹²¹³

Badania elektrofizjologiczne, w tym elektromiografia (EMG) i elektromiografia jednego włókna (SFEMG), potwierdzają tę teorię, wskazując, że największe jednostki ruchowe stają się niestabilne wraz z upływem czasu od ostrego zakażenia polio. W miarę postępu choroby dochodzi do zwiększenia drżenia (jittering) i blokowania przewodnictwa w obrębie połączeń nerwowo-mięśniowych.¹⁴¹⁵

Wpływ procesów starzenia

Inną istotną teorią jest wpływ normalnego procesu starzenia się układu nerwowego na osłabione neurony. Zgodnie z tą teorią, neurony, które przetrwały ostre zakażenie polio, ulegają szybszej degeneracji związanej z wiekiem niż neurony osób, które nigdy nie przebyły polio.¹⁶²

Warto jednak zauważyć, że samo starzenie się nie może w pełni wyjaśnić rozwoju zespołu post-polio, ponieważ normalny proces utraty komórek ruchowych przednich rogów rdzenia kręgowego i jednostek motorycznych nie staje się istotny przed 60. rokiem życia, podczas gdy zespół post-polio pojawia się często wcześniej.¹³

Uważa się, że denerwacja i reinerwacja są procesami ciągłymi, jednak gdy proces reinerwacji osiąga swoją górną granicę i nie może już kompensować postępującej denerwacji, dochodzi do utraty jednostek motorycznych i pojawienia się objawów klinicznych.⁸

Rola procesów zapalnych i immunologicznych

Kolejną rozważaną teorią patogenezy zespołu post-polio jest udział procesów zapalnych i autoimmunologicznych. Badania wykazały obecność zmian zapalnych w rdzeniu kręgowym pacjentów z zespołem post-polio oraz podwyższony poziom cytokin prozapalnych (TNF-alfa, IFN-gamma, IL-4, IL-10) w płynie mózgowo-rdzeniowym.¹⁴¹⁷

W badaniu Pezeshkpoura i Dalakasa wykazano zmiany zapalne w rdzeniach kręgowych siedmiu pacjentów z zespołem post-polio, co stanowi najsilniejsze poparcie dla zapalnego lub immunologicznego mechanizmu rozwoju tego zespołu.¹⁴

Badania proteomiczne wykazały zwiększone stężenie fragmentów białek i białek związanych z procesami zapalnymi oraz mechanizmami śmierci komórkowej, takimi jak apoptoza, w płynie mózgowo-rdzeniowym pacjentów z zespołem post-polio. Sugeruje to możliwość późnej nieprawidłowej odpowiedzi na pierwotne zakażenie lub utrzymującą się odpowiedź immunologiczną spowodowaną przetrwałymi cząstkami wirusa lub odpowiedź immunologiczną na proces neurodegeneracyjny wywołany innymi czynnikami.¹⁷¹⁸

Hipoteza przetrwałego zakażenia wirusem polio

Jedna z pierwotnych teorii sugerowała, że zespół post-polio jest spowodowany reaktywacją utajonego wirusa polio w organizmie, podobnie jak półpasiec jest reaktywacją wirusa ospy wietrznej. Teoria ta została jednak w dużej mierze zdyskredytowana przez badania laboratoryjne, które nie wykazały obecności aktywnego wirusa polio w organizmie pacjentów z zespołem post-polio.¹⁹²⁰

Badania Shariefa i współpracowników wykazały obecność przeciwciał klasy IgM przeciwko wirusowi polio oraz komórek uczulonych na wirusa polio w płynie mózgowo-rdzeniowym pacjentów z zespołem post-polio. Jednakże nie znaleziono jednoznacznych dowodów na obecność wirusa polio w płynie mózgowo-rdzeniowym tych pacjentów.²¹

Zaburzenia metaboliczne i mitochondrialne

Inna teoria zakłada, że pierwotne zakażenie wirusem polio uszkadza części dolnego mózgu, w tym potencjalnie wzgórze i podwzgórze. To zaburzenie wpływa na hormony kontrolujące metabolizm mięśni, prowadząc do zaburzenia metabolicznego podobnego do choroby mitochondrialnej, powodującego ból mięśni i uszkodzenia (poprzez rabdomiolizę), a także zmęczenie.²²

Teoria ta zakłada, że główne objawy zespołu post-polio są wynikiem zakłócenia działania mitochondriów w mięśniach i potencjalnie w nerwach. Istotnym argumentem przemawiającym za teorią zaburzeń mitochondrialnych jest to, że wyjaśnia ona objawy zmęczenia i trudności poznawcze („mgła mózgowa”), które zwykle towarzyszą zespołowi post-polio, lepiej niż teoria zmęczenia neuronalnego.²²

Mechanizmy komórkowe w zespole post-polio

W celu zrozumienia mechanizmów zespołu post-polio na poziomie komórkowym przeprowadzono szereg badań, w tym:²³

Badania histopatologiczne przekrojów rdzenia kręgowego pacjentów, którzy zmarli od 9 dni do 44 lat po ostrym porażennym poliomyelitis
Badania histochemiczne, immunocytochemiczne (dla podtypów limfocytów, antygenów MHC i N-CAM) oraz reakcje łańcuchowej polimerazy (PCR) w poszukiwaniu RNA wirusa polio w biopsjach mięśni pacjentów z objawowym lub bezobjawowym zespołem post-polio
Określenie podtypów limfocytów i krążących przeciwciał IgG lub IgM przeciwko GM1 i wirusowi polio
Badania wirusologiczne płynu mózgowo-rdzeniowego w kierunku prążków oligoklonalnych i poszukiwanie genomu wirusa polio za pomocą PCR
Badania elektrofizjologiczne, w tym elektromiografia włókna pojedynczego, gęstość włókien i makro-EMG
Spektroskopia rezonansu magnetycznego [31P] podczas wysiłku na wcześniej zajętych mięśniach w celu poszukiwania metabolicznego korelatu zmęczenia²³

Badania te wykazały, że w zespole post-polio występuje utrzymująca się dysfunkcja neuronów ruchowych w rdzeniu kręgowym, prowadząca do postępującej denerwacji mięśni i reinerwacji, widoczna najpierw w miejscach rozgałęzienia aksonów. Objawy związane są z wyczerpaniem się nadmiernie rozgałęzionych neuronów ruchowych, które po pewnym czasie nie mogą utrzymać wszystkich swoich rozgałęzień aksonalnych, co prowadzi do niepowodzenia ponownej reinerwacji.²⁴

U niektórych pacjentów z zespołem post-polio występuje również utrzymująca się aktywacja immunologiczna i obecność wadliwych cząstek wirusowych w płynie mózgowo-rdzeniowym, jednak ich rola w patogenezie zespołu post-polio pozostaje obecnie nieznana.²⁴

Zmiany w jednostkach motorycznych

Badania elektrofizjologiczne wykazały, że pacjenci, u których rozwijają się objawy zespołu post-polio, wykazują cechy ciężkiej choroby w przeszłości, w tym zmniejszenie liczby i reorganizację jednostek motorycznych. W badaniach elektromiograficznych obserwuje się cechy rozległej denerwacji i reinerwacji, wskazujące na przebyte poliomyelitis, oraz potencjały czynnościowe dużych jednostek motorycznych o zmniejszonej liczbie, co jest spójne z utratą wielu neuronów ruchowych i zwiększeniem terytorium włókien mięśniowych unerwianych przez pozostałe neurony.¹⁵

Elektromiografia krtani pacjentów wykazała ścieńczenie zapisu i obecność potencjałów o dużej amplitudzie i długości, wskazujących na wcześniejsze uszkodzenie neuronów, z reinerwacją i zwiększeniem terytorium pozostałych jednostek motorycznych.¹⁵

Czynniki ryzyka i predyktory zespołu post-polio

Nie jest jasne, dlaczego tylko niektóre osoby, które przebyły polio, rozwijają zespół post-polio. Jednak osoby, które miały ciężkie polio we wczesnym okresie życia, mogą być bardziej narażone na rozwój tego schorzenia.³

Ryzyko rozwoju zespołu post-polio jest większe u osób, które:¹⁷¹⁸

Miały cięższe objawy podczas ostrego zakażenia polio
Miały późniejszy początek polio (po wieku 10 lat)
Wymagały wentylacji mechanicznej podczas ostrej choroby
Doświadczyły większego stopnia paraliżu w czasie ostrej infekcji
Osiągnęły większy stopień powrotu do funkcji po ostrym okresie
Są płci żeńskiej (zespół post-polio częściej występuje u kobiet)

Badania epidemiologiczne wykazały również wyższe ryzyko zespołu post-polio wśród imigrantów z regionów pozaeuropejskich, szczególnie z Afryki i Azji, co może być związane z większym rozpowszechnieniem polio w tych regionach.²⁵

Implikacje kliniczne patogenezy zespołu post-polio

Zrozumienie patogenezy zespołu post-polio ma istotne znaczenie dla opracowania strategii terapeutycznych. Obecnie nie istnieje leczenie przyczynowe zespołu post-polio, a postępowanie koncentruje się na łagodzeniu objawów i poprawie funkcji poprzez minimalizowanie nadmiernego stresu metabolicznego mięśni.²⁶

Dowody sugerują, że w celu leczenia nowego osłabienia u pacjentów z zespołem post-polio wymagane są nadzorowane programy treningowe. Aktywność fizyczna, fizjoterapia i trening mięśniowy stanowią podstawę postępowania u pacjentów z zespołem post-polio, ale można również korzystać z pomocy innych specjalistów klinicznych.²⁵²⁶

Znalezienie skutecznych metod leczenia wymaga dalszych badań nad mechanizmami patogenetycznymi zespołu post-polio. Szczególnie obiecujące są badania nad rolą procesów zapalnych i autoimmunologicznych, które mogą prowadzić do opracowania terapii immunomodulujących.²⁷

Podsumowanie obecnego stanu wiedzy

Pomimo wielu lat badań, dokładny mechanizm powstawania zespołu post-polio pozostaje nieznany. Najszerzej akceptowana teoria „zmęczenia neuronalnego” zakłada, że ostre zakażenie wirusem polio prowadzi do zniszczenia neuronów ruchowych, co wywołuje kompensacyjny rozrost pozostałych neuronów i ich przekształcenie w większe jednostki motoryczne. Z czasem te powiększone jednostki motoryczne ulegają degeneracji z powodu nadmiernego obciążenia metabolicznego.²⁸²⁹

Inne proponowane mechanizmy obejmują procesy starzenia się, zaburzenia autoimmunologiczne, przetrwałe zakażenie wirusowe oraz zaburzenia metaboliczne. Prawdopodobnie w patogenezie zespołu post-polio uczestniczy kilka nakładających się mechanizmów.³⁰

Zrozumienie mechanizmów zespołu post-polio ma kluczowe znaczenie dla opracowania skutecznych strategii terapeutycznych. Chociaż obecnie nie ma leczenia przyczynowego, postępowanie objawowe, w tym kontrolowana aktywność fizyczna, fizjoterapia i leczenie bólu, może znacząco poprawić jakość życia pacjentów z zespołem post-polio.³¹³²

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Materiały źródłowe

#1 Post-Polio Syndrome Revisited
https://www.mdpi.com/2035-8377/15/2/35
Post-polio syndrome (PPS) is characterized by recrudescence or worsening of motor neuron disease symptoms decades after recovery from acute paralytic poliovirus infection, i.e., poliomyelitis. […] PPS mimics MND due to its relatively selective impairment, degeneration, or death of motor neurons in the spinal cord and brainstem. The mechanism of PPS is not well understood. Potential etiologies include: (1) re-awakening of underlying pathologies that had been masked by repair and recovery but rendered weakened due to aging-associated neuronal and fiber attrition; and (2) prior poliomyelitis causes epigenetic changes that increase vulnerability to sporadic MND. […] Although it is widely accepted that PPS is causally linked to an earlier bout of poliomyelitis, the mechanism driving the recrudescence of motor neuron disease symptoms and neurodegeneration remains unknown. One potential consideration is that compensatory responses leading to recovery from poliomyelitis or stabilization of symptoms decompensate over time, particularly with aging.
#2 Post-Polio Syndrome – Harvard Health
https://www.health.harvard.edu/a_to_z/post-polio-syndrome-a-to-z
Post-polio syndrome is an illness defined by a collection of symptoms that generally occur at least 10-20 years after infection with the polio virus. The hallmark of post-polio syndrome is new muscular weakness. […] One theory is overuse of the nerves and muscles that remained working after the initial infection. For example, if some of the nerves and muscles that are necessary for leg strength are damaged, the remaining nerves and muscles of the legs need to work harder to compensate. After many years of having to work harder, these nerves and muscles become exhausted. Some of them even die. This then forces the nerves and muscles that are left to work even harder, and so a vicious cycle sets in. […] Normal aging likely also contributes to new weakness. Nervous system damaged by polio years earlier goes through a natural aging process that includes the loss of some strength. […] One theory for post-polio syndrome is that some of the poliovirus remains alive in the brain and spinal cord. This theory is controversial.
#3
https://www.nhs.uk/conditions/post-polio-syndrome/
Post-polio syndrome is where some of these symptoms develop or get worse many years or decades after the original polio infection. […] The leading theory is that it’s the result of the gradual deterioration of nerve cells in the spinal cord (motor neurones) that were damaged by the polio virus. This would explain why the condition can take years to appear. […] It’s not clear why only some people who have had polio develop post-polio syndrome. However, those who had severe polio when they were younger may be more likely to develop the condition.
#4 POST POLIO SYNDROME – WILDROSE POLIO SUPPORT SOCIETY
https://polioalberta.ca/home/post-polio-syndrome/
Post-polio syndrome (PPS, or post-poliomyelitis syndrome or post-polio sequelae) is a condition that affects approximately 25 to 40 percent of people who have previously survived an acute attack of poliomyelitis, though more recent studies have shown that 80+% of polio survivors show symptoms of Post Polio Sequelae. The precise mechanism that causes PPS is unknown. The most widely accepted theory of the mechanism behind the disorder is neural fatigue. Poliovirus attacks specific neurons in the brainstem and the anterior horn cells of the spinal cord, generally resulting in the death of a substantial fraction of the motor neurons controlling skeletal muscles. The neural fatigue theory proposes that the enlargement of the motor neuron fibers places added metabolic stress on the nerve cell body to nourish the additional fibers. After years of use, this stress may be more than the neuron can handle, leading to the gradual deterioration of the sprouted fibers and, eventually, the neuron itself. Another theory is that people who have recovered from polio lose remaining healthy neurons at a faster rate than normal. However, little evidence exists to support this idea. Finally, it has been proposed that the initial polio infection causes an autoimmune reaction, in which the body’s immune system attacks normal cells as if they were foreign substances.
#5 The legacy of polio: 2 cases of post-polio syndrome and review
http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442022000300097
Post-polio syndrome (PPS) is a neurological disorder affecting 20-40% of paralytic and nonparalytic polio survivors, characterized by a range of neuromuscular manifestations that occur years after initial infection with poliovirus. […] The etiology and pathogenesis of PPS is unknown. It has been hypothesized that the new weakness appears to be related to degeneration of individual nerve terminals in motor units. The overuse of these motor units for years generates an overload that eventually leads them to lose their ability to respond, producing a slow deterioration which leads to a reduction in muscle strength. […] It is probably an effect of motor neuron damage during acute poliovirus infection that leads to overloading and degeneration of the remaining motor neurons in the frontal horns of the spinal column.
#6 Post-Polio Syndrome Revisited
https://pmc.ncbi.nlm.nih.gov/articles/PMC10123742/
Post-polio syndrome (PPS) is characterized by recrudescence or worsening of motor neuron disease symptoms decades after recovery from acute paralytic poliovirus infection, i.e., poliomyelitis. […] PPS uniquely differs from sporadic or primary MND due to its natural history corresponding to what is regarded as a clinical recrudescence of a childhood poliovirus CNS infection. […] The mechanism of PPS is not well understood. Potential etiologies include: (1) re-awakening of underlying pathologies that had been masked by repair and recovery but rendered weakened due to aging-associated neuronal and fiber attrition; and (2) prior poliomyelitis causes epigenetic changes that increase vulnerability to sporadic MND. […] Although it is widely accepted that PPS is causally linked to an earlier bout of poliomyelitis, the mechanism driving the recrudescence of motor neuron disease symptoms and neurodegeneration remains unknown.
#7 What are the Late Effects of Polio / Post-Polio Syndrome? â Polio Australia â Polio Health
https://www.poliohealth.org.au/late-effects-of-polio/
Years after contracting the initial polio infection, increasing numbers of polio survivors in Australia have developed a range of symptoms, now recognised as post-polio sequelae. […] The post-polio sequelae cause a range of debilitating health effects, and manifest primarily as biomechanical and neurological symptoms. The condition is referred to broadly as the Late Effects of Polio (LEoP) or, in circumstance where specific clinical diagnostic criteria are satisfied, as post-polio syndrome (PPS). […] PPS is a diagnosed neurological condition which will affect up to 40% (depending on the study) of people who had âparalyticâ polio. The main symptom of PPS is new muscle weakness that gradually worsens. […] The broader condition known as the Late Effects of Polio takes in both PPS and a host of additional âbio-mechanicalâ symptoms including: scoliosis; kyphosis; respiratory problems; dysphagia (swallowing difficulties); muscle contraction; head, neck and joint aches; chronic tendonitis; bursitis; nerve compression; osteoporosis; arthritis; and fatigue; many of which will impact on virtually every survivor of polio.
#8 Post-polio syndrome – Wikipedia
https://en.wikipedia.org/wiki/Post-polio_syndrome
Post-polio syndrome (PPS) is a group of latent symptoms of poliomyelitis (polio), occurring in more than 80% of polio infections. The precise mechanism that causes PPS is unknown. […] The most widely accepted theory of the mechanism behind the disorder is „neural fatigue”. […] The neural fatigue theory proposes that the enlargement of the motor neuron fibers places added metabolic stress on the nerve cell body to nourish the additional fibers. […] Denervation and reinnervation are going on, but the reinnervation process has an upper limit where the reinnervation cannot compensate for the ongoing denervation, and loss of motor units takes place. […] Another theory is that people who have recovered from polio lose remaining healthy neurons at a faster rate than normal. […] Finally, the initial polio infection is thought to cause an autoimmune reaction, in which the body’s immune system attacks normal cells as if they were foreign substances.
#10 Post-polio syndrome – Symptoms & causes – Mayo Clinic
https://www.mayoclinic.org/diseases-conditions/post-polio-syndrome/symptoms-causes/syc-20355669
Post-polio syndrome is a group of potentially disabling signs and symptoms that appear decades after the initial polio illness. […] There are several theories as to what causes post-polio syndrome, but no one knows for sure. […] A polio infection often damages or destroys many of these motor neurons. Because there are fewer motor neurons, the remaining neurons sprout new fibers and grow bigger. […] This promotes recovery of the use of your muscles, but it also may stress the nerve cell body to nourish the additional fibers. Over the years, this stress may be too much. This may cause the gradual breakdown of the sprouted fibers and, eventually, of the neuron itself.
#11 Post-Polio Syndrome: What It Is, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/24584-post-polio-syndrome
Post-polio syndrome (PPS) is a condition that causes gradual muscle weakness and muscle atrophy (loss) that can affect people whove had polio. PPS usually happens 10 to 40 years after youve recovered from the initial polio infection. […] Scientists dont yet know the cause of post-polio syndrome. One theory is that it could be due to the recovery from the initial polio infection. During recovery from polio, nerve cells (neurons) in the affected muscles may regrow many smaller branches (dendrites) from the large branches (axons) of nerve cells. These dendrites take over the function of neurons that the polio virus killed. […] Scientists think that, after years of functioning beyond their capacity, the nerve cells weaken and lose their ability to maintain the dendrites. The dendrites then shrink, and the whole muscle becomes weaker.
#12 Post-Polio Syndrome Revisited
https://www.mdpi.com/2035-8377/15/2/35
The extraordinarily high rate of PPS among survivors of acute poliomyelitis speaks volumes for factors related to the initial infection or mechanisms of recovery as key pathogenic mediators of PPS-associated neurodegeneration. One popular theory known as âneural fatigueâ infers that acute poliovirus infections target and kill specific spinal anterior horn cells and brainstem motor nuclei. Functional recovery is mediated by the neuritic sprouting of surviving motor neurons with attendant re-innervation of denervated skeletal muscle. The degrees to which re-innervation is effective may dictate resultant levels of strength. However, re-innervation sprouting leads to the enlargement of motor units, adding metabolic stress to remaining motor neurons. Chronically increased metabolic stress could eventually trigger a second wave of neurodegeneration and disability, corresponding with the emergence of PPS. […] Therefore, intrinsic neuronal stress related to recovery-induced expansion of the motor unit plus aging, could account for the development of PPS in long-term survivors of poliomyelitis.
#13 Post-polio syndrome | MedLink Neurology
https://www.medlink.com/articles/post-polio-syndrome
The most likely cause of post-polio syndrome is degeneration of enlarged motor units. […] It is now recognized that normal aging alone cannot explain the development of post-polio syndrome because the normal loss of anterior horn cells and motor units does not become prominent until after age 60. […] The presently accepted most likely etiologic possibility is the degeneration of enlarged motor units; however, alternative considerations include a chronic persistent poliovirus infection or an immune-mediated disease. […] After acute poliomyelitis, remaining motor neurons send out sprouts to take over degenerated muscle fibers (collateral sprouting). This results in enlarged motor units, five to 10 times larger than normal. […] On average, 30 to 40 years after acute poliomyelitis, there is disintegration of the new terminal sprouts that formed after the acute infection.
#14 Post-polio syndrome | MedLink Neurology
https://www.medlink.com/articles/post-polio-syndrome
Findings from single fiber electromyographic (SFEMG) studies reveal that the largest motor units are more likely to become unstable later in life, and with increasing time from the acute polio, neuromuscular transmission becomes more unstable, as increased jitter and blocking occur. […] The overuse of weakened muscles results in excessive muscular fatigue, which appears to contribute to the excessive metabolic demand on motor neurons and the premature exhaustion. […] The strongest support for an inflammatory or immune-mediated mechanism for post-polio syndrome stems from the study of Pezeshkpour and Dalakas in which inflammation in the spinal cords of seven post-polio patients was found. […] Studies support an immune-mediated process with the finding of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-4, IL-10) in the CSF of post-polio syndrome patients.
#15 Pharyngolaryngeal manifestations of post-polio syndrome
https://arquivosdeorl.org.br/additional/acervo_eng.asp?id=820
The most likely is that the syndrome represents a process of wear and exhaust neuronal. […] Other hypothesis consider the possibility of a continuous process of denervation-reinnervation which requires as increase of metabolic demand in the branches; with the decrease of these reserves there may be gradual loss of axonal fibers, with consequent muscular atrophy. […] Most of the electrophysiological studies shows that patients that become symptomatic years after the polio present signs of severe acute illness in the past, in other words, decreasing of number and reorganization of motor units. […] Electromyography in these patients are observed signs of extensive denervation and reinnervation, indicating previous poliomyelitis and action potentials of the large motor units and reduced in numbers, consistent finding with the loss of many motoneurons and increase of the territory of the muscle fibers innervated by neurons remaining. […] The electromyography of the patient larynx showed thinning of the trace and presence of great potentials of great amplitude and length, indicating earlier neuronal commitment, with reinnervation and increase of the territory of remaining motor units.
#16 Post-polio syndrome pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Post-polio_syndrome_pathophysiology
The precise mechanism that causes post-polio syndrome is unknown. […] Studies have shown that, compared to control populations, PPS patients lack any elevation of antibodies against the poliovirus, and because no poliovirus is excreted in the feces, it is not considered a recurrence of the original polio. Further, there is no evidence that the poliovirus can cause a persistent infection in humans. […] Several theories have been proposed to explain post-polio symptoms. One theory of the mechanism behind the disorder is that it is due to „neural fatigue” from overworked neurons. The original polio infection generally results in the death of a substantial fraction of the motor neurons controlling skeletal muscles, and the theory is that the remaining neurons are thus overworked and eventually wear out.
#17 POST-POLIO SYNDROME REPORT OF TWO CASES
http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S2462-85222018000200145
Furthermore, persistent inflammatory changes since the presentation of the initial picture during childhood have been described, considering that there has been an increase in several cytokines, mainly proinflammatory such as INF- and TNF, both in the spinal cord and in the CSF of patients with PPS. […] Recent proteomics research show increased concentrations of protein fragments and proteins related to inflammation and cell death mechanisms, such as apoptosis, in the CSF of patients with PPS. A possibility is raised of a late aberrant response to the original infection or a persistent immune response due to the persistence of viral particles or an immune response to a neurode-generative process caused by other factors.
#17 POST-POLIO SYNDROME REPORT OF TWO CASES
http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S2462-85222018000200145
Post-polio syndrome (PPS) is a neurological syndrome that appears decades after an acute episode of polio. This condition decreases functional capacity until completing affecting daily activities. This event occurs in 20-80% of the people who were affected by the polio virus. It is more frequent in women and a direct correlation between the risk of developing this syndrome and the severity of the sequelae of polio has been reported. […] The term post-polio syndrome (PPS) was finally established around the 1980’s. […] Although this is a little known entity, PPS can affect between 20% and 85% of the population with new neuromuscular symptoms that occur at least 15 years after achieving stability in patients with previous acute paralytic poliomyelitis. […] Other neurological, medical or traumatic causes that explain the clinical picture should be excluded, and some exclusion criteria should be considered, such as symptoms secondary to oropharyngeal or respiratory complications, structural radiculopathies, compressive neuropathies, degenerative arthropathies, joint instability, scoliosis and psychopathological symptoms such as anxiety syndrome, depression and sleep disorders.
#18 POST-POLIO SYNDROME REPORT OF TWO CASES
https://www.redalyc.org/journal/5609/560959323009/html/
Recent proteomics research show increased concentrations of protein fragments and proteins related to inflammation and cell death mechanisms, such as apoptosis, in the CSF of patients with PPS. A possibility is raised of a late aberrant response to the original infection or a persistent immune response due to the persistence of viral particles or an immune response to a neurode-generative process caused by other factors. […] Current studies seek to determine if there is an immunological component in PPS, since evidence has shown a correlation with the immune response to inflammation around motor neurons or muscle fibers.
#18 POST-POLIO SYNDROME REPORT OF TWO CASES
https://www.redalyc.org/journal/5609/560959323009/html/
Post-polio syndrome (PPS) is a neurological syndrome that appears decades after an acute episode of polio. This condition decreases functional capacity until completing affecting daily activities. This event occurs in 20-80% of the people who were affected by the polio virus. It is more frequent in women and a direct correlation between the risk of developing this syndrome and the severity of the sequelae of polio has been reported. […] The psychological and functional impact of this disease on patients is regarded as a challenge for the health professional, since clinical needs must be identified and current barriers care reduced. […] Although this is a little known entity, PPS can affect between 20% and 85% of the population with new neuromuscular symptoms that occur at least 15 years after achieving stability in patients with previous acute paralytic poliomyelitis.
#19 Post-polio syndrome pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Post-polio_syndrome_pathophysiology
One significant argument in favor of the mitochondrial disruption theory is that it explains the fatigue and cognitive difficulties („brain fog”) symptoms that usually accompany post-polio better than the neural fatigue theory does. […] Damage to the reticular activating system and related areas such as the thalamus can also produce most of the fatigue, „brain fog”, and dysautonomia symptoms of post-polio, and may be able to cause hormonal changes that result in progressive muscle weakness. […] An early theory stated that PPS is caused by reactivation of latent polio virus in the body, similar to the way that shingles is a reactivation of the chicken pox virus. This theory has been discredited by laboratory studies that show no active polio virus in the body.
#20 Chapter 18: Poliomyelitis | Pink Book | CDC
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-18-poliomyelitis.html
The virus enters through the mouth and multiplies in the oropharynx and gastrointestinal tract. […] Poliovirus-induced destruction of motor neurons of the anterior horn of the spinal cord and brain stem cells results in distinctive paralysis. […] After an interval of 15 to 40 years, 25% to 40% of persons who contracted paralytic poliomyelitis in childhood experience new muscle pain and exacerbation of existing weakness or develop new weakness or paralysis. This disease entity is referred to as post-polio syndrome. Post-polio syndrome is not an infectious process, and persons experiencing this syndrome do not shed poliovirus.
#21 The legacy of polio: 2 cases of post-polio syndrome and review
http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1665-50442022000300097
More than 50% death must occur in the anterior horn neuron population before weakness can be detected clinically. EMG studies suggest that many of the clinically unaffected muscles were sub-clinically involved during the acute episode of the disease. This hypothesis explains why PPS occurs after so many years and has a slow progressive course. […] Sharief et al. demonstrated the presence of immunoglobulin M antibodies against poliovirus and cells sensitized to poliovirus in the cerebrospinal fluid (CSF) of patients with PPS. However, no conclusive evidence of CSF poliovirus has been found in such patients. […] In addition, histopathological damage to the reticular activation system has been demonstrated in patients with PPS, which is probably related to cognitive performance impairment and chronic fatigue syndrome.
#22 Post-polio syndrome pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Post-polio_syndrome_pathophysiology
Another theory holds that the original viral infection damages portions of the lower brain, possibly including the thalamus and hypothalamus. This somehow upsets the hormones that control muscle metabolism, and the result is a metabolic disorder similar to mitochondrial disorder that causes muscle pain and injury (via rhabdomyolysis) and also causes the fatigue. […] The most widely accepted theory is the „neural fatigue” one. Motor neuron fibers were originally damaged by the polio virus and were subsequently over-stressed because too few surviving neurons activated too many muscles. Eventually these neurons become fatigued and die, leading to the slowly advancing loss of muscle function that is typical of post-polio. […] This theory assumes that the major symptoms of PPS are a result of some interference with the action of mitochondria in the muscles and possibly the nerves.
#23 Pathogenetic mechanisms of post-polio syndrome: morphological, electrophysiological, virological, and immunological correlations – PubMed
https://pubmed.ncbi.nlm.nih.gov/7611626/
To understand the mechanism of post-poliomyelitis muscular atrophy (PPMA) and the post-polio syndrome (PPS) in general, we performed the following studies: (1) histopathology in spinal cord sections from patients who died 9 days to 44 years after acute paralytic poliomyelitis; (2) enzyme histochemistry, immunocytochemistry (for lymphocyte subsets, MHC antigens and N-CAM) and polymerase chain reaction (PCR) for poliovirus RNA in the muscle biopsies from symptomatic or asymptomatic muscles of post-polio patients; (3) determination of lymphocyte subsets and circulating IgG or IgM antibodies against GM1 and poliovirus; (4) virological studies in the spinal fluid for oligoclonal bands and search for poliovirus genome with PCR; (5) electrophysiological studies including single fiber EMG, fiber density and macro-EMG; and (6) [31P] exercise MRS spectroscopy on previously affected muscles to search for a metabolic correlate of fatigue.
#24 Pathogenetic mechanisms of post-polio syndrome: morphological, electrophysiological, virological, and immunological correlations – PubMed
https://pubmed.ncbi.nlm.nih.gov/7611626/
These studies concluded that in PPS a continuing dysfunction is present in the spinal cord motor neurons, resulting in ongoing muscle denervation and reinnervation first evident at the axonal branch points. Symptoms are related to attrition of the oversprouting motor neurons which after a period of time cannot support all their axonal sprouts, resulting in failure of re-reinnervation. […] In some patients with PPS there is also an ongoing immune activation and presence of defective viral particles in the spinal fluid. However, their role in the pathogenesis of PPS is presently unknown.
#25 The risk of post-polio syndrome among immigrant groups in Sweden | Scientific Reports
https://www.nature.com/articles/s41598-023-33240-w
A higher relative risk in immigrants from non-Western regions are in line with our hypothesis and with earlier results, as polio has been present to a higher extent in those regions of the world, while polio is rather rare in Western regions, i.e., Europe and North America ever since the vaccination programs started in the 50ies and 60ies. […] Identifying patients with PPS is important, to be able to give treatment, even if no specific treatment exists. […] However, physical activity, physiotherapy, and muscle training are the basis of the management of PPS patients, but assistance from other clinical specialists could also be used. […] It is important for public health planners to be aware of that polio still exists in the world, and to continue to vaccinate Swedish children, and that post-polio cases will continue to emerge in Sweden.
#26 Post-polio syndrome presenting as isolated neck extensor myopathy: a case report – Chu – AME Case Reports
https://acr.amegroups.org/article/view/7667/html
INEM is one of the probable causes of head ptosis due to isolated myopathic changes resulting from chronic injury and overloading of the cervical extensor muscles. […] Our interpretation of this association is that polio left our patient with right leg weakness, a length discrepancy, and pelvic obliquity, which led to asymmetric axial loading, scoliosis, and imbalanced core muscles. Overuse and fatigue of the cervical paraspinal muscles (neck extensors) contributed to the inability of the patient to maintain an erect head position. […] There are currently no established regimens that can prevent the deterioration of PPS. Generally, the overall goal of the management of PPS is symptomatic, aiming to reduce pain and improve function by minimizing the excessive metabolic stress on the muscles. Evidence suggests that in order to treat new weakness in patients with PPS, supervised training programs are required.
#27 Post-Polio Syndrome: Symptoms, Treatment, and Outlook
https://www.healthline.com/health/post-polio-syndrome
Poliomyelitis (polio) is a severe and potentially life threatening condition caused by the poliovirus. If you had a polio infection as a child and have since recovered, its still possible to develop a complication called post-polio syndrome (PPS). […] The exact cause of PPS is unknown. Experts think PPS may develop as a result of stress on motor neurons from a previous polio infection. While you might recover from the initial infection, you may still experience a gradual deterioration of these neurons. […] Currently, theres no known treatment for PPS. Damage to the affected neurons is irreversible. […] While the exact cause of PPS is unknown, research is ongoing to discover concrete risk factors, including possible immunological links. This could mean earlier detection of PPS and possible treatments in the future.
#28 Post-Polio Syndrome Revisited
https://pmc.ncbi.nlm.nih.gov/articles/PMC10123742/
The extraordinarily high rate of PPS among survivors of acute poliomyelitis speaks volumes for factors related to the initial infection or mechanisms of recovery as key pathogenic mediators of PPS-associated neurodegeneration. […] However, re-innervation sprouting leads to the enlargement of motor units, adding metabolic stress to remaining motor neurons. Chronically increased metabolic stress could eventually trigger a second wave of neurodegeneration and disability, corresponding with the emergence of PPS. […] Therefore, intrinsic neuronal stress related to recovery-induced expansion of the motor unit plus aging, could account for the development of PPS in long-term survivors of poliomyelitis. […] A final consideration is whether PPS is actually a form of MND, including ALS or progressive muscular atrophy (PMA). This notion is supported by the overlapping symptoms in PPS and ALS or PMA.
#29 What is Post-Polio Syndrome? – Post Polio
https://post-polio.org/education/what-is-post-polio-syndrome/
Post-polio syndrome is a condition that affects the survivors of polio decades after the acute illness of poliomyelitis. The major symptoms are pain, fatigue and weakness. New weakness is considered the hallmark of post-polio syndrome. […] What causes post-polio syndrome? In the early years, there was some speculation that the cause might be a „recurrence” of polio or reactivation of the poliovirus, which is not the case. The generally accepted theory is best demonstrated by the following diagrams. […] Wiechers and Hubbell proposed that these new sprouts are not indefinitely stable…but rather degenerate over time due to an „overexertion” phenomenon resulting once again in muscle fibers that no longer contract, which a survivor recognizes as new weakness and loss of function.
#30 Theories – Post Polio
https://post-polio.org/late_effect_polio/theories/
While there is now agreement among researchers that post-polio syndrome results from degenerative changes within motor units, the triggering mechanism(s) for these changes is/are not known. […] A favored theory to explain their onset is overuse. This theory assumes that the enlarged motor units supplying post-polio muscles cannot maintain the increased metabolic activity needed over many years. […] Other theories presented to explain the triggering mechanism(s) for motor unit degeneration include: premature aging changes of motor units that were involved but did not die from the original poliovirus infection; an immunological abnormality that may be triggered by re-exposure to live poliovirus or by reactivity of persistent poliovirus fragments in the spinal cord; scarring within the spinal cord that decreases the blood supply to motor nerve cells; environmental toxins that damage polio-involved motor nerve cells at exposure levels less than that which affect normal cells; chronic high levels of stress that affect immunology and circulating anti-oxidants; and lastly, a deficiency in growth hormone that precipitates age-related degenerative changes. […] While all of these theories are plausible and none have been completely excluded, there is not enough scientific evidence to strongly support any of them at present.
#31 The value of a post-polio syndrome self-management programme – Curtis – Journal of Thoracic Disease
https://jtd.amegroups.org/article/view/44758/html
Post-polio syndrome (PPS) is a progressive neurological condition characterised by mild to extreme symptoms of fatigue, new muscular weakness and pain that emerges decades after the acute poliomyelitis viral infection. […] The pathogenesis of PPS is still not fully understood and it has taken many years of campaigning to be widely recognised as a distinct condition within the medical community. […] A tailored self-management programme for PPS can significantly improve chronic symptoms, wellbeing, physical function and the understanding of the condition. […] Fatigue, pain, atrophy and bulbar function frequently cause problems in PPS, and all responded well to the intervention. […] Without a proven pharmacological treatment the course addresses PPS fatigue through pacing techniques, knowledge of early signs of fatigue and exercise as well as addressing acceptance of individual limitations.
#32 Polio | Post-Polio Syndrome | PPS | MedlinePlus
https://medlineplus.gov/polioandpostpoliosyndrome.html
Post-polio syndrome (PPS) is a condition that affects polio survivors many years after they recovered from polio. It usually happens 15-40 years later. It is not contagious. […] People who get PPS start having new weakening in muscles that were previously affected by the polio infection. Symptoms may range from mild to serious. The symptoms of PPS include: Muscle weakness, Muscle atrophy (wasting away of muscles), Loss of muscle function, Mental and physical fatigue, Joint pain, Curving of the spine (scoliosis). […] PPS is rarely life-threatening, but the symptoms can interfere with your daily life. […] There is no cure for PPS. Treatments may help you manage your symptoms. They include: Non-fatiguing exercises (exercises that do not cause pain or fatigue that lasts more than 10 minutes). These exercises may improve muscle strength and reduce tiredness. Your provider can help you figure out which exercises are best for you.