PoliomyelitisPoliomyelitis

PoliomyelitisPoliomyelitisDisease of semi-Disease of semi-developed societiesdeveloped societies

Occurs sporadically or in Occurs sporadically or in epidemicsepidemics

First described in Egypt, First described in Egypt, major cause of morbidity major cause of morbidity and mortality until 1960sand mortality until 1960s

Large epidemics in Large epidemics in 1940s and 1950s in the 1940s and 1950s in the developed worlddeveloped world

HISTORY• 1789 - British physician Michael Underwood provides

the first clinical description of polio, referring to it as "debility of the lower extremities.“

• 1840 - German physician Jacob von Heine published a 78-page monograph which not only describes the clinical features of the disease, but also notes that its symptoms suggest the involvement of the spinal cord.

• 1908- Austrian physicians Karl Landsteiner and Erwin Popper make the first hypothesis that polio may be caused by a virus.

The word poliomyelitis is derived from polio = The word poliomyelitis is derived from polio = gray and myel = spinal cord). gray and myel = spinal cord).

Poliomyelitis is defined as an acute febrile Poliomyelitis is defined as an acute febrile illness, usually with meningitis and flaccid illness, usually with meningitis and flaccid paralysis, but without objective evidence of a paralysis, but without objective evidence of a sensory defect or cortical damage. sensory defect or cortical damage.

Paralysis is an uncommon manifestation of viral Paralysis is an uncommon manifestation of viral CNS infection. CNS infection.

Causative VirusesCausative VirusesPoliovirusesPolioviruses 1, 2, and 3 1, 2, and 3

Nonpolio EnterovirusesNonpolio Enteroviruses - Sporadic: Coxsackievirus and Echovirus - Sporadic: Coxsackievirus and Echovirus - Epidemic: Enterovirus 71 is the only non-polio - Epidemic: Enterovirus 71 is the only non-polio serotype associated with large outbreaks (100s of serotype associated with large outbreaks (100s of cases of paralytic disease )cases of paralytic disease )

West Nile Virus West Nile Virus - This is clearly the most common cause of - This is clearly the most common cause of poliomyelitis in the United States in the past poliomyelitis in the United States in the past several years.several years.

Pathogenesis and Pathology of EnterovirusesPathogenesis and Pathology of Enteroviruses

Enteroviruses have similar pathogenesis but different Enteroviruses have similar pathogenesis but different target organs.target organs.

They inhabit the GI tract and rarely cause enteric They inhabit the GI tract and rarely cause enteric disease. disease.

The incubation period is usually between 7 and 14 The incubation period is usually between 7 and 14 days but may be as short as 2 days and as long as 35 days but may be as short as 2 days and as long as 35 days. days.

Viremia spreads the virus to involve target organs Viremia spreads the virus to involve target organs (spinal cord and brain, meninges, myocardium, skin)(spinal cord and brain, meninges, myocardium, skin)

Virus is excreted in the stools for several weeks and is Virus is excreted in the stools for several weeks and is present in the pharynx 1 to 2 weeks after infection.present in the pharynx 1 to 2 weeks after infection.

Neural spread may occur in children who have Neural spread may occur in children who have unapparent infection at the time of tonsillectomy unapparent infection at the time of tonsillectomy (bulbar paralysis).(bulbar paralysis).

The anterior horns are most prominently involved, but The anterior horns are most prominently involved, but in severe cases the intermediate gray ganglia and in severe cases the intermediate gray ganglia and even the posterior horns and dorsal root ganglia are even the posterior horns and dorsal root ganglia are often affected.often affected.

Viral rather than immunopathology is responsible for Viral rather than immunopathology is responsible for disease manifestations.disease manifestations.

Clinical SyndromesClinical SyndromesAsymptomatic Infection: Asymptomatic Infection: The most common form The most common form (>90%) of infection.(>90%) of infection.

Symptomatic Illness: Symptomatic Illness: Less than 10% of infections Less than 10% of infections result in a recognized clinical illness.result in a recognized clinical illness.

Abortive Poliomyelitis (minor illness)Abortive Poliomyelitis (minor illness)

- The most common form of the diseaseThe most common form of the disease (5%) (5%). . - The patient has only a minor illness, characterized by The patient has only a minor illness, characterized by

fever, malaise, drowsiness, headache, nausea, fever, malaise, drowsiness, headache, nausea, vomiting, constipation, or sore throat in various vomiting, constipation, or sore throat in various combinations. The patient recovers in a few days.combinations. The patient recovers in a few days.

o Nonparalytic Poliomyelitis/ Aseptic MeningitisNonparalytic Poliomyelitis/ Aseptic Meningitis

- It is seen in 1-2% of infections. - It is seen in 1-2% of infections.

- Stiffness and pain in the back and neck.- Stiffness and pain in the back and neck.

- The disease lasts 2 to 10 days, and recovery is - The disease lasts 2 to 10 days, and recovery is

rapid and complete. rapid and complete.

- In a small percentage of cases, the disease - In a small percentage of cases, the disease

advances to paralysis.advances to paralysis.

Meningitis and Mild ParesisMeningitis and Mild Paresis

- The disease sometimes progresses to mild - The disease sometimes progresses to mild

muscle weakness that may be confused muscle weakness that may be confused

clinically with paralytic poliomyelitis. clinically with paralytic poliomyelitis.

- In addition to poliviruses, viruses that cause - In addition to poliviruses, viruses that cause this disease include Coxsackie B1 to B6, A7 this disease include Coxsackie B1 to B6, A7 and A9 and echoviruses 3, 4, 6, 9, 1, 14, 16, and A9 and echoviruses 3, 4, 6, 9, 1, 14, 16, 18, 19, 25, 30, 31 and 33 and rarely enterovirus 18, 19, 25, 30, 31 and 33 and rarely enterovirus 70 and 71.70 and 71.

Paralytic PoliomyelitisParalytic Poliomyelitis

- It usually occurs without an antecedent first phase. - It usually occurs without an antecedent first phase.

- The predominating sign is flaccid paralysis resulting - The predominating sign is flaccid paralysis resulting from lower motor neuron damage. from lower motor neuron damage.

- Muscle involvement is usually maximal within a few - Muscle involvement is usually maximal within a few days after the paralytic phase begins. days after the paralytic phase begins.

- The maximal recovery usually occurs within 6 months, - The maximal recovery usually occurs within 6 months, but it may take longer.but it may take longer.

- Paralytic disease is either spinal or bulbar poliomyelitis. - Paralytic disease is either spinal or bulbar poliomyelitis.

Painful muscle spasms and incoordination of non- paralysed muscles may occur

Involvement of the medulla may lead to respiratory paralysis and death

Paralysis usually develops over several days and some recovery may take place.

Any effects persisting for more than 6 months are usually permanent

Long Term SequalaeLong Term Sequalae

Among children who are paralyzed by polio:

- 30% make a full recovery

- 30% are left with mild paralysis

- 30% have medium to severe paralysis

- 10% die

Post-Poliomyelitis SyndromePost-Poliomyelitis Syndrome (PPS) (PPS)Progressive Postpoliomyelitis Progressive Postpoliomyelitis Muscle Atrophy (PPMA)Muscle Atrophy (PPMA)

A recrudescence of paralysis and A recrudescence of paralysis and muscle wasting as a result of muscle wasting as a result of physiological and aging changesphysiological and aging changes

An estimated 20-30% of polio An estimated 20-30% of polio survivors develop new symptoms survivors develop new symptoms approximately 35 years after their approximately 35 years after their initial episode of polio (range 8-71 initial episode of polio (range 8-71 years). Most cases occur before years). Most cases occur before the age of 60 years.the age of 60 years.

Symptoms are variable, and include muscular Symptoms are variable, and include muscular weakness, focal or generalized muscle atrophy, weakness, focal or generalized muscle atrophy, fatigue, pain and decreased ambulatory fatigue, pain and decreased ambulatory abilities. abilities.

The onset of PPS is correlated to the severity of The onset of PPS is correlated to the severity of the original disease. the original disease.

May result from peripheral disintegration of May result from peripheral disintegration of individual nerve terminals in motor units that individual nerve terminals in motor units that were reinnervated during recovery after the were reinnervated during recovery after the acute disease.acute disease.

Criteria For Diagnosis of Post Polio SyndromeCriteria For Diagnosis of Post Polio Syndrome

A prior episode of paralytic A prior episode of paralytic poliomyelitispoliomyelitis

EMG evidence of EMG evidence of longstanding denervationlongstanding denervation

A period of neurological A period of neurological recovery and functional recovery and functional stability preceding the stability preceding the onset of new problems onset of new problems (Usually >20 years)(Usually >20 years)

Criteria for Diagnosis of Post Polio SyndromeCriteria for Diagnosis of Post Polio Syndrome

Gradual or abrupt onset of Gradual or abrupt onset of new non-disuse weakness new non-disuse weakness in previously unaffected in previously unaffected or affected musclesor affected muscles

May be associated with May be associated with fatigue, muscle pain, joint fatigue, muscle pain, joint pain, decreased function, pain, decreased function, etc.etc.

Exclusion of other Exclusion of other conditions that may cause conditions that may cause the above featuresthe above features

PathophysiologyPathophysiology

TheoriesTheories::Remaining healthy Remaining healthy motor neurons can no motor neurons can no longer maintain new longer maintain new sproutssprouts

Decompensation / Decompensation / chronic denervation chronic denervation and reinervation and reinervation process.process.

Denervation exceeds Denervation exceeds reinervationreinervation

Theories (contd.)Theories (contd.)

Motor neuronal loss Motor neuronal loss due to reactivation of a due to reactivation of a persistant latent virus.persistant latent virus.

Infection of the polio Infection of the polio survivor’s motor survivor’s motor neuron by a different neuron by a different enterovirusenterovirus

Loss of strength Loss of strength associated with aging, associated with aging, in already weakened in already weakened musclesmuscles

Main Clinical Features of PPSMain Clinical Features of PPS

Fatigue (most common)Fatigue (most common)

WeaknessWeakness

Muscle painMuscle pain

Gait disturbanceGait disturbance

Respiratory problemsRespiratory problems

Swallowing problemsSwallowing problems

Cold intoleranceCold intolerance

Sleep apnoeaSleep apnoea

FatigueFatigue

Prominent in the early hours of the afternoonProminent in the early hours of the afternoon

Decreases with restDecreases with rest

Pathogenesis:Chronic pain / Muscle painPathogenesis:Chronic pain / Muscle pain

Sleep disorders/ respiratory dysfunctionSleep disorders/ respiratory dysfunction

Difficulty in remembering/ concentratingDifficulty in remembering/ concentrating

Decreased muscular endurance / Increased Decreased muscular endurance / Increased muscular fatigabilitymuscular fatigability

Generalized or muscularGeneralized or muscular

Swallowing ProblemsSwallowing Problems: Subclinical asymmetrical : Subclinical asymmetrical weakness in the pharyngeal constrictor muscles weakness in the pharyngeal constrictor muscles almost always present in PPMAalmost always present in PPMA

Cold IntoleranceCold Intolerance: :

- Autonomic nervous system dysfunction? - Autonomic nervous system dysfunction?

- May relate to sympathetic intermediolateral column - May relate to sympathetic intermediolateral column damage during acute poliomyelitisdamage during acute poliomyelitis

- Peripheral component may include muscular atrophy - Peripheral component may include muscular atrophy leading to reduced heat productionleading to reduced heat production

Sleep Apnoea:Sleep Apnoea: diminished muscle strength of diminished muscle strength of respiratory, intercostal & abdominal muscle groupsrespiratory, intercostal & abdominal muscle groups

Laboratory DiagnosisLaboratory DiagnosisVirus isolationVirus isolation

SerologySerology

No specific treatment is available except supportive measures in paralytic polio

An ‘Iron Lung’ ward during a 1950s epidemic in Boston

Poliovirus VaccinePoliovirus Vaccine19551955 Inactivated vaccineInactivated vaccine

19611961 Types 1 and 2 monovalent OPVTypes 1 and 2 monovalent OPV

19621962 Type 3 monovalent OPVType 3 monovalent OPV

19631963 Trivalent OPVTrivalent OPV

19871987 Enhanced-potency IPV (IPV)Enhanced-potency IPV (IPV)

Inactivated Polio VaccineInactivated Polio Vaccine

Contains 3 serotypes of vaccine virusContains 3 serotypes of vaccine virus

Grown on monkey kidney (Vero) cellsGrown on monkey kidney (Vero) cells

Inactivated with formaldehydeInactivated with formaldehyde

Contains 2-phenoxyethanol, neomycin, streptomycin, Contains 2-phenoxyethanol, neomycin, streptomycin, polymyxin Bpolymyxin B

Oral Polio VaccineOral Polio Vaccine

Contains 3 serotypes of vaccine virusContains 3 serotypes of vaccine virus

Grown on monkey kidney (Vero) cellsGrown on monkey kidney (Vero) cells

Contains neomycin and streptomycinContains neomycin and streptomycin

Shed in stool for up to 6 weeks following vaccinationShed in stool for up to 6 weeks following vaccination

Inactivated Polio VaccineInactivated Polio VaccineHighly effective in producing immunity to poliovirusHighly effective in producing immunity to poliovirus

>90% immune after 2 doses>90% immune after 2 doses

>99% immune after 3 doses>99% immune after 3 doses

Duration of immunity not known with certaintyDuration of immunity not known with certainty

Oral Polio VaccineOral Polio VaccineHighly effective in producing immunity to poliovirusHighly effective in producing immunity to poliovirus

50% immune after 1 dose50% immune after 1 dose

>95% immune after 3 doses>95% immune after 3 doses

Immunity probably lifelongImmunity probably lifelong

Risks (Vaccine-associated Paralysis)Risks (Vaccine-associated Paralysis)

- Maximum Risk (Study of 700 million doses)- Maximum Risk (Study of 700 million doses)

*1 per > 11 million vaccinees.*1 per > 11 million vaccinees.

*in a household contact 1 per 4 million *in a household contact 1 per 4 million

vaccineesvaccinees

*in a community contact 1 for every 30 million *in a community contact 1 for every 30 million

vaccineesvaccinees

*Actual risk is lower*Actual risk is lower

EpidemiologyEpidemiology Fecal oral route of transmission.Fecal oral route of transmission.

Humans are the only reservoir.Humans are the only reservoir.

Poor hygiene and sanitation promote spread which is Poor hygiene and sanitation promote spread which is favored by warm weather.favored by warm weather.

Epidemics (water-borne less so food-borne)Epidemics (water-borne less so food-borne)

Majority of infections are asymptomatic.Majority of infections are asymptomatic.

Bases of Confirmation of Suspected Cases Bases of Confirmation of Suspected Cases During OutbreaksDuring Outbreaks

1)1) Virus IsolationVirus Isolation

2)2) Clinical GroundsClinical Grounds

3)3) EpidemiologicEpidemiologic

4)4) Outcome (Death)Outcome (Death)

5)5) Loss of TrackLoss of Track

EpidemiologyEpidemiologyBefore the 20th century, there were sporadic cases of Before the 20th century, there were sporadic cases of polio; no major outbreaks occurredpolio; no major outbreaks occurred

Before the sanitary movement,Before the sanitary movement, cities had open sewers cities had open sewers or gutters which exposed individuals to the poliovirusor gutters which exposed individuals to the poliovirus

Generations of children were infected but protected (in Generations of children were infected but protected (in part) by maternal antibodiespart) by maternal antibodies

Diagnosis of polio was rare as symptoms were often Diagnosis of polio was rare as symptoms were often indistinguishable from other childhood diseasesindistinguishable from other childhood diseases

Cases of paralytic polio Cases of paralytic polio ironicallyironically began to rise due to began to rise due to

changes in public sanitation and other health changes in public sanitation and other health

measuresmeasures

The disease was more likely to take the paralytic formThe disease was more likely to take the paralytic form

in older children or adultsin older children or adults

In northern Europe and the USA, epidemics of In northern Europe and the USA, epidemics of

paralytic polio began to appear in the late 19th and paralytic polio began to appear in the late 19th and

early 20th centuries, though smallearly 20th centuries, though small

An outbreak in the USA in the summer of 1916, An outbreak in the USA in the summer of 1916,

27,000 people paralyzed, and 6,000 deaths. It 27,000 people paralyzed, and 6,000 deaths. It caused caused

widespread panic and people deserted citieswidespread panic and people deserted cities

Subsequently, epidemics were reported each summer Subsequently, epidemics were reported each summer

with major ones during 1940s-50swith major ones during 1940s-50s

The worst epidemic occurred in 1952 ~ 58,000 cases, The worst epidemic occurred in 1952 ~ 58,000 cases,

3,145 deaths, 21,269 mild to disabling paralysis3,145 deaths, 21,269 mild to disabling paralysis

More children died of polio in 1952 than any other More children died of polio in 1952 than any other

infectious diseaseinfectious disease

Global Status 1988

Polio Eradication: Status in 1998Polio Eradication: Status in 1998

GLOBAL STATUS 2004

1988 350, 0001998 1,9341999 1,186 2000 2652001 2112002 1919 2003 784 2004 1,556 2005 1831

GLOBAL POLIO VIRUS CASES

West Nile VirusWest Nile VirusSevere neurologic illness categoriesSevere neurologic illness categories

-- Meningitis-- Meningitis

-- Encephalitis-- Encephalitis

-- “Meningoencephalitis”-- “Meningoencephalitis”

-- Acute flaccid paralysis-- Acute flaccid paralysis

-- Emerging clinical syndromes-- Emerging clinical syndromes Movement disordersMovement disorders ParkinsonismParkinsonism RhabdomyolysisRhabdomyolysis

WNV-Associated Flaccid ParalysisWNV-Associated Flaccid Paralysis

Previously described; not “new” syndromePreviously described; not “new” syndrome

Relatively young; lack of premorbidity Relatively young; lack of premorbidity conditionsconditions

May have absence of fever, headacheMay have absence of fever, headache

Clinical hallmarks:Clinical hallmarks: Onset during acute infectionOnset during acute infection Asymmetry of weaknessAsymmetry of weakness Absence of sensory changesAbsence of sensory changes Elevation of CSF protein Elevation of CSF protein andand WBC WBC

WNV-Associated Flaccid ParalysisWNV-Associated Flaccid Paralysis

Multiple alternative diagnoses (stroke, GBS, Multiple alternative diagnoses (stroke, GBS, myopathy)—Rx with heparin, IVIGmyopathy)—Rx with heparin, IVIG

Syndrome actually localized to spinal anterior Syndrome actually localized to spinal anterior horn cells —resultant poliomyelitishorn cells —resultant poliomyelitis

Recognition could limit unnecessary diagnostic Recognition could limit unnecessary diagnostic procedures and treatmentprocedures and treatment

Little or no improvement (short-term)Little or no improvement (short-term)

WNV and Movement DisordersWNV and Movement DisordersTremor Tremor Static / kineticStatic / kinetic

Occasionally disablingOccasionally disabling

Sometimes associated with other virusesSometimes associated with other viruses

MyoclonusMyoclonus Upper extremity, facial involvement most frequentUpper extremity, facial involvement most frequent Nocturnal myoclonusNocturnal myoclonus

Both tremor and myoclonus —onset generally > Both tremor and myoclonus —onset generally > 5 days following initial symptoms5 days following initial symptoms

WNV and ParkinsonismWNV and Parkinsonism

Parkinsonism is frequently observedParkinsonism is frequently observed Cogwheel rigidityCogwheel rigidity BradykinesiaBradykinesia Postural instabilityPostural instability

Rest tremor not observedRest tremor not observed

Seen both in encephalitis Seen both in encephalitis andand meningitis cases meningitis cases

WNV and Movement DisordersWNV and Movement Disorders

Neuroimaging: Neuroimaging: lesions in basal lesions in basal ganglia, ganglia, thalamus, ponsthalamus, pons

Histopathology—Histopathology—virus detected in virus detected in basal ganglia, basal ganglia, thalamus, thalamus, brainstembrainstem

WNV and RhabdomyolysisWNV and Rhabdomyolysis

Rhabdomyolysis Rhabdomyolysis —acute destruction of skeletal —acute destruction of skeletal muscle cellsmuscle cells

Infrequent manifestation of viral infectionInfrequent manifestation of viral infection

September 2002— rhabdomyolysis reported in September 2002— rhabdomyolysis reported in Chicago WNV patientsChicago WNV patients

14 total cases identified14 total cases identified

Trauma, medication effect unlikelyTrauma, medication effect unlikely

Further studies to assess associationFurther studies to assess association