Poliomyelitis

Poliomyelitis Disease of semi- developed societies Occurs sporadically or in epidemics First described in Egypt, major cause of morbidity and mortality until 1960s Large epidemics in 1940s and 1950s in the developed world

HISTORY British physician Michael Underwood provides the first clinical description of polio, referring to it as "debility of the lower extremities.“Michael Underwood 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.Jacob von Heine 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 = gray and myel = spinal cord). Poliomyelitis is defined as an acute febrile illness, usually with meningitis and flaccid paralysis, but without objective evidence of a sensory defect or cortical damage. Paralysis is an uncommon manifestation of viral CNS infection.

Causative Viruses Polioviruses 1, 2, and 3 Nonpolio 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 - 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 Enteroviruses Enteroviruses have similar pathogenesis but different target organs. They inhabit the GI tract and rarely cause enteric disease. The incubation period is usually between 7 and 14 days but may be as short as 2 days and as long as 35 days. Viremia spreads the virus to involve target organs (spinal cord and brain, meninges, myocardium, skin)

Virus is excreted in the stools for several weeks and is present in the pharynx 1 to 2 weeks after infection. Neural spread may occur in children who have unapparent infection at the time of tonsillectomy (bulbar paralysis). The anterior horns are most prominently involved, but in severe cases the intermediate gray ganglia and even the posterior horns and dorsal root ganglia are often affected. Viral rather than immunopathology is responsible for disease manifestations.

Clinical Syndromes Asymptomatic Infection: The most common form (>90%) of infection. Symptomatic Illness: Less than 10% of infections result in a recognized clinical illness. Abortive Poliomyelitis (minor illness) -The most common form of the disease (5%). -The patient has only a minor illness, characterized by fever, malaise, drowsiness, headache, nausea, vomiting, constipation, or sore throat in various combinations. The patient recovers in a few days.

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

 Paralytic Poliomyelitis - It usually occurs without an antecedent first phase. - It usually occurs without an antecedent first phase. - The predominating sign is flaccid paralysis resulting from lower motor neuron damage. - The predominating sign is flaccid paralysis resulting from lower motor neuron damage. - Muscle involvement is usually maximal within a few days after the paralytic phase begins. - Muscle involvement is usually maximal within a few days after the paralytic phase begins. - The maximal recovery usually occurs within 6 months, but it may take longer. - The maximal recovery usually occurs within 6 months, but it may take longer. - 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 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 Syndrome (PPS) Progressive Postpoliomyelitis Muscle Atrophy (PPMA) A recrudescence of paralysis and muscle wasting as a result of physiological and aging changes An estimated 20-30% of polio survivors develop new symptoms approximately 35 years after their initial episode of polio (range 8-71 years). Most cases occur before the age of 60 years.

Symptoms are variable, and include muscular weakness, focal or generalized muscle atrophy, fatigue, pain and decreased ambulatory abilities. The onset of PPS is correlated to the severity of the original disease. May result from peripheral disintegration of individual nerve terminals in motor units that were reinnervated during recovery after the acute disease.

Criteria For Diagnosis of Post Polio Syndrome A prior episode of paralytic poliomyelitis EMG evidence of longstanding denervation A period of neurological recovery and functional stability preceding the onset of new problems (Usually >20 years)

Criteria for Diagnosis of Post Polio Syndrome Gradual or abrupt onset of new non-disuse weakness in previously unaffected or affected muscles May be associated with fatigue, muscle pain, joint pain, decreased function, etc. Exclusion of other conditions that may cause the above features

Pathophysiology Theories: Remaining healthy motor neurons can no longer maintain new sprouts Decompensation / chronic denervation and reinervation process. Denervation exceeds reinervation

Theories (contd.) Motor neuronal loss due to reactivation of a persistant latent virus. Infection of the polio survivor’s motor neuron by a different enterovirus Loss of strength associated with aging, in already weakened muscles

Main Clinical Features of PPS Fatigue (most common) Weakness Muscle pain Gait disturbance Respiratory problems Swallowing problems Cold intolerance Sleep apnoea

Fatigue Prominent in the early hours of the afternoon Decreases with rest Pathogenesis:Chronic pain / Muscle pain Sleep disorders/ respiratory dysfunction Difficulty in remembering/ concentrating Decreased muscular endurance / Increased muscular fatigability Generalized or muscular

Swallowing Problems: Subclinical asymmetrical weakness in the pharyngeal constrictor muscles almost always present in PPMA Cold Intolerance: - Autonomic nervous system dysfunction? - Autonomic nervous system dysfunction? - May relate to sympathetic intermediolateral column damage during acute poliomyelitis - May relate to sympathetic intermediolateral column damage during acute poliomyelitis - Peripheral component may include muscular atrophy leading to reduced heat production - Peripheral component may include muscular atrophy leading to reduced heat production Sleep Apnoea: diminished muscle strength of respiratory, intercostal & abdominal muscle groups

Laboratory Diagnosis Virus isolation Serology

No specific treatment is available except supportive measures in paralytic polio An ‘Iron Lung’ ward during a 1950s epidemic in Boston

Poliovirus Vaccine 1955Inactivated vaccine 1961Types 1 and 2 monovalent OPV 1962Type 3 monovalent OPV 1963Trivalent OPV 1987Enhanced-potency IPV (IPV)

Inactivated Polio Vaccine Contains 3 serotypes of vaccine virus Grown on monkey kidney (Vero) cells Inactivated with formaldehyde Contains 2-phenoxyethanol, neomycin, streptomycin, polymyxin B

Oral Polio Vaccine Contains 3 serotypes of vaccine virus Grown on monkey kidney (Vero) cells Contains neomycin and streptomycin Shed in stool for up to 6 weeks following vaccination

Inactivated Polio Vaccine Highly effective in producing immunity to poliovirus >90% immune after 2 doses >99% immune after 3 doses Duration of immunity not known with certainty

Oral Polio Vaccine Highly effective in producing immunity to poliovirus 50% immune after 1 dose >95% immune after 3 doses Immunity probably lifelong

 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 vaccinees vaccinees *in a community contact 1 for every 30 million *in a community contact 1 for every 30 million vaccinees vaccinees *Actual risk is lower *Actual risk is lower

Epidemiology Epidemiology Fecal oral route of transmission. Humans are the only reservoir. Poor hygiene and sanitation promote spread which is favored by warm weather. Epidemics (water-borne less so food-borne) Majority of infections are asymptomatic.

Bases of Confirmation of Suspected Cases During Outbreaks 1)Virus Isolation 1)Virus Isolation 2)Clinical Grounds 2)Clinical Grounds 3)Epidemiologic 3)Epidemiologic 4)Outcome (Death) 4)Outcome (Death) 5)Loss of Track 5)Loss of Track

Epidemiology Before the 20th century, there were sporadic cases of polio; no major outbreaks occurred Before the sanitary movement, cities had open sewers or gutters which exposed individuals to the poliovirus Generations of children were infected but protected (in part) by maternal antibodies Diagnosis of polio was rare as symptoms were often indistinguishable from other childhood diseases

Cases of paralytic polio ironically began to rise due to changes in public sanitation and other health measures The disease was more likely to take the paralytic form in older children or adults In northern Europe and the USA, epidemics of paralytic polio began to appear in the late 19th and early 20th centuries, though small

An outbreak in the USA in the summer of 1916, 27,000 people paralyzed, and 6,000 deaths. It caused widespread panic and people deserted cities Subsequently, epidemics were reported each summer with major ones during 1940s-50s The worst epidemic occurred in 1952 ~ 58,000 cases, 3,145 deaths, 21,269 mild to disabling paralysis More children died of polio in 1952 than any other infectious disease

Global Status 1988

Polio Eradication: Status in 1998

GLOBAL STATUS 2004

, , , , GLOBAL POLIO VIRUS CASES

West Nile Virus Severe neurologic illness categories -- Meningitis -- Encephalitis -- “Meningoencephalitis” -- Acute flaccid paralysis -- Emerging clinical syndromes Movement disorders Movement disorders Parkinsonism Parkinsonism Rhabdomyolysis Rhabdomyolysis

WNV-Associated Flaccid Paralysis Previously described; not “new” syndrome Relatively young; lack of premorbidity conditions May have absence of fever, headache Clinical hallmarks: Onset during acute infection Onset during acute infection Asymmetry of weakness Asymmetry of weakness Absence of sensory changes Absence of sensory changes Elevation of CSF protein and WBC Elevation of CSF protein and WBC

WNV-Associated Flaccid Paralysis Multiple alternative diagnoses (stroke, GBS, myopathy)—Rx with heparin, IVIG Syndrome actually localized to spinal anterior horn cells —resultant poliomyelitis Recognition could limit unnecessary diagnostic procedures and treatment Little or no improvement (short-term)

WNV and Movement Disorders Tremor Static / kinetic Static / kinetic Occasionally disabling Occasionally disabling Sometimes associated with other viruses Sometimes associated with other virusesMyoclonus Upper extremity, facial involvement most frequent Upper extremity, facial involvement most frequent Nocturnal myoclonus Nocturnal myoclonus Both tremor and myoclonus —onset generally > 5 days following initial symptoms

WNV and Parkinsonism Parkinsonism is frequently observed Cogwheel rigidity Cogwheel rigidity Bradykinesia Bradykinesia Postural instability Postural instability Rest tremor not observed Seen both in encephalitis and meningitis cases

WNV and Movement Disorders Neuroimaging: lesions in basal ganglia, thalamus, pons Histopathology— virus detected in basal ganglia, thalamus, brainstem

WNV and Rhabdomyolysis Rhabdomyolysis —acute destruction of skeletal muscle cells Infrequent manifestation of viral infection September 2002— rhabdomyolysis reported in Chicago WNV patients 14 total cases identified Trauma, medication effect unlikely Further studies to assess association