Acute Flaccid Paralysis Presented by: Dr. Moh’d Abu Helwah Supervised by: Dr. Afaf Al Areni

1. Acute Flaccid Paralysis Presented by: Dr. Moh’d Abu Helwah Supervised by: Dr. Afaf Al Areni

2. Differential Diagnosis of Acute Weakness: • Cerebral: Bilateral strokes, Hysteria… • Cerebellar: Acute cerebellar ataxia syndromes. • Spinal: Compressive myolopathy, Transverse myelitis…. • Peripheral nerve: Acute inflammatory demyelinating neuropathy, Toxic neuropathy, Diphtheria, Tick paralysis

3. Differential Diagnosis of Acute Weakness: • Neuromuscular junction: Botulism, Myasthenia Gravis… • Muscle disease: Acute myositis Acute inflammatory myopathies Metabolic myopathies, Periodic paralysis…

4. Acute Flaccid Paralysis • The sudden onset of generalized flaccid weakness in the absence of symptoms of encephalopathy implicates the motor unit. • AFP is an emergency in which management priorities are to support vital functions and reach a specific diagnosis in a timely manner with a focused history and physical examination.

5. Guillain-Barré Syndrome. • Poliomyelitis. • Transverse Myelitis.

6. Guillain-Barré Syndrome • It is an acute idiopathic monophasic acquired inflammatory demyelinating polyradiculoneuropathy. • GBS is the most common cause of acute flaccid paralysis in healthy infants and children.

7. Epidemiology • It has an annual incidence of 0.6 to 2.4 cases per 100,000 population and occurs at all ages and in both sexes. • The incidence is lower in children, 0.38 and 0.91 cases per 100,000 in two reports. • Occurs rarely in children younger than two years of age, but can occur in infants. • Males are affected approximately 1.5 times more often than females in all age groups.

8. GBS…Pathophysiology • Immune mediated disease. • There is no known genetic factors. • Two third of cases follow a respiratory or GI infection. • Campylobacter infection is the most common, but other organisms include CMV, EBV, HSV, Enteroviruses,… • Guillain-Barré syndrome has been reported to follow • vaccinations • epidural anesthesia • thrombolytic agents

9. GBS…Pathophysiology • The main lesions are acute inflammatory demyelinating polyradiculopathy, with acute axonal degeneration in some cases, particularly those following campylobacter infection. • Avariety of autoantibodies to gangliosides have been identified especially with axonal forms of the disease.

10. Clinical Features   Usually 2 - 4 weeks following respiratory or GI infection. • The classic presentation: Fine paresthesias in the toes and fingertips. Lower extremity weakness: symmetric & ascending. Gait unsteadiness. Inability to walk. Respiratory muscles involvement. Neuropathic pain… low back pain. • Cranial Neuropathy: Facial nerve is most commonly affected, resulting in bilateral facial weakness.

11. Clinical Features… cont By the peak of the illness,the frequency of symptoms was as follows: - 79% had neuropathic pain - 60% could not walk - 51% had autonomic dysfunction - 46% had cranial nerve involvement - 24% could not use their arms - 13% required mechanical ventilation

12. PhysicalExamination • Symmetric limb weakness • diminished or absent reflexes • Vibration and position sensation are affected in 40% of cases. • Autonomic dysfunction: Cardiac dysrhythmias. Orthostatic hypotension, hypertension Paralytic ileus Bladder dysfunction

13. Clinical Course  • >90% of patients reach the nadir of their function within two to four weeks, with return of function occurring slowly over the course of weeks to months. • The clinical course of GBS in children is shorter than in adults and recovery is more complete. • In patients who did not require mechanical ventilation, the median time to recovery of independent walking was 43 to 52 days in children compared to 85 days in adults.

14. Forms of GBS •  Acute inflammatory demyelinating polyneuropathy (AIDP): the most common form in developed countries. • Acute motor axonal neuropathy: more common in developing countries. More severe with common respiratory involvement. Strong association with campylobacter • Acute motor-sensory axonal neuropathy  • Miller Fisher syndrome: triad of external ophthalmoplegia, Ataxia, areflexia with muscle weakness. • Polyneuritis cranialis: associated with CMV infection

15. Diagnosis • Cerebrospinal Fluid: - After the first week of symptoms typically reveals: normal pressures, normal cell count and elevated proteins (greater than 50 mg/dL) - Early in the course (less than one week), protein levels may not yet be elevated, but only rarely do they remain persistently normal • Electrophysiologic studies: - Most specific and sensitive tests for diagnosis - Evidence evolving multifocal demyelination - A normal study after several days of symptoms, makes the diagnosis of Guillain-Barré syndrome unlikely.

16. Doubt the Diagnosis of GBS IF • Marked persistent asymmetry of weakness. • Persistent bladder or bowel dysfunction. • Bladder or bowel dysfunction at the onset. • Mononuclear leukocytosis in the CSF > 50. • Sharp sensory level. • Pupillary abnormalities are not seen in GBS.

17. GBS Management • Critical care monitoring autonomic and respiratory dysfunction. • Children with the following should be admitted to PICU: a. Flaccid quadriparesis b. Rapidly progressive weakness c. Reduced vital capacity (≤20 mL/kg) d. Bulbar palsy e. Autonomic cardiovascular instability N.B: Sedation and neuromuscular blockade should be avoided in ventilated patients because they obscure the course of the illness.

18. GBS Management Risk factors for respiratory failure in GBS: • Cranial nerve involvement. • Short time from preceding respiratory illness. • Rapid progression over less than 7 days. • Elevated CSF protein in the first week. • Severe weakness: unable to lift elbows above the bed unable to lift head above the bed unable to stand. • 20% of children with GBS require mechanical ventilation for respiratory failure.

19. Special Therapy Immune modulatory therapy: • Intravenous Immunoglobulins • Plasmapheresis • Both therapies have been shown to shorten recovery time by as much 50%. • Combining plasma exchange and IVIG neither improved outcomes nor shortened the duration of illness.

20. Special Therapy…cont • IVIG and plasma exchange are not recommended for ambulatory children with GBS who have mild disease or for children whose symptoms have stabilized. • IVIG and plasma exchange for children with GBS should be reserved for those with: A. Rapidly progressing weakness. B. Worsening respiratory status. C. Significant bulbar weakness. D. Inability to walk unaided.

21. INTRAVENOUS IMMUNE GLOBULIN • IVIG is preferred to plasma exchange in children because of the relative safety and ease of administration, although it has not been shown to have better results. • Randomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as plasmapheresis. • Long-term outcome, however, may not be affected. • Studies have demonstrated that one effect of the IVIG is to neutralize neuromuscular blocking antibodies.

22. IVIG Regimens • Several IVIG regimens have been utilized. One regimen includes daily IVIG for 5 days at a dose of 0.4 gm/kg/day, which results in an improvement within a mean of 2 to 3 days after the start of therapy. Other authors use 2 gm/kg of IVIG given as a single dose or 1gm/kg/day for 2 days. • One study compared the outcome of 0.4 gm/kg/day given for 3 days versus 6 days. In that study, the 6 days of IVIG was superior when “time to walking” was used as an endpoint. • When comparing treatments of 1gm/kg for 2 days versus 0.4gm/kg over 5 days, no significant difference in the effectiveness was noted in the 2 treatment regimens. However, early “relapses” were more frequently observed in the shorter treatment group.

23. Plasmapheresis • Studies in children indicate that plasmapharesis may decrease the severity and shorten the duration of GBS. • It is most beneficial when started within 7 days of the onset of symptoms but is still beneficial in patients treated up to 30 days after disease onset.

24. Management…cont • Corticosteroids are not effective and not indicated • Interferon-ß reported to be beneficial in individual cases, but its safety and efficacy have not been established in clinical trials.

25. Prognosis • In general, the prognosis in affected children is better than adults. • Recurrences are uncommon but can occur in children. Some may have a chronic progressive course, whereas others may show recurrences or relapses. • At long-term follow up, 93% were free of symptoms, and the remainder were able to walk unaided. • 50% are ambulatory by 6 mo, 70% walk within ayear of onset of the disease. • Mortality is approximately 3 to 4%, and usually is secondary to autonomic dysfunction and respiratory failure.

26. Poliomyelitis AKA: Infantile paralysis, Acute anterior poliomyelitis, Acute lateral poliomyelitis. polio= gray matter Myelitis= inflammation of the spinal cord. Poliomyelitis is caused by a virus that attacks the nerve cells of the brain & spinal cord although not all infections result in sever injuries and paralysis.

27. Poliomyelitis: Etiology Etiology: • Caused by a poliovirus. • 3 serotypes of poliovirus (genus Enterovirus). • Type 1 most frequently associated with epidemics. • Types 2 and 3 usually associated with vaccine- associated paralytic polio (VAPP).

28. Poliomyelitis • In 1% of cases virus invades CNS. • Multiplies and destroys anterior horn cells. • In severe cases, poliovirus may attacks motor neurones in brainstem, leading to difficulty in swallowing, speaking and breathing.

29. Poliovirus: Pathogenesis • Incubation period of 7 to 14. • Transmitted by oral-fecal contact. • Person-to-person spread is the most common means of transmission, followed by contaminated water. • During epidemics, it also may be transmitted by pharyngeal spread. • Poliovirus initially infects the GI tract. It may spread to lymph nodes and rarely to CNS. • The mechanism of spread of poliovirus to the CNS is not well understood.

30. Epidemiology • 3 months-16 years; rarely adults • Predominant sex: Male = Female • Improved sanitation led to many less infants being exposed to poliovirus. • When exposure occurred later and the individuals were not protected by maternal antibodies, there were polio epidemics.

31. Poliomyelitis: Incidence & Prevalence Incidence: Now rare; present in: (a) Endemic settings. (b) Small outbreaks in areas where polio eradication has occurred. (c) Rarely as vaccine-associated paralytic polio (VAPP) cases. Prevalence: • 1,486 cases in 2005; 1,593 cases in 2006. •  Endemic countries: Afghanistan, India, Nigeria and Pakistan

32. Poliomyelitis: Risk Factors • Immune deficiency • Pregnancy • Poor sanitation and hygiene •  Poverty •  Unimmunized status, especially if <5 years • Tonsillectomy: a risk factor for bulbar paralysis. • Intramuscular injections or truama Genetics: • No genetic susceptibility has been identified.

33. Clinical Presentation • The majority of patients are asymptomatic. • ~5% develop symptoms. • ~10% will show signs and symptoms of a minor GI illness, including fever, malaise, nausea, and vomiting. • 0.1% develop the paralytic form of poliomyelitis. • Symptoms of poliomyelitis always CNS specific.

34. Clinical Presentation…cont CNS manifestations: • Weakness: Vary from one muscle or group of muscles, to quadriplegia. Proximal muscles: legs more commonly than arms. Typically worsens over 2 to 3 days but sometimes can progress for up to a week. • Bulbar involvement: 5 – 35% producing dysphagia, dysarthria, and difficulty handling secretions. • There may be encephalitis, usually in infancy. • Cardiovascular & Resp. symptoms…bulbar poliomyelitis

35. Physical Exam: • Significant motor loss on affected side or limb. • Meningeal signs may be present in minor illness or early phases of paralytic polio. • Decreased deep tendon reflexes. • Muscle atrophy of affected areas. • Tone is reduced: asymmetric • The sensory examination is normal.

36. Poliomyelitis: Diagnosis  • Based on the clinical presentation. • Cerebrospinal Fluid: Leukocytosis, Increased protein, Normal glucose. • Virus recovery from stool, throat washing, blood. • Virus recovery from stool is essential to diagnosis. • Obtain stool, blood and throat samples for viral serology, demonstrating a four fold rise in IgG is helpful but not always easy. • Positive IgM is diagnostic. • Polymerase chain reaction amplification of poliovirus RNA from CSF or serologically, by comparing viral titers in acute and convalescent sera.

37. Diagnosis…cont  • Electrodiagnostic investigations reveal normal sensory nerve studies. • Motor nerve studies: show normal to mildly slowed conduction velocities and low to normal amplitudes. • MRI may be helpful to evaluate involvement of anterior horn of the spinal cord or other findings.

38. Treatment • No definitive treatment. • Mainly supportive: pain relief and physical therapy for muscle spasms. • Patients with bulbar involvement require close monitoring of cardiovascular status and autonomic dysfunction. • Mechanical ventilation: Respiratory failure. • Treatment of complications.

39. Poliomyelitis: Complications • Urinary tract infection • Skin ulcers • Traumatic injuries to affected limb(s) • Atelectasis & Pneumonia • Myocarditis • Postpoliomyelitis progressive muscular atrophy. • Postpoliomyelitis motor neuron disease.

40. Clinical Course & Outcome • About two-thirds of patients with acute flaccid paralysis do not regain full strength. • The more severe the acute weakness, the greater the chance of residual deficits, Bulbar squeals are rare. • The mortality was 5 to 10% in the era of epidemics, and approached 50% for those with bulbar involvement because of cardiovascular and respiratory complications.

41. PREVENTION OF POLIOMYELITIS

42. Polio Vaccination  • Jonas Salk created the inactivatedpoliovirus vaccine (IPV), using killed virus in 1952. • The Sabin oral poliovirus vaccine (OPV), using live attenuated virus, proved successful in 1960. • In areas of the world where polio is endemic, primary immunization is still performed with Sabin OPV. But, because it causes polio in one out of 2.5 million cases, it has been replaced by the Salk IPV in countries without polio, including the United States and most of Europe.

43. Polio Vaccination  • Multiple doses required to achieve high humeral conservation rates against all virus types • Babies are given 4 doses through out their infancy. • Adolescents and adults should get vaccinated as well. • Adolescents younger than 18 should receive the routine four doses. • You should get it if you travel outside places where polio is still epidemic.

44. What is Post Polio Syndrome ? • It is the late manifestation of acute paralytic polio. • 25-40% of people who had paralytic polio15-40yr previously. • They show symptoms of muscle and joint pain, general fatigue and weakness. Three indications of PPS: A. Previous diagnoses of polio: late effect of polio to people that got it like when they where 10 years old. B. Long interval following recovery: people usually live long but effect can occur during 30-35 years after the diagnoses. C. Gradual onset: weakness that tends to be perceptible until it interferes with daily activities.

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

46. Criteria for Diagnosis of PPS…cont • Gradual or abrupt onset of new non-disuse weakness in previously unaffected or affected muscles. • May be asssociated with fatigue, muscle pain, joint pain, decreased function, etc. • Exclusion of other conditions that may cause the above features.

47. Main Clinical Features of PPS: • Fatigue (Commonest) • Weakness • Muscle pain • Gait disturbance • Respiratory problems • Swallowing problems • Cold intolerance • Sleep apnoea

48. Management of Post Polio Syndrome • Clinical Assessment. • Exclusion of other causes of disability. • Introduction to concept of interdisciplinary team. • Follow-up as necessary

49. Transverse myelitis • Inflammation of the spinal cord causing acute/or subacute loss of motor, sensory and autonomic function, often evolves in hours or days. • Pathophysiology: presumed autoimmune mediated inflammation and demyelination of the spinal cord. • Postinfectious etiology largely predominates in children

50. Associated Conditions • Is most commonly associated with infection. • May be associated with demyelination of other parts of the central nervous system, e.g. MS, ADEM… • Connective tissue diseases, e.g. SLE, JRA, sarcoidosis, vasculitis… • Rarely seen in association with metabolic causes of myelopathy such as vitamin B12 deficiency. • ATM does not usually occur in association with inherited demyelinating diseases, e.g. leukodystrophies.