Acute Flaccid Paralysis

This presentation briefly discusses the approach to a child presenting with acute flaccid paralysis including a history and examination based distinction between its various etiologies and a summary on the diagnostic approach to such cases and their management with a brief mention on AFP surveillance.

1. Acute Flaccid Paralysis Differential diagnosis and management Dr. Ipsita Mahapatra (PGT, Pediatrics ) Gauhati Medical College and Hospital

2. Definition – Acute Flaccid Paralysis Clinical syndrome characterised by rapid onset weakness. Weakness progresses to maximum within days to weeks. ‘Acute’ : Rapid progression from onset to maximum ‘Flaccid’ : Loss of muscle tone, ‘floppy’ Absence of spasticity or other upper motor neuron signs ‘Paralysis’ : Weakness, loss of voluntary movement AFP is not a diagnosis but a broad clinical entity with an array of diagnostic possibilities.

3. Case definition of Acute Flaccid Paralysis In accordance with the Global Polio Eradication Initiative (1988), acute flaccid paralysis is defined as : Any case of AFP in a child aged < 15 years for which no obvious cause is found, Or Any case of paralytic illness in a person of any age when polio is suspected. Any case meeting this definition undergoes a thorough investigation to determine if the paralysis is caused by polio.

4. Etiologies of AFP (As per neuro-anatomical localisation) 1 . SPINAL CORD 2. ANTERIOR HORN CELL DISORDERS Acute Tranverse Myelitis Compressive myelopathy (abscess, tumor ) Anterior spinal artery syndrome Trauma Poliomyelitis Non-polio Enteroviruses

5. 3. NEUROPATHIES 4. NEUROMUSCULAR JUNCTION DISORDERS Guillain Barre Syndrome Traumatic neuritis Post diphtheric neuropathy Acute Intermittent Porphyria Tick bite paralysis, Lyme disease CMV radiculopathy (in Immunocompromised state) Heavy metal/ Organophosphorous poisoning Myathenia gravis Neuroenvenomation (Snake bite) Botulism Lambert-Eaton syndrome

6. 5. MUSCLE Inflammatory myopathies Hypokalemic periodic Paralysis Hypermagnesemia Infections (viral myositis, trichinosis)

7. The 4 most common differential diagnosis in a case of AFP are: Poliomyelitis Guillain Barre Syndrome Acute Transverse Myelitis Traumatic Neuritis

8. 1. Poliomyelitis Both the wild polio virus and the vaccine associated polio virus cause anterior horn cell affliction to result in flaccid paralysis. Children under 5 y are the most frequently affected. Symptoms : The initial symptoms of polio are non-specific and include fever, headache, vomiting, constipation, neck stiffness and pain in limbs. The paralysis follows or accompanies these symptoms. The maximal weakness evolves quickly over 1–2 d

9. Clinical charateristics : 1. Fever at onset 2. Rapid progression of paralysis within 24–48 h 3. Asymmetric, proximal > distal muscles. 4. Preservation of sensory function often with severe myalgias 5. Residual paralysis at 60 days Most of the children with paralytic polio die from complications of bulbar paralysis and respiratory failure. Management : mainly focused on meticulous supportive care.

10. 2. Guillain-Barre Syndrome With the control of polio, GBS is the most common cause of AFP in children . Worldwide its incidence is 0.6–4 cases per 100,000 per year. It most commonly occurs after an infection triggered immune mediated attack on the nerve axons or myelin. Antecedant respiratory or gastrointestinal illnesses are commonly found in the history.

11. GBS Subtypes: Acute Inflammatory Demyelinating Polyneuropathy (AIDP) Acute Motor Axonal Neuropathy (AMAN) Acute Motor Sensory Axonal Neuropathy (AMSAN) Miller-Fischer Syndrome (MFS) Most common : AIDP > AMAN but AMAN maybe equally common in Indian children. Clinical features : Initially pain, paraesthesia, or weakness in the limbs which spreads proximally ( a scending paralysis ). Risk factors for children requiring ventilation are cranial nerve involvement, increased CSF protein during first week of illness and short period between antecedent illness and the onset of symptoms.

12. Investigations : nerve conduction studies and lumbar puncture are done (to document CSF albumin-cytological dissociation ). When a child presents in the acute phase, the differentiation from polio or enteroviral myelitis can be done based on CSF. Viral myelitis would show CSF pleocytosis, which would be conspicuously absent in GBS.

13. 3. Transverse myelitis It is an acute demyelinating disorder of the spinal cord which may occur alone or in combination with demyelination in other portions of the nervous system. Cause : Believed commonly that a previous infection or immunization triggers transverse myelitis. Clinical characteristics: Acute phase of spinal shock Flaccid paraparesis or quadriparesis, urinary retention or incontinence, absent reflexes and mute plantars , sensory loss/level is frequently present . After a few weeks The signs of UMN dysfunction appear, in the form of spasticity, and hypereflexia .

14. Early and Late stages of Transverse myelitis Features Early stage Late Stage Type of Paralysis LMN type, Flaccid UMN type, Spastic Tone Decreased Increased DTRs Areflexia Hyperreflexia Babinski sign Absent Positive

15. Suspect in any child with rapid onset flaccid quadriparesis, early or persistent bladder or bowel involvement , sensory loss or sensory level on examination, with suggestion of UMN signs on examination (e.g., up going plantars ). Respiratory failure may occur in higher level lesions Urgent spinal MRI is needed to establish the diagnosis.

16. 4. Traumatic neuritis (following injection) Traumatic neuritis is suspected in cases in which there is one limb involvement. Definite history of injection in that limb (usually less than 24 h) before the onset of paralysis. Associated with pain and hypothermia of affected limbs. It is sometimes difficult to distinguish it from polio. However, sensory deficits and lack of CSF pleocytosis favour the diagnosis of traumatic neuritis. Residual sensory deficits strongly favour the diagnosis of injection neuritis.

17. Diagnostic approach to a case of AFP Information from history and a focussed neurological examination looking at onset/pattern/progression of weakness, tone, deep tendon reflexes, sensory examination, bowel and/or bladder involvement, fever at onset of paralysis and etiology specific features. Is the weakness due to a neurological cause? Rule out pseudoparalysis If neurological, is it an UMN or LMN lesion? If LMN lesion, what is the level of lesion? Likely etiology

18. Pseudoparalysis Apparent paralysis due to voluntary inhibition of motion because of limb pain or incoordination but without actual paralysis. Orthopedic complaint Causes: Trauma, fracture, sprain, arthritis/ arthalgia , joint or periosteal bleeds, joint or periarticular infections, abscess or inflammation

19. Localising the site of lesion Important points in history taking – Clues to Diagnosis Features Likely diagnosis Fever at the onset of illness Polio Loose stools/Cough 2-3 weeks prior GBS Trauma/ IM injection Traumatic neuritis Patch over tonsillar area, bull neck Diphtheria Exposure to chemicals Arsenic, Lead poisoning Abdominal Pain Porphyria, Lead poisoning

20. Features Likely diagnosis Ptosis, blurred vision, respiratory paralysis Snake bite, Botulism, GBS (Miller Fischer Variant) Recurrent flaccid paralysis Periodic paralysis - Channelopathies Dermatological manifestations: Edema , Gottron’s papules Inflammatory myopathy (Dermatomyositis) Headache, seizure, vomiting, altered sensorium Porphyria (associated encephalopathy) Ingestion of honey, canned food Botulism

21. Localising the site of lesion based on clinical signs Important points in examination Anatomical Level Clinical Signs Brain stem Altered consciousness, Cranial nerve paralysis, UMN signs Spinal Cord Bladder involvement, Sensory level, UMN signs (Below the level of lesion), Plantars extensor Anterior Horn Cell LMN type weakness, areflexia Nerve root LMN type weakness, areflexia, Peripheral nerve Sensory loss, glove and stocking sensory involvement Neuromuscular Junction Diurnal variation, Fluctuating weakness Muscle LMN weakness but reflexes preserved

22. Characteristics of common DDs of AFP Feature Poliomyelitis GBS Transverse myelitis Traumatic neuritis (following injection) Development of paralysis 24-48hrs from onset to full paralysis From hours to 4 weeks From hours to 4 days From hours to 4 days Fever at onset of weakness High, always present at onset Uncommon May be present Present, if underlying infection being treated with IM injection Paralysis Asymmetric Proximal > distal Symmetric, mostly ascending Symmetric Affects only one limb Progression of paralysis Descending Ascending

23. Feature Poliomyelitis GBS Transverse myelitis Traumatic neuritis (following injection) Sensation Intact, may have diffuse myalgia Cramps, tingling, hypoanaesthesia of palms and soles Imapired below level of lesion Maybe impaired in the distribution of the affected nerve Cranial Nerve involvement Affected in bulbar and bulbospinal variant Usually affected Absent Absent Respiratory insufficiency May be present May be present May be present Absent Autonomic signs and symptoms Rare In severe cases (BP alteration, sweating, blushing, body temp fluctuation) Present Hypothermia in affected limb

24. Feature Poliomyelitis GBS Transverse myelitis Traumatic neuritis (following injection) CSF Mild elevation of lymphocytes 10-200/ml Albumino -cytological dissociation (<10cells/ml, never >50 cells/ml) Normal (or pleocytosis) Normal Bladder dysfunction Rare Occasionally (Transient) Present – Early and persistent Never NCV studies Abnormal : Anterior horn cell disease (Normal during first 2 weeks) Abnormal : slowed conduction, decreased motor amplitudes Normal Abnormal : s/o motor-sensory axonal damage Diagnostic test Stool viral detection Nerve conduction studies MRI spine Nerve conduction studies, Electromyography

25. Based on history and examination: Flaccid paraparesis with sensory level (early bladder dysfunction) : Acute transverse myelitis, compressive myelopathy Flaccid, afebrile, symmetric para/quadriparesis (+/- bulbar and respiratory involvement) with areflexia and minimal sensory loss (but often sensory symptoms) : Acute neuropathy or polyradiculopathy ( eg. GBS) Flaccid, febrile, pure motor, asymmetric paralysis (no bladder involvement) : Enteroviral, Polio or Vaccine associated Poliomyelitis

26. 4. Flaccid motor-sensory lower limb monoparesis after IM injection : Injection neuritis 5. Ophthalmoplegia, ptosis, bulbar weakness with motor weakness : Miller-Fischer variant of GBS, Botulism, Myasthenia gravis 6. Proximal muscle weakness, muscle tenderness without sensory symptoms or signs with preserved reflexes: Viral myositis, Inflammatory myopathy ( eg : dermatomyositis)

27. Management A child with AFP is a medical emergency! Initial management (aimed at stabilisation, anticipating and identifying potential complications) Detailed history and focussed neurological examination Investigations Specific therapy

28. A. Initial Management Assess vitals Respiratory care : Detect and manage respiratory muscle weakness: irritability, sweating, poor feeding, shallow resp. efforts, air hunger, reduced SBC/chest expansion. Bulbar weakness detection and management : voice change, poor cry, pooling of secretions, gurgling sounds, difficulty in swallowing or choking on feeds Managing cardiovascular instability Rule out dyselectrolytemia and snake envenomation Rule out spinal cord pathology

29. B. Detailed history and focussed neurological exam C. Investigations The choice of the initial investigations would depend on the information gained from history and examination. Routine Blood counts, CRP, Electrolytes MRI Spine : suspicion of spinal cord compression or transverse myelitis. CSF examination : A raised CSF cell count would be seen in patients with transverse myelitis, infective myelitis viz. polio or enteroviral myelitis. A raised CSF protein with normal cell count ( albuminocytological dissociation) suggests Guillain Barre syndrome

30. 3. Nerve Conduction studies and Electro Myography (EMG) : These studies confirm the involvement of nerves and help in diagnosis of anterior horn cell diseases. These are particularly helpful to confirm Guillain Barre syndrome. 4. Creatine Kinase : Raised levels of muscle enzyme creatine kinase reflects acute muscle fibre injury and may point towards a muscle disease. In the setting of AFP this may be seen in children with viral myositis or inflammatory myopathy 5. Biochemistry: Potassium, Magnesium, Phosphate 6. ECG : To look for hypokalemia 7. Urine analysis : Urine for porpho-bilinogens , toxins: arsenic, lead etc.  

31. D. Specific therapy Once the diagnosis is ascertained, the specific treatment must be initiated. Guillain-Barre Syndrome IVIG is the treatment of choice for GBS, given the availability, ease of administration and the safety compared with plasmapheresis. It is given in the dose of 2 g/kg spread over 2–5 d or 400mg/kg/day for 5 days . Transverse myelitis High dose pulse corticosteroids are the recommended form therapy. Methylprednisolone is given in a dose of 10–30 mg/kg/d (max:1 g/d) for 5 d followed by oral prednisolone 1–2 mg/kg/d for 2 weeks and then tapered over subsequent 2–4 wk.

32. Traumatic neuritis Management is entirely supportive Hypokalemic paralysis Correction of potassium levels rapidly reverses the paralysis in these children . Poliomyelitis AFP reporting and stool collection mandatory Most of the children with paralytic polio die from complications of bulbar paralysis and respiratory failure. Management is mainly focused on meticulous supportive care with physiotherapy, ambulation and prevention of deformities.   Compressive myelopathy Spinal immobilization, neurosurgical intervention, steroids.

33. AFP Surveillance

34. Surveillance : definition Surveillance : Continuous scrutiny of all aspects of occurrence and spread of disease that are pertinent to effective control. Includes : Collection of data Analysis of data Interpretation of data Distribution of relevant data so that necessary action can be taken

35. Types of public health surveillance Passive Surveillance Data/reports are sent by designated health facilities or individuals on their own, periodically as a routine. Active surveillance A designated official, usually external to the health facility visits periodically and seeks to collect data from individuals,/registers/log books/medical records at a facility to ensure that no reports/data are incomplete or missing.

36. Global Polio eradication initiative With the launch of the Global Polio Eradication Initiative (1988), the incidence of poliomyelitis across the world has declined significantly through active surveillance , strengthening childhood immunisation using OPV, improvement in sanitation and conducting "mop up" campaigns in areas where cases of polio have been identified. The objectives of GPEI were: 1. To interrupt wild poliovirus transmission 2. To mainstream global polio eradication initiative 3. To develop products for global OPV cessation phase 4. To achieve certification of global polio eradication

37. The strategy for the eradication of polio rested on immunising every at risk child until there was no one left for the disease to transmit to and the disease would eventually die out. Current status : Only 2 countries are endemic for Polio as of 2021 : Pakistan and Afghanistan . Nigeria has reported no new cases since 2014. Africa was declared polio free in 2020. Malawi declared an outbreak of WPV type 1 on 17 February 2022. This is the first case of wild poliovirus in Africa in more than 5 years.

38. India was removed from the list of polio endemic countries in January 2012 after completing a year without reporting any case of polio in January, a major milestone in the history of polio eradication. India declared polio-free on 27 March 2014 , 3 years after the last case was reported in January 2011 in West Bengal. Globally, type 2 virus serotype was declared eradicated in 2015, and type 3 on 24 October 2019.

39. Source: mohfw / pulsepolioimmunisation

40. Under the Endgame Polio Strategy 2013-2018, India switched over to bivalent OPV in April 2016 excluding the OPV 2 strain which is mainly responsible for vaccine derived polio. Detect and interrupt all poliovirus transmission Strengthen immunization systems and withdraw OPV Contain poliovirus and certify interrupt of transmission Plan post-polio legacy. Meanwhile, inactivated polio vaccine (IPV) was introduced in 2016 with two fractional intradermal doses at 6 and 14 weeks along with bivalent OPV Endgame Polio Strategy 2019-2023 is the current strategy by the GPEI. The ultimate aim is to stop the use of the oral polio vaccines altogether

41. Goals of Polio Endgame strategy 2019 - 2023

42. AFP surveillance is the strategy to screen for circulating wild polio virus in the post-polio eradication phase.

43. Case definition of Acute Flaccid Paralysis In accordance with the Global Polio Eradication Initiative (1988), acute flaccid paralysis is defined as : Any case of AFP in a child aged < 15 years for which no obvious cause is found, Or Any case of paralytic illness in a person of any age when polio is suspected. Any case meeting this definition undergoes a thorough investigation to determine if the paralysis is caused by polio.

44. Every case of AFP <15 years must be reported. Within 48 hours of notification, a trained medical officer investigates the case, proceeds with transportation of stool samples, outbreak response immunizations (ORI) done in the affected community . A 60 day follow up examination of the case should also be done to detect presence/absence of residual paralysis.

45. Purpose of AFP surveillance Helps to detect reliably areas where poliovirus transmission is occurring. Thus, helps to identify areas of priority for focusing immunization activities. It is the most reliable tool to measure the quality and impact of polio immunization activities. For polio free certification, it is essential to provide evidence of the absence of wild poliovirus transmission through a functioning and sensitive surveillance system for at least 3 years after attaining a zero polio case status.

46. Collecting stool specimen Adequate stool: 2 stool specimen from every AFP case atleast 24 hours apart . Stool sample must be collected within 14 days of onset of paralysis to maximise the chance of isolating poliovirus. Can be collected upto 60 days. Amount: About the size of one adult thumb ( 8 grams ). Transport: The specimen should arrive at a WHO-accredited laboratory within 72 hours of dispatch in good condition (i.e. no dessication , no leakage, shipped on ice or frozen packs with adequate documentation and evidence that the reverse cold chain was maintained (2 to 8 degree celsius ).

47. Sensitivity of AFP surveillance Source : WHO best practices in active surveillance of polio eradication 2 Indicators set the gold standard for AFP surveillance quality: At least 1 case of non-polio AFP reported yearly per 1,00,000 children aged under 15 years (background rate of AFP) according to National Polio Surveillance Project. 2. At least 80% of AFP cases should have 2 adequate stool samples.

48. References Ghai Essential Pediatrics 9 th ed. WHO best practices in active surveillance of polio eradication PG textbook of Pediatrics , vol 3, Dr. Piyush Gupta Nelsons textbook of pediatrics Singhi SC, Sankhyan N, Shah R, Singhi P. Approach to a child with acute flaccid paralysis. Indian J Pediatr . 2012 Oct

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