Guillain - Barré syndrome

definition, pathogenesis, pathophysiology, clinical types, clinical presentation, diagnosis, lumbar puncture, electrophysiology , differential diagnosis , treatment , prognosis

1. Guillain - Barré syndrome Prof. Dr. Saad S Al Ani Senior Pediatric Consultant Head of Pediatric Department Khorfakkan Hospital Sharjah , UAE [email protected]

2. A collection of clinical syndromes that manifests as an acute inflammatory polyradiculoneuropathy with resultant weakness and diminished reflexes. Guillain-Barré syndrome (GBS) 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 2 https://emedicine.medscape.com

3. Overview The classic presentation is characterized by an acute monophasic , non-febrile , post-infectious illness manifesting as ascending weakness and areflexia 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 3

4. Overview (cont.) Sensory , autonomic , and brainstem abnormalities may also be seen.  With the eradication of poliomyelitis, GBS is the most common cause of acute motor paralysis in children . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 4

5. Pathogenesis The pathogenesis of GBS remains unclear. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 5 Mayo Clinic

6. Pathogenesis (cont.) Increasing data indicate that it is an autoimmune disease , often triggered by a preceding viral or bacterial infection with organisms such as: Campylobacter jejuni Cytomegalovirus Epstein-Barr virus Mycoplasma pneumoniae. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 6 Kuwabara S. Guillain-Barré syndrome: epidemiology, pathophysiology and management.  Drugs . 2004. 64(6):597-610

7. Pathogenesis (cont.) Vaccination against the: Flu Rabies Meningitis are documented precipitating factors 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 7 Kuwabara S. Guillain-Barré syndrome: epidemiology, pathophysiology and management.  Drugs . 2004. 64(6):597-610

8. Pathophysiology Two pathophysiological forms have been described: Demyelinating form of GBS Axonal forms of GBS 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 8

9. Pathophysiology (Cont.) Demyelinating form of GBS : Segmental demyelination of peripheral nerves is due to immune mediated involving both humoral and cell- mediated immune mechanisms 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 9

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11. Pathophysiology (Cont.) Axonal forms of GBS axonal degeneration may occur without demyelination or inflammation . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 11

12. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 12 Science Direct

13. Pathophysiology (Cont.) 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 13 of patients have a history of an antecedent gastrointestinal or respiratory tract infection

14. Pathophysiology (Cont.) The mechanism of disease possibly involves an abnormal T-cell response precipitated by an infection which activate CD4 +  helper-inducer T cells 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 14 Kimoto K, Koga M, Odaka M, Hirata K, Takahashi M, Li J, et al. Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies.  Neurology . 2006 Nov 28. 67(10):1837-43

15. Epidemiology The annual incidence of GBS range from 0.5-1.5 cases per 100,000 population in individuals younger than 18 years 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 15 Landaverde JM, Danovaro-Holliday MC, Trumbo SP, Pacis-Tirso CL, Ruiz- Matus C. Guillain-Barré syndrome in children aged J Infect Dis</ i >. 2010 Mar. 201(5):746-50 .

16. Epidemiology (Cont.) 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 16 Korinthenberg R, Schessl J, Kirschner J. Clinical presentation and course of childhood Guillain-Barré syndrome: a prospective multicentre study.  Neuropediatrics . 2007 Feb. 38(1):10-7. No evidence exists for any racial predilection Males appear to be at greater risk for GBS than females

17. Subtypes of GBS The clinical spectrum of GBS, which includes individual variation and variable severity of presentation, comprises the following : Acute inflammatory demyelinating polyradiculoneuropathy ( AIDP ) Acute motor axonal neuropathy ( AMAN ) Acute motor and sensory axonal neuropathy ( AMSAN ) Miller-Fisher syndrome ( MFS ) Polyneuritis cranialis 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 17 Kieseier BC, Kiefer R, Gold R, Hemmer B, Willison HJ, Hartung HP. Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system.  Muscle Nerve . 2004 Aug. 30(2):131-56

18. 1.Acute inflammatory demyelinating polyradiculoneuropathy ( AIDP ) A ccounts for 80-90% of GBS cases ( Europe and North America ) Characterized by an immune-mediated attack on myelin with infiltration of lymphocytes and macrophages with segmental stripping of myelin . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 18

19. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 19 http:// www.emgtest.com/wp-content/uploads/2012/11/GUILIAN-BARRE-SX.jpg

20. 1.Acute inflammatory demyelinating polyradiculoneuropathy ( AIDP ) (Cont.) Motor and sensory fibres are usually affected simultaneously , producing corresponding deficits. Electrophysiology shows: Slow nerve conduction velocity Prolonged F waves . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 20

21. 2.Acute motor axonal neuropathy ( AMAN )   Most commonly seen in China and Japan ( 50-60% of cases), as apposed to Western countries ( 10-20% of cases ). In this form, axonal degeneration occurs by immune attack within 1-2 weeks after infection . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 21

22. 2.Acute motor axonal neuropathy ( AMAN ) (cont.)   Specific antibodies to axonal membranes of motor fibres attack the nodes of Ranvier. This , in turn, activates complement and intrusion of macrophages into periaxonal space, resulting in destruction of axons . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 22

23. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 23 http:// www.emgtest.com/wp-content/uploads/2012/11/GUILIAN-BARRE-SX.jpg

24. 2.Acute motor axonal neuropathy ( AMAN ) (Cont.)    C jejuni  is the most common preceding infection, and antiganglioside antibodies are usually found in this type. Electrophysiology shows: Reduction in muscle action potentials with relatively preserved motor nerve conduction velocity Normal sensory nerve action potentials and F waves 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 24 Schwerer B. Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of Guillain-Barré syndrome. Microbes Infect. 2002 Mar. 4(3):373-84

25. 3.Acute motor and sensory axonal neuropathy ( AMSAN ) This type is rare and resembles AMAN except sensory nerves are also affected . This type is associated with a severe course and poor prognosis . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 25 Schwerer B. Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of Guillain-Barré syndrome. Microbes Infect. 2002 Mar. 4(3):373-84

26. 4.Miller-Fisher syndrome ( MFS ) The involvement of CNs is very distinct in this form of GBS . Ocular motor nerves (oculomotor, trochlear, and abducens) are affected and produce a triad of o phthalmoplegia, a taxia, and a reflexia. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 26

27. 4.Miller-Fisher syndrome ( MFS ) (Cont.) Electrophysiology is normal. The characteristic autoantibodies are against gangliosides GQ1b and GT1a. GQ1b plays a key role in the pathogenesis of MFS. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 27

28. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 28 Science Direct

29. Polyneuritis cranialis This is an acute onset of Multiple CN palsies (usually bilateral CN VII with sparing of CNs I and II ) Elevated cerebrospinal fluid protein Slowed nerve conduction velocity Uncomplicated recovery . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 29

30. Physical Examination An ascending motor weakness is noted along with areflexia in the classic form. Areflexia is a hallmark of GBS . Occasionally, some of the more proximal reflexes still may be elicited during the early phase of the disease. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 30

31. Physical Examination (Cont.) Of clinical value is documenting reflexes in serial exams . Progression from normoreflexia / hyporeflexia to areflexia is consistent with acute features of GBS. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 31

32. Physical Examination (Cont.) Occasionally : Autonomic instability ( 26 % ) Ataxia ( 23 % ) Dysesthesias ( 20 % ) Cranial nerve findings ( 35-50 % ), predominantly facial palsy ( Children>adult ) are noted.   19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 32 Inaloo S, Katibeh P. Guillain-barre syndrome presenting with bilateral facial nerve palsy. Iran J Child Neurol. 2014 Winter. 8(1):70-2

33. Physical Examination (Cont.) Leg weakness (i.e., foot drop) is usually noticed first and weakness eventually involves the calves and thighs . Later , respiratory muscles and upper extremities show involvement . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 33

34. Physical Examination (Cont.) Some children may become non-ambulatory . Weakness also may involve the respiratory muscles, and some children need respiratory support during the course of the disease . Mechanical ventilation is used until respiratory muscle function returns. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 34

35. Physical Examination (Cont.) The autonomic neuropathy involves both the sympathetic and parasympathetic systems; manifestations include: Orthostatic hypotension Hypertension Pupillary dysfunction Sweating abnormalities Sinus tachycardia 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 35

36. Guillain-Barré syndrome time course 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 36 https:// www.thelancet.com/action/show

37. Diagnosis The diagnosis of GBS is typically based on the presence of : Progressive ascending weakness Areflexia 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 37

38. Diagnosis (Cont.) Findings on  : Lumbar puncture Electrodiagnostic studies MRI (occasionally) Can give support for the diagnosis . Abnormalities on these studies do not develop until days to weeks after onset of symptoms. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 38

39. Diagnosis (Cont.) Findings on  : Lumbar puncture Electrodiagnostic studies MRI (occasionally) Can give support for the diagnosis . Abnormalities on these studies do not develop until days to weeks after onset of symptoms. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 39

40. Lumbar Puncture Typically , the LP findings are suggestive of demyelination (i.e., increased protein >45 mg/dL within 3 weeks of onset) without evidence of active infection (lack of CSF pleocytosis), 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 40

41. Lumbar Puncture (cont.) The CSF findings may be normal within the first 48 hours of symptoms Occasionally the protein may not rise for a week. Usually by 10 days of symptoms, elevated CSF protein findings will be most prominent . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 41

42. Lumbar Puncture (Cont.) Most patients have fewer than 10 leukocytes per milliliter, but occasionally a mild elevation (i.e., 10-50 cells/mL) is seen. Greater than 50 mononuclear cells/mL of CSF makes the diagnosis of GBS doubtful . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 42

43. Electrodiagnostic Studies Within the first week of the onset of symptoms, electrodiagnostic studies in at least two limbs reveal the following: A d ispersed, i mpersistent, p rolonged, or a bsent F response ( 88%) Increased distal latencies ( 75%) Conduction block ( 58% ) or temporal dispersion of compound muscle action potential ( CMAP ) Reduced conduction velocity ( 50% ) of motor and sensory nerves 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 43

44. Electrodiagnostic Studies (cont.) Criteria for axonal forms include: Lack of neurophysiologic evidence of demyelination Loss of amplitude of CMAP or sensory nerve action potentials to at least less than 80% of lower limit of normal values for age 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 44

45. Serum Anti-Ganglioside Antibodies In adults with GBS , serum ganglioside antibodies directed against GM1, GM1b, GD1a, and GalNAc-GDIa have been associated with  Campylobacter jejuni  infection , acute motor axonal neuropathy , a more severe course , and more residual neurologic deficits. The value of these studies as a prognostic marker in children is still under evaluation . 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 45

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47. Diagnosis (Cont.) Nearly 2 weeks after presentation of symptoms, lumbosacral MRI can show enhancement of the nerve roots with gadolinium . This imaging study has been described to be 83% sensitive for acute GBS, with nerve root enhancement present in 95% of typical cases 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 47 Gorson KC, Ropper AH, Muriello MA, Blair R. Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome.  Neurology . 1996 Sep. 47(3):813-7

48. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 48 Spinal cord lesions may be considered in the differential diagnosis: Transverse myelitis Vascular malformations Epidural abscess Cord infarctions Tumors Cord compression Enteroviral infections of the anterior horn cells Lumbosacral disk syndromes Poliomyelitis Trauma Hopkins syndrome

49. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 49 Peripheral neuropathies from the following may produce a GBS-like picture: Vincristine Glue sniffing Heavy metals poisoning Organophosphate pesticides HIV infection Diphtheria Lyme disease Inborn errors of metabolism Leigh disease Tangier disease Porphyria

50. Treatment In pediatrics, the most effective form of therapy is generally considered to be  intravenous immunoglobulin  ( IVIG ) Plasmapheresis may also be used 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 50

51. Prognosis In general, the outcome of GBS is more favourable in children than in adults the recovery period is long , often weeks to months 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 51

52. Prognosis (cont.) Rarely , it can be fatal in 5-10% of patients with respiratory failure and cardiac arrhythmia Recurrence of GBS occurs in approximately 5% of cases 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 52

53. Prognosis Overall mortality rate in childhood GBS is estimated to be less than 5 % Deaths are usually caused by respiratory failure , often in association with : Cardiac arrhythmias Dysautonomia 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 53

54. Complications of GBS The most common serious complications are: Weakness of the respiratory muscles Autonomic instability 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 54 Ilyas M, Tolaymat A. Minimal change nephrotic syndrome with Guillain-Barré syndrome. Pediatr Nephrol. 2004 Jan. 19(1):105-6

55. Complications of GBS (Cont.) 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 55 Ilyas M, Tolaymat A. Minimal change nephrotic syndrome with Guillain-Barré syndrome. Pediatr Nephrol. 2004 Jan. 19(1):105-6 Other important potential complications include: Pneumonia Ileus Adult respiratory distress syndrome constipation Septicemia gastritis Pressure sores dysesthesias Pulmonary embolus Nephropathy

56. Clinical Summary Features that would put the diagnosis in doubt include: ( 1) Marked persistent weakness ( 2) Bowel and bladder dysfunction at onset ( 3) Persistent bladder or bowel dysfunction ( 4) Mononuclear leukocytosis in the cerebrospinal fluid (>50 cells/µL ) ( 5) A sharp sensory level 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 56

57. Clinical Summary (Cont.) Features required for diagnosis are: (1) Progressive weakness of more than one extremity ( 2) Hyporeflexia or areflexia ( 3) Elevated cerebrospinal fluid protein (>45 mg/dL ) after 1 week following onset of symptoms ( 4) Slow conduction velocity or prolonged F wave on electrophysiology testing. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 57

58. Clinical Summary (Cont.) Features that rule out the diagnosis include: (1) A current history of hexacarbon abuse ( 2) Abnormal porphyria metabolism (3) Recent diphtheria infection ( 4) Evidence of polio, botulism, toxic neuropathy, tic paralysis, or organophosphate poisoning. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 58

59. References Kuwabara S. Guillain-Barré syndrome: epidemiology, pathophysiology and management.  Drugs . 2004. 64(6): 597-610 Landaverde JM, Danovaro-Holliday MC, Trumbo SP, Pacis-Tirso CL, Ruiz- Matus C. Guillain-Barré syndrome in children aged J Infect Dis</ i >. 2010 Mar. 201(5): 746-50 Kimoto K, Koga M, Odaka M, Hirata K, Takahashi M, Li J, et al. Relationship of bacterial strains to clinical syndromes of Campylobacter-associated neuropathies.  Neurology . 2006 Nov 28. 67(10):1837-43 Korinthenberg R, Schessl J, Kirschner J. Clinical presentation and course of childhood Guillain-Barré syndrome: a prospective multicentre study.  Neuropediatrics . 2007 Feb. 38(1):10-7 . Kieseier BC, Kiefer R, Gold R, Hemmer B, Willison HJ, Hartung HP. Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system.  Muscle Nerve . 2004 Aug. 30(2): 131-56 Schwerer B. Antibodies against gangliosides: a link between preceding infection and immunopathogenesis of Guillain-Barré syndrome.  Microbes Infect . 2002 Mar. 4(3): 373-84 Inaloo S, Katibeh P. Guillain-Barré syndrome presenting with bilateral facial nerve palsy.  Iran J Child Neurol . 2014 Winter. 8(1): 70-2 Ilyas M, Tolaymat A. Minimal change nephrotic syndrome with Guillain-Barré syndrome.  Pediatr Nephrol . 2004 Jan. 19(1): 105-6 Gorson KC, Ropper AH, Muriello MA, Blair R. Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barré syndrome.  Neurology . 1996 Sep. 47(3):813-7 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 59 .

60. 19/08/2018 Pediatric Guillain-Barré syndrome Prof. Dr .Saad S Al Ani 60