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Guillain barre synd

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  1. 1. Guillain-Barre Syndrome William Woodfin MD
  2. 2. K.F. 40 y.o. r/h woman 3/17 Nausea, diarrhea & severe myalgias Son dxed c rotavirus 1 wk. Previously 4/21 Creepy-crawlies legs>arms 4/25 Weakness legs progressing 4/26 Handwriting looks like hen scratch
  3. 3. K.F. 40 y.o. woman 4/28 Admitted to outside hospital. L.P. wnl EMG positive waves in some leg muscles NCVs absent H-reflexes F responses & motor latencies wnl
  4. 4. K.F. 40 y.o. woman 4/29 Transferred to PHD Hx.: diabetic x 10 yrs. hypothyroid- treatedx yrs. no sphincter disrubance aching pain low back & buttocks mild postural light headedness no SOB or palpatations
  5. 5. Exam BP 150/90 P 80 Wt. 250 lbs. Mild weakness neck flexors 4/5 biceps, grip & interossei- symmetric 2/5 iliopsoas & quadriceps 3/5 hamstrings & adductors 4/5 abductors 4/5 ankles & toes- extensors & flexors
  6. 6. Exam Sensory- intact DTRs- biceps, BR, knees are trace c reinforcement. Triceps & ankles unobtainable Plantars- flexor F to N- intact Gait- not testable
  7. 7. Lab H/H 10.3/33.5 c microcytic indices A1c Hgb 10.1 TSH 0.97 LDL 182 Serum immunofixation- wnl. No IgA def. FVCs- consistently 4+ liters
  8. 8. MRI LS spine s & c contrast- no nerve root enhancement
  9. 9. Course in hospital Treated c IVIG 0.4 gms/kgm daily x 5 Strength fluctuated only mildly Blood sugars ok in AM, high in afternoons Repeated NCVs show mild dispersion of F waves Transferred back to referring hospital 5/6
  10. 10. Telephone FU Ambulating fairly well c walker. Strength clearly improving. Still bothered by creepy-crawlies
  11. 11. What is the GBS? Due to the breadth of clinical presentation it is of limited help to try to define rigid diagnostic criteria. Thomas Munsat 1965: The GBS is easy to diagnose but difficult to define
  12. 12. The typical illness evolves over weeks usually following an infectious disease and involves: 1. Paresthesiaes usually hearld the disease 2. Fairly symmetric weakness in the legs, later the arms and, often, respiratory and facial muscles 3. Dimunition and loss of the DTRs 4. Albuminocytologic dissociation 5. Recovery over weeks to months
  13. 13. History Waldrop 1834 Olliver 1837 Landry 1859 Graves 1884 Ross & Bury 1893 Brussels Conf. 1937 Haymaker & Kernohan 1949 Waksman & Adams 1955 Miller Fisher 1956 Asbury, Aranson & Adams 1969 Guillain, Barre & Strohl 1916-1920
  14. 14. Note sur la paralysie ascendante aigue 1859 March 16- a febrile illness May 11- mild sensory symptoms in the fingers and toes June 13- knees buckle June 16- unable to walk Subsequent respiratory failure and death. Autopsy unrevealing. Peripheral nerves probably not examined
  15. 15. Late 19th century Westphal 1876- Landrys Ascending Paralysis Graves 1884- localized neurologic disease to the peripheral nerves, the nervous cords Ross & Bury 1893- 90 cases. A disease of the peripheral nerves Numerous reports emphasizing various aspects of the disease with most authors crediting Landry
  16. 16. Georges Guillain
  17. 17. Revue Neurologique 1916
  18. 18. Guillain, Barre & Strohl 1916 Revue Neurologique Two soldiers in Amiens developing paralysis and loss of DTRs. A new diagnostic feature: albuminocytologic dissociation in the CSF No mention of Landry
  19. 19. Foundations Quincke- CSF observations 25 years earlier Siccard & Foix- albuminocytologic dissociation in Potts disease Late 19th century: examination of the reflexes had become a part of the neurologic exam with appreciated as a sign of neuropathy based on observations in tabes dorsalis areflexia
  20. 20. Haymaker & Kernohan 1949 Landmark in pathological description c 50 fatal cases & detailed review of clinical findings Emphasized prominent damage to proximal nerves often at junction of ventral & dorsal roots. Little study of more distal nerves Unified findings of Landry & Guillain, Barre & Strohl
  21. 21. Waksman & Adams 1955 Experimental Allergic Neuritis First animal model of a noninfectious inflammatory neuritis Rabbit nerve and Freunds adjuvant injected intradermally Target of activated T cells uncertain
  22. 22. Asbury, Aranson & Adams 1969 19 pts. All with well developed mononuclear infiltrates in spinal roots and nerves within days of clinical onset Pathological hallmark: perivascular mononuclear inflammatory infiltrates to adjacent to the areas of demyelination
  23. 23. Overview of Adaptive Immunity Lymphocytes: command & control, identify antigen components, respond specifically, mobilize other elements and direct the attack c memory for each antigenic assault Antibodies: specialized immunoglobulin molecules directly neutralize and remove antigen
  24. 24. T lymphocytes CD8- recognize epitopes paired c MHC-I CD4- activate and control the immune response Scavenger cells break down antigen into small peptide fragments (T cell epitopes), MHC-II epitope complexes are expressed on the surface & the scavenger become an APC which docks on a CD4 c a compatible TCR. CD4 proliferates releasing cytokines.
  25. 25. Antibodies Cytokines activate other lymphocytes including B cells that differentiate into plasma cells and serve as immunoglobulin factories. Abs are Ig molecules that recognize, bind, neutralize and opsonize Ag for phagocytosis. They activate complement(membrane attack complex) & induce target cells to activate the inflammatory response
  26. 26. Cellular & Humoral Immune Mechanisms
  27. 27. Self-tolerance The process of self recognition T & B cells learn self tolerance during maturation Autoimmunity occurs when the mechanisms of self protection are defective
  28. 28. Mechanisms of Autoimmunity Molecular mimicry- microbe cell surface Ag resembles self protein. Damage results from friendly fire The inciting Ag is usually unidentified & may not exist as a single stimulus. Excessive cytokine release due to profound immune stimulus may awaken self tolerant T cells or may cause expression of MHC complexes. Self Ags bound to drugs may lose tolerated status
  29. 29. Antecedent Events: Infectious Viral: Influenza, Coxsackie, EBV, Herpes, HIV, Hepatitis, CMV, WNV Bacterial: Campylobacter jejuni, Mycoplasma, E. coli Parasitic: Malaria, Toxoplasmosis
  30. 30. Antecedent Events: Systemic disease Hodgkins CLL Hyperthyroidism Sarcoidosis Collagen Vascular d. Renal d.
  31. 31. Other antecedent events Surgery Immunization Pregnancy Envenomization Bone marrow transplantation Drug ingestion
  32. 32. Features of AIDP 2/3s have identifiable preceding event 50% begin with paresthesias followed by weakness in legs; 10% begin with arm weakness; rarely begins in face Ophthalmoplegia: partial 15%, total 5% Autonomic dysfunction in 65%, arrhythmias, hypotension,urinary retention in 10-15%, pupillary inequality
  33. 33. AIDP Progresses for days to 4 weeks 15% with severe disability Mortality 3-5% CSF: protein may be normal early, elevated in 90% by clinical nadir, cells< 10 in 95%, >50 suggests HIV EDX: prolonged F & distal motor latencies, conduction block 30-40% in routine studies
  34. 34. AIDP Pathology: immune attack directed at schwann cell plasmalemma esp. at nerve roots with IgG & complement deposits preceding demyelination
  35. 35. CIDP Evolves over months Fluctuates Respiratory failure, dysautonomia, facial weakness, ophthalmoplegia- all are rare CSF protein often highly elevated Marked slowing of motor nerve conduction Steroid responsive
  36. 36. Features of AMSAN Commonly preceded by diarrhea esp. c. jejuni Abrupt onset of weakness c rapid progression to quadriplegia & respiratory insufficiency Other features as c AIDP Longer recovery, more residual & mortality 10-15%
  37. 37. AMSAN CSF as in AIDP EDX: no response in some motor nerves, decreased amplitude of the CMAPs, fibrillations on needle study, absent SNAPs Immune attack directed at axon plasmalemma at nodes of Ranvier. Wallerian degeneration
  38. 38. Features of AMAN Often preceded by diarrhea affecting younger population in China. Sporadic in USA Prognosis similair to AIDP Mortality