1. A Case of Pediatric Pain Edward C. Jauch, MD MS FACEP Department of Emergency Medicine Dawn Kleindorfer, MD Department of Neurology University of Cincinnati College of Medicine and Greater Cincinnati / Northern Kentucky Stroke Team

2. Edward Jauch, MD, MS Case History of Present Illness 12 yo. Caucasian female who presents to the Emergency Department complaining of diffuse body pain Symptoms began one week ago originally in distal extremities but now throughout entire body Patient has missed school for the past 4 days due to pain with ambulation but she denies any weakness

3. Edward Jauch, MD, MS Case Past History Past medical history - No significant past medical history Mother notes that members of the family had a “stomach flu”, including the patient, 3 weeks ago Social history - Family recently moved to area, patient is having difficulty adjusting to new school No alcohol or drug use Review of systems - No fever, chills, chest or abdominal pain, rashes Patient states it hurts to breath

4. Edward Jauch, MD, MS Case Physical Exam VS: BP 98/60 HR 110 T 98.9 o F SaO 2 99% Tearful young female clinging to mom HEENT, pulmonary, cardiac, abdominal, extremity, skin exams all unremarkable Neuro exam - Cranial nerves intact Motor largely intact but limited by effort Sensory shows extreme sensitivity to touch in all extremities and less so on trunk Motor tone normal but reflexes absent Patient refused to walk

5. Edward Jauch, MD, MS Case Laboratory Evaluation Chest xray unremarkable CBC and renal profile normal Hepatic with mildly elevated transaminases UA and urine pregnancy negative

6. Edward Jauch, MD, MS Case Disposition Discharge diagnosis: Viral syndrome Follow-up was scheduled with the patient’s pediatrician the following week The physician also discussed with the patient’s parents that her behavior may also reflect her difficulty with her new school

7. Edward Jauch, MD, MS Case Second E.D. Visit Patient returns 2 days later now complaining of profound weakness and shortness of breath VS: BP 130/78 HR 125 T100.6 o F General exam unchanged except increased shortness of breath Neuro exam now reveals: CNI except bilateral VII nerve weakness Flaccid lower and weak upper extremities Less pain to touch but burning sensation persists Deep tendon reflexes remain absent

8. Edward Jauch, MD, MS What is Your Diagnosis?

9. Edward Jauch, MD, MS Guillain Barre Strohl Syndrome

10. Edward Jauch, MD, MS Pathophysiology First described in the 1930’s GBS is an form of acute polyradicularneuropathy Primarily due to demyelination of peripheral nerves In severe forms actual axonal damage occurs (associated with worse prognosis) Numerous precipitants have been identified

11. Edward Jauch, MD, MS Epidemiology General incidence of GBS in children range from 0.8-1.5 per 100k annually Male to female ratio of 1.5:1 No difference based on: Ethnicity Geographic local (although China with outbreaks) Socioeconomic status

12. Edward Jauch, MD, MS Pathophysiolog Pathophysiology Precipitating causes include: Prodromal viral or bacterial illness Campylobacter jejuni Chlamydia, CMV, EBV, HIV, Mycoplasma pneumoniae, Vaccinations (influenza, MMR, oral polio, Td) Pregnancy Malignancy (Hodgkins) Surgery Other (SLE, drugs) Unknown

13. Edward Jauch, MD, MS Clinical Findings Motor Ranging from mild weakness to paralysis Symmetric and ascending Cranial nerves (IV, VI, VII) but rarely bulbar Areflexia Sensory Pain or dysesthesia very common Visceral symptoms not infrequent

14. Edward Jauch, MD, MS Common Pain Syndromes in GBS Back and leg pain Similar in presentation to sciatica Affect large muscle groups Neuropathic pain Burning sensations in the extremities Visceral pain Bloating, cramping Joint pain and myalgias Affects primarily large joints

15. Edward Jauch, MD, MS Laboratory Evaluation Basic labs – Renal profile (SIADH seen in GBS) CBC Hepatic (elevations in transaminases common) Pregnancy ESR (typically < 50 mm/hr) CK (elevated in patients with significant pain) UA (proteinuria in 25%) CSF – Usually with normal opening pressure Classically with elevated protein (> 400 mg/dL) Lack of pleocytosis

16. Edward Jauch, MD, MS Specific Laboratory Evaluations Serum – Antibodies to GM1, Ga1C, or GA1NAc-GD1a gangliosides Antibodies to Campylobacter jejuni Antibodies to CMV HIV Stool cultures for C. jejuni

17. Edward Jauch, MD, MS Electromyographic Testing and Neuroimaging EMG Demonstrates Demyelination + axonal loss Diminished nerve conduction velocities Diagnosis more specific if multiple nerves involved MRI with gadolinium contrast Enhancement of cauda equina and nerve roots suggest areas of inflammation

18. Edward Jauch, MD, MS Differential Diagnosis Acute Neuropathies Critical illness neuropathy Diphtheria Porphyrias Lyme disease Toxins Tick paralysis NMJ Disorders Botulism Myasthenia gravis Myopathies Critical illness myopathy Hypocalcemia, hypokalemia Polymyositis Rhabdomyolysis CNS Disorders Acute spinal cord syndromes Transverse myelitis Poliomyelitis Rabies

19. Edward Jauch, MD, MS Forms of Guillain-Barre Syndrome Motor-sensory75% Diagnosis almost exclusively clinical Pure motor20% Autonomic dysfunction more common Miller Fisher syndrome 3% Weakness starts in eye muscles Bulbar variant 2% Weakness involves muscles of deglutition and or tongue (Dutch Neuromuscular Research Centre, Eur Neurol 2001)

20. Edward Jauch, MD, MS Treatment ABC’s Supportive and expectant care is key. Early pulmonary function tests to identify patients at risk of impending respiratory failure Recognition and treatment of autonomic instability Immunomodulating therapies

21. Edward Jauch, MD, MS Signs, Symptoms, and Paraclinical Findings in Overt Neuromuscular Respiratory Failure Signs and symptoms Air hunger Altered mentation Accessory muscle use Paradoxical respiration Inability to count to 20 in one breath Staccato speech Paraclinical findings Vital capacity < 15 ml/kg Negative inspiratory force < -25 cm H 2 0 Positive expiratory force < 40 cm H 2 0 Vital capacity drop of > 55% from supine to sitting Hypoxemia Atelectasis (Chalela, Seminars in Neurology 2001)

22. Edward Jauch, MD, MS Treatment Autonomic Dysfunction Paroxysmal hypertension Sudden swings make treatment more difficult Short acting agents safest (nitroprusside) Hypotension and orthostatic hypotension Rarely requires therapy (IV fluids) Cardiac arrhythmias Most life threatening Bradycardia treated with atropine Tachyarrhythmias may include atrial fibrillation, atrial flutter, and ventricular tachycardia, all respond to standard treatment

23. Edward Jauch, MD, MS Treatment Immunomodulating Therapies Plasma exchange Only therapy with proven benefit May require multiple exchanges Cautious use in patients with autonomic instability Immunoglobulin therapy (IV IgG) Relatively easy to administer Benefit unclear Risk of viral (hepatitis C) transmission Steroids without benefit (Cochrane Review, 2001)

24. Edward Jauch, MD, MS Treatment Pain Syndromes Deep muscle ache in low back or large muscles Nonsteroidal anti-inflammatory drugs Neuropathic pain TCA’s effective, use with caution in autonomic dysfunction Carbamazepine Joint pain Ice packs, nonsteroidal anti-inflammatory drugs Throat pain associated with intubation Intermittent cuff deflation, tracheostomy

25. Edward Jauch, MD, MS Details Admission to a high acuity area is critical for adequate patient monitoring Continuous cardiac monitoring Close respiratory observation Do not delay intubation until the patient becomes hypoxic! Neurology should be involved early on

26. Edward Jauch, MD, MS Outcome Prediction in GBS Clinical factors Advanced age Rapid symptom progression Mechanical ventilation Upper extremity involvement Inability to walk at 8 weeks Biochemical markers Anti-GM1 antibodies High CSF NSE or S100 levels Epidemiologic factors Antecedent diarrhea Campylobacter jejuni infection Cytomegalovirus infection Electrophysiologic findings Absent or reduced CMAP Unexcitable nerves Predominantly axonal involvement (Chalela, Seminars in Neurology 2001)

27. Edward Jauch, MD, MS Prognosis In general the prognosis of GBS is good Up to 85% of patients with GBS make a full recovery Mortality rates range from 2-12% 15% of patients with persistent deficits

28. Edward Jauch, MD, MS Conclusions Guillian-Barre Syndrome should no longer have significantly mortality if properly diagnosed and treated Guillian-Barre may present with pain as the primary symptom in children The key differential is primary spinal cord injury, GBS, and tick paralysis

29. Edward Jauch, MD, MS Case Outcome Patient required intubation within 24 hours of admission Plasma exchange performed 4 times over next 7 days Patient was extubated on hospital day 6 Returned to school 4 weeks from admission Patient with minimal residual leg weakness at 6 months follow-up

30. “When the end of the world comes, I want to be in Cincinnati because it's always twenty years behind the times."