GSDM: Past Present & future

1. GSDM: Past Present & future RM Clemmons, DVM, PhD, CVA, CVFT Gainesville, FL

2. German Shepherd Degenerative Myelopathy (GSDM) • A chronic, progressive neurodegenerative disease • Initial signs are due to TL spinal cord disease • Represents an autoimmune disorder

4. Signalment • Breeds • German Shepherd dogs • Belgium Shepherds • Old English Sheepdogs • Rhodesian Ridgebacks • Weimaraner • Probably Great Pyrenes • Age • > 5 years old (usually 8-9) • Sex • Equal • Onset • 1 month to 1 year • Clinical Course • Paralysis within 3 to 6 month without treatment

5. Signs of GSDM

6. Histopathology • Axon and myelin loss • Swollen axons • Patchy demyelination • Astrocyte proliferation • Increase in vasculature

7. Diagnosis • Physical and Neurologic Examination History of chronic progressive posterior paresis in susceptible breed TL (non-localized) dysfunction • Negative Neural Imaging • Normal Electrodiagnostic Exam Might have altered spinal evoked response • Abnormal CSF Lumbar CSF changes

8. Greta • Signalment • 8 yr F/S GSD • Weakness • Posterior Paresis S

9. Greta • History • Seemed to be slower over last 6 months • Trouble getting up • Vet checked for HD • Minimal response to NSAIDs • Worse over last 30 days S

10. Greta

11. Greta • Neurologic Examination • Head- -NAF • CN- -NAF • Mild Neck Pain (C6) • Forelegs- -NAF (slight dysmetria) • Rear Legs- • Slight hyperflexia L>R • CP deficits Bilaterally • Babinski L • Hypermetria • Mild Back Pain (TL) O

12. Greta • Localization of Lesion • D • A • M • N • N • I • I • I • T • T • V IVDD, GSDM T3-L3 Spinal Cord Spinal Tumor Myelitis GME O

13. Greta • Differential Dx • ? • Diagnostic Approach • ? • Treatment • ? • Problem List • GSDM • IVDD • Infect/Inflamm • Neoplasia • Posterior Paresis • Foreleg Hypermetria • Neck & Back Pain P

14. Greta- -Diagnostic Approach • MDB • CBC • Chemistry Profile • UA • Chest & Abdominal Radiographs • Abdominal Ultrasound • Neurologic Tests • EMG • CSF Analysis • Cisternal • Lumbar • MRI (Whole Spine) • Client Education P

15. Greta- -Blood work & UA • Unremarkable O

16. Greta- -Chest Rads O

17. Greta- -Abdominal Rads O

18. Greta- -Abdominal Ultrasound O

19. Greta • Differential Dx • ? • Diagnostic Approach • ? • Treatment • ? P

20. Humeral Immunity •  Circulating Immune-complexes • 59.3 + 2.5 µg/ml (normal = 18.7 + 2.5 µg/ml) • Contain  non- specific inflammatory proteins on electrophoresis

21. Cell-Mediated Immunity • Attenuated Response to Mytogens • ConA • Polkweed Mitogen • PHA • Circulating Suppressor Cells

22. Greta- -EMG • Needle EMG normal • NCV 55 m/sec • F wave present • RNS- -nondecremental • SEP- -abnormal Greta O

23. Spinal Cord Evoked Potential Normal Early DM Late DM

24. Greta- -CSF Analysis • Cisternal CSF • Color/Transparency • clear • Protein mg/dL • 15 • RBC/μL • 1 • WBC/μL • 1 • A cell differential count yielded the following: • 1% Neutrophils • 89% Lymphocytes • 10% Mononuclear phagocytes • Interpretation: • Benign CSF • Lumbar CSF • Color/Transparency • clear • Protein mg/dL • 65 • RBC/μL • 15 • WBC/μL • 2 • A cell differential count yielded the following: • 1% Neutrophils • 85% Lymphocytes • 14% Mononuclear phagocytes • Interpretation: • Albuminocytologic dissociation O

25. CSF Cholinesterase * * • Greta • AO- - 250 IU/ml • Lumbar- - 560 IU/ml normal DM inflam O

26. IgG concentration normal DM Lumbar IgG Concentration

27. Oligoclonal Bands of IgG

28. Oligoclonal Bands of IgG

29. Normal DM 2-D Electrophoresis of CSF

30. CSF Inflammatory Markers

31. MBP assay in CSF • GSDM: 4.28 ng/ml ± 2.36 • Non-Infam. ND: 0.63 ng/ml ± 0.86 (t>0.05)

32. MBP/TP ratio in CSF • GSDM: 0.092 ± 0.048 • Non-Inlfam. ND: 0.024 ± 0.020 (t>0.05)

33. Greta- -MRI Lumbar O

34. Greta- -MRI Thoracic O

35. Greta- -MRI Cervical O

36. Greta- -Assessment • MDB was essentially normal • Mild HD/hepato- -splenomegaly • EMG demonstrated alterations consistent with spinal white matter conduction delay • CSF showed TL Albuminocytologic dissociation consistent with chronic degenerative prosess • MRI did not reveal significant structural disease A

37. 123 45678 Greta- -DM Flash Test • Results came back POSITIVE • 96% sensitivity • 99% specificity Figure 3. DM Flash test. 1-4 are GSDM patients while 5-8 are GSD patients with other neurological diseases. O

38. Greta- -Final Diagnosis German Shepherd Dog Myelopathy A

39. Current Hypothesis • An Auto-Immune CNS Disease • Immune-complexes damage endothelium • Leads to perivascular fibrin deposition • Fibrin degradation leads to leukocyte infiltration • Leukocytes produce prostaglandins and leukotreines • Leads to Free-Radical production and damage • Treatment must take these steps into account

40. Comparison of GSDM & PPMS • GSDM • Progressive spinal cord disease with myelin & axonal loss • No sex predilection • Occurs in 4-6th decade of life • Course is 7-10 years • CSF oligoclonal IgG • Non-plaque forming • Increased CSF MBP • PPMS • Progressive spinal cord disease with myelin & axonal loss • No sex predilection • Occurs in 4-6th decade of life • Course is 7-10 years • CSF oligoclonal IgG • Non-plaque forming

41. Greta- -Client Education • May expect gradual return to function expecting 80% of recovery in 3 months • May continue to progress over 12-18 months • Need to monitor spleen and blood work every 6 months • Reassess as needed, changing medications when appropriate P

42. Greta- -TCVM exam • Tongue • Pale • Wet • Pulse • Weak bilaterally • Sensitivity • GB 21 • BL 18 • BL 23 • TCVM Diagnosis • Combined Qi/Yin Deficiency with Stagnation

43. Treatment • Exercise • 20-30 minutes twice a week • 1 hour once a week • sustained aerobic exercise is needed •  CNS O2 delivery

44. Treatment • Dietary Considerations • Tofu • Fresh vegetables • carrots • greens • peppers • broccoli • Ginger, garlic & mustard

45. Treatment • Supplements • Antioxidants • Membrane stabilizers • Tonics • Anti-inflammatory

46. Treatment • Medication • Aminocaproic acid (500 mg TID) • n-Acetylcysteine (25 mg/kg TID QD for 2 weeks, then TID QOD)

47. Conclusion • Degenerative Myelopathy appears to be an Autoimmune Disease and Treatment must be directed at this Process. • Exercise • Diet • Supplements • Medication Things that  CNS O2 Availability

48. TCVM for GSDM • Treat what you see • Most cases present with Wei syndrome secondary to combined Qi & Yin Deficiency • Special AP • BL-62 • Herbals • Di Huang Yin Zi Tang (Rehmannia Decoction) • HuQian Tang (Hidden Tiger Powder)

49. Di Huang Yin Zi Tang(Rehmannia Decoction) Shu Di Huang 10 gm Shan Zhu Yu 10 gm Rou Cong Rong 10 gm BaJiTian 10 gm Fu Zi 10 gm Rou Gui - An Nan 10 gm Shi Hu – fine 10 gm Mai Men Dong 10 gm Shi Chang Pu 10 gm Yuan Zhi 10 gm Fu Ling – curled 10 gm Wu Wei Zi 10 gm Powder herbs and mix thoroughly. Dosage is 0.5 gm/10lbs for 2 weeks and then 1 gm/10lbs.

50. Di Huang Yin Zi Tang(Rehmannia Decoction) Rx Principle: Nourish and tonifies kidney yin; strengthens kidney water to pacify heart fire; warm and tonifies kidney yang; and strengthen bones and sinews of lower back. Indications: Stiffness of tongue and hoarse voice; andparalysis of lower extremities. Dry mouth without thirst and deep weak pulses. Contraindications: Excess conditions with rising yang.