1. RM Clemmons, DVM, PhD, CVA, CVFT Gainesville, FL

2.  A chronic, progressive neurodegenerative disease  Initial signs are due to TL spinal cord disease  Represents an autoimmune disorder

4.  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

6.  Axon and myelin loss  Swollen axons  Patchy demyelination  Astrocyte proliferation  Increase in vasculature

7. 1. Physical and Neurologic Examination History of chronic progressive posterior paresis in susceptible breed TL (non-localized) dysfunction 2. Negative Neural Imaging 3. Normal Electrodiagnostic Exam Might have altered spinal evoked response 4. Abnormal CSF Lumbar CSF changes

8.  Signalment  8 yr F/S GSD  Weakness  Posterior Paresis S

9.  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

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

13.  Differential Dx  ?  Diagnostic Approach  ?  Treatment  ? P Problem List 1.Posterior Paresis 2.Foreleg Hypermetria 3.Neck & Back Pain 1.GSDM 2.IVDD 3.Infect/Inflamm 4.Neoplasia

14.  MDB  CBC  Chemistry Profile  UA  Chest & Abdominal Radiographs  Abdominal Ultrasound  Neurologic Tests  EMG  CSF Analysis  Cisternal  Lumbar  MRI (Whole Spine)  Client Education P

15.  Unremarkable O

16. O

17. O

18. O

19.  Differential Dx  ?  Diagnostic Approach  ?  Treatment  ? P

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

21.  Attenuated Response to Mytogens  ConA  Polkweed Mitogen  PHA  Circulating Suppressor Cells

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

23. Normal Early DM Late DM

24.  Cisternal CSF  Color/Transparency  clear  Protein mg/dL  15  RBC/ μ L  1  WBC/ μ L  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/ μ L  15  WBC/ μ L  2  A cell differential count yielded the following:  1% Neutrophils  85% Lymphocytes  14% Mononuclear phagocytes  Interpretation :  Albuminocytologic dissociation O

25. normalDMinflam * * O Greta Greta AO- - 250 IU/ml AO- - 250 IU/ml Lumbar- - 560 IU/ml Lumbar- - 560 IU/ml

26. IgG concentration DM normal

29.  Normal  DM

31.  GSDM: 4.28 ng/ml ± 2.36  Non-Infam. ND: 0.63 ng/ml ± 0.86 (t>0.05)

32.  GSDM: 0.092 ± 0.048  Non-Inlfam. ND: 0.024 ± 0.020 (t>0.05)

33. O

34. O

35. O

36.  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. POSITIVE  Results came back POSITIVE  96% sensitivity  99% specificity 1 2 3 4 5 6 7 8 Figure 3. DM Flash test. 1-4 are GSDM patients while 5-8 are GSD patients with other neurological diseases. O

38. German Shepherd Dog Myelopathy A

39.  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.  GSDM  Progressive spinal cord disease with myelin & axonal loss  No sex predilection  Occurs in 4-6 th 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 4-6 th decade of life  Course is 7-10 years  CSF oligoclonal IgG  Non-plaque forming

41.  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.  Tongue  Pale  Wet  Pulse  Weak bilaterally  Sensitivity  GB 21  BL 18  BL 23  TCVM Diagnosis  Combined Qi/Yin Deficiency with Stagnation

43.  Exercise  20-30 minutes twice a week  1 hour once a week  sustained aerobic exercise is needed   CNS O 2 delivery

44.  Dietary Considerations  Tofu  Fresh vegetables  carrots  greens  peppers  broccoli  Ginger, garlic & mustard

45.  Supplements  Antioxidants  Membrane stabilizers  Tonics  Anti-inflammatory

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

47.  Degenerative Myelopathy appears to be an Autoimmune Disease and Treatment must be directed at this Process.  Exercise  Diet  Supplements  Medication Things that  CNS O 2 Availability

48.  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)  Hu Qian Tang (Hidden Tiger Powder)

49. Shu Di Huang10 gm Shan Zhu Yu10 gm Rou Cong Rong10 gm Ba Ji Tian10 gm Fu Zi10 gm Rou Gui - An Nan10 gm Shi Hu – fine10 gm Mai Men Dong10 gm Shi Chang Pu10 gm Yuan Zhi10 gm Fu Ling – curled10 gm Wu Wei Zi10 gm Powder herbs and mix thoroughly. Dosage is 0.5 gm/10lbs for 2 weeks and then 1 gm/10lbs.

50. 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.

51. Jiu Chao Huang Bai150 gm Jiu Chao Zhi Mu30 gm Shu Di Huang60 gm Su Zhi Gui Ban120 gm Bai Shao60 gm Hu Gu60 gm (Substitute Chuan Niu Xi) Suo Yang45 gm Gan Jiang15 gm Chen Pi60 gm Powder herbs and mix thoroughly. Dosage is 0.5 gm/10lbs for 2 weeks and then 1 gm/10lbs.

52. Rx Principle: Nourishes yin; causes fire to descend; and strengthens bones and sinews. Treats a atrophy disorders by drying the damp and strengthening the kidney. Indications: Weakness in lower back and knees; deterioration of the sinews and bones with general reduction of function; wasting of muscle of the rear legs and feet; and difficult walking. Associated with red tongue and deep, weak pulses. Contraindications: Not for atrophy due to spleen and stomach deficiency or invasion of damp-heat.

53.  AP  Cervical points  BL10  GB 21  Lumbar points  GV 14  Bai Hui (EA & Moxa)  BL40  BL62  Other points  ST 36  SP 6  LI 10  LIV 3  Herbal  Hu Qian Tang  Walking Tiger Formula  Jing Tang  Di Huang Yin Zi  Rehmannia Formula for Paralysis  Jing Tang

54.  Stem Cell Therapy  Currently temporary effects  Epimedium Powder  Spinal EA  Polypeptides  Neuroregenerative Peptide  Gelsolin  Improved Diagnostics  Alternatives to SOD1  Perhaps altered ubiquitin pathway