1. Degenerative Myelopathy Copyright University of Florida 1998 Of German Shepherd Dogs A chronic, progressive neurodegenerative disease Initial signs are due to TL spinal cord disease Represents an auto- immune disorder

2. Degenerative Myelopathy Copyright University of Florida 1998 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

3. Degenerative Myelopathy Copyright University of Florida 1998 Similar Conditions in Human Beings Multiple Sclerosis –Immune-related demyelinating disorder Amyotrophic Lateral Sclerosis –Axonal losing disease Genetic Free-radical association

4. Degenerative Myelopathy Copyright University of Florida 1998 Progression

5. Degenerative Myelopathy Copyright University of Florida 1998 Early Clinical Signs Mild Spinal Ataxia –Diminished Proprioception –Slight Hyper-reflexia in Rear Legs Rear Leg Weakness –Slight Muscle Atrophy Occasionally, Atypical LMN Dysfunction

6. Degenerative Myelopathy Copyright University of Florida 1998 Late Clinical Signs Severe Spinal Ataxia –Conscious Proprioceptive Deficits –Unconscious Proprioceptive Deficits –Crossed-extensor Reflex –Babinski’s Sign

7. Degenerative Myelopathy Copyright University of Florida 1998 Late Clinical Signs Severe Motor Weakness –Loss of Weight Bearing –Moderate Rear Leg Muscle Atrophy

8. Degenerative Myelopathy Copyright University of Florida 1998 Histopathology Axon and myelin loss –Swollen axons –Patchy demyelination Astrocyte proliferation Increase in vasculature

9. Degenerative Myelopathy Copyright University of Florida 1998 Diagnosis Physical and Neurologic Examination –History of chronic progressive posterior paresis in susceptible breed –TL (non-localized) dysfunction

10. Degenerative Myelopathy Copyright University of Florida 1998 Diagnosis EMG –Needle EMG- -normal –NCV- -normal –Repetitive Nerve Stimulation- -non- decremental –Spinal Evoked Potential- -abnormal

11. Degenerative Myelopathy Copyright University of Florida 1998 Spinal Evoked Potential a. Normal b. Early DM c. Late DM

12. Degenerative Myelopathy Copyright University of Florida 1998 Diagnosis CSF tap (lumbar) –Increased protein with normal cells –Elevated inflammatory proteins –Increased acetylcholinesterase levels (2 X normal)

13. Degenerative Myelopathy Copyright University of Florida 1998 Diagnosis Spinal Radiographs –Plain radiographs- -spondylosis & spinal arthritis –Myelography- -no significant lesions Immune Studies

14. Degenerative Myelopathy Copyright University of Florida 1998 CSF Analysis Lumbar CSF tap and analysis –Normal cellularity –Slight to moderate increase in protein content 80-120 mg/dl Normal BB Barrier –258.4 + 92.7

15. Degenerative Myelopathy Copyright University of Florida 1998 2-D Electrophoresis of CSF NormalDM

16. Degenerative Myelopathy Copyright University of Florida 1998 CSF Cholinesterase

17. Degenerative Myelopathy Copyright University of Florida 1998 CSF Inflammatory Markers Increased Inflammatory Markers –IL6 –ICAM –Leukotreine C, D, E No Markers for: –viral and bacterial infection –prion infection –TNF

18. Degenerative Myelopathy Copyright University of Florida 1998 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