gsdm: past present & future
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GSDM: PAST PRESENT & FUTURE
RM Clemmons, DVM, PhD, CVA, CVFTGainesville, FL
German Shepherd Degenerative Myelopathy
(GSDM) A chronic, progressive
neurodegenerative disease
Initial signs are due to TL spinal cord disease
Represents an autoimmune disorder
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
Signs of GSDM
Histopathology
Axon and myelin loss Swollen axons Patchy demyelination
Astrocyte proliferation
Increase in vasculature
Diagnosis1. Physical and Neurologic Examination
History of chronic progressive posterior paresis in susceptible breed
TL (non-localized) dysfunction
2. Negative Neural Imaging3. Normal Electrodiagnostic Exam
Might have altered spinal evoked response
4. Abnormal CSFLumbar CSF changes
Greta
Signalment
8 yr F/S GSD Weakness Posterior Paresis
S
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 daysS
Greta
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
Greta Localization of
Lesion D A M N N I I I T T VO
T3-L3 Spinal Cord
IVDD, GSDM
MyelitisGME
Spinal Tumor
Greta Differential Dx
?
Diagnostic Approach ?
Treatment ?
P
• Problem List1. Posterior Paresis
2. Foreleg Hypermetria
3. Neck & Back Pain
1. GSDM2. IVDD3. Infect/Inflamm4. Neoplasia
Greta- -Diagnostic Approach
MDB CBC Chemistry Profile UA Chest & Abdominal
Radiographs Abdominal Ultrasound
Neurologic Tests EMG CSF Analysis
Cisternal Lumbar
MRI (Whole Spine)
Client EducationP
Greta- -Blood work & UA Unremarkable
O
Greta- -Chest Rads
O
Greta- -Abdominal Rads
O
Greta- -Abdominal Ultrasound
O
Greta
Differential Dx ?
Diagnostic Approach ?
Treatment ?
P
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
Cell-Mediated Immunity
Attenuated Response to Mytogens ConA Polkweed Mitogen PHA
Circulating Suppressor Cells
Greta- -EMG Needle EMG normal NCV 55 m/sec F wave present RNS- -nondecremental SEP- -abnormal
O
Greta
Spinal Cord Evoked Potential
NormalEarly DMLate DM
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
dissociationO
CSF Cholinesterase
normal DM inflam
*
*
O
• Greta• AO- - 250 IU/ml• Lumbar- - 560 IU/ml
Lumbar IgG Concentration
IgG
con
cent
ratio
n
DM normal
Oligoclonal Bands of IgG
Oligoclonal Bands of IgG
2-D Electrophoresis of CSF
Normal DM
CSF Inflammatory Markers
ICAM IL6 NSE Ubiq. S100 Neop.DM Mean 1.5 1.2 1.1 0.9 0.4 1.1
SD 0.7 0.6 0.7 0.9 0.5 1.0Freq. 0.9 0.9 0.8 0.6 0.4 0.7
NIFD Mean 0.8 0.3 0.7 0.3 0.2 0.8SD 0.8 0.8 0.5 0.8 0.4 1.0
Freq. 0.7 0.2 0.7 0.2 0.2 0.5
MBP assay in CSF
GSDM: 4.28 ng/ml ± 2.36
Non-Infam. ND: 0.63 ng/ml ± 0.86
(t>0.05) M
BP0
2.5
5
7.5
10
DM cont
trt
Oneway Analysis of MBP By trt
MBP/TP ratio in CSF
GSDM: 0.092 ± 0.048
Non-Inlfam. ND: 0.024 ± 0.020
(t>0.05)m
bp/tp
0
0.025
0.05
0.075
0.1
0.125
0.15
DM cont
trt
Excluded Rows 1
Oneway Analysis of mbp/tp By trt
Greta- -MRI Lumbar
O
Greta- -MRI Thoracic
O
Greta- -MRI Cervical
O
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
Greta- -DM Flash Test
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
GRETA- -FINAL DIAGNOSISGerman Shepherd Dog
Myelopathy
A
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
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
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 appropriateP
Greta- -TCVM exam Tongue
Pale Wet
Pulse Weak bilaterally
Sensitivity GB 21 BL 18 BL 23
TCVM Diagnosis
Combined Qi/Yin Deficiency with Stagnation
Treatment
Exercise
20-30 minutes twice a week
1 hour once a week
sustained aerobic exercise is needed
CNS O2 delivery
Treatment
Dietary Considerations
Tofu Fresh vegetables
carrots greens peppers broccoli
Ginger, garlic & mustard
Treatment
Supplements
Antioxidants Membrane stabilizers Tonics Anti-inflammatory
Treatment
Medication
Aminocaproic acid (500 mg TID)
n-Acetylcysteine (25 mg/kg TID QD for 2 weeks, then TID QOD)
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
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) Hu Qian Tang (Hidden Tiger Powder)
Di Huang Yin Zi Tang(Rehmannia Decoction)
Shu Di Huang 10 gm Shan Zhu Yu 10 gmRou Cong Rong 10 gmBa Ji Tian 10 gm Fu Zi 10 gm Rou Gui - An Nan 10 gmShi Hu – fine 10 gmMai Men Dong 10 gmShi Chang Pu 10 gm Yuan Zhi 10 gmFu 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.
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.
Hu Qian Tang (Hidden Tiger Powder)
Jiu Chao Huang Bai 150 gmJiu Chao Zhi Mu 30 gmShu Di Huang 60 gmSu Zhi Gui Ban 120 gmBai Shao 60 gmHu Gu 60 gm (Substitute Chuan Niu
Xi)Suo Yang 45 gmGan Jiang 15 gmChen Pi 60 gm
Powder herbs and mix thoroughly. Dosage is 0.5 gm/10lbs for 2 weeks and then 1 gm/10lbs.
Hu Qian Tang (Hidden Tiger Powder)
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.
Greta- -TCVM Therapy 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
GSDM Future Stem Cell Therapy
Currently temporary effects
Epimedium Powder Spinal EA
Polypeptides Neuroregenerative
Peptide Gelsolin
Improved Diagnostics Alternatives to
SOD1 Perhaps altered
ubiquitin pathway
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