Chronic Degenerative Radiculomyelopathy (CDRM)

Chronic Degenerative Radiculomyelopathy (CDRM)

TABLE OF CONTENTS

What is CDRM ?

Chronic Degenerative Rediculomyelopathy is also known as Canine Degenerative Myelopathy (DM), German Shepherd Dog myelopathy and progressive myelopathy. This is a non painful, chronic, progressive spinal cord disease.

It's a relatively commonly made diagnosis in middle aged to old German Shepherd Dogs.

DM is an insidious disease which affects middle-aged to older dogs, with an onset range of 5 to 14 years of age.

The aetiology of DM is unknown, however research has identified a genetic mutation (SOD-1) which is associated with an increased risk of the disease. Many breeds may experience a spinal cord disease (myelopathy) which is chronic and progressive (degenerative); however its important to know if they are caused by the same immune-related disease which characterises DM in GSD's.

Clinical presentation is of a chronic progressive paraparesis (weakness) developing non ambulatory paraparesis to tetra paresis.

Research has identified a gene that is associated with an increase in risk of this disease.

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As the disease progresses, the spinal cord deteriorates leading to worsening of the clinical signs and eventually paralysis of the hind quarters. DM is a devastating disease!

Breeds prone to DM

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DM was previously regarded as a disease of German Shepherd Dogs, however in more recent times, the disease has been identified in many other breeds and is no longer considered to be a disease of "large breed dogs".

Breed examples prone to CDRM include;

  • Great Pyrenean Mountain Dog
  • Weimaraner
  • Belgian Shepherd Dog
  • Boxers

Confirmation of the diagnosis is important in other breeds, before assuming that they have DM seen in German Shepherd Dogs.

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Pathogenesis

Degenerative myelopathy (DM) in dogs is an idiopathic neurodegenerative disease which primarily affects the spinal cord of middle aged to older dogs. It's over represented in the German Shepherd Dog and Pembroke Welsh Corgi as well as being reported in a variety of other breeds.

DM is a slowly progressive, debilitating disease and neuroanatomic localisation is from T3 - L3 spinal cord segments. The pathways that carry neural information in the spinal cord loose their insulating coat of myelin (demyelination) and begin to fragment. The neurons which produce the signals then begin to die (axonal degeneration), resulting in loss of motor control in the pelvic limbs.

Diagnosis of DM is made by a history of chronic progressive spinal ataxia and weakness of the pelvic limbs that may have a waxing and waning course or be steadily progressive. This is supported by the neurological findings of a diffuse thoracolumbar spinal cord dysfunction.

Localising Neurologic Lesions Using the NeuroMap: Spinal Cord
Localising Neurologic Lesions Using the NeuroMap: Spinal Cord

DM can also progress to the thoracic limbs and affect the pathways that control breathing and brain stem function.

The aetiology of DM is unknown, however research has identified a genetic mutation (SOD-1) which is associated with an increased risk of the disease. SOD 1 is a gene that encodes an enzyme (superoxide dismutase) which is responsible for destroying free radicals within the body.

Free radicals are reactive elements that are part of the natural defence mechanism; however they become harmful when they are produced in excessive quantities, causing cell death and a variety of degenerative diseases.

A DNA test for the SOD-1 mutation is offered by many laboratories, however this genetic test does NOT identify dogs that are affected by this disorder, it only identifies dogs that are at risk of developing clinical signs, but this does not necessarily mean they will go on to do so.

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The same gene mutation can also cause a form of human motor neuron disease called Amyotrophic Lateral Sclerosis (ALS).

Two copies of the abnormal gene have to be present for the disease to develop.

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DM is not a straight forward disease and it has been confirmed in some dogs with only one copy of the abnormal gene. This suggests that there are other genetic or environmental influences which determine whether a dog will develop this disease.

The underlying pathophysiology of DM remains unclear.

Clinical Signs

Initial clinical signs may be mild with a gradual onset; subtle weakness of one hind limb. Signs progress over months eventually leading to paralysis of the hind limbs.

  • Mono-paresis
  • Bilateral paresis
  • Ataxia
  • Proprioceptive deficits
  • Scuffing of the pelvic limb paws
  • Abnormal wearing of nails
  • Crossing pelvic limbs in gait
  • Falling over when turning
  • Difficulty getting up
  • Difficulty descending stairs / slopes
  • Muscle atrophy of pelvic limb musculature
  • Urinary + faecal incontinence
  • Paralysis of pelvic limbs
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Degenerative Myelopathy is a disease which affects other breeds, however the German Shepherd Dog is over represented.

Degenerative Myelopathy is a non painful disease which leads to paralysis of the pelvic limbs and may also progress cranially along the spinal cord to eventually affect the thoracic limbs.

Diagnostic Tests

  • Cerebrospinal fluid (CSF) Tap; this is sampling of the fluid which surrounds the spinal cord for analysis and exclusion of other disease processes. These show an elevated cerebral spinal fluid (CSF) protein in the lumbar cistern
  • Blood Tests; this is to rule out possible metabolic causes of spinal cord dysfunction for example cobalamin deficiency and also for genetic testing for the degenerative myelopathy associated genetic mutation
  • Electromyographic (EMG) examination reveals no lower motor unit disease, supporting the localization of the disease process in the white matter pathways of the spinal cord. Spinal cord evoked potentials recorded during the EMG do show changes which help determine the presence of spinal cord disease
  • Radiography (x-rays); is an imaging technique using X-rays, gamma rays, or similar ionising radiation and non-ionising radiation to view the internal form of an object. Radiographs of the spinal column including myelography are normal (other than old age changes) in DM.
  • Magnetic Resonance Imaging (MRI); is a type of scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body

DM is a presumptive diagnosis and based on the signalment of the dog, clinical signs and the elimination of other possible diseases. A DM diagnosis can only be confirmed on post mortem by microscopic examination of the spinal cord.
The image above shows cross sections go the spinal cord from a normal dog (on right) and a dog with DM (on left). The loss of the blue-staining tissue in the spinal cord with DM shows loss of the normal nerve tissue that conducts signals from the brain to the limbs.
The image above shows cross sections go the spinal cord from a normal dog (on right) and a dog with DM (on left). The loss of the blue-staining tissue in the spinal cord with DM shows loss of the normal nerve tissue that conducts signals from the brain to the limbs.

DM Treatment + Management

DM is an irreversible and progressive disease, which carries a poor prognosis and there are no specific treatments available. However conservative treatments embracing a multimodal approach can help to slow the progression of the disease and maintain a good quality of life support for months to years.

There are some reports which suggest that supplementation with combinations of antioxidants may help slow the progression of the disease.

Conservative (non-surgical)

The integrative medical approach to DM treatment:

Important conservative treatments embracing a multimodal approach;

  • Physiotherapy
  • Hydrotherapy
  • Dietary supplementation
  • Medication
  • Other supportive measures
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Conventional medicine has little to offer canine patients with DM. However, informed use of programmed exercise, certain vitamins and selected drugs have delayed or prevented progression of dogs with DM. While these treatment modalities have been directed at suppression of the clinical signs, little has been done to prevent the development of this autoimmune disease.

Exercise:

The importance of regular aerobic exercise is supported by research and studies with many of the goals of treatment in DM being achievable through regular controlled exercise. A combination of walking and swimming is reported to significantly improve the quality of the dog's life.

In older patients, particularly those with arthritis, gradually building the exercise plan and incorporating proprioceptive enriched balance work is important. In addition, understanding the principles of rest in relation to planned exercise assists in recovery rates and exercise tolerance progression.

Exercise is extremely important in maintaining the well being of affected dogs, alongside optimising muscle tone, maintaining good circulation and positively impacting the general conditioning of the dog.

Off lead exercise is not useful or effective in dogs with DM. Controlled organised movement sequences graduated over a planned time frame achieve the best results.

Supplementation:

Dietary and dietary supplement management of DM has not received great attention. We are now aware that diet may have a powerful influence on the development of chronic degenerative diseases and new information suggests that dietary regulation might play a more significant role in the progression and development of diseases like MS.

Elimination of toxins from pre-processed food may assist in preventing a number of immune-related disorders. The current treatment of DM is designed to suppress the immune disease, but does nothing to correct the immune alterations which led to the disease state. Diet might help in correcting this defect and allow the immune system in DM dogs to stabilise.

Supplements (dietary):

Vitamins:

B-Complex: B vitamins are water soluble and any excess amount will be eliminated through the urine. They may help in neural regeneration and should be given to dogs with DM as there is altered absorption of some B vitamins, which supplementation can correct.

Yeast: Nutritional yeast, in powder or flake form, is a good source of the B-complex vitamins, trace minerals, and some protein.

Antioxidants: Vitamin E: This is an important nutrient which has been shown to have a number of physiologic and pharmacologic effects. It is a potent antioxidant and reduces fat oxidation and increases the production of HDL cholesterol. At higher doses it also reduces cyclooxygenase and lipooxygenases activities, decreasing production of prostaglandins and leukotreines. As such, it is a potent anti-inflammatory drug. It will reduce platelet function and prolong the bleeding time slightly in healthy individuals. There is no known side-effects to vitamin E at levels less than 4000-6000 IU per day (except in cats, where levels >400 IU/day might create hepatolipidosis). This drug slows the progression of DM and corrects for low serum and tissue levels.

Vitamin C: Works with vitamin E and helps regenerate vitamin E, potentiating its antioxidant effect.

Selenium: This is an important mineral which has antioxidant properties similar to vitamin E. Vitamin E can replace the requirement for selenium in the body, but selenium cannot substitute for vitamin E.

Membrane stabilizers: Omega-3 fatty acids: EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the constituents of fish oils that act as anti-inflammatory agents and may be worth trying if the dog has an autoimmune disorder or arthritis.

Gammalinolenic acid: Borage oil, evening primrose oil or black currant oil, are natural sources of gammalinolenic acid, a fatty acid which is hard to get in the diet. GLA is an effective anti-inflammatory agent with none of the side effects of anti-inflammatory drugs. It also promotes healthy growth of skin, hair, and nails. It may be good for skin conditions, arthritis, and autoimmune disorders. It takes six to eight weeks to see changes after adding GLA to the diet.

Coenzyme Q = Co-Q-10, is a natural substance that assists in oxidative metabolism. It may improve the utilization of oxygen at the cellular level, and patients with heart, muscle and nerve problems.

Medication:

Over the last 2 decades, there are 2 medications which appear to prevent progression or result in clinical remission of DM in many (up to 80%) dogs. These medications are aminocaproic acid (EACA) and n-acetylcysteine (NAC).

Other Supportive Measures:

Heartworm medication: As some heartworm medications increase immune responsiveness, these are not recommended, with a product that does not alter the immune system being advocated instead.

Flea prevention: Many of the old and new flea product can cause problems when certain neurological conditions are present.

Acupuncture: The traditional Chinese art of insertion of needles into various specific points of the body (with injection of small amounts of fluid or electrical stimulation) has been shown to provide analgesia and relief from acute and chronic pain. This has the advantage of having none of the side-effects of analgesic drugs. In addition, acupuncture can do no harm. In DM, acupuncture slows the condition, but does not stop the progress.

Dietary Cartilage: In many cases of degenerative joint disease with arthritis, recent studies have suggested that glycosaminoglycans and chondroitin sulfate may help reduce pain and inflammation from osteoarthritis, assisting in the healing process.

Stress Reduction: DM progresses at different rates and "stress" plays a role in its advancement. Minimising stressful situations is important where possible. While anaesthesia does not appear to cause problems with DM; in the past, even minor invasive surgical procedures can result in a marked increase in clinical signs of DM. Unfortunately, the worsening caused by surgical stress can be irreversible.

The combination of aminocaproic acid, N-acetylcysteine, dietary supplements and programmed exercise is the best treatment discovered to date.

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DM cases are not limited to just the breeds listed above as other breeds have been reported and evidenced to have this debilitating condition. Check out this interesting article: https://www.veterinary-neurologist.co.uk/resources/Canine-degenerative-myelopathy-NSDTRetPK.pdf

References

Alexander de Lahunta, Eric Glass, Marc Kent, Small Animal Spinal Cord Disease, de Lahunta's Veterinary Neuroanatomy and Clinical Neurology, 10.1016/B978-0-323-69611-1.00010-4, (267-311), (2021).

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2794-9. doi: 10.1073/pnas.0812297106. Epub 2009 Feb 2. PMID: 19188595; PMCID: PMC2634802.

Coates JR, Wininger FA. Canine degenerative myelopathy. The Veterinary clinics of North America Small animal practice. 2010;40(5):929-50. doi:10.1016/j.cvsm.2010.05.001.

Kathmann I, Cizinauskas S, Doherr MG, Steffen F, Jaggy A. Daily controlled physiotherapy increases survival time in dogs with suspected degenerative myelopathy. Journal of veterinary internal medicine / American College of Veterinary Internal Medicine. 2006;20(4):927-32.

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