Degenerative myelopathy in dogs treatment. Degenerative Myelopathy in Dogs: Causes, Diagnosis and Care

Degenerative myelopathy is a slowly progressive disease of the spinal cord and lower motor neurons, predominantly affecting the thoracolumbar region. It has been known for many years in German Shepherds, and over the years various theories have been put forward about its etiology. The recent discovery of genetic predisposition has changed the perception and understanding of this disease; the disease is associated with the appearance of a functional mutation in the superoxide dismutase gene. The mode of inheritance appears to be autosomal recessive, so affected dogs have two copies of the mutated gene. Mutations in the superoxide dismutase gene are present in a small percentage of people with amyotrophic lateral sclerosis (ALS).

Clinical signs

Degenerative myelopathy is now known to affect many dog breeds, but is most common in German Shepherds, Pembroke Welsh Corgis, Chesapeake Retrievers, and Boxers. Bernese Mountain Dogs are also affected, but they have a different mutation in the same gene. Affected dogs are usually elderly, and the disease typically presents with signs of pelvic limb weakness and ataxia, often initially asymmetrical. Manifestations are initially localized in the T3-L3 segments of the spinal cord. Over time, the weakness progresses to paralysis, and the chest limbs are affected. If the patient's life is then maintained, then the signs progress to a generalized lesion of the lower motor neurons with loss spinal reflexes and muscle atrophy and lesions cranial nerves.

Diagnostics

Diagnosis is based on the exclusion of compression or inflammatory disease using MRI or myelography and CSF analysis. Affected dogs give positive results a genetic test for mutation of the superoxide dismutase gene, which is carried out at OFFA. It is very important to understand that other diseases should be ruled out first, since the test demonstrates a genetic predisposition, but does not confirm a disease state. A complicating factor is that many older dogs have chronic diseases intervertebral discs type 2 and other comorbidities that may interfere with their gait, so a thorough and complete clinical and diagnostic examination in combination with genetic testing.

Treatment

Currently, treatment is aimed at providing a balanced diet enriched with antioxidants and maintaining the mobility of the animal. Optimal rehabilitation programs are not currently available, however, it is known that rehabilitation plays an important role in the treatment of people with ALS, but too much exercise stress may be harmful. More treatments will inevitably emerge in the future, but prevention is better than cure, and the prudent use of genetic analysis in breeding decisions can help eliminate or at least reduce the incidence of this neurodegenerative disease.

Links:

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF et al (2009) GenomeRwide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 106, 2794R 2799.
Wininger FA, Zeng R, Johnson GS, Katz ML, Johnson GC, Bush WW, Jarboe JM, Coates JR. Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense mutation. J Vet Intern Med. 2011 SepROct;25(5):1166R70.
Coates JR, Wininger F.A. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 2010 Sep; 40(5):929R50.

Canine Degenerative Myelopathy (DM)- Degenerative Myelopathy (DM) - a severe progressive neurodegenerative disease that leads to paralysis lower extremities.

The disease is caused by impaired conduction of motor neurons of the spinal cord due to degeneration of nerve endings.

Canine DM was first described over 35 years ago as a spontaneously occurring disease of the spinal cord in adults. It was believed that it is characteristic only for the breed German Shepherd, which is why it was also called German Shepherd myelopathy. On July 15, 2008, a mutated DM gene was found in 43 breeds, including the Rhodesian Ridgeback.

The first signs of the disease appear already in adult dogs, in most - at the age of 7-14 years. In the initial stages, the animal has a loss of coordination, then ataxia of the lower extremities develops. The duration of the disease in most cases does not exceed three years. In the last stages of myelopathy, the dog has practically no reflexes of the hind limbs, paralysis occurs. Then the lesion spreads to the forelimbs. At the same time, signs of damage to the upper motor neurons appear, which leads to ascending paresis of all limbs and general muscle atrophy. There comes a complete paralysis of the limbs of the dog.

Degenerative myelopathy is characterized by an autosomal recessive pattern of inheritance.

Due to the fact that many diseases of the spinal cord can have similar clinical features, without DNA testing, the definitive diagnosis of denerative myelopathy can only be made post-mortem after a histological examination.

The main reason for the development of DM is a mutation in the superoxide dismutase 1 (SOD1) gene, which leads to a change in the protein sequence (amino acid substitution E40K).

DM carriers (having 1 copy of the mutation) will not show symptoms; however, it must be borne in mind that such a dog will pass on the “sick” gene to its offspring, so only a pure partner should be selected.

Of particular danger is that when mating two carriers of Degenerative Myelopathy, there is a very high probability of having puppies affected by myelopathy (M / M), up to 25% of the offspring will be sick, and 80% of them will have this disease clinically.

There is no cure for DM. Since it serious disease manifests itself only in adult dogs, a preliminary diagnosis can only be made using a genetic study.

Diagnostics

To diagnose DM, a genetic test has been developed that can be performed at any age. Conducting a DNA test will reduce the frequency of birth of sick dogs. The test is recommended for dogs of all breeds.

A DNA test detects a defective (mutant) copy of a gene and a normal copy of a gene. The result of the test is the definition genotype, according to which animals can be divided into three groups: healthy (clear, homozygotes for a normal copy of the gene, NN), carriers (carrier, heterozygotes, NM) and patients (affected, homozygotes for mutation, MM).

DNA Test for Degenerative Myelopathy

in Moscow, the test can be taken at the Laboratory "Chance Bio", in St. Petersburg at the Zoogen Laboratory. They take blood or buccal epithelium (from behind the cheek). Results are ready in 45 days.

Canine degenerative myelopathy, also known as chronic degenerative radiculomyelopathy and German shepherd herpetic myelopathy, is an inherited disease that causes fibers in the brain, spinal cord, and nerves to break down over time. It usually shows up in dogs as young as seven years old and is more common in some breeds. Canine degenerative myelopathy usually results in weakness and loss of coordination at first, and as the disease progresses it causes complete paralysis and usually death. The condition is not curable and treatment is focused on keeping dogs comfortable for as long as possible. If you see signs of degenerative myelopathy in your dog, check with your veterinarian so they can advise you on your options and provide any assistance they can. Here's what you should know about the symptoms, causes, and treatment of degenerative myelopathy in dogs.

Symptoms of Degenerative Myelopathy in Dogs

Symptoms of degenerative myelopathy in dogs usually appear after the age of seven, but may appear as early as five years of age. They gradually get worse over time and it can take years before the front and back legs are completely paralyzed. Fortunately, most dogs do not suffer from the pain associated with the condition, although their quality of life can be severely affected and the condition is usually fatal. However, the time it takes for the disease to progress can vary greatly. Some dogs are completely paralyzed within a few months, while others survive with the condition for three or more years. Here general symptoms degenerative myelopathy in dogs.

Hindleg dragging or knuckle rolling
Ulcers or scuffed nails hind legs
Stickiness or lameness in the hind feet that gradually move towards the front feet
Difficulty walking, jumping or moving
Loss of balance and coordination
Amyotrophy
Increased hind leg paralysis (general paralysis usually occurs within 6-12 months of initial symptoms)
incontinence
bedsores
Weight gain
retention of urine
urinary tract infection
Skin lesions from urine burn
Increased paralysis of the front legs (usually general paralysis for several years after initial symptoms)
Difficulty chewing and swallowing
Labored breathing

Causes of Degenerative Myelopathy in Dogs

Degenerative myelopathy in dogs is caused by a genetic mutation, especially in the superoxide dismutase 1 (SOD1) gene, which is the same gene that is associated with Lou Gehrig's disease in humans. This mutation is almost certainly passed on as a recessive trait to puppies, as it is more common in some pedigreed dogs.

Degenerative myelopathy is most common in German Shepherds, Boxers, and Pembroke Welsh Corgis. Several other breeds can inherit the disease, including the Cardigan Welsh Korgis, Collies, Retrievers, Rhodesian Ridgebacks, Siberian Huskies, Weimaraners, and Wolfdog guides.

Treatment for Degenerative Myelopathy in Dogs

(Picture Credit: Jeff Greenberg/UIG via Getty Images)

Treatment for degenerative myelopathy in dogs is focused on providing support and comfort for affected animals to maintain quality of life, as there is no way to cure the condition or stop its progression. Certain exercises and physical therapy can reduce muscle damage and help maintain some mobility for as long as possible. If your dog has been diagnosed with degenerative myelopathy, your veterinarian can instruct you on the correct areas and activities that can help your dog maintain muscle strength and the ability to balance and walk for some time. Water exercises and hydrotherapy can also be helpful.

Dogs can move for longer periods of time using a wheelchair, but as the condition progresses, they will become more bedridden. It is important to provide dogs with soft, clean bedding that needs to be changed frequently to prevent sores. Dogs may need to go on a diet to prevent weight gain.

New therapies and treatments are still being researched, although none have yet been proven to reduce the impact of degenerative myelopathy in dogs. Your veterinarian will be able to give you the best recommendations for continuing treatment and caring for your individual needs of your dog.

Canine Degenerative Myelopathy (DM)- a severe progressive neurodegenerative disease that leads to paralysis of the lower extremities.

The disease is caused by impaired conduction of motor neurons of the spinal cord due to degeneration of nerve endings.

Canine DM was first described over 35 years ago as a spontaneously occurring disease of the spinal cord in adults. It was thought to be unique to the German Shepherd breed, which is why it was also called German Shepherd Myelopathy. Later, DM was identified in a number of breeds - the Pembroke Welsh Corgi, Boxer, Rhodesian Ridgeback, Chesapeake Bay Retriever.

The first signs of the disease appear already in adult dogs, in most - at the age of 8-14 years. In the initial stages, the animal has a loss of coordination, then ataxia of the lower extremities develops. The duration of the disease in most cases does not exceed three years. In the last stages of myelopathy, the dog has practically no reflexes of the hind limbs, paralysis occurs. The damage then spreads to upper limbs. At the same time, signs of damage to the upper motor neurons appear, which leads to ascending paresis of all limbs and general muscle atrophy. There comes a complete paralysis of the limbs of the dog.

Degenerative myelopathy is characterized by an autosomal recessive pattern of inheritance.

The main reason for the development of DM is a mutation in the superoxide dismutase 1 (SOD1) gene, which leads to a change in the protein sequence (amino acid substitution E40K).

There is no cure for DM. Since this severe disease only occurs in adult dogs, a preliminary diagnosis can only be made through genetic testing.

DIAGNOSTICS

To diagnose DM, a genetic test has been developed that can be performed at any age. A DNA test detects a defective (mutant) copy of a gene and a normal copy of a gene. The result of the test is the definition genotype, according to which animals can be divided into three groups: healthy (homozygotes for a normal copy of the gene, NN), carriers (heterozygotes, NM) and patients (homozygotes for mutation, MM).

Conducting a DNA test will reduce the frequency of birth of sick dogs. The test is recommended for dogs of all breeds.

Clinical signs

Degenerative myelopathy is now known to affect many dog breeds, but is most common in German Shepherds, Pembroke Welsh Corgis, Chesapeake Retrievers, and Boxers. Bernese Mountain Dogs are also affected, but they have a different mutation in the same gene. Affected dogs are usually elderly, and the disease typically presents with signs of pelvic limb weakness and ataxia, often initially asymmetrical. Manifestations are initially localized in the T3-L3 segments of the spinal cord. Over time, the weakness progresses to paralysis, and the chest limbs are affected. If the patient is then kept alive, signs progress to generalized lower motor neuron involvement with loss of spinal reflexes and muscle atrophy and cranial nerve involvement.

Diagnostics

Diagnosis is based on exclusion of compressive or inflammatory disease using MRI or myelography and CSF analysis. Affected dogs test positive for the superoxide dismutase gene mutation test performed at OFFA. It is very important to understand that other diseases should be ruled out first, since the test demonstrates a genetic predisposition, but does not confirm a disease state. A complicating factor is that many older dogs have chronic type 2 intervertebral disc disease and other comorbidities that can interfere with their gait, so a thorough and complete clinical and diagnostic evaluation should be performed in combination with genetic testing.

Treatment

Currently, treatment is aimed at providing a balanced diet enriched with antioxidants and maintaining the mobility of the animal. Optimal rehabilitation programs are not currently available, however, rehabilitation is known to play an important role in the treatment of people with ALS, but too much exercise can be harmful. More treatments will inevitably emerge in the future, but prevention is better than cure, and the prudent use of genetic analysis in breeding decisions can help eliminate or at least reduce the incidence of this neurodegenerative disease.

Links:

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF et al (2009) GenomeRwide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 106, 2794R 2799.
Wininger FA, Zeng R, Johnson GS, Katz ML, Johnson GC, Bush WW, Jarboe JM, Coates JR. Degenerative myelopathy in a Bernese Mountain Dog with a novel SOD1 missense mutation. J Vet Intern Med. 2011 SepROct;25(5):1166R70.
Coates JR, Wininger F.A. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 2010 Sep; 40(5):929R50.

Degenerative myelopathy in dogs is a gradually progressive lower motor neuron pathology of the spinal cord that predominantly affects the thoracolumbar regions. For many years this disease tracked in German Shepherds. Recent studies have shown that a genetic predisposition plays a greater role in the development of the disease. The disease is associated with the manifestation of a functional mutation in the superoxide dismutase gene. An autosomal recessive inheritance pattern is suggested, in which affected dogs have two copies of the gene with signs of mutation.

Symptomatic picture

The disease appears at about 8-14 years of age. The first symptom is a violation of the coordination of the pelvic limbs. The gait of the animal becomes wobbly, "drunk", the rear part collapses in different directions when moving. Reduced control of the pelvic region of the limbs and trunk leads to the fact that the dog constantly touches objects. It drifts, often hits various obstacles and the edges of doors. The dog makes a support on the back of the fingers, dragging them and sometimes erasing the horny part to the bone with the formation of ulcers.

The degree of manifestation of signs may vary depending on the duration, localization of degenerative processes. As the disease progresses, the limbs become weaker, making it difficult for the dog to stand. Weakness increases gradually until the animal loses the ability to walk.

The clinical picture can develop over 6-12 months, and sometimes longer, before complete paralysis develops. A significant manifestation is the violation of the separation of urine, feces, since paralysis affects not only the musculoskeletal system, but also the urinary system and intestines. This is manifested by incontinence of feces and urine.

Important! This disease is not accompanied painful sensations unless there are other pathologies.

At the moment, it has become known that degenerative myelopathy affects not only German Shepherds, but also many other dog breeds: Pembroke Welsh Corgis, Boxers, Chesapeake Retrievers, and so on. In Bernese Mountain Dogs, the mutation in the superoxide dismutase gene manifests itself somewhat differently. Mestizos are not immune from the manifestation of the disease. In general, the disease usually manifests itself in older dogs (over 8 years old) as follows:

The support ability of the hind limbs of the animal is impaired;
Inability to maintain one posture;
Lost muscle mass;
Reduced skin sensitivity of the pelvic limbs;
Controlled urination and defecation is disturbed;
Gradually, complete or partial paralysis develops, spreading to other departments, in particular - chest.

Signs of degenerative myelopathy in dogs, despite the vivid manifestations, may also be the result of other inflammatory processes in the body. Therefore, diagnosis must be carried out at the first signs in order to exclude or confirm those diseases that can be treated.

How does degenerative myelopathy progress?

The disease usually begins in thoracic region spinal cord. In the process of studying this pathology, destruction of the white matter in this section was noted. It contains those tissues that transmit movement commands to the limbs from the brain, as well as carry out sensory feedback from the limbs to the brain. As a result of the destruction of these fibers, the connection between the brain and limbs is disrupted.

The picture of the development of the pathology is as follows: the dog develops signs of weakness of the pelvic limbs, followed by ataxia (in which the coordination of movement of various muscle groups is disturbed). At the same time, at the very beginning, they can make themselves felt asymmetrically. The main manifestations concern the spinal cord T3-L3. Gradually, weakness progresses and paralysis develops, which spreads to the chest limbs. The dog can no longer control urination.

Provided that the life of the animal is maintained, the signs continue to progress until the lower motor neutrons are involved in the degenerative processes, in which the spinal reflexes are lost. Damage to the cranial nerves and muscle atrophy develops. The disease acquires a generalized character, that is, it has spread to significant areas of organ systems and tissues. Degenerative myelopathy, when spreading to the chest, destroys not only the myelin sheaths of nerve tissues, but also the nerve fiber itself.

Reasons for development

The causes of this pathology have not been identified. Even though there is a clear relationship between genetic predisposition and the development of the disease, to prove and predict the development of the disease due to the presence gene mutations failed. The disease can manifest itself even in those dogs that are bred from two absolutely healthy parents who were carriers of the SOD1 type gene ().

The dog breeds most susceptible to this pathology are the German Shepherd, Collie, Pembroke, Boxer, Cardigan Welsh Corgi, Irish Setter, Chesapeake Bay Retriever, Poodle and Rhodesian Ridgeback. But this does not mean that this pathology cannot develop in other breeds. It has been proven that large breeds of dogs are most often among sick animals.

Important! Medicines for this disease was not invented, and therefore there is no chance of recovery. The disease will progress in any case.

Diagnostics

Conducted mainly differential diagnosis, in which inflammatory and compression diseases are excluded. It is carried out using MRI or myelography (depending on the hardware veterinary center), as well as CSF analysis. Affected animals give a positive response to a genetic test that detects a gene mutation. The test is carried out predominantly in OFFA. In general, the following activities are carried out:

Laboratory tests for the presence of pathogens;
The functionality of the thyroid gland is checked;
MRI and CT to detect lesions of the spinal cord.

It must be understood that in this case, diagnosis is needed precisely to exclude other pathologies. The test will only reflect the predisposition by gene, but not the condition itself of the diseased dog. The diagnostic process is further complicated by the fact that many older animals can simultaneously have diseases of the intervertebral discs, other diseases that also have gait disturbance and other similar symptoms in their symptoms. That is why the diagnosis still needs to be carried out in parallel with the genetic test. In general, the following pathologies can be identified, which, unlike degenerative myelopathy, are treatable:

Diseases of the intervertebral discs type II;
Orthopedic diseases, expressed in the pathology of the joints, muscles or skeleton as a whole;
Pathology of bone development or dysplasia hip joint;
tumors;
cysts;
Injuries;
Infectious diseases of the spinal cord;
Stenosis of the lumbosacral region, accompanied by narrowing of the lower part of the spine or pelvic bone.

Degenerative myelopathy, unlike these pathologies, is not treated, and the symptoms are practically not stopped. An animal can be fully diagnosed with 100% certainty only posthumously at autopsy. That is why the disease is determined by the method of exclusion. What is the help to a sick animal with such a pathology?

Myelopathy treatment

The current treatment for canine degenerative myelopathy is more focused on providing the animal with a balanced diet that is enriched with antioxidants. It is also necessary to maintain the mobility of the animal. Any rehabilitation programs that will give a positive trend in the course of the disease have not yet been developed.

As a preventive measure further dissemination owners of dogs that are at highest risk of developing the disease should use genetic testing. It will show the predisposition of the animal to pathology. Therefore, only after such an analysis can a decision be made on further breeding. This approach allows not only to eliminate, but to reduce the incidence of this degenerative disease.

What can be said about those animals that are already sick. In this case, only supportive therapy is offered. Special exercises can help, which will delay the atrophy of the limbs and spinal cord. It is also important to monitor the weight of the animal, which, due to lack of movement, can gain excess weight and further aggravate its condition with an additional load on the spine.

Important! It is worth noting that it is possible and necessary to maintain the mobility of the animal, but there are cases when, due to excessive load, the disease progressed even faster.

Pathology develops quite quickly - in just 6-9 months after the diagnosis is established. Therefore, constant monitoring of the condition of the animal, frequent examinations by a neurologist, urine tests for infectious disease are mandatory.

Gradually, the animal will lose the ability to move independently. Therefore, you need to provide the dog with a special pillow, the position of which must be constantly changed. This will prevent the development of bedsores. It is worth consulting with a veterinarian separately regarding the prevention of the development of a urinary tract infection.

It is recommended that long-haired dogs be shorn to reduce the chance of skin lesions. It is also possible to provide mobility to the dog with the help of a trolley specially equipped for this. A recumbent animal suffers not only from incontinence of feces, urine, but also from limiting the possibility of self-hygiene. You can apply the following methods and means to maintain normal life animal:

The owners wash the dog quite often - literally twice a week. At proper care behind the coat and skin can prevent the development of bedsores. It will also help to get rid of unpleasant odors, prevent infection of the animal and skin. With frequent washing, moisturizers for the skin of the animal are used to prevent dryness of the integument.

If we talk about the prevention of the disease, then the answer is unequivocal. There is no need to talk about preventive measures, since degenerative myelopathy cannot be prevented. In dogs that have developed paralysis, veterinarians recommend euthanasia. Thus, the animal will not suffer from pathological degenerative processes that spread throughout the body, which cannot be stopped.

Degenerative myelopathy is a progressive disease of the spinal cord in aging dogs. The disease develops gradually and becomes clinically significant between the ages of 8 and 14 years. The first sign of the onset of the development of the disease is a deterioration in coordination (ataxia) of the pelvic limbs. The dog's gait becomes wobbling, the back of the dog falls from side to side. Decreased control of the pelvis and limbs leads to the fact that the dog can touch objects, it can skid, it can also hit the edges of doors and other obstacles. When supporting, the dog can lean on the back of the fingers, drag them, sometimes erasing the claws to ulcers and bones. The degree of manifestation of certain signs is different and depends on the degree of duration and localization of the lesion. As the disease progresses, the limbs become weak and the dog begins to stand with difficulty. Weakness gradually increases until the dog stops walking completely. Clinical Development may vary from 6 months to 1 year, sometimes more than a year before complete paralysis occurs. A significant symptom is also a violation of the separation of feces and urine, since destructive processes affect not only the work of the limbs, but also the work of the intestines and Bladder. This can be manifested by incontinence of urine and even feces. It is important to know that this disease is not accompanied by pain, if there are no concomitant painful other pathologies, that is, the dog does not experience pain.

What happens in degenerative myelopathy?

Degenerative myelopathy usually begins in the thoracic region of the spinal cord. Pathological examination revealed destruction of the white matter of the spinal cord. White matter contains those fibers that transmit motor commands from the brain to the limbs and sensory information from the limbs to the brain.

The essence of tissue destruction is demyelination (destruction of the myelin sheaths of uneven fibers), as well as loss of axons (loss of the fiber itself). These processes lead to disruption of communication between the brain and limbs. Recent studies have identified a gene responsible for the occurrence of the disease, the presence of which significantly increases the risk of developing the disease.

How is degenerative myelopathy diagnosed?

Degenerative myelopathy is a diagnosis of exclusion. This means that it is required to exclude other diseases that could lead to a similar condition and, excluding them, we make a diagnosis of a degenerative process. For such diagnostics, such diagnostic tests as myelography and MRI, CT are used. The only way to make a definitive diagnosis is to examine the spinal cord itself at autopsy, if one is performed. Destructive changes in the spinal cord are found that are characteristic of degenerative myelopathy and are not characteristic of other diseases of the spinal cord.

What diseases can manifest in the same way as degenerative myelopathy?

Any disease that affects a dog's spinal cord can cause symptoms such as loss of coordination and weakness in the limbs. Since many of these diseases can be effectively treated, it is important to carry out the necessary tests and investigations to make sure that the dog does not have any of these diseases. The most common cause of pelvic limb weakness is herniated discs. With hernias of the first and second types, paresis or paralysis of the pelvic limbs can be observed. A herniated disc can usually be detected with spinal x-rays and myelography, or with more advanced imaging such as CT or MRI. Diseases such as tumors, cysts, infections, trauma, and stroke should be considered. Similar diagnostic procedures allow the diagnosis of most of these diseases.

How is degenerative myelopathy treated?

Unfortunately no effective treatment of this pathology, which would clearly show the ability to stop or slow down the progression of degenerative myelopathy. The discovery of a gene that determines the risk of developing degenerative myelopathy in dogs may provide a future opportunity to find a way to solve the problem. Meanwhile, the quality of life of a sick dog can be improved through measures such as good care, physical rehabilitation, pressure ulcer prevention, urinary infection monitoring, and ways to increase mobility through the use of carts when possible.

Canine Degenerative Myelopathy (DM)- Degenerative Myelopathy (DM) is a severe progressive neurodegenerative disease that leads to paralysis of the lower extremities.

The disease is caused by impaired conduction of motor neurons of the spinal cord due to degeneration of nerve endings.

Canine DM was first described over 35 years ago as a spontaneously occurring disease of the spinal cord in adults. It was thought to be unique to the German Shepherd breed, which is why it was also called German Shepherd Myelopathy. On July 15, 2008, a mutated DM gene was found in 43 breeds, including the Rhodesian Ridgeback.

Degenerative myelopathy is characterized by an autosomal recessive pattern of inheritance.

The main reason for the development of DM is a mutation in the superoxide dismutase 1 (SOD1) gene, which leads to a change in the protein sequence (amino acid substitution E40K).

There is no cure for DM. Since this severe disease only occurs in adult dogs, a preliminary diagnosis can only be made through genetic testing.

Diagnostics

DNA Test for Degenerative Myelopathy

d.v.s. Kozlov, N.A., Zakharova, A, A.

Introduction

Degenerative myelopathy (DM) is a slowly progressive, incurable degenerative disease of the central nervous system adult dogs of medium and large breeds, in which both upper and lower motor neurons are damaged, which leads to paralysis, followed by muscle atrophy. Averill in 1973 first described DM in dogs. In 1975, Griffiths and Duncan published a series of clinical cases with signs of hyporefrexia involving nerve roots and called this disease degenerative radiculomyelopathy. Although most of the dogs in those early studies were German Shepherds, other breeds were also represented. However, for many years DM was considered a disease of German Shepherds. Some breeds have histologically confirmed DM: German Shepherd, Siberian Husky, Small and Large Poodle, Boxer, Pembroke and Cardigan Welsh Corgi, Hatchet Bay Retriever, Bernese Mountain Hood, Kerry Blue Terrier, Golden Retriever, American Eskimo Dog, Irish Soft Coated Wheaten Terrier, and Pug .

Research results and discussion

The clinical picture of DM typically consists of slowly progressive, non-painful Th3–L3 myelopathy in older large breed dogs. Degenerative myelopathy manifests at age five or more, but the median age of onset is neurological symptoms considered nine years old for large breed dogs and 11 years old for welsh corgis. At the initial stages of the development of the disease, degenerative proprioceptive ataxia and asymmetric spastic paraparesis are noted, with the preservation of spinal reflexes. There may be a tremor of the pelvic limbs when maintaining weight. The initial clinical signs of spinal cord dysfunction are often mistaken for hip dysplasia, which may also be present in a patient with this spinal cord disorder. In 10%-20% of affected dogs, the patellar reflex is reduced or absent in one or both limbs. In the presence of normal or increased tone of the pelvic limbs and no atrophy of the quadriceps femoris, this loss of the patellar reflex reflects dysfunction of the sensory components of the reflex arc. What this has to do with axonopathy in DM is unknown, perhaps it is part of the pathological process and reflects lesions in the L4-L5 segments of the spinal cord or age-related neuropathy not associated with DM. In the future, paraplegia develops, moderate loss of muscle mass and a decrease or absence of spinal reflexes on the pelvic limbs. The disease usually progresses over 6-12 months (longer in small dogs than large dogs) and many owners opt for euthanasia due to the patient's inability to move independently. As the disease progresses, the thoracic limbs (paraplegia, paraparesis) are involved in the pathological process, severe loss of muscle mass on the pelvic limbs, the dog loses the ability to retain urine and feces. In the later stages of the development of the disease, tetraplegia and signs of damage to the brain stem are observed. Difficulty swallowing, tongue movement, lack of ability to bark; decreased or absent skin reflexes; severe loss of muscle mass; urinary and fecal incontinence.

The etiology of degenerative myelopathy has been studied by many scientists. Immunological, metabolic or nutritional, oxidative stress, excitotoxicity (pathological process leading to death nerve cells under the action of neurotransmitters capable of hyperactivating NMDA and AMPA receptors) and the genetic mechanism were investigated as the pathogenesis of degenerative myelopathy. Several scientific works were associated with violations immune system in dogs suffering from this disease, however, they turned out to be unproven. This is not an inflammatory disease of the spinal cord. Attempts to isolate the retrovirus in the lesions were unsuccessful. Treatment of dogs with DM with glucocorticosteroids, vitamins E and B 12 (often used because of their role in the treatment of other degenerative neurological disorders), and aminocaproic acid has not been shown to slow disease progression. Many other treatments have been used, but none of the procedures has contributed notable changes in the development of this disease. The long-term prognosis is not favorable and many owners decide to euthanasia.

Uniformity clinical signs, histopathology, age and breed predisposition of dogs suggests the hereditary nature of the disease. Recently, DM has been associated with mutations in the superoxide dismurtase 1 (SOD1) gene. A mutation in the SOD1 gene is known to cause amyotrophic lateral sclerosis (ALS) in humans, also known as Lou Gehrig's disease. The Greek origin of the word amyotrophy means "muscles without nutrition". The lateral location in the spinal cord of axonal disease and sclerosis means that the axons are damaged and replaced by sclerotic or "scar" tissue. DM dogs are considered as a spontaneous model of human ALS. A DNA test based on the SOD1 mutation is currently available for dogs. Canine degenerative myelopathy is believed to be inherited in an autosomal recessive manner. Dogs homozygous for the mutation are at risk of developing DM and will pass on one chromosome with the mutated allele to all their offspring. Some dogs are homozygous recessive on DNA testing and have two mutant alleles, but are free of clinical signs, indicating age-related incomplete penetrance. Heterozygotes are only considered carriers of DM and are able to pass on the mutation in the SOD1 gene to half of their puppies. However, studies conducted by Zeng R. et al. on 126 dogs with histopathologically confirmed DM revealed 118 recessive homozygotes for the mutation and 8 heterozygotes among them.

Conclusion

The life-time diagnosis of DM is based on the recognition of the progression of clinical signs, followed by a system of diagnostic measures aimed at excluding other diseases of the spinal cord. Intervertebral extrusion or disc protrusion is by far the most significant clinical disorder to be distinguished from DM. It should be remembered that older dogs can simultaneously suffer from degenerative myelopathy and also have one (or more) moderate disc herniation. Neoplasia is also a diagnosis that must be differentiated by MRI from DM. Analysis of cerebrospinal fluid can help rule out meningitis. The definitive diagnosis of DM is based on the characteristic histopathological abnormalities in the spinal cord at autopsy.

Literature

Handbook of Veterinary Neurology, 5th Edition by Michael D. Lorenz, BS, DVM, DACVIM, Joan Coates, BS, DVM, MS, DACVIM and Marc Kent, DVM, BA, DACVIM, 2011.
Practical Guide to Canine and Feline Neurology, 3rd edition, by Curtis W. Dewey and Ronaldo C. da Costa, 2015.
Veterinary Neuroanatomy and Clinical Neurology, 3rd Edition
By Alexander de Lahunta, Eric N. Glass, MS, DVM, DACVIM (Neurology) and Marc Kent, DVM, BA, DACVIM, 2009.
Accumulation and aggregate formation of mutant superoxide dismutase 1 in canine degenerative myelopathy. Nakamae S., Kobatake Y.,Suzuki R, Tsukui T, Kato S, Yamato O, Sakai H, Urushitani M, Maeda S, Kamishina H. 2015
Breed distribution of SOD1 alleles previously associated with canine degenerative myelopathy. Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. 2014. Journal of Veterinary Internal Medicine published by Wiley Periodicals,