A two-year-old Arabian horse with cerebellar abiotrophy, showing stiff awkward gait, and upper range of unnatural head bob. Though this horse had a relatively mild case, it could never be ridden.
Varies by severity, severely disabled animals may be euthanized for humane reasons.
Frequency
Varies by species and breed
Cerebellar abiotrophy (CA), also called cerebellar cortical abiotrophy (CCA), is a geneticneurological disease in animals, best known to affect certain breeds of horses, dogs and cats. It can also develop in humans. It develops when the neurons known as Purkinje cells, located in the cerebellum of the brain, begin to die off. These cells affect balance and coordination. They have a critical role to play in the brain. The Purkinje layer allows communication between the granular and molecular cortical layers in the cerebellum. Put simply, without Purkinje cells, an animal loses its sense of space and distance, making balance and coordination difficult. People with damage to the cerebellum can experience symptoms like unsteady gait, poor muscle control, and trouble speaking or swallowing.[1]
Abiotrophy means the loss of a vital nutritive factor. The cause of cerebellar abiotrophy is not known, but it is thought to be due to an intrinsic metabolic defect.[2]
In most cases, the Purkinje neurons begin to die off shortly after the animal is born and the condition is noticeable when the animal is less than six months old, though sometimes the onset of symptoms is gradual and the animal is much older before the owner or caretaker notices a problem.
The condition in Kerry Blue Terriers is sometimes called progressive neuronal abiotrophy.[3] Other terms used to describe the condition in dogs include cerebellar cortical atrophy and postnatal cerebellar cortical degeneration.[4]
Cerebellar abiotrophy in horses was originally thought to be a form of cerebellar hypoplasia (CH) and was described as such in older research literature. However, it was discovered that in horses, the die-off of purkinje cells began after the animal was born, rather than occurring in utero. Cerebellar hypoplasia is distinctly different in that it is a condition from a lack of these cells being formed during the development of the cerebellum. CH has been found in several species, including cats, dogs, cows and sheep.
There are other diseases that lead to cerebellar degeneration, but the loss of Purkinje cells is a clear way to diagnose cerebellar abiotrophy, and the combination of clinical signs is sufficiently unique that cerebellar abiotrophy can easily be distinguished from other conditions, even in a living animal.
Clinical signs
Symptoms of cerebellar abiotrophy include ataxia or lack of balance, an awkward wide-legged stance, a head tremor (intention tremor) (in dogs, body tremors also occur), hyperreactivity, lack of menace reflex, stiff or high-stepping gait, coarse or jerky head bob when in motion (or, in very young animals, when attempting to nurse), apparent lack of awareness of where the feet are (sometimes standing or trying to walk with a foot knuckled over), poor depth perception, and a general inability to determine space and distance. The symptoms, when taken as a group, are distinctive and not easily mimicked by other illnesses, though certain types of neurological injury and infection need to be ruled out. Verifying the diagnosis in a laboratory setting is possible only by examining the brainpost-mortem to determine if there has been a loss of Purkinje cells.[5]
Most affected animals have normal intelligence and mildly affected animals can, in theory, live out a normal lifespan. However, affected animals are quite accident-prone, and for this reason many animals that develop cerebellar abiotrophy, particularly horses, are euthanized for humane reasons. Horses may experience difficulty stepping up and over objects, run into fences, fall easily, and even if allowed to mature to full growth, are generally considered unsafe to ride. Dogs may need lifetime assistance with tasks such as climbing stairs.[5]
In horses, the symptoms may worsen from the time of onset for six to 12 months, but if not severe enough to mandate euthanasia, they stabilize over time. In some dog breeds, symptoms appear to progressively worsen, but research is not consistent on this point. There also is some evidence that affected animals partially compensate for the condition by cognitively learning alternative methods for moving or to determine distance, and thus appear to improve because they become less accident-prone.
Horses
Cerebellar abiotrophy is best known as a condition affecting Arabian horses. It has also been observed in the Welsh pony and cob, the Australian pony,[6]Curly horse,[7]Miniature horse, the Gotland Pony, one Eriskay Pony, and possibly the Oldenburg. Most foals appear normal at birth, with symptoms noticeable at an average age of four months, though there have been cases where the condition is first seen shortly after birth and other cases where symptoms are first recognized in horses over one year of age.
Breeds DNA tested that reveal some carrier lines, but to date no affected animals, include the Welsh pony and the Trakehner. However, other breeds heavily influenced by Arabian breeding, such as the Thoroughbred and the American Saddlebred, do not appear to carry the mutation.[7]
In horses, cerebellar abiotrophy is believed to be linked to an autosomalrecessive gene. This means it is not sex-linked, and the allele has to be carried and passed on by both parents in order for an affected animal to be born. Horses that only carry one copy of the gene may pass it on to their offspring, but themselves are perfectly healthy—without symptoms of the disease. Because it is recessive, the allele for cerebellar abiotrophy may pass through multiple generations before it is expressed.
A DNA test which identifies markers associated with cerebellar abiotrophy became available in 2008.[8] The test was refined to identify the most likely mutations, and retesting of earlier samples based on an earlier indirect marker test developed by UCD,[9] indicated a 97% accuracy rate for the old test relative to the newer version, with no false negatives.[10] The causative mutation was identified on the gene TOE1 in 2011.[11] Research on cerebellar abiotrophy and the DNA test was led by the Veterinary Genetics Laboratory at the UC Davis School of Veterinary Medicine. Researchers working on this problem include Drs. Cecilia Penedo and Leah Brault. Dr. Ann T. Bowling made significant early contributions to the genetics research on cerebellar abiotrophy.
↑ Sandy J, Slocombe R, Mitten R, Jedwab D (2002). "Cerebellar abiotrophy in a family of Border Collie dogs". Veterinary Pathology. 39 (6): 736–738. doi:10.1354/vp.39-6-736. PMID12450206.
1 2 Brault L. S. (2011). "The frequency of the equine cerebellar abiotrophy mutation in non-Arabian horse breeds". Equine Veterinary Journal. 43 (6): 727–731. doi:10.1111/j.2042-3306.2010.00349.x. PMID21496100.
↑ Buijtels J, Kroeze E, Voorhout G, Schellens C, van Nes J (2006). "Cerebellar cortical degeneration in an American Staffordshire terrier". Tijdschrift voor Diergeneeskunde. 131 (14–15): 518–522. PMID16916197.
Bibliography
deLahunta, Alexander; deLahunta, Alexander (1983). Veterinary Neuroanatomy and Clinical Neurology (2nded.). Philadelphia: Saunders. ISBN0-7216-3029-4.
deLahunta, Alexander; Summers, Brian Alan; Cummings, John Thomas (1995). Veterinary neuropathology. St. Louis: Mosby. ISBN0-8016-5063-1.
Cerebellar abiotrophy in horses
Adams, Ragan; Mayhew, Ian G. (April 1985). "Neurologic Diseases". Veterinary Clinics of North America: Equine Practice. 1 (1): 209–234. doi:10.1016/S0749-0739(17)30778-2. PMID3000543.
AHA Equine Stress, Research; Education Committee (August–September 2007). "Caution and Knowledge"(PDF). Modern Arabian Horse: 100–105. Archived from the original(PDF) on 2009-03-03.
Baird JD, Mackenzie CD (January 1974). "Cerebellar hypoplasia and degeneration in part-Arab horses". Australian Veterinary Journal. 50 (1): 25–28. doi:10.1111/j.1751-0813.1974.tb09367.x. PMID4819469.
Beatty, Margaret T.; Leipold, H.W.; Cash, W.; etal. (1985). "Cerebellar Disease in Arabian Horses". Proceedings of the 21st annual convention of the American Association of Equine Practitioners. pp.241–255.
Beech, Jill (1976). "Cerebellar Hypoplasia". Proceedings of the Twenty-Second Annual Convention of the American Association of Equine Practitioners. Dallas, Texas: 77–78.
Björck G, Everz KE, Hansen HJ, Henricson B (May 1973). "Congenital cerebellar ataxia in the gotland pony breed". Zentralbl Veterinarmed A. 20 (4): 341–354. doi:10.1111/j.1439-0442.1973.tb00892.x. PMID4199630.
Palmer AC, Blakemore WF, Cook WR, Platt H, Whitwell KE (July 1973). "Cerebellar hypoplasia and degeneration in the young Arab horse: clinical and neuropathological features". Veterinary Record. 93 (3): 62–66. doi:10.1136/vr.93.3.62. PMID4748678. S2CID441746.
Sponseller, Max (1967). "Equine cerebellar hypoplasia and degeneration". Proceedings of the 13th annual convention of the American Association of Equine Practitioners. pp.123–126.
The Scottish Terrier, popularly called the Scottie, is a breed of dog. Initially one of the highland breeds of terrier that were grouped under the name of Skye Terrier, it is one of five breeds of terrier that originated in Scotland, the other four being the modern Skye, Cairn, Dandie Dinmont, and West Highland White terriers. They are an independent and rugged breed with a wiry outer coat and a soft dense undercoat. The first Earl of Dumbarton nicknamed the breed "the diehard". According to legend, the Earl of Dumbarton gave this nickname because of the Scottish Terriers' bravery, and Scotties were also the inspiration for the name of his regiment, The Royal Scots, Dumbarton’s Diehard. Scottish Terriers were originally bred to hunt vermin on farms.
Dwarfing is a process in which a breed of animals or cultivar of plants is changed to become significantly smaller than standard members of their species. The effect can be induced through human intervention or non-human processes, and can include genetic, nutritional or hormonal means. Used most specifically, dwarfing includes pathogenic changes in the structure of an organism, in contrast to non-pathogenic proportional reduction in stature.
The silver or silver dapple (Z) gene is a dilution gene that affects the black base coat color and is associated with Multiple Congenital Ocular Abnormalities. It will typically dilute a black mane and tail to a silvery gray or flaxen color, and a black body to a chocolaty brown, sometimes with dapples. It is responsible for a group of coat colors in horses called "silver dapple" in the west, or "taffy" in Australia. The most common colors in this category are black silver and bay silver, referring to the respective underlying coat color.
The Anglo-Arabian, also known as the Anglo-Arab, is a horse breed that originated in France by cross-breeding a Thoroughbred with an Arabian. The Anglo-Arabian has origins tracing back to the Limousin Horse. It was officially recognized by Emperor Louis Philippe I and produced by the Haras National du Pin. The Anglo-Arabian has long legs, a refined head, larger hindquarters, and are most commonly seen in gray, bay, or chestnut. To be recognized as an Anglo-Arabian with the Arabian Horse Association, the horse must have at least 25% Arabian blood. There are no color or height restrictions to be registered. Due to its lineage and physique, the Anglo-Arabian is utilized for sports-related activities such as dressage, show jumping, endurance, and cross-country.
Purkinje cells or Purkinje neurons, named for Czech physiologist Jan Evangelista Purkyně who identified them in 1837, are a unique type of prominent large neurons located in the cerebellar cortex of the brain. With their flask-shaped cell bodies, many branching dendrites, and a single long axon, these cells are essential for controlling motor activity. Purkinje cells mainly release GABA neurotransmitter, which inhibits some neurons to reduce nerve impulse transmission. Purkinje cells efficiently control and coordinate the body's motor motions through these inhibitory actions.
Cerebellar hypoplasia (CH) is a neurological condition in which the cerebellum is smaller than usual or not completely developed. It has been reported in many animal species.
Wobbler disease is a catchall term referring to several possible malformations of the cervical vertebrae that cause an unsteady (wobbly) gait and weakness in dogs and horses. A number of different conditions of the cervical (neck) spinal column cause similar clinical signs. These conditions may include malformation of the vertebrae, intervertebral disc protrusion, and disease of the interspinal ligaments, ligamenta flava, and articular facets of the vertebrae. Wobbler disease is also known as cervical vertebral instability (CVI), cervical spondylomyelopathy (CSM), and cervical vertebral malformation (CVM). In dogs, the disease is most common in large breeds, especially Great Danes and Doberman Pinschers. In horses, it is not linked to a particular breed, though it is most often seen in tall, race-bred horses of Thoroughbred or Standardbred ancestry. It is most likely inherited to at least some extent in dogs and horses.
Progressive retinal atrophy (PRA) is a group of genetic diseases seen in certain breeds of dogs and, more rarely, cats. Similar to retinitis pigmentosa in humans, it is characterized by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness. The condition in nearly all breeds is inherited as an autosomal recessive trait, with the exception of the Siberian Husky (inherited as an X chromosome linked trait) and the Bullmastiff (inherited as an autosomal dominant trait). There is no treatment.
Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with a broad variety of tumors including lung cancer, ovarian cancer, breast cancer, Hodgkin’s lymphoma and others. PCD is a rare condition that occurs in less than 1% of cancer patients.
Equine polysaccharide storage myopathy is a hereditary glycogen storage disease of horses that causes exertional rhabdomyolysis. It is currently known to affect the following breeds American Quarter Horses, American Paint Horses, Warmbloods, Cobs, Dales Ponies, Thoroughbreds, Arabians, New Forest ponies, and a large number of Heavy horse breeds. While incurable, PSSM can be managed with appropriate diet and exercise. There are currently 2 subtypes, known as Type 1 PSSM and Type 2 PSSM.
Canine degenerative myelopathy, also known as chronic degenerative radiculomyelopathy, is an incurable, progressive disease of the canine spinal cord that is similar in many ways to amyotrophic lateral sclerosis (ALS). Onset is typically after the age of 7 years and it is seen most frequently in the German shepherd dog, Pembroke Welsh corgi, and boxer dog, though the disorder is strongly associated with a gene mutation in SOD1 that has been found in 43 breeds as of 2008, including the wire fox terrier, Chesapeake Bay retriever, Rhodesian ridgeback, and Cardigan Welsh corgi. Progressive weakness and incoordination of the rear limbs are often the first signs seen in affected dogs, with progression over time to complete paralysis. Myelin is an insulating sheath around neurons in the spinal cord. One proposed cause of degenerative myelopathy is that the immune system attacks this sheath, breaking it down. This results in a loss of communication between nerves in lower body of the animal and the brain.
Lavender foal syndrome (LFS), also called coat color dilution lethal (CCDL), is an autosomal recessive genetic disease that affects newborn foals of certain Arabian horse bloodlines. Affected LFS foals have severe neurological abnormalities, cannot stand, and require euthanasia shortly after birth. The popular name originates due to a diluted color of the foal's coat, that in some cases appears to have a purple or lavender hue. However, not all foals possess the lavender coat colour, and colouring can range from silver to light chestnut to a pale pink. Carrier horses have no clinical signs and DNA testing can determine if a horse carries the gene.
The severe combined immunodeficiency (SCID) is a severe immunodeficiency genetic disorder that is characterized by the complete inability of the adaptive immune system to mount, coordinate, and sustain an appropriate immune response, usually due to absent or atypical T and B lymphocytes. In humans, SCID is colloquially known as "bubble boy" disease, as victims may require complete clinical isolation to prevent lethal infection from environmental microbes.
Brown-Vialetto-Van-Laere syndrome (BVVL), sometimes known as Brown's syndrome, is a rare degenerative disorder often initially characterized by progressive sensorineural deafness.
Shivers, or equine shivering, is a rare, progressive neuromuscular disorder of horses. It is characterized by muscle tremors, difficulty holding up the hind limbs, and an unusual gait when the horse is asked to move backwards. Shivers is poorly understood and no effective treatment is available at this time.
Ann Trommershausen Bowling was an American scientist who was one of the world's leading geneticists in the study of horses, conducting research in the areas of molecular genetics and cytogenetics. She was a major figure in the development of testing to determine animal parentage, first with blood typing in the 1980s and then DNA testing in the 1990s. She later became known for her studies of hereditary diseases in horses and equine coat color genetics, as well as research on horse evolution and the development of horse breeds. She studied the population genetics of feral horses, did considerable work to help preserve the Przewalski's horse, and was one of the founding members of the international project to map the horse genome. She was an adjunct professor at the University of California, Davis (UCD), and at the time of her death in 2000 was the executive associate director of the Veterinary Genetics Laboratory (VGL) there. Her unexpected death on December 8, 2000, at age 57 was attributed to a massive stroke.
Spinocerebellar ataxia type 1 (SCA1) is a rare autosomal dominant disorder, which, like other spinocerebellar ataxias, is characterized by neurological symptoms including dysarthria, hypermetric saccades, and ataxia of gait and stance. This cerebellar dysfunction is progressive and permanent. First onset of symptoms is normally between 30 and 40 years of age, though juvenile onset can occur. Death typically occurs within 10 to 30 years from onset.
Hyperkalemic periodic paralysis is a genetic disorder that occurs in horses. It is also known as Impressive syndrome, after an index case in a horse named Impressive. It is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis.
Cerebellar degeneration is a condition in which cerebellar cells, otherwise known as neurons, become damaged and progressively weaken in the cerebellum. There are two types of cerebellar degeneration; paraneoplastic cerebellar degeneration, and alcoholic or nutritional cerebellar degeneration. As the cerebellum contributes to the coordination and regulation of motor activities, as well as controlling equilibrium of the human body, any degeneration to this part of the organ can be life-threatening. Cerebellar degeneration can result in disorders in fine movement, posture, and motor learning in humans, due to a disturbance of the vestibular system. This condition may not only cause cerebellar damage on a temporary or permanent basis, but can also affect other tissues of the central nervous system, those including the cerebral cortex, spinal cord and the brainstem.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
