Cerebellar Abiotrophy in Horses: Symptoms, Risk Factors & Prognosis

Equine Cerebellar Abiotrophy (CA) is an uncommon neurodegenerative disorder that mostly affects Arabian horses, although it can occur in other breeds. Cerebellar Abiotrophy causes the death of certain brain cells, leading to issues with movement and balance. ^[1][2][3]

The horse’s brain is responsible for managing and regulating all bodily functions and behaviors. The cerebellum, located at the back of the brain beneath the occipital lobes, plays a vital role in coordinating and fine-tuning motor movements. ^[4]

Cerebellar Abiotrophy is a genetic disorder that occurs when a horse inherits two copies of the CA gene, one from each parent. Affected horses may show signs such as uncoordinated movements, head shaking, and frequent stumbling.

Horses with only one copy of the CA gene are carriers of the disorder. They don’t show symptoms of CA, but can pass the gene to their offspring.

To prevent Cerebellar Abiotrophy, breeders use genetic testing to avoid mating two carrier horses, reducing the chance of producing affected foals. Understanding and managing CA helps ensure the health and well-being of horses.

The Equine Cerebellum

The cerebellum is a part of the horse’s brain located at the back, beneath the occipital lobes. This small area is an important hub for coordinating and fine-tuning motor movements and maintaining balance.

The cerebellum processes sensory input from the spinal cord, sensory systems, and other parts of the brain to understand the intended movement and compares the intent against what the horse is actually doing. ^[4][5]

If there’s a difference, the cerebellum corrects it by sending messages through special cells called Purkinje cells to other parts of the brain that control muscles. This ensures actions like walking, trotting, and jumping are smooth and accurate. ^[5]

In addition to motor coordination, the cerebellum maintains balance and posture by continuously adjusting muscle activity in response to changes in the environment or internal cues. It also plays a key role in motor learning, helping horses refine their movements through practice. ^[5]

Cerebellar Abiotrophy

Cerebellar Abiotrophy (CA) is caused by a genetic mutation in the CYP27A1 gene, which affects cholesterol metabolism. This mutation disrupts normal neuron development in the cerebellum, leading to the premature death of Purkinje cells. ^[2][6]

Purkinje cells are fundamental to motor control, as they integrate and process information related to movement and balance. These neurons fine-tune movements by sending signals to the deep cerebellar nuclei, which regulate the horse’s muscle activity and balance.

As Purkinje cells degenerate due to the genetic mutation, the cerebellum’s ability to regulate and fine-tune motor control is compromised. This results in symptoms such as uncoordinated movements (ataxia), balance issues, and intention tremors.

CA is inherited in an autosomal recessive pattern, meaning that a horse must inherit two copies of the mutated gene, one from each parent, to exhibit the condition. ^[7]

Risk Factors

Cerebellar Abiotrophy (CA) is most commonly associated with Arabian horses. Specific bloodlines within the breed show a higher susceptibility, indicating a genetic predisposition linked to certain family lines. ^[3][7][8]

Although CA is most frequently observed in Arabians, it can also occur in other breeds such as: ^{[1][2][3][8][9]}

• Danish Sport Horse
• Trakehner
• Welsh Pony
• Oldenburg
• Gotland Pony
• Eriskay Pony
• Icelandic Horse

Genetic Disorders in Arabian Horses

Arabian horses are prone to several autosomal recessive inherited diseases, including: ^[10]

• Cerebellar Abiotrophy (CA)
• Lavender Foal Syndrome (LFS)
• Severe Combined Immunodeficiency (SCID)
• Occipitoatlantoaxial Malformation (OAAM)

Historically, Arabian horses were exported from the Middle East to various stud farms overseas. The number of horses transported was often small, resulting in new populations founded by only a limited number of individuals. This created a genetic bottleneck, meaning the new populations had reduced genetic diversity compared to the original ones. ^[11]

The reduced genetic variation in these new populations increases the prevalence of recessive genetic disorders. With fewer genetic variants and higher chances of inbreeding, there is a greater likelihood of mating between closely related horses carrying the same genetic mutations, leading to an increased incidence of these inherited diseases. ^[11]

Symptoms

Foals with Cerebellar Abiotrophy (CA) typically appear normal at birth but start to show clinical signs of the disorder later. Symptoms usually begin to appear between 4 weeks and 6 months of age, with the timing varying among individuals. ^{[1][2][3][6][8][9][10][11]}

Initially, the signs may be subtle, but they become more pronounced as the horse matures and the cerebellum’s function deteriorates. Horses with CA exhibit several distinct symptoms related to motor coordination and balance:

• Ataxia: Uncoordinated movements that make the horse appear wobbly or clumsy, particularly when walking or trotting.
• Startle Reflex: Affected horses may startle easily and fall over.
• Intention Tremors: Shaking of the head, either horizontal or vertical, particularly noticeable when the horse attempts to perform precise movements or focus on an object. Affected foals may exhibit intention tremors while trying to nurse.
• Awkward Stance: The horse adopts a wide-based stance, with its legs spread farther apart to maintain balance and compensate for instability. Additionally, the affected horse may exhibit stiff or rigid muscles and display jerky or erratic movements.
• Dysmetria: Difficulty in judging the distance and speed of movements, leading to over- or under-shooting when reaching for objects or performing tasks.
• Hypermetria: Exaggerated movements where the horse overextends its limbs beyond the normal range of motion.

Since CA primarily affects the cerebellum, which is responsible for coordinating movement and balance, it typically does not impact most cranial nerves. Cranial nerves, which control functions like facial sensation, eye movement, and chewing, are managed by different brain regions, including the brainstem. ^[2][3]

As a result, reflexes involving cranial nerves, such as blinking (palpebral reflex) and responses to visual or auditory stimuli, usually remain intact. However, the menace reflex is often impaired or absent in horses with CA, meaning affected horses may not respond appropriately to a threatening gesture. ^[1][2]

Diagnosis

Diagnosing Cerebellar Abiotrophy (CA) in horses involves a thorough approach to accurately identify the condition and rule out other similar disorders. ^[3]

Clinical Examination

Diagnosis begins with a thorough clinical examination. A veterinarian observes the horse for symptoms such as:

• Uncoordinated movements
• Balance issues
• Intention tremors
• Wide-based stance

A detailed physical and neurological examination assesses motor function, coordination, and balance, helping to distinguish CA from other neurological disorders with similar symptoms.

Diagnostic Testing

Horses suspected of having Cerebellar Abiotrophy require thorough testing to accurately identify the condition. ^[2][3]

The process begins with bloodwork to check for secondary conditions, though these results are usually normal in horses with CA. Diagnostic imaging, including head and cranial cervical X-ray, may be necessary to exclude traumatic or congenital abnormalities that could mimic CA symptoms.

Cerebrospinal fluid (CSF) analysis (i.e. “spinal tap”), rules out other conditions such as Equine Protozoal Myeloencephalitis (EPM), particularly in horses from regions where EPM is prevalent.

Immunological testing on serum and CSF further assists in confirming the diagnosis by excluding EPM and similar diseases. Together, these diagnostic tools provide a comprehensive evaluation to confirm CA and differentiate it from other potential causes of neurological signs.

Differential Diagnosis

When diagnosing Cerebellar Abiotrophy (CA) in horses, it is essential to distinguish it from other conditions with similar clinical signs, including: ^{[2][3][12][13][14]}

• Equine Protozoal Myeloencephalitis (EPM): Caused by the parasite Sarcosystis neurona, EPM leads to neurological symptoms like ataxia, particularly in horses from endemic areas. It is confirmed through serological testing and cerebrospinal fluid analysis. EPM often presents with a broader range of neurological signs compared to CA.
• Cerebellar Hypoplasia: This condition involves the underdevelopment of the cerebellum, resulting in symptoms such as uncoordinated movement and balance issues. Unlike CA, which develops gradually within the first 6 months, cerebellar hypoplasia is present at birth.
• Vascular Anomaly: Vascular anomalies involve abnormalities in blood vessels, including malformations, abnormal connections, or disruptions in normal blood flow. These conditions are usually associated with a history of trauma or other vascular issues, and may be characterized by ataxia and balance issues.
• Neoplasia (Tumors): Tumors in the brain or spinal cord, while very rare in horses, can cause neurological deficits such as ataxia. Neoplasia is often accompanied by other signs of brain dysfunction and is diagnosed using imaging techniques like MRI or CT scans.

Combining these diagnostic methods ensures a comprehensive evaluation to confirm CA and rule out other potential causes of neurological symptoms.

Treatment and Prognosis

Currently, there is no cure for Cerebellar Abiotrophy (CA) in horses, and the prognosis is guarded due to the progressive nature of the condition. As CA progresses, horses may experience worsening symptoms over time, and euthanasia may be warranted.^[3][15]

Although CA is incurable and affected horses tend to deteriorate, careful management and supportive care can help maintain some level of comfort and functionality, particularly in mild cases. Some horses begin to stabilize once they reach maturity. ^[2][16]

Owners and caretakers can implement the following practices to support mildly affected horses:

• Environmental Modifications: Ensuring a safe environment is fundamental for horses with reduced motor function. Remove obstacles and hazards that could cause injury to a horse with uncoordinated movements.
• Physical Therapy: Gentle exercises and physical therapy can help maintain muscle strength and coordination.
• Veterinary Care: Regular check-ups with a veterinarian experienced in neurological disorders can help monitor the horse’s condition and adjust care as needed.

Management and Prevention

Breeders play a crucial role in preventing Cerebellar Abiotrophy (CA) by making informed breeding decisions. Genetic testing is an essential tool for identifying horses that carry the CA gene.

When two carrier horses are bred together, there is a 25% chance that resulting foals will inherit two copies of the mutated gene and develop CA. To reduce the likelihood of producing affected foals, breeders should avoid mating two carrier horses. ^[17]

If a carrier horse is bred with an unaffected horse (one without the mutation), foals produces will not develop CA. However, there is a 50% chance that resulting foals will inherit one copy of the mutated gene and be a carrier.

By prioritizing genetic testing and responsible breeding practices, breeders can significantly contribute to the health and well-being of the horse population, reducing the incidence of CA.

Genetic Testing

Genetic testing has enabled better management and prevention of Cerebellar Abiotrophy (CA) in horses. The process begins with collecting a DNA sample, typically from hair follicles with roots attached.

In the laboratory, DNA is extracted and analyzed for mutations in the CYP27A1 gene, which is associated with CA. Techniques such as polymerase chain reaction (PCR) or sequencing are used to detect these genetic mutations. ^[9][10]

The results from the genetic test are categorized as follows:

• N/N (Normal/Unaffected): The horse has two copies of the normal gene, indicating that it does not carry or exhibit CA. Such horses are neither affected by CA nor carriers of the mutated gene.
• N/CA (Carrier): The horse has one normal allele and one mutated allele. This horse does not show clinical signs of CA but can pass the mutation to its offspring.
• CA/CA (Affected): The horse has two copies of the mutated allele, resulting in clinical signs of CA, such as uncoordinated movements and balance issues.

Summary

Cerebellar Abiotrophy (CA) is a genetic disorder mainly affecting Arabian horses, causing motor and balance issues.

• CA is inherited in an autosomal recessive pattern, requiring two copies of the mutated gene from the parents for the condition to manifest.
• Symptoms include uncoordinated movements, intention tremors, and an awkward stance.
• Diagnosis may include clinical examination, blood tests, imaging, and excluding other neurological conditions.
• Genetic testing is used to identify carriers of the CA gene, guide breeding decisions, and prevent the production of affected foals.