Genetic Disorders
If you ever thought it wasn't important to educate yourself about equine diseases, specifically those relating to arabian horses, here's what you might consider:

The mysterious guttural pouch
While the function of the guttural pouch in athletic performance is unclear, disease of the area can be deadly

( A HORSE'S guttural pouch is the Bermuda Triangle of horse anatomy. Though the area can be well defined and located, it remains somewhat a mystery as to its purpose. Diseases that occur in this region can be quite severe, and, like the Bermuda Triangle, small problems can have deadly consequences.
Guttural pouch diseases do not occur frequently. They represented less than 0.5% of all cases presented to the Western College of Veterinary Medicine in California over a two-year period. But the potential adverse effects of these conditions on the individual horse warrant attention and discussion.

What is a guttural pouch?

A guttural pouch is an air-filled out-pouching of the auditory or Eustachian tube. While all mammals have auditory tubes, not all have these pouches. Horses, mules, and donkeys have the largest, with one pouch lying on each side of the back of the throat.

Eustachian tubes extend from the inner surface of each eardrum to the sides of the pharynx. The pharynx is the large opening in the back of the mouth/throat where the nasal passages and the oral cavity join before separating into the trachea (airway) and the esophagus (feeding tube). Eustachian tubes connect to this large pharyngeal cavity as slit-like openings on either side of the back of the throat.

Auditory tubes serve an important function by regulating pressure on the eardrums. (Some children have had surgery to implant drainage tubes in the Eustachian tubes to reduce earaches.) The outer ear of all animals is exposed to atmospheric pressure while the inner ear and the ends of the auditory tubes are exposed to the pressure within the throat, which can be very different.

As a horse or human ascends a high mountain, the atmospheric pressure becomes lower. If the pressure is severe enough, the eardrum begins to bulge outward, and, if not for the auditory tubes, it probably would rupture. The auditory tubes, however, allow the body to equalize this pressure.

Each time an individual swallows, the pharyngeal or lower end of the tube opens. If the outer ear pressure is higher, some air is taken into the tube until the pressure on both sides of the eardrum is equalized. The reverse occurs if the outside pressure is less than the inner pressure.

Because the horse spent much of its evolutionary development on flat grassland, pressure regulation does not appear to be a factor in explaining the extreme size of the equine guttural pouch. More recent research points to its ability to significantly cool the horse's brain by moving air in and out of the guttural pouch as probably its key function.

The exercising horse generates a tremendous amount of heat because of the massive amount of muscular work required for high-speed motion. This heat must be removed from the body or internal temperatures will rise to debilitating levels. Many large arteries and veins that supply the head and brain are closely associated with the inner lining of the guttural pouches.

Researchers now believe that heat is removed from the exercising horse's brain via transfer from the blood to the air in the guttural pouch and then out through the pharynx. This mechanism also provides a clue as to why diseases occur in this anatomical area and why those diseases can be deadly.

Potential for disaster

With each swallow, air enters or leaves the guttural pouch of the horse. This means that any bacteria, fungi, or other infectious agents inhaled or ingested by the horse have ready access to both pouches. These potentially disease-causing particles can enter the pouches and usually become trapped in the mucus that lines these structures.

Most of the time, the horse's immune system successfully destroys these agents, but bacteria or fungi occasionally survive and continue to grow by invading the lining of the pouches.

The guttural pouch is a two-chambered space separated by the stylohyoid bone, and it can hold roughly 20 ounces of fluid or air. The medial or innermost chamber has several important blood vessels and nerves located on its surface. These nerves are responsible for various crucial body functions, such as breathing, swallowing, and chewing.

The lateral or outermost chamber is associated with more nerves and contains the internal carotid artery and the maxillary-facial vein. Proximity of the guttural pouches and the nerves, arteries, and veins associated with them also exposes these critical structures to infection and damage. The design of the guttural pouch is a beneficial marvel for the horse, but it also is a potential disaster waiting to happen.


There are three main diseases of the guttural pouch. The first is guttural pouch tympany.
Horses with this problem are born with a defect that causes the pharyngeal opening of the Eustachian tube to act like a one-way valve. Air can get in, but it cannot get out. This condition usually occurs in only one pouch, but it can affect both.

Because it is a problem present from birth, most cases of tympany are noted within the first few days of a foal's life. Several recent studies have looked at the genetic component of guttural pouch tympany, and links with the disease have been made to some Arabian and Hanoverian bloodlines.

Horses with tympany show massive swelling of the neck and throatlatch. If this swollen area is tapped with a finger, it resonates like a drum, which gives the condition its name. Affected horses might exhibit mild discomfort or be unable to breathe and swallow correctly if the swelling is severe enough.

Diagnosis is made based on the observed swelling and the foal's age, then the condition usually is confirmed by radiographs and endoscopic examination. Surgical correction is the treatment of choice, and one-sided tympany usually is easily corrected with a favorable prognosis. Those rare foals with both pouches affected require a much more complicated surgery and have a less favorable outcome, though recent advances employing laser surgery could soon improve their chances.

Pus-filled pouches

Guttural pouch empyema, or the presence of pus in the pouches caused by bacterial growth, is more common than tympany. Empyema usually occurs following an infection of the pharynx. Often significant infection can be present before external swelling of the pouch is noted.

The most common organism involved is Streptococcus equi, the causative agent of strangles. Horses with strangles often have abscesses in the pharynx that rupture and drain, which allows Streptococcus bacteria to gain entry into the guttural pouch. This bacterial strain can live in the guttural pouch for weeks to months causing a large amount of mucus that contains white blood cells from the immune system, bacteria, and necrotic tissue from the guttural pouch. A thick, pasty material develops that is not easily drained away.

The top part of the pouch might contain more fluid, but the bottom of the pouch holds a thicker material of almost cottage-cheese consistency with occasional solid masses of debris called chondroids.
An affected horse will show a persistent, creamy discharge, usually from one nostril. When the horse lowers its head to graze, the discharge usually increases as gravity allows more pus to exit the pouch into the pharynx and flow out the nasal passage.

Initially, these horses are rarely sick, but chronic infection will result in progressive weight loss, debilitation, and potential damage to the nerves and vessels within the pouch.

If the nerves become involved, horses can exhibit difficulty eating and swallowing. They also can have difficulty breathing. Research has shown that one potential cause of laryngeal paralysis, or roaring, is infection of the guttural pouch. Dorsal displacement of the soft palate, which also affects breathing, can be a complication. If the facial nerves are affected, some horses also might develop a drooped lip or ear.

Some cases of empyema resolve themselves without treatment as the pus eventually drains from the pouch. The majority of horses, however, will require aggressive flushing of the pouch and antibiotic therapy. Specialized catheters are placed in the affected pouch, and large volumes of fluids are repeatedly flushed in and out with significant pressure.

If the condition is chronic and severe enough, surgery sometimes is needed to drain the pouch. This is especially true if large chondroids have formed. Though the surgical approach is technically difficult, horses that receive treatment before damage occurs to nerves and blood vessels show good response and might recover fully.

Danger to carotid artery

Guttural pouch mycosis is the most serious of the three pouch diseases and is caused by the presence of fungi in the pouch. Aspergillus, Candida, Penicillium, and Mucor are the fungi most commonly found; they easily are encountered in hay, forage, and other parts of the horse's natural environment.

Fungal infections in the guttural pouch usually begin over one of the main arteries that traverse the pouch walls. Interestingly, research has shown that a defect in the artery wall is necessary for the fungal infection to start and that restricting blood flow through the artery might cure the condition without other treatment. If the mycosis is not resolved, however, the fungal infection slowly will erode the walls of the blood vessel, and the horse will begin to bleed.

The first sign of guttural pouch mycosis might be intermittent bleeding from one nostril, or epistaxis. If this mild bleeding is allowed to continue untreated, the blood vessel eventually will rupture, and the horse will bleed to death.

Fungal damage also can occur to the nerves within the walls of the pouches. Horses with this condition, even if they are treated and do not succumb to bleeding, could remain unable to eat and swallow. They often lose tremendous amounts of weight and eventually die.

Treatment involves a complicated surgery to ligate or tie off the blood vessels traveling through the affected pouch. Balloon catheters and surgical lasers now are being used in these procedures, but the prognosis for these horses remains guarded.

Antifungal medication is administered along with surgery for optimal chances of return to function in these cases. If the diagnosis can be made early, there is a better chance that surgery can be done and that no permanent damage will occur to crucial blood vessels and nerves.

Pay close attention

Few other areas in the horse's body are as important to its ability to function as an athlete but can lead to its destruction. Add the fact that the guttural pouches cannot be seen and are difficult to comprehend even with a description.

Yet, knowing about their existence, their function, and the signs of possible disease might allow you seek early treatment for your horse. Problems in this area do not happen often, but when they do, quick response could save a horse's life.

Equine neonatal isoerythrolysis (NI) is a condition of foals that are born healthy, but develop a possibly life-threatening hemolytic anemia within hours to a few days after the ingestion of their mare’s colostrum. This condition occurs as a result of a hypersensitivity reaction between the mare’s antibodies in the colostrum and inherited antigens from the sire that are present on the foal's red blood cells.

Erythrocyte Antigens

Antigens that are present on the red blood cells define the blood group system(s) to which the horse belongs. According to the International Society for Animal Genetics, there are seven blood groups: A, C, D, K, P, Q, and U. Each group corresponds to a specific gene that contains two or more alleles that vary in combination. These blood group genes code for surface molecules that contain antigenic sites known as "factors." Each factor is specific within each blood group. There are variable numbers of factors for each group.

Table 1. Equine blood groups and factors within each group. The factors that have been associated with NI are highlighted in blue. Group Factor A a, b, c, d, e, f, g C a D a, b, c, d, e, f, g, h, i, k, l, m, n, o, p, q, r K a P a, b, c, d Q a, b, c U a

Red blood cell (RBC) antigens are clinically detected by three main tests: (1) agglutination, (2) complement-mediated lysis of test cells by antibodies directed against RBC alloantigens, or (3) antiglobulin tests.1 A genetic marker report can be created for an individual horse that will include the following information: (1) Sample identification of horse including name, registration number, color, sex, year of birth, breed, sire name, sire registration number, dam name, and dam registration number; (2) Blood group factors; (3) Protein variants (although these factors have no known medical or performance significance); and (4) Markers recognized by various testing techniques applied. These genetic marker reports may provide information to help manage neonatal isoerythrolysis.2
Because these inherited blood factors are involved in the NI hypersensitivity reaction, NI is a genetic disease. These blood factors vary in structure and in their antigenicity (potency of antigenic response). NI occurs at different frequencies in horse foals versus mule foals, and in standardbreds versus thoroughbreds.

Table 2. Frequency of neonatal isoerythrolysis in foals among Standardbreds, Thoroughbreds, and mules expressed as a percentage of all births. Breed Prevalence of NI Standardbreds 2% Thoroughbreds 0.05% mules 8-10%


Neonatal isoerythrolysis is a type II hypersensitivity reaction (Fig 1). In this type of reaction, initial exposure to an antigen from a non-native cell will induce B lymphocytes to produce antibodies against offending "foreign" antigens that are present on the non-native cells. Antibody production will decrease as the offending antigens are removed from circulation. Upon re-exposure to the same cells containing these offending antigens, a greatly intensified secondary immune response to these antigens will occur. In one study, the following antigens were identified as having produced an immunologic response leading to the production of anti-RBC antibodies (see highlighted factors in Table 1): Ca, Aa, Ab, Da, Dc, Df, Ka, Pa, Ua, Qrs, Qb, Qc, and Qa.3,7 Specifically, the Qa and Aa antigens are named historically as causing the most severe immunologic reactions.3

Mares can become sensitized (immunologically stimulated) to the offending foreign RBC antigens of the sire or foal if an event occurs which exposes the mare to these antigens (Fig. 2). These events include exposure to offending RBC antigens via blood leakage through the placenta during pregnancy or delivery, previous blood transfusions, or the administration of vaccines containing equine tissue products. The exact mechanism of sensitization at delivery is unclear at this time.4, 5 With pregnancy-related sensitization, the mare is sensitized to the stallion’s RBC antigens that differ from her own RBC antigens. Once the mare has been exposed to these antigens, she will respond immunologically by producing an alloantibody (usually IgM antibodies initially, then IgG antibodies). Subsequent immunologic memory can persist for many years. This sensitization after initial exposure (usually after the first pregnancy) is usually minimal. However, if repeated exposure to the same offending RBC antigens occurs with subsequent pregnancies, then alloantibody production will increase considerably.5

Once the mare has become sensitized to specific RBC antigen(s), subsequent foals are at risk for development for NI if they are sired by the same stallion. Adverse reactions can occur with one or more antigen types simultaneously. Because of the type of placentation In horses, the alloantibodies responsible for NI do not cross the placenta, but are secreted into the colostrum. Foals will develop to term and be born without any side effects from the mare’s immunologic response to these offending antigens. When the young foal ingests its mare’s colostrum, the colostral antibodies will be absorbed into the circulation of the foal during the first few hours after birth until "gut closure" occurs and macromolecules cannot be directly absorbed into the blood from the intestinal tract. Absorption of maternal colostral antibodies is important for the foal’s immune system function (passive transfer); however, harmful antibodies against the foal’s erythrocyte antigens also are absorbed. These harmful alloantibodies bind to offending antigen(s) on the foal’s RBCs, causing hemagglutination and extravascular or intravascular hemolysis. The higher the mare’s antibody titer to the offending RBC antigen at parturition, the higher the risk will be for development of NI. Resulting signs of NI may be subclinical or clinical. 

Figure 1. Illustration representing the attachment of alloantibody to incompatible antigens on the surface of the foal's erythrocytes.

Pathogenesis of Equine Neonatal Isoerythrolysis:  Figure 2A, 2B: Flow charts depicting the development of neonatal isoerythrolysis in foals. A- initial sensitization, B- subsequent breedings.

Major Erythrocyte Antigens Involved in Neonatal Isoerythrolysis

Five major erythrocyte antigens are involved in the development of NI in foals. These antigens include:

1. Qa antigen: This antigen and the Aa antigen (below) are responsible for 90% of all cases of NI in horses;7 however, the Qa antigen is extremely rare in Standardbreds (Table 3). Mares that do not possess the Qa and/or Aa antigens (~19% of Thoroughbreds and ~17% of Standardbreds) are at the greatest risk for development of NI.3

2. Aa antigen: This RBC antigen has been found in the sera of both Standardbreds and Thoroughbreds (Table 3). It is commonly involved with NI as is the Qa antigen (above).

3. Ca antigen: Approximately 20% of Standardbreds and 10% of Thoroughbreds produce antibodies to this RBC antigen. However, antibodies that are reactive with this blood group are found in other species, suggesting that Ca may be a common environmental antigen. It is also hypothesized that antibodies to this blood group are natural antibodies that may occur without exposure to a RBC containing this antigen. This blood antigen may play an important role in a type of antibody-mediated immunosuppression in horses that possess it. These antibodies appear to attack fetal RBCs that cross over to the mare before the mare is able to mount an immune response to other RBC antigens such as the Aa group.8

4. Qc (lysin) and Db (agglutin) antigens: One study has indicated that these antigens are involved in some cases of NI. Antibody titers to the Qc antigen were elevated at parturition, but decreased over the next 4 months.7

5. Donkey RBC antigen: In one experimental study, the risk of an incompatible mating between a horse and a donkey (or the chance of a mare becoming sensitized to this antigen) was 100%. This high rate of sensitization may be due to a naturally occurring antibody that horses possess to this factor, differences in placentation in mule pregnancies, or differences in the antigenicity of this factor. Because clinical NI in mule foals only occurs ~8-10% of the time, it is suggested that many mule foals may have subclinical NI because the concentration of colostral antibodies against the foal’s RBCs that is required to cause overt clinical signs may differ between horse and mule foals.

6  Table 3. Genes Aa and Qa and their associations with various breeds of horses.1 Breed Gene Frequency of Aa Gene Frequency of Qa Thoroughbred 0.151 0.388 Standardbred 0.435 1.000* Arabian 0.182 0.794 Quarterhorse 0.510 0.825 Morgan 0.432 0.994 * = 1.000 means that all individuals in that specific breed are negative for that allele (factor).

Clinical Presentation of Neonatal Isoerythrolysis

Clinical signs of NI may be subclinical or clinical. Foals appear healthy at birth and the onset of clinical signs occurs from several hours to as late as seven days after ingestion of colostrum. Clinical signs may vary depending upon the antigen involved, the concentration of alloantibodies in the colostrum, and the timing of colostrum administration.5 The major clinical signs also depend upon the degree of hemolysis.

Foals with NI usually become progressively lethargic, weak, and depressed. Mucous membranes may become pale and later icteric (Fig. 3). The degree of icterus is dependent upon time and the amount of hemolysis that occurs (Fig. 4). In cases where severe anemia is present, there will be a marked hemoglobinemia and hemoglobinuria (Fig. 5). Because of the reduced oxygen carrying capacity of the anemic blood, breathing may become shallow, rapid, and labored. Tachycardia also may develop. Foals with severe hypoxia may convulse or become comatose and die. Foals that are severely affected may develop shock and die quickly (within 6-8 hours postpartum) before icterus can occur. Generally, death may occur if NI is not recognized and treated quickly. 

Figure 3. Icterus of the sclera and mucous membranes in a foal may indicate hemolysis of several hours duration. 

Figure 4. The yellow discoloration of plasma from a neonatal foal indicates icterus. Figure 5. Red-brown discoloration of the urine (left) suggests hemoglobinuria, hematuria, or myoglobinuria; however, red discoloration of the plasma (right) indicates that hemoglobinemia is present and this probably produced the hemoglobinuria.

The presence of anemia in a foal can be documented quickly, easily, and economically by performing a packed cell volume (PCV). Once the presence of anemia is verified, several causes of blood loss, including NI, should be considered in the differential diagnosis (Table 4).

Table 4. Differential diagnoses for a foal with anemia. Blood loss from iatrogenic or obstetrical causes* Perinatal hemorrhage (intra-abdominal, intra-thoracic, and other forms of soft tissue hemorrhage)* Thrombocytopenia* Hereditary bleeding disorders* Neonatal Isoerythrolysis Snake venom intoxication Infection Disseminated intravascular coagulation (DIC) * Total bilirubin concentration of plasma usually within reference interval.

To determine if the foal has nursed and absorbed colostral antibodies, a measurement of the foal’s IgG concentration should be performed. Various methods can be used to measure antibody concentration in serum, plasma, or whole blood, including latex agglutination tests, zinc sulfate turbidity, and enzyme immunoassay (CITE® or SNAP® tests). Foal IgG levels greater than 800 mg/dl are generally considered indicative of adequate passive transfer.10

Foals with NI, anemia will have a decreased packed cell volume (PCV, hematocrit) and RBC count. PCV values may be <20%. The hemoglobin concentration may be increased (with intravascular hemolysis) or decreased, depending upon the time course of disease and blood sample procurement. Hemoglobinemia or icterus may be observed in the plasma of the PCV specimen following centrifugation. Mule foals also may be thrombocytopenic. Routine biochemical abnormalities may include hyperbilirubinemia (mainly unconjugated bilirubin) and possible electrolyte disturbances (e.g, hyperkalemia) from hemolysis. Urinalysis may reveal hemoglobinuria.

Definitive diagnosis of NI requires the demonstration of immunoglobulin on the surface of the foal’s RBCs. The detection of maternal antibody can be confirmed via screening the mare’s serum, plasma, or colostrum for reactivity with the sire’s RBCs. If the sire’s RBCs are not available, a panel of RBC bearing different blood groups may be used instead. High titers of alloantibody from the dam will result in agglutination. Lower titers may require the addition of a source of complement (such as fresh normal rabbit serum) to induce hemolysis. These lytic tests are believed to be a somewhat more reliable indicator for the presence of alloantibody directed toward the foal’s RBC.1, 4, 5

Treatment of NI

Note: Diagnosis and treatment of neonatal isoerytholysis should only be performed by a licensed veterinarian. Treatment protocols are determined by the veterinarian based on the patient's clinical signs and physical condition.
Prognosis of the disease is dependent upon the severity of the hemolysis, when the condition is diagnosed and when therapy is instituted. Once diagnosed as NI, it is important to immediately stop the further ingestion of colostrum by the foal. This will prevent the intake of more alloantibodies against the foal’s erythrocytes from the mare. Due to the anemic and consequent hypoxic state, the foals are usually exercise-intolerant, so stress should be minimized. Foals should be provided with warmth and appropriate antimicrobial therapy, as they may not have adequate levels of maternal antibody. Supplemental oxygen may be necessary in hypoxic foals.

Supportive care is needed until the foal recovers. Intravenous fluid therapy helps promote diuresis to reduce the potentially harmful levels of hemoglobin in the kidney. Acid-base disturbances should also be corrected. A blood count of less than 3 x 106 RBCs/mL or PCV less than 10-15% warrants a transfusion to provide the foal with needed RBCs. However, it is important to ensure that the donated blood does not possess antibodies to the foal’s RBCs. Finding an appropriate donor may be a difficult task, however, as there is a high prevalence of Qa and Aa in the normal equine population. Because the dam’s RBCs do not possess these offending antigens on their surface, the mare may represent a convenient donor choice if the mare’s RBCs are washed to remove the plasma along with its alloantibodies to the foal’s RBCs. The same applies for mule foals; washed RBCs from the dam may be the most convenient choice for a transfusion. If the mare’s blood is unavailable, then a crossmatched donor’s blood that does not have an immune response with the antibodies present in the mother’s serum can be used.

Prevention of NI

The main methods used to prevent NI are as follows:
Identify broodmares that are negative for the Qa and/or Aa erythrocyte antigens. This can be done as previously discussed via blood typing in a genetic marker report or by a simple cross match. These mares are at highest risk for developing alloantibodies to "offending" antigens on the sire's or foal's RBCs.2
Identify sires that are positive for the Qa and Aa antigens, if they are to be bred to mares that are negative for Qa and/or Aa antigens. This will help prevent broodmares from becoming sensitized to these two main offending antigens.

Determine the probability of NI in unintended or potentially incompatible matings. If an unintended or potentially incompatible mating results, the mare’s serum is collected two weeks prior to parturition and tested against known blood cell groups or against the sire’s red blood cells. The presence of hemolysis or agglutination suggests that NI will develop.4,9

Withhold the mare's colostrum from the foal until it is proven to be safe or gut closure has occurred and macromolecules cannot be absorbed. If NI is a potential problem that may develop from the ingestion of colostrum, then colostrum can be withheld from the foal until a crossmatch is performed between the mare’s serum and the offspring’s RBCs. If agglutination or hemolysis is present, then NI may occur and the mare's colostrum should be withheld from the foal. Passive transfer can still be accomplished by foster feeding the foal provided that the material (colostrum from another mare or plasma) is devoid of antibodies that could result in NI.9 The foal should be foster fed for 2-3 days until gut closure occurs.

Perform a Jaundice Foal Agglutination (JFA) test. This is a field screen test to detect NI. The foal's RBCs are exposed to the mare's colostrum or serum. If the cells agglutinate, then NI may develop. Results of the JFA test have been shown to correlate well with the standard hemolytic assay. The JFA test also may be able to detect antibody that is not identified on the standard agglutination tests. Control tubes are used to ensure that the test has been performed correctly. Positive reactions at 1:16 or greater suggest incompatibility and the risk of NI.1

Equine Neonatal Isoerythrolysis

Howard P. Bouchelle, III, DVM; Perry J. Bain, DVM, PhD; Paula M. Krimer, DVM, DVSc; and Kenneth S. Latimer, DVM, PhD Class of 2003, University of Florida College of Veterinary Medicine, Gainesville FL (Bouchelle) and Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388 (Bain, Krimer, Latimer)


Seizures are relatively uncommon in horses compared with other species. Seizures in foals may be caused by neonatal septicemia, hypoxic ischemic encephalopathy (HIE), metabolic disturbances such as hypoglycemia and electrolyte abnormalities, bacterial meningitis or abscess, viral encephalitis, medications, liver failure, trauma, and congenital anomalies.1 The term epilepsy refers not to a specific disease but to a heterogeneous group of chronic disorders characterized by a tendency to have recurrent seizures without precipitating factors.2 This definition includes those seizure disorders caused by genetically determined primary brain dysfunction (ie, inherited epilepsy) and those that appear to be associated with insults such as brain infections and trauma. Seizures are diagnosed by their clinical manifestations and the diagnosis often is supported by epileptiform events (eg, spikes, sharp waves, and spike-and-wave discharges) on the electroencephalogram (EEG). These discharges may be localized to a small brain area (partial or focal), several sites (multifocal), or may involve large areas of both hemispheres simultaneously (generalized). Extensive descriptions of epilepsy are available in the medical literature. However, in veterinary medicine, information is almost exclusively limited to dogs and cats.3 Epilepsy has been rarely documented in horses. It has been observed in certain lines of Arabian foals, but detailed information is lacking. The present retrospective study describes the clinical presentation, diagnostic features, treatment, outcome, and familial tendency in 22 Arabian foals examined at the Veterinary Medical Teaching Hospital (VMTH) of the University of California at Davis over a 20-year period.

Materials and Methods
Medical records of foals admitted to the VMTH between 1985 and 2005 were reviewed. For inclusion in the study, foals had to be of the Arabian breed, between 1 day and 1 year old, and diagnosed with epilepsy. Information on signalment, history (including onset and duration of clinical signs before presentation), physical examination, diagnostic tests, and treatment was identified in the medical records. Neonatal foals with a clinical diagnosis of septicemia, HIE, or metabolic disorders were excluded. Telephone interviews were conducted with owners and referring veterinarians to obtain information regarding long-term outcome.

Results Twenty-five Arabian foals were admitted to the VMTH for recurrent seizures. Of these, 22 foals met the criteria for inclusion in the study. All 22 foals had a history of multiple generalized or partial seizures of 1 to 60 days duration before presentation. The majority (73%) were presented to the VMTH within 1 day of onset of clinical signs. Sixty-four percent were females. Median age at onset was 2 months (range, 2 days to 6 months). Five of the foals were <1 month of age.

Clinical signs noted at presentation included decreased-to-absent menace response (55%), blindness (50%), and abnormal mentation (disorientation, lethargy, obtundation [15%]). Foals <2 weeks of age were not included in the 55%, because absence of a menace response is normal in this age group. Blindness had been undetected by the owners in 5 foals; in other foals it was noted up to 2 weeks before presentation. One foal was hyperesthetic and had decreased proprioception in all 4 limbs. Seizures were observed at the VMTH in 64% (14/22) of the foals. Pre-ictal signs included behavior alterations (1/14), chewing and salivation (2/14), and hyperesthesia (1/14). However, most foals (9/14) had no obvious pre-ictal signs. The seizures ranged from focal head twitches and nystagmus that progressed to generalized tonic seizures followed by clonic motor activity in 3 foals, whereas 11 had only spontaneous generalized tonic seizures followed by clonic seizures, wide-eyed stare, opisthotonus, trismus, and excessive sweating. The duration of the episodes lasted from a few seconds to 5 minutes; in 12 foals the seizure lasted <1 minute. Seizures could be induced in 2 foals by handling. Nine of 14 foals received a single dose of diazepam IV (5–20 mg) to control the seizures. Three of 14 foals had multiple doses (3–4) of diazepam IV for a total of 25 mg. A 1-month-old filly received midazolam in addition to diazepam to control the episodes. Only 1 filly did not receive any anticonvulsant because she died while obtaining imaging diagnostics. A postmortem examination was not performed on this filly.

The most common postictal signs were blindness (100%) followed by obtundation, lethargy, and disorientation (55%). Other less common postictal signs were hyperesthesia, ataxia, proprioceptive deficits, mydriasis, and salivation. Cutaneous abrasions, scleral injection, decreased gastrointestinal motility, and decreased suckle reflex were observed in one third of the foals. Concurrent diseases were present in 11 of 22 foals and included pneumonia (n  9), corneal ulceration (n3, 1 foal had an enucleation due to complications), uroperitoneum (n  1), umbilical hernia (n 1), ventricular septal defect (n  1), and thrombophlebitis (n  1).

Diagnostic tests performed included a CBC and serum biochemistry (n  21), electroencephalogram (n  13), cisternal cerebrospinal fluid (CSF) tap (n  8), cranial radiographs (n  8), computed tomography (CT, n 5), and magnetic resonance imaging (MRI, n  1). Other diagnostics included thoracic and abdominal radiography, ultrasonography, and cervical radiography. Abnormalities on the CBC included mature neutrophilia (n 3) and hyperfibrinogenemia (n 3). In most cases, these abnormalities were consistent with an inflammatory leukogram attributable to concurrent disease (eg, pneumonia). All other CBC results were within the reference range. The most consistent abnormalities on serum biochemistry were increased creatine kinase (CK, n  15, 863–7,062 U/L; reference range, 119–287 U/L), and glucose (n 4, 143–244 mg/dL; reference range, 80–107 mg/dL). One foal with uroperitoneum had mild metabolic acidosis with hyponatremia, hypochloremia, and hyperkalemia. These electrolytes derangements, however, were not thought to be the inciting cause of the seizures because the abnormalities were mild and the foal had a history of recurrent seizures of several days duration. The organisms isolated from transtracheal washes of the foals with pneumonia included Streptococcus zooepidemicus, S viridans, Actinobacillus, Bacillus spp, Enterococcus, Escherichia coli, Pseudomonas spp, Rhodococcus equi, and mixed growth.

Of 8 foals from which CSF was obtained, 5 had no cytologic abnormalities and 3 had xanthochromia. Radiographs of the cranium (n5) were normal. CT was unremarkable in 3 foals; 1 foal had cerebral edema, and the filly that died had a fracture of the basisphenoid bone and multifocal extradural hematomas thought to be the result of trauma. No abnormalities were observed on the 1 MRI.

Electroencephalography was performed in 13 foals using standard VMTH protocols for electrode placement (Fig 1 Most patients were sedated with α2 agonists, either xylazine or detomidine. Nine EEGs were abnormal but only the 5 most recent recordings were available for review. All figures are illustrated using a transverse bipolar montage. Additional channels for electrocardiography (EKG) and electroculography (EOG) were included. Some form of epileptiform activity consisting of spikes (duration <70 milliseconds), sharp waves (70–200 milliseconds), spike-and-wave discharges, or multiple spike complexes was detected in each of these recordings. With the exception of 1 foal in which rare sharp waves occurred in the parietal parasagittal region, the majority of these events occurred in the central region. Voltage maximum was frequently midline, but at times localized to the left or right indicating that these events were multifocal in some foals. In addition, brief (<2 seconds) bursts of rhythmic theta activity (Fig 2ranging from 4–6 Hz, was a consistent finding, but in 1 foal this activity was replaced by focal 6 Hz spike-and-wave discharges (Fig 3 ). The distribution of this theta activity was typically in the central or parietal region, primarily midline. Quasiperiodic sharp slow waves were noted in 2 of the EEGs (Fig 4 ). Intermittent beta activity was noted in a single EEG (Fig 5Most of the above described paroxysmal activity occurred superimposed on background activity that was high amplitude and low frequency. Normal transients of sleep, such as sleep spindles and K complexes (Fig 6 ) often were present, indicating a state of non–rapid eye movement (REM) sleep. Periods of drowsiness and arousal were also recorded in each patient. REM sleep was recorded in 1 foal and included intermittent paroxysmal discharges (Fig 7Photic stimulation, using frequencies between 2 and 30 Hz both individually and with a period of crescendo and decrescendo, was performed in 2 foals. In both patients, an increase in the number and duration of spindles (with a frequency of 10–12 Hz) was associated with 10 Hz stimulation (Fig 8 ), but no driving response or epileptiform activity was provoked.

The dosage of phenobarbital used was variable. It was difficult to determine mg/kg dosages in some instances because body weights were not consistently recorded. The reported loading dosage was 2 to 13 mg/kg (mean dosage of 8 mg/kg) of body weight followed by adjusted PO doses every 12 hours according to effect and serum phenobarbital concentrations. Trough concentrations were 6 to 43 µg/mL with a mean of 26 µg/mL. Potassium bromide (KBr) was used in 3 of 20 foals in addition to phenobarbital. The loading dosage of KBr was 150 and 100 mg/kg in 2 and 1 foal, respectively, followed by a maintenance dosage of 25 mg/kg PO q24h. The dosage of phenobarbital in these foals was not adjusted when KBr was added. Other treatments included supportive therapy with fluids, vitamin E, selenium, antibiotics, and anti-inflammatory drugs (eg, flunixin meglumine) for foals with concurrent diseases.

Telephone interviews were performed for all foals that were discharged from the VMTH (n). Owners reported that all 21 foals recovered uneventfully. The duration of treatment ranged from 2.5 to 9 months. While on treatment at home, only 1 foal had 2 mild seizures. Upon discontinuation of the antiepileptic drugs, the foals were not observed to have seizures and did not require additional treatment. All foals were of Egyptian lineage. Four of the owners reported that they had owned other affected foals in the past. Two clients were aware of the condition and only brought the foal that was having frequent seizures. The other 2 owners thought their foals were experiencing colic. One of these clients brought the foal to the VMTH because it appeared blind. In addition, 2 pairs of foals from different farms had the same dam (different mare for each pair). Upon additional questioning, it appeared that both mares had epileptic episodes when they were a few months old, which resolved by 1 year of age with no treatment. The sire of 1 of the previous foals had a seizure and went blind for a month when it was a few months old but then recovered.

The International League Against Epilepsy (ILAE) classifies epilepsy in humans as generalized, localization-related (eg, focal, partial), and unclassified.4 These were further subdivided into idiopathic (primary) and symptomatic or cryptogenic (secondary). The idiopathic epilepsies in humans have no specific cause and are thought to be associated with a genetic etiology, normal brain, early onset (childhood or adolescence), and good antiepileptic drug (AED) response with a favorable prognosis. The symptomatic epilepsies on the other hand have a known cause that involves brain pathology, onset at any age, and variable response to treatment and variable prognosis. In cryptogenic epilepsies, the etiology cannot be identified. The benefits of classifying epileptic events are numerous, among them the potential to perform clinical and research studies of specific epileptic disorders worldwide, provide appropriate AED choices, and establish a prognosis. In veterinary medicine, epilepsy classification has been attempted in dogs.3,5 Although there are numerous case reports of known causes of seizures in horses, there is limited information regarding idiopathic epilepsy (IE).6,7

IE is a diagnosis of exclusion and a genetic origin is suspected. There have been major advances in understanding the genetic basis of monogenic or Mendelian IE in humans. However, there has been slower progress in understanding the more common familial IEs that manifest themselves as complex non-Mendelian traits.8 Many of the monogenic IEs are ion voltage-mediated (eg, sodium, potassium) and receptor-mediated (eg, gamma-aminobutyric acid [GABA], nicotinic, acetylcholine) channelopathies.9 In the foals of this report, other potential causes of epilepsy were ruled out. The signalment (Egyptian Arabian foals), history including familial predisposition, and unremarkable physical examination, laboratory and imaging findings supported the diagnosis of IE. There is only 1 report that described epilepsy in horses under 2 years of age from a purebred Arabian farm of Egyptian lineage.7 The author used the term “juvenile idiopathic epilepsy” as the affected horses ranged from 18 days to 18 months of age. The age of onset of clinical signs in our foals was 2 days to 6 months, with the majority having the first seizure within the first 2 months of life. Pre-ictal signs are not always observed. Mittel observed that seizures lasted between 10 to 45 seconds and could be induced by handling or were spontaneous. Clinically, the seizures in these foals were characterized by generalized tonic seizures followed by clonic seizures that lasted few seconds to 5 minutes. Inducible seizures were observed in 2 foals. Postictal signs were similar in both studies, with blindness being the most consistent finding. However, Mittel reported that blindness lasted up to 3 minutes, except for 1 foal in which it persisted 7 days, whereas in our foals blindness lasted a few minutes to 3 weeks. With the exception of blindness, the neurologic status between seizures was normal in the foals from both studies. In addition, several foals sustained abrasions and contusions as a consequence of seizure-induced trauma that in 1 foal resulted in death. Trauma is an important factor in the management of affected foals. They should have headgear in place, padded stalls, and deep bedding until the seizures are well controlled with anticonvulsants. Pneumonia was the most common concurrent disease in these foals. Pneumonia could have been a coincidental finding because many of these foals came from farms where respiratory diseases may have occurred, or it may have been the result of aspiration caused by an unrecognized decreased or weak swallowing reflex as a postictal event. Affected foals should be restricted from nursing or eating until the postictal phase is over. Such foals therefore would require appropriate supportive care to provide for nutritional and hydration needs.

The initial response to AED was favorable for most foals in our study. The wide range of AED dosage prescribed for affected foals indicates that each foal must be treated as an individual in terms of dosage used. Dosages of diazepam used to control seizures in horses range from 0.01 to 0.4 mg/kg and are given once intravenously.10 Diazepam clearance is longer in foals younger than 21 days old, and caution must be taken to avoid drug accumulation if repeated doses are required.11 Diazepam has a rapid onset of action and short duration (10–15 minutes) and therefore is a good drug to manage emergency situations or infrequent seizures. However, diazepam is not a good choice for long-term control of seizures. Studies on constant rate infusion (CRI) of diazepam in horses with seizures are lacking. In addition, CRI must be undertaken in intensive care units with trained personnel. Midazolam also is being used more frequently in equine neonates. Midazolam has anxiolytic and sedative effects, is rapidly absorbed and distributed, and has few adverse effects, making it ideal for use in children undergoing medical procedures or anesthesia.12,13

Phenobarbital has been the drug of choice to manage long-term seizures in horses. The recommended loading dosage of phenobarbital in horses ranges from 12 to 20 mg/kg IV, diluted in 1 L of saline or dextrose and administered over a 30 minute period, followed by 6 to 12 mg/kg PO q12h.14,15 The half-life of phenobarbital in the horse ranges from 6.5 to 17.3 hours.16 Therapeutic concentrations of phenobarbital in humans range from 15 to 40 µg/mL. Therapeutic concentrations for horses are unknown. Phenobarbital concentrations should be considered therapeutic on an individual basis when seizures are controlled without compromising the normal functioning of the patient (eg, excessive sedation) and not necessarily the need to reach a fixed reported therapeutic concentration. Proposed duration of AED therapy in horses has been a minimum of 6 months of fully controlled seizures at which time the patient can be slowly weaned off the drug. One suggested weaning schedule is to decrease the dosage by 20% every 2 weeks.17 There is little information available concerning adverse effects of phenobarbital in horses other than somnolence and increases in gamma glutamyl transferase activity.18,19

KBr is another AED used in humans, dogs and horses. Currently, there are 2 pharmacokinetic studies on the use of bromide in horses.20,21 The study by Fielding determined that the elimination half-life of a single IV administration of sodium bromide at a dosage of 30 mg/kg is shorter in the horse (approximately 5 days) compared with other species (9.4, 14, and 37 days in humans, cows, and dogs, respectively).22–24 From this study, a dosage of 34 mg/kg/d of IV NaBr would be required to maintain a steady state concentration of 1,000 mg/L,20 which is within the therapeutic range of 880–3,000 mg/L in epileptic dogs when KBr is the only AED used.25 In the second study, loading doses of KBr at 120 mg/kg PO daily over 5 days and maintenance doses of 90 mg/kg of KBr administered PO once daily resulted in serum bromide concentrations within the therapeutic range for seizure management in other species.21 However, extrapolations from other species may not apply to the horse as already evidenced by differences in elimination half-life. Proposed dosages of KBr in the horse are 25 mg/kg PO q24h with 20% increases or decreases as needed every 2 weeks.17 KBr was used in 3 foals in which seizures were multiple, frequent, and difficult to manage with phenobarbital. Bromoderma tuberosum, acneiform papules, tetraparesis, tetra-ataxia, and pancreatitis are some examples of bromide toxicity in other species.26–28 KBr is absorbed through intact skin, and clients must be instructed to wear gloves during administration. Potassium bromide is not metabolized in the liver, making it safe for use in patients with hepatopathies. Other AEDs that have been used in foals are phenytoin, primidone, and pentobarbital.1,7

In human medicine, the diagnosis of epilepsy is made primarily on clinical grounds. EEG can contribute to the diagnostic refinement and overall management of patients with epilepsy.29 On the other hand, the interictal EEG cannot diagnose epilepsy, exclude it, or predict the likelihood for seizure relapse once therapy is discontinued. However, EEG examinations revealing persistent paroxysmal activity are useful in that they indicate that therapy should not be discontinued. Various epileptic syndromes have been classified according to EEG findings in humans.29 Determination of the specific type of epilepsy is important when choosing an appropriate AED, because some AEDs may be harmful or not useful. Unfortunately, very little information on equine EEG is available, particularly in young horses. Mysinger et al did serial studies on 6 normal foals between 3 and 200 days of age.30 Using Redding's technique for electrode placement, he described a high-voltage, low-frequency pattern early on that matured into a low-voltage, high-frequency pattern with age.31 Spindle activity was detected in a few recordings. One of the figures, taken from a 5-day-old foal, reveals a brief burst of rhythmic 4.5 Hz theta activity that appears to be voltage maximal near the vertex. Thus, the presence of this particular activity in our epileptic animals may be a normal finding. In people, bursts of fast beta activity are associated with the use of certain drugs such as barbiturates and benzodiazepines. Their presence in a single recording was attributed to administration of midazolam for seizure control in 1 foal. Spike-and-wave discharges (singly or in complexes), spikes, multiple spike complexes, and sharp waves are paroxysmal events associated with a diagnosis of epilepsy in humans. Our EEG findings suggest a focal onset of seizures in these foals. Additional EEG studies are indicated in both normal and affected horses. Blindness is an uncommon phenomenon of epileptic disorders in humans, and it may occur in the pre-ictal, ictal, or postictal phase.32 Ictal cortical blindness may be a sole epileptic phenomenon or accompanied by alterations in consciousness or motor impairment that can last for minutes up to days as occurred in the foals of this study.32

Based on owners' information (ie, related affected horses), breed and lineage, and age at onset of epilepsy (with no identifiable cause), we concurred with Mittel's term “juvenile idiopathic epilepsy” for this syndrome in Arabian foals of Egyptian lineage.7 This syndrome has an early onset of clinical signs (days to months of life) but appears to be self-limiting, disappearing by 1 to 2 years of age. The condition has no sex predilection and is clinically characterized by recurrent generalized seizures that are manageable with commonly used AEDs. Blindness, disorientation, and evidence of trauma in Arabian foals should prompt investigation of seizures. clinicopathologic data and imaging studies in affected patients are normal if no concurrent diseases or complications develop. The long-term prognosis is good with no apparent permanent sequela. The potential for concurrent diseases and secondary trauma should be considered in affected foals. Other causes of epilepsy should be ruled out, even in young Arabian horses, and it should not immediately be assumed that the patient has IE solely based on breed and lineage. Clinical, pedigree, and genetic analyses of IE in Arabian horses are needed.

The authors thank Dr Barry Tharp from the Department of Neurology at UCDMC for reviewing the manuscript and EEG records; and Mr John Doval from the Department of Veterinary Surgery and Radiology, Media Lab, University of California Davis for technical support.

Bernard W.V. Jump-starting the dummy foal (neonatal maladjustment syndrome/hypoxic ischemic encephalopathy). Proceedings of the 49th Annual Convention. New Orleans, LA American Association of Equine Practitioners (AAEP) 2003. November.
Sengoku A. The contribution of J.H. Jackson to present-day epileptology. Epilepsia. 2002. 43:6–8. Find this article online
Berendt M., and Gram L. Epilepsy and seizure classification in 63 dogs: A reappraisal of veterinary epilepsy terminology. J Vet Intern Med. 1998. 13:414–420. Find this article online
ILAE. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989. 30:389–399. Find this article online
Podell M., Fenner W.R., and Powers J.D. Seizure classification in dogs from a nonreferral-based population. J Am Vet Med Assoc. 1995. 206:1721–1728. Find this article online
Sweeney C., and Hanson T. Narcolepsy and epilepsy. In: N.E. Robinson, ed Current Therapy in Equine Medicine 2. Philadelphia, PA WB Saunders 1987. 349–353.
Mittel L. Seizures in the horse. Vet Clin North Am Equine Pract. 1987. 3:323–332. Find this article online
Gardiner M. Genetics of idiopathic generalized epilepsies. Epilepsia. 2005. 46:15–20 Suppl. Find this article online
Mulley J.C., Scheffer I.E., Petrou S., and Berkovic S.F. Channelopathies as a genetic cause of epilepsy. Curr Opin Neurol. 2003. 16:171–176. Find this article online
Furr M.O. Seizure disorders. Proceedings of the 15th Annual Veterinary Forum. Lake Buena Vista, FL American College of Veterinary Internal Medicine (ACVIM) 1997. March.
Norman W.M., Court M.H., and Greenblatt D.J. Age-related changes in the pharmacokinetic disposition of diazepam in foals. Am J Vet Res. 1997. 58:878–880. Find this article online
Karl H.W., Rosenberg J.L., Larach M.G., and Ruffle J.M. Transmucosal administration of midazolam for premedication of pediatric patients. Anesthesiology. 1993. 78:885–891. Find this article online
Geldner G., Hubmann M., Knoll R., and Jacobi K. Comparison between 3 transmucosal routes of administration of midazolam in children. Paediatr Anaesth. 1997. 7:103–109. Find this article online
Furr M.O. Managing seizure disorders in neonatal foals. Vet Med. 1996. 8:770–778. Find this article online
Ravis W.R., Duran S.H., Pedersoli W.M., and Schumacher J. A pharmacokinetic study of phenobarbital in mature horses after oral dosing. J Vet Pharmacol Ther. 1987. 10:283–289. Find this article online
Reimer J.M., and Sweeney R.W. Pharmacokinetics of phenobarbital after repeated oral administration in normal horses. J Vet Pharmacol Ther. 1992. 15:301–304. Find this article online
Mayhew I.G. When should I start anticonvulsant therapy for a mature epileptic horse, and what medication should I use?Compendium on Continuing Education for the Practicing Veterinarian: Equine. 1998. June:744–745. Find this article online
Spehar A.M., Hill M.R., Mayhew I.G., and Hendeles L. Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal. Equine Vet J. 1984. 16:368–371. Find this article online
Knox D.A., Ravis W.R., and Pedersoli W.M. et al. Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug. Am J Vet Res. 1992. 53:706–710. Find this article online
Fielding C.L., Magdesian K.G., and Elliot D.A. et al. Pharmacokinetics and clinical utility of sodium bromide (NaBr) as an estimator of extracellular fluid volume in horses. J Vet Intern Med. 2003. 17:213–217. Find this article online
Raidal S.L., and Edwards S. Pharmacokinetics of potassium bromide in adult horses. Aust Vet J. 2005. 83:425–430. Find this article online
Vaiseman N., Koren G., and Percharz P. Pharmacokinetics of oral and intravenous bromide in normal volunteers. J Toxicol Clin Toxicol. 1986. 24:403–413. Find this article online
Ward G.M., Argenzio R.H., and Johnson J.E., and International Atomic Energy Agency, ed. Evaluation of 82Br as an extracellular water tracer in ruminants. In: Isotope Studies on the Physiology of Domestic Animals. Vienna, Austria IAEA 1972. 73–80.
Trepanier L.A., and Babish J.G. Pharmacokinetic properties of bromide in dogs after the intravenous and oral administration of single doses. Res Vet Sci. 1995. 58:248–251. Find this article online
Trepanier L.A., Van Schoick A., Schwark W.S., and Carrillo J. Therapeutic serum drug concentrations in epileptic dogs treated with potassium bromide alone or in combination with other anticonvulsants: 122 cases (1992–1996). J Am Vet Med Assoc. 1998. 213:1449–1453. Find this article online
Dreifuss F.E., and Bertram D.H. Bromide therapy for intractable seizures. Epilepsia. 1986. 27:593. Find this article online
Anzai S., Sakuhei Fujiwara., and Inuzuka M. Bromoderma. Int J Dermatol. 2003. 42:370–371. Find this article online
March P.A., Podell M., and Sams R.A. Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles. J Vet Pharmacol Therap. 2002. 25:425–432. Find this article online
Koutroumanidis M., and Smith S. Use and abuse of EEG in the diagnosis of idiopathic generalized epilepsies. Epilepsia. 2005. 46:96–107 Suppl. Find this article online
Mysinger P.W., Redding R.W., and Vaughan J.T. et al. Electroencephalographic patterns in clinically normal, sedated, and tranquilized newborn foals and adult horses. Am J Vet Res. 1985. 46:36–41. Find this article online
Redding R.W. A simple technique for obtaining an electroencephalogram of the dog. Am J Vet Res. 1964. 65:854–861. Find this article online
Shahar E., Desatnik H., and Brand N. et al. Epileptic blindness in children: A localizing sign of various epileptic disorders. Clin Neurol Neurosurg. 1996. 98:237–241. Find this article online
Website Designed by Cath copyright 2012
SC Desert Star Arabians