Neonatal Seizures

While seizures are uncommon in adult horses, the foal may seizure associated with a variety of problems. Prompt therapy to stop the seizure in progress, providing therapy to raise the seizure threshold, and attempting to determine the cause is the appropriate management protocol.

I. Signs and Symptoms

1. Subtle signs are blinking, staring, unaware of environment, lip smacking, drooling, abdominal breathing patterns.
2. Generalized convulsions or seizures seen as violent, involuntary muscle movements, opisthotonus, limb paddling and extensor rigidity.

II. Differential Diagnosis

1. Apnea - Usually secondary symptom of trauma, birth asphyxia, encephalitis, overwhelming infection, prematurity or mechanical airway obstruction.
2. Hypocalcemia: Documented case in an equine neonate associated with very low serum calcium (< 6.0 mg/dl) and seizures.
3. Terminal stages of acute overwhelming conditions.

III. Causes [1]

1. Hypoxia: associated with asphyxia.
2. Cranial Trauma [2,3]

1. Cerebral syndrome consists of blindness, depression, wandering toward the side of the lesion.
2. Midbrain syndrome

1. Hemorrhage or compression secondary to cerebral edema.
2. Depression, sluggish pupil response, strabismus, nystagmus, ataxia or extensor rigidity.

3. Brainstem - Trauma to poll.

1. Fracture of occipital and petrosal bones.
2. Cranial nerves damaged - Head tilt, facial nerve damage.
3. Optic nerve dysfunction, nystagmus, depression.
4. Dilated or non-responsive pupils associated with poor prognosis.

3. Metabolic

1. Electrolyte abnormality - Hypocalcemia as a cause in 1 foal. Mg++, Na+ abnormalities associated in infants.
2. Hypoglycemia - Paddling, recumbency, loss of cranial nerve function, blindness. Can cause permanent neuron cell death if prolonged.
3. Lysosomal storage disease in a foal with seizures.

4. Infection [3]

1. Seizures can occur as a symptom associated with septicemia without meningitis
2. Bacterial meningoencephalitis [3]

1. Organisms cultured from CSF of foals include E. coli, Klebsiella, Streptococcus, Staphylococcus aureus, Actinobacillus.

3. Viral - Congenital and acquired.

5. Idiopathic epilepsy of Arabian foals [4]

1. Starts at weanling age and can often be controlled with medication.

6. Neonatal maladjustment syndrome (See Neonatal Maladjustment Syndrome)
7. Congenital anomalies [5]

1. Dandy-Walker Syndrome with corpus callosum missing.
2. Confirm with contrast CT or MRI.

IV. Evaluation

1. History of foaling events to determine possible birth asphyxia or stress.
2. Physical exam, complete blood count with differential.
3. Serum measurements of glucose, calcium, sodium, magnesium, bicarbonate, creatinine and ammonia.
4. Arterial blood gases to determine any hypoxemia and acid-base disturbance.
5. Lumbar puncture to analyze CSF for protein, WBC, glucose levels and bacterial or viral culture. See section on CSF tap methods and interpretation.
6. CT scan, if available and problem is severe, recurrent, and non-responsive.
7. Skull radiographs if suspect direct trauma.
8. Electroencephalogram (EEG).

1. Abnormalities seen in idiopathic epilepsy of Arabians [4]
2. May document cause as primary neurologic origin.
3. May be performed standing with xylazine butorphanol sedation in some foals.

V. Treatment [1]

1. Correct primary cause if possible.
2. Maintain patent airway and administer oxygen if indicated.
3. Avoid cerebral edema - Brain herniation from cerebral edema associated with equine neonatal seizures has occurred.

1. Restrict IV fluids unless severely hypovolemic.
2. Correct decreased serum Na+ if present.
3. IV DMSO (non-label use, inform clients), administer 1 gm/kg in 20% solution (Domoso-Diamond) - Slowly I.V. [for 50 kg foal using 90% DMSO (mix 55 cc DMSO in 1 liter of 5% dextrose) give once daily for 34 days].
4. If suspect possible increased intracranial pressure opisthotonus, anisocoria, deep abdominal breathing: Give mannitol I.V. 0.25 gm/kg slowly up to q2hrs.

4. Correct metabolic imbalances

1. Glucose - In the absence of any availability of blood chemistries - Administer 5-10% dextrose 50 cc rapidly IV and 200-300 ml for next hour of glucose containing fluid (1% or 2.5% solution) and observe for improvement. If serum glucose documented to be low (<40 mg/dl; 2.2 mmol/l) give 10% dextrose I.V. (add 100 ml of 50% dextrose to 400 ml sterile water) at 120 ml/hr/50 kg. Monitor for increases in serum glucose.
2. Calcium, 2 ml/kg of 23% calcium gluconate slowly IV -over 30 minutes monitor heart rate for bradycardia or arrhythmia - Use with caution - Cardiac arrhythmias can develop.
3. Acid-base and electrolytes.

5. Use antibiotic therapy if infection present.

1. Seizures associated with septicemia not uncommon. Does not necessarily indicate meningitis or brain infection.
2. I.V. Penicillin with gentamicin or amikacin does not penetrate non-inflamed CNS.
3. If CSF tap indicates infection (bacteria on GM stain, protein >150 mg/dl and WBC > 6/ul with neutrophils) use antibiotic which penetrates CNS.

1. Trimethroprim-Sulfa - 5 mg/kg (based on trimethroprim content) given IV TID; however, very limited spectrum for organisms implicated.
2. Cefotaxime, ceftazidime, cefquinom, cefepime (3rd and 4th generation) cephalosporins reach a high concentration in the CNS, and have wide spectrum activity.
3. Chloramphenicol - Lipophilic penetrates most tissues.
4. Other antibiotics such as Penicillin G and ampicillin may cross into CNS when meninges inflamed.

6. Monitor body temperature - Prevent hyperthermia or hypothermia.
7. Anticonvulsant Therapy

1. Stopping seizure in progress.

1. Diazepam (Valium) - Give 5-15 mg slowly I.V. take several minutes before increasing at 5 mg increments; has short half-life and may need to be repeated.
2. Midazolam - 0.1 to 0.2 mg/kg for seizures or sedation - It has some advantages over diazepam: accumulate less due to water solubility, found to be more effective and safer in human neonates. It can be used as a CRI for seizuring foals because it does not accumulate to the same degree as diazepam. It is cardiovascularly safer than phenobarbital, plus can be discontinued any time. It can be used at a dose of 0.04-0.16 mg/kg/h with good success for as long as 48-72 hr.
3. Phenobarbital for prolonged and recurrent seizure
       i. Anesthesia and respiratory depression can occur at doses of 20-30 mg/kg.
4. Bromide (potassium or sodium salt) used in combination with phenobarbital to aid refractive seizures - Recommended dose 20-40 mg/kg, PO, sid, or bid in divided doses (potassium salt) or 17-30 mg/kg PO, sid or bid in divided doses (sodium salt). Bromide is generally well tolerated but side effects include gastric irritation, polyuria, sedation, ataxia. Bromide toxicosis (bromism) is characterized by neurologic signs of lethargy, disorientation, delirium, and ataxia. Bromide should not be used with renal dysfunction. Bromide intoxication should be treated with an IV infusion of normal saline to promote renal excretion.
5. Xylazine or phenothiazine tranquilizers are contraindicated since they decrease the seizure threshold.

2. Prevention - Goal is to increase seizure threshold.

1. Recommended if more than 1 seizure/day has occurred.
2. Phenobarbital
       i. Loading dose - 20 mg/kg diluted in 30 ml saline and given IV over 30 minutes.
       Editor's Comment - This dose causes severe depression.
       ii. Maintenance dose 2-9 mg/kg TID IM or IV.
       Editor's Comment - May be adequate without loading dose.
       iii. Determine blood levels - Therapeutic range 15-40 ug/ml in humans.
3. Primidone has been used in foals at 2 gm/50kg orally initially and maintenance at 0.75 gm/50kg BID orally [7]
4. Always wean off therapy over several weeks by gradually lowering the daily dose. Abrupt withdrawal may produce seizures.

VI. Prognosis

1. Neonatal maladjustment syndrome when not associated with infectious process has a good survival rate [8]
2. Associated w/septicemia - Nowadays survival rates are as high as 60-80% in advanced NICU settings.
3. Associated w/hypoglycemia - Dependent on underlying cause of hypoglycemia.
4. Trauma - Observe for trends [2,3]

1. Improvement in mentation and cranial nerves favorable sign.
2. Progressive loss of cranial nerves -poor prognosis.
3. Miotic pupils initially and then become dilated and non-responsive - Poor prognosis.
4. Coma for 36 hrs - Prognosis very poor.