Other Neurologic Conditions
Guy D. Lester
Bacterial meningitis should be suspected in a foal with neurologic disease and recent or current signs of generalized or localized sepsis. Agents causing meningitis are the same that cause systemic sepsis, most commonly bacteria such as Escherichia coli, Enterobacter spp., Salmonella spp., and Streptococcal spp.∞,1uu,194,26u Signs can include hyperesthesia, neck rigidity, varying degrees of obtundation, seizure activity, opisthotonus, limb ataxia and paresis, or specific cranial nerve abnormalities.25 The definitive diagnosis is dependent on CSF analysis, which reveals a pronounced neutrophilic pleocytosis.
Hematology and serum biochemistry reflect sepsis, and the serum IgG concentration often reflects failure of passive transfer.Antibiotic treatment should be guided by culture and sensitivity data. Successful treatment has been reported using courses of broad-spectrum third-generation cephalosporins.100 These include cefotaxime or ceftriaxone because of their excellent penetration into the central nervous system. Alternatives include ceftiofur, trimethoprim-sulfa combinations, chloramphenicol, or a combination of aminoglycoside with a β-lactam antibiotic. On the basis of data from human infants, one author has recommended the use of dexamethasone sodium phosphate (0.4 mg/kg IV q12h for 2 days).25 In many cases, once the diagnosis is made, the infectious process is well advanced both in the brain and other tissues, resulting in a poor outcome. The prognosis is fair in foals where signs are limited to hyperesthesia and neck stiffness.25
Neonatal morbidity and mortality can be attributed to equine herpesvirus 1 (EHV-1), EHV-4, equine viral arteritis (EVA), and equine influenza (EI) viruses. The respiratory system is most commonly involved.
Viral encephalitis is often quoted as an important differential for seizures in neonatal foals, but this appears to be a rare clinical entity in this age group.Head trauma occurs commonly in neonates. Foals can receive direct blows to the head after kicks from the dam or other horses, as well as from head-on collisions with stationary objects. There is often external evidence of the trauma, such as hair loss, soft tissue swelling, asymmetry of the facial contour, fracture crepitus, or blood from the nares or ear canal. A range of neurologic signs may ensue that include varying degrees of obtundation; disorientation; head pressing; compulsive walking, often in circles; and seizure. Trauma to the poll can result in vestibular and facial nerve dysfunction, ataxia, and paresis, as well as changes in mentation. The diagnosis is based on history and physical and neurologic findings but is supported by imaging. The management of CNS trauma is discussed elsewhere in this text (Chapter 35).
Benign juvenile epilepsy is a well-described neurologic entity of Arabian foals of Egyptian origin.261 The age of onset of generalized seizures varies between 2 days and 6 months of age, and the reported duration of seizures is between several seconds and 5 minutes, with most lasting less than 60 seconds. Common postictal findings include obtundation and transient blindness. Physical and neurologic examination during the interictal period is normal, but there may be electroencephalographic changes.261 As the name suggests, the condition does not persist into adulthood, with cessation seizures by 12 months of age in all foals. As described earlier, active seizures can be treated with diazepam or midazolam and prevented using oral phenobarbital (5 to 10 mg/kg PO as loading dose, followed by 2 to 5 mg/kg PO bid) or potassium bromide (100 mg/kg PO as loading dose, followed by 25 mg/kg PO q24h). Investigation of a small number of Egyptian Arabian foals with juvenile idiopathic epilepsy did not identify a link to the lavender foal syndrome (LFS) genetic mutation (see later).262
The role of glucose and electrolytes in seizure disorders should not be discounted.
Hypoglycemia, hypocalcemia, hyponatremia, or hypernatremia can all produce signs of spontaneous, involuntary muscle activity with varying degrees of consciousness. Hypoglycemia is the most common metabolic derangement in newborn foals. The response of the nervous system to low glucose is categorized as neurogenic or neu- roglycopenic.263 Neurogenic signs are related to sympathetic discharge and include tremor, tachypnea, and irritability, whereas neuroglycopenic signs relate to impaired brain energy metabolism and include reduced level of consciousness, reduced or absent sucking, hypotonia, and seizure.263 Specific electrolyte disturbances are discussed elsewhere in this text (Chapters 22, 32, and 44).Hydrocephalus is the most common congenital brain disease in foals. Distention of the cerebral ventricular system produces a loss of normal cerebral structure. It can also occur secondary to inflammatory changes associated with meningitis.25 Although pronounced doming of the skull is expected, it is relatively uncommon. Furthermore, a domed head is a physical feature of immaturity seen in premature or dysmature foals. Although signs are variable, most foals are slow and somnolent and can have additional cerebral signs of head pressing, aimless and compulsive walking, blindness, and seizure activity. The diagnosis is usually based on persistence of neurologic signs and ruling out other causes of cerebral disease. The diagnosis is confirmed using CT or MRI. Dandy Walker-like syndrome has been reported as a cause of recurrent violent seizures in a newborn foal.196 The condition involves agenesis of the corpus callosum with cerebellar vermian hypoplasia.
Tetanus is caused by the exotoxins produced by the anaerobe Clostridium tetani. Given the incubation period, clinical cases of tetanus are not likely before 7 days of age. Early signs include difficulty in locating and latching onto the teat and dysphagia. Signs then progress to include gait stiffness, elevation of the tail head, an anxious facial expression, prolapse of the third eyelid, tachycardia, and sweating.
The foal will eventually become recumbent with recurrent bouts of tonic muscle contractions, which are severe enough to mimic seizure activity. Foals are at risk of disease if the mare has not been adequately protected through vaccination or the foal has untreated failure of passive transfer of immunity. It is recommended that mares receive a booster of tetanus toxoid 28 days before the estimated parturition date. Tetanus is discussed in great detail in Chapter 35.Ivermectin and moxidectin toxicity have been described in neonatal and older foals after overdosage.264-266 Reported signs of ivermectin toxicity can include obtundation, blindness, ataxia, head pressing, and seizure and are caused by opening of GABA-gated chloride channels with resultant membrane hyperpolarization and blockade of neuronal impulses. The related antiparasite drug, moxidectin, can also cause profound obtundation and coma when overdosed in juvenile animals.267,268 Successful management of ivermectin toxicosis has included the use of intravenous lipid emulsions (20% soybean oil in water, 1.5 mL/kg IV bolus followed by 0.25 mL/kg/min for 30 minutes).264 The benzodiazepine receptor antagonist, sarmazenil (0.04 mg/kg IV q2h), has been effective in managing moxidectin toxicosis.268
Kernicterus is a rare but serious neurologic complication of neonatal isoerythrolysis (NI).269,270 The condition is also known as bilirubin encephalopathy or nuclear jaundice and results from deposition of bilirubin-IX α in the brain, primarily within the basal ganglia, cornua ammonis and substantia nigra, but also in the cortex, hypothalamus, cerebellum, and medulla.271 Bilirubin-IX α is lipid soluble and readily crosses the blood-brain barrier. The mucous membranes of affected foals are deeply icteric, and neurologic signs include altered mentation and seizures. The seizures are difficult to control, often necessitating euthanasia. In a retrospective study of 72 foals with NI, the heart rate at admission and maximum serum bilirubin concentration were significant factors in the development of kernicterus.270 The authors determined that foals with serum bilirubin concentration greater than or equal to 27.0 mg/dL (≥466.1 μmol∕L) were 17 times more likely to develop signs of kernicterus than foals with a peak bilirubin concentration less than 27.0 mg/dL.
Tin-mesoporphyrin is an inhibitor of heme oxygenase and is a recommended therapy for severe hyperbilirubinemia in human infants. The intramuscular therapy has been used in foals with NI at risk for kernicterus. The antibiotic minocycline and the hypolipidemic drug clo- fibrate have had positive effects in certain experimental models and in human neonates with hyperbilirubinemia271,274 but have not been evaluated for this purpose in foals.LFS, also referred to as coat color dilution lethal (CCDL), is an autosomal recessive gene disorder of Arabian foals of Egyptian bloodlines. The disorder is caused by a frameshift single base mutation in exon 30 of the myosin-Va gene (MYO5A), resulting in premature termination of transcription. Disruption to the myosin-Va protein is thought to affect trafficking of melanosome to the cell periphery in melanocytes and transport of glutamate receptors and secretory granules in neurons.275-278 Affected foals have a dilute coat color and are unable to achieve sternal recumbency. Severe neurologic signs include frequent episodes of opisthotonus, limb paddling, and rapid eye movements. Spontaneous death or euthanasia typically occurs before 72 hours of age. The carrier frequency of LFS in the United States is 10.3% in Egyptian Arabians and 1.8% in non-Egyptian Arabians. The disease occurs in homozygous foals, although neurologic dysfunction without coat color changes has been suspected in heterozygotes.
Glycogen storage disease IV is an autosomal recessive disease of Quarter Horses and Paint Horse breeds. The defect has been identified as a mutation in the glycogen branching enzyme, encoded by the GBE1 gene. Clinical signs of foals not stillborn or aborted include profound muscular weakness and hypothermia. Foals may succumb to hypoglycemic seizures or cardiopulmonary failure. All affected foals have reportedly died or been euthanized by 18 weeks of age.279