Clinical Commentary Congenital Malformations - Uncommon but Important Causes of Neurological Signs in Neonates A

EQUINE VETERINARY EDUCATION / AE / december 2010 599

Clinical Commentary Congenital malformations - uncommon but important causes of neurological signs in neonates A. L. Johnson School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.

When presented with a neonatal foal displaying dystocia or failure of the foal to achieve normal neurological signs, the clinician must act quickly to stabilise developmental steps such as standing unassisted and the patient and determine the aetiology of the nursing. If the placenta is available, it should be examined neurological disease. Otherwise, the disease may quickly for evidence of placentitis or failure of the cervical star to become life-threatening. The most likely disease processes rupture. Careful examination of the foal may provide to cause neurological disease in foals include metabolic evidence for prematurity, peripartum asphyxia or sepsis. derangements, infection, trauma and congenital History or evidence of neonatal isoerythrolysis should raise anomalies. As quite discrepant disease processes can concerns for kernicterus or bilirubin encephalopathy manifest very similar signs requiring urgent treatment, (Loynachan et al. 2007). Breed should also be taken into clinicians are often forced to institute treatment prior to account; Arabian foals of Egyptian breeding may have definitive diagnosis. juvenile idiopathic epilepsy (Aleman et al. 2006) or In the previous case report of hydranencephaly in a lavender foal syndrome, which causes episodic tetany foal (Baiker et al. 2010), the authors were presented with a that resembles seizures (Fanelli 2005; Page et al. 2006). neonatal foal displaying seizure activity. In these situations, Quarter Horse foals may have seizures secondary to the clinician’s immediate goal is to stop the seizure activity glycogen-branching enzyme deficiency (Valberg et al. and quickly correct any haematological and biochemical 2001). abnormalities that may be responsible. Benzodiazepines In the author’s experience, seizures and other such as diazepam are usually effective at stopping neurological signs in neonatal foals are most commonly seizures, although refractory cases may require the the sequelae of peripartum events that result in abnormal addition of phenobarbital or other anticonvulsant function of the neonatal brain. The resulting disease medications. In conjunction with treating the seizures, the syndrome is known by several different names, clinician should obtain blood samples for prompt including ‘dummy foal’ syndrome, equine neonatal determination of blood glucose and electrolyte levels. maladjustment syndrome, hypoxic-ischaemic encephalo- Hypoglycaemia is commonly documented in neurological pathy, peripartum asphyxia syndrome and neonatal neonates and immediate administration of encephalopathy. Current evidence suggests that this dextrose-containing i.v. fluids is generally recommended. syndrome is likely mediated not just by hypoxic-ischaemic Electrolyte derangements such as hyponatraemia, insults but by maternal or fetal inflammatory response hypernatraemia, or hypocalcaemia may affect the syndromes that contribute to septic encephalopathy nervous system and precipitate seizures or seizure-like (Palmer 2008). Signs of disease range from mild activity (Lakritz et al. 1992; Beyer et al. 1997). If detected, neurological dysfunction, such as poor suckle and difficulty these electrolyte abnormalities should be addressed. finding the mare’s udder, to severe signs of multi-organ Once seizure activity is controlled and the patient is involvement, including recumbency, generalised seizures, stabilised, a complete history in concert with a more necrotising enterocolitis and renal failure. Although thorough physical examination and clinicopathological neurological signs may be severe, many foals survive with assessment should aid in determining the cause of aggressive supportive care and appear to regain normal neurological disease. Important information includes the neurological function as long as irreparable damage mare’s systemic health, including any signs of illness to other essential organs, such as the kidneys and occurring during gestation as well as previous foaling gastrointestinal tract, does not occur. Sepsis is always a history and peripartum events, particularly evidence of concern in sick neonates and may complicate the recovery from neonatal encephalopathy. Furthermore, Corresponding author email: [email protected] bacteraemia can lead to direct bacterial colonisation of

the central nervous system, resulting in meningitis or even malformations, such as in the foal with agenesis of both meningoencephalomyelitis. oculomotor and trochlear nerves (Muttini 1984). Several Due to the relatively common occurrence of neonatal other congenital malformations have been implicated encephalopathy secondary to peripartum asphyxia in the pathogenesis of neurological signs in horses. A and/or sepsis, the logical course of action when faced with neonatal Quarter Horse colt with difficulty rising and an a neonate exhibiting seizures is to institute aggressive abnormal swaying stance was found to have a supportive treatment for these conditions. As Dandy-Walker-like syndrome with an aplastic cerebellar demonstrated by the previous case report (Baiker et al. vermis and ventriculomegaly of the 4th ventricle (Wong 2010), the treatment course often includes appropriate et al. 2007). This report represented the second description intravenous fluid therapy as dictated by the patient’s of a Dandy-Walker-like syndrome in the horse, as a previous glucose and electrolyte levels, plasma products case report detailed a foal with agenesis of the corpus containing high levels of immunoglobulins to combat callosum and cerebellar vermian hypoplasia (Cudd et al. failure of passive transfer and immunoglobulin 1989). Cerebellar hypoplasia has been reported in horses, consumption, antimicrobial medications to address or although the degenerative condition of cerebellar prevent sepsis, nutritional support and other supportive abiotrophy appears to be more common (Palmer et al. therapies in conjunction with careful monitoring. Many 1973; Baird and Mackenzie 1974; DeBowes et al. 1987). The foals will respond positively, although complications of forebrain malformation of semilobar holoprosencephaly sepsis may reduce the prognosis. was diagnosed in a Morgan filly with subtle behavioural If the foal does not demonstrate expected signs (Koch et al. 2005). A congenital epidermoid cyst was neurological improvement over the usual time course, the reported to cause signs of prosencephalic disease in a clinician must reassess the case and attempt to ascertain Connemara mare, although interestingly the signs did the reason for the persistence of neurological signs. In not manifest until the mare was older, likely due to general, the following scenarios should be considered: 1) enlargement of the cyst with time (Kelly and Watson 1976). accurate diagnosis and appropriate therapy but slow Hydranencephaly, the final diagnosis for the foal in the or poor response, vs. 2) accurate diagnosis but previous case report, has been rarely reported in foals. In inappropriate/insufficient therapy leading to slow or poor ruminants, hydranencephaly is most commonly the result response vs. 3) inaccurate diagnosis leading to of trans-placental viral infection and has been reported inappropriate/insufficient therapy and poor response. in association with bovine viral diarrhoea virus, blue These potential scenarios should be discussed with the tongue virus, Akabane virus and other viruses (Konno owner so that new diagnostic and therapeutic plans can et al. 1982; MacLachlan and Osburn 1983; Leipold be implemented as dictated by the case. For some et al. 1993; Hewicker-Trautwein et al. 1995). In man, patients, euthanasia may be warranted due to humane hydranencephaly develops during the prenatal period considerations or financial constraints. For other patients, and is considered to be related to a developmental or additional diagnostic tests including cerebrospinal fluid encephaloclastic process, potentially of infectious, toxic or analysis and advanced imaging, may reveal a definitive genetic origin, that affects the major vessels of the anterior diagnosis or yield important information that substantially cranial circulation (McAbee et al. 2000). As discussed by modifies the differential list. In the previous case report Baiker et al. (2010), potential causes of hydranencephaly (Baiker et al. 2010), the foal was subjected to euthanasia 3 in horses remain speculative, as the disease is so rarely days after birth due to inadequate seizure control and reported. Outside of the previous case report, definitive diagnosis was accomplished post mortem. Had hydranencephaly has only been recorded in 2 ante mortem diagnosis been desired or necessary, more intentionally aborted Haflinger fetuses diagnosed with aggressive anticonvulsant treatment could have been several severe brain abnormalities, including bilateral utilised so that advanced imaging could have been hydrocephalus internus, hydranencephaly and cerebellar pursued. In this particular case and in most cases of aplasia, associated with hydrops allantois (Waelchli and congenital brain malformations, either computed Ehrensperger 1988). tomography or magnetic resonance imaging or both In general, the prognosis for congenital brain would allow partial or complete ante mortem malformations is guarded to grave. While some conditions characterisation of the malformation. allow stabilisation of signs or mild neurological impairment, Despite the fact that the number of reported most reported malformations cause severe neurological congenital brain malformations in foals is relatively low, the dysfunction. Surgical treatments utilised in human previous case report serves as an important reminder medicine are rarely applied to equine neonates, although to include malformations on the differential list for their use is occasionally reported. In one instance, a foal neurological neonates. The most common congenital with congenital hydrocephalus was treated using a malformation appears to be hydrocephalus, with a ventriculoperitoneal shunt and this foal improved until reported incidence of 3% in one study of 608 fetuses or shunt complications occurred (Bentz and Moll 2008). foals (Crowe and Swerczek 1985). Hydrocephalus may Unfortunately, for cases of equine hydranencephaly, the occur as a single malformation or with more complex prognosis should be considered hopeless for normal

neurological function. Even in man, no effective DeBowes, R.M., Leipold, H.W. and Turner-Beatty, M. (1987) Cerebellar treatments are known and affected infants usually have abiotrophy. Vet. Clin. N. Am.: Equine Pract. 3, 345-352. markedly reduced life expectancy and may be stillborn or Fanelli, H.H. (2005) Coat colour dilution lethal (‘lavender foal syndrome’): a tetany syndrome of Arabian foals. Equine vet. Educ. die within weeks to months after birth (McAbee et al. 2000). 17, 260-263. Despite occasional instances of prolonged survival, up to Hewicker-Trautwein, M., Liess, B. and Trautwein, G. (1995) Brain lesions in 19 years, evidence of neurological improvement has not calves following transplacental infection with bovine-virus diarrhoea been documented in hydranencephalic children. virus. Zentralbl. Veterinarmed. B 42, 65-77. As demonstrated by Baiker et al. (2010), neurological Kelly, D.F. and Watson, W.J. (1976) Epidermoid cyst of the brain in the horse. Equine vet. J. 8, 110-112. neonatal foals can be challenging cases. When more Koch, T., Loretti, A., de Lahunta, A., Kendall, A., Russell, D. and Bienzle, D. common causes of neurological disease are excluded (2005) Semilobar holoprosencephaly in a Morgan horse. J. vet. and neurological signs persist or worsen during the first intern. Med. 19, 367-372. weeks of life, congenital malformations should be Konno, S., Moriwaki, M. and Nakagawa, M. (1982) Akabane disease considered. The increasing availability of advanced in cattle: congenital abnormalities caused by viral infection. imaging techniques such as computed tomography and Spontaneous disease. Vet. Pathol. 19, 246-266. magnetic resonance imaging should improve our ability Lakritz, J., Madigan, J. and Carlson, G.P. (1992) Hypovolemic hyponatremia and signs of neurologic disease associated with to diagnose and characterise these malformations. diarrhea in a foal. J. Am. vet. med. Ass. 200, 1114-1116. 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