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Basics ⬇

Outline

BASICS

Definition!!navigator!!

Neurologic, GI, and renal dysfunction with or without other evidence of primary organ dysfunction that occurs secondary to hypoxic events in the periparturient period.

Pathophysiology!!navigator!!

  • It is speculated that hypoxic events or limitations to uteroplacental blood flow initiate hypoxic–ischemic injury. Intrauterine infection may also contribute to a decrease in blood flow, oxygen delivery, and nutrient supply
  • Foals affected at birth have likely suffered hypoxia secondary to placental insufficiency, placental blood flow, gas exchange, or other in utero compromise. Foals that have peripartum asphyxia may not show neurologic signs until 24 h after birth. The delay in clinical signs in these foals may be related to the secondary reperfusion injury due to reintroduction of adequate blood flow and oxygen delivery and the formation of reactive oxygen species
  • The renal and GI systems can be affected when blood flow to the fetus is limited and redistributed to the brain and heart (away from kidneys and GI tract)

Systems Affected!!navigator!!

  • Nervous—encephalopathy is commonly suspected, with signs generally limited to the cerebrum. Behavioral abnormalities are common
  • GI—ischemic damage and reperfusion injury can lead to mucosal degeneration and subsequent ileus, bacterial translocation, and enterocolitis
  • Renal—acute renal failure (acute tubular necrosis) can occur after an ischemic episode

Incidence/Prevalence!!navigator!!

  • Relatively common in the neonate; exact incidence unknown
  • NMS or HIE is the most common cause of acquired seizures in the neonatal foal

Signalment!!navigator!!

Breed Predilections

All breeds can be affected.

Mean Age and Range

Foals may be abnormal at birth, but signs may develop at 24–48 h of age.

Predominant Sex

No sex predisposition.

Signs!!navigator!!

General Comments

Signs vary from mild depression to severe centralized seizures and generalized organ failure.

Historical Findings

Dystocia, premature placental separation (“red bag”), placentitis, prepartum illness in the mare, induced labor, and prolonged gestation are maternal factors that can put the foal at an increased risk of NMS.

Physical Examination Findings

  • Lack of interest in the mare, inability to urinate, or disorientation and “star-gazing”
  • Tongue protrusion
  • Weak/absent suckle or misdirected suckling, lack of normal nursing behavior
  • Hyperresponsiveness
  • Focal or generalized seizures
  • Diarrhea or colic may be present if there is hypoxic injury to the GI system

Causes!!navigator!!

Maternal Factors

  • Placental insufficiency or dysfunction (including twins, placentitis, fescue toxicity, premature placental separation)
  • Compromised blood flow or oxygenation secondary to colic, endotoxemia, pulmonary disease, and anemia

Peripartum Factors

  • Dystocia
  • Cesarean section and general anesthesia
  • Compression/torsion of the umbilical cord
  • Induction of labor with oxytocin
  • Uterine inertia

Foal Factors

  • Congenital cardiac abnormalities
  • Pulmonary disease
  • Anemia
  • Sepsis

Risk Factors!!navigator!!

  • Fescue toxicity in mare
  • High-risk pregnancies

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Sepsis—sepsis score, blood culture, and leukogram changes should differentiate. Foals can suffer concurrently from sepsis and NMS
  • Meningitis—fever, ataxia, depression; CSF analysis and culture can confirm
  • Trauma—historical and physical examination information may help to differentiate
  • Congenital neurologic abnormality—lack of improvement in clinical signs; neurologic deficits may not be restricted to the cerebrum
  • Kernicterus—can occur with NI and very high serum bilirubin levels

CBC/Biochemistry/Urinalysis!!navigator!!

  • CBC and biochemistry are usually normal when the primary disorder is neurologic
  • If there are significant abnormalities (neutropenia, azotemia), sepsis and multiple organ dysfunction should be suspected
  • Hypoglycemia is common if the foal has not been able to nurse adequately

Other Laboratory Tests!!navigator!!

  • Serum immunoglobulin G—low if foal has not been able to consume adequate colostrum or foal's GI tract cannot adequately absorb immunoglobulins, or mare has not produced good quality colostrum
  • Blood gas analysis—hypoventilation can occur as a result of central nervous system damage. Hypercapnia with or without hypoxemia may be seen

Imaging!!navigator!!

  • Skull radiographs or CT scan to rule out traumatic fracture as a cause of neurologic dysfunction
  • MRI—cerebral edema and necrosis with severe cases, although there may be no abnormalities seen in early or mild cases. There is limited information on the use of this imaging modality in foals with NMS

Other Diagnostic Procedures!!navigator!!

CSF aspirate—will usually be normal with NMS; rule out bacterial meningitis.

Pathologic Findings!!navigator!!

  • Consistent cerebral abnormalities have not been reported, although cerebral necrosis, edema, and hemorrhage may be seen. Uncomplicated cases have a good prognosis, so postmortem information is limited
  • Hypoxic–ischemic injury to the kidneys may result in tubular necrosis
  • Hypoxia and/or ischemia to the GI tract may cause necrosis and hemorrhage

Treatment ⬆ ⬇

Outline

TREATMENT

Aims!!navigator!!

  • Supportive care—mildly affected foals may only need to have adequate nutrition and immunoglobulin provided until they can nurse effectively on their own, usually within 2–3 days
  • Seizure control
  • Reduce or prevent further brain injury—anti-inflammatory and antiedema drugs
  • Prevent sepsis in recumbent or debilitated foals
  • Respiratory support may be needed if there is hypoventilation related to NMS

Appropriate Health Care!!navigator!!

  • Mildly affected foals may be managed with careful monitoring and tube feeding with colostrum and mare's milk, if needed
  • The majority of affected foals require inpatient medical management

Nursing Care!!navigator!!

  • Oxygen therapy when hypoxemia is present. Avoid overzealous use, especially in the presence of hypercapnia
  • Fluid therapy—maintenance fluids for foals that are transiently unable to nurse. Correct hypovolemia to maintain cerebral perfusion pressure, renal blood flow, and intestinal perfusion
  • Protect from self-trauma during seizures or struggling activity and monitor for the development of corneal ulcers or abrasions
  • Squeeze-induced somnolence using rope restraint is a potential treatment for NMS
  • Hyperimmune plasma IV if the foal has not been able to ingest adequate colostrum within the first several hours of birth

Activity!!navigator!!

Activity will be limited by the treatments required and by the neurologic and metabolic status of the foal.

Diet!!navigator!!

  • Feed via nasogastric feeding tube until a strong suckle reflex and coordinated nursing is achieved. See chapter Nutrition in foals
  • Care should be taken if GI ischemia is suspected. Foals with GI injury or ileus may require parenteral nutrition until intestinal function returns

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

For Seizure Control

(For drug information and dosages, see chapter Seizures in foals)
  • Midazolam
  • Phenobarbital
  • Phenytoin

For Treatment of Cerebral Asphyxia/Edema

  • Magnesium sulfate (50 mg/kg/h loading dose, then 25 mg/kg/h constant rate infusion)—blocks NMDA production
  • Mannitol (0.25–1.0 g/kg as a 20% solution IV)—osmotic diuretic to reduce cerebral edema
  • DMSO (0.5–1.0 g/kg as a 10% solution IV)—given shortly after the initial insult to scavenge free radicals and mediate ischemia–reperfusion injury. There is no evidence of efficacy of DMSO
  • Thiamine (5 mg/kg IV slowly or diluted in fluids every 24 h)—to support mitochondrial metabolism

For Treatment of Hypoventilation

Caffeine (10 mg/kg initial dose, then 2.5 mg/kg PRN, given PO or per rectum)—respiratory stimulant for centrally mediated hypoventilation.

Antioxidants

  • Vitamin E (alpha-tocopherol)—500–1000 IU PO every 24 h
  • Vitamin C (ascorbic acid)—50–100 mg/kg PO every 24 h

For Renal Failure

Furosemide (1–2 mg/kg IV PRN)—if signs of fluid overload are present.

For Prevention or Treatment of Sepsis

  • Broad-spectrum parenteral antimicrobials. Penicillin (22 000 IU/kg IV every 6 h) and amikacin (25 mg/kg IV every 24 h) are commonly used
  • Metronidazole (15 mg/kg PO every 12 h) may also be used if anaerobic infection is suspected or if necrotizing enterocolitis is present

Contraindications!!navigator!!

  • Corticosteroids are not indicated for the treatment of NMS
  • Ketamine and xylazine increase intracranial pressure, and should be avoided, if possible
  • Mannitol is contraindicated with cerebral hemorrhage

Precautions!!navigator!!

Aminoglycoside antimicrobials and NSAIDs should be used with caution if renal damage is suspected.

Alternative Drugs!!navigator!!

If renal compromise is suspected, a third-generation cephalosporin can be used in place of the penicillin–amikacin combination (e.g. ceftiofur 5–10 mg/kg IV every 6 h; ceftazidime 50 mg/kg IV every 6 h)

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Reevaluate at least daily for ability to stand and nurse. An adequate suckle reflex and ability to remain standing are required for reintroduction to nursing the mare. The foal may require assistance to stand as it is initially reintroduced to nursing
  • Monitor closely for signs of sepsis, as many of the risk factors for NMS also place the foal at risk of sepsis
  • Blood pressure should be monitored in more severe cases and hypotension treated in order to maintain perfusion to vital organs

Prevention/Avoidance!!navigator!!

Any potential underlying causes such as placental insufficiency, ascending uterine infection, or prolonged gestation due to fescue toxicity should be investigated in order to help prevent NMS in future foals.

Possible Complications!!navigator!!

  • Septicemia
  • Enterocolitis
  • Ventilatory failure (hypoxemia and hypercarbia)

Expected Course and Prognosis!!navigator!!

  • Prognosis is good to excellent (approximately 75% survival) for uncomplicated NMS. Mildly affected foals generally respond to treatment within several days. Foals with additional organ dysfunction require more intensive and prolonged care
  • Delayed treatment can result in failure of transfer of passive immunity and sepsis. Concurrent diseases such as sepsis will decrease the prognosis

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Sepsis
  • Enterocolitis/diarrhea

Age-Related Factors!!navigator!!

This is a condition of neonatal foals, with initial signs seen typically within 48 h of age.

Synonyms!!navigator!!

  • Neonatal maladjustment syndrome
  • HIE
  • Dummy foal
  • Barker foal
  • Neonatal encephalopathy

Abbreviations!!navigator!!

  • CSF = cerebrospinal fluid
  • CT = computed tomography
  • DMSO = dimethylsulfoxide
  • GI = gastrointestinal
  • HIE = hypoxic–ischemic encephalopathy
  • MRI = magnetic resonance imaging
  • NMDA = N-methyl-d-aspartate
  • NMS = neonatal maladjustment syndrome

Suggested Reading ⬆ ⬇

MacKay RJ. Neurologic disorders of neonatal foals. Vet Clin North Am Equine Pract 2005;21:387–406.

Paradis MR. Neurologic dysfunctions. In: Paradis MR, ed. Equine Neonatal Medicine: A Case-Based Approach. Philadelphia, PA: Saunders, 2006:179–190.

Wilkins PA. Perinatal asphyxia syndrome. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine, 3e. St. Louis, MO: WB Saunders, 2010:1324–1328.

Author(s) ⬆

Author: Eric L. Schroeder

Consulting Editor: Margaret C. Mudge

Acknowledgment: The author acknowledges the prior contribution of Margaret C. Mudge.