Cholinesteric Granuloma Encephalopathy

Robert J. MacKay • Mary O. Smith

Cholinesteric granulomas (CGs) develop in association with the choroid plexuses of the fourth ventricles and lateral ven­tricles. Up to 20% of older horses have CGs in one or both lateral ventricles, usually without adverse effect.¹ CGs are thought to develop as a chronic inflammatory reaction to cholesterol released from extravasated degenerating RBCs within the choroid plexus.

Signs can develop insidiously or appear suddenly and are usually referable to forebrain dysfunction.^2,4 Affected horses may exhibit dementia, manifested as irritability, aggression, yawning, head pressing, compulsive walking, drifting to one side when walking, circling, abnormal body posture, loss of learned skills, syncope-like attacks, seizures, blindness and lack of menace response with normal pupillary light reflexes, and reduced response to tactile stimulation of the face.^2-5 With presumed CG-associated cerebral edema, signs suggestive of brainstem compression also have been described, including stupor, limb weakness and ataxia, anisocoria, head tilt, stiffness in gait, and facial paresis. Signs are typically asymmetric or unilateral, reflecting asymmetric involvement of the lateral ventricles.

CG should be suspected in any mature horse showing signs referable to waxing and waning forebrain dysfunction. Results of CSF analysis may be normal, may show high protein concentra­tion with normal cell count, or may show mild pleocytosis notable for the presence of nondegenerate neutrophils. The diagnosis is strongly supported by advanced imaging. CT in the standing⁵ or anesthetized horse^2,3 is the diagnostic method of choice, but MRI has also been used.⁴ The finding on CT of heterodense, hyperattenuating, poorly contrast-enhancing masses in the lateral ventricles is tantamount to the diagnosis of CG. A technique for CG biopsy has been described and can be used to exclude the possibility of other choroid plexus tumors, including papillomas and ependymomas.³ At necropsy of clinically affected horses, CGs are found as brownish ellipsoid masses at least 3 cm in diameter attached to the choroid plexuses of one or both lateral ventricles. Histologically, these masses contain abundant cholesterol crystals interspersed with empty clefts, hemosiderin, and heavy infiltrations of macrophages and giant cells.

Traditionally, CGs in horses have been considered terminal and untreatable. It is clear, however, that all of the components of the pathophysiology of CG encephalopathy—namely, enlarging granulomas, hydrocephalus, and ependymal inflammation—are potentially treatable with antiinflammatory drugs. In horses with CG encephalopathy, antiinflammatory drugs, including dexamethasone, prednisolone, and phenylbutazone, have induced clinical remissions lasting from months to indefinitely. A reasonable treatment protocol includes seizure control as needed and induction of remission from clinical signs with dexamethasone (0.05 mg/kg IV or 0.1 mg/kg PO, once daily for 7 to 14 days), followed, if successful, by prednisolone (1 mg/kg PO bid), to be given indefinitely except for intermittent trials designed to test the effect of tapering the dose. Hyperosmolar IV solutions (mannitol, 0.5 to 2.0 g/kg as a 20% solution; 7.2% saline, 2 to 4 mL/kg) can be given in the acute phase to address cerebral edema and repeated as needed every 4 to 6 hours for the first 24 hours. More aggressive interven­tions, including direct drainage of CSF from enlarged lateral ventricles and surgical removal of CG by techniques adapted from human brain surgery, are also possible but have not been described. The prognosis for short- to medium-term (i.e., up to a year) maintenance of remission from clinical signs of CG encephalopathy is considered fair.