Adult, 8-year-old, female spayed, DLH cat (Felis cats)Presented to an emergency clinic with acute onset of blindness and inappetence. Owner had noted subtle change in behavior the previous day and believed the cat had been drinking and urinating more in the past 2 weeks. Physical examination: mentally dull and anxious, severely hypertensive (230 mmHg systolic on Doppler). Ophthalmic examination: no menace response, palpebral reflex present, sluggish bilateral pupillary light reflex, equivocal dazzle reflex. Hospitalized to treat (amlodipine besylate) and monitor hypertension. Tonic-clonic seizure developed 4 hours later, resolved with diazepam, but the cat remained stuporous and showed anisocoria. Euthanasia was elected.
Gross findings were very nonspecific. Tissues throughout the body were hyperemic with marked congestion seen in large abdominal veins (caudal vena cava, renal veins). Renal capsular surfaces were irregularly depressed overlying wedge shaped pale areas extending to the corticomedullary junction (chronic infarcts).
Brain: There is a large poorly demarcated wide area of pallor within each dorsal parietal lobe extending from deep white matter and encompassing full thickness of the associated overlying grey matter. Pallor is caused by marked separation and accentuation of the linear myelin sheaths in white matter and marked vacuolation (spongiform change) in the overlying grey matter. Severe neuronal degeneration, necrosis and loss is seen with shrunken, eosinophilic and angular neurons, scattered nuclear debris (karyorrhexis) and heavy complement of glial cells, gitter cells and reactive astrocytes. Occasionally, glial cells replace neurons. There are a few microhemorrhages within the area of edema and necrosis in the grey matter. Vessels within the area of pallor show severe effacement of architecture by amorphous eosinophilic material and small amount of nuclear debris (fibrinoid change). These vessels are surrounded by large clear vacuoles (perivascular edema). Blood vessels with intact walls are often lined by hypertrophic (reactive) endothelial cells and surrounded by low numbers of neutrophils, macrophages, lymphocytes and plasma cells. Multifocally throughout the section, Virchow-Robin space is markedly expanded by clear space transected by fine eosinophilic strands (edema). Leptomeninges overlying the affected gyrus are mildly expanded by edema and low numbers of mixed inflammatory cells, mostly mononuclear with occasional neutrophils. Pial arteriolar walls often contain amorphous eosinophilic as droplet
Brain, cerebrum, parietal lobes, bilateral, edema with neuronal degeneration, necrosis and loss, locally extensive, acute, severe associated with arteriolar fibrinoid change, acute, severe.
Clinical pathology: Hematology: low plate-lets with clumping observed; Serum
biochemistry: mild hyperglycemia (stress), mild hyponatremia (pressure naturiesis); Urinalysis: glucosuria, negative for protein, USG 1.010 (isosthenuria consistent with pressure diuresis).
Systemic hypertension as a clinically important condition in domestic cats was initially described in 1986.4 It has been defined as a sustained increase in systolic blood pressure > 160-170 mmHg.2 Three clinical categories are recognized and defined as:
- Stress-induced (white coat) hypertension: transitory artifactual increase (median rise of 17.6 + 5.9 mmHg) secondary to activation of the sympathetic nervous system in the classical fight or flight response;
- Secondary hypertension: most common and associated with systemic diseases or treatments including chronic renal disease, hyperthyroidism, primary hyperaldosteronism, pheochromocytoma, diabetes mellitus and erythropoietin treatment; and
- Idiopathic (primary or essential) hypertension: about 20% of hypertension in cats occurs in the absence of other demonstrable disease conditions.
Target organ damage (TOD) is a risk in the face of uncontrolled hypertension with the heart, brain, eyes and kidneys being at greatest risk. The cat of this report showed TOD in the brain as described above. Changes in the eyes and kidneys were also focused largely on vascular structures, specifically arterioles, with similar effacement by amorphous eosinophilic material with small amounts of nuclear debris, commonly known as fibrinoid change or necrosis. This cat presented with acute onset of blindness and an anxious demeanor with rapid deterioration to seizuring and stupor. This is a classical presentation for target organ damage in a hypertensive cat with the first noted sign often being acute blindness associated with catastrophic effusive retinal detachment (Fig. 2). Sudden onset of intracranial neurological signs is also common. Renal and cardiac changes are generally more insidious. Accelerated progression of chronic kidney disease and development of congestive heart failure associated with left ventricular hypertrophy, respectively, are reported.(3) Pathogenesis of the insidious conditions is poorly understood, particularly regarding cause and effect.
The risk of target organ damage rises as the blood pressure rises.(4,5) Risk is minimal at <150mmHg, mild at 150-159mmHg, moderate at 160-179mmHg and severe at >180mmHg. This cat had a recorded pressure of 230mmHg at presentation. The vascular lesions in the brain, eyes and kidneys are acute suggesting a relatively short course of hypertension in this cat. There is no evidence to suggest hyperplastic vascular changes that would be seen as a response to sustained hypertension. It has been suggested that vascular remodeling can occur within 14 days of onset of hypertension.(1)
Hypertension in this cat was considered idiopathic despite being younger than reported age of >12 years for development of idiopathic hypertension.(5) Complete histological evaluation did not show pathology consistent with any of the conditions associated with secondary hypertension. Secondary hypertension is most commonly seen in cats with chronic kidney disease (CKD) or with hyperthyroidism. Many cats with systemic hypertension show some degree of CKD. It is often unclear whether the hypertension initiates renal damage or systemic hypertension develops as a consequence of reduced renal function.
Hyperthyroidism has been considered a risk factor for systemic hypertension with recent information suggesting this risk may be overstated.(3)
Cerebrum: Fibrinoid vascular necrosis, multifocal, moderate with neuronal necrosis and edema.
This was a challenging case for most conference participants with many focusing the majority of their description on the vascular changes. Most participants described an asymmetric fibrinoid vasculitis and listed various etiologic differential diagnosis, such as feline ischemic encephalopathy, FIP, FeLV as well as hypertension. The moderator and many conference attendees stated they had not previously seen a CNS case similar to this, with the unique asymmetric fibrinoid change within vessels, and some speculated that an infarction may result in a similar lesion, although the contributor provided a convincing workup and description of a hypertension induced lesion / TOD. The lesion was described as focally extensive within the white matter, but also extending into the grey matter with areas of spongiosis, hemorrhage and neuronal necrosis. The affected vessels were described as having indistinct vessel walls and endothelium, largely obscured by dense eosinophilic debris with expansion of Virchow-Robin space by edema, similar to the contributors description above. Low numbers of mitoses were described within vessel endothelium.
The moderator discussed duration of injury as determined by relative populations of glial cells. It generally takes approximately 4-5 days to see a prominent astrocyte response; in this case there is a mild increase in the number of astrocytes, and a much more prominent increase in the number of microglial cells. Microglial cells respond more rapidly to CNS injury, generally increasing in number within 24 hours, and consequently there was speculation this lesion was approximately 2-3 days duration, which corresponds to the contributors comment above regarding the acute nature of changes in the brain.
Autoregulation of cerebral blood flow normally prevents excesses of pressure and flow within the brain that can result in excess pressure related damage; however, there are upper limits on this autoregulatory mechanism. When this mechanism fails in cases of prolonged and/or excessive systemic blood pressure, vessels become distended and endothelial tight junctions open, resulting in extravascular leakage of fluid, and edema is the end result. Depending on the severity, cerebral edema may be visible grossly along with widening and flattening of the cerebral gyri, and caudal herniation of the cerebellum through the foramen magnum due to increased intracranial pressure. Histologically, as seen in this case, vacuolation of the neuropil is present, and may be predominantly in the white matter. Vascular lesions can include arteriolar hyalinosis, which may reflect endothelial damage, and leakage of fibrin and other plasma components into the vessel wall and extravascular space; this change may occur prior to onset of fibrinoid vascular necrosis. Hyperplastic arteriosclerosis, microhemorrhages and perivascular cuffing by inflammatory cells may also be seen depending on degree and duration of hypertension.(1,4)
1. Brown CA, Munday JS, Mathur S and Brown SA. Hypertensive encephalopathy in cats with reduced renal function. Vet Pathol. 2005;42:642-649.
2. Brown S, Atkins C, Bagley R, et al. ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J Vet Intern Med. 2007;21:542-558.
3. Jepson R. Feline hypertension: Classification and pathogenesis. J Feline Med Surg. 2011;13:25-34.
4. Kent M. The cat with neurological manifestations of systemic disease: Key conditions impacting on the CNS. J Feline Med Surg. 2009;11:395-407.
5. Stepien RL. Feline hypertension: Diagnosis and management. J Feline Med Surg. 2011;13:35-43.