JPC SYSTEMIC PATHOLOGY

Nervous System

January 2023

N-M23

 

Signalment (JPC #2414433): 8-year-old spayed female domestic shorthair cat

 

HISTORY: This cat had a four-day history of hind end paresis, hyperesthesia, hypersalivation, and depression, followed by several episodes of “rage”-type activity.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebrum, hippocampus: Multifocally within the hippocampus there is liquefactive necrosis characterized by loss of neuropil with replacement by eosinophilic cellular debris and moderate numbers of gitter cells admixed with multiple foci of hemorrhage, fibrin, and edema. Vessels within affected areas are lined by hypertrophic (reactive) endothelial cells, and vessel walls are occasionally discontinuous and frequently obscured by fibrin, macrophages, and neutrophils (fibrinonecrotizing vasculitis). Vessels are surrounded by low numbers of neutrophils and gitter cells and there is mild perivascular edema. Within the affected areas, neurons frequently have shrunken, hypereosinophilic, and angular cytoplasm with pyknotic or karyolytic nuclei (neuronal necrosis) and are surrounded by moderate numbers of glial cells (satellitosis) and few neutrophils. The adjacent leptomeninges are mildly expanded by low numbers of previously described inflammatory cells admixed with mild hemorrhage, fibrin, and edema.

 

MORPHOLOGIC DIAGNOSIS: Cerebrum, hippocampus: Necrosis, liquefactive, multifocal to coalescing, marked, with hemorrhage, fibrin, edema, fibrinonecrotizing vasculitis, and neuronal necrosis, domestic shorthair, feline.

 

CONDITION: Feline ischemic encephalopathy

 

CONDITION SYNONYMS: Idiopathic cerebral ischemic necrosis  

 

GENERAL DISCUSSION:

• Feline ischemic encephalopathy sporadically occurs in mature cats, and is suspected to result from aberrant migration of Cuterebra larvae in the brain via nasal cavity invasion, although the cause has not been definitively established
• Primarily affected areas of the brain are supplied by the middle cerebral artery

 

PATHOGENESIS:

• Unknown: Ischemic mechanism suspected, but also direct toxicity suspected
• Theory: Aberrant migration of Cuterebra sp. 

• Most commonly seen in summer (July – Sept)
• Presumably, toxic effects of the parasite induce vascular spasms leading to ischemia

 

TYPICAL CLINICAL FINDINGS:

• Acute, nonprogressive forebrain signs that may resolve over time: Depression with mild ataxia, behavioral changes, seizures, blindness
• Severity of clinical signs depends on the degree and location of infarction

 

 

TYPICAL GROSS FINDINGS:

• Unilateral (occasionally bilateral but asymmetric) ischemic necrosis- sunken, depressed cerebral white and grey matter; most common in areas supplied by the middle cerebral artery; may be multifocal or involve up to 2/3 of one hemisphere
• May be cavitations with secondary ventricular dilatation
• CNS or leptomeningeal hemorrhage
• In chronic cases there can be cerebral atrophy (most severe adjacent to the middle cerebral artery of the affected hemisphere)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Necrosis of the hippocampus and brain stem
• Ischemic neuronal necrosis 
• Early inflammatory response limited due to lack of vascularization of the tissue; neutrophils (early), macrophages (later) in perivascular cuffs and in neuropil 
• +/- vascular occlusive lesions (e.g. thrombosis, vasculitis, infarction) 
• +/- parasitic tract, often in the caudate nucleus or thalamus; not associated with ischemic changes

 

ADDITIONAL DIAGNOSTIC TESTS: 

 

DIFFERENTIAL DIAGNOSIS:

Clinical 

• Hypoglycemia – symmetrical signs
• Fibrocartilagenous emboli –usually located in spinal cord
• Rabies

Microscopic 

• Feline hippocampal necrosis- similar, but usually bilateral and selective for hippocampus and piriform lobe; cats present with seizures
• Traumatic cerebral encephalopathy
• Hypoglycemia – symmetrical lesions
• Cytauxzoon felis causes random ischemic necrosis, but lacks some hallmarks of FIE; schizont-laden macrophages often occlude blood vessels

Parasites – aberrant migration 

• Dirofilaria immitis
• Baylisascaris procyonis

 

COMPARATIVE PATHOLOGY:

Ischemic encephalopathy in other species:

• Neonatal maladjustment syndrome (“barker” or “convulsive” foals) – probably due to a circulatory derangement with subsequent cerebral hypoxia, but the pathogenesis is not understood

• Anesthetic-associated cerebral hypoxia
• Intracarotid injection of drugs in horses

• Dogs - ischemia secondary to atherogenic vascular degeneration (atheroma) due to hypothyroidism; uncommon
• Raccoons - Idiopathic ischemic encephalopathy has been reported in two animals
• Bald eagles - Lead toxicity can cause ischemic injury to neuroparenchyma though not usually symmetric (Manning Vet Pathol. 2019)
• Humans - cerebrovascular accidents are often secondary to atherogenic vascular degeneration; occlusion occurs most frequently at the carotid bifurcation, the origin of the middle cerebral artery, or at either end of the basilar artery

 

REFERENCES:

1. Cantile C, Youssef, S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Saunders Elsevier; 2016: 391.
2. Manning LK, Wunschmann A, Armien AG, Willette M, et al. Lead intoxication in free-ranging bald eagles (Haliaeetus leucocephalus). Vet Pathol. 2019; 56(2):289-299.
3. Miller AD, Zachary JF. Nervous system.  In: Zachary JF, ed. Pathological Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby; 2022: 983.
4. Valli VEO, Kiupel M, Bienzle D, Wood RD.   Hematopoietic System.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Saunders Elsevier; 2016: 120-121.

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