PMC9449415_01
Magnetic resonance imaging (MRI) of a 1.25 year old Chihuahua (case 1). (A) Sagittal T2 weighted (w) post mortem MRI of the brain. Note the mild indentation of the rostral cerebellum due to increased volume of the cerebrum. Hypointense material fills the fourth ventricle (arrow), intraventricular hemorrhage is suspected. (B) Transversal T2w MRI of the cerebrum at the level of the caudal part of the hippocampus (level is indicated in the small inlay as the first red line). Note the generalized swelling of gray matter with flattened gyri and sulci (arrowheads). (C) Transversal T1w MRI of the cerebellum and brainstem (level is indicated in the small inlay as the second red line). Round, well demarcated intraaxial lesion with signal void (arrow), hemorrhage is suspected.
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F1
Post mortem MRI (Figure 1) showed generalized swelling of the gray matter in the cerebrum and cerebellum with secondary flattening of gyri and sulci.
Macroscopic and histopathological findings of a 1.25 year old Chihuahua (case 1). (A) Macroscopic image of the brain with mild narrowing of sulci and flattening of gyri interpreted as edema. (B) Histopathology of the cerebral cortex at the level of the temporal lobe with moderate, leukocytoclastic vasculitis of the leptomeningeal blood vessels with fragments of degenerated inflammatory cells (arrow in insert) visible within the destructed vascular wall (HE stain; scale bar: 50mum). (C-E) Immunohistochemistry for CD3 (C), CD20 (D) and CD204 (E) shows that the majority of infiltrating cells are comprised of T-lymphocytes [(C); CD3-positive] and macrophages [(E); CD204-positive] (Scale bars: 50 mum).
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F2
At necropsy, a moderate flattening of the gyri and narrowing of sulci of the brain (Figure 2A) was observed in conformity with the MRI results and interpreted as edema. Furthermore, primarily small to medium sized blood vessels in the gray matter and especially prominent in the leptomeninx displayed loss of integrity of the vascular wall with moderate to severe infiltration with partially degenerated lymphocytes and macrophages resembling vasculitis of the leukocytoclastic type (Figure 2B). IHC of selected sections of the CNS revealed infiltration of a moderate to high number of CD3-positive T-lymphocytes, low to moderate number of CD204-positive macrophages and few CD20-positive B-lymphocytes, respectively, in the partially destructed vascular wall and the perivascular space (Figures 2C-E).
PMC9449415_02
Macroscopic and histopathological findings of a 10 year old, mixed breed dog (case 2). (A) Macroscopic image of a transverse section of the cerebrum including the cerebral hemispheres and parts of the mesencephalon (M). The lateral ventricle of the left hemisphere displays severe, focal hemorrhage (asterisk). (B) Histopathology of the same area displayed in (A). A blood vessel shows moderate vasculitis and perivascular infiltrates consisting of lymphocytes and macrophages. The lateral ventricle and adjacent parenchyma reveal hemorrhage (asterisk) (HE stain; scale bar: 50 mum).
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F3
Macroscopically, an approximately 4 cm in diameter sized accumulation of coagulated blood was found within the lateral ventricle of the left hemisphere of the brain (Figure 3A). Furthermore, moderate to severe, lympho-histiocytic infiltrates were detected within the meninges and brain parenchyma, and associated with non-leukocytoclastic vasculitis, most frequently in the cerebral cortex, hippocampus, brain stem, and cerebellum (Figure 3B).
PMC9449415_03
Magnetic resonance imaging (MRI) of a 10.75 year old Australian Shepherd (case 3). (A) Sagittal T2 weighted (w) MRI of the brain. Note the caudal cerebral herniation (empty arrow) which causes concave distortion of the rostral cerebellum and secondary transforaminal cerebellar herniation with compression of the brainstem and an intramedullary hyperintense lesion (filled arrow). (B) Sagittal T1w MRI approximately 3 min after intravenous contrast medium application. Note that there is physiological intravenous contrast enhancement extracranially (e.g., filled arrowhead) but no contrast medium is visible in structures which physiologically take up contrast medium (empty arrowheads).
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F4
Subsequent MRI (Figure 4) showed generalized flattened sulci and reduced volume of internal and external CSF space due to swelling of the CNS parenchyma.
Macroscopic and histopathological findings of a 10.75 year old Australian Shepherd (case 3). (A) Macroscopic image of the brain stem displaying focal, severe hemorrhage within the neuroparenchyma (asterisk). (B) Histopathology of the spinal cord shows severe, multifocal vasculitis characterized by infiltrating inflammatory cells in the damaged vascular wall and the perivascular space (arrows; insert displays higher magnification of the perivascular infiltrates) at the border between white matter (W) and gray matter (G) (HE stain; scale bar: 100 mum). (C-E) Immunohistochemistry for CD3 (C), CD20 (D) and CD204 (E) shows that the majority of inflammatory cells infiltrating and surrounding damaged vessels are comprised of many (B-D) and less T-lymphocytes (C). Only very few infiltrating cells represent CD204-positive macrophages (E) (Scale bar: 50 mum).
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F5
Furthermore, there was severe, acute hemorrhage and softening of the neuroparenchyma within the brain stem (Figure 5A). Histologically, the cerebral cortex, cerebellum, brain stem as well as the spinal cord showed severe, lympho-histiocytic and plasmacytic panencephalomyelitis and meningitis with perivascular edema (Figure 5B).