Diseases / Miscellaneous / Multi-factorial / Metabolic Diseases / Chronic Wasting Disease of Deer and Elk / Detailed Disease Description:

< > Literature Reports of PATHOLOGICAL FINDINGS - (Necropsy/Post Mortem) for CWD of Deer and Elk:

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OVERALL PATHOLOGICAL FINDINGS - Editorial Comment
(Text Replicated on Overall Disease page - CWD of Deer and Elk)

Editorial Overview (Editorial Overview Text Replicated on Overall Disease page - CWD of Deer and Elk)

GROSS PATHOLOGY

  • The main gross pathological finding in deer and elk which have died of CWD or have been euthanased late in the course of the disease, is emaciation, with total loss of body fat, serous atrophy of fat and even severe muscular atrophy in terminal cases. The bone marrow may be yellow and gelatinous.
  • Other findings may include lesions of aspiration pneumonia. 
  • Particularly in Odocoileus hemionus - Mule deer the rumen contents may be excessively liquid or frothy, and sand or gravel may be notable in the rumen.

HISTOLOGY

  • The main lesions of CWD are found within the central nervous system. Typically there are changes of spongiform encephalopathy, characterized by microcavitation of grey matter and/or white matter, intraneuronal vacuolation and neuronal degeneration. Lesions are basically bilaterally symmetrical and characteristically affect some areas of the brain to a greater extent than other areas.
    • Lesions are detectable first in the dorsal motor nucleus of the vagus nerve (DMNV).
  • Amyloid plaques are readily detected by immunohistochemistry (IHC) as scrapie amyloid-immunoreactive plaques and in mule deer may be visible with specific stains e.g. Congo red.
  • Scrapie-associated fibrils may be present in the brain and the spleen of clinically affected individuals. 
  • Immunohistochemistry and Western blotting can detect the presence of PrPres in the brain and in lymphoid tissue; in elk (Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer)) PrPres is detected in lymphoid tissue only relatively late in the course of the disease while in Odocoileus spp. deer it may be detected in individuals which have not shown any clinical signs of the disease.
  • PrPCWD accumulation is detectable in the CNS by IHC prior to the development of vacuolar lesions.
  • Immunohistochemistry has detected PrPCWD in the pituitary (pars nervosa and pars intermedia), adrenal medulla and the islets of Langerhans in the pancreas.
  • Secondary lesions such as bronchopneumonia, serous atrophy of fat, gastric ulceration and adrenal cortical hypertrophy may be seen also.

Limited data on other TSE diseases is provided in literature reports below the information on CWD. Information on these diseases within the "Chronic Wasting Disease of Deer and Elk" volume of Wildpro is provided for comparative purposes and is not intended to be comprehensive.

Overall Gross / General Pathological Findings CWD of Deer and Elk
  • Gross lesions are non-specific and may include emaciation (not if the clinical course was short), aspiration pneumonia with or without fibrinous pleuritis and rumen contents may be excessively watery, sometimes frothy, sometimes containing excess sand and gravel. (J64.21.w17)
  • Weight loss, emaciation, loss of both abdominal and subcutaneous adipose tissue, serous atrophy of adipose tissue (behind the eye, around the spinal cord, in bone marrow, in joints, within the renal pelvis and around coronary arteries). The adrenal glands may be enlarged. Aspiration pneumonia is common. (B336.78.w78)

Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer):

  •  General:
    • Emaciation and a dry rough coat (pelage); normal hydration status. (J1.18.w7)
    • Emaciation with lack of body fat and in terminal cases severe muscular atrophy. (J64.11.w3)
    • Poor body condition or emaciation. (P42.12.w1)
    • Severe emaciation in free-living individuals from Colorado. (P2.43.w1)
    • Severe emaciation; total loss or serous atrophy of adipose tissue in free-living individuals from Colorado. (P4.1.w4)
    • Emaciation with generalised absence of subcutaneous and visceral adipose tissue or serous atrophy, and yellow gelatinous bone marrow, in free-living deer from Colorado. (J1.33.w10)
    • Mild to severe emaciation with reduced or absent subcutaneous, visceral and skeletal adipose tissue in four female elk from a cohort hand-reared at a wildlife research facility in Colorado in 1986. (J1.34.w6)
    • Emaciation, eyes sunken, loss of hair on one shoulder, in one seven-year-old elk bull in Korea. (J27.64.w1)
    • Emaciation and rough hair with retained winter coat in mid-summer. Two-year old female elk from a game farm in Canada, 2001. (J14.43.w1)
  • Central Nervous System:
    • No gross lesions. (J64.11.w3)
  • Digestive Tract:
    • Traumatic reticulitis and peritonitis associated with wire in 2/6 animals (incidental finding). (J1.18.w7)
    • Rumen: may be some abnormalities (excess fluid), but less apparent than in deer (Odocoileus spp.). (J64.11.w3)
  • Respiratory:
    • Aspiration pneumonia in some individuals (terminal, secondary). (J64.11.w3)
    • Aspiration pneumonia in some individuals (terminal, secondary).(P42.12.w1)
    • Sub-acute to chronic bronchopneumonia in 2/6 free-living elk from Colorado. (J1.33.w10)
    • Sublobar to lobar consolidation in frontal and caudal lung lobes, fibrinous adhesion of the lung to the thoracic wall, in one seven-year-old elk bull in Korea. (J27.64.w1)

Odocoileus hemionus - Mule deer:

  • General:
    • Emaciation (29/29). (J1.16.w10)
    • Emaciation with lack of body fat and in terminal cases severe muscular atrophy. (J64.11.w3)
    • Poor body condition or emaciation. (P42.12.w1)
    • Severe emaciation in free-living individuals from Colorado. (P2.43.w1)
    • Severe emaciation; total loss or serous atrophy of adipose tissue in free-living individuals from Colorado. (P4.1.w4)
    • Emaciation with generalised absence of subcutaneous and visceral adipose tissue or serous atrophy, and yellow gelatinous bone marrow, in free-living deer from Colorado. (J1.33.w10)
  • Central Nervous System:
    • No gross lesions. (J64.11.w3)
  • Digestive Tract:
    • Rumen: increased ruminal fluid (19/26), sand and gravel in rumen (14/26).  (J1.16.w10)
    • Rumen: contents extremely fluid or frothy; often sand or gravel noted (may be more visible due to fluid contents). (J64.11.w3)
    • Oesophagus: occasionally may be greatly dilated and filled with fluid. (J64.11.w3)
    • Rumen: may contain excessive fluid or green froth. (P42.12.w1)
    • Rumen: contents watery or frothy, and often containing sand, in 10/41 free-living deer from Colorado. (J1.33.w10)
    • Abomasum or omasum: ulcers present in 7/41 free-living deer from Colorado. (J1.33.w10)
    • Abomasal ulcers are found occasionally. (B336.78.w78)
    • Rumen may be partially filled with light-green to grey watery froth in captive individuals; this is seen rarely in free-ranging individuals. (B336.78.w78)
  • Respiratory:
    • Pneumonia (secondary) in some individuals. (J1.16.w10)
    • Aspiration pneumonia in some individuals (terminal, secondary). (J64.11.w3)
    • Aspiration pneumonia in some individuals (terminal, secondary). (P42.12.w1)
    • Sub-acute to chronic bronchopneumonia in 8/41 free-living deer from Colorado. (J1.33.w10)
    • Aspiration pneumonia is a common finding. (B336.78.w78)
  • Other: 
    • Adrenal glands: Marked enlargement in 16/41 free-living deer from Colorado. (J1.33.w10)

Odocoileus hemionus - Mule deer x Odocoileus virginianus - White-tailed deer:

  • General:
    • Emaciation with lack of body fat and in terminal cases severe muscular atrophy. (J64.11.w3)
  • Central Nervous System:
    • No gross lesions. (J64.11.w3)
  • Digestive Tract:
    • Rumen: contents extremely fluid or frothy; often sand or gravel noted (may be more visible due to fluid contents). (J64.11.w3)
    • Oesophagus: occasionally may be greatly dilated and filled with fluid. (J64.11.w3)
  • Respiratory:
    • Aspiration pneumonia in some individuals (terminal, secondary). (J64.11.w3)
  • Renal:
    • --

Odocoileus virginianus - White-tailed deer:

  • General:
    • Severe emaciation in a free-living individual from Colorado. (P2.43.w1)
    • Severe emaciation; total loss or serous atrophy of adipose tissue in a free-living individual from Colorado. (P4.1.w4)
    • Emaciation with generalised absence of subcutaneous and visceral adipose tissue or serous atrophy, and yellow gelatinous bone marrow, in free-living deer from Colorado. (J1.33.w10)
  • Respiratory:
    • Sub-acute to chronic bronchopneumonia in 1/2 free-living deer from Colorado. (J1.33.w10)

Bos taurus - Domestic cattle:

  • General:
    • Emaciation in two calves with two to three month histories of inappetance and weight loss; experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)
  • Respiratory:
    • Large pulmonary abscess in one calf without other gross findings; experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)

Other TSE Diseases

Transmissible Mink Encephalopathy:

Mustela vison - American mink:

  • General:
    • Generally "a conspicuous absence of lesions." Data from three epizootics on eight or nine mink farms in Wisconsin, USA in 1947, 1961 and 1963. (J100.115.w1)
    • No gross lesions. Data from an outbreak in Ontario, USA in 1963. (J14.9.w1)
    • No gross lesions. (J13.30.w1)
  • Central Nervous System:
    • Occasionally mild oedema of the brain. Data from three epizootics on eight or nine mink farms in Wisconsin, USA in 1947, 1961 and 1963. (J100.115.w1)
    • No gross lesions. Data from an outbreak in Ontario, USA in 1963. (J14.9.w1)

Ovis aries - Domestic sheep:

  • General:
    • Two of five affected animals were noted to be extremely thin. Following intracerebral inoculation with the Idaho strain of TME. (J240.51.w1)

Saimiri sciurius - Squirrel monkey (Cebidae - New-world monkeys (Family)):

  • General:
    • No gross lesions. (J22.169.w1)
  • Central Nervous System:
    • No gross lesions. (J22.169.w1)

Scrapie:

Ovis aries - Domestic sheep:

  • General: The carcass may be thin. There may be areas of wool loss and the skin may be rubbed raw in some places. (J64.11.w4)

Ovis orientalis - Mouflon (Ovis musimon):

  • General:
    • No gross pathology. (J3.130.w4)

Mustela vison - American mink:

  • General: No gross pathology. In 5/5 mink inoculated with brain material from a scrapie-affected Suffolk sheep. (J22.172.w1)

Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer):

  • General: No gross pathology. Following experimental infection by intracerebral inoculation of elk calves with scrapie brain. (J26.40.w1)

Bovine Spongiform Encephalopathy (BSE):

  • No specific gross lesions; there may be wasting and there may be signs of trauma secondary to ataxia in some individuals. There are variations in the distribution of lesions depending on the prion disease and on the species (and strains in at least some species) of the host. (B23.101.w4)

Acinonyx jubatus - Cheetah (Felidae - Cats (Family))

  • General:
    • No gross lesions. (J24.69.w1)
    • No gross lesions. (J2.26.w2)
    • [No gross lesions described in two animals]. (J3.135.w1)

Felis catus - Domestic cat

  • General:
    • No gross lesions. (J3.126.w4)
    • No gross lesions. (J3.127.w4)
    • No significant gross lesions. (J3.129.w3)

Felis concolor - Puma (Felis - (Genus)):

  • General:
    • No gross lesions other than bruising consistent with falling. (J3.131.w2)

Oryx dammah - Scimitar oryx:

  • General:
    • [No lesions reported]. (J3.135.w1)
Oryx gazella - Gemsbok:
  • General:
    • [No lesions reported]. (J26.25.w1)
Oryx leucoryx - Arabian oryx:
  • General:
    • Thin. Reduced fat deposits and serous atrophy of epicardial fat. (J3.127.w3)

Taurotragus oryx - Eland:

  • General:
    • No significant lesions. (J3.126.w3)

Tragelaphus angasii - Nyala:

  • General:
    • No significant lesions; general body condition good. (J26.25.w1)

Tragelaphus strepsiceros - Greater kudu:

  • General:
    • Thin. No appreciable fat deposits. (J3.127.w3)
    • No gross lesions. (J3.130.w3)
    • [No gross lesions noted]. (J3.134.w4)
  • Central Nervous System:
  • Digestive Tract:
  • Respiratory:
    • Acute aspiration pneumonia (apical lobes). (J3.127.w3)
    • Generalised pulmonary oedema. (J3.127.w3)
  • Musculoskeletal:
    • Bilateral bruising of the proximal musculature of the hind legs, particularly the left leg. (J3.127.w3)
Overall Histological, Immuno- histochemistry and Electron- microscopical Findings
  • Central Nervous System:
    • In animals with clinical CWD typical TSE lesions are seen in the parasympathetic vagal nucleus in the dorsal medulla oblongata, at the obex, also in the hypothalamus, thalamus, olfactory tracts and cortex. Spongiform change varying in severity may be seen in the thalamus and cerebellum while generally only mild lesions are present in the cerebral cortex, hippocampus and basal ganglia. (J64.21.w17)
    • Spongiform degeneration of neuropil, vacuolar degeneration and loss of neurons, mild astrocytosis. (B336.78.w78)
    • Immunohistochemistry: Patterns of immunostaining include "granularity and amorphous clumps on neuronal membranes, perivascular aggregates, and large apparently extracellular accumulations of PrPCWD." (J64.21.w17)
    • Scrapie-associated fibrils may be found. (J64.21.w17)
    • Scrapie-associated fibrils were detected in the brains of 12 free-living animals by immunohistochemical staining and in a further six by Western blot [in a paper on findings in free-ranging deer and elk in Colorado]. (P4.1.w4)
  • Spleen, tonsils, lymph nodes:
    • Lymphoid depletion may be seen in the spleen, tonsils and lymph nodes of individuals in the terminal stages of CWD. (B336.78.w78)
    • Scrapie-associated fibrils may be found. (J64.21.w17)
  • Respiratory system:
    • Bronchiopneumonia may be noted. (B336.78.w78)
  • Digestive tract: 
    • Lesions of gastric ulceration and associated peritonitis may be seen. (B336.78.w78)
  • Adrenals:
    • Adrenal cortical hypertrophy may be seen. (B336.78.w78)
  • Other:
    • Serous atrophy of fat may be seen. (B336.78.w78)

Studies of formalin-fixed tissues from mule deer, mule deer x white-tailed deer hybrids and elk: 

  • Central Nervous System:
    • Spongiform change were present in the neuropil, predominantly in the grey matter, varying in severity and were seen in the spinal cord, medulla oblongata, pons, mesencephalon, thalamus, hypothalamus and cerebellar cortex. In the olfactory regions, and specific nuclei within the thalamus, mesencephalon and medulla oblongata there was consistent extensive vacuolation. In Purkinje cells (also in other neurons in all areas of the brain), there were multiple or single intracytoplasmic vacuolations. In 11/17 mule deer but not in two elk or two hybrid deer, congophilic birefringent amyloid plaques were seen, mainly in the grey matter, being numerous in the brain stem and cerebellum but less numerous in the cerebrum; PAS-positive plaques were seen also in the mule deer but were seen only rarely in the hybrid deer and were not seen in the elk. (B296.12.w12)
      • Immunohistochemistry: Scrapie-amyloid (PrP) immunoreactive plaques were detected in 15/17 mule deer. These were found scattered throughout the brain in both grey and white matter, around blood vessels and in both the subpial and subependymal regions and were 2-4 Ám diameter, found singly or in clusters within areas of vacuolation. In the cerebellum such plaques were found in the pyramidal, molecular and granular cell layers. Immunoreactive material was noted also in neuronal perikarya. In the granular layer of the cerebellum and occasionally in the cerebral cortex circumscribed clusters of nuclei, involving 10-30 nuclei, and 0.01 mm in size were immunostained. PrP immunoreactive plaques were seen in both mule deer x white-tailed deer hybrids. These were similar in size to those seen in the mule deer but were rarely found in the subpia or the cerebellum. Circumscribed clusters of nuclei of astrocytes, neurons and microglia were found (as in mule deer), about 12-15um diameter, occasionally with a central immunoreactive deposit and mostly in the cerebral cortex. Five elk all showed the presence of PrP-immunoreactive plaques. Numerous circumscribed clusters of immunopositive nuclei of astrocytes, neurons and microglia were present, of variable size, some with a nonbirefringent amyloid plaque at the periphery and many with central immunoreactive deposits. Amyloid plaques, which were less numerous than in mule deer, were 7-17Ám diameter, some surrounded peripherally by immunopositive nuclei; they were rarely seen around blood vessels and were not present in the subpia, subependyma or cerebellum. It was considered that the presence of numerous noncongophilic, nonbirefringent, scrapie-amyloid-immunoreactive plaques in the elk might be explained by "the abundance of scrapie-amyloid precursor proteins (PrPsc) rather than scrapie-amyloid fibril". It was suggested that the differences in number and topographic distribution of amyloid plaques in the three species might be attributed to differences in route of natural inoculation, dose of infectivity, and host genotype. (B296.12.w12)

Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer):

  • Central Nervous System:
    • "Spongiform transformation of the neuropil, predominantly of the gray matter and to a lesser degree the white matter, by single or multiple intracytoplasmic vacuoles in neuronal perikaryons, and by neuronal degeneration." Charges were widespread and variable in severity. The cerebral cortex and basal ganglia were the only areas not affected. Gold sublimate stained sections revealed astrocytic hypertrophy and hyperplasia. Inflammatory changes were absent. It was noted that the hypothalamus consistently showed degenerative changes and the supraoptic and paraventricular nuclei contained specific lesions in some individuals; it was considered possible that such lesions may have affected production of antidiuretic hormone and led to the observed low urine specific gravity. (J1.18.w7)
    • Scrapie amyloid-immunoreactive plaques were found in both grey and white matter, occasionally round blood vessels but were not seen in subpial or subependymal regions. There were only a few plaques but they were large (60-150Ám diameter). A notable finding was "the presence of numerous circumscribed clusters of nuclei of neurons, astrocytes and microglia, with deposits at its center immunoreactive to anti-scrapie amyloid, of variable sizes predominantly in the grey matter, some with immunoreactive amyloid plaque at its periphery and many with immunoreactive deposit centrally which were non-birefringent." Surrounding the periphery of some condensed immunoreactive plaques were immunopositive nuclei. A further observation was the presence of intracytoplasmic scrapie amyloid-immunoreactive material, particularly in large neurons. PAS-positive, alcinophilic, argentophilic, congophilic and birefringent amyloid plaques were not observed. (J225.126.w1)
    • "Presence of scrapie-associated fibrils in the spleen and/or brain of both affected deer and elk." (J64.11.w3)
    • Lesions seen include spongiform change of the grey matter neuropil, intraneuronal vacuolation, hypertrophy and hyperplasia of astrocytes and the presence of amyloid plaques. Lesions are bilaterally symmetrical and there is no inflammation. Lesions are less severe in the olfactory tubercle and cortex, the hypothalamus and the parasympathetic vagal nucleus than in the same regions in Odocoileus spp. deer. Other regions affected include the thalamus, hypothalamus, midbrain, pons and medulla oblongata. Changes in the cerebellum, cerebral cortex, hippocampus and basal nuclei are milder. Mild white matter lesions occur (these are absent in Odocoileus spp. deer). Amyloid plaques are less easily observed than in Odocoileus spp. deer using histochemical stains but may be visualised utilising immunostaining with anti-PrP serum. (J64.11.w3)
    • Microscopic lesions typical of the TSEs: bilaterally symmetrical lesions including spongiform disruption of the neuropil of the grey matter, intraneuronal vacuolation, hypertrophy and hyperplasia of astrocytes, amyloid plaques and absence of inflammation). Amyloid plaques are relatively difficult to visualise with haematoxylin and eosin but are congophilic, PAS-positive, argentophilic and alcinophilic and they are immunoreactive with anti-PrP serum. In most affected elk severe lesions may be found in the olfactory tubercle and cortex, hypothalamus and parasympathetic vagal nucleus. (P42.12.w1)
    • Lesions were basically bilaterally symmetrical. Spongiform degeneration of the grey matter was the most striking change. Spaces within the neuropil were round to elliptical and were mainly 5-25Ám approximate diameter, with a range from barely perceptible to about 70Ám. Vacuole borders were generally distinct buy occasionally indistinct or irregular. Vacuoles were often clustered, sometimes appearing multilocular and occasionally were seen surrounding neurons (and often indenting the cytoplasm) or amyloid plaques. Vacuoles were also commonly found within neurons; these vacuoles were widely distributed in most levels of the brain. They were generally found in cells within regions of spongiform change of the neuropil. Multiple intracytoplasmic vacuoles were observed frequently, particularly within neurons in the caudal nuclei. Occasionally vacuoles displaced nuclei to the periphery of cells, this occurred particularly in Purkinje cells which frequently contained large vacuoles. Neurons which were shrunken, angular and hyperchromatic were commonly observed particularly in the cerebral cortex; these were present in smaller numbers in control (CWD-unaffected) brains and were considered to be artefacts. Central chromatolysis of the neuronal perikarya was frequently observed particularly in large multipolar neurons of the brain stem. Neuronal loss, particularly in the thalamus, could be appreciated best by comparing nuclei of affected brains with those of unaffected brains. Increased size and number of astrocytes, and their number of processes, were most evident within areas of spongiform degeneration in the thalamus and brain stem and were visualised better with Cajal's method than with haematoxylin and eosin staining. Plaques visible in Odocoileus spp. deer were not seen with various stains but did react to scrapie-amyloid antibodies. Lesions in white matter were mild, occurred mainly in the cerebrum and cerebellum and were characterised by rarefaction, particularly in the cerebellar subcortical regions. Other features were the occasional presence of spheroids and a few myelin sheathes were dilated and contained debris (from axonal degeneration); there was no significant loss of myelin. Occasional lymphocytic cuffing of blood vessels was found and sometimes mild lymphocytic infiltration of the choroid plexus however these are not unusual findings in elk. (J26.30.w1) Topographically the lesions were distributed as follows:
      • Telencephalon: Within the neocortex, mild scattered foci of spongiform degeneration in the middle and deep layers , with a few vacuolated neurons present. Mild white matter lesions were present. In the olfactory bulb and tubercle severe spongiform change disrupting the neuropil with neuronal shrinkage, prominent cytoplasmic neuronal vacuolation, neuropil disruption and astrocytosis. In the basal nuclei small scattered foci of spongiform change were common. (J26.30.w1)
      • Diencephalon: Within the thalamus, mild to moderate lesions with astrocytosis loss of neurons and spongiform degeneration. In elk lesions in the ventral rostral nucleus and the ventral nucleus were more prominent than they were in deer. Damage to the medial and lateral geniculate nuclei was considerable. Occasional small areas of rarefaction in the pineal could also be seen in animals not affected by CWD. In the hypothalamus of most deer were moderate to severe diffuse lesions with marked rarefaction and spongiform change of the neuropil together with shrinkage and angulation of neurons. In the supraoptic and paraventricular nuclei were large, optically empty vacuoles, greatly distorting most neurons in these nuclei, but the neuropil showed only mild astrocytosis, no other abnormalities. In the posterior pituitary mild spongiform change was seen, although similar changes, to a lesser degree, were seen in control non-affected animals. (J26.30.w1)
      • Mesencephalon: Generally mild changes, with mild lesions in the rostral and caudal colliculi. Lesions of individually-varying severity affected the central grey matter; lesions in the red nucleus, if present, were mild. In the substantia nigra mild spongiform and vacuolar changes were seen occasionally but unlike in deer these areas were frequently unaffected. (J26.30.w1)
      • Pons and medulla oblongata: Generally milder changes than those seen in the diencephalon, except for the conspicuous presence of vacuolated and occasionally chromatolytic neurons. The parasympathetic vagal nucleus was consistently and severely affected (less so than in deer) with severe disruption of the neuropil and numerous vacuolated and degenerate neurons. The solitary tract nucleus was mildly to severely affected in most individuals, the lateral cuneate nucleus contained mild lesions. The degree to which the pontine and medullary nuclei were affected varied considerably between individuals. (J26.30.w1)
      • Cerebellum: Most animals had mild changes in the cerebellar cortex, generally involving focal spongiform change in the molecular layer and prominent intracytoplasmic vacuolation of Purkinje cells; lesions were most numerous in the lingula, uvula and nodulus regions. (J26.30.w1)
      • Spinal cord: Usually mild lesions, with the dorsal hors showing vacuolar degeneration and slight spongy degeneration of neuropil, while white matter was generally unaffected and the spinal nerve roots and dorsal root ganglia were unaffected. (J26.30.w1)
    • Presence of abnormal fibrils (scrapie-associated fibrils) and a protease-resistant protein, molecular weight 17-30kd in extracts of brain. (J239.34.w1)
    • Scrapie-associated fibrils (SAFs) were visible in brain tissue. (J1.33.w10)
    • "Spongiform encephalopathy, characterized by microcavitation of grey and/or white matter, intraneuronal vacuolation and neuronal degeneration." (P2.43.w1, P4.1.w4)
    • Spongiform encephalopathy with microcavitation primarily of the grey matter, with single or multiple intracytoplasmic vacuoles in the neuronal perikarya and neuronal degeneration. Within areas of spongiform change could be found hypertrophy and hyperplasia or astrocytes, with fibrillary proliferation. In the telencephalon the olfactory bulbs, olfactory stria and septal nuclei were most severely affected. In the diencephalon the thalamic nucleus, supraoptic nucleus and paraventricular nucleus were most severely affected. In the mesencephalon the central grey substance and tegmental nuclei were most severely affected and in the medulla oblongata the areas most severely and consistently affected were the neurons of the reticular formation the hypoglossal nucleus, the parasympathetic vagal nucleus, the medial and lateral cuneatus nuclei and the nucleus of the spinal tract of the trigeminal nerve. In addition, lesions were sometimes present in the oculomotor nucleus, interpeduncular nucleus, red nucleus, habenular nucleus and the pons. Neurons of the cerebral cortex and cerebellum, including Purkinje cells, were affected only occasionally, as were neurons of the spinal cord grey matter; the molecular layer of the cerebellum occasionally contained small areas of microcavitation.  (J1.33.w10)
    • Spongiform encephalopathy with microcavitation mainly of the grey matter, single or multiple intracytoplasmic vacuoles in neuronal perikarya and neuronal degeneration. Lesion severity and distribution did not differ appreciably despite variations in the stage of clinical disease at euthanasia in four female elk from a cohort hand-reared at a wildlife research facility in Colorado in 1986. (J1.34.w6)
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
    • Lesions including spongiform change of the grey matter neuropil, vacuolated neurons and mild gliosis in two animals which had shown clinical signs and in one animal which had not shown clinical signs; mild spongiform change in the grey matter of the cerebrum and medulla oblongata, with a few vacuolated neurons and mild gliosis in the brain stem and spinal cord were seen in another animal without clinical signs. These and six others (total 10/17 animals) from a captive elk herd were positive for PrPres with immunohistochemistry. (J212.12.w2)
    • Spongiform change in several nuclei in the brain stem, consisting of small vacuoles in grey matter neuropil. In the peripheral cytoplasm of neurones single or small multiple vacuoles were found. In most brain sections the number of astrocytes was increased. In the cerebral cortex angular, shrunken, hyperchromatic neurons were found commonly. In the cerebellar cortex there was focal spongiform change in the molecular layer, with prominent intracytoplasmic vacuolation of Purkinje cells. (J27.64.w1)
    • Obex: moderate astrocytosis and marked neuron and neuropil vacuolation in the dorsal vagal motor nuclei, spinal tract and reticular formation. Two-year old female elk from a game farm in Canada, 2001. (J14.43.w1)
    • In 46 clinically normal elk on an infected elk farm in Saskatchewan, Canada, shown to be CWD-positive by IHC, lesions of vacuolation varied from absent (eight animals) through low-grade vacuolation of the neuropil in the DMNV only (27 animals), to more widespread vacuolation of the neuronal perikarya and neuropil, and astrocytosis (11 animals). (P46.1.w4)
    • Ultrastructural changes seen with transmission electron microscopy: "Membrane-bound vacuoles in dendrites and axons; myriads of glial filaments of hypertrophied astrocytes; numerous neuritic plaques indistinguishable from those in the brains of patients with Alzheimer's disease; abundant dystrophic neurites; Hirano bodies; and activated microglia." (J239.34.w1)
    • Ultrastructural changes seen with transmission electron microscopy: Vacuoles within the neuropil, varying in shape and size and containing secondary vacuoles and curled fragments of membrane; only neuronal elements contained membrane-bound vacuoles. In astroglial processes were bundles of large numbers of glial filaments, cross-sectioned and/or parallel-arranged. Dystrophic neurites of varying sizes, containing abnormal mitochondria at various stages of degeneration as well as numerous pleomorphic membrane-bound structures and electron-dense bodies. Collections of two or more dystrophic neurites were seen forming neuritic plaques (similar to those seen in the brain of patients with Alzheimer's disease). Additionally these were activated macrophages with numerous lysosomes, Hirano bodies and perikaryal inclusion bodies in neurons. Findings were noted to be very similar to those seen in mule deer Odocoileus hemionus affected with CWD. (J226.32.w1)
    • Ultrastructural findings: "membrane-bound vacuoles in neuronal elements, increased number of glial filaments, dystrophic neurites, numerous neuritic plaques, Hirano bodies and perikaryal inclusion bodies." (P44.38.w1)
    • By electron microscopy, scrapie-associated fibrils (SAFs) were visible in brain tissue. (J1.33.w10)
    • By negative-stain electron microscopy and immunoblotting: Abnormal fibrils, in aggregates or in isolation, short, 10-20nm diameter and consisting of one to two straight protofilaments. Using partially purified protein preparations, protein bands between 26-30 kDa were recognised by anti-scrapie amyloid antiserum by Western blotting and this reaction was confirmed by immuno-dot blot. The strength of the reaction to the protein from CWD-affected elk was weaker than that to protein from hamsters experimentally infected with scrapie, suggesting differences in strains. (J224.86.w1)
    • By electron microscopy: presence of scrapie-associated fibrils in brain tissue of the only case examined. (J1.34.w6)
    • By immunohistochemistry using monoclonal antibody (MAb) F89/160.1.5: positive staining in the brains of 4/4 CWD-affected elk and in 0/12 control (unaffected) elk. (J93.36.w1)
    • By immunohistochemistry: The presence of PrPres was detected in the brains of 10/17 elk from a captive herd. The greatest staining was in the brains of two animals with clinical signs and histological lesions of the brain consistent with CWD, followed by one animal without clinical signs but with histological lesions of the brain consistent with CWD, then an animal with histological lesions suggestive of CWD, and the least staining was seen in six animals without any clinical signs or histological brain lesions suggestive of CWD. (J212.12.w2)
    • Immunohistochemistry: Medulla oblongata, particularly at the level of the obex: strong positive reactions in the dorsal motor nucleus of the vagus, the spinal tract nucleus of the trigeminal nerve, the olivary nucleus and the reticular formation. Also positive staining in the red nucleus of the midbrain, the pontine nucleus and the greater thalamic nucleus. In the cerebral cortex and the cerebellar cortex staining was greater in the outer granular layer than in the molecular layer. Deposits included perineural aggregations, diffusely scattered granules in the grey matter, perivascular aggregations and floccular plaques. Deposits were also noted in the "cytoplasm of ependymal cells or adjacent to affected neuropil." (J27.64.w1)
    • Immunoblotting: PrPres detected by Western blotting in the brain and spinal cord (pooled sample). (J27.64.w1)
    • Immunohistochemistry: Presence of PrP: dorsal motor nuclei of the vagus stained densely and bilaterally symmetrically. Two-year old female elk from a game farm in Canada, 2001. (J14.43.w1)
    • Immunohistochemistry: In 46 clinically normal elk on an infected elk farm in Saskatchewan, Canada, shown to be CWD-positive by IHC, mild (1+) focal bilaterally symmetrical IHC staining was found in eight animals without detectable brain lesions. In 27 animals with low-grade vacuolation of the neuropil in the DMNV only IHC staining was considered to be mild (2+) to moderate (3+) and in 11 animals with more widespread vacuolation of the neuronal perikarya and neuropil, and astrocytosis staining was mild (2+) to extensive (4+). (P46.1.w4)
  • Spleen:
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
    • "Presence of scrapie-associated fibrils in the spleen and/or brain of both affected deer and elk." (J64.11.w3)
  • Lymphoid tissues:
    • "PrPCWD does not appear to accumulate in lymphoid tissue to the same degree in elk as in deer." (J223.83.w1)
    • Accumulation of PrPres in lymphoid tissues occurs relatively late in the course of CWD infection. (P40.1.w18)
  • Other tissues:
    • No consistent histopathological changes in extraneural tissues. (J1.18.w7)
    • Respiratory: congestion of lung parenchyma, multiple foci of atelectasis. Two-year old female elk from a game farm in Canada, 2001. (J14.43.w1)
    • Hepatic: Mild atrophy of lobules. Two-year old female elk from a game farm in Canada, 2001. (J14.43.w1)

Odocoileus hemionus - Mule deer:

  • Central Nervous System:
    • "Primary diffuse progressive spongiform encephalopathy." (P2.29.w1)
    • "Widespread microcavitation or spongiform transformation of the neuropil, predominantly of gray matter, single or multiple intracytoplasmic vacuoles in neuronal perikaryons and by neuronal degeneration." Varying severity of spongiform change in different areas: gray matter of the spinal cord, medulla oblongata, pons, mesencephalon, thalamus, hypothalamus, cerebellar cortex. Focal lesions were found in the cerebral cortex, with the olfactory regions of the frontal lobes particularly affected. Consistent severe lesions in specific nuclei of the thalamus, mesencephalon and medulla oblongata, with astrocytic hypertrophy and fibrillary hyperplasia visible in gold sublimate stained sections of these regions. N.B. lesions in the hypothalamus (found consistently) may be responsible for the diabetes insipidus-like polyuria/polydipsia noted in affected animals. (J1.16.w10)
    • "Histological lesions of spongiform encephalopathy." Following experimental infection by intracranial inoculation of a suspension of brain tissue from an affected mule deer. (P2.31.w1)
    • Amyloid plaques in the tissues of 13/21 animals (62%). Described as scattered argyrophilic regions seen with Bodian silver-stained sections at low magnification, diameter 14-75Ám. Large plaques only in cerebral cortical tissues, small and medium plaques in deep grey matter of various parts of brain and spinal cord. Also visible with Congo red, having distinctive negative birefringence (red to green dichromatism) with polarised light. Additionally foci of perivascular amyloid deposition: amorphous fragments at the periphery of capillaries, with more significant negative birefringence at the arterial than venous ends. Not easily visible with haematoxylin and eosin (H&E) stain; astrocytic nuclei often seen collected around the periphery of the plaques. (J42.95.w1)
    • Amyloid plaques, periodic acid-Schiff (PAS) positive; Congophilic, birefringent amyloid plaques visible in 11/17 cases. In 15/17 deer plaques were scrapie amyloid-immunoreactive. These plaques could be seen in isolation or clustered in areas with extensive vacuolation. Plaques were small (21-42Ám diameter) and were found scattered in both the grey matter and the white matter "in all areas of the brain, around blood vessels and in the subpia and subependyma." Within the cerebellum such plaques could be seen in the molecular, pyramidal and granular layers. Immunoreactive material was observed "in the neuronal perikyma in the granular layer of the cerebellum, in the brain stem and several other areas of the brain." In the granular layer of the cerebellum and occasionally in the cerebral cortex immunostained circumscribed clusters of nuclei were found. The presence of sulphated glycosaminoglycans in the scrapie amyloid-immunoreactive plaques was shown by staining with 0.3M and 0.7M MgCl2 Alcian blue. (J224.81.w1)
    • "Presence of scrapie-associated fibrils in the spleen and/or brain of both affected deer and elk." (J64.11.w3)
    • Lesions seen include spongiform change of the grey matter neuropil, intraneuronal vacuolation, hypertrophy and hyperplasia of astrocytes and the presence of amyloid plaques. Lesions are most severe in the olfactory tubercle and cortex, the hypothalamus and the parasympathetic vagal nucleus than in the same regions in Odocoileus spp. deer. Other regions affected include the thalamus, midbrain, pons and medulla oblongata. Changes in the cerebellum, cerebral cortex, hippocampus and basal nuclei are milder. Amyloid plaques, difficult to see using haematoxylin and eosin staining, may be more easily visualised with other stains, being congophilic, PAS-positive, alcinophilic and argophilic. (J64.11.w3)
    • Microscopic lesions typical of the TSEs: bilaterally symmetrical lesions including spongiform disruption of the neuropil of the grey matter, intraneuronal vacuolation, hypertrophy and hyperplasia of astrocytes, amyloid plaques and absence of inflammation). Amyloid plaques are relatively difficult to visualise with haematoxylin and eosin but are congophilic, PAS-positive, argentophilic and alcinophilic and they are immunoreactive with anti-PrP serum. Severe lesions may be found in the olfactory tubercle and cortex, hypothalamus and parasympathetic vagal nucleus.(P42.12.w1)
    • "Chromatolytic ballooned neurons with eccentric nuclei, neuronal satellitosis, single and multiple intraneuronal vacuolations, status spongiosus of the neuropil and astrocytic hyperplasia and hypertrophy. Purkinje cells, in particular, showed varying degrees of cytoplasmic vacuolations and fenestrations, and axonal vacuolation. Loss of Purkinje cells and replacement with vacuoles, reduced numbers of granule cells, numerous axonal spheroids in the granular and pyramidal layers were also found. Immunocytochemical findings include axonal spheroids immunoreactive to phosphorylated neurofilament-H, intracytoplasmic accumulation of neurofilament-H, astrocytic hyperplasia and hypertrophy as confirmed by immunoreactivity to glial fibrillary acidic protein, activated and resting microglia immunoreactive to antibody against ferritin. (J228.16S.w1)
    • Spongiform degeneration of the grey matter was the most striking change. Spaces within the neuropil were round to elliptical and were mainly 5-25Ám approximate diameter, with a range from barely perceptible to about 70Ám. Vacuole borders were generally distinct buy occasionally indistinct or irregular. Vacuoles were often clustered, sometimes appearing multilocular and occasionally were seen surrounding neurons (and often indenting the cytoplasm) or amyloid plaques. Vacuoles were also commonly found within neurons; these vacuoles were widely distributed in most levels of the brain. They were generally found in cells within regions of spongiform change of the neuropil. Multiple intracytoplasmic vacuoles were observed frequently, particularly within neurons in the caudal nuclei. Occasionally vacuoles displaced nuclei to the periphery of cells, this occurred particularly in Purkinje cells which frequently contained large vacuoles. Neurons which were shrunken, angular and hyperchromatic were commonly observed particularly in the cerebral cortex; these were present in smaller numbers in control (CWD-unaffected) brains and were considered to be artefacts. Central chromatolysis of the neuronal perikarya was frequently observed particularly in large multipolar neurons of the brain stem. Neuronal loss, particularly in the thalamus, could be appreciated best by comparing nuclei of affected brains with those of unaffected brains. Increased size and number of astrocytes, and their number of processes, were most evident within areas of spongiform degeneration in the thalamus and brain stem and were visualised better with Cajal's method than with haematoxylin and eosin staining. Irregularly rounded pale eosinophilic plaques, about 30-100um diameter, were seen particularly in the cerebral cortex and diencephalon. These were visible with haematoxylin and eosin staining, PAS positive, strongly argentophilic and with Congo red showed birefringence in polarised light: typical of amyloid. Such plaques were occasionally found in relatively normal areas of neuropil but more commonly were surrounded by vacuoles. Lesions in white matter were present only rarely. Occasional lymphocytic cuffing of blood vessels was found and sometimes mild lymphocytic infiltration of the choroid plexus however these are not unusual findings in deer. (J26.30.w1)  Topographically the lesions were distributed as follows:
      • Telencephalon: mild scattered foci of spongiform degeneration in the middle and deep layers of the neocortex, with a few vacuolated neurons present. Amyloid plaques were relatively easy to appreciate. In the olfactory bulb and tubercle severe spongiform change disrupting the neuropil with neuronal shrinkage, prominent cytoplasmic neuronal vacuolation, neuropil disruption and astrocytosis. In the basal nuclei small scattered foci of spongiform change were common.(J26.30.w1)
      • Diencephalon: Within the thalamus, mild to moderate lesions with astrocytosis loss of neurons and spongiform degeneration. Lesions in the ventral rostral nucleus and the ventral nucleus were less prominent than they were in elk. Damage to the medial and lateral geniculate nuclei was considerable. Occasional small areas of rarefaction in the pineal could also be seen in animals not affected by CWD. In the hypothalamus of most deer were moderate to severe diffuse lesions with marked rarefaction and spongiform change of the neuropil together with shrinkage and angulation of neurons. In the supraoptic and paraventricular nuclei were large, optically empty vacuoles, greatly distorting most neurons in these nuclei, but the neuropil showed only mild astrocytosis, no other abnormalities. In the posterior pituitary mild spongiform change was seen, although similar changes, to a lesser degree, were seen in control non-affected animals. (J26.30.w1)
      • Mesencephalon: Generally mild changes, with mild lesions in the rostral and caudal colliculi. Lesions of individually-varying severity affected the central grey matter; lesions in the red nucleus, if present, were mild. In the substantia nigra mild spongiform and vacuolar changes were seen and tegmental nuclei were moderately damaged.  (J26.30.w1)
      • Pons and medulla oblongata: Generally milder changes than those seen in the diencephalon, except for the conspicuous presence of vacuolated and occasionally chromatolytic neurons. The parasympathetic vagal nucleus was consistently and severely affected with severe disruption of the neuropil and numerous vacuolated and degenerate neurons. The solitary tract nucleus was mildly to severely affected in most individuals, the lateral cuneate nucleus contained mild lesions as did the median raphe. The degree to which the pontine and medullary nuclei were affected varied considerably between individuals and in deer those individuals which had shown a long clinical course of disease had the most severe involvement. (J26.30.w1)
      • Cerebellum: Most animals had mild changes in the cerebellar cortex, generally involving focal spongiform change in the molecular layer and prominent intracytoplasmic vacuolation of Purkinje cells; lesions were most numerous in the lingula, uvula and nodulus regions. (J26.30.w1)
      • Spinal cord: Usually mild lesions, occasionally moderate, with the dorsal hors showing vacuolar degeneration and slight spongy degeneration of neuropil, while white matter was generally unaffected and the spinal nerve roots and dorsal root ganglia were unaffected. (J26.30.w1)
    • "Spongiform encephalopathy, characterized by microcavitation of grey and/or white matter, intraneuronal vacuolation and neuronal degeneration." (P2.43.w1, P4.1.w4)
    • Spongiform encephalopathy with microcavitation primarily of the grey matter, with single or multiple intracytoplasmic vacuoles in the neuronal perikarya and neuronal degeneration. Within areas of spongiform change could be found hypertrophy and hyperplasia or astrocytes, with fibrillary proliferation. In the telencephalon the olfactory bulbs, olfactory stria and septal nuclei were most severely affected. In the diencephalon the thalamic nucleus, supraoptic nucleus and paraventricular nucleus were most severely affected. In the mesencephalon the central grey substance and tegmental nuclei were most severely affected and in the medulla oblongata the areas most severely and consistently affected were the neurons of the reticular formation, the hypoglossal nucleus, the parasympathetic vagal nucleus, the medial and lateral cuneatus nuclei and the nucleus of the spinal tract of the trigeminal nerve. In addition, lesions were sometimes present in the oculomotor nucleus, interpeduncular nucleus, red nucleus, habenular nucleus and the pons. Neurons of the cerebral cortex and cerebellum, including Purkinje cells, were affected only occasionally, as were neurons of the spinal cord grey matter; the molecular layer of the cerebellum occasionally contained small areas of microcavitation.  (J1.33.w10)
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
    • In both free-ranging and captive mule deer the most significant and consistent lesions were spongiform degeneration of the gray matter neuropil and intracytoplasmic neuronal vacuolation and degeneration. The areas most severely affected were the dorsal motor nucleus of the vagal nerve (DMNV), solitarious nucleus, hypothalamus, thalamus and olfactory cortex, which lesions in other regions, including the mesencephalon, metencephalon and myelencephalon were milder. Loss of neurons was seen most in the DMNV, hypothalamus and thalamus. Spongiform degeneration of the grey matter neuropil was often seen surrounding vacuolated neurons. Within the neuronal perikarya single or multiple vacuoles were present. Typical changes on the periphery of neurons and in the grey matter neuropil included microcavitation, elliptical spaces and vacuoles. The molecular layer of the cerebrum commonly contained single and multiple vacuoles. In four animals (two captive, two free-ranging) examined by staining for glial fibrillar astrocytic protein (GFAP), mild to moderate astrocytosis was seen in the thalamus, hypothalamus and the obex of the medulla oblongata. (J26.39.w1)
    • Histologically following experimental oral infection. Lesions of spongiform encephalopathy were first found at sixteen months post infection in the medulla oblongata at the lateral aspect of the parasympathetic vagal nucleus. (P2.49.w1)
    • By immunohistochemical staining: protein "antigenically indistinguishable from PrPSc" was demonstrated in 10/10 animals with CWD. (J1.33.w10)
    • With Western blotting: PrP was detected in 7/7 animals with CWD.  (J1.33.w10)
    • Ultrastructural changes seen with electron microscopy from samples of olfactory region of the frontal cortex, thalamus and midbrain of one animal. "Extensive membrane-bound vacuolation, prominent astrocytic gliosis, dystrophic neurites, amyloid plaques, autophagic vacuoles, occasional activated macrophages and spheroidal structures." (J224.85.w1); in detail:
      • Spongiform vacuoles presented the most striking observation. In the neuropil there were various shapes and sizes of vacuole, bound by a definite membrane and containing secondary vacuoles, curled fragments of membrane and "fluffy" material. These were seen mainly in neuronal elements although it was not possible always to determine whether they originated in dendrites or in axonal terminals or preterminals. Astrocytes and macrophages sometimes ensheathed vacuoles. Vacuoles were found unmyelinated and were found within myelinated processes, greatly distending the myelin sheath. Other findings included splitting at the major dense lines or intraperiod lines, and remnants of a shrunken axon with normal axoplasm adhering to the innermost layer of the myelin sheath. (J224.85.w1)
      • Astrocytic gliosis was noted, with proliferated hypertrophic astrocytes, their cytoplasmic processes filled with intermediate filaments, 10nm diameter. In many longitudinal, oblique and cross-sectional views of glial processes bundles of glial fibrils, arranged in parallel, were visible. In many astrocytic processes were large numbers of closely packed glial fibrils. In many areas there was a meshwork of interwoven astrocytic processes around, and sometimes replacing, cellular elements. Astrocytes contained more glycogen granules, membrane-bound dense bodies and mitochondria than usual. (J224.85.w1)
      • Dystrophic neurites presented a prominent finding; these contained numerous subcellular organelles, in particular mitochondria showing features of degeneration (varying from homogenisation to focal clearing), and numerous pleomorphic membrane-bound multigranular, multilamellar, multivesicular inclusion bodies, amorphous electron-dense bodies and neurofilaments. Such dystrophic neurites were unmyelinated (representing axonal terminals and preterminals) adjacent to blood vessels or astrocytic processes and myelinated (representing axonal segments). Within axons dystrophic neurites were seen in groups of two or more. (J224.85.w1)
      • Amyloid plaques were found in the cerebral cortex and medulla with a dense round core and a lucent periphery containing amyloid fibrils and ribosomes. Astrocytic processes, degenerating synapse and dystrophic neurites were present adjacent to the plaques; amyloid fibrils could be seen between neuritic processes adjacent to dystrophic neurites. (J224.85.w1)
      • Neuronal autophagic vacuoles, both small (within dystrophic neurites) and giant, were seen mainly in the cerebral cortex. Ribosomes, secondary lysosomes, myelin figures, mitochondria, vacuoles and vesicles were found within sequestered cytoplasm. Both vacuoles and vesicles were found within an electron-dense background. (J224.85.w1)
      • Additional findings included activated macrophages with numerous lysosomes and occasional spheroidal structures with defined edges, containing densely packed fibrillar material of unknown origin, many structures suggestive of degenerating microtubules trapped in filamentous masses, and vacuoles or myelin figures. (J224.85.w1)
    • PrPCWD plaques are visible with routine haematoxylin and eosin stain in a few clinically-affected individuals. Plaques may be stained clearly using immunohistochemical staining with monoclonal or polyclonal antibodies. (J64.21.w17)
    • Ultrastructural findings: "Extensive vacuolation in neuronal processes, within myelin sheaths, formed by splitting at the major dense lines or within axons; dystrophic neurites (dendrites, axonal preterminals and myelinated axons containing degenerating mitochondria and pleomorphic, electron dense inclusion bodies); prominent astrocytic gliosis, amyloid plaques, giant neuronal autophagic vacuoles and occasional spheroidal structures containing densely packed fibrillar material of unknown origin, abundant structures suggestive of degenerating microtubules entrapped in filamentous masses, vacuoles and myelin figures." (P44.38.w1)
    • By electron microscopy, scrapie-associated fibrils (SAFs) were visible in brain tissue. (J1.33.w10)
    • By immunohistochemistry using monoclonal antibody (MAb) F89/160.1.5: positive staining in the brains of 10/10 CWD-affected deer and in 0/15 control (unaffected) deer. (J93.36.w1)
    • By immunohistochemistry: Varying patterns of PrP deposition, including plaque-like structures, mainly florid plaques surrounded by a rim of spongiform vacuoles; these were particularly common in the medulla and basal ganglia. Florid plaques were present in 13/16 brains examined. Other PrP deposits seen included punctate synaptic-type and perivascular PrP deposits (particularly in areas with severe spongiform change) and both subpial and subependymal plaque-like deposits. Few PrP deposits were found in the cerebellum ; plaques were seen in the molecular and granular cell layers only rarely. (J224.102.w1)
    • By immunohistochemistry in mule deer following oral inoculation: Initial detection of PrPCWD in the brain was in the dorsal motor nucleus of the vagus nerve (DMNV). (P2.49.w1).
    • By immunohistochemistry in mule deer with natural infection: PrPCWD was found in the myenteric plexus, vagosympathetic trunk, nodose ganglion, pituitary, adrenal medulla and pancreatic islets of Langerhans, while scant or no PrPCWD was found in other nerves or ganglia (the brachial plexus, coeliac ganglion, cranial cervical ganglion, gasserian ganglion, sciatic nerve, spinal root nerves). In the pancreatic islets (which are innervated by the vagus), substantial deposits were often adjacent; it was suggested that this may indicate infection from a common nidus such as innervation by a common branch of the nerve. (J223.82.w1)
    • By immunohistochemical staining with a monoclonal antibody (F99/97.6.1): Coarse granular staining by the red chromogen, on the periphery around neurons and in the neuropil, frequently in plaques near or adjacent to glial cells, as well as stained plaques scattered throughout the neuropil, particularly in the thalamus. The olfactory cortex contained abundant PrPres. (J212.14.w1)
    • By immunohistochemical staining following experimental oral infection. PrPres first detected at six months post infection (not detected at three months p.i.), in the medulla oblongata at the lateral aspect of the parasympathetic vagal nucleus. (P2.49.w1)
    • By immunohistochemical staining following experimental oral infection. PrPCWD was detected in alimentary associated lymphoid tissue three months prior to consistent detection in brain tissue; the first area of the brain in which PrPCWD was detected was the parasympathetic vagal nucleus in the medulla oblongata. (J64.21.w17)
  • Spleen:
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
  • Lymphoid tissues:
    •  Using an immunohistochemical assay PrPres was detected in alimentary-associated lymphoid tissues (retropharyngeal lymph node, tonsil, Peyer's patch and/or ileocaecal lymph node) of fawns experimentally infected by oral inoculation, as early as 42 days after post inoculation and always in fawns examined at longer intervals post infection (53-80 days). PrPres was first detected in the retropharyngeal lymph node, Peyer's patches and ileocaecal lymph node at 42 days post infection but in the tonsil not until 78 days post infection. The cells associated with PrPres were found within germinal centres of lymphoid follicles and the staining pattern was considered to be morphologically consistent with that of follicular dendritic cells. (J223.80.w2)
    • Mild to moderate lymphoid depletion in both free-ranging and captive animals. (J26.39.w1)
    • Immunohistochemical staining: Strong positive staining of follicles in the tonsil, visceral and peripheral lymph nodes and Peyer's patches. Coarse granular staining filling germinal centres; the pattern of follicular staining suggested PrPres may be associated with the cell surface of follicular dendritic cells. (J26.39.w1)
    • By immunohistochemical staining with a monoclonal antibody (F99/97.6.1): In the palatine tonsil of 99/100 animals, extensive staining within the germinal centres of lymphoid follicles; staining was seen as coarse, granular bright red material and was present in more than 50% of the follicles in individuals which were positive for PrPres. One animal appeared to home no PrPres accumulation in the tonsil despite abundant deposition in the brain. (J212.14.w1)
    • By IHC: In the tonsils, PrPCWD was found to be concentrated primarily in the lymphoid follicle germinal centres, but also occasionally in perifollicular areas. PrPCWD was detected in 80 to 100% of follicles in the tonsils of deer with clinical CWD and in biopsies from deer with preclinical CWD, but in less than 30% of follicles in the tonsils of fawns examined seven to 11 weeks after experimental oral exposure to CWD. (J223.83.w2)
    • By immunohistochemistry in mule deer with natural infection: PrPCWD was found in the myenteric plexus, vagosympathetic trunk, nodose ganglion, pituitary, adrenal medulla and pancreatic islets of Langerhans, while scant or no PrPCWD was found in other nerves or ganglia (the brachial plexus, coeliac ganglion, cranial cervical ganglion, gasserian ganglion, sciatic nerve, spinal root nerves). In the pancreatic islets (which are innervated by the vagus), substantial deposits were often adjacent; it was suggested that this may indicate infection from a common nidus such as innervation by a common branch of the nerve. (J223.82.w1)
  • Ocular:
    • Vacuolated neurons were present in the ganglion cell layer of three deer (one captive, two free-ranging) examined. (J26.39.w1)
    • Immunohistochemical staining: positive staining in the optic nerve fibre layer, ganglion cell layer and both the inner and outer plexiform layers of the retina. (J26.39.w1)
  • Other tissues:
    • No consistent pathological changes in extra-neural tissues. (J1.16.w10)
    • No lesions visible in either free-ranging and captive animals within the digestive system, respiratory system, cardiovascular system, musculoskeletal system, urogenital system or integument, nor with one fetus. (J26.39.w1)
    • Immunohistochemical staining: no staining in either free-ranging and captive animals within the digestive system (except for associated lymphoid tissues), respiratory system (except for lymphoid follicles in the posterior nasal septum), cardiovascular system, musculoskeletal system, urogenital system or integument, nor with one fetus. (J26.39.w1)
    • By immunohistochemistry in mule deer with natural infection: PrPCWD was found in the pars intermedia and pars nervosa of the pituitary, adrenal medulla and the islets of Langerhans in the pancreas; in the pancreatic islets (which are innervated by the vagus), substantial deposits were often adjacent; it was suggested that this may indicate infection from a common nidus such as innervation by a common branch of the nerve. (J223.82.w1)

Odocoileus hemionus - Mule deer x Odocoileus virginianus - White-tailed deer:

  • Central Nervous System:
    • Scrapie amyloid-immunoreactive plaques were numerous (less numerous than those found in the brains of (Odocoileus hemionus - mule deer) and small, 21-42Ám diameter. They were found in isolation or in clusters in vacuolated areas. Plaques were present in all areas of the brain, in grey matter, white matter, around blood vessels and in the subependyma, and were observed in the subpia and in the cerebellum. Intracellular immunoreactive material was observed, mainly in neurons. There were circumscribed clusters of scrapie amyloid-immunoreactive nuclei with immunoreactive deposit, not demonstrable by Congo red staining, at the centres of the clusters; these clusters were 110-130Ám diameter and were found mainly in the cerebral cortex, predominantly in the grey matter. PAS-positive plaques were observed occasionally in brain sections; alcinophilic, argentophilic, congophilic and birefringent amyloid plaques were not observed. (J225.126.w1)
    • In some individuals prominent PrP plaques surrounded by spongiform change. (B294.10.w10)

Odocoileus virginianus - White-tailed deer:

  • Central Nervous System:
    • "Spongiform encephalopathy, characterized by microcavitation of grey and/or white matter, intraneuronal vacuolation and neuronal degeneration." (P2.43.w1, P4.1.w4)
    • Spongiform encephalopathy with microcavitation primarily of the grey matter, with single or multiple intracytoplasmic vacuoles in the neuronal perikarya and neuronal degeneration. Within areas of spongiform change could be found hypertrophy and hyperplasia or astrocytes, with fibrillary proliferation. In the telencephalon the olfactory bulbs, olfactory stria and septal nuclei were most severely affected. In the diencephalon the thalamic nucleus, supraoptic nucleus and paraventricular nucleus were most severely affected. In the mesencephalon the central grey substance and tegmental nuclei were most severely affected and in the medulla oblongata the areas most severely and consistently affected were the neurons of the reticular formation, the hypoglossal nucleus, the parasympathetic vagal nucleus, the medial and lateral cuneatus nuclei and the nucleus of the spinal tract of the trigeminal nerve. In addition, lesions were sometimes present in the oculomotor nucleus, interpeduncular nucleus, red nucleus, habenular nucleus and the pons. Neurons of the cerebral cortex and cerebellum, including Purkinje cells, were affected only occasionally, as were neurons of the spinal cord grey matter; the molecular layer of the cerebellum occasionally contained small areas of microcavitation.  (J1.33.w10)
    • In some individuals prominent PrP plaques surrounded by spongiform change. (B294.10.w10)
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
    • By electron microscopy, scrapie-associated fibrils (SAFs) were visible in brain tissue. (J1.33.w10)
    • PrPCWD plaques are visible with routine haematoxylin and eosin stain in most clinically-affected individuals, often made more visible by being surrounded by vacuoles in the neuropil. Plaques may be stained clearly using immunohistochemical staining with monoclonal or polyclonal antibodies. (J64.21.w17)
  • Spleen:
    • SAFs are readily identified in clinically affected individuals. (B294.10.w10)
  • Lymphoid tissues:
    • Immunohistochemistry: the presence of PrPCWD has been recorded in deer with natural infection. (J223.83.w1)
    • Limited evaluation has been successful in detecting the presence of PrPCWD in tonsillar biopsies from both free-ranging and captive white-tailed deer. (P40.1.w18)
  • Other Tissues:

Bos taurus - Domestic cattle:

  • Central Nervous System:
    • Isolated vacuolated neurons, a few degenerate axons and mild astrocytosis, in two calves. In one animal axonal degeneration and vacuolated neurons were present in the medulla oblongata at the level of the obex.; vacuolated neurons were found in the accessory cuneate nucleus and degenerate axons were some distance from the dorsal vagal nucleus; following experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)
    • Immunohistochemistry: Widespread PrPres in the cervical spinal cord and throughout the brain, with the exception of the cerebellar folia. The medulla oblongata and the midbrain contained the greatest staining. Staining was focal; most was concentrated within or around astrocytes. Additional staining included scattered particulate or granular staining in neuropil as well as occasional small (up to 40Ám diameter) plaques. In three calves following experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)
    • Western blotting: PrPres detected in brain material from three calves following experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)
    • Detection of SAFs: SAFs were detected in formalin-fixed brain of one calf and fresh brain of another calf, but not in the brain of a third calf, following experimental infection by intracerebral inoculation of a suspension of brain tissue from affected mule deer. (J212.13.w1)

Domestic ferret Mustela putorius fero (Mustela putorius - Polecat):

  • Central Nervous System:
    • "Non-inflammatory spongiform encephalopathy with widespread neuronal degeneration and necrosis." Experimental infection by intracranial inoculation of a suspension of brain tissue from an affected mule deer. (P2.31.w1)
    • Extensive spongiform degeneration, mainly in the gray matter neuropil of multiple brain regions, together with a reactive astrocytosis (shown by immunohistochemistry for astrocyte-specific protein glial fibrillary acidic protein. No amyloid plaques were found. (J20.251.w1)
    • Histological lesions including spongiform vacuolation and neuronal degeneration, following experimental infection by intracerebral inoculation of CWD-positive deer brain. (P40.1.w23)
    • Immunohistochemistry:
      • PrPCWD was shown by dual immunofluorescent staining to be localised at the astrocyte surface membranes and within neurons. Following experimental infection by intracranial inoculation of CWD-positive deer brain. (P40.1.w23)
    • ELISA: The presence of PrPCWD in the brain was demonstrated by ELISA following experimental infection by intracranial inoculation of CWD-positive deer brain. (P40.1.w23)
    • Western blot assay: The presence of PrPCWD in the brain was demonstrated by Western blot assay following experimental infection by intracranial inoculation of CWD-positive deer brain. (P40.1.w23)
    • Spongiform vacuolation and neuronal necrosis, following intracerebral inoculation with homogenates from CWD-positive deer brain. (P47.1.w3)
    • The presence of PrPCWD was detected by ELISA and by Western Blot assays in brains of ferrets following intracerebral inoculation with homogenates from CWD-positive deer brain. (P47.1.w3)

Mesocricetus auratus - Golden Hamster (Syrian hamster):

  • Central Nervous System:
    • Presence of PrPres detected by Western blot of whole brain homogenates from experimentally infected hamsters. (J20.251.w1)

Mus domesticus - Laboratory mouse:

  • Central nervous system:
    • Extensive perivascular amyloid deposits (accumulation of PrP) was the predominant neuropathological feature while only minimal vacuolar degeneration of the neurons and neuropil were observed, in mice experimentally infected with CWD from the brain of an infected mule deer; similar pattern of lesions following up to three mouse passages. Pathology was more severe in mice with longer incubation periods. (J233.10.w1)
      • It was noted that the neuropathology in mice infected with CWD was markedly different from any seen previously with strains of scrapie, BSE or CJD, indicating involvement of a different strain of agent.. (J233.10.w1)

Other TSE Diseases

  • The main pathological features of the TSE diseases are loss of neurons, vacuolation of neurons/neuropil and gliosis. (J252.144.w1)
  • In general in the TSE diseases in animals, spongiform change and vacuolation of the perikaryon typically have "a systematic and bilaterally symmetrical distribution and, presenting thus, are regarded as pathognomonic." Irrelevant vacuolation has been recorded in e.g. sheep, cattle (mainly in the red nucleus), pigs and cats but is generally focal and sparse. Occasional cases of TSEs are reported with minimal vacuolation. Spongiform change (vacuolation of the grey matter neuropil) does occur in other diseases including rabies and a mouse retroviral infection and in grey tremor mutant mice and the zitter rat. Demonstration of PrP by immunohistochemical staining or immunoblotting is specific for the TSE diseases. Demonstration of scrapie-associated fibrils is also specific to the TSEs. (J21.53.w1)

Transmissible Mink Encephalopathy:

Mustela vison - American mink:

  • Central Nervous System:
    • Moderate increase of glial elements, particularly astrocytes. Widespread vacuolation of the neuroglia. White matter generally unaffected. In the cerebral cortex, prominent and widespread neuronal degeneration; many neurons shrunken and hyperchromatic/ Cytoplasmic vacuolation of nerve cells noted in 3/6 mink brains examined histologically; these were seen in the midbrain and the tegument of the pons, usually clustered within one or two nuclei of this region. In the cerebellum pyknotic Purkinje cells were seen commonly. The medulla had only inconspicuous lesions and sometimes no lesions. It was noted that the neuronal vacuolation was less prominent than in scrapie. Data from three epizootics on eight or nine mink farms in Wisconsin, USA in 1947, 1961 and 1963. (J100.115.w1)
    • Degenerative change of the grey matter. Conspicuous "loosening or porous appearance of gray matter". Lesions varied from scattered patches of holes to diffuse sponginess of the neuroparenchyma, with many small neurons shrunken and deeply basophilic. Occasional vacuolation of the cytoplasm of a nerve cell. Astrocyte nuclei were increased in size and number, such that affected brain areas appeared unusually cellular. Sometimes angular projections of enlarged astrocyte cell bodies were visible, stained with eosin. The cerebral cortex was generally affected, sometimes extensively, with changes through the entire thickness of the cortex. The most severe damage often occurred affecting gyri along the midline in the rostral cerebrum - the anterior and posterior sigmoid gyri, lateral gyrus and cingulate gyrus. Regularly affected areas included the corpus striatum and the diencephalon. Data from an outbreak in Ontario, USA in 1963. (J14.9.w1)
    • Diffuse spongiform degeneration (microvacuolation) of the grey matter throughout the corpus striatum, midbrain, cerebral cortex and brainstem, together with an intense reactive astrocytosis. (J223.72.w1)
    • Spongiform change in the neuropil grey matter is generally the most striking lesion, comprising small, round, optically empty vacuoles and varying in severity from scattered patches of holes to diffuse rarefaction. Astrocytosis, with astrocyte hyperplasia and hypertrophy is also prominent. Degeneration of neurons, with shrinkage and basophilia of nerve cells, also occurs. The cerebral cortex (neocortex) regularly shows all three types of change, most severe in the gyri of the frontal lobes and particularly in the middle and deeper layers, with degeneration becoming less severe more caudally. The hippocampus is generally moderately affected while the central amygdaloid nucleus is usually severely affected. The corpus striatum and diencephalon commonly show spongiform change and astrocytosis; severe degeneration occurs in some but not all nuclei of the thalamus, particularly the caudal dorsal portion of the thalamus and the medial geniculate nucleus, while changes in the hypothalamus are distributed more uniformly. In the caudal parts of the brain lesions are more variable and less severe, so that in the pons and medulla there are more limited lesions of astrocytosis and spongiform change in nuclei including the vestibular, hypoglossal and lateral reticular nuclei and the dorsal motor nucleus of the vagus. The cerebellum and spinal cord are spared. (J64.11.w5)
    • Grey matter vacuolation, astrocytosis and neuronal degeneration. Severely affected areas in all mink with advanced clinical signs included the olfactory tubercle, septal nuclei, corpus stratum and frontal cortex, and in most individuals extended caudally in the brain to affect the thalamus, parietal cortex and hippocampus, with variable neuronal degeneration in the pons and brainstem and occasionally ischaemic necrosis of nerve cells in the cerebellum and spinal cord. (J13.30.w1)

Bos taurus - Domestic cattle:

  • Central Nervous System:
    • Following intracerebral inoculation of mink brain affected with Stetsonville strain of TME into two six-week-old Holstein bull calves. Midbrain and brain stem showed spongiform degeneration of the grey matter however there were no lesions in the cerebral cortex. (J223.72.w1)
    • Following intracerebral inoculation with Hayward isolate, Blackfoot isolate or cattle-passaged Stetsonville isolate of TME. Astrocytosis and spongiform change. Spongiform change variable from scattered patches of small holes to large areas of near obliteration of the neurophil. Astrocytosis consisted of an abundance of enlarged, often vesicular, and at times oddly shaped astrocyte nuclei in the grey matter, sometimes with little or no accompanying spongiform change. Neuronal degeneration was regularly present but generally inconspicuous, with dark shrunken neurons. There was only sparse occurrence of neurons with vacuoles, apparently empty, in the perikaryon. Most of the subcortical grey matter was affected with the most severe changes in the septal area, diencephalon and midbrain. Changes in other regions were generally less severe and were more variable. Slight to moderate lesions were seen in the corpus striatum and olfactory tubercle. In the hippocampus there was generally slight spongiform change but prominent astrocytosis. In the ventral pontine nuclei neuronal degeneration was most conspicuous. The medulla oblongata was generally more moderately affected with spongiform change and astrocytosis than was the rostral brain stem and the nucleus of the solitary tract and the nucleus of the spinal tract of the trigeminal nerve were particularly affected. The presence of vacuolated neurons was most evident in the medullary nuclei, although occurring all along the neuraxis. The cerebral cortex was generally spared except for patches of small holes found in the middle and deep layers of gyri next to the midline in the frontal lobe. There were small scattered holes of spongiform change in the molecular layer and variable proliferation of Bergman glia. In the cervical segment of the spinal cord there was slight spongiform change in the dorsal horns. (J42.113.w1)

Domestic ferret Mustela putorius fero (Mustela putorius - Polecat):

  • Central Nervous System:
    • CNS lesions, similar to those found in mink with TME but "less intense with a more focal distribution of spongiform degeneration in the cerebral cortex." (J223.72.w1)
    • Following inoculation into the body of ferrets one week prior to birth, at necropsy two years post inoculation there were histopathological lesions of vacuolation in the middle zone of both hemispheres of the cerebral cortex, being more prominent along the lateral aspects. No clinical signs of neurological illness had been seen in these animals. (J1.9.w2)

Procyon lotor - Common Raccoon:

  • Central Nervous System:
    • Following intracerebral or oral inoculation with Wisconsin isolate TME agent, lesions were found in the CNS only. In the cerebral cortex, the non-cortical telencephalon, diencephalon, mesencephalon and to a lesser degree the brain stem, there were diffuse, widespread and bilaterally symmetrical lesions consisting of grey matter vacuolation, neuronal degeneration and astrocyte hypertrophy and hyperplasia. Lesions were not found in the cerebellum or spinal cord. (J1.9.w2)
    • Electron microscopy: The main finding was the presence of well-defined electron lucent vacuolar areas within the neuropil, up to 13 microns in diameter, and most containing large numbers of kinked filaments approximately 100 nm long and less than 5 nm wide. Along the periphery of vacuoles could be found aggregates of whorled or vesicular membrane profiles, some of which could be traced back to the enclosing membrane of the vacuole, from which they originated. Following intracerebral or oral inoculation with Wisconsin isolate TME agent. (J1.9.w2)

Mephitis mephitis - Striped skunk (Mustelidae - Weasels (Family)):

  • Following intracerebral inoculation with Wisconsin isolate TME agent. Typical spongiform polioencephalopathy. The non-cortical telencephalon and the diencephalon showed severe spongiform change while the cerebral cortex contained less severe lesions of limited topographical distribution. In the second animal, which died (cause unknown) without developing any neurological clinical signs, lesions were milder in degree and more limited in distribution. (J1.9.w2)

Mesocricetus auratus - Golden Hamster:

  • Central Nervous System:
    • Midbrain and brainstem affected by mild spongiform degeneration. Following intracerebral inoculation of mink brain into weanlings, second passage and third passage in individuals showing the "hyper" syndrome". (J223.72.w1)
    • Midbrain and brainstem affected with more intense vacuolation, plus in some individuals in the cerebral cortex mild microvacuolation was found. In hamsters showing the "sleepy" syndrome. (J223.72.w1)

Saimiri sciurius - Squirrel monkey (Cebidae - New-world monkeys (Family)):

  • Central Nervous System:
    • In the cerebral cortex, corpus striatum, midbrain and pons of both animals, in the grey matter only, profound spongiform degeneration lesions. (J223.72.w1)
  • Central Nervous System:
    • "Severe spongiform poliencephalomalacia" of most of the brain grey matter. Spinal cord spongiform polioencephalopathy also but intense only in the dorsal horns. Vacuoles in the neuropil were generally 10-20Ám but occasionally up to 45 Ám. Rare vacuoles within nerve cell body cytoplasm, these being smaller in diameter than the cell nucleus. In the cerebellum vacuoles were noted only in the cortex granular layer, plus focal lesions of subjacent folia white matter. Astrocyte hypertrophy and proliferation was extensive in areas of greatest vacuolation but demyelination, microglial proliferation and inflammatory infiltrates were not seen. (J22.169.w1)
    • Electron microscopy of the cerebral cortex showed focal swelling of dendrites and axons and the presence of vacuoles within neuronal perikarya and nerve cell processes. Various shapes of membranes were seen filling large vacuoles in the neuropil. (J22.169.w1)

Capra hircus - Domestic goat:

  • "The essential degenerative lesion comprised: shrinkage and increased basophilia of neurons, mainly in the brain stem; astrocytosis; and spongiform alteration of the neuropil." In general lesions occurred in the corpus striatum, diencephalon, brain stem and cerebellum. The cerebral cortex was affected in most animals. The spinal cord was not affected except for a mild astrocytosis in the gray matter and, in the intermediate cell columns occasional vacuolated neurons in a few animals. Following intracerebral inoculation of mink brain affected by the Idaho strain of TME. (J240.51.w1)

Ovis aries - Domestic sheep:

  • "The essential degenerative lesion comprised: shrinkage and increased basophilia of neurons, mainly in the brain stem; astrocytosis; and spongiform alteration of the neuropil." In general lesions occurred in the corpus striatum, diencephalon, brain stem and cerebellum. The cerebral cortex was affected in two of five animals. The spinal cord was not affected except for a mild astrocytosis in the gray matter and, in the intermediate cell columns occasional vacuolated neurons in a few animals. Following intracerebral inoculation of mink brain affected by the Idaho strain of TME. (J240.51.w1)

Scrapie:

Capra hircus - Domestic goat:

  • Central Nervous System: Lesions were found mainly in the diencephalon, brain stem and cerebellar cortex and consisted of shrinkage and increased basophilia of neurons, sometimes with loss of neurons, cytoplasmic vacuolation of neurons particularly in the brain stem, astrocytosis (hypertrophy to definite proliferation), and scattered small vacuoles in the neuropil. Within the diencephalon there was selective damage of certain nuclei with diffuse lesions in the nucleus ventralis posterior and the lateral and medial geniculate nuclei in all of three animals; other nuclei were affected more variably. Less dramatic degeneration was present in the hypothalamus. In the midbrain there were small holes scattered throughout the tegmentum, with occasional vacuolated neurons in the substantia nigra and large cytoplasmic vacuoles in neurons of the red nucleus; in the caudal colliculus there were vacuolated neurons, intercellular holes and pronounced astrocytosis. In the pons and medulla oblongata neuronal vacuolation was prominent with astrocytosis less obvious than in the more rostral areas of the brain. The cerebellar cortex and roof nuclei demonstrated lesions including some shrunken and misshapen Purkinge cells, although most Purkinge cells were intact; there were also a few holes scattered mainly in the granular layer and special stains revealed hypertrophy of astrocytes in the granular and Purkinje cell layers as well as a meshwork of hypertrophied astrocytes in the molecular layer. The telencephalon was essentially unaffected. The cerebral cortex was unaffected except for, in one of three animals, some astrocyte hypertrophy. In the spinal cord there were a few vacuolated neurons, mainly in the lateral intercornual cell columns. No PAS positive plaques were found. (J26.17.w1)
  • Typical lesions of scrapie: focal neuronal vacuolation and degeneration, astrocytic reaction and spongiosis (vacuolation) of the grey and white matter. The medulla oblongata, pons and midbrain showed frequent vacuolation of neuronal perikarya but this was also present in the Purkinje cells and in the granular layer. Neuronal degeneration, consisting of chromatolysis, neuronophagia and the presence of dark, shrunken neurons, was seen in the cerebral and cerebellar cortex as well as in some of the thalamic nuclei. Vacuolar changes were found in the grey matter neuropil. Area affected by vacuolation included the lateral cuneate nucleus, tractus solitary nucleus and dorsal motor nucleus of the vagus within the medulla oblongata, the nucleus ventralis posterior, nucleus medialis and lateralis dorsalis and nucleus anterior ventralis in the thalamus, the hypothalamus, nucleus accumbens in the septal area and the caput of the caudate nucleus. In three herds in Italy. (J3.143.w6)
  • Immunohistochemistry: Presence of PrPSc was detected widely distributed throughout the brain, particularly in the brainstem. PrPSc was found in some neurons as fine cytoplasmic granuolations, as accumulations at the neuronal cell membrane or as fine deposits among axons in both the white and grey matter. There were also fine granulations of PrPSc around blood vessels and in the subependymal areas. (J3.143.w6)

Ovis aries - Domestic sheep:

  • Central Nervous System:
    • Characteristically lesions are found in the brain stem and include neuronal vacuolation, neuronal degeneration, loss of neurons, astrocytosis and generalised spongiform lesions (vacuolation) of the grey matter neuropil. Most vacuoles are intraneural, found in the perikaryon or neurites but some are paraneural, perineural or even not associated with the perikarya. The medulla, pons, midbrain and thalamus most commonly show vacuolation. In the medulla, pons and mesencephalon cytoplasmic vacuolation of neurons is seen as a prominent feature, with the nucleus commonly displaced in vacuolated cells by a large single vacuole or by multilocular vacuoles. Vacuoles may occasionally contain eosinophilic material which is fibrillar, globular or finely granular in appearance. Throughout the midbrain other degenerative changes of neurons may be seen such as chromatolysis, pyknosis and sclerosis, with neurons often appearing shrunken and angular and an increased basophilia of the cell body. Together with the other lesions is glial cell proliferation or hypertrophy, often of astrocytes. Cerebrovascular amyloidosis may be found in some individuals; this may be related to different stains of the agent. The presence of amyloid plaques may be confirmed using Congo red stain, looking for apple-green birefringent plaques under polarised light. Lesions may vary with the strain of the agent and the breed of the sheep, and do not necessarily correlate with the severity of clinical signs. (J64.11.w4)
    • Brain stem nuclei affected with bilaterally symmetrical lesions of progressive neuronal cytoplasmic vacuolation and shrinkage as well as varying gliosis and slight cell loss. (B292.w16)
  • Immunohistochemistry: Presence of scrapie-specific amyloid plaques which immunoreact for PrPSc.(J64.11.w4)

Ovis orientalis - Mouflon (Ovis musimon):

  • Central Nervous System:
    • Focal degeneration of neurons, vacuolation of the neuropil of the grey matter and an astrocytic reaction. Degeneration included neurons showing chromatolysis, shrinkage and hyperchromasia and neuronal perikarya vacuolation. There was variation between anatomical regions of the CNS in the degree of neuronal vacuolation and the type of neuronal degeneration predominating. There were also variations between individuals. In general regions of the CNS caudal to and including the mesencephalon showed the most apparent vacuolation of neuronal perikarya while in more rostral regions other types of neuronal degeneration were more apparent. The degree of astrocytosis did not always correlate with the severity of the other changes. (J3.130.w4)

Mustela vison - American mink:

  • Central Nervous System: 
    • Spongiform polioencephalopathy noted as the most striking finding. Most vacuoles were within the neuropil; occasionally a vacuole was seen within a neuronal cell body. Vacuoles were variable in size, mainly 8-16 Ám, some up to 28 Ám and generally appeared empty, although some contained amorphous debris. The areas most consistently and intensely affected by vacuolation included the cerebral cortex, corpus striatum, diencephalon and mesencephalon, with less consistent and less striking changes noted in the pons, while the medulla was not consistently affected by vacuolation and this was, when present, less intense than that seen in other brain regions. Areas of intense vacuolation also showed extensive astrocyte proliferation and hypertrophy. In 5/5 mink inoculated with brain material from a scrapie-affected Suffolk sheep. (J22.172.w1)
    • Electron microscopy: Presence of large vacuoles in the neuropil (3-30 Ám, mainly 6-8 Ám diameter), derived from distended and occasionally disrupted cell processes. Axons showed focal swelling and vacuoles up to 1.8 Ám diameter were seen within dendrites. In 5/5 mink inoculated with brain material from a scrapie-affected Suffolk sheep. (J22.172.w1)

Cervus elaphus nelsoni - Rocky Mountain Elk (Cervus elaphus - Red deer):

  • Central Nervous System: 
    • Brain and spinal cord: lesions of spongiform encephalopathy, including vacuolation of neuronal perikarya and neuropil, and in the same sites mild multifocal gliosis; no neuronal degeneration noted. In the brain the most severe lesions were found in the thalamus and cerebellum. Thalamus: widespread vacuolation in neuropil, but not prominent vacuolation of neuronal cytoplasm. Cerebellum: in molecular layer, vacuoles of variable size in the neuropil, and in Purkinje cells single or multiple cytoplasmic vacuoles were prominent. In the brainstem spongiform lesions were present in various nuclei, with lesions being more severe  and extensive in the pontine nucleus than in the dorsal vagal nucleus. Following experimental infection by intracerebral inoculation of elk calves with scrapie brain. (J26.40.w1)
    • Immunohistochemistry: presence of PrPres in the cerebrum, cerebellum, brainstem and spinal cord. Diffuse immunostaining through the grey matter neuropil, including in the cerebellum both granular and molecular layers. Mainly punctate and granular staining, some small aggregates, a few accumulations (plaques). Usually perineural (ring around the cell surface), occasionally large granules within the perikaryon. (J26.40.w1)
    • Immunoblotting: Western blot of brain, PrPres-positive (J26.40.w1)
    • Electron microscopy:  presence of SAF in the brain. (J26.40.w1)

Bovine Spongiform Encephalopathy (BSE):

  • CNS lesions only. "Vacuolation of neuronal perikarya and neurites, neuronal degeneration and loss, gliosis (mainly astrocytic), and amyloidosis." (B23.101.w4)

Acinonyx jubatus - Cheetah (Felidae - Cats (Family))

  • Central Nervous System:
    • In the neuroaxis, particularly the corpus striatum, midbrain and thalamic areas, severe spongiform change in the grey matter: small, various sized ovoid spaces in the neuropil, and in some neurons vacuolation within the perikarya. In the spinal cord grey matter no spongiform change or vacuolated neurons were seen, however in all tracts of the spinal cord , and extending up the pyramidal tracts in the medulla and the white matter tracts of the brain stem as far as the internal capsule area there was widespread axonal degeneration and demyelination, with macrophages visible in some empty cylinders. (J24.69.w1)
    • Brain: spongiform encephalopathy affecting the whole brain visible in haematoxylin and eosin stained sections. The most prominent feature was the neuropil vacuolation, which was noted to be similar in distribution and regional severity to that seen in domestic cats. (J2.26.w2)
    • Brain: spongiform encephalopathy in both "Duke" and "Saki". (J3.135.w1)
    • Scrapie-associated fibrils:
      • Present in fresh material from the brain. (J2.26.w2)
      • Present in "Duke" [not looked for in "Saki"]. (J3.135.w1)
    • Cortical and thalamic areas of the brain examined. Spongiosis of the neuropil was severe in the internal capsule area, less in the cortical area. In a few neurons there was vacuolation within the perikarya. Moderate gliosis was observed. (J3.141.w5)
    • Immunohistochemistry: Deposits of PrP in the neuropil and intracytoplasmic labelling of neurons. (J3.141.w5)
    • Immunoblotting: Proteinase K resistant prion protein (PrPres) was detected (major PrP fragment molecular weight 27-30 kDa) from scrapie-associated fibrils extracted from the brain. (J3.141.w5)

Bos taurus - Domestic cattle:

  • Central Nervous System:
    • Brain stem grey matter: areas of bilaterally symmetrical degenerative changes. Moderate numbers of vacuoles, ovoid or spherical (occasionally less regular), within the neuropil. Within neuronal perikarya and neurites of certain nuclei within the brain stem, mainly the dorsal nucleus of the vagus nerve, reticular formation, vestibular nuclei and red nucleus, were large well defined intracytoplasmic vacuoles, single or multiple and sometimes noted to distend the soma producing a ballooned neuron with a narrow rim of cytoplasm. Vacuoles remained clear following staining for glycogen in paraffin section and for lipids in fixed cryostat section. Also occasional spheroids, solitary necrotic neurons, sometimes intracytoplasmic neuronal aggregations of ceroid-lipofuscin pigment in areas of neuronal vacuolation (in both vacuolated and unvacuolated neurons) and sometimes a mild gliosis accompanying the degenerative changes. (J3.121.w5)
    • Brain stem lesions; severe vacuolation of both neurons and grey matter neuropil. Caudal medulla and spinal cord: moderately severe vacuolation. Basal ganglia, occipital lode of the cerebrum (hippocampus) and cerebellum (mainly central parts of the vermis): mild vacuolation. (J9.336.w1)
    • Scrapie-associated fibrils:
      • Present in the fresh brain material available from one cow (no such material available from the other individuals). (J3.121.w5)
      • Presence of SAF confirmed in brains of cattle with BSE; large numbers present in the basal ganglia. There was no correlation between the occurrence or severity of vacuolation and the number of fibrils purified from the contralateral area of the brain by detergent extraction. (J9.336.w1)

Felis catus - Domestic cat:

  • Central Nervous System:
    • "Spongiform encephalopathy characterised principally by grey matter neuronal spongiosis, vacuolation of neuronal perikarya and an astrocytic response." No significant lesions in the liver, kidney, lung or spleen. (J3.126.w4)
    • Spongiform encephalopathy with vacuolation of the neuropil and neuronal cell body vacuolation. Diffuse spongiform changes in the grey matter but most obvious in the cerebral cortex of the frontal lobe. In the cerebral cortex vacuoles were found in the cell bodies of neurons and in the brain stem vacuoles were found in nuclei. In the central grey matter around the mesencephalic aquaduct neuronal vacuoles were extremely easy to identify. It was noted that vacuoles were frequently large and that some extended into the axonal process. Moderate gliosis was seen but no plaques of amyloid material were found, even using Congo red staining. (J3.127.w4)
    • Findings in five cats. Grey matter vacuolation, extending throughout the neuraxis, predominantly spongiform change with small discrete round apparently empty spaces in the neuropil. Areas which were consistently affected more severely included the medial geniculate body of the midbrain, the thalamus and the corpus striatus, also in most cases the cerebellar cortex and (mainly the deeper layers) the cerebral cortex. Neuronal vacuolation involved single or multiple, generally large vacuoles with a well defined margin; these were found particularly in the raphe nucleus, the dorsal nucleus of the vagal nerve and the vesicular nuclei within the medulla oblongata as well as the red nucleus in the midbrain. The spinal cord sometimes showed vacuolation of the soma of neurons. Vacuolation of the white matter was observed mainly in the medulla and was associated with axonal degeneration, particularly in the pyramidal tracts. An additional finding in all the cats was an astrocyte reaction: enlarged or irregular vesicular glial nuclei, numerous in some areas, as well as increased numbers of rod-shaped microglial nuclei. (J3.129.w3)
  • Digestive Tract:
    • Immunohistochemistry: Strong staining was found in Peyer's patches from the one cat from which intestine containing Peyer's patches was available, and within neurons of the myenteric plexus of four cats. No staining was observed in mesenteric lymph nodes (J3.148.w7)
  • Spleen:
    • Immunohistochemistry: Staining was seen within some follicles of two of 13 spleens examined. This took the form of "strongly stained globular deposits within the cytoplasm of macrophage-like cells, and probably also in follicular dendritic cells, in a minority of periarticular lymphoid sheaths."(J3.148.w7)
  • Renal:
    • Immunohistochemistry: PrP staining was found in the renal glomeruli of cats with FSE. This was found also in control (FSE negative) cats however staining in control cats was weaker and was reduced or abolished following proteinase K digestion while staining in the FSE-positive cats was enhanced in the cases and slightly reduced in three cases. (J3.148.w7)
  • Other:
    • Immunohistochemistry: No staining was seen in liver, lung, heart, salivary gland, adrenal gland, pancreas, sciatic nerve, popliteal, cervical, coeliac or retropharyngeal lymph nodes, tonsil or thymus, where available. (J3.148.w7)

Felis concolor - Puma (Felis - (Genus)):

  • Central Nervous System:
    • Within the neuraxis, neuronal perikarya contained single or multiple large empty round vacuoles, some containing floccular or globular eosinophilic material. In the grey matter neuropil also multiple small vacuoles, empty; these were most conspicuous in the inferior colliculus and the cerebellar cortex (molecular and granular layers). Conspicuous microglia and astrocytes in grey matter neuropil of brain and spinal cord, also occasional microglial nodules and in the meninges a few perivascular lymphocytes. In spinal cord white matter some Wallarian type degeneration was noted with associated astrocytic gliosis. (J3.131.w2)
    • Immunohistochemistry: PrP staining in medulla and spinal cord sections took the form of granular deposits in neuronal perikarya and grey matter neuropil. (J3.131.w2)

Macaca mulatta - Rhesus monkey (Cercopithecidae - Old-world monkeys (Family)):

  • In the grey matter of the brain, particularly the cerebral cortex, conspicuous spongiform changes were seen. In the cerebral cortex the changes involved mainly the deep layers. large vacuoles, single or multiple, were found in neurons of affected areas; vacuoles distended the soma, producing ballooned cells with a narrow rim of cytoplasm. (J98.348.w1)
  • Immunohistochemistry: presence of anti-B protein immunoreactive deposits in the cerebral cortex neuropil. (J98.348.w1)

Oryx dammah - Scimitar oryx (Scimitar-horned oryx):

  • Central Nervous System:
    • Histopathological lesions. (J3.135.w1)

Oryx gazella - Gemsbok:

  • Central Nervous System:
    • Brain lesions similar to those seen in a nyala. (J26.25.w1)
Oryx leucoryx - Arabian oryx:
  • Central Nervous System:
    • Brain lesions, throughout the brain stem, consisting of vacuolation of the grey matter neuropil and vacuoles within neuronal perikarya. Equivocal mild glial changes. No observed plaques or perivascular amyloid (J3.127.w3)

Taurotragus oryx - Eland:

  • Central Nervous System:
    • Bilaterally symmetrical neuronal vacuolation of the grey matter neuropil of the brain, particularly the brain stem. (J3.126.w3)
    • Histopathological lesions of spongiform encephalopathy in three animals. (J3.135.w1)
    • Scrapie associated fibrils. Detected in the brain of one individual. (J3.135.w1)
Tragelaphus angasii - Nyala:
  • Central Nervous System:
    • Brain and cervical spinal cord: laterally symmetrical vacuolar change of the neuropil and neurons. Brain stem grey matter principally affected. Greatest lesions in the medulla oblongata (particularly the dorsal nucleus of the vagus nerve and the nucleus of the spinal tract of the trigeminal nerve) with rapid diminishment of lesions both cranially and caudally. Lesions rostral of the mesencephalon were not common and were seen in thalamic grey matter (particularly paraventricular and hypothalamic nuclei and the habenular nucleus). Also mild neuropil vacuolation in the hippocampus. In the medulla oblongata and mesencephalon, but not other regions, vacuolation of the neuropil was noted to extend into the white matter. Vacuoles in the neuropil described as "small, round, and empty". Vacuoles in the cytoplasm of neurons were "sharply defined, empty, single or multiple, and variable in size." When large single vacuoles were present they were usually eccentric and displaced Nissle material. Multiple vacuoles were frequently in ballooned neurons. The dorsal nucleus of the vagus nerve was the site of the most severe neuronal vacuolation. (J26.25.w1)

Tragelaphus strepsiceros - Greater kudu:

  • Central Nervous System:
    • Brain lesions, throughout the brain stem, consisting of vacuolation of the grey matter neuropil and vacuoles within neuronal perikarya. Equivocal mild glial changes. No observed plaques or perivascular amyloid (J3.127.w3)
    • Brain lesions: scrapie-like spongiform encephalopathy. Noted that, compared to lesions of BSE in cattle: "greater severity of the lesions in the midbrain and thalamus of the kudu relative to the lesions in its medulla oblongata and pons."(J3.130.w3)
    • In two subclinically affected animals, lesions in the medulla oblongata only, localised in distribution, bilaterally symmetrical sparse neuronal vacuolation. (J3.132.w1)
    • Brain lesions: spongiform encephalopathy with excessive vacuolation of the neuropil in the medulla.(J3.134.w4)
    • Electron microscopic examination: presence of scrapie-associated fibrils in protease-K treated detergent extracts of fresh brain stem tissue. (J3.130.w3)
    • Electron microscopic examination: presence of scrapie-associated fibrils in material prepared from the cerebral cortex and spinal cord. (J3.132.w1)
    • Electron microscopic examination: presence of scrapie-associated fibrils in material prepared from the frontal lobe and spinal cord. (J3.134.w4)
    • Immunohistochemistry: presence of a 25-28 kDa band on immunoblotting, "comparable with that identified as bovine PrP extracted from BSE-affected brain. (J3.130.w3)
    • Immunohistochemistry: presence of PrP protein detected, principally in association with vacuolation, in two subclinically affected animals. (J3.132.w1)

Creutzfeldt-Jakob Disease (CJD):

  • CNS:
    • In sporadic CJD the most consistent finding is spongiform change characterised by the presence of multiple vacuoles, 20-200 Ám diameter, in the neuropil. Such vacuoles, which may be present in any layer of the cerebral cortex, may become confluent, producing large vacuoles which may "substantially distort the cortical cytoarchitecture." Additionally, particularly in layers 3 and 5 within the cortex vacuoles may be found within the cytoplasm of the larger neurons. In most cases cortical lesions are detectable, generally accompanied by spongiform change in the basal ganglia, thalamus and cerebellar cortex. In most cases also there are cerebellar lesions; the distribution and severity of such lesions is highly variable. It is rare for confluent spongiform change to be found in the cerebellum but microvacuolar change, with 20-50 Ám diameter vacuoles in the molecular layer, may be evident. In long-standing cases status spongiosus may be present: widespread coarse vacuolation throughout the cerebral cortex with resultant collapse of the cortical cytoarchitecture, an irregular distorted rim of gliotic tissue remains, containing a few neurons. Severe neuronal loss, together with gliosis and atrophy, may be found in the basal ganglia and thalamus. In the cerebellum frequently there is irregular loss of neurons in both the granular cell and Purkinje cell populations, together with proliferation of Bergmann and radial glia. In most regions of the brain spongiform change is accompanied by neuronal loss and by gliosis (both astrocytes and microglia involved). Hypertrophy and hyperplasia of microglia are widespread within the CNS. No classical inflammatory or immune response is evident. (B297.3.w3)
      • Variations exist including extensive necrotising lesions in the white matter (panencephalic variant) and in about 10% of cases visible PrP plaques, generally in the cerebellum, with a hyaline eosinophilic core and a pale halo; these may or may not have a peripheral margin of radiating fibrils as seen in Kuru. In a few cases plaques may be found in the thalamus, basal ganglia or cerebral cortex. (B297.3.w3)
      • In familial CJD lesions may present which are similar in type and distribution to those of sporadic CJD, or there may be characteristic pathology, for example the presence of PrP plaques.(B297.3.w3)
      • In iatrogenic CJD due to peripheral inoculation the main lesions are found in the cerebellum often with marked atrophy, severe neuronal loss, gliosis and the presence of PrP plaques. There may be a more widespread PrP deposition within the granular layer. If spongiform change is present in the cerebral cortex it is generally less widespread than that seen in sporadic CJD. The basal ganglia commonly have marked spongiform change. In the spinal cord there may be plaque-like accumulations of PrP, with PrP deposition in the substantia gelatinosa and ascending pathways. (B297.3.w3)
      • In iatrogenic CJD due to central inoculation the predominant pathology is found in the cerebral cortex and is similar to that seen with sporadic CJD. (B297.3.w3)
      • In Gerstmann Straussler Scheinker syndrome (GSS): Characteristic presence of multicentric PrP plaques (large and diffuse with several core-like areas), particularly in the cerebellum (molecular layer, granular layer, occasionally white matter), also widespread in the cerebral cortex, basal ganglia, thalamus and hypothalamus. There is a variable degree of spongiform change, which may be present in the cerebral cortex, basal ganglia and thalamus but is generally not found in the cerebellar molecular layer. Additional lesions in the cerebellum include frequently severe neuronal loss and gliosis (disproportionate to neuronal loss in the cerebrum or spinal cord). In individuals with the Indiana variant of this condition, widely distributed in the cerebral cortex are neurofibrillary tangles. (B297.3.w3)
      • In Fatal Familial Insomnia (FFI): Characteristically thalamic gliosis, particularly affecting the dorsomedial nuclei and often without any spongiform change and disproportionate to the degree of neuronal loss. Occasionally there is some spongiform change in the cerebral cortex. There may be cerebellar atrophy and neuronal loss with gliosis in the inferior olivary nuclei. Other abnormalities are minor and inconsistent. (B297.3.w3)

New variant Creutzfeldt-Jakob Disease (nvCJD):

  • CNS:
    • Data from ten initial cases. Spongiform change distributed relatively sparsely throughout the cerebral cortex. Basal ganglia and thalamus showed the most evident spongiform change, neuronal loss and astrocytosis. Similar changes were present in the cerebrum and cerebellum but more focally distributed, being most evident in areas with confluent spongiform change. . Consistent and striking presence of PrP plaques, distributed extensively throughout the cerebrum and cerebellum; smaller numbers of plaques were found in the basal ganglia, thalamus and hypothlamus. Plaques were generally kuru-like (or similar to scrapie "florid plaques"), with a dense eosinophilic core and paler periphery, and were surrounded by a zone of spongiform change, which is considered unusual for this type of lesion. (J98.347.w1)
    • Immunohistochemistry: Strong staining of plaques including those visible by ordinary light microscopy and many other plaques, smaller in size, either single or in multicentric deposits. Also pericellular PrP deposition in the cerebral cortex and in the molecular layer of the cerebellum with the pattern indicating deposition around small neurons. Both plaques and pericellular deposits of PrP could be found throughout the cerebrum and cerebellum including in areas without spongiform change in the surrounding neuropil. Perivacuolar staining was seen in the basal ganglia and hypothalamus, with linear tract like deposits in the grey matter; there were also (less frequent than in the cerebrum or cerebellum) PrP plaques in these areas. (J98.347.w1). 

Kuru:

  • CNS: 
    • Formation of PrP plaques, with a hyaline eosinophilic core, a paler halo and a peripheral margin of radiating fibrils, was the principle lesion. Such plaques were most easily identified in the cerebellum but were also present at other locations in the brain. Spongiform change was present with variable distribution. (B297.3.w3)

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Authors & Referees

Authors Dr Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Suzanne I Boardman BVMS MRCVS (V.w6)

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