JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2023

N-M22 (NP)

 

Signalment (JPC #D86-506): 23-day-old turkey poult

 

HISTORY: This poult presented with a CNS disturbance.

 

HISTOPATHOLOGIC DESCRIPTION: Cerebellum and brainstem: All layers of the cerebellum are multifocally characterized by regionally extensive areas of edema and neuropil loss (liquefactive necrosis). Within in the molecular layer are scattered areas of spongiosis, hemorrhage, and few heterophils. Within the most affected area, purkinje cells are lost, leaving clear remnant spaces (empty baskets). Remaining Purkinje cells are often either degenerate with swollen, pale, vacuolated neuroplasm and loss of Nissl substance (peripheral chromatolysis); or necrotic with hypereosinophilic, shrunken, angular neuroplasm with nuclear pyknosis or karyolysis. The granular layer is multifocally thinned with marked cellular loss and necrosis. Scattered within the cortical and medullary white matter tracts are few spheroids and many gitter cells and heterophils admixed with hemorrhage, fibrin, and edema. Multifocally, vessel walls are fragmented and moth eaten with replacement by fibrin, hemorrhage, and edema (fibrinoid vascular necrosis); less affected capillaries have hypertrophic (reactive) endothelium and are occasionally partially occluded with fibrin thrombi. Multifocally the meninges are expanded by fibrin, hemorrhage, edema, and few macrophages, heterophils, and lymphocytes.  

 

Brain stem: Multifocally, there are areas of hemorrhage and spongiosis.

 

MORPHOLOGIC DIAGNOSIS: 1. Cerebellum: Necrosis, liquefactive, multifocal, marked, with Purkinje cell degeneration and necrosis, fibrinoid vascular necrosis, fibrin thrombi, and hemorrhage, turkey, avian.

2.  Brainstem: Hemorrhage and spongiosis, multifocal, mild.

 

ETIOLOGIC DIAGNOSIS: Nutritional cerebellar necrosis 

 

CAUSE: Hypovitaminosis E (Vitamin E deficiency)

 

CONDITION: Crazy chick disease; nutritional encephalomalacia

 

GENERAL DISCUSSION:  

• Vitamin E deficiencies are most commonly seen in young chicks or turkey poults, but also can be seen in piscivorous or companion birds fed a diet of improperly frozen and thawed fish or a diet containing rancid polyunsaturated fat (major source of vitamin E)
• In avian species, vitamin E deficiency causes three distinct forms (syndromes):

1. Encephalomalacia (crazy chick disease)
2. Exudative diathesis (selenium deficiency)
3. Muscular dystrophy (nutritional myopathy) 

• All forms are associated with vitamin E deficiency; yet all can be clinical treated by balancing ration with other minerals (synthetic antioxidants, selenium, and sulfur-containing amino acid)

 

PATHOGENESIS:  

• Vitamin E (antioxidant) scavenges free radicals that would otherwise react with and damage membrane lipids
• Vitamin E deficiency > loss of antioxidant protection > lipid hydroperoxide formation > peroxidative damage of membranes including capillary membranes > increased vascular permeability, thrombosis, and ischemia > tissue necrosis

 

TYPICAL CLINICAL FINDINGS:

Encephalopathy:

• Prevented by feeding synthetic antioxidants 
• Young birds usually 15 to 30 days of age, with a range of 7 to 56 days
• Acute onset of progressive ataxia, muscular weakness, spasmodic incoordination, downward / backward retraction of head, occasional torticollis, paralysis, and death

Exudative diathesis:

• Prevented by feeding adequate selenium
• Chicks often have wide-legged stance with fluid accumulation in the ventral skin and subcutis
• Sudden death

Muscular dystrophy (nutritional myopathy):

• Prevented by feeding adequate cysteine (sulfur-containing amino acid)
• May cause vague locomotor problems
• Enlarged hock disorder of turkeys: Poults develop enlarged hocks, bowed legs
• May result in increased serum creatine kinase (CK) activity

 

TYPICAL GROSS FINDINGS:  

Encephalopathy: 

• Cerebellar swelling and hemorrhage: Petechiae to large areas of hemorrhage 
  • Virtually pathognomonic in turkey poults and chicks 
  • Bing cherry or cherry red cerebellum
• Striatal hemispheres, medulla oblongata, and mesencephalon may also be affected
• Yellow-green areas of encephalomalacia may be apparent in older lesions

Exudative diathesis:

• Hydropericardium
• Greenish-blue fluid along ventral thorax and abdomen; subcutaneous edema
• Signs of muscular dystrophy may also be apparent in the same bird

Nutritional myopathy:

• White to yellow streaks in skeletal muscle of breast or legs
• Ventriculus and heart may contain gray areas of muscle degeneration Darkly mottled liver with severe hepatic lipofucinosis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

Encephalopathy:

• Necrosis of cerebellar gray and white matter, thrombosis, demyelination, edema, congestion, and hemorrhage, extending into the cerebrum in severe cases
• Neuronal degeneration, especially of Purkinje cells and large motor nuclei
• Poliomyelomalacia may be the only lesion in turkey poults

Nutritional myopathy:

• Polyphasic muscle degeneration and necrosis, +/- macrophage infiltration 
• In chronic cases, there is striated muscle regeneration, fibrosis, and mineralization
• The presence of ceroid may occur, as well as hepatocyte lipofuscinosis with green-brown intracellular pigment
• +/- muscular degeneration of the ventriculus

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Diagnosis is based on typical signs, gross lesions, and microscopic lesions
• Demyelination detected with Luxol fast blue

 

DIFFERENTIAL DIAGNOSIS:

Poultry encephalomalacia:

• Enterococcus hirae (N-B10): Young broiler chicks; gram-positive cocci; primarily brainstem 
• Mycotic: Aspergillus sp., Zygomycetes, Ochroconis gallopava (N-F03; old name Dactylaria gallopava)
• Salt toxicity: Turkey poults / broiler chicks; edema, ascites, hydropericardium, right heart hypertrophy; no laminar cortical necrosis as in swine
• Lead toxicity: CNS lesions due to vascular damage; demyelination of peripheral nerves; acid-fast intranuclear inclusions in kidney, liver, and spleen; no laminar cortical necrosis as in ruminants

 

COMPARATIVE PATHOLOGY:  

• In mammals, vitamin E / selenium imbalance is associated with the following:

1. Muscular degeneration and necrosis (white muscle disease, nutritional myopathy; M-M11)
2. Myocardial and hepatic necrosis (mulberry heart disease [C-M06] and hepatosis dietetica [C-M06])
3. Steatitis (yellow fat disease)
4. Infertility, embryonic death
5. Retinopathy

 

• Nutritional myopathy is seen in a wide range of species including: Bovidae, Antilocapridae, Firaffidae, Tragulidae, Hippopotamidae, Cervids, Monotremes and Marsupials, geckos, lambs
• Nutritional myopathy and steatitis are seen in: Camelids, Mustelids, sea lion, and primates
• Hemolytic anemia reported in: Primates, rats, horses, rhinoceros
• Dogs: Cardiac and skeletal myopathy; steatitis; "brown dog gut" (intestinal ceroidosis); retinopathy; axonal dystrophy (Pardo, Tox Pathol 2020)
• Calves: Nutritional myopathy (white muscle disease)
• Swine: Hepatosis dietetica; myocardial degeneration and necrosis (mulberry heart disease); white muscle disease
• Horses: White muscle disease; associated with equine degenerative myeloencephalopathy (N-M07), equine neuroaxonal dystrophy (axonal degeneration and eosinophilic spheroids in brainstem, but NOT in spinal cord), and retinopathy
• Marmosets and tamarins: Wasting Marmoset Syndrome; postulated to be due to vitamin E deficiency and protein deficiency secondary to chronic diarrhea; extensive type II skeletal muscle fiber atrophy, necrosis, and fibrosis, hemolytic anemia, fat necrosis, and panniculitis

 

References:  

1. Agnew D. Camelidae. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 188-189. 
2. Cantile C, et al.  Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6^th ed. Philadelphia, PA: Elsevier Saunders; 2016: 330-332. 
3. Duncan M. Perissodactyls. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 437. 
4. Fenton H, McManamon R, and Howerth E. Anseriformes, Ciconiiformes, Charadriiformes, and Gruiformes. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 698-699. 
5. Howerth EW, Nemeth NM, and Ryser-Degiorgis MP. Cervidae. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 150. 
6. Jones MEB, Gasper DJ, and Mitchell (nee Lane) E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 117-119. 
7. Matz-Rensing K and Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 345.
8. Miller MA, Porter BF. Nervous system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier; 2022: 963-964. 
9. Pardo, ID, Otis D, Ritenour HN, et al. Spontaneous Axonal Dystrophy in the Brain and Spinal Cord in Naïve Beagle Dogs. Tox Pathol. 2020;48(5):694-701. 
10. Pritzker KPH and Kessler MJ. Arthritis, Muscle, Adipose Tissue, and Bone Diseases of Nonhuman Primates. In: Abee CR, et al, eds. Nonhuman Primates in Biomedical Research. Vol 2. 2^nd ed. San Diego CA: Elsevier; 2012:654. 
11. Schmidt RE, Reavill DR, and Phalen DN. Pathology of Pet and Aviary Birds. 2^nd ed. Ames, IA: John Wiley & Sons, Inc; 2015: 9-10, 74, 116, 201-202, 230. 
12. Shivaprasad HL. Vitamin E deficiency. In: Boulianne M., ed. Avian Disease Manual. 7^th ed. Jacksonville, FL: American Association of Avian Pathologists; 2013:185-187.   
13. Stockham SL and Scott MA. Fundamentals of Veterinary Clinical Pathology. 2^nd ed. Ames, IA: Blackwell Publishing; 2008:662. 
14. Williams BH, Burek Huntington KA, and Miller M. Mustelids. In: Terio KA, McAloose D, and St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Elsevier; 2018: 287-288. 

 

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