JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2026

N-M04A

Slide A: Signalment (JPC #1895035): Male German shepherd dog

HISTORY: This dog developed an abnormal gait and had proprioceptive deficits and a progressive loss of motor nerve function.

HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Multifocally affecting all white matter funiculi and spinal nerves, there are numerous scattered dilated myelin sheaths, up to 50 µm in diameter, that are often arranged in linear chains in longitudinal sections (ellipsoids). These dilated myelin sheaths frequently lack axons and contain cellular debris and occasional gitter cells (digestion chamber) (axonal degeneration). Multifocally, there are scattered reactive astrocytes characterized by large nuclei with finely stippled chromatin and a scant amount of amphophilic, fibrillar cytoplasm. The dura is focally expanded by an island of mature woven bone surrounding a central marrow cavity that contains adipose tissue and scant hematopoietic elements (osseous metaplasia).

MORPHOLOGIC DIAGNOSIS: 1. Spinal cord, white matter; spinal nerves: Axonal degeneration, chronic, multifocal, moderate, with ellipsoids, German shepherd dog, canine.

2. Spinal cord, dura mater: Osseous metaplasia, focal, mild.

ETIOLOGIC DIAGNOSIS: Hereditary myelopathy

CONDITION: Degenerative myelopathy

CONDITION SYNONYMS: German shepherd myelopathy, progressive myelopathy, degenerative radiculomyelopathy of adult dogs

Slide B: Signalment (JPC #2082443): Tissue from a 3-month-old female Afghan hound.

HISTORY: This dog presented 7 days prior to necropsy with a 2-day history of progressive hindlimb weakness, hyperreflexia, and rigid paraplegia. The panniculus reflex was absent. No lesions were seen on radiographs.

HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Multifocally affecting all funiculi, most severely in the dorsal and ventral funiculi adjacent to midline and the ventral median fissure, there is marked bilaterally symmetrical liquefactive necrosis characterized by edema, loss of tissue architecture, and replacement by fragmented and clumped eosinophilic cellular and karyorrhectic debris admixed with many large, vacuolated macrophages (gitter cells). Within necrotic foci, there are increased numbers of prominent, ectatic, large and small caliber vessels (redundant vessels), that are multifocally surrounded by clear space (edema) and wispy eosinophilic glial strands. In less affected areas surrounding necrotic foci, there are frequent dilated myelin sheaths up to 40 µm in diameter (ellipsoids), which occasionally contain either swollen axons (spheroids) or gitter cells or cellular debris (digestion chambers), as well as low numbers of hypertrophic astrocytes with abundant cytoplasm (gemistocytes).

MORPHOLOGIC DIAGNOSIS: Spinal cord, white matter: Liquefactive necrosis, bilaterally symmetrical, multifocal, moderate (lateral funiculi) to marked (dorsal and ventral funiculi), with marked myelin sheath dilation and redundant vessels, Afghan hound, canine.

ETIOLOGIC DIAGNOSIS: Hereditary myelopathy

CONDITION: Inherited necrotizing myelopathy of Afghan hounds

SYNONYMS: Myelomalacia in Afghan hounds; hereditary myelopathy with myelinolysis in Afghan hounds

GENERAL DISCUSSION:

• Degenerative myelopathy is an inherited, idiopathic, noninflammatory disease with progressive neuronal degeneration affecting the central and peripheral nervous system (central and peripheral neuronopathy)
• Most common in German shepherds (German shepherd degenerative myelopathy), but also described in Belgium shepherd, Old English sheepdog, Chesapeake Bay retriever, Bernese Mountain dog, Rhodesian ridgeback, Weimaraner, Pembroke Welsh Corgi, boxer, Siberian huskies, and Great Pyrenees; reported recently in Hovawart dogs (Mandrioli, 2021)
• A common, slowly progressive, idiopathic, degenerative myelopathy of aging dogs, usually over 8 years of age
• Afghan hounds have an inherited necrotizing myelopathy
  • Acute, rapidly progressive, necrotizing, symmetrical spinal cord disease of young (3-12 month old) Afghan hounds recognized since the early 1960s
  • More accurately described as a “myelinopathy”
  • Also reported in miniature poodles and Kooiker dogs

PATHOGENESIS:

• Inherited or immune-mediated; In some breeds, a mutation in superoxide dismutase 1 (SOD-1) gene has been demonstrated🡪accumulation of SOD1 proteins in spinal neurons
• Used as a model for human amyotrophic lateral sclerosis (ALS)
• Afghan hound necrotizing myelopathy:
  • Autosomal recessive pattern of inheritance
  • Presumed to be metabolic or enzymatic defect involving myelin🡪florid myelinolysis and cavitation

TYPICAL CLINICAL FINDINGS:

• Insidious onset, prolonged course, progressive ataxia and muscle weakness localized to thoracolumbar spinal cord; thoracic limbs spared
• Paraparesis, weakness, truncal ataxia
• Loss of patellar reflexes- involvement of dorsal nerve roots (hence, “radiculo”-neuropathy)
• Afghan hound necrotizing myelopathy:
  • Present around 6 months of age (range 3-13 months)
  • Rapidly progressive, caudal ataxia progresses to paraplegia in few days (commonly 7-10 days), followed by phrenic paralysis (diaphragmatic failure)

TYPICAL GROSS FINDINGS:

• None in the CNS
• Atrophy of caudal axial and appendicular muscles
• Afghan hound necrotizing myelopathy:
  • Thoracic spinal cord predominantly- spongiotic changes, gray discoloration and extreme softening of all funiculi (leukomyelomalacia), occasionally resulting in cavitation
  • Rarefaction tapers cranially to the midcervical region often involving only the dorsal and/or ventral funiculus and caudally to about L5 and involving the ventral funiculus

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• In thoracic spinal cord, dorsal aspects of lateral funiculi and medial aspects of ventral funiculi most severely affected
  • Diffuse or multifocal axonal swelling, fragmentation (degeneration) with ballooning and degeneration of myelin sheaths, astrocytosis
  • Degeneration of dorsal nerve rootlets and nerves, loss of neuronal cell bodies in spinal gray matter, brainstem nuclei
• Afghan hound necrotizing myelopathy:
  • Dominant change is myelin vacuolation followed by myelinolysis (white matter predominantly affected); spares axons
  • Bilaterally symmetric pattern in ventral, lateral, and dorsal funiculi
  • Most extensive throughout thoracic segment
  • Mild lesions- vacuolated myelin sheaths
  • Severe lesions are characterized by severe cribriform change, depletion of neuroglial structures, redundant vessels, and numerous gitter cells

ULTRASTRUCTURAL:

• Initial vacuolation of myelin- splitting of lamellae at intraperiod line, expansion of extracellular space
• Fragmented and degenerate myelin phagocytosed by gitter cells, leaving microcavities

ADDITIONAL DIAGNOSTIC TESTS:

• Luxol fast blue (stains myelin), EM
• Cytology- free myelin in CSF fluid; elevated total protein of CSF

DIFFERENTIAL DIAGNOSIS:

• Causes of Wallerian degeneration: trauma, intervertebral disc disease (N-M27), lumbosacral disease, stenosis, or fibrocartilaginous emboli (N-M03)
• Giant axonal neuropathy of German shepherds: A distal axonopathy; ~15-months old; paraparesis, ataxia, megaesophagus; inherited autosomal recessive
• Giant clumps of neurofilaments accumulate at distal ends of long axons in spinal cord with degeneration of terminal ends > appears as argentophilic axonal swellings in ascending fasiculus gracilis and dorsal spinocerebellar tracts, as well as the peripheral CNS
• Afghan hound necrotizing myelopathy:
  • Because of symmetry, signalment, and no inflammation, other than gitter cells, differential diagnoses are few

COMPARATIVE PATHOLOGY:

• Dogs:
  • Canine multiple system degeneration (aka progressive neuronal abiotrophy)- Kerry blue terrier breed; autosomal recessive inheritance pattern, affects basal nuclei, substantia nigra, cerebellar cortex; described in Chinese crested and Ibizan hound breeds; mutation in gene similar to human PARK2 (gene responsible for Parkinson’s disease)
  • Multisystem neuronal degeneration of the red-coated English Cocker Spaniel- unknown pathogenesis; bilaterally symmetric diffuse nerve cell loss in first year of life
    • Other breeds have similar conditions- Cairn terrier
  • Demyelinating myelopathy in miniature poodles: Rare idiopathic demyelination of the brain stem and spinal cord in puppies
  • Leukoencephalomyelopathy- Rottweiler and Leonberger dogs; inherited, progressive disease starting after 12 months characterized by bilateral demyelination that affects cervical spinal cord
  • Recent case report of a cholesterol granuloma associated with degenerative neuropathy in the cauda equina of a Labrador retriever (Tanaka, 2022)
• Equine (N-M07): Degenerative myelopathy with myelin loss, astrocytosis, primarily dorsal funiculi but may be diffuse, onset birth to 2 years; similar presentation in Mongolian wild (Przewaski) horses potentially related to hypovitaminosis E
• Bovine: Progressive degenerative myelopathy (Weaver syndrome) in brown Swiss cattle characterized by axonal degeneration in funiculi and medulla white matter and Purkinje cell degeneration; onset usually from 5 to 8 months
• Pig: Degenerative myelopathy caused by diet deficient in pantothenic acid (Vitamin B5) (Lorenzett, 2023)
• Cat: Myelopathy similar to that seen in the German shepherd dog
• Rat: Paraparesis associated with myeloradiculopathy in senescent rats; 2 years or older, paraplegic and wasting of pelvic limbs, all funiculi affected, most severe in cranial thoracic segments

References:

1. Cantile C, Youssef S. Nervous System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:326-340.
2. De Lorenzi D, Mandara MT. The Central Nervous System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 3rd ed. St. Louis, MO: Elsevier; 2016:379, 387-388.
3. Duncan M. Perissodactyls. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:437-439.
4. Lorenzett MP, Armién AG, Henker LC, et al. Motor and somatosensory degenerative myelopathy responsive to pantothenic acid in piglets. Vet Pathol. 2023;60(1):101-114.
5. Mandrioli L, Gandini G, Gentilini F, Chiocchetti R, Turba ME, Avallone G, Pellegrino V, Menchetti M, Kobatake Y, Kamishina H, Cantile C. Degenerative Myelopathy in Hovawart Dogs: Molecular Characterization, Pathological Features and Accumulation of Mutant Superoxide Dismutase 1 Protein. J Comp Pathol. 2021;182:37-42.
6. Miller AD, Porter, BF. Nervous System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:977-979.
7. Tanaka Y, Watanabe K, Miller AD, Matsumoto K, Kobayashi Y. Cholesterol granuloma associated with degenerative neuropathy in the cauda equina of a dog. J Vet Diagn Invest. 2022;34(6):1010-1014.

Click the slide to view.

---