JPC SYSTEMIC PATHOLOGY
NERVOUS SYSTEM
February 2023
N-M27
Slide A: Signalment (JPC #4003240): 3-year-old male, intact dachshund
HISTORY: This dog had a history of hindlimb lameness progressing to paraparesis then to tetraplegia over period of 8 days. Gross pathologic changes included hemorrhage admixed with dry, crumbly, gray-white to yellow material surrounding the spinal cord in the epidural space over the body of L5. The L4/5 disk had a chalky appearance centrally compared to adjacent disks. A small focal central area of hemorrhage is present in sections of the spinal cord extending from C2-C4. There were multifocal to coalescing areas of hemorrhage in the spinal cord from C4-L7.
HISTOPATHOLOGIC DESCRIPTION: Spinal cord (cervical, lumbar, and thoracic segments):
Lumbar and thoracic spinal cord: Affecting approximately 90% of the lumbar spinal cord and 70% of the thoracic spinal cord, affecting both grey and white matter, there is extensive loss of normal architecture and marked rarefaction with cavitation and replacement by eosinophilic cellular and karyorrhectic debris, fibrin, edema, and multifocal hemorrhage (liquefactive necrosis). Areas of cavitation are most severe peripherally. The grey matter is diffusely replaced by a dense, coalescing, serpiginous band of vacuolated gitter cells admixed with few neutrophils, hemorrhage, and debris that multifocally extends into the adjacent white matter. There is extensive neuron loss; the few remaining neurons have either indistinct cell borders with pale granular to vacuolated cytoplasm and karyolytic or absent nuclei (degeneration) or are shrunken with hypereosinophilic cytoplasm and pyknotic or karyorrhectic nuclei (necrosis). The scant remaining white matter funiculi display diffuse, marked Wallerian degeneration characterized by dilated myelin sheaths that contain either swollen eosinophilic axons (spheroids) or fragments of necrotic debris and one or more gitter cells (ellipsoids or digestion chambers). The leptomeninges are infiltrated by low numbers of lymphocytes, plasma cells, and macrophages admixed with hemorrhage, fibrin, and edema. There is diffuse thickening of the dura mater with multifocal areas of mineralization. There are scattered spheroids and rare ellipsoids within the adjacent spinal nerve roots.
Cervical spinal cord: The cervical spinal cord is least severely affected; there is bilateral, focally extensive hemorrhage, fibrin, and edema limited to the dorsomedial funiculi, extending dorsally from the central canal. Within the area of hemorrhage and in the adjacent white matter there are low to moderate numbers of dilated myelin sheaths with swollen axons (spheroids, axonal degeneration). Multifocally, neurons within the grey matter are surrounded by glial cells (satellitosis).
MORPHOLOGIC DIAGNOSES:
1. Lumbar and thoracic spinal cord: Liquefactive necrosis, focally extensive to diffuse, marked, with hemorrhage, axonal degeneration, and mild lymphoplasmacytic meningomyelitis, dachshund, canine.
2. Cervical spinal cord, white matter, dorsomedial funiculi: Hemorrhage, focally extensive, moderate, with axonal degeneration.
Slide B: Signalment (JPC #4019135): 3-year-old male, Dachshund
HISTORY: The dog presented to the veterinarian with rear limb paralysis and a large bladder, and was found dead in its kennel the next morning. Gross pathologic changes included a herniated intervertebral disc with hemorrhage between T11/T12, elevation of the dorsal longitudinal ligament on the right side, and compression of the spinal cord that appeared thin, dark red to black, hemorrhagic, and malacic. The central canal and gray matter contained a dark red-to-black and necrotic tract extending from the affected spinal cord caudally to the cauda equina and cranially to the midcervical spinal cord.
HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Markedly expanding and effacing the partially ruptured central canal with discontinuous ependymal cells and infiltrating and compressing the surrounding gray matter and white matter dorsal funiculi is abundant eosinophilic, flocculent material admixed with hemorrhage, fibrin, edema, and small numbers of viable and degenerate neutrophils. Intermixed with the eosinophilic material are remnant swollen axons within dilated myelin sheaths (spheroids) and neurons that are occasionally shrunken with hypereosinophilic cytoplasm and pyknotic or karyorrhectic nuclei (necrosis). Small caliber vessels within both the adjacent gray and white matter are multifocally surrounded by increased numbers of neutrophils (perivascular cuffing). Axons located multifocally throughout the white matter and extending into the lateral funiculi of the spinal cord are occasionally either swollen (spheroids) or degenerate.
MORPHOLOGIC DIAGNOSIS: Spinal cord: Liquefactive necrosis, focally extensive, severe, with hemorrhage, dachshund, canine.
SYNONYMS: Progressive hemorrhagic myelomalacia and hematomyelia
CAUSE: Intervertebral disk protrusion/rupture
GENERAL DISCUSSION:
- Intervertebral disk degeneration occurs in all dog breeds as they age, but there is marked variation in the process for chondrodystrophic vs. non-chondrodystrophic breeds
- Chondrodystrophic breeds (CD) (e.g. Dachshund (3-7 years old), Pekingese, Corgi, Basset): All disks have abnormal nucleus pulposus (NP), which results in Hansen type I intervertebral disk (IVD) herniation
- Extrusion of degenerate nuclear material through the annulus fibrosis (AF) and ruptured dorsal longitudinal ligament into spinal canal
- Injury to spinal cord generally more severe than in type II herniation because there isn’t time for the body to compensate as there is with type II
- In Dachshunds, increased risk is associated with shorter leg and spine length indicating the severity of the chondrodystrophy; long backs in chondrodystrophic breeds is an optical illusion due to short legs
- Nonchondrodystrophic breeds (NCD): Lesions develop slowly over time with aging; more likely to have Hansen type II herniation (any breed of dog / humans / cats / other species)
- Type I herniations can occur in non-chondrodystrophic but less common
- Disk herniation:
- Dorsal herniation of disk material into spinal canal is most common cause of paresis or paralysis in dogs
- Cranial/caudal herniation: into vertebral body, forming Schmorl’s node
- Lateral herniation results in spinal nerve compression / entrapment
- Ventral herniation can occur- predisposes to spondylosis
PATHOGENESIS:
- Chondrodystrophic breeds (CD):
- Fibroblast growth factor 4 (FGF4) retrogene (mutation) affects the composition of nucleus pulposus (NP) and length/curvature of legs
- Recent report of Nova Scotia Duck Tolling Retrievers shows that the FGF4 retrogene insertion on chromosome 12 (CFA12) is associated with premature chondroid degeneration of the IVD vs. breed-matched control dogs; supporting the notion that this defect is sufficient to cause the chondrodystrophic phenotype (Murphy. Vet Pathol. 2019)
- NP of chondrodystrophic dogs contains up to twelve times more collagen than proteoglycan and degeneration starts as early as 6 months old; collagen content of IVD is up to 25% compared to a lifelong <5% in nonchondrodystrophic breeds; by 1 year old the NP is largely replaced by cartilaginous material
- Recent report of Nova Scotia Duck Tolling Retrievers shows that the FGF4 retrogene insertion on chromosome 12 (CFA12) is associated with premature chondroid degeneration of the IVD vs. breed-matched control dogs; supporting the notion that this defect is sufficient to cause the chondrodystrophic phenotype (Murphy. Vet Pathol. 2019)
- Nonchondrodystrophic breeds (NCD):
- Have more normal mucoid composition of NP until at least until middle age; NP becomes more dry and fibrous with age
- NP seldom mineralizes
- Fibrous metaplasia may occur due to focal disruption of lamellae of AF, often due to trauma; changes are usually confined to a single disk; this usually occurs in relatively young dogs
- Partial herniation of nucleus pulposus (NP) through ruptured AF; generally confined to a single disk
- Bulging of outer lamellae of AF and intact dorsal longitudinal ligament into spinal canal
- Disk protrusions are usually dorsal/dorsolateral due to eccentric location of NP and occur at sites of greatest vertebral mobility
- Ventral herniation is less common; may predispose to spondylosis
- “Schmorl’s node”: created by nuclear material that herniates through cranial or caudal cartilaginous end plates into the vertebral body
- Spinal cord injury is due to physical trauma and compression; disk material may also compress vascular supply to spinal cord segment resulting in ischemic necrosis
TYPICAL CLINICAL FINDINGS:
- Acute pain, paresis, paralysis (depending on the volume of material extruded)
- Often more severe in chondrodystrophic breeds; worse in thoracolumbar region (cervical spinal canal greater extradural space for nuclear material to occupy without compressing the spinal cord/nerves)
- Myelomalacia (ascending-descending myelomalacia): sudden onset of flaccid paralysis and sensory deficits; poor prognosis
TYPICAL GROSS FINDINGS:
- In dogs, approximately 70% of lesions will be between T12 – L2 and 15% in the cervical region
- NP: dry, gray/white or yellow, cartilaginous material
- Spinal cord/spinal canal:
- Extradural hemorrhage and bulging disk or nuclear / disk material in the spinal canal
- Hansen type I: nuclear material in the spinal canal bulging through a tear in the dorsal longitudinal ligament
- Hansen type II: intact dorsal longitudinal ligament bulging into the spinal canal from pressure by the AF
- Localized (more common) or extensive hemorrhagic myelomalacia/necrosis of spinal cord +/- ascending syndrome (ascending-descending myelomalacia)
- Develops 12-24 hours after injury -> semiliquefaction of the tissue
- Hemorrhagic myelomalacia extending away from the site of impact
- Mechanism unknown but vascular damage, hemorrhage, and/or inflammatory mediators thought to contribute
- Chronic cases: Spondylosis and possible ankylosis of joint; yellow-green discoloration of disk material; degenerative joint disease and enlargement of articular facets
ADDITIONAL DIAGNOSTICS:
- Luxol fast blue stain to identify pattern of demyelination in white matter tracts
- Alcian blue stain to identify the presence of herniated disk material
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Disk changes (CD breeds)
- Thickening of the delicate fibrocartilaginous septa between cell clusters, lobulation of NP
- Chondroid proliferation (chondroid metaplasia): Replacement of NP matrix chondroid tissue in all discs (within first year of life) that eventually degenerates and mineralizes starting at the periphery
- Eventual degeneration of the inner lamellae of the annulus fibrosis and tearing with entry of NP material; eventual degeneration of the annulus outer lamellae
- Alcian blue stain may help identify NP material in abnormal location (i.e. in AF or spinal cord)
- Disk changes (NCD breeds)
- Chondroid metaplasia of the NP with lack of mineralization as seen in CD breeds
- Vertebral changes
- Reduced thickness of the disk ->overriding of articular facets and joint instability -> degenerative disease and enlargement of articular facets -> impingement of nerves +/- compression of spinal cord -> periosteal new bone on the ventral (most common), lateral, or dorsal surfaces of the vertebrae (spondylosis)
- Spinal canal / cord changes
- Presence of disk material in spinal canal with inflammatory reaction and dural adhesions
- Wallerian degeneration
- Vertebral changes
- Chondroid metaplasia of the NP with lack of mineralization as seen in CD breeds
- Disk changes (NCD breeds)
- Rostral to site of injury white matter degeneration may be limited to ascending tracts in dorsal funiculi and superficial dorsolateral to lateral funiculi
- Caudal to site of injury white matter degeneration may be limited to descending tracts in ventral funiculi and central-lateral funiculi
DIFFERENTIAL DIAGNOSIS:
- Other causes of compressive spinal cord injury:
- Vertebral subluxation / fracture / dislocation
- Cervical stenotic myelopathy (“wobbler syndrome”, N-M02): Horses and large breed dogs; stenosis of the cervical vertebral canal with cervical spinal cord compression; lesions in the spinal cord would be identical to IVDD minus the presence of disk material
- Spinal ganglion cysts and synovial cysts reported to cause cord compression but uncommon
- Spinal canal stenosis due to degenerative joint disease of the articular facets or hypertrophy of the dorsal longitudinal ligament and/or ligamentum flavum
- Neoplasms of the meninges or nerve roots
- Developmental malformations: Atlantooccipital malformation; hemivertebrae; scoliosis; lordosis; kyphosis
COMPARATIVE PATHOLOGY:
- Equine:
- NP is more fibrous than in dogs; demarcation from AP is less distinct
- Herniation is considered rare in horses but is reported in the cervical region; although once thought that the equine NP was more fibrous than in dogs (JKP), a recent report suggests they have a similar composition (Bergmann Vet Pathol. 2018); when disk herniation lesions occur, they are more similar to type II disease and may be subclinical
- No reported cases of herniation in the TL region of the spine
- Horse spines are inflexible compared to humans and dogs and they have strong longitudinal ligaments
- Feline: Intervertebral disk degeneration only occasionally seen with advanced age
- Mice, aged: matrix degradation, protrusion into the spinal canal, cartilaginous proliferative lesions, and ossification; eosinophilic change to NP; these changes are often not examined
- Pigs, adult boars and sows: Degenerative changes similar to nonchondrodystrophic breeds; no reports of dorsal herniation of NP into the spinal canal
- Mustelids: Age-related lesion (rare)
- African hedgehogs: Must be differentiated from wobbly hedgehog syndrome
- C/S: lameness; proprioceptive deficits; urinary tract dysfunction
- Dx: narrowed intervertebral cervical and lumbar spaces and spondylosis on radiographs
- Histo: neovascularization, fissures, mineralization, and dorsal extrusion of the AF and NP into spinal canal; spheroids, edema within and around axons, and digestion chambers
- Felidae: IVD degeneration, disc herniation, and intervertebral space collapse, and degeneration of the articular facets of the vertebral bodies
- Humans: disk herniations are typically lateral; results in compression of spinal nerve roots
- Snakes: Intervertebral disks are absent and adjacent vertebrae are connected via modified ball-and-socket articular joints
References:
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- Barthold SW, Griffey SM, Percy DH. Rabbit. In: Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:105.
- Bergmann W, Bergknut N, Veraa S, et. al. Intervertebral disc degeneration in warmblood horses: morphology, grading, and distribution of lesions. Vet Pathol. 2018;55(3):442-452.
- Bergmann W, de Lest CV, Plomp S, Vernooij JCM, Wijnberg ID, Back W, Gröne A, Delany MW, Caliskan N, Tryfonidou MA, Grinwis GCM. Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization. Vet Pathol. 2022 Mar;59(2):284-298.
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- Hansen T, Smolders LA, Tryfonidou MA, et al. The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs. Vet Pathol. 2017;54(6):945-952.
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- Murphy BG, Dickinson P, Marcellin-Little DJ, Batcher K, Raverty S, Bannasch D. Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype. Vet Pathol. 2019;56(6): 895-902.
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