AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

NERVOUS SYSTEM

January 2017

N-M04

 

Signalment (JPC #1895035):  Male German shepherd dog

 

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

 

HISTOPATHOLOGIC DESCRIPTION: Spinal cord: Multifocally, affecting white matter funiculi and spinal nerves are numerous dilated axonal sheaths, up to 50 um in diameter, which, in longitudinal sections of the spinal cord are often arranged in linear chains. These dilated myelin sheaths frequently contain cellular debris and occasional gitter cells (ellipsoids) (axonal degeneration). Multifocally, there are scattered reactive astrocytes with large nuclei, finely stippled chromatin, and a scant to small amount of amphophilic, fibrillar cytoplasm. The dura is focally expanded by an island of immature woven bone surrounding a central area of adipose tissue and scant hemtopoeitic elements (osseous metaplasia).

 

MORPHOLOGIC DIAGNOSIS:  1. Spinal cord, white matter; spinal nerves:  Axonal degeneration, 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, chronic degenerative radiculomyelopathy

 

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

 

HISTORY, Slide B:  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 white matter of the dorsal funiculus and ventral funiculus adjacent to the ventral fissure, there is marked bilaterally symmetrical necrosis characterized by rarefaction, loss of tissue architecture, and replacement by fragmented and clumped eosinophilic cellular debris admixed with many large microvacuolated macrophages (gitter cells). Within affected areas, there are increased numbers of prominent ectatic large and small caliber vessels (redundant vessels), which are multifocally surrounded by clear space (edema) and wispy eosinophilic glial strands. In less affected areas surrounding necrotic foci, there are multiple foci of axonal degeneration, characterized by numerous swollen myelin sheaths up to 40 um in diameter, which occasionally contain gitter cells or cellular debris (ellipsoids).  There are also low numbers of hypertrophic astrocytes (gemistocytes) within less affected areas of gray matter adjacent to necrotic foci.

 

MORPHOLOGIC DIAGNOSIS:  Spinal cord, dorsal and ventral funiculi, white matter:  Necrosis, bilaterally symmetrical and focally extensive, with axonal degeneration and increased vascular profiles, 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:

German shepherd degenerative myelopathy

·       A common, slowly progressive, idiopathic, degenerative myelopathy of aging German shepherds and other large dogs of usually over 8 years of age

·       Rhodesian ridgebacks, Pembroke Welsh corgies, boxers, Chesapeake Bay retrievers, Siberian huskies, Bernese mountain dogs

·       Progressive ataxia referable to thoracolumbar spinal cord and muscle weakness

·       Microscopic lesions in thoracic spinal cord, diffuse or multifocal

·       Lesion characterized by ballooning and degeneration of myelin sheaths, accompanied by axonal degeneration and loss

·       Age of onset is usually 8 years

 

Afghan hound necrotizing myelopathy

·       Acute, rapidly progressive, necrotizing, symmetrical, spinal cord disease of young Afghan hounds recognized since the early 1960s

·       Also reported in miniature poodles and Kooiker dogs

·       Initially described as acute necrotizing myelomalacia; subsequent studies show florid myelinolysis and cavitation, sparing axon (leukodystrophy)

·       Age of onset is 3 to 12 months

·       Caudal ataxia progress to paraplegia in few days, followed by phrenic paralysis

·       Myelin degenerates around apparently normal axons with no inflammation

·       Principle locus is thoracic spinal cord

 

PATHOGENESIS: 

·       Unknown

·       German shepherd myelopathy may be associated with immunodeficiency and also thought to have a genetic determination

·       In some breeds, a transitional mutation in superoxide dismutase 1 (SOD-1) has been demonstrated

·       In other studies, an altered immune-mediated response has been suggested as a cause of the neurodegeneration

·       Afghan hound necrotizing myelopathy

·       Presumed to be metabolic or enzymatic defect involving myelin

·       Evidence suggests a simple autosomal recessive pattern of inheritance

 

TYPICAL CLINICAL FINDINGS:

German shepherd myelopathy

·       Affected dogs usually 5 years of age and older

·       Insidious onset, prolonged course, thoracic limbs spared

·       Initial loss of proprioception progressing to paw-dragging, crossing of limbs, hypertonia, hypermetric hind limbs, signs may be asymmetric

·       General wasting (disuse atrophy) of caudal thoracic and lumbosacral muscles

·       10-15% of cases have loss of patellar reflexes and degeneration in femoral nerves

·       Increased protein in CSF when collected from the lumbar subarachnoid space but normal when collected from the cisternal subarachnoid space

 

Afghan hound necrotizing myelopathy

·       Present around 6 months of age (range 3-13 months)

·       Stiff thoracic limbs, truncal weakness, ataxia of pelvic limbs, bunny-hopping gait, spastic paraparesis

·       Rapidly progressive, commonly paraplegic in 7 to 10 days

·       Increased spinal reflexes and tone, pelvic limb hypalgesia

·       CSF may have normal to high protein levels

 

TYPICAL GROSS FINDINGS: 

German shepherd myelopathy

·       No gross lesions

 

Afghan hound necrotizing myelopathy

·       Gray discoloration and extreme softening of all funiculi, 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: 

German shepherd myelopathy

·       Lesions throughout the spinal cord but most intense in thoracic region and dorsal spinal nerve roots

·       Specifically dorsolateral and ventromedial funiculi, cerebellar peduncles and occasionally brainstem (trapezoid body and olivary nuclei); occasionally in peripheral nerves

·       Changes include vacuolation, axonal and myelin sheath degeneration and loss of superficial (subpial) and deep fibers in both ascending and descending pathways, gliosis, and increased numbers of small blood vessels

·       Can affect all funiculi, typically bilateral but not necessarily symmetrical

 

Afghan hound necrotizing myelopathy

·       Dominant change is myelin vacuolation followed by myelinolysis

·       Bilaterally symmetric pattern in ventral, lateral, and dorsal funiculi

·       Most extensive throughout thoracic segment

·       Mild lesions are characterized by loosely arranged white matter with vacuolated myelin sheaths

·       Severe lesions are characterized by severe cribriform change, depletion of neuroglial structures, redundant vessels, and numerous gitter cells

·       Axons are commonly spared

·       Involvement of gray matter is uncommon

 

ULTRASTRUCTURAL FINDINGS:

·       Earlier lesions have intact myelin sheaths that are split at the intraperiod line

·       Cavitated areas contain demyelinated fibers that are supported by the processes of reactive astrocytes

 

ADDITIONAL DIAGNOSTIC TESTS: 

·       Luxol fast blue (stains myelin), EM

 

DIFFERENTIAL DIAGNOSIS: Microscopic

German shepherd myelopathy

·       Anything that causes Wallerian degeneration

·       Trauma, intervertebral disc disease, lumbosacral disease, stenosis, fibrocartilaginous thrombi

·       Giant axonal neuropathy of German shepherds: A distal axonopathy; ~15-months old; paraparesis, ataxia, megaesophagus; inherited autosomal recessive

·       Clumps of neurofilaments accumulate at distal ends of long axons causing degeneration> 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:

·       Canine degenerative myelopathy, Welsh corgi: Clinically and pathologically similar to human amyotrophic lateral sclerosis, because of similar lesions and involvement of superoxide dismutase 1 (SOD1) mutation

·       Giant axonal neuropathy of the German shepherd dog:  Rare disease, distal axonopathy, giant swellings of neurofilaments in spinal cord, terminal ends completely degenerate

·       Demyelinating myelopathy in miniature poodles:  Rare idiopathic demyelination of the brain stem and spinal cord in puppies

·       Equine:  Degenerative myelopathy with myelin loss, astrocytosis, primarily dorsal funiculi but may be diffuse; onset birth to 2 years

·       Bovine:  Progressive degenerative myelopathy 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

·       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, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier Ltd; 2016:330,340,382-383.

2.      De Lahunta A, Glass E. Veterinary Neuroanatomy and Clinical Neurology. 3rd ed. St. Louis, MO: Saunders Elsevier; 2009:264.

3.      Ogawa M, Uchida K, Yamato O, Inaba M, Uddin M, Nakayama H. Vet Pathol. 2014; 51(3); 591-602.

4.      Summers BA, Cummings JF, De Lehunta A. Veterinary Neuropathology. St. Louis, MO: Mosby; 1995:283-284,319-321,446-447.

5.      Miller AD, Zachary JF. Nervous system. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 6th Ed. St. Louis, MO: Elsevier; 2016:891-2.

 

 


Click the slide to view.



Click on image for diagnostic series.



Back | Home | Contact Us | Links | Help |