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4/21/2012
COMPARE THE TRAINING OF MEDICAL
AND VETERINARY PATHOLOGISTS
APPROACHING
NEUROPATHOLOGY
Brian A. Summers
Professor of Comparative Neuropathology
Royal Veterinary College
MD
DVM
PATHOLOGY
RESIDENCY ~5 YRS
(single species)
PATHOLOGY
RESIDENCY 3 YRS
(multiple species)
SUBSPECIALITY
TRAINING ~2/3YRS
(NEUROPATHOLOGY)
WHAT DOES THE VETERINATRY
NEUROPATHOLOGIST NEED?
1. DVM or equivalent, clinical practice
2. Training in veterinary pathology
…………………………………………
3. Embryology and neuroanatomy
4. Clinical neurology
5. Contemporary imaging (CT and MRI)
WHAT DOES THE VETERINATRY
NEUROPATHOLOGIST NEED?
Dr. A. de Lahunta
PROFESSOR OF ANATOMY (EMBRYOLOGY)
NEUROLOGY
NEUROPATHOLOGY
NEUROANATOMY
Vertebral canal from a 10-year-old goose.
Glycogen body
1. DVM or equivalent, clinical practice
2. Training in veterinary pathology
…………………………………………
3. Embryology and neuroanatomy – what’s
normal?
4. Clinical neurology
5. Contemporary imaging (CT and MRI)
1
4/21/2012
NEUROANATOMY
LISSENCEPHALY - OFTEN PACHYGYRIA ALSO
Dog
Opossum
CC
Cat
RC
Opossum
L3-4
N01-134
Sporadic
cerebellar
malformation.
9dy F Quarter horse foal.
Ataxia, loss of balance
and myoclonic seizures.
Developed septicemia .
IN DOMESTIC ANIMALS, THE
ABSENCE OF (OR A HYPOPLASTIC)
CORPUS CALLOSUM OCCURS IN A
VARIETY OF SETTINGS.
N01-134
NO CORPUS CALLOSUM
1552
Cerebellar vermian malformation,
lamb. “Dandy-Walker”.
2
4/21/2012
Short corpus callosum
Miller’s Anatomy of the Dog.
NEUROANATOMY:
TRACTS IN THE SPINAL CORD AND WHAT
DO YOU NEED TO KNOW?
NEUROANATOMY EXPLAINS PATHOLOGY
Spinal cord from two dogs with several months pelvic
limb ataxia; patellar reflex loss without atrophy and
nasal hypalgesia.
Diagnosis:
3
4/21/2012
NEUROANATOMY EXPLAINS PATHOLOGY
CD3
CANINE GANGLIORADICULITIS
Spinal cord from two dogs with several months pelvic
limb ataxia; patellar reflex loss without atrophy and
nasal hypalgesia.
Clue:
Ganglionitis?
Perivascular
cuffing.
Diagnosis: Ganglioradiculitis
Facial and nasal
hypalgesia.
Ataxia of gait.
Depression of
tendon reflexes.
1434
Dog – congenital defect or recent resection?
Don’t confuse canine ganglioradiculitis
with
canine polyradiculoneuritis
(Coonhound paralysis).
1434
4
4/21/2012
1434
TRACT DEGENERATION IS NEUROANATOMY
17-year-old Malaysian sun bear
20mo F Doberman Pinscher
Since 4mo – circling, propulsive,..
Dx.: Prosencephalic aplasia
1418 Collie eye anomaly - small rt optic nerve
TRACT DEGENERATION
17-year-old Malaysian sun bear
WHAT DOES THE VETERINATRY
NEUROPATHOLOGIST NEED?
1. DVM or equivalent, clinical practice
2. Training in veterinary pathology
…………………………………………
3. Embryology and neuroanatomy
4. Clinical neurology
5. Contemporary imaging (CT and MRI)
APPROACHING THE POST MORTEM
EXAMINATION OF A NEUROLOGIC CASE
Two philosophies – two pathologists:
1. It’s a neurologic case = I have to pull the brain and spinal cord,
and I better get a couple of peripheral nerves. I wonder what its
got - time will tell (hopefully)?
2. You read a summary of the clinical history and the general and
neurologic examinations – assuming they are available to you.
Formulate a neuroanatomic diagnosis and based on that, a
differential diagnosis; is it the same as the clinicians’ suggested?
Approach the PM examination attempting to confirm your
definitive diagnosis.
5
4/21/2012
CLINICAL NEUROLOGY
CLINICAL NEUROLOGY
What is/are the anatomic diagnosis?
What is/are the anatomic diagnosis?
Dropped jaw = CNV
Protruding tongue = CNXII
Adult cattle in Brazil.
Difficulty in prehending food.
Drool saliva.
Mandibular weakness.
CLINICAL NEUROLOGY
Intramedullary vs extramedullary
If intramedullary – is it involving the
pons and medulla widely or selectively
targeting motor nuclei?
If extramedullary – it must involve at
least two cranial nerves.
PROSOPIS JULIFLORA
Motor V
Prosopis juliflora intoxicosis
PROSOPIS JULIFLORA
Vet Pathology 43:695-701, 2006.
NEUROLOGY FOR PATHOLOGISTS
A novel syndrome in horses:
6-month-old male Warmblood
with progressive scoliosis of the
cervical vertebrae.
Examination:
May stumble on a thoracic limb.
Cutaneous hypalgesia on the
convex surface of the curvature.
6
4/21/2012
NEUROLOGY FOR PATHOLOGISTS
EQUINE SCOLIOSIS
ANATOMIC DIAGNOSIS ?
Vertebral column?
Spinal cord – motor?
– sensory?
Equine Veterinary Journal 36:86-92, 2004.
Dog with bilateral hemorrhagic necrosis of the
caudate nucleus.
WHAT DOES THE VETERINATRY
NEUROPATHOLOGIST NEED?
1. DVM or equivalent, clinical practice
2. Training in veterinary pathology
…………………………………………
3. Embryology and neuroanatomy
4. Clinical neurology
5. Contemporary imaging (CT and MRI)
1875
NECROTIZING ENCEPHALITIS - CHIHUAHUA
5yr F Chihuahua.
Propulsive circling
from 3 yr age.
204982
SPINAL CORD DISEASE
12yr FN DSH cat
3wk non-painful
T3-L3 myelopathy.
MRI.
T2W
GFAP
7
4/21/2012
Dog with motor V deficit: Florida – melanin or hemorrhage
T1 pre gad
Dog with motor V deficit: Florida
T2
Cavernous hemangioma
CNS EDEMA
2. GROSS EXAMINATION OF THE
NERVOUS SYTEM
Vasogenic edema - mechanical injury from space-occupying masses, trauma.
Cytotoxic edema - cellular injury from poisoning, metabolic derangements.
Horse
Brain swelling - edema – herniation
Olfactory bulb
VASOGENIC EDEMA
10yr F Percheron.
Depressed, slightly ataxic
in the pelvic limbs,
circles L.
884
8
4/21/2012
1408
5yr F Great Dane with a L cerebral mass
These two images demonstrate…
DOG WITH SUBDURAL HEMATOMA :
HERNIATION, COMPRESSION AND DURET
HEMORRHAGE
MALFORMATION - DOG
Hydrocephalus
1408 5yr F Great Dane
CAUSE - CHOROID PLEXUS TUMOR
HYDROCEPHALUS
vs
PORENCEPHALY
HYDRANENCEPHALY
SCHIZENCEPHALY
MALFORMATION - DOG
Hydrocephalus - and hydromyelia
9
4/21/2012
HYDROCEPHALUS – DOG
Non-communicating
HYDROCEPHALUS – DOG
Communicating
Clue:
communicating?
Large lateral
aperture.
1383
Hydrocephalic canine brain
1863
HYDROCEPHALUS – DOG
1yr F Rhodesian Ridgeback
Blind, propulsive, falling
to either side.
1863
HYDROCEPHALUS - DOG
10
4/21/2012
Wünschmann, A. and Oglesbee, M.
Periventricular changes associated with spontaneous canine
hydrocephalus. Veterinary Pathology 38:67-73, 2001.
PORENCEPHALY - MAN
38
Pore
Fig. 3. Brain; dog. marked internal
hydrocephalus. Unilateral cleft formation
(arrow) and contralateral tear (arrowhead).
The tear in the internal capsule is
characterized by communication between the
lateral ventricle and the former cleft. The
tissue bordering the dorsolateral aspect of the
tear is necrotic. Formalin fixation. Bottom.
Dog No. 18. Subgross illustration of the
anatomic localization of a cleft (arrow);
caudate nucleus (CN) relative to the internal
capsule (IC). The cleft forms at the transition
of the internal capsule to the putamen.
1778
Porencephaly (+ polymicrogyria) - bovine
1329
Porencephaly - dog
1778
Porencephaly (+ polymicrogyria)
7yr F Rottweiler
Vomiting, depression,
distended abdomen.
Metastatic melanoma.
11
4/21/2012
LABRADOR HYDRANENCEPHALY
LABRADOR HYDRANENCEPHALY
LABRADOR HYDRANENCEPHALY
LABRADOR HYDRANENCEPHALY
MALFORMATION: CEREBELLAR HYPOPLASIA
MALFORMATION: CEREBELLAR HYPOPLASIA
Cat
Calf
Clue:
Congenitally small
cerebellum? Examine
the transverse fibers of
the pons.
12
4/21/2012
MALFORMATION - HYPOMYELINOGENESIS
NEW BORN LAMB (E89-24)
Stunted rat terrier pups – 3/5 in litter affected
HYPOMYELINATION WITH
HYPOTHYROIDISM (Rat terrier)
SOMETIMES, DEVELOPMENT IS
JUST DELAYED.
Veterinary Pathology
2007.
7521-82
6-month-old female Percheron CC: ataxia
REACTION OF THE CNS TO INJURY
– WHAT IS THE SPECIFICITY?
13
4/21/2012
INFLAMMATION
EQUINE PROTOZOAL MYELOENCEPHALITIS
PERIVASCULAR CUFFING
GLIOSIS: DIFFUSE OR FOCAL
NEURONAL SATELLITOSIS OR NEURONOPHAGIA
DEMYELINATION
1300
EQUINE PROTOZOAL MYELOENCEPHALITIS
EQUINE PROTOZOAL
MYELOENCEPHALITIS
1496
GFAP
11 yr MN QH
3.5wk acute LH
lameness, worked on
by a chiropractor.
Clue: Spinal
cord MN injury
- examine the
ventral roots.
R
L
154, 264
CAPRINE ARTHRITIS
ENCEPHALITIS SYNDROME
153
CAPRINE ARTHRITIS ENCEPHALITIS SYNDROME
14
4/21/2012
PUG DOG ENCEPHALITIS
1768
MALTESE TERRIER ENCEPHALITIS
2.5 yr M - blind, seizures
(80 vs 95 mm)
1759
BRAIN ABSCESSES – USUALLY LARGE ANIMALS
ALPACA ABSCESS
1759
1.5yr F Alpaca.
Recumbent some months ago,
improved with antibiotics;
recumbent again, died.
Abscess
There is a potential for herniation
of the cingulate gyrus below the
falx cerebri.
Why is the subtentorial
herniation bilateral?
INCLUSION BODIES
986
DISTEMPER ENCEPHALITIS IN A LION
IHC
Bovine rabies
15
4/21/2012
PSEUDOVIRAL (RABIES) INCLUSIONS
16
4/21/2012
THE PERIVASCULAR CUFF –
INFLAMMATION VS NEOPLASIA
86-7574
CNS LYMPHOMA – HORSE (multicentric)
MAKING THE DISTINCTION BETWEEN CNS
LYMPHOMA AND LYMPHOCYTIC
INFLAMMATION CAN BE DIFFICULT.
IT IS SIMPLER IF THE LYMPHOMA IS
MULTICENTRIC; OFTEN YOU ONLY GET THE BRAIN.
Clue: sharp
margins
N93-321
CNS LYMPHOMA - HORSE
DOG – LYMPHOMA?
91-4418
DEER – LYMPHOMA?
PERIVASCULAR CUFFING WITH GLIOMA
Vimentin
17
4/21/2012
SATELLITOSIS = NEUROTROPIC VIRUS?
WHITE MATTER INJURY
DEMYELINATION
ARE THESE TERMS
INTERCHANGEABLE?
LFBCEV
Thoracic spinal cord - Dog
DEMYELINATION
DEMYELINATION
CANINE DISTEMPER: WHITE MATTER DEMYELINATION
18
4/21/2012
LFB
7yr MN mixed breed cat
Progressive weight loss
for 3 months; 1 week of loss
of balance with occasional
falling.
Exam.: animal thin, slightly
depressed; intra-abdominal
mass palpated (mesenteric
lymph node abscess).
LFB-Bielschowsky
Central pontine myelinolysis – a demyelinating disease
2002
Hypertensive encephalopathy -Cat
ASTROCYTOSIS:
COMMON IN A
VARIETY OF LESIONS
2002
hypertension cat
PAS GFAP
19
4/21/2012
IDIOPATHIC FELINE HIPPOCAMPAL NECROSIS
GLIOSIS IN EQUINE MYELOPATHY: EXAMINE
THE GLIA LIMITANS
ASTROCYTOSIS: REACTIVE VS NEOPLASTIC
EDM: GFAP/LFB
Clue: Astrocytoma
- heterogeneity
in GFAP staining.
SPONGIFORM ENCEPHALOPATHIES
SPONGIFORM ENCEPHALOPATHIES
MSUD
Boxer
(Rottweiler disease)
Hepatic encephalopathy
ACQUIRED
Infectious
Prion
Retrovirus
Rabies
Non infectious
Hepatic encephalopathy
Renal (uremic) encephalopathy
INHERITED/FAMILIAL
Cerebral edema - cattle
Maple syrup urine disease - cattle
Labrador, Malinois shepherd, Saluki
Bull mastiff - cerebellar nuclei +
hydrocephalus
Rottweiler and Boxer dogs
Toxicologic
Bromethalin
Hexachlorophene (Phisohex)
20
4/21/2012
SPONGIFORM ENCEPHALOPATHIES
NON LESIONS
Red nucleus, cattle
Oculomotor nucleus, horse
Canine
TRAUMA
AND THE NERVOUS SYSTEM
CERVICAL STENOTIC MYELOPATHY - HORSE
333
CERVICAL VERTEBRAL
MALFORMATION-MALARTICULATION
7yr F Doberman Pinscher.
Waxing and waning gait ataxia
for 2.5yr.
Caudal C6
3mo lamb.
Herd history of
soft bones.
260
VERTEBRAL FRACTURE
Cranial C7
FRONTAL BONE FRACTURE – DOG
HBC
Clue: Traumatic spinal cord
lesions commonly taper
into the dorsal funiculus.
21
4/21/2012
HEAD TRAUMA AND DIFUSE AXONAL INJURY - HORSE
DIFFUSE AXONAL
INJURY.
SEVERE HEAD INJURY
BUT NO GROSS
HEMORRHAGE.
ß-amyloid precursor protein immunocytochemistry
HEAD TRAUMA AND DIFFUSE AXONAL INJURY - HORSE
HEAD TRAUMA AND DIFFUSE AXONAL INJURY
ß-amyloid precursor protein immunocytochemistry
ß-amyloid precursor protein immunocytochemistry
H&E
Bielschowsky
IHC
DON’T FORGET THIS CAUSE OF TRAUMA
Dog
DISTRIBUTION OF
LESIONS IS CRITICAL.
22
4/21/2012
NEUROLOGIC DISEASE IN A YOUNG DOG
BRAIN LESIONS IN A DOG:
ALASKAN HUSKY ENCEPHALOPATHY
Acta Neuropathologica 100:50-62, 2000.
THE IMPORTANCE OF LESION DISTRIBUTION
IN DIAGNOSIS: BRAIN LESIONS IN A DOG
999
AUSTRALIAN CATTLE DOG POLIOENCEPHALOPATHY
Brenner O et al. Acta Neuropathologica 94:54-66, 1997. …
CHANGES IN THE NERVOUS SYSTEM
DUE TO AGING
AGING
AND THE NERVOUS
SYSTEM
Spheroids, lipofuscinosis, gliosis, corpora
amylacea, CNS myelin degeneration,
cerebrovascular amyloid, leptomeningeal
fibrosis, cholesterinic radiculopathy, PNS
myelin ballooning, Lafora bodies, dural
mineralization, Renaut bodies, vascular
encrustation.
23
4/21/2012
CEREBROVASCULAR AMYLOIDOSIS
Trichrome
Congo Red
N84-632
WHITE MATTER VACUOLATION AND GLIOSIS
N82-865
WHITE MATTER VACUOLATION AND GLIOSIS
LFB
LFB
GFAP
ISOMORPHIC GLIOSIS
SPHEROIDS
24
4/21/2012
NEUROPATHOLOGY OF AGING
ALZHEIMERS DISEASE
AGING AND THE PNS – LUMBAR DORSAL ROOTS
12yr F Irish Setter.
Large, benign lung mass,411
diffuse muscle atrophy.
AGING AND THE PNS
RENAUT BODY: EQUINE RECURRENT LARYNGEAL NERVE
AGING AND THE PNS
LFB
25
4/21/2012
ARTIFACTS
ARTIFACTS - CNS
D90-271
Bovine cerebellum
ARTIFACTS - PNS
THAT’S ALL, FOLKS.
26