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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