Neuropathology PDF

Learning Objectives Review of functional neuroanatomy & neurohistology Information enabling assessment of an abnormality in terms of Function agent a Time t lession Aetiology pathogenesis...

Learning Objectives Review of functional neuroanatomy & neurohistology Information enabling assessment of an abnormality in terms of Function agent a Time t lession Aetiology pathogenesis I diagnosis Pathogenesis v Cls Prognosis  Fundamentals Identification of an abnormality 8 criteria Presence AbsenceClassification of the lesion Location 10 groups Differential Diagnoses Aetiological Confirmation/ Morphological Elimination Process Final diagnosis The nervous system under health and disease conditions Normal anatomy (gross and microscopic)/ physiology Defense mechanism – similarities and differences Manifestation of central nervous system disorders Diagnosis of nervous system disorders Infections of the nervous system Route of entry/Defense system Contributing factors – built-in, predisposing etc, Mechanisms of entry and their fate Vulnerable periods of development Continuing, emerging and re-emerging diseases Aetiology/Epidemiology Clinical signs/Pathology Diagnosis  NEUROPATHOLOGY Overview Nerve cell (neuron) & supporting cells Enclosed in a bony box Covered by the meninges – dura pachymeninges (limits infection) – arachnoid leptomeninges (fluid-filled) – pia Primary Somatosensory Cortex coronal horizontal All the neurons contributing to the pyramidal and extrapyramidal systems should be called upper motor neurons (UMN). The anterior horn cells and the related neurons in the motor nuclei of some cranial nerves are called lower motor neurons (LMN). Cingulate gyrus, corpus callosum, mammillary body, olfactory  Mesencephalon Telencephalon Diencephalon thalamuss cerebrum Metencephalon Myelencephalon pros encephalon mesencephalon crnombencephal Autonomic Nervous System Somatic Nervous System  Cranial Nerve Mnemonic (Sensory vs. Motor) I. Olfactory Oh Some II. Optic Oh Say III. Oculomotor Oh Money IV. Trochlear To Matters V. Trigeminal Take But VI. Abducens A My VII. Facial Family Brother VIII. Vestibulocochlear (Acoustic) Vacation Says IX. Glossopharyngeal Go Best X. Vagus Vegas Buddies XI. Accessory (Spinal Accessory) After Matter XII. Hypoglossal Hours Most Similarities with other body system Neurons are surrounded by a membrane Neurons have a nucleus that contains genes Neurons contain cytoplasm, mitochondria and other "organelles"  Differences with other body system specialized projections= dendrites & axons dendrites bring information to the cell body axons take information away from the cell body communicate with each other through an electrochemical process form specialized connections: "synapses" & produce special chemicals: neurotransmitters that are released at the synapse  Did You Know?? 100 billion neurons 1 quadrillion synapses in the human brain (½ billion synapses/mm3) 100,000,000,000 neurons = 1000 km Alzheimer'sdisease 55yio to NEUROPATHOLOGY  clearstrongmessage A tiny lesion in an "eloquent" area may present striking clinical problems A large infarct in a "silent" area is missed Eg stroke patient Diverse lesions (infarcts, abscesses, tumors) in one site may produce similar problems, while similar pathologic processes at different sites will present different pictures REMEMBER opposite Cortical lesions produce contralateral visual, tactile and motor problems Feline cerebellarhypoplasia parvovirus Cerebellum is mostly responsible for coordination Basal ganglia for muscle tone pons Consciousness is lost with damage to the pontine & midbrain reticular formation Cells of nervous tissue are selectively vulnerable to various diseases/conditions eg: - Alzheimer's disease affects mainly the hippocampus & cholinergic nucleus of Maynert - Hg selectively damages the cerebellar granular neurons - Methanol poisons the retina - Poliomyelitis destroys only the anterior horn cells poliovirus spinalcord  Topics BRAIN – Congenital Anomalies – Traumatic Injuries – Infectious Diseases – Nutritional Diseases – Toxic Diseases – Neoplasia SPINAL CORD & PERIPHERAL NERVE IMMATURE NERVOUS SYSTEM  NEUROPATHOLOGY Overview Nerve cell (neuron) & supporting cells Enclosed in a bony box Covered by the meninges – dura pachymeninges (limits infection) – arachnoid leptomeninges (fluid-filled) – pia Irreversible neuronal injury = hypoxia, ischaemia, hypoglycaemia Injured neurons  shrinkage, eosinophilic cytoplasm & pyknotic credneurons  Anoxic neurons no or L t  L V  incerebellum Anoxic Purkinje cell exhibiting red neuron Hypoxic neurons exhibiting red neurons Vacoulation: Spongioform Encephalopathy sheep disease scrapie human disease jacob Prion disease BSE bovine spongiform encephalopathy Granulovacuolar bodies in neurons : Alzheimer’s disease Labilecells intestine stablecells liverkidney lung permanent cells cardiosite neurons Swollen neurons in storage disease lysosomal storage disease Central chromatolysis: Reversible change that develops during repair of a neuron that has been toside everything disconnected from its target push X Eg newcastledisease I Peripheral chromatolysis: Irreversible change  Inclusion Bodies will be dealt during discussion on viral infections numbers, location, shape, colour rabies intra cytoplasm inclusion  NEUROPATHOLOGY Supporting cell reaction A. Astrocytes (two types) – usually 2o Theonly professional phagocytes in ammonia – increase in NH3 toxicity brain l microglia cells – decrease in necrosis desperate condition – unprofessional phagocytes only act as phagocytes – gemistocytes (hypertrophy) – gliosis astrogliosis (proliferation) thehypertrophied astrocytes  Blood-Brain Barrier Typical astrocytes Capillary inflammation integrity to t permeability Brain Capillary acting highspeedair proteinaceousmaid  Name Function Ventricle Function Subfornical organ Sensory 3rd Fluid regulation Sensory & Organum vasculosum 3rd Detects peptides, fluid regulation secretory Regulates the anterior pituitary thro’ the Median eminence Secretory 3rd release of neurohormones Posterior pituitary Secretory 3rd Store and secretes oxytocin and ADH (neurohypophysis) Secretes certain proteins into the CSF Subcommissural organ Secretory 3rd (specific function unknown) Sensory & Pineal gland 3rd Secrete melatonin secretory Area postrema Sensory 4th The vomiting centre Areas devoid of BBB: circumvent region B. Microglia professional macrophage - phagocytic; microgliosis -Gitter cells( enlarged microglia with lipid granules in cytoplasm) ; neuronophagia( destruction of nerve cell by phagocytes) -Original names: -stabchenzellen (rod cells), mesoglia, nevernkitt (nerve-glue) Jg Kapggergen Microgliosis Gitter cells Infarct in the brain: Immense & extensive withlipid enlargedmicroglia in granules Gitter cells activity cytoplasm ground T Hyperactive microglia = Gitter cells  cos C. Oligodendrocyte production of myelinsheath myelinate a lot of axon - Indirect proliferate (satelitosis - acc of neurog neuralgia ) cell around damaged neurons of cns - Direct demyelination D. Myelin oligondendrocyted die 1o intact axon (damaged oligodendrocyte) 2o necrosed axon normalnotdamaged (intact oligodendrocyte) axon die myelinretractaway fromneuron PNS Schwann cells myelinate onlyone axon  Satelitosis accumulation ofneuroglia damagedneurons in ons cellsaround a cells glial neuro T Injured neuron Injured neuron  looklikesponge Eg caninedistemper neurons of oligodendrocytes oligodendrocytes axons dies y Primary Demyelination  Secondary Demyelination Hardto tell 10 a o under microscope atus t it Eti demyelination Demyelination  Congenital Anomalies Normal CSF physiology: produced by choroid plexus & brain parenchyma Lateral ventricles foramen of Monroe 3rd ventricle aqueduct of Sylvius cerebral aqueduct 4th ventricle foramina of Magendie and Luschka Subarachnoid space ultimately absorbed by arachnoid villi & through open channels around cranial & spinal nerves anycongestionwillcausepathologicalchanges  Hydrocephalus – congenital or acquired – three types external internal(most common) communicating  Hydrocephalus Hypersecretion of CSF: choroid plexus papilloma (rare) Obstructive hydrocephalus – foramina of Monroe (colloid cyst, tuberous sclerosis) – third ventricle (craniopharyngioma, pilocytic astrocytoma, germ cell tumors) – aqueduct (aqueductal stenosis or atresia, posterior fossa tumors) – foramina of Luschka or impairment of flow from the fourth ventricle fibrosis of the subarachnoid space (meningitis, subarachnoid hemorrhage, meningeal dissemination of tumors) obliteration of the subarachnoid space removing assumed Defective filtration of CSF: postulated for low-pressure hydrocephalus (rare)  Hydrocephalus (MRI) atrophy causingpressure Normal Hydrocephalus ÉÉ as  Hollow stucture It tenne Hydrocephalus Hydrocephalus Hydrocephalus  Hydrocephalus passing not fluid Stenosis of aqueduct  Hydrocephalus Atresia of aqueduct Congenital Anomalies Folicacid no Anencephaly –genetic derangements –Nutritional(folic acid def) –Infectious(bovine viral diarrhea) Anencephaly die within an hour Traumatic Injuries  Traumatic Injuries Space occupying lesions Skull fracture Laceration a deep cut Contusion injuredtissue skin whichblood capillaries no beenruptured1 Haematoma (haematocyst) aboveauramate – epidural(rupture of meningeal artery) belowauramater – subdural(rupture of bridging veins) Skull Fracture  if meningeal artery rupture epidural haematoma Intact Bridging Veins subdural hematoma CT Scan of Subdural Haematoma dm yd Subdural Haematoma Subdural Haematoma  Subdural Haematoma Bridging vein CT Scan of Epidural Haemorrhage dm  Epidural Haemorrhage meningeal a rupture  DO NOT SHAKEBABY To Avoid 2 Shaken Baby Syndrome(tearing of neuron)  Infectious Diseases Emergingdisease Primary or Secondary reemergingdisease rabies Route of Infection –Haematogenous fromblood –Adjacent Structures(dehorning enter sinus structure into brain) Egskullfracture rabiescase –Trauma/surgery Eg corneatransplant –Neural spread (remember at least 2) poor givengrowinalkaline silage soil – Listeria, rhabdovirus Facial n rabies trigemain Agents –Bacterial(listeria) inclusion bodies –Viral (remember the features) Encephalitis: Viral or Bacterial Suppurative/Purulent Meningitis  Acute suppurative meningitis congested brain structure Ice 997 Pus with engorged bv) Subacute Meningitis Why don't see sign ofinflammation anymore y u  Meningoencephalitis É cells inflammatory É Meningitis: Gram stain Phagocytosis by neutrophils G-ve cocci  commoninbrain Listeriosis: PCV I Duc 1 PVC perivascular Microabscess cuffing By NO and MO Pus x encapsulated  Listeriosis basoph hills trop peu Meningitis polymorphonuclear cells Admixture of monocytes/macrophages & PMNs Presence of phagocytosis by PMN or macrophages (efferocytosis) phagocyticcellsengulf apoptoticcellslayingcells https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140438/ Features of Viral Encephalitides(plural) encephalitis(singular) – single, multiple Paramyxorims newcastledisease rhabdovirus – intranuclear/intracytoplasmic or both herpesvirus – eosinophilic, basophilic – non-specific – usually mononuclear cells Herpes virus acute bacterial infection inflammation ofcells massivenecrosis – rarely neutrophils Pseudorabies, literia – degeneration & necrosis African swine fever  Features of Viral Encephalitides D. Neuronal necrosis – neuronophagia Microgilial engulf neuron E. Glial Proliferation – astrocytic, microglial responses F. Demyelination – Mechanisms: myelin damage anti-myelin antigen CDV destruction of oligodendrocyte destruction of neurons/axons  Viral Infection: Inclusion bodies Intranuclear Intracytoplasmic  Viral Inclusion Intracytoplasmic : Rhabdovirus (rabies) Intranuclear : Herpesvirus (Ausjesky’s) Both: Paramyxovirus, CMV (canine distemper) 10  Viral Infection:Perivascular Cuffing Normal pvc Viral Infection:Perivascular Cuffing usually I mononuclear cells Virchow-Robins space  Viral Infection: Neuronal Necrosis & Glial Proliferation Viral Infection:Demyelination Rabies: Rhabdovirus Rabies  Updates on Rabies an anciently recognised disease (Egypt, before 2300BC) Sanskrit = rabhas = to do violence Greek = lyssa (lud) = violence Latin = rabere = to be mad Lyssavirus from the Rhabdoviridae of the Mononegavirales order most of the viruses from this order affect the nervous system death rate of 55,000 people/year (90% Asia & Africa) annually ~15 million people requires post-exposure vaccination Malaysia: economic importance with respect to three NKEAs (healthcare, agriculture & tourism) HUMAN DIPLOID CELL VACCINE (HDCV) PURIFIED CHICK EMBRYO CELL VACCINE (PCEC) RABIES VACCINE ADSORBED (RVA) RABIES IMMUNE GLOBULIN (RIG)  bodies O Negi jft pggfg.gg Bullet-shaped virus Negri bodies  Classification of rabies virus Rabies virus, RABV, Genotype 1 Lagos bat virus, LBV, Genotype 2 Mokolavirus, MOKV, Genotype 3 7 Recognised Genotype Duvenhage virus, DUVV, Genotype 4 5 new bat lyssavirus: European bat virus Type 1, EBLV-1, Genotype 5 - Aravan - Khujand European bat virus Type 2, EBLV-2, Genotype 6 - Irkut -West Caucasian bat virus Australian bat virus Type 1, EBLV-1, Genotype 7 -Dakar bat virus  Rabies wilddog inMs dhole Epidemiology how S diseaseestablished developed A. endemic in wild animals in most parts of the world (in Malaysia, is it still the dog?) wild animal cycle constitutes the natural reservoir (mainly US, Europe, Africa & Australia, again in Malaysia??) B. wild animals may bite and infect domestic animals (cattle, horses, pigs, dogs and cats) which in turn may infect man occasionally wild animals may infect man directly Reservoir  Chiroptera = webbed-wing (cheir = hand; pteron = wing) A. Megachiroptera - less specialized & largely fruit- eating (flying foxes) B. Microchiroptera – more specialized & echolocating - insectivorous (insect eating, ~70%) - frugivorous (fruit eaters) - very few feed on blood & fish Current Global Rabies Distribution (November 2020)  Rabies -acquired via: - bite (rabid) - through injuries in contact with virus-ladened saliva - organ transplant Pathogenesis Inoculation small nerve endings (12-24 mm/day) CNS (replication) (200-400 mm/day) salivary glands (further replication) Incubation - depends upon the length of the nerve - average 1-3 months; (5 days – 7 years) - often the 1o wound is healed by the time of clinical presentation  Nop, I c no bone but u Rabies Did u c any must c a vet… Clinical Presentation bone? A)Furious Rabies fever, irritability, restlessness & anxiety may progress to muscle pains, salivation and vomiting after a few days to a week: stage of excitement – painful muscle spasms (triggered by swallowing of saliva or water; “bone in the throat”) – drool and learn to fear water/air (hydrophobia/aerophobia) – a few days later, lapses into coma and death. B) Dumb Rabies starts like the furious form progressing into excitement, retreats steadily and quietly downhill, with some paralysis to death diagnosis may easily be missed  Rabies DIAGNOSIS 1. History of being bitten - geographical area, type of animal, severity and site of bite 2. Animal Live - observe in the cage: If survives > 10 days, then NOT rabies Dead - brain sent to laboratory: - Negri bodies (not in all cases & rabies-like illness) Immunofluorescenceassay - IFA (poor cross-reaction between isolates) - virus isolation 3. Man Live – early stages post-infection is difficult to diagnose - clinical picture, skin biopsy, corneal impression (antibodies only appear very late)  Rabies: Immunoflouresence +ve -ve Rabies Rabies: Immunohistochemistry Rabies: Sellers Stain In dogs: ovalline hippocampus Other species: Cerebellum Spinal cord Trigeminal ganglia Equine: caudal brain stem, trigeminal ganglion, spinal cord Bovine: cerebellum, spinal cord t Caprine: cerebellum cytoplasmic Intra inclusion Bats  Districts of: Perlis state Hulu Tanah Perak Merah Districts of: Pasir Mas Kubang Tumpat Pasu Rabies Immune Belt Padang -established in 1954 Terap Kota Setar - 50-80km Pendang Sik Baling  SABAH: Constant surveillance – borders & Sabah entry& Sarawak points No immune belt set-up No rabies vaccines & vaccination of dogs allowed SARAWAK: Constant surveillance – borders & entry points No immune belt set-up Rabies vaccines & vaccination of dogs allowed  Factors affecting Rabies Re- BATS emergence Biological factors adequate shelter availability of feed resources endemicity of rabies in that area Non-biological anthropogenic activities working/living conditions accessibility to prophylaxis, knowledge on rabies BE75  x Canine Distemper Paramyxovirus (Morbilivirus group) Affects: Canidae Mustelidae (weasel) Mephitidae (skunk) Hyaenidae (hyaena) Ailuridae (red panda) Procyanidae (racoon) Pinnipediae (seal) Viveridae (binturong, civets) Felidae (Pantherinae & Felinae)  Clinical Signs Conjunctivitis Diarrhoea Fever Pneumonia Rhinitis Vomiting symptoms often exacerbated by 2o bacterial infections Encephalomyelitis, complications: Ataxia, hyperaesthesia, myoclonus I Paralysis/Paresis Progressive deterioration of mental abilities/or motor skills Seizures ("chewing gum fit") l  Clinical Signs Many dogs experience symptoms of the eye: Inflammation of the eye (either keratoconjunctivitis or chorioretinitis) Lesions on the retina Optic neuritis (may lead to blindness) Two relatively chronic minor conditions: of thickening pad nose Enamel hypoplasia Hyperkeratosis disease  PATHOGENESIS OF CANINE DISTEMPER Transmission Alveolar macrophages CD is spread through the air by infected animals coughing, sneezing, or barking. It can Bronchiol lymph nodes also be transmitted through shared food and water bowls Circulating mononuclear cells Thymus, spleen, bone marrow, lymph nodes Mononuclear cell borne virus in the periphery of epithelium (viscera & skin) perivascular spaces in the CNS Virus within the surface epithelium, glandular epthelium, cells of CNS Either recovery or continuing virus replication inflammation of brain sspinalcord Acute encephalomyelitis Hardpaddisease it survives  Paramyxovirus cytoplasmic S intranuclearinclusionbodies intra - most reliable test - Brush Border slide/smear of the bladder transitional epithelium - Diff-Quick stain - inclusions (carmine red cytoplasm & para nuclear) - 90% of the bladder cells will be +ve in the early stages - almost absent after 21 days post-onset Intra cytoplasmic inclusion body ligodendrocytes friedeggappearance Skin Urinary Bladder  Renal Pelvis Da intracytoplasmic S intranuclear inclusionbody Gastric Epithelium Bronchiole Epithelium Interstitial pneumonia causedbycanine distemper i cen pusually thick thickening of cells in lung pneumocytestypeit overlining pneumocytestype normal  Nipah Virus Encephalitis Porcine Respiratory & Encephalitis Syndrome Porcine Respiratory & Neurologic Syndrome Barking Pig Syndrome  HISTORY - Oct 1998-May 1999 Japanese Encephalitis - 265 human encephalitis with 105 deaths - initially thought to be JE - later, linked to diseased in pigs (from bats) - respiratory signs (barking pigs) - encephalitis - high mortality in young piglets - some linked 2 other species like dogs & cats - horses tested but only 2/3000 +ve - natural host = fruit bats (Pteropodidae Pteropus sp) - Kampung Sungai Nipah, Malaysia in 1998 - pigs were the intermediate hosts - subsequent NiV outbreaks, no intermediate hosts!! - Bangladesh (2004), infection via consuming contaminated date palm sap - human-to-human transmission has also been documented (hospital setting in India) - a range of clinical presentations - asymptomatic infection to acute respiratory syndrome and fatal encephalitis - incubation period (pigs) = 4-14 days  Epithelial cells Lymphatics Dendritic cells Lymphoid tissues Cape in peripheraltissue Blood vessels  TRANSMISSIBLE SPONGIOFORM ENCEPHALOPATHY (TSE) of collection lesions transmissible neurological syndromes novel infectious particle, termed prion man and other animals Characteristics: – confined to the CNS – long incubation period slowviraldisease – progressive, uniformly fatal course – typical brain histology: reactive gliosis proliferation vacuolation of neurones deposition of amyloid protein absence of an inflammatory response  TSE Scrapie = sheep & goats Bovine spongiform encephalopathy Transmissible mink encephalopathy Feline spongiform encephalopathy Exotic ungulate spongiform encephalopathy Chronic wasting disease of cervids Spongiform encephalopathy of primates Creutzfeldt-Jakob disease - man, sporadic & familial Gerstmann-Streussler disease - man, familial Fatal Familial Insomnia - man, familial Kuru - man, Fore people, New Guinea  TSE Properties of Prions: very small - about 20-30 nm in size no nucleic acid extremely resistant to inactivation by: - ultra-violet light - formaldehyde - heat can be transmitted by intra-cerebral or sub- cutaneous inoculation of infected brain tissue Transformation into a Virulent Prion  General Pathogenesis of TSE Transformation into a Virulent Prion Ingestion Injuries Duration 18-36 months, Kuru 50 years GIT Blood Vessels Peyers’s Patches mesenteric lymph nodes B lymphocytes spleen, thymus, tonsils (replication : follicular dendritic cells) GIT submucosa plexus network of autonomic nervous system Meissner's Auerbach plexus provides motor innervation spinal cord by way of dorsal route ganglia Brain  Documented cases Scrapie: 1732 – UK, 1759 Germany (1936) - endemic in UK, Europe & Nrth america Kuru: 1957 (published 1966) BSE: Nyala 1986, Kudu 1988, Cheetah – 1992, cats 1990 sCJD: 1968 vCJD: 1996  anxiety y Apprehension Low head carriage Arched back Wide-based stance Mimosa pudicaflower YEYE Obex Prion Disease:BSE in GM vacuolation neuron of Prion Disease neuron of vacuolation Creutzfeld-Jakob Disease Scrapie Scrapie: Counter-immunoperoxidase Astrocytes  Nutritional Diseases cerebro cortical necrosis 1. Polioencephalomalacia (CCN) – sheep & cattle – Malacia(softening of tissue) of grey matter esp cerebral cortex Aetiology: thiamine b1 deficiency Gross: – discoloration, separation between GM &WM Histo: – extensive neuronal degeneration & necrosis – haemorrhage, astro- & microgliosis  Nutritional Diseases 2. Thiamine deficiency mackerel herring – kittens fed oily fish(raw meat) Aetiology: – thiaminase toomuch thiaminase causing increase breakdownthiamine Lesions: – bilaterally symmetrical – oedema, haemorrhage , necrosis – gliosis Bracken tern alsocontainalotof thiaminase  Nutritional Diseases 3. Eosinophilic Meningoencephalitis – pigs Aetiology: – high salt (>2%), restricted water supply – disappears after water replenishment Pathogenesis: – cerebral oedema Lesions: perivascularcutting – pvc by eosinophils allergic parasiticreactions – loss of cortical neurons RAA renin angiotensin aldosterone  Nutritional Diseases lordosis 4. Swayback (Enzootic Ataxia) – newborn lambs Aetiology: – low copper in the diet of the dam Pathogenesis: – improper myelin formation lo demyelination – lack of cytochrrome oxidase, superoxide dismutase, caeruloplasmin Lesions: – demyelination, microgliosis  frompaint Toxic Diseases line y lipstick byron's 1. Lead Poisoning – diffuse cerebral oedema – non-specific CNS lesions intranuclear – intranuclear inclusion in renal tubule epithelium 2. Focal Symmetrical Encephalomalacia aka ftp.jttdnejdisea – enterotoxaemia (Clostridium perfringens type D) – necrosis & haemorrhage lesions Gtve bacteria Eg a concentration of concentrate overgrowth of clostridium produce of E toxins enterotoxaemia cause BBBdamage epsilon 3. Hepatic Encephalopathy  secondary to liver damage  high levels of NH3 & amines  astrocytosis akaastrogliosis as stargazing Brain of a lamb with enterotoxemia showing herniation of cerebellar vermis hepatic encephalopathy Focal symmetrical encephalomalacia Proteinaceous edema surrounding a vein in the internal capsule Submicroscopic view of FSE in the cerebellar peduncles & cerebellar white matter Degeneration of white matter in the internal capsule microglial cells engulf macrophage y becomegittercells  NEOPLASIA - primary tumours are rare & seldom metastasise Effects: - destruction of tissue - space occupying lesion 1. Astrocytoma - brachycephalic dogs - especially on the cerebral hemispheres - solitary mass  NEOPLASIA 2. Meningioma derived from the leptomeninges solitary or multiple Location: x – base of the brain – surface of the cerebellum – cerebrum – spinal cord Neoplasia: Meningioma Neoplasia: Meningioma  NEOPLASIA Other Tumours – Ependymoma – Oligodendroglioma – Medulloblastoma – Neurofibroma – Schwannoma Neoplasia:Ependymoma ependymal cells block Csf to flow hydrocephalus  Diseases of the Spinal Cord relay nerve impulse to & from centers in the brain lesions interfere with: – motor function – sensation changes seen are to those of the brain effect depends on affected areas  Diseases of the Spinal Cord Spinal Cord Compression Signs: – minor motor or sensory deficit of impairment motorsensoryneuronsinlowerlimbs – paraplegia (lower limbs) – quadriplegia (all four limbs) – loss of bladder control many aetiology/causes  Spinal Cord Compression A. Vertebral fracture/dislocation - due to : trauma - effect: compression of the cord - lesions: haemorrhage, degeneration, necrosis - severe cases: total transection of the cord  Spinal Cord Compression B. Vertebral malarticulation/malformation - Eg: cervicospinal arthropathy (Wobblers; spinal ataxia) - young thoroughbred horses - misaligned/hypermotility of cervical vertebra - C3-C4 (C1-C7) - hyperflexion excessive pressure on the cord - Great Danes & Doberman; C7 misaligned & stenosed canal of spinal cord  Spinal Cord Compression C. Meningeal abscess - epidural or subdural - compression umbilical vein cattle inflammationof pig overcome by tail docking give - omphalophlebitis; tail-biting y steelchaintopig to distract D. Neoplasia in brain I spinal cord O -1 –meningioma; neurofibroma; osteosarcoma - 2O- mammary carcinoma E. Disc protrusion for chondrodystrophic breeds longbody - associated with degenerative disease - Daschund,; Pekingese; Cocker Spaniel - compressed spinal cord or blood vessel damage  Diseases of the Peripheral Nerves regenerate if: – fibre ends are apposed - neuron is intact - viable endoneurium & perineurium - nerve growth factor (NGF) A. Degeneration (Wallerian) and Necrosis - removal performed by macrophages remove myelin sheath thatcontainlipidcholesterol - severe injury fibrosis Histo foamyappearance Causes: - trauma; prolonged compression; burns & toxins B. Tumours chicken - neurofibroma; Mareks disease  Trauma: Sweeney in Horses scapularn supra injured nervebeing q cushioned  daces lymphoid leakosis reticaloendotheliosis Marek’s Disease an surrounding nerve  Regeneration of a peripheral nerve cells of groping comingin macrophages penance 7 a 7 eosinophilic bodies missis increase cells central eccentric u chromatolysis Failedregeneration fibrosisoccur Normal Traumatic injury Colchicine Anti-NGF antibodies  macrophages engulfmyelinthat containlipid s cholestrol Wallerian Degeneration: Foamy macrophages Pathology of the Immature Nervous System same general principle holds true for the immature nature system with a few exception neurologic disorders result from damage inflicted on the growing brain and spinal cord i. before ii. during iii. immediately after birth Pathology of the Immature Nervous System EEE Damage inflicted: have serious effects on: i. multiplication ii. migration or maturation of neurons iii. formation of myelin iv. free flow of cerebrospinal fluid Consequences: i. deficiency in nerve cell numbers ii. dysplasia of nervous tissue iii. deficiency of myelin iv. hydrocephalus Pathology of the Immature Nervous System Owing the different growth rate, certain agent produces differing lesions in different system between the mature and immature body system despite the similar pathogenesis in both systems A classical example is the effect of feline parvovirus on and kittens infected while in utero (cerebellar hypoplasia) and adult (villous atrophy and bone marrow suppression) Central Nervous System Organogenesis i. Organogenesis and neuronal stage whereby the adult shape of the brain begins to form Subdivided into two main stages: a. maturation period for axonal and dendritic I growth b. period of growth in size - Iintense multiplication and myelination ii. The mature adult phase 7 Pathology of the Immature Nervous System The growth and development have their very own spurt Similarly, brains of different animal species grow at different rates and mature at different times Likewise, the growth rate and maturation period of various parts of the brain differ considerably too Eg: cellular multiplication always precede Ati th myelination  Pathology of the Immature Nervous System Depending on time of contact by an agent in utero, different changes in different part may occur This variation in susceptibility associated with growth spurts has led to the concept of BEETHEE “Vulnerable Periods of Development” which is a very important concept in understanding the pathology of the foetus Pathology of the Immature Nervous System Consideration: i. cellular pathology of the foetus and the adult is almost similar ii. a particular malformation in the foetus may be produced by one of a number of widely differing agents iii. the target organ for a pathogen in the foetus may be vary different from the target organ for that pathogen in the adult  Pathology of the Immature Nervous System In summary: a. an early effect in gestation = shape of the brain b. later; malformed cell multiplication leading to normal shape albeit with variable size of y different parts of the brain c. Latest part of development, may affect the specific unit of a structure I Pathology of the Immature Nervous System Feline Panleukopaenia In adult : intestinal and haemogram disturbances Destroys the cell of the crypt and bone marrow In kittens: cerebellum is being affected happens just before or immediately after birth at this point, normal shape but with missing details Pathology of the Immature Nervous System Prior to birth, the Purkinje cells and other neurons migrate from the sub-ependymal plate areas of the fourth ventricle At around the time of birth, a second pattern of migration occurs from the external germinal layer that lies along the external cerebellar surface Cells of this layer undergo remarkably intense period of mitotic activity in the neonatal period and migrate into the substance of the brain to form the granular layer of the cerebellum This bulk layer of the cerebellar mass (granular layer) is attacked by the virus leading to hypoplasia ext. granular layer 2 1 4th ventricle Feline: Cerebellar hypoplasia Hypoplastic Normal  Pathology of the Immature Nervous System B. Swayback/Enzootic Ataxia a state of copper (Cu) deficiency seen in only neonatal or young lambs occurs while the lamb is in utero C. Hypomyelogenesis congenita/trembling pigs/Border disease Cattle : cerebellar ataxia (hypomyelogenesis congenita) Pigs : trembling pigs/dancing pigs Lambs : Border disease/ hairy shaker disease or hypomyelogenesis congenita Hairy shakers are born with hairy hair coats and with tremors The shaking is due to the patchily distributed (lack) of myelin D. Bovine Viral Diarhoea This virus clearly affects the gut in the adult but in the foetus it affects the nervous tissue affecting the cerebellum and the eye