Final Exam- Important Concepts Flashcards
What are you assessing when you test the menace response? Why?
* the animal cannot see out of that eye, but that the lesion is not necessarily in the optic nerve or eye, but the lesion could be in the brain. If so, it is known as cortical blindness. PROSENCEPHALIC (forebrain) LESIONS.
** Menace response assess: CN II, retina, cerebellum, CN VII
Why? Because the menace pathway starts where vision left off– neurons in the occipital cortex–> motor cortex–>via internal capsule and crus cerebri to synapse with nuclei in the PONS–> contralateral cerebellar hemisphere (for coordination) –> facial nerve nucleus to drive blinking (orbicularis oris)
What are pathways that involve the optic nerve?
- Vision
- Control of eyeball movements (from the rostral colliculus, neurons project to the motor nuclei of CN III, IV, and VI of both sides) (Voluntary eyeball movement is different)
- Pupil Constriction (rostral colliculus left and right parasympathetic nuclei of the oculomotor nerve CN III)
- Control of turning of the head and neck (rostral colliculus neurons send axons which decussate and descend through th brain into the spinal cord forming the tectospinal tract– reflex turning of the head and neck towards sudden source of light or movement)
- Projections into the reticular activating formation (some neurons from the rostral colliculi project into the reticular activating formation to provide general arousal stimnuli to the cerebral cortex)
What are the 3 neurons in hearing?
SCM
Neuron 1: cell body in the spiral ganglion of CN VIII receiving impulses from the neuroepithelial cells in the spiral organ (of corti). Axon runs in CN VIII (vestibulocochlear)
Neuron 2: Located in the cochlear nuclei– many axons decussate at once forming the TRAPEZOID BODY.–> Lateral lemnicus
Neuron 3: Medial geniculate nucleus
What 3 neurons are in the taste pathway?
Neuron 1: Ganglia of CN VII (rostral 2/3 of tongue), IX (caudal 1/3), or X (tastebuds near epiglottis)
Neuron 2: Nucleus of the solitary tract
Neuron 3: Ventral group of thalamic nuclei–> cerebral cortex to the somaesthetic cortex
What 3 neurons are in smell?
Neuron 1: Olfactory neuroepithelial cell (constantly dividing and replenishing)–> axons pass through the cribiform plate and synapse with neuron 2 in the olfactory bulb
Neuron 2: Olfactory bulb–> olfactory peduncle–> divides into the medial and lateral olfactory tracts end in the Olfactory tubercle
Neuron 3: Olfactory tubercle–> axons to cerebral cortex via pyriform lobe
** No relay to the thalamus because most primitive part of the brain**
What is a seizure?
Epilepsy is idiopathic. But if they occur due to brain injury. Then injury can cause changes to inherent excitability of glutamatergic neurons. Excessive neuronal activity can cause the accumulation of potassium and glutamate if the astrocytes are dysfunctional. And the accumulation of potassium can cause depolarization of neighboring axon terminals. The accumulation of glutamate at excitatory synapses and activate post synaptic receptors.
What’s the mnemonic for the cranial nerves?
On Old Olympus’s Towering Tops A Fair Voluptuous German Vaulted And Hopped
- Olfactory
- Optic
- Oculomotor
- Trochlear
- Trigeminal
- Abducens
- Facial
- Vestibulocochlear
- Glossopharyngeal
- Vagus
- Accessory
- Hypoglossal
What are the most likely potential routes for the transport of bacteria into the CNS?
CN I (cribiform plate), II, and VII (travels with VIII through the internal acoustic meatus – susceptible to middle ear disease)
Which cranial nerves attach together and may be involved in one lesion?
CN V, VII, VIII
Innervation of the pharynx and larynx?
Pharynx- sensory- 9; musculature- 9 & 10
Larynx- sensory- 10 & 11; musculature- 10 & 11
Which is the only nerve that exits the brain dorsally? What does it do?
CN 4 (Trochlear)- exits through the orbital fissure in the dog to innervate the dorsal oblique muscle (inward eye rotation)
What part of the brain is the Abducens CN part of? What are the main functions? Dysfunction?
* Medulla
* Lateral eye movement (Lateral rectus muscle)
* Double vision; strabismus: eye deviation medially
What part of the brain is the Trochlear CN (IV) associated with? Main function? Dysfunction?
* Midbrain
* eye movement (dorsal oblique m.)
* Dorso-lateral strabismus
What part of the brain is the Vestibulocochlear CN part of? Function? Dysfunction?
* Medulla (Myelencephalon)
* Hearing and balance- horizontal and vertical eye movement
* Deafness, head tilt, nystagmus
Function of Glossopharyngeal? Dysfunction?
* Caudal 1/3 of Tongue and pharynx (sensory), carotid sinus, motor to stylopharyngeaus, PS to parotid and zygomatic salivary glands
Function of Facial CN? Dysfunction?
* Taste on rostral 2/3 of tongue, motor to muscles of facial expression, PS to mandibular, sublingual, palatine, nasal, lacrimal glands
* Paralysis of facial muscles (drooping of ear, lip, and eyelid), decreased lacrimation, decreased taste sensation
Function of Vagus? Dysfunction?
* Sensory to pharynx, larynx, and viscera, sensory to external ear canal, taste on root of tongue and epiglottis, PS to viscera
* dysphagia (difficulty in swallowing), respiratory noise (laryngeal paralysis)
Function of Accessory? Dysfunction?
* motor to trapezius and brachiocephalicus muscles
* Atrophy, dysfunction of trapezius, brachiocephalicus and sternocephalicus
Function of hypoglossal? Dysfunction?
* Motor to tongue muscles
* Paralysis and deviation of the tongue if unilateral lesion
Where does CN I exit from the skull?
Cribiform plate
Where does CN II exit from the skull?
Optic foramen
Where does CN III exit from the skull?
Orbital fissure in small animals, orbitorotundum in ruminants
Where does CN IV exit from the skull?
Orbital fissure in small animals, orbitorotundum in ruminants
Where does CN V exit from the skull?
Ophthalmic- orbital fissure
Maxillary- round foramen
Mandibular- oval foramen
Where does CN VI exit from the skull?
Orbital fissure in small animals, orbitorotundum in ruminants
Where does CN VII exit from the skull?
Internal acoustic meatus, facial canal, and then exits through the stylomastoid foramen
Where does CN VIII exit from the skull?
Stays within the skull– goes into the petrous temporal bone through the internal acoustic meatus
Where does CN IX exit the skull?
Jugular foramen within the tympano-occipital fissure
Where does CN X exit the skull?
Jugular foramen within the tympano-occipital fissure
Where does CN XI exit the skull?
Jugular foramen within the tympano-occipital fissure
External branch enters skull through foramen magnum
Where does CN XII exit the skull?
Hypoglossal canal
Which CN emerges?
Rostral alar foramen
* maxillary branch of the trigeminal nerve
What is it? What CN exits?
Stylomastoid foramen
Facial n.
Left tympanic bulla
What is a cerebral concussion?
A clinical condition characterised by temporary loss of consciousness and reflex activity following sudden head injury.
* results from rapid acceleration/ deceleration forces–> shear, tensile, and compressive strains being applied to axons, dendrites, neurons, and blood vessels +/- brain movement over bony ridges of skull
* still head is less likely to receive a concussion!!
Who is more susceptible to a concussion, a young or old animal?
Old animal because the senile brain atrophy may permit greater movement of the brain in response to head trauma (subdural haemorrhage may follow relatively minor head trauma)
What would you see with mild concussion microscopically? Severe concussion?
Mild concussion- no microscopic lesions
severe concussion- axonal degeneration and central chromatolysis of neurons, especially neurons of brainstem nuclei, and a proportion of the affected neurons may die
What is chronic traumatic encephalopathy? What contributes to neuronal loss/
Repeated episodes of concussion
** neuronal excitotoxicity due to glutamate release from damaged neurons contributes to the neuronal loss
What is cerebral contusion?
Haemorrhage into the meninges and/or about superficial or deep cerebral blood vessels as a result of head trauma
* pathogenesis of cerebral contusions is similar to concussion but the applied external force, displacement of the brain within the skull, and the induced shearing and other forces acting on the brain are all of greater magnitude–> greater blood vessel damage–> haemorrhage
What is the most common type of cerebral haemorrhage?
* leptomeninges haemorrhage
What are coup contusions? Contrecoup?
Brain moving towards the point of impact and striking the inside of the skull.
Contrecoup- also result from the sudden movement of the brain towards the point of impact–> tension on and tearing of meningeal and cortical blood vessels opposite the impact site
What is a cerebral laceration? How are they repaired?
Physical tearing of brain tissue due to trauma via penetrating or blunt trauma (contrecoup lacerations on gyri displaced over bony prominences)
* repair involves phagocytosis of necrotic debris and haemorrage by microglia (gitter cells when swollen with debris) and astrocytes proliferating and their processes (astroglial scar) and/or conventional scar tissue produced by meningeal fibroblasts
What is the problem with astroglial or collagenous scars connecting the pia mater to the brain neuropil (aka meningocerebral scars)?
* known to be epileptogenic (i.e. responsible for seizure activity)
What is Acute Brain Swelling?
Results form increased blood volume within the blood vessels of the brain (may develop within 20-30 minutes of injury) (NOT referring to oedema)
** particularly within the brain capillaries and post-capillary venules–> rapid increase in ICP and risk of caudal herniation of the hindbrain
** MAY be followed within hours to days by genuine cerebral oedema caused by increased vascular permeability
When can localized cerebral oedema occur?
Focal traumatic lesions (lacerations or haemorrhage), meningeal or brain tumours, inflammatory foci (especially abscesses)
When can generalized cerebral oedema occur?
Severe head trauma, diffuse meningitis, diffuse viral encephalitis, thiamine deficiency (polioencephalomalacia) in ruminants, clostridial enterotoxaemia, lead poisoning, and salt poisoning
How does vasogenic oedema result? What is unique about vasogenic oedema? Why does grey matter resist oedema?
* injury to vascular endothelium–> increased vascular permeability–> movement of water, sodium ions, and sometimes plasma proteins from blood into the CNS–> physical disruption of neuropil and dissection of extra-cellular oedema fluid especially along white matter tracts
* only form of CNS oedema associated with disruption of the blood brain barrier (most common form!)
* the dense tangle of neuropil in grey matter tends to resist the passage of oedema fluid
When is vasogenic oedema commonly seen?
* trauma, inflammation, haemorrhage tumours, inflammatory foci, infarcts, and contusions, thiamine deficiency
* Mulberry heart disease (vitamin E/ selenium deficiency)- inadequate anti-oxidant capacity– reactive oxygen species damage small blood vessels–> vasogenic oedema and leukoencephalomalacia
* Enterotoxaemic Colibacillosis (Oedema Disease)- young pigs with certain strains of E. coli producing shiga- like toxin type IIe. Toxin absorbs from the intestines into circulation–> binds to endothelial receptors–> vascular injury in multiple body systems (especially vasogenic oedema of the brainstem)
*Pulpy Kidney Disease (Clostridial Enterotoxaemia… aka Focal Symmetrical Encephalomalacia)– Clostridium perfringens type D from intestines into circulation–> toxin binds to enothelial receptors–> vascular injury in multiple body systems–> if they don’t die peracutelly then foci of malacia in internal capsule, thalamus, midbrain, and cerebellar peduncles
*Annual Ryegrass toxicity- Nematodes first and then Corynebacterium rathayi- toxin producing bacterium– increase vascular permeability–> pulmonary oedema and severe cerebral vasogenic oedema
What is Hydrostatic Oedema?
* Increased hydrostatic prssure within the ventricles of the brain (or in the central spinal canal) due to obstruction of flow of CSF
* Feature of internal hydrocephalus and obstructive hydromyelia
* Increased hydrostatic pressure–> movement of water from the CSF across the ependyma–>accumulation of extracellular oedema fluid in surrounding white matter–> secondary demyelination and atrophy of the adjacent white matter
What is cytotoxic oedema?
* increased intracellular fluid (e.g. akin to hydropic degeneration in other tissues)
*Most of the fluid is within astrocytes–> swelling of the cytoplasm +/- nucleus
* Caused by astrocyte injury with disruption of the membrane ATP-dependent Na+-K+ pump–> influx of sodium ions and hence water from blood, CSF, and the meagre intercellular spaces of the CNS
** Early stages of hypoxic-ischaemic injury, ammonia toxicity in hepatic and renal encephalopathy, ammonia toxicity induced by phalaris toxicity in sheep (sudden death syndrome)
What is Osmotic Oedema?
Usually referring to indirect salt poisoning to pigs (and occasionally ruminants). Water moves along osmotic gradient from the blood and CSF–> both intra-cellular and extra-cellular oedema of the brain…. develops in pigs which ahve restricted acces to water whilst consuming approx. 2% NaCl in the diet
** clinical signs develop after access to ater is restored – blindness, deafness, head pressing, convulsions start as snout tremors–> neck spasms–> opisthotonus–> pig walks backwards and sits–> lateral recumbency–> generalized clonic convulsions
** Brain becomes hyperosmolar because Na+, K+ and Cl- rush into brain to restore sodium imbalance between brain and blood during water restriction, but then when animals drink again the blood Na+ falls rapidly (brain = hyperosmolar)
** can occur with too rapid administration of IV fluids in hypernatraemic patients or too rapid correction of chronic hyponatraemia (e.g. hypoadrenocorticoid patients) by saline fluid therapy
What are some causes of cerebral hypoxia?
* Vascular obstruction (thrombosis), complete cessation of cerebral circulation (e.g. cardiac arrest), sustained hypotension (shock), hypoxaemia (severe pneumonia, severe anaemia, toxins (carbon monoxide, paracetamol, nitrite), asphyxiation, dystocia)
* Impaired cell utilization of oxygen e.g. cyanide poisoning, fluoroacetate (1080) poisoning
Why is grey matter more likely to sustain injury during a hypoxic event? What cells are most vulnerable?
* Because of the high metabolic rate and oxygen dependence of neurons, grey matter is more likely to sustain significant injruy during a hypoxic event
* Neurons and oligodendrocytes are most vulnerable to hypoxia (astrocytes are moderately resistant and microglia and vascular endothelial cells are quite resistant)
What are the most vulnerable neurons?
Deep cerebral cortical laminae, hippocampus, some basal ganglia, and the Purkinje cells of the cerebellar cortex– only a few minutes of hypoxia are sufficient to cause necrosis of these neurons
What is the pathogenesis neuronal death due to hypoxic injury? What is the process called?
** Excitotoxicity
* Hypoxia–> ATP depletion in vulnerable neurons–>intracellular release of sequestered calcium ions–> neuronal depolarisation and release of glutamate (an excitatory neurotransmitter)–> excessive release of glutamate and/or lack of clearance by astrocytes–> excessive activation of glutamate receptors of neurons–> influx of extra- cellular calcium ions into neurons–> further impairment of mitochondrial function and generation of reactive oxygen species (ROS)–> membrane and organelle damage with further influx of calcium–> activation of catabolic enzymes–> neuronal death
Other than hypoxia, what can cause excitotoxicity?
Indirect salt poisoning (osmotic oedema), lead poisoning, organomercurial poisoning, thiamine deficiency, prolonged convulsive seizures, chronic traumatic encephalopathy
Why are cerebrovascular accidents (strokes) uncommon in domestic animals?
Significant atherosclerosis or arteriosclerosis of the internal carotid or cerebral arteries is uncommon in these species
When might you see cerebral infarcts?
* cerebral trauma (thrombosis of damaged blood vessels)
* feline cardiomyopathy (atrial thrombosis–> thromboembolism of internal carotid artery)
* atherosclerosis in hypothyroid dogs
* vasculitis (immune mediated meningeal vasculitis in beagles or viral vasculitis in malignant catarrhal fever or FIP)
* Septic thromboembolism e.g. Histophilus somni in cattle, tail docking or tail bite wounds in pigs
* cattle with thiamine deficiency- thrombosis of superior sagittal venous sinus of dura mater due to severe prolonged brain oedema
* metastasis of malignant neoplasm to the brain
* feline ischaemic encephalopathy (cerebral infarction syndrome)
How are kittens and puppies different to ruminants, foals, and piglets in regards to CNS development? And therefore weeks to months post-natally?
* kittens and puppies are born with an immature NS; exposure to teratogenic agents in the first few post-natal weeks to months may cause CNS malformation in these species
* the most common effect of teratogens is selective destruction of cells via inflammation, directly, or provoking phagocytosis– embryonic/ foetal CNS responds differently than mature CNS because necrosis/ apoptosis is a normal part of CNS development in utero, necrosis induced by teratogens can cause tissue defects without inducing either gliosis or conventional scarring (fibrosis)
** Cannot mount or limited ability to mount an inflammatory response to injury but it can mount an intense macrophage response to tissue necrosis
What are dysraphic syndromes?
An abnormal seam/ dorsal midline (schisis); defective closure of the neural tube or its subsequent separation from overlying ectoderm
* combined defects of the brain, meninges, skull OR of the spinal cord, meninges and vertebrae because of their close interavtion between neuroectoderm and mesoderm during embryonic development
** Induction of mesodermal differentiation is dependent on closure of the neural tube and its subsequent separation from the overlying ectoderm (MESODERM FORMS MENINGES & neural tube separation from the overlying ectoderm–> induction of formation of the dorsal parts of the skull and the dorsal vertebral arches and overlying skeletal musculature from mesoderm)
What is the term for the entire neural tube failing to close?
Craniorhachischisis totalis
What are the dysraphic syndroms?
* anencephaly, prosencephalic agenesis, cranium bifidum, spina bifida
What is anencephaly and agenesis of the prosencephalon?
* Forms of cranioschisis in which all or part of the rostral neural tube destined to form the brain fails to close
* anencephaly- absence of the brain- results from early arrest of closure of the whole of the rostral neural tube
* prosencephalic agenesis- failure of neural tube closure rostrally–> absence of the forebrain and structures derived from it (cerebral hemispheres and eyes, for example)— meninges and other structures fail to develop over the undifferentiated neuroectodermal tissue therefore forebrain stays exposed (exencephaly)
What is cranium bifidum?
* Rostral neural tube closes- so leptomeninges form– but fails to separate from the surface ectoderm–> focal failure of induction of dorsal skull bones and overlying musculature +/- dura mater
**Meningocoele (fluid-filled meninges protrudes) OR meningoencephalocoele (brain within meninges protrudes)
What is spina bifida? What are the different kinds?
* any abnormality of dorsal vertebral arch formation– defective closure of caudal neural tube
* usually involves the lumbosacral spinal cord and vertebrae
* calves, lambs, kittens, puppies
* myeloschsis (spinal counterpart of an encephaly or prosencephalic agenesis: absence of spinal cord, meninges, dorsal vertebral arches, overlying muscle and skin along affected segments)
* Meningocoele and meningomyelocoele- spinal counterpart of cranium bifidum (meningocoele- fluid-filled meninges or meningomyelocoele- spinal cord within the meninges)
* spina bifida oculta- most common form- only abnormality dimple in the skin
* dermoid cyst- skin surface connected to supraspinous ligament or the dorsal dura mater (Rhodesian ridgeback)
What is myelodysplasia? Forms?
Malformation of the spinal cord
* spina bifida
* diplomyelia (partial or complete duplication of the cord)
* hydromyelia- dilation of the central spinal canal with excess CSF (can be acquired rarely)
* syringomyelia= a tubular fluid filled cavity (syrinx) in the spinal cord- it is not lined by ependyma
What is arthrogryposis?
* crooked joint- lambs, calves, piglets, foals
* 90% of cases result from defective innervation of muscles–> inadequate foteal muscle development during 2nd or 3rd trimester–> limb immobility–> pre-natal joint fixation over-flexion or over-extension by short muscles, tendons, ligaments
* may be accompanying scoliosis, kyphosis, lordosis (ventral deviation), torticollis (twisting along its long axis)
** arthrogryposis can lead to dystocia, stillbirth, or neonatal death
** can result from viral infection e.g. Akabane, Bluetongue, or border disease or teratogenic plant toxins
What is holoprosencephaly?
* A spectrum of forebrain malformations which typically include agenesis or severe hypoplasia of the olfactory bulbs and tracts
* cyclopia is the most severe expression (exposure to steroidal alkaloid in the plant Veratrum californicum at day 14 of gestation)
* cleft lip, clef palate, cebocephaly (“monkey face”)
What is microencephaly?
* An abnormally small (hypoplastic)brain
e.g. Akabane virus in lambs and calves, BVDV in calves, border disease virus in lambs, hog cholera in piglets, pre-natal hyperthermia in lambs
What is hydranencephaly? Porencephaly?
Lysis of brain tissue and subsequent phagocytosis–> variable degress of cavitation of the cerebral hemispheres
* cerebral ventricles (especially lateral ventricles) expand to occupy the space left by lysis of grey or white matter– (aka: ex vacuo hydrocephalus)
** Skull is usually of NORMAL shape and size in hydranencephaly because no accompanying increase in pressure within the ventricles
** Porencephaly is a less severe form of cerebral lysis that results of lysis at a later stage of foetal development–> small cavitating cysts filled with serous fluid
** common in lambs and calves– Akabane, BVDV, Bluetongue, foetal copper deficiency in lambs (swayback)
What is hydrocephalus?
Accumulation of excess CSF within the cranial cavity– accumulates due to obstruction of CSF flow, sometimes due to excessive CSF production e.g. by a choroid plexus tumour
(CSF normally drains via arachnoid villi into intra-cranial venous sinuses
What are the three types of hydrocephalus?
- Internal hydrocephalus (or non-communicating): excess CSF accumulates within expanded ventricles rostral to an OBSTRUCTIVE LESION, associated with hydrostatic CSF pressure
- Communicating hydrocephalus: Excess CSF accumulates both within the ventricles and in the subarachnoid space e.g. vit A deficiency in young growing calves or piglets–> decrease resorption of bone by osteoclasts–> inadequate remodeling of skull–> imparied venous resorption of CSF via the arachnoid villi +/- mechanical obstruction of CSF flow because of brain compression within too small a cranial space
** INCREASE HYDROSTATIC CSF PRESSURE
- Ex vacuo (compensatory) hydrocephalus: CSF filled ventricles expand passively to fill the space left by loss of brain tissue e.g. due to lysis of periventricular tissue in hydranencephaly
** NOT associated with increased CSF pressure
What is Congenital Internal Hydrocephalus?
* Common in dogs, especially brachycephalic and toy breeds
Hereford, piglets, shorthorn cattle
* Malformation and stenosis of the mesencephalic aqueduct– e.g. in utero damage to lining ependyma by canine parainfluenza virus
** Increased pressure within the ventricular system rostral to the obstruction–> malformation of the developing skull (doming or enlargement)
** can survive in first year may see poor motor skill development, slow learning e.g. house training, sleepiness, mental dullness, periodic aggression and/or seizures
What is acquired internal hydrocephalus?
* acquired due to an obstruction of CSF flow e.g. plugging of the mesencephalic aqueduct due to pus by bacterial infections or haemorrhage into ventricular system, tumours, inflammation
** manifests at an earlier stage vs. congenital because a more rapid ICP!!
What can cause cerebellar hypoplasia?
* inherited or copper deficiency, treating pregnant sows with OPs or trichlorfon, feline panleukopaenia, BVDV, hog cholera, border disease virus, canine parvo
What is cerebellar abiotrophy? Vs. Cerebellar atrophy?
*Cerebellar abiotrophy: premature or accelerated atrophy of a normally formed cerebellum; metabolic defect, inherited; purkinje cells are especially vulnerable to premature degeneration
* Cerebellar atrophy: due to onion weed, Solanum species of plants, lysosomal storage disorders, organomercurial poisoning
Hypomyelinogenesis and dysmyelination syndromes clinical signs?
Either absence or defect in myelin
* mainly affects males (X-linked recessive trait)
* generalized tremors commencing at birth, progressive ataxia with dysmyelination syndromes
* teratogenic viruses can also cause, BVDV, border disease virus
What are lysosomal storage disorders?
Substrates derived from normal cell catabolism accumulate within lysosomes rather than being degraded by lysosomal enzymes
** storage occurs in neurons and glial cells of CNS, sometimes hepatocytes, renal tubular epithelial cells, exocrine pancreatic acinar cells, macrophages, etc.
* progressive substrate accumulation –> cell swelling, cytoplasmic vacuolaton, cell dysfunction and occasionally cell death
** usually normal at birth and onset of progressive neurological signs
What does the formation of the meninges depend on?
Closure of the neural tube
What is encephalomyelitis?
Inflammation of the brain and spinal cord
What do the following terms mean: ependymitis, choroiditis, meningitis, leptomeningitis, and pachymeningitis?
* ependymitis= inflammation of the ependyma
* choroiditis= inflammation of the choroid plexus of the ventricles
* meningitis= inflammation of the meninges
* leptomeningitis= inflammation of the leptomeninges (arachnoid and pia mater)
* pachymeningitis= inflammation of the pachymeninges (dura mater)
Why is the CNS vulnerable to infection?
* functional indispensability of most parts of the CNS
* CSF is an excellent culture medium for many bacteria
*Introduced bacteria and fungi can spread rapidly and widely via CSF (e.g. along the drainage route of CSF from the leptomeninges to the brain and vice versa via the Virchow-Robin (perivascular) spaces
* Can spread rapidly WITHIN the CNS (neuropil, between neurons, and glial cells, via mobile infected leukocytes entering the CNS from circulation
* exudation of leukocytes and fibrin into CSF–> obstruction of CSF flow
*inflamm. of the CNS–> increased vasc. perm. and vasogenic oedema
* fibrous encapsulation of inflammatory/ infectious foci may not be possible (by collagen is only possible if foci impinge on the leptomeninges and major blood vessels of the CNS– where fibrocytes and fibroblasts are located)
What are the routes of infection into the CNS?
* haematogenous via arterial blood
* retrograde spread along axons of olfactory neurons or axons of peripheral or cranial nerves (e.g. rabies, Borna disease, infectious bovine rhinotrachietis, Listeria monocytogenes, TSEs)
* Direct implantation (via penetrating wound, skull fractures, contaminated migrating grass awns)
* Direct spread of infection from other sites (nasal cavity, paranasal sinuses, guttural pouch, middle or inner ear, vertebral osteomyelitis
What are the four common lesions found in inflammatory/ infectious disorders of the CNS?
* leptomeningitis (infiltration of the leptomeninges by leukocytes)
* perivascular cuffing (accumulation of leukocytes in the perivascular spaces– invaginations of pia mater)
* gliosis (reactive swelling and proliferation of glial cells- chiefly astrocytes and microglial)
* neuronal degeneration (especially in viral infections)
What are the types of inflammatory exudate in the leptomeninges and/or perivascular spaces detected by histopathology or cytological analysis post mortem that would give you clues to the likely causes?
* suppurative or fibrinous/fibrinopurulent- esp. bacteria or mycoplasmal infections, organomercurial poisoning, malignant catarrhal fever (herpes viral infection)
* lymphocytic or lymphoplasmacytic (non-suppurative)- viruses, protozoa, fungi, immune mediated disorders
* granulomatous or pyogranulomatous- fungi, granulomatous meningoencephalomyelitis (GME) of dogs, FIP, TB
* eosinophilic- metazoan parasites, Listeria monocytogenes, occasionally protozoa or fungi, rarely immune mediated
What is a common bacteria that penetrates damaged oral mucosa and ascends the Trigeminal nerve?
* Listeria monocytogenes–> trigeminal neuritis and ganglioneuritis–> unilateral microabscessation in the medulla oblongata with inflammation of the overlying leptomeninges +/- extension into the adjacent pons or rarely the cranial cervical spinal cord
What provides protection from spread to the CNS from the nasal cavity? Where are the weaknesses?
* skull and vertebrae provide some protection, but the most important barrier is the dura mater– but the dura mater can be breached especially where it is fused to the periosteum of the dorsal skull and where it is penetrated by nerve trunks (e.g. cribiform plate)
What are common causes in neonatal farm animals of leptomeningitis? What is the more common portals of entry? Often accompanied by?
* E. coli, Pasteurella species, streptococci, and salmonellae
* GI or respiratory tract, bite wounds or castration, ear notches
** often accompanied by polyarthritis, choroiditis, and sometimes endophthalmitis (inflammation of the uvea, retina, and cavities of the eyes)– the circulating bacteria may also localize in the peritoneal pleura, lungs (pneumonia), liver (multifocal hepatitis)
How does leptomeningitis present?
* periventricular cerebral abscesses, internal hydrocephalus from exudate plugging the mesencephalic aqueduct, faint cloudiness, hyperaemia +/- petechiation of the leptomeninges, cerebral oedema
** most tissue damage occurs early in bacterial leptomeningitis and the usual outcome is death– early therapeutic intervention may sterilise the infection and permit repair by fibrosis– tissue damage usually occurs too early
Where do cerebral abscesses normally occur? What bacterial species are common?
* hypothalamus and the junction of grey and white matter
* Histophilus somni septicaemia in cattle and lambs; Actinobacillus equuli bacteraemia in neonatal foals
** common in animals with septic thromboembolism from bacterial vegetative endocarditis
Where do cranial epidural abscesses usually arise?
Direct extension of bacteria from the paranasal sinuses or from extension of infection from the nasal cavity, middle ear, along cranial nerves or penetrating wounds
Where do spinal epidural abscesses usually occur?
* secondary to osteomyelitis of a vertebral body and are common in lambs, calves, and piglets (tail docking, tail bites in pigs)
** may be accompanied by leptomeningitis and/or myelitis
Where do cerebellopontine abscesses arise?
Extensions from otitis media and may be bilateral– sheep and pigs (Pasteurella multocida infections of the middle ear)
Where do hypothalamic abscesses usually result from?
Septic embolism or septic thromboembolism– cattle or dogs– migration of minute contaminated FBs e.g. grass awns that penetrate from the retrobulbar space through the orbital fissure
What will you see associated with abscesses in the CNS?
* usually involve white matter more than grey
* oedema (severe of surrounding tissue)
* develop slowly and gradually become encapsulated by fibrosis and/or astrocyte processes
** hypothalamic or cerebral abscesses which track through white matter to the ventricles–> pyencephaly = filling of ventricles by pus–> rapid increase in ICP–> death
Most viral infections are characterized by what lesions?
* non-suppurative leptomeningitis and perivascular cuffing
* lymphocytes usually predominate (some neutrophils in the early stages) (EEE has neutrophil rich inflammation and extensive cerebral necrosis)
* FIP provokes pyogranulomatous inflammation
* gliosis- oligos degenerate and die, astrocytes may degenerate or swell and proliferate– overall hiso hypercellularity (glial nodules)– many of the microglia may aggregate around the cell bodies of dead or dying neurons to form neuronophagic nodules
*neuronal degeneration/ necrosis (chromatolysis or coagulation necrosis)
* significant demyelination of the white matter– canine distemper, ovine visna, caprine arthritis encephalitis (CAE)
* ganglioneuritis (especially trigeminal ganlioneuritis)- e.g. rabies, pseudorabies, porcine enteroviruses
* viral inclusion bodies- e.g. rabies, distemper, canine adenovirus 1
What are the most common fungal and algal infections in AUS in the CNS? How do they usually come on?
* Cryptococcus neoformans (especially cats), Aspergillus, Candida, Mucor and dematiaceous species of fungi, Prototheca algal species
** usually opportunistic (usually only a mild inflammatory response- neutrophils and macrophages) in cats– more cellular and granulomatous in dogs
What are the common protozoal infections in the CNS?
* Babesia species, Theileria species, Trypanosoma species, Encephalitozoon cuniculi (rabbits and puppies), Toxoplasma gondii**, Neospora caninum **, Sarcocystitis species
What can Toxoplasma gondii cause in the CNS?
What can N. caninum cause in the CNS?
* T. gondii: Radiculitis (inflammation of spinal nerve roots) and lesions in other organs and tissues
* N. caninum: tachyzoites target neurons, ependymal cell and vascular endothelial cells in the CNS– paresis, ascending paralysis due to myelitis, polyradiculoneuritis (inflamm. of multiple spinal nerve roots and nerves), and polymyositis (inflamm of multiple skeletal muscles)
What can metazoan parasites cause in the CNS? What are some examples of metazoan parasitic infections of the CNS?
* Visceral larval migrans– migration in aberrant hosts– migration in aberrant hosts often induce a more intense reaction than migration in normal hosts
* or in normal hosts
* toruous, haemorrhagic and malacic lesions often with eosinophilic granulomatous inflammation of damaged parenchyma and overlying leptomeninges
Examples: Toxocara canis (ascarid), Angiostrongylus vasorum, Dirofilaria immitis, Stephanurus dentatus, Strongylus vulgaris, Angiostrongylus cantonensis
What is Granulomatous Meningoencephalomyelitis (GME)?
* Auto-immune disease in dogs– especially small breeds, more likely in females
* Unknown cause but likely T cell mediated delayed type hypersensitivity reaction
* perivascular cuffs of macrophages, lymphocytes, and plasma cells especially in the white matter and into the leptomeninges–> gradually increase number of macrophages to form expanding granulomas that compress the surrounding white matter–> oedema and malacia
** usually lesions are widely disseminated through brain and spinal cord, some become focal due to coalescence of multiple adjacent foci
** clinical signs depend on location of lesions but often ataxia, paresis, paralysis, seizures
What is Necrotising Meningoencephalitis (Pug Dog Encephalitis)?
* Necrotising meningoencephalitis that chiefly involves grey matter of the cerebral cortex, with some extension to the underlying white matter
* lethargy, ataxia, seizures**–> progression to coma
** unknown cause but may involve an autoimmune response to a component of the CNS by excitotoxic neuronal injury as a result of repeititive seizure activity
What is steroid responsive meningitis- arteritis in dogs?
SRMA is a polyarteritis that is thought to be immune mediated
* severe necrotising arteritis of small and medium sized meningeal arteries +/- coronary and mediastinal arteries with affected vessel walls infiltrated by lymphocytes, plasma cells, monocytes, and variable numbers of neutrophils
** especially in young beagles, respond to immunosuppressive therapy
What are TSEs?
* transmissible, non-inflammatory, degenerative disease of the CNS
* accumulation of abnormal protein known as prion protein PrPsc in Scrapie
* denaturation of protein = loss of infectivity and transmissibility
* transmission via ingestion of infectious material–> prion repilcation in monocytes/ macrophages of gut associated lymphoid tissue–> spread to regional lymph nodes and spleen–> spread to CNS via peripheral nerve axons
** incubation period is 2 months in lab to 2 years in ruminants
** “species barrier” often means other species are not as readily infected or have a longer incubation period but can be overcome
** lesions are microscopic and non-inflammatory; vacuoles in the cell bodies, dendrites and axons of neurons–> spongiosis of the neuropil in affected areas of grey matter
What is hepatic encephalopathy?
* failure of hepatic detoxicification functions or circulatory bypass of the liver
* common in ruminants and horses with hepatic failure and in dogs with portosystemic shunting and chronic hepatitis
** many of the toxins implicated are produced by normal bacterial metabolism in the GIT– ammonia is responsible for most of the structural lesions in the brain
* Ammonia accumulation by astrocytes–> cytotoxic oedema–> altered gene expression and neurotransmission +/- disruption of the BBB
Why is thiamine (vitamin B1) key to the CNS? What happens with thiamine deficiency to the CNS?
* it is a critical factor for various enzymes in carbohydrate metabolism and also functions in axonal condution, synaptic transmission and oligodendrocyte metabolism
* thiamine deficiency–> CNS depletion of high energy phosphates e.g. ATP and decreased glucose utilization by neurons–> burst of neuronal activity with increased lactate formation–> excitotoxic injury to vulnerable neurons
** In ruminants thiamine deficiency is known as polioencephalomalacia (PEM)
What are some of the causes of thiamine deficiency in ruminants?
* Abrupt alternation of ruminal microflora (thiamine in ruminants is from the synthetic activity of ruminal bacteria)– especially carbohydrate rich and roughage poor diets
* destruction of thiamine within the GIT e.g. by thiaminases in bracken fern
* Inactivation of thiamine by excess dietary sulphate, sulphide, or elemental sulphur
* Production of inactive thiamine analogues by bacteria (e.g. in cobalt deficiency or in ruminants fed molasses)
* decreased absorption or increased faecal excretion of thiamine
What age and species are thiamine deficiencies normally found in? What are the clinical signs of thiamine deficiency?
* most common in young cattle and sheep
* Clinical signs: anorexia, dullness, head pressing, central blindness, muscle tremors, teeth grinding, salivation, nystagmus, opisthotonus (state of severe hyperextension), seizures, recumbency, coma and death
** acute diffuse cerebral oedema, in severe cases bilaterally symmetrical malacia of cerebrocortical grey matter especially in the parietal and occipital lobes
** early administration of thiamine may be curative– so always give with neurological disease
What are some causes of thiamine deficiency in carnivores? Clinical signs?
* Thiaminase naturally present in many species of fish
* Excessive cooking of meat or excessive heating of tinned food during manufacture
* preservation of meat with sulphur dioxide
** Clinical signs: salivation, anorexia, bradycardia (cardiac muscles dependence on pyruvate), ataxia, inco-ordination, mydriasis, sluggish pupillary reflexes, ventroflexion of the neck, and seizures
Why is copper needed? What species are copper deficiencies normally seen and how?
* Coppe is an integral component of several enzyme systems and of the plasma protein ceruloplasmin
* CNS disease is usually a problem in sheep and goats
* Can be seen as primary due to copper deficient soils and inadequate intake from forage OR secondary due to interference with absorption due to antagonism by dietary molybdenum, zinc, cadmium, iron or inorganic sulphates
Clinical signs of Copper Deficiency
* Sway back in lambs (may be present at birth) or delayed up to 6 months
* enzootic ataxia (normal at birth but develop a swaying hindlimb ataxia in the first 6 months of life)
* swayback affected lambs may be blind deaf, and apathetic, lie prostrate with flaccid paralysis and will fall when attempting to move
** gross brain lesions: hydranencephaly or porencephaly may be present
** microscopic CNS lesions: chromatolysis, variable neuronal necrosis and Wallerian degeneration
What has Vitamin E Deficiency been linked to?
Equine degenerative myeloencephalopathy (EDM)- a slowly progressive degenerative disorder of horses and other equidae
** clinical signs often emerge at 6 months of age and often mimic those of the wobbler syndrome
* progressive Wallerian degeneration in all spinal funiculi but especially in the ascending dorsolateral (spinocerebellar) and descending ventromedial (motor) tracts
What species is lead poisoning normally seen? From what?
Dogs and cattle
* sources of lead include discarded car batteries, old petrol, old flaking or peeling lead paint, emissions from smelters contaminating pastures etc
What happens in acute lead poisoning? Chronic? Effects of lead poisoning?
* acute- absorbed lead is deposited especially in the liver and kidneys
* chronic- lead deposition in bone is important with slow continuous turnover and gradual elimination in bile and urine
** Effects: liver, kidneys, bone marrow (red cell production), vascular endothelium, GIT, brain, peripheral nervous system (demyelination)…. vasogenic oedema, astrocyte cytotoxicity, congestion and petechiation of the brain and/ or leptomeninges
What is Nigropallidal Encephalomalacia of Horses?
* prolonged ingestion of yellow star thistle or Russian knapweed
* hot dry summers when thistle remains green and not other plants
* clinical signs: drowsiness, persistent chewing, difficulty in prehension of food and drinking of water–> death from starvation and/or dehydration
** gross brain lesions in the globus pallidus and substantia nigra
** unknown pathogenesis but likely from ROS
What is Mycotoxic Leukoencephalomalacia of Horses
* mouldy feed contaminated by fungus, Fusarium moniliforme
Clinical signs: abrupt onset of drowsiness, impaired vision, depression, head pressing, ataxia, weakness, circling, aimless wandering, pharyngeal paralysis
** death normally within a few days of the onset of symptoms
** often large oedematous areas and malacia with haemorrhage
What species are impacted by phalaris toxicity? What are the three syndromes seen in most common species?
* sheep, cattle and horses
* toxic indole alkaloids
Sheep: 1. Sudden death cardiac syndrome (specific toxin that cannot cross the BBB but affects autonomic innervation of the heart)
- Polioencephalomalacia- like Sudden death syndrome (found dead within a few hours of exposure– peracute ammonia toxicity likely)
- Subacute to Chronic Staggers Syndrome (repeated exposure to phalaris– termors, hyperexcitability, hindlimb weakness, etc.)
What are the most common primary neoplasms in middle aged or older dogs? Cats?
Glial cell origin– astrocytoma most common
* Meningioma in cats > 10 years of age (most common spinal cord tumour of cats and cattle is lymphoma)
What happens with senile degenerative lesions in domestic animals?
* senile atrophy common, grossly discoloured gray-yellow
* meningeal collagenisation (fibrosis) and osseous metaplasia– thickening of intra-cranial dura mater due to collagen deposition +/- osseous metaplasia is common in older cats and dogs— chiefly involves dorsal dura mater which may become firmly anchored to the calvarium
** cholesteatomas of the choroid plexus- 15-20% of aged horses develop space occupying cholesterol granulomas within the choroid plexus, especially the fourth ventricle– may obstruct CSF flow–> acquired internal hydrocephalus (thought to result from haemorrhage into the choroid plexus from head trauma)
Where are alpha 2 receptors?
* In the CNS (brain stem- sedation!, CV regulating centre, dorsal horn of spinal cord- analgesia!, thalamus- analgesia!, sympathetic neurones- analgesia)
* In the periphery (autonomic ganglia, in blood vessels)
What happens when alpha 2 receptor is bound presynaptically? Postsynaptically?
* Presynaptically - inhibition of noradrenaline release (effectively a negative feedback mechanism)
* Postsynaptically- contraction of vascular smooth muscle
What do alpha-2 agonists do?
Why do alpha 2 agonists cause profound bradycardia? What other cardiovascular effects?
* acts on the central medullary cardiovascular center
* decreased CO (increased afterload, coronary artery vasoconstriction)
* increase in blood pressure and then decrease (binds initially to the postsynaptic receptors on the peripheral alpha 2 receptors)—> then that causes a REFLEX BRADYCARDIA (takes more time to get into the CNS)
Why do you have muddy mucous membranes and reduced coronary perfusion with alpha 2 agonists?
* coronary and small peripheral arteries larger ratio of post synaptic alpha 2: alpha 1 receptors
** not that clinically relevant- except that you will notice the muddy mucous membranes– the coronary arterial vessels are the real clinically relevant piece
What are the metabolic effects of alpha 2 agonists?
* Hyperglycaemia- due to inhibition of insulin release
* Inhibition of lipolysis
* impairment of temp regulation (giving to a cow in the yard would be a consideration)
* kidney diuresis- due to inhibition of renine release (clients may say they took the animal home and they peed a lot)
With premedication with alpha 2 agonists vs. acepromazine, what does it mean for the main anaesthetic drug?
** you need LESS alpha 2 agonists for premedication vs. acepromazine
What premedication would you use in a dog with heart failure or any debilitated condition?
Opioids, NOT alpha 2 agonists
When are phenothiazine derivatives used (acepromazine)? How are they described?? Why?
Preanaesthetic/ calming
(can be used for floating a horse, orally for dogs and cats in the car)
** Described as “dirty drugs” because they bind to a lot of different receptors
Mechanism of action of phenothiazines? What is important to remember about what it does NOT do?
Alpha adrenoceptor BLOCKADE: Hypotensive… different than alpha 2 agonists.
*** NO analgesia
What is acepromazine typically used for (phenothiazine derivative)? Warnings?
* Premed
* Hypotension
* Decreased PCV
* Do not use in a shocked animal, colic, seizure threshold, potentiation of anaesthetic effect (meaning you need LESS ANAESTHESIA!)
**(do not give to Boxer dogs– more predisposed to tumours– therefore more likely to seizure if there is one there)
When are Benzodiazepines used in vet medicine? Mechanism of action? What is so good about these drugs? How about with cats?
* Sedative and anxiolytic (thunderstorms)– muscle relaxation
* allosteric effect on the GABA receptor (inhibitory neurotransmitter)– & increase– improve the binding of GABA to its own receptor therefore INCREASE THE INHIBITORY EFFECT OF GABA
** minimal cardiovascular effects
* a single IV injection will stimulate cats appetite
When are Butyrophenones used?
* Reduced motor activity and catalepsy through central dopamine and noradrenaline blockade
* On pigs!!
What happens as cardiac output falls to drug concentration reaching the brain in the blood?
As CO decreases, a larger amount of drug will reach the brain. The brain’s blood concentration is FIXED. So the proportion of blood reaching the brain will increase if CO drops.
What general problems will you see if the problem is in the brain?
* Mentation
* Cranial nerve tests
* Gait
What problems will you see if the problem is in the spinal cord?
* Gait
* Proprioception function tests- which limbs are normal and which are abnormal?
* Reflexes: UMN or LMN lesion
What would you see with signs of a cerebral syndrome (lesion)?
* Normal gait
* Seizures
* altered mental status
* altered behaviour
* pacing, circling, head pressing
* postural reactions depressed contralaterally (Right sided lesions= Left side of body problem)
* Vision impairment (contralateral) with normal pupillary light reflexes (PLRs)
What problems might you see with diencephalic syndrome?
* Normal gait
* altered mental status
* altered behaviour
* trembling, pacing, wandering, hiding, tight circling, head pressing
* vision impairment if the optic chiasm is affected +/- loss of PLRs
* abnormal temperature regulation
* abnormal appetite with hyperphagia or complete anorexia
* endocrine abnormalities: hyperadrenocorticism (dogs), diabetes insipidus (electrolyte imbalances)
What problems might you see with midbrain syndrome?
* weakness and paralysis in all four limbs/ or hemisigns if unilateral lesion
* increased reflexes and muscle tone (contralateral or ipsilateral)
*postural reaction deficits contralaterally or ipsilaterally
*mental depression, stupour and coma if large lesions (reticular activating system)
* ipsilateral lesion of CN III
* Hyperventilation
What problems might you see with pontomedullary syndrome?
* Weakness or paralysis in all four limbs or ipsilateral, normal, or increased reflexes or muscle tone in all four limbs
* Postural reaction deficits in limbs on the side of the lesion or all four limbs
* Multiple cranial nerve deficits (V through XII)
* Jaw paralysis and facial sensation loss (V)
* Depressed palpebral reflex (V and VII)
* Facial paralysis (VII)
* Head tilt, falling, nystagmus (vestibular signs, VIII)
* Pharyngeal/ oesophageal/laryngeal paralysis (IX, X)
* Tongue paralysis (XII)
What problems might you see with cerebellar syndrome?
* Hypermetria (goose stepping gait)
* Truncal ataxia
* intention tremors of head and eyes (nystagmus)
* broad based stance
* postural reactions present but exaggerated
* menace deficit but normal vision
* decerebellate posture
What do you think when you see circling?
Vestibular or prosencephalic disease
What do you think when you see a wide based stance?
Vestibular or cerebellar
What do you think when you see ataxia?
Spinal cord or brainstem
What do you think when you see hypermetria?
Cerebellar
What is proprioception mediated by?
Conscious: cerebral cortex; Unconcious: cerebellum
* normal function requires:
- intact peripheral receptors and nerves
- uncompromised spinal cord
- intact brain (cerebral hemisphere and/or cerebellum)
- intact motor pathways
- normal muscle function
What are 3 brain stem nuclei of descending motor paths? Are they extra pyramidal or pyramidal?
- Red nucleus- rubrospinal tract
- Vestibular nucleus- vestibulo-spinal tract
- Reticular formation- reticulospinal tract
** Brain stem pathways are EXTRA pyramidal
What is the corticospinal tract? Is it pyramidal or extra? How does it run?
Motor tract originating from the cerebral cortex– PYRAMIDAL TRACT because it traverses the medullary pyramids on the way to the spinal cord
** Pyramidal tracts do not synapse until LMN is reached
* Cortex–> internal capsule–> cerebral peduncles–> medulla
Pyramidal vs. extra pyramidal tracts
* Pyramidal are CORTICAL in origin
* Extra are BRAINSTEM in origin ( and more important in movement in domestic animals)
what part of the funiculi is made up of UMNs facilitating flexor muscle activity? Extensor?
Flexor= lateral funiculus
Extensor= Ventral funiculus
What part of the brain has the thalamus/ hypothalamus and geniculate bodies?
Diencephalon (part of the prosencephalon with the telencephalon)
What does the brainstem include?
Midbrain, pons, medulla oblongata
Forebrain functions
*perception of sensory input, initiation of motor activity, integration/ association of information, Cranial nerves I & II
Midbrain function?
* Thoroughfare for ascending and descending information
* major upper motor neuron nuclei for movement
* Cranial nerves III and IV
* Consciousness
What is the function of the hindbrain?
* Thoroughfare for ascending and descending information
* Major UMN nuclei for movement
* Coordination of muscle activity (cerebellum)
* Cranial nerves V to XII
* regulation of many organ functions (cardiovascular, respiratory, gastrointestinal)
What are the types of neuro receptors? How long?
Why have fast and slow neurotransmitters?
Anatomical columns of neurons- dorsal, intermediate, and ventral each have a functional arrangement, what is it?
* Dorsal column- sensory
* intermediate column- visceral motor (ONLY IN THE THORACIC, LUMBAR, and SACRAL SEGMENTS)
* ventral column- somatic motor
What are spinal nerves? What are intervertebral foramina? What lies within the intervertebral foramen?
The joining of the dorsal and ventral roots.
Intervertebral foramina- gaps between adjacent vertebral arches and are the point of entry/exit of the spinal nerve
** Spinal ganglia neurons lie within the intervertebral foramina
What is the internal capsule?
Corticospinal tract constitutes a large part of the internal capsule- carrying motor information from the primary cortext to the lower motor neurons in the spinal cord
How does the corona radiata and crus cerebri relate?
Above the basal ganglia the corticospinal tract is part of the corona radiata, below the basal ganglia the tract is called the crus cerebri (part of the cerebral peduncle) and below the pons it is referred to as the corticospinal tract
What connects the third ventricle to the lateral ventricles? What connects the third ventricle to the fourth ventricle?
Interventricular foarmina connects the third ventricle to the lateral ventricles
* mesencephalic aqueduct- connects the third (into the diencephalon) and fourth ventricles (mesencephalon)
Why do the veins of the nervous system lack valves frequently?
So that they can form veinous sinuses which act as “fluid cushions”
Where does the epidural space not exist?
Above the mid-cervical region because the periosteum fuses with the dura mater. Haemorrhage can force an epidural space in the brain
What are the fine meningeal filaments that cross the arachnoid space between the arachnoid mater and the pia mater?
Arachnoid trabeculae
Falx cerebri vs. tentorium cerebelli
Falx cerebri- separates two cerebral hemispheres from the ethmoid bone (cribiform plate) to the osseous tentorium.
Tentorium cerebelli separates the cerebral hemispheres from the cerebellum– from the petrosal crest to the osseous tentorium, bilaterally. (divides the cranial vault into the rostral and caudal fossa- with the cerebellum and caudal brainstem)
Venous drainage of the brain
What does the rhombencephalon refer to? What part of the ventricular system is in the rhombencephalon? How about the rest of the ventricular system?
Metencephalon- pons and cerebellum
myelencephalon- medulla
Where is the internal vertebral venous plexus?
What is the only consistent spinal artery? What does it turn into? Where?
The ventral spinal artery is the major supply to the lateral and ventral grey matter and the ventral white matter. At the foramen magnum or C1, it becomes the basilar artery supplying the brain.
** two dorsolateral arteries are not present in all regions
** Radicular arteries occur at each intervertebral foramen (supplied from the vertebral, intercostal, lumbar, and sacral arteries)– they follow the spinal roots entering the vertebral canal and split into dorsal and ventral radicular branches which anatastamose with the longitudinal arteries
What supplies the base of the brain? Which also supply the Circle of Willis?
Who has the rostral and caudal retes?
Basilar a. (continuation of ventral vertebral a.) and the internal carotid aa. (left and right)
** ruminants and pigs have the rostral and caudal retes– any blood vessel that breaks up into a plexus and then back into a single blood vessel
What is the path of blood supply from the heart to the brain?
Left and right common carotid aa. come off the brachiocephalic trunk (2nd branch off the aorta)
* off the of the left and right subclavians the vertebral aa. come off, which anastamose to supply the ventral vertebral a. which becomes the basilar a.
Name the arterial supply to the brain from a lateral aspect. What are the three major meningeal branches?
Meningeal branches: rostral, middle, and caudal meningeal arteries
What is the infundibular recess? optic recess? suprapineal recess?
The continuation of the third ventricle into the hypophyseal stalk.
** optic recess- in the wall of the third ventricle just dorsal to the optic chiasm
** suprapineal recess- a small extension of the third ventricle lying dorsal to the pineal gland
What drains the CSF? Where are they?
* Lateral apertures openings between the fourth ventricle and the subarachnoid space at the level of CN VIII
* Arachnoid villus act as one way valves- the pressure of the CSF is normally higher than venous system so CSF flows through the villi into the blood– in venous sinuses
What is peripheral sensitisation? Why does it exist?
* Direct consequence of tissue trauma and inflammation- inflammatory mediators from damaged cells (H+, K, PG), plasma releasing bradykinin, platelets releasing serotonin, macrophages releasing cytokines, mast cells releasing histamine, etc.
** Reduction of activation threshold for AP because of sensitizing soup of chemical mediators
** Secondary to inflammation, enhance perception of pain to promote healing and protect against future damage
What is central sensitisation?
Indirect consequence of tissue trauma and inflammation. Constant activation of peripheral receptor- glutamate, asparate, and substance P are released– constant activation of AMPA and neurokinin receptor on dorsal horn–> activation of NMDA receptors which increases excitability of dorsal horn projection neurons, expansion of receptive fields, increased response both nociceptive (hyperalgesia) and allodynia (non-nociceptive stimnuli)
What is the difference between wind-up, hyperalgesia, and central sensitisation?
Wind-up (chronic pain): a frequency dependent increase in the excitability of spinal cord neurones evoked by electrical stimulation of afferent C-fibres.
Central sensitization: enhancement in the function of neurons and circuits in nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as well as to reduced inhibition– due to plasticity of the somatosensory NS in response to activity, inflammation, and neuronal injury. Allodynia accompanies. Occur after the same stimulation happens again and again.
Hyperalgesia: an increased sensitivity to pain by cytokines, chemokines
Where does serotinin work?
* Serotonin- Raphe Magnus
Norepinephrine- Locus ceruleus
What are the 3 prevertebral ganglia that Splanchnic nerves synapse within the body cavity deep in viscera? What leaves these ganglia and who do they travel with?
* Coeliac, cranial mesenteric, and caudal mesenteric ganglia– the postsynaptic fibres travel with blood vessels to terminate in the abdominal organs
What supplies the sympathetic innervation of the head? What is the actual nerve called that it runs in, what does that nerve consist of? And run within?
Fibres from C8 to T7 ascend via the cervicosympathetic trunk
* vagosympathetic trunk consists of the cervicosympathetic trunk going to the head and the vagal fibres descending to the body.
** it is located in the carotid sheath of the neck
Where is the cranial cervical ganglion located? Where do the fibres exiting this ganglion go?
Deep to the tympanic bulla. The fibres travel in association with arteries to supply the head.
Where does parasympathetic supply to the head arise from?
Parasympathetic nuclei of cranial nerves III, VII, and IX
** PS nucleus of III in the mesencephalon- supplies the iris, ciliary body and travels to the eye, via the orbital fissure with the oculomotor nerve- responds to increasing light. Efferent discharge causes miosis.
** PS supply to the salivary glands via cranial nerves VII and IX- nuclei are located in the myelencephalon
Where does the vagus separate from the vagosympathetic trunk?
* at the middle cervical ganglion and after traversing the thorax and splitting and reforming into the dorsal and ventral branches continues through the diaphragm to the abdominal viscera– stopping around the distal colon. The rest of the colon and caudal PS supply comes from the sacral segments
What is unique about the enteric system? What are the two plexi that control gut secretion and motility?
Has intrinsic activity so can function in isolation from the CNS but also responsive to it. Receptor cells are located in the gut wall and synapse with interneurons, which synapse with local motor neurons causing reflex excitation or inhibition.
* submucosal plexus- gut secretion controller
* myenteric plexus- gut motility controller
What would you think if you saw anisocoria?
Lesion in one of the CNIIIs- whole thing picked off therefore absence of parasympathetic control of pupillary constriction in one side
What would you think if you saw absent direct papillary light reflex in the affected eye but normal consensual reflex in the other eye?
CNIII lesion, lack of PS supply. If the lesion was in the right CNIII, you would see an absent PLR in the righ teye when the light was shone into it but a present PLR in the left eye.
What would you think if you saw stabismus or an abnormal oculocephalic reflex?
(Deviation of the eyeball within the orbit)
CN III lesion (potentially)
Why are lesions affecting the sympathetic supply of the eye more common? What is the loss of sympathetic supply called? What does that look like?
The pathway is long. Lesions in the cervical spinal cord, thorax, neck, or tympanic bullae can affect sympathetic supply.
** Called Horner’s Syndrome
* Meiosis (small pupil on affected side), ptosis (drooping eyelid on affected side), enophthalmos (sunken eyeball, with third eyelid protrusion as a result)
C6- large transverse process
T11 anticlinal
Where does the diaphragmatic crura insert?
On the ventral aspect of L3 & L4, so the ventral margin of these vertebral bodies may be indistinct
What components of the vertebral column should be evaluated in turn?
( Lumbar vertebra, lateral and ventrodorsal projections)
- Vertebral body
- Vertebral end-plate
- Intervertebral disc space
- Vertebral canal
- Intervertebral foramen
- Pedicles and Dorsal Lamina
- Dorsal Spinous Process
- Transverse Processes
- Articular facet joints
arrow heads- calvarium
Arrow- cribiform plate
Why are both radiographs and ultrasound limited in their ability to diagnose neurological disease?
* Radiographs detect changes to bone– but may be useful in trauma (though CT is preferred), neoplaisa of teh skull or vertebra, intervertebral disc degeneration, discospondylitis, hydrocephalus with an open fontanelle (CT or MRI required to confirm diagnosis)
* Ultrasound cannot penetrate through dense bone- it can evaluate neural tissue but opportunities are limited since the brain and spinal cord are encased by bone– only in hydrocephalus with an open fontanelle and intra-operative ultrasound examination
Why is Computed Tomography superior for bony structures? What else?
It is a cross sectional imaging modality which avoids superimposition of structures. More sensitive to detecting bone lysis vs. radiographs. Good for eval of skull or vertebral fractures or malformations.
* CT is sensitive for detection of acute haemorrhage– more rapid to acquire than MRIs– preferred for acute head or spinal trauma
* herniation of mineralized intervertebral discs (MRI or myelography +/- CT if NO disc mineralization)
What is Magnetic Resonance Imaging best for?
* Excellent soft tissue constrast, also cross- sectional so avoids superimposition of structures (like CT)
* Modality of choice for both brain and spinal cord lesions
* soft tissue contrast, fluid accumulations
* can be used with gadolinium contrast medium
** UNLIKE CT, MRI can be used to evaluate the surrounding meninges and peripheral nerves
What are the three kinds of oedema that occur in the brain?
- Vasogenic- increased permeability of vascular endothelium- in white matter
- Cytotoxic oedema- no confined to white matter, results in fluid accumulation within cells due to hypoxia and failure of ATP sodium pumps in the cellular membrane
- Periventricular oedema- obstructive hydrocephalus. CSF seeps through the compromised ependymal lining, extening into the brian parenchyma a few mm from the ventricular walls
WHat kind of oedema in each?
A. Vasogenic oedema
B. Cytotoxic
C. Periventricular
A. Metastatic haemangiosarcoma
B. Focal haemorrhage due to a haemorrhagic stroke
Vertebral formula in the dog, cat, and horse?
dog & cat- c7 t13 L7 s3 c20-23
horse- c7 t 18 L 6 S 5 c 15-21
What is all this? What does it do? Innervation?
Semicircular ducts with ampulla enlargements– 3 semicircular ducts in each ear located at right angles to each other. Each duct has an ampulla at one end that contains sensory region (CRISTA- the ride of cells).
The ampulla’s sensory region senses dynamic position due to movement of endolymph. Cilia of Hair cells located on the crista project into cupula (GELATINOUS). Cupula readily deflected by movement of endolymph created by rotation or deceleration of head.
Innervation- Vestibular branch of the Vestibulocochlear nerve CN VIII
What are the auditory ossicles? What is their purpose?
Stapes, incus, malleus (SIM!) - can be moved by contraction of tensor tympani m. (attached to malleus) and stapedius m. (attached to stapes)
Changes air vibrations (sound waves) into mechanical movement through auditory ossicles
What is the membranous labyrinth of the inner ear surrounded by? What is IN the membranous labyrinth?
Surrounded by perilymph, endolymph inside
What are the three regions of bony labyrinth of the inner ear? What about membranous labyrinth?
Hair cell with 40-80 cilia sticking up into cupula and endolymph– with one kinocilium
* Movement of cilia towards or away from kinocilium results in depolarization or hyperpolarization of hair cell and excitation or inhibition of firing of neuron at base of hair cell
Maculae inside saccule (vertical plane) and utricle (horizontal plane)
* Monitors position of head with respect to gravity
KC and cilia project into otolithic membrane (gelatinous matrix containing otoliths)
** pull of gravity on otolithic membrane causes shearing force on cilia
In the cochlea, what are the two longitudinal canals with perilymph?
** cochlear duct adherent to walls of spiral canal– subdividing perilymphatic space into 2 longitudinal canals: scala vestibuli & scala tympani
What is the basilar membrane? What is its function?
Part of cochlear duct adjacent to scala tympani (ends at the cochlear window to the tympanic cavity)
** transduces sound into nerve impulses
** contains hair cells with tips of cilia embedded in gelatinous tectorial membrane (cochlear hair cells have no kinocilia)
** Base of hair cells in contact with nerve endings leading to neurons in spiral ganglion (in modiolus)– Cochlear branch of the CN VIII
How does hearing work?
vibration of tympanic membrane–> vibration of auditory ossicles–> vibration of stapes against vesticular window–> waves in perilymph ascend spiral in scala vestibuli (descend scala tympani to be dissapated through cochlear window)–> waves in endolymph of cochlear duct–> vibration of basilar membrane–> distortion of hair cell cilia resting againts tectorial membrane (gel inside the cochlea)–> depolarization of hair cells–> impulse in cochlear nerve
When CN VIII unites as vestibulocochlear nerve, where does it go?
Unites and travels to brainstem through internal acoustic meatus of temporal bone
What nerve supplies the tensor tympani m.? How about the stapedius m?
Tensor tympani muscle- CN VII
Stapedius- CN V (branch of the mandibular division)
Where are the vestibular nuclei? Where do the afferents come from? Efferents go to?
4 paired nuclei in the dorsal pons and the medulla adjacent to the lateral wall of the 4th ventricle
* Receive afferents from CNVIII and send efferents to: spinal cord- lateral and medial vestibulospinal tracts, brainstem, and cerebellum
What do the lateral and medial vestibulospinal tracts do?
Allow coordination of position and activity of the limbs, neck, and trunk with movements of the head
What are the terminations of the efferents from the vestibular nuclei to the brainstem?
- Terminate in motor nuclei of CN III, IV, and IV to change eye position to accomodate changes in head position
- Project to the reticular formation to provide afferents to the vomiting centre (motion sickness)
- Projections to the cerebral cortex via the thalamus must exist to allow conscious recognition of balance
What are the three possible dysfunctions of the vestibular centre? What are the 3 clinical signs of vestibular disease?
CN VIII, receptors in the inner ear (peripheral vestibular disease), or as a results of disease of the cerebellum (central vestibular disease)
** Three clinical signs: head tilt (to the side of the lesion), nystagmus (fast phase away from the side of the lesion), and circling (falling or rolling to the side of the lesion)
If vestibular disease is suspected, what might make you think central vestibular disease?
* Nystagmus that is vertical, nystagmus that changes direction, the presence of proprioceptive deficits (indicative of long tract signs), presence of other cranial nerve deficits (in particular CN V, IX, X)
What are clinical signs seen with cerebellar disease?
* Hypermetric gait
* Truncal Sway
* Wide based stance
* Tremors (especially intention tremors)
* Vestibular signs (positional nystagmus, pendular nystagmus)
* Lesions of the rostral cerebellum (especially severe ones) will result in decerebellate rigidity– extended forelimbs, flexed hips and an extension of the head and neck (similar to star gazing); all of which occurs with patient in lateral recumbency
* Absent menace response (seen with either large lesions usually, or congenital lesions of the cerebellum)
Where are the motor centres for the extrapyramidal system located?
Midbrain & hindbrain
Are there descending spinal pathways coming from the cerebellum?
No! It can only modify function through inhibiton– like your Mother saying “no!”
What is an intention tremor?
Termor of parts of the body exacerbated by attempts at precise movement– which goes away with sleep– tremor is a result between agonist and antagonist muscle groups (which is how the cerebellum normally fine- tunes movement)
What is the function of the cerebellum?
* Pre-control & Control of posture/ movement (input from special senses of course, cerebrum’s motor centre tells the cerebellum what it is planning to do via the pontine or olivary nuclei, GTOs and MSs send proprioceptive info to the cerebellum via spinocerebellar pathways to inform position of limbs in 3D space
** Ipsilateral function since one half of the cerebellum controls contralateral motor centres of the pyramidal and extrapyramidal systems– therefore ends up ipsilateral
