NMSK - week 7 cranial nerves and neurological clinical examination

LOs for this week: Explain the concept of lateral inhibition Describe the functional arrangement of retinal ganglion cells Describe the higher order processing of visual information Discuss possible causes of seizures and know what epilepsy (epilepsies) is (are) Explain the general mechanisms of action of anticonvulsant drugs Specify the anticonvulsant drugs mainly used in the treatment of epilepsy in small animDescribe a seizure and explain what is happening in the brain during a seizure Give examples of other conditions that an owner could confuse with a seizure List the intra- and extra- cranial causes of seizures Use the results of the neurological examination to localise the lesion Explain the mechanism of action of two commonly used anti-epileptic drugs Explain the concept of half-life and the clinical implication for dosing regimes. List the general pathological processes represented by the VITAMIN D mnemonic Understand the importance of a problem list in addressing clinical scenarios Understand the concept of the sign time graph. Describe the course of the cranial nerves as they pass from the brain into the extracranial space

what is meant by the association cortex?

• a series of interconnected regions that are responsible for ‘higher functions’ including controlling voluntary initiation of function and movements

what areas can we map on the brain?

• visual

• auditory

• somatosensroy

• olfactory

• motorDescribe the course of the cranial nerves as they pass from the brain into the extracranial space

what are the 3 building blocks for visual processing?

• photoreceptors (in the eye that contain rods and cones)

• visual pathways (connects eye to brain)

• Brodman’s area 17-19, visual cortex (in the occipital lobe)

how can we use experimental electrophysiology

• record from and label cells using microelectrons (look at what stimuli result in what outcome)

• functional MRI - look at the changes between oxygenated and deoxygenated blood

what is the structure of the retina?

3 layers:

1. Ganglion cells - produce white matter tract to transmit information to the brain via the optic nerve

2. Bipolar cells, amacrine cells (connect widely) and horizontal cells (connect horizontally) - opportunity for processing at the level of the retina before transmission to the cortex

3. Photoreceptors - transduction of photon energy into membrane depolarisation and action potentials (rods and cones)

what is retinal electrophysiological recording?

• one to one relationship at the receptor level

• complex multimodal relationship at the ganglion cell layer

• there’s not a direct line from photoreceptor cells to optic cells

what are the modes of ganglion cell responses?

• single cell recording with small visual stimulus

• small field (fovea)

• large field (periphery)

• lateral inhibtion

what is meant by lateral inhibition?

The ganglion cell is stimulated by a central region but around this region there’s an area of inhibition, which if stimulated inhibits anything else within the field of view

• improves edge detection

• improves localisation

if you shine a light on it/leave it in darkness, shows a normal response. If they’re on the edge of the light source they show an enhanced response and if they’re in the corner, show an even more enhanced response - enables us to observe edges.

what is meant by the gain and transcience of ganglion cell response?

• gain = horizontal cells, wide receptive fields (field adaption)

• Transcience - altered temporal responses

what is the proportion of sustained vs transient ganglion cell response

80:20%

how many different modes of ganglion cell responses reported in the cat are there?

• 23 including response to moving stimuli

what is the lateral geniculate nucleus

• similar receptive fields as ganglion cells

• just a relay bod

• different modalities and sides kept separate and in ordered patterns

• gating from other regions of the brain can be demonstrated

In this nucleus the neurones synapse with the optic radiation nerve → occipital cortex. Very little processing takes place here, however there is the opportunity for the brain to produce some gating to this information

where do the optic radiations go?

• into Brodman’s area 17

• pyramidal cells which integrate information from the geniculate radiation project to surrounding areas

what is Brodman’s area 17

• novel forms of visual fields:
  

  • simple cells - can be mapped with spots of light

  • complex cells - respond to bars of light/an edge of specific orientation

  • hypercomplex cells (end stopped complex) - bar of light must be correct length

where does the information go from Brodman’s area 17?

• into areas 18,19 and beyond (association cortex)

• localisation vs recognition

• increasingly difficult to identify recognition patterns

How do we see colour?

• this is an additional tier of information processed by the brain

• 3 colour cones: red, green and blue

define a seizure

• temporary, abnormal, electro-physiological phenomena of the brain, resulting in abnormal synchronisation of electrical neuronal activity. Due to temporary abnormal electrical activity of a group of brain cells

define epilepsy

• a disease of the brain characterised by an enduring predisposition to generate epileptic seizures (it’s a description, not a diagnosis)

• applied as having 2 unprovoked epileptic seizures greater than 24 hours apart

what are convulsions

• sudden and often violent motor activity of cerebral or brainstem origin

• may also occur in the absence of an electrical cerebral discharge e.g. in response to hypotension, hypoxia

• not all epileptic seizures cause convulsions

how is epilepsy characterised?

• recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly and excessive neuronal discharge

what % epileptic dogs are there?

0.6-0.75

what are the 2 kinds of epilepsy?

• focal and generalised

what are 3 causes of epilepsy?

• idiopathic

• structural

• unknown

when does epilepsy become a full seizure?

• when it moves from being localised to affecting a large area of the brain

what’s an example of a structural cause of a seizure?

intracranial/cerebral pathology:

• vascular

• inflammatory/infectious

• traumatic

• anomalous/developmental

• neoplastic and degenerative

• diseases confirmed by diagnostic imaging

• CSF exam

• DNA testing or on PM

what are idiopathic epileptic seizures caused by?

• unknown, what idiopathic means

• may be a genetic link

• no structural cause

what are the 4 stages of a seizure

• prodrome

• aura/pre-ictus

• ictus or seizure

• post-ictus

what is status epilepticus

• SE = neurological emergency with a mortality of up to 25%

• continuous epileptic seizure activity lasting longer than 5 minutes or as 2+ seizures with incomplete recovery of consciousness interictally

• or continuous seizure activity for longer than 30 minutes

how do we treat seizures?

• caused by an imbalance of inhibitory and excitatory activity in the brain

• antiepileptic/anticonvulsive drugs restore the balance by facilitating inhibitory activity

how does seizure treatment work?

• altering intrinsic membrane potentials (predominantly Na+ channels)

• increasing inhibitory transmitter function, primarily in the GABA system

• decreasing excitatory transmitter function, primarily glutamate system

what are the main, licensed drugs used for seizure treaments?

Benzodiazepines (short term use)

Barbiturates (long term use)

Imepetoin

KBr

• primarily affect the GABA_A receptor for Cl-

what is a simplification of how the seizure treatment works?

1. membranes are polarised by active transport and passage of electrolytes

2. seizures involve uncontrolled depolarisation of nerve cells and networks

3. anticonvulsants act by altering passage of electrolytes across membranes to produce hyperpolarisation

4. hyperpolarised membranes are harder to depolarise so seizure activity stops

what are we aiming to do with giving treatment for seizures?

• control the seizures

• reduce their frequency as much as possible

what do we need to consider when giving seizure drugs and how do we determine the dosage that needs to be given?

• need to consider dosage - what will be effective? is it in the safe zone?

• give a starting dosage for 2 weeks

• ask the owner on review about any clinical signs e.g. barbiturates make pets very sleepy

• assess on whether to make the dosage higher or lower

What foraminae are highlighted here and which nerves emerge from them?

Top to bottom:

Optic canal - CN II

Orbital fissure: Opthalmic division of CN V and nerves to extrinsic muscles of the eyeball

Rostral alar foramen/round foramen - passage of the maxillary division of CN V

what is different about the orbital fissure in pigs and small ruminants?

• it’s fused with the round foramen to form the foramen orbitorotundum

name the 12 cranial nerves

1. olfactory

2. occipital

3. occulomotor

4. trochlear

5. trigeminal

6. aducens

7. facial

8. vestibulocochlear

9. glassopharyngeal

10. vagus

11. accessory

12. hypoglossal

what are the 3 parts of the trigeminal nerve

• V1 = opthalmic branch

• V2 = maxillary branch

• V3 = mandibular branch

where does the olfactory nerve exit the skull?

• cribiform plate (nerve travels down cerebrum to olfactory bulb through cribiform plate to voreronasal organ)

where does CN II leave the skull?

• optic foramen/canal

where does CN III leave the skull?

• orbital fissure

where does CN IV leave the skull?

• orbital fissure

where do the V1, V2 and V3 branches of CN V leave the skull?

V1 - orbital fissure

V2 - rostral fissure

V3 - oval foramen

where does CN VI leave the skull?

• orbital fissure

where does CN VII leave the skull

• srylomastoid foramen

• facial canal

where does CN VIII leave the skull?

• passes through internal acoutsic meatus (with CN VII) from the medulla oblongata to the vestibulocochlear organ in the temporal bone

where does CN IX leave the skull?

• jugular foramen

where does CN X leave the skull?

• jugular foramen

where does CN XI leave the skull?

• jugular foramen and foramen magnum

where does CN XII leave the skull?

• hypoglossal canal/foramen

which nerve arises from the pons?

• CN V - trigeminal

what 4 nerves emerge from the orbital fissure?

1. oculomotor

2. trochlear

3. abducens

4. V1 of trigeminal

outline whether the cranial nerves are Sensory, motor or both

CN I - S

CN II - S

CN III - M

CN IV - M

CN V - B

CN VI - M

CN VII - B

CN VIII - S

CN IX - B

CN X - B

CN XI - M
CN XII - M

what could an owner confuse a seizure with and why?

• convulsions

• vestibular disease

• stroke

• all involve being unable to stand, head tilt/eyes rapidly moving back and forth and maybe ataxia

what is the difference between intra- and extra-cranial causes of seizures?

• intra originate in the brain (structural and functional)

• Extra have causes outside of the brain

How can we subdivide intra-cranial causes of seizures?

• structural lesions (vascular, inflammatory/infectious, traumatic, congenital, neoplastic disease)

• No lesion is present that’s primary (functional or idiopathic epilepsy)

what are features of extra-cranial seizures?

Metabolic:

• multifocal neurological examination - neurological deficits to the forebrain and NMSK system

• inter-ictal signs usually present - ‘good’ and ‘bad’ days

• symmetrical neurological signs most commonly seen

Toxic seizures:

• not usually recurrent, discrete time period

• myoclonus and twitching are common features

• often accompanied with GI signs

Anoxic:

• associated cardiorespiratory signs

• associated triggers leading to increased vagal tone

what are features of intracranial seizures?

Symptomatic:

• altered mentation

• blindness

• relentless pacing/circling

• loss of learned behaviour

Idiopathic:

• onset b/w 6 months and 6 years of age

• normal inter-ictally

• recurrent seizures

• breed predisposition

what are some diseases often mistaken for seizures?

• syncope

• weakness

• movement disorders

• narcolepsy

• myokymia and neuromyotonia

• myotonia

• postural myoclonus (idiopathic head bobbing)

• vestibular episode

what are some intracranial causes of seizures?

• idiopathic epilepsy

• congenital disease e.g. hydrocephalus/storage disease

• infectious meningoencephalitis

• non-infectious meningoencephalitis

• trauma

• CNS neoplasia

• nutritional e.g. thiamine deficiency

• Vascular e.g. cerebrovascular accident e.g. infarction or haemorrhage

what are some metabolic causes of extracranial diseases?

1. Metabolic:

   • hypoglycamia

   • hypocalcaemia

   • hyoernatremia

   • hepatic encephalopathy

   • uremia

   • hyperlipoproteinemia

   • hypertensive encephalopathy

   • phlycythemia

what are some toxicity causes of extracranial causes of seizures?

• lead toxicity

• metaldehyde poisoning

• ethylene glycol poisoning

• strychnine toxicity

• choclate

• alpha-chloralose

• chlorinated hydrocarbons

• xylitol

what is an anoxic cause of extracranial seizures?

• hypoxia e.g. cardiac or respiratory insufficiency

Outline the:

a) mechanism of action

b) elimination of half-life

c) approximate time to steady state

d) whether it’s used as a first/second treatment

of Phenoarbital

1. Acts on GABA receptors which increase synaptic inhibition - is a barbiturate

2. 40-90 hours given every 12 hours

3. 7-10 hours

4. first line treatment

Outline the:

a) mechanism of action

b) elimination of half-life

c) approximate time to steady state

d) whether it’s used as a first/second treatment

of KBr

1. acts on neuronal Cl- channels, causing hyperpolarisation of neuronal membranes, raising seizure threshold

2. 24 days in dogs, 10 days in cats

3. up to 4 months in dogs, 6 weeks in cats

4. both

Outline the:

a) mechanism of action

b) elimination of half-life

c) approximate time to steady state

d) whether it’s used as a first/second treatment

Imepitoin

1. Activates receptors for GABA, increases GABA effects. Blocks some Ca2+ channels, less Ca2+ moves into the cell, preventing nerve impulses from being transmitted, thus reducing seizures

2. 1.5-2hours

3. 3 hours to reach a steady state

4. 2nd - do not use as a 1st treatment in cases of cluster seizures or status elipticus.

what are the 3 groups of cranial nerves

• special senses (CN I, II, VIII)

• Innervation of head muscles (CN III, IV, VI, XII)

• Innervation of structures originating from brachial arches (CN V, VII, IX, X, XI)

Name the nuclei of the cranial nerves

1. mesencephalon, midbrain

2. metencephalon, cerebellum and pons

3. myelencephalon (medulla oblongata)

How are the nuclei arranged?

• in uniformed locations

how do the cranial nerves egress?

• passage through foramina of the skull

• individually or in groups

Outline olfaction

• olfaction and gustation

• chemical senses

• chemical substances stimulate special sensory cells and generate an action potential

• impulse is transported via sensory afferent fibres to the brain

• these fibres run in cranial nerves

Outline the sense of smell

• olfactory organ is particularly well developed in dogs (200 more time sensitive than in humans)

• important for orientation in the environment

• olfactory mucous membrane in the nasal fundus = olfactory region

• covered in olfactory epithelium

• contains olfactory neurosensory cells

dog is macrosmatic

has a large olfactory region, 15-20 x larger than in humans

how do the olfactory nerves go from the nose to the brain?

• through the ethmoid bone

• in the nasal cavity we have scrolls of bone called turbinates which are attached to the ethmoid bone, therefore theese are called the ethmoid turbinates

what is contained in the olfactory epithleium

• cilia

• olfactory neurosensory cells

• bulbs of dendrites → dendrites → axon (olfactory fibre)

• supporting cells

• basal cells

what is unique about olfactory cells?

• continuously replaced by division of basal cells

• live only 30-60 days

• nerve cells are replaced regularly (even in adults)

what kind of cells are olfactory cells

• primary sensory cells

what is the passage of the olfactory fibres through the ethmoid bone known as?

• cribriform plate

what is the key information for olfactory nerve - CN I?

• Enters olfactory bulb

• sensory nerves

• special visceral afferent fibres

• composed of many fibres = processes of olfactory cells of olfactory epithelium (receptor cells)

• fibre bundles = olfactory filaments passes through cribriform plate

• surrounding meningeal sheets include subarachnoideal space - potential routes for infection

where is the brain region for CN I?

cerebrum

what is the funciton (and functinal component) of CN I?

smell (SVA)

what form of clinical exam can we use to detect problems with CN I?

• only owner’s observation - it’s very complex to test

what is an example of clinical signs seen after injury of CN I?

• anosmia - loss of smell

outline the key information of the CN II

• enters into the diencephalon

• sensory nerve

• special somatic afferent fibres

• brain tract b/w retina (receptor) and diencephalon (origin)

• in the optic chiasm, the fibres decussate

• passes through the optic canal

what is special about the optic nerve?

• myelinated by oligodendrocytes not schwann cells

• this makes it involved in the CNS not the PNS

what is the optic chiasm

• where the optic nerves cross over and joint together before entering the optic canal

• not all nerves decussate

• some of the left nerves go into the left forebrain, some cross over and enter the right forebrain (same on other side)

outline the pathway of conscious vision

1. eye

2. optic nerve

3. optic chiasm

4. optic nerve

5. lateral geniculate nucleus

6. occipital cortex (prosencephalon)

outline the optic pathway of the pupillary light response - mesencephalon one

1. optic nerve → optic chiasm → optic nerve → lateral geniculate nucleus

2. optic nerve → optic chiasm → optic nerve → prectal nucleus (bypasses lateral geniculate) → parasympathetic nucleus III → CN III

outline the optic pathway of the menace response

1. optic nerve → optic chiasm → optic nerve → lateral geniculate nucleus → occipital cortex → motor cortex → parasympathetic nucleus III → pontine nucleus (in cerebellar cortex) → motor nucleus 3 → CN VII → blink

what is meant by peripheral blindness - what is affected?

• absent vision without PLR

affected:

• retina

• pre chiasmal optic nerve

• post chiasmal optic nerve

what is meant by central blindness and what is affected?

• absent vison with PLR

affected:

• lateral geniculate nucleus

• occipital cortex

summarise CN II: name and number, brain region, function (functional components), clinical exam and clinical signs seen after injury

1. optic - II

2. diencephalon

3. vision (SSA)

4. menace response

5. anopsia - loss of vision

outline CN VIII

• 2 components - vestibular nerve (balance) and cochlear nerve (hearing)

• sensory nerve

• SSA

• medulla oblongata

• passes through internal acoustic meatus into petrosal bone

• special sense of balance and hearing

what is the topographical course for VIII

• enters petrosal bone through internal acoustic meatus with VII

summarise CN VIII: name and number, brain region, function (functional components), clinical exam and clinical signs seen after injury

1. vestibulocochlear nerve - VIII

2. medulla

3. balance and hearing (SSA)

4. hearing - horizontal and vertical eye movement

5. defness, head tilt (constant), nystagmus

outline CN III

• ventral midbrain

• motor nerve

• GSE - general somatic efferent

• 6 muscles

• 4 go to the eyeball and to the levatory of upper eyelid: dorsal rectus, medial rectus, ventral rectus, ventral oblique

outline CN III

• visceral efferent (PS)

• pre-ganglionic from PS nucleus - midbrain

• passes through orbital fissure

• synapses in ciliary ganglion

• M. spincter pupillae and M. ciliaris

what is anisocoria and what kind of issue is it?

• a clinical representation of different sized pupils

• autonomic issue

How can we identify aniscoria and what 2 kinds are there

• imbalance between sympathetic and parasympathetic supply

• sympathetic dilates - absence leads to a small pupil that won’t dilate in darkness (horner’s syndrome)

• parasympathetic constricts - absence leads to dilated non-responsive pupil

How is the iris controlled?

• parasympathetic - craniosacral → constriction

• sympathetic - thoracolumbar → dilation

name 4 symptoms of Horner’s syndrome

1. meiosis

2. enophthalmus

3. ptosis

4. 3rd eyelid potrusion