Module 8 Neurosciences Flashcards
Glial cells - Astrocytes
Metabolic support and regulation of blood-brain barrier (BBB)
Glial cells - Microglia
Function as phagocytes
Presence of microglia can indicate an infection
Glial cells - Oligodendrocytes
CNS myelinating glia
Schwann cells
PNS myelinating glia
Sutures of the skull
strong immovable fibrous joints:
Sagittal
Coronal
Lambdoid
Pterion (middle meningeal artery is deep to this)
Fontanelles
large gaps between the flat bones in fetus and newborn
Most close during first year of life
Corpus callosum
Formed by myelinated axons connecting the two cerebral hemispheres
Divided into rostrum, genu, body and splenium (front to back)
Cerebral white matter tracts (3)
Association fibres: connect cortical areas within hemisphere (short/long association fibres)
Named longitudinal bands (superior longitudinal fasciculus)
Commissural fibres: connect cortical areas of the two hemispheres
Corpus callosum/anterior commissure
Projection fibres: connections between cortex and subcortical structures (thalamus, basal ganglia)
Internal capsule (thalamocortical fibres)
Frontal lobe function
Primary motor cortex: Controls the execution of skilled voluntary movements
Pre-motor and supplementary motor areas: Planning of movement
Frontal eye fields: Turning of eyes in parallel at the same time
Brocca’s area: Formulation of the motor components of speech. Damage can lead to difficulty with speech production
Prefrontal cortex (pink area), plays important roles in the processing of intellectual and emotional events…
Parietal lobe function
The parietal lobe contains the postcentral gyrus, which is the primary receiving area for somatosensory information from the periphery – somatosensory information is related to bodily sensations such as pressure, pain, temperature, touch…
Temporal lobe function
Primary auditory cortex
auditory association area - Wernickes area
occipital lobe function
Visual cortex
Association areas
Anterior temporal AA: Storage of previous sensory experiences. Stimulation may cause individual to recall objects seen or music heard in past
Posterior parietal AA: Visual information from occipital cortex and somatosensory information from parietal cortex is integrated into concepts of size, form and texture = stereogenesis. An appreciation of body image also assembled here e.g. a body scheme that can be appreciated consciously – so that we know at all times where our body parts are located in relation to the environment. Critical for producing appropriate body movements.
Prefrontal AA: Integration centre for multiple somatosensory inputs. Has links with all other sensory areas, limbic system and thalamus. Top-down (executive) processing of sensory and motor information.
The eyelids (palpebrae)
Palpebral fissure: space between theeyelids when they are open
The layers of theeyelids, from anterior to posterior consist of:
Skin: innervated by trigeminal nerve (CN V)
Subcutaneous tissue
Voluntary muscle: orbicularis oculi (CN VII)
The orbital septum: separates superficial eyelid structures from the periorbital fat
The tarsus: dense connective tissue, gives the eyelid its shape
The conjunctiva: mucous membrane which extends onto the eyeball but stops at the cornea
The upper and lowereyelids are similar in structure except for two additional muscles in the uppereyelid:
Levator palpebrae superioris: voluntarily elevates upper eyelid, innervated by CN III
Superior tarsal muscle: involuntarily elevates upper eyelid, innervated by sympathetic nervous system
Lacrimal gland and lacrimal apparatus
Lacrimal fluid (tear) production is an autonomic secretomotor function
Lacrimal gland sits in the superolateral corner of the orbit
Innervated by parasympathetic nerve fibres from brainstem
These nerve fibres travel first in branches of the facial nerve (CN VII) and then trigeminal nerve (CN V)
Lacrimal apparatus: lacrimal gland and series of ducts draining tear fluid away from the eye
Lacrimal puncta associated with the lacrimal caruncle
Lacrimal canaliculi
Lacrimal sac
Nasolacrimal duct -> inferior meatus of nasal cavity
Anatomy of the eyeball
Three layers for most of eyeball:
Retina (photoreceptors)
Choroid (very vascular)
Sclera (protective covering)
Cornea: clear protective membrane anterior to iris, pupil and lens.
Avascular – nutrients from tear fluid
Three spaces inside eyeball: anterior, posterior and vitreous chambers
Aqueous humour (similar to blood plasma) secreted by ciliary body. Fills the anterior and posterior chambers
Vitreous humour (jelly) in vitreous chamber
Scleral venous sinus = drainage site for aqueous humour into venous circulation
Ora serrata = junction between retina and ciliary body
The posterior retina as seen through an ophthalmoscope - key structures
Optic disc: exit point for the optic nerve
Central retinal artery: supplies the retina
From the ophthalmic artery (internal carotid artery branch)
Macula lutea: contains a high concentration of cone cells
Fovea: densest concentration of cone cells at centre of macula – high acuity vision
Cones vs rods
Cones are responsible for high acuity, daylight and colour vision whereas rods are specialised to detect dim light and night vision (but not colour).
Retina cells - layers
The retina contains a number of different cell types and layers:
Pigmented epithelium: light absorbing cells next to the choroid
Neural retina: photoreceptors (rods and cones) and glial cells
Bipolar cells (interneurones)
Ganglion cells: axons form the optic nerve
Light has to physically travel through the ganglion cell and bipolar cell layers to reach the photoreceptors
Fovea versus periphery of retina cell layout
1 cone/1 bipolar cell to 1 ganglion cell at fovea
More visual detail/clarity
Multiple rods/cones/bipolar cells to 1 ganglion cell at periphery of retina
Less detail/clarity
Forming an image on the retina
Light is refracted by the cornea and lens
Passes through the aqueous and vitreous humours
Image is projected onto the retina upside down (inverted) and reversed.
The optic nerve exits the orbit at the optic canal
Visual cortex of occipital lobe processes the image and corrects it, combining information from both eyes to form a single image (binocular vision)
Optic chiasm
The left and right optic nerves (CN II) converge in the midline at the optic chiasm (crossing)
The optic chiasm lies just superior to the pituitary gland and midbrain
Visual fields and optic nerve route
Nasal (medial) retina perceives the temporal visual field (outer half)
Nerve fibres decussate at optic chiasm to the other side
Temporal retina perceives the nasal visual field (inner half)
Nerve fibres do not decussate at optic chiasm
Synapse at Lateral geniculate nucleus of thalamus
Projections to visual cortex via the optic radiations
Optic radiations (2)
Meyer’s loop: pathway from inferior retina carrying superior visual field information from opposite side (contralateral superior quadrant)
Nerve fibres pass through temporal lobe to lower bank of calcarine sulcus
Baum’s loop: pathway from superior retina carrying inferior visual field information from opposite side (contralateral inferior quadrant)
Nerve fibres pass through parietal lobe to upper bank of calcarine sulcus
Right monocular vision loss (anopia) caused by…
lesion of right optic nerve e.g. due to optic neuritis would cause
Bitemporal hemianopia caused by….
optic chiasm lesion e.g. pituitary adenoma
Complete left homonymous hemianopia caused by…
complete lesion of right optic tract/radiation/primary visual cortex
Left inferior quadrantanopia caused by…
partial lesion of optic tract/radiation i.e. Baum’s loop
Corneal reflex
Afferent limb: ophthalmic division of the trigeminal nerve (CN Va) in response to corneal irritation – cornea is extremely sensitive
Interneurone
Efferent limb: facial nerve (CN VII)
Orbicularis oculi muscle contracts to close the eyelids
Iris and pupil constriction and dilation
The iris has two layers of smooth muscle:
Sphincter (constrictor) pupillae: constricts the pupil, Parasympathetic neurons cause contraction of the pupil – oculomotor nerve (CN III)
Dilator pupillae: dilates the pupil, Sympathetic neurons cause dilation of the pupil
Pre-ganglionic neurons from T1 spinal cord segment
Post-ganglionic neurons from the superior cervical ganglion travel along internal carotid artery and branches to reach iris
Pupillary light reflex
Afferent (sensory) neurons in the optic nerve transmit the signals to the pretectal nucleus of the midbrain
Neurons from the pretectal area transmit signals to both Edinger-Westphal nuclei of the midbrain
Pre-ganglionic parasympathetic fibres travel in oculomotor nerves (CN III) to ciliary ganglia
Post-ganglionic parasympathetic neurons from the ciliary ganglia run to sphincter pupillae
Both pupils constrict
Ciliary muscle (body)
Ring-shaped layer of muscle attached to the lens via suspensory ligaments (zonular fibres)
Controlled by parasympathetic nerve fibres from Edinger-Westphal nucleus (CN III)
Ciliary muscle contracts via pns: lens relaxes and becomes more convex in shape
Near vision
Ciliary muscle relaxes: lens stretches and becomes less convex
Distant vision
Focusing light on the retina distnt vs naer
Distant objects: Light rays are hitting the eye in a parallel fashion and don’t need to be refracted much
Close objects: Light rays diverge as they hit the eye and need to be refracted more
Accommodation reflex
Afferent limb: visual pathway including the visual cortex
Visual cortex determines an image is out of focus
signal to Edinger-Westphal parasympathetic nucleus
Efferent limb:
Edinger-Westphal parasympathetic nucleus in midbrain
Pre-ganglionic parasympathetics travel in oculomotor (CN III) to ciliary ganglion
Post-ganglionics travel to iris (constrict pupil) and ciliary muscle (contract muscle, lens becomes convex)
Oculomotor nucleus in midbrain also causes medial rectus muscles to contract – eyes converge towards nose
Problems with focusing images on to retina
Myopia: short-sighted
Eye is abnormally long and focuses distant objects in front of the retina
Corrected using a concave external lens
Hyperopia: long-sighted
Eye is abnormally short and focuses near objects behind the retina
Corrected using a convex external lens
Astigmatism: abnormal curvature of lens or cornea, cannot focus light on a small spot
Presbyopia: loss of accommodation with age – difficulty reading
Extraocular muscles (7) and innervation
Levator palpebrae superioris - CNIII Oculomotor
Superior rectus - CNIII Oculomotor
Inferior rectus - CNIII Oculomotor
Medial rectus - CNIII Oculomotor
Lateral rectus - CNVI Abducens
Superior oblique - CNIV Trochlear
Inferior oblique - CNiii Oculomotor
Course of CN III, IV and VI
All three enter travel from the brainstem through the cavernous sinus and enter the orbit through the superior orbital fissure
The somatic motor nuclei for oculomotor and trochlear (CN IV) nerves are both in the midbrain, while the abducens nerve (CN VI) motor nuclei are in the pons.
The trochlear nerve (CN IV) is unusual – emerges from the posterior aspect of the midbrain and decussates
Actions of extraocular muscles
Superior rectus: primary action is elevation, secondary actions include adduction and medial rotation of the eyeball.
Inferior rectus: primary action is depression, secondary actions include adduction and lateral rotation of the eyeball.
Medial rectus: adduction of the eyeball.
Lateral rectus: abduction of the eyeball.
Superior oblique: depresses, abducts and medially rotates the eyeball.
Inferior oblique: elevates, abducts and laterally rotates the eyeball.
Testing extraocular muscle function e.g. right eye
Right eye
Look right - Lateral rectus
Then up - Superior rectal
Then down - inferior rectus
Look left - medial rectus
Then up - Inferior oblique
Then down - superior oblique
ACh at synapses
SYNTHESIS by choline acetyltransferase
acetyl CoA and choline -> acetylcholine
UPTAKE into vesicles via vesicular transporter
RELEASE: action potential reaches terminal activates calcium channels calcium influx fusion of vesicles and release of ACh
PRE-SYNAPTIC RECEPTORS: Some may be activated by excess ACh. Others may respond to other neurotransmitters. In either case the result is inhibition of further ACh release (or occasionally increased ACh release)
BREAKDOWN/METABOLISM: ACh is broken down into acetate and choline by acetylcholinesterase. This mechanism prevents further receptor activation.
ACTION AT RECEPTOR:
Neurons and muscle: nicotinic AChR = ligand-gated ion channel, passes Na+ and K+ -> depolarisation = excitatory response.
Muscarinic AChR = G protein-coupled receptor, activation of Gq -> calcium signalling excitatory
Noradrenaline at synapse
SYNTHESIS:
1: tyrosine via tyrosine hydroxylase DOPA
2: DOPA via DOPA decarboxylase dopamine
3: UPTAKE into vesicles via vesicular transporter
4: Then dopamine via dopamine-β-hydrolase noradrenaline
PRE-SYNAPTIC RECEPTORS: Some may be activated by excess NA. Others may respond to other neurotransmitters. In either case the result is inhibition of further NA release (or occasionally increased NA release)
α2 adrenergic receptors are particularly important for autoregulation – feedback inhibition.
BREAKDOWN/METABOLISM: can occur inside presynaptic cell, or postsynaptic cell or extracellularly by:
MAO = monoamine oxidase (inhibition of MAO leads higher concentration of monoamines in the cytoplasm)
COMT = catechol-o-methyltransferase
NON-NEURONAL UPTAKE:
¼ taken up into non-neuronal cells
EMT (Extraneuronal monoamine transport)
lower affinity and higher capacity
Also transports dopamine, serotonin and histamine.
NEURONAL UPTAKE:
¾ of released noradrenaline taken up to presynaptic terminal,
NET (the norepinephrine transporter)
high affinity and low capacity.
Inhibited by cocaine, amphetamine, tricyclic antidepressant drugs.
Glutamate at synapse
SYNTHESIS
In neurons:
Glutamine -> via glutaminase -> glutamate
UPTAKE: Glu is taken up by EAAT (Excitatory Amino Acid Transporter) into neurons and astrocytes.
UPTAKE:
In astrocytes, Glu via glutamine synthase Gln which is transported out of the astrocyte and into the neuron by GlnT (glutamine transporter).
NMDA receptors – role in synaptic plasticity
Mechanisms of Long-Term Potentiation (LTP)
A: Infrequent synaptic activity
-> just AMPA receptors activated.
B: After conditioning train of stimuli
->mGluR activated, NMDA channels unblocked
->↑Ca signalling
=> ultimately results in changes in gene expression
NMDA receptors – role in excitotoxicity
Excessive activation of NMDA, AMPA and mGluR receptors
=>Large influx of Ca2+
->↑glutamate release
->Activation of proteases and lipases
->Activation of NO synthase ROS
->Arachidonic acid release free radicals and inhibition of glutamate uptake
Excitotoxic cell death in stroke and neurodegenerative diseases
GABA at synapse
SYNTHESIS
In neurons:
Glutamate -> via glutamic acid decarboxylase GABA
UPTAKE:
GABA is taken up by GAT (GABA Transporter) into neurons (GAT1) and astrocytes (GAT3).
GAT inhibited by tiagabine (epilepsy)
METABOLISM/BREAKDOWN:
GABA is broken down by GABA transaminase in astrocytes
Inhibited by vigabatrin (epilepsy)
Intrinsic vs extrinsic brain tumours
EXTRINSIC
Primary tumours arise from bone, meninges (dura), nerve.
May be metastatic from malignancy elsewhere
INTRINSIC
Primary tumours arise from cells normally comprising the brain or spinal cord
Type and location differs in children vs adult brain tumours
Adults
Supratentorial location
Glioblastoma (grade 4 astrocytoma), meningioma, metastases
Development of glioblastoma from
low grade astrocytoma
Children
Infratentorial
Pilocytic astrocytoma
Medulloblastoma
Clinical Presentation low grade vs high grade brain tumours
Low grade tumours – brain can accommodate growth and slow pressure rise, so more likely to present with seizures or focal neurology
High grade tumours – brain struggles with rapid pressure rise; more likely to present with pressure symptoms
Symptoms and Signs of raised Intra-cranial Pressure (ICP)
Headache (especially in mornings)
Balance / co-ordination difficulties
Drowsiness / reduced Glasgow coma scale
Vomiting / nausea
Visual loss / papilloedema (chronic rise in ICP)
Pupils – loss of reaction & dilated
Cushing’s triad – bradycardia, hypertension, decreased respiration
Opisthotonus (extensor spasms, back arching)
Cognitive changes
Brain tumour nomenclature & WHO grading
Grade 1: low grade – curative with surgery
Grade 2: astrocytoma (low grade)
Grade 3: anaplastic astrocytoma
Grade 4: high grade astrocytoma (glioblastoma) – death with one year of diagnosis
Most likely mets to the brain
Most likely to come from breast, lung, bone, melanoma or renal. Others can spread to the brain but rarely
Histological grading of Astrocytomas and clinical presentation
1 Pilocytic Astrocytoma
2 Diffuse Astrocytoma - May be long history, seizures, relatively well, younger age group
3 Anaplastic Astrocytoma - May be more unwell, shorter history, slightly older.
Some will have progressed from known Grade 2 tumour.
4 Glioblastoma (GBM) - Usually short history (<3 months) especially of headache and personality change
Glioblastoma- Histology
Pseudo-pallisading necrosis (elongated nuclei stacked in rows; in response to hypoxia & necrosis)
Microvascular proliferation
Meningioma
Usually benign slow growing extrinsic tumour, derived from dura or arachnoidal cells , 90% supratentorial
Epilepsy – medical definition
A disorder of the brain characterised by an enduring / recurrent predisposition to generate seizures.
Seizure – medical definition
An abnormal, paroxysmal cerebral neuronal discharge that results in alteration of sensation, motor function, behaviour or consciousness
Classification of major seizure types - Primary generalised
loss of consciousness from start, no focal or local onset, symmetrical bilaterally, synchronous (involving both cerebral hemispheres at onset); 40% of all seizures. Subtypes:
A) GTC (grand-mal) – evolves from tonic to clonic activity. This is a discrete type and does not include partial seizures that generalise secondarily.
B) Clonic – fairly symmetric, bilateral synchronous, semi-rhythmic jerking of UL and LL’s, usually EF and KE.
C) Tonic– sudden sustained increased tone with guttural cry or grunt as air forced through adducted vocal cords.
D) Atonic – (‘drop attacks’) – sudden brief loss of tone that may cause falls.
D) Myoclonic – shock-like whole body jerking (generalised EEG discharges).
E) Absence – (‘petit mal’) – impairment of conscious level with mild or no motor involvement. Typical and atypical subtypes – atypical = more heterogenous / more variable EEG pattern than typical absence, seizures may last longer.
Classification of major seizure types - partial
implies only one hemisphere involved at onset. About 57% of all seizures. New onset partial seizure represents structural lesion until proven otherwise.
A) Simple Partial (no impairment of consciousness), may be mainly motor, sensory (somatic/special), autonomic, higher function disturbance.
B) Complex Partial: includes above plus any alteration of conscious level, from overtly impaired conscious level to automatisms such as lip smacking, chewing, picking, with autonomic aura such as ‘epigastric rising’ sensation.
Classification of major seizure types - onset and type description
B1): Onset was simple partial, became complex partial – i.e., simple partial that evolved to include some alteration of consciousness, and may have an aura a) without automatisms, b) with automatisms.
B2): Purely complex at onset, i.e., alteration of consciousness at onset a) without automatisms (impaired conscious level only) or b) with automatisms.
C): Partial seizures ‘with secondary generalisation’:
1) Simple partial evolving to generalised
2) Complex partial evolving to generalised
3) Simple partial to complex partial to generalised (i.e., difficult to classify, 3% of all seizures).
Signs of a seizure having occurred
Lateral tongue laceration
Urinary incontinence
Post-ictal paralysis aka ‘Todd’s Paralysis / Paresis. Phenomenon of partial or total paralysis, typically hemiparesis; more common in patients with structural lesion as source of seizure. Resolves over hours; due to depletion of neurones in wake of extensive electrical discharges of a seizure; aphasia and hemianopia also may occur.
Prolactin levels increase after ES, not NES, may be useful adjunct in equivocal cases (72% accurate).
Signs of pseudo-seizure (non-epileptic)
Arching back – 90% specific for NES.
Weeping, forced eye closure, bilateral shaking with persevered awareness, clonic arm or leg movements that are out of phase, pelvic thrust, presentation altered by distraction – NES features.
Prolactin levels increase after ES, not NES, may be useful adjunct in equivocal cases (72% accurate).
Status epilepticus
Intractable episode of seizure activity.
Seizures lasting > 5mins,
Or: persistent seizure after 1st and 2nd line AED’s administered.
Mean duration 1.5 hours, mortality 2%.
Irreversible changes from repetitive electrical discharges appear in neurons as early as 20 mins, cell death may occur from 60 mins onwards.
Work-up: airway, oxygen, IV access, IV fluids, bloods (electrolytes), BP and ECG monitoring, EEG, LP.
First line drugs: benzodiazepine, IV lorazepam, diazepam or IM midazolam.
Second line: load with levetiracetam, phenytoin or fosphenytoin.
Avoid narcotics and phenothiazines.
If no response, discuss with anaesthetics and ITU, intubate, ventilate and fully sedate.
What is the most common cause of intractable TLE?
Mesial temporal sclerosis
Hippocampal
amygdala
Very general overview of blood supply to the brain areas
Forebrain supplied mostly by branches of internal carotid artery (ICA)
Brainstem & Cerebellum supplied by branches of vertebral arteries
Arteries of the posterior circulation brain
Posterior cerebral
Superior cerebellar
Pontine
Labyrinthine
Anterior inferior cerebellar
Basilar artery
Posterior inferior cerebellar
Posterior spinal
Anterior spinal
Vertebral arteries <- Subclavian
Arteries of the anterior circulation S->i Brain
Anterior cerebral
Anterior communicating artery
Middle cerebral
Lenticulostriate
Anterior choroidal
Posterior communicating
Opthalmic
Internal carotid
Arteries of the brain (S->I)
Anterior cerebral
Anterior communicating artery
Middle cerebral
Lenticulostriate
Anterior choroidal
Posterior communicating
Opthalmic
Internal carotid
Posterior cerebral
Superior cerebellar
Pontine
Labyrinthine
Anterior inferior cerebellar
Basilar artery
Posterior inferior cerebellar
Posterior spinal
Anterior spinal
Vertebral arteries <- Subclavian
Ophthalmic Artery
Supplies structures of the eye and the orbit
Central retinal artery supplies retina
Central retinal artery occlusion most common type of eye stroke.
Medical emergency
Anterior Choroidal Artery SUPPLIES and effect of a stroke
Supplies:
Parts of the visual system: optic tract/radiations, lateral geniculate body of the thalamus
Choroid plexus in lateral ventricles, parts of the putamen, internal capsule and hippocampus
Strokes:
Variety of signs and symptoms
Motor and visual
Anterior Cerebral Artery branches supply
Run in the great longitudinal fissure and connect with each other via the anterior communicating artery.
Continue as pericallosal arteries to supply corpus callosum.
Has cortical and deep (central/penetrating) branches.
Cortical branches supply:
Medial aspect of the frontal and parietal lobes (green area on image)
Deep branches (medial striate artery) supply:
Anterior portion internal capsule
Head of caudate nucleus (basal ganglia)
Occlusion of Anterior Cerebral Artery ->
Contralateral hemisensory loss which may predominantly affect the lower limb and trunk (due to necrosis of the medial aspect of the primary somatosensory cortex)
Contralateral hemiparesis which may predominantly affect the lower limb and trunk (due to necrosis of the medial aspect of the primary motor cortex)
Cognitive and behavioural changes (frontal lobe involvement)
Middle Cerebral Arteries branches supply
Main continuation of the ICAs and run in the lateral fissure.
Cortical and deep (central/penetrating) branches
Cortical branches supply:
Lateral aspect of the frontal, parietal and temporal lobes:
the lateral parts of the motor and somatosensory cortices
language areas (Broca’s and Wernicke’s) – in dominant hemisphere (usually left hemisphere)
Deep branches (lenticulostriate arteries) supply:
Part of the basal ganglia
Genu and limbs of internal capsule
Occlusion of Middle Cerebral Artery
most commonly affected
Complete unilateral occlusion is a devastating lesion with a high mortality and severe long-term disability
Contralateral hemisensory loss which may predominantly affect the upper limb and face (due to necrosis of the lateral aspect of the primary somatosensory cortex)
Contralateral hemiparesis which may predominantly affect the upper limb and face (due to necrosis of the lateral aspect of the primary motor cortex)
Aphasia (if the dominant, usually left, cerebral hemisphere affected)
What anatomical feature is a risk factor for ischemic cerebral infarction in patients with internal carotid artery occlusion.
A small (<1 mm in diameter) or absent ipsilateral posterior communicating artery is a risk factor for ischemic cerebral infarction in patients with internal carotid artery occlusion.
Posterior Inferior Cerebellar Artery
Originate just inferior to the basilar artery
Supply:
Lateral medulla
Posterior inferior cerebellum
Anterior inferior cerebellum
Lateral medullary (Wallenberg) syndrome
Most common syndrome of posterior circulation strokes
Following acute ischaemic infarct of the lateral medulla, caused by occlusion of:
PICA
Intracranial portion of vertebral arteries
Symptoms:
Vestibulo-cerebellar: vertigo, falling towards side of lesion, nystagmus
Autonomic dysfunction:Horner syndrome
Sensory symptoms: loss of pain and temperature sensation over the contralateral side of body
Motor symptoms: ipsilateral bulbar muscle weakness
Basilar Artery
Formed by the vertebral arteries at the pontomedullary junction
Travels in the anterior pons
The main branches of the basilar artery are:
Anterior inferior cerebellar arteries (AICA)
Cerebellum
Labyrinthine artery
Inner ear
Pontine arteries
Pons
Superior cerebellar arteries (SCA)
Cerebellum
Bifurcates to give off Posterior Cerebral Arteries
Occlusion of the Basilar Artery
Most cases are fatal
Neuro-interventional emergency
Acute infarcts in allanatomical areas supplied by the branches of the basilar artery:
Brainstem (Midbrain; pons)
Cerebellar hemispheres
Both occipital lobes
PICA, AICA, SCA & Cerebellar Strokes signs
Occlusion of the PICA:
Headache, nausea and vomiting, vertigo, horizontal ipsilateral nystagmus, limb and gait ataxia.
Most frequent (?)
Occlusion of the SCA:
Gait ataxia, dysarthria, limb dysmetria, ipsilateral lateropulsion
As frequent as PICA occlusions
Occlusion of the AICA:
Vertigo, ataxia, tinnitus, hearing loss, ipsilateral facial paralysis.
What can differentiate AICA strokes from PICA and SCA strokes
Presentations can often be atypical or overlap, in particular for haemorrhagic infarcts but auditory involvement and peripheral facial palsy differentiate AICA from SCA and PICA strokes.
Posterior Cerebral Arteries
Supply the midbrain (basilar artery contributes)
Cortical and deep (central/penetrating) branches
Cortical branches supply:
Occipital lobe, inferior portion temporal lobes
Splenium of corpus callosum
Deep branches supply:
Thalamus, subthalamus, hippocampus
Choroidal plexus (via posterior choroidal artery)
Occlusion of Posterior Cerebral Artery
Occlusion to midbrain branches:
Extraocular muscles paresis or palsy (damage to CN III and/or its nuclei)
Occlusion to occipital lobe branches:
Contralateral homonymous hemianopia due to loss of blood supply to the visual cortex and optic pathway on one side
Occlusion to diencephalon branches:
Thalamic syndrome: severe pain, contralateral hemisensory loss, and flaccid hemiparesis
Occlusion to hippocampal branches:
Interferes with declarative memory
Arteries of the Spinal Cord
Blood supply from the vertebral arteries:
Anterior spinal Artery
Posterior Spinal Arteries
Reinforced by radicular branches of:
Ascending cervical arteries
Intercostal and subcostal arteries
Lumbar Arteries
The greater anterior radiculomedullary artery (of Adamkiewicz)
The anterior spinal artery supplies the anterior 2/3rds of the spinal cord
The posterior spinal artery supplies the posterior 1/3rd of the spinal cord
The greater anterior radiculomedullary artery (of Adamkiewicz)
Supplementary supply (in some ONLY supply) to lower spinal cord (T8-L3)
Present in ~85% of individuals
Usually unpaired, left dominance
In levels T8 -L3 back surgery, surgeons should take great care to avoid which anatomical structure?
surgery in this area of the lower back should avoid compromise of The greater anterior radiculomedullary artery (of Adamkiewicz) as it is a major source of blood to lower thoracic and upper lumbar cord levels.
Occlusion of the Posterior Spinal Arteries
Posterior spinal arteries supplies posterior 1/3 spinal cord
Dorsal column-medial lemniscus pathway
Fine, discriminative touch
Vibration
Proprioception
Occlusions of PSpA:
Usually bilateral
Loss of proprioception (joint position) vibration and fine touch below level of lesion
Ataxia (due to loss of proprioception)
When unilateral: loss is ipsilateral (aka same side of the occlusion)
Occlusion of the Anterior Spinal Artery
Anterior spinal artery supplies anterior 2/3 spinal cord
Ascending and descending pathways
Spinothalamic tract: pain and temperature
Occlusions of ASpA:
Bilateral paraplegia or tetraplegia
Bilateral loss of pain and temperature sensation
The meninges
Dura mater: thickest membrane, protects the CNS and attaches to skull and vertebrae
Periosteal/endosteal layer (outer)
Meningeal layer (inner)
Arachnoid mater: deep to the dura mater, space between upper two membranes is called subdural space. Does not enter sulci. Deep to this is cerebrospinal fluid (CSF)
Subarachnoid space
Pia mater: internal layer, lies on the surface of the brain and spinal cord. Enters sulci.
Innervation of the meninges
Only dura mater: no sensory innervation for arachnoid and pia mater
Dura innervated mainly by branches of the three divisions of the trigeminal nerve (CNV) as well as C2 and C3 spinal nerves
Common source of some forms of headache e.g. due to dehydration
Describe the fate of each meningeal layer as spinal nerves leave the spinal cord
Dura mater blends with the epineurium layer of the spinal nerves
The arachnoid mater and pia mater merge with the perineurium of the spinal nerve
What connects the spinal cord to the surrounding dura
Denticulate ligaments (pia mater) firmly attach spinal cord to surrounding dura
The ventricular system
Cerebrospinal fluid (CSF) produced by choroid plexus
Ventricular system in the brain composed of:
Two lateral ventricles
Interventricular foramen
Third ventricle
Cerebral aqueduct
Fourth ventricle
Median aperture and lateral apertures
CSF circulates around brain and spinal cord in the subarachnoid space
Arachnoid villi/granulations allow CSF to drain into dural venous sinuses
Dural venous sinuses
Venous sinuses are located between periosteal and meningeal layers of dura
Superior sagittal sinus +
Inferior sagitall sinus and Great cerebral vein -> straight sinus
=> Confluence of sinuses -> transverse -> sigmoid -> internal jug.
Dural reflections
Falx cerebri: separates the two cerebral hemispheres
Tentorium cerebelli: separates the cerebellum from the cerebrum
Diaphragma sellae: separates the pituitary gland from the cerebrum
Cavernous sinus
Laterally sup -> inf:
Oculomotor
Trochlear
Ophthalmic branch of CNV
Maxillary branch of CNV
Medial to lateral
Internal Carotid
Abducens nerve
The scalp anaomty
S skin
C connective tissue (dense)
A aponeurotic layer (epicranial aponeurosis)
L loose connective tissue
P pericranium (periosteum of skull)
Emissary veins
Veins from the scalp that travel through the skull to drain into the dural venous sinuses
Form anastomoses with diploic veins running through the diploe of the skull as well as the intracranial cerebral veins
Potential route of infection resulting from scalp lacerations
Epidural space
Potential space in the cranium: fills with fluid only in pathological conditions
Actual space in the vertebral canal: it contains venous blood vessel plexuses
Subdural space
Potential space: fills with fluid only in pathological conditions
Subarachnoid
An actual space which is filled with cerebrospinal fluid
There are 4 types of intracranial haemorrhage
Epidural/extradural - blood has collected between the inner surface of the skull and the outer (periosteal) layer of the dura. These haemorrhages are usually associated with a history of head trauma and skull fracture.
The source of bleeding is usually arterial, most commonly from a torn middle meningeal artery.
Subdural (commonly involving cerebral veins draining into superior sagittal venous sinus)
Subarachnoid haemorrhage (commonly from a ruptured cerebral artery)
Intracerebral
Structure of the blood brain barrier
Tight junctions/no fenestrae,
presence of thick basal lamina basement membrane,
presence of astrocyte endfeet.
List two areas of the brain that do not have a BBB so that they can allow movement of hormones into the circulation.
Posterior pituitary and median eminence of hypothalamus.
Name two types of molecules that can diffuse passively from the blood into the brain.
Gases
Lipophilic small molecules
Impact of the BBB on drug delivery to the brain with examples
Small, uncharged and lipid-soluble molecules cross readily
E.g. ethanol, caffeine, nicotine, heroin, and methadone
Central capillaries express enzymes that degrade certain chemicals
E.g. peptidases, acid hydrolases, monoamine oxidase
-> break down enkephalins, noradrenaline, dopamine
Transporter proteins used for amino acids, glucose etc.
Solute carrier superfamily (SLC) – don’t directly use ATP or couple to electron transport facilitated diffusion
E.g. transporters for glutamate, glucose, nucleosides, ions, exchangers
ATP-binding cassette transporters (ABC) active transport
E.g. P-glycoproteins, multi-drug resistance proteins (MDRs) – have broad specificity
Some drugs use these transporters to get in
E.g. System L (heterodimer of SLC7A8 and SLC3A2)
Transports:
L-DOPA (Parkinson’s disease)
Baclofen (for spasticity)
Gabapentin (for chronic pain and epilepsy)
Some drugs are extruded from the brain by transporters – these are efflux pumps
members of ABC (ATP-binding cassette) transporter superfamily e.g. P-glycoprotein, Multi Drug Resistant Proteins, Breast Cancer Resistance Protein
clinical consequences = minimal effectiveness of some drugs in some patients e.g.
HIV drugs in AIDS dementia
anti-bacterials in CNS infections
anticonvulsants in epilepsy
chemotherapy on brain tumours
Relationship between disease & the BBB: Inflammation
nflammation can drastically increase access of drugs to the brain
Bacterial protein lipopolysaccharide can increase permeability of BBB
Ways to get drugs across the BBB
Give very high doses systemically
Use of prodrugs e.g. levodopa
Invasive drug delivery
intracavity implants e.g. carmustine implants (Gliadel®) for high-grade malignant glioma
administration directly into CNS by intrathecal or intracerebroventricular injection using implanted reservoirs or pumps
disruption of BBB e.g. with mannitol, ultrasound
Nanoparticulate delivery systems
Neural crest cells give rise to cells that form most of the …. and the ….
in 4 areas
Neural crest cells give rise to cells that form most of the peripheral nervous system and the autonomic nervous system
Cranial: exclusive to the head and neck, becomes a wide variety of structures
Enter the pharyngeal arches to form facial bones
Cardiac
Vagal/sacral (opposite ends of neural tube)
Trunk (can’t become bone or cartilage)
Skull development
Viscerocranium (blue)
Formed by neural crest cells
Frontal
Sphenoid
Ethmoid
Zygomatic
Maxilla
Mandible (and hyoid)
Squamous part of temporal bone
Neurocranium (red)
Formed by paraxial mesoderm (somites)
Petrous part of temporal bone
Parietal
Occipital
Neural crest derivatives (6)
Viscerocranium
Peripheral nervous system:
Sensory neurons (primary/1st order afferents) and dorsal root ganglia
Cranial nerve sensory ganglia (CNs V, VII, IX, X)
Schwann cells (myelin)
Autonomic nervous system:
Sympathetic chain and pre-aortic ganglia
Postganglionic/postsynaptic autonomic neurons
Parasympathetic (enteric) ganglia of the GI tract
Melanocytes of skin and hair follicles (Module 1)
Adrenal medulla chromaffin cells (Module 6)
Conotruncal ridges/septum and endocardial cushions of the developing heart (Module 3)
Development of the spinal cord
Ependymal/neuroepithelial layer around the future central canal: CNS stem cells
Neuroblasts which form motor neurons and interneurons
Glioblasts which form glial cells e.g. astrocytes
Neuroblasts start to form the mantle layer (gray matter)
Then, the mantle layer of the developing spinal cord divides into:
A dorsal alar plate (sensory): forms the dorsal horn
Receives endings of the sensory afferent neurons (formed by neural crest cells)
Alar plate neuroblasts become interneurons
A ventral basal plate (motor): forms the ventral horn
Contains cell bodies of developing motor neurons
Also forms the intermediate/lateral horn of the sympathetic nervous system – preganglionic neurons
Alar and basal plates grow towards each other to form the H-shaped gray matter of the spinal cord
primary brain vesicles
Prosencephalon: forebrain
Mesencephalon: midbrain
Rhombencephalon: hindbrain
Primary brain vesicles dilate further to become secondary brain vesicles
Prosencephalon (forebrain) becomes telencephalon and diencephalon
Mesencephalon (midbrain) persists and grows further
Rhombencephalon (hindbrain) becomes metencephalon and myelencephalon
Brain flexures
Two major brain flexures start to develop during week 5:
Cervical flexure: junction of hindbrain and spinal cord, soon disappears as a flexure
Cephalic (mesencephalic) flexure: midbrain, persists as a flexure between midbrain and forebrain
Pontine flexure later forms and helps to divide the hindbrain into the metencephalon (rostral) and myelencephalon (caudal)
Secondary Brain vesicles fate
Telencephalon => Cerebrum
Diencephalon => thalamus, hypothalamus, epithalamus, retina
Mesencephalon => Midbrain
Metencephalon => Pons and Cerebellum
Myelencephalon => Medulla
Development of the ventricles
Central cavity of the neural tube enlarges in four areas to form the fluid-filled ventricles of the brain
Two lateral ventricles form within the cerebral hemispheres (telencephalon)
Third ventricle forms within the diencephalon
Cerebral aqueduct forms within the midbrain (mesencephalon)
Fourth ventricle forms within the hindbrain (rhombencephalon)
Cerebral hemisphere development
The cerebral hemispheres (telencephalon) grow posteriorly and laterally to completely cover the diencephalon and midbrain
The surfaces of the cerebral hemispheres start to crease and fold: sulci and gyri
Increased surface area to allow for a greater concentration of neurons
Gyri and sulci continue to form throughout the fetal period
Lissencephaly (smooth brain) and microcephaly if this process is disrupted
Spina bifida occulta
Occulta is often called hidden spina bifida, as the spinal cord and the nerves are usually normal and there is no opening on the back. In this form of spina bifida, there is only a small defect or gap in the small bones (vertebrae) that make up the spine, which occurs in about 12% of the population. In many cases, spina bifida occulta is so mild that there is no disturbance of spinal function at all. Most people are not aware that they have spina bifida occulta, unless it is discovered on an x-ray performed for an unrelated reason. However, one in 1,000 individuals will have an occult structural finding that leads to neurological deficits or disabilities as bowel or bladder dysfunction, back pain, leg weakness or scoliosis.
Spina bifida cystica - Meningocele
Meningocele occurs when the bones do not close around the spinal cord and the meninges are pushed out through the opening, causing a fluid-filled sac to form. The meninges are three layers of membranes covering the spinal cord, consisting of dura mater, arachnoid mater and pia mater. In most cases, the spinal cord and the nerves themselves are normal or not severely affected. The sac is often covered by skin and may require surgery. This is the rarest type of spina bifida.
Spina bifida cystica - Myelomeningocele
Myelomeningocele accounts for about 75% of all spina bifida cases. This is the most severe form of the condition in which a portion of the spinal cord itself protrudes through the back. In some cases, sacs are covered with skin, but in other cases, tissue and nerves may be exposed. The extent of neurological disabilities is directly related to the location and severity of the spinal cord defect. If the bottom of the spinal cord is involved, there may be only bowel and bladder dysfunction, while the more severe cases can result in total paralysis of the legs with accompanying bowel and bladder dysfunction.
Obstructive hydrocephalus
Excessive amounts of cerebrospinal fluid in the ventricles within the brain – raised ICP
Obstructive hydrocephalus: occlusion of one part of ventricular system, dilation of ventricles preceding blockage
Communicating hydrocephalus
Excessive amounts of cerebrospinal fluid in the ventricles within the brain – raised ICP
Communicating hydrocephalus: dilation of entire ventricular system e.g. due to inadequate reabsorption of CSF, choroid plexus tumour
Congenital hydrocephalus
is often associated with spina bifida
Spina bifida can impair normal CSF flow due to abnormal tension on spinal cord
Treatment for hydrocephalus
Ventriculoperitoneal (VP) shunt: CSF drains into peritoneal cavity via subcutaneous tubing
Anencephaly
The neural tube fails to close in the cranial region, affecting brain development. Fetus/neonate is not viable
Encephalocele
herniation of the brain and meninges through an opening in the cranium e.g. due to failure of the occipital bone to form properly
Brain and/or meninges sit within a skin-covered sac
Olfactory neurones
These are sensitive for one specific odorant each (see different colours)
Their axons cross the cribiform plate
They synapse with the mitral cell dendrites, within glomerulus grouping with neurones of the same type
Olfactory nerve
CN I
Olfactory signals are projected towards the UNCUS (inner temporal) and then the limbic cortex
Smell pathology
Hyposmia (partial loss) or anosmia (complete loss of smell)
Viral infections
Inhalation of toxic compounds
Old age
Trauma
Neurodegenerative diseases – Parkinson’s, Alzheimer’s
Hyperosmia (heightened sensitivity to smells)
Hormonal – pregnancy
Dysomia (unusual/bad smells) Phantosmia (smelling non-existent things)
Brain tumours, space occupying lesion, epilepsy
3 receptor classes in taste
Na Channel
H Channel
G-protein coupled receptors
Gustatory nerve pathways
From the type II/III cells in the taste buds taste follows the typical organisation of sensory pathways:
Bipolar neuron with a ganglion outside the CNS
Synapsing onto cells localised in a CNS nucleus in the medulla oblongata
Axons travelling from these cells will cross over and reach the thalamus
Third cell body is in the thalamus
Axons from there travel to the sensory cortex
Taste travels via CN VII (Anterior 2/3 tongue), CN IX (Posterior 1/3), and CN X (Oropharynx)
Third-order neurones
located in the ventral posterior nucleus of the thalamus and project to primary somatosensory cortex
Dorsal column - medial lemniscal pathway
Fine touch, vibration, proprioception
AB fibres
1st order neurone enters spinal cord, travels up in dorsal column, synapses with 2nd order in nuclei, decussates in medulla, travels to Thalamus to synapse with 3rd order in Ventro posterolateral nucelei
Anterolateral spinothalamic pathway
Pain, temperature, crude touch, pressure
Ad, C fibres
1st order neurone enters spinal cord, synapses with 2nd order, decussates in spinal cord at entry level, travels up to Ventro posterolateral nuclei of thalamus to synapse with 3rd order
Rexed’s laminae
Dorsal horn split into areas of specific function
The trigeminal system
Principal sensory nucleus: receives information on light touch/pressure from ipsi face
Spinal trigeminal: receives information on pain/temp from ipsilateral face
Both go to ventral posterior medial nuclei of the thalamus then to cortex
Spinocerebellar pathways
Both posterior & anterior spinocerebellar tracts carry non-conscious proprioceptive information to the ipsilateral cerebellum.
Posterior tract does not cross
Anterior crosses twice
So both provide input to the ipsilateral cerebellar hemisphere
Spinal cord lesions: Laterality of signs – a rule
If a lesion occurs ABOVE the level at which a pathway has decussated, the signs will be CONTRALATERAL to the lesion
If a lesion occurs BELOW the level at which a pathway has decussated, the signs will be IPSILATERAL to the lesion
Brown-Séquard lesion
A rare condition that results from an injury to one side of the spinal cord.
Ipsilateral loss of motor and fine touch, contralateral loss of pain
Dorsal column fasciculi
Trunk and lower limbs -> fasciculus gracilis -> Gracile nucleus (Medial)
Arm and hand => fasciculus cuneatus -> cuneate nucleus (lateral)
Lateral vs ventromedial pathways (roughly)
Lateral - Voluntary movement of distal musculature (fine control) – direct cortical control
Ventromedial - Posture and locomotion – brainstem control
Corticospinal pathways
Cortex -> internal capsule -> medulla ->
Majority (85-90%) of fibres decussate in the caudal medulla
Some (10-15%) decussate at level of synapse in the spinal cord
Some remain ipsilateral - don’t decussate
(ie. some cranial nerves - corticobulbar)
Rubrospinal & Vestibulospinal Tracts
Rubrospinal & vestibulospinal tracts influence flexor or extensor muscle tone
Rubrospinal - From red nucleus in brainstem (midbrain)
Mainly proximal upper limb & trunk muscles
Excite flexor LMN
Inhibit extensor LMN
Vestibulospinal – From vestibular nuclei in brainstem (pons/medulla)
Antigravity
Excites extensor LMN
Inhibits flexor LMN
Reticulospinal tracts
Ventromedial Pathways
Control posture of the trunk and antigravity muscles of the limbs
Pontine reticulospinal:
Enhances antigravity reflexes of spinal cord
Helps maintain a standing position
Medullary reticulospinal:
Liberates antigravity muscles from reflex control (i.e. dampens down spinal reflex to optimize muscle tone)
Helps maintain a standing position
Activity in both tracts is controlled by descending signals from cortex
A fine balance is required between the two to maintain posture
LMN vs UMN lesion
UMN lesion causes:
Spastic paralysis
Hyper-reflexia
No muscle wasting
LMN lesion causes:
Flaccid paralysis
Hypo-reflexia
Muscle wasting
Fasciculations
Flexor reflex (withdrawal reflex)
More complicated, involves interneurones in several spinal segments
Helps elicit forceful, coordinated contraction
polysynaptic path activated by pain afferents (nociceptors) – activation of flexor motoneurones at several spinal segmental levels for rapid, coordinated limb withdrawal
Crossed extensor reflex
When withdrawing one foot, quadriceps in opposite leg extend knee to bear additional weight (prevents falling)
polysynaptic path activated during flexor reflex to cause extension of opposite limb to maintain balance.
Stretch reflex
monosynaptic path (2 neurones one synapse) – controls muscle length by contracting same muscle; polysynaptic path to relax antagonist (reciprocal innervation)
Golgi tendon reflex-
polysynaptic path opposite effect of stretch reflex – controls muscle tension by relaxing same muscle; contracts antagonist
Protects muscle from producing too much tension (overstretching) and tearing or breaking tendons
What would happen to reflexes above a spinal cord lesion, at the same level and below this level?
Above - no change
At same level - absent/weak
Below - Initially absent (spinal shock) then exaggerated
Cervical sympathetic ganglia
Superior cervical ganglia (C2/C3 vertebral level): postganglionic sympathetic nerve fibres from here travel to the head via periarterial nerve plexi surrounding the internal and external carotid arteries
Middle cervical ganglia (C6 vertebral level) for C5 and C6 spinal nerves
Inferior cervical ganglia (AKA stellate ganglia, C7/T1 vertebral level) for C7 and T1 spinal nerves. Lie anterior to neck of C7 transverse process and neck of first rib
Also form periarterial nerve plexi around the vertebral arteries
Horner’s syndrome
Loss of sympathetic function in the eye area
Constricted pupil (miosis): loss of dilator pupillae function in iris
Partial ptosis: loss of superior tarsal muscle function in upper eyelid
Anhidrosis: reduced sweating on ipsilateral side of head and neck
Potential aetiologies:
Blunt force trauma or stab injuries e.g. to the root of the neck
Iatrogenic causes e.g. neck surgeries such as thyroidectomy
Tumours e.g. Pancoast tumour at apex of lung, thyroid cancer
Multiple sclerosis and spinal cord lesions above T2/T3 level
Cervical rib: an anatomical variation that may compress the sympathetic chain e.g. at C7
Course of preganglionic parasympathetic fibres in the head
Edinger-Westphal nucleus (midbrain) ->CN III Oculomotor nerve -> Ciliary ganglion
Superior salivatory nucleus (pons) -> CN VII Facial nerve
(greater petrosal nerve) -> Pterygopalatine ganglion
Superior salivatory nucleus (pons) -> CN VII Facial nerve (chorda tympani) -> Submandibular ganglion
Inferior salivatory nucleus (pons) -> CN IX Glossopharyngeal nerve (lesser petrosal nerve) -> Otic ganglion
Pterygopalatine ganglion
(in pterygopalatine fossa)
CNVII Parasympathetic postganglionic nerve fibres to lacrimal gland travel in branches of CN Va and Vb: increased tear production
Also innervation of nasal mucosa via CN Vb branches: increased mucus production
Submandibular ganglion
(deep to mandible)
CNVII Parasympathetic postganglionic nerve fibres to submandibular gland travel in lingual nerve (CN Vc branch): increased saliva production
Otic ganglion
(in infratemporal fossa)
CN IX Parasympathetic postganglionic nerve fibres to parotid gland travel in auriculotemporal nerve (CN Vc branch): increased saliva production
Parasympathetic innervation of lacrimal gland
Sup. salivatory -> Greater petrosal CNVII -> Pterygopalatine ganglion -> zygomatic nerve CNVb -> zygomaticotemporal nerve CNVb -> Lacrimal nerve CNVa
Lacrimal reflex (crying)
Afferent limb = branches of CN Va
Plus infraorbital nerve of CN Vb if lower eyelid conjunctiva irritated
Efferent limb = parasympathetic nerve fibres
Parasympathetic preganglionics from superior salivatory nucleus in pons – located near to CN VII motor nucleus (for corneal/blink reflex i.e. orbicularis oculi muscle)
Preganglionic nerve fibres run in greater petrosal nerve (CN VII) to pterygopalatine ganglion
Parasympathetic postganglionics then run in CN Vb branches (zygomatic, zygomaticotemporal) and CN Va (lacrimal nerve and branches) to lacrimal gland
Hypothalamus nucelei examples
Paraventricular and supraoptic nuclei produce ADH and oxytocin
Dorsomedial nucleus and suprachiasmatic nucleus involved with control of circadian rhythms (sleep/wake cycle)
Ventromedial nucleus and lateral areas of hypothalamus (not shown) involved with control of food and fluid intake
Mammillary body/nucleus is part of limbic system (see later lecture)
Anterior parts of hypothalamus help to regulate parasympathetic brainstem nuclei
Posterior parts of hypothalamus help to regulate areas of the brainstem associated with the sympathetic nervous system
Brainstem areas regulating cardiovascular function
Nucleus tractus solitarius (NTS) is an important relay nucleus in the medulla, receiving sensory information from baroreceptors, chemoreceptors and other receptors in organs such as the heart and lungs
Rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) are important for the baroreceptor reflex:
RVLM neurons are important for maintaining a baseline level of sympathetic nervous system activity (sympathetic tone)
CVLM neurons are GABAergic – can inhibit the RVLM
Activation of the baroreceptor reflex causes CVLM to inhibit RVLM activity, leading to a decrease in heart rate and blood pressure (due to reduced sympathetic nervous system activity and reduced vasoconstriction)
Nucleus ambiguus also receives projections from the NTS to elicit reflex bradycardia during the baroreceptor reflex (parasympathetic innervation of the sinoatrial node via CN X)
Brainstem areas regulating respiratory function
Nucleus tractus solitarius (NTS) is an important relay nucleus in the medulla, receiving sensory information from baroreceptors, chemoreceptors and other receptors in organs such as the heart and lungs
In the chemoreceptor reflex, the NTS excites the RVLM to increase sympathetic nervous system activity – increase in blood pressure due to increased vasoconstriction
CVLM not involved with chemoreceptor reflex
NTS activates nucleus ambiguus neurons to also elicit bradycardia – leads to only a slight change in HR during activation of chemoreceptor reflex
The rostral ventral respiratory group (rVRG) contains neurons involved with inspiration that receive sensory information from the NTS e.g. chemoreceptors
rVRG neurons project to phrenic motor nucleus in ventral horn of C3 – C5 spinal cord
Activation of the rVRG causes contraction of the diaphragm via the phrenic nerve – inspiration
Caudal ventral respiratory group (cVRG) contains neurons associated with expiration
Diencephalon components
Thalamus
Hypothalamus
Epithalamus (e.g. pineal gland)
Subthalamus (e.g. subthalamic nucleus)
Blood supply to thalamus =
Blood supply to thalamus = posterior cerebral artery and posterior communicating artery
Thalamic nuclei
Lateral nuclear group (biggest group)
Ventral posterolateral nucleus (VPL): third order neurons for dorsal column and spinothalamic tracts to the primary somatosensory cortex
Ventral posteromedial nucleus (VPM): third order neurons for trigeminothalamic tracts (from face) to the primary somatosensory cortex
Lateral geniculate nucleus (to primary visual cortex) and medial geniculate nucleus (to primary auditory cortex)
Anterior nuclear group: receive information from the limbic system and influence emotions, memory formation
Medial nuclear group: single large nucleus called the dorsomedial nucleus. Associated with olfaction and integrating sensory and motor information – lots of connections to prefrontal cortex
Reticular nucleus: partially surrounds thalamus, function poorly understood
Internal capsule
Bundle of projection fibres to and from the cerebral cortex
Anterior limb: connects anterior nuclei of thalamus with cingulate gyrus, dorsomedial nucleus with prefrontal cortex
Posterior limb: connects VPL nucleus and VPM nucleus with primary somatosensory cortex
Also contains upper motor neurons from primary motor cortex for corticospinal and corticobulbar (cranial nerve) tracts
Internal capsule blood supply
The blood supply to the internal capsule is from perforating branches of the internal carotid (anterior choroidal) artery, middle cerebral (lateral or lenticulostriate) and anterior cerebral (medial striate) arteries.
The medial striate arteries supply the anterior limb and genu of the internal capsule
The lateral striate (lenticulostriate) arteries supply the anterior limb, genu and much of the posterior limb of the internal capsule
The striate arteries do not have a significant collateral blood supply - end arteries (anend artery is the only supply of oxygenated blood to a portion of tissue)
Internal capsule ischaemic stroke
Signs and symptoms:
Weakness of the face, arm, and/or leg (pure motor stroke)
Pure motor stroke caused by an infarct in the internal capsule is the most common lacunar syndrome
Upper motor neuron signs
Hyperreflexia, Babinski sign, Hoffman response is present, clonus, spasticity
Mixed sensorimotor stroke
Since both motor and sensory fibres are carried in the internal capsule, a stroke to the posterior limb of the internal capsule (where motor and sensory fibres for the limbs and trunk are located) can lead to contralateral weakness and contralateral sensory loss
Signs to exclude an internal capsule stroke
NB: The presence of the following cortical signs may exclude an internal capsule stroke:
Gaze preference or gaze deviation: motor cortex damage (unable to move the eyes due to frontal eye field lesion)
Expressive or receptive aphasia: due to damage to Wernicke’s and Broca’s areas of the cortex
Visual field deficits: e.g. due to primary visual cortex involvement
Visual or spatial neglect: usually associated with right parietal lobe lesions
If any of these signs are present, the patient may have a cortical stroke, not an internal capsule stroke
Examples of UMN, LMN lesions and “in between”
UMN - Stroke
Brain tumour
Multiple sclerosis
Subarachnoid haemorrhage
LMN - Polio
Guillain Barre syndrome
Trauma
Disc prolapse
Somewhere in between
MND (sometimes)
Spinal cord injury (sometimes)
B12 deficiency
e.g.:
mononeuropathy
multiple mononeuropathy (=mononeuritis multiplex)
(symmetrical) polyneuropathy
plexopathy
radiculopathy
polyradiculoneuropathy
mononeuropathy - Bell’s palsy, carpal tunnel
multiple mononeuropathy - Hereditary neuropathy with pressure palsies (HNPP), sarcoids, amyloid
(symmetrical) polyneuropathy - DM, alcohol
plexopathy
radiculopathy at spinal root
polyradiculoneuropathy
Consequences of LMN impairment
Falls / trips / stumbles / clumsiness
Damage and poor healing
Pressure sores (especially if sensory nerves also involved)
Abnormal positioning and postures
Contractures
Charcot joints (not related to CMT)
If associated with sensory nerve impairment pain is often a feature
Guillain Barre syndrome
Acute inflammatory demyelinating polyneuropathy
Often preceding infection
Rapid onset and progression of weakness (may be distal / proximal / descending / ascending)
Common involvement face, respiratory
Numbness and tingling extremities +/- pain +/- sensory loss
Acute assessment and management of Guillain Barre syndrome
FVC
Bulbar function
ECG – autonomic
DVT prophylaxis
Early liaison with AICU
IVIG (plasma exchange)
What cell is found at motor neurone ganglion tha =t is inhbiotioty
Renshaw cell – inhibitory interneuron – produces glycine (antagonised by strychnine – Agatha Christie)
MND
Irreversible progressive
Typically asymmetric limb weakness
Little / no sensory involvement
UMN and LMN signs in same territory
Fasciculations
20% bulbar features at presentation
Later respiratory involvement
Median survival 30 months (but diagnostic delay 1y)
Riluzole
Supportive treatment – NIV / RIG
ALS (amyotrophic lateral sclerosis) – mixed UMN and LMN
PMA (progressive muscular atrophy) – pure LMN
PLS (primary lateral sclerosis) – UMN – ascending spastic tetraparesis
PBP (Progressive bulbar palsy) (but UMN features)
5% hereditary; remainder unknown cause – genetic predisposition / heavy metal /chemical exposure / smoking / strenuous exercise
Internal structure of brainstem in cross-section - 3 main parts (not midbrain, pons, medulla)
Tectum (roof): found in the midbrain e.g. superior and inferior colliculi
Tegmentum: cranial nerve nuclei and tracts located here plus ascending sensory pathways from spinal cord (+ some descending motor pathways e.g. rubrospinal tract from red nucleus)
Basal part: descending pathways from cerebral cortex e.g. corticospinal tract fibres in pyramids, cerebral peduncles
Rostral midbrain contents
Two cerebral peduncles (crus cerebri) on ventral side with descending fibres from cerebrum (pyramidal tracts)
Corpora quadrigemina (colliculi): tectal roof over the cerebral aqueduct:
- Superior colliculus - regulation of movements in response to vision – saccadic eye movements, orienting head and eyes toward a stimulus.
- Origin of the tectospinal pathway
Edinger-Westphal nucleus: parasympathetic nucleus, involved in pupillary light reflex - Lesion causes ipsilateral loss of accommodation and pupillary light reflex
Red nucleus: rubrospinal tract, connections to cerebellum. Role in controlling flexor muscle tone - Lesion can cause tremor/ataxia on contralateral side along with motor deficits
Rostral midbrain in cross-section
Two cerebral peduncles (crus cerebri) on ventral side with descending fibres from cerebrum (pyramidal tracts)
Corpora quadrigemina (colliculi): tectal roof over the cerebral aqueduct:
- Superior colliculus - regulation of movements in response to vision – saccadic eye movements, orienting head and eyes toward a stimulus.
- Origin of the tectospinal pathway
Edinger-Westphal nucleus: parasympathetic nucleus, involved in pupillary light reflex - Lesion causes ipsilateral loss of accommodation and pupillary light reflex
Red nucleus: rubrospinal tract, connections to cerebellum. Role in controlling flexor muscle tone - Lesion can cause tremor/ataxia on contralateral side along with motor deficits
Substantia nigra: part of basal ganglia, affected by Parkinson’s disease
Oculomotor nucleus: lesion here leads to eye in ‘down and out’ position, divergent squint, ptosis
Spinal lemniscus: tract carrying contralateral spinothalamic (sensory) fibres
Medial lemniscus: tract carrying contralateral dorsal column (sensory) fibres
Medial longitudinal fasciculus: tract connecting many brainstem nuclei including vestibular nuclei and the oculomotor, trochlear and abducens nuclei – important for coordinating eye movements
What in the midbrain helps coordinate eye movements in response to sound?
Medial longitudinal fasciculus: tract connecting many brainstem nuclei including vestibular nuclei and the oculomotor, trochlear and abducens nuclei – important for coordinating eye movements
Caudal midbrain
Two cerebral peduncles (crus cerebri) on ventral side with descending fibres from cerebrum (pyramidal tracts)
Inferior colliculus: regulation of movements in response to sound
Important relay point for auditory information travelling from the cochlea to primary auditory cortex. Startle reflex
Trochlear nucleus: damage here leads to contralateral loss of superior oblique function, diplopia
CN IV LMNs decussate before emerging on posterior aspect of caudal midbrain – only CN LMNs to do this
Rostral Pons in cross-section
Nuclei for four cranial nerves : trigeminal (CN V), abducens (VI), facial (VII), vestibulocochlear (VIII)
Cerebellar peduncles: tracts to and from cerebellum
Trapezoid body: decussation site for nerve fibres from cochlear nuclei in central auditory pathway (see auditory system lecture)
Caudal pons in cross section
Abducens nucleus: damage to LMNs here or in the CN VI nerve leads to binocular horizontal diplopia. Inability to abduct ipsilateral eye
Facial motor nucleus: damage to LMNs here or in CN VII will lead to ipsilateral facial palsy
Medulla oblongata key structures and nucleio
Continuous with spinal cord at the foramen magnum
Two ventral ridges (pyramids) formed by the corticospinal tracts – decussation site
Major nuclei in medulla:
Spinal trigeminal nucleus (sensory – pain/temperature e.g. from facial skin via trigeminal nerve )
Nucleus tractus solitarius/nucleus of the solitary tract/NTS: major relay point for visceral sensation e.g. via the vagus nerve from gut
Nuclei for glossopharyngeal (CN IX), vagus (X) and hypoglossal (XII) nerves
Gracile nucleus (nucleus gracilis) and cuneate nucleus (nucleus cuneatus) for dorsal column pathway
Superior olivary (hearing) and inferior olivary nuclei (motor coordination)
Hypoglossal
Describe caudal vs rostral medulla in cross section - key differencw
Rostral (‘open’) medulla in cross-section
Caudal (‘closed) medulla in cross-section
Cranial nerve efferent (motor) nerve fibres
Somatic efferents: lower motor neurons innervating skeletal muscle formed by somites
Also known as general somatic efferents (GSEs)
Found throughout the body, usually have cell bodies in ventral horn of spinal cord e.g. lower motor neurons to limbs
Also have lower motor neuron cell bodies in brainstem nuclei for specific cranial nerves:
Run in the oculomotor (CN III), trochlear (CN IV) and abducens (CN VI) nerves to supply the extraocular muscles
Run in the hypoglossal nerve (CN XII) to supply muscles of the tongue
Branchial efferents: lower motor neurons innervating skeletal muscle formed by pharyngeal (branchial) arches
Also known as special somatic efferents (SSEs)
Lower motor neuron cell bodies found in brainstem nuclei for specific cranial nerves:
Run in the mandibular division of the trigeminal nerve (CN Vc) to supply the muscles of mastication (chewing)
Run in the facial nerve (CN VII) to supply the muscles of facial expression
Run in the glossopharyngeal (CN IX) and vagus (CN X) nerves to supply skeletal muscles in the pharynx and larynx
Run in the accessory nerve (CN XI) to supply sternocleidomastoid and trapezius
Visceral efferents: autonomic neurons
Also known as general visceral efferents (GVEs)
Parasympathetic preganglionic cell bodies found in brainstem nuclei for specific cranial nerves
Run in the oculomotor nerve (CN III) to supply smooth muscle of iris (sphincter pupillae) and ciliary body
Run in the facial nerve (CN VII) to supply lacrimal glands, sublingual and submandibular glands
Run in the glossopharyngeal nerve (CN IX) to supply the parotid gland
Run in the vagus nerve (CN X) to supply a wide range of thoracic and abdominal viscera
Cranial nerve afferent (sensory) nerve fibres
Somatic afferents: conveying sensory information from the periphery (outside world)
Also known as general somatic afferents (GSAs)
Touch, temperature, proprioception, pain and pressure
Cell bodies found in ganglia associated with the following cranial nerves:
All three divisions of trigeminal nerve (CN V) e.g. conveying touch sensation from skin of face
Also found in small numbers in the facial nerve (CN VII), glossopharyngeal nerve (CN IX) and vagus nerve (CN X) – convey sensory information from the external ear and external acoustic meatus, clinically relevant for referred pain
Special somatic afferents convey information from the unique, highly-specialised sensory receptors of the retina (CN II optic nerve) and inner ear (CN VIII vestibulocochlear nerve) – special senses of vision, hearing, balance
Visceral afferents: conveying sensory information from internal organs (viscera) and mucosal linings
Also known as general visceral afferents (GVAs)
Often found in the same locations as autonomic visceral efferents, but visceral afferents are not autonomic i.e. they aren’t motor
Cell bodies found in ganglia associated with the following cranial nerves:
CN X (vagus) mostly contains visceral afferents from thoracic and abdominal organs – around 80% of its the nerve fibres
Some visceral afferents run in CN IX e.g. from carotid sinus for the baroreceptor reflex
A very small number run in CN VII to convey sensation from mucosal lining of nasal cavity, sinuses – don’t need to know this
Special visceral afferents convey information from the unique, highly-specialised sensory receptors of the tongue (taste buds) and olfactory epithelium (for sense of smell)
Glossopharyngeal (IX) and vagus (X) nuclei
Nucleus of solitary tract/nucleus tractus solitarius or just NTS (CN IX and X): visceral sensations (e.g. taste), relay point for some reflexes e.g. baroreceptor reflex
Spinal trigeminal nucleus (CN IX and X): receives pain and temperature sensation via these nerves from pharynx, external ear
Inferior salivatory nucleus (CN IX): parasympathetic preganglionics to parotid gland
Nucleus ambiguus (CN X): LMNs to pharyngeal and laryngeal muscles, parasympathetic preganglionics to the heart.
Dorsal motor nucleus of the vagus nerve (CN X): parasympathetic e.g. to respiratory tract, GI tract
Accessory (XI) and hypoglossal (XII) nuclei
Spinal accessory nucleus: LMN cell bodies in C1-C5 ventral horns for sternocleidomastoid and trapezius
Hypoglossal nucleus (CN XII): LMN cell bodies for all muscles of the tongue except palatoglossus
Findings following each cranial nerve lesion and causes
CN I Fracture of cribriform plate Anosmia (loss of smell); cerebrospinal fluid rhinorrhea
CN II Direct trauma to orbit or eyeball; fracture involving optic canal Loss of pupillary constriction
Pressure on optic pathway; laceration or intracerebral haemorrhage/ischaemia in temporal, parietal, or occipital lobes of brain Visual field defects.
CN III Orbital fracture; thrombosis involving cavernous sinus; aneurysms Dilated pupil; ptosis; eye turns “down and out;” pupillary reflex on side of lesion will be lost.
CN IV Stretching of nerve during its course around brainstem; fracture of orbit Inability to look down when eye is adducted
CN V Injury to terminal branches (particularly CN Vc) in roof of maxillary sinus; pathological processes affecting trigeminal ganglion Loss of pain and touch sensations in affected trigeminal dermatome; paresthesia; masseter and temporalis muscles do not contract; deviation of mandible to side of lesion when mouth is opened
CN VI Orbital fracture, cavernous sinus thrombosis Eye fails to move laterally; diplopia on lateral gaze.
CN VII Laceration or swelling in parotid region Paralysis of facial muscles; eye remains open; angle of mouth droops; forehead does not wrinkle
Fracture of temporal bone As above, plus associated involvement of cochlear nerve and chorda tympani; dry cornea; loss of taste on anterior two thirds of tongue Stroke affecting UMNs Forehead wrinkles because of bilateral innervation of frontalis muscle, otherwise paralysis of contralateral facial muscles
CN VIII Tumor of nerve (acoustic neuroma/schwannoma) Progressive unilateral hearing loss; tinnitus (noises in ear); vertigo
CN IX Brainstem lesion or deep laceration of neck Loss of taste on posterior third of tongue; loss of sensation on affected side of soft palate
CN X Brainstem lesion or deep laceration of neck Sagging of soft palate; deviation of uvula to normal side; hoarseness due to paralysis of vocal folds
CN XI Neck laceration Paralysis of sternocleidomastoid and trapezius; drooping of ipsilateral shoulder
CN XII Neck laceration; fractures of base of skull Protruded tongue deviates toward affected side; dysarthria
Brainstem cranial nerve nuclei lesions:
oculomotor
Edinger-Westphal nucleus (parasympathetic for CN III)
Trochlear
Mesencephalic nucleus
Chief trigeminal
spinal trigeminal
Abducens
Superior salivatory nucleus (parasympathetic for CN VII)
Cochlear and vestibular nuclei (CN VIII afferents)
Nucleus tractus solitarius (CN VII, IX, X afferents)
Inferior salivatory nucleus (parasympathetic for CN IX)
Nucleus ambiguus (CN IX and CN X)
Dorsal motor nucleus of vagus nerve (CN X)
Hypoglossal
oculomotor - eye down and out
Edinger-Westphal nucleus (parasympathetic for CN III) - Loss of ipsilateral pupillary reflex
Trochlear - vertical diplopia
Mesencephalic nucleus - loss of jaw proprioception
Chief trigeminal - loss of light touch, vibration
spinal trigeminal - loss of ipsi pain and temperature
Abducens - horizontal diplopia
Superior salivatory nucleus (parasympathetic for CN VII) - loss of saliva secretion (except parotid)
Cochlear and vestibular nuclei (CN VIII afferents) - imbalance and hearing loss
Nucleus tractus solitarius (CN VII, IX, X afferents) - loss of visceral senstion from vagus, loss of chemical reflexes
Inferior salivatory nucleus (parasympathetic for CN IX) - loss of parotid secretions
Nucleus ambiguus (CN IX and CN X) - swallowing problems, deviated away uvula
Dorsal motor nucleus of vagus nerve (CN X) - loss of PS function
Hypoglossal - tongue deviated towards lesion
Glossopharyngeal nerve (CN IX) arises from and function
Glossopharyngeal nerve arises posterior to the olive of the medulla
Exits the intracranial cavity through the jugular foramen to reach the superior and inferior ganglia of the glossopharyngeal nerve
locations of CN IX afferent cell bodies
CN IX sensory functions:
Somatic afferents (cell bodies in superior ganglion)
Convey sensation from oropharynx, posterior 1/3 of tongue and from tympanic membrane to the spinal trigeminal nucleus
Visceral afferents (cell bodies in inferior ganglion)
Convey taste sensation from posterior 1/3 of tongue to NTS
Convey information from carotid sinus and carotid body to NTS
CN IX motor functions:
Branchial efferents innervate the stylopharyngeus muscle (formed from 3rd pharyngeal arch).
LMN motor nucleus = nucleus ambiguus
Visceral efferents (parasympathetic preganglionics) from inferior salivatory nucleus supply the parasympathetic innervation of parotid gland via the otic ganglion
Testing the glossopharyngeal nerve (CN IX) and lesions
The glossopharyngeal nerve innervates the posterior 1/3rd of the tongue and mucosal lining of the oropharynx. When this is touched (e.g. by a tongue depressor) the gag reflex is elicited, the soft palate elevates and the pharynx constricts
Gag reflex stops objects from entering the throat (except during swallowing) – helps to prevent choking.
Afferent limb = CN IX (NTS and spinal trigeminal nucleus), efferent limb = CN X (nucleus ambiguus)
Isolated CN IX lesions are rare: combined CN X and XI lesions more common e.g. compression by a tumour at the jugular foramen (bulbar palsy)
Reduced or absent gag reflex with soft palate deviation away from lesion, impaired taste/sensation from posterior 1/3 of tongue, reduced salivary production from ipsilateral parotid gland
Vagus nerve (CN X) arises and function
Emerges from brainstem posterior to the olive of the medulla and inferior to rootlets of glossopharyngeal nerve
Exits intracranial cavity through jugular foramen to reach the superior (jugular) and inferior (nodose) ganglia of the vagus nerve – locations of CN X afferent cell bodies
Left and right vagus nerves travel through the neck to the thoracic cavity alongside common carotid artery and internal jugular vein
Visceral afferents (cell bodies in inferior ganglion):
Sensory information conveyed to NTS from laryngopharynx, larynx, trachea, oesophagus, thoracic/abdominal viscera
Also information from chemoreceptors in aortic arch (to monitor blood CO2 etc.) and taste from epiglottis to NTS
Somatic afferents (cell bodies in superior ganglion)
Convey sensation from external ear and external acoustic meatus to spinal trigeminal nucleus
Branchial efferents: motor innervation to all pharyngeal and laryngeal muscles (from 4th and 6th pharyngeal arches) except for stylopharyngeus (CN IX) and tensor veli palatini (CN Vc).
Motor nucleus = nucleus ambiguus. Efferent limb of gag reflex
Visceral efferents: parasympathetic preganglionics from dorsal motor nucleus of the vagus nerve to thoracic and abdominal viscera e.g. lungs, GI tract.
Also nucleus ambiguus for parasympathetic preganglionics to the heart.
Lesions to root (origin) of the vagus nerve (e.g. a brainstem lesion) are associated with dysarthria (weakness of laryngeal muscles) and dysphagia (weakness of pharyngeal and laryngeal muscles)
Recurrent laryngeal nerve lesions may also cause vocal cord paresis/paralysis e.g. injury during thyroid surgery
Soft palate deviation with uvula deviated to the unaffected side
Lesions to root (origin) of the vagus nerve (e.g. a brainstem lesion)
Lesions to root (origin) of the vagus nerve (e.g. a brainstem lesion) are associated with dysarthria (weakness of laryngeal muscles) and dysphagia (weakness of pharyngeal and laryngeal muscles)
Recurrent laryngeal nerve lesions may also cause vocal cord paresis/paralysis e.g. injury during thyroid surgery
Soft palate deviation with uvula deviated to the unaffected side
Accessory nerve (CN XI) arises and function and lesions
Accessory nerve arises from spinal accessory nucleus in posterolateral ventral horn of the cervical spinal cord (C1 – C5 spinal cord levels)
CN XI emerges from lateral aspect of spinal cord (between ventral and dorsal spinal nerve roots) and ascends to enter foramen magnum
Soon exits intracranial cavity again with CN IX and CN X via jugular foramen
Branchial efferent innervation to sternocleidomastoid, trapezius
CN XI passes laterally between internal carotid artery and internal jugular vein
Enters posterior triangle and runs from one-third of the way down posterior border of SCM to two-thirds of the way down anterior border of trapezius
CN XI lesions e.g. due to a stab injury to the posterior triangle of the neck
Drooping of the shoulder (trapezius paralysis) on the ipsilateral side and difficulty turning head to the contralateral side (sternocleidomastoid paralysis) against resistance
Hypoglossal nerve (CN XII) arises and function and lesions
Hypoglossal rootlets emerge on ventral aspect of medulla between pyramid and olive
Nerve exits intracranial cavity via the hypoglossal canal
Somatic efferent innervation to the tongue muscles
Extrinsic muscles (genioglossus, hyoglossus and styloglossus but not palatoglossus – CN X) of ipsilateral side of tongue
Intrinsic muscles of ipsilateral side of tongue
Some somatic efferents from C1 and C2 spinal nerves also travel in hypoglossal nerve to reach infrahyoid muscles
CN XII at risk during surgery involving the carotid arteries or the deep tissues superior to the larynx
Crosses superficial to internal and external carotid arteries as well as lingual and facial arteries
Hypoglossal unilateral LMN lesion: protruded tongue deviates to the side of the lesion
Which nerve is at risk during surgery involving the carotid arteries or the deep tissues superior to the larynx
CN XII at risk during surgery involving the carotid arteries or the deep tissues superior to the larynx
Crosses superficial to internal and external carotid arteries as well as lingual and facial arteries
Bulbar and pseudobulbar palsies
Disruption of lower cranial nerve motor function (CN IX, X, XII) – also sometimes CN VII
Bulbar palsy:
Bilateral LMN lesions associated with cranial nerve nuclei in the medulla (‘bulb’).
E.g. nucleus ambiguus, dorsal motor nucleus of vagus nerve, hypoglossal nucleus
Dysphagia. Dysarthria. Flaccid, fasciculating tongue. Gag reflex may be absent.
Some causes = lesions of CN IX, X and XII, myasthenia gravis, muscular dystrophies, brainstem tumours.
Pseudobulbar palsy:
Bilateral supranuclear UMN lesions resulting in weakness of tongue and pharyngeal muscles.
More common than bulbar palsies
Dysarthria - high-pitched slurred speech. Dysphagia. Emotional lability. Tongue paralysis. Exaggerated jaw jerk and gag reflexes (increased tone).
Some causes = cerebrovascular events (e.g. bilateral internal capsule strokes), motor neurone disease, multiple sclerosis, severe traumatic brain injury.
Trigeminal nerve arises and roots
Emerges from ventrolateral pons
Sensory root (somatic afferents)
Touch, pressure, pain, proprioception and temperature
Convey sensory information from scalp, dura mater, face, nasal cavities, paranasal sinuses, palate, temporomandibular joint, oral cavity, teeth, conjunctiva and cornea
Cell bodies in trigeminal ganglion (Gasserian ganglion)
Motor root (branchial efferents from first pharyngeal arch)
Associated with mandibular division of trigeminal nerve (CN Vc)
Innervate muscles of mastication (temporalis, masseter, medial pterygoid and lateral pterygoid)
Also other nearby muscles such as mylohyoid, anterior belly of digastric, tensor tympani and tensor veli palatini
Cell bodies in trigeminal motor nucleus of pons
Also has an important role in distributing the parasympathetic postganglionic nerve fibres (visceral efferents) to their targets in the head e.g. eye, lacrimal gland, salivary glands
CN V does not convey any parasympathetic preganglionics
More on this in the autonomic nervous system lecture in case 8.02
Trigeminal nerve divisions S or M or mixed
Ophthalmic division (sensory): Va or V1
Passes through superior orbital fissure
Transmits sensory information from orbit, forehead, anterior scalp, most of skin of nose
Test: cotton wool on forehead, corneal reflex test
Maxillary division (sensory): Vb or V2
Passes through foramen rotundum
Transmits sensory information from upper lip, maxillary teeth, skin of cheek and nostrils, nasal cavities
Test: Cotton wool on cheek
Mandibular division (mixed): Vc or V3
Passes through foramen ovale
Sensation from lower lip, mandibular teeth, anterior tongue, skin overlying the mandible, external ear
Motor innervation to muscles of mastication
Test: Cotton wool on jaw. Clench teeth and feel for muscle mass. Jaw jerk reflex
Trigeminal nerve foramina
Va -> superior orbital fissure
Vb -> foramen rotundum
Vc -> foramen ovale
Trigeminal cave (Meckel’s cave)
Trigeminal ganglion sits in a depression in the middle cranial fossa known as the trigeminal cave
Covered superiorly by dura mater
Trigeminal cave can be accessed via the oral cavity and foramen ovale during some surgical procedures e.g. trigeminal ganglion block (Gasserian gangliolysis) to treat trigeminal neuralgia
How can trigeminal ganglion be accessed most easily for surgery?
Trigeminal cave can be accessed via the oral cavity and foramen ovale during some surgical procedures
Trigeminal cutaneous nerve branches
Ophthalmic division (Va):
Supraorbital and supratrochlear nerves innervate skin of forehead and anterior scalp and emerges from orbit via supraorbital foramen or notch
Lacrimal nerve innervates lacrimal gland and helps convey parasympathetic nerve fibres to this gland
Maxillary division (Vb)
Infraorbital nerve innervates skin of cheek and upper lip and emerges from infraorbital foramen of maxilla
Zygomaticotemporal nerve innervates lateral skin of the forehead and helps convey parasympathetic nerve fibres to the lacrimal gland
Mandibular division (Vc)
Auriculotemporal nerve innervates skin of external ear and temporal region (lateral scalp)
Buccal nerve innervates skin of cheek and mucous membrane on inside of cheek
Lingual nerve is important for conveying sensory innervation from the tongue (CN Vc somatic afferents for touch/temperature + CN VII visceral afferents for taste via the chorda tympani)
Mental nerve innervates skin of lower lip and chin and emerges from mental foramen of mandible
Trigeminal sensory pathways
Touch/pressure/pain/temp pathways:
Cell bodies for 1° neurons in trigeminal ganglion
Synapse on nuclei in pons or medulla e.g. chief sensory or spinal trigeminal
Proprioceptive pathway (Vc):
Cell bodies for 1° neurons in mesencephalic nucleus of midbrain
Synapse alongside this nucleus
Some fibres synapse instead on motor neurons in trigeminal motor nucleus – jaw jerk reflex
2° neurons decussate and ascend in trigeminothalamic tract to ventral posteromedial (VPM) nucleus of thalamus
3° neurons project from VPM of thalamus to primary somatosensory cortex via the posterior limb of the internal capsule and then the corona radiata
Muscles of mastication, their innervation and function
Muscles of mastication (Vc)
Act on the temporomandibular joint (TMJ)
Masseter: elevation of mandible
Deep part of masseter helps with retraction
Superficial part has helps with protrusion of the mandible
Temporalis: mainly elevation of mandible but also retraction using the more posterior muscle fibres
Medial pterygoid: elevation and protrusion of mandible
Unilateral movement = small grinding movements during chewing
Lateral pterygoid – protrusion of mandible. Helps suprahyoid muscles to depress mandible
Depression of mandible is mainly via gravity and suprahyoid muscles
Unilateral movement = swings jaw to contralateral side e.g. when chewing
Temporomandibular disorders such as bruxism can cause visible/palpable enlargement of masseter and temporalis
Bruxism
unconscious grinding of teeth
Temporomandibular disorders such as bruxism can cause visible/palpable enlargement of masseter and temporalis
Testing trigeminal nerve function
Cutaneous sensation (e.g. cotton wool)
Corneal reflex - (tests CN Va and VII - touching the cornea should cause involuntary, bilateral blinking)
Jaw jerk reflex (tests CN Vc - jaw deviates to side with the lesion)
Lesions of the trigeminal nerve
Trigeminal nerve lesions may occur for many reasons e.g. due to craniofacial trauma, compression by an intracranial tumour or aneurysm, cavernous sinus thrombosis
A unilateral complete trigeminal nerve lesion may cause widespread anaesthesia of the:
Corresponding anterior half of the scalp
Ipsilateral half of face (except for skin over the angle of the mandible) and the cornea and conjunctiva
Ipsilateral mucous membranes of the nose, mouth, and anterior part of the tongue
As well as ipsilateral paralysis of the muscles of mastication
Herpes zoster virus can cause lesions of the trigeminal nerve and/or ganglion
Ophthalmic division (Va) is most commonly affected, with painful vesicular rash and ulceration of skin (and often cornea) in the corresponding dermatome - shingles
Two major parts to facial nerve:
Facial nerve motor root: cell bodies in facial motor nucleus of pons
Intermediate nerve (nervus intermedius) – sensory and parasympathetic nerve fibres
Both roots emerge from the brainstem together at the pontomedullary junction and pass through internal acoustic meatus alongside the vestibulocochlear nerve (CN VIII)
Facial nerve enters the facial canal in the petrous part of the temporal bone
Facial nerve motor root
Facial nerve motor root:
roots emerge from the brainstem together at the pontomedullary junction and pass through internal acoustic meatus alongside the vestibulocochlear nerve (CN VIII)
Facial nerve enters the facial canal in the petrous part of the temporal bone
Motor root exits facial canal via stylomastoid foramen, then branches in parotid gland
Branchial efferents innervate muscles formed from 2nd pharyngeal arch:
Muscles of facial expression
Stylohyoid
Stapedius (in middle ear for dampening loud noises)
Posterior belly of digastric (anterior belly innervated by CN Vc).
Chorda tympani runs with the facial nerve motor root before entering the middle ear cavity (tympanic cavity) – important pathway for visceral afferents from the tongue and parasympathetic innervation to the sublingual and submandibular salivary glands
Intermediate nerve of CN VII (nervus intermedius)
Geniculate (sensory) ganglion – cell bodies of afferents travelling in the CN VII intermediate nerve
CN VII sensory root (+ parasympathetic preganglionic fibres)
Parasympathetic secretomotor innervation (visceral efferent) to lacrimal, sublingual and submandibular glands
Cell bodies of preganglionic neurons in superior salivatory nucleus
Visceral afferents convey sensory information from anterior 2/3 of tongue (taste)
Cell bodies in geniculate ganglion
Somatic afferents (pain, touch, temperature) from external ear and external acoustic meatus
Cell bodies in geniculate ganglion
Tongue innervation
Touch, pressure, temperature, proprioception, pain (somatic afferents)
Anterior 2/3 of tongue = CN Vc (lingual nerve)
Posterior 1/3 of tongue = CN IX glossopharyngeal nerve
Taste sensation (visceral afferents)
Anterior 2/3 of tongue = CN VII (chorda tympani)
Posterior 1/3 of tongue = CN IX glossopharyngeal nerve
Epiglottis = CN X vagus nerve
Motor function (somatic efferents)
Muscles of tongue innervated by CN XII hypoglossal nerve
Five major CN VII motor branches:
Temporal
Zygomatic
Buccal
Mandibular
Cervical
Muscles of facial expression
Modiolus is the common attachment site for muscles acting on the oral aperture (mouth)
Occipitofrontalis (frontal and occipital muscle bellies are connected by the epicranial aponeurosis of the scalp)
Frontalis elevates eyebrows and wrinkles forehead
Occipitalis pulls scalp posteriorly
Orbital group:
Orbicularis oculi orbital part (forcible closure of eye) and palpebral part (gentle closure of eye)
Corrugator supercilii (draws eyebrows medially and inferiorly)
Oral group:
Orbicularis oris (closure of mouth, pursing lips)
Buccinator (blowing, mastication, sucking)
Zygomaticus major and minor (pull angle of mouth superiorly and laterally)
Risorius (pulls angle of mouth laterally)
Mentalis (protrudes lower lip)
Levator and depressor groups of muscles (pull lips superiorly or inferiorly
Platysma: tenses skin of neck and depresses angle of mouth
Nasal group of muscles (alter shape of nostrils, wrinkle the nose) – less powerful, don’t need to know
CN VII motor pathways (corticobulbar tract)
Upper motor neurons (UMNs) project from the primary motor cortex to the facial nerve motor nucleus
Upper motor neurons for the upper half of the face project bilaterally from both primary cortices (left and right) to both left and right facial motor nuclei
Pathway for control of muscles such as orbicularis oculi and frontalis
Upper motor neurons for the lower half of the face only project to the contralateral motor nucleus
Pathway for control of muscles such as orbicularis oris and zygomaticus major
CN VII motor neuron lesions
UMN unilateral lesions
lead to paralysis (facial hemiplegia) of contralateral lower facial muscles (contralateral paralysis with forehead sparing)
Most commonly associated with stroke
Other causes could be multiple sclerosis, intracerebral tumours, subdural haemorrhage
LMN unilateral lesions
Bell’s palsy: unilateral LMN lesion caused by inflammation of facial nerve motor root as it passes through skull, or compression of the nerve at the stylomastoid foramen or inside the parotid gland
Unable to close ipsilateral eye properly
Ipsilateral corneal reflex absent
Loss of taste sensation from ipsilateral anterior 2/3 tongue – may also report metallic taste
Hyperacusis in ear on affected side (stapedius muscle)
May be caused by herpes zoster e.g. shingles affecting geniculate ganglion, with ipsilateral facial palsy and a vesicular rash on the ear – Ramsey Hunt syndrome
When testing CN VII, assess for lesions in nearby structures to help identify where the lesion is along the pathway of the nerve
Is the palsy UMN or LMN? Is there forehead-sparing (UMN)?
Convergent squint - CN VI (abducens) affected?
Is CN VIII affected e.g. hearing loss or balance disturbances?
Is the lacrimal gland affected?
Is salivation affected?
Issues with taste from anterior 2/3 of tongue?
Stapedius – noise sensitivity (hyperacusis)?
Is the palsy UMN or LMN? Is there forehead-sparing (UMN)? Yes = UMN lesion
Convergent squint - CN VI (abducens) affected? = brainstem lesion with CNVI
Is CN VIII affected e.g. hearing loss or balance disturbances? Lesion in temporal bone
Is the lacrimal gland affected?
Is salivation affected?
Issues with taste from anterior 2/3 of tongue?
Stapedius – noise sensitivity (hyperacusis)?
=> all more likely to be UMN or early on CNVII path
If these are unaffected, the lesion will likely be at the stylomastoid foramen or further into the face
Is there swelling of the parotid gland?
Or, is this Bell’s palsy without a known aetiology?
CNVII
Laceration or swelling in parotid region ->
Fracture of temporal bone ->
Stroke affecting UMNs->
Laceration or swelling in parotid region -> Paralysis of facial muscles; eye remains open; angle of mouth droops; forehead does not wrinkle
Fracture of temporal bone -> As above, plus associated involvement of cochlear nerve and chorda tympani; dry cornea; loss of taste on anterior two thirds of tongue
Stroke affecting UMNs-> Forehead wrinkles because of bilateral innervation of frontalis muscle, otherwise paralysis of contralateral facial muscles
Types of nociceptors
Fast, short, sharp, first pain (Aδ)
Slower, duller, longer, second pain (C)
How can “pain” nerves travel originally
Travel up or down in Lissauer’s tract (a few spinal segments)
Descending control of pain systems
Hypothalamus
Peri-aqueductal grey (PAG - midbrain)
Rostral Ventromedial Medulla (RVM): raphe nuclei (serotonergic) Off cells – anti-nociceptive, activated by opioids
On cells – pro-nociceptive, inhibited by opioids
Dorsolateral pons (locus coeruleus, A7, A5?):
Alpha1: excitatory
Alpha2: inhibitory
Beta: excitatory
Common types of chronic pain
Cancer Pain
Neuropathic pain
Visceral pain
Allodynia
pain from a normally non-noxious stimulus
Depression core symptoms
Depression for 2 weeks
Loss of interest in pleasurable activities
Increased fatigability or decreased energy
The Cognitive Triad
Negative thoughts about self, world, and future
Triad of Modern General Anaesthesia
ANALGESIA
ANAESTHESIA
MUSCLE RELAXATION
I.v. anaesthetics
Thiopentone
Barbiturate, act on GABA channels, defined end point, ↓ BP and ↑ HR, depress ventilation, depress CBF, hepatic metabolism, renal excretion, long t1/2 (~12 hours)
Ketamine
Dissociative anaesthesia, NMDA receptor antagonist, airway & CVS stability, analgesia, hallucinogenic, hepatic metabolism, renal excretion, t1/2 (~1.5 hours)
Etomidate
Not water soluble, Imidazole structure, acts on GABA channels, CVS stable, depress ventilation, depress CBF, adreno-cortisol suppression, hepatic & plasma metabolism, renal excretion, t1/2 (~75 mins)
Propofol - most commonly used
Not water soluble, Phenol ring structure, acts on GABA channels, ↓ BP, depress ventilation, depress CBF, hepatic & extra hepatic metabolism, renal excretion, biphasic half life (initial distribution t1/2 (~2-8 mins), terminal 4-7 hours)
Volatile Anaesthetic Agents “gas”
Isoflurane
Minimum Alveolar Concentration 1.2% of alveolar air needed to induce anaesthesia , B/G 1.4, pungent
Sevoflurane
MAC 2.0, B/G 0.59, pleasant smelling
Desflurane
MAC 6.0, B/G 0.42, irritating resp
Halothane
MAC 0.75, B/G 2.4, tolerable smell
Nitrous oxide
MAC, B/G 0.47, odourless, analgesic (gas & air), a gas
Muscle Relaxation - anaesthesia
Depolarising - SUXAMETHONIUM
Non depolarising ATRACURIUM, rocuronium, vecuronium - slower onset and offset
How can we record brain oscillations in the cerebral cortex?
The Electroencephalogram (EEG)
Measurement of generalized cortical activity
Noninvasive, painless
Diagnose neurological conditions such as epilepsy, sleep disorders, research
What can generate very rhythmic, self sustaining, discharge patterns even when no external input
The Thalamus can act as a powerful pacemaker
Thalamus can generate very rhythmic, self sustaining, discharge patterns even when no external input
Thalamus => Cortex = excited cortical neurons
Circadian Rhythms
The Suprachiasmatic Nucleus: A Brain Clock
Intact SCN produces rhythmic message: SCN cell firing rate varies with circadian rhythm
Light sensitive input pathway - output: circadian rhythmicity of behaviour, hormone levels, sleeping and waking, metabolism, feeding, drinking.
Typical hypnogram of adult sleep
Regularly repeating 90 minute cycle
Progression through different sleep stages
Thalamus closed to external stimuli during non-REM sleep,
In REM it is not open to external sensations, but emotions, motivations, and memories => vivid dreams near awaking
Increased REM duration during sleep period
Sleep stages and brain oscillations
Stage 1: Transitional sleep. Alpha rhythms of relaxed waking becomes less regular and wane and eyes start to make slow, rolling movement. It is fleeting and only last a few minutes.
Theta waves
Stage 2: Slightly deeper, may last 5-15 mins. Includes occasional 8-14Hz sleep spindle generated by a thalamic pacemaker). And high-amplitude K-complex. Eye movements almost cease.
Sleep spindles
Stage 3: Large amplitude, slow delta rhythms. Eye and body movements usually absent.
Stage 4: Deepest stage of sleep: Large EEG rhythms of 2Hz or less. Can last 20-40 mins.
more delta waves
REM: Sleep will lighten from stage 4 to stage 2 (for about 15 mins) before entering brief period of REM. Frequent eye movements, fast EEG rhythms.
Low voltage, high frequency
Stage 1 sleep
Stage 1: Transitional sleep. Alpha rhythms of relaxed waking becomes less regular and wane and eyes start to make slow, rolling movement. It is fleeting and only last a few minutes.
Theta waves
Stage 2 sleep
Stage 2: Slightly deeper, may last 5-15 mins. Includes occasional 8-14Hz sleep spindle generated by a thalamic pacemaker). And high-amplitude K-complex. Eye movements almost cease.
Sleep spindles
Stage 3 and 4 sleep
Stage 3: Large amplitude, slow delta rhythms. Eye and body movements usually absent.
Stage 4: Deepest stage of sleep: Large EEG rhythms of 2Hz or less. Can last 20-40 mins.
more delta waves
REM sleep
REM: Sleep will lighten from stage 4 to stage 2 (for about 15 mins) before entering brief period of REM. Frequent eye movements, fast EEG rhythms.
Low voltage, high frequency
Physiological changes during non-REM & REM sleep
Non-REM sleep
Steady HR, BP and respiration rate
Muscles relaxed
REM sleep
Fluctuating HR, BP and respiration rate
Skeletal muscles profoundly relaxed (though body movements may occur)
Sleep aids memory before learning:
The hippocampus offers a short term reservoir/temporary information store, for new memories. BUT it has a limited storage capacity (e.g. a USB memory stick). Exceed its capacity and you may not be able to add more information or, equally as bad, you may overwrite one memory with another (called interference forgetting).
How does the brain deal with this capacity issue?
Sleep: Acts as a file-transfer mechanism. It moves recently required information to more permanent, long-term storage locations, freeing up short term memory stores.
Result? We awake with a refreshed short-term storage and greater ability for new learning.
Sleep aids memory after learning:
Sleep protects newly acquired information and affords immunity against forgetting: memory consolidation.
Which sleep period offers a greater memory saving benefit: NREM or REM?
For fact based, text-book like memory: Early night sleep, rich in deep NREM
NREM sleep can also help you to recover memories you could not retrieve before sleep e.g. like a computer file that has become corrupted and inaccessible, sleep helps to repair those memories and can allow you to retrieve them the following morning.
NREM also very important for ‘forgetting information we no longer need’. We actively delete memories during NREM to improve learning efficiency and improve the ease of memory recollection.
REM sleep helps the brain to gather disparate sets of knowledge fostering impressive problem solving abilities.
What are the neural mechanisms of sleep?
Serotonin (raphe nucleus), noradrenaline (locus coreolus), acetylcholine
Diffuse modulatory systems control rhythmic behaviours of thalamus, which controls EEG rhythms of cortex. Sleep related rhythms of the thalamus ‘gate’ the flow of sensory information to the cortex
Hypothalamic SCN provides circadian drive
Pontine (ACh) REM-on cells - increased firing prior to inducing REM sleep
Raphe/LC (5HT/NA) REM-off cells - decreased firing of pontine cells, inducing non-REM sleep
Sleep pressure
Sleep pressure
Adenosine levels increase every waking minute.
The longer you are awake, the more adenosine you will accumulate = sleep pressure.
Adenosine acts on the sleep promoting centres (and turns down wakefulness centres).
When adenosine concentration levels peak an irresistible urge for sleep occurs (in most people after about 12-16 hours of being awake)
Caffeine is an adenosine receptor antagonist as so temporarily reduces sleep pressure.
Rapid eye movement disorder
Normally pons instrumental in inhibiting muscle tone during REM sleep (pontine reticulospinal pathways) to prevent the ‘acting out’ of dreams.
Muscle tone is not prevented in this condition thus can act out their dreams.
Narcolepsy
Attacks of sleep at times and places where sleep does not normally occur e.g. in the car whilst driving. Maybe associated with loss of hypocretin.
Insomnia
Characterised as a chronic inability to fall asleep despite appropriate opportunities to do so.
signs of Skull Fracture and treatment
Raccoon eyes – bleeding into anterior skull base
CSF leak – from tear in dura
Otorrhea
Rhinorrhea
Hemotympanum
Cranial nerve dysfunction
Battle’s sign - bruising behind ear
Most isolated skull fracture managed conservatively, subgaleal or scalp haematoma included
If open (including into the ear/nose/facial air sinus) risk of CSF leak and meningitis - patient should be given Meningitis vaccine
Most leaks stop but refer ENT or Neurosurgery
Fractures in children need follow up to avoid ‘growing fractures’
Extradural (epiddural) haematoma - who affected most, ow it presents and caused, investigation and findings
Young people
Lucid interval
Usually associated with temporal skull fracture
Tearing of vessel such as middle meningeal artery
Blood between skull and dura
CT – convex ‘lenticular’
Midline shift and brain compression
Subdural Haematoma - who affected most, ow it presents and caused, investigation and findings
Elderly ; alcoholics – shrunken brains
Tearing of veins between dura and brain
Bleed into the subdural space
May resolve with medical management – stop anticoagulation +/- steroids
Ct: concave
Varying density
Midline shift and brain compression
Brain Contusions
Commonest where brain impacts on base of skull - poles of each lobe
bruising
Subarachnoid Haemorrhage - who affected most, ow it presents and caused, investigation and findings
Bleed into subarachnoid space
Ruptured aneurysm ‘berry’
Trauma – most common cause
CT subarachnoid haemorrhage basal cisterns containing blood
Diffuse Traumatic Axonal Injury
Most severe type of concussion
Tearing of axons
CT may be “NAD”
MRI will show microhaemorrhages and swelling
Patient may be much worse clinically than imaging suggests
Duret haemorrhage midbrain
Post mortem: Axonal spheroids, Microglial clusters
Normal intercranial pressure
10-20mmHg
Transtentorial hernia
Increased intercranial pressure forces the movement of brain tissue from one intracranial compartment to another
Third nerve palsy – fixing and dilating of pupils on of the first signs
Tonsillar herniation
Movement of the cerebellar tonsils through the foramen magnum
Brainstem compression -> cardiorespiratory arrest
‘Coning’
Cushing response – decreased consciousness, bradycardia, hypertension
Usually irreversible
Glasgow coma score
The GCS is scored between 3 and 15, 3 being the worst, and 15 the best.
Best Eye Response
1 - No eye opening.
2 - Eye opening to pain.
3 - Eye opening to verbal command.
4 - Eyes open spontaneously.
Best Verbal Response.
1 - No verbal response
2 - Incomprehensible sounds.
3 - Inappropriate words.
4 - Confused
5 - Orientated
Best Motor Response. (6)
1 - No motor response.
2 - Extension to pain.
3 - Flexion to pain.
4 - Withdrawal from pain.
5 - Localising pain.
6 - Obeys Commands
Coma Scores
13 or higher mild brain injury,
9 to 12 moderate injury
8 or less severe brain injury (coma)
Post Concussion Syndrome
Headache 30% persist >2/52
Dizziness – non specific
Lethargy
Depression
Lack of concentration
Transient ischaemic attack
Symptoms last < 24 hours (WHO definition)
Note:
Most TIA resolve within 1 hour
Some TIA are due to primary haemorrhage (0.5%)
Amourosis fugax
A retinal TIA
Transient monocular blindness, painless.
Types of stroke percentages
Ischaemic stroke 85 %
Intracerebral haemorrhage 10 %
Sub-arachnoid haemorrhage 5 %
The ischaemic penumbra
Region of brain at risk to persistent infarct
S&S posterior vs anterior stroke
Posterior:
Ipsilateral cranial nerve palsy with contralateral motor and/or sensory deficit
Bilateral motor and/or sensory deficit
Disconjugate eye movement
Cerebellar dysfunction, e.g. ataxia
Isolated homonymous hemianopia
Anterior
Loss of awareness of one
side of body
‘Difficulty’ speaking
Both
Slurred speech
Weakness
Loss of sensation
Loss of vision
Strokes affect on optic pathway and outcome
Pre-chiasmal lesionswill result in anipsilateral monocular visual field defect
Post-chiasmal lesionswill result inhomonymous visual field defects of the contralateral side
Homonymous contralateral quadrantanopia (optic radiation)
temporal lobe - homonymous upper quadrantanopia
parietal lobe - homonymous lower quadrantanopia
OCSP Classification (Bamford)
TACS
Motor or sensory hemiparesis
Homonymous hemianopia
Higher cortical dysfunction
PACS
Any combination of 2 of the above, or isolated cortical dysfunction
LACS
Motor and/or sensory hemiparesis (at least 2 of 3 of face hand and leg involvement)
Ataxic hemiparesis
POCS
Multiple signs and symptoms as described
OCSP - Total anterior circulation syndrome
Motor or sensory hemiparesis and
Homonymous hemianopia and
Higher cortical dysfunction
OCSP - Partial anterior circulation syndrome
Isolated higher cortical dysfunction or
Any combination of 2 of:
Hemiparesis
Homonymous hemianopia
Higher cortical dysfunction
OCSP - Lacunar syndrome
Pure motor stroke or
Pure sensory or
sensorimotor stroke or
ataxic hemiparesis
OCSP - Posterior circulation syndrome
Isolated hemianopia, brainstem or cerebellar
Which vascular territory is most likely affected and what is their OCSP classification?
(1) Patient present with bumping into things and is found to have a hemi-anopia in his left visual field of both eyes.
(2) Patient has an expressive dysphasia and a right-sided homonymous hemi-anopia
(3) Patient has a hemi-paresis on the left side affecting motor and sensory function, there are no cranial nerve signs or ataxia.
(1) Patient present with bumping into things and is found to have a hemi-anopia in his left visual field of both eyes.
= Posterior circulation syndrome
(2) Patient has an expressive dysphasia and a right-sided homonymous hemi-anopia
= Partial anterior circulation syndrome
(3) Patient has a hemi-paresis on the left side affecting motor and sensory function, there are no cranial nerve signs or ataxia.
= Lacunar syndrome
Treatment for ishaemic strokes
Thrombolysis
- Alteplase
- Tenecteplase
Time window
- 4.5 hours – standard imaging
Mechanical thrombectomy (MT) for large vessel occlusion (LVO) in conjunction with iv Recombinant tissue plasminogen activator
Treatment for TIA
TIA and minor stroke (NIHSS<4):
Aspirin + Clopidogrel 21 days
Then clopidogrel indefinitely
If clopidogrel resistance
Aspirin + Ticagrelor 30 days
Then clopidogrel or Ticagrelor indefinitely
Or Aspirin & dipyridamole
Haemorrhagic Stroke: Treatment
Reverse anticoagulation
Warfarin - PCC (e.g. octaplex)
NOACs – idarucizimab for dabigatran, adenexat-alpha (FXa inhib)
Blood pressure
aggressive lowering of BP may reduce haemtoma growth (INTERACT trial)
Guidelines: lowering BP <140 mmHg in the first hour of admission may reduce disability (INTERACT-2 trial)
Surgery
craniotomy and evacuation
external ventricular drain to relieve hydrocephalus
Where is inner ear
Housed in the petrous part of the temporal bone
External acoustic meatus and middle ear located laterally
Internal acoustic meatus located medially
What does inner ear contain (2)
Bony and membranous labyrinth
Bony labyrinth
Composed of the:
Vestibule
Three semicircular canals: Anterior, posterior, lateral
Cochlea
Periosteum-lined cavities in temporal bone which contain perilymph (clear fluid)
Vestibule has oval window on lateral wall and is the central space in the bony labyrinth
Membranous labyrinth
Composed of endolymph-filled spaces:
Semicircular ducts (in canals)
Cochlear duct (in cochlea)
Utricle and saccule (in vestibule)
Cochlear duct is for sense of hearing
Semicircular ducts, utricle and saccule are part of the vestibular apparatus (for sense of balance)
Cochlear structure
Cochlea: bony structure which twists on itself 2½ - 2¾ times around the modiolus (central column)
Base of cochlea faces posteromedially
Apex faces anterolaterally
Wide base of modiolus is near internal acoustic meatus
Associated with branches of the cochlear part of CN VIII
Thin bony spiral lamina (lamina of the modiolus)
Cochlear duct circles around the modiolus
Cochlear duct
Endolymph-filled cochlear duct (scala media) has two perilymph-filled canals next to it:
Scala vestibuli: continuous with vestibule
Scala tympani: separated from middle ear by round window
Continuous with each other at the helicotrema (narrow slit at cochlear apex)
Cochlear canaliculus: connection between perilymph-filled scala tympani and subarachnoid space
Spiral organ
Spiral organ: organ of hearing
Spiral ligament (lateral wall): thickened layer of periosteum
Vestibular membrane (roof): separates endolymph in cochlear duct from perilymph in scala vestibuli
Basilar membrane (floor): separates endolymph in cochlear duct from perilymph in scala tympani
Transmission of sound
Sound waves entering the external ear strike the tympanic membrane, causing it to vibrate
Vibrations initiated at the tympanic membrane are transmitted through the ossicles of the middle ear and their articulations
The base of the stapes vibrates with increased strength and decreased amplitude in the oval window
Vibrations of the base of the stapes create pressure waves in the perilymph of the scala vestibuli
Pressure waves in the scala vestibuli cause displacement of the basilar membrane of the cochlear duct
Short waves (higher frequency/pitch) cause displacement
near the oval window
Longer waves (lower frequency/pitch) cause more distant
displacement, nearer to the helicotrema at the apex of the
cochlea
Movement of the basilar membrane activates the hair cells
of the spiral organ
Action potentials conveyed by the cochlear nerve to the
brain
Vibrations are transferred across the cochlear duct to the perilymph of the scala tympani
Pressure waves in the perilymph are dissipated (dampened) by the secondary tympanic membrane at the round window into the air of the tympanic cavity
Vestibulocochlear nerve (CN VIII)
Cochlear (acoustic/auditory) nerve: neuronal cell bodies in spiral ganglion
Vestibular nerve: neuronal cell bodies in vestibular ganglion
Both travel together as CN VIII through internal acoustic meatus to reach dorsal and ventral cochlear nuclei of rostral medulla
Central auditory pathway
CN VIII through internal acoustic meatus to reach dorsal and ventral cochlear nuclei of rostral medulla - Project to both sides of the brainstem and primary auditory cortex
Dorsal and ventral cochlear nuclei contain cell bodies of second order neurons
Second order neurones from cochlear nuclei ascend in the pons:
Many decussate in trapezoid body and synapse in contralateral superior olivary nucleus
Some from ventral cochlear nucleus don’t decussate but synapse in ipsilateral superior olivary nucleus instead
Some from dorsal cochlear nucleus decussate but don’t synapse at all in pons and continue to ascend to midbrain
Neurones ascend via lateral lemniscus from superior olivary nucleus to synapse in inferior colliculus (midbrain)
Dorsal part of the inferior colliculus receives projections from neurones responding to low frequency sounds:
Ventral part receives projections from neurones responding to high frequency sounds
Auditory information is then processed and relayed to the medial geniculate nucleus of the thalamus.
Neurones ascend from medial geniculate nucleus (thalamus) through the internal capsule to the primary auditory cortex of the temporal lobe
Descending auditory tracts
Primary auditory cortex also has descending fibres to superior olivary nucleus (olivocochlear fibres) as a form of feedback
Connections to CN V and CN VII motor nuclei to cause reflex contraction of tensor tympani and stapedius muscles in response to loud sounds
Conductive hearing loss
associated with conductive part of hearing pathway
External ear disorders e.g. foreign bodies or build-up of wax in external acoustic meatus
Middle ear causes e.g. otitis media, rupture of tympanic membrane (eardrum)
Sensorineural hearing loss
associated with neural part of hearing pathway
Includes cochlear damage as well as lesions to central auditory pathway (brainstem, thalamus or primary auditory cortex)
Presbycusis: age-related hearing loss
Romberg’s test and sign
We remain stable if we have 2 out of Visual, Proprioceptive, Vestibular; If we lose 2 inputs we become unstable
Romberg’s test: Patient closes eyes standing straight
Negative Romberg test = patient remains steady
Positive Romberg test = patient falls
Tests for dorsal column issues; as vision is removed and vestibular is not active.
Two parts to vestibular system
Dynamic and static Labyrinth
Dynamic labyrinth: semicircular canals - what does what
Semicircular canals convert rotational motion of head/body into neural impulses - Superior, posterior and lateral semicircular canals
Superior: lateral flexion of head
Posterior: nodding of head
Lateral: Shaking head
Canals are arranged in a mutually perpendicular manner (superior, lateral, posterior) to cover 3 planes of motion
Signalling from a canal can be increased or decreased depending on direction of movement
Act to move eyes and neck in response to head movement (vestibulo-ocular reflex)
Static labyrinth: utricle and saccule
The maculae provide information on head position relative to the trunk and can sense linear acceleration
Otoconia of otolithic membrane in the maculae help to deflect hair cells within the endolymph
Utricular macula detects horizontal acceleration e.g. driving
Saccular macula detects vertical acceleration e.g. falling
Rotational acceleration detected by
Cupula at end of the semi-circular canals
Central vestibular pathways
The central processes of vestibular neurons from the semicircular canals synapse with descending motor neurons in the medial vestibular nuclei
Medial vestibulospinal tract (medial VN) projects to cervical cord bilaterally
For accessory nerve for movement of head
The central processes of vestibular neurons from the utricle and saccule synapse with descending motor neurons in the lateral vestibular nuclei
Lateral vestibulospinal tract (lateral VN) descends to all levels of cord, ipsilateral
Innervates extensor muscles of lower limb (anti-gravity muscles)
Cerebellum has a modulatory role
Vestibulo-ocular reflex
The vestibulo-ocular reflex allows for conjugate eye movement, coordination of eye and head movements and visual fixation
Via the medial longitudinal fasciculus
Forming a 3d image - scanning
Rapid eye movements when scanning immediate surroundings
Saccades = scanning
Moving the eye to collect impressions and construct an image
Vertigo
hallucination of movement i.e. spinning
Central vertigo or peripheral vertigo
mismatch between balance inputs
Meniere’s disease
Increase in endolymph
nausea, vertigo, hearing loss
Motion sickness
disconnection of visual and vestibular inputs can trigger nausea
Nystagmus + e.g. If left side is damaged
Nystagmus is continuous, uncontrolled movement of the eyes
Involves the vestibulo-ocular reflex
Biphasic or jerk nystagmus is the most common type
Characterised by slow drift in one direction, followed by fast correction/recovery in the opposite direction
The direction of the fast phase designates the direction of the nystagmus
Normally: Eyes slowly move away from increased activity/Eyes move towards decreased activity = head looks right => eyes look left
e.g. If left side is damaged .: decreased activity => eyes move towards left side then cortex corrects it to midline
Benign paroxysmal positional vertigo (BPPV) and treatment
Most common cause of peripheral vertigo
Displacement of otoconia (calcium carbonate crystals) into semi-circular canals - most commonly posterior noticed when nodding head or turning over in bed
Epley manoeuvre – uses gravity to pull otolith debris out of affected semicircular canal and into the utricle
Sequential movement of the head into four positions (for ~30 seconds each)
Most common canal affected by bppv
most commonly posterior semicircular canal - noticed when nodding head or turning over in bed
Caloric reflex test
Test of vestibular function: temperature-induced nystagmus
Cold water syringed into external acoustic meatus while patient is supine with their head raised 30 degrees from the couch
Allows their lateral (horizontal) semicircular canals to be in a vertical position
Cold water will cool the endolymph in the lateral semicircular canal
Closest one to the external acoustic meatus
Cooling inhibits firing of ipsilateral vestibular afferents
Normal response is nystagmus
Cold water: fast phase is in the direction of the opposite ear being irrigated e.g. to the right side of the left ear
Warm water: nystagmus with a fast phase to the same side being irrigated
COWS: Cold water, Opposite side; Warm water, Same side
Damage to basilar pons =>
Locked in syndrome
Significant loss of function associated with corticobulbar and corticospinal tracts
Paralysis of most motor functions including limbs and functions associated with motor cranial nerves
Only blink and vertical gaze retained
Planning of movement cortex areas
M1: primary motor cortex
PMA: premotor cortex - plays a role in movements that require visual guidance
SMA: Supplementary motor area (SMA) receives inputs from basal ganglia and cerebellum. Has an important role in coordinating voluntary movement.
Primary somatosensory - plays a role in movements that require visual guidance e.g. paying attention to spatial arrangements of objects in the visual field. Integrates somatosensory and visual inputs to area 6
posterior parietal AA - integrates visual inputs
Cerebellum actions
Operates at an unconscious level
Controls maintenance of equilibrium (balance)
Influences posture and muscle tone
Coordinates movements
Detects errors (compares intended movements to actual movements)
Plays a major role in attention and planning of motor learning (automaticity)
Cerebellum has 3 main functional regions
Spinocerebellum:
Midline vermis and surrounding paravermis
Receives major spinal cord inputs
Principally from spinocerebellar tracts
Regulates axial muscle tone and posture
Somatotopically organised
Neocerebellum:
Remainder (and vast majority) of cerebral hemispheres)
Receive major pontocerebellar fibres
Muscular coordination, trajectory, speed and force
Vestibulocerebellum:
Flocculonodular lobe (& posterior vermis)
Connections with vestibular & reticular nuclei
Balance/equilibrium
Status of head position & control of eyes
Axial muscle control
Cerebellar peduncles
Superior peduncle:
Mainly efferent fibres
Main output route of cerebellum
Emerge from cerebellar nuclei
Synapse with contralateral red nucleus and ventrolateral nucleus of thalamus
Middle peduncle:
Mainly afferent fibres
2nd limb of di-synaptic pathway linking cerebral cortex with cerebellar cortex
Fibres originate in contralateral pontine nuclei
Inferior peduncle:
Mainly afferent fibres
Bring information from medulla and spinal cord
Terminate in cerebellar cortex
Inputs and outputs of the cerebellum
cortex -> pons -><- Cerebellum
Vestibular nucleus -> <-
Inferior olive -><-
Spinal cord ->
Red nucleus <-
Cerebellar disease/damage causes ipsilateral symptoms:
Ataxia:
Disturbance of voluntary movement
Tremor (no resting tremor) when carrying out motor tasks
Errors in direction, range, rate and force of movement
Hypotonia: reduced muscle tone
Dysdiadochokinesia: no rapidly alternating movements
Pendular reflexes: no limit by stretch reflexes
Nystagmus: rhythmical eye movements (linked to vestibular system)
Intention tremor: tremor when coming to the end of a determined and visually directed movement
Gait ataxia: wide stance gait
Dysmetria: lack of coordination – overshoot/undershoot of intended position
Tonsillar herniation
Descent of cerebellar tonsils (+/- brainstem) below the foramen magnum
Cause?
Secondary sign of intra-cranial mass effect (e.g. tumour, haemorrhage, abscess etc). Will displace cranial fossa structures inferiorly.
Outcome?
If brainstem is compressed respiratory and cardiac centres will be interrupted in medulla and pons (life threatening)
Chiari malformations
Skull not large enough
Displaces structures inferiorly
Interrupts CSF flow
Outcome?
Chiari type I: Displaces cerebellum - headaches, visual disturbances, nystagmus, ataxia (usually non-life threatening)
Chiari II: Displaces cerebellum & brainstem – life threatening
The basal ganglia are composed of:
the caudate nucleus and putamen (collectively known as the striatum)
Globus Pallidus (two divisions):
Internal Globus Pallidus (GPi)
External Globus Pallidus (GPe)
the subthalamic nucleus
Substantia Nigra (two divisions):
Substantia Nigra pars reticulata (SNr)
Substantia Nigra pars compacta (SNc)
Basal ganglia action at rest:
At rest, basal ganglia have an inhibitory influence on thalamus thus reducing thalamic input to cortex
Cortico-striatal pathway - specific areas of cerebral cortex target different parts of striatum:
sensory and motor areas > Putamen
association areas and frontal eye fields > Caudate nucleus
The corticostriatal pathway output/nerve types
The corticostriatal pathway consists of glutamatergic excitatory input from the cerebral cortex to the striatum
Striatal neurones are medium spiny type and are mainly GABAergic
Basal ganglia direct vs indirect pathways
Activation of DIRECT pathway reduces basal ganglia output and thus increases thalamic activity (thereby increasing motor activity of cortex)
Pathway: cortex -> striatum -> globus pallidus, pars interna -> thalamus -> motor cortex
Activation of INDIRECT pathway increases basal ganglia output and thus decreases thalamic activity (thereby decreasing motor activity of cortex)
Pathway: cortex -> striatum -> globus pallidus, pars externa -> subthalamic nucleus -> globus pallidus, pars externa -> thalamus -> motor cortex
Substantia nigra pars compacta (SNc) action on bsal ganglia
Dopamine maintains the balance through its actions at different dopamine receptors on striatal projections neurones:
Dopamine increases transmission along the DIRECT pathway through activation of D1 receptors.
Dopamine decreases transmission along the INDIRECT pathway through activation of D2 receptors.
Making the thalamus and cortex more easily excited
Parkinson’s in the basal ganglia pathways
The indirect pathway predominates making the thalamus & cortex less easily activated
This is because normally, Dopamine increases transmission along the DIRECT pathway through activation of D1 receptors and decreases transmission along the INDIRECT pathway through activation of D2 receptors.
Multiple sclerosis (MS) definition
Plaques of demyelination in the white matter of the central nervous system
Multiple because they are separated in time and space
Sclerosis because they are firm as a result of astrocytic scarring
Environment and gene effect on MS
EBV
Being truly negative protects
Symptomatic EBV infection doubles chance (infectious mononucleosis)
Molecular mimicry?
Sunshine (UVB) & Vitamin D
Incidence increases with latitude
High vitamin D relatively protective
Low vitamin D may be result of environment, lifestyle &/or genes
Tobacco smoking
Increases risk by 50% ?contributes to female:male ratio?
Females:Males 3:1
Ways MS can progress
Prodromal phase
could be decades
Clinically isolated syndrome (CIS)
majority go on to develop MS
Primary progressive MS (PPMS)
15%
Relapsing remitting MS (RRMS)
85%
Secondary progressive MS (SPMS)
20-60% of RRMS
Multiple sclerosis Common presentations & findings
Unilateral optic neuritis
Blurred vision with associated pain on movement
Partial myelitis
Extremity and torso impaired sensation, weakness, and/or ataxia
Focal sensory disturbance
Limb paraesthesias, abdominal or chest banding [dysesthesia]
Lhermitte phenomenon
Brainstem syndromes
Internuclear ophthalmoplegia
Vertigo
Hearing loss
Facial sensory disturbance
Internuclear ophthalmoplegia
Eyes don’t move together
MS diagnosis
Clinical history/examination
History = process
Examination = location
Lumbar puncture (CSF)
Oligoclonal bands (OCBs)
IgG immunoglobulins secreted by plasma cells in the CNS, when compared to serum analysis (paired samples)
Present in 95% of MS patients
Clinicoradiological
Dissemination in space (DIS)
The presence of demyelinating lesions in distinct CNS anatomical locations
Infratentorial
Juxtacortical
Cortical
Periventricular
Spinal cord
Dissemination in time (DIT)
The development of new demyelinating lesions over time
Multiple distinct clinical attacks
Development of a new T2 lesion on follow-up MRI
A single MRI if simultaneous presence of gadolinium-enhancing (acute) and non-enhancing lesions (chronic) at one time
A single clinical attack with cerebrospinal fluid–specific oligoclonal bands
MS mimics
Other demyelinating diseases
E.g. neuromyelitis optica (anti-AQP4)
Infections
E.g. Lyme disease (Borrelia burgdorferi)
Metabolic diseases
E.g. B12deficiency
Systemic diseases
E.g. neurosarcoidosis
Other
E.g. vasculitis
Key pathology of MS
Central nervous system
Inflammation
Demyelination
Astrocytic scarring (gliosis)
Neurodegeneration (axons/nerve cell loss)
Little known
Mild Cognitive Impairment vs dementia
Mild Cognitive Impairment
Can affect memory, language, problem solving and visual spatial awareness.
Big difference from dementia is that is does not greatly affect daily living.
5-20% of those over 65 have it.
10-15% develop dementia later.
Dementia Definition
Cognitive impairment: decline in both memory and thinking sufficient to impair personal ADLs
Problems with the processing of incoming information - problems with maintaining and directing attention
Clear consciousness
Above syndrome present for
>= 6 months
Dementia diagnosis
History:
Explore change in cognition, behaviour and psychological symptoms.
Impact of daily functioning
Risk
Most important diagnostic information is the course of symptoms over time. Patient wont be able to tell you- Collateral is KEY.
Why have they come now.
Examination:
Physical- Neurological and CVS.
Mental state Examination:
Appearance and Behaviour
Speech
Mood (subjective and objective)
Thought (form and content)
Perception
Cognition
Insight
Cognitive Assessment
Most commonly used is the Addenbrookes (ACE-III)
Investigations
Blood
ECG
CT/MRI head.
If unclear may consider SPECT
or DAT scan.
Normal does not exclude dementia
Alzheimer - presentation, pathology, RF
Presentation:
Amnesia: Recent memories lost first
Aphasia: Word finding problems
Agnosia: Recognition problems
Apraxia: Inability to carry out skilled tasks
Atrophy of hippocampus, parietal, temporal
Plaque formation - Beta amyloid prevent cell-cell interaction
Neurofibrillary tangles - Tau - prevent cell transport
Cholinergic loss.
Age is most common risk factor
Genetic link more with early onset
Vascular risk factors
Low IQ
Head injury.
Vascular dementia - presentation, pathology, RF
Stepwise progression.
Symptoms reflect the sites of lesions
Maybe patchy with some cognition can be spared
Neurological signs maybe present.
Often see night time confusion,
Due to infarcts- single or multiple
Can be caused by thrombo-embulus or arteriosclerosis
Small vessel disease can be noted on scan
Older Age
More in Males
Smoking
HTN
Diabetes
HF
Hypercholesterolemia
Lewy Body dementia - presentation, pathology, RF
Two of three should alert you:
Fluctuating confusions with marked variation in levels of alertness.
Vivid visual hallucinations
Spontanous parkinsonian signs.
Consider in those with repeated falls, syncope and transient loss of consciousness.
Eosinophilic intracytoplasmic neuronal structures.
Found in brainstem, neocortex and cyngulate gyrus.
Risk factors unknown
Parkinsons dementia
Have motor symptoms of Parkinsons disease for at least one year prior to the start of cognitive symptoms.
Very similar in presentation to Lewy Body: Fluctuating confusions with marked variation in levels of alertness.
Vivid visual hallucinations
Spontanous parkinsonian signs.
Frontal Temporal Dementia
Uncommon.
Generally a younger age of onset.
Symptom profile:
Personality changes- impulsivity and inappropriate.
Language changes- slowed, struggle with word finding and placement.
Reduced Mental functioning
Memory Problems.
Causes of neuronal cell death
Excitotoxicity
Oxidative stress - ROS
Nitric Oxide - ROS
Unfolded protein response
upregulates molecular chaperone proteins
Abnormal proteins are tagged with ubiquitin
Protein misfolding response in brain disease
In neurodegenerative diseases there is an accumulation of abnormally folded proteins - or a failure of the normal cellular mechanisms for their disposal
The spread of Alzheimer’s - Braak
Early (entorhinal cortex & hippocampus)
Intermediate (limbic lobe, amygdala)
Late ( association areas of neocortex & finally to sensory/motor)
Lewy bodies
Abnormal protein accumulations in the cytoplasm of surviving neurones
Rounded intraneuronal structures with white ‘halo’
Major constituent is alpha-synuclein (hallmark of PD) - Synucleinopathy
Lewy body pathology begins in olfactory bulbs and medulla
Spreads through 6 Braak stages
To pons, midbrain, limbic lobe, amygdala, neocortex
Huntington’s disease
Signs:Chorea – spontaneous, irregular jerky movements
Dementia
Changes in mood & personality
An inherited, autosomal dominant condition with mean age of onset of 40: 35-150 CAG repeats in the huntingtin gene (chr 4)
Leads to abnormally long polyglutamine inclusions
This is toxic to neurones; predominantly in the striatum, but also in cortex
Highly disabling and progressive average life expectancy after diagnosis is 15 years
Left vs right parietal damage
Left: Impaired verbal short term memory (can only repeat back 2-3 letter at a time)
Agraphia (inability to communicate through writing)
Dyscalculia (difficulty in performing calculations)
Right: Constructional apraxia (inability to copy drawings or manipulate objects to form patterns or designs)
Disengagement – cannot shift attention from one stimulus to another
Impaired visual short term memory
Anosognosia (a deficit of self-awareness – patients are unaware of the existence of their disability
Hemineglect left vs right parietal damage
Left hemisphere lesion = neglect not as severe
Right hemisphere lesion = left neglect
RIGHT LESION BAD
The limbic system function
Processing and responding to pain and intense emotions e.g. fear, anger, joy
Regulation of visceral responses to emotion (e.g. autonomic responses to stress)
Helps regulate other body processes e.g. sleep, appetite, sexual function
Important roles in memory, motivation and learning
Components of the limbic system
Limbic cortex: ring of cortex formed by cingulate gyrus, hippocampus and parahippocampal gyrus
Subcortical nuclei: amygdala, nucleus accumbens, septal nuclei, hypothalamus
Receives many inputs from elsewhere in the brain and has many outputs
Where does papez circuit start and end
Hippocampus is the start and end of the circuit. Fornix connects hippocampus to hypothalamus
Short-term memory
Short-term memory: recalled minutes, hours after a stimulus
Working memory: conscious ability to manipulate information held in short-term memory
Problem solving, reasoning
Awareness of emotional or social cues during conversations
Working memory controlled by lateral prefrontal cortex and association areas of temporal and parietal lobes
Long-term memory
Long-term memory: recalled weeks, months, years after a stimulus with structural changes in neurons e.g. protein synthesis, increased synaptic strength, increased neuronal excitability
Declarative (explicit) memory: can be put into words
Semantic memory: common knowledge e.g. names of countries
Episodic memory: personal experiences e.g. a party you attended
Non-declarative (implicit) memory: semi-automatic learning
Procedural memory: learning and performing motor skills (‘muscle memory’)
Amnesia types
Amnesia is the loss of declarative memory
Retrograde amnesia = unable to remember events from before an injury
Anterograde amnesia = unable to remember new events after an injury
Procedural memory is unaffected but unable to recall practicing tasks or skills
Declarative memory stages
Encoding:
Processing information into a representation of a memory
Improved by paying attention, mood, drawing connections between information
Consolidation
Stabilising memories
Synaptic connections become stronger with repeated activation (long-term potentiation)
Medial temporal lobe directs storage of memories across large networks of neurons elsewhere - engrams (basic unit of memory)
Retrieval
Accessing and using memories in different ways e.g. recall, recognition
Prefrontal cortex and cingulate cortex play key roles e.g. learning
Important for learning e.g. spaced retrieval practice
Structures contributing to memory
Medial temporal lobe (hippocampus, amygdala, parahippocampal cortex) has major role in memory and connections to many other structures
Lateral prefrontal cortex: keeps working memory ‘on-task’. Involved in processing and retrieving declarative memory
Association areas in temporal, parietal and occipital lobes: declarative memory and integrating sensory perceptions
Cingulate cortex: helps direct attention and processes emotions in relation to memory, especially anterior cingulate cortex.
Cerebellum and striatum (basal ganglia): procedural memory e.g. learning how to play a musical instrument. Adjusting and refining movements
Thalamus: anterior nuclei have a key role in episodic memory
Anterior hippocampus lesion
Bilateral lesions of the anterior hippocampus can cause anterograde amnesia
Left and right hippocampal formations have different roles in relation to declarative memory
Left hippocampus helps to encode verbal memories
Right hippocampus helps to encode spatial memories
London taxi drivers have greater right posterior hippocampal volume, but reduced anterior volume
Complex mental map of London, but there’s a trade-off: less able to learn new visuospatial skills
Blood supply to hippocampus
Blood supply to hippocampus = anterior choroidal artery branches
Some branches from posterior cerebral artery to posterior hippocampus
Clinical relevance: temporal lobe epilepsy surgery
Cingulate cortex
Key part of Papez circuit – receives projecting fibres from anterior nucleus of thalamus and is continuous with parahippocampal gyrus
Perception of pain and role in emotional regulation
Learning and memory – positive emotional responses promote learning
Autonomic area – specifically related to visceral responses that occur during sad emotional states
Other roles in bladder control, speech, executive function
Links to insular cortex – self-awareness, interoception
Role in mood disorders like depression. Cingulate cortex lesions or reduced activity can cause indifference to pain or emotional stimuli - flattened affect, low motivation
Blood supply = anterior cerebral artery
Amygdala
Located more anteriorly in medial temporal lobe
Extensive connections to and from other parts of limbic system – helps react to the world around you e.g. threats
Processing fear, stressful stimuli
Overactivity = anxiety, aggression, defensiveness
Connections to autonomic and endocrine pathways e.g. to increase heart rate
Role in appetite
Helps regulate sexual function (especially restraint)
Blood supply = anterior choroidal artery
Reward centres: nucleus accumbens and septal area
Nucleus accumbens
Role in addictive behaviours
Motivation, reward-based learning
Septal nuclei
Roles in pleasure, social connection, empathy
Patients with lesions can display antisocial behaviour
Wernicke-Korsakoff syndrome
Wernicke’s encephalopathy = acute confusion, loss of coordination and gaze paralysis (ophthalmoplegia)
Small haemorrhages in mammillary bodies and damage to connections with hippocampi
Results from chronic alcoholism – vitamin B1 (thiamine) deficiency
Repeated episodes may cause Korsakoff’s psychosis
Anterograde amnesia
Confabulation – patient creates fictitious memories but believes they are real
Kluver-Bucy syndrome
Bilateral temporal lobe lesions e.g. bilateral stroke, traumatic brain injury, neurodegenerative disorders
Bilateral destruction of amygdala
Hyperorality (compulsion to put objects in mouth)
Placidity - fear and aggression may be absent
Hypersexuality – loss of restraint
Visual agnosia – difficulty recognizing familiar objects or faces
Which type of meningitis causes a Purpuric Rash
Purpuric Rash of Meningococcal meningitis
Meningococcal meningitis
Purpuric Rash, most common
Common organism causes of meningitis
Neisseria menigitidis
Streptococcus pneumoniae
Listeria moncytogenes
Haemophilus influenza
Viral (lots of them!)
Pneumococcal meningitis
more common in the elderly and in alcoholics
infection may spread from an adjacent site
Can occur with a chest infection (if you get meningitis, pneumonia and endocarditis it is called Osler’s triad)
Mortality remains very high at 15-40% and neurological sequelae continue to occur in up to 50% of survivors
Osler’s triad
Osler’s Triad (Austrian syndrome) is a rare but deadly triad comprising meningitis, endocarditis, and pneumonia.
Pathogenesis of pneumococcal meningitis
nasopharyngeal colonisation and requirement to evade the local immune response
bacteraemia and activation of complement and coagulation
inflammatory mediators facilitate crossing of the blood brain barrier
bacteria multiply in the CSF and trigger massive inflammation in sub-arachnoid space
Meningitis diagnosis at the bedside
Symptoms
Fever and headache are important but non-specific
Meningism carries greater diagnostic weight, but can occur in other diseases
Signs
neck flexion
Kernig’s sign
Brudzinski’s sign
tripod sign
Listeria meningitis
Listeria monocytogenesis an important bacterial pathogen in neonates, immunosuppressed patients, older adults, pregnant women, and, occasionally, previously healthy individuals
Listeria is intrinsically resistant to ceephalosporins – you need to use a penicillin
Tuberculous meningitis
Continuous headache and fever of more than 14 days duration
focal neurological deficit
progressive cerebral dysfunction
evidence of tuberculosis elsewhere (not always)
