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
