Module 8 Neurosciences Flashcards

Question

Right monocular vision loss (anopia) caused by...

Answer 1

lesion of right optic nerve e.g. due to optic neuritis would cause

Answer 2

optic chiasm lesion e.g. pituitary adenoma

Answer 3

complete lesion of right optic tract/radiation/primary visual cortex

Answer 4

partial lesion of optic tract/radiation i.e. Baum’s loop

Answer 5

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

Answer 6

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

Answer 7

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

Answer 8

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

Answer 9

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

Answer 10

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

Answer 11

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

Answer 12

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

Answer 13

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

Answer 14

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.

Answer 15

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

Answer 16

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

Answer 17

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.

Answer 18

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).

Answer 19

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

Answer 20

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

Answer 21

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)

Answer 22

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

Answer 23

Adults Supratentorial location Glioblastoma (grade 4 astrocytoma), meningioma, metastases Development of glioblastoma from low grade astrocytoma Children Infratentorial Pilocytic astrocytoma Medulloblastoma

Answer 24

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

Answer 25

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

Answer 26

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

Answer 27

Most likely to come from breast, lung, bone, melanoma or renal. Others can spread to the brain but rarely

Answer 28

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

Answer 29

Pseudo-pallisading necrosis (elongated nuclei stacked in rows; in response to hypoxia & necrosis) Microvascular proliferation

Answer 30

Usually benign slow growing extrinsic tumour, derived from dura or arachnoidal cells , 90% supratentorial

Answer 31

A disorder of the brain characterised by an enduring / recurrent predisposition to generate seizures.

Answer 32

An abnormal, paroxysmal cerebral neuronal discharge that results in alteration of sensation, motor function, behaviour or consciousness

Answer 33

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.

Answer 34

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.

Answer 35

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).

Answer 36

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).

Answer 37

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).

Answer 38

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.

Answer 39

Mesial temporal sclerosis Hippocampal amygdala

Answer 40

Forebrain supplied mostly by branches of internal carotid artery (ICA) Brainstem & Cerebellum supplied by branches of vertebral arteries

Answer 41

Posterior cerebral Superior cerebellar Pontine Labyrinthine Anterior inferior cerebellar Basilar artery Posterior inferior cerebellar Posterior spinal Anterior spinal Vertebral arteries <- Subclavian

Answer 42

Anterior cerebral Anterior communicating artery Middle cerebral Lenticulostriate Anterior choroidal Posterior communicating Opthalmic Internal carotid

Answer 43

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

Answer 44

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

Answer 45

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

Answer 46

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)

Answer 47

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)

Answer 48

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

Answer 49

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)

Answer 50

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.

Answer 51

Originate just inferior to the basilar artery Supply: Lateral medulla Posterior inferior cerebellum Anterior inferior cerebellum

Answer 52

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

Answer 53

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

Answer 54

Most cases are fatal Neuro-interventional emergency Acute infarcts in all anatomical areas supplied by the branches of the basilar artery: Brainstem (Midbrain; pons) Cerebellar hemispheres Both occipital lobes

Answer 55

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.

Answer 56

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.

Answer 57

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)

Answer 58

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

Answer 59

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

Answer 60

Supplementary supply (in some ONLY supply) to lower spinal cord (T8-L3) Present in ~85% of individuals Usually unpaired, left dominance

Answer 61

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.

Answer 62

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)

Answer 63

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

Answer 64

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.

Answer 65

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

Answer 66

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

Answer 67

Denticulate ligaments (pia mater) firmly attach spinal cord to surrounding dura

Answer 68

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

Answer 69

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.

Answer 70

Falx cerebri: separates the two cerebral hemispheres Tentorium cerebelli: separates the cerebellum from the cerebrum Diaphragma sellae: separates the pituitary gland from the cerebrum

Answer 71

Laterally sup -> inf: Oculomotor Trochlear Ophthalmic branch of CNV Maxillary branch of CNV Medial to lateral Internal Carotid Abducens nerve

Answer 72

S skin C connective tissue (dense) A aponeurotic layer (epicranial aponeurosis) L loose connective tissue P pericranium (periosteum of skull)

Answer 73

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

Answer 74

Potential space in the cranium: fills with fluid only in pathological conditions Actual space in the vertebral canal: it contains venous blood vessel plexuses

Answer 75

Potential space: fills with fluid only in pathological conditions

Answer 76

An actual space which is filled with cerebrospinal fluid

Answer 77

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

Answer 78

Tight junctions/no fenestrae, presence of thick basal lamina basement membrane, presence of astrocyte endfeet.

Answer 79

Posterior pituitary and median eminence of hypothalamus.

Answer 80

Gases Lipophilic small molecules

Answer 81

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

Answer 82

nflammation can drastically increase access of drugs to the brain Bacterial protein lipopolysaccharide can increase permeability of BBB

Answer 83

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

Answer 84

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)

Answer 85

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

Answer 86

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)

Answer 87

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

Answer 88

Prosencephalon: forebrain Mesencephalon: midbrain Rhombencephalon: hindbrain

Answer 89

Prosencephalon (forebrain) becomes telencephalon and diencephalon Mesencephalon (midbrain) persists and grows further Rhombencephalon (hindbrain) becomes metencephalon and myelencephalon

Answer 90

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)

Answer 91

Telencephalon => Cerebrum Diencephalon => thalamus, hypothalamus, epithalamus, retina Mesencephalon => Midbrain Metencephalon => Pons and Cerebellum Myelencephalon => Medulla

Answer 92

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)

Answer 93

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

Answer 94

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.

Answer 95

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.

Answer 96

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.

Answer 97

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

Answer 98

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

Answer 99

is often associated with spina bifida Spina bifida can impair normal CSF flow due to abnormal tension on spinal cord

Answer 100

Ventriculoperitoneal (VP) shunt: CSF drains into peritoneal cavity via subcutaneous tubing

Answer 101

The neural tube fails to close in the cranial region, affecting brain development. Fetus/neonate is not viable

Answer 102

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

Answer 103

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

Answer 104

CN I Olfactory signals are projected towards the UNCUS (inner temporal) and then the limbic cortex

Answer 105

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

Answer 106

Na Channel H Channel G-protein coupled receptors

Answer 107

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)

Answer 108

located in the ventral posterior nucleus of the thalamus and project to primary somatosensory cortex

Answer 109

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

Answer 110

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

Answer 111

Dorsal horn split into areas of specific function

Answer 112

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

Answer 113

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

Answer 114

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

Answer 115

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

Answer 116

Trunk and lower limbs -> fasciculus gracilis -> Gracile nucleus (Medial) Arm and hand => fasciculus cuneatus -> cuneate nucleus (lateral)

Answer 117

Lateral - Voluntary movement of distal musculature (fine control) – direct cortical control Ventromedial - Posture and locomotion – brainstem control

Answer 118

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)

Answer 119

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

Answer 120

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

Answer 121

UMN lesion causes: Spastic paralysis Hyper-reflexia No muscle wasting LMN lesion causes: Flaccid paralysis Hypo-reflexia Muscle wasting Fasciculations

Answer 122

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

Answer 123

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.

Answer 124

monosynaptic path (2 neurones one synapse) – controls muscle length by contracting same muscle; polysynaptic path to relax antagonist (reciprocal innervation)

Answer 125

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

Answer 126

Above - no change At same level - absent/weak Below - Initially absent (spinal shock) then exaggerated

Answer 127

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

Answer 128

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

Answer 129

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

Answer 130

(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

Answer 131

(deep to mandible) CNVII Parasympathetic postganglionic nerve fibres to submandibular gland travel in lingual nerve (CN Vc branch): increased saliva production

Answer 132

(in infratemporal fossa) CN IX Parasympathetic postganglionic nerve fibres to parotid gland travel in auriculotemporal nerve (CN Vc branch): increased saliva production

Answer 133

Sup. salivatory -> Greater petrosal CNVII -> Pterygopalatine ganglion -> zygomatic nerve CNVb -> zygomaticotemporal nerve CNVb -> Lacrimal nerve CNVa

Answer 134

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

Answer 135

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

Answer 136

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)

Answer 137

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

Answer 138

Thalamus Hypothalamus Epithalamus (e.g. pineal gland) Subthalamus (e.g. subthalamic nucleus)

Answer 139

Blood supply to thalamus = posterior cerebral artery and posterior communicating artery

Answer 140

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

Answer 141

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

Answer 142

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 (an end artery is the only supply of oxygenated blood to a portion of tissue)

Answer 143

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

Answer 144

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

Answer 145

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

Answer 146

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

Answer 147

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

Answer 148

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

Answer 149

FVC Bulbar function ECG – autonomic DVT prophylaxis Early liaison with AICU IVIG (plasma exchange)

Answer 150

Renshaw cell – inhibitory interneuron – produces glycine (antagonised by strychnine – Agatha Christie)

Answer 151

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

Answer 152

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

Answer 153

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

Answer 154

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

Answer 155

Medial longitudinal fasciculus: tract connecting many brainstem nuclei including vestibular nuclei and the oculomotor, trochlear and abducens nuclei – important for coordinating eye movements

Answer 156

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

Answer 157

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)

Answer 158

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

Answer 159

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

Answer 160

Rostral (‘open’) medulla in cross-section Caudal (‘closed) medulla in cross-section

Answer 161

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

Answer 162

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)

Answer 163

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

Answer 164

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

Answer 165

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

Answer 166

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

Answer 167

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

Answer 168

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

Answer 169

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

Answer 170

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

Answer 171

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

Answer 172

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

Answer 173

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

Answer 174

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.

Answer 175

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

Answer 176

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

Answer 177

Va -> superior orbital fissure Vb -> foramen rotundum Vc -> foramen ovale

Answer 178

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

Answer 179

Trigeminal cave can be accessed via the oral cavity and foramen ovale during some surgical procedures

Answer 180

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

Answer 181

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

Answer 182

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

Answer 183

unconscious grinding of teeth Temporomandibular disorders such as bruxism can cause visible/palpable enlargement of masseter and temporalis

Answer 184

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)

Answer 185

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

Answer 186

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

Answer 187

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

Answer 188

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

Answer 189

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

Answer 190

Temporal Zygomatic Buccal Mandibular Cervical

Answer 191

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

Answer 192

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

Answer 193

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

Answer 194

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?

Answer 195

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

Answer 196

Fast, short, sharp, first pain (Aδ) Slower, duller, longer, second pain (C)

Answer 197

Travel up or down in Lissauer’s tract (a few spinal segments)

Answer 198

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

Answer 199

Cancer Pain Neuropathic pain Visceral pain

Answer 200

pain from a normally non-noxious stimulus

Answer 201

Depression for 2 weeks Loss of interest in pleasurable activities Increased fatigability or decreased energy

Answer 202

Negative thoughts about self, world, and future

Answer 203

ANALGESIA ANAESTHESIA MUSCLE RELAXATION

Answer 204

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)

Answer 205

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

Answer 206

Depolarising - SUXAMETHONIUM Non depolarising ATRACURIUM, rocuronium, vecuronium - slower onset and offset

Answer 207

The Electroencephalogram (EEG) Measurement of generalized cortical activity Noninvasive, painless Diagnose neurological conditions such as epilepsy, sleep disorders, research

Answer 208

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

Answer 209

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.

Answer 210

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

Answer 211

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

Answer 212

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

Answer 213

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

Answer 214

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

Answer 215

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

Answer 216

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)

Answer 217

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.

Answer 218

Sleep protects newly acquired information and affords immunity against forgetting: memory consolidation.

Answer 219

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.

Answer 220

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

Answer 221

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.

Answer 222

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.

Answer 223

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.

Answer 224

Characterised as a chronic inability to fall asleep despite appropriate opportunities to do so.

Answer 225

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’

Answer 226

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

Answer 227

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

Answer 228

Commonest where brain impacts on base of skull - poles of each lobe bruising

Answer 229

Bleed into subarachnoid space Ruptured aneurysm ‘berry’ Trauma – most common cause CT subarachnoid haemorrhage basal cisterns containing blood

Answer 230

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

Answer 231

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

Answer 232

Movement of the cerebellar tonsils through the foramen magnum Brainstem compression -> cardiorespiratory arrest ‘Coning’ Cushing response – decreased consciousness, bradycardia, hypertension Usually irreversible

Answer 233

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)

Answer 234

Headache 30% persist >2/52 Dizziness – non specific Lethargy Depression Lack of concentration

Answer 235

Symptoms last < 24 hours (WHO definition) Note: Most TIA resolve within 1 hour Some TIA are due to primary haemorrhage (0.5%)

Answer 236

A retinal TIA Transient monocular blindness, painless.

Answer 237

Ischaemic stroke 85 % Intracerebral haemorrhage 10 % Sub-arachnoid haemorrhage 5 %

Answer 238

Region of brain at risk to persistent infarct

Answer 239

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

Answer 240

Pre-chiasmal lesions will result in an ipsilateral monocular visual field defect Post-chiasmal lesions will result in homonymous visual field defects of the contralateral side Homonymous contralateral quadrantanopia (optic radiation) temporal lobe - homonymous upper quadrantanopia parietal lobe - homonymous lower quadrantanopia

Answer 241

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

Answer 242

Motor or sensory hemiparesis and Homonymous hemianopia and Higher cortical dysfunction

Answer 243

Isolated higher cortical dysfunction or Any combination of 2 of: Hemiparesis Homonymous hemianopia Higher cortical dysfunction

Answer 244

Pure motor stroke or Pure sensory or sensorimotor stroke or ataxic hemiparesis

Answer 245

Isolated hemianopia, brainstem or cerebellar

Answer 246

(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

Answer 247

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

Answer 248

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

Answer 249

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

Answer 250

Housed in the petrous part of the temporal bone External acoustic meatus and middle ear located laterally Internal acoustic meatus located medially

Answer 251

Bony and membranous labyrinth

Answer 252

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

Answer 253

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)

Answer 254

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

Answer 255

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

Answer 256

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

Answer 257

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

Answer 258

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

Answer 259

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

Answer 260

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

Answer 261

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)

Answer 262

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

Answer 263

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.

Answer 264

Dynamic and static Labyrinth

Answer 265

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)

Answer 266

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

Answer 267

Cupula at end of the semi-circular canals

Answer 268

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

Answer 269

The vestibulo-ocular reflex allows for conjugate eye movement, coordination of eye and head movements and visual fixation Via the medial longitudinal fasciculus

Answer 270

Rapid eye movements when scanning immediate surroundings Saccades = scanning Moving the eye to collect impressions and construct an image

Answer 271

hallucination of movement i.e. spinning Central vertigo or peripheral vertigo mismatch between balance inputs

Answer 272

Increase in endolymph nausea, vertigo, hearing loss

Answer 273

disconnection of visual and vestibular inputs can trigger nausea

Answer 274

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

Answer 275

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)

Answer 276

most commonly posterior semicircular canal - noticed when nodding head or turning over in bed

Answer 277

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

Answer 278

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

Answer 279

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

Answer 280

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)

Answer 281

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

Answer 282

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

Answer 283

cortex -> pons -><- Cerebellum Vestibular nucleus -> <- Inferior olive -><- Spinal cord -> Red nucleus <-

Answer 284

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

Answer 285

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)

Answer 286

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

Answer 287

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)

Answer 288

At rest, basal ganglia have an inhibitory influence on thalamus thus reducing thalamic input to cortex

Answer 289

sensory and motor areas > Putamen association areas and frontal eye fields > Caudate nucleus

Answer 290

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

Answer 291

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

Answer 292

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

Answer 293

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.

Answer 294

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

Answer 295

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

Answer 296

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

Answer 297

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

Answer 298

Eyes don't move together

Answer 299

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

Answer 300

Other demyelinating diseases E.g. neuromyelitis optica (anti-AQP4) Infections E.g. Lyme disease (Borrelia burgdorferi) Metabolic diseases E.g. B12 deficiency Systemic diseases E.g. neurosarcoidosis Other E.g. vasculitis

Answer 301

Central nervous system Inflammation Demyelination Astrocytic scarring (gliosis) Neurodegeneration (axons/nerve cell loss) Little known

Answer 302

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

Answer 303

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

Answer 304

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.

Answer 305

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

Answer 306

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

Answer 307

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.

Answer 308

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.

Answer 309

Excitotoxicity Oxidative stress - ROS Nitric Oxide - ROS

Answer 310

upregulates molecular chaperone proteins Abnormal proteins are tagged with ubiquitin

Answer 311

In neurodegenerative diseases there is an accumulation of abnormally folded proteins - or a failure of the normal cellular mechanisms for their disposal

Answer 312

Early (entorhinal cortex & hippocampus) Intermediate (limbic lobe, amygdala) Late ( association areas of neocortex & finally to sensory/motor)

Answer 313

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

Answer 314

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

Answer 315

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

Answer 316

Left hemisphere lesion = neglect not as severe Right hemisphere lesion = left neglect RIGHT LESION BAD

Answer 317

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

Answer 318

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

Answer 319

Hippocampus is the start and end of the circuit. Fornix connects hippocampus to hypothalamus

Answer 320

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

Answer 321

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’)

Answer 322

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

Answer 323

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

Answer 324

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

Answer 325

Bilateral lesions of the anterior hippocampus can cause anterograde amnesia

Answer 326

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

Answer 327

Blood supply to hippocampus = anterior choroidal artery branches Some branches from posterior cerebral artery to posterior hippocampus Clinical relevance: temporal lobe epilepsy surgery

Answer 328

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

Answer 329

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

Answer 330

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

Answer 331

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

Answer 332

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

Answer 333

Purpuric Rash of Meningococcal meningitis

Answer 334

Purpuric Rash, most common

Answer 335

Neisseria menigitidis Streptococcus pneumoniae Listeria moncytogenes Haemophilus influenza Viral (lots of them!)

Answer 336

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

Answer 337

Osler's Triad (Austrian syndrome) is a rare but deadly triad comprising meningitis, endocarditis, and pneumonia.

Answer 338

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

Answer 339

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

Answer 340

Listeria monocytogenes is 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

Answer 341

Continuous headache and fever of more than 14 days duration focal neurological deficit progressive cerebral dysfunction evidence of tuberculosis elsewhere (not always)