Anatomy

Cerebrum & the Cerebral Cortex (the surface)

Lobes  2 hemispheres
 separated by
longitudinal
fissure & falx
cerebri of dura
mater
 Connected by
corpus callosum
(white matter
structure)
 Grey matter
 Unmyelinated
axons
 Processing and
cognition
 White matter
 Myelinated axons
 Glial cells
 Insula
 self-awareness,
perception, and
cognition
 Associated with
limbic system
 Emotions
 Memory
 Learning
 Olfaction
Gyrus  Sulci & Gyri
 Divided by
longitudinal fissure
Brodmann
Areas

Homunculus  Homunculus
 Opposite ½
(precentral represented
and post  It’s represented
central gyri) “Upside down”
 Greater
representation =
more sensitive
 Cerebral Dominance
Dominant Dominant Non-dominant
vs (often: left) (often: right)
Non-dominant Nomenclature: Dominant hemisphere – The hemisphere more
important for the comprehension and production of language
 Language perception  Spatial perception
 Speech  Facial recognition
 Handedness  Facial expression, body language
 Music

 https://www-clinicalkey-com.ezp.imu.edu.my/#!/content/book/3-s2.0-B9781455728596000221?scrollTo=%23hl0001062
 Those skills above are generally controlled by those hemispheres
 LEFT HEMIS IS ALWAYS MORE LIKELY TO BE DOMINANT
 Almost all right handers are left hemis. dominant (95%)
 MOST left handers are right hemis. dominant too!!! (but a smaller percentage)

Frontal Lobe

Primary motor  Controls movement of voluntary muscles on contralateral side

area (4)  Precentral gyrus
 Receives info from
 cerebellum & globus pallidus (regulate motor activity)
 somatosensory afferents (proprioception and tactile inputs)
Pre-motor area (6)  For movements that require visual guidance (eg: reach for cup)
 Receives info from
 Cerebellum (through VN nucleus of thalamus)
 Posterior parietal cortex (PPC) (integrated somatosensory and visual info)
Supplementary  Complex movements & learning new motor sequences
motor area (6)  Connected to – basal ganglia through thalamic nuclei
FLOW: Planning (secondary motor - Supplementary + Premotor) + Execution (Primary motor to descending path)
Frontal eye field (8)  Conjugate movement of eyes to opposite side
 Lesion: eyes look to side of lesion
 Middle frontal gyrus
Broca’s area  Regulates coordinated movement for MOTOR SPEECH (lips, tongue, palate larynx and pharynx)
(44,45)
(you’ll have this on both hemispheres, but the DOMINANT one is clinically important! Damage to the non-dominant one has no
effects)
Prefrontal cortex  Regulation of visceral, emotional and cognitive processes
(9-12)  Anterior to precentral area
 Parietal Lobe
(aka. Post-central gyrus)
 3 parts
 1) Post-central gyrus - the ones in yellow below (?)
-Posterior parietal lobule-
 2) Inferior parietal lobule
 3) Superior parietal lobule
Primary somatic  Localizes, analyses, discriminates different modalities of cutaneous & proprioceptive senses
sensory area  Post central gyrus (& extends- see slides)
(3, 1, 2)
Secondary somatic
sensory
So-maes-thetic  Receives and integrates different sensory modalities (think: parietal = powerful)
association area  Stereognosis - recognize objects by shape, texture, consistency, without vision
 Agnosia - difficulty or inability to recognize object
(aka Posterior  Astereognosia - can't recognize object felt with hand of contralateral side
Parietal  Proposnogsia – can’t recognize face
Association Area)  Others: visual agnosia
 Superior parietal lobule (& extends – see slides)
(5 & 7)

 Inferior Parietal Lobule

 Lesion  Gerstmann Syndrome (see below)
 Occipital Lobe
Primary Visual Area  Receives input of
(V1)  Optic radiation (axons) from LATERAL geniculate nucleus (LO) of the thalamus

(17)
Association visual  Helps us recognize what we see by relating to past visual experiences (eg: colour)
processing areas (3 4 5 – F C M)
 V3 – form
(V2,3 and 5)  V4- colour
(18, 19)  V5- motion

Temporal Lobe

Primary Auditory  Receives input from

Area (41)  Auditory radiation from MIDDLE (MA) geniculate body
Association auditory
area (42)
Wernicke’s area 22)  SENSORY SPEECH (for UNDERSTANDING)
 Connected to Broca’s area via arcuate fasciculus
 Speech

(Dominant hemisphere- usually left)

Wernicke’s Area  Comprehension

(22, sensory speech area)  Recognition of familiar sounds and words
Angular gyrus  Stores visual images
(39)  Recognizes objects by sight
 In inferior parietal
Supra-marginal gyrus (40)  Recognizes objects by touch and proprioception
Broca’s Area (motor  Stimulates LOWER MOTOR NEURON for COORDINATED MOVEMENTS of spoken speech
speech area)

Language Disorders
(Aphasia – acquired disorder of language due to brain damage)
 General 22  word deafness (can hear but cannot interpret)
(lesions) (wernicke’s)
39  word blindness (can see but cannot interpret)
(angular gyrus)  Alexia – can’t read
 Agraphia – can’t write
40  astereognosis
Broca’s Area  Motor aphasia
 Possibly: telegraphic speech
Aphasia Wernicke’s Broca’s Conduction
(Sensory/ receptive) (Motor/ expressive)
Comprehension No insight Has insight Has insight (good
comprehension)
Fluency Fluent Not fluent (“broken boca” Fluent (but can be halting
Lacks melody sometimes)
Paraphasia (pronounce
wrong syllables)
Content Mostly function words (“word Mostly content words
salad”) (telegraphic - we can get gist)
Others Problem often together with Possibly irritable, disturbed Damage to arcuate fasciculus
angular gyrus
*Problem NAMING OBJECTS
*Problem REPEATING
WORDS upon request

Other Cortical Disorders

Apraxia (ideomotor  Most commonly involved  Motor disorder
 type-  Posterior Parietal  Patient can’t perform/ coordinate learned movements (eg: using tools - though
Dominant Cortex (of dominant they understood and are willing)
hemisphere hemisphere- often:  Eg: can’t cut bread
lesion) left)
 NOTE!!!!!!!!! MANY TYPES OF APRAXIA – ideomotor, constructional, conceptual,
gait, speech
 Usually, lesion is in small area of the NON-DOMINANT LOBE
 In this case (ideomotor)  mostly in dominant lobe

Gerstmann’s (Dominant  Inferior Parietal Lobule  Agnosia (finger)

Syndrome hemisphere (of PPC)  Acalculia
lesion)  ANGULAR GYRUS  Agraphia
(usmle)  Alexia/ dyslexia
 Left-Right confusion

Summaries
Frontal Parietal
Testing Cognitive Skills
 White matter
Commissural  Connects corresponding regions of 2 hemisphere
fibers  Corpus callosum
 Anterior and posterior commissure
 Fornix
 Habenular commissure

Association fibers  Connects cortical regions of same hemisphere

 Cingulum
 Uncinate fasciculus
 Superior and inferior longi. Fasciculus
 Fronto-occipital fasciculus

Projection fibers  White fibres - Afferent and efferent nerve fibres passing to Internal Capsule
and from brain stem to entire cerebral cortex
 Internal capsule
 Corona radiata
 Cortico spinal tract
 Sensory tract

Limbic System
What  Neuronal circuitry controlling emotional behaviour and motivational drives
 Where subcortical structures meet cerebral cortex
 Highly connected to nucleus accumbens (in basal ganglia) – brain’s pleasure center
 Works by influencing endocrine and ANS
More info Components Neuronal structures involved in Responsible for
Thalamus Olfaction  Think: RLSP progression
Hypothalamus Emotion (and motivation)  Feed
Hippocampus – learning, long term Learning and long term memory  Feel
memory  Fuck
Amygdalae – adds emotional colour to ANS function  Fight
memories  Flee
Mammillary bodies Behaviour modulation
Anterior thalamic nuclei
Cingulate gyrus
Entorhinal cortex

Pics  Hippocampus – red

 Cingulate gyrus – yellow
  Thalamus and hypothalamus added

More info  Behaviour – depends on emotion, motivation, arousal and experience

 Basic emotions (6)  happiness, anger, disgust, fear, sadness + SURPRISE
 Limbic system and PLEASURE
 highly connected to NUCLEUS ACCUMBENS (pleasure center) – drugs, arousal
 Dopaminergic neurons in meso-limbic dopamine path modulate responses
 Meninges & the Ventricular System

Meninges
Pics

Layers Dura  Thick (& vascular)  Dura mater septa (4) – see pic on left too
 Endosteal (periosteal) layer
 Meningeal layer
*only 1 layer in spinal chord
 Ends at SV2
 DURAL VENOUS SINUS BETWEEN  IJV
 BS  middle meningeal artery and vein
  InnervationTrigeminal nerve

Arachnoid  Web-like (& AVASCULAR)

 Ends at SV2
 Subarachnoid space continuous with that of spinal cord – with CSF
 CSF  sub-arachnoid granulations  dural venous sinus (re-enters circulation)
 Subarachnoid cisterns

 Optic disc oedema

 A sleeve of subarachnoid space extends around optic nerve
  Increased ICP/ CSF pressure  papilloedema (don’t do lumbar puncture as sudden fluid
withdrawal may cause cerebral brainstem herniation  fatal)
Pia  Thin (& vascular)
 Becomes filum terminale at L1, Ends at coccyx
Meningeal Spaces

Applied Anatomy Haematoma and Haemorrhage

Epidural  Middle meningeal  Skull fracture  Transient loss of
(extradural) artery (esp: anterior consciousness  lucid
Haematoma branch of interval  rapid
MMA at deterioration
(extradural pterion) *can have mass effects due to
haemorrhage) haematoma (GCS score falls)

 Hyperdense
blood
collections do
not cross suture
lines
*SubDural  SUPERIOR  Usually SLOW DEVELOPING
haematoma cerebral vein
rupture (“bridging
veins”)

(think:
Dreamworks sign
– a person on a
 Crescent-
crescent moon)
shaped blood
collection of
MRI
 Crosses suture
lines
 Midline shift
 Acute
(hyperdense) or
chronic
(hypodense)
*Subdural  Superior cerebral  Traumatic  Headache, confusion
haemorrhage vein rupture posterior  Memory disturbance
brain
displacement
*Subarachnoid  Rupture of  Severe HT  Increased ICP
haemorrhage!!! cerebral arteries esp  Headache – “worst
(esp: berry headache of my life/
aneurysm) THUNDERCLAP
(“OUCHHH”) HEADACHE”
 LOC
 Possible coma and death,
ischaemic infarct,  Suspect if all 3
hydrocephalus lumbar
puncture is
 stained with
blood /
xanthochromic
(though by right
LP is CI)
Intraparenchymal  Charcot-  Systemic HT
haemorrhage Bouchard mostly
microaneurysms(s  Can be
mall blood vessels) secondary to
 Most often: reperfusion
lenticulostriate injury in
vessels (putamen ischaemic
of basal ganglia of stroke
MCA)

Meningitis
 Cause
 Mostly Neisseria gonorrhoea, s. pneumoniae
 Pathogenesis
 Immune response  cerebral oedema  raised ICP
 Cranial herniation
 Reduction of cerebral perfusion
 Death
Ventricles
 Components
 Lateral
 3rd – slit-like cleft between 2 thalami
 4th
 Central canal of medulla oblongata and spinal cord
Lateral
3rd

4th Floor

Central Canal  4th ventricle  terminal ventricle

 CSF
Function  Cushions and protects CNS from trauma
 Mechanical buoyancy and support for brain
 Nourishes CNS
 Removes metabolites from CNS
 Reservoir + assists regulation of skull contents
 Path for pineal secretions (eg: melatonin) to reach pituitary
Formation  CHOROID PLEXUS – mostly in lateral ventricles
 CP – modified ependymal cells
 EPENDYMAL CELLS in ventricles
 Brain substances
Circulation Reabsorption of CSF back into dual venous sinus
 CSF pressure> sinus pressure

CSF Flow
 In ventricle
 Pulsation of artery in choroid plexus
 Cilia and microvilli of ependymal cells
 In subarachnoid space
 Pulsation of cerebral & spinal arteries
 Movements of vertebral column
 Respi & coughing
 Changing positions
Blood-CSF barrier  Can pass
(in choroid plexus)  Water
 Glucose
(blood CSF)  Gas
 Lipid-soluble substances
 Cannot pass (thus: protect from potentially harmful substances)
 Macromolecules (eg: protein, hexose)
  Components of barrier (blood  CSF) (think: choroidal)
 Endothelial cells (with closed fenestrations)
 Continuous endothelial basement membrane
 Scattered pale cells with flattened processes!!
 Continuous choroidal epithelial basement membrane
 Tight junctions (of choroidal epithelial cells)
Blood-CSF barrier (above) Blood brain barrier

*tight junctions most effective

Applied anatomy Hydrocephalus
 Increase CSF volume  ventricular dilation +/- increase ICP Dilated ventricles !!
 Types
 Communicating
 D/t decreased absorption by arachnoid granulations (eg: post-meningitis
scarring)
 Normal Pressure Hydroceph (NPH) - Adam’s triad – think of 3Ws: wet,
wobbly and whacky!
 Episodic CSF pressure increase in elderly
 Non-communicating (obstructive – eg: stenosis of aqueduct)
 Hydroceph mimics – ex vauco ventriculomegaly
 CSF and ICP normal actually
 Due to decreased brain tissue (eg: Alzheimer’s)
 Congenital (child) Acquired (adult)
 Cause  Cause
 Cerebral aqueduct block  Infection – eg: narrowing of lumen after
 Absorption problem infection
 Tumour
Hydrocephalus + interferes with brain tissue development  Less likely to have hydrocephalus as sutures
have already been closed (bone fuse)
 More likely to compress brain tissue
 Blood Supply (Brain and Spinal Chord)

Brain
General  Main contributing arteries
 Vertebral (2)
 Internal carotid (2) – branches of 1st part of subclavian artery
 Supply
 Cerebrum  Circle of Willis branches
 ACA – branches of ICA  LEG
 MCA – continuation of ICA  FACE AND HANDS (all but leg)
 Note: for internal capsule, genu corresponds to head (supplied by ICA mostly). Genu
affected  CN affected
 PCA – branches of basilar  EYE
 Pons and Spinal chord  Vertebral artery branches (smaller)
 Anterior vs Posterior Circulation  Division : the POSTERIOR COMMUNICATING ARTERIES!
 Anterior
 Posterior: Vertebro-basilar arterial system (aka POSTERIOR CIRCUL ATION OF BRAIN)
 TIA of VBA (esp: elderly HT pts)
 VISION LOSS (post. cerebral artery), homonymous hemianopia
 Loss of balance, vertigo

 Cerebral arteries control (VC and VD)

 1) concen. Of O2, CO2 and H+ (low O2  VD)
 2) nerves (sympathetic  VC)
 Flow kept quite constant (flow= pressure/ resistance)
 No blood flow to brain
 8-10 seconds of blood flow interruption  unconscious
 1 min  neuronal damage (check)
 5 min  irreversible damage (but brain damage MAYY be reversed if blood flow ca be
restored after 5 mins)
 ICA  Route
 Common carotid  carotid canal  cavernous
sinus  branches
 Branches (distal to cavernous sinus)  OPAA  before
continuing as MCA
 Ophthalmic
 Posterior communicating
 Anterior choroidal (motor control, vision)
 Anterior cerebral
 Segments

Vertebral  Route
Artery  Subclavian arteries  foramen transversarium (C6-C1)  suboccipital triangle  foramen magnum
 Branches
(& the  Cranial portion
vertebro-  Meningeal branches
basilar  Spinal arteries
arterial  1 ANTERIOR SPINAL – occlusion: MEDIAL MEDULLARY SYNDROME
system)  2 posterior
 PICA – occlusion: LATERAL MEDULLARY SYNDROME
 Medullary arteries
 Basilar artery (formed by joining of 2 vertebral arteries)
 Branches
 Pontine
 Labyrinthine
 AICA
 Superior cerebellar
 Posterior cerebral
 Clinical Significance
https://litfl.com/brainstem-rules-of-4/
 Medullary syndromes  SEE REMINDER NOTES!!!!!!!!!! BETTER
Medial Medullary Syndrome Lateral Medullary Syndrome
(aka WALLENBERG syndrome)
(Anterior Spinal artery problem) (PICA problem)

 MMS can also be caused by: infarct of VERTEBRAL  “Don’t PICA horse (hoarseness) that starts the race
arteries LATe, can’t EAT (dysphagia) and talk and would puke
instead”
Circle of  Blood usually doesn’t cross their
Willis zones unless there’s some
BLOCKAGE (collateral circulation)
 Specific
Supply
And
Occlusions

ACA MCA* PCA

 Frontal and parietal lobe (medial)  All lobes but occipital (lateral)  Occipital lobe
 Corpus callosum (anterior 4/5th)  Parts of basal ganglia  Temporal lobe (lower)
 Internal capsule (anterior limb –  Globus pallidus  Thalamus
lacunar branches)  Caudate  Midbrain
 Putamen
 Internal capsule (posterior limb) 0
lenticulostriate
 Corona radiata
OCCLUSION
ICA occlusion VBA Occlusion

 Basiliar artery stroke– locked- in syndrome

 Aware but cannot move or communicate verbally due to
complete paralysis of nearly all voluntary muscles in the
body except for vertical eye movements and blinking.
 Spinal Chord
General  Arteries
 Main longitudinal arteries
 Anterior spinal (1)
 Posterior spinal (2)
 Below cervical level – support via
 Segmental spinal and radicular arteries
 Extra feeders – Great anterior medullary artery of Adamkiewicz
 Branches
 Outside cranial cavity  spinal and muscular (occipital muscles)
 Inside (as above)

Posterior
Spinal
Anterior
Spinal
Segmental,  Segmental (reinforcing arteries entering by the intervertebral
radicular foramina)  split into 2 radicular arteries
and Feeder  ADDITIONAL FEEDER ARTERIES (via intervertebral foramina)
Arteries  Eg: GAMAA!!!!! (main one)
 Great Anterior Medullary Artery of Adamkiewicz
 Aka: Artery of Adamkiewicz, Arteria radicularis
magna
 Special segmental artery (dominant)
 Major supply of lower 2/3 of spinal chord
 Usually on left side.. from aorta
Spinal  Veins
Veins  6 longitudinal channels

 Veins connected by VASACORONA  Internal vertebral

venous plexus  segmental veins
 Impt: METASTASIS. Valveless.
 Embryology

Derivatives
 Brainstem

General
Brain Stem
 Midbrain
Exterior Anterior

Posterior
Interior Superior
Colliculus
Level

 Superior colliculus (in MIDBRAIN) – think RED NUCLEUS!!!!!

Inferior
Colliculus
Level
 BLOOD
SUPPLY of
MIDBRAIN

Pons
Exterior Anterior
Posterior

 Cerebellopontine angle (above, right) (CN 6 7 8

there)

 Vestibulo schwannoma/ acoustic neuroma

common here

 Ipsilateral hearing loss/ tinnitus,

41isequilibrium (VIII)
 Nystagmus (flocculus compression)
 Facial paralysis (VII)
 Trigeminal palsy (V)
 Reduced corneal reflex (V, VII)
 Ipsilateral cerebellar signs
 Caudal Trigeminal
/Interior nucleus level

(cranial)

Facial
colliculus
level

(caudal)
 Medulla
Exterior Anterior

Posterior
 Exterior Olivary
Nucleus
(Inf.  sup.) level

See ENTIRE olivary nuclei & inferior cerebellar peduncle – think: olivary
nucleus level
Sensory
Decussation
Level

(crossing
fibres: DC
tract)

 See huge PYRAMIDS and no inferior cerebellar peduncles – think: sensory

decussation
 Motor
Decussation
level

(crossing
fibres: CS
tract)

 Note: Trigeminal Nerve Nuclei

 Motor
 Muscles of mastication – PONS
 Sensory
 Head & Neck
 Pain, temp – MEDULLA (spinal nucleus)
 Touch, pressure – PONS (main nucleus)
 Proprioception – MIDBRAIN (mesencephalic nucleus)

BLOOD
SUPPLY to
Medulla
 Others
Direct and  Involves midbrain – Superior colliculus, pretectal nucleus, Edinger
Indirect light Westphal (PS) nucleus
reflex

Reticular  Function  Consciousness

formation  What
 Diffusely arranged nuclear mass
 Connections to cerebrum, thalamus and hypothalamus
 Damaged  possibly unconscious
 Clinical Medulla Lateral Medullary PICA occlusion “Don’t PICA horse that can’t EAT but vomits laterally
Application Syndrome instead”
(Wallenberg’s Syndrome)  Hoarseness & Dysphagia (damage to vagus and
accessory)
 Vomiting
 Gait coordination and balance problems
(spinocerebellar tracts)
 Loss of spinal lemniscus skills (contralateral)
Medial Medullary Vertebral/  Ipsilateral tongue deviation (damage to hypoglossal
Syndrome Anterior Spinal nerve fibres)
Artery  Contralateral hemiparesis/ hemiplegia (corticospinal
occlusion fibres of pyramidal tract)
 Contralateral loss of dorsal column (medial lemniscus)
skills

Midbrain Weber’s Syndrome Perforating  Ipsilateral CN III palsy: down and out position, ptosis,
branches of and mydriasis (ie, damage to parasympathetic fibers of
basilar artery CN III)
 Contralateral hemiplegia (corticospinal) and
(Ventral lesion) hemiparesis of lower face (corticobulbar)

Benedikt Syndrome PCA/  Ipsilateral CN III palsy, diplopia, mitosis, mydriasis, loss
perforating of accommodation reflex
branches of  Contralateral loss of dorsal column (medial lemniscus)
basilar arteries skills
 Cerebellar ataxia: involuntary movements (eg:
(Tegmen-tum contralateral flapping tremor)
of midbrain and
cerebellum.
Involves red
nucleus )
 Physiology

Ascending and Descending Tracts

 Coordination of voluntary movements

Motor α Motoneurones γ Motoneurones

Neurones  Innervate extrafusal skeletal muscle fibres  muscle  Innervates intrafusal fibres (component of muscle spindle)
contraction  Muscle spindle  senses muscle LENGTH (vs. golgi
 Muscle stretched  increases alpha-motor neurone TENdon that senses TENsion)
discharge  γ Motoneurones  adjust sensitivity of muscle spindles
 Muscle spindles increase firing rate due to
 1) Mechanical stretch
 2) Increased activity in gamma efferent fibres
(causing ends of the spindle to contract, but
center can’t so it’s stretched)
 COACTIVATION  so muscle spindle remains sensitive to changes in muscle length, even as muscle contracts and shortens
 Descending fibres of motor pathways send motor impulses to (& stimulates)
 Extrafusal fibres  contraction
 Intrafusal fibres  maintains SPINDLE TENSION AND SENSITIVITY (so changes in muscle length still sent to brain)
*but in reflexes (eg: stretch  we talk about afferent sensory + alpha motor (no gamma))
Muscle Tone  What  Partially contracted state of muscle
 Function
 Maintains body posture
 Provides background contraction for voluntary activity
 UMN UMN LMN
and Function  Modify muscle activity  Contraction
LMN  Nutrition for muscle
Movement
Control

Cortical Cortex  FUNCTION: Planning (supplementary + premotor cortex Execution (Primary motor
cortex)
 How
 Pyramidal tract
 Tracts
 CS – lateral (fine movements) and anterior (postural movements)
 CB – head and neck
 Extra-pyramidal tract
 Tract
 Pontine and medullary reticulospinal tract
 Tectospinal tract
 Rubrospinal tract
 Lateral vestibulospinal tract
 Olivospinal
  Tracts related to – basal ganglia, red nucleus, reticular formation, vestibular
nucleus
 Function: Muscle tone, posture, equilibrium
Sub-Cortical Cerebellum  Balance and eye movements  Functional divisions
(archi-)  Vermis – control of neck & axis
 Voluntary movement  Intermediate – distal limbs
 Motor planning (neo-) (lat)  Lateral – plan sequential movements
 Motor execution (paleo-) (timing?)
(mid)  Input
 COORDINATES and  Central
ADJUSTS ongoing  Cortex  lateral cerebellum
movements  smooth,  Vestibular nuclei  floccular
precise, directed nodular lobe
movements!  Olive  basal ganglia
 Muscle tone and reflexes  Reticulocerebellar tract  vermis
 Peripheral
 Via SC tract
 Anterior – carrying impulses
that stimulate alpha motor
 neurones
 Post – from proprioceptors
 Output
 To reticular formation, basal ganglia,
thalamus etc  coordination,
sequential movements
Basal Ganglia  Cognitive control  Circuits
 Reflex  Caudate – cognitive control (eg:
 Muscle tone deciding path)
 End: Premotor cortex
 Putamen – patterns of movement (eg:
running from lion)
 End: motor cortex
 NT
 Dopaminergic
 GABAnergic
 Cholinergic
 Adrenaline, serotonin, enkephalin
 Disorders
 Hypokinetic – akinesia, bradykinesia
 Hyperkinetic – chorea, athetosis,
ballism
Reticular  Relay station between cortex  Muscles that help us maintain upright,
Formation and spinal chord balanced posture
 Pontine – w/ input from  Soleus
(anti-gravity vestibular nuclei   Long extensors
muscle tone) excitatory input to  Gluteus maximus
antigravity muscles  Quadriceps femoris
 Medullary – input from CS  Muscles of back
and RS  inhibit pontine
system
SIMPLY PUT
  ASCENDING – RAS
 DESCENDING –
RETICULOSPINAL tract
(facilitates/ inhibits volun.
Movement, but MAINLY  PRO-
EXTENSORS!!!! (anti-gravity
muscles)
 Visceral control centers 
vomiting, repsi

Vestibular Nuclei  Facilitate tone of anti-gravity  Give rise to medial and lateral
muscle (pro-extensor) vestibulospinal tract
(anti-gravity  Adjust position of body parts  Inputs from: vestibular apparatus (SC
muscle tone) and eyes canal, saccule and utricle)

Red nuclei  Rubrospinal tract (originates  Activates  Flexors

from red nucleus)  Like  Inhibits  Extensors
secondary motor system (lateral
motor)
 Discrete distal movements
(esp: upper limb)
 Not as fine/ controlled
as the CS tract
Spinal Lower Motor
Neurone

UMN system Corticospinal Cerebellar Extrapyramidal System

& major (cortico-striae-reticulospinal system)
functions Initiation of voluntary movement Coordination of movement Body tone/ posture

Equilibrium
 From cerebral cortex From brain stem
(passing through medullary pyramids of
medulla)
Voluntary control Involuntary and autonomic control

Regulation of body posture and postural reflexes

Main Reflexes Muscle Spindle Golgi Tendon Organ

 Related to alpha and gamma fibres  Tendon organs activated

 Increased afferent discharge
MOA  Stretching of muscle SPINDLE (spindle measures  Excessive muscle TENsion (TENdon – TENsion) 
length)  contraction of stimulated muscle + inhibits relaxation of stimulated muscle + contraction of
antagonist (so: muscle back to normal) antagonist
 Eg: knee-jerk
Function  Maintains muscle length  Prevent muscle and tendon damage
 Maintains JOINT POSITION and POSTURE
 Maintains muscle tone
More info  Monosynaptic, ipsilateral  Polysynaptic
 Major factor in postural control  threshold/
sensitivity of stretch reflexes

Flexor Crossed- extensor Superficial reflexes

 Stimuli: pain  Ipsilateral flexion + contralateral  Eg: plantar and abdominal reflex
 Polypsynaptic, ipsilateral extension  Cutaneous stimulation
 Protective
Postural  General Principles
reflexes  Upper centres MASK reflexes integrated by lower centres
 Decorticate  LOSS of cortical reflexes
  Everything else  express what’s below it
 Preparations (named after what’s BELOW it?)

Cerebrum Placing and Hopping

Optical Righting
Midbrain Labyrinthine  Head righted whatever the body position
 How
(righting  Unequal stimulation of labyrinths  vestibulospinal pathways  neck muscle tone
reflexes) adjusted  righting of head
Neck  How
 Neck twisted  neck muscles stretched  impulses to “right” the body go down 
rest of body rotates in the same direction as head
Body on Head  How
 Impulses from body  neck muscles stimulated  head righted
Body on Body  How
 Head held down (while neck twisted
in one direction)
 Pressure on one side of body (eg:
from below)  righting of body

Vestibular Placing  Animal blindfolded  falls  mid-fall, it prepares body for landing
Reaction
Medulla Tonic labyrinthine  Can ignore. Involves vestibulocochlear nerve
 reflex  Extension
 Rigidity
 Max – when supine (extensor tone)
 Vestibulospinal tracts stimulate lower MN

 Min – when prone (flexor tone)

 Stimulation of labyrinths by gravity decreases
Tonic neck reflex Effect of neck position on limbs
 Head turned to one side  Head up – legs flexed  Head down – hands
 “FENCING” position flexed
(in normal adult, tonic
neck and labyrinthine
reflex balance each
other out so you don’t
see these signs)

Spine Stretch reflexes

Supporting reaction
(positive and negative)
Crossed extensor
reflex
Decerebrate Type Decorticate Decerebrate
and Cerebrum lesion (transection at superior border of PONS – so midbrain
Decorticate (1 or 2 corticospinal tracts damaged) removed!)
rigidity
 Path

 Rubrospinal tract (facilitates flexion of upper limb  Rubrospinal tract not intact
esp) still intact
Expression of  Reflexes integrated by SUBCORTICAL structures  Reflexes integrated by MEDULLA and SPINAL CORD
___reflexes expressed expressed
 Rubrospinal tract (originating from  Rubrospinal tract (originating from midbrain)
midbrain, which usually causes flexion) still NOT intact – so no flexion, all extension
intact – some flexion in arms???  Cerebral cortex and cerebellum usually inhibit
action of reticulospinal (voluntary action, esp.
extension for pontine part) and vestibulospinal
(pro-extensor) tracts – now, lost
 Reticulospinal – gamma rigidity
 Effects  Placing reaction
(Disruption of…)  Hopping reaction (hops to balance when pushed
laterally)
 Optical righting reflexes

*Normally integrated in cortex

Posture and Gait  Decerebrate posture  Decorticate posture
 Upper limbs flexed  All limbs extended
 Wrists and fingers too  Adduction too
 Adduction too  Wrist pronation, finger flexion
 Lower limbs extended  Legs – plantarflexion too
 Internally rotated too
 Plantar flexion too

 Gait
 Hemiplegic gait
 Decortication on left  rigidity on right
(bilateral hemiplegic position, vs. unilateral in post-
stroke patients)

Midbrain and Type Midbrain Lesion Spinal Lesion

Spinal Lesions
 Path

Expression of  Level – ABOVE midbrain  Reflexes integrated by the SPINAL CORD expressed
___reflexes  Reflexes integrated by the MIDBRAIN, MEDULLA
and SPINAL CORD expressed
Effects  Decerebrate rigidity submerged in phasic
(Disruption of…) activities (?)
 Standing up, walking
*Righting reflexes present
Rigidity
 Postural
Reflexes
Summary

Orientation of  Cues used

body in space  Visual
 Vestibular
 Proprioceptive
 Exteroceptive
 Vision

REFER TO SLIDES!!! THIS IS INSUFFICIENT

Main pics
Movement
 To remember action: the abduction and adduction are reversed as compared to how they appear in the pic above (except for MR and
LR)
So: SO action – DOWN (counterintuitive) and OUT (abduction)
Hyperopia
Myopia
Astigmatism

 Astig- curvature not uniform

Photochemistry RODS
of Vision  Light activates rhodopsin  activates transducin (to bind to GTP)
 Activated transducin converts cGMP to 5-GMP
 LESS cGMP now  Na+ channels close and less Na+ enter
hyperpolarization of the outer segment (?)

CONES
 Photopsin

Seeing at Night
Rhodopsin-Retinal visual cycle
 Principle – Bright light bleaches/ decomposes rhodopsin (needed
for night vision)  needs Vit.A/ all-trans-retinol to reform
(think: rhodopsin
RHODOPSIN and  All-trans retinol  11-cis retinol (by isomerase)
vitamin A)  Vit. A def
 Most common cause of preventable blindness
 Night blindness (nyctalopia), corneal opacity etc
Optical pathway
Optic lesions

Visual 6 steps
Processing  Light detected by rods and cones on 2D surface
 Transformed into 3D rep
 Segregation (parallel processing)– eg: form, colour, depth,
perception, motion
 Binding – recombining data  unified percept
 Pattern recognition
 Localization of objects in visual world
 Hearing and equilibrium

MUST USE SLIDES

Hearing
Pics
Process Hearing Process (think: K+, Kinocilium, King)
 Eardrum vibrates
 Ossicles (MIS) vibrate
 Vibration of the oval window
 Movement of fluid in cochlea
 Vibration of BASILAR membrane (of the cochlea duct)
 Receptor hair cells BEND
 K+ INFLUX (and Ca2+ too) into hair cells (depolarization)
 Action potential
 Auditory (cochlear) nerve transmits signals (action potentials) to the
brain
 BALANCE/ EQUILIBRIUM
Pics
(Position- Utricle
and saccule )

Pics
(Balance – semi
circular canals)
 Balance/ Linear Acceleration  Body thrust FORWARD (accelerates)
Equilibrium process  statoconia (with greater mass inertia
(saccule and utricle with than fluid) fall backwards on hair cell cilia
the maculae)  info of disequilibrium sent to nervous
centers
 person feels like they were falling
BACKWARDS
 Person AUTOMATICALLY LEANS
FORWARD

Head Rotation  Semi-circular canals DON’T maintain equilibrium

(semi-circular canals and  Semi-circular canals “ PREDICT” rotation (start/stop and direction)
cristae ampullaris)
Vestibulo-ocular *similar to oculo-cephalic reflex, except this isn’t activated by visual stimulus. Eyes move in response to stimulation (movement
reflex of head detected by semi-circular canals, or by hot/cold temp, etc). But, when eyes are open  additional function of eye
fixation (?)
(“Caloric reflex”)
Remember vid of spinning girl
(gaze stabilization  Head suddenly rotated
on non-moving   semi-circular ducts send signals
object )   eyes rotate in a direction OPPOSITE and EQUAL to head rotation (maintains STEADY GAZE)

 In brainstem lect  stimulation by cold water instead

Meniere’s  What  IDIOPATHIC endolymphatic hydrops (a lot of endolymph in the semi circular canals)
 Symptoms (TRIAD)
 EPISODIC – Vertigo, Tinnitus, Low-pitch hearing loss
All the HEARING TESTS IN THE SLIDES
 Cranial Nerves

Mnemonics
CN – “Oh Oh Oh To Touch And Feel Virgin Girl’s Vagina And Hymen”
Type – “Some Say Marry Money But My Brother Says Big Brains Matter Most” (S: Sensory – M: Motor – B: Both)
Number Name Type Function
I Olfactory S 1) Olfactory (smell) info from nose
II Optic S 1) Visual info from eye
III Oculomotor M 1) Eye Movement (all other muscles)
2) Pupil constriction
3) Lens shape (accommodation)
4) Eyelid opening (levator palpebrae)
IV Trochlear M 1) Eye movement – SO4 (Superior oblique)
V Trigeminal B 1) Sensory – sensation from face, ant. 2/3 of tongue (lingual branch)
(ear too!) 2) Motor – Muscles of mastication, dampen loud noises (tensor tympani)
VI Abducens M 1) Eye movement – LR6 (Lateral Rectus)
VII Facial B 1) Sensory – taste from ant. 2/3 of tongue (chorda tympani)
(ear too!) 2) Motor – Facial expression muscles (inc. eye closing – orbicularis oculi), dampens loud noises (stapedius)
3) Tear and salivary glands (Submandibular, Sublingual)
VIII Vestibulocochlear S 1) Hearing and equilibrium
IX Glossopharyngeal B 1) Sensory – taste and sensation from post. 1/3 of tongue
2) Motor– swallowing, elevation of pharynx and larynx (stylopharyngeus)
3) Glands (parotid)
4) Monitoring CAROTID body and sinus chemo/barorecep. (respectively)
X Vagus B 1) Sensory– taste from supraglottic region, parasympathetic to thoracoabdominal viscera!!!!!!!!
 Largest PS nerve (Respi & GI tract!!!!!!!!!!!!)
2) Motor – swallowing, soft palate elevation, midline uvula, talking, cough reflex
3) Monitoring AORTIC arch chemo/baro-recep.
XI Accessory M 1) Cranial - oral cavity, pharynx larynx soft palate
(Spinal) 2) Spinal - Eg: Turn head (SCM), Shrug shoulder (Trapezius)
XII Hypoglossal M 1) Tongue movement
 Anatomy and Functional Components
General  Somatic vs Visceral
 Somatic – from somites  muscles, skin, joints
 Visceral – derived from branchial arches
 Specific (5 7 9 10) – SpV ones
1st V3 Jaw muscles
2nd VII Facial muscles
rd
3 IX Pharyngeal muscles
4th X Pharynx, Larynx muscles
 General
 Smooth muscles and glands of Respi & GIT  Divison  sulcus limitans?
 Salivary glands
 Cough reflex
 Smell and Taste
 Parasympathetic cranial nerves (3 7 9 10)
III Sphincter pupillae (light reflex-
pupil constriction)
VII Submandibular, Sublingual,
Lacrimal glands
IX Parotid glands
X Glands and SM of
 Repi
(longest PS  GI
nerve)  Urinary tract
CN and Vessel
pathways

(base of skull,
superior view)

*4 above pons but 1 & 2 not at brain stem

CN Nuclei in
brainstem
 Cranial Nerves
MORE INFO CLINICAL RELEVANCE
Olfactory  Bipolar  piercing cribriform plate of ethmoid bone  join olfactory  Anosmia – injury to ant. Cranial fossa (severing
bulb (end in TEMPORAL bone, NO thalamic relay to cortex) axons of olfactory nerves), before epilepsy
 SMELL MOA – cilia react with odorant protein  CSF rhinorrhoea – CSF running through ethmoid
bone (like a runny nose)

Optic  OPTIC NERVE (SPECIAL)  Tunnel vision

 formed from Ganglion cells! (develop as evagination from  Increased CSF pressure (eg: glaucoma) affects
diencephalon) optic nerve peripheral vision loss
 Nerve SUROUNDED by  Multiple sclerosis
 CRANIAL MENINGES (Dura mater)  Thick myelin around optic nerve (thus eye often
 Sub-arachnoid space with CSF affected first)
 Nerve CONTAINS  Internuclear Ophthalmoplegia (INO  I/NO)
 Central artery and vein of retina  Ipsilateral adduction (medial) failure,
 Occlusion (eg:AS) – sudden vision loss (usually complete Nystagmus Opposite
TRANSIENT visual field defect)  d/t MLF damage (CN 3 and CN 6 can’t
 Cell stations communicate well and coordinate
 1) Ganglion cells conjugate horizontal gaze)
 2) LGB  Cause: MS, stroke
 Important parts in the pathway  Vision loss (note: pathology of retina is detected by
 Superior colliculus – initiate visual reflexes (eg: tracking) field of vision (see pic on right)
 Pretectal nuclei (eg: pupillary reflexes)
  Trauma to right half of occipital lobe – left field of
vision lost

Oculomotor  Muscles supplied – MR, IR, SR, IO, LPS (levator palpebrae superioris-  Loss of light reflex (MOST COMMON!!!!!) (+
between SO and SR) possible dilation – paralysis of sphincter pupillae)
 Nucleus in midbrain  Oculomotor nerve MOST SUPERFICIAL on
Motor Nucleus extra-ocular muscles – LR6SO4 (Rest- 3) lateral wall of cavernous sinus (/ cranial
fossa)  most commonly compressed in
Parasympathetic light reflex and accommodation head injury  light reflex lost  pupil
nucleus (Edinger dilated on affected side
Westphal)  Argyll Robertson pupil
 NEUROSYPHILITIC LESION (think: syph!)
 Supply of muscles  Pretectal nucleus lesion
 Effects
 NO
 Pupillary light reflex
 HAVE
 VERY SMALL PUPIL (constricted)
 Accommodation reflex
 Loss of accommodation reflex
 PTOSIS (paralysis of LPS)
  Lateral strabismus / squint (“down and
out“ according to USMLE}
 Complete paralysis of same side’s extraocular
muscles (eg: due to thrombosis?)  unopposed
action of opposite muscles (eg: lateral rectus)
 Diplopia on looking up/ medially

 Reflexes

Pupillary Light Reflex Accommodation Reflex

Pupillary  Pupillary light reflex (see left pic) – to regulate
Light Reflex LIGHT INTENSITY

 Optic nerve  Optic chiasma (bypass LGB

and goes to) Pretectal nucleus of that side
(midbrain) post-synaptic fibres enter
Edinger-Westphal Parasympathetic nucleus
on BOTH SIDES  OCULOMOTOR nerve  inf.
Division  ciliary ganglion and short ciliary
nerve  bilateral constriction of pupils
 (sphincter pupillae)
 Swinging-flashlight test (CN II, III)

Accommo-  3 effects (3C)

dation Reflex  Convergence, Constricted pupils (reduce
blurring), Convexity increase
(PARA-  Normal vision path past LGB till VISUAL CORTEX
SYMPATHEIC)   FRONTAL EYE FIELD straight to Edinger
Westphal (lateral) and Motor (medial) nucleus
 Oculomotor nerve  Inferior division 
 Constriction and increased convexity
 Ciliary ganglion  Short ciliary nerve
 sphincter pupillae
(contraction)
 Ciliary muscle (contraction) 
relaxes suspensory ligament
 lens more convex
 Convergence
 Branch to the medial rectus
(contraction)
Trochlear  Only CN emerging DORSALLY (then to sup. Orbital fissure)  Diplopia on looking down
 Nucleus at midbrain
 Eye deviation: (medial and up)
 Function – innervates SO muscle  INFERO-MEDIAL rotation (medial
 “can’t see FLOOR in CN 4 damage”
rotation but ABDUCTION)
Trigeminal  Largest cranial nerve (vagus: longest) (longest intra-cranial = V1
abducens)  Headache (d/t common cold, eye inflammation 
 3 branches (cells bodies in the trigeminal ganglia) (CN exit: SRO) V1 irritation)
 Corneal reflex (“5 7”) – bilateral
 Afferent Part- ophthalmic branch of trigeminal
nerve (nasociliary branch – iris)
 Efferent part – facial nerve (orbicularis oculi
contraction) (CHECK)
For example: -LEFT EYE PROBLEM-
Lesion @ V1 Lesion @ 7
Direct - -
Consensual - Have
V1 – ophthalmic  Lateral wall of cavernous sinus  superior consensual
division orbital fissure  Consensual meaning, if I poke the eye in
(sensory)  Innervates – anterior half of scalp, forehead, question (left), will the right eye close?
external nose, upper eyelid, whole of eye,  Lacrimation (same branches, but loss of reflex
paranasal sinuses doesn’t preclude emotional tears)
 3 branches  1 of which: nasociliary
 Main sensory for – cornea, ciliary body, iris V2
(corneal reflex)  Clinical relevance – extract upper tooth – numb
superior alveolar nerve (br. of MAXILLARY)
V2- maxillary  Path
division  Lateral wall of cavernous sinus  foramen V3
(sensory) rotundum (exits cranial cavity)   Extract lower tooth – numb inferior alveolar nerve
infraorbital foramen (br. of MANDIBULAR)
 Innervates – skin between lower eyelid and  Inf. alv. Nerve  mandibular foramen 
upper lip (maxillary sinus, cheek, gums, upper mandibular canal
teeth, lower eye lid, side of nose, upper lip)  Extract lower tooth
 Problems
V3 –  Path  Problem in moving lower jaw
mandibular  Foramen ovale  divisions  Loss of sensation over cheek and lower lip
division  short trunk – motor  Cause
(sensory-motor)  ant. Trunk – all motor, 1 sensory (buccal  Too much lidocaine  numbness in
– skin of cheek, mucous mem., lower 3  the teeth (inferior alveolar nerve block)
 molar?)  the lower lip and chin (mental nerve
 post. trunk – all sensory, 1 motor block – branch of inf. alv)
(mylohyoid) (see slides)  front two-thirds of the tongue (lingual
 Auriculotemporal nerve nerve block)f
 Inferior alveolar nerve  Trigeminal nerve lesion
 Lingual nerve (joined by chorda  Tests
tympani of 7th CN)  Sensory test
 Corneal reflex (disappearance – often,
lesion of ophthalmic nerve)
 Innervation  Motor test (learnt in CSSC. If not, edit to
include explanation)
 1) Contraction of masseter (paralysed
side won’t move laterally against
reisistance)
 2) Jaw jerk
 Sensory problems- trigeminal neuroglia
(intermittent acute pain)
 Maxillary –between mouth and orbit (eg:
nose)
Sensory below upper lip (lower teeth, lower lip, ant. 2/3 of  Mandibular – between chin and upper ear/
tongue, chin (as mental nerve)), side of face and ear temporal region
Motor Muscles of mastication (pterygoids, temporalis,  Laser ablation of trigeminal ganglion – to
masseter) treat PAIN
(only motor
for trigem) Mylohyoid, anterior belly of digastric (they help to open
mouth + steady hyoid bone during jaw movement)

 Trigeminal Nuclei – SEE PIC (3 sensory, 1 motor)

 Motor  Muscles of
mastication
Sensory Spinal Think: ST
(SpV –  Pain, temp
CN 5 7 9
10)
Main Think: medial
sensory lemniscus
 Touch,
pressure,
propriocep
.
Mesen-  Propriocep.
cephalic
Abducens  Nucleus at pons (inferior) – facial colliculus  Damaged  eye deviation: Medial
 Function – lateral rectus (abduction)
Facial  Nucleus (many)  Tympanostomy  do at INFERIOR QUADRANT!!
Motor Main motor Facial colliculus – formed by  NOT post./ sup. Quad as it may hurt the chorda
nucleus ABDUCENS nucleus and not facial! tympani
 Muscles of facial expression  UMN and LMN lesions
 Post. belly of digastric
 Stylohyoid
 Auricular muscles

Superior Parasympathetic
salivatory (Submandibular, sublingual,
nucleus lacrimal glands)
+
Lacrimal nucleus

(snells-
“Parasympathetic
nucleus”) LMNL
Sensory Nucleus of anterior 2/3rd of tongue via chorda
tractus solitarius tympani branch (taste) (“facial nerve lesion”)
(Same sided – think: Lame, Same)
(sensory root= All face muscles palsy
nervus  Eg: Bell’s Palsy
intermedius)  What  inflammation of facial nerve 
Spinal nucleus of touch/ pain from external ear facial palsy
trigeminal (SpV)  LMN lesion of CNVII BEYOND
STYLOMASTOID FORAMEN (most common
(Incorporates non- traumatic cause)
info from CN 5 7  Viral (herpes)
9 10)  Parotid patho (tumour, parotitis, surg.)
 Compression forceps delivery (kids
don’t have the mastoid bone to protect
yet)
 For snell’s, they classify the nuclei as  Idiopathic
  Motor  Features
 Parasympathetic  Marked facial asymmetry
 Sensory

 Key ones
 Path  Forehead not wrinkled
 Pons  internal acoustic meatus  facial canal  facial/  Eyelid not closed (d/t o.o. Also,
geniculate ganglion  genu  exits skull via stylo-mastoid eyeball rolled up)
foramen parotid gland  branches  Flat nasolabial fold
 Geniculate – sensory ganglion (synapse of the things above)  Angle of mouth drooping
 Associated near parotid gland – ECA, rectomandibular vein  Loss of corneal reflex (rmb: 5 7!!!
 Branches – Two Zebras Bit My Coccyx Afferent 5, efferent 7)
 Hard to keep food in mouth when
chewing/ air in buccinator (buccinator
paralysis)
 Branches (special)  Slurred speech (weak facial muscles)
Greater Petrosal Nerve Parasympathetic secretomotor to
lacrimal gland (eye) *VS: Bulbar palsy – LMN lesion affecting CN 9-11
N. to stapedius Dampens sound acoustic reflex
Inability = hyperacusis (everything loud) UMNL
Chorda tympani Joins lingual nerve (innervation for
sensation)  innervation for taste (ant. (“supranuclear lesion”)
2/3rd of tongue) (Opposite side)
Only lower muscles palsy
 Manifestations – opposite side
 Only lower half severely affected as
 Lower half – only connected to contralateral
hemis
 Upper half- connected with both hemis by
corticonuclear fibres
 Fun fact – smiling and other emotional
 movements usually preserved d/t separate
path for these movements :o

Vestibulocochlear  Vestibular component (balance and equilibrium)  Deafness

 Fibres from (receptors in vestibular organs)  Tests (512 Hz)
 Static (linear) – utricle and saccule (for position)
 Dynamic (rotatory) – semi-circular canals (for
movement)
 To
CEREBELLUM  Vestibulo-cerebellum path 
flocculonodular node
Brain stem  Via medial longitudinal fasciculus
(with CN 3, 4, 6 nuclei – eye
movement)
 Move head to maintain visual
fixation
 Extraocular muscles fix gaze! 
Vestibulo-ocular reflex 
mechanism for nystagmus
Spinal cord  Vestibular spinal tract  ant. Horn
 muscle tone  Vertigo
  Nuclei (4)  Feeling of disorientation
 Nuclei  May be accompanied by – nausea, nystagmus,
 Lateral hearing loss
 Lateral – descend as vestibulospinal tract
 Medial Central Peripheral
 Superior “Base of brain” “Internal ear”
 Inferior  Multiple sclerosis  Labyrinthitis
 Neurosyphilis  Vestibular
 Cochlear component (hearing)  Vertebrobasilar neuronitis
 Fibres for hearing originate in organ or corti (internal ear)  ischaemia  Benign positional
spiral ganglion  cochlear nuclei  impulses sent to Superior  Trauma vertigo
olivary nucleus & Inferior colliculus  auditory cortex  Acoustic neuroma  Meniere’s disease
 Both cortices get input from both ears (as auditory paths
decussate)
 Nuclei
 Nuclei
 Anterior (via trapezoid body  to SON of medulla)
 Posterior
 From
 Spinal ganglion of the cochlea
 Perception
Pitch  Primary auditory cortex
 Cochlear nuclei
Loudness  Varying thresholds of cochlear cells
 Number of cells stimulated
Localization  SON - Superior olivary nuclei
 In general
 Both bipolar neuron types (vestibular and cochlear ganglion) in
internal ear
 Both exit together via internal acoustic meatus
Glossopharyngeal  Path  Injury/ lesion to glossopharyngeal
 Exits at jugular foramen (between ICA and ECA)  No pharyngeal gag reflex (damage to afferent
  Nucleus limb – but don’t do in CSSC. It tests for nucleus
Motor Nucleus ambiguus  Innervates Stylopharyngeus ambiguus- 9, 10, 11)
(elevates larynx)  Vs: cough reflex (vagus – superior internal
(main motor) laryngeal nerve)
 Loss of carotid sinus reflex (barorecep. reflex)
 Dysarthria (slurred speech)
 Eg: Bulbar palsy
 LMN palsy affecting CN 9 -12
 Loss of taste sensation from posterior 1/3rd of
tongue
Inferior salivatory  Parasympathetic  Loss of salivation
nucleus  Controls nerve fibres causing
salivation (parotid) Random pic
(PS)
Sensory Nucleus of tractus  Taste – post. 1/3rd of tongue
solitatrius  General visceral sensations –
carotid sinus, aortic body
Spinal nucleus of  General sense (pain temp touch) –
trigeminal middle ear & tonsil (eg: tonsillitis
pain!)
(SpV –  Facial n.  external ear
incorporates  Pharyngeal plexus
sensory info from  Lingual -sensation – post. 1/3rd
dif. Nerves – 5 7 9
10)

Vagus  General info  Syringing  vagus richly supplies internal tympanic

 Only cranial nerve extending beyond head and neck membrane  vagus stimulated  GIT stimulated 
  Path may vomit
 Medulla  jugular foramen  Meningitis
 2 ganglia near foramen – superior and inferior  Ant. and mid cranial fossa
 Joined by CN 11 root  Headache
 Passes into internal carotid sheath between ICA and IJV  Late vomiting possibly (due to increased
 Nuclei (level of inferior olivary nucleus of medulla) ICP)
Motor Nucleus  Muscles of palate, pharynx and larynx  Posterior cranial fossa
ambiguus via combined Cranial Accessory XI and  Cervical nerve – neck pain
vagus X  Vagus – EARLY vomiting
(main motor)  Including PALATOGLOSSUS (of soft  Superior external/ recurrent laryngeal prob 
palate) hoarseness
 Parkinson’s  Dorsal nucleus may be damaged
pretty early! (before tremors even)
 Vasovagal syncope – loss of consciousness d/t vagus
nerve activation – eg: sight of blood, emotional
distress
 Controls HR  Anesthesia to larynx
Dorsal  Parasympathetic fibres to RESPI and  Ipsilateral loss of cough reflex
nucleus of GIT (until right 2/3rd of colon)!!!! (and  Muscle paralysis
vagus heart?) Palate  Food regurgitation from nose
Sensory Nucleus of  Taste (most posterior tongue,  UVULA DEVIATION to NORMAL
tractus epiglottis) SIDE!!!!!!! (tongue – deviates to
solitarius  Carotid sinus afferent (carotid sinus AFFECTED side)
reflex from CN9) Pharyngeal  Dysphagia
Spinal  Touch pain temp of outer ear, larynx  Loss of pharyngeal gag reflex
trigeminal etc (eating) (efferent limb damage)
nucleus (Spv)  Visceral sensation from upper respi
and parts of GIT (eg: oesophagus) Laryngeal  Slurred speech (dysarthria –
muscle weakness)
 Dysphonia (difficulty producing
(speaking) adequate voice  horseness –
complete loss)
  Aphonia

 Branches (see slides for supply/ innervation)

 Meningeal
 Auricular
 Superior laryngeal  divides into
 External laryngeal – cricothyroid (tensor) (think: ”ECT”)
 Internal laryngeal – sensation of laryngeal mucosa (involved
in cough reflex – breathe in some specially prepared solution
through nebulizer)
 Recurrent laryngeal
 Cardiac- 2 on each side
 Pulmonary plexus
 Oesophageal plexus
 Abdomen
Accessory  Nuclei
 Motor - Nucleus ambiguus
 2 roots/ divisions
Cranial  From medulla (nucleus ambiguus)
 Joins vagus  fibres to
 larynx, pharynx, soft palate
Spinal  From lateral aspect of ventral horn
 Innervates
 trapezius, SCM
 Path
 Leaves cranium via jugular foramen
Hypoglossal  Anatomy  XII (hypoglossal) palsy
 Nucleus (in medulla)  Tongue deviation to affected side
 In open medulla  see hypoglossal trigone (medial to vagal (unopposed action of opposite side tongue
trigone) (vagal = “lateral and below”) muscles)
 Dysarthria possible (slurring)
 Most associated with HYPOGLOSSAL!!!!
(most of the consonants produced by the
tongue)
 Hypoglossal – SUPERFICALLY
LOCATED!!! (external injury more
common than for glosso)
 Atrophy possible
 Function
 Hypoglossal nerve problems may affect strap
 Innervates
muscles!!! (infrahyoid muscles) – careful in
 tongue muscles (intrinsic and extrinsic)  speech and
thyroidectomy!
swallowing
 Styloglossus, hyoglossus, genioglossus (see above)
 NOT Palatoglossus (by VAGUS)
Pathology
 Stroke
Background Info  Cerebrovascular disorders (in general)
 Brain disorder caused by pathology of the blood vessels
 Pathogenic mechanisms
 Thrombotic occlusion (progressive occlusion) – commonly MCA - over ruptured AS plaque
 Embolic occlusion (sudden) (MOST COMMON!)
 Vascular rupture/ haemorrhage
 Hypoperfusion/ hypoxia  common during CVS surgeries, watershed areas esp

Stroke Stroke Global Cerebral Ischaemia

(CVA- focal) (CVA)
 Acute, focal brain dysfunction (>24 hrs) due to vascular  Generalized reduction in cerebral perfusion – eg: cardiac
Vs. disease (ischaemic/ haemorrhagic/ hypoxic)  liquefactive arrest, shock
necrosis  Range of clinical manifestations
Global Cerebral  Irreversible neuronal damage after 5 mins  Mild – transient post ischaemic confusion
Ischaemia  Most vulnerable: “vulnerable hippos need PURE water”  Severe – coma, brain death
Hippocampus, Neocortex, Purkinje cells (in cereBELLUM),  “Watershed” infarcts – usually at most distal portions of
watershed area arterial territories (least blood supply)
 Non-epileptic
 Stroke
classification
 Cause of ISCHAEMIC strokes (occlusion)– TOAST classfication

1) large-artery atherosclerosis
2) small-vessel occlusion
3) cardioembolism
4) stroke of other determined etiology
5) stroke of undetermined etiology
ISCHAEMIC
Risk Factors Fixed Modifiable
 Age, gender (male) race (African- Caribbean esp),  Virchow’s triad (and things affecting that)
genetics  BP, heart disease, DM
 Previous vascular event  Smoking, alcohol
 High oestrogen (oestrogen – pro-inflammatory and
thrombotic effects..)
 Note: oestrogen generally keeps blood vessels flexible
though? So post-menopause – BP increases
Pathogenesis
Symptoms Background  Sudden onset
Info  Acute neuro signs depend on – location, amount of brain compromised, duration of decreased blood flow,
status of collateral vessels, intrinsic vulnerability of brain (HIPPO thig)
General
 Motor (contralateral side)
 hemiparesis, hemiplegia
 Sensory (contralateral side)
 Loss of sensation/ abnormal on one side
 Vision changes (dimness, blurring) – one eye esp
 Hearing changes – dizziness, poor balance etc
 Language
 Difficulty speaking (eg: slurred)
 Perception
 Confusion
LAYMAN – “FAST”
Facial Droop
Arm weak
Speech difficulties
Time (call for help + note the time)
Deficits Based on Lobes Based on Arteries
Frontal Anterior cerebral artery (uncommon)
 Personality and behavioural change frontal and parietal lobe deficits
 Can’t solve problems
 Contralateral hemiparesis (leg esp)
 Urinary incontinence
 Confusion, mutism, grasp reflex, gait apraxia
etc

Parietal Middle cerebral artery (COMMON)

 Attention deficits just NO occipital lobe deficit
 Contralateral hemispatial neglect syndrome
 Contralateral hemiparesis (ARM and FACE
 esp) (think: the most common type affects
arms and face)
 Hemianesthesia
 Dysarthria
 Astereognosis
 Dominant sphere (left) affected
 Global aphasia (can’t comprehend/
formulate language)
 Contralateral homonymous hemianopia
 More info - stroke, trauma, tumors,
infection, or following surgery.
Vascular and neoplastic (malignant or
benign tumours) lesions from the
optic tract, to visual cortex can cause
a contralateral homonymous
hemianopsia
 Non-dominant sphere affected
 Hemineglect (sensory)

Temporal Posterior cerebral artery

 Agnosias mostly occipital lobe deficits
 recognition deficit  Contralateral homonymous hemianopia,
 auditory agnosia unilateral cortical blindness, 3rd CN palsy
 prosopagnosia  Macular (fine detail) vision spared –
 fusiform gyrus damage (temporo- macular vision region supplied by both
occipital) PCA and MCA
 Alexia (dominant hemis)
 Memory loss (transient)
 Hemiballismus – abnormal invol.
movements of limbs (STN)

Occipital
  Visual field defects
 Contralateral hemianopia
 Qua-dra-ta-nopia with macular sparing
Global lesions
 Severe cognitive deficits (dementia)
 Can’t answer simple qns
Stroke
Syndromes
 Gross  Middle cerebral artery infarct
Morphology
Histo
 Imaging  1) NON-contrast CT!! – exclude haemorrhage (before tPA given) – MAIN
 Widely available with shorter scanning times
 Not as great for acute attacks (6 hr +  good)
 Ischaemic infarct  DARK
 Vs TUMOUR (solid)  WHITE on CONTRAST CT! – see imaging table below

TACS PACS LACS POCS

 2) MRI
 BETTER FOR ACUTE ATTACKS!
 When there’s diagnostic uncertainty
 MRI detects ischaemic changes faster (in minutes) than CT (in hours)
 Problem – seen in WHITE

***once CT m/ MRI confirms  PACS  PACI (I for infarct)

Tx  tPA (if within 3-4.5 hrs of onset + no haemorrhage risk)
 Thrombectomy (large artery occlusions)
Prevention  Aspirin, clopidogrel
 Control risk factors well (like BP)
DD  Hypoglycaemia
TRANSIENT  Brief, reversible focal neurologic dysfunction (deficits due to focal ischaemia)
ISCHAEMIC  <24hrs (mostly <15 min)
ATTACK  NO acute infarction
 HAEMORRHAGIC CVA
What  Cerebral artery rupture (usually d/t AS/ HT!!!)  inflammation of brain tissue  increased ICP  damage both hemispheres
 Often fatal
 2 main ones – subarachnoid and intraparenchymal
Subarachnoid Subarachnoid Intraparenchymal
haemorrhage Cause  Cerebral artery (BERRY ANEURYSM) rupture!!!!  HT!!!!!! (charcot-bouchard – HT)
vs  Cause: unknown/ genetics  Systemic coagulation disorders
Intra-  Predisposing: smoking, HT  Amyloid angiopathy
parenchymal  ANTERIOR COMMUNICATING ARTERY esp! (then  Vasculities, aneurysms, vascular
MCA) malformations
 Extension of traumatic haematoma
 Rupture of intraparenchymal haemorrhage into
ventricular system, vascular malformation,
hypocoagulopathy, tumour
Where  MCA – lenticulostriate branches (putamen of
BG)
 Basilar artery – pontine perforation
 Thalamus etc
Clinical picture  Sudden excruciating headache (occipital)   Varied
THUNDER CLAP  Slow chronic dementing disease
 LOC  Rapid death
More info  Investigations  HT effect on brain
 LP & CSF – uniformly blood stained in 3 bottles =  Massive HYPERTENSIVE INTRACEREBRAL
SAH HAEMORRHAGE
 CT scan/ MRI  HT  BV abnormalities
 Arteriography  Larger arteries  accelerated AS
 Smaller arteries  hyaline
arteriolosclerosis
 Severe cases  frank necrosis
 HT  BV wall damage
 Wall weakening and dilation 
Charcot-Bouchard
 microaneurysm (in lenticulostriate
branch of MCA)  rupture
 Lacunar infarcts, slit haemorrhages, HT
enceph

Morpho

 Extending into ventricles here

FUN FACT  Young, healthy patients  consider unusual causes (like haemophilia)
 Neoplastic Lesions of the Brain

General  Key characteristics

 Not that common – 10% of cancers (but most common childhood neoplasm)
 Older people esp -50+
 Location
 Adults – supratentorial
 Kids – Infratentorial
 No distinction between benign and malignant
 No detectable precursor stages
 Rarely spread out of CNS – rare to see in LP
 WHO grades – I to V (pleomorphism, mitosis, necrosis)
 Location determines effects

 Classification
  Glioma
 Neuroglial cell arising tumours – astrocytoma, oligodendroglioma, ependy-moma
 Location
 Adults – cerebral hemisphere mostly
 Kids – cerebellum, brain stem mostly (spinal cord – rare)

 Adult/ child classification

 Doesn’t mean all of them can’t be in the other (adult/ child). Can, but a lot less likely

Adult Primary Brain Tumours (4 main)

Description Morphology Investigations, Tx & others
Diffuse  Very common  Grade II – well-differentiated
Astrocytoma  Where - Cerebral hemis  Grade III/ IV – anaplastic
 Cause (pleomorphism)
 Low-grade astrocytoma (like  Grade IV – Glioblastoma multiforme
Grade II) (with haemorrhage and necrosis)
 Mutations in IDH1 and IDH2  “Butterfly glioma” – can cross
(isocitrate dehydrogenase) corpus callosum
 High-grade astrocytoma (eg:  Pseudopallisading cells
Grade IV)
 Loss of function mutation in
TUMOUR SUPPRESSOR GENES
(p53 and RB)
 No risk factors!
 Oligodendro-  Deletions of chromosomes 1p and 19q  Gross  Better prognosis than astrocytoma!
glioma  think: Olivia (oligo) is GRUMPY  Infiltrative  Responsive to tx
(1p) as there are 19 people in the  Gelatinous gray masses (+
queue (19q) for the fried egg and possibly focal haemorrhages)
chicken  Often calcified
 40+ y/o  Histo
 Where – cerebral hemis (frontal/  “Fried egg cells” – round nuclei +
temporal esp) clear cyto
 “Chicken wire” capillary pattern

Ganglio-  Mix of GLIAL elements (eg: 

gliomas astrocytoma) + NEURONS
 Presentation – seizures possible
Meningioma  Arise from: ARACHNOID  Gross  Dura attachment possible (“tail”)
meningothelial cells  External surface of the brain
 How: acquired LOSS OF FUNCTION (doesn’t invade) + ventricles
(an “oma” that is mutation in NF2 tumour suppressor
TRULY benign. gene (chromo. 22)
 Think: “2!”- MeningioMa,
But, can still be Psammoma – 2 Ms. NF2. Chromo
malig. But rare) 22.
 Females esp
 Presentation – seizures possible +  Histo
focal neurologic signs  Many (don’t matter tbh).. eg:
 Psammomatous
meningioma (one sub type,
see below)
 Psamomma bodies
 (laminated
calcifications): papillary
thyroid ca, serous
cystadenoma of ovary
 Anaplastic (malignant) – the
rest seem to be benign

Hemangioblastoma  Associated
 VHL
 Retinal angiomas
 Secondary polycythaemia possibly
Pituitary Adenoma  Non-functioning/ hyperfunctioning
(lactotrophs esp)
Schwannoma  Where: cerebellar pontine angle  S-100 protein expressed
 Involves: CN 7 & 8 esp
 Associated with: NF2

Childhood Primary Brain Tumours (3 main)

 Description Morphology Investigations and Tx
Pilocytic  Most common paediatric brain  Grade I
Astrocytoma tumour (80% - check)  Cystic/ solid
 Benign behaviour (is largely benign,  Well circumscribed
(mostly benign!) though some could be malignant?)  GFAP + (some protein)
 Mutations in BRAF gene (think” kids  Bipolar cells with long, thin hair like
BARF a lot on their Pillows) processes
 Cerebellum (posterior fossa) esp  Rosenthal fibres- eosinophilic,
corkscrew fibers (think: kids like to
ride the corckscrew)

Medulloblastoma  Most common MALIGNANT brain  Morpho  Highly malignant!!! But with
tumour in childhood  Can go up and involve the aggressive treatment, 5-year survival
 Where: cerebellum!!!! meninges rate ~75%
(meduLLoblastoma – cerebeLLum)
 More info
 Can compress 4th ventricle 
noncommunicating
hydrocephalus  Histo
 can send “drop metastases” to  Homer-Wright rosettes (center:
spinal chord (think: “dropping the meshwork of fibres) (homer
bomb” that kid has malignant simpson is MUDDLED)
brain tumour)

 Sheets of anaplastic small blue

 cells (above)
Ependymoma  From: ependymal lining  Gross
(ventricles ,central canal of spinal  Solid/ papillary masses from
cord) ventricle floor
 Who
 Children - <2 esp!! (4th ventricles
esp)
 Adults – spinal cord esp
 Can cause hydrocephalus
 Malignant  Histo
 Perivascular pseudorosettes
(tumour cells around blood
vessels)

 Rod-shaped blepharoplast
Craniopharyngioma  Most common childhood  Gross
supratentorial tumour  “Motor oil- like” fluid in tumour
 From remnants of Rathke pouch (cholesterol crystals)
Pinealoma  Pineal gland tumour (like germ cell
tumours like seminoma)
 Parinaud syndrome (inc. vertical gaze
palsy)
 Precocious puberty
 Others
Description Morphology Investigations and Tx
Primary  Mostly – diffuse large B cell  Investigations
CNS lymphomas  EBV positive (almost always)
Lymphoma  Most common CNS neoplasm in  Aggressive, poor response to therapy
immunosuppressed (vs. other lymphomas outside brain
 Immunosuppressed  EBV which have god response to chemo…)
reactivated  lymphoma

Germ cell tumours  Where: midline – esp: pineal/

suprasellar regions
 Who: <20, M esp
 Most common: germinoma
 Equivalents: dysgerminoma,
seminoma
 Clinical features
Metastatic  Mostly carcinomas  Gross
tumours  Esp from: lungs, breast, kidney, GI,  Sharply demarcated masses
skin (melanoma) (often at gray-white
junction!!!!!) + cerebral oedema

 Surrounding reactive gliosis

 In GENERAL
Clinical Features Diagnosis Prognosis
 Depends in location  Diagnosis  Problems caused by a brain tumour don't
 Cerebellum – ataxia (kids esp)  Contrast-enhanced CT always resolve as soon as the tumour is
 Localized permanent neuro deficit  MRI removed or treated.
 Cranial nerve palsy  Management / further investigation  For example, some people have persistent
 Epilepsy (almost all brain tumours)  Biopsy & histology (eg: after resection) weakness, epileptic fits (seizures),
 Increased ICP effects difficulty walking, and speech problems.
 headache (worse on lying and
straining)
 vomiting
 brady
 Frontal tumour – asymptomatic
 Intracranial Infections

(STUDY FROM SLIDES!!! This is only keykeykey points)

General Info  CSF

 Low immunoglobulin levels
 Low protein content
 Note: CNS itself no lymphocytes – depend on migration
 BBB & Blood-CSF barrier

 Pathogenesis
 Random
 Increased ICP  CI of LP (still acceptable in sub-arachnoid….raise in ICP not as much apparently)
 Incubate CSF at 37 deg
Meningitis  Main features
 Neck and back stiffness!!!
 Photophobia
 Headache
 Nausea & vomiting

*Mening can have positive KERNIG (pain on extending leg in THAT position) and BRUDZINKI signs (flex neck, legs also
flex). NOTE: kernig  may also be sub-arachnoid haemorrhage

 Kids
 Buldging frontanelle
 Opis-tho-tonos
 Strange high-pitched cry
 Fever, convulsion persistent vomiting
Purulent Meningococcal  This + Hib + s. pneumoniae (the first 3)
(Bacterial)  polysaccharide capsule
(Neisseria  IgA protease
meningitidis)  Gram-negative diplococci
 Esp. Saudi
 *no. 1 in TEENS (think: Neisseria)
Hib  Gram-negative bacilli, which requires factors X & V (5 & 10) for
growth
 Complication – many, including sensorineural hearing loss
 *kids esp
Pneumococcal  Gram- positive diplococci
 ** most common in general
(s. pneumonie)
Listeria
monocytogenes
Neonatal  GBBHS, E. coli
meningitis
Tuberculous
meningitis
Aseptic Enterovirus  Echovirus – types 70 & 71 esp
(Viral & Fungal) HSV2  Type 1 above belt, type 2 below belt
(herpes)  Intranuclear inclusions
*viral – mostly Cryptococcus  Assos. with pigeon rearing
mild & self- neoformans  India ink preparation – encapsulated yeast seen
limiting  Culture: sabouraud’s dextrose agar (cream-coloured colonies)
 Encephalitis  Meningoencephalitis possible (eg: through cribiform plate of the ethmoid in Naegleria fowleri)
 Features
 Altered personality
 Ataxia
 Upgoing plantar response
 Signs of cerebral/ brain stem failure
 Signs of brain swelling
Cerebral abscess  Assos. with
 middle ear/ mastoid and sinus disease
 congenital heart disease
 S. milleri !!!
 No LP (CI)!! If pus culture necessary, use burr-hole
Poliomyelitis  Sabin vaccine > salk
 Disease of the ANTERIOR HORN CELLS  LMN damage
Rabies  HYDROPHOBIA (vs meningitis: photosensitivity)
 Negri bodies (intracytoplasmic inclusions)
 Defer debridement (may make it worse)
 Often die from lung complications
Spongiform  Prion-related
Encephalopathies
 UMNL and LMNL

CLINICAL UMNL LMNL

FEATURES Strength  Weak (spastic paresis)  Weak (flaccid paralysis)
(May have COMPLETE paralysis)
Tone  Hypertonia (stiff)… possibly:  Hypotonia (flaccidity)
 “Clasp-knife” type  initial resistance
(“catch”) when limb is flexed, then speedy
movement (as resistance quickly decreases)
 Cogwheel rigidity (Parkinson’s)
 Sustained clonus
Reflexes  Hyperreflexia  Hyporeflexia/ areflexia

(early stage may be hypotonic)

Muscle Atrophy  No  YES

(but possible disuse atrophy)

Fasciculations  No  YES
Extensor  Yes
plantar reflex
(positive
Babinski’s sign)
Impaired  YES
superficial
reflexes
 (Abdominal and
cremasteric)
Pattern of  “Pyramidal distribution”  Possible foot drop and high stepping gait (if CPN is
Weakness/  Upper – Flexors stronger affected)
posture/ gait  Lower – Extensors stronger
 “Hemiplegic posture”
 Arm flexion, hand floppy
 Hip & knee EXTENSION
 Foot PLANTARFLEXION
 CIRCUMDUCTION on
walking

NOTE – technically, the presentations are either due to pyramidal tract/ extrapyramidal tract problems
 Pyramidal (more “specialized”)– Babinski sign positive, cremasteric and superficial abdominal reflexes
negative, loss of fine-skilled voluntary movements
 Extrapyramidal – severe paralysis, hypertonicity/ spasticity, hyperreflexia, clasp-knife reaction
UMNL LMNL
Background  Where  Where
info  Motor cortex  Ant. Horn in spinal cord  Ant. Horn in spinal cord  motor end plates
 AKA  Ipsilateral
 Long / pyramidal (corticospinal) tract signs
 Contralateral
Possible  CVA  Peripheral neuropathies – eg: causing LL paraesthesia
Diseases  Brain trauma  Radiculopathies
 Spinal cord injuries  Anterior horn cell disease (classified here..) – eg: ALS causing
 Demyelination fasciculation
 Osteophyte compressing nerve root
 Cut peripheral nerve
Motor Neuron Disease (some)
 Grading
Systems

Investigations  SCANS ARE BEST!!!!!!

 1) CT BEST!!!!! -
 2) MRI
 Nerve studies
 Nerve conduction studies
 EMG

More Info  Facial weakness

 UMN- Lower part affected
 Lower part – only supplied by 1 side
 Upper part spared – supplied by both sides of brain
 LMN – BOTH upper and lower parts of face affected
 Motor Neuron Disease
 Can affect upper and lower motor neuron (but not all)
 NO SENSORY EFFECTS
 Main presentation
  ALS – lateral CS tract with amyotrophy (can affect both UMN and LMN)
 Primary lateral sclerosis – UMN affected
 Progressive muscular atrophy – LMN affected
 Progressive bulbar palsy- lower cranial nerve nuclei affected (dysarthria, dysphagia, fasciculations etc)

Investigations

CT MRI
Non-contrast Contrast
Ischaemic DARK Ischaemic WHITE
infarct Infarct
(thrombotic) *check: internal (good for acute)
capsule infarct is the
opp (white?)
Haemorrhagic WHITE Tumour WHITE Tumour WHITE
infarct

Headache
 Major Mental Illnesses

Neurotransmitter table

 Note:
 Schizo
 Negative symptoms  d/t SEROTONIN HYPOTHESIS (high sero  block dopa in mesocortical path)
 We can rmb it as atypical anti-psych focusing on negative symptoms more – so it’s special in inhibiting 5HT >> D2 (I think)
 Inhibit serotonin  more dopa in mesocortical path  less neg symptoms
 Typical antipsych and mania drugs same (block D2 more)

Schizophrenia Depression Mania

What  Split MIND (not personality)  Mania pt – almost always
 Split of normal links between perception, BIPOLAR
mood, thinking, behaviour and contact with  As 90% of MANIAC
reality patients develop
 Irreversible deterioration of mental functions DEPRESSION

Diagnostic  Characterstic symptoms Major Depressive Disorder – DSM-5  1 week or more of EEI mood
Criteria  Disturbance (6 months or more) criteria (5+ from below)  Elevated
 At least 1 month of active phase symptoms  1 2 weeks or more of either/ both  Expansive (grandoise/
 2+ from below (5)  Feeling depressed (/ irritable in excessively friendly)
 Positive symptoms (abnormal young)  Irritable
functions developed)  Anhedonia (lose interest/ *May have transient depression
 Delusions (false beliefs/ pleasure)
misinterpretation)  4+ from below (4+3)
 Hallucination (abnormal  Physical (think: depressed person
perceptions, esp. auditory) can’t sleep, eat etc)
 Disorganized speech  Fatigue !!!
 Grossly disorganized/ catatonic  Significant weight change or
behaviour appetite disturbance (usually  During that time 3+ from
 Negative symptoms (reduction of a decrease) below (7) – Mania  DIG
normal function)  Sleep disturbance (insomnia FAST
 affective flattening (restricted or hypersomnia)  Distracted
emotional expression)  Psychomotor effects (“slow”  Impulsivity - Excessive
speech/ movement) incvolvement in
  a-log-ia (unwillingness to speak/  Psychological pleasurable activities
decreased fluency)  Feelings of worthlessness (eg: shopping spree,
 a-volition (little initiative in goal-  Can’t concentrate- sexual indiscretion, poor
directed behaviour) Diminished ability to think or business choices)
*When NOT acute, acute phase symptoms occur in a concentrate; indecisiveness  Grandiosity – inflated
attenuated form (eg: odd beliefs but not straight  Recurrent thoughts of death, self-esteem
up delusion) recurrent suicidal ideation  Flight of ideas
without a specific plan, or a  Increase goal-directed
 Social/ occupational dysfunction suicide attempt or specific Activity/ psychomotor
 Interpersonal relationships, work, self-care plan for committing suicide Agitation
 Less Sleep needed
(USMLE says 5 or more out of 9 of the  Talkative
below)
Symptoms Main symptoms - 4 As Other Symptoms (on top of diagnostic  Loss of weight (over-active)
 Association loosening criteria below)  Bright clothes
(apart from  Shift in topic with no logical connection  Body ache, headache  Hallucinations
diagnostic  Autism  Low sex drive
criteria)  Changes in Affect (mood and what you show on  Changes to your menstrual cycle
face is dif)  Constipation
 Ambivalence (want to do something, but do  Hallucination
something else?) 

Clinical Features – ACUTE

 MAINLY
 Lack of insight!!!!!!!
 Auditory hallucination
 Affective flattening (restricted emotinal
expression)
 Ideas of reference (thinks they caused smth
to happen but they didn’t)
 Suspicious
 Appearance and behavious fairly normal
 Preoccupied with something though – eg:
religion, thoughts
 Laugh without reason, social withdrawal
 Speech
 Association loosening, neologisms, flighty
ideas
 Thought disorder
 Block, delusions
 Perceptual disturbance
 Hallucinations (no stimulus)
  Illusions (have stimulus but misinterpreted)
 Impaired
 Concentration, memory and INSIGHT!

Clinical Features – CHRONIC

 Underactivity, withdrawal, apathy
 Hallucinations
Subtypes  Hebephrenic (CHILDISH mostly)  Mania (BP-I )
 Catatonic (PSYCHOMOTOR disturbance mainly)  More serious – full
 Paranoid (hallucinations) – better prog. blown mania
 Simple (negative symptoms esp)  Hypomania (BP-II)

Who  M and F equal  Females more (25%)

 M onset earlier
 Lower social class (social drift?)

Atiology BIOPSYCHOSOCIAL!!!!!!

 Some genetic link (polygenic)  Some genetic link (higher risk in  MOST GENETICALLY
 Neuro dysfunction those with firstdegree relatives – LINKED!!!
 Birth complication (LBW, injuries etc) alcoholism, bipolar, depression)  NT issues (below)
 Hypofrontality (low blood flow to frontal  Psychological theories
cortex)  Loss of loved object
 Biochemical (see TRACTS and TABLE below)  Maternal deprivation (<11 y/o)
 Dopamine hypothesis  Learned helplessness
 Serotonin hypothesis  Perfectionist etc
 Others (environemental)  Aaron Beck’s triad  Negative
 Personality, forced migration, isolation, family view on SEF
envionment (double bind)  Self
 Environment
 Future
 Sociological
  Endocrine/ drugs
 NT issues (below)
Impt tracts DOPAMINE-RELATED TRACTS
MESOLIMBIC
(positive symptoms esp)
 Dopamine hypothesis
 Overactivity of DOPA (positive symptoms)

MESOCORTICAL
(negative symptoms esp)
 Serotonin hypothesis
 Serotonin overactivity  INHIBITION of
Dopa in the mesocortical path (negative
symptoms) (counter-intuitive!!!)
NIGROSTRIATAL
 If blocked: extrapyrimidal AE, like drug-induced
parkinson’s

TUBERO-HYPOPHYSEAL
 Dopamine = PIH.
 If blocked: increased prolactin release from
pituitary  hyperprolactinaemia)

*Dopamine tracts:
MIDBRAIN  limbic system/ cortex
*these tracts involved in memory and reward too
Prognosis  No cure but can manage  Can recover  Much recurrence
 Pharmaco, therapy  Pharmaco, therapy, ECT (can use
for schizo too but less so)
  Interesting: dys-thy-mia (less severe
depression for most of the day, for 2
or more years)  poorer outcome

Neurotransmitters
Schizophrenia Depression Mania
THINK Overall Stimulation Overall Depression Overall Stimulation
Dopamine
 In mesoLIMBIC pathway (D2 and D4)
 Explains positive symptoms esp
Serotonin
 Serotonin and dopamine neurones (brain stem   Low 5HT d/t low plasma tryptophan
basal ganglia)  low metabolite CSF 5- HIAA
 Serotonin regulates dopamine release (more sero
 less dopa (serotonin hypothesis) in
mesocortical path  negative symptoms
 LSD = serotonin agonist (psychotic features)
NE* Ambiguous
(acute)/ (chronic)
Glutamate
 Excess glutamate receptor (???)
 NOTE: proposed that schizophrenia results from
hypofunction of NMDA Receptor (more assos.
with negative symptoms) – yota uno
GABA
 Less GABA recep
Other  Excess cortisol
abnormalities  In depressed: Stress  hypo
(CRH)  pituitary (ACTH) 
adrenal glands (cortisol) 
negative feedback on hypo here
 FAILS  so: excess cortisol
More info  Decrease in caudate nucleus size  Imbalance of dopamine and
GABA

Recreational Drug Use

General Info  Males esp, malays esp

 Every drug affects patient’s eyes (pupils/ conjunctiva)
 Other drugs not covered
 Cocaine – a euphoric high, then a crash (can be more hostile even when not taking drug)
 LSD (acid) – intense hallucinations + euphoria
Drug Abuse Drug Abuse Dependence (worse)
And Habitual taking of illegal drugs
Dependence  Depressed, violent, nervous  12 months
Signs  Change in appearance/ functioning  3+ of the below (2+5)
 Insomnia  Physical
 Physical complications  Tolerance
 Accidents  Withdrawal
 Withdrawals  Psych
 Legal/ social problem – financial problems, family request  Larger amounts/ longer periods than intended
help  Can’t cut down
 Drug related behaviours more important than
others
 Much time spent on drug related behaviours
 Continued use despite problems
NOTE:
 Psych/ social stimuli may trigger cravings – may have
symptoms resembling withdrawals
 Single exposure – can relapse (reinstatement effect)
 Dependence  Ventral tegmental area (in midbrain) has both nicotinic and GABA receptors
explanation  GABAnergic neurones express μ & delta opioid receptors
(MEDICAL)  μ opioids activate receptors  nucleus accumbens (pleasure center) overall stimulatory effects
 Decrease GABA release
 Increase DOPAMINE release  EUPHORIA

 This pathway of positive reinforcement is also involved in  Food, reward, sex

Opiates Cannabis Amphetamine Ecstasy

(Marijuana, Weed) (ICE) (MDMA- METH)
 Poppy plant Grass/ pot/ dope/ ganja  Methylene-Dioxy-
 Examples Metham-phetamine
 Opium, Morphine ,  Longer lasting & more
Codeine , Heroin toxic than ICE
 Night club drug
Characteristic  Depressant  Hallucinogen  Stimulant  Hallucinogen
MAIN EFFECT HIGH/ EUPHORIC RELAXED VIOLENT SOCIABLE AND AGREEABLE
AND (stimulant) (depressant) (+ some euphoria) (“YES”)
SYMPTOMS (stimulant) (stimulant)

(refer to slides)  Pain relief  Confusion, Paranoia  Alertness  Hallucination

 Pinpoint pupils  Red eyes  Persecutory delusions  Hyperthermia (due to
 Physical dependence occurs  Slothy (think something bad is increased serotonin -
soon  Hallucinations (possible) happening/ will occur) possibly fatal)
 Reduced appetite  INCREASED appetite  Arrhythmia + circulatory  Arrhythmia  death
collapse  later seizures,  Flashbacks (a “trip” way
coma after the drug was
 Hallucinations taken.. months even..?)
 Reduced appetite  Reduced appetite
Long Term  INFECTIONS/ ULCERS!!! VERY VARIED  May cause schizophrenia  May cause
Effects (esp: HIV)  Lung problems (eg: lung (due to increased PARKINSON’S
  Heart and lung problems cancer) DOPAMINE levels) (DECREASED
(refer to slides)  Lower sperm count DOPAMINE levels –
substantia nigra
damage?)
Duration  Up to 3 hours
 Takes a long time to leave
body (1 month)
 Can usually detect all these
drugs in urine
Dependence  High risk!!!
 Overdose can cause death
(street heroin quite impure)
Withdrawal  Occurs FEW HOURS after  Speed Crash  No clear withdrawals
stopping drug  Rebound depression,
 Duration – few days (won’t fatigue
die)
 Symptoms
 Cravings
 Restlessness
 GIT: cramps, diarrhoea,
vomiting
 Fluids: Perspiration,
lacrimation, runny nose
 Insomnia
 Joint pains
Tx  Methadone
 Bu-pre-nor-phine
 Nal-trex-one (naltrexone for
trex back to being sober)
(some of these can be used for
other drugs too)
 Solvents Alcohol
Info  Glue, petrol, cleaning fluid, aerosol etc  GGT – sensitive indicator of alcohol use
 Teens esp  AST 2x ALT (“toAST 2 ALcohol”)
Symptoms EUPHORIA
 Like alcohol  blurred vision, slurred speech, ataxia, nausea
 Possible death
 Solvent toxicity
 Asphyxiation
Long Term
Effects
Dependence  Can’t control
 Continue despite harm
 Tolerance
 Withdrawal
Tx  Nal-trex-one (for opioid withdrawal tx too)

Dementia and Alzheimer’s

Background  Normal Benign senescence (age-related forgetfulness)  can recall most things but SLOW
Info  less able to perform complex task/ learn
 no loss of language ability
 Neurodegen. Disorders  loss of neurons  problems with cognition/ movement with intact consciousness
 Cognition  learning, thinking, reasoning, problem solving, decision making, and attention + remembering
Dementia  Clinical condition  decline in cognitive function
 Memory impairment with  AAAE (aphasia, apraxia, agnosia, executive dysfunction (cognition))
 PROGRESSIVE (slow), except
 Vascular  step-ladder, quick decline
 CJD (quick)
 Other causes of dementia not in notes below
  Intracranial tumour (inc: haematoma), endocrine, vitamin deficiency (inc. folate and niacin - pellagra), toxins (inc.), metabolic
uraemia (hypoglycaemia etc)
 REVERSIBLE causes of dementia (do tests to exclude these!)
 Pseudodementia (due to DEPRESSION)
 Hypothyroidism
 Neurosyphilis – test: FBA-ATS (symptoms: ataxia, urinary incontinence, hx. multiple sex partners)
 B12 def
 Developmentally delayed (esp: Down Syndrome)  increases risk of dementia
 Down syndrome  increased Alzheimer’s risk  APP on chromo 21
 Dementia in elderly  1) Alzheimer’s, 2) Vascular dementia
 Terms associated with dementia catastrophic reaction, confabulation (confusion, unintentionally giving wrong info)
 Rehab/ tx
 Meaningful, realistic goals
 Look out for caregiver’s depression

Dementia
Cause Features Morphology More Info
Alzheimer’s  Altered proteins Preclinical Gross  Decreased ACh
(Global)!!!  ApoE-2  Appears normal  Widespread cortical  Enzyme for ACh
 ApoE-4 – promotes beta  Hippocampus may be affected atrophy (hippocampus synthesis (choline
(degenerative) amyloid accumulation way before symptoms esp, with granulo- acetyltransferase)
 APP, presenilin-1 and 2 vacuolar degen.) – greatly reduced
(familial AD forms, earlier Mild narrowing gyri widening (note: but AChE
onset)  Some memory loss and sulci also reduced)
 APP = amyloid confusion  D/t clusterin (plasma
precursor protein  Trouble with daily tasks, money protein)
 Presenilin is the  Mood and personality changes
 catalytic subunit of Histo
gamma secretase Moderate (already pretty bad) *GREATER AMOUNTS THAN
enzyme (which  Difficulty recognizing people NORMAL OF…
cleaves APP  Language and motor difficulty
embedded in cell  Repetitive statements
membrane  beta movement
amyloid)  WANDERING
 PSEN I mutation  Loss of impulse control -eg:
(most common cause random undressing
of alzheimer’s)  Catastrophic reaction  Senile neuritic plaques
abnormal PS1 (emotional outburst/ (white arrow)
catalytic subunit overreaction) can hurt  Extracellular β-
more of the caregiver amyloid
hydrophobic form of  Hallucination  Can cause amyloid
beta amyloid angiopathy 
produced  Severe intracranial
aggregation  CAN’T recognize loved ones haemorrhage
 Menopausal oestrogen  Incontinence
deficiency  can cause  Can’t communicate  Neurofibril-lary tangle
neurodegen.  Loss of self (black arrow)
 Not fatal – but can die of other  Hyperphosphorylated
stuff tau proteins
 Hard to swallow- aspiration (insoluble)
 Leads to
pneumonia
 Oxidative damage,
 Infections, seizures (rare)
inflammation

*LOSS OF CHOLINERGIC
NEURONS IN FOREBRAIN NUCLEI

Vascular  Multiple infarcts/ ischaemia  1st - Step-wise decline in other Histo  CT/ MRI – multiple
 (AS etc) causing COGNITIVE function  Amyloid deposition in cortical/ subcortical
 Demyelination/ axonal  2nd - Late-onset memory tunica media infarcts
loss problems
 Breakdown of BBB/
Blood-CSF barrier
 Hx
 HTN
 Hyperlipidaemia
 DM
Lewy Body  Cognitive and motor  Visual HaLEWCYcinations Histo  Mixed/ co-morbid 
Dementia (parkinsons) symptoms <1 (hallucinations)  Intracellular LEWY Alzheimer’s, VBI and
year apart (usually  Dementia - with fluctuating BODIES (in cortex) LBD can occur tgt
MOVEMENT disorder first) cognition and alertness  α-synuclein
 If >1 year – dementia (intracellular
secondary to parkinson’s eosinophilic
inclusions with clear
halo)

Frontotemporal  Degenerative (tauopathy, like  SUBTLE memory impairment Histo  Detection

Dementia (FTD) alzheimers)  Memory and calculation  Pick bodies (round)  MoCA > MMSE
(Pick’s disease)  Hereditary/ sporadic MOSTLY preserved abnormal tau  Montreal
 PROMINENT PERSONALITY accumulation Cognitive
CHANGE!!!! (P for Pick, P for Examination
! MANY THINGS personality)
AFFECTED!  Loss of impulse control
  Apathy, no sympathy
 Odd jocularity
(uncontrollable laughter)
(think: P for  Hyperorality (compulsive
Pick, eating/ talking etc) and
Personality and other compulsive behaviour
Poker (joker))  Speech - APHASIA- Language
impairment
 includes content reduction
(Wernicke affected) (broca
too possibly?)
 Movement – bradykinetic,
apraxic gait, incontinence
Huntington’s  HUNTington gene  CAG  Dementia
repeats on chromo. 4 (4  Movement problems – chorea
(USMLE extra) letters in HUNT) etc
 Caudate (think: basal  Behaviour – aggression,
ganglia) loses depression
 ACh and
 GABA
(but more dopa)
*striatonigral prob
Infective  ABNORMAL PRION protein in  Rapidly progressive dementia Gross  Increased 14-3-3
(CJD – brain (PrPSC)  MYOCLONUS + Ataxia  Spongiform cortex protein in CSF
Creutzfeldt-
Jakob disease) (“Croitz- felt yacoub”) Histo
 Prions
(USMLE extra)
 Pharmacology

 Sesation, hypnotic, anxiolytic  newer Non-BZD hypnotics – Zolpidem etc

Neurotransmitters and Intro to pharmaco

Neurotransmitters – background info

 NT characteristics
 Higher concentration in synaptic area
  Released by electrical/ chemical stimulation (calcium-dependent mechanism)
 Synaptic mimicry
 Random fun facts
 Depression – sympathetic deficiency state
 How drugs acting on these receptors work (I think. Check)
 Drug (eg: barbiturate)  modulates effects at the receptor (eg: binds to something (eg: GABA recep, and increase affinity of GABA to the recep)
 affects “gate” for NT (eg: more opening and closing of Cl- channels for more Cl- to enter)  effect (hyperpolarization)  INHIBITORY (so we
say barbiturates, and GABA, are inhibitors – of action potentials)

Neurotransmitters (CNS)
Note: Find specific examples ON THE SLIDES!!!
ACh Excitatory  Functions
 Arousal (wakefulness), short-term memory, learning and movement
(but  Related drugs
inhibitory at  Parasympathomimetic effect (increase ACh!!!) – AchE inhibitors (for alzheimer’s) (eg:
heart) tacrine)
 Central anticholinergic action – muscarinic blockers in parkinson’s (eg: benztropine)
Biogenic NE Excitatory  Functions  Dopamine &
Amines  arousal, wakefulness, mood, CV regulation serotonin 
 Related drugs associated with
 Sympathomimetic action – CNS stimulants (eg: nausea and
amphetamine), MAOI (eg: phenelzine), TCA (eg: vomiting
amitriptyline)  Vomiting Centre
Dopamine Excitatory  Functions  CTZ
 Emotion, reward system (pleasure), motor control  NE, Dopa, Sero
(but  Related drugs  Imbalance 
inhibitory at  Antidopaminergic action – eg: antipsychotics (may cause depression,
some parts drug-induced parkinsons’) (eg: chlorpromazine) psychosis
of the brain)  Fun fact on
NE Excitatory  MOA Histamine:
 Inhibitory  Excitatory effects – α1 and β1 (VC, increase HR)  Metab, temp.
 Inhibitory effects – α2 and β2 (VD, bronchodilation etc) control,
! Serotonin ! Inhibitory  Functions hormone reg,
 Feeding behaviour, body temperature, modulation of sleep-wake cycle
(eg: inhibits sensory paths (including nociception), mood, etc
dopa) sleep/wakefulness
 Related drugs
 SSRI
Amino Acids ! GABA ! Inhibitory  MOA (main inhibitor)
 Increases Cl- into postsynaptic neuron  hyperpolarization (thus: inhibitory)

 Related drugs
 Sedative-hypnotics (eg: barbiturates) and anti-convulsants (eg: gabapentin)
Glycine Inhibitory  MOA
 Increases Cl- flux into postsynaptic neuron  hyperpolarization
 Related drugs
 Blocked by strychnine (spinal convulsant)
Glutamate Excitatory  MOA
 Na+ influx into postsynaptic neuron  depolarization
 Background
 Main glutamatergic pathways – see slides
 Glutamate receptors
 Ionotropic – eg: NMDA (blocked by phencyclidine and ketamine)
 Metabotropic
  Related drugs
 NMDA antagonist - Memantine (tx alzheimer’s and dementia)
 Antagonize NMDA as excessive activation after neuronal injury may cause cell death
Neuro- Substance P Excitatory  Functions
peptides  Mediates nociception (pain) in spinal chord
Met-enkephalin Generally  Mediates analgesia & other CNS effects
inhibitory

Mode of Action
On ION CHANNELS
Voltage gated Ligand Gated
Info  Open/ close in response to fluctuations in membrane potential  Open/ close in response to binding of ligand (NT)
MOA  Resting potential  voltage-gated channels closed
 Depolarized membrane  conformational change  open
voltage-gated channel
 Excitatory  means there’s depolarization (Na+ or Ca2+)
 Inhibitory  means there’s hyperpolarizartion (Cl- influx/
K+ efflux)
Drugs affecting  Anticonvulsants (eg: phenytoin)
 LA and some GA
 Eg: lidocaine blocks Na+ channels
(but most therapeutically impt CNS drugs act on synapses)
On SYNAPTIC TRANSMISSION
MOA  Pre-synaptic effect - affect NT’s
 Synthesis, storage, release, reuptake, degradation
Eg
 Anxiolytics, Sedatives and Hypnotics

General  Stages of sleep (5)

 1,2 – non-deep sleep
 3,4 – deep sleep
 5 – REM (+ active brain with dreams)
 Overall classification
 Draw on one note (based on final notes)
 Sedative Hypnotic
 Reduces excitement/ Calms down
Drowsiness/  DROWSINESS mainly (but could also cause sleep)  SLEEP- INDUCING MAINLY (induces/ maintains… DEEPER
Sleep sleep)
 Similar to normal arousable sleep
Dose- dependant  DOSE  DOSE
effects  Therapeutic doses – anxiolytics  Larger doses - GA
 Larger doses – hypnosis (trance-like, highly suggestible)
Affects  Affects limbic system – regulates thoughts and mental  Affects midbrain and ascending RAS which maintain
function (depresses CNS) wakefulness

MOA and Pharmaco actions Uses AE More Info (Pk etc)

BARBITURATES MOA  Sedative-hypnotic  Drug hangover,  Pk
 PROLONG DURATION of  Anaesthesia confusion!!  Many preparations
(think: LONG chloride channel opening (think:  Anticonvulsant  Drug AUTOMATISM (keep  Thiopental
barbarians… the BarbiDURATes – prolong  Psychoanalysis taking drug as forgot if  Rapid onset
worst) duration) (hard to lie) took alr)  Short acting – as
 GABA mimetic effect!  Hyperbilirubinemia  Metabolic tolerance of rapid redistribution
Phenobarbital  Additional effect  blocks (in kids) barbiturates and other to fatty areas
(long acting) excitatory glutamate receptors  Increased drugs  Barbiturate poisoning
activity of  Enzyme induction by  Signs
Pentobarbital Pharmaco actions glucoronyl barbiturates (by  Flabby pt
(short acting)  CNS depression (dose- transferase by increasing size of SER)  Coma
dependant effects) enzyme  Drugs metab. by  Bullous
Thiopental  Sedation  hypnosis  GA induction  CYP450 too need eruptions!! (esp:
(ultra short  coma  death bilirubin higher doses to offset coma)
acting, rapid  Disrupts balance conjugated enzyme induction  Hypotension, shock
onset) between REM and non- faster   Abuse liability  Renal and pulmonary
REM excreted  Withdrawal symptoms!!! problems
  Shortens time needed to through bile (v severe)  Tx
fall asleep  The “HIGH DOSE” effects  Gastric lavage
 Increases sleep duration discussed earlier  Supportive measures
 Long-acting – anti-  Hepatotoxicity  Forced alkaline
convulsant  Rashes and some diuresis (eg: mannitol,
 Hyperalgesia (increased pain swellings (like allergic rxn) sodium bicarb.)
sensitivity)
 HIGH DOSE  CI: PORPHYRIA (think:
 CVS – Decrease BP, HR and vampires don’t like
depress myocardium barbies!!)
 Respi – depress respiration  Barbiturates induce
(Cheyne-stokes breathing, ALA synthase in mito
pulmonary oedema etc)  increase porphyrin
 GIT, bladder, uterus – synthesis  porphyria
relaxation (so: less pee) and neurotoxicity

BENZODIAZEPINE MOA  Alcohol  Drowsiness, confusion!!  BZD> barbiturates

(BZD)  BZD binds to GABA receptor withdrawal  High dose - Impair  Less drowsiness than
(allosteric site)  increases treatment psychomotor functions barb (so: can use as
Diazepam affinity of GABA for GABA-  Night terror, sleep (intellectual functioning, daytime anxiolytic-
(long-acting) binding site  INCREASES walking (reduces motor dexterity impaired) sedative in sub-hypnotic
FREQUENCY of chloride channel N3 and REM)  Tolerance with some doses)
Lorazepam opening  more  Panic disorder (though less than  Less distortion of sleep
(Intermediate hyperpolarization (thus reducing (DOC: alpra-zolam) barbiturates) (Triazolam architecture (doesn’t
acting) neural excitability)  Insomnia esp) affect REM sleep High
 GABA facilitatory effect!  Anxiety neurosis  Insomnia, malaise therapeutic index
Midazolam  Preanaesthetic  Rebound insomnia  Has specific antidote for
(short-acting) Pharmaco Actions  Skeletal muscle (triazolam) poisoning!!! (CVS and
 Sleep relaxant  Weakness, dry mouth, respi depression etc)
Triazolam  Hasten sleep onset  Anticonvulsant vision blur – FLU-MA-ZENIL
(problematic)  Reduces intermittent waking  Tremors, convulsions  Cause – excessive
 Increases total sleep time  Bad dreams, delirium BZD, IV anaesthesia
  Less deep sleep, more non-  Flu-nitra-zepam – DATE  BZD antagonist
deep sleep RAPE DRUG!  sedation,  Abolishes hypogenic,
 Analgesia (diazepam) (vs. amnesia psychomotor and
hyperalgesia above?)  Caution cognitive effects of
 Decreases nocturnal acid  Liver disease BZD
secretion – prevents stress  Alcohol  Quick onset (a
ulcers  BZD potentiates second)
 Anterograde amnesia (loss of effects of other  Pref. to let pt. recover
memory for events occurring CNS depressants on own if a chronic
forward in time/ recent events –  CI dependant to avoid
used for anxiety etc)  Pregnancy - cross withdrawals
 Reduces anxiety placenta, in milk (overdose isn’t fatal)
 Sedative and hypnotic  Acute angle closure  No hyperalgesia
 Anticonvulsant glaucoma  High/ hypnotic doses –
 Muscle relaxant (barbiturates: NO CVS/ respi problems
no muscle relaxant prop.)  No automatism (though
still have amnesia)
 No enzyme induction
property (no metabolic
tolerance)
 Low abuse liability (but
still have potential!!
Withdrawal seizures
possible too but less
severe)
 ATOM have higher
addictive potential
(d/t shorter half lives)
(USMLE extra)
 Alprazolam
 Triazolam
 Oxazepam
  Midazolam
 Pk
 Midazolam – NOT given
orally
 LOT safer (Lorazepam,
Oxazepam, Temazepam) –
don’t need phase I metab
(assos. w/CYP450 in liver)
 Fewer drug
interactions
 Safer in pt with
hepatic impairment

NEWER Zolpidem!!!!!!! (BESTTTTT)  Advantages

NON-BZD  Non-BZD hypnotic (but  NO effect on stages of
HYPNOTICS selectively binds to BZ1 receptor) sleep!!!
 Minimal day time
Zolpidem sedation
(longest  Minimal rebound
acting) *Zaleplon  half life TOO short (so insomnia/ withdrawal
used for: sleep-onset insomnia. For effects on stoppage
Zopiclone onset and MAINTENANCE insomnia  Rare – tolerance, physical
 try other drugs like zolpidem and dependence, abuse
Zaleplon esZopiclone  Less hangover (short half
(shortest life)
acting)  Disadvantages
 No anticonvulsant/
muscle relaxant
properties
ATYPICAL  Act through NON- GABAnergic  Anxiety  Dose-dependent pupillary  Advantages
ANXIOLYTICS systems!!!  Esp: chronic constriction (think:  Less abuse liability
 Partial agonists at brain with some “buspi- pupi”)  No withdrawal reactions
 Buspirone 5HT1A (serotonin) receptors hostility  Paraesthesia  Less impairment of
 Tachy, nervousness psychomotor skills
 GIT distress  Doesn’t potentiate CNS
depression of alcohol
 Disadvantages
 Slower onset than BZD
PROPANOLOL  Decreases symptoms of
sympathetic overactivity d/t
anxiety
OTHER SEDATIVE MELATONIN!  Jet lag (actually used to induce sedation. The rest – more of sedation as a side effect)
HYPNOTICS Triclofos  Similar to chloral hydrate (other sedative)
Hydroxyzine  Antihistaminic
Promethazine
Ramelton  Selective agonists to MT1 and MT2 subtypes of melatonin receptors (tx for insomnia)
Ethanol/ ALC  Anxiolytic, sedative effects

Anti-Parkinson’s Drugs

Parkinson’s Background
Causes Possibly hereditary Sporadic
 Defective autophagy and lysosomes  poor  Toxins (eg: MPTP – contaminant in illegal drugs –
clearance of proteins and organelles metab to MPP+  toxic to S.N)
 Eg. of mutations  Drugs
 PINK1, PARKIN, alpha-synuclein gene  Antipsychotics
 Pheno-thiazines (like chlorpromazine)
*Parkinson’s: about ALPHA- SYNUCLEIN  Butyro-phenones (like haloperidol)
*vs. alzheimers: about BETA AMYLOID  Ris-peri-done
 Metoclopramide – tx nausea and vomiting (drug-
induced parkinsonism. Rmb GI lecture)
 Pathogenesis  Imbalance between dopamine and ACh
 Lack of dopamine
 Normally: substantia nigra produces dopamine  sent to striatum (nigrostriatal pathway)  stimulates
cerebral cortex (initiates movement)
 In PD: Neuronal degeneration (depigmentation) in the substantia nigra (pars compacta) (of the basal
ganglia, in midbrain)  less dopamine
 DOPAMINE LEVELS
 Low – Tremors, akinesia/ bradykinesia
 High – Chorea (dance- like movements)
 Excess ACh (see left)

Main movement problems TRAPS

Tremor  Resting tremor
Rigidity  Stiff muscles, Jerky movements, cogwheel-rigidity
Akinesia/  Loss of voluntary movement (“mask-face”)
Bradykinesia  Slow movements/ Weak/ fatigue
Postural Instability  Increased fall risk, broad-based stance
(occurs later in disease)
Shuffling Gait
Histo  Lewy bodies – composed of α-synuclein (intraCellular eosinophilic inclusions)
 Drug overview
 BALSA  Bromocriptine, Amantadine, Levodopa (with carbidopa), Selegiline (and COMT inhibitors), Antimuscarinics
Dopaminergic Dopamine Precursor Levodopa (+ Carbidopa)  Esp
Agents  Bradykinesia
 Rigidity
 Carbidopa
 Prevent peripheral breakdown
 Prevent peripheral AE
Dopamine Agonist Bromocriptine  Adjuvant to levo (but can use to prevent)
Inhibits MAO-B Selegiline  Adjuvent to levo
dopamine inhibitors
metabolism COMT Tolcapone  Adjuvent to levo
inhibitors
Stimulate release and reduce Amantadine  Adjuvant to levo
uptake of Dopamine
Anticholinergics Benztropine  Esp: TREMORS, rigidity

MOA and Pharmaco actions Uses AE

Dopamine Precursor  Levodopa crosses BBB (by  Bradykinesia  Levodopa alone – more PERIPHERAL AE
amino acid transporter)   Rigidity  GIT – nausea and vomiting
Levodopa decarboxylated to (not as great for  CVS – arrhythmias, postural hypotension
+ Carbidopa dopamine tremor)  Levodopa + Carbidopa -more CENTRAL AE (“DOM”)
 Carbidopa given to reduce  Dyskinesia (other movement disorders)
peripheral conversion to  When – long-term levodopa use
dopamine  So: some delay levodopa use/ use little levodopa
 By inhibiting dopamine + other drug (ARGUABLE)
decarboxylase in gut  On-off phenomena (fluctuating motor response)
and blood  Why- wearing-off/ end-of-dose akinesia
 Previously – only 1-3%  “On”- low levodopa levels, symptoms controlled
 reach brain. Now -  “Off” – no levodopa effect (PD symptoms return)
~10%  Can use other drugs to increase dopamine levels
for longer
 Mental disturbance – delusions, hallucinations
Dopamine Agonist  Binds to D2 receptors at  Adjuvant with  GIT – nausea, vomiting
striatal neurons levodopa  CVS- arrhythmias, postural HT
Bromocriptine (lower dose)  CNS – hallucination, delirium (like levodopa + carbidopa)
for
 Response
fluctuations
 Dyskinesia
Inhibits MAO-B  Dyskinesia (esp. face)
dopamine inhibitors  Selegiline
metabolism Selegiline  Abdominal pain, dizziness
COMT  Tolpacone
inhibitors  Abdominal pain, cough
Tolca-PONE

Stimulate release and reduce  Antiviral – MOA unclear  Adjuvant with  CVS
uptake of Dopamine levodopa  CNS

Amantadine
Anticholinergics  Reduce cholinergic activity  TREMORS  Tachycardia
 Rigidity  DUCA
Benztropine “PARK your Mercedes BENZ”
 Anti-Epileptics

Epilepsy Background
Definitions Seizure  Transient alteration of behaviour
 Due to – disordered, synchronous, rhythmic firing of populations of brain neurones
Epilepsy  Chronic disorder of recurrent seizures
Convulsion  Involuntary spasmodic contractions of skeletal muscles
Causes  Genetics/ hereditary
 Brain lesions – eg: trauma during delivery
 Infections – eg: meningitis (increase ICP), abscess
 Metabolic d/o (thus increasing excitatory stimulus to brain) – hyperpyrexia, hypoglycaemia, hypocalcaemia
 Sudden drug withdrawal (rebound phenomenon) – alc, barbiturates :O
 Others (more random)- TV, disco flashes, loud music
Patho Too much Excitation Too little Inhibition
(depolarization) (hyperpolarization)
NT & Ionic effects NT & Ionic effects
Too much: Glutamate & Aspartate Too little: GABA
THUS THUS
too much: Inward Ca+ and inward Na2+ (result: excitation) Too little: Inward Cl-, Outward K+ (result: excitation)
 Epilepsy
Classi-fication

Generalized
Aura Loss of Loss of Postural Control More Info EEG
conscious-
ness
Grand Mal Yes Yes Yes – FALL  Severe form  Bilateral, diffused,
(Status high-voltage
PHASES epilepticus) – polyspikes (10-30
 TONIC Grand mal with Hz/sec)
 Opis-tho-tonus NO recovery of  Phases
(STIFFENING) consciousness  Fast, repetitive
 Epileptic cry (laryngeal between attacks spikes
muscles contract)  > 5 mins =  Generalized spikes
 Incontinence MEDICAL  Attenuation
 Cyanosis EMERGENCY
 CLONIC (status
 Clonic jerks, bite tongue epilepticus)
 Salivary frothing
  Eyes blinking
 POST-ICTAL STUPOR (5-30
mins)
 Unresponsive
 Drooling
 Confusion, amnesia
 Limp
Petit mal - - -  SUBTLE  3Hz spikes
(absence) MOVEMENTS – (generalized,
blank stare, rapid symmetric)
blinking of
eyelids, chewing/
move mouth
 Children esp
Atonic - YES YES- FALLS or head to one side  NO post-ictal  Brief generalized
(Akinetic) confusion spikes  diffused slow
(often waves
“drop” seizure mistaken
as
fainting)
Tonic seizures - - (MAY fall)  STIFF and fixed  Fast activity, low-
EXTENDED limbs voltage waves
(“stiffness”)  RIGID VIOLENT
muscular
contractions

Myoclonic - - -  SUDDEN, BRIEF  2Hz spikes (low during

skeletal muscle SLEEP)
contraction (jerky
movements)
 Parts/ entire
 body affected
 Esp. during SLEEP
Clonic - - -  REPETETIVE  10Hz (fast activity) and
CONTRACTIONS slow waves (think:
(“contraction”) (JERKS) “c10nic”)
 NO stiffness
(“tonic”)
Partial (single area of brain) and Unclassified Seizures
Aura Loss of Loss of More Info
consciousness Postural
Control
Simple Partial - - - The Simple one has many Symptoms :O
(Jacksonian)
 Motor symptoms
 Unilateral CLONIC movement in ONE GROUP of
muscle gradual SPREAD to ADJACENT group
 Possible grimacing (may be contraversive)
 Somatosensory symptoms
 Visual hallucinations
 Scotoma, flashes of light, blurring
 Auditory hallucinations
 Ringing/ hissing noise
 Tingling of contralateral body and face
 Autonomic symptoms
 Sweat, flush, pallor, epigastric sensations
 EEG – repetitive sharp waves over specific “lines” only and
not all (corresponding to specific. parts of brain)
 Complex partial YES PARTIAL PARTIAL  AUTOMATISM!!!!
(PSYCHOMOTOR)  Doing things unconsciously, won’t follow commands
 Repetitive behaviours
 EEG (find out more)

Partial seizures YES YES YES

evolving to
generalized
seizures
Febrile  In KIDS- omes with HYPERPYREXA
(USMLE says NOT
epilepsy)
Infantile spasm  Generalized tonic clonic seizures - Has PROGRESSIVE
MENTAL RETARDATION
Tx  Suppresses seizures, doesn’t cure  mostly take drugs for life
 GOAL
 NO seizure, NO adverse effects
 Monotherapy preferred
 If not working
 Switch drug / add another drug (with different MOA from original)
 USE - in order of choice
Grand mal  Sodium valproate
(tonic-clonic)  PHENYTOIN
 Carbamazepine, barbiturates
Status epilepticus  BZD: Diazepam and Lorazepam
 Phenytoin
 Barbiturates
Petit mal  Ethosuximide/ Sodium valproate
(Absence)  Clonazepam
Myoclonic  Sodium valproate
Partial  Phenytoin (P for partial, P for pheny)
 Carbamazepine
 Sodium valproate
Febrile  Diazepam (give Diazepam to those in Diapers - rectally)
Neuropathic pain  Carbamazepine
 Gabapentin
 MODE OF ACTION
Reduces excitatory Inhibit Na+ channels Inhibit glutamate Block glutamate receptors Inhibit
GLUTAMATE activity  Inhibit glutamate RELEASE release (direct) (NMDA/ AMPA) glutamate
Synthesis
 Phenytoin  Phenytoin  NMDA receptor antagonist  Sodium
 Sodium valproate  Phenobarbital  Fel-ba-mate, sodium valproat
 Carbamazepine  Lamotrigine valproate e
 AMPA antagonist
 Topiramate,Phenobarbital,
Lamotrigine
 Inhibit use-dependant Na+ channels
(inhibit action potential)  prolong
inactivated state  reduce chance of
activation  reduces glutamate
release
Reduce excitatory Inhibit N-type Ca2+channels Inhibit T-type Ca2+ channels
Ca2+ activity  Lomotrigine  Ethosuximide (think: eThosuximide)
 Gabapentin  Sodium valproate
 Causes decreased glutamate release  Inhibits low threshold calcium current

NOTE: N&T Ca2+ channels @ neurones ( L- type: HEART)

Enhances inhibitory Activate GABA receptors Inhibit GABA transaminase Inhibit GABA uptake Activate glutamic acid
GABAnergic activity (which breaks down GABA) transporter DEcarboxylase
(for GABA synthesis)
 Phenobarbital  Sodium valproate  Sodium valproate  Sodium valproate
(barbiturates)  Viga-batrin  Tiagabine
 BZD
 Causes opening of Cl-  Causes increase in  Less uptake = more  Rate limiting enzyme
channels neuronal concentration available  more activated  Increased
of GABA inhibitory actions of GABA synthesis
GABA at GABA-A
receptors
 Some Key Drugs
Uses AE Pk and more info
Phenytoin  Antiepileptic PHENYTOIN  Oral/ IV
 1st choice for  P-450 induction (enzyme inducer)  IV – Fos-phenytoin (prodrug)
 Partial seizures (esp.  Hirsutism and acne converted to phenytoin
complex partial)  Enlarged gums (gingival hyperplasia) + facial  Narrow therapeutic index (so:
 2 choice for
nd
feature coarsening monitor)
 Grand mal epilepsy  Nystagmus (at toxic doses)  Eliminated by zero-order kinetics
 Status epilepticus  Yellow-brown skin (higher chance of toxicity with
 Others  Teratogenicity (fetal hydantoin syndrome) dose increase)
 Trigeminal neuralgia  Cleft lip and palate  Can’t just use the same dose for
 Ventricular arrhythmias  Microcephaly dif brands (suboptimal/ toxic
d/t digitalis toxicity  Hypoplastic phalanges plasma levels possible
 Osteopenia/ osteomalacia
 Inhibited absorption (and other deficiencies)
 Folic acid  megaloblastic anaemia, spina
bifida (vs. carbamazepine: aplastic anaemia)
 Vitamin K  haemorrhage
 Vitamin D  Rickets, osteomalacia
 Neuropathy
 RARE Others
 SJS
 DRESS syndrome
 SLE-like syndrome
 Toxicity  SAD: sedation , ataxia, diplopia
 Sudden withdrawal – seizures
 Arrhythmia (at toxic doses)
 Inhibits insulin release
 Lymphadenopathy
Carbamazepine  Antiepileptic  Drowsiness, dizziness, headache  Structurally related to TCA
 2nd choice -  Ataxia, diplopia  Blocks Na+ channels and reduce
PSYCHOMOTOR (simple  Water retention (as ADH stimulated) the release of dif NTs
complex partial) epilepsy  CarbaMazepine.. Water retention (flip the
 Most (except absence) M)
 Others  Long term use (CarbaMAZEpine –think: Mazie
 Trigeminal neuralgia has long LASHes)
 Maniac depressive  Leukopenia
psychosis (where there’s  Aplastic anaemia (vs. pheny: megaloblastic)
an increase in all the NT)  SLE
 Hepatitis
Sodium Valproate!  Antiepileptic (broad-spectrum) VALPROATTTE  Oral
 Partial seizures  Vomiting  Highly protein bound (stays for
 Generalized seizures  Ataxia long in body)
 1st  Liver toxicity
 Grand mal  Pancreatitis (rare)
 Absence (w/  Rashes
ehtosuxamide)  Ovarian disease (eg: PCOS)
 Myoclonic  Alopecia
 Tonic, clonic and atonic  Tremor
seizures Teratogenicity (spinal bifida!!!)
 Others Thrombocytopenia
 Trigeminal neuralgia  Extra weight gain
 Maniac depressive
psychosis
 TARDIVE DYSKINESIA
Ethosuximide  Antiepileptic EFGHIJK – quite general
 Abscence seizures (think:  Ethosuximide causes Eosinophilia,
“sux to have absence  Fatigue
seizures”)  GIT distress
 Headache
 Itching (rashes, hives)
  sJs
 Kills bone marrow (bone marrow depression)
Barbiturates  Antiepileptic  Sedation + See “anxiolytics” notes
 Grand mal seizures
 Status epilepticus
 NEONATES (think:
“phenoBABYtol”)
BZD  Antiepileptic  Sedation + See “anxiolytics” notes
 Diazepam
 Status epilepticus
 Febrile seizures
 In kids, given
rectally
 Lorazepam
 Status epilepticus
 Clonazepam
 Absence
 Some: myoclonic,
akinetic seizures
Gabapentin  Antiepileptic  Sedation  Structurally resembles GABA
(newer)  ADJUVENT  Ataxia  Inhibits N-type Ca2+ channels
 Grand mal
 Partial seizures
 Others (MAIN USE TBH)
 Neuropathic pain
 Post herpetic neuralgia
EXTRA - “My mates are SSSSSnakes” - “S”  Glutamate AMKA receptor
Topiramate inhibitor
 Sedation, slow cognition, stones (kidney), skinny
(weight loss), sight & speech problems
EXTRA – Vigabatrin  Permanent vision loss (“blind as a BAT”)
 Enzyme Inducers Enzyme inhibitors
 Phenytoin  Sodium valproate
 Carbamazepine
 Barbiturates
 Increases metabolism of
 OC Pills
 Steroids
 Folic acid, vit D and vit K

Antidepressants

Background  Depression - Most common mood (affective) disorder  think: LESS SYMPATHETIC ACTIVITY
 Range: Mild-severe (psychotic: with hallucinations)
 Increases risk of heart disease, cancer and suicide etc
 Tx
 Psychological – CBT, Interpersonal therapy (mild-moderate cases)
 Pharmaco – anti-depressants (for more severe cases)
 ECT – for VERY SEVERE and URGENT case (w/ psychotic symptoms)  induce mild seizure to maybe induce neuronal
rewiring
 Anxiolytics (eg: BZD) are USEFUL ADJUVENTS
 NOTE
 Drugs take time (several weeks)  After remission, continue same  Withdrawals (after 8 weeks + of
before taking effect – don’t decide dose for use)
to switch dose or drug till  6 months - normally  need TAILING OFF ( 4 weeks+)
 4 weeks - normally  1 year– elderly  2 weeks gap when switching
 6 weeks - elderly  2 years – recurrent depression drugs
 Types Unipolar  See mental illness notes
(Major depressive disorder)
Bipolar  See mental illness notes (mood fluctuations)
(Manic-depressive disorder)
Dys-thy-mia  Low-grade depression without enough other clinically significant symptoms
Aetio and Monoamine Hypothesis Neuro-trophic Hypothesis
pathogenesis (“BDNF LOSS”)
 Deficiency (quality and quantity) of sympathetic Think: “stressy – depressy”
monoamine NT (at cortex/ limbic system)  Normally: BDNF – a NT
 Dopamine  activates tyrosine kinase receptor B (in neurons and
 Serotonin (5HT) glia)
 NE (though other lect. says – ambiguous)  Regulates - Plasticity, Resilience, Neurogenesis 
promotes dendritic sprout formation (check)
 Stressed  increased glucocorticoids  Loss of BDNF
(brain-derived neurotrophic factors)  less sympathetic
action (depression)
Pic
 MOA Use AE Pk and More Info
TCA  Inhibits reuptake of  SEVERE  Blocks other receptors (undesirable)  Classification
Serotonin and NE ENDOGENOUS Blocks muscarinic recep  Less sedation
~ pramine into presynaptic DEPRESSION!!!!!  atropine-like (anticholinergic) effects  Withdrawn pt
(clomipramine neuron (at SERT and  Others (not so impt) “DUCAT”  Imi-pra-mine
, imipramine) NET)  Nocturnal  Dry mouth  Marked sedation
 increase their enuresis  Urinary retention  Caution in BPH!!!  Anxious,
~ triptyline concentration in (imipramine)  Constipation agitated pt
(amitriptyline) synaptic cleft in CNS  Panic disorder  Accommodation loss & IOP  Ami-trip-
(and periphery)  OCD increase…Vision blurring  Caution in tyline
 elevates mood  Chronic Glaucoma pt!!!
neuropathic pain  Tachy
 Eating disorders, Blocks alpha-adrenergic recep
“MOST ADHD, phobia,  Orthostatic HT
EFFECTIVE, but narcolepsy etc  Arrhythmia, Tachycardia
DANGREOUS AE”
 Cardiac conduction defect (if overdose)
*Caution: heart disease pts
(onset: 1-2
Blocks histamine recep
weeks)
 Sedation
 Confusion
 Overly effective effects – mania, agitation,
lowers seizure threshold (seizure)
 “TriCyCliCs”- Cardiotoxicity, Convulsion
(seizure), Coma
 WEIGHT GAIN!!!! (and increased appetite)
 In non-depressed person – anxiety
 Respi depression (if overdose)
 Potentiates exogenous and endogenous
sympathomimetics
 SSRI  Inhibits serotonin  Depression  SEROTONIN SYNDROME (AAA) with MAOI  Less/ NO weight
reuptake (at SERT)  Anxiety  SSRIs  increase serotonin levels gain!!!!
Fluo-xe-tine at pre-synaptic  Impulse control  MAOIs inhibit serotonin (and NE) metab
Ser-tra-line membrane disorders (OCD,  increase serotonin levels
impulsive buying,  Now, serotonin levels TOO HIGH
kleptomina)  3 As
 PTSD  Increased Activity
 NM – hypertonia,
“Overall similar hyperreflexia, seizure
effectiveness to (rare) etc
TCA (EXCEPT in  Autonomic instability
severe  Hyperthermia, diaphoresis,
depression) cardiovascular collapse
but more SAFE  Altered mental status
(delirium)
 MOST  Tx: cyproheptadine (sero antag.)
COMMONLY
 Serotonin sym: in anything that
PRESCRIBED”
increases serotonin by a lot
 Psych : SSRI, MAOI, TCA etc
 Non-psych: tramadol, onan etc
 Sexual dysfunction!!! (impt esp. if pt is of
reproductive age)
 Others
 Impairment of skilled task (eg: driving)
 Withdrawal symptoms
 Need to TAIL OFF
 Headache, insomnia
 Nervousness
 GI disturbances (diarrhoea etc)
 May increase suicidal thoughts
(counteractive)
MAOI MAO = enzymes that  Non-selective  DRUG INTERACTIONS  MAOIs in general
 degrade monoamines  Mood elevation  “MAO Takes
Phenel-zine NE and serotonin (in both “CHEESE REACTION”!!! (with some foods) Pride In
Iso-carbox- depressed and  Foods high in TYRAMINE (a.a that Shanghai” 
azid  Non-selective MAOI normal) regulates BP) and DOPAMINE trigger it Tranylcypromine,
 Inhibit MAO  Cheese, beer, wines Phenelzine,
Moclo-bemide enzyme  Pickled meat and fish Isocarboxazid,
(selective) irreversibly  Yeast extract Selegiline
 Selective MAO-I  MAOIs inhibited in the neurones (wanted  Sub-types
“NOT USED  Inhibits MAO-A effect) AND GIT (unwanted!!)  MAO-A Inhibitors
MUCH” SELECTIVELY  Can’t break down TYRAMINE well   Depression tx
and REVERSIBLY excess tyramine in body  enhanced  MAO-B inhibitors
NT release to dangerous levels (eg:  Parkinsons tx
Thus  Increase levels NE) (though USMLE says “tyramine (B looks like
of monoamine NT: displaces other NT like NE in synaptic P)
Dopa, Serotonin, NE cleft”) increase sympathetic  Duration of action
activation  HYPERTENSIVE CRISIS  Nonselective 
 Tx: phentolamine effects last 2-3
TCAs weeks after
Severe toxicity resembling ATROPINE stopping
POISONING (anti-cholinergic)  Selective MAOIs
MAOIs  Especially
Serotonin syndrome (as before) suitable
Others  Elderly
 Hypertensive crisis (?)  Heart disease
 Amphetamines pts
 Certain anaesthetic agents
 Cough and cold remedies
 Antiparkinsonian drugs

 Other AE
 Lowered convulsive threshold
(seizures)
  Weight gain!!!
 Hepatotoxicity (“hepatotoxicity for the
one with Hypertensive crisis”)
 Anticholinergic effects
 CNS stimulation
SNRI  Inhibits serotonin  Anxiety, depression
and NE reuptake  ADHD, autism,
Venla-faxine fibromyalgia, PTSD,
Dulo-xetine menopause

Atypical  Mirtazapine  Trazodone  TraZZZoBONE

antidepressants (think: moaning  Sedation
MYRTYLE… she’s not  “Boner” – think: penis priapism
Mirta-zapine typical) – think: 2
Tra-zodone  Blocks 5HT2
receptor (how
does this work
to tx
depression??
Cause this
reduces the
blockage of
dopa?)
 Blocks α2
adrenorceptor
 so now
more
sympathetic
NE
discharge +
enhanced 5-
HT release
  α2 normally
sympatholyt
ic – inhibits
NT release
Atypical  Schizophrenia
antipsychotics  Bipolar disorder
 RESISTANT major
Olan-zapine depression

Antipsychotics (Neuroleptics)

Antipsychotics (eg: for Schizophrenia)

(think: block DOPA)
Typical (-“aZine”)
HIGH receptor D2/ 5-HT2A ratio - MUCH EPS
MOA Effects Uses AE (9)
CHLOR-  Block D2 >>> 5HT2A Block DAMH  Schizo!!!!! (9)
PROMAZINE  So, increase cAMP in all (+ Behavioral  Drug-induced akinesia &
CNS dopaminergic  Dopaminergic blockade symptoms) Pseudodepression
(and other pathways  All 4 paths, but only  Bipolar  Toxic confusional state
phenothiazines) useful for mesolimbic (manic phase) (delirium)(antimuscarinic
path (useful: tx pos.  Antiemesis actions)
symptoms) (promethazin Neurologic  EXTRA-PYRIMIDAL
 α-adrenergic blockade e) SYMPTOMS (d/t
Central (in RAS) (but dopamine receptor
 Sedation considered blockade in basal
  Chronic – bad (impair lower ganglia)– AdAPTS
normal functioning) potency, less  Acute Dystonia –
 Acute – good (for EPS compared muscle spasm/
agitated pts) to other AE) stiffness (eg:
Peripheral torticollis,
 Orthostatic hypo laryngospasm)
(hours-days after use)
 Muscarinic blockade (if it  Aka-this-ia - restless
blocks NICOTINIC… not (days- months)
much effect)  Parkinsonism
 Anticholinergic effects (pseudo) –
 “UNIVERSAL bradykinesia (days-
TRUTH”  DUCA months)
 Dry mouth  Tardive dyskinesia -
 Urination chorea (months-yrs)
difficulty  *Seizures (rare)
 Constipation  Tx: benztropine (except
 Accommodation dyskinesia – atypical
loss (and rise in antipsych (clozapine)
IOP) ANS  Antimuscarinic (DUCA)
 H1 blockade  Alpha receptor blockade
effects (orthostatic hypo,
can’t cum, sedation)
Metabolic  Weight gain (serotonin
blockade)
 Hyperglycaemia,
hyperlipidaemia
Endocrine  Antag. Dopa (PIH) 
Hyperprolactinaemia
 F  amenorrhoea,
galactorrhoea,
infertility
  M (think: “less
male”) -libido loss,
impotence, infertility
Toxic and  Agranulocytosis
allergic  Skin cholestasis (by
inhibiting bile flow) &
Jaundice
 Skin eruption
Ocular  Chlorpromazine – corneal
deposits
(extra: thioridazine –
retinal deposits)
Others  QT prolongation
NEUROLEPTIC  In those genetically
MALIGNANT predisposed (extremely
SYNDROME!!! sensitive to
(NMS) extrapyramidal effects)
 EXCESSIVELY RAPID
BLOCKADE of dopamine
(life- receptors
threatening)  MUSCLE RIGIDITY
 HYPERTHERMIA
 Dysautonomia
(altered BP and PR)
 DD: serotonin syndrome,
malignant hyperthermia
(d/t inhaled anesthetic +
succinylcholine)
 Tx: dantrolene,
diazepam, bromocriptine
(dopa agonist), cool down
fever (physical measures)
  change to atypical
drug after recovery
Haloperidol  Block D2>>> 5HT2A  Dopa blockade (main)  Schizo!!!!!  HIGH potency (more EPS)
 Some α blockade (+ symptoms)
(a butyro-  Minimal M blockade  Bipolar
phenone) (manic phase)
 Huntington’s
chorea,
tourette’s
Thiothixene
ACUTE  Typical antipsych: Chlorpromazine (IM) OR Haloperidol (serenace) (IM)
PSYCHOSIS  Non compliant pt.  Depot injection (0 order kinetic- same amnt released at each T1/2)
 Haloperidol (deep IM- 4 wks)
 Flu-phe-nazine (deep IM- 2-4wks)

Atypical (“-aPine”)
(think: block SEROTONIN)
PREFERRED - LOW receptor D2/ 5-HT2A ratio -LITTLE EPS (more selective for mesolimbic path)
MOA Uses AE
Clozapine  Block 5HT2A>>D2  Schizo  Aranulocytosis!!!!! (clozapine, NOT
(less extra-pyramidal ( + AND – symptoms) olanzapine)
effects) (main MOA)  Clozapine: mostly for REFRACTORY schizo  Was banned, now back for refractory pt tx
 High affinity to pts  Watch bone marrow CLOZely with
these 5HT-2  -ve symptoms esp CLOZapine – FBC weekly (6 months)
receptors which  Bipolar  Autonomic side effects (α1, muscarinic block)
are involved in  Major depression  Exception: SIALORRHOEA instead of dry
BOTH positive and mouth (“wet pillow syndrome”)
negative  Metabolic syndrome: WEIGHT GAIN!!!!! (esp:
symptoms clozapine, olanzapine, quetiapine) – increased
risk of DM, HTN etc
 Sedation
 Prolong QT
Olanzapine!!!  PREFERRED ( I think..)  Autonomic side effects (DRY MOUTH)
 less dangerous!!!!!  Weight gain
Others (can
ignore):
“-peridone”
“-isdone”

Drugs for Mania (BIPOLAR d/o)

(think: block DOPA)
MOA Uses AE Pk and more info
Lithium!!!  Block D2>>> 5HT2A LITHIUM IS “LiTTTHIUM (batteries)”  For all these
 Hypothesis (3) POWERFUL  Low antipsych and
(lithium Mimicking Na  BIPOLAR (mood Thyroid antidepressants –
carbonate)  Lithium – monovalent cation  mimics role stabiliser) (hypothyroidism) caution when
of Na+ in excitable tissues  PROPHYLAXIS Teratogen stopping drug
 Enters voltage-gated Na+ channels BUT NOT  Mania and  Pregnancy cat-D (possible
PUMPED OUT BY Na-K-ATPase (thus Li+ Acute mania (first trimester) withdrawal)
accumulate in cells) (prophylaxis TPI narrow (monitor  Long Duration of
 DEPOLARIZATION OF CELL (despite partial and frequently) action
loss of intracellular K+) treatment)  Heart (ebstein anomaly)  Need FREQUENT
Affecting the second messenger system  Depressive  Insipidus (nephrogenic MONITERING of
IP3 Path inhibition!!! Adenylyl Cyclase path episodes DI) serum drug levels
inhibition  RESISTANT  d/t inhibition of  Clinically
 Inhibit ino-sitol  Inhibits NE DEPRESSION action of ADH effective – 0.5-
phosphatase sensitive adenylyl (used as adjuvant  + think of other renal 1mmol/L
enzyme  deplete cyclase  has with drug interactions   TOXIC
substrate for IP3 antimanic and antidepressants) Lithium toxicity (d/t  >1.5mmol/L
production  less antidepressant FULL RENAL  Lithium +
IP3  less calcium actions EXCRETION) valproate used
 Nausea and most
 release from ER to vomiting, slur,  Check thyroid,
activate protein ataxia, seizures renal and Na+
kinase – such possible function/ levels
activation is Diuretics before starting
usually increased  Increase activity of lithium, then
in manic episodes) reabsorptive regularly after
mechanism (esp: loop
diuretics)
 Other drugs: ACEI,
NSAIDs

Na+ depletion
 Eg: LOW SALT DIET (bc
HT pt etc)  increase
lithium reabsorption
by PROXIMAL tubule
 reduces rate of
excretion  toxicity

 Unwanted Movements
(tremor)

Anticonvulsants  SEE ANTIEPILEPTIC LECT  Maniac episodes  Valproate

 PROPHYLAXIS  Birth defect – CI in
Valproate!! pregnant / child-
Carba- bearing age
mazepine
Lamotrigine
Atypical  SEE above  Maniac episodes
antipsychotics

Olanzapine
Antidepressants  Depressive
episodes
 Use with
mood
stabilizing
drugs – avoid
hypomania

General Anaesthetics

General Info  GA (inhaled/ IV)

 What
 controlled, reversible loss of consciousness
 Loss of ALL BODY REFLEXES and SENSATIONS (particularly pain)
 Components (RASH)
 Reflex suppression (autonomic reflex– BP, HR)
 Analgesia
 Skeletal muscle relaxation
 Hypnosis (sedation, lack awareness)
 GA stages for old drugs (eg: ether) – not for modern
 Phases  Induction, maintenance, recovery (consciousness and protective physiological reflexes regained)
 If drug
 Causes post-op nausea and vomiting  give ani-emetic at start and end (prevent ASPIRATION)
 Weak analgesic/ muscle relaxant  use strong adjunct analgesic/ muscle relaxant (compensate)
 “Inducing agent”  induction of anaesthesia
 Balanced Anaesthesia  use of combination of drugs to accomplish all components of GA
Premedication fast induction of anaes PREMEDICATION / PREANAESTHETIC MEDS
(see table)

+ IV anaesthetics
(THIOPENTAL etc)
 Inhaled anaes maintenance
Muscle relaxants Facilitate tracheal intubation

Opioid analgesics

 Special ANALGESICS
Opioids (narcotic  IV/ epidural/ intrathecal (into spinal cord)
analgesics)

(eg: Fen-ta-nyl)

Neurolept analgesia  Calm, NO loss of consciousness

 Droperidol
(eg: Dro-peri-dol)  only used for PERIOPERATIVE NAUSEA these days (otherwise not used anymore)
 Adverse effects  HyPOtension, QT prolongation, respi depression, , chest wall rigidity etc

 Together (Droperidol + Fentanyl)  similar to state of dissociative anaesthesia

 Use  minor surgical procedures (endoscopy, burn dressings)
 Inhaled Alveolar air  Blood  Brain
Anaesthetics
Uptake and Elimination rate depend on
Properties of anaesthetic agent Physiological Factors
BLOOD: gas partition coefficient OIL: gas partition coefficient Respiratory Rate Cardiac Output
 Solubility in BLOOD  Solubility in FAT  Higher rate = faster  Higher CO  higher
induction and elimination pulmonary blood flow 
faster induction and
elimination
 Measure of SPEED (of  Measure of POTENCY
recovery and induction)  High solubility in fat
 Low solubility in blood  HIGH POTENCY
 RAPID  PROPORTIONAL rlsp
 INVERSE rlsp  Potency= 1/ MAC

*MAC (a measure of
potency) Minimum
Alveolar Concentration of an
inhaled anaesthetic in alveoli
needed to produce surgical
stage of anaesthesia in 50%
of patients (the IV equivalent
is ED50)
 So: HIGH blood and oil solubility (eg: Halothane)
 Slower induction and recovery, higher potency

General GABA facilitator(/ Decrease duration of Block glutamate at Affect neuronal Inhibit neuronal output
mechanisms of mimicker) at GABA-A opening of Na+ NMDA receptor membrane proteins  from internal
GA receptor  increase channels (that are disrupt neuronal firing pyramidal layer of
influx of Cl-  reduce nicotinic receptor and sensory process in cerebral cortex 
excitability of neuron activated) – less thalamus  loss of motor activity reduced
depolarization consciousness and
analgesic effects
 Barbiturates  Isoflurane  Ketamine
 BZD  Enflurane
 Propofol

Inhaled Anaesthetics
State Gas Volatile liquid
N2O (SAFEST) Halothane Iso-flurane Sevo-flurane Des-flurane
Induction and  FAST  SLOWER  FAST  FAST  RAAAAAPID
recovery
Anaesthesia  Less Potent  Potent  Less potent  Potent  Potent
Analgesia  STRONG!!!!!!!!!  Weak
Muscle relaxant  NO (NO for N2O)  Strong (used in  Some  No (but increases Some
O&G – uterine sensitivity to muscle
relaxation) relaxants)
Odour  Pleasant  Pungent  Not pungent  Pleasant
(so pungent that
things “flu-away”)
Preferred Use  Mask induction of GA  ASTHMATICS!  NEUROSURGERY  Children  DAY surgery
in kids (imagine a child (think: Iso-flurane,
(combined with O2 angel coughing) eyesore (the
and eg: sevoflurane)  Children (not brain))
 Dental procedures hepatotoxic to (depresses
(analgesia) them) cortical EEG
 activity)
AE
Post-op Nausea  Yes  No  No  Yes (shivering too)  Yes
and vomiting
CVS  Hypo  Hypotension (VD)
 Arrhythmia
 Brady, Decreased
CO
Respi  Dilates bronchi!  Respi reflexes–  Respi reflexes
salivation, cough, stimulated
laryngospasm
(not good for kids)
Hepatotoxicity  HEPATITIS
(H for Halo and
Hepato)
Nephrotoxicity  Yes
(imagine an S twisting
into a kidney??)
Malignant  Yes  Yes
Hyperthermia (in susceptible
individuals 
(think: the bad abnormal
(hep and ryanodine
nephrotoxicity receptor 
causing ones) just sustained Ca2+
keep getting release from
worse  ) sarcoplasmic
reticulum)
More Info  Administer with  CHEAP  Use special heated
OXYGEN (avoid (i$oflurane) vaporizer
diffusion hypoxia)  No sensitisation of
 If not heart to
  when N2O adrenaline (?)
discontinued,
speedy
elimination and
displacement of
O2 in alveoli!!!!
 hypoxia
 Second gas effect
(when a 2nd inhaled
agent is co-
administered, will
have same high flow
rate as N2O)

IV Anaesthetics
Pro-po-fol Thiopentone Sodium BZD Ketamine
(Preferred) (Barbiturate)
Induction and  FAST  FAST  SLOWER (1 min)  FAST
recovery  Generally (except  ULTRA-SHORT ACTING!!
BZD)– 1 arm-brain (highly lipid sol  high
circulation (11s) redistribution in adipose
 Short duration of  quick recovery)
action
Anaesthesia  YES  Yes  Yes  Yes - DISSOCIATIVE
anaesthesia
Analgesia  No  Poor  Poor  Yes
Muscle relaxant  No  Poor  Yes  Yes
Preferred Use  Sedation for  BRAIN TUMOURS (reduces  Pre-medication (prior to  Children (tolerate drug better-
outpatient intracranial pressure) (think: anaesthesia!) think: Thailand cave)
procedures/ prolonged Barbiturate for Brain tumour)  Day surg (short acting)  Short procedures
sedation in ICU  NARCOANALYSIS (“truth  Endoscopy, Cardiac  Burn dressings, Angiographies
  Mechanical serum”) catheterization,
ventilation/ endoscopy  Short procedures angiographies
AE
Post-op nausea  No (is an anti-emetic!!)
and vomiting
CVS  Hypotension  CVS depression  Increased BP, HR, CO (AE? Idk)
 Bradycardia  Tx: Fluma-zemil (by inhibiting NE uptake at
nerve terminals)
Respi  Respi depression (in long  Respi depression
procedures)  Tx: Flumazenil
 Laryngospasm
Others  Pain at injection site  CI – acute intermittent  Anterograde amnesia  ADDICTIVE
PORPHYRIA (induces enzyme  EMERGENCE DELIRIUM
that causes porphyin syn.) (unpleasant psychological
 Shivering reactions during recovery) 
 Delirium scary dreams, disorientation
 Amnesia
More Info  Prodrug
 FOS-pro-po-fol
General Info  Benefits of using IV + inhaled anaesthetics
 Can reduce dosage of inhaled agent
 Produces effects that can’t be attained with inhalation agent alone
 IV anaesthetics
 Crosses BBB, facilitated by  HIGHER: unbound fraction, lipid solubility, non-ionized form
 Recovery depends on redistribution (thiopentone)

Key points from the Not so Impt Lectures

 Physiology of Pain and nociception
Definition  Pain - Unpleasant/ emotional experience originating in real/ potentially damaged tissue
 Nociception – unconscious activity induced by HARMFUL STIMULUS applied to sensory receptors
Types of  A delta – fast pain (pin prick) – acute pain (protective)
fibres  Myelinated
 Responds to – mechanical (& mechano-thermal) stimuli
 C- slow pain (dull) – chronic pain (pathological)
 Unmyelinated
 Responds to – Mechanical, thermal and chemical stimuli
Categories  Somatogenic - localized physical cause
 Nociceptive – responds well to analgesics
 High pain threshold
 Neuropathic – harder to treat
 Burning, tinging, pins and needles
 Examples
 Causalgia
 Spontaneous burning pain long after seemingly trivial injuries
 Often assos. with
 hyperalgesia, allodynia (pain from non-painful stimulus due to central sensitization)
 reflex sympathetic dystrophy (shiny skin + more hair+ excessive NE sympathetic fibre growth)
 Tx: alpha blockers
 Thalamic syndrome
 Types
 Central – eg: post-stroke
 Peripheral – eg: diabetic neuropathy
 Visceral (C fibres)
 Visceral - Poorly localized pain (diffuse stimulation of pain nerve endings)
 Vs parietal pain- localized pain
 Psychogenic
Principal  Tissue damage  release chemical mediators (brady, PG)  activate nociceptors  release substance P and CGRP  effects (inc.
BV dilation, oedema etc)
 Inflammatory pain  inv. Inflammatory soup (chemicals released on tissue damage)  hyperalgesia/ allodynia
  Inflammatory soup  acidic combination of bradykinin, PGE2, serotonin, histamine
 Referred pain (and referred hyperalgesia)
 Dermatomal rule
 Convergent projection theory (skin + viscera  same tract  but brain processes it as skin)
 Phantom limb pain
 Cortical plasticity
 Sensory input cut off  brain can reorganize (eg: changes in the thalamus VPN – ventro-posterior nucleus)
 Stimulation of sensory pathway at any point  sensation projected to site of receptor (even though it doesn’t exist
anymore)
 Headache
 No pain receptors at brain  but pain receptors @ surrounding structures
 Impulses via CN 5 & CN 9
 Headache mediated by
 Mechanical and chemical recep
 Pain processing - TTPM
 Transduction, transmission, perception, modulation
 Modulation – passes through PAG (periaqueductal gray matter)
 Blocking pain signals to brain
 Endogenous opioids – spinal cord, medulla, PAG
 Endorphins
 Dynorphins
 Enkephalins
 Serotonin and NE
 Central pain pathways
 Spinothalamic (body) and Trigeminal (face)  intensity, location, quality of pain
 Parabrachial nucleus (in pons), thalamus assess unpleasantness and autonomic activation (see slides)
 Pain & parts of brain involved in processing nociceptive signals
 Tension headache - anterior cingulate gyrus
 Migraine – frontal cortex
 Phantom – cerebellum
 Chronic back pain – midbrain
 Touching thermal grill (then intense burning sensation) – anterior cingulate + insula cortex
  Gate theory – rub a painful area to increase other innocuous stimuli  reduces pain sensation (involves A beta fibres- touch,
pressure
 Application – TNS: Transcutaneous Nerve Stimulation (thing pa has)

Development of the CNS and Pharyngeal Arches

General Derivatives

 Main points
 Post. horn cell (sensory nuclei) – from Alar plate (“APS”)
 Anterior horn cell (motor nuclei)– from Basal plate (“BAM”)
  Dorsal root ganglion – from neural crest cells
 Brain/ spinal cord – mostly from Mantle layer of neural tube
CNS cells  Oligodendrocytes – myelin sheath
 Astrocytes - most abundant!!!!  BBB, maintains nutrition
 Microglia – immune cells (phagocytic)
 Ependymal cells
Neural crest
derivatives

 Others
 Parafollicular cells of thyroid (secrete calcitonin)
 More info
 Cranial ganglia – 5-10 (except 6)
 Autonomic ganglia – sympathetic, parasympathetic (GIT)
General Pharyngeal  Primitive pharynx – somatic mesoderm
Arch  Endoderm  form branchial/ pharyngeal pouches
 Ectoderm  form pharyngeal grooves/ clefts
 Neural crest cells  pharyngeal arches
 Arch  CmNA  cartilage, muscle, nerve, artery
Development Mesodermal
tables Derivatives
of
Pharyngeal
Arches

 Cartilage component pics (1st, 2nd)

 Can usually see – 1-4 (5 disappear, 6th mostly hidden)

 Derivatives
of
Pharyngeal
clefts(out)
and Pouches
(in)

 Pharyngeal pouches
 Development
of the
Tongue

Congenital Neural Tube General  Neuropores don’t fuse (4th week)

Abnormalities defect  Persistent connection between amniotic cavity and spinal canal
 Assos.
 maternal diabetes
 folate def.
 Diagnosis
 12 weeks  US/ AFP (but AFP normal in spina bifida occulta)
 Increase AChE (confirmatory)
Spina bifida occulta

 Posterior (caudal) neuropores fail to close (no herniation)

 Tuft of hair/ skin dimple at back
 NO AFP increase
 Meningocele  Meninges herniate through bony defect

Myelomeningocele  Meninges and NEURAL TISSUE herniate

Myelo-schisis  Posterior neuropore fail to close
(Ra-chi-schisis)  Exposed unfused neural tissue
without skin/ meningeal covering
 Assos. with  ANENCEPHALY!!! +
motor and sensory deficits
Exencephaly  No vault of skull, malformed brain exposed
Anencephaly  Failure of rostral (anterior) neuropore to close No forebrain/ TELENCEPHALON
 Blind, deaf, unaware of surroundings, can’t feel pain
 Clinical finding: polyhydramnios (as no swallowing center)
Microcephaly  Smaller than normal cranium & brain
 Cause – rubella, toxoplasma gondii, CMV
Holoprosencephaly  PROSENCEPHALON doesn’t divide  loss of midline structures (monoventricle)
 Cause – possibly the mutation in SHH (sonic) & other genes
 CYCLOPIA!!!! + moderate cleft lip/palate
 Assos. – trisomy 13, fetal alc. syndrome

Other CNS  REELIN polymorphism  associated with AUTISM

congenital  Abnormal neuronal migration and positioning  microceph, seizures, schizo
defects
Pharyngeal Lateral cervical cyst  Neck swelling @ anterior border of SCM
clefts  Cause – unclosed cervical sinus
Branchial fistula/ sinus  Channel connecting cervical cyst to neck surface/ pharynx

Persistent ACCESSORY  Cause – pharyngeal pouches that persist

GLANDULAR TISSUE along
the pathway
Craniofacial defects  Cause – neural crest cell disruption
 Other syndromes  Treacher Collins syndrome, Pierre robin syndrome, Di George syndrome
(more for dentistry)

Tongue Aglossia
Macroglossia  Cause – generalized muscle hypertrophy
Microglossia
Hemiglossia  Suppression of lateral lingual swelling
Bifid tongue  Failure of fusion of 2 lateral lingual swellings
Trifid tongue  Failure of fusion of 3 lateral lingual swellings
Ankyloglossia  Tongue-tie
 Cause – short frenulum – imperfect separation of tongue from floor
Thyroid Thyroglossal cyst  Where -along migratory path of thyroid (near midline of neck)
Thyroglossal fistula  Cause – infection of thyroglossal cyst
Ectopic thyroid  Where -along migratory path of thyroid
Accessory thyroid tissue  Cause – remnants of thyroglossal duct
Thyroid agenesis
Congenital hypothyroidism
 Coma and Brainstem Death
Definitions  Coma
 Unrousable Unresponsiveness
(prolonged unconsciousness – loss of reaction to external stimuli)
Causes of
Coma

 Other – surgical causes

 Hypoglycaemia symptoms due to – sympathetic nervous system, neuroglycopenia
Examination Level of
consciousness

(GCS)

 Max 15, Min

 Motor Physical  Posture (decerebrate/ decorticate)
Examination  Tone
 Movement
 Power
 Reflexes
Brainstem Pupillary
reflexes Oculo-cephalic  How  turn (usually unconscious) pt’s head side to side
(Doll’s eye)  Results
 Normal (positive)  “fixed gaze”  eyes move in opposite direction with respect to
head to stabilize image
 Negative  eyes fixed with respect to head
 CI
 Cervical spine injury
Vestibulo-  How  pour cold water into ear (tbh: can be other stimulus too like just closing eyes and
ocular turning head, as the fluid movement in semi-circular canals will participate in reflex and
(Caloric) there’ll be eye movement. With eyes open, there’s the additional effect of fixation.)
 Results
 Normal (positive) horizontal nystagmus (fast phase away from irrigated side)
Motor reflexes  Corneal (V1, VII)
within cranial  Gag (IX, X)
nerve  Cough (air through nebulizer)
distribution
Altered Minimally  Altered consciousness with periods of awareness – may respond to stimuli (in those periods)
conscious conscious state!!  Req. total nursing care
states Persistent  Apparently awake- but unresponsive
vegetative  Brainstem intact but much CORTICAL DAMAGE
state !! (vege > 1  MAY – move limbs purposelessly + may have CN and spinal reflexes
month)  Req. total nursing care
“Locked-in”  Conscious – can’t speak/ move
syndrome  Much BRAINSTEM DAMAGE
Delirium  Confused state
 Restless, hallucinations
Brain Death  Permanent and irreversible loss to all brain functions (including brainstem)
 3 components
 Apnoeic Coma (on vent)
 Identifiable significant medical event leading to brain death
 Absent brainstem reflexes
 The above + motor exam (extra?)
 Additional tests – apnoea with no respiratory effort when ventilator off
 PCO2 rises above 50mmhg
 Treat/ correct everything else first (eg: hypoglycaemia) to exclude those before declaring brain death
 Test twice 6-24hrs apart, 2 dif doctors (one not on med team. Can’t be on surgical transplant team)