Neuroscience review Brain Cerebrum o Grey Matter Large neurons:
projection fibers (ascending and descending pathways) Medium
neurons: commissural fibers (between hemispheres) Small neurons:
association fibers (within hemisphere) o White Matter Corona
Radiata Internal Capsule o Cortex: Frontal lobe: primary motor
cortex, prefrontal cortex, premotor cortex, supplementary motor
cortex Parietal lobe: primary somatosensory cortex Occipital lobe:
primary visual cortex (calcarine sulcus) Temporal lobe: primary
auditory cortex o Subcortical: Hippocampus Amygdala Basal ganglia
Striatum (innervated by substantia nigra pars compacta, modulates
input from cortex and output from thalamus, important in Parkinsons
disease) o Dorsal Striatum: putamen, caudate nucleus o Ventral
Striatum: nucleus accumbens, olfactory tubercle Globus pallidus
(forms lentiform nucleus with putamen) Substantia nigra (pars
compacta, pars reticulate) Lateral Ventricles Rhinencephalon
Olfactory bulb, tract Anterior commissure Diencephalon o
Epithalamus o Third Ventricle o Thalamus o Hypothalamus Optic
Chiasma o Subthalamus o Pituitary gland Brain stem o Midbrain
Tectum: inferior and superior colliculi Tegmentum: ventral
tegmental area, Red Nucleus, crus cerebri Mesencephalic duct (of
Sylvius) Cerebral peduncle Pretectum o Pons Respiratory centre:
pneumotactic centre, apneustic centre Cranial nerve nuclei: pontine
nucleus of trigeminal nerve sensory branches, motor nucleus for
trigeminal nerve, abducens nucleus, facial nerve nucleus,
vestibulocochlea nuclei, superior and inferior salivatory nuclei o
Medulla Oblongata Medullary pyramids Cranial nerve nuclei: nucleus
ambiguus, dorsal nucleus of vagus nerve, hypoglossal nucleus,
solitary nucleus Cerebellum o Vermis o Hemispheres
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Vascular supply - Vertebral Arteries Basilar Artery - Basilar
Artery + Internal Carotid Arteries Circle of Willis o Anterior,
Middle, Posterior Cerebral Arteries o Anterior, Posterior
Communicating Arteries
Cranial nerves 1) Olfactory 2) Optic 3) Oculomotor 4) Trochlear
5) Trigeminal 6) Abducent 7) Facial 8) Vestibulocochlea 9)
Glossopharyngeal 10) Vagal 11) Accessory 12) Hypoglossal Spinal
Cord - Extends from foramen magnum, terminates in conus medullaris
with filum terminale, forming cauda equina at L1-L2 - White matter:
spinal tracts - Grey matter o Dorsal horn: sensory, Ventral horn:
motor, Lateral horn (T1-L2): autonomic o Spinal nerve: union of
dorsal sensory and ventral motor roots o Sympathetic fibers
originate from lateral horn, exits spinal cord via ventral roots,
white rami communicans to sympathetic ganglion, post-ganglionic
grey rami communicans rejoins spinal nerves to innervate glands,
smooth and cardiac muscle - 8 cervical (C1 above C1 vertebra, C8
below C7 vertebra), 12 thoracic, 5 lumbar, 5 sacral, 1 coccyx
Pathways - Ascending (Sensory) o Spinothalamic: pain, temperature,
touch, pressure Decussates at level of spinal cord o Dorsal Column
Medial Lemniscus: vibration, conscious proprioception Decussates at
level of medulla o Spinocerebellar: subconscious proprioception
Does not decussate - Descending (Motor) o Pyramidal Corticospinal
(rest of body) Decussates at level of medulla Corticobulbar (for
head and neck) o Extra-pyramidal Tectospinal Vestibulospinal
Reticulospinal Rubrospinal Sensory system - 1st order neuron o
Receptors: Crude touch, pressure, pain, fine touch, vibration,
conscious and subsconscious proprioception Skin, skeletal muscles,
joints, viscera o Dorsal root ganglion o Synapses at dorsal horn of
spinal cord nd - 2 order neuron o Axon travels along the ascending
tracts o Decussates o Synapses at thalamus, cerebellum rd - 3 order
neuron o Cerebral cortex or cerebellum Motor system - Upper motor
neuron o Motor center of cerebral cortex o Axons pass through
corona radiata, internal capsule, to midbrain and medulla oblongata
o 80% decussate o Synapses at anterior horn of spinal cord
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Lower motor neuron o Carries action potential to neuromuscular
junction o Synapses on voluntary muscles
Organisation - Somatic nervous system o Sensory o Motor -
Visceral nervous system o Sensory o Motor Sympathetic (T1-L2)
Nicotinic acetylcholine receptor: ligand gated ion channel
Parasympathetic (craniosacral outflow) Muscarinic acetylcholine
receptor: GPCR that uses 2nd messenger to modify ion channels CN 3,
7, 9, 10 o 3: Intraocular muscle for pupil size and lens thickness
o 7: Glands of head o 9: Parotid gland o 10: Parasympathetic
stimulation of visceral organs up to 2/3 of proximal transverse
colon S2-4: rest of GIT General Function - Sensory system: collect
information about state of organism and environment - Motor system:
organize and generate actions - Association systems: linking
sensory and motor components to provide basis for higher order
brain functions o Association cortex occupies majority of cortex
(sensory and motor cortices account for ~20%)
Neurohistology - CNS o
Frontal: guiding complex behaviour by planning responses to
ongoing stimulation Temporal: recognition and identification of
highly processed sensory information Parietal: attention and
awareness of the body and stimuli that act on it
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Neurons: functional cells Induces depolarization along processes
and axons Neurotransmitter production Glial cells: supporting cells
Astrocytes: blood brain barrier Oligodendrocytes: myelination of
nerve axons Ependymal cells: lining of ventricles Microglia:
macrophages for brain Neurons: transmit signals Motor:
neuromuscular junction Sensory: receptors (baro, chemo, mechano,
noci, osmo, photo, proprio, thermo receptors) C fibers: slower due
to unmyelinated fibers (thermal, mechanical, chemical) A fibers:
faster due to myelination (sharp pain) Schwann cells: myelination
of axons Satellite cells: similar to astrocytes and Schwann
cells
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PNS o
o o
Reflex - Pathway o Receptor responds to stimuli o Afferent
sensory carries stimuli to CNS o Integration of information in CNS
Monosynaptic Polysynaptic o Efferent motor neuron carries impulse
Polysynaptic: involves inhibitory interneuron to relax opposing
muscle o Effector: contraction and relaxation - UMN: loss of
inhibition by UMN, hence hyper-reflexia and clonus may be observed
- LMN: loss of innervation by LMN, hence muscle is unable to
respond to stimulus
Neurophysiology - Action potential o Resting membrane potential
At equilibrium, there is a balance of opposing forces Concentration
gradient causing K+ to move out of the cell and Na+ to enter the
cell Opposing electrical gradient that increasingly tends to stop
K+ from moving across membrane Na+K+ ATPase: for every 2K+
transported into the cell, 3Na+ are removed Net loss of one
positive ion from cell, leading to hyperpolarization o Ionic basis
Na+ channels open, influx reaches threshold, firing off action
potential Na+ channels closed and becomes refractory K+ channels
are opened during depolarization and continues to leave the cell,
causing membrane potential to return to resting state K+ channels
are slow to close, causing hyperpolarization Factors affecting AP
propagation
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Axon diameter: larger less resistance Membrane conductance:
leaks charge if poorly insulated Myelination: nodes of Ranvier
saltatory conduction Membrane capacitance: current is used up
charging the membrane o Clinical relevance: Multiple sclerosis:
demyelination and inflammation along axonal pathways Toxins:
tetrodotoxin (puffer fish) / saxitoxin (red tide) blocks Na+
channel -toxin (scorpion) slows inactivation of Na+ channel
Dendrotoxin (wasp) / apamin (bee) blocks K+ channel Synapses o
Transmission AP arrives at synaptic bouton, deploarization opens
voltage gated Ca2+ channels Influx of Ca2+ promotes vesicle
(containing neurotransmitter) attachment to presynaptic releasing
sites Vesicle membrane fuses with presynaptic membrane and contents
are released into synaptic cleft Transmitter diffuses across cleft
and binds to postsynaptic receptors Excitatory or Inhibitory Bound
receptors cause change in postsynaptic membrane potential,
magnitude depends on amount Effect terminated by 1) enzymatic
destruction, 2) reuptake, 3) outward diffusion, 4) uptake by glial
cells Type: summation allows subthreshold EPSP/IPSP to influence AP
production (balance) Excitatory Increases membrane permeability to
Na+, increasing resting membrane potential Neurotransmitters:
glutamate and aspartate Extremely widespread throughout CNS
(cholinergic system is used in brain for learning and memory, and
primarily in the PNS) Inhibitory Increases membrane permeability to
K+ or Cl- reducing resting membrane potential Neurotransmitters:
GABA and glycine Found mainly in spinal cord interneurons Amines:
dopamine, noradrenaline, adrenaline, serotonin May be excitatory or
inhibitory depending on the specific receptor Clinical relevance:
Sarin and organophosphates inhibit acetylcholinesterase
-bungarotoxin (Bungarus multicintus) irreversible nicotinic
acetylcholine receptor inhibitor Atropine (Atropa belladonna)
competitive muscarinic acetylcholinereceptor antagonist Aricept
acetylcholinesterase inhibitor used for treatment of Alzheimers
Disease
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Spinal cord level - C3, 4 and 5 supply the diaphragm (the large
muscle between the chest and the belly that we use to breath). - C5
also supplies the shoulder muscles and the muscle that we use to
bend our elbow . - C6 is for bending the wrist back. - C7 is for
straightening the elbow. - C8 bends the fingers. - T1 spreads the
fingers. - T1 T12 supplies the chest wall & abdominal muscles.
- L2 bends the hip.
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L3 straightens the knee. L4 pulls the foot up. L5 wiggles the
toes. S1 pulls the foot down. S3, 4 and 5 supply the bladder, bowel
and sex organs and the anal and other pelvic muscles.
Memory Basic processes - Encoding: perceptual and sensory
information is transformed - Storage: process which information is
retained - Retrieval: process which we recover information and
become consciously aware - Stages: young tend to have problems with
attention and encoding, elderly tend to have problems with
retrieval o Sensory input sensory memory Unattended information is
lost o Attention working (short term memory in hippocampus)
Requires maintenance, unrehearsed information is quickly lost o
Encoding long-term memory (in cortex) Some information may be lost
over time o Retrieval to short-term memory Types Sensory Memory o
Very short term, temporary recollection o Large capacity, very
short duration, dependent on attention Attention is the gate that
lies between sensory and working memory (very selective) Working
Memory o Short term o Sensations which are attended to become
encoded in short-term memory o Limited capacity, short duration o 7
+/- 2 bits of information, usually lasts about 30 seconds o
Transferred to long term memory by encoding Long term Memory o
Memories of the past which form knowledge base o Infinite in
capacity and duration o Encoding depends on feelings, emotions, and
is hence coloured (selective encoding) o Elaborative rehearsal to
organise memory o 2 types of memory Explicit: items, events,
meanings, episodic, semantic Implicit: unconscious, programmed into
cerebellum, eg. cycling, etc o Problems lie in retrieval Tip of
tongue Freudian slip Requires specificity as encoding (context,
state, mood) Association networks: different parts of brain stores
different parts of the same memory To retrieve information, brain
performs complex chain of chemical and electrical functions As one
ages, these cells, synapses and systems deteriorate and function
less efficiently Aging does not generally affect sensory or
long-term memory Short term memory declines with age o Mild decline
in memory o Slowing in rate of information processing o But does
not affect daily function, nor acutely exacerbate
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Ageing -
Dementia - Clinical syndrome o Progressive o Global
deterioration in cognitive function o In a clear state of
consciousness o Sufficiently severe to interfere with social and
occupational function - Epidemiology o Exponential increase in age
specific dementia prevalence as age increases o Dementia prevalence
in societies will increase due to increased life expectancy o Often
unrecognised and misdiagnosed and viewed as inevitable ageing -
Cost o Healthcare costs, lost productivity o Emotional,
psychological and practical problems for caregivers o Early
treatment Proven effective treatments available Prevents costly and
inappropriate treatment Avoids trauma of misdiagnosis Prepares
patients and families to settle financial, legal, treatment and
care plan issues - Early symptoms o Difficulty learning and
retaining new information o Language problems o Difficulty handling
complex tasks o Alterations in behaviour o Loss of reasoning
ability o Loss of spatial ability and orientation o No acute
exacerbation: not to be confused with delirium (due to general
medical condition) - Types o Alzheimers Disease (amnesia, aphasia,
apraxia, agnosia) o Lewy Bodies o Vascular o Frontotemporal Types
Progressive mutism Semantic dementia Early stages Personality
changes Changes in social conduct Loss of emotional warmth -
Prevention o Risk factors o Disease process and modifiers o
Biomarkers and neuroimaging o Lifestyle interventions Social
networks, mental activities, physical activity Reduce vascular risk
Enhance cognitive reserve Reduce stress Diet: wine/alcohol o
Pharmaceutical and non-pharmaeutical treatments Symptomatic
treatment Cholinergic drugs (acetylcholinesterase inhibitors) o
Tacrine, donepezil, galantamine, rivastigmine Glutaminergic drugs o
Memantine Anti-psychotic drugs o Cultural issues - Imaging o Medial
temporal lobe (hippocampus) o Increasing Alzheimers Disease
enlarging temporal horn (normally not seen, indicates atrophy of
hippocampus) o Modalities: CT, MRI, PET, MRA, fMRI - Markers o Beta
amyloid and tau proteins
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Burden of disease (infarcts, white matter lesions) Neuronal
loss
Communication Language - Interplay of: o Form: sounds, formation
of sentences, function: verbal and non-verbal communication,
content: meaning - And social interaction, different parts of the
brain hold different skills, brain lesions may allow compensation
of communication function - Good speech: cadence, speed, pitch,
volume Communication deficits - Types o Aphasia o Apraxia o
Dysarthria o Right hemisphere / cognitive communication deficits -
Caused by: o Stroke o Dementia o Traumatic brain injury o Motor
neuron disease o Cancer o Diseases of mouth, throat, lungs -
Results in social isolation due to o Reduced communicative
effectiveness o Difficulties with daily activities o Emotional
frustration and reduced self-esteem Pathways - Somatosensory
information is relayed to the primary sensory cortex - Sight is
seen and relayed to the primary visual cortex - Speech is heard and
relayed to the primary auditory cortex - Signals are propagated to
Wernickes area where the signals are understood - Brocas area then
responds with the desired expression and signals are sent to the
primary motor cortex - Primary motor cortex then relays signals to
the appropriate muscles for the production of speech
Cognitive-neuropsychological model
Lesion Middle Cerebral Artery - Supplies lateral surface of
brain o Upper division Motor and sensory of face, arm and hand:
contralateral facial and upper limb weakness Frontal lobe Brocas
area: non-fluent, expressive aphasia o Lower division Temporal lobe
Wernickes area: fluent, receptive aphasia, auditory neglect
Aphasia - Brocas (non-fluent) o Good comprehension at simple
level, slow, laborious expression, consists mostly of content words
(nouns) o Short utterances, intact self-monitoring/awareness -
Wernickes o Impaired comprehension o Long, grammatically accurate
but empty speech, filled with neologisms or jargons, beating about
the bush o Poor self-awareness - Global o Severe impairment in all
language functions, stereotypical or over learned phrases o May be
better at nonverbal tasks, due to impairments in understanding and
talking Diagnosis - Past medical history, current case history,
subjective assessment (physical status, behaviour) - Screen o
Receptive language Understanding questions Following instructions
(without visual cues) o Expressive language Naming objects (may
need prompting, context of object) Conversation Reading Writing -
Understanding o Attention: reduce distractions, face to face, one
person at a time o Content: speak slowly, key words, break down
instructions, repetition o Cues: supplement with gestures,
pictures, drawings, elaborate with contextual information -
Expressing o Time: allow time for them to think of words, search
for clues o Questions: binary choices, yes/no questions o
Alternatives: gestures, pointing to objects and pictures, writing,
drawing Apraxia - Difficulties in speaking as a result of
impairment in capacity to plan or program movements for speech -
Due to damage to left side of brain o Left frontal, temporal,
parietal lobe o Left insula and left basal ganglia - Co-occurs with
aphasia in 80% of cases, not a result of muscle weakness - Clinical
features: o Speech sounds in words may be distorted, left out or
repeated o Difficulty in arranging order, groping for the right
word o Difficulty with the correct word o Short functional phrases,
writing may be better o Inconsistent errors, with slow labored rate
of speech Dysarthria - Disturbance to muscular control, may involve
damage to brain (cerebral cortex, cerebellum, basal ganglia) or
physical structure (oral structures, throat, lungs) - 5 categories
o Respiration: short phrases, running out of breath, uncoordinated
speech-breathing pattern o Phonation: breathy, hoarse,
strained/strangulated Parkinsons dysphonia: tremulous voice, watery
and leaky o Articulation: slurred speech, unclear lip and lingual
sounds o Resonance: hyper/hypo nasal speech Flaccid dysarthria:
nasopharyngeal carcinoma, myasthenia gravis, LMN lesion Causing
weakness of vocal muscles, leading to flaccid dysarthria and
hyponasal speech o Prosody: monopitch, monoloud, uncontrolled
changes in loudness and pitch Cerebellar dysarthria: lack of
coordination, staccato, monotonous, may shout all the time UMN
lesion: pseudobulbar (lesion above medulla) palsy, spastic
dysarthria, gravelly voice, tongue is not moving well Pseudobulbar
palsy UMN: dysphagia, distorted gag reflex, spastic tongue, brisk
jaw jerk Bulbar palsy LMN: dysphgia, chewing difficulty,
fasciculation of tongue, absent/normal reflexes
Cognitive-communication deficits
Stress Stress -
Communication deficits often arising from right MCA infarct and
traumatic brain injury Intact concrete and simple functional
communication Deficits in cognition: attention, memory, problem
solving Deficits in communication: pragmatics, higher level
language function, difficulties with social rules of normal
conversation
Brain -
Threat or perceived threat to organisms homeostasis Evokes
reaction in the brain That activates physiological symptoms in the
body Response is proportional to the significance of the stressor,
intensity and chronicity o Acute: minutes, hours immune enhancement
o Chronic: hours, days onwards immunosuppression Function may be
enhanced with stress, but if cannot be resolved through adaptation,
results in withdrawal or anxiety o Extremes: mutism,
confrontational Amygdala o Inner most part of brain, anterior to
hippocampus o Fear, stress response, elicits and sustains anxiety
symptoms Locus ceruleus o Bluish tint grossly o Releases
norepinephrine and induces corticotrophin releasing hormone from
hypothalamus (adrenal glands) Nucleus accumbens o Reward mechanisms
with fibres to prefrontal cortex Thalamus o Arousal, sleep,
sensorimotor gating Hypothalamus o Stress response,
sleep/wake/appetite regulation Hippocampus o Memory and emotion,
storage of anxiety related information Prefrontal cortex o Decides
actions and responds accordingly, motor cortex fibres as well
Responds via sympathetic nervous system, and hypothalamus-pituitary
axis (primarily stress hormones cortisol, adrenaline) GIT o Least
important to stress, hence to the extent of expulsion and
defecation o Limbic system increases stimulation of mast cells in
the enteric nervous system inflammatory bowel disease Brain o
Increased glucocorticoids decreased brain derived neurotrophic
factor decreased dendritic branching neuron atrophy and death o
Chronic stress hippocampus atrophy, amygdala hypertrophy Increased
risk of premature death (suicides), higher frequency of adverse
health behaviours, increased risk of IHD and respiratory problems
Overall: o Fight or flight: aggression, conflict, flee,
withdrawal
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Body -
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Clinical significance - Early depression: if untreated may cause
hippocampus to decrease significantly in size o Due to possibility
of neurogenesis in adults, where regenerated neurons will migrate
to area of need o Decreased BDNF in depressed patients Stress
coping - Problem solving: solve problems of stress, organization -
Emotion oriented Neurobiology
Avoidance oriented: avoid activities that induce stress, or
cause regret in future Supportive behaviour: befriending
Counteract: tone down expectations
Sleep and wake Definition - Reversible state of decreased
responsiveness to the environment - Behavioural quiescence -
Species specific posture - Sequence of physiologic sleep stages Why
Restorative function Thermoregulation, energy conservation Memory
consolidation and information processing, brain development and
growth: spatial memory replay during sleep in hippocampus, synapses
and connections strengthen during sleep performance is proportional
to hippocampus activity Development of oculomotor control Immune
function, preservation and protection Synaptic plasticity and
remodelling: inspires insight increased ability to see patterns
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Sleep-wake behaviour - Wakefulness: aware of oneself and the
environment, cerebral cortex is active - REM sleep: unconscious,
cerebral cortex is active, paralysis of skeletal muscles, dreams
and saccadic eye movements - Non-REM sleep: unconscious, with
reduced cortical activity, reduced muscle tone Tests Sleep-wake
scoring o Electroencephalogram, electrooculogram, electromyogram
Reflects summation of extracellular currents (microvolt scale with
poor spatial resolution) During sleep, neurons tend to fire with
increased synchronicity, EEG shows large steady waves Clinical
sleep study o Electrocardiogram, airflow sensors, oximetry, nasal
pressure, oesophageal pressure, body position, respiratory effort
Awake with eyes closed o EEG: predominance of alpha wave activity
in 8-13 Hz range o EOG: predominance of alpha wave activity in 8-13
Hz range (leak from EEG channel) o EMG: tonic Stage 1 sleep:
transition from wakefulness to non-REM sleep o EEG: disappearance
of alpha wave activity, appearance of low voltage theta activity in
4-7 Hz range o EOG: appearance of slow eye movements, undulating
waves o EMG: tonic, but slightly attenuated Stage 2 sleep o EEG:
appearance of K complexes (large fluctuations) and sleep spindles
(fast frequency) on background of mixed frequency o EOG: no eye
movements, may have deflection o EMG: tonic Slow-wave sleep (stage
3 and 4) o EEG: appearance of high amplitude delta activity 8 hours
a day with ear plugs is not allowed Exponential decrease in
exposure with increase in dB o Presbyacusia Age induced, >60
years incidence increases to 23-30% Due to chronic damage o
Ototoxicity Drug induced, bilateral, aminoglycosides, loop
diuretics (disruption of electrolyte balance in scala media) o
Acoustic neuroma Vestibular schwannoma, presses on nerve Unilateral
in nature MUST be excluded (MRI to check) May press on brainstem,
cerebellum, 5th nerve, 7th nerve late presentation: clumsiness o
Central auditory processing disorder Anything along pathway Sound
interpretation problems, unable to understand instructions
Singapore tests have not found local normal yet
Assistive devices - Hearing aids o Amplifies sound o Processor
that digitizes and filters sound o May be behind ear or in canal -
Bone anchored hearing aids o Aids in improving bone conduction -
Implantable hearing aid o Clipped to ossicles o Magnetic vibrator
to enhance ossicular vibration - Cochlear implants o Electrodes
coiled around cochlea o Direct nerve stimulation, coiled around
full length of cochlea o Able to mimic tonotopicity - Brain stem
implant, cochlear nucleus
Touch Dermatomes
Neuroaxis - Skin - Peripheral nerve o Compression Median nerve:
wrist (carpal tunnel syndrome), cubital fossa Ulnar nerve: wrist,
medial epicondyle Radial nerve: proximal to wrist, elbow, spiral
groove of humerus (most common) o Peripheral neuropathy Genetic:
Friedreichs ataxia, Charcot-Marie-Tooth syndrome Metabolic:
diabetes mellitus (most common, symmetrical), chronic renal
failure, porphyria, amyloidosis, liver failure, hypothyroidism
Toxic: drugs, organic metals, heavy metals, excess vitamin B6
Inflammatory: Guillain-Barre Syndrome, systemic lupus
erythematosus, Sjogrens syndrome Vitamin deficiencies: B12, A, E,
B1 Others: malignancy, HIV, radiation, chemotherapy - Nerve
roots/plexus - Spinal cord o Brown Sequard Syndrome: ipsilateral
UMN weakness, ipsilateral proprioception and vibration loss (dorsal
column medial lemniscus), contralateral pain and temperature loss
(spinothalamic) - Brain o Stroke May have sensory stroke/transient
ischaemic attack (loss of sensory but no motor weakness)
Summary
Pain -
Unpleasant sensory and emotional experience associated with
actual or potential tissue damage Protective mechanism: to remove
tissue from pain stimulus
Classification - Duration: acute, chronic - Region and system o
Location: headache, back pain, pelvic pain, etc o Body system:
myofascial, rheumatic, neurologic, vascular - Aetiology o
Somatogenic Nociceptive Stimulation: thermo-, chemo-, mechano-
receptors Superficial or deep Neuropathic Peripheral or central
Burning, tingling, electrical, stabbing, or pins and needles o
Psychogenic Nociceptors - Pain receptors do not adapt, continuous
excitation will become progressively greater (hyperalgesia)
Classification Fast pain Slow pain Description Sharp, pricking,
acute, electric Burning, aching, throbbing, chronic Location
Superficial tissues Skin and deep tissues Transmission A fibres
(myelinated) 6-30 m/second C fibres (unmyelinated) 0.5-2 m/second
Analgesia - Input: peri-aqueductal grey (midbrain), raphe magnus
nucleus (lower pons), pain inhibitory complex (spinal cord) -
Opiate system: endorphins and encephalins are endogenously
produced, opiate receptors present in CNS Treatment - Chronic pain
o Diagnosis: location, mode of onset, provoking and relieving
factors, quality of pain, duration, severity o First tier: NSAIDs,
transcutaneous electrical nerve stimulation (TENS), psychological
therapy, nerve blocks o Second tier: opioids, neurolysis, thermal
procedures o Advanced: neurostimulation, implantable drug pumps,
surgical intervention, neuroablation - Medication: nociceptors
(analgesics, NSAIDs, opioids), neuropathic (anti-depressants,
anti-convulsants), anti-spasms
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Adjunct: injections (anaesthetics, steroids), nerve blocks,
physiotherapy, TENS, acupuncture, psychological support,
surgery
Movement Tract Cortex: higher functions o Integration of sensory
inputs (somatosensory, visual, auditory, olfactory cortices) o
Understanding of sensory inputs (Brocas area, Wernickes area,
visual association, auditory association cortices) o Processing of
algorithms (frontal lobe) o Planning and decision (pre-frontal
area) o Execution of motion (motor cortex) Brainstem: conduit for
essential tracts and repository of nuclei for cranial nerves
Cervical cord: conduit for essential tracts, primarily serves upper
limb function Thoracic cord: conduit for essential tracts,
primarily serves chest and abdomen Lumbar cord: conduit for
essential tracts, primarily serves lower limbs Sacral cord: conduit
for essential tracts, primarily serves perineum (and bottom of
feet)
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Somatotopy - Motor homunculus o Legs: central area, face:
parietal area, hands: in between specific infarction may result in
specific motor loss - Spinal cord o Syringomyelia: widened central
canal within spinal cord compresses upper limb fibres, leaving
lower limb motor and sensory function relatively intact, also, the
lesion tends to widen laterally and rostral/caudally, leaving the
dorsal column medial lemniscus tract intact and the paralysis may
spread to involve the lower limb Neuroaxis - UMN lesion:
hyper-reflexia, hypertonia o Cortex Infarction/lesion contralateral
UMN hemiplegia + contralateral 7th nerve UMN palsy Middle cerebral
artery: most common artery to be blocked, requires at least 15
ml/100g/min of blood flow Below threshold levels in
haemorrhage/thromboembolism damage occurs Seizure: inappropriate
neuron firing, epilepsy: recurrent seizures (injury, malformation,
etc) Subcortical area Diencephalon: CN I, II Brain stem Midbrain:
CN III, IV III: eye is down and out, testing of 4th nerve causes
intorsion of eyeball (look at medial vessels), ptosis (LPS,
compensated by frontalis), loss of accommodation (ciliary muscle) o
Recovery horizontal movement may return first o Eye lesions: linked
to thyroid and myasthenia gravis (orbit or muscle problems) Medial
longitudinal fasciculus (MLF), parapontine reticular formation
(PPRF) lesion o Frontal eye field pushes eyes to opposite side,
damaged in stroke eyes may be diverted to the ipsilateral side as
the lesion o Frontal eye field (Brodmanns area 8) when activated
sends signals to MLF of ipsilateral eye and PPRF of contralateral
eye, causing activation of the medial rectus of the ipsilateral eye
and lateral rectus of contralateral eye allowing coordinated
movement o Lesion in MLF: failure to adduct eye on the same side of
lesion causing nystagmus in contralateral eye when looking away
from the lesion due to diplopia: internuclear ophthalmoplegia
Horners syndrome: sympathetic interruption ptosis, miosis,
enophthalmos, +/- anhidrosis Eye problems: look for lipid deposits,
xanthylasmata at eye bags, arcus cornealis around iris Pons: CN V,
VI, VII, VIII VI: longest intracranial course easily damaged Pons
infarction/lesion contralateral UMN hemiplegia + ipsilateral 7th
nerve LMN palsy o Bells phenomenon: eye rolls up as attempt is made
to close eye, due to 7th palsy, orbicularis oculi is unable to
completely close eye VII: common sites posterior fossa, pons,
petrosal, parotid, peripheral (5 Ps) o Bells palsy: 7th nerve
lesion, UMN contralateral face below brows affected, LMN
ipsilateral face above and below brows affected o Common causes:
inflammation (treated with steroids, acyclovir), good recovery o
May have synkinesis: false innervation due to wrong nerve
regeneration Medulla: CN IX, X, XI, XII XII: stick out tongue,
innervation responsible for pushing tongue in contralateral
direction, lesion to nerve will cause the tongue to point toward
affected side (+ fasciculation and atrophy in LMN)
o o
o Cerebellum: look at balance and coordinationo Spinal cord
Lumbar signs may be due to thoracolumbar spinal cord lesions, as
the fibres may continue down before exiting the spinal column
Spinal shock: in the first week of damage, UMN damage may present
as LMN due to spinal shock
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LMN lesion: hypo-reflexia, hypotonia o Anterior horn cells
Non-length dependent pattern of weakness and loss of reflexes
proportionate to weakness Reflex loss due to denervation and
atrophy Fasciculations and wasting Wallerian degeneration/death of
anterior horn cells causes sporadic random firing of neuron causing
fasciculations and twitching of specific muscle fibres Example:
amyotrophic lateral sclerosis (Lou-Gehrigs disease, Motor Neurone
Disease) Not length dependent, furrows on tongue with
fasciculation, involvement of swallowing muscles, speech loss,
respiratory muscles weakness may also be present, bulbar atrophy o
Spinal roots: radiculopathy/polyradiculopathy specific root motor
and sensory function may be lost o Plexus Important due to
co-localization of many peripheral nerves o Peripheral nerve
Demyelinating disease: reflex is lost due to increased transmission
time Symptoms: weakness, loss of reflexes, relatively little
wasting, sensory abnormalities, proximal and distal neurological
deficits Mononeuritis multiplex: classic cause Mycobacterium leprae
o Sciatica: Foot drop, numbness, weakness of dorsi/plantar flexion,
eversion and inversion o Upper limb: median nerve on one arm, ulnar
on the other o Sural nerve below lateral malleolus grossly
thickened Axon disease: length dependent deficit (Wallerian
degeneration from point of damage) Symptoms: weakness, loss of
reflexes, wasting, loss of sensation, paraesthesia, dysaesthesia,
lancinating pain, allodynia, hyperalgesia (abnormal sensations),
length dependent deficits Mononeuropathy: one nerve, mononeuritis
multiplex: single nerve damage in multiple locations Diffused
polyneuropathy: glove and stocking deficits, stockings before
gloves, length dependent o Diabetes mellitus, Guillain Barre
syndrome Specific examples Median neuropathy o Thenar eminence
atrophied o Sensation: loss of sensation over median 3.5 fingers o
Benedicts sign: thumb and index finger are extended when
hand/fingers are flexed Ulnar neuropathy o Guttering on dorsum of
hand due to atrophy of intrinsic muscles (interosseous), abduction
of fingers and extension of interphalangeal joints are lost,
allowing for unopposed flexion of proximal finger flexors producing
a claw o Claw: ulnar paradox, more distal the damage, the worse the
claw appears o Sensation: loss of sensation of medial 1.5 fingers o
Froments sign: flexor pollicis longus (median nerve) compensates
for weak adductor muscle (ulnar nerve), causing flexion of the
interphalangeal joint of the thumb to maintain grip Radial
neuropathy o Signs: wrist drop (extensor weakness), decreased elbow
flex (brachioradialis weakness) o Commonly due to compression of
radial nerve at spiral groove of humerus weak extensors but triceps
are normal (Saturday night palsy) Others o Hip adduction: obturator
nerve o Extension of knees: femoral nerve abnormal knee reflex
Neuromuscular junction
o
Most common disorder: myasthenia gravis ACh receptors are
targeted by immune system decreased receptors and resulting in
failure of transmission Common presentation: ptosis, diplopia due
to fatigue, dysphonia, dysarthria, respiratory weakness, proximal
weakness o Edrophonium/Tensilon test: reversible ACh-esterase
inhibitor increases ACh in NMJ by reducing breakdown o In
myasthenia gravis, muscle weakness is reduced, in muscle weakness
from cholinergic crisis resulting from too much stimulation,
increase in ACh will worsen weakness o Treatment: allow receptors
to regenerate by stopping the immune process
o Muscle
Lambert Eaton Myasthaenic Syndrome (LEMS): autoantibodies
targeting presynaptic voltage gated Ca2+ channels at NMJ o 60%
associated with underlying malignancy, especially small cell lung
cancer
Intrafusal muscle fibres innervated by alpha motor neurons,
interneurons of anterior horn, gamma motor neurons, Renshaw cells,
granule cells Weakness may be due to muscle not in optimal position
Tends to show patchy muscle weakness, not glove and stocking loss
in the case of peripheral length dependent neuropathy
Abnormal movement - 4 categories o Automatic: learned,
conditioned, packaged algorithm o Voluntary Parakinesia:
intentional movement to hide involuntary movement Supranuclear gaze
palsy: failure of depression and elevation, but physical
manipulation allows eyes to increase range o Semi-voluntary
Tourettes syndrome: motor ticks, can be controlled, but the urge is
uncomfortable o Involuntary: unable to be controlled Benign
essential tremors: no resting tremors, no akinesia, no rigidity,
tremor of voice, intention tremors Chorea: involuntary, irregular,
purposeless, non-rhythmic, abrupt, rapid, unsustained movements
that seem to flow from one body part to another (extra-pyramidal
system) Associated with: CHOREA o Cirrhosis: Wilsons disease o
Hereditary: Huntingtons Disease, Acanthocytosis o Oestrogens:
Chorea gravidarum (in pregnancy), oral contraceptive pill (OCP) o
Rheumatic fever: Sydenhams chorea o Endocrinopathy: Diabetes
mellitus (hyperglycaemic hemi-chorea, damage to basal ganglia),
thyrotoxicosis o Autoimmune disease Athetosis: similar to chorea,
slow, writhing continuous, involuntary and fluid movements
Ballismus: violent large amplitude choreic movements of proximal
parts of limbs, causing flinging and faliling limb movements Lesion
in contralateral subthalamic nucleus and/or connections or
contralateral striatum Myoclonus: sudden, brief, shock-like
involuntary movements caused by contractions or inhibition, usually
arrhythmic, but can be rhythmical May have specific triggers
(sound, light), may be generalised or focal Causes: cortical
(myoclonic epilepsy), brainstem (hyperekplexia), spinal cord
(segmental or propriospinal myoclonus) Normal myoclonus: hypnogogic
myoclonus, in response to stimuli - Tone o Generalised dystonia
Twisted, eyes closed Abnormal tone May have blepharospasm o
Psychogenic dystonia with sensory trick o Paroxysmal dyskinesia:
various dyskinesia that occur, persist for a length of time, and
disappear - Spasticity o Advantage Helps patients to ambulate,
stand or transfer Maintains muscle bulk Prevents DVT, osteoporosis,
pressure ulcer formation over bony prominences o Disadvantage
Deformities (dislocation, contractures, or scoliosis) Impaired
activities of daily living, decreased mobility Skin breakdown,
pain/abnormal sensory feedback Poor weight gain Sleep disturbance,
depression Treatment for hyperkinetic disorders - Treat underlying
condition - Benzodiazepines - Neuroleptics - Dopamine depletors -
Surgery - Botulinum toxin Red flags - Symmetry of signs - No
tremulousness - Rapid deterioration - Autonomic symptoms
predominate - Pyramidal or cerebellar signs
-
Alien limb phenomenon Poor response to dopaminergic drugs
