Neurology Flashcards
Describe the anatomy of the cerebrum and the functions of each lobe
Left and right hemispheres separated by falx cerebri (dura mater)
- Outer grey matter: involved in processing and cognition
- Inner white matter: contains glial cells and myelinated axons connecting the grey matter
Frontal lobe: higher intellect, personality, mood, social conduct and language (dominant hemisphere)
Temporal lobe: memory and language (including hearing as this is location of primary auditory cotex)
Parietal lobes:
- Language and calculation in dominant hemisphere
- Visuospatial function in non-dominant hemisphere
Occipital lobe: consists of primary visual cortex therefore involved in vision
Where are the following areas located?
Wernicke’s area
Primary motor cortex
Primary visual cortex
Primary auditory cortex
Primary sensory cortex
Broca’s area
Wernicke’s area: temporal lobe (dominant hemisphere)
Primary motor cortex: frontal lobe
Primary visual cortex: occipital lobe
Primary auditory cortex: temporal lobe (dom hemisphere)
Primary sensory cortex: parietal lobe
Broca’s area: temporal lobe (dominant hemisphere)
What is the function of the cerebellum?
- Co-ordination
- Involved in planning movements and motor learning
- Important in visually guided movements
- Receives proprioception information therefore allows error correction
- Controlling balance
What are the different parts of the basal ganglia?
What is the funciton of the basal ganglia?
Input nuclei (receive info): caudate nucleus and putamen (neostriatum)
Intrinsic nuclei (process info): external globus pallidus, subthalamic nucleus and pars compacta of the substantia nigra
Output nuclei: internal globus pallidus
Function: provides a feedback mechanism to the cerebral cortex, modulating and refining cortical activation (preventing unwanted movements)
What are the different parts of the brainstem?
What are the functions of the brainstem?
Midbrain, Pons, Medulla
Functions:
- Controls flow of messages between brain and rest of body
- Controls basic body functions eg. swallowing, breathing, HR, BP, consciousness
Where is cerebrospinal fluid produced?
What is the function of cerebrospinal fluid?
CSF is produced in the choroid plexus of the lateral, third and fourth ventricles
- The choroid plexus is lined with cubodial epithelial cells that filter blood plasma to produce CSF
Function:
- Protection (limit neuronal damage in cranial injury)
- Bouyancy: prevents excessive pressure on the brain
- Chemical stability: allows proper functioning of the brain
Describe the flow of CSF
- CSF flows from lateral ventricles through foramen of Monro to 3rd ventricle through cerbral aquaduct to the 4th ventricle
- 4th ventricle lies between pons and medulla oblongata in the brainstem
From 4th ventricle
- Central spinal canal (bathe SC)
- Subarachnoid cisterns (between arachnoid and pia mater): here, the CSF is reabsorbed back into the circulation
Describe the visual pathway
- The contralateral visual field will project onto the temporal portion of the retina
- The ipsilateral visual field will project onto the nasal/medial portion of the retina
eg. the right visual field will project onto the temporal portion of the left retina and the nasal portion of the right retina - The optic nerve carries information from the ipsilateral eye
- At the optic chiasm, the nasal retinal fibres decussate
- The optic tract carries information from the contralateral visual field
- The optic radiations are projections from the lateral geniculate body to the primary visual cortex
Result: the visual field is represented in the cortex on the contralateral side eg. left visual field seen on the right side of the cortex
What would be the result of a lesion in the right optic nerve?
Monocular vision loss
- Lesion of the optic nerve of one eye will lead to loss of visual field of that entire eye
- The left eye will still be able to visualise the whole visual field
What would be the result of a lesion in the optic chiasm?
What is the main cause of a lesion here?
Bitemporal Hemianopia
- Loss of nasal retinal fibres of both eyes which carry the information about the temporal visual field
- Leads to the loss of temporal vision field in both eyes
Main cause: pituitary lesion
What would be the result of a lesion in the optic tract
Contralateral Homonymous Hemianopia
- Lesion in the optic tract will affect the nasal retinal fibres of the contralateral eye and the temporal retinal fibres of the ipsilateral eye
- Both of these sets of fibres carry information about the contralateral visual field
- Results in loss of the contralateral visual field in both eyes
What are the two main speech areas and where are they found?
What are their functions?
Broca’s area and Wernicke’s area
- Found in the temporal lobe on the dominant side (usually LHS)
Broca’s area: production of speech
Wernicke’s area: comprehension of speech
What would damage of Broca’s area result in?
Expressive aphasia
- Difficulty generating speech
- Will understand what’s being said but won’t be able to generate speech
What would damage of Wernicke’s area result in?
Receptive aphasia ie. difficulty understanding speech
Describe the anatomy of the spinal cord (white and grey matter)
Outer white matter (myelinated tracts that travel up and down the SC) and inner grey matter (cell bodies)
Posterior/Dorsal: sensation
- Dorsal horn contains neurons receiving somatosensory information from the body which is transmitted via ascending pathways to the brain
Anterior/Ventral: motor
- Ventral horn contains contains motor neurons that recieve information from the brain (descending tracts) and exit the spinal cord to innervate skeletal muscle
- Intermediate horn: contains neurons of the parasympathetic NS, found in cervical and sacral regions
- Lateral horn: contains neurons of the sympathetic NS, found in thoracic and lumbar regions
At which level does the spinal cord finish and what is the clincial relevance of this?
L1/L2
- At this point, it has given off all roots and produces the cauda equina
- L3/L4 is the location of a limbar puncture: to avoid SC damage
- If a patient presents with UMN signs, the lumbar spine is not involved (image more rostral (toward head)
What are the main ascending tracts in the spinal cord?
How many neurons are involved in ascending pathways?
Ascending = sensory
- Dorsal column tracts: light touch, vibration and proprioception
- Spinothalamic tracts: pain and temperature (faster conducting fibres)
3 neurons involved:
- 1: detects the stimulus and transmits information to SC
- 2: transmits info up the SC to the thalamus
- 3: from thalamus to cerebral cortex
Describe the dorsal column pathway
- Ascending tract relaying information about proprioception, light touch and vibration
1st neuron:
- Transmits tactile stimulus from skin to dorsal horn
- At the dorsal horn, the 1st order neuron bifurcates: one branch into deep dorsal horn and the other travels up the Medial Lemniscal Pathway (dorsal funiculus) of the dorsal column via the fasciculus cuneate (upper limbs) or gracile (lower limbs)
- 1st order fibres synapse at dorsal column nuclei (in brainstem): either at the Gracile or Cuneate nucleus
- These synapse with 2nd order neurons which decussate at level of medulla oblongata and travel up the medial lemniscus to terminate in the thalmus
- 3rd order fibres travel up the internal capsule to the sensory cortex
Describe the spinothalamic pathway
Sensory, ascending pathway relaying info about pain and temperature
- Nociceptive receptors (free nerve endings) detect pain/temp and relay info via 1st order neuron to the deep dorsal horn
- 2nd order neuron begins at the deep dorsal horn and decussates at the level of the spinal cord
- 2nd order fibres travel up the antero-lateral funiculus, through the brainstem to the thalamus and terminate
- 3rd order fibres travel up internal caupsule and terminate at the sensory cortex
What are the main descending tracts in the CNS?
How many neurons are involved in descending tracts?
Pyramidal: voluntary control of the musculature of the body and face
- Corticospinal tracts: supplies musculature of body
- Corticobulbar tracts: supplies musculature of the face
Extrapyramidal: involuntary and automatic control of all musculature
- Vestibulospinal: balance and posture
- Reticulospinal: medial pathway facilitates voluntary movement and increases muscle tone. the lateral pathway does the opposite
- Rubrospinal: fine control of the hand
2 neurons are involved in descending tracts
Describe the corticospinal pathway
- A descending pathway, a pyramidal tract
- Voluntary control of the body
Origin: primary motor cortex
- 1st order fibres travel down through internal capsule through the brainstem until the medulla
- At the junction of the medulla and the SC, 85% of fibres decussate to form the lateral corticospinal tract
- the remaining 15% uncrossed fibres descend as the anterior corticospinal tract
- The lateral corticospinal tract terminates on the lower motor neurons in the anterior horn of the SC
- Anterior corticospinal tract fibres decussate at the level where they synapse with LMNs (at the level of the SC)
Differentiate an upper and lower motor neuron
- an upper motor neuron (UMN) is a neuron whose cell body originates in the cerebral cortex or brainstem and terminates within the brainstem or SC
- a lower motor neuron (LMN) connects the UMN to the skeletal muscle it innervates
- The cell body is found in the brainstem or SC and the axon forms the somatic motor part of the peripheral NS
What are the signs of an UMN lesion
- Weakness
- Hypertonia (inc. tone): loss of modulatory role of UMN on muscle tone (loss of inhibition of neurons)
- Hyperreflexia
- Spacticity
- Positive Babinski’s sign ie. abnormal plantar reflex
- No wasting as muscle is still supplied
- No fasciculations as muscle still innervated
What are the signs of a LMN lesion?
- Flaccid muscle weakness or paralysis: muscle receives weak or no signal to elicit voluntary contraction
- Muscle atrophy: due to lack of support from LMN
- Hypotonia
- Hyporeflexia/Areflexia: efferent part of the reflex arc is damaged
- Fasciculations: when motor neurons are damaged, they can fire spontaneous action potentials causing contractions in the fibres of the motor unit
Describe 3 patterns of sensory loss
- Length dependent neuropathy
- Affects the longest nerves first (distal leg then distal arm)
- ‘Gloce and stocking neuropathy’ - Transverse thoracic spinal cord lesion
- Numbness affecting the trunk and below (distal SC lesion)
- No change in arms as not length dependent - Brown-Sequard
- Half lesion in the SC - loss of dorsal column function on one side and spinothalamic function on the other
What is the role of spinal reflexes?
Why do they occur?
What does it mean if there are loss of muscle reflexes?
What nerve roots are checked through spinal reflex of the knee, ankle, bicep and tricep?
How do UMN and LMN lesions affect reflexs?
Role: protective role
- A signal is sent to the SC indicating muscle stretch and the SC corrects it by telling the same muscles to contract
Loss of muscle reflexes either:
- Sensory neuropathy (loss of sensory fibres) or motor problem (inability of muscle to contract)
Knee: L3/4
Ankle: L5/S1
Bicep: C5/6
Tricep: C7
UMN lesin: hyperreflexia, LMN lesion: hyporeflexia
What nerves are in the arm and what type of innervation do they supply and to what?
Radial Nerve:
- Motor innervation: all extensors
- Sensory innervation: snuff box
Axillary nerve:
- Motor innervation: deltoid extension
- Sensory: skin covering the detoild muscle and the shoulder (regimental badge)
Median Nerve:
- Motor: forearm flexors and LOAF muscles in the hand (lateral 2 lumbricals, opponens pollicis, abductor pollicis brevis, flexor pollicis brevis
- Sensory: supplies lateral palm of the hand
Ulnar nerve:
- Motor: fine motor movements of the hand (everything except the LOAF)
- Sensation: everything except that supplied by median nerve
What nerves are in the leg and what type of innervation do they supply and to what?
Femoral nerve:
- Motor: hip flexion and knee extension
- Sensory: front of thigh
- Runs alongside femoral artery and vein
Sciatic nerve:
- Motor: hamstrings (posterior thigh muscles)
- Splits into two at the bottom of the legs:
- tibial nerve supplies calf muscles
- peroneal nerve passes neck of fibula and prone to injury. Supplies sensory innervation to front of calf and top of foot. Injury also causes foot drop
Give 3 examples of factors affecting consciousness
- Trauma - Hypoxia
- Elevated ICP - Sepsis
- Fever - Metabolic
- Hypothermia - Medications eg. sedatives
- Seizure
- Hypotension
What investigation can be used to assess consciousness?
Glasgow Coma Scale
What are the principles for assessing patients using the GCS?
Eye Opening
- Spontaneous 3. Open to verbal command
- Open to pain 1. None
Verbal Response
- Orientated - time, place, person
- Confused 3. Inappropriate
- Incomprehensible 1. None
Motor Response
- Obeys command
- Localises pain (supra-orbital press, trap squeeze)
- Normal flexion 3. Abnormal flexion
- Extension 1. None
In what situations could the eye and motor components of the GCS not be assessed?
Eye: if eyes are swollen
Motor:
- If patient has received muscle relaxants
- Difficult to assess after trauma (eg. if potential SC injury, could be paralysed/don’t want to move patient)
NB want to give the patient the best score possible because it’s related to prognosis eg. if one arm flexes and one extends, give a 3 for motor
How would a coma be determined with GCS?
- GCS of 3
ie. inability to obey command, open eyes to pain or speak
How is a head injury classified using the GCS?
Minor head injury: GCS 14-15
Moderate: 9-13
Severe: <8
List the cranial nerves
CN I - Olfactory
CN II - Optic
CN III - Occulomotor
CN IV - Trochlear
CN V - Trigeminal (3 branches)
CN VI - Abducens
CN VII - Facial
CN VIII - Vestibulocochlear
CN IX - Glossopharyngeal
CN X - Vagus
CN XI - Accessory
CN XII - Hypoglossal
Which cranial nerves have sensory or motor (or both) functions?
Sensory - CN I, II, VIII
Motor - CN III, IV, VI, XI, XII
Both - V, VII, IX, X
What is the function of the olfactory nerve?
What tract does this nerve run in?
What situations would cause lose in function?
- Sensory
Function: smell (associated with taste)
Tract: olfactory cells of nasal mucosa → Olfactory bulbs → Pyriform cortex
Loss of function with altered CN I
- Alzheimer’s and Parkinson’s: lost or reduced sense of smell
- Traumatic brain injury: sheers the olfactory nerve
- If lost slowly it’s hard to pick up
What is the function of CN II?
What is the pathway for imformation with this nerve?
How do you examine CN II?
- Optic nerve, sensory function
Function: vision
Pathway: retinal ganglion cells → optic chiasm → thamalus → primary visual cortex in the occipital lobe
Examination: AFRO
- (visual) Acuity: snellen chart
- (visual) Fields: confrontation and compare to own visual field
- Reflexes: direct and indirect (shine light into one pupil - that pupil should constrict (direct) as should the other pupil (indirect))
- Opthalmoscope (optic discs): swollen/blurry edges indicates papilloedema caused by raised ICP
- Additional: blind spot and colour blindness
What is the function of CN III?
What structures are innervated?
What would damage of this nerve cause?
- Oculomotor nerve, motor function
Component 1: Motor
- Function: Movement of the eyeball and lens accomodation
- Structures: inferior oblique, superior, medial and inferior recti muscles, levator papebrae superioris
Component 2: Parasymathetic
- Function: pupil constriction
- Structures: ciliary muscle and pupillary constrictor muscles
CN III palsy: eye looks down and out, ptosis of eyelid, dilated pupil
What is the function of CN IV?
What structures are innervated?
Where is the nucleus located?
Describe the syndrome where there is damage to this nerve
- Trochlear nerve, motor component
Function: depresses the adducted eye and intorts the abducted eye
- Contralateral (decussates)
Structures: superior oblique muscles
Nucleus: midbrain
Palsy: difficulty looking down and will experience double vision when looking down eg. when reading
Which cranial nerve decussate to the contralateral side?
CN II (Optic) and CN IV (trochlear)
What is the function of CN VI?
What structures does it innervate?
Where is the nucleus located?
- Abducens nerve, motor component
Function: abducts the eye in the horizontal plane (eyeball movement)
Structures: lateral recti muscles
Nucleus: Pons
What occurs with palsy of the CN VI?
What can cause CN VI palsy?
- Failure of abduction
- See two images side by side: horizontal diplopia
- Can be a sign of raised ICP (due to long intracranial course)
Describe internuclear ophthalmoplegia
What condition is the commonly seen in?
Disorder of conjugate gaze (ie. eyes moving in unison)
- Failure of adduction of the affected eye with nystagmus on lateral gaze in the contralateral eye
- Difficulty looking to one side
- Can be unilateral or bilateral
Results from lesion of the medial longitudinal fasciculus (connects CN III and IV nuclei)
- Commonly seen in MS
What is Horner’s Syndrome?
List 3 potential causes
- A clinical sign resulting from ipsilateral disruption of cervical/thoracic sympathetic chain
Consists of:
- myosis, ptosis, apparent enophthalmos and anhidrosis
Potential causes:
- Congenital, brainstem stroke, cluster headache
- Apical lung tumour (Pancoast tumour), MS
- Carotid artery dissection, syringomyelia
What are the divisions of CN V?
What is the function of CN V?
What structures does it innervate?
Trigeminal nerve, sensory and motor components
Divisions:
- Ophthalmic (V1), Maxillary (V2), Mandibular (V3)
Sensory component
- Sensory input from face (ophthalmic, maxillary and mandibular components) and anterior 2/3 of tongue
- Nucleus in pons and medulla
Motor component
- Function: mastication
- Structures: masseter, temporalis, medial and lateral pterygoids
- Nucleus in pons
What viral disease can affect CN V and how is it treated?
Herpes Zoster Ophthalmicus aka shinges
- Viral disease characterised by unilateral, painful rash on one or more dermatome distributions of CN V (usually ophthalmic division)
- High risk: elderly and immunocompromised
- Treated with oral aciclovir
What is the class, action and indication of acyclovir?
Class: Anti-viral
Indication: Herpes simplex virus and Varicella zoster virus
Action:
- A guanosine derivative, converted to triphosphate by infected host cells
- Acyclovir triphosphate inhibits DNA polymerase, terminating the nucleotide chain and inhibiting viral DNA replication
What is the function of CN VI and what structures does it innervate?
- Facial nerve, sensory and motor components
Motor component
- Function: muscles of facial expression
Sensory component
- Function: taste
- Structures: anterior 2/3rd of tongue
Parasympathetic component
- Function: salivation and lacrimation
Structures: Salivary and lacrimal glands
Describe what would be seen with UMN and LMN facial weakness
UMN: weakness of inferior facial muscles, no weakness of eye closer
LMN: weakness of superior and inferior facial muscles
What cranial nerves does the corneal reflex test?
- Assess CV V and VII nerve reflexes
Lightly touch cornea with cotton wool:
- Afferent: V
- Efferent: VII
Should get bilateral blinking response
What is the function of CN VIII?
What structures are innervated?
Vestibulocochlear, sensory component
Vestibular component
- Function: balance
- Structures: nerve endings within the semi-circular canals → cerebellum and spinal cord
Cochlear component
- Function: hearing
- Structures: cochlear → auditory cortex in the temporal lobes
What cranial nerves are involved in bulbar function?
What is bulbar function?
- CN IX (glossopharyngeal), X (vagus), XI (Accessory), XII (hypoglossal)
Function: speech and swallowing
What is the function of CN IX?
What structures are innervated?
Glossopharyngeal nerve, sensory and motor components
Sensory component
- Function: Taste, proprioception for swallowing, BP receptors
- Structures: posterior 1/3rd of tongue, pharyngeal wall. carotid sinuses
Motor component
- Function: swallow and gag reflex, lacrimation
- Structures: pharyngeal muscles, lacrimal glands
Parasympathetic component
- Function: saliva production
- Parotid glands
What occurs in CN IX palsy?
Soft palate on side of lesion will not elevare
- Deviation of uvula away from side of the lesion
What is the function of CN X?
what structures are innervated?
Sensory component
- Function: chemoreceptors, pain receptors, sensation
- Structures: blood oxygen conc, carotid bodies, resp and GI tratcs, external ear, larynx and pharynx
Motor component
- Function: HR and stroke volume, peristalsis, air flow, speech and swallowing
- Structures innervated: pacemaker and ventricular muscles, SM of GI tract, SM of broncial tubes and muscles of larynx and pharynx
Parasympathetic function
- Strutures: smooth muscles and glands innervated by same areas as motor component as well as thoracic and abdominal areas
What is the function of CN XI?
What structures does it innervate?
Spinal accessory nerve, motor component
- Function: head rotation and shoulder shruging
- Structures: sternocleidomastoid and trapezius muscles
What is the function of CN XII and what structures odes it innervate?
CN XII: hypoglossal
- Function: speech and swallowing
- Structures: tongue
How would lesions of CN XII present?
- Tongue deviates toward side of lesion
- Wasting and fasciculations of tongue: LMN lesion
Define the action potential
- Explain how changes in ions causes an action potential
= Chemical change into electrical change to cause action in the muscle
- Resting potential of neuon: -70mV
- Depolarisation is caused by Na (sodium) ion influx
- Repolarisation is caused by K (potassium) eflux
- Too much K is released so get hyperpolarisation which then normalises to end at the resting potential
- This electrical change is propagated down the nerve to cause action in the muscle or to send information to the brain
Define a seizure
A sustained and synchronised electrical discharge in the brain causing symptoms or signs (that can be elicited/seen/observed)
ie. bursy of electrical activity in the brain that is sustained and prolonged
Define epilepsy
A tendency to have recurrent unprovoked seizures
What can cause seizures?
- Anything disrupting brain function
Provoked seizures:
- Disturbances in electrolytes, bleeding, scarring, alcohol withdrawal
Seizures are rarely triggered but sometimes can be associated with:
- Stress, fatigue, alcohol, not taking medication
Describe the mechanisms involved in seizures
- Spread of electrical activity between cortical neurons is normally restricted and synchronous dischange takes place in small groups only
- During a seizure, large groups of neurons are activated repetitively and hypersynchronously
- Failure of inhibitory synaptic contact between neurons
- A change in Ca or K causes a shift of electrical activity, predisposing the neuron to fire off (hyperpolarisation)
- Brain senses high freq firing off and floods area with inhibitory neurotransmitters to dampen the bursts
- Causes high voltage, spike-and-wave activity on the EEG (electrophysiological hallmark of epilepsy)
What are the inhibitory and excitatory neurotransmitters and what do they cause?
Inhibitory neurotransmitters: GABA and glycine
- Action on GABA receptors
- Causes Cl- influx
Excitatory neurotransmitters: glutamate
- Acts on NMDA/AMPA/Glutamate receptors
- Causes Na+/Ca2+ influx
Clinically, how does a seizure progress?
- Tonic phase (generalised increase in muscle tone) due to high frequency discharge
- When inhibitory neurot. take effect, they cause intermittent neuron activity (brief periods of depolarisation followed by hyperpolarisation): clonic phase (jerking)
- Generalised tonic-clonic seizure aka bilaterally convulsive
What are the 2 main types of seizures?
- Generalised tonic-clonic seizures (bilaterally convulsive)
- Partial seizures: seizure activity is confined to one area of the cortex, which can either remain focal or spread to generate activity in both hemispheres
What are the classifications of epilepsy?
- Focal/Localised
- Partial: area of abnormality in an otherwsie normal brain eg. scarring after head injury, abscess, stroke
- Generalised
List 3 precipitating factors in epilepsy
- Genetic predisposition
- Trauma and surgery: scarring
- Intracranial mass lesions
- Cerebral infarct
- Photosensitivity
- Drugs: alcohol and alcohol withdrawal
- Stroke
Describe the pathophysiology of partial epilepsy
- Seizure starts in a particular area that can remain focal or spread
- Area of abnormality causes irritation and the discharge could stay local, spread slighly or spread across the whole brain, causing a bilaterally consulsive seizure
- Partial epilepsy can therefore cause a generalised seizure (spread from single focus): secondary generalisation of the partial seizure
Diagnostically, how can a partial seizure be determined?
- If discharge is restricted to an area, signs or symptoms will also be resitricted to that area of the brain
eg. jerking of the left arm indicates lesion in the right motor strip, or blobs of colour seen in the left visual field indicate lesion in the right occipital lobe
If there is a focal lesion: positive neurological symptoms at onset
- Positive motor phenomenon: twitch/jerk/spasm
- Positive sensory phenomenon: burning/tingling
- Positive visual: shapes, blobs, recognised memory
Describe what happens in generalised epilepsy
- If the brain has a genetically driven change in balance of neurotransmitters / how receptors respond to neurotransmitters / pharmacology etc.
- Brain fires off all at once in generalised onset without warning (arises so quickly)
What are you looking for when taking a history from a patient who had a seizure?
Patient:
- presenting complaint
- past medical history (is it provoked - alcohol withdrawal)
- predisposing factors to epilepsy?
- Eye witnesses eg. if unconscious
What ivnestigations can be done for a patient who has had a seizure?
Imaging: CT or MRI (picks up more cortical abnormalities than CT)
EEG (Electroencephalography)
- Can be abnormal in epilepsy
- Can identify characteristic brain changes
- Can help classify if generalised or focal
What is the risk of recurrance after a patient has had 1 seizure?
Risk of 2nd seizure is 40%
Recurrance with abnormal EEG/scan/big RF in family history: 60%
Normal EEG/scans/no RFs: 20%
If two seizures: recurrance is 60%
What is status epilepticus?
What can cause it?
Status epilepticus is when a seizure persists for longer than 5 minutes
- Can be caused if tablets were vomited up, forgot to take tablets or the patient has an infection
What is the treatment for status epilepticus?
Medical emergency
- Two courses of benzodiazepine
- If this doesn’t work, give IV anti-epileptic drugs followed by anaethesia
At what stage is epileptic treatment started?
If recurrance risk is equal to or > 60% ie. has had 2+ seizures or 1 seizure and abnormal scans/EEG/RF in family history
What medication is suggested for the following types of epilepsy:
Focal
Generalised
Focal: lamotrigine, carbamazepine (older), levetiracetam (new)
Generalised: sodium valporate, levetiracetam, lamotrigine
What epileptic medication is not advised for young females?
Sodium valporate
- Only give if necessary; causes problems with growth of foetus, IQ, increases risk of malformation)
What is the treatment for epilepsy?
Medical:
Focal: lamotrigine, levetiracetam, carbamazepine
Generalised: lamotrigine, levetiracetam, sodium valporate
- epilepsy responds well to treatment: 70% sympton free after 1st/2nd drug
If drugs dont work:
- Minimise seizure severity and danger of seizures
- Minimise neurological side effects
Surgery:
- Single lesion, where lesion can be reached and removal without causing neurological deficit
What is the class, indication, action and side effects of carbamazepine
Class: anti-eptileptic drug
Indication: (focal) epilepsy and neuropathic pain
Action:
- Voltage gated Na channel antagonist on pre-synpatic membrane
- Reduces pre-synaptic excitability
- Blocks Na influx, reduces neuronal excitability and decreases the action potential
Side Effects:
- dizziness, dry mouth, ataxia
What is the class, indication, action and side effects of Lamotrigine?
Class: anti-epileptic
Indication: epilepsy and despressive episodes in bipolar disorder
Action:
- Inhibits voltage-gated sodium channels or calcium channels (voltage gated sodium channel antagonist)
- Acts on presynaptic neuronal membrane
- Reduces presynaptic excitability
- Reduces both neuronal excitability and action potential
Side Effects:
- nausea, vomiting diarrhoea
What is the class, indication, action and side effects of levetiracetam?
Class: anti-epileptic
Indication: epilepsy
Action:
- Is a SV2A vesicle antagonist
- SV2A is a vesicle protein needed for neurotransmitter release
- Inhibits neurotransmitter release
SE: headache, fatigue, anxiety
What is the class, indication, action and side effects of Sodium Valporate
Class: anti-epileptic
Indication: epilepsy, bipolar disorder and depression
Action:
- GABA metabolism inhibitor
- Inhibits GABA degrading enzymes
- Increased GABA (inhibitory neurotransmitter) dampens the AP
SE:
- confusion, behavioural disturbances, GI side effects
- avoid if possible in young women (problems with developing foetus)
What is the class, indication, action and side effect of diazepam?
Class: benzodiazepine
Indications: status epilepticus, anxiety, alcohol withdrawal, muscle spasm
Action:
- GABA receptor agonist
- Increases GABA affinity for the GABA receptor
- GABA binding to receptor increases chloride flow through chloride channels
- Causes hyperpolarisation
Side Effects:
- insomnia, sedation, ataxia
What is the class, indication, action and side effect of phenytoin?
Class: anti-epileptic
Indication: epilepsy and trigeminal neuralgia
Action:
- Acts as a voltage-gated Na sodium channel blocker on pre-synaptic neuronal membrane
- Limits AP transmission therefore limiting spread of seizure activity
Side Effects:
- insomnia, headache, rash
Define a subarachnoid haemorrhage
A bleeding into the subarachnoid space, the space between the arachnoid and pia mater
What is the most common cause of a subarachnoid haemorrhage?
Trauma
What is the most common cause of a spontaneous subarachnoid haemorrhage (SAH)?
Aneurysm (localised dilatation of an artery)
What are the predisposing factors to a subarachnoid haemorrhage (SAH)?
- Smoking
- Female
- HTN
- Positive family history
- ADPCK (autosomal dominant polycystic kidney disease)
- Coarctation of the aorta
What is the clinical presentation of a subarachnoid haemorrhage?
- Thunderclap headache (sudden onset headache, peaks within sec-mins)
- Syncope/Collapse, seizures
- Visual, speech and limb disturbances eg. difficulty speaking, using RHS of body (helps determining localisation of the aneurysm)
- Nausea, vomiting
- Sentinel headache (preceeds by days/weeks)
Define syncope
Temporary loss of consciousness usually related to insufficient blood flow to the brain aka fainting
What would be the clinical examination findings for a patient with a SAH?
- Photophobia
- Meningism: clinical syndrome of headache, neck stiffness and photophobia
- Neck stiffness
- Visual problems: serious
- Raised ICP: can cause double vision from CN VI/III palsy
- Speech and limb disturbances
- CV problems
- Pulmonary oedema
Describe the pathophysiology of a SAH caused by an aneurysm
- Haemodynamic stress: aneurysms form at branch points of arteries where there is maximum haemodynamic stress
- Extensive inflammation and immunological reactions occur with unruptured intracranial aneurysms and may be related to aneurysm formation and rupture
- Inflammation causes dilatation of the blood vessel and repair processes hold the aneurysm in check
- If repair processes are overwhelmed: rupture
Intracranial blood vessels lie in the subarachnoid spaceses, so aneurysms form here and rupture to produce a SAH
- If aneurysm is near pia mater, it can break through causing parenchymal haemorrhage
- If it ruptures through arachnoid mater, subdural haemorrhage
What are 2 non-aneurysmal causes of SAH (not trauma)?
- Some tumours can bleed
- Arteriovenous malformation (AVM): an abnormal connection between artery and vein ie acts as a shortcut. This induces haemodynamic stress on vessels supplying brain due to lack of capillaries
How is the prognosis for a subarachnoid haemorrhage determined?
GCS and WFNS
- Low GCS/High WFNS = poorer prognosis
WFNS Grade I-V
GCS 15: Grade I
GCS 13-14 without deficit: Grade II
GCS 13-14 with deficit: Grade III
GCS 7-12: Grade IV
GCS 3-6: Grade V
Fisher Grade (using CT)
- Classification of thickness of blood in basal system
- Thicker blood: more complicated
What are the investigations for a SAH?
CT
- Confirms diagnosis and gives clues to aetiology
- Can also diagnose complications eg. infarction, haematoma, hydrocephalus
- First investigation of choice
Lumbar Puncture
- Assessing CSF for presense of RBC
- Strong clinical suggestion of SAH but most sensitive after 12 hours after symptom onset (can be negative within 2 hours of onset)
- Xanthochromia: yellowing of CSF due to RBC breakdown ie. bilirubin
CT angiography
DSA (Digital Subtraction Angiogram)
- Not first line but gold standard
- Cannulate femoral artery and pass catheter up to take images of blood vessels
Common findings: hyponatraemia and elevated troponin
What resusitation is needed for a patient following a SAH?
- Bed rest
- Fluids: 2-3l normal saline
- Anti-embolic stokcings
- Nimodipine: Ca channel antagonist
- Analgesics
What is the management for a SAH?
Aim: to prevent the biggest complication (re-haemorrhage)
Surgical clipping
- Used to exclude aneurysm from circulation
- Difficult with an acute SAH in first 24-48hours: brain is swollen, some hydrocephalus and touching the brain
Endovascular
- Stents, coils, glue
Conservative management
Outline 3 complications of subarachnoid haemorrhages
Re-haemorrhage
- Biggest complication, more common in poor grade patients
- Immediate repair of aneurysm reduces rebleeding risk
Hydrocephalus
- Imbalance of CSF within the ventricular system caused by overproduction or underdrainage
- Obstruction due to clots/underdrainage due to inflam changes
- May need LP or shunt
Delayed ischaemia (day 3-10)
- The blood from ruptured aneurysm can induce changes in microcirculation and induce spasms causing microcirulation to shut down
- This leads to new neurological deficit and progressive deterioration in level of consciousness
- Management: fluid, nimodipine
Hyponatraemia
- Causes cerebral oedema and raised ICP
Cardiopulmonary complications
- Symp. stimulation and catecholamine release can lead to myocardial injury, elevated troponin in 35%
Seizures (usually due to rerupture)
DVT
Differentiate between primary and secondary headache syndromes and list the types of each
Primary: headache is the diagnosis
- Migraine
- Trigeminal Autonomic Cephalgias eg. cluster hedache
Secondary: headache is caused by another pathology
- Thunderclap headache
- High-pressure headache
- Low-pressure headache
- the neuralgias
What is one of most important aspects for investigating a PC of headache?
What features are important?
History
- Personal history of migraine or tendency (previous migraines, perimenstrual headache, undeserved hangovers)
- How many headache types does the patient experience?
For each headache type:
- Age of onset
- Define pattern: chronic headache (>15 headache days per month)/ episodic / new type
- Onset (time to peak) and progression (peak within 1 minute unlikely to be migraine)
- Location, character, intensity
- Precipitating/Exacerbating factors (feautires of high/low pressure headaches): precipitated by poor sleep, high pressire worse when coughing/bending over, migraine relieved by a dark room
- What patient does during attack: going to bed/quiet room likely to be migraine, will not sleep, pace and hit head against wall likely to be a cluster headache)
Remember to do PMH, DH, SH (skipping meals exacerbates migraines), FM
What is the aim of investigations with a headache and list 3 investigations that may be carried out
Investigations are carried out to exclude secondary causes (no value for migraine)
- Blood pressure
- ECG, urinalysis
- Bloods eg. ESR, CRP, FBC
- brain CT/MRI: in case of stroke
- lumbar puncture: to exclude haemorrhage
- CT/MRI angiogram/venogram
What features would indicate the need for imaging with a PC of headache?
RED FLAGS
SSSNOOPPP / CSF
- Systemic symptoms
- Secondary RFs
- Seizures
- Neurological symptoms (weakness, double vision, nerve palsies)
- Older
- Onset
- Papilloedema
- Progression (inc. attack frequency, change in nature)
- Precipitated by cough, exertion, sleep
- Change in nature of headache (or new headache)
- Systemic symptoms/signs
- Focal neurological deficit
What is a tension-type headache
List it’s diagnostic criteria
= doesn’t bother patient, tight band around the front that’s been present for years and has no associated symptoms
- Usually re-diagnosed as migraine
Diagnostic criteria:
- At least 10 episodes of headache occuring <1 day/month on average (<12 days/year) and fulfilling the other criteria
- Lasting 30mins-7days
- At least two of: bilteral location, pressing or tightening, not aggrevated by routine physical activity
- Both of: no nausea of vomiting, no more than one of photophobia or phonophobia (dislike of loud sounds)
Describe the pathophysiology of migraines
Primary headache
- complex interaction between primary afferent nociceptive neurons, trigeminovascular system, brainstem, thalmus, hypothalmus, cortex
- it’s a brain disorder
- Calcitonin Gene Related Peptide (CGRP) has a role
Outline the phases of a migraine
Prodrome
- lasts hours-days
- Yawning, depression, polyuria, irritability, sensitive to light and sound, poor sleep, food cravings
Aura
- lasts 5-60mins ie. transient
- visual (99%) > sensory > language > motor
- Evolves
- Positive and negative elements eg. visual: flashing lights (positive) or holes in vision (negative)
- Fully reversible
- Persistent aura symptoms over may hours may indicate stroke
Headache
- lasts 4-72hours
- Throbbing headache
- Nausea and/or vomiting
- Photophobia and phonophobia
- Worse with activity
Postdrome
- 24-48hours
- May get depression/poor conc/fatigue whereas some get a high after (euphoria)
Outline the ICHD-3 diagnosis for migraines
At least 5 attacks fulfilling the following:
- attacks last 4-72 hours (when untreated)
- headache has at least two of the following: unilateral location, pulsating quality, moderate/severe pain intensity, aggrevation by/causing avoidance of routine physical activity eg. walking, climbing stairs
- At least one or both of the following during a headache: nausea and/or vomiting, photophobia and phonophobia
If someone presents to A&E with their first headache, cannot diagnose migraine and need to consider secondary causes as there is no history of migraines to base diagnosis on
- Can be chronic (>15/month) or episodic (<15/month)
Outline the acute treatment for migraines
- No opiates: exacerbate headache
- SImple analgesics: high-dose aspirin or ibuprofen (restrict to two days a week)
- Triptans: start with sumatriptan. All triptans are absorbed in GI tract so not useful if patient is vomiting. Should start working after 3rd migraine and be pain free after 2hours. Only work once headache starts
Early or persistant vomiting:
- Add anti-emetic eg. metroclopramide
If there’s no response to initial treatment:
- Try other triptans
- Try triptan and NSAID combination
Outline the prophylactic therapy for migraines
Lifestyle:
- trigger avoidance: migraines don’t like regularity so go to sleep and wake up at the same time, don’t sleep meals
- identify and treat medication overuse: address opiate use, NSAIDs and ibuprofen
- use headache diaries
Medication:
- consider if migraine is disabling and reducing QoL eg. frequent attacks >1/week or prolonged/severe
- Can try: propanolol, antitriptyline, candesartan
- For each medication, determine efficacy at 3 months, want a 30-50% reduction in frequency and severity
What is the clinical presentation of a cluster headache
Primary headache, one of the three trigeminal autonomic cephalgias
- Usually affect men > women
- comes in bouts, often at the same time of year
- Lasts several weeks-months
- freq. ranging from alternate days to 8 times a day lasting between 15min - 3hrs
AKA suicide headache
- unilateral, short-lasting, associated with autonomic signs
- orbital, supra-orbital and/or temporal pain
- restless, agitated
Outline the diagnostic criteria for a cluster headache
At least 5 attack fulfilling the following:
Severe/very severe unilateral orbital, supraorbital and/or temporal pain lasting 15min-3hours (untreated)
Occuring with a frequency btn one every other day to 8/day
Either or both of the following:
- A sense of restlessness or agitation
- At least 1 of the following ipsilateral to the headache: conjunctival lacrimation, nasal conjestion and/or rhinorrhoea, eyelid oedema, forehead and facial sweating, forehoead and facial flushing, sensation of fullness in the eye, miosis and/or ptosis
Outline the history seen with a raised pressure headache
- worse lying flat, improves with sitting/standing
- worse in the morning (lying all night)
- persistent nausea/vomiting
- worse on Valsalva (coughing, laughing, straining)
- worse with physical exertion
- transient visual obstruction which change in posture: vision disappears when bending down and straightening up
- some overlap with migraine findings
List 3 examination findings that may be seen with a raised pressure headache
- optic disc swelling (papilloedema)
- impaired visual acuity / colour vision
- restricted visual fields and enlarged blind spot
- 3rd nerve palsy
- 6th nerve palsy (false localising sign)
- Focal neurological sins
Outline the clinical presentation of a thunderclap headache
- marker of a secondary headache
- ‘first and worst headache’
- sudden onset with peak within 1-5minutes
- severe headache
- typical duration >1hr
List 3 causes of a thunderclap headache
- suarachnoid haemorrhage
- intracerebral haemorrhage
- arterial dissection
- cerebral venous sinus thrombosis (brain equivalent of a DVT)
- ischaemic stroke
- bacterial meningitis
- spontaneous intracranial hypotension
How do you investigate a thunderclap headache?
- treat as a medical emergency
- non-contrast CT within 12hr of onset
- if normal CT, do a LP (looking for blood breakdown products seen with a subarachnoid haemorrhage)
- If normal CT and LP, consider: MRI, MRI/CT angiogram, MRI/CT venogram looking for cerebral venous sinus thrombosis
Outline the clinical features of a low pressure headache
What is the pathophysiology of a low pressure headache?
- worse on sitting/standing up
- relieved by lying down (opposite to high pressure)
Patho: results from CSF leakage
- loss fo CSF volume causes traction on the meninges, cerebral/cerebellar beins and CN V, IX and X
List 2 causes of a low pressure headache
- Post-lumbar puncture, most resolve spontaneously
- Spontaneous intracranial hypotension, results from spontaneous dural tear and can occur following Valsalva
Define a stroke
The sudden death of brain cells due to lack of oxygen, caused by sudden blockage of blood flow or rupture of an artery to the brain
List 3 risk factors for the development of a stroke
- Hypertension
- Atrial fibrillation: abnormal atria, blood becomes stagnant and clots, of which bits can break off and travel to the brain
- Diabetes
- Smoking
- Hypercholesterolaemia and poor diet
- Excess alcohol consumption
What are the three main causes of stroke?
- clot occluding the artery (ischaemic stroke)
- intracranial haemorrhage (bleeding into the brain)
- subarachnoid haemorrhage (bleeding around the brain)
Outline the blood supply to the brain
Two paired arteries that supply blood: vertebral arteries and internal carotid arteries
Each internal carotid artery gives rise to:
- posterior communitcating artery
- anterior cerebral artery
- they then continue as the middle cerebral artery
Each vertebral artery gives rise to:
- anterior and posterior spinal arteries
- posterior inferior cerebellar arteries
- posterior cerebral arteries (terminal branches of the vertebral arteries
- the two vertebral arteries then converge to form the basilar artery
Arterial Circle of Willis
- Three main constituents: anterior cerebral arteries, internal carotid arteries (continue as middle cerebral), posterior cerebral arteries
Anterior cerebral arteries: anteromedial portion of the cerebrum
Middle cerebral arteries: lateral portion of the brain
Posterior cerebral arteries: medial and lateral portions of the posterior cerebrum
How do you determine what vessel has been affected?
Large vessel ie. ACA, MCA, PCA
- cortical signs (dep. on side of damage)
- involves cortex of brain
Small vessel
- no cortical signs
Posterior circulation
- crossed signs and cranial nerve findings
Compare the cortical signs seen with a stroke on the right and left
Right:
- Right gaze preference: tend toward side of stroke if hemispheric insult (LHS will cease to exist so eyes tend right)
- Neglect: Loss of one side of your sensorium ie. whole left side ceases to exist, loss of response to any stimulation from LHS (someone standing on your left asking you a question)
- Inattention: milder form of neglect, preferential attention ot the unaffected side
Left:
- Left gase preference
- Neglect/inattention to RHS
- Aphasia: Brocca’s area and Wernicke’s area tend to be on the left
Outline the clinical features seen with a stroke due to abnormality of the middle cerebral artery
Supplies the lateral cortex
- arm > leg weakness
LHS:
- speech centres and motor strip
- Aphasia and lose ability to move the right side
RHS:
- neglect, inattention, won’t be able to move LHS
- disorientation, apraxia, constructional impairment (inability to assemble/draw objects)
Outline the clincial features seen with a stroke due to an abnormality of the anterior cerebral artery
Frontal lobe infarct
- leg > arm weakness (leg represented closer to the midline of the motor homunculus), grasp
- isolated leg weakness
- cognitive: mute, perservation (repetation of a word, phrase), absence of willpower, personality changes
Outline the clinical features seen with a stroke due to an abnormality of the posterior cerebral artery
- Hemianopia (blindness over half the field of vision)
- Cognitive: memory loss/confusion, alexia (inability to recognise written words/letters)
Outline the pathology of expressive aphasia
aka Brocca’s aphasia
- Brocca’s area: the area involved with speech production
- aphasia: can comprehend speech but cannot produce speech ie. non-fluent speech
- very frustrating
- close to the motor strip therefore usually accompanied by right sided weakness
Outline the pathology of receptive aphasia
aka Wernicke’s aphasia
- Wernicke’s area: involved in speech comprehension and checks what the person themselves are saying to make sure it’s right
- aphasia: fluent speech (can produce words but nonsense) but can’t comprehend speech
- no weakness (not near motor strip)
What is global aphasia?
both receptive and expressive aphasia ie. occurs in a big stroke
List 3 risk factors for a small vessel stroke
What are the main types of small vessel strokes?
RFs:
- hypertension
- hyperlipidaemia
- diabetes
- tobacco use
- sleep apnoea
Main types:
- pure motor symptoms
- pure sensory
- sensorimotor
Outline the range of clinical presentations that can be seen with a brainstem stroke
usually a combination of cranial nerve abnormalities and crossed motor/sensory findings
- double vision
- facial numbness and/or weakness
- slurred speech
- difficulty swallowing
- ataxia
- vertigo
- nausea and vomiting
- hoarseness
List 3 causes of a intracranial haemorrhage
- untreated HTN
- aneurysm
- bleeding into a tumour
- anticoaguable state
- trauma
- AV malformation
How does hypertension cause an intracranial haemorrhage and how would it present?
- spontaneous rupture of a small artery deep in the cortex
Typical sites:
- cerebellum, basal gangila, pons
Typical presentation:
- typically awake and stressed
- then abrupt onset of symptoms with acute decompensation and smooth progression
- rapid progression within first few minutes
How would a cerebellar and pontine haemorrhage present?
Cerebellar:
- vomiting, ataxia
- eye deviation away from side of bleed
- small, sluggish pupils
Pontine:
- very bad
- pinpoint but reactive pupils
- abrupt onset of coma
- ataxic breathing pattern
How are strokes diagnosed?
CT
- non-contrast most widely used (cheap, quick, availability)
- can see intracranial haemorrhages (bleeding seen immediately)
- with contrast may help identify aneurysms, AV malformations
- less sensitive for early phases in infarct: CT shows bruising, and the brain doesn’t bruise/swell immediately with infarct
- Acute (4hr) infarction not seen on CT but subacute (4 days) can be seen
MRI
- More sensitive for early phases of infarct
- superior for showing underlying structural lesions
How are ischaemic strokes managed?
IV recombinant tissue plasminogen activator (tPA): gold standard
- catalyses the convertion of plasminogen to plasmin, which promotes fibrin clot lysis
dissolves the blood clot and restores blood flow to the cerebrum, while reducing injury to the brain
- IV tPA window: 4.5hours from beginning of stroke
Mechanical retrieval
- often used in adjunct with tPA
- feed catheter into brain and physically remove the clot
Blood thinning:
- high risk of TIA or ischaemic stroke: dual antiplatleet therapy
- low risk: aspirin until discharge then clopidogrel
- with AF: NOAC or warfarin
BP management if systolic BP >150
Glucose management
What is the class, indication and action of alteplase?
Class: recombinant tissue plasminogen activator (rtPA)
Indications:
- Acute ischaemic stroke within 4.5hours of onset
- MI within 12hours of onset
- Massive pulmonary embolism
Action:
- Catalyses the conversion of plasminogen to plasmin
- promotes fibrin clot lysis
Define multiple sclerosis (MS)
An inflammatory demyelinating disease of the CNS resulting in loss of neurological function
- Disruption of the myelin of spinal nerve and brain cells
List 3 potential causes of multiple sclerosis
- Genetic factors
- Lack of sunlight / Vit D exposure
- Viral trigger
- Multifactorial (overweight btn 14-18, smoking w/ genetic risk, male w/ genetic risk)
Outline 3 syndromes that may develop into multiple sclerosis
Optic Neuritis
- Inflammation of the optic nerve damaging myelin
- Desaturation of red colours and blurry image
- Painful visual loss that comes on over a few days
- May resolve after a few weeks
- 50% develop MS by 15 years (risk dependent on MRI and presence of oligoclonal bands)
Transverse Myelitis
- Inflammation of the spinal cord
- weakness and difficulty walking and difficulty swinging arms
- Sensory loss
- Incontinence
Clinical Isolated Syndromes
- episode of neurological disability due to focal CNS inflammation
- single MS attack
- can include optic neuritis and transverse myelitis
- if oligoclonal bands are present: just call it MS
- may not necessarily be related to MS eg. due to infection
Radiologically Isolated Syndromes
- incidental finding but no MS symptoms
- can cause unnecessary stress
Define the clinical subtypes of multiple sclerosis
Relapsing remitting (70%)
- unpredictable attacks which may or may not leave permanent deficits followed by periods of remission
- if left untreated: will stop having attacks, will become continuous and become more disabled
Primary progressive
- Steady increase in disability without attacks
Secondary progressive
- initially relapsing-remitting MS that suddenly begins to decline without periods of remission
Progressive relapsing
- Steady decline since onset with super-imposed attacks
Outline the range of clinical presentations seen with multiple sclerosis
These deficits develop gradually, last 24 hours and may gradually improve over days-weeks
Central:
- fatigue, cognitive impairment, depression, unstable mood
Visual:
- nystagmus (repetitive, uncontrolled eye movements)
- optic neuritis, diplopia (double vision)
Speech: dysarthria (slow, slurred speech)
Throat: dysphagia (difficulty swallowing)
MSK:
- weakness, spasms, ataxia
Sensation:
- pain, hypoethesias (reduced sense of touch), paraesthesia (abnormal sensations eg. tingling)
Bowel:
- incontinence, diarrhoea or constipation
Urinary:
- incontinence, frequency or retention
What features in a patient’s history would indicate MS?
- neurological symptoms that develop over a few days
- symptoms last for 24hours
- a history of transient neurological symptoms that have lasted for >24 hours and spontaneously resolved
- hidden relapses (need to ask specifically): optic neuritis, transverse myelitis, bladder symptoms
What features in a patient’s history would exlcude a diagnosis of MS?
- sudden onset
- peripheral signs eg. glove and stocking distribution, fasciculations, muscle wasting
- major cognitive involvement early on
- reduced level of consciousness
- prominent seizures
- pyrexia/evidence of infection
- normal MRI
How do you diagnose multiple sclerosis?
Need evidence of 2 or more episodes of demyelination disseminated in space and time
- Space: two different areas of the brain causing different neurological signs/symptoms
- Time: occur at two separate times (could be years apart)
Clinical diagnosis based on history, examination and investigation
MRI:
- Brain and cervical spine with contrast
- Evidence of demyelination in two regions can indicate dissemination in space
- enhancing and non-enhancing areas of demyelination can indicate dissemination in time
Lumber Puncture:
- CSF oligoclonal bands (need matched blood sample)
- immunological bands seen in blood and CSF due to immune reaction
- Also seen in other conditions
Bloods: to exclude other conditions
- B12/Folate, ESR, CRP
Visual Evoked Response (VERS)
- measures conduction of nerve signals in optic nerve to look for subclinical optic neuritis
CXR: exclude sarcoidosis
Differentiate between relapse and a psuedo-relapse of multiple sclerosis
Relapse: usually involves a new neurological deficit that lasts for >24 hours in the absence of pyrexia or infection
Pseudo-relapse: the re-emergence of previous neurological symptoms or signs related to an old area of demyelination in the context of heat (summer) or infection
Outline the treatment for a MS relapse
- not all relapses need treatment
- steroids may speed up recovery from relapse with no effect on progression of disease
- if appropriate: physiotherapy +/- occupational therapy
steroid regime:
- methylprednisolone (IV for 3 days or oral for 5 days) AND PPI (omeprazole) for gastroprotection
What is the class, indication and action of methylprednisolone?
Class: corticosteroid (glucocorticoid)
Indication:
- replacement therapy in adrenal insufficiency
- post-transplantation immunosuppression
- treatment of exacerbation of a number of inflammatory conditions (ezcema, RA, IBD, MS)
- treatment of acute asthma
Action:
- bind to glucocorticoid receptors
- causes up-regulation of a variety of anti-inflammatory mediators and down-regulation of pro-inflammatory mediators
- this provides immunosuppression
Outline the management for relapsing MS
Disease modifying therapies:
- Alemtuzumab: two short courses over a year then further treatment if needed. Stops relapses in 40% however high risk of secondary autoimmune problems
- Natalizumab: monthly infusions, very effective for treatment of relapses
Stem Cell Transplants:
- autologous haematopoietic stem cell transplant
- approved in UK for aggressive relapsing remitting MS
Define the criteria for both primary and secondary progressive MS
Primary Progressive:
- at least 1 year of disease progression
- MRI scans support MS diagnosis
- Oligoclonal bands support MS diagnosis
Secondary Progressive:
- RRMS in past but now progressive disease without relapses or inflammation on scan
What management options are available for progressive MS?
Biotin
- dietary supplement, high dose vitamin
- May lead to some symptom relief and mild improvement
- high doses may help with some symptoms of weakness, bladder problems associated with progressive MS
Rehabilitation / Symptom management
- no disease modifying treatment for secondary progressive
- most treatment aimed at rehabilitation
control of symptoms: bladder, fatigue, mood, spasticity, mobility
Outline the epidemiology of MS in scotland
- Scotland has the highest incidence and prevalence of MS in the world
- 1 in 600 Scots have MS
Give an example of a disorder of the neuromuscular junction
Myasthenia Gravis
Outline the function of the following fibres in the peripheral NS:
Large, myelinated fibres
Thinly myelinated fibres
Small, unmyelinated fibres
Large, myelinated fibres:
- proprioception, vibration, light touch
Thinly myelinated fibres:
- light touch, pain, temperature
Small, unmyelinated fibres:
- light touch, pain and temperature
How would neuropathy at the following sites present:
Motor
Sensory: large and myelinated
Sensory: small and lightly myelinated / unmyelinated
Autonomic
Motor: weakness / muscle atrophy
Sensory (large, myelinated):
- sensory ataxia (loss of co-ordination), loss of proprioception, loss of vibration sense, numbness, tingling
Sensory (thinly myelinated / unmyelinated):
- impaire pin prick, temperature, painful burning, numbness and tingling
Autonomic: postural hypotension, erectile dysfunction, GI disturbance, abnormal sweating
Outline the clinical presentation of length-dependent axonal neuropathy
- age >50
- diffuse involvement of peripheral nerves
- length dependent: starts in toes/feet, then fingers/hands ie. starts distal
- symmetrical
- slowly progressive
- no significant sensory ataxia (reduced pin prick seen distally)
- sensory symptoms precede motor symptoms
- usually don’t see weakness
List 3 causes of length-dependent axonal neuropathy
- usually idiopathic- diabetes
- alcohol
- nutritional eg. B12 deficiencies
- immune mediated eg. RA, lupus, vasculitis
- infection eg. HIV, Hep B and Hep C
- Neoplastic eg. myeloma
- critical illness
- renal failure, hypothyroidism
Define Guillain-Barre syndrome
A disorder in which the body’s immune system attacks part of the peripheral nervous system (specifically the myelin sheath of axons)
- Can be a medical emergency if left untreated
Outline the cause and pathophysiology of Guillain-Barre syndrome
Cause:
- post-infectious autoimmune aetiology eg. campylobacter, CMV
- immune system fights campylobacter bacteria, some of which looks like the myelin sheath, therefore the immune system gets confused and in a few weeks, it senses the myelin sheath as campylobacter so mounts an immune response
- Problem lies within the myelin sheath
How does Guillian-Barre syndrome present?
- length dependent polyneuropathy
- progressive weakness over days
- flaccid quadriparesis with areflexia
- +/- respiratory/bulbar/autonomic involvement
How would the following muscle disorders present:
- Proximal limb
- Face
- Eyes
- Bulbar
- Neck and spine
- respiratory
- myocardial
Proximal limb
- weakness eg. shoulder girgle (difficulty raising arms above head)
Face
- Facial weakness
- Myopathic facies (sunken cheeks, bilateral ptosis, inability to lift corners of mouth)
Eyes
- Ptosis, ophalmoplegia (paralysis of muscles within / surrounding the eye)
Bulbar (nerves coming out of medulla)
- Dysarthria (slurred/slow speech), dysphagia (dificency generating or understanding speech)
Neck and spine
- Head drop, scoliosis
Respiratory
- breathlessness, esp. lying flat due to diaphragmatic weakness
Myocardial
- Exercise intolerance, palpitations
What is Myasthenia Gravis?
- Autoimmune disorder of the neuromuscular junction
- Fatiguable weakness of ocular, bulbar, neck, respiratory and/or limb muscles
What are the two major components of the brain controlling the motor aspect?
Basal ganglia: modulates and refines cortical activity
Cerebellum: co-ordinates voluntary movement
What is the epidemiology for parkinson’s?
(Age, gender etc.)
- more common in men
- prevelance rises exponentially >60 years (median age of onset is 70yrs)
- mean duration diagnosis to death is 15 years
- many genes identified in hereditary Parkinson’s esp. PAK8
Outline the pathology of Parkinson’s disease
- loss of dominergic neurons within the substantia nigra
- dopamine: neurotransmitter in the basal ganglia
- surviving neurons contain Lewy bodies: abnormally folded proteins made of either a-synuclein or ubiquitin
- Parkinson’s clinical manifests agyer loss of approx. 50% of dopaminergic neurons
outline the pathological progression of Parkinson’s disease
Lew bodies can be present up to 20 years prior to presentation
- Substantia nigra contains Lewy bodies when patient presents
Stages:
1-2: medulla/pons anterior olfactory nucleus
- presymptomatic or pre-motor ie. loss of sense of smell
3-4: midbrain ie. substantia nigra pars compacta
- Parkinsonism only becomes evident after extensive nigral damage
5-6: neocortex involvement
- Development of PD dementia
Outline the clinical presentation of Parkinsonism
Collection of motor symptoms:
Bradykinesia
- slowness in initiation of voluntary movement with progressive reduction in speed and amplitude with repetitive actions
At least one of:
- Muscular rigidity
- Resting tremor
- Postural instability
Outline the clinical presentation of Parkinson’s
First: loss of sense of smell
Parkinsonism
Neuropsychiatric:
- dementia, depression, anxiety
Autonomic:
- constipation, urinary urgency/nocturia
- erectile dysfunction
- excessive salivation/sweating
- postural hypotension
Sleep
- REM sleep behaviour disorder, daytime somnolence
List 3 differentials for Parkinson’s
- benign tremor disorders
- Dementia with Lewy bodies
- vascular parkinsonism (small vessel disease in the basal ganglia)
- Parksinson plus disorders eg. multiple system atrophy
- Drug-induced parkinsonism/tremor
Outline how Parkinson’s disease is diagnosed
PD is largely a clinical diagnosis
Investigations:
- Funcitonal imaging: imaging of presynaptic dopaminergic function is abnormal in degenerative parkinsonism (loss of tails of putamen and asymmetric in PD)
- Structural Imaging: CR/MRI brain is normal in PD but abnormal in vascular parkinsonism and Parkinson plus disorder
- Bloods: if tremor is present may do TFTs, copper
What are the pharmacological and clinical aims of Parkinson’s disease management?
Pharmacological: restore dopamine levels
Clinical: improve motor symptoms / improve quality of life
Outline the management for treating the motor symptoms of Parksinson’s disease
- Levadopa: offers to those in early stages of PD whose motor symptoms impact their quality of life
For those in early stages of PD whose motor symptoms do not impact their quality of life offer:
- dopamine agonist eg. apomorphine, pramipexole
- levadopa
- monoamine oxidase-B inhibitors (MAO-B inhibitors)
For those with Parkinson’s who have developed dyskinesia or motor flucuations despite optimal levadopa therapy offer:
- dopamine agonists, MAO-B inhibitors or COMT (catechol-o-methyltransferase) inhibitors in adjuvant to levadopa
Advanced PD: Deep brain stimualtion of subthalamic nuclei
Outline the class, indication and action of levodopa
Class: dopamine precursor
Indication: Parkinson’s disease
Mechanism of action:
- pro-drug
- crosses the blood brain barrier and is taken up by dopaminergic neurons where it is converted to dopamine in pre-synaptic terminals
- striatal dopaminergic neurotransmission increased
- co-prescribed with dopa-decarboxylase (decreases the amount of levodopa converted at the periphery to ensure max. levodopa reaches the brain)
Outline the class, indication and action of apomorphine
Class: dopamine agonist
Indication: Parkinson’s disease
Mechanism of action:
- stimualtes post-synaptic dopamine receptors
- non-selective D1 and D2 dopamine subfamily of receptors
- this upregulates receptors and increases sensitivity to endogenous dopamine
- early on prescribed as monotherapy, later in combination with levodopa
Outline the class, indication and action of entacapone
Class: catechol-o-meythltransferase (COMT) inhibitor
Indication: Parkinson’s disease (given in adjuvant with levodopa and dopamine decarboxylase inhibitor)
Action:
- prevents the peripheral breakdown of levodopa by inhibiting COMT (the breakdown products of levodopa cannot cross the blood brain barrier)
- therefore more levodopa reaches the brain
State 3 side effects of levodopa, entacapone and apomorphine
Levodopa:
- dyskinesia, compuslive disorders, hallucinations, nausea, GI upset
Entacapone:
- dyskinesia, nausea, abdominal pain, vomiting, dizziness
Apomorphine:
- pain at site of injection, nausea, vomiting
How is deep brain stimulation of the subthalamic nucleus used in parkinson’s disease?
Used in advanced PD
- implant stimulating wires into the subthalamic nucleus which enables ability to get aorund some abnormal brain signalling due to parkinson’s
- helps manage motor control (about 5-10yrs od motor management)
Define dementia
Progressive cognitive decline
- interfers with the ability to function and work or usual activities and
- represents a decline from previous levels of functioning and performing and
- is not explained by delirium or major psychiatric disorders
What domains are involved in the cognitive or behavioural impairment that occurs in dementia
Minimum of two of the following:
- memory
- executive function
- language
- apraxia / visuospatial
How do you assess a patient in your history taking for possible dementia?
Generic history
- PC, HPC, FH
- PMH: vascular disease, stroke, trauma, cancer
- DH: prescribed medication, opiates
- Take a history from next of kin
Cognitive History
- memory: repetitive questions/conversations, misplacing personal items, forgetting events
- executive fxn: poor understanding of safety risks, inability to manage finances, poor decision-making ability
- visuospatial: inability to recognise faces/common objects
- language: difficulty thinking of common words while speaking
What tests are available to assess memory?
- Folstein MMSE (30marks) - very quick
- Addenbrooke’s Cognitive Assessment (ACE): 100 marks, takes 20 minutes
What categories are involved in the Addenbrooke’s Cognitive Assessment (ACE)?
What is the purpuse of ACE?
- Attention/Concentration
- Fluency
- Language
- Visuospatial
- Memory
Purpose:
- Determine severity and pattern of impairment of a patient with dementia
How is attention assessed in ACE?
- orientation (place, time)
- digit span (3 objects, repeat back)
- serial 7s (100-7 etc) / spell WORLD backwords
How is memory assessed in ACE?
Memory: episodic, semantic and working
Episodic:
Recall: give name and address 3 times
Recongition/Recall: ask same address at end of test
Semantic:
- general knowledge
- ask to say weird words aloud eg. dough, height, pint
- identify objects eg. pen
How is fluency assessed in ACE?
Fluency is part of executive function
Trail’s test: joining A to 1, B to 2 etc.
- Knowing rules and carrying them out
How is visuospatial function assessed in ACE?
What is visuospatial function?
Visuospatial: visual processing and accurately localising objects (ability to localise objects in space)
Impairment: difficulty recognising faces/objects and inabbility to localise objects
Assessment:
- draw overlapping pentagons
How does scoring in ACE correlate to dementia?
Overall Score: 100
- <88: excludes dementia
- >83 supports dementia
- always consider not only the score and pattern but potential confounders eg. depression or anxiety
What do deficits in the following categories in ACE correlate to in terms of type of dementia
Episodic memory
Semantic memory
Attention/Concentration
Naming fluency
Visuospatial
Episodic memory: Alzheimer’s
Semantic memory: semantic dementia
Attention/Concentration: Delirium
Naming fluency: progressive non-fluent aphasia
Visuospatial: Parkinson’s disease
Outline the clinical features of dementia
- deterioration from high levels of function
- memory loss
- cognitive impairment
- language problems
- visuospatial dysfunction
- impairment of intellectual ability
- personality changes
- impact on social/occupational function
- decline in emotional control/motivation
- consciousness preserved
- chronic duration >6 months
State some differential diagnoses for dementia
AV DEMENTIA
- *A**lzheimer’s disease
- *V**ascular dementia
- *D**rugs, Depression, Delirium
- *E**thanol
- *M**etabolic
- *E**ndocrine (tyroid, diabetes)
- *N**eurological
- *T**umour, Toxin, Truama
- *I**nfection
- *A**utoimmune
Outline the clinical presentation of Alzheimer’s dementia
Failing memory
- Amnestic = altered episodic memory
- progressive loss of ability to learn, retain and process new information
Cognitive decline
- non-amnestic - language/writing/reading
Psychiatric: personality/mood changes
Neurological
- primative reflexes, postural abnormalities
Memory loss, disorientation, dysphasia
Variation with age of onset, disease progression, disease duration, symptoms at onset
What pathological changes are seen with Alzheimer’s disease?
Preclinical Alzheimer’s
- entorhinal and hippocampus begin to atrophy with associated neuronal loss
- changes can begin years before symptoms appear
- memory loss = first sign of Alzheimer’s disease
Mild-Moderate AD
- cerebral cortex atrophy with more neuronal loss
- Mild: memory loss, confusion, poor judgement, mood changes
- moderate: inc. memory loss and confusion, problems recognising people, difficulty with language
Severe AD
- severe cortical atrophy throughout whole neocortex with associated pathology
- enlargement of ventricles, loss of white matter
What abnormal structures are seen in Alzheimer’s disease?
- Amyloid plaques
- Neurofibrillary tangles
How do amyloid plaques form in the brain?
- amyloid precursor proteins: ubiquitous, transmembrane proteins that sit in the cytoplasm
- normally, APP moves out of the membrane and cleaved into soluble APP-alpha, which has a normal function within the brain
amyloidogenic state:
- differemt enzymes work of APP and cleaves it within the membrane domain and forms amyloid B-peptide (Aß) which is released into the ECM
- APP changes from alpha-helices to beta-pleated sheets, triggering an inflammatory response resulting in tau aggregates and amyloid plaques resulting in neuronal loss and cognitive decline
What are neurofibrillary tangles?
Main component: paired helical filaments (PHFs)
- Consist of micotubule-associated protein Tau
Tau: microtubule associated protein
In Alzheimer’s disease: Tau is hyperphosphoylated
- the microtubules (normally arranges parallel) collapse into twisted strands called tangles
What is vascular dementia?
- Dementia caused by a reduction in blood flow to the brain, caused by a series of mini-strokes (transient ischaemic attacks (TIAs))
- this causes damage to the brain thus impacts memory
outline the clinical presentation of vascular dementia
- stepwise progression: constant for a long time then sudden decline which is constant for a while then repeat
- memory impairment
- lack of insight (no awareness of losing memory)
How is dementia with Lewy bodies characterised?
- visual hallucinations
- fluctuating consciousness
- progressive cognitive decline
- sleep behaviour disorder
- strongly associated with Parkinsonism and shares many of its features
Outline the pathology of dementia with Lewy Bodies
cortical lewy bodies
- aggregates of a-synuclein as the protein is misfolded into B-pleated sheet structure than than a-helices
- these further aggregate into higher-order insoluble structures (fibrils) which are the building blocks of lewy bodies
Differentiate Parkinson’s disease and dementia with lewy bodies
Primary pathology:
PD: nigrostriatal pathway
Dementia w/ LB: cerebral cortex
Clinical effect:
PD: extrapyramidal movement disorder
Dementia w/LB: dementia
