Neurology Flashcards
What is the central nervous system?
The brain and spinal cord
What does the peripheral nervous system consist of?
12 pairs of cranial nerves, which connect the brain/brainstem and head and neck
31 pairs of spinal nerves
What are the two divisions of the autonomic nervous system?
Sympathetic
Parasympathetic
Where does sympathetic outflow come from?
The thoracic and lumbar cord
Where does parasympathetic outflow come from?
The brainstem via cranial nerves and the sacral cord
Where is the motor cortex?
At the precentral gyrus
Where is the somatosensory cortex?
At the postcentral gyrus
Where are the pyramids?
In the medulla
What is the internal capsule?
A big white matter tract running between the deep brain structures
What does the diencephalon consist of?
Thalamus
Hypothalamus
What is the thalamus responsible for?
Motor control
Sensory relay
Visual processing
What are the basal ganglia?
Caudate
Putamen
Globus pallidus
Where does the spinal cord start and end?
Starts just below the medulla
Ends at L1-L2
How many pairs of cervical nerves are there?
8
How many pairs of thoracic nerves are there?
12
How many pairs of lumbar nerves are there?
5
How many pairs of sacral nerves are there?
5
How many pairs of coccygeal nerves are there?
1
From what level does the brachial plexus originate?
C5-8 and T1
What do the spinal nerves contain?
Mixed somatic nerves comprised of motor fibres for skeletal muscles and sensory fibres (pain, temperature, touch, pressure, vibration, proprioception)
Joined by sympathetic fibres
Where within the grey matter of the spinal cord do motor neurons terminate?
In the ventral grey horn
Where within the grey matter of the spinal cord do sensory neurons terminate?
In the dorsal root ganglion
What is a dermatome?
An area of skin supplied by a single spinal nerve
What is a myotome?
Muscles supplied by a single spinal nerve
What do the ascending tracts within the cord (white matter) do?
Carry sensory information from the periphery to the CNS
What do the descending tracts within the cord (white matter) do?
Carry motor information from the CNS to the periphery
What are interneurons?
Neurons that allow reflexes by joining a sensory neuron directly to a motor neuron, bypassing the CNS.
What are the two main ascending tracts in the spinal cord?
- Spinothalamic tract
2. Dorsal column pathway
What information is carried by the dorsal column?
Touch (particularly fine touch)
Proprioception
What information is carried by the spinothalamic tract?
Pain and temperature
Crude touch
Describe the path taken by the spinothalamic tract
Cell body is in the dorsal root ganglion
–> Projects to the dorsal grey horn and synapses with a second neuron.
–> Axons decussate via ventral white commissure
–> Ascend towards thalamus
–> Synapse with 3rd neuron in the thalamus
–> Axons project to somatosensory cortex
(Tract runs contralateral to the side of the body that it receives fibres from as decussation happens almost immediately)
Describe the path taken by the dorsal column pathway
Cell body is in the dorsal root ganglion
- -> axons ascend in the dorsal columns towards the cuneate/gracile fasciculus
- -> For upper limb, synapse with second neuron in cuneate fasciculus
- -> For lower limb, synapse with second neuron in gracile fasciculus
- -> Axons decussate in the medulla then ascend in the medial lemniscus
- -> Synapse with 3rd neuron in the thalamus
- -> Axons project to somatosensory cortex
What are the key descending tracts in the spinal cord?
Lateral and ventral corticospinal tracts
Do the corticospinal tract fibres decussate and where?
Ventral corticospinal tract does not decussate
Lateral corticospinal tract fibres decussate at the pyramids
Describe the path taken by the corticospinal tracts
~85% of the fibres decussate at the pyramids to form the lateral CST
~15% of the fibres remain ipsilateral to form the ventral CST
–> upper motor neuron synapses with lower motor neuron in the ventral grey horn
–> axon leaves in the spinal nerve
Which cranial nerves arise from the brain and which arise from the brainstem?
I and II arise from the brain
III-XII arise from the brainstem
What is the mnemonic for remembering which cranial nerves carry sensory/motor or both?
Some Say Money Matters But My Brother Says Big Brains Matter Most
Which cranial nerves also carry parasympathetic fibres?
III, VII, IX, X
oculomotor, facial, glossopharyngeal, vagus
What does cranial nerve I do?
Olfactory
Sensory: smell
Axon bundles travel through cribriform plate –> olfactory bulb –> tracts –> temporal lobe
Connects with limbic system
What does cranial nerve II do?
Optic
Sensory: vision
Fibres travel from retina –> primary visual cortex (medial aspect of occipital lobe, calcarine sulcus)
Right and left visual cortices receive information from both eyes about opposite side of visual field
What does cranial nerve III do?
Oculomotor
Motor and parasympathetic
Motor to most of extraocular muscles (medial rectus, superior rectus, inferior rectus, inferior oblique, levator palpebrae superioris)
Parasympathetic: innervates sphincter to pupillae –> constriction in response to light
What does cranial nerve IV do?
Trochlear
Motor - innervates superior oblique
What does cranial nerve V do?
Trigeminal
Sensory fibres: extensive distribution in the head, touch, pressure, pain, temperature, proprioception from TMJ and muscles of mastication
Motor fibres: Muscles of mastication
3 divisions: ophthalmic (S), maxillary (S), mandibular (S&M)
What does cranial nerve VI do?
Abducens
Motor
Innervates lateral rectus
What does cranial nerve VII do?
Facial
Sensory: taste anterior 2/3 of the tongue
Motor: muscles of facial expression
Parasympathetic: Lacrimal gland, submandibular and salivary glands
What does cranial nerve VIII do?
Vestibulocochlear
Sensory
Afferents from vestibular apparatus (balance) and cochlea (hearing)
What does cranial nerve IX do?
Glossopharyngeal Sensory: Taste - posterior 1/3 of the tongue General sensation from pharynx, eustachian tube and posterior 1/3 of tongue Motor: One muscle of the pharynx Parasympathetic: parotid gland
What does cranial nerve X do?
Vagus
Sensory: General sensation external auditory meatus, tympanic membrane, pharynx, larynx, oesophagus
Motor: Muscles of soft palate, pharynx and larynx
Parasympathetic: Thoracic and abdominal viscera
What does cranial nerve XI do?
Accessory - 2 parts
- Cranial part (joins the vagus)
- Spinal part
- Arises from ventral horn spinal cord C1-C5
- Travels up through foramen magnum
- Leaves again through jugular foramen
- Innervates sternocleidomastoid and trapezius
What does cranial nerve XII do?
Hypoglossal
Motor: tongue muscles
Why do the forehead muscles still work in the case of an upper facial motor neuron lesion?
The upper part of the facial motor nerve receives input from both sides, but the lower part of the facial motor neuron receives input from only the lower side.
What are the two layers of the dura mater?
Periosteal (outer)
Meningeal (inner)
What are the deeper pockets of the subarachnoid space called?
Cisterns
Where are the meningeal vessels?
In the extradural space
Where are the bridging veins?
In the subdural space
Where is the circle of Willis and its branches?
In the subarachnoid space
What is the cauda equina?
Lower spinal nerves at the bottom of the spinal cord below L1-2 level
Where is a lumbar puncture performed?
Below L2 level (L3-4 or L4-5)
From where do the left and right vertebral arteries arise?
From the subclavian arteries
What are the terminal branches of the internal carotid artery?
Anterior cerebral artery
Middle cerebral artery
From where does the lateral surface of the brain receive its blood supply?
Mostly from the middle cerebral artery
What is Broca’s area and where is it?
On the lateral surface of the cerebrum anterior to the middle cerebral artery.
Function: motor speech
What is Wernicke’s area and where is it?
On the lateral surface of the cerebrum posterior to the middle cerebral artery.
Function: comprehension
From where does the medial surface of the brain receive its blood supply?
Mostly from the anterior cerebral artery
Where is the lower limb represented?
Medial surface of the cerebral hemisphere (anterior cerebral artery territory)
Where are the upper limb and face represented?
Lateral surface of the cerebral hemisphere (middle cerebral artery territory)
Which vessels supply the internal capsule, basal ganglia and hypothalamus?
Perforating vessels from the anterior and middle cerebral arteries
Which vessels supply the midbrain and hypothalamus?
Perforating vessels from the posterior cerebral artery
From where does the spinal cord receive its blood supply?
From paired posterior spinal arteries and one anterior spinal artery
Reinforced by supply from radicular vessels
What is the usual cause for extradural haemorrhage?
Trauma resulting in bleeding from the middle meningeal artery as a result of a skull fracture
How does extradural haemorrhage normally present?
Usually following head injury, although may be delayed
Headache, drowsiness and neurological deterioration from brain compression
How does extradural haemorrhage appear on CT?
Acute bleed appears hyperdense on CT
Convex - does not conform to surface of the brain
Bleeding limited by suture lines
Possible midline shift due to compression of the brain
What is the usual cause of subdural haemorrhage?
Trauma, typically from a fall leading to bleeding from dural bridging veins
How does subdural haemorrhage usually present?
Bleeding is low pressure, so results in a gradual rise in intracranial pressure over several weeks or months, leading to gradual cognitive deterioration. Most likely in elderly, dementia patients, alcohol abusers and shaken babies.
How does subdural haemorrhage appear on CT scan?
Chronic bleed appears hypodense (dark)
Concave shape, conforms to the surface of the brain
Bleeding crosses suture lines
Midline shift may be present due to compression of the brain
What is the most common cause of subarachnoid haemorrhage?
Ruptured aneurysm on a cerebral artery
How does subarachnoid haemorrhage present?
Sudden onset severe ‘thunderclap’ headache
May have seizures
May be conscious/unconscious, may have reduced GCS
How does subarachnoid haemorrhage appear on imaging?
Acute bleed appears hyperdense on CT (bright white)
Blood seen in fissures, cisterns and sometimes ventricles
What is the most common cause of intracerebral haemorrhage?
Aneurysm rupture
How does intracerebral haemorrhage usually present?
Depends on cause, size of bleed and brain region affected
Can cause coma, confusion, weakness, seizures
How does intracerebral haemorrhage appear on CT?
Acute bleed –> hyperdense
Blood seen in the substance of the brain
Mass effect (e.g. midline shift) seen if large
What are the possible infective causes of meningitis?
Bacterial
Fungal
Viral
Parasitic
What are the possible non-infective causes of meningitis?
Paraneoplastic
Drug side effects
Autoimmune (e.g. vasculitis/SLE)
Name three routes of infection for meningitis
- Contiguous spread e.g. from nasal carriage, otitis media, sinusitis
- Haematogenous spread (i.e. bacteraemia)
- Neurosurgical complications
Why is CNS infection so difficult for the body to clear?
The brain is protected by the blood-brain barrier, which prevents the immune system from attacking brain tissue. However, if pathogens manage to cross the barrier, they are then isolated from the immune system and can spread without resistance.
What is the classic triad or meningitis symptoms?
- Fever
- Headache
- Neck stiffness
What other symptoms besides the classic triad can meningitis cause?
- Nausea and vomiting
- Photophobia
- Irritability
- Confusion
- Sleepiness
- Lethargy
- Purpuric rash
If a patient with suspected bacterial meningitis presents to the GP, what should they do?
Administer IM benzylpenicillin immediately and send the patient to hospital
What are the first management steps in the hospital for a patient with suspected meningitis?
- Assess GCS (eye response, verbal response, motor response)
- Blood cultures
- Administer broad spectrum antibiotics - cefotaxime or ceftriaxone (assuming patient isn’t allergic to penicillin). If patient has recently travelled, administer vancomycin too due to risk of penicillin resistance.
- Steroids (IV dexamethasone) to reduce inflammation
- Lumbar puncture to give definitive diagnosis
What are the contraindications for lumbar puncture?
- Raised ICP
- Petechial rash
- Abnormal clotting/patient on anticoagulants
- Suspicion of spinal abscess
Which patients should have a CT head before proceeding to lumbar puncture?
- Those aged 60+
- Immunocompromised
- History of CNS disease
- Seizure < 1 week
- GCS < 14
- Focal neurological signs
- Papilloedema/other signs of raised ICP
Which meningitis-causing organism appears on gram film as gram negative (pink) diplococci?
Neisseria meningitidis
Why is Neisseria meningitidis the most common cause of meningitis in children and young adults?
Due to high level of nasal colonisation
What meningitis-causing organism appears as gram positive (purple) diplococci?
Streptococcus pneumoniae
What meningitis-causing organism appears as gram positive bacilli?
Listeria spp
What meningitis-causing organism appears as gram positive individual cocci?
Group B streptococcus
Which meningitis-causing organisms appear as gram negative rods?
- Haemophilus influenzae B
2. E coli
Which organisms cause chronic meningitis?
- Mycobacterium tuberculosis
- Syphilis
- Cryptococcal (fungus)
Which types of bacterial meningitis are more likely to affect neonates?
Group B strep
E coli
Which types of bacterial meningitis are more likely to affect children?
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae B
Which types of bacterial meningitis are more likely to affect adults?
Neisseria meningitidis
Streptococcus pneumoniae
Which types of bacterial meningitis are more likely to affect the elderly?
Neisseria meningitidis
Streptococcus pneumoniae
Listeria
What are the characteristics of CSF with bacterial infection?
Cloudy appearance
High white cell count
High protein
Low glucose
What are the characteristics of CSF with viral infection?
Clear appearance
High white cell count with lymphocytes
High protein
Normal glucose
Who needs to be notified in cases of meningitis?
All cases must be reported to Public Health immediately
For Neisseria meningitidis - identify close contacts and administer single dose of ciprofloxacin or rifampicin as a prophylactic measure.
What is encephalitis?
Inflammation of the cerebral cortex
What are the usual causes of encephalitis?
Viruses, particularly HSV and VZV
How does encephalitis usually present?
A flu-like illness that progresses to altered GCS with possible confusion, drowsiness and coma
Fever, seizures and memory loss may also be present
Possible meningeal irritation too –> meningoencephalitis
How is encephalitis managed?
MRI head
Lumbar puncture with viral PCR
Mostly supportive treatment with neuro rehabilitation
IV acyclovir if caused by HSV or VZV
Which organism found globally in soil produces spores that cause tetanus?
Clostridium tetani
What toxins are produced by Clostridium tetani and what do they do?
- Tetanolysin (destroys tissue)
- Tetanospasmin (causes muscle contraction and spasms by binding to neurons and travelling retrogradely along axons)
How is symptomatic tetanus managed?
Muscle relaxants
Paracetamol
Immunoglobulin to mop up unbound toxins
Metronidazole
How is rabies managed?
Symptomatic rabies cannot be treated
Pre-exposure prophylaxis via vaccination in endemic areas
Post-exposure prophylaxis via vaccination and immunoglobulin therapy
What should all patients with CNS infections be tested for?
HIV
What are (usually) the three main branches coming off the aortic branch?
- Brachiocephalic trunk
- Left common carotid artery
- Left subclavian artery
What does the brachiocephalic trunk divide into?
Right common carotid artery
Right subclavian artery
What are the four segments of the internal carotid artery?
- Cervical (in the neck - mobile)
- Petrous (in the temporal bone - fixed)
- Cavernous (in the cavernous sinus)
- Supraclinoid (intradural)
Why were strokes a much more common consequence of road traffic collisions before the advent of seatbelts?
Because of the potential for dissection of the carotid artery at the point where it enters the skull base.
Which important vessel comes off of the cavernous internal carotid artery?
Ophthalmic artery
Why do some people have worse strokes than others?
Depends on collateral blood supply and how well it can compensate for routes being blocked.
What are the consequences of injuries to the cavernous sinus?
Pain
Cranial nerve deficits
What surrounds the internal carotid artery in the cavernous sinus?
Sympathetic plexus
Venous blood supply
Cranial nerves: III, IV, V and VI
Why do the basal ganglia and internal capsule suffer irreversible damage very quickly?
They are supplied by perforating vessels, with no alternative circulation in case of a blockage.
Dissection of which arteries can occur simply by tipping the head back too vigorously?
Vertebral arteries
Which artery supplies the medulla and inferior cerebellum?
Posterior inferior cerebellar artery
The vertebral arteries unite to form a single basilar artery. Which arteries come off the basilar artery?
- Multiple perforating arteries to the brainstem
- Bilateral anterior inferior cerebellar arteries
- Bilateral superior cerebellar arteries
From where do the posterior cerebral arteries arise?
From the terminal bifurcation of the basilar artery
Which structures are supplied by perforating arteries from the posterior cerebral artery?
Thalamus
Geniculate bodies
Cerebral peduncles
Tectum
What are the three types of primary headache?
- Migraine
- Cluster
- Tension type
Name some causes of secondary headache
Meningitis Subarachnoid haemorrhage Giant cell arteritis Idiopathic intracranial hypertension Medication overuse
Which aspects of a patient’s history of headache would prompt investigation/referral?
- Age >50
- History of HIV/cancer/trauma/cerebral vein sinus thrombosis risk factors
- Changing personality/cognitive dysfunction
- Vomiting with no other obvious cause
Which characteristics of a patient’s headache would prompt investigation/referral?
- Jaw claudication or visual disturbance
- Severe eye pain
- Changing in frequency, characteristics or associated symptoms
- Postural associations
- Sudden onset/thunderclap
- Triggered by exercise or valsalva
- Focal neurological symptoms (e.g. limb weakness, aura)
What signs on examination of a patient with headache would prompt referral/investigation?
- Fever
- Altered consciousness
- Neck stiffness
- Other abnormal neurological examination
What are the ‘red flags’ for headache, which prompt urgent investigation?
- New headache with history of cancer
- Cluster headache
- Seizure
- Significantly altered consciousness, memory, confusion, coordination
- Papilloedema
What are the ‘orange flags’ for headache, which prompt monitoring and a low threshold for investigation?
- New headache where diagnostic pattern not emerged after 8 weeks
- Exacerbated by exercise or valsalva
- Headache associated with vomiting
- Headache for some time that has changed significantly
- New headache if >50 years
- Headache that wakes patient from sleep
What are the ‘yellow flags’ for headache, which prompt management and possible follow-up?
- Diagnosis of migraine or tension type headache
- Weakness or motor loss
- Memory loss
- Personality change
What should be asked about when taking a history for headache?
- Types/number
- Time (onset/duration/frequency/pattern)
- Pain (severity, type, site, spread)
- Associated (nausea, vomiting, photophobia, phonophobia, cranial autonomic features e.g. red eye, watery eye, blocked nose)
- Triggers
- Response
- Between attacks (normal/persisting symptoms)
- Any change in attacks
What are the diagnostic criteria for migraine without aura?
5 attacks with the following features:
- Lasting 4-72 hours
2: Two of the following: unilateral, pulsing, moderate-severe, aggravation by routine physical activity - During headache at least one of the following: nausea, vomiting, photophobia and phonophobia
Also, not attributed to another disorder
What is an ‘aura’ that can sometimes accompany migraine?
Usually occurs before headache, but can occur during
Most common - visual aura e.g. zig zags, flashing lights
Also sensory aura e.g. tingling on one side
Speech/language-related aura e.g. problems saying/understanding words
What are the diagnostic criteria for tension type headache?
> 10 attacks occurring <1 day/month or <12 days a year and:
- Lasts 30 minutes to 7 days
- Two of the following: bilateral, non-pulsating, mild/moderate intensity, not aggravated by routine physical activity
- No nausea/vomiting and no more than one of photophobia/phonophobia
Also, not attributed to any other disorder
Cluster headaches are less common than tension and migraine headaches. What are the diagnostic criteria?
At least five headache attacks with the following:
- Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
- Headache is accompanied by ipsilateral cranial autonomic features and/or a sense of restlessness or agitation
- Frequency varies from 1 every other day to 8 per day
Not attributed to another disorder
Classical trigeminal neuralgia is a common secondary cause of headache. What are the diagnostic criteria?
At least three attacks of facial pain with the following:
- Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated.
- Headache accompanied by ipsilateral cranial autonomic features and/or a sense of restlessness/agitation
- Pain has at least three of the following four characteristics:
i) Recovering in paroxysmal attacks from a fraction of a second to 2 minutes
ii) Severe intensity
iii) Electric shock-like, shooting, stabbing
iv) Precipitated by innocuous stimuli to the affected side of the face
Also - no clinically evident neurological deficit
Which drugs can be used for acute treatment of migraine?
Normal treatment: Oral triptan with NSAID/paracetamol
Consider anti-emetic
Which drugs should not be used to treat migraine?
Ergotamines (old drugs that were used in the past) and opiates
Which patients should not be prescribed triptans?
Those with heart disease
How do triptans work?
5-HT1 receptor agonists - cause vasoconstriction in the brain and inhibit the release of inflammatory peptides like CGRP and substance P.
Name some triptans
Rizatriptan Zolmitriptan Sumatriptan Almotriptan Eletriptan Naratriptan
What drugs should be offered as a first line preventative treatment for migraine?
Topiramate or propranolol
What other treatments besides topiramate and propranolol may be helpful for prevention of migraine?
Acupuncture
Amitriptyline
Riboflavin vitamin B2 (400mg once a day)
Botox type A for prophylaxis of chronic migraine if all else fails
What is the most common cause of secondary headache?
Medication overuse
How is subarachnoid haemorrhage managed?
Resuscitation
Nimodipine
Early intervention to prevent further bleeding (radiological/surgical)
Monitor for complications
What are the features of headache caused by raised intracranial pressure?
- Worse on waking, coughing, sneezing, straining, lying down
- Nausea and vomiting
- Papilloedema
What are the risk factors for idiopathic intracranial hypertension?
Obesity
Drugs e.g. tetracycline
What would CT scan and LP show in the case of idiopathic intracranial hypertension?
Both would be normal, but LP opening pressure would be high.
How is idiopathic intracranial hypertension managed?
- Lifestyle modification
- Monitor visual fields
- Drugs: acetazolamide/topiramate/diuretics
- May require repeated LPs, shunt, optic nerve sheath fenestration
What are the diagnostic criteria for giant cell arteritis?
3 of the following:
- Age >50
- New headache or new type of localised pain
- Temporal artery abnormality: tenderness, decreased pulsation
- ESR elevated >50
- Abnormal temporal artery biopsy
What kind of visual disturbances are more likely to be associated with ophthalmology rather than neurology?
Monocular visual patterns
How can we differentiate between a surgical problem and a medical problem with CN III?
CN III (oculomotor) has parasympathetic fibres running along the outside, which are responsible for pupillary light reflex. If the pupil is affected, this could mean that something is compressing the nerve as the parasympathetic fibres are affected. If only motor function is impaired, there is no surgical problem and the patient can be managed as an outpatient.
What is the normal cause of medical problems with CN III?
Microvascular disease, usually as a result of diabetes. The only treatment is to optimise diabetic control.
What is internuclear ophthalmoplegia?
Asymmetric nystagmus, which results in double vision - caused by a lesion of the medial longitudinal fasciculus, which connects CN VI nucleus to CN III nucleus to move the eyes simultaneously.
What does internuclear ophthalmoplegia almost always signify in young people?
Multiple sclerosis
What is Horner’s syndrome?
Miosis (constricted pupil), drooping eyelid and decreased sweating on one side of the face caused by damage to the sympathetic chain
What causes lateral medullary syndrome?
Acute ischaemic infarct of the lateral medulla.
What are the ipsilateral features of lateral medullary syndrome?
Horner's syndrome Limb ataxia Loss of pain and temperature sensation in the face Reduced corneal reflex Dysarthria Dysphagia
What are the contralateral features of lateral medullary syndrome?
Loss of pain and temperature sensation
What is Brown-Sequard syndrome?
A rare neurological condition with hemiparaplegia on one side and hemianaesthesia on the other caused by an incomplete spinal cord lesion.
- Ipsilateral corticospinal tract dysfunction
- Ipsilateral dorsal column dysfunction
- Contralateral spinothalamic tract dysfunction
What is multiple sclerosis?
An inflammatory demyelinating disease affecting the CNS that causes progressive disability over time following an initial relapsing/remitting course.
What are the general features of active MS lesions?
- Demyelination with breakdown products
- Variable oligodendrocyte loss
- Hypercellular plaques
- Perivenous inflammatory filtrate (mainly macrophages and T-lymphocytes)
- Extensive blood-brain barrier disruption
- Older plaques may have central gliosis
What are the general features of inactive MS lesions?
- Demyelination without breakdown products
- Variable oligodendrocyte loss
- Hypocellular plaques
- Variable inflammatory infiltrate
- Moderate to minor blood-brain barrier disruption
- Plaques gliosed
What are the common sites of plaque formation in MS?
Cerebral hemispheres Spinal cord Optic nerves Medulla and pons Cerebellar white matter
What features of MS relate to the spinal cord?
Weakness Paraplegia Spasticity Tingling Numbness Lhermitte's sign (electric shock going down back of neck to spine, then may radiate out of limbs) Bladder dysfunction Sexual dysfunction
What features of MS relate to the optic nerves?
Impaired vision
Eye pain
What features of MS relate to the medulla and pons?
Dysarthria
Double vision
Vertigo
Nystagmus
What features of MS relate to the cerebellar white matter?
Dysarthria
Nystagmus
Intention tremor
Ataxia
What are the types of disease progression in MS?
- Relapsing/remitting MS
- Primary progressive MS (progression from onset)
- Secondary progressive MS (initial relapsing/remitting followed by progression)
- Progressive/relapsing MS (progression from onset with relapses)
What are the diagnostic criteria for MS?
- Two or more CNS lesions disseminated in time and space (i.e. having an effect on more than one occasion and in more than one area of the CNS)
What investigations can be carried out for MS?
- Neurological examination
- MRI
- CSF
- Evoked potentials
What might be seen in CSF analysis in MS?
IgG oligoclonal bands in CSF that are not present in serum –> indicates immunoglobulin synthesis within the CSF
What is the main drug used to treat MS?
Interferon-beta (Betaferon)
What drugs can be used to treat mild to moderate spasticity associated with MS?
Oral medications e.g. baclofen, diazepam, dantrolene, clonidine, tizanidine
What can be used to treat severe spasticity associated with MS?
Invasive procedures such as intrathecal baclofen and functional neurosurgical procedures
What drugs can be used to treat tremor associated with MS?
Beta blockers (e.g. propranolol) Low-dose barbiturates (e.g. phenobarbitone, primidone) Gabapentin Isoniazid Carbamazepine Clonazepam
What non-pharmacological treatments can be used to treat tremor associated with MS?
Orthotic devices - wrist bands containing small weights, computer-controlled mechanical damping devices
Thalamic surgery - stereotactic thalamotomy, thalamic electrostimulation
What treatments are available to treat erectile dysfunction in men with MS?
- Self-administered intracorporeal injection of papverine or prostaglandin E1
- Surgically implanted penile prostheses
- Oral yohimbine taken 1-2 hours before intercourse
What drugs can be used to treat pathological laughing and crying associated with MS?
- Low dose amitriptyline
- Levodopa
- Bromocriptine
What drugs can be used to treat anxiety associated with MS?
Alprozolam
Diazepam
What exacerbates fatigue associated with MS?
Heat
What are the clinical indicators of poor prognosis MS?
- Male gender
- Late age at onset
- Early motor, cerebellar and sphincter symptoms
- Short inter-attack interval
- High number of early attacks
- Early residual disability
What treatment can be used to hasten recovery from an acute exacerbation of MS?
Oral/intravenous methylprednisolone
What is a functional neurological disorder?
Symptoms in the body, apparently caused by nervous system dysfunction, without being caused by physical neurological disease or disorder.
What is a dissociative/conversion disorder?
A partial/complete loss of normal integration between memories of the past, awareness of identity, immediate sensations and control of bodily movements.
What is somatisation?
Repeat presentation of physical symptoms in spite of repeated negative findings/reassurances from professionals
What is hypochondriasis?
Persistent preoccupation with the possibility of having one (or more) serious/progressive medical disorders
What are the four main symptom groups in terms of functional neurological disorders?
- Sensory (brain normally ‘gates’ sensations by filtering out some stimuli, this can be disturbed in functional disorders)
- Concentration/memory/fatigue
- Motor (positive/negative - extra movements/failure of movements)
- Seizures
How do functional seizures present, in comparison to epileptic seizures?
- Gradual onset
- Prolonged duration (>90s, but can be >20 minutes)
- Fluctuating severity
- Post-ictal emotional upset, but not confusion
- Hip thrusting/back arching, side to side movement
- Memory of event may be preserved
- Closed eyes
What other types of disorders are associated with functional neurological disorder?
- Other functional disorders (e.g. IBS/chronic pain)
- Other comorbid neurological conditions (e.g. MS)
Name 4 types of dissociative/conversion disorders
- Dissociative amnesia
- Dissociative fugue
- Dissociative stupor
- Trance/possession disorders
La belle indifference is sometimes associated with functional neurological disorders. What is it?
A paradoxical absence of psychological distress despite apparently serious illness/symptoms
How do functional neurological disorders present on examination?
Examination findings inconsistent with physiology, e.g. sensory abnormalities that are non-dermatomal and therefore don’t have a neurological cause, inconsistency between voluntary movements (impaired) and automatic movements (preserved) e.g. Hoover’s sign
What is a stroke?
A clinical syndrome caused by cerebral infarction or haemorrhage, typified by rapidly developing signs of focal and global disturbance of cerebral functions lasting more than 24 hours or leading to death
What is a TIA?
A transient ischaemic attack - an acute loss of cerebral or ocular function with symptoms lasting <24h caused by inadequate cerebral or ocular blood supply as a result of low blood flow, ischaemia or embolism associated with disease of the blood vessels, heart or blood.
85% of strokes are ischaemic. What happens in ischaemic stroke?
A blood vessel in the brain gets blocked, usually from an atherosclerotic plaque embolus.
15% of strokes are haemorrhagic. What causes haemorrhagic stroke?
Bleeding from a blood vessel within the brain, usually as a result of high blood pressure.
What focal neurological deficits can be caused by stroke?
- Facial weakness
- Limb weakness
- Sensory loss
- Speech problems
- Visual defects
- Problems with perception/balance/coordination
Which neurological deficits might be caused by infarct in the middle cerebral artery territory?
- Facial weakness
- Weakness/sensory loss in upper limb
- Speech problems
Which neurological deficits might be caused by infarct in the anterior cerebral artery territory?
- Weakness/sensory loss in lower limb
Which neurological deficits might be caused by infarct in the posterior cerebral artery territory?
- Visual defects
- Problems with perception
Which neurological deficits might be caused by infarct in the posterior circulation?
Disorders of balance and coordination
What are the differential diagnoses for stroke/TIA?
- Hypoglycaemia
- Labyrinthine disorders (e.g. labyrinthitis, vestibular neuronitis, BPPV, Meniere’s disease)
- Migrainous aura
What scoring system is used to assess the risk of stroke within the next 7 days for a patient who has suffered a TIA?
ABCD2 score
How is ABCD2 score calculated?
A - Age (1 point if 60+)
B - BP (1 point if 140/90 or greater)
C - Clinical features (2 points for unilateral weakness, 1 point for speech disturbance without weakness)
D - Duration (2 points for 60 minutes or longer, 1 point for 10-59 minutes)
D- Diabetes (1 point)
What TIA patients are considered ‘high risk’?
ABCD2 score 4 or more or any of the following: - Atrial fibrillation - More than one TIA in a week - TIA whilst on anticoagulant
How are low risk TIA patients managed?
- To see specialist within 7 days of symptom onset
- Start statin
- Start antiplatelets (clopidogrel/aspirin)
- No driving until specialist seen
How are high risk TIA patients managed?
- To see specialist within 24 hours of symptom onset
- Start statin
- Start antiplatelets (clopidogrel/aspirin)
- No driving until specialist seen
Briefly describe what happens at the neuromuscular junction
- Motor neuron depolarisation causes an action potential to travel down the nerve fibre to the neuromuscular junction
- Depolarisation of the axon terminal causes an influx of calcium, which triggers fusion of the synaptic vesicles and release of neurotransmitter (ACh)
- ACh diffuses across the synaptic cleft and binds to AChR on the postsynaptic membrane
- Local depolarisation of sarcolemma
- Voltage gated sodium channels open
- Depolarisation of the sarcolemma travels down T-tubules and causes release of calcium from sarcoplasmic reticulum
- Release of calcium from SR triggers contraction
What three things does efficient neuromuscular junction transmission require?
- Clustering of AChR
- Release of ACh from the presynaptic vesicle
- Removal of ACh from the neuromuscular junction
Myaesthenia gravis is an autoimmune condition. Patients with this condition normally produce antibodies to one of which two proteins?
- AChR
2. MuSK (muscle specific kinase protein)
Seronegative myaesthenia gravis patients often have a low affinity antibody against what?
Clustered AChR
How does myaesthenia gravis typically present?
Usually present first with extraocular weakness, then develop limb and bulbar weakness (leading to dysarthria, nasal speech, swallowing difficulties, weak chewing)
Fatigability is a hallmark symptom of myaesthenia gravis. What is it?
Worsening weakness after prolonged and sustained muscle contraction.
How does myaesthenia gravis affect tendon reflex and sensation?
It doesn’t. They are normal.
Describe two tests for myaesthenia gravis
- Ice pack test - apply to ptotic eye for 2-5 minutes. Positive test if >2mm improvement in ptosis
- Cogan’s lid twitch - ask patient to look down, then straight ahead again. Lid will overshoot before returning to resting position.
What are the 5 subgroups of myaesthenia gravis?
- Ocular myaesthenia gravis
- Early onset AChR myaesthenia gravis <40
- Late onset AChR myaesthenia gravis >40
- MuSK myaesthenia gravis
- Seronegative myaesthenia gravis
What feature is seen in most patients with early onset AChR myaesthenia gravis and may be present mildly in patients with ocular or seronegative myaesthenia gravis?
Thymus hyperplasia
What feature is seen in patients with late onset AChR myaesthenia gravis?
Thymus atrophy
What investigations should be carried out for myaesthenia gravis?
Antibody tests (AChR and MuSK) EMG CT chest (some patients have thymoma)
Myaesthenic crisis is a medical emergency. What are the features?
Respiratory failure (quiet breathing, reduced chest expansion, tachycardia)
Impaired swallow
Severe limb weakness
What is the best investigation to perform for suspected myaesthenic crisis?
FVC - if <1L or <15ml/kg, ITU admission required
What factors can exacerbate myaesthenia gravis?
- Infection
- Stress
- Withdrawal of cholinesterase inhibitors when symptoms not fully controlled
- Rapid introduction/increase of steroids
- Electrolyte imbalance (hypokalaemia, hypophosphataemia)
- Anaemia
- Medications, e.g. some antibiotics, penicillamine, succinylcholine, quinidine, procainamide, beta blockers, CCBs, lithlium, chlorpromazine, phenytoin, cisplatin, Botox.
What drugs can be used to manage myaesthenia gravis?
- ACh esterase inhibitors e.g. pyridostigmine
- Steroids - prednisolone
- Steroid-sparing agents - azathioprine, ciclosporin, methotrexate, mycophenolate mofetil
What non-pharmacological treatment options are available for myaesthenia gravis?
- Plasma exchange
- IV immunoglobulin
- Consider thymectomy if onset <65 years
Lambert-Eaton Myaesthenic Syndrome (LEMS) is an autoimmune disorder. These patients produce antibodies to which proteins?
Voltage-gated calcium channels at the pre-synaptic membrane
What other disorders are associated with LEMS?
Cancer (50-60%)
Type 1 diabetes
Thyroid disease
What MSK symptoms are associated with LEMS?
Proximal muscle weakness, particularly in the lower limbs
Diminished/absent reflexes
What autonomic features are associated with LEMS?
Dry mouth
Sphincter problems
Postural hypotension
Erectile dysfunction
What does EMG usually show in LEMS patients?
Reduction in compound muscle action potential with subsequent increase of more than 100% with repetitive stimulation
What are the red flags for LEMS?
Rapid progression
Early distal muscle involvement
Dysarthria (motor speech disorder)
Erectile dysfunction
What drug can be used to treat LEMS and how does it work?
3,4 diamino pyridine - blocks K channels in the nerve terminal
What causes congenital myaesthenic syndrome?
Mutations in the genes that encode NMJ proteins
What condition is caused by autoantibodies to voltage-gated potassium channels in the nerve terminal?
Neuromyotonia
What are the features of neuromyotonia?
Hyperexcitability leading to:
- Cramps
- Fasciculations
- Hyperhidrosis
- Myokymia (unilateral lid twitch)
- Fatigue
- Exercise intolerance
- Stiffness
Name some differential diagnoses for epilepsy
- Postural syncope
- Cardiogenic syncope
- Migraine
- Hypoglycaemia
- Benign paroxysmal positional vertigo
- Dystonia
- TIA
- Parasomnia
- Non-epileptic seizure
- Hyperventilation
- Cataplexy
Transient loss of consciousness can be caused by primary or secondary disturbances of brain function. What are the primary disturbances?
Epilepsy
Non-epileptic seizures
What secondary disturbances of brain function can lead to transient loss of consciousness?
Cardiac problems
Low blood pressure
What is the definition of an epileptic seizure?
A paroxysmal event in which changes of behaviour, sensation or cognitive processes are caused by excessive, hypersynchronous neuronal discharges in the brain.
What is shown on an EEG during an epileptic seizure?
Large spikes due to summation of potentials from excessive, hypersynchronous neuronal discharges.
What are the main characteristics of epileptic seizures?
- Duration 30-120 seconds
- ‘Positive’ ictal symptoms (e.g. excess movement, feeling, hearing, seeing)
- ‘Negative’ postictal symptoms (e.g. lack of movement)
- Stereotypical seizures (usually the same for that person)
- May occur from sleep
- May be associated with other brain dysfunction e.g. injury, tumour, stroke, abnormal development, scarring
- Typical seizure phenomena e.g. lateral tongue bite, deja vu
What is the most common type of epilepsy?
Temporal lobe epilepsy
How does a tonic-clonic seizure present?
A tonic phase with rigid movements followed by a clonic phase with larger movements, then a postictal ‘negative’ phase.
A patient is not responding to commands, but making autonomous movements such as repetitive swallowing and lip smacking. What kind of seizure is this?
A partial temporal lobe epileptic seizure
A patient is conscious but seems to lose control of their limbs on one side. What kind of seizure is this?
A partial seizure involving the prefrontal cortex
What is the definition of syncope?
A paroxysmal event in which changes in behaviour, sensation and cognitive processes are caused by an insufficient blood or oxygen supply to the brain.
What are the main characteristics of syncope?
- Situational (e.g. hot, dehydrated)
- Typically from standing (though may occur from sitting)
- Rarely from sleep
- Presyncopal symptoms e.g. nausea, lightheadedness
- Duration 5-30 seconds
- Recovery within 30 seconds
- Can involve shaking
What are the main characteristics of non-epileptic seizures?
- Situational (usually a scenario that leads up to them)
- Duration 1-20 minutes
- Dramatic motor phenomena or prolonged atonia
- Eyes closed
- Ictal crying and speaking
- Surprisingly rapid or slow postictal recovery
- History of psychiatric illness/other somatoform disorders
- Often starts with tremor rather than tonic-clonic movements, amplitude of movements changes but not frequency
What is focal epilepsy?
Epilepsy associated with a focal brain abnormality, patients can have secondary generalised seizures or partial seizures with or without loss of consciousness.
What is the first line treatment for focal epilepsy?
Carbamazepine
Lamotrigine (women of childbearing age)
What is genetic generalised epilepsy?
A type of epilepsy with no associated brain abnormality that usually manifests before the age of 30.
Seizure types include:
- Absence seizures
- Myoclonic seizures
- Primary generalised tonic-clonic seizures
What is the first line treatment for generalised epilepsy?
Valproate (most effective)
Lamotrigine can be given to women of childbearing age
What are the three potential targets for epilepsy medication?
- Presynaptic neuron
- Inhibitory interneuron
- Postsynaptic neuron
How do carbamazepine and lamotrigine work?
Blocking voltage-gated sodium channels in the presynaptic neuron, stopping the Na+ influx that drives action potentials.
How do pregabalin and gabapentin work?
Blocking voltage-gated calcium channels in the presynaptic neuron, preventing exocytosis of the neurotransmitter
SV2A (synaptic vesicle glycoprotein 2A) is required for release of neurotransmitter from vesicles. Which drug inhibits this protein?
Levetiracetam
How does retigabine work?
Increases the activity of the voltage-gated K+ channel at the presynapse, allowing more K+ to escape and decreasing neuronal excitability
What is the target of benzodiazepines, barbiturates, felbamate and topiramate at the presynaptic neuron?
GABA(A) receptor
Which drug increases GABA levels by inhibiting GABA transaminase in the inhibitory interneurons?
Vigabatrin
Which drug increases GABA levels by inhibiting the GABA transporter?
Tiagabine
Name 3 drugs that inhibit glutamate receptors at the postsynaptic neuron to reduce excitability
- Perampanel
- Felbamate
- Topiramate
What non-pharmacological treatments can be used for epilepsy?
Resective surgery
Vagal nerve stimulator
What are the three main types of clinical presentation for brain tumours?
- Focal deficits (depending on location and anatomical specialisation)
- Epilepsy/seizure disorder
- Raised intracranial pressure
What is a glioma?
A metastatic tumour of the glial tissue
Why can’t diffuse gliomas be cured surgically?
They infiltrate diffusely into the brain tissue, meaning that it is impossible to remove all of the tumour cells, so the tumour recurs from the infiltrating cells left behind.
How are primary CNS tumours classified?
WHO classification based on a mixture of histopathological and molecular features (if molecular testing available - otherwise just based on histology “NOS”)
Assigned a grade 1-4 based on ‘biological potential’ where 1 is essentially benign and 2-4 become more aggressive.
How is the WHO grading scheme applied to astrocytomas?
Grade 1 - pilocytic astrocytoma - good prognosis
Grade 2 - diffuse astrocytoma - nuclear atypia (>5 years)
Grade 3 - diffuse astrocytoma - mitotic activity (2-5 years)
Grade 4 - diffuse astrocytoma - necrosis and proliferation (<1 year)
What are the three types of adult diffuse glioma?
- Astrocytoma IDH mutant (grade 2-4)
- Oligodendroglioma IDH mutant and 1p/19q deleted (grade 2-3)
- Glioblastoma multiforme IDH wild-type (grade 4)
What mutation is present in most low grade diffuse gliomas and some higher grade gliomas?
Isocitrate dehydrogenase 1 (IDH1)
What molecular feature is considered a defining feature of oligodendrogliomas?
Codeletion of 1p19q
Grade 2-4 astrocytomas may have which molecular features?
Always IDH mutation
May also have ATRX and p53 mutations
NOT 1p19q codeleted
Glioblastoma Multiforme IDH wild-type is a diffuse astrocytic grade 4 tumour. What would be seen on histology of this tumour?
Mitoses, necrosis and vascular proliferation
Pilocytic astrocytoma is a grade 1 tumour predominantly seen in children. Where is it found and what defining feature is often seen on histology?
Usually found in cerebellum, but can also appear at optic nerves or hypothalamic/midline structures.
Rosenthal fibres often seen on histology.
What is a medulloblastoma?
A primitive tumour of the cerebellum, usually seen in childhood, high malignant potential (therefore grade 4) but may respond well to surgery and chemo.
Mutations in which genes may be seen in medulloblastoma?
SHH, Wnt, N-MYC, C-MYC
From where do meningiomas arise?
From the dura mater
What are the most common primary cancers that end up in the brain?
- Lung (45%)
- Breast
- Melanoma
- GI tract
- Kidney
Why should you never perform a lumbar puncture without doing a CT scan first if there is a suspicion of raised intracranial pressure?
Raised intracranial pressure can lead to herniation of brain tissue. Removal of CSF can exacerbate the pressure gradient and increase the chance of a fatal hernia developing.
What are the four types of herniation that can develop in the brain?
- Lateral tentorial (uncal) hernia
- Tonsillar herniation
- Subfalcine cingulate gyrus herniation
- Central diencephalic herniation
Why might a lateral tentorial hernia cause pupillary dilatation?
From compression of CNIII (oculomotor)
Besides CNIII, what other structures can become compressed as a result of a lateral tentorial hernia?
- Posterior cerebral artery
- Contralateral cerebral peduncle (motor fibres) –> hemiparesis ipsilateral to the lesion
- Brainstem
Why might a mass lesion in the brain cause localised hydrocephalus despite a decreased volume in CSF?
Due to obstruction of CSF flow
What is encephalopathy?
Reduced level of consciousness/diffuse disease of brain substance (usually non-infective but multiple aetiologies)
What two signs can indicate meningeal irritation?
- Kernig’s sign (unable to straighten leg >135 degrees without pain)
- Brudzinki’s sign (severe neck stiffness causes hips and knees to flex when neck is flexed)
What are the signs of papilloedema as seen on fundoscopy?
- Venous engorgement
- Optic disc blurring
- Haemorrhage near optic disc
- Loss of venous pulsation haemorrhages
What does bilateral papilloedema indicate?
Raised intracranial pressure
What are the risks of lumbar puncture?
- Headache
- Infection
- Damage to spinal cord/haematoma
- Cerebral herniation and death
What investigations should be performed on CSF?
- Opening pressure
- Protein and glucose
- Microscopy, culture and sensitivity
- Viral and bacterial PCR
(Take blood simultaneously to compare CSF and serum glucose levels)
What will the CSF results of an acute bacterial infection show?
- Raised opening pressure
- Cloudy CSF
- Neutrophils
- High protein
- Low CSF:plasma glucose ratio
What will the CSF results of a viral infection show?
- Raised opening pressure
- Clear CSF
- Lymphocytes
- Normal/high protein
- Normal CSF:plasma glucose ratio
What does bloodstained CSF indicate?
Subarachnoid haemorrhage
What are the features of HSV encephalitis?
Fever, headache, lethargy, behavioural change.
May progress to focal signs, seizure, coma.
How is HSV encephalitis treated?
10mg/kg aciclovir IV tds
How does CJD present?
Neurodegenerative changes - behavioural changes, cognitive decline, eventual coma, death
What is progressive multifocal leukoencephalopathy?
Progressive inflammation of white matter, caused by JC (John Cunningham) virus (present in 90% of population)
Which patients are at risk of progressive multifocal leukoencephalopathy?
Immunocompromised, e.g. AIDS, transplant patients
What are the features of progressive multifocal leukoencephalopathy?
Motorsensory changes, personality changes, speech and visual disturbances
How is progressive multifocal leukoencephalopathy treated?
Assisting reversal of immune system, e.g. stop natazilumab, start HAART for HIV
What is the most common cause of dementia?
Alzheimer’s disease
What are the three main histopathological features of Alzheimer’s disease?
Amyloid-beta plaques
Neurofibrillary tangles with Tau protein
Lewy bodies
Why do amyloid-beta plaques form?
Amyloid-beta peptide misfolds and becomes sticky.
How does Tau cause neurofibrillary tangles?
Tau normally stabilises microtubules, but a misfolded version results in tangle formation.
Individuals with trisomy 21 are more likely to develop Alzheimer’s. Why is it thought that this happens?
APP (amyloid precursor protein) gene is on chromosome 21 - it is thought that this could result in these individuals producing more amyloid-beta and somehow developing Alzheimer’s more readily as a result.
What other pathological features are found in the brain of a person with Alzheimer’s disease besides plaques and tangles?
- Damaged mitochondria
- Inflammation of the brain more likely
Name some of the presenting features of Alzheimer’s disease
- Memory loss
- Poor judgement (–> bad decision)
- Loss of spontaneity and sense of initiative
- Taking longer to complete normal tasks
- Repeating questions
- Trouble handling money and paying bills
- Wandering and getting lost
- Losing things/misplacing them in odd places
- Mood/personality changes
- Increasing anxiety and/or aggression
- Problems recognising family and friends
- Hallucinations, delusions, paranoia
- Impulsive behaviour e.g. undressing at inappropriate times/places, vulgar language
Name some of the severe clinical features of Alzheimer’s disease
- Inability to communicate
- Weight loss
- Seizures
- Skin infections
- Difficulty swallowing
- Groaning, moaning or grunting
- Increased sleeping
- Loss of bowel and bladder control
How long after diagnosis do Alzheimer’s patient normally die?
8-10 years
What sorts of things are tested when assessing a patient with suspected Alzheimer’s?
- Semantic history, e.g. “Name as many animals as you can”
- Immediate and delayed recall
- Phonemic fluency e.g. “How many words beginning with C can you think of?”
What kind of neuroimaging is used to diagnose Alzheimer’s (although not definitively)?
Usually structural MRI
Sometimes might use CT head
What features might be seen on neuroimaging in Alzheimer’s disease?
Atrophy, particularly of the hippocampus
What drugs are given to treat mild to moderate Alzheimer’s?
Cholinesterase inhibitors, e.g.
donepezil
rivastigmine
galantamine
What drug is sometimes given to treat moderate to severe Alzheimer’s?
Memantine - NMDA (glutamate) receptor antagonist
Name some risk factors for Alzheimer’s disease
- Genetics
- Head injury
- Obesity
- Smoking
- Physical inactivity
- Poor cognitive reserve
- Hypertension
- Stroke
- Diabetes
- Hypercholesterolaemia
Bipolar patients seem to have a lower incidence of Alzheimer’s. Why?
Lithium appears to affect the accumulation of Tau.
Where do upper motor neurons go?
From the motor cortex to the medulla
Where do lower motor neurons go?
From the motor cortex to the spinal cord
Which motor neurons supply the oropharyngeal muscles?
Bulbar (upper) motor neurons
Which motor neurons supply the limb muscles?
Somatic (lower) motor neurons
Where in the spinal cord does the lower motor neuron (and the afferent sensory fibre) synapse?
In the anterior horn
What is primary lateral sclerosis?
Degeneration of upper motor neurons only
What is primary muscular atrophy?
Wasting of the muscles caused by degeneration of lower motor neurons only.
Amyotrophic lateral sclerosis makes up 90% of motor neuron disease cases. What is it?
A mixture of both upper and lower motor neuron degeneration.
How are the three different presentations of motor neuron disease?
- Limb onset (75%)
- Bulbar onset (affecting speech and swallow) (25%)
- Respiratory onset (<1%)
What are the upper motor neuron symptoms that occur in the limb?
Pyramidal weakness (preferentially spares antigravity muscles - ones that help maintain upright posture) Spasticity (abnormal muscle tightness due to prolonged contraction)
What are the lower motor neuron symptoms that occur in the limb?
Wasting
Weakness
Fasciculations
What are the red flags for motor neuron disease?
- Relentless progressive disability
- Presence of both upper and lower motor neuron pathology (e.g. wasting and stiffness)
- Weakness in the absence of sensory symptoms (MND only affects motor pathways)
What are the bulbar features of motor neuron disease?
Dysarthria (slurred/quiet speech, particularly when tired)
Dysphagia
Excessive saliva
Choking sensation especially when lying flat
Tongue fasciculations
What are the limb features of motor neuron disease?
Focal weakness Falls/trips (due to foot drop) Loss of dexterity Muscle wasting Muscle twitching/fasciculations Cramps No sensory features
What are the respiratory features of motor neuron disease?
Hard to explain respiratory symptoms Shortness of breath on exertion Excessive daytime sleepiness Fatigue Early morning headache Orthopnoea (SOB when lying down)
What are the cognitive features associated with motor neuron disease?
Behavioural change Emotional liability (not related to dementia) Fronto-temporal dementia
What factors are NOT supportive of motor neuron diagnosis?
- Bladder/bowel involvement (Olaf’s nucleus unaffected)
- Prominent sensory symptoms
- Double vision/ptosis (oculomotor system unaffected)
- Improving symptoms
Give some examples of things that contribute to the development of motor neuron disease.
Smoking
Somatic mutation
Genetic predisposition
Chemical exposure
What three types of genes are implicated in motor neuron disease?
- Genes involved in protein homeostasis
- Genes involved in altered RNA-binding proteins
- Genes involves in cytoskeletal proteins
Which drug is used in motor neuron disease and can prolong a patient’s life for about 3 months?
Riluzole (inhibits glutamate release)
What non-pharmacological treatment is often used to improve quality of life and prolong survival in patients with motor neuron disease?
Non-invasive ventilation
What is spinomuscular atrophy?
A genetic condition found in children - mutation in SMM1 gene results in breathing difficulties and difficulties using arms and walking etc.
What treatments are available for spinomuscular atrophy?
- Gene therapy using a viral vector to insert functioning SMM1 (very expensive, only useful for young children who aren’t immune to the viral vector yet)
- Antisense oligonucleotides
Brainstem death occurs when the reticular activating system is affected. What are the criteria for brainstem death that must be met for organ donation to proceed?
- Pupils fixed and dilated
- Corneal reflex absent
- Caloric vestibular reflex absent
- Cough reflex absent
- Gag reflex absent
- No response to pain
- No independent respiratory activity
What are the 4 types of sensory fibres?
Large diameter: 1. A-alpha (proprioception) 2. A-beta (light touch, pressure, vibration) Small diameter: 3. A-delta (cold) - myelinated 4. C-fibres (heat) - unmyelinated
Name three common mononeuropathies
- Carpal tunnel syndrome
- Ulnar neuropathy
- Peroneal neuropathy
What neuropathological features occur if the A-alpha fibres are affected?
Loss of proprioception, e.g. balance problems
What neuropathological features occur if the A-beta fibres are affected?
Loss of light touch, vibration, pressure sensations
Which sensory fibres are most at risk of damage?
C-fibres due to lack of protective myelination
What is usually the first symptom of small fibre damage?
Burning pain sensation
What feature is characteristic of sensory ataxia?
Worsening of ataxia when eyes closed/in the dark
What are the three main types of clinical presentation in peripheral neuropathy?
- Symmetrical sensorimotor (distal limbs affected on both sides)
- Asymmetrical sensory (proximal, unilateral)
- Asymmetrical sensorimotor (distal limbs, asymmetrical distribution)
Symmetrical sensorimotor neuropathy is the most common type of peripheral neuropathy. How does it normally present?
- Longer fibres affected first –> symptoms start distally, especially in toes
- Initially sensory, so tingling, numbness and pain occur first
- Motor symptoms appear later
Asymmetrical sensory neuropathy involves patchy distribution of sensory symptoms as the dorsal root ganglia are affected. Which two diseases are associated with it?
Sjogren’s disease
Coeliac disease
How can nerve conduction studies differentiate between demyelinating and axonal conditions?
Demyelination results in slow conduction velocities
Axonal problems result in reduced amplitudes of potentials
What disease is present in 50% of patients with axonal neuropathy?
Diabetes
Aside from nerve conduction studies, what other neurophysiological test can be used in diagnosing peripheral neuropathies?
Quantitative sensory testing
What is chronic idiopathic axonal polyneuropathy?
- Chronic (develops over at least 6 months)
- Idiopathic (no identifiable aetiology)
- Axonal (Axons affected, usually length-dependent)
What is the umbrella term used for all hereditary chronic neuropathies?
Charcot Marie Tooth disease
What is Guillain-Barre syndrome?
An acute polyneuropathy, usually demyelinating (although there are also axonal motor and axonal sensorimotor versions)
What are the clinical features of Guillain-Barre syndrome?
- Rapid ascending paralysis and sensory deficits (hours to days)
- Often preceding infection
How should Guillain-Barre syndrome be treated?
- Immediate intravenous immunoglobulin infusion or plasma exchange
- Monitor respiratory function
- ITU admission
- Refractory GBS may require further IVIG doses
What is the definition of a stroke?
A sudden onset of focal neurological signs, of presumed vascular origin, lasting longer than 24 hours
What is the definition of a transient ischaemic attack?
A sudden onset of focal neurological signs, of presumed vascular origin, lasting less than 24 hours
What is the difference between a haemorrhagic stroke and an ischaemic stroke?
A haemorrhagic stroke involves bleeding in to the brain
An ischaemic stroke involves an interruption to the blood supply
How do ischaemic and haemorrhagic strokes show up on CT scans?
An ischaemic stroke will show up as a dark area
A haemorrhagic stroke will show up as a bright white area
What are the symptoms of stroke/TIA in the carotid territory?
- Face/arm/leg weakness
- Dysphasia
- Amaurosis fugax
What are the symptoms of stroke/TIA in the posterior circulation?
- Dysarthria
- Dysphagia
- Diplopia
- Dizziness
- Ataxia
- Diplegia
What is a lacunar infarction?
Occlusion of the deep penetrating arteries, which affects a small volume of subcortical white matter.
What are the lacunar syndromes?
- Pure motor hemiparesis
- Ataxic hemiparesis
- ‘Clumsy hand’ and dysarthria
- Pure hemisensory
- Mixed sensorimotor
When a patient presents with a stroke, a CT scan is done immediately. Why is a follow-up MRI also performed?
- CT cannot usually diagnose an infarct in the acute phase
- MRI more sensitive for picking up abnormalities such as demyelination, mass lesions, microhaemorrhages and lacunar/posterior circulation infarcts.
- Comparison of ADC (apparent diffusion coefficient) and DWI
What should normally be administered to a stroke/TIA patient immediately to break down an acute clot?
IV tissue plasminogen activator e.g. alteplase 0.9mg/kg
Who should not be given alteplase?
- Patients with hypertension due to increased risk of haemorrhage
- Recent major surgery (within past 3 monhts)
- Brain malignancy
What is another acute management option for stroke/TIA besides thrombolysis?
Mechanical thrombectomy
What medication should a stroke/TIA patient take in the long term?
Antiplatelet: Aspirin 300mg for 2 weeks Clopidogrel lifelong Hypertension medication (standard management) Statin Anticoagulant if evidence of AF
How should high risk TIAs be managed?
- Antiplatelet therapy - 300mg aspirin for 2 weeks, switch to clopidogrel
- MRI
- Carotid dopplers to check for stenosis of internal carotid
- 24/72 hour ECG to check for episodes of AF
Which patients with carotid stenosis should be referred to the vascular team?
Those with >50% stenosis
How is severe stenosis of the carotid artery treated?
Two options:
- Carotid endarterectomy (pull the clot out - need to get the whole clot otherwise bits can break off and cause a stroke)
- Carotid stenting
What is the main cause of brain haemorrhage?
Hypertension
What are the other causes of brain haemorrhage besides hypertension?
- Trauma
- Anti-coagulation
- Tumour
- AVM
What are the five steps for managing a haemorrhagic stroke?
- ABCDE - monitoring with regular neuro-observations
- Blood pressure management
- Bleeding tendency? E.g. coagulopathy/low platelets/medication
- Check for underlying malformation (further imaging) e.g. tumour,
aneurysm, AVM) - Neurosurgical intervention
What can happen following a seizure that is sometimes misdiagnosed as a stroke?
Todd’s paresis (post ictal weakness)
What are the two broad categories of head injury?
- Blunt/non-missile
- Penetrating/missile
What focal injuries can be caused as a result of blunt trauma to the head?
- Scalp: contusions, lacerations
- Skull: fractures
- Meninges: haemorrhage, infection
- Brain: contusions, lacerations, haemorrhage, infection
What is a contusion?
A bruise
What injuries can be caused as a result of diffuse brain lesions?
- Diffuse axonal injury
- Diffuse vascular injury
- Hypoxic ischaemic change
- Swelling
What sort of fractures are caused by flat surfaces?
Linear fractures
Extradural haematoma is usually associated with what?
A skull fracture
Extradural haematomas are found in 15% of fatal head injuries. How can they cause death?
- Brain displacement
- Raised ICP
- Herniation
What is the usual cause of subdural haematoma?
Tears in bridging veins (the ones that go from the surface of the brain to the inner surface of the dura mater)
What can a chronic subdural haematoma be mistaken for in elderly patients?
Dementia - can cause progressive cognitive decline
What is the usual cause of subarachnoid haematoma?
Burst aneurysm
How do superficial and deep cerebral and cerebellar haemorrhages appear on imaging?
Superficial haemorrhages are more likely due to severe contusion and appear as one large bleed.
Deep haemorrhages are related to diffuse axonal injury and present as many small bleeds.
What is the major cause of CNS infection?
Skull fracture
What is a ‘contrecoup’ lesion?
A lesion that appears away from the site of impact, usually the inferior surface of the frontal lobe
Contrecoup lesions are more common in which type of head injuries?
People who have been hit on the back of the head
What three things cause brain swelling in trauma patients?
- Congestive brain swelling due to vasodilation and increased cerebral blood volume
- Vasogenic oedema caused by extravasation of oedema fluid from damaged blood vessels
- Cytotoxic oedema due to increased water content of neurons and glia
Which areas of the brain are particularly vulnerable to hypoxia-ischaemia following head trauma?
Hippocampus
Purkinje cells of cerebellum
Chronic traumatic encephalopathy is a long term condition that can result from head injury. What are the features?
- Personality change e.g. irritability, impulsivity, aggression
- Memory loss –> dementia
- Gait problems
- Speech problems
- Parkinsonism
Chronic traumatic encephalopathy is associated with pathology in which protein in 85% of cases?
TDP-43
What would you expect to see on imaging for chronic traumatic encephalopathy?
- Atrophy of neocortex, hippocampus, diencephalon and mamillary bodies
- Neurofibrillary and astrocytic tangles
- Thin corpus callosum
- Wide lateral ventricles
- Tau deposits, particularly around blood vessels
Name 2 ‘hardware problem’ neurodegenerative movement disorders
- Parkinson’s disease
2. Huntington’s disease
Name 3 movement disorders due to ‘circuit problem’ with no cell loss or structural changes
- Essential tremor
- Dystonia
- Tourette
What are the three cardinal features of Parkinson’s?
- Bradykinesia/akinesia
- Tremor (at rest)
- Rigidity
What sort of problems can bradykinesia associated with Parkinson’s cause?
- Problems with doing up buttons, using a keyboard
- Writing smaller
- Deterioration in walking e.g. small steps, dragging one foot
- Decreasing amplitude/accuracy of repetitive movements e.g. foot tapping
Describe the tremor associated with Parkinson’s disease
- Present at rest
- May be unilateral
- Often asymmetrical
What symptoms are associated with rigidity due to Parkinson’s disease?
- Pain (not well localised, usually a dull ache)
- Difficulty turning in bed
What pathological features are present in a brain affected with Parkinson’s?
- Loss of substantia nigra in the mesencephalon
- Presence of Lewy bodies (microscopic)
What three types of drugs are available for treatment of Parkinson’s disease?
- MAO-B inhibitors
- Dopamine agonists
- L-Dopa
Which of the Parkinson’s drugs is the most powerful?
L-Dopa
What motor complications can occur in late stage Parkinson’s?
- Medication doesn’t work as well as previously
- Hyperkinetic, choreiform movements when drugs work
- Fixed, painful dystonic posturing when drugs don’t work
- Unpredictable loss of mobility (freezing)
MAO-B inhibitors are the least powerful of the Parkinson’s drugs, but they help some patients. Name two.
- Rasagiline
2. Selegiline
Dopamine agonists reduce the risk of dyskinesias in the short-medium term in Parkinson’s. Name two.
Ropinirole
Pramipexole
Rotigotine (patches)
Which Parkinson’s patients should be started on dopamine agonists as a first line treatment?
Patients under 60
Which Parkinson’s patients should be started on L-Dopa as a first line treatment?
Patients over 60
What non-motor problems are associated with Parkinson’s disease due to disturbances in the dopamine system?
- Depression and other psychiatric problems
- Dementia
- Autonomic problems e.g. constipation, urinary frequency
What is essential tremor?
Tremor usually on action, not at rest with gradual worsening and no increased tone
What drugs can be used in the treatment of essential tremor?
- Beta blockers (but not in asthma/diabetes)
- Primidone (barbiturate)
- Gabapentin (anticonvulsant)
