NEURO Flashcards
Name 3 types of primary headache
No underlying cause
- Migraine
- Tension headache
- Cluster headache
Name 2 types of secondary headache
Underlying cause
- Meningitis
- Subarachnoid haemorrhage
- Giant cell arteritis
- Idiopathic intracranial hypertension
- Medication overuse headache
Give an example of a tertiary headache
Trigeminal neuralgia
Give 6 questions that are important to ask when taking a history of headache
- Time = onset, duration, frequency, pattern
- Pain = severity, quality, site, spread
- Associated symptoms - n/v, photophobia, phonophobia
- Triggers/aggravating/relieving factors
- Response to attack = is medication useful?
- What are the symptoms like between attacks?
Give 5 red flags for suspected brain tumour in a patient presenting with a headache
- New onset headache and history of cancer
- Cluster headache
- Seizure
- Significantly altered consciousness, memory, confusion
- Papilloedema
- Other abnormal neurological exam
How long do migraine attacks tend to last for?
Between 4-72 hours
Briefly describe the pathophysiology of migraines
- Cerebrovascular constriction –> aura, dilation –> headache
- Spreading of cortical depression
- Activation of CN V nerve terminals in meninges and cerebral vessels
what are the main triggers of migraines?
CHOCOLATE
C - chocolate H - hangovers O - oral contraceptives C - cheese O - orgasms L - lie-ins A - alcohol T - tumult i.e. loud noises E - exercises
Describe the pain of a migraine
A symptoms:
- Unilateral
- Throbbing
- Moderate/severe pain
- Aggravated by physical activity
What other symptoms may a patient with a migraine experience other than pain?
B symptoms:
- Nausea
- Photophobia
- Phonophobia
- Aura
What is a prodrome for migraines?
Precedes migraine by hours-days
- yawning
- food cravings
- changes in sleep, appetite or mood
what is a migraine aura?
Precedes migraine attacks and can be a variety of symptoms
- Visual = lines, dots, zig-zags
- somatosensory = paraesthesia, pins and needles
Dysphagia
Ataxia
what are the differential diagnoses for a migraine?
- Other headache type
- Hypertension
- TIA
- Meningitis
- Subarachnoid haemorrhage
What is the diagnostic criteria for a migraine?
- classified as with or without aura
- at least 2 of:
- unilateral pain (usually 4-72hrs)
- throbbing-type pain
- moderate > severe intensity
- motion sensitivity
plus at least 1 of:
- nausea/vomiting - photophobia/phonophobia
there must also be a normal examination and no attributable cause
How can migraines be subdivided?
- Episodic with (20%)/without (80%) aura
2. Chronic migraine
what is the treatment for migraines
- triptans e.g. sumatriptan
- NSAIDs e.g. naproxen
- anti-emetic e.g. prochlorperazine
- AVOID opioids and ergotamine
How does triptan work?
Selectively stimulates 5-hydroxytryptamine (serotonin) receptors in the brain
How long do tension headaches usually last for?
From 30 minutes to 7 days
what are tension headaches?
most common chronic daily and recurrent headache
Can be episodic <15 days/month or chronic >15 days/month (for at least 3 months)
There is no known organic cause, however a number of triggers exist
Would a patient with a tension headache experience any other symptoms other than pain?
NO
Nausea, photophobia and photophobia would NOT be associated
How do you treat a tension headache?
avoidance of triggers and stress relief
symptomatic relief:
- aspirin
- paracetamol
- ibuprofen / diclofenac
- AVOID OPIOIDS
limit analgesics to no more than 6 days per month to reduce risk of medication-overuse headaches
what is the clinical presentation of a cluster headache?
- rapid onset excruciating pain, classically around the eye (or temples/forehead)
- pain is unilateral and localised.
- pain rises to crescendo over a few minutes and lasts for 15-160 minutes, once or twice daily (usually around the same time)
- ipsilateral autonomic features:
- watery/bloodshot eye
- facial flushing
- rhinorrhoea (blocked nose)
- miosis (pupillary constriction) +/- ptosis
How can cluster headaches be subdivided?
Episodic = >2 cluster periods lasting 7 days - 1 year separated by pain free periods lasting >1 month Chronic = attack occur for >1 year without remission or remission lasting <1 month
How long do cluster headaches tend to last?
Between 15 minutes and 3 hours
Mostly nocturnal
what is the treatment for cluster headaches?
FOR ACUTE ATTACKS:
- analgesics are unhelpful
- 15L 100% O2 for 15mins via non-rebreather mask
- triptans e.g. sumatriptan
What is the most common type of secondary headache?
Medication overuse headache - episodic headache becomes daily chronic headache
Describe the pain of trigeminal neuralgia
- Unilateral face pain
- Severe intensity
- Electric shock like, shooting, stabbing or sharp
- No radiation beyond the trigeminal distribution
Describe the epidemiology of trigeminal neuralgia
Peak age = 50-60 years
Women > men
Give 3 causes of trigeminal neuralgia
- Compression of trigeminal nerve by a loop of vein or artery
- Aneurysms
- Meningeal inflammation
- Tumours
How long does the pain associated with trigeminal neuralgia usually last for?
A few seconds
Maximum 2 minutes
What is the treatment for trigeminal neuralgia?
Carbamazepine - suppresses attacks
Less effective options = phenytoin, gabapentin and lamotrigine
Surgery = microvascular decompression, gamma knife surgery
What features might be present in the history of a headache that make you suspect meningitis?
- Pyrexia
- Photophobia
- Neck stiffness
- Non-blanching purpura rash
At what level is a lumbar puncture done and why is an LP done?
L3/4 or L4/5
To obtain a CSF sample
What does a small response on an nerve conduction study suggest?
There is axon loss
What does a slow response on an nerve conduction study suggest?
There is myelin loss
Define encephalopathy
Reduced level of consciousness/diffuse disease of brain substance
Define neuropathy
Damage to one or more peripheral nerve, usually causing weakness and/or numbness
Define myelitis
Inflammation of the spinal cord
Define meningitis
Infection and inflammation of the meninges of the brain
it is a notifiable disease
Name 3 bacterial organisms that cause meningitis in adults
- N. meningitidis
- S. pneumoniae
- H. influenzae
Name 2 bacterial organisms that cause meningitis in neonates
- E.coli
2. Group B strep - strep agalactiae
Name 3 viruses that can cause meningitis
- Enterovirus (most common viral)
- HSV
- CMV
- Varicella zoster virus
Name 2 organisms that can cause meningitis in immunocompromised patients
- CMV
- Cryptococcus
- TB
- HIV
- herpes simplex
Give the main triad of symptoms of meningitis
Headache + neck stiffness + fever
what are the symptoms of meningitis
- Neck stiffness
- Photophobia
- Papilloedema (due to increased ICP)
- Petechial non-blanching rash
- Headache
- Fever
- Decreased GCS
what are the signs of meningitis
Kernig’s sign = unable to straighten leg more than 135 degrees without pain when hip is flexed to 90 degrees
Brudzinski’s sign = severe neck stiffness cause hip and knees to flex when neck is flexed
How would you describe the rash associated with meningococcal sepsis?
Petechial non-blanching rash
What investigations might you do in someone you suspect has meningitis?
- Blood cultures (pre LP)
- Bloods - FBC, U+E, CRP, ESR, serum glucose, lactate
- Lumbar puncture (contraindicated with raised ICP)
- CT head - exclude lesions
- Throat swabs - bacterial and viral
What is the treatment of bacterial meningitis?
- ABCDE + support
- Empirical therapy = IV Benzylpenicillin
Assess GCS - First line = Ceftriaxone / Cefotaxime
- Add IV Benzylpenicillin for rash
- Penicillin allergy = Chloramphenicol
- Immunocompromised ( Risk of Listeria) = Amoxicillin / Ampicillin
oral dexamethasone to reduce cerebral oedema
What is the treatment of viral meningitis?
Watch and wait
acyclovir
What is the treatment for meningococcal septicaemia?
IV BENZYLPENICILLIN (in community)
IV CEFOTAXIME (in hospital)
What can be given as prophylaxis against meningitis?
IV CIPROFLOXACIN (all ages and pregnancy) and IV RIFAMPICIN (all ages but NOT pregnancy)
For which bacteria is meningitis prophylaxis effective against?
N. meningitidis
Give 4 potential adverse effect of a lumbar puncture
- Headache
- Paraesthesia
- CSF leak
- Damage to spinal cord
What investigations would you do on a CSF sample?
Protein and glucose levels
MCS
Bacterial and viral PCR
When would you do a CT before an LP?
>60 Immunocompromised History of CNS disease New onset/recent seizures Decreased GCS Focal neurological signs Papilloedema
What is the colour of the CSF in someone with a bacterial infection?
Cloudy (normally it is clear)
Give 4 reasons why a lumbar puncture might be contraindicated
- Thrombocytopenia
- Delay in Abx admin
- Signs of raised ICP
- Unstable cardio or resp systems
- Coagulation disorder
- Infections at LP site
- Focal neurological signs
Define encephalitis
Infection and inflammation of the brain parenchyma
In what group of people is encephalitis common?
Immunocompromised
the infections are most frequent in children and elderly
What area of the brain does encephalitis mainly affect?
Frontal and temporal lobes
what are the viral causes of encephalitis
- Herpes simplex (most common)
- CMV
- Epstein Barr
- varicella zoster
- HIV
- measles
- mumps
what are the non-viral causes of encephalitis
- Bacterial meningitis
- TB
- Malaria
- Lyme’s disease
Name the main triad of symptoms of encephalitis
Fever + headache + altered mental state
what is the clinical presentation of encephalitis?
begins with features of viral infection:
- fever, headaches, myalgia, fatigue, nausea
progresses to:
- personality & behavioural changes
- decreased consciousness, confusion, drowsiness
- focal neurological deficit - hemiparesis, dysphagia
- seizures
- raised ICP and midline shift
- coma
What would the LP show from someone with encephalitis?
- CSF shows elevated lymphocyte count
- viral detection by CSF PCR
What investigations might you do on someone with encephalitis?
- MRI - shows areas of inflammation, may be midline shifting
- EEG - periodic sharp and slow wave complexes
- lumbar puncture
- blood and CSF serology
What is the treatment for encephalitis?
- IV Acyclovir immediately - even before investigation results
- Primidone = anti-seizure medication if needed
- IV benzylpenicillin if meningitis is suspected
How does herpes zoster occur?
Reactivation of varicella zoster virus, usually within the dorsal root ganglia
where does herpes zoster commonly occur?
- thoracic nerves
- ophthalmic division of trigeminal nerve
- cervical, lumbar and sacral nerve roots
what is the clinical presentation of herpes zoster?
- Pain and paraesthesia in dermatomal distribution priced rash for days
- Malaise, myalgia, headache and fever can be present
- Can be over a week before eruption appears
- Rash - consists of papules and vesicles
RESTRICTED to SAME DERMATOME:
• Neuritic pain
• Crust formation and drying occurs over the next week with resolution in 2-3 weeks
• Patients are infectious until lesions are dried
• RASH DOES NOT EXTEND OUTSIDE DERMATOME
Describe the treatment for herpes zoster
Antiviral therapy within 72 hours of rash onset - ACYCLOVIR or VALICICLOVIR or FAMCICLOVIR
Analgesia - IBUPROFEN
Briefly describe the pathophysiology of herpes zoster
Latent virus is reactivated in dorsal root ganglia –> travels down affected nerve via sensory root in dermatomal distribution –> perineural and intramural inflammation
What dermatome is herpes zoster most likely to affect?
Thoracic nerves
Then ophthalmic division of trigeminal
Give 2 complications of herpes zoster
- Ophthalmic branch of trigmeinal = damages sight
2. Post herpetic neuralgia - pain lasts >4 months after
What is MS?
A chronic autoimmune, T-cell mediated inflammatory condition of the CNS characterised by multiple plaques of demyelination within the brain and spinal cord, occurring sporadically over years
Briefly describe the pathophysiology of MS
- Autoimmune inflammation causes CD4 mediated destruction of oligodendrocytes
- This causes demyelination of CNS neurones. The myelin sheath regenerates but is less efficient
- Repeated demyelination leads to axonal loss and incomplete recovery between attacks
- Poor demyelination healing results in relapsing and remitting symptoms
- Multiple areas of sclerosis (scar tissue) form along neurones which slow/block conduction of signals thus impairing movement and/or sensation
What is MS characterised by?
Disseminated in space and time
Hypercellular plaque formation
BBB disruption
what are the different types of MS?
- Relapsing remitting (80%)
- secondary progressive MS
- primary progressive MS
what are the causes/risk factors of MS?
Unknown Environment and genetic components - exposure to EBV in childhood - low levels of sunlight and vitamin D - female - white - living far from equator
Describe the epidemiology of MS
Presenting between 20-40 y/o
Females > Males
More common in white populations
what are the symptoms of MS?
TEAM
- Tingling
- Eye = optic neuritis
- Ataxia
- Motor - spastic paraparesis, pyramidal weakness (UL = extensors, LL = flexors)
- swallowing disorders
- bladder incontinence
- dizziness, falls
- constipation
- fatigue
- cognitive impairment, depression
what are the signs of MS?
- Lhermitte sign - electric jolt felt down the spine when flexing neck
- Uhthoff phenomenon - symptoms worse with heat, e.g. hot bath/exercise
What can exacerbate the symptoms of MS?
Heat (e.g. a warm shower)
Name 3 differential diagnosis’s of MS
- SLE
- Sjogren’s
- AIDS
- Syphilis
What investigations might you do in someone to see if they have MS?
● Symptoms must be disseminated in time and space
MRI = gold standard
- GD-enhancing plaques
● Lumbar puncture = oligoclonal IgG bands
● Bloods = rule out other causes
What is the diagnostic criteria for MS?
> 2 CNS lesions disseminated in time and space (>2 attack affected different parts of the CNS)
Describe the non-pharmacological treatment for MS
must notify DVLA
Regular exercise, smoking and alcohol cessation, low stress lifestyle
Psychological therapies
Speech therapists
Physio and OR
Describe the pharmacological treatment for MS
acute relapse
- steroids = IV METHYLPREDNISOLONE
chronic/frequent relapse
- biological - SC BETA INTERFERON (contraindicated in pregnancy)
- DMARDs - IV alentuzumab, IV natalizumab
What symptomatic treatments can you give to those with MS?
Spasticity
- BACLOFEN (GABA analogue, reduces Ca2+ influx)
- TIZANIDINE (alpha-2 agonist)
- BOTOX INJECTION (reduces ACh in neuromuscular junction)
urinary incontinence = catheterisation
incontinence
- DOXAZOSIN (anti-cholinergic alpha blocker drugs
What medication might you give to someone to reduce the relapse severity of MS?
Short course steroids - methylprednisolone
Define epilepsy
Recurrent, spontaneous, intermittent abnormal electrical activity in part of the brain, manifesting seizures
Define epileptic seizure
Paroxysmal event in which changes of behaviour, sensation or cognitive processes are caused by excess, hypersynchronous neuronal discharge in the brain
Give 5 causes of epilepsy
- Idiopathic (2/3)
- cortical scarring
- tumour
- stroke
- alzheimers dementia
- alcohol withdrawal
What 2 categories can epileptic seizures be broadly divided into?
- Focal epilepsy - only one portion of the brain is involved
- Generalised epilepsy - whole brain is affected
Give 2 examples of focal epileptic seizures
- Simple partial seizures
2. Complex partial seizures
Give 3 examples of generalised epileptic seizures
- Absence seizures
- Tonic-clonic seizure (grand mal)
- Myoclonic seizure (isolated jerking)
- Atonic seizure (floppy)
- tonic seizure (high tone)
- clonic seizure (jerking)
what are the different components of an epileptic seizure?
- prodrome
- aura
- post-ictal
What is aura?
- Part of the seizure where the patient is aware & often precedes other manifestations
- Eg. strange feelings in gut, déjà vu, strange smells, flashing lights
- Often implies a partial seizure
If a patient experienced epilepsy with aura, what other symptoms would they get?
Strange feeling in gut
Deja vu
Strange smells
Flashing lights
Name 3 post-ictal symptoms
- Headache
- Confusion
- Myalgia
- Temporary weakness (focal seizure)
What is the diagnostic criteria for epilepsy?
At least 2 or more unprovoked seizures occurring >24 hours apart
One unprovoked seizure + probability of future seizures
Epileptic syndrome diagnosis
What is the treatment for focal epileptic seizures?
Lamotrigine = 1st line Carbamazepine = 2nd line
How do lamotrigine and Carbamazepine work?
Inhibit pre-synaptic Na+ channels so prevent axonal firing
What is the treatment for generalised epileptic seizures?
Sodium valproate = 1st line
Lamotrigine = 2nd line
How does sodium valproate work?
Inhibits voltage gated Na+ channels and increases GABA production
What medication can control seizures?
Diazepam or lorazepam
What possible surgery could you do to treat epilepsy?
Vagal nerve stimulation
Resection of affected area
Give 4 potential side effects of anti-epileptic drugs (AED’s)
- Cognitive disturbances
- Heart disease
- Drug interactions
- Teratogenic
Give 4 differential diagnosis’s of epilepsy
- Syncope
- Non-epileptic seizure
- Migraine
- Hyperventilation
- TIA
Define syncope
Insufficient blood or oxygen supply to the brains causes paroxysmal changes in behaviour, sensation and cognitive processes
Caused by sitting/standing
5-30 seconds duration
Define non-epileptic seizure
Mental processes associated with psychological distress causes paroxysmal changes in behaviour, sensation and cognitive processes
1-20 minute duration
Closed eyes and mouth
A patient complains of having a seizure. An eye-witness account tells you that the patient had their eyes closed, was speaking and there was waxing/waning/pelvic thrusting. They say the seizure lasted for about 5 minutes. Is this likely to be an epileptic or a non-epileptic seizure?
A non-epileptic seizure
A patient complains of having a seizure. An eye-witness account tells you that the patient was moving their head and biting their tongue. They say the seizure lasted for just under a minute. Is this likely to be an epileptic or a non-epileptic seizure?
An epileptic seizure
A patient complains of having a ‘black out’. They tell you that before the ‘black out’ they felt nauseous and were sweating. They tell you that their friends all said they looked very pale. Is this likely to be due to a problem with blood circulation or a disturbance of brain function?
This is likely to be due to a blood circulation problem e.g. syncope
Name 3 intra-cranial haemorrhages
- Sub-arachnoid haemorrhage
- Sub-dural haemorrhage
- Extra-dural haemorrhage
What can cause a subarachnoid haemorrhage?
- Traumatic injury
- Berry aneurysm rupture
(70-80%) - at common points round Circle of Willis - Arteriovenous malformations (15%) - abnormal tangle of blood vessels connecting arteries and veins
- Idiopathic (15-20%)
Give 3 risk factors for a subarachnoid haemorrhage
Hypertension
Known aneurysm
Previous aneurysmal SAH
Smoking
Alcohol
Family history
Bleeding disorders
- associated with berry aneurysms:
- Polycystic Kidney Disease
- Coarctation of aorta
- Ehlers-Danlos syndrome & Marfan syndrome
Briefly describe the pathophysiology of a subarachnoid haemorrhage
- tissue ischaemia - less blood, O2 and nutrients can reach the tissue due to bleeding loss -> cell death
- raised ICP - fast flowing arterial blood is pumped into the cranial space
- space occupying lesion - puts pressure on the brain
- brain irritates meninges - these inflame causing meningism symptoms. This can obstruct CSF outflow -> hydrocephalus
- vasospasm - bleeding irritates other vessels -> ischaemic injury
what are the symptoms of a subarachnoid haemorrhage?
- sudden onset excruciating headache - thunderclap, worst headache, typically occipital
- sentinel headache - before main rupture, sign of warning leak
- nausea
- vomiting
- collapse
- loss of/depressed consciousness
- seizures
- vision changes
- coma - can last for days
what are the signs of a subarachnoid haemorrhage?
signs of meningeal irritation
- Kernig’s sign (can’t straighten leg past 135 degrees)
- neck stiffness
- Brudzinski’s sign (Severe neck stiffness causes a patient’s hips and knees to flex when the neck is flexed)
- retinal, subhyaloid and vitreous bleeds
- worse prognosis
- with/without papilloedema
- neurological signs - e.g. 3rd nerve palsy
- increased BP
What investigations might you do to see if someone has a subarachnoid haemorrhage?
- urgent Head CT = star pattern (diagnostic)
- Lumbar Puncture = xanthochromia -> RBC breakdown (only if normal ICP and after 12 hrs)
- MR/CT angiography - to establish source of bleeding
Describe the treatment for a subarachnoid haemorrhage
- NIMOPIDINE for 3 weeks -> CCB which prevents vasospasm so reduces cerebral ischaemia
- surgery = endovascular coiling
- IV fluids - maintain cerebral perfusion
- ventricular drainage for hydrocephalus
Give 3 possible complications of a subarachnoid haemorrhage
- Rebleeding (common = death)
- Cerebral ischaemia
- Hydrocephalus
- Hyponatraemia
What can cause a subdural haematoma?
Head injury –> vein rupture
Describe the pathophysiology of a subdural haematoma
- bleeding from bridging veins into the subdural space forms a haematoma
- then bleeding stops
- weeks/months later the haematoma starts to autolyse - massive increase in oncotic and osmotic pressure. Water is sucked in and haematoma enlarges
- gradual rise in ICP over weeks
- midline structures shift away from side of clot - causes tentorial herniation and coning
What causes water to be sucked up into a subdural haematoma 8-10 weeks after a head injury?
Clot starts to break down and there is massive increase in oncotic pressure –> water is sucked up by osmosis into the haematoma
Give 3 risk factors of a subdural haematoma?
- Elderly - brain atrophy, dementia
- Frequent falls - epileptics, alcoholics
- Anticoagulants
- babies - traumatic injury (“shaking baby syndrome”)
what are the signs and symptoms of a subdural haematoma?
SYMPTOMS:
- Fluctuating GCS
- Headache
- Confusion - may fluctuate
- Drowsiness
- physical and intellectual slowing
- personality change
- unsteadiness
SIGNS
- raised ICP - seizures
- localising neurological signs (unequal pupils, hemiparesis)
Name 3 differential diagnosis’s of a subdural haematoma
- Stroke
- Dementia
- CNS masses (tumour vs abscess)
What are the investigations for a subdural haematoma?
- CT SCAN:
- crescent shaped haematoma = BANANA SHAPE (clot turns from white to grey over time)
- unilateral
- shows midline shift
- crescent shaped haematoma = BANANA SHAPE (clot turns from white to grey over time)
- MRI SCAN
What is the treatment for a subdural haematoma?
SURGERY
- 1* = irrigation via burr-hole craniostomy
- 2* = craniotomy
IV MANNITOL - to reduce ICP
address cause of trauma
What can cause an extradural haematoma?
Traumatic head injury resulting in a skull fracture (often temporal bone) –> middle meningeal artery rupture –> bleed
what is the pathophysiology of extradural haematoma?
Blood accumulates rapidly in the space between the dura and the skull (over minutes to hours)
After a lucid interval there is:
- rapid rise in ICP
- pressure on the brain
- midline shift
- tentorial herniation
- coning
what is the clinical presentation of an extradural haematoma?
- initial injury followed by lucid period
- period of rapid deterioration
- rapid decline in GCS
- increasing severe headache
- vomiting
- seizures
- hemiparesis
- coma
- UMN signs
- ipsilateral pupil dilation
- bilateral limb weakness
- deep and irregular breathing - due to coning
- late signs = bradycardia and raised BP
- death from respiratory arrest
What investigations might you do to see if someone has an extradural haematoma? What are the results
CT SCAN
- lens shaped haematoma = LEMON SHAPE
- doesn’t cross suture lines
- shows midline shift
SKULL X-RAY
- fracture lines may be seen
LP is CONTRAINDICATED
What do the ventricles do to prolong survival in someone with an extradural haematoma?
Get rid of CSF to prevent rise in ICP
What is the treatment for an extradural haematoma?
STABILISE PATIENT
URGENT SURGERY
- clot evacuation
- ligation of bleeding vessel
IV MANNITOL
- to reduce ICP
airway care
- intubation and ventilation
Give 3 differences in the presentation of a patient with a subdural haematoma in comparison to an extradural haematoma
- Time frame: extra-dural symptoms are more acute
- GCS: sub-dural GCS will fluctuate whereas GCS will drop suddenly in someone with an extra-dural haematoma
- CT: extra-dural haematoma will have a lens appearance whereas subdural will have a crescent shaped haematoma
Define weakness
Impaired ability to move a body part in response to will
Define paralysis
Ability to move a body part in response to will is completely lost
Define ataxia
Willed movements are clumsy, ill-direction or uncontrolled
Define involuntary movements
Spontaneous movement independent of will
Define apraxia
Disorder of conscious organised pattern of movement or impaired ability to recall acquired motor skills
Give 3 things that modulate LMN action potential transmission to effectors
- Cerebellum
- Basal ganglia
- Sensory feedback
Give 3 disease that are associated with motor neurone damage
- Motor neurone disease
- Spinal atrophy
- Poliomyelitis
- Spinal cord compression
Give 3 pathologies that are associated with ventral spinal root damage
- Prolapsed intervertebral disc
- Tumours
- Cervical or lumbar spondylosis
Name a disease associated with NMJ damage
Myasthenia Gravis
Describe the pyramidal pattern of weakness in the upper limbs
Flexors are stronger than extensors
Describe the pyramidal pattern of weakness in the lower limbs
Extensors are stronger than flexors
What is a UMN?
A neurone that is located entirely in the CNS
Its cell body is located in the primary motor cortex
Give 3 causes of UMN weakness
- MS
- Brain tumour
- Stroke
- MND
Give 4 sites of UMN damage
- Motor cortex lesions
- Internal capsule
- Brainstem
- Spinal cord
Give 4 signs of UMN weakness
- Spasticity
- Increased muscle tone (hypertonia)
- Hyper-reflexia
- Positive babinski’s reflex
Give 4 signs of LMN weakness
- Flaccid
- Hypotonia
- Hypo-reflexia
- Muscle atrophy
- Fasciculation’s
Define motor neurone disease (MND)
A group of neuro degenerative disorders that selectively affect the motor neurons
Most in the anterior horn, cells of the spinal cord and the motor cranial nuclei
There are no sensory problems
Does MND affect UMN or LMN?
Both UMN and LMN can be affected
Does MND affect eye movements?
Never affects eye movements (clinical feature of myasthenia gravis)
Does MND cause sensory loss or sphincter disturbance?
No (clinical feature of MS)
What is the epidemiology of MND?
- relatively uncommon
- males > females (3:2)
- often fatal in 2-4 years
What is the clinical presentation of MND?
- results in mixed UMN and LMN presentation (LMN symptoms predominate)
- wrist drop/foot drop
- change in appearance of hands - wasting
- gait disorders/tendencies to trip
- excessive fatigue
What investigations might you do in someone you suspect to have MND?
Head/spine MRI Blood tests = muscle enzymes, autoantibodies Nerve conduction studies EMG Lumbar Puncture
What is the diagnostic criteria for MND?
LMN + UMN signs in 3 regions
El Escorial criteria
- Presences of LMN and UMN degeneration and progressive history
- Absence of other disease processes
What is the treatment for MND?
- MDT care
- anti-glutaminergic drugs - ORAL RILUZOLE - Na+ channel blocker, inhibits glutamate release
- Drooling - ORAL PROPANTHELINE or ORAL AMITRIPTYLINE
- Dysphagia: NG tube
- Spasms: ORAL BACLOFEN
- Non-invasive ventilation
- Analgesia e.g. NSAIDs - DICLOFENAC
Give 3 limb onset symptoms of MND
- Weakness
- Clumsiness
- Wasting of muscles
- Foot drop
- Tripping
Give 3 respiratory onset symptoms of MND
- Dyspnoea
- Orthopnoea
- Poor sleep
Would you do a LP in a patient that has a raised ICP?
NO
LP is contraindicated if they have a raised ICP due to the risk of coning
Give 4 signs of raised ICP
- Papilloedema
- Focal neurological signs
- Loss of consciousness
- New onset seizures
What is the treatment for raised ICP?
Osmotic diuresis with mannitol
Explain the ICP/volume curve
Volume increase –> ICP plateau (compensate) –> rapid ICP increase
What are the 4 cardinal presenting symptoms of brain tumours?
- Raised ICP –> headache, decrease GCS, n+v, papilloedema
- Progressive neurological deficit –> deficit of all major functions (motor, sensory, auditory, visual) + personality change
- Epilepsy
- lethargy/tiredness - caused by pressure on brainstem
You ask a patient with a brain tumour about any facts that aggravate their headache, what might they say?
- Worse first thing in the morning
2. Worse when coughing, straining or bending forward
Name 2 differential diagnosis’s for a brain tumour
- Aneurysm
- Abscess
- Cyst
- Haemorrhage
- Idiopathic intracranial hypertension
What investigations might you do in someone you suspect to have a brain tumour?
CT/MRI head and neck
Biopsy - via burr hole
blood tests - FBC, U&E, LFTs, B12
LP = CONTRAINDICATED (high ICP)
Where might secondary brain tumours arise from?
- non-small cell lung cancer
- small cell lung cancer
- breast
- melanoma
- renal cell carcinoma
- GI
Describe the treatment for secondary brain tumours
- surgery - if age <75yrs
- radiotherapy
- chemotherapy
- palliative therapy
From what cells to primary brain tumours originate?
Glial cells (gliomas)
- Astrocytoma (85-90%)
- Oligodendroglioma
Other primary = meningioma, schwannoma, medulloblastoma
Describe the WHO glioma grading
Grade 1 = benign paediatric tumour
Grade 2 = Pre-malignant tumour (benign)
Grade 3 = ‘Anaplastic astrocytoma’ (cancer)
Grade 4 = Glioblastoma multiforme (GBM) - malignant
Describe the epidemiology of grade 2 gliomas
Disease of young adults
Give 3 causes of grade 2 glioma deterioration
- Tumour transformation to a malignant phenotype
- Progressive mass effect due to slow tumour growth
- Progressive neurological deficit form functional brain destruction by tumour
Describe the common pathway to a GBM (grade 4 brain tumour)
Initial genetic error of glucose glycolysis –> Isocitrate Dehydrogenase 1 mutation –> excessive build up of 2-hydroxyglutarate –> genetic instability of glial cells –> grade II-IV glioma transform into glioblastoma
Give 5 good prognostic factors for GBM
- <45 y/o
- Aggressive surgical therapy
- Good performance post-surgery
- Tumour that has transformed from previous lower grade tumour
- MGMT mutant - will respond will to chemo
Describe the treatment for GBM
- Resective surgery
- Adjuvant chemotherapy with Temozolomide
- Dexamethasone - reduces tumour inflammation/oedema
- anticonvulsants - oral carbimazepine
- palliative care
How does Temozolomide work in treatment for GBM?
Methylates guanine in DNA making replication impossible
MGMT gene reverses it = tumour resistance
Define dementia
A set of symptoms that may include memory loss and difficulties with thinking, problem solving or language
There is a progressive decline in cognitive function
Describe the epidemiology of dementia
Rare <55
10% of people >65
20% of people >80
Give 3 causes of dementia
- Alzheimer’s disease (50%)
- Vascular dementia (25%)
- Lewy body dementia (15%)
- Fronto-temporal (Pick’s)
- Huntington’s
- Liver failure
- Vitamin deficiency - B12 or folate
Give 3 risk factors of dementia
- Family history
- Age
- Down’s syndrome
- Alcohol use, obesity, HTN, hyperlipidaemia, DM
- Depression
- ? Head injury
Describe the pathophysiology of Alzheimer’s disease
Degeneration of temporal lobe and cerebral cortex, with cortical atrophy
Accumulation of beta-amyloid peptide –> progressive neuronal damage, neurofibrillary tangles, increase in number of amyloid places and loss of ACh
what is the clinical presentation of Alzheimer’s Disease
● Memory - episodic and semantic ● Language - difficulty understanding or finding words ● Attention and concentration issues ● Psychiatric changes, e.g. withdrawal, delusions ● Disorientation, e.g. time and surroundings
Give 2 histological signs of Alzheimer’s dementia
- Plagues of amyloid
2. Neurofibrillary tangles
25% of all patients with Alzheimer’s Disease will develop what?
Parkinsons
What does vascular dementia often present with?
● Characterised by stepwise progression - Periods of stable symptoms, followed by a sudden increase in severity
● Presentation varies massively but can include:
- Visual disturbances,
- UMN signs (e.g. muscle weakness, overactive reflexes, clonus),
- attention deficit,
- depression,
- incontinence,
- emotional disturbances
○ If infarct was subcortical, then expect to see dysarthria and parkinsonisms
Describe the pathophysiology of Lewy body dementia
● Characterised by eosinophilic intracytoplasmic neuronal inclusion bodies (Lewy bodies) in the brainstem and neocortex
● Also see substantia nigra depigmentation and amyloid deposits
what are the clinical features of Lewy body dementia
● Dementia is often presented initially
○ Memory loss, spatial awareness difficulties,
loss of cognitive function
● Parkinsonisms, e.g. tremor, rigidity, change in gait
● Visual hallucinations
● Sleep disorders, restless leg syndrome
Frontal lobe atrophy is seen on an MRI, what kind of dementia is this patient likely to have?
Fronto-temporal
= frontal and temporal lobe atrophy
Give 3 symptoms of Fronto-temporal dementia
● Onset tends to be insidious and progressive
● Present with 3 main symptoms:
○ Behavioural issues, e.g. loss of inhibition/empathy, compulsive behaviours, difficulty planning
○ Progressive aphasia, e.g. slow, difficult speech, grammatical errors
○ Semantic dementia, e.g. loss of vocabulary, problems understanding
What is functional memory dysfunction?
Acquired dysfunction of memory that significantly affects a person’s professional/private life in absence of an organic cause
How could you determine whether someone has functional memory dysfunction or a degenerative disease?
When asked the question ‘when was the last time your memory let you down?’, someone with functional memory dysfunction would give a good detailed answer whereas someone with degenerative disease would struggle to answer
What investigations can you do in primary care to determine whether someone might have dementia?
- Good history of symptoms
- 6 item cognitive impairment test (6CIT)
- Blood tests - FBC, liver biochemistry, TFTs, vitamin B12 and folate
- Mini mental state examination = screening
What questions are asked in 6CIT?
- What year is it?
- What month is it?
- Give an address with 5 parts
- Count backwards from 20
- Say the months of the year in reverse
- Repeat the address
What secondary care investigation can you do to investigate a dementia diagnosis?
Brain MRI - where and extent of atrophy
Brain function tests = PET, SPECT and functional MRI
Brain CT
Myeloid and tau histopathology
Name the staging system that classifies the degree of pathology in AD
Braak staging
Stage 5/6 = high likelihood of AD
Stage 3/4 = intermediate likelihood
Stage 1/2 = low likelihood
Give 3 ways in which dementia can be prevented
- Smoking cessation
- Healthy diet
- Regular exercise
- Low alcohol
- Engaging in leisure activités
What support should be offered to patients with dementia?
Social suport
Cognitive support
Specialist memory service
What medications might you use in someone with dementia?
Acetylcholinesterase inhibitors - increase ACh = donepezil, rivastigmine Control BP (ACEi) to reduce further vascular damage
What is myasthenia gravis?
Autoimmune disease against nicotinic acetylcholine receptors in the neuromuscular junction
what is the pathophysiology behind myasthenia gravis?
Autoantibodies (IgG) attach to ACh receptor and destroy them –> fewer action potentials fire –> muscle weakness and fatigue
what are the causes/risk factors for myasthenia gravis?
If <50 = associated with other AI conditions (pernicious anaemia, SLE, RA) and more common in women
If >50 = associated with thymic atrophy, thymic tumour, SLE and RA and more common in men
what are the clinical features of myasthenia gravis?
- Muscle weakness
- Increasing muscular fatigue
- Ptosis
- Diplopia
- Myasthenic snarl
- Tendon reflexes normal but fatigable
● Weakness is more marked in proximal muscles ● Weakness might be seen in: ○ Small muscle of the hands ○ Deltoid and triceps muscles ○ Bulbar muscles ○ Muscles involved in chewing ● No muscle wasting, sensation is unimpaired ● Seizures can occur
What muscle groups are affected in myasthenia gravis?
muscle groups affected in order:
- extra-ocular
- bulbar - chewing and swallowing
- face
- neck
- trunk
What can weakness due to myasthenia gravis be worsened by?
Pregnancy Hypokalaemia Infection Emotion Exercise Drugs (opiates, BB, gentamicin, tetracycline)
What investigations might you do to see if someone has myasthenia gravis?
- mostly clinical examination
- positive tensilon test
- anti-AChR antibodies
- TFTs
- EMG
- CT of thymus
- crushed ice test - ice is applies to ptosis for 3 mins, if it improves it is likely to be myasthenia gravis
Give 3 possible differential diagnosis’s for myasthenia gravis
- MS
- Hyperthyroidism
- Acute Guillain-Barre syndrome
- Lamert-Eaton myasthenia syndrome
What is treatment for myasthenia gravis?
Anti-cholinesterase = pyridostigmine
Immunosuppression = prednisolone (with alendronate - bisphosphonate)
Steroids can be combined with azathioprine or methotrexate
Thymectomy
When is a thymectomy considered as a treatment for myasthenia gravis?
Onset <50 y/o and it is poorly controlled
Give a complication of myasthenia gravis
Myasthenic crisis
Weakness of respiratory muscle during relapse
Treatment = plasmapheresis and IV immunoglobulin