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Phase 2A > Neurology 2 > Flashcards

Neurology 2 Flashcards

1
Q

what is the epidemiology of cauda equina syndrome?

A
  • rare, occurring mainly in adults but can occur at any age
  • occurs in around 2% of herniated discs
  • common cause is lumbar disc herniation at L4/5 and L5/S1
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2
Q

what is the causes/risk factors of cauda equina syndrome?

A
  • herniation of lumbar disc; most commonly at L4/5 and L5/S1
  • tumours/metastases
  • trauma
  • infection
  • spondylolisthesis
  • post-op haematoma
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3
Q

what is the pathophysiology of cauda equina syndrome?

A
  • nerve root compression caudal to the termination of the spinal cord at L1/2
  • usually large central disc herniations at L4/5 or L5/S1 levels
  • generally S1-S5 nerve root compression; important in bladder function
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4
Q

what is the clinical presentation of cauda equina syndrome?

A
  • major difference between cauda equina and lesions
    higher up in the cord is that leg weakness is flaccid and areflexic (LMN) and not spastic and hyperreflexic
  • bilateral sciatica
  • saddle anaesthesia
  • bladder/bowel dysfunction
  • erectile dysfunction
  • variable leg weakness that is flaccid and areflexic
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5
Q

what is sciatica?

A

sciatica is pain, numbness and a tingling sensation that

radiates from lower back and travels down one of the legs to the foot and toes

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6
Q

what are differential diagnoses of cauda equina syndrome?

A

conus medullaris syndrome, vertebral fracture, peripheral neuropathy, mechanical back pain

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7
Q

what is used to diagnose cauda equina syndrome?

A
  • MRI to localise lesion
  • knee flexion; test L5-S1
  • ankle plantar flexion (downwards); tests S1-S2
  • straight leg raising; L5,S1, root problem; people with acute disc can barely get leg off bed
  • femoral stretch test; L4 root problem
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8
Q

what is treatment of cauda equina syndrome?

A

refer to neurosurgeon ASAP to relieve pressure or risk irreversible paralysis/sensory loss/incontinence!:
• microdiscectomy - may tear dura
• epidural steroid injection - more effective for leg pain
• surgical spine fixation if vertebra slipped
• spinal fusion reduces pain from motion and nerve root inflammation

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9
Q

what is multiple sclerosis? what areas of the nervous system does it affect?

A
  • chronic autoimmune, T-cell mediated inflammatory disorder of the CNS in which there are multiple plaques of demyelination within the brain and spinal cord, occurring sporadically over years
  • disease of the CNS with oligodendrocytes targeted, affects the white matter of brain
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10
Q

what is the epidemiology of multiple sclerosis?

A
  • begins in early adulthood
  • more common in females than males
  • presentation is typically between 20-40yrs
  • presentation after 60 yrs is rare
  • more common in white populations
  • more common the further from the equator you go; rare in tropical countries
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11
Q

what are the causes/risk factors of multiple sclerosis?

A
  • not understood
  • combination of genetic and environmental factors
  • female
  • white
  • living far from equator e.g. southern and northern hemispheres
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12
Q

what are environmental factors for MS?

A
  • exposure to Epstein-Barr virus (EBV) in childhood may predispose to the later development of MS in a genetically susceptible host
  • low levels of sunlight and vitamin D may be a risk factor: early exposure to sunlight/vit D is important and vitamin D status relates to prevention of MS and fewer symptoms and fewer new lesions on MRI in established MS
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13
Q

what is the pathophysiology of MS?

A
  • autoimmune mediated demyelination at multiple CNS sites resulting in discrete plaques of demyelination affecting the white matter
  • T cells activate B cells to produce autoantibodies against myelin
  • once T lymphocytes cross the blood-brain barrier they can cause a cascade of destruction to the neuronal cells in the brain
  • this results in demyelination and conduction disruption along axons
  • although the myelin sheath does regenerate, the new myelin is less efficient and is temperature dependant, and when exposed to high heat conduction through new myelin decreases drastically
  • plaques of demyelination are perivenular (occur around a vein), occur everywhere in the CNS but have a predilection for distinct CNS sites
  • PNS myelinated nerves are not affected since their myelin is Schwann cell based and these Schwann cells are unaffected since their myelin has different antigens to the CNS myelin produced by oligodendrocytes
  • repeated demyelination leads to axonal loss and incomplete recovery between attacks
  • poor demyelination healing results in relapsing and remitting symptoms
  • multiple areas of sclerosis form along neurones which slow/block signal conduction thus impairing movement/sensation
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14
Q

what distinct CNS sites does perivenular demyelination tracts occur at in MS?

A
  • optic nerves
  • around ventricles of the brain
  • corpus callosum
  • brainstem and cerebellar connections
  • cervical cord (corticospinal tract and dorsal columns)
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15
Q

what are types of MS?

A
  • relapsing and remitting (80%)
  • secondary progressive MS
  • primary progressive MS (10%)
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16
Q

what are clinical features of relapsing and remitting MS?

A
  • most common pattern of MS
  • symptoms occur in attacks (relapses) with onset over days and typically recovery over weeks
  • periods of good health or remission are followed by sudden symptoms or relapses
  • patients may accumulate disability over time if they do not recover fully after relapses
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17
Q

what are clinical features of secondary progressive MS?

A
  • follows on from relapsing and remitting MS
  • late stage of MS that consists of gradually worsening symptoms with fewer remissions
  • 75% of patients with relapsing-remitting MS will eventually evolve into a secondary progressive MS 35yrs after onset
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18
Q

what are clinical features of primary progressive MS?

A
  • gradually worsening disability without relapses or remissions
  • typically presents later and is associated with fewer inflammatory changes on MRI
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19
Q

what are the clinical presentations of MS?

A
  • usually presents in young adults 20-40 yrs
  • monosymptomatic initially, rarely polysymptomatic
  • symptoms may worsen with heat/exercise as new myelin is inefficient and doesn’t perform well in heat (Uhthoff’s phenomenon)
  • unilateral optic neuritis
  • numbness of tingling in the limbs
  • leg weakness
  • brainstem demyelination
  • cerebellar symptoms, disorders of balance, coordination and speech
  • trigeminal neuralgia
  • constipation
  • spasticity and weakness can result in stiffness/tightness of muscles that can interfere with normal movement, speech and gait
  • intention tremor
  • bladder dysfunction
  • sexual dysfunction
  • cognitive decline
  • amnesia
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20
Q

what is Uhthoff’s phenomenon?

A
  • symptoms may worsen with heat/exercise as new myelin is inefficient and doesn’t perform well in heat
  • occurs in MS
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21
Q

what are features of unilateral optic neuritis in MS?

A
  • pain in one eye on eye movement

* reduced central vision

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22
Q

what are features of brainstem demyelination in MS?

A
  • diplopia, vertigo, facial numbness/weakness, dysarthria or dysphagia
  • clumsy/useless hand or limb due to loss of proprioception (often a dorsal column spinal plaque)
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23
Q

what are differential diagnoses of MS?

A

hereditary spastic paraplegia, cerebral variant of SLE, sarcoidosis or HIV

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24
Q

what is used to diagnose MS?

A
  • diagnosis requires two or more attacks affecting different parts of the CNS; that is 2 CNS lesions disseminated in time and space i.e. cannot diagnose MS after one potential relapse
  • exclude differentials with FBC, inflammatory markers, U+E’s, LFT’s, glucose, HIV serology, auto-antibodies, Ca2+ and vitamin B12
  • MRI scan brain and cord
  • lumbar puncture
  • electrophysiology (delayed nerve conduction suggests demyelination)
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25
Q

how is MRI brain and cord scan used to diagnose MS?

A
  • diagnostic, if history matches
  • 95% have periventricular lesions
  • over 90% show discrete white matter abnormalities
  • multiple scattered plaques are usually seen
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26
Q

how is lumbar puncture used to diagnose MS?

A
  • CSF examination shows oligoclonal IgG bands in over 90% cases, but these are not specific to MS
  • CSF cell count may be raised
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27
Q

what is the treatment of MS?

A
  • encourage stress-free life
  • if poor diet and sun exposure then give vitamin D
  • aggressive treatment of stem cell transplant
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28
Q

what is the treatment of acute relapse in MS?

A

IV methylprednisolone for less than 3 days can help shorten acute relapse; use steroid sparingly and aim to use less than twice a year

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29
Q

what is treatment of frequent relapse in MS?

A
  • SC interferon 1B or 1A are anti-inflammatory cytokines and can help reduce relapses by 30% in active relapse-remitting MS and can reduce lesion accumulation (side effects: flu symptoms, depression, abortion)
  • disease modifying agents: monoclonal antibodies (IV alemtuzumab and IV natalizumab) and dimethyl fumarate
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30
Q

what monoclonal antibodies are used to treat frequent relapses in MS?

A

IV alemtuzumab and IV natalizumab

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31
Q

what is alemtuzumab? how is it used to treat MS? what are its side effects?

A
  • CD52 monoclonal antibody that targets T cells
  • side effects: infections, and while immune system reconstitutes itself, you can get autoimmune disease (thyroid, skin and kidney)
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32
Q

what is natalizumab? how is it used to treat MS? what are its side effects?

A
  • acts against VLA-4 receptors that allow immune cells to cross the BBB, thus it reduces amount of immune cells that can enter the CNS and cause damage
  • side effects: antibody-mediated resistance, progressive leucoencephalopathy (disease of white matter due to lack of immune defence)
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33
Q

what is the symptomatic treatment of MS?

A
  • spasticity; all anti-spastics can result in weakness
  • urinary urgency and frequency: intermittent self-catheterisation
  • incontinence: anti-cholinergic alpha-blockers
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34
Q

what are some anti-spasticity drugs?

A
  • physiotherapy
  • baclofen
  • tizanide
  • botox injection
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35
Q

what is baclofen? how is it used to treat symptomatic MS?

A

GABA analogue that reduces Ca2+ influx, surpasses release of excitatory neurotransmitters

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36
Q

what is tizanidine? how is it used to treat symptomatic MS? what are some side effects?

A
  • alpha 2 agonist
  • contraindicated in hepatic impairment
  • S/E; dry mouth, hypotension, acute hepatitis
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37
Q

how is botox used to treat symptomatic MS?

A

reduces ACh in neuromuscular junction thus
less spasticity
• only has transient effect (2-12 weeks) and risk of dysphagia

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38
Q

what is the life-expectancy for MS? what do they often die of?

A

life-expectancy for people with MS is 5-10 years below average; they often die from aspiration pneumonia due to their dysphagia and swallowing difficulties

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39
Q

what is the epidemiology of myasthenia gravis?

A
  • more common in females than males, although over 50 it is more common in males
  • peak age of incidence at 30yrs in women
  • peak age of incidence at 60yrs in males
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40
Q

what are the causes/risk factors for myasthenia gravis?

A
  • if under 50 yrs, then MG is commoner in women and is associated with other autoimmune disease e.g. pernicious anaemia, SLE and rheumatoid arthritis and thymic hyperplasia
  • if over 50 yrs, then MG is commoner in men and is
    associated with thymic atrophy or thymic tumour, rheumatoid arthritis and SLE
  • transient MG is sometimes caused by D-penicilliamine treatment for Wilson’s disease
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41
Q

what is the pathophysiology of myasthenia gravis?

A
  • autoimmune disease mediated by antibodies against nicotinic acetylcholine receptors (nAChR) in the NMJ, interfering with the neuromuscular junction via depletion of working post-synaptic receptor sites
  • this is achieved by immune complex deposition of anti-nAChR IgG and complement at the post-synaptic membranes, causing interference with and destruction of receptors
  • both B and T cells are implicated
  • this blocks the excitatory effect of ACh on the nicotinic receptors (since there are less receptors) resulting in muscle weakness
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42
Q

what is the clinical presentation of myasthenia gravis?

A
  • increasing muscular fatigue
  • limb muscles (proximal), speech and facial expression are commonly affected
  • look for ptosis (drooping of upper eyelid), diplopia (double vision) and myasthenic snarl on smiling
  • respiratory difficulties can occur in generalised myasthenia
  • tendon reflexes are normal but may be fatiguable - disappear following repetitive activity
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43
Q

what muscles are affected by myasthenia gravis, in order?

A
  • extra-ocular
  • bulbar - swallowing and chewing
  • face
  • neck
  • trunk
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44
Q

what is done on examination to elicit fatiguability in myasthenia gravis?

A
  • ask patient to count to 50; as they reach the higher numbers, their voice becomes less audible
  • hold your finger up high and ask the patient to keep looking at it, without lifting head up - after a few seconds, they will be unable to keep their eyes raised
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45
Q

what is weakness in myasthenia gravis worsened by? what drugs can worsen it?

A

weakness is worsened by pregnancy, hypokalaemia, infection, emotion, exercise and drugs (opiates, beta-blockers, gentamicin and tetracycline)

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46
Q

what are differential diagnoses of myasthenia gravis?

A

MS, hyperthyroidism, acute Guillain-Barre syndrome, Lambert-Eaton myasthenic syndrome

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47
Q

what is Lambert-Eaton myasthenic syndrome? how is it different from myasthenia gravis?

A
  • paraneoplastic condition, most often seen with small cell lung cancer
  • causes defective ACh release at the neuromuscular junction resulting in proximal limb weakness with some absent reflexes
  • weakness tends to improve after exercise, unlike in MG
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48
Q

what is used to diagnose myasthenia gravis?

A
  • serum anti-nAChR
  • electromyography and nerve conduction study
  • CT of thymus to look for hyperplasia, atrophy or tumour
  • ptosis improves by >2mm after ice application to the shut affected lid for >2mins (non-invasive, cheap test)
  • tensilon test: IV edrophonium (short-acting anti-cholinesterase) given and muscle power increases within seconds (rarely used to diagnose due to side effects)
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49
Q

how is serum anti-nAChR used to diagnose myasthenia gravis? what is done if it is negative?

A
  • raised in 90%

* if negative then look for MuSK (muscle specific tyrosine kinase) antibodies (anti-MuSK)

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50
Q

how is electromyography used to diagnose myasthenia gravis?

A
  • EMG will detect myaesthenia gravis: ACh does not activate the muscle cells properly resulting in weakness
  • use a needle to detect the electrical activity from muscle
  • a characteristic decrement occurs in evoked muscle action potential during repetitive stimulation
  • single-fibre EMG of orbital muscles is more sensitive than repetitive stimulation and shows block and jitter
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51
Q

what are treatments of myasthenia gravis?

A
  • symptom control
  • immunosuppression
  • thymectomy (if onset <50yrs and disease is poorly controlled with anti-cholinesterases)
  • myasthenic crisis
  • anti-cholinesterases
  • steroids
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52
Q

how are anti-cholinesterases used to treat myasthenia gravis? what is an example? what are some side effects?

A
  • anti-cholinesterases increase the amount of ACh in the NMJ
  • e.g. oral pyridostigmine
  • side effects: increased salivation, lacrimation, sweats, vomiting, miosis (excessive pupillary constriction), diarrhoea
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53
Q

how are steroids used to treat myasthenia gravis? what are some drugs that are used and their side effects?

A

• used to treat relapses or if there is no response to pyridostigmine, start low starting dose with dose increased per week; reduce dose on remission (may take months)
- give osteoporosis prophylaxis such as bisphosphonates
- S/E; weakness
• steroids may be combined with oral azathioprine or oral methotrexate as the disease becomes more general

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54
Q

what is myasthenic crisis? what is it treated with?

A

• weakness of the respiratory muscles during a relapse can be life-threatening
• monitor FVC
• treat with plasmapheresis (antibody removal) + IV
immunoglobulin and identity and treat causes of therelapse

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55
Q

what is weakness or paresis?

A

impaired ability to move a body part in response to will

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56
Q

what is paralysis?

A

where the ability to move a body part in response to will is completely lost

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57
Q

what is ataxia or incoordination?

A

willed movements are clumsy, ill-directional or uncontrolled

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58
Q

what are involuntary movements?

A

spontaneous movement of a body part, independently of will

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59
Q

what is apraxia?

A

disorder of consciously organised pattern of movement or impaired ability to recall acquired motor skills

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60
Q

what are the stages in the organisation of movement?

A
  1. idea of the movement, initiated in association areas of cortex
  2. activation of UMNs in the pre-central gyrus
  3. impulses travel to LMNs and their motor units via the CST
  4. activity of the cerebellum and basal ganglia is modulated
  5. further modification of movement depending on sensory feedback
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61
Q

where are LMNs located?

A

located in the anterior horns of the spinal cord and in cranial nerve nuclei in the brainstem

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62
Q

what is a motor unit? what does it consist of? what are different sizes of motor units?

A
  • alpha motor neurone (LMN) + axon + skeletal fibres it innervates
  • different motor neurones innervate different numbers of muscle fibres, the less fibres that are innervated, the greater the variation of movement
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63
Q

how is muscle tone regulated?

A
  • stretch receptors in muscle (muscle spindles) are innervated by gamma motor neurons
  • muscle stretched leads to afferent impulses from muscle spindles being sent, causing reflex partial contraction of muscle
  • disease states e.g. spasticity and rigidity alter muscle tone by altering the sensitivity of this reflex
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64
Q

what are potential sites of damage along the motor pathway?

A
  • motor nuclei of cranial nerves
  • motor neurones in spinal cord
  • spinal ventral roots
  • peripheral nerves
  • neuromuscular junction
  • muscle
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65
Q

what are UMN signs?

A

everything goes up:
- spasticity (increased muscle tone)
- brisk reflexes e.g. tendon and jaw reflexes
- plantars are upturned on stimulation (positive Babinski sign)
- characteristic pattern of limb muscle weakness (pyramidal pattern):
• upper limbs extensor muscles are weaker than flexors
• lower limb flexor muscles are weaker then extensors
• finer, more skilful movements are impaired

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66
Q

what are LMN signs?

A

everything goes down:

  • flaccid (reduced muscle tone)
  • muscle wasting
  • fasciculation: visible spontaneous contraction of motor units (not enough to diagnose LMN, need weakness too)
  • reflexes depressed or absent
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67
Q

what is motor neurone disease? what is it also referred to?

A
  • cluster of major degenerative diseases characterised by selective loss of neurones in motor cortex, cranial nerve nuclei and anterior horn cells
  • sometimes referred to as amyotrophic lateral sclerosis
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68
Q

what is the epidemiology of MND/ALS?

A
  • relatively uncommon
  • more common in males than females
  • median age of onset is 60yrs
  • often fatal in 2-4yrs
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69
Q

what is the aetiology/risk factors for MND/ALS?

A
  • usually sporadic and of unknown cause
  • no established risk factors
  • 5-10% cases are familial
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70
Q

what is a genetic component of MND/ALS?

A
  • linked to a mutation in the free radical scavenging enzyme superoxide dismutase (SOD-1)
  • also linked to TDP-43, C9ORF72 and FUS
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71
Q

what is the pathophysiology of MND/ALS?

A
  • degenerative condition affecting motor neurones, namely anterior horn cells
  • there is relentless and unexplained destruction of upper motor neurones and anterior horn cells in the brain and spinal cord
  • causes both UMN and LMN dysfunction
  • upper and lower motor neurones are affected but there is no sensory loss or sphincter disturbance - this is what distinguishes MND from MS and polyneuropathies
  • MND never affects eye movements - distinguishing it from myasthenia gravis
  • caused reactive oxygen species which damage DNA, lipids and proteins
  • most patients die within 3 years from respiratory failure as a result of bulbar palsy (impairment of CN 9,10,11,12) and pneumonia
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72
Q

what distinguishes MND from MS and polyneuropathies?

A

upper and lower motor neurones are affected but there is no sensory loss or sphincter disturbance - this is what distinguishes MND from MS and polyneuropathies

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73
Q

what distinguishes MND from myasthenia gravis?

A

MND never affects eye movements

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74
Q

does MND affect UMNs and/or LMNs?

A

BOTH

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75
Q

what is the prognosis of MND?

A

most patients die within 3 years from respiratory failure as a result of bulbar palsy (impairment of CN 9,10,11,12) and pneumonia

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76
Q

what are the 4 main clinical patterns of MND?

A
  1. amyotrophic lateral sclerosis (ALS); UMN + LMN
  2. progressive muscular atrophy (PMA); LMN only
  3. progressive bulbar palsy (PBP); LMN only
  4. primary lateral sclerosis (PLS); UMN only
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77
Q

what are clinical features of amyotrophic lateral sclerosis?

A

UMN and LMN
• most common
• loss of motor neurones in motor cortex and anterior horn of the cord
• weakness + UMN signs + LMN wasting/fasciculations, usually in one limb
• split hand sign thumb side of the hand seems adrift due to excessive wasting around it; there is much less hypothenar wasting
• cramps are a common but non-specific symptom
• wrist and foot drop

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78
Q

what are clinical features of progressive muscular atrophy?

A

LMN only
• LMN only presentation with weakness, muscle wasting and fasciculations usually starting in one limb and gradually spreading to involve other adjacent spinal segments
• affects distal muscle group before proximal

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79
Q

what are clinical features of progressive bulbar palsy?

A

LMN only
• affects only lower cranial nerves (CN 9,10,11,12) and nuclei initially
• dysarthria, dysphagia, nasal regurgitation of fluids and choking
• LMN lesion of the tongue and muscles of talking and swallowing; flaccid, fasciculating tongue (like a sack of worms), jaw jerk is normal/absent, speech is quiet, hoarse or nasal

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80
Q

what are clinical features of primary lateral sclerosis?

A 
UMN only
• least common
• loss of Betz cells in motor cortex
• mainly UMN signs + marked spastic leg weakness, with progressive tetraparesis and pseudobulbar palsy
• no cognitive decline
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81
Q

what are the differential diagnoses of MND?

A
  • MS or polyneuropathies
  • myasthenia gravis
  • diabetic amyotrophy
  • Guillain-Barre syndrome
  • spinal cord tumours
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82
Q

how can MS/polyneuropathies be differentiated from MND?

A

no sensory loss or sphincter disturbance in MND

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83
Q

how can myasthenia gravis be differentiated from MND?

A

MND never affects eye movements

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84
Q

what is used to diagnose MND?

A
  • diagnosed based on clinical findings
  • brain/cord MRI (helps exclude structural causes)
  • lumbar puncture (excludes inflammatory causes)
  • nerve conduction studies and electromyography (denervation of muscles due to LMN degeneration is confirmed by EMG)
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85
Q

what are features of definite, probable, possible and suspected MND in clinical diagnosis?

A
  • definite: LMN and UMN signs in 3 regions
  • probable: LMN and UMN signs in 2 regions
  • probable with lab support: LMN and UMN signs in 1 region, or UMN sign in more than 1 region and EMG showing acute denervation in more than 2 limbs
  • possible: LMN and UMN signs in 1 region
  • suspected: LMN or UMN signs only, in 1 or more regions
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86
Q

how are antiglutamergic drugs used to treat MND? what is an example? what is its action and side effects?

A
  • oral riluzole; an Na+ channel-blocker that inhibits glutamate release
  • prolongs life by 3 months
  • raises LFT’s so monitor these
  • S/E; vomiting, raised pulse, headache, vertigo
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87
Q

what is used to treat drooling due to bulbar palsy, dysphagia and spasms in MND? what can be given for analgesia?

A
  • drooling: oral propantheline or oral amitriptyline
  • dysphagia: blend food, NG tube, percutaneous catheter gastrostomy
  • spasms: oral baclofen
  • analgesia: NSAIDs or opioids
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88
Q

what is Guillain-Barre syndrome?

A

an acute inflammatory demyelinating ascending polyneuropathy affecting the peripheral nervous system (Schwann cells targeted) following an upper respiratory tract or GI infection

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89
Q

what is the epidemiology of Guillain-Barre syndrome?

A
  • more common in males than females
  • peak ages 15-35 yrs and 50-75 yrs
  • the most common acute polyneuropathy
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90
Q

what are infective causes of Guillain-Barre syndrome?

A
  • Campylobacter jejuni
  • cytomegalovirus (CMV)
  • mycoplasma
  • herpes zoster
  • HIV
  • Epstein-Barr virus (EBV)
  • in some cases no obvious infection can be found
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91
Q

what are risk factors for Guillain-Barre syndrome?

A
  • history of respiratory or GI infections 1-3 weeks prior to onset
  • vaccinations have been implicated
  • incidence decreases during pregnancy but increases in months afterwards
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92
Q

what is the pathophysiology of Guillain-Barre syndrome? what does the nerve cell damage consist of?

A
  • GBS is usually triggered by infection e.g. Campylobacter jejuni, EBV or cytomegalovirus (CMV)
  • these infectious organisms may share the same antigens as those on the Schwann cells, such as ganglioside GM and GQ1b, leading to autoantibody mediated nerve cell damage formation via molecular mimicry
  • nerve cell damage consists of damage to the Schwann cells and thus demyelination resulting in the reduction in peripheral nerve conduction, resulting in an acute polyneuropathy
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93
Q

what is the clinical presentation of Guillain-Barre syndrome?

A
  • 1-3 weeks post infection a symmetrical ascending muscle weakness starts; this may advance quickly, affecting all limbs at once and can lead to paralysis
  • the proximal muscles are more affected e.g. trunk, respiratory and cranial nerves (especially CN7)
  • in 20%, respiratory muscles and facial muscles are affected; respiratory involvement requires ITU admission
  • back/limb pain is common but sensory signs may be absent
  • sensory signs include paraesthesias, but there are very few sensory signs
  • reflexes are lost early in the illness
  • autonomic features such as sweating, raised pulse, BP changes and arrhythmias may be present
  • there is a progressive phase for up to 4 weeks, followed by recovery
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94
Q

what are differential diagnoses of Guillain-Barre syndrome?

A

other causes of acute paralysis e.g. hypokalaemia, stroke, brainstem compression, encephalitis, spinal cord compression, poliomyelitis, vasculitis, myasthenia gravis

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95
Q

what is used to diagnose Guillain-Barre syndrome?

A
  • nerve conduction studies (show slowing of conduction, prolonged distal motor latency and/or conduction block)
  • lumbar puncture (done at L4; CSF has raised protein but normal WCC)
  • spirometry (to monitor FVC if respiratory involvement)
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96
Q

what is the treatment of Guillain-Barre syndrome?

A
  • if FVC <1.5L/80% then ventilate and admit to ITU and monitor FVC 4hourly
  • IV immunoglobulin for 5 days
    • decreases the duration and severity of paralysis
    • contraindicated in patients with IgA deficiency; screen for deficiency beforehand
  • plasma exchange
  • LMWH and compression stockings to reduce risk of venous thrombosis
  • prognosis is good with 85% making a complete/near-complete recovery, but 10% are unable to walk along at 1 year, mortality is 1%
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97
Q

what are the 6 mechanisms that can cause nerve malfunction?

A
  1. demyelination (e.g. Guillain-Barre)
  2. axonal degeneration
  3. compression (e.g. carpal tunnel syndrome)
  4. infarction (e.g. polyarteritis nodosum)
  5. infiltration (e.g. leprosy)
  6. Wallerian degeneration
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98
Q

how does Wallerian degeneration cause nerve malfunction in peripheral neuropathies?

A

process that results when a nerve fibre is cut or crash and the distal part of the axon that is separated from the neurone’s cell body degenerates

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99
Q

what are types of peripheral nerve disease?

A
  • neuropathy
  • mononeuropathy
  • mononeuritis multiplex
  • polyneuropathy
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100
Q

what is mononeuritis multiplex?

A
  • pathological process where several individual nerves are affected
  • term is used if 2 or more peripheral nerves are affected, when causes tend to be systemic
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101
Q

what is polyneuropathy?

A
  • diffuse, symmetrical disease usually commencing peripherally
  • can be motor, sensory, sensorimotor and autonomic
  • classified into demyelinating and axonal types
  • widespread loss of tendon reflexes is typical, with distal weakness and distal sensory loss
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102
Q

what are causes of mononeuritis multiplex? (WARDS PLC)

A

WARDS PLC:

  • Wegener’s granulomatosis
  • Aids/Amyloid
  • Rheumatoid arthritis
  • Diabetes mellitus
  • Sarcoidosis
  • Polyarteritis nodosa
  • Leprosy
  • Carcinoma
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103
Q

what is carpal tunnel syndrome?

A
  • the most common mononeuropathy and entrapment neuropathy

* results from pressure and compression on the median nerve as it passes through the carpal tunnel in the wrist

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104
Q

what is the epidemiology of carpal tunnel syndrome?

A
  • more common in females than males since women have narrower wrists but similar-sized tendons to men
  • usually idiopathic
  • usually in those over 30
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105
Q

what is carpal tunnel syndrome associated with?

A
  • hypothyroidism
  • diabetes mellitus
  • pregnancy (third trimester)
  • amyloidosis including in dialysis patients
  • obesity
  • rheumatoid arthritis
  • acromegaly
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106
Q

what is the clinical presentation of carpal tunnel syndrome?

A
  • symptoms are intermittent and onset is gradual
  • aching pain in the hand and arm especially at night, can wake patient up
  • paraesthesiae in median nerve distribution
  • relieved by dangling the hand over the edge of the bed (“wake and shake”)
  • may be sensory loss and weakness of abductor pollicis brevis +/- wasting of the thenar eminence
  • light touch, 2-point discrimination and sweating may be impaired
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107
Q

what are differential diagnoses of carpal tunnel syndrome?

A

peripheral neuropathy, motor neurone disease and MS

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108
Q

how is electromyography used to diagnose carpal tunnel syndrome?

A
  • see slowing of conduction velocity in the median sensory nerves across the carpal tunnel
  • prolongation of the median distal motor latency
  • helps to confirm lesion site and severity
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109
Q

what is Phalen’s test? what does it help diagnose?

A
  • patient is asked to hold their wrists in complete and forced flexion for 30-60 seconds
  • characteristic symptoms (e.g. burning, tingling or numb sensation over the thumb, index, middle and ring fingers) conveys a positive test result and suggests carpal tunnel syndrome
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110
Q

what is Tinel’s sign? what does it help diagnose?

A
  • a way to detect irritated nerves
  • lightly tapping (percussing) over the nerve to elicit a sensation of tingling in the distribution of the nerve
  • in carpal tunnel syndrome Tinel’s sign is often positive, causing tingling in the thumb, index, middle finger and the radial half of the 4th digit
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111
Q

what is the treatment of carpal tunnel syndrome?

A
  • wrist splint at night
  • local steroid injection
  • decompression surgery (carpal tunnel ligament is cut to reduce pressure)
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112
Q

what is the median nerve? what does it innervate?

A
  • C6-T1
  • median nerve is the nerve of precision grip
  • LOAF: 2 lumbricals, opponens pollicis, abductor pollicis brevis, flexor pollicis brevis
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113
Q

what are features of anterior interosseous nerve lesions?

A
  • median nerve branch
  • due to trauma
  • weakness of flexion of the distal phalanx of the thumb and index finger
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114
Q

what are features of ulnar nerve mononeuropathy?

A
  • C7-T1
  • vulnerable to elbow trauma
  • most often, compression occurs at the epicondylar groove or at the point where the nerve passes between the 2 heads of flexor carpi ulnaris (true cubital tunnel syndrome)
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115
Q

what are signs of ulnar nerve mononeuropathy?

A
  • weakness/wasting
  • wasting of the hypothenar eminence, thus weak little finger abduction
  • sensory loss over medial 1.5 fingers and ulnar side of hand
  • flexion of 4th and 5th DIP joint is weak
  • with lesions at the wrist (digitorum profundum intact), claw hand is more marked
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116
Q

what is there weakness/wasting of in ulnar mononeuropathy?

A

• medial (ulnar side) wrist flexors
• interossei - cannot cross the fingers in the good
luck sign
• medial 2 lumbricals - claw hand

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117
Q

what is treatment of ulnar nerve mononeuropathy?

A
  • rest and avoiding pressure on the nerve

- night time soft elbow splinting may be required

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118
Q

what are features of the radial nerve?

A
  • C5-T1
  • nerve opens the fist
  • may be damaged by compression against the humerus
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119
Q

what are signs of radial nerve mononeuropathy?

A
  • test for wrist and finger drop with elbow flexed and arm pronated
  • sensory loss is variable; the dorsal aspect of the root of the thumb (anatomical snuff box) is most reliably affected
  • muscles involved (brachioradialis, extensors, supinators, triceps)
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120
Q

what are causes of brachial nerve mononeuropathy?

A
  • trauma
  • radiotherapy
  • prolonged wearing of a heavy rucksack
  • neuralgic amyotrophy
  • thoracic outlet compression (also affects vasculature)
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121
Q

what are features of phrenic nerve mononeuropathy?

A
  • C3,4,5 keeps the diaphragm alive

- consider phrenic palsy if orthopnoea (SOB when lying flat) with raised hemidiaphragm on CXR

122
Q

what are causes of phrenic nerve mononeuropathy?

A
  • lung cancer
  • myeloma
  • thymoma
  • cervical spondylosis/trauma
  • phrenic nucleus lesion e.g. MS
  • thoracic surgery
  • C3-5 VZV
  • HIV
  • muscular dystrophy
123
Q

what is meralgia paraesthetica?

A

antero-lateral burning thigh pain from entrapment of the lateral cutaneous nerve of the thigh (L2-L3) under the inguinal ligament

124
Q

what are features of sciatic nerve lesions?

A
  • L4-S3
  • damaged by pelvic tumours or fractures to pelvis or femur
  • lesions affect the hamstrings and all muscles below the knee, resulting in foot drop
  • there is also loss of sensation below the knee laterally
125
Q

what are features of common peroneal nerve damage?

A

• L4-S1
• originates from the sciatic nerve just above the knee
• often damaged as it winds round the fibular head due to trauma or siting cross-legged
- foot drop
- weak ankle dorsiflexion/eversion
- sensory loss over dorsum (top) of foot

126
Q

what are features of tibial nerve lesions?

A
  • L4-S3
  • originates from the sciatic nerve just above the knee
  • lesions lead to an inability to stand on tiptoe (plantarflexion), invert the foot or flex the toes
  • also sensory loss over the sole
127
Q

what are some mostly motor polyneuropathies?

A
  • Guillain-Barre syndrome
  • lead poisoning
  • Charcot-Marie-Tooth syndrome
128
Q

what are some mostly sensory polyneuropathies?

A
  • diabetes mellitus
  • renal failure
  • leprosy
129
Q

what are some causes of polyneuropathies? give examples for each

A
  • metabolic: diabetes mellitus, renal failure, hypothyroidism, hypoglycaemia
  • vasculitides: polyarteritis nodosa, rheumatoid arthritis, Wegener’s granulamatosis
  • malignancy: paraneoplastic syndromes, polycythaemia rubra vera
  • inflammatory: Guillain-Barre syndrome, sarcoidosis
  • infections: leprosy, HIV, syphilis, Lyme disease
  • nutritional: decreased; vit B12, B1, E, B6 and folate
  • inherited syndromes: Charcot-marie-tooth, porphyria
  • drugs/toxins: lead, arsenic, alcohol, vincristine, cisplatin, metronidazole
130
Q

how are polyneuropathies diagnosed?

A
  • history; time course, precise nature of symptoms and any preceding or associated events
  • ask about travel, alcohol and drug use, sexual infections and family history
  • if there is palpable nerve thickening then think of leprosy or Charcot-Marie-Tooth
  • examine other systems for clues to causes e.g. alcoholic liver disease
131
Q

what are some preceding or associated events that may lead to polyneuropathies?

A
  • diarrhoea and vomiting before Guillain-Barre syndrome
  • weight loss in cancer
  • arthralgia from a connective tissue disease
132
Q

what are features of sensory neuropathy in polyneuropathies?

A
  • numbness/paraesthesia
  • affects extremities first; glove and stocking distribution
  • difficulty handling small objects such as buttons
  • signs of trauma e.g. finger burns or joint deformation may indicate sensory loss
  • diabetic and alcoholic neuropathies are typically painful
133
Q

what are features of motor neuropathy in polyneuropathies?

A 
• often progressive (may be rapid)
• weak or clumsy hands
• difficulty walking or breathing
• LMN lesion:
- wasting and weakness is most marked in the distal muscle of the hands and feet - foot or wrist drop
- reflexes are reduced or absent
134
Q

what are brainstem problems caused by in cranial nerve lesions?

A
  • tumour
  • MS
  • trauma
  • aneurysm
  • vertebral artery dissection resulting in infarction
  • infection - cerebellar abscess from ear
135
Q

what is the clinical presentation of CN3 palsy?

A
  • ptosis; dropping eyelids
  • fixed dilated pupil; loss of parasympathetic outflow from Edinger-Westphal nucleus which supplies the pupillary sphincter and ciliary bodies;
    lens accomadation
  • eye down and out
136
Q

what are causes of CN3 palsy?

A
  • raised ICP
  • diabetes
  • hypertension
  • giant cell arteritis
137
Q

what is the clinical presentation of CN4 palsy?

A
  • usually innervates superior oblique muscle

- results in a head tilt to correct the extortion that results in diplopia on looking down e.g. walking downstairs

138
Q

what are causes of CN4 palsy?

A

trauma to the orbit - rare

139
Q

what is the clinical presentation of CN6 palsy?

A
  • usually innervates the lateral rectus muscle which abducts

- eyes will be adducted

140
Q

what are causes of CN6 palsy?

A
  • MS
  • Wernicke’s encephalopathy
  • pontine stroke - presents with fixed small pupils +/- quadriparesis
141
Q

what are causes of CN3,4,5 palsy?

A

• stroke
• tumours
• Wernicke’s encephalopathy
- presents as non-functioning eye

142
Q

what is the clinical presentation of CN5 palsy?

A
  • jaw deviates to side of lesion (ipsilateral)

- loss of corneal reflex

143
Q

what are causes of CN5 palsy?

A
  • trigeminal neuralgia (pain but no sensory loss)
  • herpes zoster
  • nasopharyngeal cancer
144
Q

what is the clinical presentation of CN7 palsy?

A

facial droop and weakness

145
Q

what are causes of CN7 palsy?

A
  • Bells palsy is the most common lesion of the facial nerve - will see dribbling out the side of mouth
  • fractures of the petrous bones
  • middle ear infections
  • inflammation of the parotid gland, which facial nerve passes through
146
Q

what is the clinical presentation of CN8 palsy?

A
  • hearing impairment

- vertigo and lack of balance

147
Q

what are causes of CN8 palsy?

A
  • the vestibulocochlear nerve runs very close to the bone
  • is also very affected by surrounding tumours - if a tumour arises in the internal acoustic meatus then this will press on the vestibulocochlear and facial nerve
  • skull fracture
  • toxic drug effects
  • ear infections
148
Q

what is the clinical presentation of CN9 and CN10 palsy?

A
  • gag reflex issues
  • swallowing issues
  • vocal issues
149
Q

what is a cause of CN9 and CN10 palsy?

A

jugular foramen lesion

150
Q

what is autonomic neuropathy?

A

sympathetic and parasympathetic neuropathies may be isolated or part of a generalised sensorimotor peripheral neuropathy

151
Q

what are causes of autonomic neuropathy?

A
  • diabetes mellitus
  • Guillain-Barre and Sjogren’s syndrome
  • HIV
  • SLE
152
Q

what is the sympathetic clinical presentation of autonomic neuropathy?

A
  • postural hypotension
  • ejaculatory failure
  • reduced sweating
153
Q

what is the parasympathetic clinical presentation of autonomic neuropathy?

A
  • erectile dysfunction
  • constipation
  • nocturnal diarrhoea
  • urine retention
154
Q

what is used to diagnose polyneuropathy?

A
  • FBC, ESR, glucose, U+E, LFT, TSH, B12
  • ANA, ANCA, anti-CCP
  • CXR
  • urinalysis
  • lumbar puncture and specific genetic testing for inherited neuropathies e.g. Charcot-Marie-Tooth
155
Q

what is the treatment of polyneuropathy?

A
  • treat the cause
  • foot care and shoe choices are important in sensory neuropathies to minimise trauma
  • splinting of joints helps to prevent contractures (shortening and hardening of muscles and tendons) in prolonged paralysis
  • for vasculitic causes, steroids/immunosuppressants may help
  • treat neuropathic pain with oral amitriptyline or oral nortriptyline
156
Q

what is the pain, weakness and reflex affected by a L2 nerve root lesion?

A
  • pain: across upper thigh
  • weakness: hip flexion and adduction
  • reflex affected: nil
157
Q

what is the pain, weakness and reflex affected by a L3 nerve root lesion?

A
  • pain: across lower thigh
  • weakness: hip adduction, knee extension
  • reflex affected: knee jerk
158
Q

what is the pain, weakness and reflex affected by a L4 nerve root lesion?

A
  • pain: across knee to medial malleolus
  • weakness: knee extension, foot inversion and dorsiflexion
  • reflex affected: knee jerk
159
Q

what is the pain, weakness and reflex affected by a L5 nerve root lesion?

A
  • pain: lateral shin to dorsum of foot and great toe
  • weakness: hip extension and abduction, knee flexion and foot and great toe dorsiflexion
  • reflex affected: great toe jerk
160
Q

what is the pain, weakness and reflex affected by a S1 nerve root lesion?

A
  • pain: posterior calf to lateral foot and little toe
  • weakness: knee flexion, foot and toe plantar flexion, foot eversion
  • reflex affected: ankle jerk
161
Q

what is the epidemiology of primary brain tumours?

A
  • primary brain tumour incidence is around 8 per 100,000; secondary brain tumours are more common
  • 16th most common adult cancer, but is a disproportionate killer in young adults (below 40), if they have a tumour at 40 they probably won’t make it to 50
  • 2nd most common paediatric cancer, below leukaemia
  • account for less than 2% of all malignant tumours but 20% of childhood cases
  • in adults, the majority are supratentorial
  • in children, the majority occur in the posterior fossa
  • majority are gliomas (glial cell in origin)
  • astrocytoma is the most common primary brain tumour
162
Q

what is the type of most primary brain tumours?

A

gliomas (glial cell in origin)

  • astrocytoma (85-90%)
  • oligodendroglioma (5%)
163
Q

what is the most common primary brain tumour?

A

astrocytoma

164
Q

what are risk factors for primary brain tumours?

A
  • primary tumours are more common in affluent groups
  • ionising radiation
  • vinyl chloride
  • immunosuppression
  • family history/genetics
165
Q

what is the grading of astrocytoma?

A

grade I to IV

166
Q

what is grade I astrocytoma? what is its prognosis? what are some features of it?

A

pilocytic astrocytoma

  • good prognosis
  • completely benign
  • paediatric tumour; mainly seen in children
167
Q

what is grade II astrocytoma? what is its prognosis? what are some features of it?

A

diffuse astrocytoma

  • > 5 year prognosis
  • premalignant tumour
168
Q

what is grade III astrocytoma? what is its prognosis? what are some features of it?

A

anaplastic astrocytoma

  • 2-5yrs prognosis
  • malignant
  • see active growth and mitotic activity on microscope
169
Q

what is grade IV astrocytoma? what is its prognosis? what are some features of it?

A

glioblastoma multiforme

  • <1 year prognosis
  • most common phenotype
  • active growth, mitotic activity, necrosis and vascular proliferation
  • very malignant
170
Q

what will all gliomas progress to eventually?

A

given enough time, all gliomas will progress to become glioblastoma multiforme, except pilocytic astrocytic

171
Q

what is the common pathway to a malignant glioma? how does it occur?

A
  • occurs especially in those under 50-60
  • initial genetic error is of glucose glycolysis
  • mutation of isocitrate dehydrogenase I (IDH-1)
  • results in the excessive build up of 2-hydroxyglutarate
  • this triggers genetic instability in glial cells and subsequent inappropriate mitosis, leading to cancer
172
Q

what is the less common pathway to a malignant glioma? how does it occur?

A
  • more common in those over 50-60
  • no IDH-1 mutation
  • instead they have a catastrophic genetic mutation
  • resulting in very poor prognosis even for ‘low grade’ tumours
173
Q

what are features of oligodendroma?

A
  • most common in 40s-50s
  • arise from oligodendrocytes
  • grow slowly, usually over several years
  • calcification is common
  • may have seizures
  • WHO grade II
  • all are IDH-1 mutation positive
174
Q

what are other types of primary brain tumours (5%)?

A
  • gliomas
  • ependymomas
  • meningiomas
  • neurofibromas (Schwannomas)
  • craniopharyngiomas
175
Q

what are features of ependymomas?

A
  • primary brain tumour
  • arise from ependymal cells
  • line the ventricles and spinal cord
176
Q

what are features of meningiomas?

A
  • primary brain tumour
  • more common in older people and women
  • benign and arise from the arachnoid mater and may grow to a large size, usually over years, pushing it into the brain
177
Q

what are features of neurofibromas?

A
  • primary brain tumours

- solid benign tumours that arise from the Schwann cell and occur principally in the cerebellopontine angle

178
Q

what are features of craniopharyngiomas?

A
  • very rare benign tumours

- often diagnosed in younger patients

179
Q

how do brain tumours affect intracranial pressure? why?

A

tumours act as space-occupying lesions within the

brain and result in an increase in ICP

180
Q

what is the intracranial pressure like in primary brain tumours?

A
  • initially when the tumour is small, there will be no symptoms despite the rising ICP, this is because initially the brain is compliant and is able to remove CSF from the ventricles into the spinal cord in order to offset the increase in pressure
  • however, there comes a point where no more CSF can be relocated - at this point there is very sharp and rapid rise in ICP resulting in symptoms and eventually death if nothing is done
  • the rising pressure results in a midline shift of the brain and herniation through the foramen magnum which results in brain damage resulting in local and systemic symptoms
181
Q

what are the 4 cardinal presenting symptoms of primary brain tumours?

A
  • symptoms of raised ICP
  • progressive neurological deficit
  • epilepsy/seizure
  • lethargy/tiredness caused by pressure on the brainstem
182
Q

what are symptoms of a raised ICP?

A
  • progressive headache
  • drowsiness
  • +/- vomiting
  • cardinal sign is papilloedema
183
Q

what are symptoms of progressive headache due to a raised ICP in primary brain tumours? what is the pain like? what is the pain increased/relieved by?

A
  • is worse on waking from sleep in the morning, because at night you don’t pee thus there is an accumulation of fluid resulting in increased pressure and pain
  • pain can be so bad that it wakes patient up
  • pain is increased by coughing, straining and bending forwards (increased venous pressure in brain)
  • sometimes is relieved by vomiting since this reduces fluids and pressure
184
Q

what are symptoms of papilloedema due to headache due to increased ICP in primary brain tumours?

A
  • swelling of the optic disc due to obstruction of venous return from the retina due to the raised ICP
  • loss of crisp optic nerve head margins
  • venous engorgement
  • retinal oedema
  • haemorrhages
  • NOTE: this can take days to become apparent
185
Q

what progressive neurological deficits are seen in primary brain tumours in the temporal lobe?

A

dysphasia, amnesia

186
Q

what progressive neurological deficits are seen in primary brain tumours in the frontal lobe?

A

hemiparesis, personality change, Broca’s dysphasia,

lack of initiative, unable to plan tasks

187
Q

what progressive neurological deficits are seen in primary brain tumours in the parietal lobe?

A

hemisensory loss, reduction in 2-point discrimination,

dysphasia, astereognosis (unable to recognise object from touch alone)

188
Q

what progressive neurological deficits are seen in primary brain tumours in the occipital lobe?

A

contralateral visual defects

189
Q

what progressive neurological deficits are seen in primary brain tumours in the cerebellum? (DASHING)

A

DASHING:

  • Dysdiadochokinesis (impaired rapidly alternating movement)
  • Ataxia
  • Slurred speech (dysarthria)
  • Hypotonia
  • Intention tremor
  • Nystagmus
  • Gait abnormality
190
Q

what are features of epilepsy/seizure in primary brain tumours?

A
  • sinister when of recent onset
  • partial/focal seizures are more common with tumours:
    • motor
    • sensory
    • temporal lobe pattern: olfactory aura or deja vu or a funny feeling in the gut/stomach a few minutes before and/or during the seizure
191
Q

what are differential diagnoses of primary brain tumours?

A 
other causes of space-occupying lesion:
• aneurysm
• abscess
• cyst
• haemorrhage
• idiopathic intracranial hypertension
192
Q

what is used to diagnose primary brain tumours?

A
  • CT and MRI
  • blood tests e.g. FBC, U+Es, LFTs, B12 etc.
  • biopsy
  • lumbar puncture is contraindicated
193
Q

how is CT and MRI sued to diagnose primary brain tumours?

A
  • MRI is superior for posterior fossa lesions
  • determines the size and location of lesions
  • high grade tumours have irregular edges and high growth rate
194
Q

how is biopsy used to diagnose primary brain tumours?

A
  • via skull burr-hole

* to determine cancer grade and confirm diagnosis

195
Q

how is lumbar puncture used to diagnose primary brain tumours? why is it contraindicated?

A

lumbar puncture is contraindicated when there is any possibility of a mass lesion since withdrawing CSF may provoke immediate coning (herniation of the brain through the foramen magnum resulting in brainstem compression as it passes through foramen
magnum) and potential death

196
Q

what is the treatment of primary brain tumours?

A
  • surgery to remove mass if possible
  • chemotherapy for glioma
  • oral dexamethasone
  • anticoagulants e.g. oral carbamazepine
197
Q

what chemotherapy is given for primary brain tumours?

A
  • given at the same time as surgery and then for first 6 weeks post-op
  • e.g. temozolomide
  • however not all tumours are sensitive to temozolomide; some are tumours have high methyl-guanine-methyltransferase (an enzyme that reverses the therapeutic effect of temozolomide)
  • best to determine if tumour is sensitive before administration
198
Q

what are features of oral dexamethasone given for primary brain tumours?

A
  • most powerful synthetic steroid
  • rapidly improves brain performance in all tumours
  • reduces tumour inflammation/oedema
  • must give no later than 14:00 since it keeps patient awake
199
Q

what are the commonest neoplasms to metastasise to the CNS in order, to cause a secondary brain tumour?

A
  • non small cell lung carcinoma (most common)
  • small cell lung carcinoma
  • breast
  • melanoma
  • renal cell
  • GI
200
Q

what is the treatment of secondary brain tumours?

A
  • surgery if age <75yrs
  • radiotherapy
  • chemotherapy
  • palliative therapy
201
Q

what is meningitis?

A

inflammation of the meninges; can be bacterial/viral/fungal

202
Q

what is encephalitis?

A

inflammation of the brain; usually viral

203
Q

what is encephalopathy?

A
  • reduced level of consciousness/diffuse disease of brain substance
  • usually non-infective with multiple aetiologies
204
Q

what is polyradiculopathy?

A
  • inflammation of the nerve roots e.g. cauda equina

- HIV, CMV, syphilis

205
Q

what is myelitis?

A

inflammation of the spinal cord

206
Q

what is the epidemiology of meningitis?

A
  • occurs in people of all age groups but more common in infants, young children and the elderly
  • meningococcal disease is a notifiable disease to public health england
207
Q

what are causes of meningitis in adults and children?

A
  • Neisseria meningitidis; gram negative diplococci transmitted by droplet spread
  • Streptococcus pneumoniae/Pneumococcus
  • less common is Haemophilus influenza, due to the introduction of a vaccine
208
Q

what is the aetiology of meningitis in pregnant women/older adults?

A

Listeria monocytogenes; this is found in cheese, this is why pregnant women told to avoid it

209
Q

what is the aetiology of meningitis in neonates?

A
  • Escheria coli

* group B haemolytic streptococcus; Streptococcus agalactiae

210
Q

what is the aetiology of meningitis in immunocompromised people?

A
  • cytomegalovirus
  • Cryptococcus neoformans
  • Mycobacterium tuberculosis
  • HIV
  • herpes simplex virus
211
Q

what are risk factors for meningitis?

A
  • intrathecal drug administration
  • immunocompromised
  • elderly
  • pregnant
  • bacterial endocarditis
  • crowding
  • diabetes
  • malignancy
  • IV drug abuse
212
Q

what is the pathophysiology of meningitis?

A
  • microorganisms reach the meninges either by direct extension from the ears, nasopharynx, cranial injury or congenital meningeal defect or by bloodstream spread
  • immunocompromised patients are at risk of infection with unusual organisms
213
Q

what is the pathophysiology of acute bacterial meningitis?

A
  • typically sudden
  • Neisseria meningitidis is transmitted by droplet spread
  • can lead to meningococcal septicaemia
  • the pia-arachnoid is congested with polymorphs
  • a layer of pus forms which may organise to form adhesions causing cranial nerve palsies and hydrocephalus
214
Q

what is meningococcal septicaemia?

A
  • when bacteria invades into blood
  • presence of endotoxin in bacteria leads to an inflammatory cascade
  • petechial rash + signs of sepsis = meningococcal septicaemia
215
Q

what is the triad of meningitis?

A

headache, neck stiffness, fever

216
Q

what is the clinical presentation of acute bacterial meningitis?

A

• onset is typically sudden
• papilloedema
• there is usually intense malaise, fever, rigors, severe
headache, photophobia and vomiting within hours or minutes
• patient is irritable and prefers to lie still
• neck stiffness, positive Kernig’s and Brudzinski’s
sign can appear within hours
• meningococcal septicaemia is associated with a
non-blanching petechial and purpuric skin rash
• altered mental state (reduced GCS) with high fever; often absent
• seizures and focal CNS signs
• progressive drowsiness, materialising signs and cranial nerve lesions indicate complication e.g. venous sinus thrombosis, severe cerebral oedema or cerebral abscess

217
Q

what are features of papilloedema in acute bacterial meningitis?

A
  • swelling of optic disc on fundoscopy
  • usually bilateral
  • can occur over hours to weeks
  • caused by raised ICA
218
Q

what is the clinical presentation of viral meningitis?

A
  • benign, self-limiting condition lasting 4-10 days
  • headache may follow for some months
  • predominantly lymphocytic inflammatory CSF reaction without pus formation
  • little or no cerebral oedema unless encephalitis develops
219
Q

what is the clinical presentation of chronic meningitis?

A

• Mycobacterium tuberculosis
• long history and vague symptoms of headache, anorexia and vomiting
• signs of meningeal triad are often absent or late
brain is covered in a viscous grey-green exudate with numerous meningeal tubercles

220
Q

what are differential diagnoses of meningitis?

A
  • aseptic meningitis, due to tumour
  • sub-arachnoid haemorrhage
  • encephalitis; altered mental state is the predominant symptom
221
Q

what is used to diagnose meningitis?

A
  • blood cultures before lumbar puncture
  • blood tests; FBC, U+E, CRP, serum glucose
  • lumbar puncture at L4; if unable to perform within 30 mins give empirical antibiotics
  • CT head
  • throat swabs
  • pneumococcal and meningococcal serum PCR
222
Q

how is lumbar puncture used to diagnose meningitis?

A
  • send for microscopy and sensitivity

* can give headache, paresthesia, CSF leak and spinal cord damage

223
Q

what are the typical results of bacterial meningitis in a lumbar puncture?

A
  • cells: neutrophil polymorphs
  • protein: raised
  • glucose: low
224
Q

what are the typical results of TB meningitis in a lumbar puncture?

A
  • cells: lymphocytes
  • protein: raised
  • glucose: low/normal
225
Q

what are typical results of viral meningitis in a lumbar puncture?

A
  • cells: lymphocytes
  • protein: normal
  • glucose: normal
226
Q

what are indications for CT before lumbar puncture in meningitis diagnosis?

A
  • age more than 60
  • immunocompromised
  • history of CNS disease
  • new onset/recent seizures
  • decreasing conscious levels (GCS < 14)
  • focal neurological signs
  • papilloedema
227
Q

what indicates meningococcal septicaemia?

A

non-blanching petechial or purpuric rash

228
Q

what is the diagnosis/treatment of meningococcal septicaemia?

A
  • must give immediate IV benzylpenicillin (in community) or IV cefotaxime (in hospital)
  • lumbar puncture is not performed if meningococcal sepsis due to risk of coning of cerebellar tonsils and raised ICA
  • diagnosis confirmed by blood cultures
229
Q

what is the treatment of bacterial meningitis?

A
  • IV cefotaxime or IV ceftriaxone (can give IV chloramphenicol if severe anaphylaxis with penicillin)
  • if over 50 or immunocompromised then add IV amoxicillin to cover Listeria
  • consider steroids e.g. oral dexamethasone to reduce cerebral oedema
  • consider IV vancomycin in return travellerse
  • prophylaxis for contacts (oral ciprofloxacine or rifampicin)
  • complications include hearing loss seizures
230
Q

what is the epidemiology of encephalitis?

A
  • infections are most frequent in children and elderly; mainly viral cause
  • more common in the immunocompromised
231
Q

what are some viral causes of encephalitis?

A

Herpes simplex virus 1 and 2, Varicella zoster, Epstein Barr, Cytomegalovirus, HIV, mumps, measles

232
Q

what are some non-viral causes of encephalitis?

A
  • bacterial meningitis
  • TB
  • malaria
233
Q

what are the risk factors for encephalitis?

A
  • extremes of age

- immunocompromised

234
Q

what is the pathophysiology of encephalitis?

A
  • infection and inflammation of the brain parenchyma
  • disease which mostly affects the frontal and temporal lobes resulting in decreased consciousness, confusion and focal signs
235
Q

what is the clinical presentation of encephalitis? what is the triad?

A
  • whole brain affected; problems with consciousness (global defect in higher functioning as well as drowsiness etc.) compared to meningitis
  • insidious onset (days) or can be abrupt
  • begins with fever, headaches, myalgia, fatigue and nausea
  • triad: fever + headache + altered mental status
  • may have signs of meningitis - this is known as meningo-encephalitis which consists of inflammation of meninges and brain parenchyma
  • there may be a history of travel and/or animal bite
236
Q

what does encephalitis progress to?

A
  • personality and behavioural changes - common early manifestation
  • decreased consciousness, confusion, drowsiness
  • focal neurological deficit: hemiparesis and dysphasia
  • seizures
  • raised ICP and midline shift may occur resulting in coning
  • coma
237
Q

what are the differential diagnoses of encephalitis?

A
  • meningitis
  • stroke
  • brain tumour
238
Q

what is used to diagnose encephalitis?

A
  • MRI
  • electroencephalography (periodic sharp and slow wave complexes)
  • lumbar puncture
  • blood and CSF seology is usually helpful
239
Q

how is MRI used to diagnose encephalitis?

A
  • shows areas of inflammation and swelling, generally in the temporal lobes in HSV encephalitis
  • may be midline shifting due to raised ICP
240
Q

how is lumbar puncture used to diagnose encephalitis?

A
  • CSF shows elevated lymphocyte count
  • viral detection by CSF PCR is highly sensitive for Herpes simplex and Varicella zoster
  • however a false-negative may occur within the first 48hrs of symptom onset
241
Q

what is the treatment of viral encephalitis?

A
  • if viral e.g. herpes simplex or varicella zoster then immediate treatment with anti-viral e.g. IV aciclovir, even before the investigation results are available
  • early treatment can reduce mortality and long neuro damage
242
Q

what is the treatment of encephalitis if meningitis is suspected?

A

emergency IM benzylpenicillin

243
Q

what is herpes zoster? what is it caused by?

A
  • shingles
  • caused by reactivation of varicella zoster virus (chickenpox), usually within the dorsal root ganglia
  • primary infection with VZV causes chickenpox, following which the virus remains latent in sensory ganglia
  • development of shingles may indicate a decline in cell-mediated immunity such as that due to age or malignancy
244
Q

what is the epidemiology of herpes zoster?

A
  • 90% of children have been exposed to chicken pox (varicella zoster) before they are aged 16
  • can effect all ages but seen as a disease of the elderly
  • incidence and severity increase with age
  • shingles cannot be caught from contact with a person with chickenpox
245
Q

what are risk factors for herpes zoster?

A
  • increasing age
  • immunocompromised
  • HIV, Hodgkin’s lymphoma and bone marrow transplants
246
Q

what is the pathophysiology of herpes zoster?

A
  • viral infection affecting peripheral nerves
  • when latent virus is reactivated in the dorsal root ganglia it travels down the affected nerve via the sensory root in dermatomal distribution over a period of 3-4 days
  • resulting in perineural and intramural inflammation
  • in immunocompromised patients, the most frequent site of reactivation is the thoracic nerves followed by the opthalmic division of the trigeminal nerve
  • can also affect the cervical, lumbar and sacral nerve roots
  • person with weeping shingles rash can cause chickenpox in non-immune people after close contact
247
Q

what is the clinical presentation of herpes zoster?

A
  • 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
248
Q

what are features of rash in herpes zoster?

A
  • consists of papules and vesicles restricted to the 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
249
Q

what are differential diagnoses of herpes zoster?

A
  • before rash appears the pain may come from chest or there may be abdominal pain; may think cholecystitis or renal stones
  • cluster headaches or migraine
  • atopic eczema, contact dermatitis or herpes simplex or impetigo
250
Q

what is used diagnose herpes zoster?

A
  • clinical diagnosis

- eruption of rash is virtually diagnostic

251
Q

what is used to treat herpes zoster?

A
  • oral antiviral therapy begun within 72hrs of rash onset
  • oral aciclovir 5 times daily or oral valivivlovir twice daily or oral famciclovir twice daily
  • rapid treatment start to minimise risk of peripheral herpetic neuralgia
  • topical antibiotic treatment for secondary bacterial infection
  • analgesia
252
Q

what are complications of treatment for herpes zoster?

A
  • damage to opthalmic branch of trigeminal nerve

- post-herpetic neuralgia

253
Q

what are features of post herpetic neuralgia?

A
  • pain lasting for more than 4 months after developing shingles
  • occurs in 10% of patients; often elderly
  • burning, intractable pain
  • responds poorly to analgesics
254
Q

what is the treatment of post herpetic neuralgia?

A
  • tricyclic antidepressant e.g. oral amitriptyline
  • anti-epileptic e.g. oral gabapentin
  • anti-convulsant e.g. oral carbamezapine
255
Q

what is ataxia?

A

ataxia is the name given to a group of neurological disorders that affect balance, coordination and speech

256
Q

what are symptoms and signs of cerebellar dysfunction?

A
  • dysarthria - slurring of speech
  • dysphagia - difficulty swallowing
  • clumsiness of arms and legs
  • intention tremor
  • unsteadiness when walking
  • stumbling and falls
  • cognitive problems
  • nystagmus
  • limb and gait ataxia
257
Q

what are the different types of ataxia?

A
  • congenital ataxias e.g. cerebellar dysgenesis
  • diseases where ataxia is one of many features - usually autosomal recessive disorders
  • episodic ataxia - bouts of attacks of symptoms then resolve and recur
  • autosomal recessive ataxia
  • autosomal dominant ataxia
  • sporadic ataxia
258
Q

what is Friedreich’s ataxia?

A
  • ataxia of gait and limb
  • absent reflectors
  • complications include diabetes and cardiomyopathy
259
Q

what is autosomal dominant ataxia?

A

spinocerebellar ataxia 6 (SCA 6)

260
Q

what is the most common ataxia in the UK?

A

spinocerebellar ataxia 6 (autosomal dominant)

261
Q

what are features of spinocerebellar ataxia 6?

A
  • most common ataxia in the UK
  • slowly progressive ataxia with dysarthria, dysphagia, gait ataxia (balance problems) and nystagmus
  • symptoms starts from late 40s to early 50s
262
Q

how is MRI used to diagnose cerebellar disease?

A

look for:
• cerebrovascular damage e.g. posterior circulation stroke affecting the cerebellum
• primary tumours e.g. acoustic neuroma or hemangioblastoma
• secondary tumours
• hydrocephalus
• MS

263
Q

what are examples of SSRIs?

A

Citalopram, Fluoxetine, Sertraline

264
Q

what are indications for SSRIs?

A
  • first line treatment for moderate to severe depression and in mild depression if other treatments fail
  • panic disorder or obsessive compulsive disorder
265
Q

what is the mechanism of action of SSRIs?

A
  • SSRIs preferentially inhabit neuronal reuptake of serotonin (5-HT) from the synaptic cleft, so increase its availability for neurotransmission
  • thus it improves mood and physical symptoms in depression and relives symptoms of panic
266
Q

what are adverse effects/contraindications of SSRIs?

A
  • common side effects are GI disturbance, appetite and weight disturbance and hypersensitivity reactions
  • hyponatraemia may occur
  • suicidal thought/behaviours may be increased and the drug lowers the seizure threshold and can prolong QT interval
  • used with care in people with peptic ulcers, epilepsy, hepatic impairment and may not be effective in young people
  • contraindicated with other monamine oxidase inhibitors as may cause serotonin syndrome due to increased serotonin levels
  • also contraindicated with other drugs that prolong QT interval
  • may also increase bleeding when used with anticoagulants
267
Q

what is an example of tricyclic antidepressants?

A

amitriptyline

268
Q

what is an indication for tricyclic antidepressants?

A

as a second line treatment for moderate to severe depression where SSRIs are ineffective

269
Q

what are mechanisms of action of tricyclic antidepressants?

A
  • inhibit neuronal uptake of serotonin (5-HT) and noradrenaline from the synaptic cleft so increase the availability for neurotransmission
  • improve mood and physical symptoms
  • they also block a wide range of receptors which accounts for their extensive side effects
270
Q

what are adverse effects/contraindications of tricyclic antidepressants?

A
  • dry mouth, constipation, urinary retention, blurred vision, sedation, hypotension, arrhythmias, QT and QRS prolongation, hallucinations and sexual dysfunction
  • use with caution in people particularly at risk of adverse effects i.e. elderly, people with CV disease or epilepsy
  • contraindicated with MAOIs as serotonin levels can get too high
271
Q

what are examples of benzodiazepines?

A

diazepam, lorazepam

272
Q

what are indications for benzodiazepines?

A
  • first line treatment of seizures and status epilepticus
  • management of alcohol withdrawal reactions
  • short term treatment of severe anxiety or insomnia
273
Q

what are mechanisms of action of benzodiazepines?

A
  • benzodiazepines target the GABA-a receptor, which is a chloride channel that opens in response to binding by GABA (inhibitory neurotransmitter)
  • opening the channel allows chloride to enter, making the cell more resistant to depolarisation
  • they facilitate the enhanced binding of GABA to GABA-a receptors and have a widespread depressant effect on synaptic transmission
  • can thus cause reduced anxiety, sleepiness, sedation and anti-convulsion
274
Q

what are adverse effects/contraindications of benzodiazepines?

A
  • cause dose dependent drowsiness, sedation, coma and in overdose the loss of airway reflexes which can lead to coma and death
  • use with in the elderly, those with respiratory or heaptic impairment and neuromuscular disease
  • have increased sedative effects when used with other drugs such as alcohol and opioids, and use with cytochrome P450 inhibitors e.g. amiodarone or macrolides may increase their effects
275
Q

what are examples for anticonvulsants?

A

carbamezepine, gabapentin, pregabalin

276
Q

what are indications for carbamezepine?

A
  • first line treatment for epilepsy - specifically for partial/focal seizures with/ without secondary generalisation and for primary generalised seizures
  • trigeminal neuralgia to control pain and reduce attack severity
277
Q

what are mechanisms of action for carbamezepine?

A
  • incompletely understood - inhibits neuronal Na+ channels, stabilising resting membrane potential and reducing neuronal excitability
  • this may inhibit spread of seizure activity in epilepsy and control neuralgic pain by blocking synaptic transmission in the trigeminal nucleus
278
Q

what are adverse effects/contraindications of carbamezepine?

A
  • most common is GI disturbance, dizziness and ataxia (loss of motor control), hypersensitivity skin rash, oedema and hyponatraemia
  • contraindicated in prior anti-epileptic hypersensitivity syndrome (severe rash, fever, lymphadenopathy)
  • used with caution in hepatic, renal and cardiac disease
  • carbamezepine reduces efficacy of drugs metabolised by p450 enzymes e.g. warfarin, oestrogens, progesterones
  • effects are increased by cytochrome p450 inhibitors
  • efficacy reduced by drugs that lower seizure threshold e.g. SSRIs
279
Q

what are indications for gabapentin and pregabalin?

A
  • partial/focal epilepsies, usually as add on when other drugs such as carbamezepine are insufficient
  • also used for neuropathic pain, migraine prophylaxis and generalised anxiety disorder
280
Q

what are mechanisms of action of gabapentin and pregabalin?

A
  • gabapentin is closely related to GABA, the main inhibitory neurotransmitter in the brain
  • it binds voltage sensitive Ca2+ channels, where it prevents inflow of Ca2+ and thus inhibits neurotransmitter release, interfering with synaptic
    transmission and reducing neuronal excitability
281
Q

what are adverse effects/contraindications of gabapentin and pregabalin?

A
  • generally is better tolerated than other anti-epileptics, main side effects are drowsiness, dizziness and ataxia
  • use with care in renal impairment
  • sedative effects will be enhanced when used with other sedating drugs
282
Q

what are examples of dopaminergic drugs?

A

levodopa

283
Q

what are indications for dopaminergic drugs?

A

Parkinsons

284
Q

what are mechanisms of action of dopaminergic drugs?

A
  • in Parkinson’s there is a deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra to the basal ganglia, causing the basal ganglia to exert greater inhibitor effects on the thalamus and reduces excitatory input to the motor cortex, generating features of Parkinson’s
  • treatment increases dopaminergic stimulation to the basal ganglia; dopamine itself cannot cross the blood-brain barrier, but levodopa is a precursor of dopamine that can enter the brain
  • once in the brain it can be converted to dopamine in dopaminergic neurones
285
Q

what are adverse effects/contraindications of dopaminergic drugs?

A
  • nausea, drowsiness, confusion, hallucinations, hypertension
  • effects wear off towards the end of dosage intervals
  • increasing the dose can lead to excessive movement causing the ‘on/off effect’
  • use with care in the elderly and those with existing cognitive disease
  • use with caution in CVS disease
  • always given alongside a decarboxylase inhibitor such as Co-Careldopa to reduce levodopa’s peripheral conversion before it is able to enter the brain; this reduces nausea and lowers dose required
  • do not use with antipsychotics as they contraindicate the effects of levodopa
286
Q

what is an example of a dopamine depleting drug?

A

reserpine

287
Q

what are indications for a dopamine depleting drugs?

A
  • to treat dyskinesia in Huntington’s disease

- also can be used at antipsychotic and antihypertensive drug

288
Q

what are mechanisms of action of dopamine depleting agents?

A
  • monoamine neurotransmitters are dopamine, serotonin, adrenaline and serotonin
  • irreversibly blocks the vesicular monoamine transporter (VMAT) which normally transports free intracellular noradrenaline, serotonin and dopamine for release across the synapse
  • thus the post synaptic cells is not activated and symptoms decrease - the effects are long lasting until VMAT is replenished
289
Q

what are adverse effects/contraindications of dopamine depleting agents?

A
  • most common are nasal congestion, GI disturbance and drowsiness/dizziness
  • may cause hypotension and bradycardia so use with care in patients with CVS disease
  • may also worsen asthma
290
Q

what are examples of triptans?

A

sumatriptan, rizatriptan

291
Q

what are indications for triptans?

A

used in the treatment of migraines and cluster headaches

292
Q

what are mechanisms of action of triptans?

A
  • action is attributed to their agonist effects on serotonin 5-HT-1b and 1d receptors in cranial blood vessels, causing their constriction and subsequent inhibition of pro-inflammatory neuropeptide release
  • may also work on serotonin receptors in nerve endings to relieve pain through the decrease in levels of substance P
293
Q

what are adverse effects/contraindications of triptans?

A
  • most common side effect is recurrence of migraine; more than there was without drug
  • there is a rare risk of coronary spasm and cardiac events
  • contraindicated in patients with previous/current severe CVD or stroke
  • use with caution in older people and being with family history of CVD, stroke, diabetes and high cholesterol
294
Q

what are examples of monoamine oxidase inhibitors?

A

selegiline, rasagiline

295
Q

what are indications for monoamine oxidase inhibitors?

A
  • for the treatment of Parkinson’s disease and Alzheimer’s disease
  • can also be used to treat atypical depression
296
Q

what are the mechanisms of action of monoamine oxidase inhibitors?

A
  • monoamine neurotransmitters are dopamine, serotonin, adrenaline and serotonin
  • act by inhibiting the activity of monamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and increasing their availability
  • MAO-B is preferentially targeted in Parkinson’s and Alzheimer’s disease as this is found to be increased
297
Q

what are adverse effects/contraindications of monoamine oxidase inhibitors?

A
  • hypertensive crisis may occur if large amounts of tyramine (an amine broken down by MAO) are consumed, so patient must cut down on aged cheeses and alcohol
  • should not be used with other psychoactive drugs such as antidepressants and adrenaline
298
Q

what are examples of acetylcholinesterase inhibitors?

A

rivastigmine, donepezil

299
Q

what are indications for acetylcholinesterase inhibitors?

A
  • used for treatment of Alzheimer’s disease, Lewy body dementia and Parkinson’s
  • myasthenia gravis
300
Q

what are the mechanisms of action of acetylcholinesterase inhibitors?

A
  • inhibits the breakdown of acetylcholine by blocking the site of acetylcholinesterase
  • in neurodegenerative disorders they are used to treat the memory and learning deficit symptoms, which improve due to the role of acetylcholine in cognition
  • in myasthenia gravis there are too few acetylcholine receptors, so with acetylcholinesterase blocked and acetylcholine transmission is increased, then acetylcholine can bind to the few receptor more easily and trigger more muscular contractions
301
Q

what are adverse effects/contraindications of acetylcholinesterase inhibitors?

A
  • actions on parasympathetic nervous system may cause bradycardia, hypotension, hypersecretion, bronchoconstriction and GI tract hyper motility
  • can also cause prolonged muscular contraction
  • contraindicated in urinary retention due to obstruction
  • use with care in people with CVS disease i.e. arrhythmias and in asthmatics

Phase 2A (28 decks)

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