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Year 4 - Neurology + Special Senses > Neuro - Multiple Sclerosis > Flashcards

Neuro - Multiple Sclerosis Flashcards

1
Q

What is a relative afferent pupillary defect (RAPD)?

A

RAPD = sign of optic neuropathy (CN II)

  • Sign of pathology in; optic nerve (proximal to chiasm), retina or eye itself
  • Detected via ‘swinging light test’ - shine light into one of the pt’s eyes, then the other and then back to the first eye
    • Normal = pupil remains constricted (equal direct and consensual constriction)
    • RAPD = pupil appears to dilate when light is move from unaffected eye to the affected one (direct light response < consensual light response)
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2
Q

Optic Neuritis:

  • What is it?
  • What causes it?
  • Feature of ON?
  • Management?
A

Optic neuritis = demyelinating inflammation of the optic nerve (CN II)

Causes:

  • Multiple sclerosis (ON is often the 1st symptom)
  • Diabetes
  • Syphilis

Features:

  1. unilateral ↓ in visual acuity (over hours-days)
  2. poor discrimination of colours ‘red desaturation’ - red colour appears ‘washed out’ in affected eye
  3. eye pain - worse on movement
  4. RAPD
  5. central scotoma - partial visual loss / blind spot
  6. Pale optic disc on fundoscopy (papillitis = inflammation of optic nerve head)

Management:

  • Steroids e.g. Methyl Prednisolone 1g oral / IV once daily for 3 days (morning)
    • If partial response, extend course to 5 days
  • Recovery = 4-6 weeks
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3
Q

What investigations might you do in a pt with optic neuritis?

A

Tests looking for evidence of systemic inflammation (in which ON is a feature):

  • CRP, ESR - inflammation markers
  • Serology for autoimmune conditions:
    • ANA, ANCA, ds-DNA, ENA, anticardiolipin antibodies, serum ACE
    • +ve result on the above could indicate; GPA, EGPA, antiphospholipid syndrome, sarcoidosis etc.
  • Serology for infectious triggers (rare cause of ON):
    • HIV, syphilis, hepatitis B and C
  • Antibodies for neuromyelitis optica (Devic’s disease):
    • anti-AQP4 (auto-antibodies against aquaporin 4)
    • anti-MOG (auto-antibodies against myelin oligodendrocyte glycoprotein)
    • anti-NF (auto-antibodies against neurofascins)
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4
Q

In which areas of the nervous system could a pathology cause unsteadiness of gait i.e. gait ataxia?

A
  1. Cerebellum + cerebellar connections to brain - CEREBELLAR ATAXIA
    • Stacatto dysarthria (DANISH)
    • Sudden, ipsilateral arm + leg weakness = stroke
  2. Dorsal columns of the spinal cord - SENSORY ATAXIA
    • L’Hermitte’s sign - tingling/electrical sensation in back + limbs when flexing or extending head (spinal cord specific)
    • Tight band-like sensation around torso
    • Urinary urgency + frequency (rarely seen in peripheral nerve pathology)
    • Other symptoms as in peripheral nerves below …
  3. Peripheral nerves / nerve roots (large myelinated fibres) - SENSORY ATAXIA
    • Altered sensation e.g. parasthesia, numbness
    • Balance worse in the dark/when eyes shut (due to loss of vision to balance self + proprioceptive impairment)
  4. Vestibular apparatus + connections
    • Vertigo (worse on head movement)
    • Nausea / vomiting
    • Sometimes hearing loss and/or tinnitus
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5
Q

What are some of the risks of steroids acutely?

A
  • GI disturbance - give PPI
  • Agitation / restlessness
  • Insomnia
  • Steroid psychosis - behavioural change
  • Weight gain
  • Avascular necrosis of femoral head (rare)
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6
Q

What tests need to be done prior to a course of steroids?

A

Check for signs of systemic infection!!

(steroids = immunosuppresive)

  • FBC
  • U+Es
  • eGFR - assess renal function
  • Blood glucose
  • CRP / ESR
  • Urine dipstick - UTI
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7
Q

What blood test is important in a pt with a high signal lesion of the posterior cervical cord on MRI?

(seen in image)

A

Serum B12

  • Vitamin B12 deficiency can produce ↑ T2-weighted signal (white lesion) or ↓ T1-weighted signal of the posterior or lateral spinal cord - mainly cervical or upper thoracic segments
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8
Q

What is a MRI brain scan with injection of Gadolinium contrast used for?

A

Gadolinium contrast = highlights areas of BBB breakdown - which suggests active / recent inflammation

  • Sometimes done in the context of multiple sclerosis to differentiate old vs new white-matter lesions
    • Old lesions - inactive inflammation
    • New lesions - active/recent inflammation
  • Evidence of new + old lesions = typical of relapsing-remitting MS ‘lesions disseminated in time and place’
  • T2 weighted image - will show BOTH old + new white-matter lesions (white lesion contrasted against grey coloured white-matter) - left image
  • T1 weighted image + Gadolinium contrast - shows ‘new’ white-matter lesions (as white lesion against grey coloured background) - right image
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9
Q

What do lesions typical of multiple sclerosis look like on T2 MRI?

A
  • They appear as small high signal lesions (white in contrast to background)
  • Lesions can be in many locations, but one common one is periventricular white matter
    • Here a lesion perpendicular to the long axis of the ventricles is typical of a demylinating lesion
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10
Q

How are acute, MS relapses managed?

A

1st line = High-dose steroids e.g. Methyl Prednisolone​

  • In patient –> IV Methyl Prednisolone 1g OM, for 3 days (morning)
  • Out-patient –> Oral Methyl Prednisolone 500mg OM, for 5 days (just as effective as in-patient IV)

Notes:

  • Steroids ↓ length of acute relapse but do not alter degree of recovery
  • Beneficial effects of successive steroid courses tend to diminish
  • Check for presence of infections BEFORE prescribing
  • If patient is diabetic then close serum glucose monitoring
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11
Q

What are the criteria for a MS patient to recieve ‘disease-modifying treatment’?

A

Patient must have 2 or more significant relapses over a 2 year period

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12
Q

Describe the common course of multiple sclerosis?

A

Often it presents as relapsing-remitting (RR-MS) i.e. several episodes of symptoms with recovery in between and good seperation between episodes.

It can then develop into Secondary Progressive MS (SPMS) and become a steady decline in function over time.

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13
Q

What does the drug Baclofen do?

A

Used to manage msucle spasticity

(such as that caused by spinal cord injury or MS)

  • Uses:
    • ↓ muscle spasticity
    • hiccups / muscle spasms near end of life
  • MoA: deriative of GABA –> acts on GABAB receptors in spinal cord and brainstem
  • Side effects:
    • Sedation - dose required for spasticity management causes this
    • Dizziness
    • Insomnia
    • Nausea / vomiting
    • Urinary retention / constipation
    • If stopped suddenly –> seizures / rhabdomyolysis
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14
Q

How is neuropathic pain described?

What symptoms can appear alongside it?

How is it managed in MS?

A

Neuropathic Pain - MS

  • Neuropathic pain = burning or stabbing
  • Common accompanying symptoms:
    • paradoxical numbness
    • paraesthesia
    • hyperpathia (an increased sensitivity to painful stimuli)
    • allodynia (when a non-painful stimulus is perceived as painful)
      • e.g. pain induced by bedclothes touching the feet
  • Gabapentin can be used for neuropathic pain in MS
    • Is an AED (voltage-gated Ca2+ channels)
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15
Q

How does oxybutynin work?

A

Oxybutynin:

  • Uses:
    • Urinary frequency / urgency / incontinence
  • MoA:
    • Inhibits muscarinic ACh receptors
    • This inhibits parasympathetic stimulation of bladder detrusor muscle
    • Results in ↓ urgency and frequency
  • Side effects (anti-cholinergic):
    • Dry mouth
    • Constipation
    • Drowsiness
    • Dizziness
    • Difficulty urinating
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16
Q

Bladder dysfunction is a feature of MS.

What forms can this take and why might you have to be cautious in prescribing oxybutynin?

A
  • Bladder dysfunction in MS i.e. ‘neuropathic bladder’ can take the form of:
    • Urgency, frequency
    • Incontinence / overflow incontinence
  • If pt with MS has ↓ bladder emptying and thus overflow incontinence a post-micturition bladder scan is needed!
    • Oxybutynin –> will improve urgency / frequency / incontinence if pt has normal complete bladder emptying
    • Oxybutynin –> will worsen overflow incontinence by making the pt retain more urine (which is indicated if there is incomplete bladder emptying)
  • Bladder scan results + action:
    • significant residual volume → intermittent self-catheterisation
    • no significant residual volume → anticholinergics (e.g. oxybutynin) may improve urinary frequency
17
Q

Name some drugs that can be used in the management of neuropathic pain?

A

Common neuropathic pain treatment:

  • Pregabalin (often used 1st)
  • Gabapentin
  • TCAs (low dose) e.g. amitriptyline or nortriptyline
    • Anticholinergic side effects: sedation, dry mouth, difficulty in micturition and confusion
  • Duloxetine (SNRI) - uses less due to GI side effects
  • Trigeminal pain:
    • carbamazepine or oxcarbazepine

Alternatives:

  • Capsaicin cream
  • Lidocaine patches
  • Nerve blocks
  • Epidurals
18
Q

A 32 year old female with MS attends her GP concernd she may be experiencing a relapse. Which of the following symptoms are common during an MS relapse?

  • Attacks of altered awareness/loss of consciousness
  • Excessive daytime sleepiness
  • Fluctuating diffuse sensory symptoms in limbs, trunk and face
  • Headache
  • Urinary symptoms: frequency, urgency and retention
A

Urinary symptoms: frequency, urgency and retention

19
Q

A 28 year old man present with walking difficulties. He has weakness and brisk reflexes in all four limbs. MRI scanning reveals changes of CNS inflammation. Which of the following inflammatory conditions does not mimic MS?

  • Anticardiolipin antibody syndrome
  • Devic’s syndrome (neuromyelitis optica)
  • Neurosarcoidosis
  • Polymyositis
  • Sjogren’s syndrome
A

Polymyositis

(inflammatory muscle disease, thus produces LMN signs)

  • Devic’s syndrome (neuromyelitis optica)
    • inflammatory disease of the CNS that causes 1) optic neuritis 2) longitudinally extensive transverse myelitis (inflammation spanning > 3 vertebral segments on MRI)
  • Anticardiolipin antibody syndrome / Neurosarcoidosis / Sjogren’s syndrome:
    • inflammatory diseases that can cause CNS lesions similar to MS
20
Q

What is multiple sclerosis?

A

Multiple sclerosis = chronic autoimmune disorder characterised by demyelination in the CNS

  • 3 x more common in women
  • most common age = 20-40yrs
  • more common at higher latitudes
  • Genetic element: monozygotic twin concordance = 30%
21
Q

What are the common subtypes of MS?

A
  1. Relapsing-remitting (RR-MS):
    • Commonest form (~85% of cases)
    • acute attacks (~1-2 months) followed my period of remission
  2. Secondary progressive MS (SPMS):
    • RR-MS which deteroriates (neurological signs between relapses)
    • ~ 65% of RR-MS develop SPMS within 15 years of diagnosis
    • Common features = gait & bladder disorders
  3. Primary progression MS (PPMS):
    • ~ 10% of cases
    • more common in elderly onset
22
Q

What are the diagnostic criteria for MS?

A

2 or more attacks / relapses!!

  • These attacks need to be evidence by either:
    • clinical evidence of 2 or more lesions OR
    • clincal evidence of 1 lesion + resonable historical evidence of 1 attack

Note: these criteria fufill the picture of MS being disseminated in both TIME (multiple attacks) and SPACE (multiple lesions)

23
Q

What are the symptom features of MS?

A
  • Visual:
    • Optic neuritis (commonly 1st feature):
      • unilateral ↓ in visual acuity (over hours-days)
      • poor discrimination red colours
      • eye pain - worse on movement
      • RAPD
    • optic atrophy / optic neuropathy - vision loss
    • Uhthoff’s phenomenon - worsening of vision following rise in body temperature
    • internuclear opthalmoplegia - affected eye fails to look medially (towards contralateral side) + other eye exhibits nystagmus
      • Lesion is in medial longitudinal fasciculus (MLF) which carries info and direction of eye movement
  • Sensory:
    • paraesthesia (pins/needles)
    • numbness
    • trigeminal neuralgia or neuropathy (pain or numbness)
    • Lhermitte’s syndrome - paraesthesia sensation in back + limbs when flexing or extending head
  • Motor:
    • Spastic weakness - commonly in legs (e.g. ankle clonus)
      • velocity-dependent ↑ in tone when passively stretching muscle
      • ↑ reflexes
    • Foot-drop / slapping - pt often describes fatiguable gradual onset of weakness e.g. walk X distance then foot-drop
  • Brainstem:
    • slurred speech
    • vertigo
    • diplopia
  • Cerebellar:
    • ataxia - more often seen during acute relapse than as PC
    • tremor (intention)
    • DANISH
  • Other:
    • urinary incontinence (can be overflow incontinence)
    • constipation
    • sexual dysfunction
    • intellectual deterioration
    • fatigue
24
Q

What investigations might you do in a pt with suspected MS?

A

Beside:

  • Full neurological exam
  • ECG - arrhythmias can cause thromboemboli which affect nervous system

Bloods:

  • FBC (infection), LFTs, TFTs, U+Es - baseline, can impact drug choice / dosing
  • B12 & folate - deficiency can cause CNS symptoms

Scans / Other:

  • MRI:
    • T2 weighted high signal lesions
    • periventricular plaques
    • Dawson fingers (often seen on FLAIR images) - hyperintense lesions penpendicular to the corpus callosum (see pic)
  • LP:
    • Oligoclonal bands (and not present in serum)
    • ↑ intrathecal synthesis of IgG
25
Q

What disease-modifying drugs are used to manage MS?

What are the criteria for their use?

A

Disease-modifying drugs (MS):

  • Beta-interferon
    • ↓ relapse rate by up to 30%
    • does NOT ↓ disability
  • Natalizumab - recombitant monoclonal antibody
    • antagonises integrin alpha-4 beta-1 on surface of leucocytes - thus inhibiting migration of leucocytes across the BBB
  • Fingolimod - immuno-modulater
    • sphingosine 1-phosphate receptor modulator
    • prevents lymphocytes from leaving lymph nodes
  • Alemtuzumab
  • Glatiramer acetate - immuno-modulater

Criteria:

  • Relapsing-remitting:
      • 2 relapses in past 2 years + able to walk 100m unaided
  • Secondary progressive disease:
      • 2 relapses in past 2 years + able to walk 10m (aided or unaided)
26
Q

What specific MS-related issues are targets for drug treatment?

A
  • Fatigue:
    • 1st –> exclude anaemia, thyroid disorders, depression etc.
    • 2nd –> if clear of above then trial amantadine or modafinil
    • adjuvent: mindfulness training
  • Spasticity:
    • 1st line = baclofen or gabapentin
    • 2nd line = diazepam, dantrolene and tizanidine
    • adjuvent: physio + stretching
  • Neuropathic pain - low dose AED:
    • 1st line = gabapention or pregabalin
    • 2nd line = carbamazepine or oxcarbazepine
  • Bladder dysfunction:
    • Oxybutynin - if no significant post-micturition residual bladder vol. on US
  • Oscillopsia - objects in visual field appear to oscillate/unstable
    • 1st line = gabapentin
27
Q

What common sites in the CNS might you find MS lesions?

A
  • Optic nerve
  • Corpus callosum
    • Periventricular
    • Juxtacortical
  • Cerebellum
  • Brainstem
  • Spinal cord

Year 4 - Neurology + Special Senses (12 decks)

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