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what is MS characterised by?
lesions separated both in space and time in the CNS
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which 'matter' of the brain, spinal cord and optic nerves does MS affect?
white matter
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what is a plaque?
foci of inflammation and demyelination
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what is the evolution of a plaque?
- early stage: local breakdown of the BBB
- then evidence of inflammation with oedema, loss of myelin
- eventually CNS scar tissue - gliosis
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what is lost and what is preserved in an MS plaque?
- myelin lost
- axon preserved
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what is the pathological process that causes the PROGRESSIVE phase of MS?
axonal loss
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what is the pathology behind relapses and remissions?
- when the plaque is very pathologically active you get relapse
- then it becomes a shrunked area of sclerosis - with little clinical deficity - remission
- partly due to remyelination
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what is the difference between PNS neuroregeneration and CNS?
- CNS: more inhibitory influences of glia etc
- wheras PNS: injury immediately elicits migration of phagocytic cells etc to the lesion and get sprouting of axons
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what is the cause of MS?
environmental agent eg virus (EBV), - triggers the condition in a genetically susceptible individual
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what makes a person genetically susceptible to MS?
HLA DR1b-1501
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what are the environmental factors associated with MS?
- infectious agent EBV
- fatty fish
- vitamin D
- smoking
- migration age- ie if born in an area of high risk for MS, will carry that risk if they emigrate to an area of lower risk, only if migration occurs AFTER mid teens. eg the hypothetical virus is acting in the first decade of two of life
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which parts of the world is MS more common in?
temperate rather than tropical climate
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what is the f:m ratio?
3:1
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typical age of onset?
20-30s
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UK prevalence of MS?
1/1000
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name 3 common modes of presentation of MS?
- sensory disturbance
- limb weakness
- visual disturbance
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what is the characteristic visual disturbance of MS?
optic (retrobulbar) neuritis
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what are the symptoms of optic neuritis?
- pain on ocular movement
- blurred patchy vision - may proceed to compolete monocular blindness in d or w
- loss of colour vision - red
- central field loss
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what are the signs of optic neuritis on examination? (remember AFRO)
- A: reduced VA, ishihara plates test
- F: central scotoma
- R: RAPD
- O: disc swollen - pallor
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how long does it take for a bout of optic neuritis to resolve? and what is pt left with?
- period of weeks to months
- but pt may still have some visual impairment
- fundoscopy: optic disc pallor due to optic atrophy
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sometimes optic disc swelling and papilloedema can look similar on fundoscopy, how can you tell difference between the 2 clinically?
- papilloedema: visual acuity is relatively preserved
- and only field defect: enlargement of physiological blind spot
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if a single episode of optic neuritis is bilateral, does that make it more or less likely to be due to MS?
less
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what other visual disturbances are there in MS?
- diplopia: assoc with BS vertigo, nausea - indicate BS plaque
- INO: MLF
- cerebellar ataxia
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what may a lesion in the dorsal columns of the cervical spinal cord cause?
Llhermitte phenomenon: rapid tingling sensations shooting down arms or legs on neck flexion
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what is Uhtoff phenomenon?
motor, sensory or visual symptoms temporarily worsen due to rise in temperature eg after a HOT BATH or exercise or fever
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what is myelitis?
spinal cord inflammation
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what are the symptoms of myelitis? think from top of body down
- MOTOR AND SENSORY
- 1. tight band around trunk or limbs
- 2. constipation
- 3. urinary frequency / urgency
- 4. sexual dysfunction
- 5. heavy legs
- 6. legs give way
- 7. sensory
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What are 4 main factors looking for O/E if suspect spinal cord sydrome in MS?
- 1. spastic paraparesis or tetraparesis
- 2. sensory level
- 3. sphincter dysfunction
- 4. JPS loss - joint position sense
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what are 5 features of spastic paraparesis?
- 1. increased tone
- 2. increased power
- 3. brisk reflexes, clonus
- 4. gait abnormality
- 5. pyramidal pattern of weakness is the same as UMN
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What is i) incomplete ii) complete lesion of the spinal cord called?
- i) hemicord lesion - Brown Sequard syndrome
- ii) transverse myelitis
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what are the sensory symptoms of MS?
- numbness
- coldness
- pins and needles
- swelling
- tightness
- may be radicular - limbs or lower trunk
- onset: few days and resolution in few weeks or months
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what are the motor problems of MS?
- paraplegia: impairment in motor or sensory function in lower limbs
- spasticity
- brisk reflexes - upgoing plantars
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if pain was a presenting symptom of MS, what may it be?
trigeminal neuralgia - due to BS plaque
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what are the 4 temporal courses of MS?
- 1. relapsing remiting: 70-80%
- 2. secondary relapsing: 10-20%
- 3. primary progressive
- 4. progressive relapsing
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what are the brainstem and cerebellar symptoms of MS?
- double vision
- oscillopspia: images in visual fields tend to oscillate - may cause dizziness and nausea
- lateral gaze palsy
- skew deviation
- dizziness, vertigo
- nystagmus: ataxic nystagmus is found with an INO
- facial numbness: pins and needles, neuralgia (CNV)
- slurred speech
- clumsy drop things
- unsteady - drunk like
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what are the signs on examination fo brain stem/cerebellar syndrome in MS?
- INO
- ataxia
- spastic tetra or hemiparesis (note NOT PARAPLEGIC - cos not just legs in brainstem syndrome)
- broken pursuits
- nystagmus
- facial paraesthesia, palsy
- dysarthria
- rubral or Holmes' tremor
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what is a rubral or holmes tremor? and cause?
- wing beating type of tremor
- combination of rest, action and postural tremors
- caused by cerebellar damage
- what does ataxia mean?
- lack of coordination of muscle movements
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how is MS diagnosed? 2 main things
- can be clinical
- dissemination of disease activity in time
- dissemination of disease activity in space - ie more than one site
- nb - 2 optic nerves is one site, whole region of cord eg cervical is one site
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name 3 investigations used to detect MS
- 1. MRI
- 2. VEP: delayed central conduction in the visual pathways eg a result of previous subclinical optic neuritis
- 3. CSF: raised protein - Ig. detection of oligoclonal bands by electrophoresis - indicate local synthesis of Ig in CNS.
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name 2 differentials for progressive MS
- 1. MND
- 2. spinal and cerebellar degenerations
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name 3 differentials for relapsing and remiting disease
- 1. sarcoidosis
- 2. SLE
- 3. TIA
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what is the DD of single episode of optic neuritis? and how rule out? and how different from MS?
- optic nerve compression
- usually more slow onset and progressive
- rule out: MRI
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what are the important DD of spinal cord syndrome?
- spinal cord compression
- if more slower onset: vit B12 deficiency causing SCDCS
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what is DD if has only motor signs and no sensory?
- MND - distinguish as it also has LMN signs with MS doesnt
- other name for MND is amyotrophic lateral sclerosis
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what is DD for brainstem syndromes
- tumours
- BS encephalitis
- cranial polyneuritis
- arnold-chiari malformation: downward displacements of cerebellar tonsils through foramen magnum
- vascular disease
- MRI and CSF can distinguish
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what is it called when there is a monophasic illness characterised by widespread multifocal demyelination in isolation? how can tell difference between MS?
- acute disseminated encephalomyelitis
- of after infection: post infectious encephalomyelitis
- Multiple ares of demyelination separated in space BUT NOT IN TIME
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how are acute relapses of MS treated?
- if severe enough to limit function eg due to limb weakness or visual failure then treat with high dose iv or oral methylprednisolone 500mg-1g
- for 3-5 days
- must exclude UTI before starting steroids
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which 2 drugs are used to reduce the rate of progression and relapses of MS? and SE
- interferon beta: SE flu like symptoms, CI in pregnancy
- glatiramer: fewer SE but worse ISR (injection site reactions)
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which newer drug is twice as effective as glatiramer? what type of drug? SE?
- monoclonal antibody natalizumab against integrin adhesion molecule
- SE: PML - progressive multifocal leucoencephalopathy
- alternative: mitoxantrone - anthracycline derivative but SE cardiotoxicity, acute leukaemia
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which drugs are used to control spasticity, flexor spasms? what is SE?
- baclofen: sedative at high dose
- dantrolene (use in NMS too due to rigidity)
- diazepam
- SE: weakness, drowsy
- inject botox into affected muscles
- cannabinoids - sativex
- PHYSIO! - stretch exercises
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which drugs are used to control cerebellar tremor?
- clonazepam
- isoniazid with pyridoxine
- gabapentin
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which drugs are used to control fatigue?
- amantadine
- selegiline
- modafinil: anti narcolepsy drug
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which drugs are used to control bladder disturbances?
- anticholinergic: oxybutinin or tolterodine or solifenacin
- relax detrusor muscle
- intermittent self catheterisation if post micturition bladder RV > 100ml
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which drugs are used to control depression?
- TCA amitriptyline
- SSRI: sertraline
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which drugs are used to control erectile impotence?
- PDE5 inhibitors
- sildenafil
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which drugs are used to control pain, paroxysmal symptoms inc seizures?
- carbamazepine
- gabapentine
- amitriptyline
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which drugs are used to control constipation?
- bulking agents: eg fybogel - ispaghula husk
- stool softeners: eg docusate
- senna
- movicol - polyethylene glycol
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