multiple sclerosis.txt

  1. what is MS characterised by?
    lesions separated both in space and time in the CNS
  2. which 'matter' of the brain, spinal cord and optic nerves does MS affect?
    white matter
  3. what is a plaque?
    foci of inflammation and demyelination
  4. 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
  5. what is lost and what is preserved in an MS plaque?
    • myelin lost
    • axon preserved
  6. what is the pathological process that causes the PROGRESSIVE phase of MS?
    axonal loss
  7. 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
  8. 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
  9. what is the cause of MS?
    environmental agent eg virus (EBV), - triggers the condition in a genetically susceptible individual
  10. what makes a person genetically susceptible to MS?
    HLA DR1b-1501
  11. 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
  12. which parts of the world is MS more common in?
    temperate rather than tropical climate
  13. what is the f:m ratio?
  14. typical age of onset?
  15. UK prevalence of MS?
  16. name 3 common modes of presentation of MS?
    • sensory disturbance
    • limb weakness
    • visual disturbance
  17. what is the characteristic visual disturbance of MS?
    optic (retrobulbar) neuritis
  18. 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
  19. 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
  20. 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
  21. 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
  22. if a single episode of optic neuritis is bilateral, does that make it more or less likely to be due to MS?
  23. what other visual disturbances are there in MS?
    • diplopia: assoc with BS vertigo, nausea - indicate BS plaque
    • INO: MLF
    • cerebellar ataxia
  24. 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
  25. 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
  26. what is myelitis?
    spinal cord inflammation
  27. what are the symptoms of myelitis? think from top of body down
    • 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
  28. 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
  29. 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
  30. What is i) incomplete ii) complete lesion of the spinal cord called?
    • i) hemicord lesion - Brown Sequard syndrome
    • ii) transverse myelitis
  31. 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
  32. what are the motor problems of MS?
    • paraplegia: impairment in motor or sensory function in lower limbs
    • spasticity
    • brisk reflexes - upgoing plantars
  33. if pain was a presenting symptom of MS, what may it be?
    trigeminal neuralgia - due to BS plaque
  34. what are the 4 temporal courses of MS?
    • 1. relapsing remiting: 70-80%
    • 2. secondary relapsing: 10-20%
    • 3. primary progressive
    • 4. progressive relapsing
  35. 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
  36. 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
  37. 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
  38. what does ataxia mean?
    lack of coordination of muscle movements
  39. 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
  40. 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.
  41. name 2 differentials for progressive MS
    • 1. MND
    • 2. spinal and cerebellar degenerations
  42. name 3 differentials for relapsing and remiting disease
    • 1. sarcoidosis
    • 2. SLE
    • 3. TIA
  43. 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
  44. what are the important DD of spinal cord syndrome?
    • spinal cord compression
    • if more slower onset: vit B12 deficiency causing SCDCS
  45. 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
  46. 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
  47. 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
  48. how are acute relapses of MS treated? what must be excluded first?
    • 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
  49. what effect does steroids have when give in acute relapse of MS?
    • only shorten duration of relapse
    • not affect eventual clinical outcome
  50. 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)
  51. how can a pt qualify for interferonB or glatiramer?
    at least 2 signify relapses within the past 2 years to qualify for treatment
  52. 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
  53. 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
    • gabapentin
    • PHYSIO! - stretch exercises
  54. why do you need to be careful not to give such high dose of drugs to treat spasticity?
    don't reduce tone too far as some patients require the increased tone to walk as they use their spastic leg as a stick
  55. what is a sequelae of spasticity?
    contractures - so may need physic and botox to reduce tone in muscle
  56. which drugs are used to control cerebellar tremor?
    • clonazepam
    • isoniazid with pyridoxine
    • gabapentin
  57. which drugs are used to control fatigue?
    • amantadine
    • selegiline
    • modafinil: anti narcolepsy drug
  58. 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
    • botox
  59. which drugs are used to control depression?
    • TCA amitriptyline
    • SSRI: sertraline
  60. which drugs are used to control erectile impotence?
    • PDE5 inhibitors
    • sildenafil
  61. which drugs are used to control pain, paroxysmal symptoms inc seizures, tonic muscle spasm, burning pain, trigeminal neuralgia?
    • carbamazepine
    • gabapentine
    • amitriptyline
  62. which drugs are used to control constipation?
    • bulking agents: eg fybogel - ispaghula husk
    • stool softeners: eg docusate
    • senna
    • movicol - polyethylene glycol
  63. which MRI is used in MS?
    FLARE like T2: better to see periventricular lesions more clearly as CSF is dark in flare
  64. where are the areas of demyelination found in MS?
    • white matter of brain and spinal cord
    • close to post capillary venules (perivenular)
  65. which specific sites of CNS does MS affect?
    • periventricular region in cerebral hemispheres
    • corpus callosum
    • brainstem: MLF
    • cerebellum, cerebellar peduncles
    • cervical cord
    • optic nerve
  66. what are the 2 types of optic neuritis and how tell clinically?
    • optic nerve head = papilitis: pink swollen disc
    • optic nerve behind the eye = retrobulbar neuritis = disc looks normal
  67. if you see optic atrophy, what do you think has gone on?
    optic neuritis a few weeks ago
  68. what is devic's syndrome? and other name? how different from MS?
    • when optic neuritis happens together with transverse myelitis
    • aka neuromyelitis optica
    • not MS because brain MRI normal and LONGITUDINALLY extensive cord lesion
  69. what are the similarities and differences between papilitis and papilloedema?
    • similarity: both swollen discs
    • papilitis: early profound loss in vision with central scotoma, impaired colour vision, pain on eye movement
    • papilloedema: LATE stage - enlarged blind spot
  70. what are oligoclonal bands?
    several intense bands of staining for IgG on Western blotting
  71. what is ADEM and when does it typically present?
    • acute demyelinating encephalomyelitis
    • presents following viral illness or vaccination
  72. what is PML? cause? and who more likely?
    • progressive multifocal leucoencephalopathy
    • JC papovirus
    • HIV pts
  73. which vitamin deficiency can cause central demyelination?
  74. how do you treat ADEM?
    • iv methylpred
    • then ivig
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multiple sclerosis.txt