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what is MS characterised by?
lesions separated both in space and time in the CNS
which 'matter' of the brain, spinal cord and optic nerves does MS affect?
what is a plaque?
foci of inflammation and demyelination
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
what is lost and what is preserved in an MS plaque?
- myelin lost
- axon preserved
what is the pathological process that causes the PROGRESSIVE phase of MS?
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
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
what is the cause of MS?
environmental agent eg virus (EBV), - triggers the condition in a genetically susceptible individual
what makes a person genetically susceptible to MS?
what are the environmental factors associated with MS?
- infectious agent EBV
- fatty fish
- vitamin D
- 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
which parts of the world is MS more common in?
temperate rather than tropical climate
what is the f:m ratio?
typical age of onset?
UK prevalence of MS?
name 3 common modes of presentation of MS?
- sensory disturbance
- limb weakness
- visual disturbance
what is the characteristic visual disturbance of MS?
optic (retrobulbar) neuritis
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
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
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
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
if a single episode of optic neuritis is bilateral, does that make it more or less likely to be due to MS?
what other visual disturbances are there in MS?
- diplopia: assoc with BS vertigo, nausea - indicate BS plaque
- INO: MLF
- cerebellar ataxia
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
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
what is myelitis?
spinal cord inflammation
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
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
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
What is i) incomplete ii) complete lesion of the spinal cord called?
- i) hemicord lesion - Brown Sequard syndrome
- ii) transverse myelitis
what are the sensory symptoms of MS?
- pins and needles
- may be radicular - limbs or lower trunk
- onset: few days and resolution in few weeks or months
what are the motor problems of MS?
- paraplegia: impairment in motor or sensory function in lower limbs
- brisk reflexes - upgoing plantars
if pain was a presenting symptom of MS, what may it be?
trigeminal neuralgia - due to BS plaque
what are the 4 temporal courses of MS?
- 1. relapsing remiting: 70-80%
- 2. secondary relapsing: 10-20%
- 3. primary progressive
- 4. progressive relapsing
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
what are the signs on examination fo brain stem/cerebellar syndrome in MS?
- spastic tetra or hemiparesis (note NOT PARAPLEGIC - cos not just legs in brainstem syndrome)
- broken pursuits
- facial paraesthesia, palsy
- rubral or Holmes' tremor
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
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
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.
name 2 differentials for progressive MS
- 1. MND
- 2. spinal and cerebellar degenerations
name 3 differentials for relapsing and remiting disease
- 1. sarcoidosis
- 2. SLE
- 3. TIA
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
what are the important DD of spinal cord syndrome?
- spinal cord compression
- if more slower onset: vit B12 deficiency causing SCDCS
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
what is DD for brainstem syndromes
- BS encephalitis
- cranial polyneuritis
- arnold-chiari malformation: downward displacements of cerebellar tonsils through foramen magnum
- vascular disease
- MRI and CSF can distinguish
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
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
what effect does steroids have when give in acute relapse of MS?
- only shorten duration of relapse
- not affect eventual clinical outcome
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)
how can a pt qualify for interferonB or glatiramer?
at least 2 signify relapses within the past 2 years to qualify for treatment
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
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)
- SE: weakness, drowsy
- inject botox into affected muscles
- cannabinoids - sativex
- PHYSIO! - stretch exercises
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
what is a sequelae of spasticity?
contractures - so may need physic and botox to reduce tone in muscle
which drugs are used to control cerebellar tremor?
- isoniazid with pyridoxine
which drugs are used to control fatigue?
- modafinil: anti narcolepsy drug
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
which drugs are used to control depression?
- TCA amitriptyline
- SSRI: sertraline
which drugs are used to control erectile impotence?
- PDE5 inhibitors
which drugs are used to control pain, paroxysmal symptoms inc seizures, tonic muscle spasm, burning pain, trigeminal neuralgia?
which drugs are used to control constipation?
- bulking agents: eg fybogel - ispaghula husk
- stool softeners: eg docusate
- movicol - polyethylene glycol
which MRI is used in MS?
FLARE like T2: better to see periventricular lesions more clearly as CSF is dark in flare
where are the areas of demyelination found in MS?
- white matter of brain and spinal cord
- close to post capillary venules (perivenular)
which specific sites of CNS does MS affect?
- periventricular region in cerebral hemispheres
- corpus callosum
- brainstem: MLF
- cerebellum, cerebellar peduncles
- cervical cord
- optic nerve
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
if you see optic atrophy, what do you think has gone on?
optic neuritis a few weeks ago
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
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
what are oligoclonal bands?
several intense bands of staining for IgG on Western blotting
what is ADEM and when does it typically present?
- acute demyelinating encephalomyelitis
- presents following viral illness or vaccination
what is PML? cause? and who more likely?
- progressive multifocal leucoencephalopathy
- JC papovirus
- HIV pts
which vitamin deficiency can cause central demyelination?