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?
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
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?
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
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
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
3. urinary frequency / urgency
4. sexual dysfunction
5. heavy legs
6. legs give way
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?
oscillopspia: images in visual fields tend to oscillate - may cause dizziness and nausea
lateral gaze palsy
nystagmus: ataxic nystagmus is found with an INO
facial numbness: pins and needles, neuralgia (CNV)
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)
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
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
2. spinal and cerebellar degenerations
name 3 differentials for relapsing and remiting disease
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
arnold-chiari malformation: downward displacements of cerebellar tonsils through foramen magnum
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