Multiple Sclerosis Flashcards
What is multiple sclerosis?
Chronic, immune mediated ,inflammatory condition of the central nervous system
The CNS is comprised of..
The brain
Brainstem
Spinal cord
Which group of patients is MS most commonly seen in?
Young people
What is the pathological hallmark of multiple sclerosis?
Demyelination
What is demyelination?
Damage to the myelin sheath surrounding neurons
Leads to scarring and secondary neuronal cell loss - irreversible neurological damage
Describe the typical course of MS
Relapsing-remitting
Unpredictable in individuals
Progressive disability
Mean age of onset of MS
30 years old
Aetiology of MS
Unknown- abnormal immune reaction to unknown environmental trigger in genetically predisposed individual
Concordance of MS in twins
20-35% in monozygotic twins
Dizygotic 5%
Risk factors for MS
Genetics Infection - EBV Geographic latitude - more common further from equator; risk changes at 10 years old Sunlight exposure - inverse relationship Obesity during adolescence Smoking Female
What cell is responsible for producing the myelin sheath and are destroyed in MS?
Oligodendrocytes
What type of cells are oligodendrocytes?
Glial cells - support neurons
Pathological process of MS
Activation of myelin reactive T lymphocytes
Disruption of BBB
Pro-inflammatory response and cell recruitment in CNS
- B cells, microglia, macrophages
Antibody-mediated response
MS plaques with myelin reactive T cells, B cells and macrophages
Inflammation, scarring and axonal injury (loss)
Clinical manifestation depends on location of plaques
What are microglia?
Macrophages of CNS
Classic plaque sites in MS
Optic nerves Spinal cord Brainstem Cerebellum Juxtacortical white matter Periventricular white matter
What plaque site gives rise to the most common presenting symptom for MS?
Optic nerve - vision blurry.
Optic atrohpy - optic disc pale and small
Examine fundi
Patient may be unaware they had optic neuritis
What presenting symptom can indicate an MS plaque in the brainstem?
Opthalmaplegia
What is a relapse in MS?
Episode of exacerbation of symptoms followed by period of remission in 90%
Do symptoms resolve in remission phase of relapsing-remitting course of MS?
Sometimes
As disease progresses patient may be left with residual damage from relapse
What is primary progressive MS?
PPMS
Subtype in 10-15%
Sustained rogression of disease severity from onset
May have periods where disease is not active or non-progressive but no evidence of remission
What is secondary progressive MS?
Developed by 50% of patients with relapsing remitting MS after 15 years of onset
Disease course changes with gradual worsening of neurological function. Relapses may still occur but not remission
What is Clinically Isolated Syndrome (CIS) - MS?
Describes first clinical episode of MS
No previous evidence of demyelination clinically or on imaging
Oligoclonal bands in CSF may be used to support diagnosis
Three characteristic clinical features of MS
Optic neuritis
Lhermitte phenomenon
Internuclear opthalmoplegia
What is lhermitte phenomenon?
Uncomfortable electric shock sensation triggered by neck flexion
Signs of internuclear opthalmoplegia (INO)?
Ask patient to look left
- left eye nystagmus
- right eye cannot adduct
Which part of the brainstem is susceptible to demyelination and will result in INO?
Pons
Other symptoms of MS common to neurological conditions
Motor weakness
Diplopia
Gait disturbance
Bladder/bowel dysfunction
Four groups of clinical manifestations of MS
Visual
Motor and coordination
Sensory and autonomic
Cognitive and psychological
What is optic neuritis?
Inflammation of the optic nerve
Presenting features of optic neuritis
Blurred vision Visual loss Pain - behind eye and on movement Scotoma - partial field loss Poor colour differentiation Relative afferent pupillary defect Optic nerve swelling
Eye movement disorders typically occur due to lesions of…
The brainstem
Which two common eye movement disorders are caused by brainstem lesions?
Abducens palsy
Internuclear opthalmoplegia
Demyelination of which tract leads to INO?
Medial longitudinal fasciculus
What does the medial longitudinal fasciculus connect?
Abducens nucleus complex with contralateral oculomotor complex
In INO if looking to the right, what are the signs in each eye?
Right will abduct, left will remain central
In abducens palsy what happens in right eye when looking to the right if the right abducens nerve is affected?
Remains central - cannot abduct
What is the prominent motor feature in MS?
Progressive paraparesis and upper motor neuron signs
What are upper motor neuron signs?
Spasticity
Hyperreflexia
Reduced power
Motor and coordination abnormalities in MS may present as which syndrome?
Typcial clinical syndrome
Which 2 conditions are included in typical clinical syndrome (MS)?
Transverse myelitis
Cerebellar syndrome
What is transverse myelitis?
Focal inflammation within the spine
Sensory and motor symptoms below level of lesion
Can have bladder/bowel involvement
Usually sensory level corresponding to the lesion
What must be excluded in diagnosis of transverse myelitis?
Compressive pathology eg metastatic cord compression
Cerebellar syndrome - symptoms
Ataxia Slurred speech Intention tremor Nystagmus Vertigo clumsiness
Sensory and autonomic symptoms of MS
Paraesthesia Pain Heat sensitivity (Uhthoff phenomenon) Sexual dysfunction Bladder & bowel dysfunction
What is the Uhthoff phenomenon?
Heat sensitivity - MS
Cognitive and psychological manifestations of MS
Cognitive impairment
Fatigue
Depression
Memory, attention, concentration
How is MS diagnosed?
Primarily clinical - MS attack
Supported by MRI images of scarring or lesions
What is an MS attack?
an episode of neurological symptoms that relate to an inflammatory demyelinating lesion.
Lasts > 24 hours with or without recovery.
Typically sensory disturbances, motor weakness, or visual complaints.
How many days must be between MS attacks to count as a separate episode?
More than 30 days
Which criteria is used in the diagnosis of MS?
McDonald Criteria
Principle of the MacDonald criteria
Demyelinating lesions are disseminated in time and space
2 attacks - disseminated in time
2 lesions - disseminated in space
MacDonald criteria for diagnosis of MS
≥2 attacks with objective clinical evidence of ≥2 lesions: MS diagnosed
≥2 attacks but objective clinical evidence for only one lesion: evidence of dissemination in time, but not space. MS diagnosed if dissemination in space shown on MRI or subsequent clinical attack representing new area.
Single attack with objective clinical evidence of one lesion: clinically isolated syndrome. MS diagnosed once proof of both dissemination in time and space.
Single attack with objective clinical evidence of ≥2 lesions: clinically isolated syndrome. MS diagnosed once proof of dissemination in time.
Which scan can be used in correlation with the MRI to diagnose MS?
MRI may be used to show dissemination in time by the simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time, or by a new gadolinium-enhancing lesion(s) on follow-up MRI
Show active lesions, and older lesions
Differentials to MS
Infection Other demyelinating conditions Malignancy Metabolic disorder Systemic inflammatory conditions - SLE, sarcoidosis
Condition with similar phenotype to MS
Devic’s - Neuromyelitis optica
Neuromyelitis optica spectrum disorders
Hallmark of neuromyelitis optica spectrum disorders
Acute attack of bilateral optic neuritis or transverse myelitis
How does NMOSD differ to MS?
Conditions similar presentation but more severe in NMOSD
What antibody is formed in neuromyelitis optica spectrum disorder?
IgG autoantibody to aquaporin 4 (AQP4)
Treatment of NMOSD
Corticosteroids
Plasma exchange for refractory cases
Investigations for MS
Bloods
Oligoclonal bands on CSF
Visual Evoked Response
Antibody testing
Which blood tests are required in diagnosis of MS?
FBC CRP/ESR LFTs, U&Es, Bone profile (calcium) Glucose, HbA1c TFTs Haematinics HIV test
How is CSF sample acquired and what sample is required alongside CSF to confirm MS diagnosis?
Lumbar puncture
Serum sample
Oligoclonal bands must be absent in serum, present in CSF
Which conditon is diagnosed by identical oligoclonal bands in both the CSF and serum?
Rheumatoid arthritis
What does the visual evoked response involve in diagnosis of MS?
Electrical activity measured over the occipital cortex in response to light
Assesses evidence of previous asymptomatic episodes of optic neuritis
Up to 90% of individuals will have a persistent abnormality on VER following an acute episode at one year.
Which 2 antibodies are common to NMOSD and can exclude MS as diagnosis?
Both AQP4 and myelin oligodendrocyte glycoprotein (MOG) antibodies are associated with NMOSD.
Three categories of MS management to consider
General care
Acute relapses
Disease modifying treatment
Symptoms targeted in MS treatment
Bladder dysfunction Depression Fatigue Spasticity Poor motor function
How is bladder dysfunction treated in the general management of MS
Anticholinergics - oxybutynin for detrusor overactivity
Botulism injection
Catheter for urinary retention
How is bowel dysfunction treated in the general management of MS
(Constipation, poor evacuation and incontinence)
Dietary changes
Laxatives
Enema
How is depression treated in the general management of MS
SSRIs
Duloxetine may be used if co-existing neuropathic pain or fatigue
How is fatigue treated in the general management of MS
Non-pharmacological eg physical activity
Treat depression
Pharm - modafinil
How is gait impairment treated in the general management of MS
OT
Physio
Walking aids, wheelchair
How is pain treated in the general management of MS
Amitriptyline , Gabapentin, Pregabilin
How is spasticity treated in the general management of MS
Physio
Baclofen
Botulism
Treatment of acute relapse of MS
Steroids: oral methylprednisolone 0.5 g daily for five days, OR Intravenous methylprednisolone 1 g daily for 3-5 days
Gastroprotection: proton pump inhibitor
Discuss risk/benefit of treatment: particular attention to acute changes in blood glucose and mental health
When can recovery from acute relapse be expected after treatment?
2-3 months in most cases
May be residual functional disabilities
Aim of disease modifying therapies in MS
Decrease relapse frequency and slow progression
Two criteria for initiating DMT in MS
No evidence of non-relapsing progressive MS
Sustained disability due to MS: measured on Expanded Disability Status Scale (EDSS). Score should be < 7.0 (i.e. at least ambulant with two crutches).
Examples of DMTs in MS
Interferon beta Glatiramer acetate Teriflunomide Alemtuzumab Cladribine Natalizumab
Median time of PPMS and requiring a walking aid
8 years
Factors linked to prognosis in MS
Disease type: RRMS better prognosis than PPMS. Most patients with RRMS eventually develop SPMS.
Recovery following first attack: incomplete recovery associated with worse prognosis
Clinical manifestations at onset: pyramidal, brainstem, and cerebellar symptoms (poor prognosis). Sensory symptoms, optic neuritis (favourable prognosis).
Pregnancy: protective during pregnancy. Increased risk of relapse in postpartum period.
Imaging: lesion load and cerebral atrophy linked to prognosis (higher burden and increased atrophy have worse prognosis).
Which disease type of MS has better prognosis?
Relapsing remitting MS
