Multiple Sclerosis Flashcards
What is multiple sclerosis?
It is a a chronic and progressive autoimmune condition that involves demyelination of the central nervous system
What is myelin?
It is the sheath that covers the axons of neurones in the central nervous system
What is the function of myelin?
It allows quick transmission of electrical impulses between neurones
What cells produce myelin in the peripheral nervous system?
Schwann cells
What cells produce myelin in the central nervous system?
Oligodendrocytes
What is the pathophysiological cause of multiple sclerosis?
There is inflammation around the myelin sheath, which results in the infiltration of immune T-cells that then cause damage
This affects the transmission of electrical signals along the nerve
What hypersensitivity reaction occurs in multiple sclerosis?
Type IV
Which nervous system is affected in multiple sclerosis - central or peripheral?
CNS
What are the four classifications of multiple sclerosis?
Clinically Isolated Syndrome (CIS)
Relapsing Remitting MS (RRMS)
Secondary Progressive MS (SPMS)
Primary Progressive MS (PPMS)
What is clinically isolated syndrome?
It refers to the first, single episode of demyelination, resulting in neurological clinical features that persist for a period greater than 24 hours
Why does clinically isolated syndrome not obtain in a diagnosis of multiple sclerosis?
This is due to the fact that the lesions have not ‘disseminated in time and space.’
Does clinically isolated syndrome result in multiple sclerosis?
These individuals may or may not go on to develop multiple sclerosis
What clinically isolated syndrome feature estimates a higher risk of multiple sclerosis development?
There are features of multiple sclerosis on MRI scans
What is the most common classification of multiple sclerosis at initial diagnosis?
Relapsing remitting multiple sclerosis (RRMS)
What is RRMS?
It is characterised by relapsing episodes of disease followed by periods of remission
Describe the cycle associated with RRMS
During the relapsing episodes, clinical features usually have a gradual onset over a few days, which then stabilise to persistent clinical features for a period of days to months
There is then a period of remission of varying duration
In what two ways can RRMS be classified?
Disease activity (active/non-active)
Disease progression (worsening/non-worsening)
What does active disease refer to?
The development of new clinical features or the appearance of new lesions on MRI
What does worsening disease refer to?
The overall worsening of disability from initial diagnosis
What is SPMS?
It is characterised as initial relapsing-remitting disease that has progressed into a state of incomplete remission with worsening clinical features
In what two ways can SPMS be classified?
Disease activity (active/non-active)
Disease progression (progressing/non-progressing)
What does progressing disease refer to?
The the overall worsening of disease over time (regardless of relapses)
What is PPMS?
It is characterised by continuous worsening of disease from initial diagnosis without remission periods
Which age group tend to be affected by PPMS?
> 50 yrs old
In what two ways can PPMS be classified?
Disease activity (active/non-active)
Disease progression (progressing/non-progressing)
What is different about multiple sclerosis classifications compared to other condition classifications?
These classifications are not separate conditions, and instead should be thought of as a spectrum of disease activity
What are the seven risk factors of multiple sclerosis?
Female Gender
Young Age (20-40 Years Old)
Family History
Smoking
Obesity
Epstein Barr Virus (EBV)
Reduced Vitamin D Exposure
What are the eighteen clinical features of multiple sclerosis?
Optic Neuritis
Sixth Cranial Nerve Palsy
Diplopia
Paraesthesia
Numbness
Trigeminal Neuralgia
Bell’s Palsy
Horner’s Syndrome
Lhermitte’s Sign
Hoffman’s Sign
Intention Tremor
Muscle Spasticity
Erectile Dysfunction
Urinary Incontinence
Urinary Retention
Vertigo
Ataxia
Lethargy
What is the most common clinical feature of multiple sclerosis?
Optic neuritis
What is optic neuritis?
It refers to demyelination and inflammation of the optic nerve
What are the eight causes of optic neuritis?
Multiple sclerosis
Diabetes
Syphillis
Sarcoidosis
SLE
Measles
Mumps
Lyme’s disease
What is the most common cause of optic neuritis?
Multiple sclerosis
What are the five clinical features associated with optic neuritis?
Unilateral Central Vision Loss
Colour Vision Impairment
Painful Eye Movements
Relative Afferent Pupillary Defect (RAPD)
Central Scotoma
What colour vision impairment is associated with multiple sclerosis?
Red desaturation
What is red desaturation?
It involves patients visualising red objects as pink
What is RAPD?
It is a condition in which pupils respond differently to light stimuli shone in one eye at a time
Specifically, when shining light into one eye, both pupils should constrict
This constriction should remain when the light is then shone into the other eye
However, in RAPD, when the light is then shone into the other eye, dilatation occurs
What is central scotoma?
It refers to an enlarged blind spot
What two investigations are used to diagnose optic neuritis?
Fundoscopy
MRI of Brain & Orbits With Contrast
What are the two signs of optic neuritis on fundoscopy?
Optic disc swelling, or in severe cases optic disc atrophy
RAPD
How do we manage optic neuritis?
We urgently refer patients to ophthalmology
It is then treated with high dose steroids
How long does it take to recover from optic neuritis following treatment?
4-6 weeks
What is the general function of CN VI?
It innervates the lateral rectus muscle to allow lateral eye movement
What are the three clinical features of CN VI palsy?
Conjugate Lateral Gaze Disorder
Papilloedema
Internuclear Opthalmoplegia
What is another term for conjugate lateral gaze disorder?
Horizontal diplopia
What is conjugate lateral gaze disorder?
It is defined as defective abduction (medial deviation)
Specifically, when individuals look laterally in the direction of the affected eye, the affected eye will not be able to abduct
For example, in a lesion affecting the left eye, when looking to the left, the right eye will adduct and the left eye will remain in the middle as the muscle responsible for making it move laterally is not functioning
What is intranuclear ophthalmoplegia?
It refers to incoordination of eye movements
What is Bell’s palsy?
It is is defined as idiopathic facial nerve palsy, in which there is no known cause for the damage caused to the facial nerve
What is Horner’s syndrome?
It is a condition in which there is disruption of the sympathetic nerve pathway between the brain stem and the face/eyes
What is Lhermitte’s sign?
It is an electric shock sensation travelling down the spine and into the limbs when flexing the beck
What does Lhermitte’s sign indicate in terms of multiple sclerosis?
It indicates disease in the dorsal column of the cervical spine
What causes Lhermitte’s sign?
It is caused by stretching the demyelinated dorsal column
What is Hoffman’s sign?
It involves flexion and adduction of the thumb and flexion of the index finger following a foreceful flick of the examiners thumb on the patient’s middle finger nail
What is intention tremor?
It refers to a tremor that becomes obvious and often exaggerated as the need for precise motor movement increases
What is ataxia?
It is defined as uncoordinated movements
What are the two classifications of ataxia?
Sensory
Cerebellar
What is sensory ataxia?
It refers to a loss in proprioceptive sense
What is a clinical sign of sensory ataxia?
Positive Romberg’s test
What is cerebellar ataxia?
It refers to problems with the cerebellum coordinating movement
What phenomenon do multiple sclerosis features follow?
Uhthoff’s phenomenon
What is Uhthoff’s phenomenon?
It means that clinical features worsen in hot conditions, for example when a patient is taking a hot bath or during exercise
What two things are known to improve the clinical features of multiple sclerosis?
Pregnancy
Postpartum period
What is a key characteristic of multiple sclerosis clinical features? What does this mean?
The lesions disseminate in time and space
In multiple sclerosis, lesions vary in their location over time, resulting in different nerves becoming affected and therefore different clinical features
In most cases, how is multiple sclerosis diagnosed?
Clinically
What clinical criteria is used to aid diagnosis of multiple sclerosis?
Posers criteria
What do we have to remember when diagnosing multiple sclerosis clinically?
A diagnosis can only be made with evidence of at least two separate attacks, although this may include signs of attacks on an MRI scan
In PPMS, how long do clinical features need to progress for before a diagnosis to be obtained?
> 1 year
What three investigations can be used to confirm multiple sclerosis diagnosis?
MRI Scan
Lumbar Puncture
Visual Evoked Potential Tests
What are the five features of multiple sclerosis on MRI scans?
Demyelination
Myelin Sheath Inflammation
High Signal T2 Lesions
Periventricular Plaques
Dawson Fingers
What is Dawson fingers?
It refers to hyper-intense lesions perpendicular to the corpus callosum
What criteria is used to interpret multiple sclerosis on an MRI scan? Why?
MacDonald criteria
It allows collation of clinical features and scan features to make a diagnosis
What MRI contrast is used to aid diagnosis of multiple sclerosis?
Gadolinium
What is a lumbar puncture?
It involves the insertion of a needle into the subarachnoid space of the spinal cord, specifically between L3 and L4 vertebrae, to collect a sample of CSF
What is a sign of multiple sclerosis on lumbar puncture?
Oligoclonal bands
What are oligoclonal bands?
They are bands of immunoglobulins
The oligoclonal bands should only be present in CSF not serum for a diagnosis of multiple sclerosis. Why?
This indicates that there is inflammation of the central nervous system only
What are visual evoked potential tests?
They are tests used to test optic nerve conduction
It involves the monitoring of brainwaves whilst a patient is shown light patterns
What is a sign of multiple sclerosis in visual evoked potential tests?
There is a decreased transmission rate of electrical signals from the eye to the brain, however preserved waveform
How do we manage acute MS relapses?
High dose steroids
What steroid is used to treat acute MS relapses?
Methylprednisolone
What are the two prednisolone regimes that can be used to treat acute MS relapses?
500mg orally for 5 days, which can be administered at home
1g IV for 3-5 days, which has to be administered in hospital
In which two cases would we chose IV prednisolone over oral to treat acute MS relapses?
In individuals where oral treatment has failed previously
In individuals where relapses are severe
In order to reduce the risk of side effects, what is the maximum times a year that steroids should be prescribed to multiple sclerosis patients?
3 times per year
What is the aim of acute MS relapse treatment?
To shorten the period of relapse
They are unable to prevent further relapse or prevent disease progression
Why is it important that we conduct blood tests and urinalysis when MS patients have an acute relapse?
To investigate for underlying infection
If positive, antibiotics can be administered, which will in turn resolve the relapse clinical features
In what way do we symptomatically manage fatigue?
Amantadine
However, other underlying causes such as anaemia, thyroid disease and depression need to be excluded first
In what two ways do we symptomatically manage muscle spasticity?
We can administer antispasmodics, such as baclofen, gabapentin, diazepam, dantrolene and tizanidine
We can offer physiotherapy
Which two pharmacological management options are first line to symptomatically manage muscle spasticity?
Baclofen
Gabapentin
How do we symptomatically manage neuropathic pain?
We can administer medications, such as duloxetine, amitriptyline, gabapentin or carbamazepine
In what two ways do we symptomatically manage urinary problems?
We can administer anticholinergic medications, such as tolterodine or oxybutynin
We can advise intermittent self catheterisation
How do we determine which management option should be used for urinary problems?
US scan - to assess bladder emptying
In cases where there is a significant residual volume, then intermittent self-catheterisation is recommended
In cases where there is no significant residual volume, anticholinergics are recommended
How can we symptomatically manage constipation?
We can administer laxative medications, such as senna, sodium picosulfate or bisacodyl
How can we symptomatically manage erectile dysfunction?
We can administer medications, such as sildenafil
What is a side effect of sildenafil?
Blue vision
What are two contraindications of sildenafil?
Nitrates - isosorbide mononitrate
Nicorandil
In what two ways do we symptomatically manage depression?
We can administer antidepressant medications, such as sertraline, fluoxetine or citalopram
We can offer cognitive behavioural therapy
What is the aim of disease modification therapies?
To induce long term remission with no evidence of disease activity
They don’t slow down the progression of disease
In which two circumstances, is disease modification therapy considered?
In relapsing-remitting multiple sclerosis, in which there has been two relapses within the past two years and individuals are able to walk 100m unaided
In secondary-progressive multiple sclerosis, in which there has been two relapses within the past two years and individuals are able to walk 10m aided or unaided
What are five disease modification therapies used in multiple sclerosis?
Natalizumab
Ocrelizumab
Fingolimod
Beta-Interferon
Glatiramer Acetate
What is the first line disease modification therapy?
Natalizumab
