Multiple Sclerosis Flashcards
Define MS [2]
Multiple sclerosis is a chronic disease characterised by inflammation, demyelination, gliosis, neuronal loss.
When does MS generally present? [2]
40-50 years, peak age of incidence Primary Progressive (PPMS) tends to show up later in life (50s/60s)
Describe the course of a typical MS relapse [2]
A few days gradual onset of symptoms [1] then it takes a few weeks to stabilize and they recover slowly in hospital. [1]
How could an MS attack present?
Describe 2 vague symptoms and 8 focal symptoms
Vague symptoms - Fatigue - Headache Focal symptoms - Sensory disturbance - Limb weakness - Visual symptoms - Myelitis - Vertigo - Ataxia - Sphincter disturbance - Mental changes
Explain why optic neuritis occurs and the symptoms [5]
Optic neuritis
- Unilateral decrease in visual acuity over hours or days
- Visual loss: central scotoma to complete visual loss
- Pain on moving the eye as this irritates dural membrane around eye
- Poor discrimination of colours, ‘red desaturation’
- Swelling and/or atrophy of the optic disc (papillitis)
- Relative afferent pupillary reflex
- Double vision
What is Uthoff’s phenomenon [1]
Symptoms returning transiently following hot bath or physical exercise ie rise in body temp
- What are the types of myelitis? [1]
2. What are the effects of myelitis? [3]
- Partial (one sided) or transverse (complete)
- Weakness & UMN syndrome below the level of the myelitis
- The affected level may have hyperaesthesia (physical hypersensitivity)
- Bladder & Bowel Symptoms
How would a brainstem relapse present? [4]
- Cranial Nerve Involvement
- Cerebellum (Vertigo, ataxia, nystagmus)
- Can affect the sensory fibres or UMNs
- Internuclear Opthalmoplegia (unable to perform lateral conjugate gaze)
What is internuclear ophthalmoplegia? [3]
Due to a lesion in the medial longitudinal fasciculus, which connects the IIIrd, IVth and VIth cranial nuclei [1]
Impaired adduction of the eye on the same side as the lesion
Horizontal nystagmus of the abducting eye on the contralateral side
What does RAPD show in MS?
What kind of sensory symptoms can occur in an MS relapse? [4]
Impaired afferent conduction in CN II, lesion in the pupillary reflex pathway
Numbness, tingling, lack of sensation or pain are common, facial pain (trigeminal neuralgia)
What kind of motor symptoms come with an MS relapse? [2]
What signs of lesions affecting motor can we see? [4]
Monoparesis
Paraparesis
Muscle spasticity, stiffness and weakness (~80%)
Spasticity usually affects legs more than arms.
Mobility issues (~75%)
Demyelination of cerebellar pathways can lead to ataxia
Upper limb intention tremor is common due to thalamus and basal ganglia involvement
Signs
- Increased tone
- Hyperreflexia
- Extensor plantar responses
How do we diagnose MS? [1]
Name 2 criteria
Remember MS is recurrent episodes of demyelination disseminated by time & space, just one episode isnt yet MS [1]
Symptooms should last >24h
Either clinically using Poser’s Criteria
Or by MRI using Macdonald’s Criteria
How does MS appear on an MRI, explain how an early vs late plaque would look differently [2]
- Sites of recent inflammation show up as white lesions or plaques
- Dawsons fingers
- Axonal loss then appears as black holes and in severe cases as cerebral atrophy
If you are unsure its MS after an MRI, what other tests can be done? [3]
- Evoked potentials - repetitive stiimulation of brain or peripheral nerves then measuring electric potentials, need abnormalities on 1 or more EP studies
- Bloods looking for other inflammatory conditions
- CXR for inflammatory conditions like Sarcoidosis
- CSF results - oligoclonal bands, raised intrathecal IgG levels, high protein pleocytosis.
What are the types of MS? [5]
- Relapsing Remitting (RRMS) 85% of cases at the outset
- Secondary Progressive (SPMS)
- Primary Progressive (PPMS)
- Sensory MS
- Malignant MS
Describe the pattern of Relapsing Remitting MS? [1]
Episodes of demyelination causing varying severity of symptoms with complete recovery [1] between relapses
(most eventually become SPMS)
Describe the pattern of Secondary Progressive MS?
A progressive neurological disability after an initial RRMS course.
Describe the pattern of Sensory MS? [1]
Minor episodes of sensory symptoms with good recovery
Describe the pattern of primary progressive MS? [1]
Progressively worsening disability right from the outset
What would indicate a worse prognosis for MS? [6]
- Male
- Older
- Multifocal Signs/Symptoms
- Motor Symptoms
- Close 1st & 2nd relapse
- Lots of relapses in the 1st 5 yrs
Whats different about Primary Progressive MS? [2]
Whats the prognosis?
It usually presents in the 50s or 60s rather than in youth
No gender predisposition
Poor Prognosis
Autoimmune inflammatory diseases
What is Devic’s Disease? [2]
Neuromyelitis Optic Spectrum Disorder
It used to be considered a varient of MS but is now considered its own clinical entity.
Its myelitis and optic neuritis [1] mediated by aquaporin-4 antibodies [1] and treated with immunosuppression
How do we treat an acute relapse of MS? [4]
- Look for an underlying infection
-1st line: oral methylprednisolone 0.5g daily for 5 days - Rehabilitation
- Symptom treatment
- If failed or not tolerated on severe relapse: admission for IV methylprednisolone
Also vaccinate against viral infections to reduce future relapses
What are disease modifying treatments? [2]
Treatments that reduce the relapse rate [1]
however they dont slow progression or reduce the severity of the disease [1]
What are the types of disease modifying treatments? [4]
Beta-interferons SC
Glatiramer acetate
natalizumab
fingolimod
What are the side effects of 1st line disease modifying treatments? [3]
- Flu-like Symptoms
- Abnormal blood count or liver function
- Injection site reaction
Name one side effect of Fingolimod tablets? [3]
Macular oedema, hepatotoxicity, heart block (initiation requires cardiac monitoring).
All these disease modifying treatments are immunosupressants. What conditions does this increase your risk of? [4]
Other infections and autoimmune conditions such as:
- Autoimmune Thyroid Disease
- Immune Thrombocytopenic Purpura
- Goodpasture’s Disease
- Progressive Multifocal Leukoencephalopathy (PML) - natalizumab
What is PML and how does it relate to MS? [2]
How will it affect an MS patient management? [1]
Progressive Multifocal Leukoencephalopathy
A severe demyelinating disease of the brain caused by the JC virus [1]
People on MS disease modifying treatments are predisposed to PML [1] so get an annual MRI and JC antibody blood/urine tests every 6 months [1]
We also give symptomatic treatment to help people manage MS, such as [8]
Fatigue - amantadine
Spasticity - baclofen, gabapentin
Bladder dysfunction - intermittent self catheterisation
Oscillopsia - gabapentin
Whos included in an MS MDT? [8]
- MS nurse
- Physiotherapy
- Occupational Therapy
- Dieticians
- Speech & Language Therapists
- Psychology/Psychiatry
- Continence Advisors
- Rehab Specialists
What is L’hermittes Sign? [2]
A sudden electric shock travelling down your neck into your spine [1] and sometimes to your limbs when you bend you head forward. [1]
Risk factors
EBV
* People with EBV antibody-positive serology have a 5.5 times greater risk of MS than those without
* Hypothesised that primary EBV infection increases blood-brain barrier permeability to lymphocytes
Cigarette smoking
Vitamin D
* A prospective case-control study of 7 million military personnel found the risk of MS decreased with higher Vitamin D levels
Latitudinal gradient.
◆ Higher prevalence further from the equator:
■ Migrants acquire the MS risk of their destination if they move before the age of 14.
How does MS affect conception or miscarriage?
How does pregnancy affect MS relapse frequency, compare intrapartum to postpartum.
MS does not affect conception or increase the risk of miscarriage
Treatment should not be deferred because they wish to have children in the future
Having MS does not necessarily make a pregnancy high risk and should not limit birthing options
During pregnancy many find their symptoms improve and experience fewer relapses. However, ~25% of women will relapse within 3 months postpartum
Pathophysiology: MS
It is thought to be an autoimmune mediated (mostly T cell activated) response, that results in 2 distinct phases:
* Inflammatory
T-lymphocyte activation and interaction with CNS endothelial cells, leading to inflammatory cytokine and macrophage induced demyelination
Degenerative
Demyelination leads to affects axonal support and membrane potentials
Eventual degeneration and loss over time
MS lesions develop by:
Dissemination in space
Dissemination in time
Dissemination in space (DIS)
* Development of lesions in different anatomical locations within the CNS
* Demonstrated on MRI by
* ≥1 T2 hyperintense lesion characteristic of MS
* In 2 or more of: periventricular, cortical or juxtacortical and infratentorial brain regions or the spinal cord
Dissemination in time (DIT)
* Development of new CNS lesions appearing over time
* Demonstrated on MRI by
* Simultaneous gadolinium (Gd) enhancing and non enhancing lesions at any time or
* New T2 hyperintense or Gd enhancing lesions compared to a baseline MRI
Investigations: bloods
FBC
Rule out evidence of anaemia (macrocytic in B12 deficiency) and malignancy (thrombocytopenia in lymphoma)
Inflammatory markers (e.g. CRP and ESR)
Elevated in infections of the CNS or vasculitides
LFTs
Chronic liver disease can cause polyneuropathy and hepatic encephalopathy
U&Es
Calcium
Hypocalcaemia classically presents with paraesthesia and tetany
Glucose
Peripheral neuropathy secondary to poor diabetic control
TFTs
Hypothyroidism can present with fatigue, muscle weakness, constipation, slowed movement and thought processing
Vitamin B12
Severe deficiency leading to subacute combined degeneration of spinal cord
HIV serology
Progressive multifocal leukoencephalopathy due to reactivation of the JC virus
Lesions occur anywhere in the CNS mimicking MS
When would an MRI spine be indicated?
- Suggestion of spinal cord lesion
- Primary progressive pattern
- MS in atypical demographic
- To confirm diagnostic confidence of MRI brain
Spasticity/mobility issues
1st, 2nd, 3rd line.
1st line: consider baclofen or gabapentin (off label)
Gabapentin is now a Class C controlled drug due to risk of addiction and respiratory depression (especially in existing opioid users)
Also useful in MS neuropathic pain
2nd line: consider tizanidine or dantrolene
3rd line: consider a benzodiazepine
Botox
Cannabinoid preparations (e.g. nabiximols).
When would intermittent self catheterisation be indicated?
Incomplete voiding leads to frequent urinary tract infections, and can be managed with intermittent self-catheterisation (ISC) or suprapubic catheters.
