MS Flashcards
Define MS [1]
Describet the pathophysiology [+]
Multiple sclerosis (MS) is a chronic and progressive autoimmune condition involving demyelination in the central nervous system. The immune system attacks the myelin sheath of the myelinated neurones.
Pathophysiology:
- Myelin covers the axons of neurones and helps electrical impulses travel faster. Myelin is provided by cells that wrap themselves around the axons: Oligodendrocytes in the central nervous system & Schwann cells in the peripheral nervous system
- Multiple sclerosis affects the central nervous system (the oligodendrocytes). Inflammation and immune cell infiltration cause damage to the myelin, affecting the electrical signals moving along the neurones
- When a patient presents with symptoms of an MS attack (e.g., an episode of optic neuritis), there are often other demyelinating lesions throughout the central nervous system, most of which are not causing symptoms
- In early disease, re-myelination can occur, and the symptoms can resolve. In the later stages of the disease, re-myelination is incomplete, and the symptoms gradually become more permanent.
- A characteristic feature of MS is that lesions vary in location, meaning that the affected sites and symptoms change over time. The lesions are described as “disseminated in time and space”.
Which factors may influence the liklihood of MS? [4]
- Multiple genes
- Epstein–Barr virus (EBV)
- Low vitamin D
- Smoking
- Obesity
- Geographic latitude: prevalence of MS increases the greater the distance north or south from the equator. Migration after puberty carries risk from former geographic location.
What are the classical plaque sites for MS? [7]
What does this mean for what the presentation might be for MS? [5]
Optic nerves: affects 40% during course of disease. Presenting demyelinating event in 20%.
Spinal cord: affects 50-75% during course of disease. Majority associated with concomitant brain lesions. Predilection for cervical spine.
Brainstem: may present with ophthalmoplegia (e.g. intranuclear ophthalmoplegia).
Cerebellum: characteristically causes ataxia and gait disturbance.
Juxtacortical white matter (near the cerebral cortex).
Periventricular white matter (near the ventricular system).
Describe the different classifications of MS
Relapsing-remitting MS (RRMS):
- subtype in 85-90% of cases.
- Episodes of exacerbation in symptoms termed relapses followed by periods of recovery termed remissions.
- During early stages, symptoms may completely remit. As diseases progresses likely to retain residual damage with each relapse.
Primary progressive MS (PPMS):
- subtype in 10-15%.
- Sustained progression of disease severity from onset.
- May have periods where disease is not active or non-progressive, but no evidence of clinical remission.
Secondary progressive MS (SPMS):
- 50% of patients with RRMS will develop this subtype within 15 years of onset.
- A progressive neurological disability after an initial RRMS course.
- Following RRMS phenotype, disease course changes with gradual, sustained worsening in neurological function.
- Relapses may still occur but without remission.
Describe the features of MS with regards to:
- Vision [3]
- Pain [4]
- Muscles [3]
Vision:
- 1 in 4 cases of MS present with optic neuritis : temporary vision loss (including a scotoma), colour blindness and painful eye movements
- Examination may reveal internuclear ophthalmoplegia or a pale optic disc on fundoscopy
Pain:
* Trigeminal neuralgia
* Optic neuritis
* Chest tightness (or banding)
* Lhermitte’s phenomenon
Muscle:
* Spasticity usually affects legs more than arms.
* Can be associated with spasms that may disturb sleep and lead to falls and issues with mobility
* Weakness usually affects both lower limbs > one lower limb > upper and lower limb same side > an upper limb
What may examination of eye reveal in a person presenting with ?optic neuritis in MS [2]
- Examination may reveal internuclear ophthalmoplegia or a pale optic disc on fundoscopy
Describe other features of MS [+]
Fatigue
- Exhaustion
Mobility issues:
- Demyelination of cerebellar pathways can lead to ataxia
- Upper limb intention tremor is common due to thalamus and basal ganglia involvement
Bladder and bowel dysfunction
- Constipation
- UTIs
- Increased frequency and urgency
Sexual dysfunction
Depression and anxiety
Cognitive impairment
Describe the presentation of optic neuritis [4]
What is it specifically caused by? [1]
presents with unilateral reduced vision, developing over hours to days.
Key features are:
* Central scotoma (an enlarged central blind spot)
* Pain with eye movement
* Impaired colour vision
* Relative afferent pupillary defect
NB:
A relative afferent pupillary defect is where the pupil in the affected eye constricts more when shining a light in the contralateral eye than when shining it in the affected eye. When testing the direct pupillary reflex, there is a reduced pupil response to shining light in the eye affected by optic neuritis. However, the affected eye has a normal pupil response when testing the consensual pupillary reflex.
Describe the different eye movement abnormalities that might occur in MS
Lesions affecting the oculomotor (CN III), trochlear (CN IV) or abducens (CN VI) can cause double vision (diplopia)
Internuclear ophthalmoplegia
A lesion in the abducens (CN VI) causes a conjugate lateral gaze disorder.
- Conjugate means connected. Lateral gaze is where both eyes move to look laterally to the left or right.
- When looking laterally in the direction of the affected eye, the affected eye will not be able to abduct
- For example, in a lesion involving the left eye, when looking to the left, the right eye will adduct (move towards the nose), and the left eye will remain in the middle.
Describe the pathophysiology and presentation of internuclear opthalmoplegia [+]
Internuclear ophthalmoplegia is caused by a lesion in the medial longitudinal fasciculus.
The nerve fibres of the medial longitudinal fasciculus connect the cranial nerve nuclei (“internuclear”) that control eye movements (the 3rd, 4th and 6th cranial nerve nuclei). These fibres are responsible for coordinating the eye movements to ensure the eyes move together.
It causes impaired adduction on the same side as the lesion (the ipsilateral eye) and nystagmus in the contralateral abducting eye.
slides on where a lesion is
Desribe how eye sight would be impacted in INO if the right eye was affected? [1]
If affected, when looking to the right, the right eye will abduct but the left will remain central (failure in adduction).
What is transeverse myelitis? [1]
Describe the presentation of transverse myelitis [2]
Transverse myelitis:
- focal inflammation within the spine.
Characterised:
- by sensory and motor symptoms below the level of the lesion (e.g. paraesthesia, weakness).
- Bladder/bowel involvement may be present and usually there is a sensory level that corresponds to the level of the lesion.
- Must exclude compressive pathology in first instance (i.e. metastatic cord compression).
Describe the investigations for MS [+]
MS is primarily a clinical diagnosis, which is supported by the use of MRI
- Patients with suspected MS should be referred to a neurologist who specialises in neuroinflammatory disorders
- The diagnosis of MS is based on the clinical presentation (called an ‘attack’ or ‘relapse’), which is then confirmed by objective clinical evidence.
The McDonald criteria provides recommendations for the diagnosis of MS based on MRI findings (brain +/- spinal cord) and clinical presentation. MRI is the imaging of choice for identification of demyelinating lesions within the CNS.
The criteria can get quite niche, but these general principles apply:
* ≥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.
Describe why a LP might be indicated in a patient with ?MS? [1]
How would you intepret a positive result? [1]
Cerebrospinal fluid (CSF) can be analysed following a lumbar puncture to assess for CSF-specific oligoclonal bands.
- Oligoclonal bands refer to bands of immunoglobulins
- test is considered positive if oligoclonal bands identified in the CSF are not present in the serum.
- Therefore, a paired serum sample should be taken at the time of the lumbar puncture.
Describe the management for acute relapses of MS [2]
Before treating a relapse, it is essential to rule out infection, which can lead to a deterioration in symptoms.
The principle management of an acute relapse or ‘attack’ in RRMS is the use of corticosteroids.
- oral methylprednisolone 0.5 g daily for five days, OR Intravenous methylprednisolone 1 g daily for 3-5 days
- Gastroprotection: proton pump inhibitor
A number of drugs have been shown to reduce the risk of relapse in patients with MS. Typical indications for disease-modifying drugs include: [2]
relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
Describe the disease modifying drugs used in MS [5+]
natalizumab
* a recombinant monoclonal antibody that antagonises alpha-4 beta-1-integrin found on the surface of leucocytes
* inhibit migration of leucocytes across the endothelium across the blood-brain barrier
* generally considered to have the strongest evidence base for preventing relapse of the disease-modifying and hence is often used first-line
* given intravenously
ocrelizumab
* humanized anti-CD20 monoclonal antibody
* like natalizumab, it is considered a high-efficacy drug that is often used first-line
* given intravenously
fingolimod
* sphingosine 1-phosphate (S1P) receptor modulator
* prevents lymphocytes from leaving lymph nodes
* oral formulations are available
beta-interferon
* not considered to be as effective as alternative disease-modifying drugs
* given subcutaneously/intramuscularly
glatiramer acetate
* immunomodulating drug - acts as an ‘immune decoy’
* given subcutaneously
* along with beta-interferon considered an ‘older drug’ with less effectiveness compared to monoclonal antibodies and S1P) receptor modulators
Most commonly, patients with RRMS and two clinically significant relapses over the last two years may be initiated on first-line DMTs (e.g. [3]).
Most commonly, patients with RRMS and two clinically significant relapses over the last two years may be initiated on first-line DMTs (e.g. Interferon beta, Teriflunomide or Alemtuzumab).
conjugate horizonal gaze palsy, nystagmus in abducting eye
A 30-year-old woman presents with loss of vision in her right eye associated with pain on eye movement. Six months ago she presented with tingling and numbness in her left hand - multiple sclerosis
Lethargy, optic neuritis, paraesthesia, spastic weakness - multiple sclerosis
type IV hypersensitivity reaction
L afferent pupillary defect
