Multiple Sclerosis and Inflammatory CNS Diseases Flashcards
What is multiple sclerosis?
An autoimmune, inflammatory demyelinating disorder of the CNS.
In MS, patches of scar tissue known as plaques form over the demyelinated areas preventing what?
Nerve communication.
Progression of symptoms in MS correlates to what?
Plaque dissemination of areas of the brain/spinal cord controlling affected areas.
MS is more common in which sex?
Females 3:1.
Initial presentation of MS typically in which decades?
30s and 40s.
What are the various clinical courses of MS?
- Relapsing remitting.
- Secondary progressive.
- Progressive relapsing.
- Primary progressive.
What are the clinical features of Multiple Sclerosis?
- Pyramidal dysfunction.
- Optic neuritis.
- Sensory symptoms.
- Lower urinary tract dysfunction.
- Cerebellar and brain stem features.
- Cognitive impairment.
What are the symptoms of pyramidal dysfunction seen in MS?
In the extensors of upper limbs and the flexors of lower limbs, there will be:
- Increased tone.
- Spasticity.
- Weakness.
Describe optic neuritis?
Painful progressive visual loss over 1-2 weeks.
Often associated with MS.
If unilateral, RAPD (relative afferent pupillary defect) may be observed.
Most cases improve over time.
What are the sensory symptoms experienced in MS?
- Pain.
- Paraesthesia (pins + needles).
- Dorsal column loss: impaired/lost ability to sense vibration and proprioception.
- Numbness.
- Trigeminal neuralgia.
If cerebellar dysfunction is present in MS, what signs will be observed?
- Ataxia.
- Intention tremor.
- Nystagmus.
- Past pointing.
- Pendular reflexes.
- Dysdiadochokinesia.
- Dysarthria.
What is ataxia?
Lack of voluntary coordination of muscle movements e.g. gait abnormality, changes to speech and eye movement abnormalities.
What is past pointing?
Pointing beyond the finger in the finger-nose test.
What are pendular reflexes?
When reflex is elicited, limb stimulated swings like a pendulum.
What is dysdiadochokinesia?
Inability to perform rapid alternating movement, e.g. tapping the right hand fast on the back of the left hand.
What is dysarthria?
Difficult or unclear articulation of speech that is otherwise normal.
What features of brain stem dysfunction may be seen in MS?
- Diplopia: CN VI palsy.
- Facial weakness: CN VII palsy.
What is internuclear ophthalmoplegia?
Disorder of conjugate lateral gaze resulting in impaired adduction.
Attempting to gaze contralaterally (in relation to affected eye) results in minimal adduction - if any.
The contralateral eye abducts with nystagmus.
What causes internuclear ophthalmoplegia?
Injury or dysfunction (MS) in the medial longitudinal fasciculus.
What signs and symptoms are seen in internuclear ophthalmoplegia?
- Distortion of binocular vision.
- Failure of adduction resulting in diplopia.
- Nystagmus in adducing eye.
- Eye lag.
What features of lower urinary tract dysfunction are seen in MS?
- Frequency.
- Nocturia.
- Urgency.
- Urge incontinence.
- Retention.
How is fatigue managed in MS?
- Amantadine.
- Modafinil if sleepy.
- Hyperbaric oxygen.
By what criteria is MS diagnosed?
- At least 2 episodes suggestive of demyelination.
- Dissemination in time and place.
- McDonald criteria.
What are the various differential diagnosis of MS?
- Vasculitis.
- Granulomatous disorder.
- Vascular disease.
- Structural lesion.
- Infection.
- Metabolic disorder.
How is a diagnosis of MS made clinically?
- MRI.
- CSF.
- Neurophysiology.
- Blood tests.
What blood tests will come back negative in MS?
- Plasma viscosity, FBC, CRP.
- Renal liver bone profile.
- Auto anti-body screen.
- Borellia, HIV, syphilis serology.
- B12 and folate.
What findings in CSF may suggest MS?
Oligclonal bandS i.e. more than one.
Why are oligoclonal bandS present in CSF of MS?
In MS antibodies cross the BBB to attack myelin surrounding nerves resulting in high level of antibodies in CSF.
Oligoclonal bandS shows >2 bands and thus presence of disease activity - though this may not necessarily be MS. But is MS in >90% of cases.
Management of mild acute exacerbation of MS?
Manage symptoms.
Management of moderate acute exacerbation of MS?
Oral steroids.
Management of severe acute exacerbation of MS?
Admit to hospital/ IV steroids.
Management of pyramidal dysfunction in mild acute exacerbation of MS?
For weakness and spasticity:
- Physio.
- Occupational therapy.
- Anti-spasmodic agent.
Management of spasticity in mild acute exacerbation of MS?
- Physio.
- Oral meds: Baclofen, Tizanidine.
- Botulinum toxin.
- Intrathecal Baclofen/ Phenol.
How are intrathecal drugs administered?
Into the spinal canal or subarachnoid space.
Management of sensory symptoms in mild acute exacerbation of MS?
- Anti-convulsant e.g. Gabapentin.
- Anti-depressants e.g. Amitriptyline.
- TENS machine.
- Acupuncture.
- Lignocaine infusion.
What causes lower urinary tract dysfunction in MS?
- Increased tone at bladder neck.
- Detrusor hypersensitivity.
- Detrusor sphincter dyssenergia.
What is detrusor sphincter dyssenergia?
Bladder outlet obstruction from detrusor muscle contraction with concomitant involuntary urethral sphincter activation.
Associated with neurologic conditions.
Management of lower urinary tract dysfunction in MS?
- Bladder drill.
- Anti-cholinergics e.g. Oxybutynin.
- Desmopressin.
- Catheterisation.
What is bladder drill/training?
Aims to slowly stretch the bladder to hold larger volumes and make the bladder muscle less overactive with time to allow more bladder control.
First line disease modifying therapy in multiple sclerosis?
- Interferon-beta: Avonex, Rebif, Betaseron, Extavia.
- Glitiramr Acetate (Copaxone).
- Tecfedira.
Second line disease modifying therapy in multiple sclerosis?
- Monoclonal antibody: Tysabri, Lemtrada, Zymbrata.
- Fingolimod.
Third line disease modifying therapy in multiple sclerosis?
Mitoxantrone.
Describe Interferon-beta & Copaxone, and their effect on multiple sclerosis?
- Injectable: SC, IM.
- Decrease relapse rate by 1/3.
- Decrease severity of relapses by 1/3.
- Some effect on disability.
Both comparable efficacy.
Describe Tecfidera and its role in MS?
- Oral drug.
- First line indication in relapsing remitting MS.
- 44% reduction in relapse rate.
- Unclear long term data.
Describe Fingolimod and its role in MS?
- Oral drug.
- Sphingosine 1-phosphate (S1P) modulator.
- > 50% reduction in relapse rate.
- Significant effect on disease progression.
- NICE & SMC approved as second line in MS.
Describe the monoclonal antibodies: Tysabri, Lemtrada & Ocrelizumab, and their role in MS?
- Single disease modifying therapies in highly active relapsing remitting multiple sclerosis.
- Used in those with rapidly evolving severe relapsing remitting MS.
- Those with high disease activity despite interferon treatment.
Describe the use of the monoclonal antibody Ocrelizumab in MS?
- Used in early primary, progressive MS.
- Delays progression by 25%.
Integrins α4β1 mediates what in MS?
Trans-endothelial migration of activated T-cells across the BBB in Experimental autoimmune encephalomyelitis.
Describe the inflammatory cascade in MS?
- Immune cells pass through BBB from systemic circulation.
- Immune cells may reactivate and produce cytokines.
- Immune cells mount autoimmune attack against myelin in the CNS.
What is the mode of action of Tysabri in MS?
- Binds to Integrin-α4β1 to block its interaction with VCAM-1 and prevent leukocyte migration into brain tissue. This reduces inflammation and prevents lesion formation.
- Inhibits ongoing CNS inflammation by mediating leukocytes already present in CNS by interrupting interaction between α4-integrin-expressing leukocytes and extracellular matrix proteins to cause apoptosis.
