Multiple Sclerosis Flashcards by Aliya Hussain

What is Multiple Sclerosis (MS)?

Inflammatory demyelinating disorder of the CNS; characterised by plaques that are disseminated in time and place

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Occurrence of MS?

More common in females (3 : 1)

Initial presentation is commonly in 30s-40s; however, it can also be diagnosed in teens, young adults and other age groups

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Factors influencing development of MS?

Genetic factors - there is a clear link:
• 1st degree relative affected - 3-4% lifetime risk of MS
• Tayside and Orkney have the highest no. of diagnoses per annum; higher risk in Scottish

Environmental factors are important, mainly vit D level:
• Higher incidence and prevalence the further north/south of the equator you go
• Lower incidence and prevalence closer to the equator

Triggers - uncertain; a potential trigger is any infection, activating the immune system and triggering autoimmunity

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Clinical courses of MS?

Relapsing and remitting (RRMS) - a time of symptoms is followed by a period of no symptoms

Secondary progressive - tends to follow RRMS in the majority of patients
Symptoms gradually get worse; some people may still get relapses but do not tend to make a full recovery afterwards

Progressive relapsing - progressive worsening of the condition from the beginning (similar to primary progressive MS)

Primary progressive - gradually get worse over time, rather than appearing as sudden attacks (relapses)

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Broad clinical features of MS?

Pyramidal dysfunction

Optic neuritis

Sensory symptoms

Lower urinary tract dysfunction

Cerebellar and brain stem features

Cognitive impairment

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Signs of pyramidal dysfunction?

Examination of tone:
• Increased tone that is velocity-dependent (spasticity)

Examination of power:
• Weakness in the upper limb extensors; flexors will be strong
• Weakness in the lower limb flexors; extensors will be strong `

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What is optic neuritis?

Inflammation of the optic nerve, causing painful visual loss (usually lasting 1-2 weeks before improving)

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Occurrence of optic neuritis?

50% of MS cases present with this; MS is a major cause and should always be considered

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Signs of optic neuritis?

RAPD (relative afferent pupillary defect) - issue in the afferent pathway affects the efferent pathway and thus pupillary response on the swinging light test

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Sensory symptoms that occur in MS?

Pain

Paraesthesia

Loss of proprioception and vibration (dorsal column)

Numbness

Trigeminal neuralgia (common in MS)

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Pattern of sensory loss in MS?

Does not follow a specific dermatome of peripheral cutaneous nerve

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Signs of cerebellar dysfunction in MS?

Ataxia

Intention tremor

Nystagmus

Past-pointing (during finger-nose test)

Pendular reflexes - not brisk but involve less dampening of the limb movement than is usually observed with a deep tendon reflex; patients with cerebellar injury may have a knee jerk that swings backwards and forwards several times

Dysdiadokinesis - poor rapid hand movement coordination

Dysarthria

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Signs of brain stem dysfunction?

Diplopia (CN IV palsy)

Facial weakness (CN VII palsy)

If both of these signs are present, it is unlikely to be a Bell’s palsy; rather, it indicates a central issue

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What is internuclear ophthalmoplegia?

Very common sign of damage to the ipsilateral medial longitudinal fasciculus

MS UNTIL PROVEN OTHERWISE

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Signs of internuclear ophthalmoplegia?

Distortion of binocular vision

Failure of adduction leads to diplopia

Nystagmus in the abducting eye

Lag of one eye behind the other

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Signs of lower urinary incontinence?

Frequency, nocturia

Urgency and urge incontinence

Retention

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Describe fatigue as a symptom of MS

A major feature is overwhelming physical and mental fatigue

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Management of fatigue in MS?

Amantadine (anti-viral and anti-parkinsonian drug; it used for fatigue in MS)

If sleepy, modafinil

Hyperbaric O2

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Requirements for a diagnosis of MS to be made?

AT LEAST 2 EPISODES suggestive of demyelination

Dissemination in time and place

Differential diagnosis of MS?

Vasculitis

Granulomatous disorder

Vascular disease

Structural lesions

Infection

Metabolic disorders, e.g: B12 and folate deficiency

Ix for MS?

MRI scan (CT scan is relatively insensitive for it)

Lumbar puncture (CSF sample) shows:
• OLIGOCLONAL BANDS IN CSF (present in 90+% of cases, so be cautious when these are absent)

Neurophysiology

Blood tests (these are used to rule out other diagnoses and, for a diagnosis of MS, should be -ve):
• PV, FBC, CRP
• Renal, liver, bone profile
• Auto-antibody screen
• Borellia, HIV and syphilis serology
• B12 and folate levels

3 levels of management of MS?

Acute exacerbation
Symptomatic treatment
Disease modifying therapy:
• Initiation of therapy
• Escalation to 2nd line

Types of acute MS exacerbation and how each is treated?

Mild - symptomatic treatment

Moderate - oral steroids (500mg methylprednisolone for 5 days)

Severe - admit to hospital and administer IV steroids (1000mg of IV methylprednisolone over 3 days)

Symptomatic treatment is used for what in MS?

Pyramidal dysfunction, e.g: spasticity, weakness

Lower urinary tract dysfunction

Sexual dysfunction

Fatigue

Sensory symptoms

Tremor

Treatment of pyramidal dysfunction?

Physiotherapy Occupational therapy Specific treatments for spasticity inc. physiotherapy and anti-spasmodic agents: • Oral medications, e.g: baclofen, tizanidine • Botulinum toxin • Intrathecal baclofen / phenol

Sensory symptoms that may occur in MS?

Pain Paraesthesia Numbness Trigeminal neuralgia

Treatment of sensory symptoms in MS?

Pharmaceutical therapy: • Anti-convulsants, e.g: Gabapentin • Anti-depressant, e.g: amitriptyline TENS machine Acupunture Lignocaine infusion (given on the ward)

Types of lower urinary tract dysfunction that may occur in MS?

Increased tone at bladder neck (can cause poor stream and urinary retention) Detrusor hypersensitivity (causes frequency and nocturia) Detrusor sphyncteric dyssenergia (causes the feeling of wanting to pass but being unable to)

Symptoms of lower urinary tract dysfunction?

Frequency and nocturia Urgency and urge incontinence Retention

Treatment of lower urinary tract dysfunction in MS?

Anti-cholinergics, e.g: oxybutynin Desmopression (used occasionally, e.g: for travel) Catheterisation (for urinary retention)

Other drugs that are used in MS?

Cannabis sativa

Progression of untreated MS?

Sub-clinical MS is followed by a period where the patient is monosymptomatic Eventually, they develop relapsing-remitting MS, followed by secondary progressive MS As a person progresses through these stages: • Cognitive dysfunction increases • MRI lesion burden and acute MRI activity increases and then drops off • Level of disability increases • Brain volume decreases •

Lines of therapy in disease modification of MS?

1st line therapy: • Interferon Beta (Avonex, Rebif, Betaseron, Extavia) • Glitiramer Acetate (Copaxone) • Tecfedira 2nd line therapy: • Monoclonal antibody (Tysabri, Lemtrada, Zymbrata) • Fingolimod 3rd line therapy: • Mitoxantrone

Efficacy of interferon beta and Copaxone (glitiramer acetate)?

Decrease relapse rate by 1/3rd Decreased severity of relapses by 50% Effect on disability Both are comparable regarding efficacy

Administration of interferon beta and Copaxone?

Interferon beta is administered via a subcutaneous injection Copaxone is administered intramuscularly

Uses of tecfidera?

1st line indication in RRMS (relapsing-remitting MS) An oral agent that reduces relapse rate

What is fingolimod?

Shingosine-1-phosphate (S1P) inhibitor It is an oral agent used as 2nd line therapy in MS It has a significant effect on disease progression and reduces relapse rates by >50%; there is a greater reduction in risk of disability progression with earlier fingolimod Must be monitored for 24 hours following tablet ingestion, as there is a risk of heart block; if the patient's HR eventually increases, they can be sent home

Uses of monoclonal antibodies in MS?

Single disease modifying therapies in highly active RR MS: • Rapidly evolving and severe RR MS • Patient with high disease activity despite interferon treatment

Describe the inflammatory cascade in MS

1. Immune cells from the systemic circulation pass through the BBB (transendothelial migration), by using the α4β1-integrin molecules on their cell surfaces to bind to VCAM-1 on the BB 2. Immune cells may reactivate and produce cytokines 3. Immune cells mount an autoimmune attack against myelin

Mode of action of Tysabri (AKA natalizumab)?

Leukocytes typically migrate from the blood to the tissue and are then primed for activation Tysabri binds to the α4β1-integrin molecules on the cell surfaces of the leukocytes, preventing VCAM-1 binding; there is not transendothelial migration across the BBB This is followed by modulation of leukocyte apoptosis

What is Progressive Multifocal Leukoencephalopathy (PML)?

A catastrophic viral disease characterised by progressive damage/inflammation of the white matte of the brain at multiple locations It is caused by the JC virus, which is normally present and kept under control by the immune system; it is harmless except in cases of weakened immune systems

Causes of PML?

JC virus +ve Assoc. with all 2nd line therapies: • Monoclonal antibody (Tysabri, Lemtrada, Zymbrata) • Fingolimod

Uses of Mitoxantrone?

Used for relapsing progressive MS; it reduces the occurrence of relapses

Administration of Mitoxantrone?

12 infusions are given over 2 years

Adverse effects of Mitoxantrone?

Cardiac toxicity (dose-related)