Multiple Sclerosis
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- Created by: LBCW0502
- Created on: 05-04-21 17:37
State the epidemiology of MS
More prevalent further away from the equator (North or South). Unknown cause. More prevalent in Scotland compared to England. More common in women than men. Diagnosed in 20s/30s. 100 people diagnosed in the UK.
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State the aetiology of MS
Unknown cause. Environment factors include: Epstein–Barr virus, autoimmune reaction, genetics, exposure to sunlight
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Outline the pathogenesis of MS
Immune cells penetrate BBB, cause damage to the myelin sheath (covering of nerve cells), issues with the conduction of impulses in the NS. More damage, more severe symptoms, little repair occurs.
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Describe the clinical categories of MS (1)
Relapsing/remitting MS – most common, 80% of patients, develop symptoms (relapse), symptoms get better over, symptoms appear again another year, cycle repeats. Patients may develop some disability with relapses of MS. 50% with relapsing/remitting MS go on
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Describe the clinical categories of MS (2)
Primary progressive MS – from the point of diagnosis/developing MS, disability/symptoms gradually worsen over time, occurs in 20% of patients, more difficult to treat.
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Describe the clinical categories of MS (3)
Secondary progressive MS, disabilities become worse. 50% with relapsing/remitting MS go on to develop secondary progressive MS (disability gets worse over time)
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Which tools are used to diagnose MS?
McDonald Criteria, MRI (check lesions/damage, which occurs during relapse), clinical symptoms, lumbar puncture (sample of cerebral spinal fluid), visual evoked potentials (less common).
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State features of the McDonald Criteria
Evidence of damage to CNS, dissemination in time (clinical relapses identified at different points in time), dissemination in space (MRI lesions in different areas of CNS).
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State features of MRI for the diagnosis of MS
White spots on the scan, inflammatory damage in the brain, location of damage in the brain/spinal cord determines the type of symptoms.
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State features of lumbar puncture
Oligoclonal bands (little IgG antibodies collecting together in the CNS, but in MS, there is movement of immune cells/antibodies into the CNS), oligoclonal bands (more found in spinal fluid) – good indicator for the diagnosis of MS
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What is VEP?
Visual Evoked Potential. Measures speed of nerve conduction along sensory nerves to brain using electrodes on skin, delays indicate damage to nerve pathway
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Describe the symptoms of MS (1)
Range from a tingling sensation to worse symptoms next year. Symptoms of the spinal cord include spasticity (increase in tightening of muscles, abnormal movement, ranges from mild to severe), bladder/bowel dysfunction (incontinence, constipation), leg we
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Describe the symptoms of MS (2)
MS affecting the cerebellum can affect balance, cause dizziness, tremor, and ataxia. MS affecting areas involved with thought and emotion (cerebral cortex, hypothalamus, limbic system) can affect cognition, cause depression and mood swings
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Describe the symptoms of MS (3)
Symptoms not associated with a single area include fatigue, speech, and swallowing, pain (neuropathic pain, muscle pain - patients might delay visiting an HCP). Difficult to predict what disease course a patient might have
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What is used to monitor the effectiveness of disease-modifying drugs?
The expanded disability score (diagram)
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What is an acute MS relapse?
Acute neurological disturbance lasting at last 24 hours
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What is used to treat an acute MS relapse?
Corticosteroids. For disabling relapse, shortens the duration of relapse, with no effect on functional outcome. Methylprednisolone 1g IV 3/7 or 500 mg PO od 5/7. Prednisolone 40-60 mg and wean (limited evidence). Steroids are offered if relapse is severe
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What is spasticity?
Increased muscle tone. Occurs in up to 75% of patients. Can lead to pain and limited mobility
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What are the treatment options for spasticity?
Baclofen. Tizanidine, gabapentin, dantrolene, benzodiazepines. Sativex (cannabinoid) – not considered cost-effective by NICE. Botulinum (severe focal spasticity). IT baclofen pump. Physiotherapy
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Describe features of baclofen (1)
Most widely used anti-******* agent. Chemically analogous to g-aminobutyric acid (GABA). Reduces stretch reflex activity thereby reducing clonus and involuntary spasms. Adverse effects can limit the maximum tolerated dose.
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Describe features of baclofen (2)
Dose titration should be slow to allow tolerance to drowsiness to develop. Intrathecal baclofen may be used for patients with severe spasticity who do not respond to oral treatment. Baclofen must be withdrawn slowly to avoid precipitating seizures or with
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Describe features of Tizanidine
Alpha2-adrenoceptoragonist. Similar effects on the stretch reflex to baclofen. Slow dose titration required to prevent excessive drowsiness
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Describe features of Dantrolene
Acts directly on skeletal muscle leading to fewer central side effects. Limited by a reduction in muscle strength it causes. Careful liver function monitoring required
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State a feature of benzodiazepines
Drug-induced sedation and long term use associated dependence limit use
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What other agents are used to treat spasticity?
Gabapentin – useful for pain associated with spasms. Botulinum – useful when spasticity is a problem in a single limb or muscle – not first line. Cannabis – Sativex nasal spray in the process of applying for a license
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What are the symptoms of bladder dysfunction?
Common in up to 75% of MS patients. Urgency of micturition. Urinary frequency. Incontinence. Nocturia. Incomplete bladder emptying.
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What are the non-pharmacological treatments for bladder dysfunction?
Intermittent self-catheterisation and surgery
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What are the pharmacological treatments for bladder dysfunction? (1)
Antimuscarinic agents e.g. oxybutynin, tolterodine, can be used to stabilize detrusor muscle (provided incomplete bladder emptying is not a problem). All can cause anticholinergic side effects.
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What are the pharmacological treatments for bladder dysfunction? (2)
Desmopressin an antidiuretic hormone analogue that increases water resorption in the kidney, can be used to treat nocturnal enuresis. Patients must be monitored carefully to avoid fluid overload. Not recommended in patients with CVD
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What are the treatments for bowel dysfunction?
Both constipation and faecal incontinence can occur in MS. Constipation can be treated with laxatives. Faecal incontinence (less common) can be treated with loperamide if necessary. (Constipation overflow should be excluded before loperamide is considered
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Describe features of sexual dysfunction
Can arise from spinal cord lesions, or be secondary to bladder problems, fatigue and spasticity. Erectile dysfunction. Can be a symptom of MS, an underlying psychological
problem, or drug-induced e.g. baclofen. Treatment with PDE-5 inhibitor (sildenafil)
problem, or drug-induced e.g. baclofen. Treatment with PDE-5 inhibitor (sildenafil)
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What are the treatments for pain?
Usually neuropathic or muscular. Pharmacological: amitriptyline, pregabalin, gabapentin, duloxetine, carbamazepine, simple analgesics such as paracetamol, NSAIDs. Non-pharmacological: exercise, physiotherapy, positional training
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What are the treatments for fatigue?
Most common and disabling complaint. Pharmacological: Amantadine, modafinil, hydroxycobalamin (limited evidence for all). Non-pharmacological: amending lifestyle to optimise energy e.g nutrition, relaxation techniques, sleep hygiene, treating depression,
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What are the treatments for depression?
Pharmacological: Antidepressant medication. Non-pharmacological: Cognitive behavioural therapy.
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What are the treatments for cognitive decline?
Pharmacological: disease-modifying drugs may help slow decline. Non-pharmacological: Psychological support, memory aids
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Why are disease-modifying drugs useful in the treatment of MS?
Reduce the number of relapses. Reduce the severity of relapses. Show some evidence of delaying disease progression and/or disability. Some may prevent or delay a second clinical attack (relapse) for individuals with clinically isolated syndrome (CIS)
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Give examples of disease-modifying drugs used to treat MS relapses (1)
Highly effective DMTs. Moderately effective DMTs. Alemtuzumab (used freely for different types of MS but restricted to severe MS due to hepatic damage). Patients recently diagnosed with MS – dimethyl fumarate, interferon beta, teriflunomide, ocrelizumab (
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Give examples of disease-modifying drugs used to treat MS relapses (2)
Alemtuzumab – IV treatment for 5 days in year 1, 3 days in year 2 (induction – short periods of treatment). Cladribine – 10 days in year 1, 10 days in year 2 (tablets). Natalizumab – infusion once a month. Dimethyl fumarate – tablet
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Which factors need to be considered when discussing MS management with a patient?
PMH, vaccine history (can’t have live vaccines during immunosuppressive treatment), MHx and allergies, lifestyle factors, EDSS, decision aids, side effects, family planning (drugs might be teratogenic), hard decisions (start treatment early for long-term)
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Which parameters are check during screening tests?
FBC, LFTs, renal function tests, infection markers, thyroid tests, blood pressure, heart rate, weight, pulmonary function, ophthalmology.
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What are the practical considerations for MS management? (1)
Switching between DMTs (risk of relapse vs risk of adverse effects due to additive exposure, half-life and duration of immunosuppressive effect). Family planning and types of contraception (IUD, LNG-IUS, IMP, sterilization - additional contraception not
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What monitoring is required?
Blood tests, MRI scan, treatment efficacy, side effects, managing infection risk, Blueteq (managing cost of the drugs), EDSS, interactions
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Which infection risks need to be monitored?
TB. Hepatitis B/c. Herpes virus. PML. HIV. HPV. Opportunistic infections. Respiratory tract infections. Urinary tract infections. GI infections
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Describe features of progressive multifocal leukoencephalopathy (1)
CNS infection with the John Cunningham Virus (JCV). Leads to irreversible neurological disability or death. Natalizumab, Dimethyl Fumarate, and Fingolimod
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Describe features of progressive multifocal leukoencephalopathy (2)
Risk factors: Prior exposure to JCV, Previous treatment with immunosuppressants, Use of natalizumab for more than 2 years (PML not seen after 6 months of stopping natalizumab). Early signs: progressive speech deficits, hemiparesis or seizures, similar to
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Which factors need to be considered when planning for surgery? (1)
Assess risk of infection vs benefit of DMT. Significance of immunosuppression. Duration of immunosuppression. Optimum timing when least immunosuppressed e.g. for ocrelizumab 4-6 months since last infusion.
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Which factors need to be considered when planning for surgery? (2)
Can treatment be delayed e.g. natalizumab to 8 weekly. Alemtuzumab and cladribine, delay where possible until immune reconstitution has occurred, 6-12 months after last dose
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Which factors need to be considered when stopping DMTs?
Relapse. EDSS > 7. Intolerance
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What are the emerging therapies for MS?
Mitoxantrone – unlicensed use. Siponimod. Ozanimod. Ofatumumab. Ponesimod. Diroximel Fumarate. Ublituximab. Evobrutinib. Simvastatin
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Other cards in this set
Card 2
Front
State the aetiology of MS
Back
Unknown cause. Environment factors include: Epstein–Barr virus, autoimmune reaction, genetics, exposure to sunlight
Card 3
Front
Outline the pathogenesis of MS
Back
Card 4
Front
Describe the clinical categories of MS (1)
Back
Card 5
Front
Describe the clinical categories of MS (2)
Back
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