Multiple Sclerosis Flashcards
Summarise a MS case in an introduction. What are the key points? (5)
Type
Duration
Treatment
Major neurological deficits + complications
Major functional + psychosocial consequences
“Mr CD is a 60 year old man with a 15-year history of multiple sclerosis, that has transitioned from RRMS to SPMS, currently being treated with beta-interferon, on a background of comorbid COPD and depression. Mr CD’s MS- related disability has been gradually progressing and he is now wheelchair-bound due to weakness and ataxia. Major issues identified are Mr CD’s dissatisfaction and poor adherence with his injection-based treatment, severe bladder dysfunction, poorly managed depression and low social support.
Symptoms of MS you need to ask for in P? (8) What is the key information you need to extract from the history?
Symptoms (start top-down)
Seizure
Cognitive impairment
Visual (acuity, pain on movement, loss of central vision – optic neuritis)
Cerebellar – ataxia, tremor, dysarthria
Spastic paresis, quadriparesis, hemiparesis
Limb paraesthesiae (posterior column, ML, internal capsule)
Urinary urgency / incontionence / retention
Faecal incontinence
Need to extract the type based on Hx.
- Is there a progression without flare-ups? (i.e. PPMS)
- Flare-ups followed by worsening symptoms (i.e. SPMS)
Risk factors/triggers for MS (attacks?) - for R in pricmcp (6).
Other than the FH - Think of getting someone pregnant
Bend-over (Lhermit’s - flexing the neck)
Hot/Heat (Utoff’s)/Being born in a temperate place
Exercise (sex)
Impregnate (infection + Pregnancy)
RF for disease: Family History, Place of Birth (x10 risk if born in a temperate climate)
RF for attacks:
Uhthoff’s phenomenon - heat worsens Sx
Lhermitte’s sign (flexing the neck)
Infection, fever, pregnancy & exercise
Types of MS (4) - in order of frequency.
Relapse-Remitting (90%)
Secondary progressive (50-75% within 15y)
Primary Progressive (10%)
Progressive relapsing (<5%)
What are common symptoms of MS and what is your approach to managing them?
Head-to-toe
Seizure - antiepileptics, rule out infection/tumour, assess fitness for driving
Cerebellar ataxia / tremor - falls prevention strategies, PT/OT, walking aids, clonazepam, propranolol
Heat-sensitive symptoms - CCBs
Cognitive impairment - memory aids, cholinesterase inhibitor
Painful spasms - baclofen, diazepam, dantrolene
Bladder dysfunction - incontinence pads, bladder training/habit, oxybutynin (overactive bladder), IDC or alpha-blocker (overflow)
Bowel - incontinence pads, monitor constipation
Sexual - lubricants, sildenafil, consider referral to IVF
MS - PRICMCP?
P: date dx, initial symptoms (head-to-toe) - seizure, stroke, cerebellar ataxia, optic neuritis, visual problems, stroke-like symptoms, paresis, parasthesiae, bladder/faecal. What is the type of MS? (i.e. RR, PS, SP…etc)
R: FH, place of birth (temperate), Heat (Uhtoff), flexing the neck (Lermit’s), Infection, Exercise, Pregnancy
I: how was the dx established? MRI, LP, clinical (met McDonald’s criteria - at least 2 lesions clinically/radiologically)?
C:
- Disease (above - especially disability resulting from the disease: incontinence, autonomic dysreflexia) + Falls, Aspiration, Contractures, Pressure sores.
- Drug side effects (especially PML, infection / meningitis, arrhythmia, Hepatitis, depression [IFN]). Injection site reactions, infusion reactions***.
M:
- Current & previous drug regime
- Symptom Mx: CCB (heat-sensitive symptoms), tremor (propranolol, clonazepam), spasticity (baclofen, diazepam), pain (anti-depressants, anticonvulsants), bladder dysfunction (oxybutynin if urge incontinence), constipation (laxatives), fatigues (amantidine), sexual (sildenafil), IDC/SPC…etc.
- Is the patient compliant?
C: current symptoms (mobility, sexual dysfunction, ADLs, work). Did symptoms resolve or still there? Plan for further therapy? Any active problems.
P: understanding of prognosis (15y from diagnosis - the majority will have disability that stops them from working / help with normal activities), understanding of complications
MS - clinical examination. Routine neuro + what 4?
A full CN, UL, LL exam and;
Look specifically for…
- INO + decreased VA + RAPD. ***MUST DO FUNDOSCOPY (optic atrophy)
- Cerebellar signs (ataxia, tremor, nystagumus)
- Transverse myelitis (LMN at the level of lesion + UMN below)
- Mention bradycardia (Fingolimod)
What is your approach to investigating this patient with MS? What investigations would you like to see?
T: confirm Dx.
- Based on symptoms (e.g. patient had 2 clinical attacks) the patient fulfills time criteria (+/- space).
- However, I would like to review MRI looking for ≥2 lesions affecting ≥2 regions of the CNS (space) + simultaneous enhancing + non-enhancing lesion (time)
- LP (oligoclonal band of IgG1, elevated protein, mononuclear cell pleocytosis)
- VEP (slowed EP suggestive of myelin loss) - indicates previous optic neuritis - important if there is only one clinically detectable lesion present to fulfil the criteria
Exclude other dx
- Rule out infection (septic workup, CSF MCS), stroke, malignancy (send cytology & flow-cytometry)
Severity
- Review MRI trends & disease burden: number of lesions, areas affected, the rapidness of progression
- Look for Gadolinium enhancement suggestive of active disease
Treatment baseline bloods + Screen for Complications
- Bladder scan, consider urodynamics
- FBC (cytopaenia), EUC (GBM-GN), LFTs (hepatitis), TSH (alemtuzumab), CRP (infection), Vitamin D (replace if low)
- Urine MCS (alemtuzumab - GBM, UTI), ECG (fingolimod-bradycardia)
What are 3 common neurological findings of MS of Transverse myelitis?
Sensory, motor, autonomic impairment below the level of the lesion
C5-T1 lesion: UMN + LMN signs (upper limb), UMN signs (lower limb)
T1-T12 lesion: UMN (lower limb) – most common
L1-S5: UMN + LMN (lower limb)
Ask autonomic dysreflexia
What is autonomic dysreflexia? why do you get it?
- Cord involvement above T6
- Uninhibited (exaggerated) sympathetic response to noxious stimuli below the level of injury → vasoconstriction + HTN
- Due to loss of compensatory dilatation of splanchnic vascular bed
What is “objective clinical evidence” used in MacDonald’s criteria?
Abnormality on
- Neurological examination or
- MRI or
- Visual evoked potentials
That corresponds to the anatomical location suggested by symptoms of a current or previous attack
What qualifies as MS according to 2017 MacDonald’s criteria?
Key summary;
- 2** x dissemination in **time and space criteria
- If only 1 time or space criteria are met based on hx/exam, you can fulfill the rest with MRI (i.e. lesions ≥2 anatomical areas or old+new lesions demonstrating dissemination in time)
In more detail;
- History of ≥2 clinical MS attacks (i.e. time) and
- Objective clinical evidence of ≥2 lesions (i.e. space) or
- Clinical evidence of 1 + reasonable historical evidence of prior attack involving lesion in distinct anatomical location
- History of ≥2 clinical MS attacks (i.e. time) and clinical evidence of only 1 (but without evidence of prior attacking lesion in distinct location)
* Need dissemination in space – MRI (hyperintenst T2 – in ≥2 of 4 regions of CNS), or another attack in different site - History of 1 clinical MS attack (i.e. time) and clinical evidence of ≥2 lesions (i.e. space; clinically isolated syndrome – CIS)
* Need dissemination in time: MRI – simultaneous gad-enhancing/nonenhancing lesions, new hyperintense T2/Gad enhancing lesions on FU, new clinical evidence or presence of CSF – oligoclonal bands.
What are the 4 anatomical locations in the CNS for Space criteria for MS?
Juxta-cortical
Periventricular
Infratentorial (Cerebellar)
Spinal cord
What do you mean by dissemination in space? (2)
What do you mean by dissemination in time? (2)
What are the differentials in MS long case?
Vascular (ischaemic stroke, SVT)
Infection (syphilis, lyme, HTLV-1)
Toxins (drugs – PML – progressive multifocal leuko-encephalopathy)****
Autoimmune / inflammatory – vasculitis (SLE, Sjogrens, Behcets)
Metabolilc: B12 deficiency (SDSC)
Infiltrative – sarcoids
Neoplastic - CNS lymphoma, paraneoplastic
If spinal cord disease – rule out SC compression and Subacute combined degeneration of the cord
DDx for optic neuritis? (6)
MS-associated:
- MS – typically unilateral
- MOGEM (MOG-associated encephalo-myelitis) – bilateral
-
NMOSD (neuromyelitis optica spectrum disorder) – bilateral (
Transverse myelitis with longitudinally extensive SC lesion spanning ≥3 vertebral segments + bilateral optic neuritis)
General:
- Vascular (stroke, thrombosis)
- Infection/inflammatory/infiltrative
- Trauma/Toxins
- Autoimmnue - SLE
- Malignancy/Metabolic - paraneoplastic
What are the differential ddx of a large acute lesion on MRI in patients with MS on tx? (4)
-
Tumefactive demyelination – acute, tumor like MS variant with ≥2cm lesions, often with oedema + ring enhancement
- Rapidly responsive to steroid treatment
- PML
- CNS malignancy
- Otherwise as per VITAMIN
How would you go about investigating suspected MS?
Test to confirm
- MRI (sens 90%, spec 75%) – also helpful to exclude stroke
- VEP: delayed in 80% → indicates previous optic neuritis
- LP: oligoclonal band (IgG), altered IgG: Albumin ratio, ↑MBP
Exclude
- Confirm drug history: Natalizumab, JCV PCR in CSF (PML)
- AQP-4, MOG-Ab
- Consider other differentials: ANA, ENA, syphilis, ACEi, lyme serology, paraneoplastic Ab panel, AI encephalitis panel
Severity
- Review previous MRI – how many & how quickly did lesions develop? Burden of disease (≥3 lesions → ↑ risk of relapse)
- Presence of oligoclonal bands (↑ risk of relapse)
Treatment baseline
- FBC (fingolimod – leukopaenia)
- PLT (Alemtuzumab – ITP)
- TSH (Alemtuaumab – Grave’s)
- LFTs (interferon-beta, Daclizumab)
- JCV PCR (natalizumab)
- ECG (fingolimod – 1st dose Bradycardia)
Screen complications - as above
How does typical MS lesion appear on MRI (3)?
•Ovoid appearance
•T2 hyper-intense lesion
•Dawson finger appearance: characteristic peri-ventricular lesions arranged at right angles to corpus callosum
What oral MS drugs do you know of and what are the side effects? (2 each)
Fingolimod → 1st dose bradycardia (fingering makes your heart stop, and go crazy!) – cryptococcal meningitis, hepatitis
Teriflunomide → Terrible hair (loss) – so need to wear HAT (Hepatitis)
Dimethyl fumarate → Diarrhoea, PML
What SC/IM drugs do you know of & what are the side effects (2 drugs, 1 each)?
- Interferon-beta → ↑ LFTs, flu-like symptoms, injection site
- Glatiramer → Glamer (good for pregnancy). No serious side effects but low efficacy.
What MS drugs are injectables (3) and what are the side effects (1 each)
Natalizumab – PML (monthly injection).
Alemtuzumab (yearly) – ****immune disease*: Graves, ITP, haemolytic anaemia, GBM GN
Ocrelizumab – infusion reactions, HBV flare
Management of acute MS?
Rule out & treat an infection. Pseudorelapses are exacerbation or recurrence of previously improved symptoms and are caused by infection.
- IV Methyl-prednisolone 1g daily for 5 days
- Plasma exchange +/- IVIG if poorly responsive
What are the most important psychosocial factors to address in the MS long case? (5)
Mental health
Sexual function
Reproductive plans
Financial support given progressive disability
Advanced care plans
Should you treat MS as a flare when the patient has sensory symptoms only? why?
When symptoms are only sensory in nature – these syndromes tend to resolve without disability and the risk of a methylprednisolone pulse is therefore not warranted
How is spasticity in MS treated? (3 options)
Baclofen is first-line – start low and titrate cautiously due to drowsiness and the risk of causing flaccidity which may worsen mobility***
Clonazepam or diazepam can be used at night to reduce nocturnal spasms
Occasionally, affected muscle groups can be treated with Botox (generally used in patients who are not independent with transfers and mobility)
Patients with MS can get ‘paroxysmal’ symptoms of dystonic posturing and tonic spasms.
What medication can be used to reduce these symptoms?
CBZ
How common is fatigue as a major symptom in MS? How should you approach it? (3 non-pharm, include 2 meds)
Fatigue affects 75% of patients with MS and is a major impact on QoL
The approach should be similar to other patients:
- Rule out contributing medical pathology – anaemia, thyroid imbalance and infection
- Optimise sleep, including screening for and treating RLS, nocturia, nocturnal spasms
- Screen for and treat mood disturbance
Medication has poor efficacy but can be tried if symptoms remain significant (Amantadine, Modafinil)
How should you approach new urinary incontinence in a patient with MS?
- Rule out infection with an MSU; treat if present
- Rule out urinary retention with a bladder scan
- Treat as urge incontinence if the above not found
How should you manage urge incontinence non-pharmacologically in patients with MS?
- Rule out exacerbators such as infection regularly
- Use incontinence pads for minor leakage
- Suggest regular timed voids to prevent episodes
- Consider pharmacotherapy if the above is unsuccessful or inadequate (e.g. anticholinergic)
What medications can be used to treat refractory or unacceptable urge incontinence in MS? (5)
- Oxybutynin
- Solifenacin/darifenacin
- Tolterodine
- Mirabegron
- Intravesical botulinum toxin
What is your approach to an MS patient with high residual urine volumes?
- Intermittent self-catheterization for the patient with sufficient cognition and dexterity
- IDC or SPC otherwise
What lifestyle factors should be optimised to augment your management of MS?
- Smoking cessation – reduces progression of disease
- Maintain activity – helps to maintain function and QoL
- Reduce alcohol intake – improves self-reported function
- Encourage a healthy, varied diet – for general health maintenance
What general advice about pregnancy and MS should you give women who wish to fall pregnant?
Pregnancy does not alter the prognosis/course of MS significantly
The risk of relapse in pregnancy is lower, but made up for a higher risk in the 3 months post-partum
How should MS medications be managed pre-conception? What agents require special attention? (2)
Often medications can be suspended prior to conception as the risk of relapse is low, but this needs to be weighed carefully*** (buzz word) with regard to:
- Risk of relapse based on activity of the disease
- Teratogenicity of medications
- The severity of previous relapses and current function
Remember: I’m pregnant - what TF?
Teriflunomide is category X and has a very prolonged half-life – needs to be ‘washed out’ with cholestyramine
Fingolimod is category D and must be stopped
Other drugs may be continued if risk of relapse is unacceptable
When should MS treatments be restarted post-partum?
•Generally at two weeks, to allow adequate wound healing if present
How does treatment for MS affect vaccination advice?
Seasonal influenza vaccination should be offered – it confers no increased risk of a relapse
The use of live vaccines depends somewhat on the type of therapy
Interferon and glatiramer are likely safe
Live vaccines should not be given to patients receiving agents that affect lymphocytes such as t_eriflunomide, fingolimod, dimethyl fumarate, natazliumab and ocrelizumab_
MS: General approach to follow-up – what would you monitor? (5)
MS symptoms
Impact on the patient with jobs, ADLs, family.
ECG for bradycardia (Fingolimod)
Urine for protein (Alemtuzumab - GBM GN)
Bloods: FBC (cytopenia), EUC (anti-GBM GN), LFT (hepatotoxicity), CRP (infection), TSH (AI thyroid disease with Alemtuzumab)
What is this patient’s prognosis (MS)?
15 years after 1st episode – 80% will have significant symptoms that will prevent them from working and require help with normal activities
If MRI normal, single abnormality – only 10% will develop second episode in 10 years
If MRI abnormal, 80% will develop further episodes
What are the risk factors for PML in patients with Natalizumab? (3)
JCV Ab positive
>2 years of use
prior immunosuppression
What is CIS and what is your approach to managing it?
CIS = Single attack of demyelination reflecting a focal or multifocal event.
Perform MRI with contrast to look for evidence of dissemination of time & space
If not LP looking for oligoclonal bands
If MRI is abnormal (i.e. demyelinating lesion suggestive of MS) → risk of progression is 60% therefore need to treat or closely monitor.
RIS (radiological isolated lesion) → if no clinical symptoms then monitor closely.
What is your approach to managing this patient’s MS?
Goals: slow progression, prevent complications, improve function.
Confirm Dx: MRI (+gad, look for dissemination in time & space), CSF (oligoclonal bands), VEP (slowing). identify subtype.
A: screen & treat contributory factors & secondary causes
- Depression
- Infection, Malignancy, Stroke
Screen for complications
- Disease: collateral from family (seizure), MMSE (dementia), assess fitness to drive, bladder scan
- Drugs: bloods (cytopaenia, hepatitis, renal impairment in GBM ass. Alemtuzumab, TSH, urine for GN [alem], ECG (bradycardia with Fingolimod), septic screen
T: non-pharm
- Educate patient + family: nature of progressive disease with disability, managing flares
- Many support group + organisations for MS
- Life-style changes: smoking cessation (slows progression!), maintain activity, reduce ETOH (falls), healthy-diet. Weight loss + quit smoking is important (they worser disease activity)
- Falls prevention: PT (balance/mobility aids), OT (home mods), night lights, vital calls
- Infection: influenza but avoid live (dep on drugs), hygiene, contacts
- Age appropriate malignancy screening
- Incontinence: timed-voids, incontinence pads, self-catheter vs. SPC (dep on dexterity/cognition)
T: Pharm
- Immunomodulators: which route would be most appropriate? can a patient self inject (S/C), oral?, injections.
-
Symptom Mx
- Seizure meds, heat-sens symptoms (CCB), tremor (propranolol, clonazepam),
- cognitive (aricept), painful spasms (cannabioids, botox, baclofen, diazepam, dantrolene)
- incontinence (oxybutynin or alpha-blocker), laxatives for constipation
- sexual (sildenafil)
Involve - MS nurse**, continence nurse**, urology, neuropsychology, NDIS, employment services, family for support, SW (financial help), AH, dietician, neurologist
Ensure F/U and monitor for symptoms, complications (as above) of therapy, impact on patient.
Natalizumab - needs to be on 6m surveillance for PML.
Fingolimod - cautions prior to starting? (3)
- Cannot be given to those without VZV immunisation or previous exposure + immunity
- Screen for HSV, Hepatitis, TB
- ECG - will prolong QT
is there anyway to distinguish MS from Storke on clinical grounds? (2)
MS patients do not develop cortical symptoms e.g. neglect and aphasia
Please summarise the course of this patient’s symptoms of multiple sclerosis.
Commonly asked question - so take a good chronological hx of symptomatology.
What are the most common psychosocial issues faced by MS patient? (4)
Mobility
Ability to work
Family planning (due to disease + treatment)
Mood
