Mitigating Multiple Sclerosis Risks & Symptoms · 3/1/2017 · Mitigating Multiple Sclerosis Risks...

Mitigating Multiple Sclerosis Risks & Symptoms

Stephen Krieger, MDAssociate Professor of NeurologyIcahn School of Medicine at Mount SinaiAttending NeurologistCorinne Goldsmith Dickinson Center for Multiple SclerosisMount Sinai Medical CenterNew York, New York

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• No labs• Injection technique

education

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Prior to GA

Prior to IFNβs

While on GA

While on IFNβs

• CBC, LFTs• Injection

technique education

• CBC and LFT 1, 3, 6 mofollowing tx initiation; Q3-6 mothereafter

• Thyroid function tests Q6 mo as clinically indicated

• Injection site reactions• Flulike symptoms, mood

symptoms• Adherence

• No labs• Injection site reactions• Immediate post-injection

reaction education• Adherence

Monitoring MS: DMT Side Sffects/AEs

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Monitoring MS: DMT Side Effects/AEs

• Determine if patient has contraindications

• If no contraindications present:

• Obtain recent (within 6 mo) CBC and LFT

• Check VZV antibody titers; postpone treatment for 1 month and vaccinate if negative

• Obtain baseline ECG

• Obtain baseline ophthalmologic examination

Prior to fingolimod While on fingolimod• All patients must have First Dose Observation

for signs and symptoms of bradycardia for ≥6 h after first dose with hourly pulse and bpmeasurement; obtain ECG at the end of the observation period

• Ophthalmologic examination 3-4 mo after treatment initiation

• Consider stopping therapy if serious infection develops

• Avoid live attenuated vaccines during treatment and for at least 2 mo after stopping therapy

• Check LFTs regularly, as needed

• Awareness of PML risk: 10 cases as of Jan 2017

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• Exclude pregnancy• Obtain recent (within 6

mo) CBC and LFT• Screen for latent

tuberculosis with TB skin test or quantiferongold

• Check BP

Prior to teriflunomide While on teriflunomide• Monitor LFTs at least monthly for 6 mo

after teriflunomide initiation; consider additional monitoring when teriflunomide is given with potentially hepatotoxic drugs.

• Consider treatment discontinuation if serum transaminase levels increase >3 times ULN

• Consider suspending treatment and using accelerated elimination procedure if serious infection develops; discontinue if liver injury suspected to be from teriflunomide and start elimination

• Ensure family planning education

• Adherence


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• Obtain recent (within 6 mo) CBC

Prior to DMF/BG-12 While on DMF/BG-12• Obtain CBC Q6 mo after treatment

initiation at minimum and every 6 months for lymphopenia

• Education regarding gastro-intestinal side effects and their management

• Education regarding flushing side effects and their management

• Adherence to twice-daily schedule

• Awareness of PML risk: 5 cases as of Jan 2017


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• Obtain recent (within 6 mo) CBC, LFTs

• Check serum JC Virus Ab status

Prior to natalizumab While on natalizumab• Check CBC and LFTs at least Q6M• Check anti-JC virus antibody serostatus

Q6M if seronegative• Observation and monitoring for

signs/symptoms of PML: ~700 cases as of Jan 2017

Natalizumabexposure NopriorISuse PriorISuse

1‒24months 0.56/1,000 1.6/1,000

25‒48months 4.6/1,000 11.1/1,000

JCV-antibodystatus

Negative

≤0.09/1,000

Positive

PriorISuse?


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• Obtain recent (within 6 mo) CBC, LFTs, BMP, TFTs, UA

• At time of influsion:• Antypyretics• Antihistamine• IVSM• Hydration• Acyclovir

Prior to alemtuzumab While on alemtuzumab - for 48M

• Check CBC Monthly• screen for ITP

• Check UA Monthly• screen for glomerular disease

• Check TFTs quarterly• screen for thyroid disease

• Skin checks annually• screen for skin cancer

• Self monitoring for infection/comorbid disease


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Infection Risk Mitigation Principles:

Infection Screening:Panel of infection exposures help to constrain DMT choices

•JC antibody and index (Natalizumab, Fingolimod, DMF)•TB: Quant gold or PPD (Teriflunomide, B cell agents)•VZV for immunity (Fingolimod)•Hepatitis panel: (Teriflunomide, B cell agents)

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Special Case: De-Escalation after Natalizumab

A ratio of risk/benefit ratios:

Risk/benefit of continuing Natalizumab

Risk/benefit of cessation & de-escalation

Questions/issues:

• PML risk stratification: Risk of continuation of natalizumab• Disease risk: prior/on natalizumab disease activity, relapses/MRI,

rebound risk:• Patient-specific issues and comorbidities mitigating DMT selection• Post natalizumab de-escalation strategy: No washout, consider

IVSM

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• WHEN to de-escalate: consider the three-factor model

Natalizumabexposure

No Prior IS Use Prior IS Use

1–24 months ~1:1,288 ~1:454

25–48 months ~1:241 ~1:85

• 1) JCV Ab, 2) prior immune suppression, 3) duration on Natalizumab• Patient and physician risk tolerance, perception of risk


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Restore Study:Cree et al 2012: Pharmacokinetics and dynamics of NTZ cessation

Fox et al conclude: “RESTORE data confirm a high rate of recurrence of MRI and clinical MS disease activity, starting at approximately week 12, during a 24-week interruption of natalizumab therapy and suggest that the risks of treatment interruption, even with the [other agents] used in this study, appear to outweigh the theoretical benefits.”


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Restore Study:Cree et al 2012: Pharmacokinetics and dynamics of NTZ cessation

• Natalizumab concentration and receptor saturation falls off at 12-16 weeks• Return of MRI disease activity to pre-natalizumab levels around week 16

after natalizumab cessation corresponded with immune parameters returning to levels expected for non-natalizumab–treated patients.


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MS Symptom Management:The “Other Side” of Treating MS

• Fatigue

• Spasticity

• Mobility

• Bladder Dysfunction

• Pain and Paroxysmal symptoms

• Depression

• Pseudobulbar Affect

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Leslie is a 47-year-old African American woman who is seeing you for the first time. HistoryDiagnosed with MS in 1990; subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but had started using a wheelchair outside of the house and had to stop working as an accountant.

MS Symptom Management: Case Study

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Recent SymptomsHospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab.

Current ConditionUses a wheelchair outside of the house; no function in left arm; legally blind. Has a 7-hour-per-day home health aide.

Current ComplaintSignificant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her.

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ExamAlert with severe dysarthria, some drooling. Bilateral INOs with facial weakness.

Visual Can read with right eye

Motor Triplegic with residual strength in RUE ~4/5Increased tone in all extremitiesLEs stiff with decreased ROM and clonus at ankles

Sensory Painful, dysesthetic loss of all modalities in legs

Bladder/Bowel IncontinentCurrently using pads

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Basic Concepts in Managinga Patient With Advanced MS• Reconsidering when “there’s nothing you can do” for

an MS patient• Have a broad concept of what it is to do something• Find an “in” to benefiting the patient

• There is almost always something that can be done for a patient

• Sometimes doing something means undoing what has previously been done (eg, addressing polypharmacy)

• Improve patient QoL and physician patient satisfaction scores…

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Importance of MS Symptom Management: 8 of 11 Quality Measures

Multiple Sclerosis Measurement Set

Fall risk screening for patients with MS• Percentage of patients with MS who were screened for fall risk in the past 12 months

Bladder infections for patients with MS• Percentage of patients with MS who have had a bladder infection in the past 12 months

Exercise and appropriate physical activity counseling for patients with MS• Percentage of patients with MS who were counseled on the benefits of exercise and

appropriate physical activity for patients with MS in the past 12 months

Fatigue outcome for patients with MS• Percentage of patients with MS whose most recent score indicates results are maintained

or improved on a validated fatigue rating instrument for patients with MS in the past 12 months

Rae-Grant A, et al. Neurology. 2015;85(21):1904-08.

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Importance of MS Symptom Management: 8 of 11 Quality Measures

Rae-Grant A, et al. Neurology. 2015;85(21):1904-08.

Multiple Sclerosis Measurement SetCognitive impairment for patients with MS

• Percentage of patients ≥18 years old with MS who were tested for cognitive impairment in the past 12 months

Clinical depression screening for patients with MS• Percentage of patients ≥12 years old with MS who were screened for clinical

depression using an age-appropriate standardized depression screening tool at least once in the past 12 months

Depression outcome for patients with MS• Percentage of patients ≥12 years old with MS whose most recent score indicates

results are maintained or improved on a validated depression screening instrument for patients with MS in the past 12 months

Maintained or improved baseline QoL for patients with MS• Percentage of patients with MS whose most recent score indicates results are

maintained or improved on an age-appropriate QoL tool in the past 12 months

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Fatigue: Perhaps the Most Common Symptom

• Treatable factors preventing restorative sleep• Insomnia• Anxiety and depression• Spasticity• Pain• Urinary frequency• RLS-type symptoms

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Fatigue: A Systematic Approach

Fatigue, tiredness, or decreased energy?(common medical causes ruled out)

Symptoms of sleepiness, insomnia, snoring, restless legs

Mood fluctuations, anhedonia, or lassitude?

Quantify and consider pharmacologic

treatment of fatigue

Screen for depression

Screen for sleep disorder (evaluate with ESS, PSQI,

sleep log, RLS questionnaire, or polysomnography, or refer

to sleep clinic)

Persistent fatigue despite

treatmentTreat sleep disorder Treat depression

N N

Y

Y Y

N

Y

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Pharmacologic Approaches

• Treatments shown to be effective in randomized, double-blind, placebo-controlled trials

• Amantadine-antiviral, dopamine agonist, antiglutamate

• About 1/3 of patients with mild to moderate fatigue report significant short-term improvement• Dosage: 100mg bid, a drug holiday for 2 days/wk

prolongs effect• Nausea, lightheadedness, insomnia, follow LFT,

confusion, hallucination, dry mouth, livedo reticularis, peripheral edema

Multiple Sclerosis Council for Clinical Practice Guidelines.1998.

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Modafinil• FDA-approved in 1999 as a “wake-promoting” agent for the treatment of excessive

daytime sleepiness in patients with narcolepsy• Mixed results in randomized trials

• In a single-blind crossover study by Rammohan et al, MS patients treated with 200 mg/day modafinil for 2 weeks showed a significant improvement in FSS* vs placebo, but treatment with 400 mg/day did not produce a statistically significant difference (N=72)

• Moller et al did not see a significant improvement in FSS scores using the same dose in an 8-week, randomized, placebo-controlled double-blind study (N=121)

• Stankoff et al also did not see a difference in MFIS** in a 5-week, randomized, double-blind, placebo-controlled parallel group study of up to 400 mg/day modafinil (N=115)

• Guidance on using modafinil• Like CNS stimulant, promoting daytime wakefulness with fewer adverse effects and less

abuse potential• Up to 200 mg bid • If a second daily dose is required, administer before 1:00 PM to prevent adverse effect on

nocturnal sleep • Interference with BCPs may necessitate use of alternative forms of birth control • Drug holidays maintain sensitization

1. Rammohan KW, et al. J Neurol Neurosurg Psychiatry. 2002;72(2):179-83.; 2. Moller F, et al. Mult Scler 2011;17(8):1002-9.; 3. Stankoff B et al. Neurology. 2005;64(7):1139-43.; 4. Lapierre Y, et al. Int MS J. 2007;14(2):64-71.

*FSS, Fatigue Severity Scale; **MFIS, Modified Fatigue Impact Scale.

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• Methylphenidate and dextroamphetamine*• Lisdextroamphetamine (pro-drug)*• Atomoxetine• 4-aminopyridine (4-AP)

• K channel blocker, improve nerve impulse-prolongs APD

• 4-AP: 5mg tid up to 10mg tid; paresthesias, abdominal pain, confusion and seizure

*Potential for abuse and dependence. Not studied in MS patient populations.

Other Agents

CASE STUDY: Leslie is a 47-year-old African American woman who is seeing you for the first time.

History: Diagnosed with MS in 1990; subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant. Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of the house; no function in left arm; legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent, currently using pads.

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Types of Spasticity

• Phasic – intermittent spasms which may or may not be painful

• Tonic – stiffness, fatigue and poor mobility (modified Ashworth scale)

• May be coexistent or be present independently

• Treatment options may differ depending on predominance of type

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Goals of Managing Spasticity

• Improve functional ability and independence

• Improve ambulation

• Decrease pain associated with spasticity

• Prevent or decrease incidence of contractures

• Facilitate hygiene

• Ease rehabilitation procedures

• Save caregiver’s time

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The First Step in the Effective Management of Spasticity:

Remove noxious, painful stimuli

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Exercises and Therapy

• Stretching

• Range of motion

• Weight-bearing

• Inhibitory casting

• Consider early rehab/PT referrals even in mild disease

• Pool therapy

• Aerobic exercise

• EMG biofeedback

• Electrical stimulation

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Managing Spasms and Stiffness

• Baclofen

• Tizanidine

• Clonazepam

• Gabapentin

• Dantrolene

• Dopamine agonists

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Other Medications

• Gabapentin• Works best for phasic component, but also some effect

on tonic spasticity• May help break the pain/spasticity cycle

• Levetiracetam, carbamazepine, oxycarbamazepine, zonisamide, lamotrigine and topiramate can be used for phasic spasticity

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Botulinum Toxin

• 2 serotypes – A and B• 1:40 dosing ratio A:B• Prevents release of acetylcholine from nerve

terminals• Causes local weakness of muscle• Best for distal, smaller muscles• Best used as an adjunctive to other therapies• Also note utility in sialorrhea• Limited by dosage range, can only inject q3 months

Montvale N, et al. Physicians Desk Reference. 2010;64.

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Intrathecal Baclofen for Spasticity


History: Diagnosed with MS in 1990; subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant. Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of the house; no function in left arm; legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent, currently using pads.

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CONTEXT

PARTICIPATION

ACTIVITY

Mobility/Gait Impairment

• Different pathologies and impairments result in abnormal or reduced walking in MS

• Multiple factors contribute:• Weakness and spasticity

from pyramidal tract lesions• Loss of proprioception and

coordination from dorsal column and cerebellar lesions

• Vestibular and visual dysfunction

• Cognitive and mood disturbance

• Pain

IMPAIRMENT

PATHOLOGY

MS-related Impairment

DorsalPyramidal Cerebellar

Sensory LossWeakness Ataxia

Reduced Walking

Impact on Individual

Personal Factors• Age• Gender• Coping• Style• Past/current experience• Attitude

Environmental Factors• Social attitudes• Architecture• Careers• Resources• Climate

Pearson O, et al. QJM. 2004;97(8):463-75.

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Mechanisms of Ambulation Impairment• Poor hip thrust

• Weak dorsiflexion

• Heel cord tightening

• Agonist-antagonist mismatch

• Spasticity

• Edema

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Mobility

Causes• Weakness • Spasticity• Ataxia• Fatigability• Pain• Altered gait mechanics

Treatment Strategies• Conditioning programs• Adaptive exercises• Orthotics/AFO• Stabilizers• Transfer training

Devices• Cane• Crutch• Walker• Ankle – foot orthosis• Wheelchair fitting

• Manual• Powered • Scooter

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Pharmacologic Treatment of Mobility Impairment: Dalfampridine

• Two phase 3 clinical trials demonstrated significant improvement in walking ability of patients with 4 primary forms of MS• Consistent improvement in walking in 35-43% of

patients using the Timed 25-Foot Walk Test• Generally well tolerated within the recommended

dose of 10 mg twice daily• Common side effects: mild dizziness, GI discomfort,

and some agitation or wakefulness• The risk for more serious and intolerable adverse

events such as seizures increases at higher doses (20 to 30 mg twice daily)

1. Hayes K, et al. Neuropsychiatr Dis Treat. 2011;7:229-39. 2. Goodman A, et al. Lancet. 2009;373)9665):732-38.3. Goodman AD, et al. Ann Neurol. 2010;68(4):494-502.


History: Diagnosed with MS in 1990; subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant. Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of the house; no function in left arm, legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent; currently using pads.

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Bladder Dysfunction:Symptom-Based Pathophysiology

• Storage Deficit: Spastic Bladder• Urgency• Urge incontinence• Frequency• Nocturia & eneuresis

• Emptying Deficit: Hypotonic bladder• Hesitancy• Double voiding• Poor force of stream• Bladder insensitivity

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Bladder Management

• Check for infection with urinalysis and culture—upper-tract disease is less common

• Check for post-void residual with ultrasound or catheterization

• Based on results of the above, develop a plan with a practical knowledge of hand strength and coordination; keep perspective about Foley

• Ask patient to return if dysynergic; consider urodynamic testing, cystometry

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Interventions for Storage DysfunctionGENERIC DOSE FORMS SCHEDULE DRUG CLASS RATIONALE ADVERSE EVENTS

Oxybutynin 5 mg BID, TID AnticholinergicMusculotropic

Detrusor hyperreflexia

Dry mouth, dry eyes, blurry vision, constipation, sedation, cognitive impairment, bladder retention

Oxytrol Patch 5, 10, 15 mg Qday

Tolterodine 1, 2 mg BID Antimuscarinic Detrusor hyperreflexia

Same as oxybutinin, but less frequent

TolterodineExt. Release

4 mg Qday

Hyocyamine 0.125, 0.15 mg Q4-6 hrs Anticholinergic Detrusor hyperreflexia

Same as oxybutinin

HyocyamineExt. Release

0.375 mg Qday-BID

Propantheline 7.5, 15 mg TID Anticholinergic Detrusor hyperreflexia

Same as oxybutinin

Flavoxate 100 mg 1-2 BID-TID Musculotropic Detrusor hyperreflexia

Same as oxybutinin

Imipramine 10, 25, 50 mg 25-50 mg qhs Tricyclic Detrusor hyperreflexia

Bladder retention, orthostasis, constipation

Desmopressin Nasal soln10μg/sprayOral tablets 0.2 mg

1-4 puffs qhs0.1-0.5 mg

Vasopressin analog

Nocturia or frequency

Edema, hyponatremia, headache, weight gain

Doxazosin 1, 2, 4, 8 mg 1-8 mg qhs Alpha blocker Detrusor-sphincter dysynergia

Orthostatic hypotension, incontinence

Terazosin 1, 2, 5, 10 mg 1-10 mg qhs Alpha blocker Detrusor-sphincter dysynergia

Same as doxazosin

Tamsulosin 0.4 mg 0.4-0.8 mg qhs Alpha blocker Detrusor-sphincter dysynergia

Same as doxazosin

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Interventions for Voiding Dysfunction• Alpha-1 antagonists

• Relaxation techniques

• Double voiding

• Intermittent catheterization

• Indwelling catheters (Foley/SP)

• Surgical procedures-Diversions

CASE STUDY: Leslie is a 47-year-old African American woman who is seeing you for the first time. History: Diagnosed with MS in 1990, and subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant. Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of house; no function in left arm; legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent; currently using pads.

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Treatment for Pain/Paroxysmal Symptoms• Anticonvulsants

• Carbamazepine, gabapentin, levetiracetam, topiramate, pregabalin, zonisamide, and lamotrigine

• Antidepressants• Duloxetine, tricyclic antidepressants

• IV methylprednisolone 1000 mg/d for 3-5 days• Topical analgesics

• Lidocaine• Baclofen, 5mg tid to 10-20mg tid• Trigeminal rhizotomy or instillation of glycerol• Trigeminal decompression • Gamma knife

CASE STUDY: Leslie is a 47-year-old African American woman who is seeing you for the first time. History: Diagnosed with MS in 1990, and subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant . Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of the house; no function in left arm; legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent; currently using pads.

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Depression in MS: Cause and Effect• Mood disorders (major depression, dysthymia,

bipolar, panic and generalized anxiety) are common in multiple sclerosis, more so than in other chronic diseases

• Unpredictability of MS• Depression can be from the disease itself or as a

reaction to the diagnosis and lifestyle changes that may be necessary

• May be a side effect of interferon therapy• Mood changes increase MS symptoms

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Depression Rapid Screening

US Preventive Services Task Force recommends a brief 2-question screening test for assessing depression

Wallin MT, et al. J Rehab Res Dev. 2006;43(1):45-62.

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Cognitive Screening and Evaluation• Regular screening

• Modify activities to reduce risk of injury• Adjust significant others’ expectations• Adjust DMT

• Consider primary MS processes, as well as secondary causes• Fatigue; drug therapy; depression; comorbid disease• Treat fatigue, depression, sleep hygiene• Limit sedative drugs; modify environment;

anticholinesterases

CASE STUDY: Leslie is a 47-year-old African American woman who is seeing you for the first time. History: Diagnosed with MS in 1990, and subsequently had a series of attacks that included ON, myelopathy with paraparesis, and brainstem symptoms, followed by a progressive course. In 1996, she started treatment with IFN β-1a, but also started using a wheelchair outside of the house and had to stop working as an accountant. Recent Symptoms: Hospitalized for presumed aspiration pneumonia and UTI/urosepsis that required a prolonged stay in subacute rehab. Current Condition: Uses a wheelchair outside of the house; no function in left arm; legally blind. Has a 7-hr-per-day home health aide. Current Complaint: Significant lower extremity pain and daytime somnolence and fatigue. Previously prescribed modafinil, which did not help and makes her nauseated. She has transferred to you after her previous neurologist said there was nothing else he could do for her. Exam: Alert with severe dysarthria, some drooling. Bilateral INOs with facial weakness. Visual: Can read with right eye. Motor: Triplegic with residual strength in RUE ~4/5; increased tone in all extremities; LEs stiff with decreased ROM and clonus at ankles. Sensory: Painful, dysesthetic loss of all modalities in legs. Bladder/Bowel: Incontinent; currently using pads.

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1. Mobility / triplegia: Need for increased care at home; motorized wheelchair

2. Spasticity: PT eval; ROM exercises; consider pharmacologic intervention/LE botox/baclofen pump evaluation

3. Drooling / aspiration pneumonia: Address siallorhea; consider botox to parotids

4. Pain: Consider pain from spasticity and dysesthesia; both can be addressed

5. Fatigue and somnolence: Consider interrupted sleep due to pain; spasticity; urinary frequency or immobility. Address these and reassess daytime somnolence. Without this, modafinil won’t help!

Getting From “I CAN’T HELP YOU” To “WHERE DO I START?”

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6. Bladder: Urinary retention and incontinence are likely; urology evaluation; may benefit from Foley (administered by HHA); consider suprapubic cath

7. Polypharmacy: Does she need to be on IFN β-1a SC? How would you evaluate the risk-benefit ratio here?

8. Stress/Depression and psychosocial issues: Pursue this; consider social work involvement, supportive psychotherapy, refer patient to the resources of professional societies like NMSS

This is as severe a case as we are likely to see in the clinic.This same type of process should be appliedto patients who are not as severely affected.

Getting From “I CAN’T HELP YOU” To “WHERE DO I START?”

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Documenting Your Plan in the EHR• Assessment: 4-5 line summary• Plan

• 1. Diagnostic Plan -- includes things such as:

• ADEM vs MS• NMOSD vs MS• RRMS vs SPMS,

• 2. Disease Modifying Plan – includes things such as:

• DMT selection and rationale, Risk Mitigation issues• Recent MRI – evidence of disease activity• Next-step DMTs discussed

• 3. Symptomatic Plan – includes things such as strategies being used/considered for:

• Fatigue• Gait/Falls• Spasticity• Depression• Etc.

Mitigating Multiple Sclerosis Risks & Symptoms

Stephen Krieger, MDAssociate Professor of NeurologyIcahn School of Medicine at Mount SinaiAttending NeurologistCorinne Goldsmith Dickinson Center for Multiple SclerosisMount Sinai Medical CenterNew York, New York

Mitigating Multiple Sclerosis Risks & Symptoms · 3/1/2017 · Mitigating Multiple Sclerosis Risks...

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Transcript of Mitigating Multiple Sclerosis Risks & Symptoms · 3/1/2017 · Mitigating Multiple Sclerosis Risks...