mitigating multiple sclerosis risks & symptoms · 3/1/2017 · mitigating multiple sclerosis...
TRANSCRIPT
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
2
• No labs• Injection technique
education
Sta
rt
Th
er
ap
y
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
3
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
Sta
rt
Th
er
ap
y
4
• 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
Monitoring MS: DMT Side Effects/AEs
Sta
rt
Th
er
ap
y
5
• 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
Monitoring MS: DMT Side Effects/AEs
Sta
rt
Th
er
ap
y
6
• 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?
Monitoring MS: DMT Side Effects/AEs
Sta
rt
Th
er
ap
y
7
• 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
Monitoring MS: DMT Side Effects/AEs
Sta
rt
Th
er
ap
y
8
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)
9
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
10
• 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
Special Case: De-Escalation after Natalizumab
11
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.”
Special Case: De-Escalation after Natalizumab
12
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.
Special Case: De-Escalation after Natalizumab
13
MS Symptom Management:The “Other Side” of Treating MS
• Fatigue
• Spasticity
• Mobility
• Bladder Dysfunction
• Pain and Paroxysmal symptoms
• Depression
• Pseudobulbar Affect
14
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
15
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.
16
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
17
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…
18
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.
19
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
20
Fatigue: Perhaps the Most Common Symptom
• Treatable factors preventing restorative sleep• Insomnia• Anxiety and depression• Spasticity• Pain• Urinary frequency• RLS-type symptoms
21
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
22
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.
23
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.
24
• 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.
26
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
27
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
28
The First Step in the Effective Management of Spasticity:
Remove noxious, painful stimuli
29
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
30
31
32
33
Managing Spasms and Stiffness
• Baclofen
• Tizanidine
• Clonazepam
• Gabapentin
• Dantrolene
• Dopamine agonists
34
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
35
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.
36
Intrathecal Baclofen for Spasticity
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.
38
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.
39
Mechanisms of Ambulation Impairment• Poor hip thrust
• Weak dorsiflexion
• Heel cord tightening
• Agonist-antagonist mismatch
• Spasticity
• Edema
40
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
41
42
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.
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.
44
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
45
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
46
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
47
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.
49
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.
51
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
52
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.
53
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.
55
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?”
56
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?”
57
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