Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
CANE, WALKER, WHEEL CHAIR, BEDPATIENTS WITH PROGRESSIVE MULTIPLE SCLEROSIS AND THE NURSING CARE THAT MATTERS
HEIDI MALONI, PHD NP MSCN
LISA MITCHELL, MSN, MSCN
CAMI VAN WYHE, BSN, MSCN, CHPN
DISCLOSURES
• We have nothing to disclose
OBJECTIVES
1. Have knowledge of the pathophysiology of progressive multiple sclerosis
2. Develop skills to guide patients through a progressive disease course in terms of building self‐management and recognizing morbidity risk
3. Understanding how to optimize function and manage symptoms important to patients with concern for maintaining employment, DMT use, and building self‐management skills
4. Recognize the role of the nurse in palliative and end of life care
BACKGROUND: MULTIPLE SCLEROSIS (MS)
• MS: Most common disabling neurologic condition of young adult
• Characterized by relapses and remissions of neurologic events
• Ultimately a progressive course
• Immune modulating treatments are effective in early, inflammatory disease , limiting relapses, disease progression and CNS lesions seen on magnetic resonance imaging.
The disease gradually changes from the inflammatory process seen in RRMS to a more steadily progressive phase characterized by nerve damage or loss.
• Radiologically isolated syndrome (RIS)
• Clinically Isolated syndrome (CIS)
• Recognized as first clinical presentation of MS
• Relapsing‐remitting (RRMS) disease
• Progressive disease
• Primary progressive (PPMS)
• Secondary progressive (SPMS)
EDSS = Expanded Disability Status Scale.Adapted with permission from JS Wolinsky; Kurtzke JF. Neurology. 1983;33:1444-1452.
DISEASE PROGRESSION/EDSS
6
Dis
abili
ty
Time
0 1 1.5 2 2.5 3 3.5 4.545.55
6.567.57 8 8.5 9.59 10
NormalNeurologic
Exam
MinimalDisability
IncreasedLimitation in
Walking Ability
Need forWalking
Assistance
Restrictionto
Wheelchair
HelplessBed
Patient
Death
EDSS
SPMS
RRMSPreclinical
Measures of Brain VolumeRelapses and ImpairmentMRI Burden of Disease
MRI Activity
CASE T.D.• 52 year old M diagnosed 23 years ago
• Relapse free for past nine years
• EDSS: 5.5
• Symptoms: Fatigue; urinary urgency and frequency; occasional involuntary bowel; ataxia, spasticity, weakness right side with foot drop.
• Uses Bioness as ambulation aid
• Some concerns by work supervisor for job performance
• Medication: amantadine, dalfampridine, tolterodine, docusate, Vitamin D, tizanidine, dimethyl fumarate
• MRI: moderate amount of T2 hyperintensities, one cortical lesion; thinning of corpus collosum, mild brain atrophy; no new or enhancing lesions since scan in 2015.
TRANSITIONING
• What are clues to progressive MS for T.D.?
• What questions will T.D. ask the nurse?
• What support does the nurse offer?
PMS‐ DEFINE…
• Gradual deterioration in disability after a period of relapsing remitting
• Growing accrual of disability independent of relapse
• 50% of the world’s 2‐3 million people with MS are progressive MS
• Worsening defined as 0.5 or 1 point EDSS sustained over 3‐6 months
• Often takes 3 years to recognize
• Tremlett study of 2,837‐median time to cane or EDSS of 6: 27.9 years
Pons
Thalamus
Tperiventricular white matter f MS Lesions
Subpial cortex
leptomeninges
Thalamus and ponsSpinal cordOptic nerve
retina
Lesion that canBe seen in SPMS
opticalcoherencetomography
Topographyof theMS Lesion
NEUROPATHOLOGY OF PROGRESSION• Prominent pathological feature of progressive MS
• Brain atrophy
• Cortical demyelination
• Failure of remyelination
• Diffuse pathology in normal appearing white and grey matter
• Active plaques with inflammation rare in progressive MS
• Lesions shrink. Loss of lesion volume contributes to brain atrophy
• T‐cell and B‐cell infiltrates in brain and spinal cord can decrease with age and disease duration
IMAGING DIFFERENCES IN PMS
• More spinal and brainstem lesions• Relative paucity of new enhancing brain lesions over time
• A subset pf PPMS do have active MRI• Decrease in new T2 lesions• MRI spectroscopy‐ greater tissue destruction• Prominence of brain atrophy (cortical vs ventricular enlargement)• Cortical lesions more common resulting in cognitive dysfunction• Atrophy of spinal cord• Optical Coherence Tomography: lower measure of retinal fiber layer and macular volume
T2 sagittal image of cord atrophy
Thinning corpus collosum; enlarged ventricles; extensive cortical atrophy and cortical lesions
T1 GD enhancing on PMS with inflammation
CONUNDRUM OF TREATMENTS
Clinical trial outcomes What to measure
• MRI: Brain atrophy and Diffusion Tensor Imaging (DTI)
• MS Functional Composite (MSFC)
• Optical Coherence Tomography (OCT)
Treatments to date have mostly proven inadequate
• Simvastatin
• NeuroVax
• CD20 on B cells (rituximab and ocrelizumab)
• Phenytoin, oxcarbazepine
• Lipoic acid, Idebenone, Biotin
• Natalizumab, siponimod, mastininib
• Lithium
• Dronabinol
• Amiloride, fluoxetine, riluzole
SECONDARY PROGRESSIVE MS
• How does one know when a patient transition from RRMS to SPMS ?
• Is a DMT indicated or useful?
• The patient is reluctant to stop the DMT‐ afraid of relapse and disease progression
• The patient may say, “I have relapses all the time”
• How does the health care provider respond?
DIAGNOSING PMS
• Secondary progressive MS is defined retrospectively once a sustained period of worsening neurologic impairment has been established over at least 6 to 12 months
• Clinical diagnosis based on patient history.• May have relapse in the SPMS stage and MRI GD lesions
• New and enhancing lesions (hallmark of inflammatory dz.)• Full year of gradual progression• Differentiating incomplete recovery from relapse and disability is difficult for patients and clinicians
• Progressive myelopathy (spastic, ataxic paraparesis and sphincter dysfunction)• Progressive cerebellar, cognitive• Age
CASE AND DISABILITY OVER TIME
• Does TD meet criteria for active or inactive MS?........with progression or without progression?
• EDSS: worsening of 0.5 sustained over 3‐6 month• No evidence for clinical or radiologic activity in over three years
• Would you stop dimethyl fumarate?• How would you start the conversation around disease transition from RRMS to
SPMS?
If TD discontinues his “MS” drug , how might his care change?What are the critical issues at this juncture?How do you influence QOL ?
EMPLOYMENT AND PROGRESSIVE MS
CASE STUDY: ANN• 42yr F with 16yr hx of MS with active disease
• Divorced, lives with 2 sons (15 and 20) and SO
• Web developer
• 50% SC
• Initial MS symptoms: feet numbness and weakness
• Hx of spasticity, fatigue, bladder and gait dysfunction
• EDSS 6
• DMTs: interferons, glatiramer acetate, fingolimod
• Quit her job 3mo ago : fatigue, falls and cognitive difficulties (concentration and memory)
• Removed from 2 contracts
• Negative evaluation
• Now experiencing depression, visual difficulties and gait dysfunction
QUESTIONS TO GUIDE PATH
• Who do I tell and when?• Where do I find support?• Is disclosing my health status to my benefit or is it detrimental?
• How long will I be “normal”?• Do I really need this equipment?• Can I get by with not telling anyone?• When is a good time to reveal my health status?
EMPLOYMENT AND MS
60% employed at time of dx• 20 ‐ 40% remain employed after dx
• Causes of unemployment involve MS symptoms, MS subtype, length of disease and demographic factors
• Stop working before retirement age
TO DISCLOSE OR NOT
There is no one "right" time or place to disclose your disability. Select a confidential place in which to disclose, and allow enough time for the person to ask questions. Do not dwell on the limitations of your disability. You should weigh the pros and cons of disclosure at each point of the job search, recruitment, and hiring process and make the decision to discuss your disability when it is appropriate for you.
Retrieved from: https://www.dol.gov/odep/pubs/fact/ydw.htm
Employment and Progressive MS (cont’d)
Americans with Disabilities Act• Prohibits discrimination against individuals with disabilities in all areas of public life,
including jobs, schools, transportation, and all public and private places that are open to the general public
• Same rights and opportunities as everyone else• Civil Rights law est. 1990• 5 Titles• Title 1 (Employment)
• Provides for same employment opportunities and benefits available to people without disabilities
• Regulated and enforced by the U.S. Equal Employment Opportunity Commission (EEOC)
• Reasonable accommodation
AMERICANS WITH DISABILITIES ACT
• Reasonable Accommodation
• modification or adjustment to a job or the work environment that will enable an applicant or employee with a disability to participate in the application process or to perform essential job functions
• No specific policies that employers must follow
• The accommodation does not cause a hardship
• Removing job function
• Creating new jobs
• Providing personal items
Retrieved from https://www.nationalmssociety.org/Living‐Well‐With‐MS/Work‐and‐Home/Employment/Accommodations
ELEMENTS OF AN ACCOMMODATION LETTER• Identify yourself as a person with a
disability
• State that you are requesting accommodations under the ADA (or the Rehabilitation Act of 1973 if you are a federal employee)
• Identify your specific problematic job tasks
• Identify your accommodation ideas
• Request your employer's accommodation ideas
• Refer to attached medical documentation (if appropriate)
• Ask that your employer respond to your request in a reasonable amount of time
REASONABLE ACCOMMODATION
• Does not necessarily improve job satisfaction and length of employment based upon a 2015 survey conducted of 9 NMSS chapters
• N=746 employed with MS
• Diverse population; various geographical areas
• 25% requested reasonable accommodations
• 87.7% granted
EMPLOYMENT AND PROGRESSIVE MS
Family Medical Leave Act• Est. 1993• Eligible
• Employer has ≥ 50 employees• Pt has worked for at least 12mo• Pt has worked at 1250 hrs/12mo
• Use• 12 weeks protected leave/12mo
• Serious health condition• Military family leave• Expanding your family
COGNITIVE DYSFUNCTION
• What is cognitive dysfunction? • The mental process of how we obtain
knowledge and understanding through our thoughts, experiences and senses is impaired
• 50 – 60% affected (Holland, Schneider, Rapp, & Kalb, 2011)
• Can vary significantly in type and severity
• Negative impact on employment and social activities
NP CONSULTATION• Cognitive Screening initially• Minimal Assessment of Cognitive Function In MS (MACFIMS)
• 7 tests• Assesses the primary domains affected
• processing speed/working memory, new learning and recent memory, spatial processing and higher executive function
• Length: 90 minutes or longer• Support diagnosis of cognitive dysfunction• Treatment
• Cog Rehab• Tools to improve/coping with dysfunction
• Accommodations are often challenging to implement (Leslie, Kinyanjui, Bishop, Rumrill, & Roessler, 2015)
COGNITIVE DYSFUNCTION
• Psychosocial Implications
• Denial, anxiety, ability to care for self, level of independence
• Impaired relationships with friends and family, change of role within the family
• Impaired communication with health care team, adherence with medication regimen and case management
• Ability to complete job tasks, impact upon relationships at work (subordinates, peers & supervisors)
SUPPORT
• Social Worker• NMSS Support Groups• Service Connection
• MS Disability Questionnaire (MS‐DBQ)
• Social Security Disability Insurance (SSDI)
• Assistive Devices• Cane, Bioness, Motorized Scooter
• Vehicle Modification• Home Safety Evaluation
• Home Modifications• Home Improvement Structural
Alterations (HISA) Grant• Assistive tools
DMTS AND PROGRESSIVE MS
PATIENT QUESTIONS WHILE TRANSITIONING
• What DMTs are still options?
• Why do you want me to stop DMTs?
STOPPING DMTS
• Why do you want me to stop DMTs?• Disease no longer requires medication to treat acute inflammation• No active disease ≥ 2yrs
• Clinical judgement• EDSS• MSQoL, FAMS, MSQLI
• Not often administered: time consuming • 90% will remain relapse free• Cost• Benefits vs. harm
(Birnbaum, 2017)
WHAT DMTS ARE STILL OPTIONS?
DMTs are an option for those with active diseaseOcrelizumab
• 1st DMT for PPMS and RRMS• Action
• Humanized anti ‐ CD20 Monoclonal AntibodyMonoclonal Antibody (MAB) =One + All the same + One thing that sticks to another
• Binds to CD20 on the surface of B cells and reduces the number of circulating B cells
• Function of B cells• Make antibodies• Contributes to inflammation in MS
OCRELIZUMAB CLINICAL TRIALS
PPMS
• ORATORIO
• N = 732
• Placebo
• risk of progression of clinical disability by 24%
• time required to walk 25ft by 29%
• volume of brain lesions
RRMS
• OPERA 1 and OPERA II
• N = 1656
• Compared with interferon beta 1a
• ARR by up to 47% over 2 yrs
• progression of disability on EDSS by 40%
• active inflammation on MRI up to 95%
• total damage on MRI up to 83%
OCRELIZUMAB
• Evaluation by Neurology Clinical Provider
• Criteria for Use (CFU)
• Lab workup
• MRI
• Immunizations
• Submission of NF consult
• Infusion orders
OCRELIZUMAB LAB WORK UP
Baseline• Comprehensive metabolic panel• Quantiferon‐TB gold• Hepatitis B Core Ab• Hepatitis B Surface Ag• Hepatitis B Surface Antibody• Hepatitis C Panel• MMR panel• VZV antibody• CBC and diff• βHCG• HIV
q6mo
• Quantiferon‐TB gold
• Hepatitis B Core Ab
• Hepatitis B Surface Ag
• Hepatitis B Surface Antibody
• Hepatitis C Panel
• LFTs
• CBC and diff
• βHCG
OCRELIZUMAB
• Dosing
• Initial Dose
• 300mg on Day 1 and Day 15
• Approx. 2.5hrs or longer
• Subsequent Doses
• 600mg q6mo (24 weeks)
• Approx. 3.5hrs or longer
• Delayed or missed doses
• Administer ASAP
• Schedule next dose 6mo after the missed dose is given
INFUSION CONSIDERATIONS
• Premedicate
• Steroid and antihistamine before infusion
• Micron in‐line filter
• Managing Infusion Reactions
• Mild to Moderate
• rate by 50% from onset and maintain for 30min
• rate as described in Infusion Rate Tables, if tolerated
• Severe
• Interrupt infusion and administer appropriate supportive treatment
• Resume infusion only after all symptoms have resolved
• rate by 50% at time of infusion reaction
• rate as described in Infusion Rate Tables, if tolerated
• Life Threatening
• STOP infusion immediately
• Administer supportive treatment
PATIENT COUNSELING
• Infusion Reactions• Lessen symptoms, premedicate
• Monitor at least 1hr post infusion
• Risk of Infections• Weakened immune system
• Educate pt to notify HCP of any signs of infection• Cold, cough, herpes or shingles
• Respiratory infections most common
• Vaccinations• Complete 6 wks prior to infusion
• No live attenuated or live vaccines
• Increase risk of malignancies• Breast cancer
• Pregnancy• Notify HCP if pt plans to become pregnant or if they
are pregnant
• Herpes B Virus Reactivation• PML
• 5 cases
• ↑with prior Natalizumab use > 2yrs
CASE STUDY FOLLOW UP: ANN • 46yr F with 20yr hx of MS with active disease• Divorced, lives with 2 sons, and SO• Former Web developer• 100% SC • Initial MS symptoms: feet numbness and
weakness• Hx of spasticity, fatigue, bladder and gait
dysfunction• EDSS 7• DMTs: interferons, glatiramer acetate,
fingolimod• Quit her job 3mo ago : fatigue, falls and
cognitive difficulties (concentration and memory)
• Removed from 2 contracts• Negative evaluation
• Now experiencing depression, visual difficulties and gait dysfunction
• Neuropsychology consult
• Initially denied for SSDI; successful with resubmission
• 100% SC; submission of MS‐DBQ
• Quickie wheelchair
• Home modifications
• Legally blind
• Support of SO and children
• Enhancing lesion while on fingolimod
• Ocrelizumab
• HHA
“I HAVE MS, BUT MS DOESN’T HAVE ME”
PATIENT STATEMENT
QUESTIONS THAT GUIDE YOUR PATH• Who do I tell and when?• Where do I find support?• Is disclosing my health status to my benefit or is it detrimental?• How long will I be “normal”?• Do I really need this equipment?• Can I get by with not telling anyone?• When is a good time to reveal my health status?• Other ideas???
PALLIATIVE CARE IN PROGRESSIVE MULTIPLE SCLEROSIS
WHAT IS PALLIATIVE CARE
World Health Organization defines palliative care‐ “An approach that improves the quality of life of patients and their families facing the problem associated with life‐threatening illness, through prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.”
WHY PALLIATIVE CARE IN MS?
End of Life is difficult to detect in MS, but the severely affected MS patient needs symptom management , much like a cancer patient.
Bridging the gap of the unmet needs of the progressive MS patient can help them achieve the Quality of Life they desire
Longer survival rates have been documented with early integration of palliative care in MS
WHY PALLIATIVE CARE IN MS? CONTINUED
Nursing care is enhanced with palliative care to help understand the experience of the MS patients and help them through acceptance, coping, self‐resilience , helplessness, and growth.
PALLIATIVE CARE: PART OF THE TEAM
MS is a complex disease that presents in a chronic progressive nature, both physically and psychologically. Managing the symptoms can be difficult and frustrating for the patient if the try and navigate alone. Including palliative care into the interdisciplinary team can benefit everyone.
PALLIATIVE CARE DOMAINS
https://www.nejm.org/doi/full/10.1056/NEJMra1404684
WHEN TO THINK ABOUT PALLIATIVE CARE IN MS
Key indicators include• Before cognition is on a steady decline• Swallowing issues• Aspiration pneumonia • Recurrent infections• Marked decline in physical status• Some models encourage the addition of the palliative care team upon the diagnosis of a serious neurological disease like Progressive MS
HOW DO I KNOW MY PATIENT IS READY?
Patients give you indicators they are ready for this difficult discussion by dropping key phrases“I feel like such a burden”“I am getting worse”“What’s the point of living”“I can’t wait to be fixed/cured”“I can’t tolerate anymore”
These phrases indicate a need to explore palliative care to help their journey in more intensive symptom management. Remember holistic care is a hallmark of palliative care balancing their physical, emotional, and spiritual well being to the best they can be at any given time with their disease.
WHAT THEY HELP MANAGE
• Quality of Life
• Pain
• Spiritual Distress
• Psychological Distress
• Long Term Care Goals
LONG TERM CARE GOALS
• Advanced Directive
• Durable Power of Healthcare
• Do Not Resituate Orders
• Tube Feedings
• Ventilator
• Dialysis
COMMUNICATION
• Having regular discussions with your patient ensure you know and understand their needs, wishes, and plans.
• Ensuring you have meaningful conversations with the patient ensures you follow their treatment course.
• Using interviewing skills to achieve this domain is imperative
INTERVIEWING TOOLS
S‐Setting up the interviewP‐assessing the Patient’s PerceptionI‐obtaining the patient’s InvitationK‐giving Knowledge and informationE‐responding to EmotionS‐Summarizing the discussion
CAREGIVER ROLES
• Palliative care is no different than other disciplines regarding treatment of the caregiver as an extension of the patient
• Keeping in mind the issues that care givers may face when their loved one enter palliative care
• Helping them cope with the diagnosis plays an important role
• Respecting the patient’s wishes first, but incorporating the ideas of the caregiver can build a bridge in care.
• Their presence can keep the patient focus on what can I do, instead of what scares them.
CAREGIVER BURDEN
Caregiver role strain/burden/stress is defined as a strain or load carried by a person caring for a chronically ill, disabled, or elderly family member. Physical, psychological, emotional, social, financial, and spiritual stressors, as a result of caring for their family members, build up and cause a strain on the care givers life resulting in emotional feelings they struggle to understand and contain.
REFERENCES• Birnbaum, G. (2017). Stopping disease modifying therapy in nonrelapsing multiple sclerosis. International Journal of MS
Care, 11‐14.
• Brandis, M., & Reitman, N. C. (2018, August 15). https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/14_TwP_PalliativeCare.pdf.Retrieved from https://www.nationalmssociety.org/: https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/14_TwP_PalliativeCare.pdf
• Chiu, C.‐Y., Chan, F., Sharp, S., Dutta, A., & Hartman, E. B. (2015). Employment as a health promotion intervention for persons with multiple sclerosis. Work, 749‐756.
• CMSC MRI Guidelines 2018 Consortium of MS Centers MRI ProtocoL and Clinical Guidelines for the Diagnosis and follow‐up of MS 2018 revised guidelines.
• Davies, F., Wood, F., Brain, K.E., et al., (2016). The transition to secondary progressive multiple sclerosis. An exploratory qualitative study of health professionals’ experience. International Journal of MS Care, 18, 257‐264.
• Department of Veterans Affairs. (n.d.). Criteria For Use. Retrieved from Pharmacy Benefits Management: https://vaww.cmopnational.va.gov/cmop/PBM/Clinical%20Guidance/Forms/AllItems.aspx?Paged=TRUE&p_SortBehavior=0&p_FileLeafRef=Meperidine%2c%20Criteria%20for%20Use%2epdf&p_ID=443&RootFolder=%2fcmop%2fPBM%2fClinical%20Guidance%2fCriteria%20For%20Use&PageFirst
• Dubey, D., Sguigna, P., & Stuve, O. (2018). Managing Disability in progressive multiple sclerosis. Current Treatment Options Neurology, 18‐27.
• Encarnacao, P., Oliverira, C. C., & Martins, T. (2018). Suffering, a Concept Present in Non‐Cancer Patients: Multiple Scerosis Patients. International Journal of Caring Sciences, 572‐578.
• Feinstein, A., Freeman, J, & Lo, A. (2015). Treatment of progressive multiple sclerosis: What works, what does not work, and what is needed. Lancet Neurology, 14, 194‐207.
REFERENCES• Golla, H., Galushko, M., Pfaff, H., & Voltz, R. (2014, March). Multiple sclerosis and palliative care‐perceptions of
severely affected multiple sclerosis patients and their health professionals: a qualitative stidy. BMC Palliative Care. Retrieved from bmcpalliatcare.biomedcentral.com/.
• Grazioli, E., Yeh, A., Benedict, R., Parrish, J., & Weinstock‐Guttman, B. (2008). Cognitive Dysfunction in MS: Bridging the gap between neurocognitive deficits, neuropsychological batteries and MRI. Future Neurology, 49‐59.
• Halper, J. (2000). The Evolution of Nursing Care in Multiple Sclerosis . International Journal of MS Care, 14‐22.• Job Accommodation Network. (n.d.). How to request an accommodation: accommodation form letter. Retrieved
from Job Accommodation Network web site: https://askjan.org/media/accommrequestltr.cfm?cssearch=1910262_1
• Kelley, A. S., & Morrison, R. S. (2015). Palliative Care for the Seriously Ill. The New Englund Journal of Medicine, 747‐755.
• Kurtzke, J.F. (1983). Rating neurological impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology, 33, 1444‐1452.
• Leslie, M., Kinyanjui, B., Bishop, M., Rumrill, P., & Roessler, R. (2015). Patterns in workplace accommodations for people with multiple sclerosis to overcome cognitive and other disease related limitations. NeuroRehabilitation, 425‐437.
• Li, J., Fitzgerald, S., Bishop, M., Rumrill, P., & Wang, F. (2015). Disease‐related and functional predictors of employment status among adults with multiple sclerosis. WORK: A Journal of Prevention, Assessment & Rehabilitation, 789‐797.
• Lublin, F. D., Reingold, S.C., Cohen, J, A., Cutter, G. R., Per Soelberg, S., Thompson, A., J., et al. (2014). Defining theclinical course of multiple sclerosis: The 2013 revisions. Neurology, 83(3), 278‐286.
REFERENCES• Mahad, D. H., Trapp, B. D., & Lassman, H. (2015). Pathological mechanisms in progressive multiple sclerosis.
Lancet Neurology, 14(2), 183‐193.• National Multiple Sclerosis Society. (n.d.). Reasonable Accommodation Worksheet. Retrieved from National MS
Society: https://www.nationalmssociety.org/Living‐Well‐With‐MS/Work‐and‐Home/Employment/Accommodations
• Ontaneda, D., & Fox, R. J. (2015). Progressive Multiple Sclerosis. Current Opinion Neurology, 237‐243.• Planche, V., Gibelin, M., Cregut, D., Pereira, B., & Clavelou, P. (2015). Cognitive impairment in a population based
study of patients with multiple sclerosis: differences between late relapsing remitting, secondary progressive and primary progressive multiple sclerosis. European Journal of Neurology, 282‐289.
• Reich, D.S., Lucchinetti, C.F., & Calabresi, P. (2018). Multiple sclerosis. New England Journal of Medicine, 378, 169‐180.
• Shenton, D. (2015, April 27). https://ehospice.com/international_posts/world‐hospice‐and‐palliative‐care‐news‐roundup‐27‐april‐2015/. Retrieved from https://ehospice.com/: https://ehospice.com/international_posts/world‐hospice‐and‐palliative‐care‐news‐roundup‐27‐april‐2015/
• Reich, D.S., Lucchinetti, C.F., & Calabresi, P. (2018). Multiple sclerosis. New England Journal of Medicine, 378, 169‐180.
• Salzar, J., Svenningsson, R., Alping, P. et al. (2016). Rituximab in multiple sclerosis. A retrospective observational study on safety and efficacy. Neurology, 87, 1‐8.
• Shirani, A., Okuda, D. T., & Stuve, O. (2016). Therapeutic advances and future prospects in progressive forms of multiple sclerosis. Neurotherapeutics,13, 58‐69.
• Tremlett, H., Paty, D., & Devonshire, V. (2006). Disability progression in multiple sclerosis is slower than previously reported. Neurology, 66, 172‐177.
THANK YOUQUESTIONS?