ARTICLE OPEN ACCESS

Neuromyelitis optica spectrum disorderPatient experience and quality of life

Janine Beekman PhD Aysha Keisler PhD Omar Pedraza MPH Masayuki Haramura PhD

Athos Gianella-Borradori MD Eliezer Katz MD John N Ratchford MD Gerard Barron BSc

Lawrence J Cook PhD Jacinta M Behne MS Terrence F Blaschke MD Terry J Smith MD and

Michael R Yeaman PhD

Neurol Neuroimmunol Neuroinflamm 20196e580 doi101212NXI0000000000000580

Correspondence

Dr Beekman

JanineBeekmanipsoscom

or Dr Yeaman

MRYeamanuclaedu

AbstractObjectiveTo gain insights into NMOSD disease impact which may negatively affect QoL of patientstheir families and social network

MethodsThe current study used validated instruments to assess physical emotional and socioeconomicburden of NMOSD on QoL among 193 patients

ResultsA majority of patients reported an initial diagnosis of a disease other than NMOSD Overalltwo-thirds of patients reported NMOSD as having a strong negative impact on physical health(Short Form-36 [SF-36] score 271 plusmn 391) whereas emotional well-being was relativelyunimpaired on average (SF-36 score 540 plusmn 449) A subset of patients reported having thehighest category of emotional health despite worse physical health or financial burden sug-gesting psychological resilience Pain (r = 061) and bowelbladder dysfunction (r = 041)imposed the greatest negative physical impact on overall QoL In turn ability to work correlatedinversely with worsened health (r = minus068) Increased pain reduced sexual function inability towork and reduced QoL had greatest negative impacts on emotional well-being Dissatisfactionwith treatment options and economic burden correlated inversely with QoL

ConclusionsCollectively the current findings advance the understanding of physical emotional social andfinancial tolls imposed by NMOSD These insights offer potential ways to enhance QoL bymanaging pain enhancing family and social networks and facilitating active employment

From the Ipsos Public Affairs (JB AK OP) Washington DC Chugai Pharmaceutical Co Ltd (MH) Chuo-ku Tokyo Japan Chugai Pharma USA Inc (AG-B) Berkeley Heights NJViela Bio (EK JNR) 1 MedImmune Way Gaithersburg MD MedImmune Ltd Riverside Building (GB) Granta Park Cambridge UK Department of Pediatrics (LJC) University ofUtah Salt Lake City UT The Guthy-Jackson Charitable Foundation (JMB) Beverly Hills Departments of Medicine and of Molecular Pharmacology (TFB) Stanford UniversitySchool of Medicine Stanford CA Department of Ophthalmology and Visual Sciences (TJS) Kellogg Eye Center and Division of Metabolism Endocrine and Diabetes Department ofInternal Medicine University of Michigan Medical School Ann Arbor MI Department of Medicine (MRY) University of California Los Angeles Los Angeles Divisions of MolecularMedicine and Infectious Diseases Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance CA

Go to NeurologyorgNN for full disclosures Funding information is provided at the end of the article

The Article Processing Charge was funded by The Guthy-Jackson Charitable Foundation

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CC BY-NC-ND) which permits downloadingand sharing the work provided it is properly cited The work cannot be changed in any way or used commercially without permission from the journal

Copyright copy 2019 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology 1

Neuromyelitis optica spectrum disorder (NMOSD) is a po-tentially life-threatening neuroinflammatory disease targetingthe optic nerve spinal cord and brain1ndash4 Relapses result incumulative neurologic disabilities are unpredictable and areinterspersed with remissions Increased diagnostic accuracy andincreased health care provider awareness have resulted in in-creased prevalence up to 10100000 in some geographicregions5ndash8 This estimate equates to gt15000 US patients andgt100000 cases worldwide NMOSD disproportionately affectsfemales (up to 71)910 Positive antindashaquaporin-4 (AQP4)antibody neuromyelitis optica (NMO-IgG) is the most com-mon disease serotype however titers fail to predict diseasecourse1112 Recent evidence1314 suggests that cases positive forantindashmyelin oligodendrocyte glycoprotein (MOG) antibody(MOG-IgG) are pathogenically distinct from NMOSD

Although studies suggest therapeutic benefit no treatment ofNMOSDhas been found to be safe and effective in prospectiveadequately powered clinical trials However recent results fromphase IIb and phase III trials are encouraging15ndash17 In thesetrials biologic therapeutics being evaluated include those tar-geting the complement C5 protein the intereukin-6 receptorand CD-19 protein on B cells In addition new and importantscientific insights have recently shed light on key mechanismsunderpinning NMOSD pathogenesis that may represent tar-gets for next-generation therapeutics18ndash21

By comparison few studies have systematically examined theimpact ofNMOSDon quality of life (QoL) in well-characterizedcohorts22ndash25 Therefore The Guthy-Jackson Charitable Foun-dation Alexion Pharmaceuticals Chugai Pharmaceutical CoMedImmuneViela Bio and Ipsos Public Affairs conducteda cooperative study of NMOSD patient experience and QoLThrough an interactive survey format patient-reported clinicaldemographic and experiential data were systematically collectedfrom geographically dispersed patients with NMOSD acrossNorth America The current analyses yielded novel insights thatmay afford potentially modifiable aspects of personal or clinicalcare to improve QoL in patients with NMOSD

MethodsClinical research standards

Human subjects protectionThe study was conducted in accordance with 45 Code ofFederal Regulations Part 46 and the US Department of Healthand Human Services policies regarding conductance of HumanSubject Research Protocols survey instruments (figure e-1linkslwwcomNXIA120) and informed consent documents

were approved by a central institutional review board Writtenand verbal consentassent were obtained before enrollment

Special population complianceThe online survey instrument was compliant with theAmericans with Disabilities Act Participants were given theoption of completing the survey with assistance of a relativefriend or caregiver if physical impairments precluded in-dependent participation

Study goals and design

Study goalsGoals were (1) to gain understanding of the natural history ofNMOSD from a patient-reported perspective and (2) to as-sess NMOSD patient QoL using a rigorous survey method-ology comprising standardized and NMOSD-specific QoLmeasures Both goals were intended to identify how NMOSDaffects patients and in so doing identify those aspects thatmight be modified

Study designThis study used a cross-sectional survey design Comparativedisease data were derived from published studies which usedidentical standardized measures and for which parallel de-mographic and QoL data sets were available

Survey themesThe survey instrument assessed multiple disease impacts us-ing quantitative Likert scales with dynamic ranges respectiveof each theme

Health-related QoLThree validated scales were used to assess the impact ofNMOSD on health-related QoL (1) select items from theRole-Physical and Role-Emotional subscales of the ShortForm-36 (SF-36) measured the impact of NMOSD onphysical and emotional health26 Scores on the SF-36 sub-scales ranged from 0 to 100 (100 = highest functioning and0 the lowest) The scale is normalized to average US indi-viduals having a score of 50 (2) the MS QoL scale27 mea-sured effects of pain bowel and bladder and sexual function(3) the Impact of Visual Impairment Scale assessed of visualimpairment affected perceived QoL28

Perceived impact of NMOSD on daily livingParameters were measured by (1) overall QoL (distinct fromhealth-related QoL) (2) perceived impact on career (3) sociallife (4) personal relationships (5) reproduction choices (6)NMOSD-related pregnancy complications and (7) degree towhich living situation was determined by necessity

GlossaryANOVA = analysis of variance AQP4 = aquaporin-4 GJCF = Guthy-Jackson Charitable Foundation MOG = myelinoligodendrocyte glycoprotein NMO = neuromyelitis optica NMOSD = neuromyelitis optica spectrum disorder QoL =quality of life SF-36 = Short Form-36

2 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

Diagnostic experienceMeasures included date of initial diagnosis (monthyear) pre-senting symptoms and diagnostic history including time be-tween first symptoms initial diagnosis and NMOSD diagnosis

Treatment experienceThe following data were collected treatment history reason fortreatment change date of most recent treatment change per-ceived effectiveness of current NMOSD treatment concernsregarding current treatment and outlook on future treatment

Relapse experienceRelapses in the previous year were measured using severalaspects of impact and severity including total number andfrequency of clinically-confirmed relapses number requiringinpatient hospitalization treatment regimens received forrelapses average duration of relapses and frequency ofemergencyurgent care for NMOSD

Health care experienceEvolution of patient interactions with health care professionalswas assessed by first presentation to a health care provider withsymptoms consistent with NMOSD initial referral to anNMOSD specialist specialty of physician diagnosingNMOSD factors influencing choice of current physician fre-quency of scheduled clinical evaluations and level of satisfac-tion with NMOSD physicianhealth care provider

Economic burdenSpecific financial impact of NMOSD was estimated via timespent traveling tofrom medical appointments method oftransportation need for in-home professional care total costsand annual out-of-pocket expenses for care financial supportreceived burden of monthly out-of-pocket expenses andperceived sufficiency of health care insurance

Future uncertaintyFuture concerns of worsening of disease and unpredictabledevelopment of improved therapies were assessed

Survey translationTranslation of the survey into Spanish involved a 2-stepprocess First a native-speaking translation linguist revieweddocuments against the source English file for consistencyterminology and syntax Next a computer-aided translationtool (Translation Workspace XLiff Editor v2491)29 wasapplied to review the instrument in contextual modules re-solving semantic ambiguity

Eligibility and enrollment

EligibilityParticipants were recruited from an opt-in digital mailing listof 2000 individuals in the NMO advocacy community whorequested information Those fulfilling inclusion criteria werestudy eligible self-reported established diagnosis of NMO orNMOSD3031 and the ability to read textual content or hearquestions audibly and respond to questions

Enrollment and implementationEligible subjects were consented and enrolled The survey in-strument was implemented either by telephone or via an onlineinterface Both modalities offered assistance through a clinicalstudy coordinator and provided options allowing completion in1 session or to complete over multiple sessions Patient-reported clinical data assessed are summarized in figure e-1(linkslwwcomNXIA120) Survey completion most com-monly occurred in the patient or caregiver residence Care-givers sometimes assisted the patient and investigator in use ofthe computer interface or in patient historical recall

Informatics and data securityStudy data were collected using a web-accessible electronicdata capture system with access limited to qualified studypersonnel Each patient data set was curated for quality in-ternal consistency and completeness

Statistical analysesDescriptive statistics (medians or interquartile ranges for nu-meric variables counts or percentages for categorical variables)were evaluated to assess cohort demographic diversity Pairwiseanalysis of variance (ANOVA) χ2 tests and Pearson or Spear-man correlation analyses were used to assess magnitude andorientation of relationships between or among study variablesAll analyses were performed in SPSS v 25032 Probability values(p) lt005 and correlation values (r) gt or lt 05 were consideredsignificant

Data availabilityDeidentified data obtained using the survey instrument usedin the current study (figure-e1 linkslwwcomNXIA120)will be made available to qualified research personnel in ac-cordance with institutional review board policies and uponrequest approximately 6 months following the final publica-tion date

ResultsCohort demographics

Sex race and ethnicityThe study population was predominantly female (N = 171886) and comprised diverse racialethnic backgrounds 715Caucasianwhite 161 African Americanblack 67 Asian(AS) 67HispanicLatinao or Spanish American 05NativeAmerican 10Pacific Islander and 26Other The distributionexceeds 100 because individuals could select multiple categoriesThe sample was predominantly English speaking 2 participantsrequested the Spanish survey Race and ethnicity distribution wasgenerally representative of the US population but reflecteda smaller proportion of HL participants than expected

EducationTwenty-eight percent reported completing a primary or highschool education or general educational development (figure1A) Twenty-one percent hold an associates or technical

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 3

degree 306 hold a bachelorrsquos degree and 181 havea postgraduate education or professional degree Typical ofonline survey research the sample skewed slightly to a greaterproportion of subjects having a higher level of education thanthe general US population

Employment statusApproximately 35 of the study cohort (N = 67) reportedcurrent employment (figure 1A) ranging from full-time(ge40 hwk 212) to part-time work Nine unemployedrespondents (46) reported that they are actively seeking em-ployment Of those unemployed 18 are full-time homemakersor caregivers 22 are retired and 1 is a studentMost unemployedrespondents (637 N = 79) reported being disabled

IncomeHousehold annual income varied widely among the studysubjects (figure 1A) The study population comprised a smallerproportion of participants who earned less than $10000 peryear compared with the broader US demographic

Residential status and childrenStudy participants resided in one of 43 US states and theDistrict of Columbia whereas 11 participants resided inCanada The modal state of residence was California (N =27 148) The majority of participants (705) livedwith their spousepartner 383 with their children104 were living alone at the time of study Nonereported living with domestic assistance or in an

Figure 1 (A) Demographic patterns among the present study cohort

(B) Relationship between physical and emotional healthfunctioning in NMOSD Criteria were based on SF-36 role-physical and role-emotional health measures The relativesize of the circle represents the number of respondents witha given score Most respondents fell within one of 3 catego-ries as labeled Note that the upper left category representsa particularly resilient group of patients with very poorphysical health but very robust emotional health

4 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

institutional domicilecare facility Most participants(731) had children

Survey assistance and future researchNineteen participants (lt10) received assistance in surveycompletion One participant participated by telephone Over92 of study subjects (N = 179) would consider participatingin a future study whereas 8 (41) declined consideringa future survey and 6 (31) declined to answer this question

Overall QoL

Physical and emotional healthRole-physical scores were relatively low but exhibited widevariability (median = 271 plusmn 361) Role-emotional

functioning was near-average with broad variance(median = 540 plusmn 449) Data exhibited bimodal distribu-tion with participants chiefly reporting either low or highfunctioning (figure 1B) Although physical and emotionalhealth were positively correlated (r = 0513 p lt 005) thedata also highlighted a complex health continuum(figure 1B)

Comparative QoLTo contextualize NMOSD QoL SF-26 data were comparedwith data examining other autoimmuneinflammatory dis-orders (table 1) Where results are summarized physicallyNMOSD impact on QoLwas rated similarly to systemic lupuserythematosus Emotional impact of NMOSD was rated as

Table 1 Comparative impact and determinants of NMOSD impact on QoL

Comparative

Sample size

Physicala Emotionala

SourceDisease cohort M SD M SD

Current study 193 271 391 540 449 mdash

Other NMOb 30 360 107 467 109 Zhao et al14

MSc 368 180 NA 520 NA Riazi et al35

Parkinson diseasec 227 190 NA 340 NA Riazi et al35

Systemic lupus erythematosus 1316 363 415 545 439 Wolfe et al36

Amyotrophic lateral sclerosis 679 182 331 473 462 Jenkinson et al37

Rheumatoid arthritis 13722 399 420 635 424 Wolfe et al36

NI rheumatic disorders 3623 395 416 656 414 Wolfe et al36

Antiphospholipid syndrome 270 435 496 568 494 Georgopoulou et al33

Fibromyalgia 2733 192 323 439 439 Wolfe et al36

Determinant Range Mean SD

Overall QoL 1ndash6 458 141

Bodily pain 1ndash6 360 131

Impaired career 1ndash6 330 196

Ability to work at job 1ndash6 319 196

Affected choice whether to have children 1ndash6 211 188

NMOSD-specific issue

Bowelbladder function interfering with normal activities 1ndash5 226 128

Interfered with day-to-day work (inside or outside the home) 1ndash5 276 125

Satisfaction with sexual function 1ndash5 240 123

Social and personal relationships

Social life 1ndash10 540 305

Personal and family relationships 1ndash10 566 280

Abbreviations MCS = Mental Health Component NA = not available NI = non-inflammatory NMO = neuromyelitis optica PCS = Physical ComponentSummary QoL = quality of life SF = Short Forma SF-36 scores on role-physical (physical functioning) and role-emotional (emotional functioning) of respondents diagnosed with NMO or NMOSD vs othercomparison conditions of similar heterogeneityb Zhao et al report the SF-36 PCS score andMCS Summary Scale a broader scale which contains the role-physical and role-emotional subscales but capturesa broader range of physical and mentalemotional functioningc Riazi et al did not report SDs for subscale means

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 5

equivalent to MS systemic lupus erythematosus and anti-phospholipid syndrome

NMOSD-specific experience

Impact of disease on QoLSpecific impacts of NMOSD on QoL are summarized in table1 On average NMOSD imposed a significant negative effect(mean = 458 plusmn 141 scale 1ndash6 [1 = least impact 6 = greatestimpact]) gt70 reported QoL to be greatly affected Deter-minants most associated with negative QoL were pain impacton career and ability to work Other factors were painimpairing day-to-day tasks impact on social activities bowelbladder dysfunction and satisfaction with sexual function Ofinterest diagnosis of NMOSD failed to strongly influence thedecision to have children

Initial presenting Symptom(s)The most common initial presenting symptoms (table 2)were numbness andor tingling (684) difficulty walking(544) and visual disturbances (528) Other pre-senting symptoms are as in figure-e1 (linkslwwcomNXIA120)

Accuracy of initial diagnosisNearly two-thirds of the cohort (N = 125 648) reported aninitial diagnosis other than NMOSD The most frequent wereMS (N = 80 414) or nonspecific optic neuritis (N = 44227) (table 2)

Demographics and serologic statusParticipants ranged in age from 19 to 76 years (mean = 492 plusmn128 years) whereas 13ndash73 years (mean = 447 plusmn 125 years)at diagnosis and 3months to 22 years (mean = 50 plusmn 38 years)from diagnosis to study enrollment Eighty-two percent carrythe diagnosis of NMO (N = 158) whereas 181 (N = 35)were diagnosed with NMOSD Among the entire study co-hort 118 (611) reported being antindashaquaporin 4 antibody(NMO-IgG) seropositive 41 (212) NMO-IgG seronega-tive and 34 (176) did not know

Diagnostic or treatment delaysTime from initial symptoms to correct diagnosis ranged from0 (ie immediate NMO diagnosis) to 40 years (mean = 33 plusmn63 years) The time from correct diagnosis to treatmentinitiation ranged from 0 to 11 years (mean = 6 months plusmn 17years) The median timespan between first symptom andcorrect diagnosis was 6 months and the median interval tospecific treatment initiation was 3 weeks

Perceived efficacy of current treatmentThe mean rating of perceived effectiveness of current treat-ment across all participants was 82 plusmn 23 on the followingscale (1ndash10) 10 = treatment works very well 1 = treatmentdoes not work well or at all The most common medicationswere rituximab (606) prednisonecorticosteroids (202)and mycophenolate mofetil (171) Of treatments beingprescribed for at least 10 of study subjects those receiving

rituximab or mycophenolate mofetil reported highest per-ceived efficacy whereas azathioprine was lowest (table 3)Four participants reported currently receiving no treatmentand 35 (181) reported ldquootherrdquo treatments

Concerns about treatment optionsMore than 50 of participants (518) reported havingconcerns regarding their NMOSD treatment mostly focusedon future effectiveness (table 3) Eighty-eight participants(456) reported NMO medication changes over their dis-ease course The majority of these patients (N = 48 545)reported changes because of poor efficacy whereas 32

Table 2 Symptoms and diagnoses of initial diseaseepisode among patients with NMOSD

Counta Percenta

Initial symptoms

Numbnesstingling 132 684

Difficulty walking 105 544

Vision problems 102 528

Pain 95 492

Fatigue 66 342

Bladder control problems 51 264

Paralysis 45 233

Spasticity (sudden involuntary contraction ofa muscle)

45 233

Bowel control problems 30 155

Protracted vomiting 25 130

Cognitive problems (such as memory moodand mental effectiveness)

27 140

Protracted hiccups 21 109

Excessive daytime sleepiness 22 114

Depression 20 104

Insomnia 17 88

Emotional symptoms 14 73

Sexual dysfunction 10 52

Initial diagnoses

MS 80 640

Optic neuritis 44 352

Transverse myelitis 37 296

Depression 12 96

Lupus 9 72

Stroke 5 40

Abbreviation NMO = neuromyelitis opticaa Patient may have reported more than 1 diagnosis before NMOSD

6 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

(364) reported intolerable side effects Three patients(34) changed medication during pregnancy 4 (45)participated in a clinical trial and 10 (114) changed therapybecause of cost (table 3)

Impact of relapsesTable 4 summarizes relapse frequency among study partic-ipants Fifty-two patients (269) reported no relapsesAmong the remaining 141 patients 115 (815) reportedrelapses requiring hospitalization whereas 26 (185) hadrelapses managed as outpatients Forty-five participants(233) reported 6 or more relapses with 2 patients having

ge6 in the previous year One-hundred twenty-one patientshad not visited an emergency department because of relapsein the past year whereas 6 others visited an emergency de-partment ge6 times Relapses were reported as lasting lt4weeks by 95 participants (492) (table 4) 8 patients (41)reported relapses lasting gt6 months Most participants whoexperienced relapses in the past year were treated with eitherIV or (44) or oral steroids (44)

Health care experienceThe distribution of health care professionals initially soughtby patients for care is summarized in table 5 Primary care

Table 3 Perceived effectiveness concerns and history of treatment among patients with NMOSD

Current treatment Count Percent Rating of current treatment SD Range

Rituximab 117 606 876 188 1ndash10

Prednisonecorticosteroid 39 202 769 253 2ndash10

Mycophenolate mofetil 33 171 830 211 2ndash10

Azathioprine (Imuran) 28 145 739 236 2ndash10

PLEX 12 62 900 148 5ndash10

Investigational drugclinical trial 3 16 1000 mdash mdash

Cyclophosphamide 1 05 800 mdash mdash

Tocilizumab 1 05 1000 mdash mdash

Count Percent

Treatment concern

Future treatment effectiveness 56 560

Side effects 46 460

Ongoing significant disability 23 230

Ongoing relapses 19 190

Discomfort during administration 13 130

Inconvenience 11 110

Impact on pregnancy decisions 7 70

Treatment history

Azathioprine 47 534

Prednisonecorticosteroid 47 534

Mycophenolate mofetil 30 155

Rituximab 21 239

PLEX 16 182

IVIG 6 88

Cyclophosphamide 5 57

Investigational drugclinical trial 4 45

Abbreviations IVIG = intravenous immunoglobulin NMO = neuromyelitis optica PLEX = plasma exchangeParticipants could be taking more than 1 medication rating of current treatment captures the specific medication listed in the table and any othermedications or treatments they were currently undergoing

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 7

physicians (N = 48 249) and general neurologists (N =47 245) were most commonly consulted initially followedby emergency department physicians (N = 41 212) Themost common initial referral was to a general neurologist(N = 77 398) Fifty-two patients (269) were referred toNMOSD specialist neurologists 40 (207) to an ophthal-mologist and 26 (134) to a gastroenterologist Generalneurologists were the most common specialists prescribingmedications (906)

Nearly one-half of the study cohort (N = 82 424) wereexamined by their doctor every 6 months most commonlycoincident with rituximab infusion Thirty-three percent (N =64) of patients saw their doctor at 3-month intervals 16(83) once per year 26 (N = 5) every month and 6(31) only at the time of relapse The remainder reportseeing their doctor ldquoas neededrdquo (N = 4) or not at all (N = 1)

Economic burden of disease

Costs attributable to diseaseStudy participants rated monthly out-of-pocket expenses dueto NMOSD as 571 plusmn 312 on a 10-point scale ranging from noburden (1) to significant burden (10) As summarized in table5 prescription medicines accounted for the greatest portionof NMOSDmedical costs for most patients (N = 88 456)many specified rituximab infusions as the single largest costThe sole factor predictive of financial burden was receivingplasma exchange therapy during relapse Twenty-five (13)reported travel costs tofrom health care providers as ac-counting for the greatest cost whereas 18 (9) stated

hospitalization accounted for greatest cost Eleven percent(N = 21) reported that an in-home professional caregiverprovides service Other significant costs reported were herbalsupplements psychologist visits or medical costs not coveredby Medicare

Total costsBeyond subjective financial burden of disease the total annualexpenses reported by the cohort as a whole was $1109357 oran average of $5748 per respondent (table 5) The mostfrequently reported cost was prescription medication with140 participants (735) reporting an average out-of-pocketcost of $1876 annually Unprompted (not an original cate-gory of out-of-pocket costs) 3 participants reported lost in-come at an average of $65000 annually Although nota categorical option 23 respondents reported paying forspecialists (including psychologists) out-of-pocket at an av-erage of $1554 annually A large number of participants (N =124 642) reported travel costs to medical appointments atan average of $468 per respondent The largest total cost out-of-pocket was for hospitalization accounting for $304410annually in the sample or an average of $7248 per re-spondent (N = 42 218) Caregiver or support was anotherhigh cost accounting for $70580 annually in the sample or anaverage of $3361 per respondent (N = 21 109)

Financial support for careThe majority of study participants (N = 142 736) reportedthat health insurance sufficiently covered prescribed NMOSDmedicines Among those with insufficient health insuranceexpensive copayment and insurer denials were common

Table 4 Total and annual relapse profile of study participants

Relapse frequency 0 1 2 3ndash5 6+

Relapses ever experienced

Relapses experienced 52 33 22 38 45

Relapses requiring hospitalization 26 40 18 35 18

Relapses in the previous year

Relapses experienced 85 34 7 9 2

Relapses requiring hospitalization 23 17 6 6 0

No of emergency department visits 121 30 18 18 6

Relapse duration Count Percent

1ndash7 d 30 227

1ndash2 wk 37 280

2ndash4 wk 28 212

1ndash2 mo 12 91

3ndash4 mo 11 83

5ndash6 mo 6 45

More than 6 mo 8 61

8 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

Table 5 Health care professionals encountered and annual expenses due to NMOSD

Health careprofessional

Physician first to evaluatesymptoms

Specialist first toreceive referral

Physician whodiagnosed NMOSD

Physician currently prescribingmedications

Neurologist(nonspecialist)

47 77 99 175

Neurologist (NMOspecialist)

24 52 83 mdash

Ophthalmologist 21 40 11 0

Neuro-ophthalmologist 1 3 3 0

Rheumatologist 4 5 0 1

Gastroenterologist 1 26 16 0

Orthopedist 1 3 0 0

MS specialist 0 4 4 5

Primary care physician 48 1 0 11

Emergency departmentphysician

41 1 1 0

Hematologist 0 1 0 13

Physiatrist 0 0 0 1

Other 5 8 5 4

Out-of-pock expenses N Minimum Maximum Median

Prescription medicine(s) 140 $25 $30000 $540

Travel to clinical care 124 $10 $10000 $115

Emergencyurgent care 48 $50 $15000 $275

Medical supplies 52 $50 $3000 $330

Hospitalization 42 $100 $150000 $1950

Caregiver or service 21 $50 $14000 $1500

Support groups 7 $8 $360 $100

Other costs 58 $80 $125000 $1700

Category of expenseaTotal cost to samplerespondents

No of respondents reportingcost

Average annual cost perrespondent

Prescription medicine(s) (includinginfusions)

$262598 140 $1876

Emergencyurgent care $61275 48 $1277

Hospitalization $304410 42 $7248

Travel costs for medical care $58003 124 $468

Caregiver or support services $70580 21 $3361

Medical supplies $34173 52 $657

Support group $1838 7 $263

Supplements $1000 1 $1000

Specialists $35750 23 $1554

Lost income $195000 3 $65000

Health insurance deductible $23330 9 $2592

Other costs (unspecified) $61400 4 $15350

Continued

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 9

reasons Twenty-four study participants (126) reportedreceiving financial support for their NMOSD treatmentlargely in the form of disability insurance clinical trial par-ticipation or support from friends and family

Correlation analysisTo examine predictors of overall QoL ANOVA was used todetect correlates among individual factors including timesince diagnosis total relapse number (a surrogate of diseaseseverity) and current treatments (overall and specifically forrelapses) Neither time since diagnosis nor current treat-ment regimen was predictive of overall QoL however thenumber of relapses correlated significantly with overall QoL(p = 0001) with greater numbers of relapses diminish-ing QoL

Other potential correlates affecting QoL in NMOSD wereexplored using a matrix Pearson or Spearman correlation

analysis of primary data elements As shown in table 6 mul-tiple correlations were identified as trending to positively ornegatively affecting QoL

DiscussionThe primary goal of this study was to determine the impactand correlates of NMO on patient QoL in a standardizedmanner using validated measures of physical and emotionalhealth impact on daily activities potentially affecting QoL Byexamining specific tangible domains of QoL in parallel toperceived overall QoL the patient experience regarding howthis rare disease affects daily life was revealed

Several important themes were identified among the currentstudy cohort First NMOSD typically has strong negativeeffects on physical functioning Physical functioning was

Table 5 Health care professionals encountered and annual expenses due to NMOSD (continued)

Category of expenseaTotal cost to samplerespondents

No of respondents reportingcost

Average annual cost perrespondent

Collective sample $1109357 193 $5748

Abbreviations NMO = neuromyelitis optica QoL = quality of lifea For each cost category respondents rated the largest burden on QoL and estimated annual expense for each Costs were totaled by category and averagedfor cost-per-respondent and cost-in-sample estimates Note Other costs category included specialists estimated lost income health insurance deductiblesand unspecified costs

Table 6 Exploratory correlation analyses among study data elementsdagger

10 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

lower in the study cohort than in the general population andon par with individuals having MS or systemic lupuserythematosus33ndash36 The predominant physical issues affect-ing QoLwere bodily pain bowel and bladder dysfunction andvisual impairment These factors inversely correlated withability to work the limitation of which negatively affectedQoL Age was positively associated with many QoL measuressuch as pain suggesting that disease increasingly negativelyaffctes QoL over time Worse physical functioning also cor-related with greater uncertainty about the future Notablyanti-AQP4 antibody serostatus reported as negative or un-known correlated with less impact on QoL than detectableanti-AQP4 antibody This relationship is similar to that oftenobserved in AQP4 antibodyndashpositive and MOG antibodyndashpositive phenotypes11ndash14 Conversely seronegative statuscarried a significantly higher financial burden

By comparison emotional health was in general un-impaired suggesting that poor physical health does notnecessarily correspond to diminished emotional healthAlthough some study participants exhibited congruentemotional and physical health a subset of participantsreported the highest level of emotional health despite seri-ously impaired physical health This inverse relationshipsuggests a degree of psychological resilience in somepatients despite physical impairment Likewise a portion ofparticipants reported that their disease had a positive effecton their social relationships One possible explanation forsuch positive impact is that their disease provoked supportnetwork involvement These findings are consistent with theconcept and impact of psychological resilience38 which cantranslate to effective personal strategies of coping withhealth-related challenges39

The constellation of presenting symptoms in many patientsresulted in an initial diagnosis of MS Inaccurate diagnosiscombined with delay of appropriate therapy can negativelyaffect long-term outcomes in NMOSD40 However recentimplementation of international consensus criteria31 has in-creased the timeliness and accuracy of diagnosis and shouldimprove care in early disease41 The number duration andseverity of relapses varied widely across the study cohort Thisobservation corresponds to the absence of a standardizeddefinition and diagnostic algorithm for differentiating bonafide relapses from unrelated symptoms

Not surprisingly participants reporting higher treatmentratings also experienced higher physical and emotional func-tioning and higher QoL Similarly worse functioning wasassociated with larger financial burden These themes areconcordant with those of previous studies222341 Of interestpatients receiving nonspecific immune-suppressing treat-ments tended to rate their regimens more negatively whereasthose on target-specific treatments (eg biologics) rated theirtreatments more positively Impact of NMO on QoL ex-tended beyond physical and emotional costs respondentsreported a high financial burden particularly for prescription

medicines travel costs hospitalization and specialist careFurthermore the per-respondent cost and total cost estimatesin this study provide a useful estimate of personal and healthcare costs of NMOSD to society

Results of the current study emphasize the significant negativeimpact NMOSD can have on patient QoL particularly inrelation to physical disability pain bowel and bladder dys-function or visual impairment42ndash46 These manifestationscorrespond to reduced ability to work at a job or perform dailyactivities and a decreased QoL which also reconcile withnegative impacts of anxiety disability or depression inNMOSD2547 Factors contributing to these adverse out-comes may include (1) delayed or inappropriate treatmentdue to initial misdiagnosis (2) real or perceived efficacy orlack of efficacy of current treatment options (3) lack ofa standard definition of relapse and (4) disease-specificeconomic burden These issues underscore the importance ofrecent advances in diagnostic timeliness and accuracy as wellas ongoing clinical trials intended to establish the first ap-proved therapies for NMOSD Prospectively global collabo-ration aimed at implementation of a standard relapsedefinition and severity score should contribute to improvedclinical care Likewise the pursuit of predictive biomarkers ofrelapse to allow mitigating interventions and the initiation ofstudies aimed to durably restore immune tolerance as a cura-tive therapy hold promise for increasingly effective medicalsolutions for NMOSD patients Synergistic and prospectiveapproaches such as these aimed at addressing disease causesand effects hold great promise to significantly add to the QoLfor patients with NMOSD other patients with rare diseaseand beyond4849

AcknowledgmentThe authors are deeply grateful to the patients whovolunteered to participate in this research Alexion Pharma-ceuticals provided input into the study design and courtesyreview of the manuscript Special appreciation is expressed toMs Megan Weber for analytic support This collaborativeproject was supported in-part by The Guthy-JacksonCharitable Foundation Alexion Pharmaceuticals Inc ChugaiPharmaceuticals Co Ltd Viela Bio and MedImmune Ltd

Study fundingThis study was sponsored in part by The Guthy-JacksonCharitable Foundation Alexion Pharmaceuticals Inc ChugaiPharmaceutical Co Ltd Viela Bio and MedImmune Ltd

DisclosureJ Beekman is an employee of Ipsos Public Affairs a researchfirm paid to conduct this research study A Keisler was anemployee of Ipsos Public Affairs a research firm paid toconduct this research study O Pedraza is an employee ofIpsos Public Affairs a research firm paid to conduct this re-search study M Haramura is an employee of Chugai Phar-maceutical Co Ltd which is conducting clinical trialsfocused on NMOSD and a sponsor of the current study

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 11

A Gianella-Borradori was an employee of Chugai Pharma-ceutical Co Ltd which is conducting clinical trials focusedon NMOSD and a sponsor of the current study E Katz andJN Ratchford are employees of Viela Bio which is con-ducting a clinical trial focused on NMOSD and a sponsor ofthe current study G Barron is an employee of MedImmunewhich is conducting a clinical trial focused on NMOSD anda sponsor of the current study LJ Cook and JM Behne aresupported in part by The Guthy-Jackson Charitable Foun-dation which is a sponsor of the current study TF BlaschkeTJ Smith and MR Yeaman are advisors to The Guthy-Jackson Charitable Foundation which is a sponsor of thecurrent study Go to NeurologyorgNN for full disclosures

Publication historyReceived by Neurology Neuroimmunology amp NeuroinflammationJanuary 11 2019 Accepted in final form April 8 2019

Appendix Authors

Name Location Role Contributions Disclosure(s)

JennineBeekmanPhD

Ipsos PublicAffairsWashingtonDC

Author Designedconceptualizedthe studyacquired the dataanalyzed the datainterpreted thedata and draftedthe manuscriptfor intellectualcontent

Dr Beekman isan employee ofIpsos PublicAffairs a researchfirm paid toparticipate in thisresearch study

AyshaKeislerPhD

Ipsos PublicAffairsWashingtonDC

Author Designedconceptualizedthe studyacquired thedata analyzedthe datainterpreted thedata and draftedthe manuscriptfor intellectualcontent

Dr Keisler was anemployee ofIpsos PublicAffairs a researchfirm paid toparticipate in thisresearch study

OmarPedrazaMPH

Ipsos PublicAffairsWashingtonDC

Author Designedconceptualizedthe studyacquired the dataanalyzed the datainterpreted thedata and draftedthe manuscriptfor intellectualcontent

Dr Pedraza is anemployee ofIpsos PublicAffairs a researchfirm paid toparticipate in thisresearch study

MasayukiHaramuraPhD

ChugaiPharmaceuticalCo Ltd

Author Designedconceptualized thestudy interpretedthe data andreviewed andrevised themanuscript forintellectualcontent

Dr Haramura isan employee ofChugaiPharmaceuticalCo Ltd which isconductingclinical trialsfocused onNMOSD

AthosGianella-BorradoriMD

Chugai PharmaUSA Inc

Author Designedconceptualizedthe studyinterpreted thedata andreviewed andrevised themanuscript forintellectualcontent

Dr Gianella-Borradori was anemployee ofChugaiPharmaceuticalCo Ltd which isconducting clinicaltrials focused onNMOSD anda sponsor of thisstudy

Appendix (continued)

Name Location Role Contributions Disclosure(s)

EliezerKatz MD

Viela Bio Author Designedconceptualizedthe studyinterpreted thedata andreviewed andrevised themanuscript forintellectualcontent

Dr Katz is anemployee of VielaBio which isconductinga clinical trialfocused onNMOSD anda sponsor of thisstudy

John NRatchfordMD

Viela Bio Author Designedconceptualizedthe studyinterpreted thedata andreviewed andrevised themanuscript forintellectualcontent

Dr Ratchford isan employee ofViela Bio which isconductinga clinical trialfocused onNMOSD anda sponsor of thisstudy

GerardBarronBSc (Hons)

Viela Bio Author Designedconceptualizedthe studyinterpreted thedata andreviewed andrevised themanuscript forintellectualcontent

Mr Barron is anemployee ofMedImmunewhich isconductinga clinical trialfocused onNMOSD anda sponsor of thisstudy

LawrenceJ CookPhDMStat

University ofUtah Salt LakeCity UT

Author Designedconceptualizedthe studyacquired thedata analyzedthe datainterpreted thedata andreviewedrevisedthe manuscriptfor intellectualcontent

Dr Cook issupported in-partby The Guthy-JacksonCharitableFoundationwhich isa sponsor of thisresearch

Jacinta MBehne MS

Guthy-JacksonCharitableFoundationBeverlyHills CA

Author Designedconceptualizedthe studyinterpreted thedata and revisedthe manuscriptfor intellectualcontent

Ms Behne issupported in-partby The Guthy-JacksonCharitableFoundationwhich isa sponsor of thisresearch

Terrence FBlaschkeMD

StanfordUniversity PaloAlto CA

Author Designedconceptualizedthe studyinterpreted thedata and revisedthe manuscriptfor intellectualcontent

Dr Blaschke is anAdvisor to TheGuthy-JacksonCharitableFoundationwhich isa sponsor of thisresearch

Terry JSmith MD

University ofMichigan AnnArbor MI

Author Designedconceptualizedthe studyanalyzed thedata interpretedthe data anddrafted themanuscript forintellectualcontent

Dr Smith is anAdvisor to TheGuthy-JacksonCharitableFoundationwhich isa sponsor of thisresearch

Michael RYeamanPhD

University ofCalifornia losAngeles CA

Author Designedconceptualizedthe studyanalyzed thedata interpretedthe data anddrafted themanuscript forintellectualcontent

Dr Yeaman is anAdvisor to TheGuthy-JacksonCharitableFoundationwhich isa sponsor of thisresearch

12 Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 NeurologyorgNN

References1 Weinshenker BG Wingerchuk DM Neuromyelitis spectrum disorders Mayo Clin

Proc 201792663ndash6792 Akaishi T Nakashima I Sato DK et al Neuromyelitis optica spectrum disorders

Neuroimaging Clin N Am 201727251ndash2653 Marignier R Cobo Calvo A Vukusic S Neuromyelitis optica and neuromyelitis optica

spectrum disorders Curr Opin Neurol 201730208ndash2154 Whittam D Wilson M Hamid S et al Whatrsquos new in neuromyelitis optica A short

review for the clinical neurologist J Neurol 20172642330ndash23445 Flanagan EP Cabre P Weinshenker BG et al Epidemiology of aquaporin-4 auto-

immunity and neuromyelitis optica spectrum Ann Neurol 201679775ndash7836 Houzen H Kondo K Niino M et al Prevalence and clinical features of neuromyelitis

optica spectrum disorders in northern Japan Neurology 2017891995ndash20017 Sepulveda M Aldea M Escudero D et al Epidemiology of NMOSD in Catalonia

influence of the new 2015 criteria in incidence and prevalence estimates Mult SclerEpub 2017 Oct 1

8 Pandit L Asgari N Apiwattanakul M et al Demographic and clinical features ofneuromyelitis optica a review Mult Scler 201521845ndash853

9 Bukhari W Prain KM Waters P et al Incidence and prevalence of NMOSD inAustralia and New Zealand J Neurosurg Psych 201788632ndash638

10 Papp V Illes Z Magyari M et al Nationwide prevalence and incidence study ofneuromyelitis optica spectrum disorder in Denmark Neurology 2018101212

11 Pittock SJ Lucchinett CF Neuromyelitis optica and the evolving spectrum of auto-immune aquaporin-4 channelopathies a decade later Ann NY Acad Sci136620ndash39

12 Kessler RA Mealy MA Jimenez-Arango JA et al Anti-aquaporin-4 titer is not pre-dictive of disease course in neuromyelitis optica spectrum disorder a multicentercohort study Mult Scler Relat Disord 201717198ndash201

13 Zamvil SS Slavin AJ Does MOG Ig-positive AQP4-seronegative opticospinal in-flammatory disease justify a diagnosis of NMO spectrum disorder Neurol Neuro-immunol Neuroinflamm 20152e62 doi101212NXI0000000000000062

14 Jarius S Ruprecht K Kleiter I et al MOG-IgG in NMO and related disordersa multicenter study of 50 patients Part 1 frequency syndrome specificity influence ofdisease activity long-term course association with AQP4-IgG and originJ Neuroinflamm 201613279

15 Alexion Pharmaceuticals Alexion announces successful phase 3 PREVENT study ofSoiris (Eculizumab) in patients with neuromyelitis optica spectrum disorders(NMOSD) Available at alexionpharmacompress-release Accessed March 252019 Also see ClinicalTrialsgov NCT01892345

16 Chugai Pharmaceutical Co LTD Chugai presents results from phase III study ofsatralizumab in NMOSD at ECTRIMS 2018 Available at chugai-pharmcojpAccessed March 25 2019 Also see ClinicalTrialsgov NCT02028884

17 VielaBio Inc A double-masked placebo-controlled study with open label period toevaluate MEDI-551 in neuromyelitis optica and neuromyelitis optica spectrum dis-order Available at ClinicalTrialsgov NCT02200770 Accessed March 25 2019

18 Bradl M Reindl M Lassmann H Mechanisms for lesion localization in neuromyeltisoptica spectrum disorders Curr Op Neurol 201831325ndash333

19 Papadopoulos MC Bennett JL Verkman AS Treatment of neuromyelitis opticastate-of-the-art and emerging therapies Nat Rev Neurol 201410493ndash506

20 Sato DK Callegaro D Lana-Peixoto MA et al Seronegative neuromyelitis opticaspectrummdashthe challenges on disease definition and pathogensis Arq Neuropsiq201472445ndash450

21 Kim SH KimHJ A step forward towards personalized immunosuppressive therapy inneuromyelitis optica spectrum disorder J Neurol Neurosurg Psych 201788619

22 Moore P Jackson C Mutch K et al Patient-reported outcome measure for neuro-myelitis optica pretesting of preliminary instrument and protocol for further de-velopment in accordance with international guidelines BMJ Open 20166e011142

23 Eaneff S Wang V Hanger M et al Patient perspectives on neuromyelitis opticaspectrum disorders data from the PatientsLikeMe online community Mult SclerRelat Disord 201717116ndash122

24 Schmidt F Zimmermann H Mikolajczak J et al Severe structural and functionalvisual system damage leads to profound loss of vision-related quality of life in patientswith neuromyelitis optica spectrum disorders Mult Scler Relat Disord 20171145ndash50

25 Shi Z Chen H Lian Z et al Factors that impact health-related quality of life inneuromyelitis optica spectrum disorder anxiety disability fatigue and depressionJ Neuroimmunol 201629354ndash58

26 Ware JE Sherbourne CD The MOS 36-item Short-Form Health Survey (SF-36) IConceptual framework and item selection Med Care 199230473ndash483

27 Vickrey BG Hays RD Harooni R et al A health-related quality of life measure formultiple sclerosis Qual Life Res 19954187ndash206

28 Weih LMHassell JB Keeffe JE Assessment of the impact of vision impairment InvestOphthal Vis Sci 200243927ndash935

29 Lionbridge Technologies Inc Translation Workspace XLiff editor version 2491WalthamLionbridge 2018 Available at Lionbridgecom Accessed March 25 2019

30 Wingerchuk DM Lennon VA Pittock SJ et al Revised diagnostic criteria for neu-romyelitis optica Neurology 2006661485ndash1489

31 Wingerchuk DM Banwell B Bennett JL et al International consensus diagnosticcriteria for neuromyelitis optica spectrum disorders Neurology 201585177ndash189

32 IBM SPSS Statistics Software Version 250 Armonk IBM Corporation 2017Available at IBM SPSS Software Accessed March 25 2019

33 Georgopoulou S Efraimidou S MacLennan SJ et al Antiphospholipid (Hughes)syndrome description of population and health-related quality of life (HRQoL) usingthe SF-36 Lupus 201524174ndash179

34 Jenkinson C Fitzpatrick R Swash M et al The ALS Health Profile Study quality oflife of amyotrophic lateral sclerosis patients and careers in Europe J Neurol 2000247835ndash840

35 Riazi A Hobart JC Lamping DL et al Using the SF-36 measure to compare thehealth impact of multiple sclerosis and Parkinsonrsquos disease with normal populationhealth profiles J Neurol Neurosurg Psych 200374710ndash714

36 Wolfe F Michaud K Li T et al EQ-5D and SF-36 quality of life measures in systemiclupus erythematosus comparisons with rheumatoid arthritis non-inflammatoryrheumatic disorders and fibromyalgia J Rheum 201037296ndash304

37 Jenkinson C Hobar J Chandola T et al Use of the short form health survey (SF-36)in patients with amyotrophic lateral sclerosis tests of data quality score reliabilityresponse rate and scaling assumptions J Neurol 2002249178ndash183

38 Ong AD Bergeman CS Bisconti TL et al Psychological resilience positiveemotions and successful adaptation to stress in later life J Personal Soc Psych200691730ndash749

39 Tugade MM Fredrickson BL Feldman-Barrett L Psychological resilience and pos-itive emotional granularity examining the benefits of positive emotions on coping andhealth J Pers 2004721161ndash1190

40 Borisow N Mori M Kuwabara S et al Diagnosis and treatment of NMO spectrumdisorder and MOG-encephalitis Front Neurol 20189888

41 Hyun JW Jeong IH Joung A et al Evaluation of the 2015 diagnostic criteria forneuromyelitis optica spectrum disorder Neurology 2016861772ndash1779

42 Zhao S Mutch K Elsone L et al Neuropathic pain in neuromyelitis optica affectsactivities of daily living and quality of life Mult Scler J 2014201658ndash1661

43 Sakakibara R Neurogenic lower urinary tract dysfunction in multiple sclerosis neu-romyelitis optica and related disorders Clin Auton Res Epub 2018 Aug 3

44 Methley AM Mutch K Moore P et al Development of a patient-centered conceptualframework of health-related quality of life in neuromyelitis optica a qualitative studyHealth Expect 20172047ndash58

45 Mutch K Zhao S Hamid S et al Bladder and bowel dysfunction affect quality oflife a cross sectional study of 60 patients with aquaporin-4 antibody-positiveneuromyelitis optica spectrum disorder Mult Scler Relat Disord 20154614ndash618

46 Chanson J-B Zephir H Collongues N et al Evaluation of health-related quality of lifefatigue and depression in neuromyelitis optica Eur J Neurol 201118836ndash841

47 Chavarro VS Mealy MA Simpson A et al Insufficient treatment of severe depressionin neuromyelitis optica spectrum disorder Neurol Neuroimmunol Neuroinflamm20163e286 doi101212NXI0000000000000286

48 Yeaman MR Jackson V Rare to the Rescue The Scientist 2018 Available at the-scientistcom Accessed March 25 2019

49 Jackson V Yeaman MR The Power of Rare New York Simon amp Schuster 2017Available at simonandschustercomThe-Power-of-Rare Accessed March 25 2019

NeurologyorgNN Neurology Neuroimmunology amp Neuroinflammation | Volume 6 Number 4 | July 2019 13

DOI 101212NXI000000000000058020196 Neurol Neuroimmunol Neuroinflamm

Janine Beekman Aysha Keisler Omar Pedraza et al Neuromyelitis optica spectrum disorder Patient experience and quality of life

This information is current as of June 20 2019

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