Translation, Adaptation and Validation of the European Portuguese Version of the NMS-Quest for Parkinson's Disease

ARTIGO ORIGINAL 6 Re is a Cien í ica da O dem dos Médicos www.ac amedicapo uguesa.com RESUMO In odução: Os sin omas não-mo o es da doença de Pa kinson são ainda pouco econhecidos, apesa do impac o na qualidade de ida e na mo alidade. O Ques ioná io de Sin omas Não-Mo o es é uma e amen a álida e con iá el pa a a aliação dos sin omas não-mo o es nou os idiomas. O obje i o des e es udo é aduzi , adap a e alida a e são po uguesa do Ques ioná io de Sin omas Não-Mo o es. Ma e ial e Mé odos: A acei abilidade oi a aliada a a és da ampli ude de alo es, e ei o de e o e de chão. A iabilidade oi medida em e mos de consis ência in e na (al a de C onbach) e de ep odu ibilidade (coe icien e de co elação in aclasse). Pa a a alidade de c i é io, o Ques ioná io de Sin omas Não-Mo o es oi compa ado com a escala Mo emen Diso de s Socie y – Uni ied Pa kinson’s Disease Pa e I. A alidade con e gen e oi a aliada a a és de co elações en e o Ques ioná io de Sin omas Não-Mo o es, Mo e- men Diso de s Socie y – Uni ied Pa kinson’s Disease Pa e III, pon uação na Mini-Men al S a e Examina ion, du ação de doença e se e idade de doença. Resul ados: Rec u ámos 79 doen es com doença de Pa kinson, com idade média de 67,2 ± 10,7 anos e uma du ação média de doença de 10,8 ± 8,8 anos. A e são po uguesa do Ques ioná io de Sin omas Não-Mo o es e elou p op iedades psicomé icas ade- quadas. O ques ioná io (al a de C onbach = 0,862) e os seus domínios demons a am uma consis ência in e na adequada, com exce- ção do domínio ca dio ascula (al a de C onbach = 0,173). Em e mos de alidade, e i ica am-se co elações o es en e a maio ia dos domínios do Ques ioná io de Sin omas Não-Mo o es e as dimensões co esponden es da Mo emen Diso de s Socie y – Uni ied Pa kinson’s Disease Pa e I. A pon uação o al do Ques ioná io de Sin omas Não-Mo o es mos ou co elações mode adas com a du ação e se e idade da doença, se e idade dos sin omas mo o es, não-mo o es e dis unção cogni i a. Discussão: Es e é o p imei o es udo a aduzi , adap a e alida uma e amen a equen emen e u ilizada pa a as eio de sin omas não mo o es na doença de Pa kinson. Conclusão: A e são po uguesa do Ques ioná io de Sin omas Não-Mo o es é uma e amen a álida e con iá el pa a a alia os sin- omas não-mo o es nos doen es com doença de Pa kinson. Pala as-cha e: Doença de Pa kinson/diagnós ico; Exame Neu ológico; Inqué i os e Ques ioná ios; Po ugal; Psicome ia; Rep odu- ibilidade dos Tes es; T adução T ansla ion, Adap a ion and Valida ion o he Eu opean Po uguese Ve sion o he NMS-Ques o Pa kinson’s Disease T adução, Adap ação e Validação da Ve são Po uguesa do Ques ioná io de Sin omas Não-Mo o es pa a a Doença de Pa kinson 1. Neu ology Depa men . Cen o Hospi ala e Uni e si á io de Coimb a. Coimb a. Po ugal. 2. Neu ology Depa men . Faculdade de Medicina. Uni e sidade de Coimb a. Coimb a. Po ugal.  Au o co esponden e: F adique Mo ei a. [email p o ec ed] Recebido: 19 de no emb o de 2019 - Acei e: 21 de ab il de 2020 | Copy igh © O dem dos Médicos 2021 Alexand a SILVA1, Tiago PEDRO2, F adique MOREIRA1 Ac a Med Po 2021 Jan;34(1):6-11 ▪ h ps://doi.o g/10.20344/amp.13160 ABSTRACT In oduc ion: Non-mo o symp oms a e unde ecognized ea u es o Pa kinson’s disease ha impai quali y o li e and inc ease mo a- li y. In his s udy, we aim o ansla e, adap and alida e he Eu opean Po uguese e sion o he “Non-Mo o Symp oms Ques ionnai e”, which has p o en o be a alid and eliable measu emen ool o non-mo o symp oms in o he languages. Ma e ial and Me hods: Accep abili y was e alua ed ega ding he ange o alues, ceiling and loo e ec s. Reliabili y was measu ed in e ms o in e nal consis ency (C onbach’s alpha) and ep oducibili y (in a-class co ela ion coe icien ). Fo c i e ion alidi y analysis, Mo emen Diso de s Socie y – Uni ied Pa kinson’s Disease Pa I domains’ sco es we e compa ed o hose o he “Non-Mo o Symp- oms Ques ionnai e”. Fo con e gen alidi y, co ela ions be ween he “Non-Mo o Symp oms Ques ionnai e” and he Mo emen Diso - de s Socie y – Uni ied Pa kinson’s Disease Pa III, Mini-Men al S a e Examina ion sco e, disease du a ion, and se e i y we e ob ained. Resul s: Se en y nine Pa kinson’s disease pa ien s we e ec ui ed, wi h a mean age o 67.2 ± 10.7 yea s and a disease du a ion o 10.8 ± 8.8 yea s. The Eu opean Po uguese e sion o he “Non-Mo o Symp oms Ques ionnai e” o al sco e was ee o signi ican ceiling and loo e ec s. Wi h he excep ion o he ca dio ascula domain, adequa e o e all in e nal consis ency was achie ed. The ques ionnai e domains and he co esponding Mo emen Diso de s Socie y – Uni ied Pa kinson’s Disease Pa I dimensions we e signi ican ly co ela ed, al hough he o al ques ionnai e sco e was modes ly co ela ed wi h disease du a ion and se e i y, mo o and non-mo o symp oms se e i y and cogni i e dys unc ion. Discussion: This is he i s s udy o ansla e, adap and alida e a widely used sc eening ins umen o non-mo o symp oms o Eu- opean Po uguese speaking Pa kinson’s disease pa ien s. Conclusion: The Eu opean Po uguese e sion o “Non-Mo o Symp oms Ques ionnai e” is a alid and eliable ool o sc eening non- mo o symp oms in pa ien s wi h Pa kinson’s disease. Keywo ds: Neu ologic Examina ion; Pa kinson Disease/diagnosis; Po ugal; Psychome ics; Rep oducibili y o Resul s; Su eys and Ques ionnai es; T ansla ing Co ec ion/ E a a: h ps://www.ac amedicapo uguesa.com/ e is a/index.php/amp/a icle/ iew/16510 ARTIGO ORIGINAL R e i s a C i e n í i c a d a O d e m d o s M é d i c o s w ww. a c a m e d i c a p o u g u e s a . c o m 7 INTRODUCTION Pa kinson’s disease (PD) is a mul isys em neu ode- gene a i e diso de , commonly known by i s ca dinal mo- o ea u es, such as b adykinesia, igidi y, and emo .1 Howe e , non-mo o symp oms (NMS) including cogni i e impai men , psychia ic, sleep, au onomic, gas oin es inal and senso y dis u bances a e ound in he majo i y o PD pa ien s2 and may p ecede he de elopmen o mo o dys- unc ion.1,3 NMS may ha e a g ea e impac on quali y o li e han mo o symp oms, wi h se e al s udies showing a nega i e ou come on he quali y o li e o pa ien s wi h PD.4–7 I s se e i y has been ecen ly shown o inc ease he isk o mo ali y among Po uguese PD pa ien s.8 Despi e being highly p e alen and po en ially ea able, hey a e s ill in- su icien ly diagnosed and emain unde ecognized in o e 50% o he consul a ions pe o med by neu ologis s.9 F e- quen ly used scales and sco es do no adequa ely de ec hese non-mo o symp oms,10 which make he de elopmen o an easy, as and eliable NMS sc eening ool, impe a i e. The NMS Ques ionnai e (NMS-Ques ) is a sel -comple - ed pa ien ques ionnai e comp ising 30 quali a i e ques- ions ha assess he p esence o all impo an non-mo o symp oms h ough a dicho omic “yes” o “no” answe . The o iginal English e sion was designed in 2006 o be a quick sc eening ool used by neu ologis s o pe cei e he pa ien ’s NMS bu den du ing he p e ious mon h. The ques ionnai e akes om 10 o 15 minu es o comple e a e which he i ems can be combined in o nine domains: gas oin es- inal (8 i ems), u ina y ac (2 i ems), sexual unc ion (2 i ems), ca dio ascula (2 i ems), apa hy/a en ion/memo y (3 i ems), hallucina ions/delusions (2 i ems), dep ession/ anxie y/anhedonia (2 i ems), sleep/ a igue (5 i ems), pain (1 i em) and miscellaneous (3 i ems). Since he e is no Po uguese e sion o he NMS-Ques , sel - ansla ed e sions a e o en used in clinical p ac ice. Ou s udy aims o ansla e, adap and alida e he o iginal NMS-Ques e sion o he Eu opean Po uguese language, ollowing in e na ional guidelines o adap a ion o ques ion- nai es. MATERIAL AND METHODS Pa icipan s and selec ion Pa ien s diagnosed acco ding o he Uni ed Kingdom Pa kinson’s Disease Socie y B ain Bank C i e ia11 we e consecu i ely ec ui ed om ou Mo emen Diso de s Uni be ween June and Oc obe 2019. Cogni i e dys unc ion was sc eened using Mini-Men al S a e E alua ion (MMSE) and he ollowing cu -o s we e applied: ≤ 15 i illi e a e, ≤ 22 i 1 - 11 yea s o educa ion and ≤ 27 i mo e han 11 yea s.12 Cogni i e and debili a ing de ici s (e.g. blindness) we e es ablished as exclusion c i e ia. Sociodemog aphic da a we e collec ed ega ding gende , age, and li e acy. Clinical aspec s including disease du a ion, Hoehn and Yah (H&Y) scale, Mo emen Diso de s Socie y-Uni ied Pa kinson’s Disease Ra ing Scale (MDS-UPDRS) – Pa I and III, and MMSE scale we e e alua ed by he same neu- ologis . Each ques ionnai e was applied in a p i a e oom and checked o missing answe s. In o med consen was ob ained om all pa icipan s and ou p o ocol was ap- p o ed by he local E hics Commi ee ( e e ence numbe CHUC-116-19). NMS-Ques ansla ion and adap a ion The ansla ion, adap a ion and alida ion p ocess ol- lowed he ins uc ions p o ided by he Mo emen Diso - de s Socie y upon eques and he s udy was conduc ed acco ding o he Good Clinical P ac ice guidelines.13 The o iginal English e sion o NMS-Ques was i s ansla ed in o Po uguese by wo independen bilingual expe s and a consensual e sion was ob ained a e g amma ical and seman ic compa ison. Then, he consensus e sion was back- ansla ed in o English by ano he bilingual speake unawa e o he o iginal scale o ule ou seman ic disc ep- ancies be ween he o iginal and he ansla ed e sion o he scale. The Po uguese e sion o NMS-Ques was e- iewed by an expe ienced clinician and highly knowledge- able in Mo emen Diso de s o es o con en alidi y, and i was applied in a p e es ing ial wi h 10 PD pa ien s in o de o assess cul u al di e ences and sensi i i ies. A inal Po uguese e sion o NMS-Ques was c ea ed a e wa ds and is p esen ed in Appendix 1 (see Appendix 1: h ps:// www.ac amedicapo uguesa.com/ e is a/index.php/amp/ a icle/ iew/13160/Appendix_01.pd ). Da a analysis Desc ip i e s a is ics we e used o sample demog aph- ic cha ac e iza ion and ques ionnai e esul s. Con en alid- i y was achie ed h ough expe e iew. Fo analysis pu - poses, he i ems we e g ouped in o nine domains ollowing he ecommenda ions o he Mo emen Diso de s Socie y: diges i e (i ems 1 o 7), u ina y (i ems 8 and 9), apa hy/ a en ion/memo y (i ems 12, 13, and 15), hallucina ions/ delusions (i ems 14 and 30), dep ession/anxie y (i ems 16 and 17), sexual unc ion (i ems 18 and 19), ca dio ascula (i ems 20 and 21), sleep diso de s (i ems 22 o 26), and miscellany (i ems 10, 11, 27, 28, and 29). One poin was sco ed in case o a posi i e answe o each ques ion and ze o poin s in case o a nega i e esponse. The inal sco e o each domain was hen calcula ed and pa ien s wi h a leas one posi i e answe we e conside ed o ha e co e- sponding symp oms o ha domain. Fo con e gen alidi y, co ela ions be ween NMS- Ques domains and MDS-UPDRS Pa III, MMSE sco es, and disease du a ion and se e i y we e pe o med using he Spea man co ela ion coe icien (ρ). Co ela ions we e conside ed e y s ong when a coe icien was g ea e han 0.90, s ong i be ween 0.70 and 0.90, mode a e i be ween 0.50 and 0.70, weak i be ween 0.30 and 0.50 and e y weak i below 0.30.14 C i e ion alidi y was analyzed by co ela ing NMS-Ques and MDS-UPDRS Pa I domains sco es using Spea man co ela ion coe icien (ρ). Some MDS-UPDRS Pa I i ems we e g ouped in o a common di- mension compa able o ha in he NMS-Ques , al hough Sil a A, e al. Po uguese e sion o he NMS-Ques o Pa kinson’s disease, Ac a Med Po 2021 Jan;34(1):6-11 ARTIGO ORIGINAL 8 Re is a Cien í ica da O dem dos Médicos www.ac amedicapo uguesa.com sexual unc ion (NMS-Ques ) and dopamine dys egula ion synd ome (MDS-UPDRS Pa I) we e le wi hou possible compa ison. The accep abili y was e alua ed in e ms o ange o alues, ceiling and loo e ec s. An e ec ≤ 15% is conside ed accep able. In e nal consis ency o each domain was es ed using C onbach’s alpha and alues ≥ 0.70 we e conside ed adequa e indica o s o eliabili y. The es - e es and in a- a e eliabili y we e assessed using in a-class co ela ion (ICC) based on an absolu e-ag eemen , 2-way mixed-e ec s model. A coe icien ≥ 0.70 was deemed as accep able.14 The s a is ical analysis was execu ed using IBM SPSS e sion 25 wi h a le el o signi icance se a 0.05. RESULTS A o al o 79 PD pa ien s we e included, he majo i y o which we e males (57%; n = 45). The pa icipan s had a mean age o 67.2 ± 10.7 yea s ( ange 35 - 87) and a mean disease du a ion o 10.8 ± 8.8 yea s. The mean H&Y s age was 2.3 ± 0.6 (3.8%, n = 3 in s age 1; 67.1%, n = 53 in s age 2; 25.3%, n = 20 in s age 3; 3.8%, n = 3 in s age 4). The MDS-UPDRS-Pa III mean sco e o mo o symp oms se e i y was 30.7 ± 13.0 and he MDS-UPDRS-Pa I mean sco e o non-mo o symp oms se e i y was 10.5 ± 4.9. The clinical and demog aphic ea u es a e shown in Table 1. Accep abili y As shown in Table 2, gas oin es inal symp oms we e he mos common and we e epo ed by 82.3% (n = 65) o pa ien s, ollowed by sleep diso de s (81.0%; n = 64). Hallucina ions and/o delusions we e p esen in 27.8% (n = 22) o pa ien s and we e he leas equen . All domains showed a loo e ec , wi h hallucina ions/delusions being he mos p ominen (72.2%). Apa om he diges i e and miscellany domains, all o he s showed a ceiling e ec , he highes (68.4%) being p esen ed by he dep ession/anxie y dimension. The NMS-Ques o al sco e was ee o signi i- can ceiling (2.5%) and loo (1.3%) e ec s. Reliabili y Ou Po uguese e sion o he NMS-Ques exhibi ed an o e all C onbach’s alpha o 0.862 and an ICC o 0.848. Fo each domain, he alpha coe icien s anged om 0.183 o 0.902. Excep o he ca dio ascula domain (0.183), he diges i e (0.764), u ina y (0.840), apa hy/a en ion/memo y (0.803), hallucina ions/delusions (0.885), dep ession/anxi- e y (0.874), sexual unc ion (0.902), sleep diso de s (0.810) and miscellaneous symp oms (0.730) we e ound o be in e nally consis en . The o e all esul s o he ICC we e equi alen , indica ing sa is ac o y es - e es eliabili y. Validi y C i e ion alidi y analysis is shown in Table 3. All NMS- Ques and ela ed MDS-UPDRS-Pa I domains we e posi- i ely co ela ed wi h a signi icance alue below 0.001. The co ela ion coe icien s anged om 0.361 (miscellaneous symp oms) o 0.911 (hallucina ions/delusions). S ong co - ela ions we e ob ained be ween he diges i e, u ina y, apa- hy/a en ion/memo y, dep ession/anxie y, ca dio ascula Sil a A, e al. Po uguese e sion o he NMS-Ques o Pa kinson’s disease, Ac a Med Po 2021 Jan;34(1):6-11 Table 1 – S udy sample cha ac e is ics Fea u es Age (yea s)*67.2 ± 10.7 Gende , M/F (%M) 45/34 (57) Yea s o educa ion*6.7 ± 4.3 Disease du a ion*10.8 ± 8.8 H&Y s age, % (n) 13.8 (3) 267.1 (53) 325.3 (20) 43.8 (3) MMSE sco e*27.3 ± 2.7 MDS-UPDRS-Pa I sco e*10.5 ± 4.9 MDS-UPDRS-Pa III sco e*30.7 ± 13.0 * Values a e mean ± s anda d de ia ion H&Y: Hoehn & Yah scale; MDS-UPDRS: Mo emen Diso de s Socie y - Uni ied Pa kin- son’s Disease Ra ing Scale; MMSE: Mini-Men al S a e Examina ion Table 2 – Desc ip i e analysis and psychome ic indica o s o NMS-Ques domains NMS-Ques domain Accep abili y Reliabili y % (n) Range Mean ± SD Ceiling e ec , % Floo e ec , % ICC C onbach’s alpha Diges i e 82.3 (65) 0.0 - 7.0 2.7 ± 2.1 1.3 17.7 0.741 0.764 U ina y 72.2 (57) 0.0 - 2.0 1.3 ± 0.9 59.5 27.8 0.839 0.840 Apa hy/A en ion/Memo y 74.7 (59) 0.0 - 3.0 1.8 ± 1.2 43.0 25.3 0.798 0.803 Hallucina ions/ Delusions 27.8 (22) 0.0 - 2.0 0.5 ± 0.8 20.3 72.2 0.885 0.885 Dep ession/Anxie y 77.2 (61) 0.0 - 2.0 1.5 ± 0.8 68.4 22.8 0.876 0.874 Sexual unc ion 62.0 (49) 0.0 - 2.0 1.2 ± 0.9 53.2 38.0 0.902 0.902 Ca dio ascula 70.9 (56) 0.0 - 2.0 0.9 ± 0.7 24.1 29.1 0.173 0.183 Sleep diso de s 81.0 (64) 0.0 - 5.0 2.4 ± 1.9 21.5 19.0 0.804 0.810 Miscellany 67.1 (53) 0.0 - 5.0 1.6 ± 1.6 8.9 32.9 0.729 0.730 To al - 2.0 - 28.0 13.7 ± 6.3 2.5 1.3 0.848 0.862 ICC: in aclass co ela ion coe icien ; SD: s anda d de ia ion ARTIGO ORIGINAL R e i s a C i e n í i c a d a O d e m d o s M é d i c o s w ww. a c a m e d i c a p o u g u e s a . c o m 9 Sil a A, e al. Po uguese e sion o he NMS-Ques o Pa kinson’s disease, Ac a Med Po 2021 Jan;34(1):6-11 and sleep diso de s domains and hei co esponding MDS- UPDRS-Pa I dimensions. The equency o hallucina- ions and/o delusions in he NMS-Ques p esen ed a e y s ong co ela ion wi h he hallucina ions/psychosis i em in he MDS-UPDRS-Pa I, while he equency o miscellane- ous symp oms was weakly co ela ed wi h pain and o he sensa ions on he espec i e scales. The e we e no logical ma ches o he NMS-Ques sexual domain and he dopa- mine dys egula ion synd ome in he MDS-UPDRS-Pa I. Cons uc alidi y was assessed compa ing he NMS- Ques domain sco es wi h clinical indica o s. The co ela ion ma ix is shown in Table 4. The majo i y o he NMS-Ques dimensions p esen ed a weak o mode a e co ela ion wi h he MDS-UPDRS-Pa I sco e, excep o he sexual unc- ion domain. The domains conce ning diges i e, ca dio- ascula and sleep diso de s exhibi ed e y-weak o weak co ela ions wi h mo o symp oms se e i y (MDS-UPDRS- Pa III sco e). Rega ding cogni i e unc ion, he diges i e, apa hy/a en ion/memo y, hallucina ions/delusions, and de- p ession/anxie y domains we e nega i ely co ela ed wi h he MMSE sco e. Howe e , he sexual unc ion domain was posi i ely co ela ed wi h a highe cogni i e s a us. Only domains conce ning hallucina ions/delusions and sleep diso de s showed posi i e and e y weak o weak co ela ions wi h disease du a ion. In e ms o disease se- e i y, he diges i e, u ina y, ca dio ascula , sleep diso de s and miscellany domains we e posi i ely co ela ed wi h he H&Y s age. These co ela ions we e conside ed e y weak o weak. DISCUSSION Ou s udy is he i s Eu opean Po uguese ansla ion and adap a ion o he o iginal English e sion o he NMS- Ques ha ollows he in e na ional equi emen s o scale alida ion. Gi en hei high p e alence and bu den, we p o- ide a eliable and alid sc eening ins umen o non-mo o symp oms in PD. The NMS-Ques di e s om all o he non- mo o symp oms ques ionnai es due o i s sel -comple ed and quali a i e na u e. I can be easily illed ou by pa ien s du ing o e en be o e consul a ions. I allows us o o e - come some o he ime es ain s du ing ollow-up consul- a ions and he pa ien s’ emba assmen in epo ing hei symp oms. Table 3 – Spea man co ela ion coe icien s (ρ) be ween NMS-Ques and MDS-UPDRS-Pa I dimensions NMS-Ques domain MDS-UPDRS-Pa I domain ρ* Diges i e 1.11 Cons ipa ion p oblems 0.767 U ina y 1.10 U ina y p oblems 0.750 Apa hy/A en ion/Memo y 1.1 Cogni i e impai men 1.5 Apa hy 0.813 Hallucina ions/Delusions 1.2 Hallucina ions, psychosis 0.911 Dep ession/Anxie y 1.3 Dep essed mood 1.4 Anxious mood 0.752 Sexual unc ion - Ca dio ascula 1.12 Ligh headedness 0.822 Sleep diso de s 1.7 Sleep p oblems 1.8 Day ime sleepiness 1.13 Fa igue 0.784 Miscellany 1.9 Pain and o he sensa ions 0.361 -1.6 Dopamine dys egula ion synd ome - MDS-UPDRS: Mo emen Diso de s Socie y Uni ied Pa kinson’s Disease Ra ing Scale *All co ela ion coe icien s we e signi ican a p < 0.001. Table 4 – Spea man co ela ion coe icien s (ρ) be ween NMS-Ques dimensions and o he applied scales o disease s ages NMS-Ques domain MDS-UPDRS-Pa I MDS-UPDRS-Pa III MMSE Disease du a ion H&Y s age Diges i e 0.569*0.492*-0.244*0.181 0.354* U ina y 0.352*0.193 -0.091 -0.099 0.233* Apa hy/A en ion/Memo y 0.613*0.111 -0.223*0.081 0.197 Hallucina ions/Delusions 0.344*0.167 -0.241*0.297*0.116 Dep ession/Anxie y 0.540*0.220 -0.326*-0.057 0.211 Sexual unc ion 0.058 -0.077 0.329*0.102 -0.007 Ca dio ascula 0.520*0.263*-0.169 0.076 0.358* Sleep diso de s 0.537*0.373*-0.163 0.302*0.441* Miscellany 0.462*0.087 -0.064 0.126 0.250* *p < 0.05 H&Y: Hoehn & Yah scale; MDS-UPDRS: Mo emen Diso de s Socie y - Uni ied Pa kinson’s Disease Ra ing Scale; MMSE: Mini-Men al S a e Examina ion ARTIGO ORIGINAL 10 Re is a Cien í ica da O dem dos Médicos www.ac amedicapo uguesa.com The Po uguese NMS-Ques showed adequa e psycho- me ic p ope ies in he ields o accep abili y, eliabili y, and alidi y. The o e all sco e did no show any ceiling and loo e ec s, al hough hey we e p esen in mos o he domains ha con ained a small numbe o i ems due o he inc eased likelihood o sco ing he highes and lowes possible on hose i ems. The ca dio ascula NMS-Ques domain did no each accep able in e nal consis ency and es - e es eliabili y in ou s udy. This domain is composed o one i em sc eening o dizziness seconda y o o hos a ic hypo en- sion and ano he ega ding he equency o alls. Al hough o hos a ic hypo ension may indeed p omp pa ien s o all, mo o complica ions (pos u al ins abili y, gai eezing, dys- kinesias) ha e been es ablished as majo isk ac o s o alling,15–17 which may explain he low in e nal consis ency coe icien ob ained. O he NMS-Ques domains such as gas oin es inal and miscellaneous symp oms showed only ma ginally accep - able in e nal consis ency. The gas oin es inal domain in- cludes one i em conce ning cons ipa ion while also sc een- ing o in es inal incon inence. Al hough bo h can be p esen a he same ime, we ound ha obs ipa ion was epo ed by 58.2% o pa ien s and in es inal incon inence by 8.9%, which is consis en wi h p e ious s udies18,19 bu e lec ed on a lowe C onbach’s alpha coe icien . Only i e pa ien s epo ed hese symp oms simul aneously and had a longe disease du a ion when compa ed wi h he o e all sample (mean 17.2 yea s). Mo eo e , he miscellany domain is composed o i ems ha canno i in any o he o he ca ego- ies. The e o e, i is expec ed ha hese symp oms a e no consis en ly p esen among pa ien s wi h PD. Signi ican co ela ions be ween all NMS-Ques do- mains and he co esponding i ems on he MDS-UPDRS- Pa I we e ound. Hallucina ions and/o delusions showed he s onges associa ion wi h he ma ching i em on ou ‘gold-s anda d’ scale, bu he miscellaneous clus e showed a weak co ela ion p obably due o concep ual di e ences. The miscellany domain in he NMS-Ques comp ises i ems es ing o pain, weigh changes, swelling, swea ing and diplopia while he co esponding MDS-UPDRS-Pa I i em only men ions pain, ingling, and c amps. Rega ding cons uc alidi y, we we e able o es ablish signi ican co ela ions be ween each NMS-Ques domain and disease- ela ed a iables (MDS-UPDRS-Pa I, MDS- UPDRS-Pa III, MMSE, disease du a ion, and H&Y s age). Diges i e and ca dio ascula symp oms p esen ed he s onges co ela ions wi h disease se e i y, bu no wi h disease du a ion, which is in line wi h B aak’s pa hological indings whe e he degene a ion o he au onomic ne ous sys em and lowe b ain s em p ecedes ha o he co ex as he disease sp eads.20 The se e i y o mo o symp oms was mainly co ela ed wi h he p esence o diges i e symp oms. These symp oms may an icipa e he mo o mani es a ions o he disease, and pa icula ly dysphagia, cons ipa ion, and ecal incon inence can be caused o wo sened by gas- oin es inal muscles dysmo ili y.21 In e es ingly, sexual unc ion was he only domain exhib- i ing a posi i e co ela ion wi h he MMSE sco e, indica ing ha sexual pe o mance was highly dependen on cogni- i e s a us. This e ec has been epo ed in men, whe e de- c eased cogni i e unc ion was associa ed wi h less sexual in e es and loss o libido.22 The e is a lack o compa able da a wi h o he NMS- Ques alida ion s udies. To ou knowledge, only he I alian ansla ion and alida ion23 ollowed a simila me hodology, bu he di e ences in he g ouping o he i ems p e en ed us om d awing di ec compa isons. When compa ed wi h he o iginal scale alida ion coho ,24 ou pa ien s had a highe disease du a ion (10.8 ± 8.8 s 6.4 ± 4.3 yea s), lowe dis- ease se e i y (2.3 ± 0.6 s 2.5) and we e sligh ly younge (67.2 ± 10.7 s 68.1 ± 10.3 yea s old). These ac s could explain he epidemiological di e ences be ween he e- quency o non-mo o symp oms obse ed and ha epo ed on he o iginal scale alida ion and gene al s udies. While me a-analyses show ha u ina y p oblems a e he mos p e alen among PD pa ien s a ound he wo ld,25 sleep/ a igue, and ca dio ascula symp oms we e epo ed o be he mos equen in he Po uguese popula ion.26 The e a e limi a ions o ou s udy wo h men ioning. Fi s , ou sample was also smalle compa ed o ha o he o iginal scale alida ion (79 s 123 pa ien s), bu simila o o he ansla ions and alida ions.23,27 The majo i y o he pa ien s had mild o mode a e s ages o he disease, which may unde es ima e he epo ing o symp oms ypi- cal o ad anced s ages (memo y loss, apa hy, dep ession, e c.)28 and in luence he gene alizabili y o he esul s. Fu- u e s udies conce ning he applicabili y o he NMS-Ques in ad anced s ages o he disease a e equi ed. Also, ou ‘gold-s anda d’ scale (MDS-UPDRS-Pa I) does no include i ems enqui ing o sexual dys unc ion symp oms ha could be used o he alidi y analysis o he sexual unc ion do- main o he NMS-Ques . Finally, he g ouping o con a y o un ela ed symp oms may ha e led o he low in e nal con- sis ency and c i e ion alidi y obse ed in some domains, espec i ely. CONCLUSION The Po uguese e sion o he NMS-Ques is a use ul sc eening ool o non-mo o symp oms in PD pa ien s ha mee s he alidi y and eliabili y equi emen s in he majo i y o i s domains. Ca dio ascula and gas oin es inal sco es should be in e p e ed ca e ully. We ecommend he ou ine use o NMS-Ques in he ou pa ien se ing o help diagnose and ea iden i ied symp oms. ACKNOWLEDGMENTS We hank Joana Lopes and Sónia Sac amen o o hei help du ing ansla ion and pa ien ec ui men . PROTECTION OF HUMANS AND ANIMALS The au ho s decla e ha he p ocedu es we e ollowed acco ding o he egula ions es ablished by he Clinical Re- sea ch and E hics Commi ee and o he Helsinki Decla a- ion o he Wo ld Medical Associa ion. Sil a A, e al. Po uguese e sion o he NMS-Ques o Pa kinson’s disease, Ac a Med Po 2021 Jan;34(1):6-11 ARTIGO ORIGINAL R e i s a C i e n í i c a d a O d e m d o s M é d i c o s w ww. a c a m e d i c a p o u g u e s a . c o m 11 Sil a A, e al. Po uguese e sion o he NMS-Ques o Pa kinson’s disease, Ac a Med Po 2021 Jan;34(1):6-11 DATA CONFIDENTIALITY The au ho s decla e ha ing ollowed he p o ocols in use a hei wo king cen e ega ding pa ien s’ da a publica- ion. CONFLICTS OF INTEREST The au ho s epo no con lic s o in e es . FUNDING SOURCES This esea ch ecei ed no speci ic g an om any und- ing agency in he public, comme cial, o no - o -p o i sec- o s. REFERENCES 1. Kalia LV, Lang AE. Pa kinson’s disease. Lance . 2015;386:896–912. 2. 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