Con inuous Subcu aneous Apomo phine
In usion be o e Sub halamic Deep B ain
S imula ion: A P ospec i e, Compa a i e
S udy in 20 Pa ien s
Gus a o Fe n
andez-Paja ín, MD, PhD,
1,2,
*
Angel Sesa , MD, PhD,
1,2
Begoña A es, MD, PhD,
1,2
Isabel Jiménez-Ma ín, MD, PhD,
1,2
Miguel Gelabe , MD, PhD,
3
Edua do A
an-Echabe, MD, PhD,
2,3
José Luis Relo a, MD, PhD,
4
and Al onso Cas o, MD, PhD
1
ABSTRACT: Backg oundBackg ound: S udies compa ing he clinical e ficacy o apomo phine in usion (APO) wi h
subsequen sub halamic deep b ain s imula ion (STN-DBS) in ad anced Pa kinson’s disease (aPD) a e cu en ly
lacking. Re ospec i e da a ha e shown ha pa ien s ea ed wi h APO a e usually olde , ha e a mo e
p olonged disease, and a mo e se e e pheno ype.
Objec i eObjec i e: To compa e he benefi o APO wi h ha o STN-DBS on mo o , non-mo o , cogni i e, and quali y o
li e in he same pa ien when gi en sequen ially.
Me hodsMe hods: We p ospec i ely analyzed 20 aPD pa ien s o e 3 di e en ea men phases: baseline (op imized
medical ea men ), du ing APO ea men , and du ing subsequen STN-DBS ea men . The APO and STN-DBS
phases we e s able o 6 mon hs, and e alua ion o he di e en ea men s was sepa a ed by 6 mon hs.
Resul sResul s: Compa ed o baseline, APO, and STN-DBS educed mean daily o ime by 70.5% and 89.3% (P=0.012),
espec i ely, and sco es o Unified Pa kinson’s Disease Ra ing Scale (UPDRS) IV by 27.5% and 80.5% (P≤0.001),
Non-mo o symp oms scale (NMSS) by 24.6% and 49.3% (P≤0.001), Mon gome y Asbe g dep ession scale
(MADRS) by 7.4% and 39.0% (P=0.27), S a ks ein apa hy scale (SAS) by 51.1% and 39.9% (P=0.734),
Pa kinson’s disease sleep scale 2 (PDSS-2) by 25.7% and 56.7% (P≤0.001), and Pa kinson’s disease
ques ionnai e 39 i em (PDQ-39) by 39.6% and 64.9% (P≤0.001). Global cogni ion did no change wi h ei he
he apy, bu phone ic fluency wo sened a e STN-DBS compa ed o APO (P=0.022).
ConclusionsConclusions: Bo h APO and STN-DBS imp o ed mo o and non-mo o symp oms and quali y o li e compa ed o op imized
medical ea men in aPD. O e all, STN-DBS was he mos e ec i e ea men , bu APO showed a p onounced benefi on
mo o symp oms. E ec i e ea men o aPD should no be delayed, e en when wai ing o su ge y.
Apomo phine in usion (APO) and sub halamic deep b ain s imu-
la ion (STN-DBS) ha e p o en e ficacy o he ea men o
ad anced Pa kinson’s disease (PD, aPD) and a e widely used in
clinical p ac ice. Howe e , he le el o scien ific e idence
suppo ing each o hese ea men s di e s. Al hough se e al p o-
spec i e, andomized, and mul icen e clinical ials suppo he
use o STN-DBS, only 1 andomized, double-blind clinical ial,
he TOLEDO s udy
1,2
has been unde aken wi h APO.
1,2
Despi e i s long-s anding use, many s udies ha suppo he use
o APO a e e ospec i e and wi h small sample sizes.
3–10
In
e ms o mo o symp oms, STN-DBS seems o p o ide g ea e
clinical imp o emen han APO, which is gene ally es ic ed o
1
Depa men o Neu ology, Hospi al Clínico Uni e si a io de San iago, San iago, Spain;
2
G upo Clínico de T as o nos del Mo imien o, Ins i u o de In es igacion
Sani a ia de San iago de Compos ela (IDIS), San iago, Spain;
3
Depa men o Neu osu ge y, Hospi al Clínico Uni e si a io de San iago, San iago, Spain;
4
Depa men
o Clinical Neu ophysiology, Hospi al Clínico Uni e si a io de San iago, San iago, Spain
*Co espondence o: D . Gus a o Fe nandez Paja ín, Depa men o Neu ology, Hospi al Clínico Uni e si a io de San iago, T a esía da Choupana
s/n; 15706, San iago de Compos ela, Spain; E-mail: [email p o ec ed]; [email p o ec ed]
Keywo ds: Pa kinson’s disease, sub halamic deep b ain s imula ion, apomo phine, de ice-aided he apies.
Rele an disclosu es and conflic s o in e es a e lis ed a he end o his a icle.
This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion-NonComme cial-NoDe i s License, which pe mi s use and dis ibu-
ion in any medium, p o ided he o iginal wo k is p ope ly ci ed, he use is non-comme cial and no modifica ions o adap a ions a e made.
Recei ed 30 Ma ch 2021; e ised 15 July 2021; accep ed 15 Augus 2021.
Published online 9 Oc obe 2021 in Wiley Online Lib a y (wileyonlinelib a y.com). DOI: 10.1002/mdc3.13338
1216 MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338
© 2021 The Au ho s. Mo emen Diso de s Clinical P ac ice published by Wiley Pe iodicals LLC. on behal o In e na ional Pa kinson and Mo emen Diso de Socie y.
RESEARCH ARTICLE
CLINICAL PRACTICE
in usion du ing he pa ien ’s waking hou s and shows a a iable
e ec on dyskinesia. Bo h ea men s a e well ole a ed by PD
pa ien s wi h no mal cogni ion.
The EUROINF 2 s udy collec s da a om pa ien s ea ed
wi h he 3 de ice-aided he apies o aPD—APO, STN-DBS,
and le odopa-ca bidopa in es inal gel in usion. The pa ien s
ea ed wi h APO a e usually olde , wi h longe disease du a ion
and mo e se e e symp oms han pa ien s ea ed wi h STN-
DBS.
11
This is he cu en medical p ac ice because aPD pa ien s
mee ing he c i e ia o STN-DBS a e usually ecommended his
he apy. This gi es ise o a significan bias when e alua ing
APO o compa ing APO wi h STN-DBS because many pa ien s
ea ed wi h APO do no mee he c i e ia o STN-DBS.
4,7
To da e, only 2 non- andomized and p ospec i e s udies ha e
compa ed APO and STN-DBS in pa ien s mee ing he c i e ia
o STN-DBS.
12,13
In bo h, APO was o e ed because o he
long wai ing lis o STN-DBS ea men . In he fi s s udy, he
au ho s analyzed he clinical and neu opsychological e olu ion a
12 mon hs o 13 pa ien s ea ed wi h APO and 12 ea ed wi h
STN-DBS. The pa ien s who unde wen STN-DBS had be e
esul s o educ ion o o ime, dyskinesia, and o al an i-
pa kinsonian medica ion. Howe e , hey showed wo se e bal
fluency and Neu o-Psychia ic In en o y sco es.
12
In he second
s udy, he au ho s e alua ed memo y, execu i e, and isuospa ial
unc ion a 6 and 12 mon hs in 9 pa ien s ea ed wi h STN-
DBS and 7 ea ed wi h APO. They obse ed a s a is ically sig-
nifican decline in e bal fluency and naming speed a 6 mon hs
a e he in e en ion. This was no obse ed in he APO
g oup.
13
We, he e o e, unde ook a s udy o compa e he e ec o
APO and subsequen ly STN-DBS in he same pa ien .
Me hods
This s udy was a p ospec i e, non- andomized, obse a ional
s udy compa ing APO and STN-DBS, conduc ed by he Mo e-
men Diso de Uni o he Hospi al Clínico Uni e si a io de
San iago de Compos ela, Spain, om Ma ch 2017 o Feb ua y
2020. Inclusion c i e ia we e (1) pa ien s wi h aPD selec ed o
bila e al STN-DBS who s a ed APO while wai ing o su ge y,
a he disc e ion o hei neu ologis ; (2) minimum expec ed
APO du a ion o 6 mon hs; and (3) in o med consen ob ained.
STN-DBS c i e ia we e based on he Co e Assessmen P og am
o Su gical In e en ional The apies in Pa kinson’s Disease
(CAPSIT-PD)
14
wi h some modifica ions including (1) ad anced
s age PD; (2) disease du a ion o e 5 yea s; (3) educ ion in
Unified Pa kinson’s Disease Ra ing Scale (UPDRS) pa III
mo o sco es o e 50% a e le odopa o apomo phine challenge
es ; (4) age below 71 yea s; (5) magne ic esonance imaging wi h
no significan ascula damage o s uc u al abno mali ies;
(6) absence o significan cogni i e decline acco ding o selec ed
neu opsychological scales; (7) lack o se ious psychia ic condi-
ions, excep d ug-induced psychosis; (8) absence o on- ime
majo gai p oblems; (9) good gene al heal h; and (10) ealis ic
expec a ions. Exclusion c i e ia included (1) pa ien s wi h p e i-
ous STN-DBS; (2) pa ien s p e iously ea ed wi h APO (p e i-
ous apomo phine pen injec ion was pe mi ed); and (3) pa ien s
p e iously ea ed wi h le odopa in usion.
Clinical Assessmen
The clinical assessmen included (1) mo o : o daily hou s
(an a e age o he p e ious week), UPDRS pa III, UPDRS
pa IV and dyskinesia sco e (sec ion A om UPDRS pa IV);
(2) concomi an medica ion use: le odopa and le odopa equi a-
len daily dose (LEDD);
15
(3) non-mo o : Non-Mo o Symp-
oms Scale (NMSS), Ques ionnai e o Impulsi e-Compulsi e
Diso de in Pa kinson’s Disease-Ra ing Scale (QUIP-RS),
Mon gome y Asbe g dep ession scale (MADRS), S a ks ein apa-
hy scale (SAS), and Pa kinson’s disease sleep scale 2 (PDSS-2);
(4) cogni ion: Ma is a ing demen ia scale (MDRS) and e bal
fluency; and (5) quali y o li e: Pa kinson’s disease ques ionnai e
39 i em (PDQ-39).
We e alua ed he pa ien s a 3 di e en ime poin s: (1) base-
line (op imized medical ea men ; ON-MED); (2) APO (in he
4 weeks be o e he STN-DBS su ge y); and (3) STN-DBS
TABLE 1 Pa ien s’baseline cha ac e is ics
n=20
Age 59.30 6.40
Sex (male) 10
PD e olu ion (y) 8.40 3.60
UPDRS III o meds 38.41 10.91
Pas impulse con ol diso de 3
TABLE 2 T ea men cha ac e is ics o pa ien s ecei ing
apomo phine in usion
n=20
Du a ion o APO (mon hs) 9.35 2.46
APO dose (mg/day) 75.5 20.73
APO hou s (day) 15.6 2.78
Ad e se e ec s 6 (30%)
Nodules (complica ed) 2
Nausea 0
Somnolence 1
Rash 0
Illusion 1
Impulse con ol diso de 1
Hypo ension 0
Edema 1
MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338 1217
FERN
ANDEZ-PAJARÍN G. ET AL. RESEARCH ARTICLE
(on s im/on meds; a 6 mon hs a e su ge y). In his way, wi hin a
ime ame o 12–18 mon hs, all pa ien s we e e alua ed in 3 sepa-
a e clinical ea men se ings, each o hem s able o a leas
6 mon hs.
The ollowing we e excluded o he analysis: (1) pa ien s
who wi hd ew om APO, ei he olun a ily o because o a
medical indica ion; (2) pa ien s ea ed wi h APO o o e
12 mon hs; (3) pa ien s who did no e en ually ge STN-DBS
su ge y; (4) pa ien s who did no s op APO wi hin he fi s
4 weeks a e su ge y; (5) pa ien s wi h se e e complica ion du -
ing o immedia ely a e su ge y; and (6) pa ien s wi h a majo
complica ion in he fi s 6 mon hs a e STN-DBS su ge y,
in ol ing pa ial o o al emo al o he s imula ion sys em. Da a
de i ed om hese assump ions we e analyzed sepa a ely.
TABLE 3 Resul s o clinical assessmen s o all 3 ea men s
On-MED APO STN-DBS
p alue
On-MED s.
APO
p alue
On-MED s.
STN-DBS
o ime (hou s) 5.15 2.41 1.52 1.53 0.55 0.84 ≤0.001 ≤0.001
UPDRS II on 8.20 3.83 6.40 3.72 4.90 4.68 0.033 ≤0.001
UPDRS III on 12.75 5.41 11.60 6.43 9.90 6.03 0.365 0.004
UPDRS IV 7.45 2.46 5.40 2.54 1.45 1.79 0.017 ≤0.001
Dyskinesia sco e 3.05 2.11 3.20 2.31 0.65 1.18 1 ≤0.001
LEDD (mg) 1432 483 1712 532 776 340 0.003 ≤0.001
Le odopa (mg) 1149 447 846 420 695 319 0.002 ≤0.001
NMSS
a
53.65 27.83 40.45 28.18 27.20 18.60 ≤0.001 ≤0.001
Sleep/ a igue 11.15 5.33 7.90 5.06 3.20 3.78 0.002 ≤0.001
Mood 13.80 11.19 9.85 14.18 7.65 8.45 0.001 0.001
Gas oin es inal 4.05 5.61 4.00 5.28 2.65 4.16 0.703 0.514
U ina y 6.60 5.34 5.00 5.01 6.10 4.77 0.182 0.922
Sexual 6.00 6.62 4.45 5.61 2.80 4.70 0.256 0.08
Miscellaneous 10.05 7.17 7.45 8.55 3.85 4.37 0.006 ≤0.001
MADRS 13.45 10.98 12.45 9.29 8.20 8.38 0.152 0.024
SAS 6.90 7.17 3.10 2.88 4.15 5.64 0.41 0.41
QUIP-RS 2.20 2.88 2.65 6.73 0.90 3.06 0.767 0.691
PDSS-2 22.75 8.33 16.90 8.63 9.85 5.57 ≤0.001 ≤0.001
MDRS 135.75 4.29 135.70 5.66 135.20 7.14 0.937 0.937
Phone ic fluency 12.40 4.73 13.50 4.08 10.80 4.72 0.07 0.07
Seman ic fluency 16.60 4.39 16.85 4.28 14.75 3.82 0.93 0.091
PDQ-39 32.08 12.49 19.37 12.48 11.27 9.41 ≤0.001 ≤0.001
Mobili y 46.38 25.49 22.00 25.03 12.84 15.65 ≤0.001 ≤0.001
Daily li e ac i i ies 39.98 22.03 19.17 15.96 10.21 12.44 ≤0.001 ≤0.001
Emo ional wellbeing 39.56 19.00 30.62 19.42 21.48 15.56 0.071 0.006
S igma 22.51 32.98 15.31 24.79 4.38 9.54 0.058 0.009
Social suppo 5.41 12.16 6.25 21.44 1.25 5.59 0.484 0.484
Cogni ion 12.42 10.09 14.70 15.48 8.14 12.52 1 0.086
Communica ion 17.49 19.84 15.41 18.58 14.59 23.71 0.748 0.748
Bodily discom o 34.99 25.73 20.00 21.02 8.76 14.93 ≤0.001 ≤0.001
Values a e mean s anda d de ia ion; In bold, p< 0.05.
a
Fo NMSS sco es, he ca dio ascula , pe cep ual p oblems, and a en ion/memo y domains a e no ep esen ed because o he high numbe o esul s wi h a sco e o 0.
1218 MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338
RESEARCH ARTICLE LACK OF STUDIES COMPARING APO AND STN-DBS
S a is ical Analysis
Da a a e exp essed as a pe cen age o quali a i e a iables and
as mean and s anda d de ia ion o quan i a i e a iables. To
de e mine s a is ical di e ences be ween he 3 ea men s, we
applied analysis o a iance (ANOVA) o epea ed measu es
o he F iedman es (equi alen o he epea ed measu es
ANOVA o nonpa ame ic da a), depending on he pa ame -
ic o nonpa ame ic da a dis ibu ion. Pos hoc es s we e pe -
o med o e alua e he di e ence be ween pai s o ea men s:
pai ed es , a e he ANOVA, o Du bin-Cono e es , a e
F iedman’s es .TheP alues o hese we e adjus ed using he
me hod o Benjamini–Hochbe g, o con ol he alse
disco e y a e.
To e alua e he magni ude o he change o each ea men ela-
i e o baseline, we calcula ed he ela i e change (RC =mean
[ ea men baseline] 100/baseline mean) and he e ec size
(ES =mean [ ea men baseline]/s anda d de ia ion baseline
mean).
16
Values o ES be ween 0.20 and 0.49 a e conside ed a
small e ec size, alues be ween 0.50 o 0.79 a e conside ed a mod-
e a e e ec size, and alues ≥0.80 a e conside ed a la ge e ec size.
17
Resul s
A o al o 24 pa ien s pa icipa ed in he s udy. Fou pa ien s
wi hd ew because o hei own decision, hospi aliza ion o
TABLE 4 Magni ude o change om baseline in clinical pa ame e s and size e ec o each ea men
Rela i e change om baseline (%) Size e ec
APO STN-DBS p alue
a
APO STN-DBS
o ime (hou s) 70.49 89.32 0.012 1.51 1.91
UPDRS II on 21.95 40.24 0.033 0.47 0.86
UPDRS III on 9.02 22.35 0.022 0.21 0.53
UPDRS IV 27.52 80.54 ≤0.001 0.83 2.44
Dyskinesia sco e +4.92 78.69 ≤0.001 –1.14
LEDD (mg) +19.55 45.81 ≤0.001 –1.36
Le odopa (mg) 26.37 39.51 0.024 0.67 1.02
NMSS
b
24.60 49.30 ≤0.001 0.47 0.95
Sleep/ a igue 29.15 71.30 ≤0.001 0.61 1.49
Mood 28.62 44.57 0.923 0.35 0.55
Gas oin es inal 1.23 34.57 0.514 0.01 0.25
U ina y 24.24 7.58 0.182 0.30 0.09
Sexual 16.67 53.33 0.256 0.15 0.48
Miscellaneous 25.87 61.69 0.099 0.36 0.86
MADRS 7.43 39.03 0.27 0.09 0.49
SAS 55.07 39.86 0.734 0.53 0.38
PDSS-2 25.71 56.70 ≤0.001 0.70 1.55
PDQ-39 39.62 64.87 ≤0.001 1.02 1.67
Mobili y 52.57 72.32 0.026 0.96 1.32
Daily li e ac i i ies 52.05 74.46 0.003 0.94 1.35
Emo ional wellbeing 22.60 45.70 0.064 0.47 0.95
S igma 31.94 80.54 0.319 0.22 0.55
Social suppo +15.53 76.89 0.484 –0.34
Cogni ion +18.36 34.46 0.086 –0.42
Communica ion 11.89 16.58 0.748 0.10 0.15
Bodily discom o 42.84 74.96 0.002 0.58 1.02
In bold, p< 0.05 and size e ec >0.80.
a
Pai ed es a e ANOVA be ween APO and STN-DBS e alua ions.
b
Fo NMSS, ca dio ascula , pe cep ual p oblems and a en ion/memo y domains a e no ep esen ed because o he high numbe o esul s wi h a sco e o 0.
MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338 1219
FERN
ANDEZ-PAJARÍN G. ET AL. RESEARCH ARTICLE
d ug-induced psychosis (see Discussion), ex ended APO o e
12 mon hs, and hea pacemake implan a ion. This las pa ien is
s ill being ea ed wi h APO, wi h a mode a e clinical esponse.
The baseline and APO cha ac e is ics o he emaining 20 pa ien s
a e in Tables 1 and 2.
Table 3 shows he esul s o each mo o , non-mo o and
cogni i e e alua ion, concomi an medica ion use, and quali y o
li e a iables, and he pai - o-pai analysis o he baseline e alua-
ion. Table 4 displays he magni ude o he change in hese
pa ame e s o each de ice-aided he apy ela i e o baseline.
Mo o Ou come and Medica ion
Compa ed o baseline, mean daily o ime was educed by 70.5%
wi h APO and 89.3% wi h STN-DBS, showing a la ge e ec
size in each case (1.51 and 1.91, espec i ely) (Fig. 1). The di e -
ence be ween hese ea men s was s a is ically significan
(P=0.012). Mean UPDRS IV sco e imp o ed by 27.5% a e
APO and by 80.5% a e STN-DBS, wi h a la ge e ec size in
each case (0.83 and 2.44, espec i ely). The di e ence be ween
APO and STN-DBS was significan (P≤0.001). Mean dyskine-
sia sco e did no imp o e wi h APO, bu showed a 78.7% educ-
ion a e STN-DBS, wi h a la ge e ec size (1.14). STN-DBS
significan ly imp o ed mean UPDRS III sco e compa ed o
baseline and APO (P=0.004 and P=0.022, espec i ely).
Mean daily le odopa dosage was educed by 26.8% a e APO
(mode a e e ec size, 0.67) and by 39.5% a e STN-DBS (la ge
e ec size, 1.02). Despi e his, mean LEDD was inc eased by
19.6% wi h APO. The di e ence be ween APO and STN-DBS
was s a is ically significan o bo h le odopa dose educ ion
(P=0.024) and LEDD educ ion (P≤0.001).
Non-Mo o Ou come
Compa ed o baseline, mean NMSS sco e was educed by 24.6%
wi h APO, nea o a mode a e e ec (0.47) (Fig. 2). The sleep/
a igue domain had he mos p onounced imp o emen , and was
he only domain ha achie ed a mode a e e ec size. A e
STN-DBS, mean NMSS sco e was educed by 49.3% wi h a
la ge e ec size (0.95). Sleep/ a igue and miscellaneous domains
had he la ges e ec sizes, ollowed by he mood domain. The
di e ences be ween APO and STN-DBS we e s a is ically signi -
ican o o al NMSS sco e (P≤0.001) and sleep/ a igue
(P≤0.001). Mean sco e o dep ession, assessed using MADRS,
did no imp o e wi h APO, bu was educed by 39.0% a e
STN-DBS (P=0.024), wi h a mode a e e ec size (0.49). Ne -
e heless, he di e ence be ween ea men s was no s a is ically
significan . Mean sco e o apa hy, e alua ed using SAS,
imp o ed o a g ea e ex en wi h APO, 55.1%, wi h a mode a e
e ec size (0.53), han wi h STN-DBS, 39.9%, bu did no each
s a is ical significance. QUIP-RS sco e did no show eliable
FIG 1. Change in mo o and concomi an medica ion use ela i e o baseline o each ea men .
1220 MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338
RESEARCH ARTICLE LACK OF STUDIES COMPARING APO AND STN-DBS
changes o e he s udy pe iod (see discussion). Finally, mean
PDSS-2 sco e was imp o ed by 25.7% wi h APO and by 56.7%
wi h STN-DBS, achie ing a mode a e e ec size (0.70) and la ge
e ec size (1.55), espec i ely. The di e ence be ween APO and
STN-DBS was s a is ically significan (P≤0.001).
Cogni ion
The global cogni i e s a us o he pa ien s emained unchanged
ei he wi h APO and STN-DBS. Nei he MDRS no any o i s
subscales showed s a is ically significan di e ences be ween he
3 ea men phases. Howe e , when e bal fluency was specifi-
cally assessed, we ha e obse ed a wo sening a e he STN-DBS
su ge y. Phone ic fluency was significan ly educed wi h STN-
DBS compa ed o APO (P=0.022) and also educed compa ed
o baseline, close o s a is ical significance (P=0.07). Seman ic
fluency also showed lowe alues a e he STN-DBS, al hough
hey did no each s a is ical significance.
Quali y o Li e
Compa ed o baseline, bo h APO and STN-DBS esul ed in a
subs an ial imp o emen in pa ien s’quali y o li e (Fig. 3). Mean
o al PDQ-39 sco e was educed by 39.6% wi h APO and
64.9% wi h STN-DBS, bo h achie ing a la ge e ec size (1.02
and 1.67, espec i ely). Mobili y and daily li e ac i i ies showed
g ea e imp o emen wi h APO wi h a la ge e ec size and
bodily discom o wi h a mode a e e ec size. STN-DBS eached
a la ge e ec size in mobili y, daily li e ac i i ies, emo ional
wellbeing, and bodily discom o , and had a mode a e e ec size
on s igma. The di e ences be ween APO and STN-DBS we e
s a is ically significan o o al PDQ-39 sco e (P≤0.001), mobil-
i y, daily li e ac i i ies, and bodily discom o .
Discussion
To ou knowledge, his is he fi s p ospec i e s udy ha com-
pa es APO and subsequen STN-DBS in he same pa ien . Ou
uni p e iously published he da a o 18 pa ien s ea ed wi h
APO be o e he STN-DBS su ge y.
10
In ha scena io, we had
obse ed ha , despi e no eaching he e ec i eness o
STN-DBS, APO had achie ed adequa e con ol o he disease
when he con en ional o al/ ansde mal medica ion was no lon-
ge e ec i e. In addi ion o he lack o andomized and p ospec-
i e s udies compa ing hese 2 ea men s, he da a de i ed om
ecen s udies
1,4,5,7,11
e eal ha pa ien s ea ed wi h APO a e
usually in a much mo e ad anced s age han STN-DBS pa ien s.
APO and SNT-DBS bo h esul ed in subs an ial mo o
imp o emen s in his s udy, educing daily o ime and he com-
plica ions esul ing om con en ional medica ion. In bo h cases,
he e ec o SNT-DBS was supe io o APO, no ably in he case
o UPDRS IV sco e. Dyskinesia, which imp o ed d ama ically
FIG 2. Change in non-mo o sco es ela i e o baseline o each ea men .
MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338 1221
FERN
ANDEZ-PAJARÍN G. ET AL. RESEARCH ARTICLE
a e STN-DBS su ge y, did no wo sen wi h APO, despi e he
LEDD inc ease. The APO e ec on dyskinesia emains con o-
e sial. S udies ha e shown ei he imp o emen
6,18–20
o no
change.
4,7,9,10,12
A compensa o y hype sensi i i y o he D1
ecep o s in PD has been linked o dyskinesia,
21,22
bu i migh
be balanced by a dec ease in he dopamine gic pulsa ile
s imulus.
17
UPDRS III sco e a e STN-DBS su ge y, e alua ed in he
ON s im/on meds si ua ion, was significan ly lowe compa ed o
APO. The mos comp ehensi e s udies o STN-DBS also dem-
ons a e his imp o emen in compa ison o con en ional medi-
ca ion.
23,24
This is no easy o explain. On one hand, he e ec
o STN-DBS on emo usually exceeds ha o medica ion, and
in ac , se e e emo is a common indica ion o su ge y.
25
On
he o he hand, i is belie ed ha le odopa has a g ea e e ec
on dis al akinesia.
26,27
This opinion is s ill con o e sial.
28
Ne e -
heless, wha is consis en h oughou hese s udies is ha he
ON s im/on meds si ua ion ob ains he bes esul s.
STN-DBS esul ed in a subs an ial o e all e ec on non-
mo o symp oms, measu ed by he NMSS scale, whe eas he
impac o APO was mo e modes . The e was a la ge di e ence
o he o al sco e, howe e , despi e sco es o indi idual
domains we e lowe a e STN-DBS—excep o u ina y
symp oms—only he sleep/ a igue domain showed di e ences
be ween ea men s. In ou s udy coho , he non-mo o symp-
oms bu den was low. Pa ien s we e selec ed o STN-DBS, and
he e o e, we e in an ea ly ad anced s age, so ca dio ascula o
cogni i e i ems we e sca cely ep esen ed. Compa ed o baseline,
STN-DBS was mo e beneficial o dep essi e mood, whe eas
APO was mo e beneficial o apa hy, al hough he di e ences
be ween ea men s we e no significan . In ou s udy, dep ession
and apa hy sco es a e he STN-DBS we e simila o hose
ound in o he s udies.
23,24
Sleep quali y significan ly imp o ed
wi h bo h ea men s, al hough STN-DBS showed g ea e bene-
fi han APO. In addi ion o changes in sleep s uc u e, in aPD,
insomnia eflec s a p olonged o pe iods, because o insu ficien
dopamine gic eplacemen du ing he nigh .
29
The imp o emen
in sleep quali y is mainly d i en by he noc u nal mo o con ol
achie ed wi h STN-DBS, whe eas he e ec o APO is ocused
on waking hou s.
O e all cogni ion did no change wi h APO o STN-DBS.
Phone ic fluency significan ly wo sened a e he STN-DBS
compa ed o APO. I was also educed ela i e o baseline e alu-
a ion, close o s a is ical significance. In almos all STN-DBS
s udies, execu i e unc ion assessmen shows a mild wo sening
a e su ge y, which is mo e p onounced in he case o phone ic
fluency. This wo sening could be ela ed o he s imula ion o
he sub halamic nucleus i sel .
30,31
Ne e heless, se e al ac o s
FIG 3. Change in pa ien ’s quali y o li e (PDQ-39 and i s domains) ela i e o baseline o each ea men .
1222 MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338
RESEARCH ARTICLE LACK OF STUDIES COMPARING APO AND STN-DBS
can play a ole, such as cu en di usion o non-mo o egions o
he sub halamic nucleus
32
o ce ain ajec o ies o he elec-
odes.
33
These ac o s ha e no been adequa ely e alua ed.
The pa ien ’s quali y o li e imp o ed subs an ially a e bo h
APO and STN-DBS, bu he g ea es imp o emen occu ed
a e STN-DBS. Fo all PDQ-39 domains, sco es we e lowe
a e STN-DBS ea men .
Finally, 4 pa ien s wi hd ew om he s udy, bu only 2 we e
ela ed o APO. One pa ien s opped APO by his own decision
a e a ew weeks, and ano he pa ien de eloped a psycho ic
episode ha equi ed hospi al admission. Al hough APO was
s opped, he pa ien s’symp oms emained unchanged, so STN-
DBS was no longe a ea men op ion. None o 3 pa ien s wi h
a p e ious medical his o y o impulse con ol diso de de eloped
hese symp oms. Only 1 pa ien expe ienced mild hype sexuali y
and hobbyism wi h APO.
Ou s udy has some limi a ions. The sample size was small, how-
e e , i is b oadly simila o some APO p ospec i e s udies, pa icu-
la ly conside ing ha all pa ien s in ou s udy also unde wen STN-
DBS su ge y. Ou s udy design a oided possible biases om he
pa ien ’sp ofile. Howe e , he APO phase may be nega i ely
influenced by some pa ien ’s p e ious nega i e opinion o APO,
which was used only as a b idge he apy be o e he desi ed STN-
DBS. In addi ion, he open-label assessmen s o ou comes could
ha e inc eased he di e ence be ween he ea men s. The e olu-
ion o he disease is ine i able, bu in he con ex o aPD, his
would be minimized o e a 6-mon h in e al and, a he same ime,
clinical s abili y would be gua an eed wi h each ea men .
In conclusion, APO and STN-DBS bo h ma kedly imp o ed
mo o and non-mo o symp oms and quali y o li e compa ed o
baseline in aPD pa ien s. Cogni ion was unchanged by ei he
ea men . O e all, STN-DBS was he mos e ec i e ea men ,
howe e , in he se ing o p ominen pu e dopamine gic fluc ua-
ions, APO had a e y obus mo o benefi , a supe io o p e-
iously desc ibed. As no ed abo e, mos pa ien s ea ed wi h
APO a e in a mo e ad anced phase han hose ea ed wi h
STN-DBS. Fo non-mo o symp oms, al hough beneficial, APO
e ec was mo e modes han p e iously epo ed. We canno
discoun ha his migh be ela ed o ea ing pa ien s wi h a less
ad anced disease in his s udy.
We would like o highligh he need o be p oac i e in he
ea men o aPD, and o selec and adminis e an app op ia e
ea men . De ice-aided he apies, bo h su ge y and in usion, a e
able o p o ide a subs an ial imp o emen in aPD pa ien s’symp-
oms and should no be delayed. A pa ien who canno unde go
STN-DBS su ge y immedia ely should be on an e ec i e ea -
men , such as APO, du ing he wai ing ime.
Au ho Roles
(1) Resea ch p ojec : A. Concep ion, B. O ganiza ion,
C. Execu ion; (2) S a is ical Analysis: A. Design, B. Execu ion,
C. Re iew and C i ique; (3) Manusc ip P epa a ion: A. W i ing
o he Fi s D a , B. Re iew and C i ique.
G.F.P.: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B
A.S.: 1A, 1B, 1C, 2A, 2C, 3A, 3B
B.A.: 1C, 3B
I.J.M.: 1C, 2A, 2C, 3B
M.G.: 1C
E.A.: 1C
J.L.R.: 1C
A.C.: 1C, 3B
Disclosu es
E hical Compliance S a emen : The s udy was ca ied ou
ollowing he Decla a ion o Helsinki o he Wo ld Medical
Associa ion and app o ed by he Resea ch E hics Commi ee o
San iago (P ojec iden ifica ion code 2018/339). In o med con-
sen was ob ained om each pa ien o om hei ela i es, a e
a ull explana ion o he p ocedu es. We confi m ha we ha e
ead he Jou nal’s posi ion on issues in ol ed in e hical publica-
ion and a fi m ha his wo k is consis en wi h hose guidelines.
Funding Sou ces and Conflic o In e es : No specific
unding was ecei ed o his wo k. The au ho s decla e ha
he e a e no conflic s o in e es ela ed o his wo k.
Financial Disclosu es o P e ious 12 Mon hs: G.F.P. has
ecei ed hono a ia om I al a maco and Zambon and sponso ship
om I al a maco and Bos on Scien ific. A.S. has ecei ed hono a ia
om B i annia and E e Pha ma and sponso ship om I al a maco
and Bos on Scien ific. B.A. has ecei ed hono a ia and sponso ship
om AbbVie. M.G. has ecei ed sponso ship om Bos on Scien-
ific. J.L.R. has ecei ed g an s om Ins i u o de Salud Ca los III.
I.J.M., E.A., and A.C. ha e no disclosu es. ■
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1224 MOVEMENT DISORDERS CLINICAL PRACTICE 2021; 8(8): 1216–1224. doi: 10.1002/mdc3.13338
RESEARCH ARTICLE LACK OF STUDIES COMPARING APO AND STN-DBS
