Ci a ion: López-Gómez, J.J.; Izaola-
Jau egui, O.; Almansa-Ruiz, L.;
Jiménez-Sahagún, R.; P imo-Ma ín,
D.; Ped aza-Hueso, M.I.; Ramos-
Bachille , B.; González-Gu ié ez, J.;
De Luis-Román, D. Use o Muscle
Ul asonog aphy in Mo pho unc ional
Assessmen o Amyo ophic La e al
Scle osis (ALS). Nu ien s 2024,16,
1021. h ps://doi.o g/10.3390/
nu16071021
Academic Edi o : Robe o Iacone
Recei ed: 10 Ma ch 2024
Re ised: 28 Ma ch 2024
Accep ed: 29 Ma ch 2024
Published: 31 Ma ch 2024
Copy igh : © 2024 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
nu ien s
A icle
Use o Muscle Ul asonog aphy in Mo pho unc ional
Assessmen o Amyo ophic La e al Scle osis (ALS)
Juan J. López-Gómez 1,2,* , Ola z Izaola-Jau egui 1,2, Lau a Almansa-Ruiz 3, Rebeca Jiménez-Sahagún1,2,
Da id P imo-Ma ín1,2 , Ma ía I. Ped aza-Hueso 4, Bea iz Ramos-Bachille 1,2, Jaime González-Gu ié ez 1,2
and Daniel De Luis-Román1,2
1Se icio de Endoc inología y Nu ición, Hospi al Clínico Uni e si a io de Valladolid, 47003 Valladolid, Spain;
[email p o ec ed] (B.R.-B.)
2Cen o de In es igación en Endoc inología y Nu ición, Uni e sidad de Valladolid, 47003 Valladolid, Spain
3Facul ad de Medicina, Uni e sidad de Valladolid, 47003 Valladolid, Spain
4Se icio de Neu ología, Hospi al Clínico Uni e si a io de Valladolid, 47003 Valladolid, Spain
*Co espondence: [email p o ec ed]
Abs ac : Amyo ophic la e al scle osis (ALS) is a p og essi e disease wi h a high p e alence o
malnu i ion ha can in luence p ognosis. The main objec i e o his s udy is o compa e he alidi y
o muscle ul asonog aphy in he diagnosis o malnu i ion and he p ognosis o pa ien s wi h ALS.
Me hods: This is a p ospec i e obse a ional s udy ha analyzes he nu i ional s a us o pa ien s a
he beginning o nu i ional moni o ing. The mo pho unc ional assessmen included he examina ion
o an h opome ic a iables such as weigh , heigh , body mass index (BMI), a m ci cum e ence, and
cal ci cum e ence. Addi ionally, elec ical bioimpedanciome y (BIA) was used o measu e elec ical
pa ame e s and es ima e o he ele an me ics. Muscle ul asonog aphy
®
(quad iceps ec us emo is
(QRF)) assessed muscle mass pa ame e s, including muscle a ea index (MARAI), an e opos e io
diame e o he QRF (Y-axis) (cm), ans e se diame e o he QRF (X-axis) (cm), and he sum o he
quad iceps hickness (RF+VI) (cm), as well as muscle quali y pa ame e s such as echogenici y and he
Y–X index. Resul s: A o al o 37 pa ien s diagnosed wi h amyo ophic la e al scle osis (ALS) we e
included in his s udy. O hese pa ien s, 51.4% we e men. The mean age was 64.27 (12.59) yea s. A
o al o 54.1% o he pa ien s had a bulba onse o amyo ophic la e al scle osis, and 45.9% had spinal
onse . The pe cen age o subjec s wi h malnu i ion diagnosed by he Global Leade ship Ini ia i e on
Malnu i ion (GLIM) c i e ia was 45.9% o pa ien s. The e was a di ec co ela ion be ween muscle
mass pa ame e s assessed by muscle ul asonog aphy (RF+VI) and ac i e mass ma ke s measu ed
by bioimpedanciome y (body cellula mass index (BCMI) ( = 0.62;
p< 0.01)
, a - ee mass index
(FFMI) ( = 0.75; p< 0.01), and appendicula skele al mass index (ASMI)
( = 0.69; p< 0.01
)). The e
was a di ec co ela ion be ween echogenici y and esis ance ( = 0.44; p= 0.02), as well as be ween
he a - ee mass index and he Y–X index ( = 0.36; p= 0.14). Addi ionally, he e was a nega i e
co ela ion be ween echogenici y and BCMI ( =
−
0.46; p< 0.01) and ASMI ( = 0.34; p= 0.06).
Pa ien s wi h low quad iceps hickness (male < 2.49 cm; emale < 1.84 cm) showed an inc eased isk
o hospi al admission adjus ed by age, sex, and p esence o dysphagia (OR: 7.84 (CI 95%: 1.09–56.07);
p- alue = 0.04)
, and pa ien s wi h low-quali y mass (Y–X index < 0.35) had a highe isk o hospi al
admission adjus ed by age, sex, and p esence o dysphagia (OR: 19.83 (CI 95%: 1.77–222.46); p- alue
= 0.02). Conclusions: In pa ien s wi h ALS, ul asonog aphy echogenici y was in e sely ela ed o
BCMI, FFMI, and ASMI, and he Y–X index was di ec ly ela ed o FFMI. The lowes qua iles o
quad iceps hickness and Y–X index a e isk ac o s o hospi al admission.
Keywo ds: muscle ul asonog aphy; amyo ophic la e al scle osis; mo pho unc ional assessmen ;
bioimpedanciome y
Nu ien s 2024,16, 1021. h ps://doi.o g/10.3390/nu16071021 h ps://www.mdpi.com/jou nal/nu ien s
Nu ien s 2024,16, 1021 2 o 13
1. In oduc ion
Mo o neu on diseases a e a g oup o ch onic, p og essi e neu odegene a i e diso de s
ha a ec he cen al ne ous sys em. The mos equen disease is amyo ophic la e al
scle osis (ALS), wi h an incidence o 2.8 new cases pe 100,000 people in Eu ope and a
p e alence o 5.4 cases pe 100,000 people [
1
]. This disease can p esen symp oms such
as muscle weakness, especially in he a ms and legs, al e a ions in speech, swallowing,
o b ea hing, as well as emo ional p oblems [
2
]. These ci cums ances can lead o an
inc eased isk o malnu i ion a diagnosis in hese pa ien s, which can be obse ed in up
o 46% o pa ien s [
3
]. Malnu i ion in pa ien s wi h ALS can lead o an inc eased isk
o mo ali y and complica ions. I has been obse ed ha malnu i ion de e mined by
subjec i e global assessmen (SGA) was an independen isk ac o o mo ali y (HR: 4.6
(CI 95% 1.5–13.9)) [
3
]. The e o e, medical nu i ional he apy (MNT) plays an impo an
ole in he managemen o hese diseases since malnu i ion, weigh loss, and impai ed
muscle unc ion can a ec he quali y o li e o pa ien s wi h ALS [4].
Nu i ional e alua ion is an impo an pa o he diagnosis and moni o ing o MNT.
In pa ien s wi h ALS, nu i ional assessmen is complex and usually limi ed o an h o-
pome ic pa ame e s. I has been p oposed o moni o nu i ional ea men in ela ion
o changes in body weigh and body mass index [
5
]. Howe e , hese measu emen s can
o en be in e e ed wi h by mul iple issues, such as unc ional impai men , and hey do no
adequa ely e lec changes in he pa ien ’s body composi ion.
In body composi ion assessmen , some me hods a e limi ed o esea ch due o hei
di icul y in accessing and pe o ming (ai -displacemen ple hysmog aphy,
in i o
neu on
ac i a ion analysis, iso ope dilu ion, and o al body po assium coun ). The e a e also o he
echniques, such as compu ed omog aphy (CT) scanning and DEXA, bu hey a e no
commonly used due o echnical di icul ies. Finally, he e a e me hods, such as bioelec ical
impedanciome y and classical an h opome y, used in ou ine clinical p ac ice due o hei
easy implemen a ion, accessibili y in consul a ion, and ep oducibili y [
6
]. The use o body
composi ion assessmen echniques associa ed wi h es s ha e alua e unc ionali y in
nu i ional assessmen gi es ise o a new concep : he mo pho unc ional assessmen o
nu i ional assessmen [7].
In his con ex , he use o muscle ul asonog aphy has p o en o be a new dynamic
al e na i e o he quan i a i e and quali a i e assessmen o muscle [
8
]. Ul asonog aphy
has become a use ul ool o nu i ional assessmen due o i s abili y o de e mine he dep h
o subcu aneous a and lean body mass in a non-in asi e manne . Simple equipmen
is used o pe o m his es , and wi h skilled hands, i can ake li le ime. S udies ha e
shown ha ul asonog aphy has adequa e eliabili y and alidi y o he assessmen o
nu i ional s a us [
9
]. The e o e, muscle ul asonog aphy may be a p omising echnique
in hese pa ien s since i quan i ies changes in muscle s uc u es du ing malnu i ion and
can p o ide in o ma ion on unc ional changes. On he o he hand, i is simple and can be
pe o med in he consul a ion o bedside, a oiding unnecessa y pa ien a el.
In pa ien s wi h ALS, he assessmen o body composi ion is complex due o he
echnical di icul y in ca ying i ou due o he mobili y and a ailabili y o he pa ien .
Fu he mo e, he exis ing e idence is sca ce due o he low p e alence o he disease.
Nu i ional ul asonog aphy can be a complemen a y ool o he diagnosis and moni o ing
o malnu i ion. Howe e , he e a e some limi a ions, such as clea measu emen c i e ia
and he choice o he mos app op ia e muscle g oup. A alida ion o his es is equi ed
in di e en pa hologies wi h he es ablishmen o no mali y alues and he compa ison
wi h o he me hods wi h mo e expe ience and e idence [7].
The main objec i e o his s udy is o compa e he use ulness o muscle ul asonog a-
phy in he diagnosis o malnu i ion wi h espec o common echniques such as handg ip
s eng h and impedanciome y in pa ien s wi h ALS. Ou hypo hesis is ha ul asonog a-
phy muscle quan i y measu es ( ec us emo is (RF) hickness and ec us emo is + as us
in e medius (RF+VI) hickness) and quali y measu es (Y–X index and echogenici y) a e co -
ela ed wi h body composi ion measu ed by impedanciome y and handg ip s eng h and
Nu ien s 2024,16, 1021 3 o 13
ha a lowe RF+VI and highe echogenici y a e associa ed wi h a g ea e isk o hospi al
admission and dea h.
2. Ma e ials and Me hods
2.1. Design
This is an open, p ospec i e obse a ional s udy ha analyzes he nu i ional s a us o
pa ien s a he beginning o nu i ional moni o ing. Once he pa ien s signed he in o med
consen and we e included in his s udy, an anamnesis was conduc ed o collec da a on
a ilia ion, pe sonal his o y, e olu ion o he disease, and nu i ional his o y. In addi ion,
an h opome y, bioimpedanciome y, handg ip s eng h, and muscle ul asonog aphy
e alua ions we e pe o med. A eco d o medical nu i ional he apy was aken bo h
du ing he ini ial consul a ion and he pa ien ’s ollow-up. The esul s o all pa ame e s
we e eco ded in he same isi .
This s udy was conduc ed be ween Janua y 2021 and Sep embe 2022 in pa ien s
e e ed o he ou pa ien Clinical Nu i ion Clinic a he Uni e si y Clinical Hospi al o
Valladolid. The pa ien was ollowed up acco ding o eal-wo ld clinical p ac ice, and he
da a collec ion o e olu ion pa ame e s was closed in Janua y 2023.
2.2. S udy Subjec s
The inclusion c i e ia we e pa ien s wi h amyo ophic la e al scle osis who we e
o e 18 yea s old. The exclusion c i e ia we e he pa ien ’s inabili y o ully ambula e,
neu odegene a i e disease o he han ALS, decompensa ed li e pa hology, ch onic kidney
disease s age IV o highe , o ailu e o sign he in o med consen by he pa ien .
This s udy complied wi h he guidelines o human esea ch es ablished in he Decla-
a ion o Helsinki. This s udy was app o ed by he Medical Resea ch E hics Commi ee
(CEIm) o he Heal h A ea o Valladolid Eas wi h he code 22-2910; a e ha , he da a
collec ion p ocess began. All pa ien s had signed he in o med consen p io o inclusion in
his s udy.
2.3. Va iables
The a iables collec ed we e classi ied in o clinical a iables, mo pho unc ional as-
sessmen (an h opome ic a iables, body composi ion a iables, and unc ional a iables),
and ou come a iables. Clinical a iables included age (yea s), sex (male/ emale), and
ype o amyo ophic la e al scle osis (spinal/bulba ).
The mo pho unc ional assessmen included he ollowing:
-
An h opome ic a iables: usual weigh (kg), ac ual weigh (kg), heigh (m), body
mass index (ac ual weigh /heigh x heigh (kg/m
2
)), a m ci cum e ence (cm), and cal
ci cum e ence (cm).
-
Elec ical bioimpedanciome y (BIA) was pe o med wi h a bioimpedanciome e (BIA
101 Anni e sa y; EFG Ake n). The BIA was pe o med be ween 8:00 and 9:15, a e an
o e nigh as and a e a ime o 15 min in he supine posi ion. The BIA measu ed he
ollowing aw elec ical da a: esis ance (ohm), eac ance (ohm), and phase angle (º).
The ollowing body composi ion pa ame e s we e es ima ed using alida ed o mulas
in Bodyg am
®
so wa e, h ps://www.ake n.com/en/p oduc s-and-solu ions/da a-
analysis-so wa e/bodyg am-dashboa d/ (Access da a: 29 Ma ch 2024) (EFG, Ake n,
Pisa, I aly): a mass index (FMI) (kg/m
2
), a - ee mass index (FFMI) (kg/m
2
), muscle
mass index (MMI) (kg/m
2
), and body cell mass index (BCMI) (kg/m
2
). Appendicula
skele al muscle mass index (ASMI) (kg/m2) was measu ed by Se gi’s o mula [10].
-
Muscle ul asonog aphy (quad iceps ec us emo is (QRF) and as us in e medius
(VI)) o he dominan lowe ex emi y was ca ied ou wi h a 10–12 MHz p obe and a
mul i equency linea ma ix (Mind ay Z60, Mad id, Spain). The measu emen s o
ul asonog aphy we e made wi h he pa ien in a supine posi ion [
8
]. The ollowing
muscle quan i y pa ame e s we e measu ed: muscle a ea (cm
2
), muscle a ea index
(muscle a ea/heigh
×
heigh ) (cm
2
/m
2
), an e opos e io diame e o he QRF (Y-axis)
Nu ien s 2024,16, 1021 4 o 13
(cm), ans e se diame e o he QRF (X-axis) (cm), and he sum o he an e opos e io
diame e s o QRF and he as us in e medius (RF+VI) (cm) [11].
The ollowing muscle quali y pa ame e s we e also de e mined: Y–X index ( ela ion
o he an e opos e io diame e (Y-axis) o he ans e se axis (X-axis) o he QRF). On
he o he hand, he muscula echogenici y o he QRF was also de e mined, conside ing
he ans e sal sec ion o he muscle as a egion o in e es (ROI) as he a ea o QRF. The
g ayscale anges om 0 (black) o 255 (whi e). The alue is shown as a pe cen age (%) wi h
espec o he maximum (255) [
11
]. The Image J
®
p og am e sion 1.54 (Na ional Ins i u es
o Heal h NIH, Be hesda, MD, USA) was used o de e mine echogenici y; his p og am is a
me hod o ea adiological images de eloped by he Na ional Heal h Ins i u e (NIH) [
12
].
We conside ed muscle mass (RF+VI) and muscle quali y (Y–X index) pa ame e s as
dicho omic a iables. These a iables we e plan ed as low and high muscle mass: low
RF+VI (male < 2.49 cm; emale < 1.84 cm) and low Y–X index (<0.35). These alues a e
ob ained by he median o alues in he sample s a i ied by sex.
The diagnosis o malnu i ion was made using he Global Leade ship Ini ia i e on
Malnu i ion (GLIM) c i e ia [
13
] h ough compliance wi h an e iological c i e ion and a
pheno ypic c i e ion. A 3-day nu i ional su ey was conduc ed o e alua e in ake, and
he pa ien ’s nu i ional equi emen s we e e alua ed using he Ha is–Benedic equa-
ion [
14
]. The loss o muscle mass was measu ed wi h ASMI es ima ed by bioelec ical
impedanciome y (low muscle mass: 7 kg/m2in men and 5.5 kg/m2in women) [15].
The ou come a iables we e he admission o a hospi al wa d o he dea h o he
pa ien du ing he e alua ion pe iod ( om inclusion in his s udy o he end o da a
collec ion). These a iables we e collec ed wi h da a linkage o he egional elec onic clinic
his o y egis y.
The a iables s udied as po en ial con ounde s we e age, sex, clinical onse o amy-
o ophic la e al scle osis, ime om i s symp oms o diagnosis, and ime om diagnosis
o e alua ion in he Clinical Nu i ion Uni .
2.4. Da a Analysis
S a is ical analysis was pe o med wi h he SPSS 15.0 package (SPSS Inc., Chicago, IL,
USA), o icially licensed by he Uni e si y o Valladolid. A no mali y analysis o con inuous
a iables was pe o med using he Kolmogo o –Smi no es . No mal con inuous a iables
a e exp essed as mean (s anda d de ia ion) and non-no mal con inuous a iables as median
(in e qua ile ange). The quali a i e a iables a e ep esen ed wi h he numbe and
pe cen age wi h espec o he o al.
Di e ences be ween pa ame ic con inuous a iables we e analyzed wi h he unpai ed
S uden ’s - es , and di e ences be ween non-pa ame ic a iables we e analyzed wi h he
Mann–Whi ney U es . A co ela ion analysis was pe o med o e alua e he ela ionship
be ween he quan i a i e a iables. A bina y logis ic eg ession was pe o med in a mul-
i a ia e analysis o e alua e he ela ionship o he a iables wi h he p ognosis, and a
su i al analysis was conduc ed using log- ank and Kaplan–Meie cu es. Quali a i e
a iables will be exp essed as pe cen ages (%) and analyzed wi h he chi-squa ed es (wi h
Fishe and Ya es co ec ion when i is necessa y).
3. Resul s
3.1. Sample Desc ip ion
A o al o 37 pa ien s diagnosed wi h amyo ophic la e al scle osis (ALS) we e included
in his s udy. O hese pa ien s, 51.4% we e men. The mean age was 64.27 (12.59) yea s.
A o al o 54.1% o he pa ien s had a bulba onse o amyo ophic la e al scle osis, and
45.9% had spinal onse . The median ime be ween diagnosis o ALS and mo pho unc ional
assessmen was 10.5 (4–30) mon hs.
All pa ien s wi h ALS ollowed in he Clinical Nu i ion Uni in he s udy pe iod we e
e alua ed. All pa ien s ag eed o pa icipa e, and he e was no abandonmen . The loss
Nu ien s 2024,16, 1021 5 o 13
o ollow-up was caused by he dea h o pa ien s. Fi e pa ien s (13.5%) we e unable o
unde go he muscula ul asonog aphy due o hei clinical s a e.
The mo pho unc ional assessmen a iables a e shown in Table 1.
Table 1. Mo pho unc ional assessmen a iables and di e ences be ween sexes.
To al Men Women p-Value
An h opome y
BMI (kg/m2)26.52 (4.51) 27.46 (4.54) 25.45 (4.37) 0.20
%weigh loss 5.29 (6.07) 4.74 (4.70) 6.06 (7.76) 0.59
A m ci cum e ence (cm) 27.09 (2.27) 27.58 (2.11) 26.56 (2.37) 0.20
Cal ci cum e ence (cm) 34.08 (3.91) 34.53 (4.08) 33.59 (3.78) 0.49
Bioelec ical Impedanciome y
Resis ance (ohm) 575.24 (112.07) 508.33 (64.33) 655.53 (104.98) <0.01
Reac ance (ohm) 50.64 (15.41) 44.06 (10.57) 58.53 (16.88) <0.01
Phase angle (◦) 5.13 (1.50) 5.02 (1.25) 5.26 (1.79) 0.66
ASMM (kg) 17.57 (4.00) 20.48 (2.42) 14.07 (2.36) <0.01
ASMI (kg/m2)6.53 (1.03) 7.12 (0.74) 5.82 (0.89) <0.01
FFM (kg) 46.99 (10.07) 54.48 (6.75) 38.01 (4.23) <0.01
FFMI (kg/m2)17.45 (2.15) 18.89 (1.57) 15.72 (1.33) <0.01
BCM (kg) 22.82 (6.99) 26.31 (6.41) 18.62 (5.24) <0.01
BCMI (kg/m2)7.97 (2.08) 8.56 (1.91) 7.27 (2.12) 0.08
FM (kg) 22.09 (8.26) 21.63 (7.61) 22.65 (9.21) 0.73
FMI (kg/m2)8.38 (3.25) 7.61 (3.00) 9.31 (3.40) 0.14
Muscle Ul asonog aphy
MARFI (cm2/m2)1.29 (0.51) 1.44 (0.57) 1.14 (0.41) 0.09
Y-axis (cm) 1.17 (0.35) 1.29 (0.38) 1.03 (0.25) 0.03
X-axis (cm) 3.27 (0.63) 3.47 (0.59) 3.05 (0.61) 0.06
RF+VI (cm) 2.18 (0.68) 2.49 (0.66) 1.84 (0.54) <0.01
SCAT (cm) 1.07 (0.72) 0.59 (0.31) 1.37 (0.41) <0.01
Y–X index 0.36 (0.09) 0.37 (0.10) 0.34 (0.09) 0.41
Echogenici y (%) 61.77 (4.63) 61.67 (4.49) 61.86 (4.29) 0.91
MUSCLE STRENGTH
Handg ip s eng h (kg) 14.54 (9.67) 16.81 11.50 0.15
BMI, body mass index; ASMM, appendicula skele al muscle mass; ASMI, appendicula skele al mass index;
FFM, a - ee mass; FFMI, a - ee mass index; BCM, body cell mass; BCMI, body cell mass index; FM, a mass;
FMI, a mass index; MARFI, muscle a ea ec us emo is index (cm/m
2
). X, ans e sal ec us emo is axis; Y,
an e opos e io ec us emo is axis; RF+VI, ec us emo is + as us in e nal; SCAT, subcu aneous adipose issue.
3.2. Malnu i ion and Ul asonog aphy in ALS Pa ien s
The pe cen age o subjec s wi h malnu i ion diagnosed by GLIM c i e ia was 45.9%
o pa ien s. The e we e di e ences in muscle mass pa ame e s in ul asonog aphy bu no
in muscle quali y pa ame e s o a issue (Table 2).
Table 2. Di e ences in ul asonog aphy pa ame e s by diagnosis o malnu i ion.
Malnu i ion No Malnu i ion p-Value
Sex (male/ emale) 52.9%/47.1% 56.3%43.8% 0.72
MARFI (cm2/m2)1.13 (0.49) 1.46 (0.52) 0.08
Nu ien s 2024,16, 1021 6 o 13
Table 2. Con .
Malnu i ion No Malnu i ion p-Value
Y-axis (cm) 0.99 (0.32) 1.37 (0.27) <0.01
X-axis (cm) 3.24 (0.68) 3.33 (0.60) 0.69
RF+VI (cm) 1.81 (0.64) 2.61 (0.46) <0.01
SCAT (cm) 0.95 (0.45) 0.94 (0.63) 0.96
Y–X index 0.30 (0.06) 0.42 (0.09) <0.01
Echogenici y (%) 62.94 (4.87) 60.43 (4.29) 0.17
MARFI, muscle a ea ec us emo is index (cm/m
2
); X, ans e sal ec us emo is axis; Y, an e opos e io ec us
emo is axis; RF+VI, ec us emo is + as us in e nal; SCAT, subcu aneous adipose issue.
3.3. Ul asonog aphy and O he Body Composi ion Va iables in ALS Pa ien s
The e was a di ec co ela ion be ween BMI and Y–X index and be ween b achial
ci cum e ence and Y–X index. The e was a nega i e co ela ion be ween o al muscle mass
measu ed by ec us emo is and as us in e nal (RF+VI) and he pe cen age o weigh loss,
as well as be ween b achial ci cum e ence and echogenici y (Table 3).
Table 3. Co ela ion be ween ul asonog aphy and pa ame e s o an h opome y assessmen .
RF+VI MARFI Echogenici y Y–X Index
%WL = −0.42; p= 0.04 * = −0.15; p= 0.47 = 0.04; p= 0.85 = −0.37; p= 0.07
BMI (kg/m2) = 0.33; p= 0.06 = 0.05; p= 0.78 = −0.04; p= 0.83 = 0.40; p= 0.02 *
B aquial ci cum e ence (cm) = 0.34; p= 0.06 = 0.17; p= 0.36 = −0.43; p= 0.02 * = 0.37; p= 0.04 *
Cal ci cum e ence (cm) = 0.34; p= 0.06 = 0.26; p= 0.14 = −0.27; p= 0.16 = 0.18; p= 0.33
%WL, pe cen age weigh loss; MARFI, muscle a ea o ec us emo is index; RF+VI, ec us emo is + as us in e nal;
BMI, body mass index; * p< 0.05.
The e was a di ec co ela ion be ween ac i e mass ma ke s o bioimpedanciome y
(BCMI, FFMI, and ASMI) and muscle mass pa ame e s o nu i ional ul asonog aphy
(RF+VI and muscle a ea o ec us emo is index (MARFI)). I we measu e he quali y
pa ame e s o muscle ul asonog aphy (echogenici y and Y–X index), he e was a di ec
co ela ion be ween echogenici y and esis ance and be ween a - ee mass index and Y–X
index, and he e was a nega i e co ela ion be ween echogenici y and body cellula mass
index (BCMI) and appendicula skele al mass index (ASMI) (Table 4). The e we e no
co ela ions in he emale g oup due o he small sample size.
Table 4. Co ela ion be ween ul asonog aphy and pa ame e s o bioelec ical impedanciome y.
RF+VI SCAT MARFI Echogenici y Y–X Index
Resis ance (ohm)
=
−
0.59; p< 0.01 *
= 0.59; p< 0.01 * = −0.5; p< 0.01 * = 0.44; p= 0.02 * = −0.19; p= 0.28
Reac ance (ohm) = −0.06; p= 0.72 = 0.42; p= 0.02 * = 0.24; p= 0.19 = −0.07; p= 0.72 = −0.05; p= 0.76
Phase angle (◦) = 0.28; p= 0.11 = 0.04; p= 0.83 = 0.54; p< 0.01 * = −0.30; p= 0.10 = 0.07; p= 0.71
BCMI (kg/m2) = 0.62; p< 0.01 * = −0.26; p= 0.16 = 0.64; p< 0.01 *
=
−
0.46; p< 0.01 *
= 0.27; p= 0.14
FFMI (kg/m2) = 0.75; p< 0.01 *
=
−
0.53; p< 0.01 *
= 0.52; p< 0.01 *
=
−
0.38; p= 0.04 *
= 0.36; p< 0.01 *
FMI (kg/m2) = −0.04; p= 0.83 = 0.59; p< 0.01 * = −0.17; p= 0.34 = 0.25; p= 0.19 = 0.26; p= 0.15
ASMI (kg/m2) = 0.69; p< 0.01 *
=
−
0.42; p= 0.02 *
= 0.58; p< 0.01 *
=
−
0.40; p= 0.03 *
R = 0.34; p= 0.06
MARFI, muscle a ea o ec us emo is index; RF+VI, ec us emo is + as us in e nal; SCAT, subcu aneous adipose
issue; * p< 0.05.
The e was a di ec co ela ion be ween handg ip s eng h and Y–X index ( = 0.46;
p= 0.01)
; and RF+VI ( = 0.44; p= 0.02). The e was a nega i e co ela ion be ween handg ip
Nu ien s 2024,16, 1021 7 o 13
s eng h and echogenici y ( =
−
0.44; p= 0.02). The e we e no di e ences i i was s a i ied
by sex (Figu e 1).
Nu ien s 2024, 16, x FOR PEER REVIEW 7 o 13
Figu e 1. Rela ionships be ween muscle quali y a iables (echogenici y and Y–X index) and hand-
g ip s eng h.
3.4. Rela ionship be ween Mo pho unc ional Va iables and P ognosis
In ou sample, ou pa ien s (10.8%) died. The e we e 11 pa ien s (29.7%) who needed
admission o he hospi al o any eason. The causes o admission we e espi a o y ( ou
pa ien s (10.8%)), diges i e ( ou pa ien s (10.8%)), and o he causes ( wo pa ien s (8.1%).
The e we e no diffe ences in muscle mass pa ame e s o ul asonog aphy be ween
pa ien s who died and hose who did no . The pa ien s who died had mo e echogenici y
(Table 5). In pa ien s who we e admi ed o any eason, we obse ed low alues o muscle
mass pa ame e s (Y-axis, RF+VI) and diffe ences in muscle quali y pa ame e s (Y–X index
and echogenici y) (Table 5).
Table 5. Diffe ences in nu i ional ul asonog aphy in ela ion o he admission and dea h.
Dea h No Dea h p-Value Admission No Admission p-Value
Gende (M/F) 5.3/16.7 94.7/83.3 0.34 21.1/38.9 78.9/61.1 0.29
Nu i ional Ul asonog aphy
MARFI (cm
2
/m
2
) 1.28 (0.27) 1.29 (0.54) 0.97 1.07 (0.46) 1.40 (0.52) 0.08
Y-axis (cm) 1.03 (0.22) 1.19 (0.36) 0.39 0.95 (0.28) 1.27 (0.33) 0.01
X-axis (cm) 3.44 (0.36) 3.25 (0.66) 0.57 3.31 (0.61) 3.26 (0.65) 0.83
RF+VI (cm) 1.66 (0.30) 2.26 (0.69) 0.09 1.65 (0.44) 2.42 (0.64) <0.01
SCAT (cm) 0.97 (0.54) 0.96 (0.54) 0.97 1.01 (0.43) 0.94 (0.57) 0.71
Y–X index 0.29 (0.06) 0.37 (0.10) 0.19 0.28 (0.06) 0.39 (0.09) <0.01
Echogenici y (%) 66.92 (3.03) 61.28 (5.26) <0.05 64.90 (4.05) 60.59 (5.43) 0.03
M, male/F, emale; MARFI, muscle a ea o ec us emo is index; RF+VI, ec us emo is + as us in-
e nal; SCAT, subcu aneous adipose issue.
We conside ed muscle mass (RF+VI) and muscle quali y (Y–X index) pa ame e s as
dicho omic a iables (low RF+VI (male < 2.49 cm; emale < 1.84 cm); low Y–X index
(<0.35)). Pa ien s wi h low muscle (RF+VI) mass de e mined by ul asonog aphy showed
an inc eased isk o admission adjus ed by age, sex, and p esence o dysphagia (OR: 7.84
(CI 95%: 1.09–56.07); p- alue = 0.04), bu no associa ion was obse ed wi h he isk o dea h
(OR: 2.89 (CI 95%: 0.22–37.84); p- alue = 0.42). Pa ien s wi h low-quali y mass (Y–X index)
had a highe isk o admission adjus ed by age, sex, and p esence o dysphagia (OR: 19.83
(CI 95%: 1.77–222.46); p- alue = 0.02); howe e , hey did no ha e an inc eased isk o
dea h.
Kaplan–Meie cu es show an inc ease in admission in hose who had a lowe alue
o Y–X index (<0.35) (Figu e 2) and an inc ease in admission in hose who had a lowe
alue o RF+VI (male < 2.49; emale < 1.84) (Figu e 3). The e we e no diffe ences in su -
i al.
Figu e 1. Rela ionships be ween muscle quali y a iables (echogenici y and Y–X index) and handg ip
s eng h.
3.4. Rela ionship be ween Mo pho unc ional Va iables and P ognosis
In ou sample, ou pa ien s (10.8%) died. The e we e 11 pa ien s (29.7%) who needed
admission o he hospi al o any eason. The causes o admission we e espi a o y ( ou
pa ien s (10.8%)), diges i e ( ou pa ien s (10.8%)), and o he causes ( wo pa ien s (8.1%).
The e we e no di e ences in muscle mass pa ame e s o ul asonog aphy be ween
pa ien s who died and hose who did no . The pa ien s who died had mo e echogenici y
(Table 5). In pa ien s who we e admi ed o any eason, we obse ed low alues o muscle
mass pa ame e s (Y-axis, RF+VI) and di e ences in muscle quali y pa ame e s (Y–X index
and echogenici y) (Table 5).
Table 5. Di e ences in nu i ional ul asonog aphy in ela ion o he admission and dea h.
Dea h No Dea h p-Value Admission No Admission p-Value
Gende (M/F) 5.3/16.7 94.7/83.3 0.34 21.1/38.9 78.9/61.1 0.29
Nu i ional Ul asonog aphy
MARFI (cm2/m2)1.28 (0.27) 1.29 (0.54) 0.97 1.07 (0.46) 1.40 (0.52) 0.08
Y-axis (cm) 1.03 (0.22) 1.19 (0.36) 0.39 0.95 (0.28) 1.27 (0.33) 0.01
X-axis (cm) 3.44 (0.36) 3.25 (0.66) 0.57 3.31 (0.61) 3.26 (0.65) 0.83
RF+VI (cm) 1.66 (0.30) 2.26 (0.69) 0.09 1.65 (0.44) 2.42 (0.64) <0.01
SCAT (cm) 0.97 (0.54) 0.96 (0.54) 0.97 1.01 (0.43) 0.94 (0.57) 0.71
Y–X index 0.29 (0.06) 0.37 (0.10) 0.19 0.28 (0.06) 0.39 (0.09) <0.01
Echogenici y (%) 66.92 (3.03) 61.28 (5.26) <0.05 64.90 (4.05) 60.59 (5.43) 0.03
M, male/F, emale; MARFI, muscle a ea o ec us emo is index; RF+VI, ec us emo is + as us in e nal; SCAT,
subcu aneous adipose issue.
We conside ed muscle mass (RF+VI) and muscle quali y (Y–X index) pa ame e s
as dicho omic a iables (low RF+VI (male < 2.49 cm; emale < 1.84 cm); low Y–X index
(<0.35)). Pa ien s wi h low muscle (RF+VI) mass de e mined by ul asonog aphy showed
an inc eased isk o admission adjus ed by age, sex, and p esence o dysphagia (OR: 7.84
(CI 95%: 1.09–56.07); p- alue = 0.04), bu no associa ion was obse ed wi h he isk o
dea h (OR: 2.89 (CI 95%: 0.22–37.84); p- alue = 0.42). Pa ien s wi h low-quali y mass (Y–X
Nu ien s 2024,16, 1021 8 o 13
index) had a highe isk o admission adjus ed by age, sex, and p esence o dysphagia (OR:
19.83 (CI 95%: 1.77–222.46); p- alue = 0.02); howe e , hey did no ha e an inc eased isk
o dea h.
Kaplan–Meie cu es show an inc ease in admission in hose who had a lowe alue
o Y–X index (<0.35) (Figu e 2) and an inc ease in admission in hose who had a lowe alue
o RF+VI (male < 2.49; emale < 1.84) (Figu e 3). The e we e no di e ences in su i al.
Nu ien s 2024, 16, x FOR PEER REVIEW 8 o 13
Figu e 2. Kaplan–Meie cu es o su i al and isk o admission ela ed o Y–X index in uppe
qua ile pa ien s (Q1, Q2) (black) (16 pa ien s (43.2%)) s. lowe qua ile (Q3, Q4) pa ien s (g ey) (16
pa ien s (43.2%)).
Figu e 3. Kaplan–Meie cu es o su i al and isk o admission ela ed o ec us emo is and
as us in e nal (RF+VI) in uppe qua ile pa ien s (Q1, Q2) (black) (15 pa ien s (40.5%)) s. lowe
qua ile (Q3, Q4) pa ien s (g ey) (17 pa ien s (45.9%)).
4. Discussion
The pa ien s wi h amyo ophic la e al scle osis and malnu i ion had lowe alues o
an e opos e io diame e o muscle mass and lowe pa ame e s o muscle quali y in mus-
cle ul asonog aphy (MUS). The e was an in e se co ela ion be ween weigh loss and
muscle mass by MUS, and he e was a ela ion be ween body cellula mass index and
muscle mass and quali y pa ame e s measu ed by MUS. Low muscle mass and quali y
de e mined by MUS had an inc eased isk o admission o any cause.
Classical an h opome y in ALS is he mos common pa ame e o diagnose malnu-
i ion and o moni o he nu i ional ea men . A s udy om Li e al. showed ha pa ien s
wi h ALS had a lowe alue o body mass index (BMI) han con ols (ALS: 23.52 (3.11)
kg/m2; no ALS: 24.75 (3.34) kg/m2), and hey had a median weigh loss o 4.11% (−9.32–
0.56) [16]. In ou sample, BMI and weigh loss we e sligh ly highe han in his s udy. This
condi ion could be based on he ime om i s symp oms o diagnosis and e e al o he
Clinical Nu i ion Uni ; in ou case, his delay was 10.5 mon hs. The ea ly e e al o he
Clinical Nu i ion Uni has shown a dec ease in diagnosis o malnu i ion in hese pa ien s
[17]. A lowe body mass index is ela ed o poo su i al in pa ien s wi h ALS, and a BMI
in high anges can be p o ec i e o hese pa ien s, al hough weigh gain o loss depends
on he como bidi ies o pa ien s (nu i ional s a us, espi a o y unc ion, o pa ien s’
Figu e 2. Kaplan–Meie cu es o su i al and isk o admission ela ed o Y–X index in uppe
qua ile pa ien s (Q1, Q2) (black) (16 pa ien s (43.2%)) s. lowe qua ile (Q3, Q4) pa ien s (g ey)
(16 pa ien s (43.2%)).
Nu ien s 2024, 16, x FOR PEER REVIEW 8 o 13
Figu e 2. Kaplan–Meie cu es o su i al and isk o admission ela ed o Y–X index in uppe
qua ile pa ien s (Q1, Q2) (black) (16 pa ien s (43.2%)) s. lowe qua ile (Q3, Q4) pa ien s (g ey) (16
pa ien s (43.2%)).
Figu e 3. Kaplan–Meie cu es o su i al and isk o admission ela ed o ec us emo is and
as us in e nal (RF+VI) in uppe qua ile pa ien s (Q1, Q2) (black) (15 pa ien s (40.5%)) s. lowe
qua ile (Q3, Q4) pa ien s (g ey) (17 pa ien s (45.9%)).
4. Discussion
The pa ien s wi h amyo ophic la e al scle osis and malnu i ion had lowe alues o
an e opos e io diame e o muscle mass and lowe pa ame e s o muscle quali y in mus-
cle ul asonog aphy (MUS). The e was an in e se co ela ion be ween weigh loss and
muscle mass by MUS, and he e was a ela ion be ween body cellula mass index and
muscle mass and quali y pa ame e s measu ed by MUS. Low muscle mass and quali y
de e mined by MUS had an inc eased isk o admission o any cause.
Classical an h opome y in ALS is he mos common pa ame e o diagnose malnu-
i ion and o moni o he nu i ional ea men . A s udy om Li e al. showed ha pa ien s
wi h ALS had a lowe alue o body mass index (BMI) han con ols (ALS: 23.52 (3.11)
kg/m2; no ALS: 24.75 (3.34) kg/m2), and hey had a median weigh loss o 4.11% (−9.32–
0.56) [16]. In ou sample, BMI and weigh loss we e sligh ly highe han in his s udy. This
condi ion could be based on he ime om i s symp oms o diagnosis and e e al o he
Clinical Nu i ion Uni ; in ou case, his delay was 10.5 mon hs. The ea ly e e al o he
Clinical Nu i ion Uni has shown a dec ease in diagnosis o malnu i ion in hese pa ien s
[17]. A lowe body mass index is ela ed o poo su i al in pa ien s wi h ALS, and a BMI
in high anges can be p o ec i e o hese pa ien s, al hough weigh gain o loss depends
on he como bidi ies o pa ien s (nu i ional s a us, espi a o y unc ion, o pa ien s’
Figu e 3. Kaplan–Meie cu es o su i al and isk o admission ela ed o ec us emo is and as us
in e nal (RF+VI) in uppe qua ile pa ien s (Q1, Q2) (black) (15 pa ien s (40.5%)) s. lowe qua ile
(Q3, Q4) pa ien s (g ey) (17 pa ien s (45.9%)).
4. Discussion
The pa ien s wi h amyo ophic la e al scle osis and malnu i ion had lowe alues o
an e opos e io diame e o muscle mass and lowe pa ame e s o muscle quali y in muscle
ul asonog aphy (MUS). The e was an in e se co ela ion be ween weigh loss and muscle
Nu ien s 2024,16, 1021 9 o 13
mass by MUS, and he e was a ela ion be ween body cellula mass index and muscle mass
and quali y pa ame e s measu ed by MUS. Low muscle mass and quali y de e mined by
MUS had an inc eased isk o admission o any cause.
Classical an h opome y in ALS is he mos common pa ame e o diagnose mal-
nu i ion and o moni o he nu i ional ea men . A s udy om Li e al. showed ha
pa ien s wi h ALS had a lowe alue o body mass index (BMI) han con ols (ALS: 23.52
(3.11) kg/m
2
; no ALS: 24.75 (3.34) kg/m
2
), and hey had a median weigh loss o 4.11%
(
−
9.32–0.56) [
16
]. In ou sample, BMI and weigh loss we e sligh ly highe han in his
s udy. This condi ion could be based on he ime om i s symp oms o diagnosis and
e e al o he Clinical Nu i ion Uni ; in ou case, his delay was 10.5 mon hs. The ea ly
e e al o he Clinical Nu i ion Uni has shown a dec ease in diagnosis o malnu i ion in
hese pa ien s [
17
]. A lowe body mass index is ela ed o poo su i al in pa ien s wi h
ALS, and a BMI in high anges can be p o ec i e o hese pa ien s, al hough weigh gain o
loss depends on he como bidi ies o pa ien s (nu i ional s a us, espi a o y unc ion, o
pa ien s’ mobili y) [
18
]. Body composi ion and i s componen s could help us o selec he
be e nu i ional ea men o pa ien s.
In his s udy, body composi ion was assessed by bioelec ical impedanciome y and
muscle ul asonog aphy. Bioelec ical impedanciome y could be used o measu e body
composi ion h ough he es ima ion o body compa men s and body cellula i y unc ion
and hyd a ion h ough he elec ical pa ame e s. Pa ien s in ou sample had simila alues
o a - ee mass index (46.99 kg) o o he s udies wi h pa ien s wi h ALS and highe alues o
a mass index (22.09 kg); o example, compa ed o he Li e al. s udy (FFM: 47.83 kg; FMI:
17.42 kg) [
16
]. The phase angle was 5.02 (1.25)
◦
in men and 5.26 (1.79)
◦
in women; hese
alues we e lowe han hose om he gene al popula ion o indi iduals o eigh y o mo e
yea s (men: 5.3
◦
(IC95%: 4.5–6.0); women: 5.4
◦
(IC95%: 5.3–5.6)) [
19
]. These pa ame e s
show he changes in body composi ion ha could be masked by a no mal BMI, and hey
can be ela ed o he pa ien ’s p ognosis [
20
]. Func ional assessmen by handg ip s eng h
showed a signi ican dec ease in pa ien s wi h espec o he gene al popula ion [
21
] and
he sample wi h ALS om Musa o e al., which showed a mean handg ip s eng h o 22
(6.2) kg [22].
Quad iceps ul asonog aphy is a no el echnique o assess body composi ion (muscle
and a mass) in pa ien s a isk o malnu i ion o diagnose malnu i ion and sa copenia
and e alua e p ognosis. This echnique has no been well s udied in pa ien s wi h ALS,
bu i has been s udied in o he indi iduals a isk o malnu i ion as olde pa ien s a e
hip ac u e (quad iceps hickness (RF+VI): 2.22 (0.65) cm) [
23
] o pa ien s wi h s oke
wi h no mal nu i ional s a us (quad iceps hickness: pa aly ic, 3.32 cm; non-pa aly ic,
3.45 cm) [
24
]. The alues a e highe han hose o ou sample in ela ion o he muscle
p og ession o he disease. Values o muscle quali y canno be compa ed because hey
a e no measu ed, o he measu emen o echogenici y was no pe o med wi h he same
me hod we used.
The ESPEN guidelines in neu ology ecommend sc eening o malnu i ion (BMI
and weigh loss) a diagnosis and du ing he ollow-up [
5
]. In pa ien s wi h amyo ophic
la e al scle osis, body composi ion can be ela ed o hese low alues o BMI, especially in
pa ien s wi h <18.5 kg/m
2
; hese da a ha e been seen in he Ba one e al. s udy in pa ien s
who had unde gone pe cu aneous endoscopic gas os omy (PEG), which showed low
alues o body cellula mass and phase angle in unde weigh pa ien s [
25
]. This ela ion
canno be clea ly diagnosed in pa ien s wi h highe alues o BMI wi hou weigh loss.
In a p e ious s udy om ou g oup, 48.4% o pa ien s had malnu i ion acco ding o he
GLIM c i e ia, and 71% we e a isk o wi h malnu i ion acco ding o subjec i e global
assessmen (SGA); hese di e ences could be ela ed o he di icul assessmen o muscle
mass [
3
]. Muscle ul asonog aphy can be a use ul ool o assess malnu i ion in pa ien s
wi h no weigh loss o low BMI. This s udy showed lowe alues o muscle quan i y ( ec us
emo is hickness (Y-axis) and quad iceps hickness (RF+VI)) and lowe alues o muscle
quali y (Y–X index) wi hou changes in muscle a ea. The alues obse ed in pa ien s wi h
