Neuroscience & Medicine, 2013, 4, 140-144 Published Online September 2013 (
Assessment of Global Fatigue in Multiple Sclerosis: A
Spanish Language Version of the CGI and PGI Fatigue
Steven D. Targum1, Pablo Richly2, Vladimiro Sinay2,3, Daniel Goldberg-Zimring1, Facundo Manes2
1Clintara LLC, Boston, USA; 2Institute of Neurosciences at Favaloro University, Buenos Aires, Argentina; 3Institute of Cognitive
Neurology (INECO), Buenos Aires, Argentina.
Received May 13th, 2013; revised June 5th, 2013; accepted June 30th, 2013
Copyright © 2013 Steven D. Targum et al. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background: Fatigue is often identified as weakness following muscular exertion in patients with multiple sclerosis
(MS) but may be associated with other physical, cognitive and emotional symptoms. Objective: To develop a Spanish
language global impression of fatigue scales to evaluate symptoms of fatigue distinct from a particular disease. Methods:
50 ambulatory patients with MS attending a clinical institute in Argentina consented to participate in this reliability
study. The Spanish language version of the Clinical and Patient Global Impressions of Fatigue (CGI-S-F and PGI-S-F)
instruments were administered with the Massachusetts General Hospital cognitive and physical functioning question-
naire (MGH-CPFQ). Results: The CGI-S-F and PGI-S-F scores were well correlated with each other (p < 0.00005).
The mean CGI-S for fatigue was 2.28 ± 1.07 (SD) and PGI-S for fatigue was 2.30 ± 1.16 (p = ns) reflecting borderline
to mild perception of fatigue. The total MGH-CPFQ was 16.68 ± 4.32. Both CGI-S-F and PGI-S-F measures were cor-
related with the MGH-CPFQ: CGI-Severity (r = 0.632; p < 0.00005); PGI-Severity (r = 0.717; p < 0.00005). Conclu-
sions: In this study, the Spanish language versions of the CGI-S-F and PGI-S-F were reliable measures in an MS popu-
lation and can be useful and easily applied metrics in a busy clinical practice.
Keywords: Reliability; Multiple Sclerosis; Span ish; Global Assessment; Fatigue; Psychometrics; Treatment Response
1. Introduction
Approximately 50% to 60% of patients with Multiple
Sclerosis (MS) describe fatigue as one of their most
troubling symptoms, regardless of their disease course or
level of disability [1]. Fatigue symptoms are often pre-
sented as part of the symptom cluster of MS and have
been associated with regional cerebral brain atrophy in
these patients [2-4]. In MS, fatigue is often experienced
as weakness following muscular exertion (muscular fa-
tigue) and may precede the other evolving symptoms of
the disease [5]. In addition, Krupp and Elkins [6] found
that following continuous effort. MS patients performed
worse than control subjects on tests of visual and verbal
memory reflecting the impact of mental fatigue. MS pa-
tients with symptoms of fatigue may have greater work
and/or social performance difficulties and develop more
health problems than less fatigued patients [7,8]. In the
United States, the Social Security Administration recog-
nizes fatigue as a significant cause of unemployment
among people with MS [1].
The perception of fatigue may reflect different issues
including muscular weakness, lassitude, daytime sleepi-
ness, and/or the inability to focus [9-12]. Arnold [13]
delineated three distinct categories of fatigue related to
physical, cognitive, and emotional symptoms. The physi-
cal symptoms of fatigue include reduced activity, low
energy, tiredness, decreased physical endurance, increas-
ed effort to do physical tasks, general weakness, heavi-
ness, slowness or sluggishness, non-restorative sleep, and
sleepiness. Clearly, many patients with MS experience
these symptoms. However, addition al cogn itiv e and emo-
tional symptoms may also be associated symptoms of
fatigue. The cognitive symptoms include decreased con-
centration, decreased attention, decreased mental endur-
ance, and slowed thinking. The emotional (affective)
symptoms of fatigue include decreased motivation or
initiative (apathy), decreased interest, feeling overwhelmed,
feeling bored, aversion to effort, and feeling low. There-
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Assessment of Global Fatigue in Multiple Sclerosis: A Spanish Language Version of the CGI and PGI Fatigue Scales 141
fore, the subjective experience and differential descrip-
tion of fatigue symptoms may differ markedly between
In clinical practice, the evaluation and treatment of fa-
tigue may be complicated because it is often part of the
symptom cluster of MS, but can also be a symptom of
another disorder distinct from MS, or a side effect of the
medications used in the treatment of MS [10,11]. Fur-
thermore, adding additional medications to treat the iden-
tified symptoms of fatigue adds risk because of the pos-
sibility of inducing additional adverse symptoms as a
consequence of the intervention.
There are several instruments used to assess fatigue
including the 9-item self-report fatigue severity scale
(FSS), more comprehensive instruments examining vital-
ity and inertia, and performance-based measures specifi-
cally related to MS [5,14-16]. The 11-item fatigue ques-
tionnaire has been used in clinical trials to assess symp-
toms of fatigue, and the fatigue descriptive scale (FDS)
distinguishes fatigue at rest, during exercise, and wors-
ening with exertion [15-17]. Alternatively, Schwid and
colleagues [14] developed a quantitative, performance-
based measure of motor fatigue using three exercise pro-
tocols to distinguish fatigue from weakness in individual
muscles. Bakshi et al. [18] used the FSS and expanded
disability status scale (EDSS) [19] to study fatigue and
examine its relationship to depression and disability in 71
patients with multiple sclerosis. They reported that fa-
tigue was significantly correlated with depression in
these MS patients but was not associated with physical
disability as measured by th e EDSS.
Although useful in many instances, these aforemen-
tioned rating tools may be too time consuming for use in
a busy clinic or limited in scope to either the clinician’s
or subjects’ personal interpretation (e.g., FSS). In a busy
clinical setting, it would be helpful to have a simpler,
faster, yet reliable metric tool that can quickly assess
both the clinician’s and subject’s independent assessment
of fatigue symptoms. The Clinical Global Impression of
sev er ity sca le ( CGI -S) and related patient version (PGI-S)
are easily understood, single score metrics that can be
useful for this purpose [20,21]. Targum et al. [22] de-
veloped and validated a modified form of the CGI and
PGI severity scales to specifically assess the severity of
symptoms of fatigue in central nervous system (CNS)
populations. This modified CGI severity scale for fatigue
(CGI-S-F) provides specific “targeted” symptoms of fa-
tigue to facilitate specific symptom identification and
adds scoring anchors to improve the precision needed to
assess these symptoms [23]. For this study, we translated
these companion global assessment instruments into Spa-
nish and assessed the utility and reliability of the Span-
ish-version CGI-S-F and PGI-S-F in an ambulatory clini-
cal population of patients with MS.
2. Methods and Materials
2.1. Study Description and Subject Population
50 ambulatory patients with MS consented to participate
in the assessment of a newly developed, Spanish-lan-
guage global assessment scale for fatigue. All subjects
were attending the Institute of Cognitive Neurology
(INECO) located in Buenos Aires, Argentina, and were
randomly selected to participate in the study between
August 2011 and January 2012.
Clinicians administered the CGI-S-F scale to all sub-
jects who independently completed the PGI-S-F and the
Massachusetts General Hospital Cognitive and Physical
Functioning Scale (MGH-CPFQ). The MGH-CPFQ is a
7-item patient-rated instrument that has been shown to be
both valid and reliable in clinical trials [24].
2.2. Description of the Instruments
Both the CGI-S-F and PGI-S-F were designed as an-
chored instruments rated from 1 to 7 with increasing se-
verity of fatigue based upon the last 7 days [22]. The
descriptive anchors specifically focus on the identified
symptoms of fatigue. For instance, a global severity
score of 3 reflects mild fatigue whereas a severity of 4
reflects moderate fatigue. Both instruments include the
same generic, yet “targeted” descriptors of possible
symptoms that may be associated with fatigue in any
medical condition, including MS.
For instance, the PGI-S descriptor refers to the indi-
vidual (patient) completing the self-rating instrument and
reads as follows in English:
Symptoms of fatigue may include effects on your phys-
ical wellbeing (such as low or decreased energy, tired-
ness, decreased physical endurance or ability to sustain
physical activity, general weakness, heaviness in the
arms or legs, general heaviness, slowness or sluggish-
ness, sleepiness, increased effort with physical tasks) on
your mood state (decreased motivation or interest, de-
creased effort or initiative), or your cognitive abilities
(such as decreased concentration, decreased attention,
slowed thinking, reduced mental sharpness).
The English versions of the CGI-S-F and PGI-S-F
were translated into Spanish by one of the authors (FM)
and cross-validated back into English prior to its use in
the current study.
The MGH-CPFQ is a validated patient-rated scale
scored from 1-6 with increasing severity that individually
evaluates 7 distinct items: Motivation/Enthusiasm, Wake-
fulness/Alertness, Energy, Focus/Attention, Recall, Abil-
ity to find words, and Sharpness/Mental acuity.
2.3. Statistical Analyses
Statistical analyses included intra-class correlations, Pear-
Copyright © 2013 SciRes. NM
Assessment of Global Fatigue in Multiple Sclerosis: A Spanish Language Version of the CGI and PGI Fatigue Scales
son’s correlation coefficient, and paired t-test compari-
sons. The MGH-CPFQ was used to validate the PGI and
CGI fatigue instruments.
3. Results
3.1. Demographics
50 subjects attending an outpatient clinic for multiple
sclerosis consented to participate in this study. There
were 12 men and 38 women. The mean age of the group
was 41.6 11.6 (SD) years.
3.2. Reliability
Both PGI-S and CGI-S were reliable measures of fatigue
in this MS population. The mean scores for the PGI-S
and CGI-S revealed borderline to mild fatigue although
the scores ranged from 1 (normal) to 5 (marked fatigue).
There were no statistically significant differences be-
tween the patient-rated and clinician-rated global meas-
ures of fatigue. The mean PGI-S score was 2.30 1.16
(SD) and th e mean CGI-S wa s 2.28 1.07 (t = 0.89; df =
98; p = ns). The in tra-class correlation between the clini-
cian-rated CGI-S and patient-rated PGI-S was r = 0.9465
(p < 0.0001).
3.3. Validation of the Global Impressions
The MGH-CPFQ was included in this study to assess the
validity of the CGI-S and PGI-S for fatigue. The mean
MGH-CPFQ score was 16.68 4.48. Most subjects per-
ceived mild cognitiv e or physical symptoms although the
scores ranged from 1 to 5 in this ambulatory population.
Most of these MS subjects did not equate the experience
of fatigue related to their illness with any impairment of
motivation, alertness, energy, focus, or their cognitive
The Pearson’s correlation with the total MGH-CPFQ
score was 0.631 6 f or the PGI -S an d 0.7 173 fo r th e CGI -S.
Both CGI-S and PGI-S scores were highly correlated
with the total MGH-CPFQ (p < 0.001) and each of the
individual 7 it ems.
Table 1 reveals the mean CGI-S scores and the Pear-
son’s correlation for each of the individual CPFQ items.
4. Discussion
In this study, a Spanish language version of a validated
global assessment instrument (the PGI and CGI for se-
verity of fatigue) was both reliable and valid when ad-
ministered to a population of ambulatory patients with
MS. Each of the seven items of the MGH-CPFQ was
highly correlated with the CGI-S and PGI-S for fatigue
reflecting the validity of the instrument.
Table 1. Pearson Correlation: CGI-S Fatigue with individ-
ual MGH-CPFQ items in an MS population (n = 50).
Comparison MGH-CPFQ
(mean ± SD)
correlation p-value
CGI-S to Motivation 2.40 ± 1.07 0.560 <0.005
CGI-S to Wakefulness 2.40 ± 0.86 0.521 <0.005
CGI-S to Energy 2.76 ± 1.04 0.501 <0.005
CGI-S to Focus 2.36 ± 0.88 0.609 <0.005
CGI-S to Recall 2.44 ± 0.86 0.528 <0.005
CGI-S to Ability 2.22 ± 0.58 0.456 <0.005
CGI-S to Sharpness 2.10 ± 0.58 0.480 <0.005
Fatigue symptoms often present as part of the symp-
tom cluster of MS as weakness following muscular exer-
tion and/or cognitive deficits [5,6]. However, in this
study the majority of MS subject’s perceived their global
fatigue as only borderline or mild severity (mean PGI-S
score of 2.30). These global scores were essentially
equivalent to the scores obtained from a healthy, com-
parison group (mean PGI-S = 2.39), and substantially
lower than the scores for subjects with psychiatric disor-
ders (mean PGI-S score = 3.92) examined in the United
States [22]. The MGH-CPFQ scores submitted by the
MS patients were also similar to the healthy controls in
the US study [22]. Therefore, these MS subjects did not
equate the fatigue often related to their illness with im-
pairment of motivation, energy, focus, or with their cog-
nitive abilities. Although this finding may be due to cul-
tural or geographical differences related to fatigue per-
ception, it is more likely due to the specific, relatively
stable patients making routine visits to this specific am-
bulatory clinic and the broad diversity of fatigue symp-
tom severity observed in MS patients. The extremely
high correlation noted between the PGI-S and CGI-S
scores (r = 0.9465) suggests that the patient perceptions
are at least consistent with the independent clinical j udg-
ment of the clinician.
Fatigue symptoms can impact productivity, interper-
sonal relations, and the sense of well being across the
CNS spectrum including patients with depression, multi-
ple sclerosis, and schizophrenia [5,7-9,12,13].
Our objectives of this stud y were to develop a Spanish
language version of the validated CGI fatigue scale and
apply it in a different CNS population. A limitation of
this study is that we do not compare our CGI fatigue in-
strument with other commonly used, but longer fatigue
instruments, like the FSS or the revised 11-item fatigue
questionnaire [5,17]. In addition, we did not include the
EDSS [19] as an independent measure of disabling dis-
tinct from fatigue. Our intent was not to replace these
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Assessment of Global Fatigue in Multiple Sclerosis: A Spanish Language Version of the CGI and PGI Fatigue Scales 143
tools but to design a simple, reliable single item metric
that would be applicable for both clinicians and patients.
The PGI-S and CGI-S instruments that we have devel-
oped do provide a single item, overall impression that
assesses three distinct categories of fatigue related to
physical, cognitive, and emotional symptoms. Both the
English and Spanish language versions offer detailed
descriptors of these three categories to facilitate symptom
identification and customized scoring anchors to facili-
tate accurate scoring.
We have now employed the CGI fatigue instrument in
American psychiatric patients (Major Depressive Disor-
der and schizophrenia) and healthy controls, and in a
second study of Latin patients with multiple sclerosis. In
each group, there was a high correlation between the
CGI-S and PGI-S as well as high correlations with the
MGH-CPFQ providing a validation of the instrument. In
both studies, the CGI-S and PGI-S were easily under-
stood and administered by both the clinic staff and con-
senting subjects. Consequently, we believe this instru-
ment can be a meaningful metric when app lied in a busy
clinic setting to reliably gauge symptoms of fatigue dis-
tinct from the specific CNS di sor de r bei n g tr eat ed.
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