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Emotional Lability in MND: Relationship to cognition and psychopathology and impact on caregivers


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Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway dysfunction in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and is reported to occur in 19-49% of patients. The Emotional Lability Questionnaire (ELQ), is specifically designed to detect EL as reported by MND patients and as observed by their carers. The aims of this study were to 1) validate the Italian version of the ELQ; 2) investigate the relationship between EL and presence of cognitive dysfunction; 3) investigate the relationship between EL and presence of psychopathology. Forty one MND patients, 39 caregivers and respective control groups composed of 39 subjects and 39 partners/friends were tested. The Italian version of the ELQ was found to have good psychometric properties. Seventy-one per cent of patients reported suffering from EL. Correlations were found between bulbar involvement and EL, and between bulbar involvement and low performance on tests of fluid intelligence and working memory. However, the cognitive profile did not correlate with any aspect of EL. The findings suggests that damage to different neurological pathways underlie cognitive change and EL, which supports the concept of MND/ALS as a multisystem disorder. Moreover the outcomes suggest that EL affects patients' everyday life with the increased anxiety and emotional frailty. The findings suggest that those involved in the care of MND patients should be more aware of the effects of EL in the management of the disease.
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Emotional Lability in MND: Relationship to cognition and
psychopathology and impact on caregivers
A. Palmieri
, S. Abrahams
, G. Sorarù
, L. Mattiuzzi
, C. D'Ascenzo
, E. Pegoraro
, C. Angelini
Department of Neurosciences, University of Padova, Italy
Department of Psychology, University of Edinburgh, Scotland, UK
Department of Psychology, University of Padova, Italy
abstractarticle info
Article history:
Received 5 August 2008
Received in revised form 23 October 2008
Accepted 30 October 2008
Available online 21 December 2008
Emotional Lability
Emotional Lability (EL) is a well recognized symptom of cortico-bulbar pathway dysfunction in Motor
Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS), and is reported to occur in 19-49% of patients.
The Emotional Lability Questionnaire (ELQ), is specically designed to detect EL as reported by MND
patients and as observed by their carers. The aims of this study were to 1) validate the Italian version of
the ELQ; 2) investigate the relationship between EL and presence of cognitive dysfunction; 3) investigate
the relationship between EL and presence of psychopathology. Forty one MND patients, 39 caregivers and
respective control groups composed of 39 subjects and 39 partners/friends were tested. The Italian version
of the ELQ was found to have good psychometric properties. Seventy-one per cent of patients reported
suffering from EL. Correlations were found between bulbar involvement and EL, and between bulbar
involvement and low performance on tests of uid intelligence and working memory. However, the
cognitive prole did not correlate with any aspect of EL. The ndings suggests that damage to different
neurological pathways underlie cognitive change and EL, which supports the concept of MND/ALS as a
multisystem disorder. Moreover the outcomes suggest that EL affects patients' everyday life with the
increased anxiety and emotional frailty. The ndings suggest that those involved in the care of MND
patients should be more aware of the effects of EL in the management of the disease.
© 2008 Elsevier B.V. All rights reserved.
1. Introduction
Emotional Lability (EL), is the involuntary occurrence of laughter
and crying in the absence of a corresponding change in affect. It was
rst reported in Motor Neuron Disease (MND) in the last century and
was found to occur in 19%-49% of Amyotrophic lateral Sclerosis (ALS)
patients [1,2], the most common form of MND. EL is most often
present in patients who have pseudo-bulbar symptomatology [1,3].
Nevertheless, few studies have undertaken a systematic investigation
of this phenomenon and hence it remains poorly understood.
In 1997 Moore and colleagues validated the CNS-LS (Centre of
Neurological Study-Lability Scale) in ALS patients; a seven-item, self
report measure of affective lability composed of two subscales
measuring labile laughter and labile tearfulness [4]. The CNS-LS
represents a good clinical instrument, but lacks the details necessary
to permit a thorough exam of the nature and the pervasiveness of
emotional lability in the MND population. More recently, Newsom-
Davies and colleagues [3] developed the Emotional Lability Ques-
tionnaire (ELQ), a measurement scale specically designed to assess
MND patients which includes a self-rated version for patients and
independent-rated version for caregivers. The ELQ was modied from
the Pathological Laughter and Crying scale [5] which was rst
developed for stroke patients. The ELQ presents good psychometric
properties and in depth exploration of emotion and expression, such
as the introduction of the abnormal smilingsubscale. We set out to
validate an Italian version of the ELQ, to produce a measure able to
detect lability in an Italian population of MND patients, and to
distinguish between pathological laughing, crying and smiling.
A second aim of this study was also to investigate the relationship
between EL and cognitive decits, which are found in some patients
with MND. Although EL can be found in patients with frontal and
temporal lobe involvement, the traditional view is that EL is due to
damage to pathways that arise in the motor areas of the cerebral
cortex and descend to the brainstem and inhibit putative centres for
laughter and crying. Recent neuroanatomical ndings suggest that the
critical areas are in the cerebro-ponto-cerebellar pathways [6,7]. The
abnormal cognitive prole found in MND/ALS is well-known, and
consists of predominant executive dysfunction and in some cases
language and memory dysfunction [811,4347]. Visuospatial func-
tions appear well preserved. This prole of impairment is consistent
with frontotemporal involvement as found in neuroimaging studies of
MND patients [1214]. In one of the largest studies of cognition in ALS
Journal of the Neurological Sciences 278 (2009) 1620
Corresponding author. Department of Neurosciences, University of Padova, via
Giustiniani 5, 35128 Padova, Italy. Tel.: +39 0498215321; fax: +39 0498751770.
E-mail address: (A. Palmieri).
0022-510X/$ see front matter © 2008 Elsevier B.V. All rights reserved.
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to date [15], 47% of patients showed executive dysfunction, and 15% of
them had severe cognitive impairment with features that were
consistent with fronto-temporal dementia. The presence of cognitive
impairment in MND appears more prominent in patients with
pseudo-bulbar palsy [10,16]. In previous studies emotional lability
was also found to signicantly correlate with bulbar scores [3].
However, the relationship between EL and cognitive dysfunction in
MND has received little attention other than a small study reported by
McCullagh et al. [17] in which a difference was found between 8 ALS
patients with EL and 10 patients without, in errors on Wisconsin Card
Sorting Test.
Moreover, the relationship between EL and psychopathology has
not previously been investigated in MND. Estimated prevalence rates
for depression or mild depressive-symptomatology has appeared low,
between 0-44% in MND populations [1821]. In recent studies
depression has appeared to be relatively more common (prevalence
rates up to 50%), as were other forms of psychological distress, and
was not associated with illness severity and functional status [22].
Estimated prevalence rates for anxiety have ranged 11-30% [2325].A
number of studies have shown the importance of including patients'
families in psychological research on MND. Social factors have been
reported to be the best predictor of ALS patients' self-esteem during
the disease [26]. In addition Gauthier et al. [27] found that patients'
level of disability and caregivers' depression were related with
caregivers' perception of burden. While Goldstein [23] showed that
carers also demonstrated signs of anxiety and depression, with the
latter correlating with aspects of the patients' functional impairment.
Carers depression and strain appeared to be related to their
attributional style and perceived strain was greater in carers who
viewed their partners' illness as having a more global impact on their
lives [28]. Hence, our third aim was to investigate the relationship
between EL and psychological status in patients and their caregivers.
2. Methods
2.1. Participants
We recruited 41 patients with Motor Neuron Disease via
Neurosciences Department of Padua, in the period from March 2007
and November 2007. The sample consisted of 16 females and 25
males; 32 of 41 had ALS, 6 had Primary Lateral Sclerosis,1 was affected
by Progressive Bulbar Palsy, 1 was affected by Progressive Muscular
Atrophy and 1 had Flail Arm Syndrome. Mean age of the sample was
58.19 (11.59sd, range 23-77). Mean educational level was 9.39 years.
All of the ALS patients fullled the criteria of probableor denite
ALS [29]. We excluded patients with a clinical diagnosis of dementia
according to Neary's criteria [30], those in receipt of 24-hour care and
those with cerebral injury or cerebrovascular accident. We assessed
their respective caregivers in 39 cases of 41; two patients reported not
to have a single referential caregiver. The carers sample consisted of 11
males and 18 females (mean age was 52.56, 15.42 sd); 74% of them
were the patient's spouse. More detailed data of patients and
caregivers are showed in Table 1.
We also tested as controls 39 healthy subjects. The control group
did not signicantly differ from the patient group in gender, age and
educational level. Thirty-nine pseudo-caregivers (i.e. who spent the
day with the 39 healthy subjects) were also tested. The pseudo-
caregivers did not signicantly differ from the carers in gender, age
and educational level. Similar exclusion criteria were applied.
2.2. ELQ translation and back-translation
The original Emotional Lability Questionnaire, [3] consisted of two
components: the self-rated version, given to MND patients, and the
independent rated version given to carers. Each questionnaire
contains 33 items, including three subscales measuring: Laughing
(11 items), Crying (11 items), and Smiling (11 items). The questions
refer to the patients' condition during the past four weeks and the
answers are given on a four-point Likert scale. The higher the score,
the higher the level of perceived emotional lability.
The translation and back-translation process included three phases:
the rst, in which two native Italian speakers uent in English, translated
the original version of the ELQ; then, using the back-translation approach,
two native English speakers uent in Italian, translated the English version
to Italian. In the third phase, four raters compared the two versions. No
relevant differences between the original and back-translated versions of
the questionnaires were found.
2.3. Procedure
MND patients and caregivers were interviewed separately by a
psychologist, following neurological examination. The interview took
an average of 1.5 h to complete. The same method was employed to
assess controls and pseudocaregivers. The ELQ, both self-rated and
independent rated versions, and other psychodiagnostic instruments,
were administered as a structured interview to each participant. MND
patents were asked to return to our Neurological department no
longer than two months after rst assessment, for a more compre-
hensive neuropsychological test battery. The great majority of patients
(93%) accepted. The complete neuropsychological evaluation took
an average of 1 h, however not every patient was able to complete
all of the tasks due to severity of motor impairment or bulbar
2.4. Neuropsychological measures
Thirty-eight of 41 MND patients undertook the neuropsychological
battery, which was designed to assess intelligence, executive
functions, memory and language. An initial general screening was
undertaken using the Mini Mental State Examination [32]. Intelligence
was assessed with the Raven's Coloured Matrices [33] and with the
Brief Intelligence Test (T.I.B.), designed to estimate pre-morbid
intellectual ability [34]. Executive functions were explored using the
Modied Wisconsin Card Sorting Test [35],Phonemic Verbal Fluency (F,
A,S) [36],Digit Span Backward [37],Trail Making Test A and B. The latter
was performed according to Reitan's protocol [38]. Long and short-
tem Memory were respectively investigated with Babcock's Prose [36],
Verbal Digit Span Forward [37] and Corsi Blocks tapping test [36].
Language was investigated with Semantic verbal uency (modied
Table 1
Features of MND patients and caregivers
Patients(n=41) Values
Men,n(%) 25(60.9)
Mean age(SD) 58.19(11.6)
Mean educational level (years)(SD) 9.4(4.5)
Mean length from diagnosis (months)(SD) 40.58(33.8)
Spinal onset(%) 30(73.2)
Married,n(%) 33(80.4)
Mean MRC upper limbs (SD) 38.6(10.9)
Mean MRC lower limbs(SD) 29.2(11.5)
Mean ALSFRS-R(SD)[31] 32.7(7)
Men,n(%) 11(28.2)
Mean Age(SD) 52.5(15.4)
Mean educational level (years)(SD) 9.4(4.8)
Spouses 29(74.4)
Sons or daughters 7(17.9)
Parent 1(2.6)
Brothers or sisters 2(5.2)
ALSFRS-r = Amyotrophic Lateral Sclerosis Functional Rating Scale Revised; MRC upper
and lower = Medical Research Council scale applied to upper extremities (maximum
score= 50) and applied to lower extremities (maximum score = 40).
17A. Palmieri et al. / Journal of the Neurological Sciences 278 (2009) 1620
version from Spinnler) [37]. To exclude the effect of dysarthria on
verbal uency, both phonemic and semantic, a motor control
condition was performed in which patients were asked to read
aloud all the words generated previously during the task as quickly as
possible and the examiner recorded the time taken to perform this
phase. The difference between the specied time for the generation
condition and the time taken for the control condition, the uency
index () was calculated according to guidelines of Abrahams et al.
(Neuropsychologia, 38:734-747, 2000) [11].
2.5. Psychodiagnostic measures
Depression was assessed using the Beck Depression Inventory (BDI)
[39]. State and trait anxiety were respectively evaluated with
Spielberger's State and Trait Anxiety Inventory (STAIY-1andSTAIY-2)
[40]. Emotional fragility and sense of inadequacy were investigated with
Emotional Fragility questionnaire (FE) [41], a questionnaire focusing on
sense of frailty and inadequacy.
2.6. Functional measures
The Amyotrophic Lateral Sclerosis Functional Rating Scale Revised
(ALSFRS-R) is a 12-item scale, in which the patient's functioning for
each item is rated on a scale from 0 (unable to attempt the task) to 4
(normal function). This scale includes evaluation of swallowing,
speech, and respiratory function, and both strength and function of
the upper and lower extremities musculature. Medical Research
Council scale (MRC) was used to obtain a more specic strength
measure for upper and lower extremity muscles groups.
3. Statistics
3.1. Validation of the Italian version of the ELQ
Spearman's correlations were applied to establish the internal validity
of the ELQ, both self-rated and independent rated versions, between
Laughing, Crying, Smiling subscales and global scores. Spearman's
correlation was also undertaken to explore construct validity, separately
for patients and controls group, and for caregivers and pseudo-caregivers.
MND characteristics (including age, educational level, time since onset,
onset of disease in terms of bulbar or limb, functional scores such as
ALFRS-R and MRC for upperand lower districts) were compared with ELQ
scores with Spearman's correlation.
3.2. Neuropsychological and psychopathological battery and ELQ scores
The cognitive and psychopathological data were analyzed with
Mann Whitney U non-parametric tests (as the data were not normally
distributed), comparing patients' performance with controls.
In order to identify differences between ALS (33) and ALS patients
with prevalent UMN (PLS), LMN (PMA) or bulbar involvement (PBP)
(8) a Mann Whitney U non parametric test has been used for
neuropsychological test and psycopathological and emotional lability
questionnaires applied at the two groups.
Spearman's correlations between ELQ data and the neuropsycho-
logical and psychopathological variables were applied to those
variables on which the ALS group were impaired. Due to the number
of correlations signicance was set at p= 0.01 to reduce the incidence
of Type 1 errors.
4. Results
No signicant differences were identied between ALS, and ALS
patients with prevalent UMN (PLS), LMN (PMA) or bulbar involvement
(PBP) (Mann Whitney non parametric test pN0.05) (Supplemental Table).
4.1. Validation of the Italian version of the ELQ
Seventy-one per cent of patients indicated that they suffered from
at least of one of the three emotional lability domains (Laughter,
Crying, Smiling), as opposed to 5% of healthy controls.
Signicant results relating to validity are displayed in Tables 2
and 3. In addition, correlational analyses were used to explore the
relationship of EL to demographic variables and clinical data. MND
patients displayed a positive correlation between time since onset of
disease (in months) and Laughing (r= 0.48; pb0.00). Global Lability
revealed a signicant correlation with ALFRS-R total scores (r= 0.36;
pb0.01); in particular, signicant correlations were found between
Global Lability and ALSFRS-R 1-language (r= 0.50; pb0.000) and
ALSFRS-R 3 -swallowing (r=0.47; pb0.001). The MRC did not exhibit
any signicant correlations.
4.2. Neuropsychological battery and ELQ
Neuropsychological results are reported in Table 4.Inthe
comparison of the patient and control groups, MND patients showed
a trend towards impaired performance on digit span backwards and
Corsi block tapping test and were signicantly impaired relative to
controls on the Raven's Coloured Progressive Matrices. No signicant
correlations were found between neuropsychological performance
and emotional lability. Semantic Verbal Fluency Index was found to
correlate with level of swallowing (ALSFRS-R 3) (r=0.49; pb0.00).
MRC did not exhibited any signicant correlation with these cognitive
4.3. Psychodiagnostic questionnaires and ELQ
Thirty-nine per cent of MND patients revealed BDI scores from 16
to 33; 34% showed the presence of state anxiety (STAY-Y1) and trait
anxiety (STAI Y-2) with greater than one standard deviation above the
Table 3
Statistically signicant correlations between ELQ items for the controls and pseudo-
caregivers groups
ELQ scores correlating Spearman's
Within self-rated version(ncontrols= 39):
Laughter-Total 0.91 0.000
Crying-Total 0.69 0.000
Smiling-Total 0.50 0.001
Within independent-rated version(npseudo-caregivers= 39):
Laughter-Total 0.94 0.000
Crying-Total 0.43 0.000
Smiling-Total 0.76 0.000
Smiling- Laughter 0.72 0.000
Between self-rated and independent-rated version
Self/Laughter-Independent/Smiling 0.82 0.000
Self/Laughter-Independent/Total 0.57 0.000
Table 2
Statistically signicant correlations between ELQ items for the patients and caregivers
ELQ scores correlating Spearman's
Within self-rated version (npatients = 41):
Smiling-Total 0.52 0.000
Within independent-rated version (ncaregivers= 39):
Crying-Total 0.69 0.000
Between self-rated and independent-rated version
Self/Laughter-Independent/Laughter 0.57 0.000
Self/Total-Independent/Total 0.51 0.000
Self/Laughter-Independent/Total 0.46 0.000
Self/Total-Independent/Laughter 0.57 0.000
18 A. Palmieri et al. / Journal of the Neurological Sciences 278 (2009) 1620
cut off; 51% of patients' scores were greater than the 75th percentile in
Emotional Fragility questionnaire. While, 18% of caregivers had
depression scores from moderate to severe on the BDI; 79% showed
STAI-Y1 scores over the clinical cut off, and 44% were over the clinical
cut off on the STAI-Y2; 46% went greater than the 75 percentile of
emotional fragility scores. Scores for the BDI, STAI Y1 and STAI Y2
revealed signicant differences between patients and healthy con-
trols. Caregivers had signicantly greater scores on the BDI and STAI
Y2 than pseudocaregivers. The results are presented in Table 5.
Finally, psychological results obtained from questionnaires admi-
nistered to the four groups were compared with Spearman correla-
tions with ELQ scores. In the ALS/MND patients ELQ Global Lability
correlated with state anxiety (STAI Y1) scores, (r=0.36. pb0.01) and
with Emotional Fragility questionnaire scores (r=0.4; pb0.00). The
Crying subscale showed a signicant correlation with Emotional
Fragility (r=0.44; pb0.00), BDI scores (r= 0.41; pb0.00), STAI Y1
(r=0.38; pb0.01), STAI Y 2 (r=0.37; pb0.01). In caregivers, Smiling
subscale of independent rated version showed a strong trend towards
a signicant correlation with Emotional Fragility questionnaire at our
raised signicance threshold (r=0.33; pb0.05). No signicant correla-
tion were found in healthy controls and pseudo-caregivers with
respect to emotional lability and psychopathological features.
5. Discussion
The Italian version of the ELQ showed good internal validity as
determined by the relationship between the subscales (Laughing,
Crying, Smiling) and global scores. Construct validity was corroborated
by signicant correlations between self rated version subscales and
independent rated version subscales. Seventy-one per cent of MND
patients reported that they suffered from at least one of the three
aspects of emotional lability. This percentage appears greater than
reported in previous studies [1,2,42]. MND patients displayed a
positive correlation between time since onset of disease (in months),
Laughing and Smiling. Global Lability (total score derived from sum of
the three subscales) was signicantly related to ALFRS-R total scores
and in particular with Language and Swallowing items. Our ndings
are therefore consistent with the view that the Emotional Lability
correlates with disease progression and bulbar symptomatology [3].
The neuropsychological battery revealed signicantly impaired
performance in the MND group in the Raven's Coloured Progressive
Matrices only as compared with controls. Two tests of working
memory, Digit Span Backward and Corsi Block Tapping test, showed
trends towards an impairment. Although the Raven's matrices is
considered to be a test of uid intelligence it can also be viewed as
reliant on other more specic cognitive processes such as working
memory, attention and problem solving and hence is dependent on
intact executive functions. However, our group, unlike many
previous studies, did not display a decit on other tests of executive
processes such as Verbal Fluency, Trail Making Test and the
Wisconsin Card Sorting Test. Moreover, the neuropsychological
scores did not correlate signicantly with any aspect of emotional
lability. This data are in contrast with McCullogh's and colleagues
study [17], who implicated an association between prefrontal cortex
dysfunction, as represented by decits on the Wisconsin Card
Sorting Test and emotional lability. Cognitive change in MND has
been previously associated with extra-motor frontotemporal dys-
function [1214] while it is possible that dysfunction of cerebro-
cerebellar pathways are involved in the regulation of emotional
expression [7].
The current ndings suggest that not only the upper motor
neurons are involved with cognitive dysfunction in MND and
emotional lability, but other neuronal pathways not fully character-
ized yet may play a role, providing support for the concept of MND as a
multisystem disorder.
With regard to the presence of psychopathology in MND, the
scientic literature varies: the two most common features investi-
gated, depression and anxiety have been reported in 0-44% and 10-36%
of cases respectively. In our sample, 36% of patients showed a level of
depression from moderate to severe, while very high levels of anxiety
were reported with 70% exhibiting a high level of state anxiety and 60%
and high level of trait anxiety. Furthermore high levels of emotional
fragility were reported in 48% of cases. Wicks demonstrated that the
estimated prevalence of mood disorder amongst patients with ALS
may vary signicantly depending on the measure used [21]. Regardless
of the lack of unanimous consensus of standard utilization of
psychopathological measures, it was clear that our sample of MND
patients revealed predominant anxiety, but with also depression and
emotional fragility in many cases.
Moreover, the current study revealed a relationship between total
scores on the ELQ and both state anxiety and Emotional Fragility
indicating an association between lability and psychopathology in
MND patients. The Crying subscale showed a signicant relationship
Table 5
Participants psychopathological features and signicant results
MND (SD)N=41 Controls (SD) n= 39 Mann Whitney UCoefcient Caregivers (SD) n=39 Caregiver's control (SD) n= 39 Mann Whitney UCoefcient
BDI 15.92 (11.55) 7.38 (6.03) U=1203 (pb0.00 0) 10.71 (6.48) 5.94 (6.30) U=1137 (pb0.000)
STAI Y1 43.48 (13.45) 35.20 (9.66) U= 1085 (pb0.005) 47.76 (10.05) 35.64 (9.19) U=1247 (pb0.000)
STAI Y2 44.39 (12.43) 32.56 (15.84) U=1155.5 (pb0.000) 41.97 (8.61) 37.76 (9.45) U= 966.5 (pb0.05)
FE 74.2 (29.53) 58.27 (24.49) U=1011 (pb0.05) 65.68 (24.21) 59 (27.04) U=86.5 (p=0.312)
Signicant results are highlighted in bold.
BDI = Back Depression Inventory; STAI = State-Trait anxiety Inventory; Y1 = State Form; Y2 = Trait Form; FE = EmotionalFragility.
Table 4
Neuropsychological assessment of patients and controls
Patients nMean
(SD) n=38
Controls Mean
(SD) n=39
General Screening
MMSE 28.26 (1.77)n=28 28.51(1.79) 326 0.375
Rs CPM 28.76(5.61)n=38 31.86(3.98) 332.5 0.002
TIB 108,78(6,54)n=30 104,41(9) 470 0.594
Digit Span Forward 5.51 (0.94)n=30 5.94(1.59) 468 0.233
Digit Span Backward 3.3(0,81)n=24 3.72(1.38) 411 0.052
Babcock Prose 12.36(2,56)n=30 12.97(2.40) 450.5 0.309
Corsi Blocks Tapping 5 (1.02) n=30 5.5(1.24) 490 0.037
Semantic Fluency 35.19(12.46)n=30 37.02 (10.95) 381 0.714
Semantic Index(S) 2,44 (0,95) n=30 2,51 (1,21) 429 0.838
Phonemic Fluency 30.55 (11.15) n=30 32.47 (13.36) 374 0.381
Phonemic Index (P) 5.1(2.32)n=30 5.1(1.96) 466.5 0.714
TMT A 44.6 (7.43) n=24 51.37 (30.50) 349 0.411
TMT B 126.88 (110.73) n=24 120.09 (33.62) 442.5 0.494
TMT A-B 82.28 (106.37)n=24 68.71(60.23) 467 0.381
WCST (categories) 3.90 (1.89) n=24 4.41(1.56) 324 0.309
WCST (errors) 17.35(13.38)n=24 13.37 (8.31) 447.5 0.199
8.74(9.61)n=24 5.7(4.58) 439 0.254
pb0.01 andpb0.05 are highlighted in bold.
MMSE = Mini Mental State Examination; RsCPM = Raven's Coloured Matrices; TIB = Brief
Intelligence Test; TMT = Trail Making Test; WCST = Wisconsin Cards Sorting Test
Modied Version (Nelson).
19A. Palmieri et al. / Journal of the Neurological Sciences 278 (2009) 1620
with all psychopathological measures. These ndings suggest that the
presence of psychopathological symptoms in MND patients may be a
predisposing factor for emotional lability or in contrast that such
psychopathology may be a reaction to emotional lability. Interviews
with carers also demonstrated clear evidence of psychopathology with
20% reporting depression from moderate to severe levels on the BDI,
while 85% and 72% showed state and trait anxiety scores over the
clinical cut off, respectively. As for the relationship between patients
and carers mood, some data in the literature have reported an
association [2328] but despite high levels of affective conditions in
our patients and carers we did not nd an association.
In conclusion, emotional lability appears to be more prevalent in
the MND population than previously thought. However cognitive
change was not associated with the presence of lability suggesting
differential neurological pathways and indicating that extramotor
involvement in MND is widespread. Moreover, the lack of ability to
control one's own emotions and the expression of inconsistent
emotions, seems to relate to high levels of anxiety and emotional
frailty in people with MND. Hence, the relatively low number of
patients' asking for a drug treatment for emotional lability [42] may
not be representative of real discomfort caused by such emotion
dyscontrol. Clinicians should be more aware of the effects of emotional
lablity and provide appropriate support to the both the patients and
caregivers during the course of the illness.
We thank patients and caregivers for participating to this study.
This work was supported by COFIN 2006062912-001 and a
Telethon grant to C.A.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jns.2008.10.025.
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20 A. Palmieri et al. / Journal of the Neurological Sciences 278 (2009) 1620
... Another assessment tool, the "emotional lability questionnaire" (ELQ) has also been validated in ALS. It extends the period over which symptoms are assessed from one up to four weeks prior to screening, which helps to capture patients who experience less frequent episodes (45,46). In addition to PCL, it also includes a specific section on abnormal smiling. ...
... One of the strengths of the ELQ is that it includes the caregiver's perspective, which helps to identify lack of insight if significantly discordant scores are given by the patient and the carer. Interestingly, in ALS, there is significant agreement between patient and caregiver scores, indicating that patients are keenly aware of PCL symptoms (45). This concordance contrasts with behavioral deficits in ALS-FTD, where patient reports may differ substantially from caregivers reports (47). ...
... A study of PCL in ALS found an association between PCL and poor performance in executive tasks, implicating pre-frontal cortical areas in the disorder (20). Other studies, in contrast have found no such associations (8,45). Systematic studies of social cognition in patients with PCL are lacking. ...
Full-text available
Pathological crying and laughing (PCL) has significant quality-of-life implications in amyotrophic lateral sclerosis (ALS); it can provoke restrictive life-style modifications and lead to social isolation. Despite its high prevalence and quality of life implications, it remains surprisingly understudied. Divergent pathophysiological models have been proposed, centered on corticobulbar tract degeneration, prefrontal cortex pathology, sensory deafferentation, and impaired cerebellar gate-control mechanisms. Quantitative MRI techniques and symptom-specific clinical instruments offer unprecedented opportunities to elucidate the anatomical underpinnings of PCL pathogenesis. Emerging neuroimaging studies of ALS support the role of cortico–pontine–cerebellar network dysfunction in context-inappropriate emotional responses. The characterization of PCL-associated pathophysiological processes is indispensable for the development of effective pharmacological therapies.
... The PLC and cognitive function were negatively affecting the social functioning and quality of life in ALS individuals and their families (4,5,26,27). The PLC symptoms were keenly awarded by patients and caregivers (28). While patients' reports may differ substantially from caregivers' reports in cognitive dysfunction or behavioral deficits (29), there is little information about the possible relationships of these phenomena. ...
... A previous study reported correlations between bulbar involvement and emotional lability and between bulbar involvement and executive impairment. However, other cognitive profiles have not been reported to correlate with PLC (28). In this study, cognitive dysfunction was not associated with the presence of PLC in ALS using a multivariate regression model. ...
Full-text available
Objective: This study aimed to explore the prevalence and clinical correlates of pathological laughter and crying (PLC) in patients with amyotrophic lateral sclerosis (ALS). Methods: A total of 1,031 ALS patients were enrolled between August 2012 and August 2019. The PLC was recorded by a face-to-face interview. Other characteristics of patients, including depression, anxiety, cognition, and behavior function, were also evaluated. The potential associated factors of PLC were explored using forward binary regression analysis. Survival was analyzed in groups using propensity score matching (PSM) and Cox proportional hazards models. Results: The prevalence of PLC was 11.4% in all patients at baseline. Bulbar-onset and female patients had higher prevalence of PLC. The multivariate regression analysis indicated that PLC in ALS was associated with bulbar onset ( p < 0.001), late disease stage ( p < 0.001), and higher score in the Hamilton Depression Rating Scale (HDRS) ( p = 0.012). The higher score of HDRS was significantly and independently associated with PLC occurrence in bulbar-onset patients ( p = 0.032). The late disease stage was related to PLC occurrence in spinal-onset patients ( p < 0.001). After comparison with matched pairs by using PSM, PLC at baseline had no impact on survival. Conclusion: PLC was not uncommon in ALS, especially in bulbar-onset and female patients. We highlighted that the emotional state other than cognitive function had possible relationship with PLC in ALS.
... The differential diagnosis may require a detailed assessment of a patient's functional and cognitive capabilities. It needs to be emphasized that EL is considered a separate disorder, as no correlation has been found in any aspect of cognitive profile and EL in ALS patients [19]. ...
... Due to its clinical characteristics, EL causes important distress to ALS patients and their proxy. For this reason, the majority of publications focus on the psychological, social and therapeutic aspects of the syndrome [10,11,15,19,21,22]. Although the EL does not correlate with depression [18,[23][24][25], an ascending social isolation may indeed result in development of mood alterations, depression and further functional impairment [26,27]. ...
Full-text available
Amyotrophic lateral sclerosis (ALS) is a fast progressing neurodegenerative disease leading to quadriplegia, anarthria and respiratory insufficiency. A large variety of phenotypes and disability progression requires individually tailored management. Identification of predictors of poor prognosis may not only improve management, but also allow for more precise patients' stratification for clinical trials or research studies. The aim of the study was to investigate the influence of emotional lability present at disease onset on ALS progression by exploring its direct impact on the decay of the ALS Functional Rating Scale-Revised (ALSFRS-R). The study was performed in a group of 1145 patients from Germany, Poland, Portugal and Turkey between 2014 and 2018. The analysis showed that the presence of emotional lability at ALS onset was linked to a faster decline of ALSFRS-R (0.70 vs 0.50, p<0.0001), in case of either bulbar (0.80 vs 0.65, p<0.05) or limb disease onset (0.59 vs 0.46, p <0.01). It was most prominent in the bulbar subscore of ALSFRS-R. A multiple regression analysis showed a direct influence of emotional lability at ALS onset on disease progression, regardless of age, gender, site of onset, weight loss, cognitive impairment and diagnosis delay (β=0.071; p=0.019). It can therefore be concluded that the presence of emotional lability at the disease onset is an independent factor of faster disease progression in ALS.
... von der erlebten Emotion abweichend [13]. Wenngleich der PBA bei vielen neurologischen Erkrankungen auftritt, tritt er neben demSchlaganfallbeiderALSamhäufigstenauf,wobeiKomorbidi-tätsratenvonbiszu50%beobachtetwerden [13].Solcheunkontrollierbaren verhaltensbezogenen Veränderungen können zu Be-schämung beim Patienten, bei der Familie oder anderen Kontaktpersonen führen [14] und stellen ein erhebliches soziales Problem fürdieBetroffenendar [15].DementsprechendwirktsichderPBA negativ auf die Lebensqualität des Patienten aus und geht mit höherer Ängstlichkeit und Depressivität sowie einem niedrigeren sozialen Funktionsniveau einher [14,16,17]. ...
... In nur einer bisherigen Interventionsstudie [58] wurde die emo-tionaleLabilitätbzw.derpseudobulbäreAffektexplizitintegriert. Vor dem Hintergrund, dass dieses Phänomen zu großem Leid bei denBetroffenenundAngehörigenführt [16,17],solltedieserAspekt hinsichtlich eingeschränkter Emotionskontrolle bzw. Emotionswahrnehmung unbedingt als eigener Baustein in psychotherapeutische Maßnahmen bei dieser Population integriert werden. ...
Zusammenfassung Dieser narrative Review soll einen breiten Überblick zur psychosozialen Belastung bei Patienten mit Amyotropher Lateralsklerose (ALS) und diesbezüglichen psychotherapeutischen Interventionen vermitteln. Die ALS ist eine unheilbare, schnell fortschreitende neurodegenerative Erkrankung, in deren Verlauf es zur Schwächung bzw. zum Schwund fast aller Muskeln des Körpers kommt: dies macht schließlich nicht nur die Bewegung, sondern auch die Nahrungsaufnahme, Atmung und Kommunikation des Patienten unmöglich. Neben den vorwiegend motorischen Symptomen kommt es auch zu kognitiv-emotionalen bzw. verhaltensbezogenen Veränderungen und Störungen, die die Lebensqualität der Betroffenen zusätzlich stark beeinträchtigen können. Entsprechend dieser schweren Symptomatik und der negativen Prognose kann es zu ausgeprägten psychosozialen Belastungen einschließlich erhöhter Depressivität und Ängstlichkeit, Hoffnungslosigkeit bis hin zu Sterbewunsch und Suizidalität kommen. Viele Studien weisen auf den entscheidenden Einfluss psychosozialer Aspekte bei der Aufrechterhaltung der Lebensqualität bei ALS-Patienten hin. Dennoch ist der Forschungsstand zu psychotherapeutischen Interventionen bei ALS-Patienten bislang äußerst dürftig. Neben dem generellen Mangel an Interventionen und methodischen Schwachstellen bei der Evaluation ihrer Wirksamkeit lassen sich in den Interventionen nur wenig Inhalte finden, die dem palliativen Charakter sowie den spezifischen Symptomen der Erkrankung wie z. B. der eingeschränkten Kommunikation oder Problemen bei der Emotionsregulation Rechnung tragen. Weitere Forschung im Bereich psychosozialer Interventionen bei ALS-Patienten ist daher von hoher Relevanz. Wissenschaftliche Ansätze könnten z. B. darin bestehen, die bei anderen schwerwiegenden Erkrankungen als wirksam erwiesenen Therapiekonzepte auf die spezielle Gruppe von ALS-Patienten zu übertragen. Neben einer inhaltlichen Anpassung sollte auch die Anwendbarkeit der Therapieverfahren mit alternativen Kommunikationswegen, z. B. via Sprachcomputer oder Brain-Computer-Interfaces, untersucht werden.
... The ECAS-CI adds up and complements the currently available range of disease-specific/-nonspecific, behavioural tools that have been standardized in Italy within the ALS population, namely, the Emotional Lability Questionnaire (ELQ) [16], the Dimensional Apathy Scale [17], the State-and Trait-Anxiety Inventory-Form Y (STAI-Y) [18], the ALS Depression Inventory-12 (ADI-12) [19] and the Beaumont Behavioural Inventory (BBI) [15]. However, at variance with them, the ECAS-CI is less time-consuming, as well as embedded within a full, ALS-specific cognitive and behavioural screener, whose section that assesses cognition has been extensively examined for its clinimetrics and feasibility in Italy, i.e. the ECAS [10,20,21]. ...
Full-text available
Background This study aimed at providing diagnostic properties and normative cut-offs for the Italian ECAS Carer Interview (ECAS-CI). Materials N = 292 non-demented ALS patients and N = 107 healthy controls (HCs) underwent the ECAS-CI and the Frontal Behavioural Inventory (FBI). Two ECAS-CI measures were addressed: (1) the number of symptoms (NoS; range = 0–13) and (2) that of individual symptom clusters (SC; range = 0–6). Diagnostics were explored against an FBI score ≥ than the 95th percentile of the patients’ distribution. Results Both the NoS and SC discriminated patient from HCs. High accuracy, sensitivity, and specificity were detected for both the NoS and SC; however, at variance with SC, the NoS showed better post-test features and did not overestimate the occurrence of behavioural changes. The ECAS-CI converged with the FBI and diverged from the cognitive section of the ECAS. Discussion The ECAS-CI is a suitable screener for behavioural changes in ALS patients, with the NoS being its best outcome measure (cut-off: ≥ 3).
... Other psychologically significant reactions are resentment, thirst for compensation, hatred, emotional lability, loss of hope, and even suicidal ideation [11,12]. Although psychological and psychotherapeutic interventions are usually suggested to deal mainly with anxious or depressive symptoms, they become relevant, albeit with different connotations at different stages of the disease. ...
Objective: The current study aimed to describe the implementation of a structured psychoeducational intervention in Amyotrophic Lateral Sclerosis (ALS), identifying the needs of both patients and their caregivers. Methods: Five patients and thirteen caregivers attended eight psychoeducational group meetings at the Respiratory Rehabilitation Unit of IRCCS Santa Maria Nascente of Fondazione Don Carlo Gnocchi, Milan (Italy) and eight participants underwent semi-structured interviews once the group sessions ended. Group sessions and semi-structured interviews were audio-recorded and transcribed verbatim. Then, data obtained by group meetings' transcripts have been analysed using the grounded theory (GT) paradigm, while those obtained by interviews have been analysed using the interpretative phenomenological analysis (IPA). Results: The analysis of the meetings allowed us to identify seven main themes: "practical advice", "explanation of the pathology", "recognition of emotions", "adaptation", "family and relationships", "being caregiver of oneself", and "sharing". Twenty-one sub-themes also emerged from the transcripts' analysis. The analysis of the interviews allowed us to deduce the main reasons to participate (i.e., to have information and to be able to share experiences), the positive and negative aspects of the experiences. These results suggested the usefulness of psychoeducational groups in the regular clinical practise to allow patients and caregivers to share advice, emotions, and experiences with others in the same situation. Conclusions: This study displays the utility of psychoeducational group intervention in supporting people with ALS and their caregivers because of two main reasons: first for the psychoeducation provided by professionals; second for the possibility of sharing experiences and emotions with people in the same situation.
... This is of particular relevance in amyotrophic lateral sclerosis (ALS), where the reported prevalence of PLC symptoms is reported to be present in 25-50% of patients (4). Patients with bulbar onset symptomatology appear disproportionately affected (5), possibly reflecting greater brainstem pathology within the ALS clinical spectrum (6,7). This is consistent with an increased incidence of PLC in neurodegenerative conditions with significant atrophy impacting brainstem and cerebellum integrity (8). ...
Full-text available
Pseudobulbar affect is a disorder of emotional expression commonly observed in amyotrophic lateral sclerosis (ALS), presenting as episodes of involuntary laughter, or crying. The objective of the current study was to determine the association between frequency of pathological laughter and crying (PLC) episodes with clinical features, cognitive impairment, and brainstem pathology. Thirty-five sporadic ALS patients underwent neuropsychological assessment, with a subset also undergoing brain imaging. The Center for Neurological Study Lability Scale (CNS-LS) was used to screen for presence and severity of pseudobulbar affect (CNS-LS ≥ 13) and frequency of PLC episodes. Presence of pseudobulbar affect was significantly higher in bulbar onset ALS ( p = 0.02). Frequency of PLC episodes was differentially associated with cognitive performance and brainstem integrity. Notably pathological laughter frequency, but not crying, showed a significant positive association with executive dysfunction on the Trail Making Test B-A ( R ² = 0.14, p = 0.04). Similarly, only pathological laughter frequency demonstrated a significant negative correlation with gray matter volume of the brainstem ( R ² = 0.46, p < 0.01), and mean fractional anisotropy of the superior cerebellar peduncles (left: R ² = 0.44, p < 0.01; right: R ² = 0.44, p < 0.01). Hierarchical regression indicated brainstem imaging in combination with site of symptom onset explained 73% of the variance in pathological laughter frequency in ALS. The current findings suggest emotional lability is underpinned by degeneration across distinct neural circuits, with brainstem integrity critical in the emergence of pathological laughter.
... Explicit psychological reactions to such a condition imply resentment, hate, emotional lability (Palmieri et al., 2009) and suicidal ideation (Palmieri et al., 2010), but also hope (Oster & Pagnini, 2012), and these reactions have been commonly described together with the degradation of empathic traits (Pick, Kleinbub, Mannarini, & Palmieri, 2019). Overall, however, in terms of prevalence, the most reported psychopathological features of ALS are anxiety (values of around 30% up to 70%) and depression (values of around 40% up to 70%; Kurt, Nijboer, Matuz, & Kübler, 2007;Taylor, Wicks, Leigh, & Goldstein, 2010;Wicks et al., 2007). ...
Scarce literature has been dedicated to the psychological treatment of amyotrophic lateral sclerosis (ALS). However, there have been some encouraging findings, such as in hypnosis-based studies, which revealed patient improvements in anxiety, depression and quality of life (QoL). We replicated such a design of a pragmatic study on empathy-based supportive counseling treatment in four weekly domiciliary sessions. Twenty-one people with ALS (pALS) consecutively attending the Motor Neuron Disease Center of Padova University were recruited to the study; in total, 21 pALS who did not undergo any kind of psychological treatment served as the control group. In the treatment group, depression, anxiety and QoL (measured respectively with the HADS-D, HADS-A and ALSSQOL-R) were assessed at pre- and post-treatment levels and at 3- and 6-month follow-ups. Statistical mixed-model regression analyses revealed that in the treated group, perceived conditions of anxiety, depression and QoL were significantly stable compared to worsening in the control patients. Interestingly, there were improvements in the QoL domains “Interaction”, “Emotion” and “Physical” at the 6-month follow-up. Overall, even if not directly comparable, our current results on support-based counseling, though interesting, seem not to reach the efficacy of a hypnosis-based study in which the observed dimensions were significantly improved with respect to the baseline. The implications of our results from a psychodynamic perspective are highlighted.
... As a result of this standardization, it is possible to find, for example, Italian (Palmieri et al., 2009), Dutch (Raaphorst et al., 2010), and French (Kilani et al., 2004) studies that all assessed the same WCST outcome measure according to the same manual in healthy controls and in patients with ALS diagnosed according to the same criteria. Undesired conceptual heterogeneity ("apples and oranges") and undesired researcher degrees of freedom ("garbage") should not present a major problem when aggregating across these studies. ...
Full-text available
Replication studies, pre-registration, and increases in statistical power will likely improve the reliability of scientific evidence. However, these measures face critical limitations in populations that are inherently difficult to study. Members of difficult-to-study populations (e.g., patients, children, non-human animals) are less accessible to researchers, which typically results in small-sample studies that are infeasible to replicate. Nevertheless, meta-analyses on clinical neuropsychological data suggest that difficult-to-study populations can be studied in a reliable way. These analyses often produce unbiased effect-size estimates despite aggregating across severely underpowered original studies. This finding can be attributed to a neuropsychological research culture involving the non-selective reporting of results from standardized and validated test procedures. Consensus guidelines, test manuals, and psychometric evidence constrain the methodological choices made by neuropsychologists, who regularly report the results from neuropsychological test batteries irrespective of their statistical significance or novelty. Comparable shifts toward more standardization and validation, complete result reports, and between-lab collaborations can allow for a meaningful and reliable study of psychological phenomena in other difficult-to-study populations.
... Patients with pseudobulbar affect or pathological crying and laughing exhibit sudden situation-inappropriate emotional responses (120-122) which may have a negative impact on their quality of life (123) and lead to social isolation or social stigma. It is most commonly associated with UMN-type bulbar dysfunction (124), but frontal abnormalities, executive dysfunction, basal ganglia pathology and impaired cerebellar gating mechanisms have also been linked this symptom (27,122,(125)(126)(127)(128). ...
Full-text available
Amyotrophic lateral sclerosis (ALS) is now universally recognised as a complex multisystem disorder with considerable extra-motor involvement. The neuropsychological manifestations of frontotemporal, parietal and basal ganglia involvement in ALS have important implications for compliance with assistive devices, survival, participation in clinical trials, caregiver burden, and the management of individual care needs. Recent advances in neuroimaging have been instrumental in characterising the biological substrate of heterogeneous cognitive and behavioural deficits in ALS. In this review we discuss the clinical and radiological aspects of cognitive and behavioural impairment in ALS focusing on the recognition, assessment, and monitoring of these symptoms.
Amyotrophic lateral sclerosis is a disease characterized by: (1) muscular atrophy with fibrillary twitchings, (2) spasticity with evidence of lesions of the upper motor neurons and (3) symptoms of disorder in the brain stem, especially its bulbar portion. Although Charcot 1 (1870) was first to differentiate ordinary muscular atrophy and amyotrophic lateral sclerosis, he said little about psychic disturbances not essential to a diagnosis of the disease but sometimes associated with it. Westphal² (1885) and Zacher³ (1886), in isolated cases, noted amyotrophic lateral sclerosis associated with dementia paralytica. Oppenheim and Siemerling⁴ (1886) were the first to consider and separate various types of purely bulbar palsy. They thought that the explosive emotional reactions in such cases were due to lesions of the upper motor neurons that end in the nuclei. Marie⁵ (1892), thinking psychic disturbances fairly common in amyotrophic lateral sclerosis, was among the first to call
Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions \`disinhibit' or \`release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.
The difficulties inherent in obtaining consistent and adequate diagnoses for the purposes of research and therapy have been pointed out by a number of authors. Pasamanick12 in a recent article viewed the low interclinician agreement on diagnosis as an indictment of the present state of psychiatry and called for "the development of objective, measurable and verifiable criteria of classification based not on personal or parochial considerations, but on behavioral and other objectively measurable manifestations."Attempts by other investigators to subject clinical observations and judgments to objective measurement have resulted in a wide variety of psychiatric rating scales.4,15 These have been well summarized in a review article by Lorr11 on "Rating Scales and Check Lists for the Evaluation of Psychopathology." In the area of psychological testing, a variety of paper-and-pencil tests have been devised for the purpose of measuring specific