Neurocase
The Neural Basis of Cognition

ISSN: 1355-4794 (Print) 1465-3656 (Online) Journal homepage: https://www.tandfonline.com/loi/nncs20

Acute loss of psychic self-activation after cardiac
arrest and delayed bilateral pallidal lesions on
brain MRI
Olivier Martinaud, Floriane Le Goff, Jasmine Carlier, Dorothée Pouliquen,
Emmanuel Gérardin & Arnaud Savouré
To cite this article: Olivier Martinaud, Floriane Le Goff, Jasmine Carlier, Dorothée Pouliquen,
Emmanuel Gérardin & Arnaud Savouré (2019): Acute loss of psychic self-activation
after cardiac arrest and delayed bilateral pallidal lesions on brain MRI, Neurocase, DOI:
10.1080/13554794.2019.1608263
To link to this article: https://doi.org/10.1080/13554794.2019.1608263

Published online: 25 Apr 2019.

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NEUROCASE
https://doi.org/10.1080/13554794.2019.1608263

Acute loss of psychic self-activation after cardiac arrest and delayed bilateral
pallidal lesions on brain MRI
Olivier Martinauda,b, Floriane Le Goffa, Jasmine Carliera, Dorothée Pouliquena, Emmanuel Gérardinc
and Arnaud Savouréd
a

Department of Neurology, Rouen University Hospital, Rouen, France; bNeuropsychologie et Imagerie de la Mémoire Humaine, Normandie
University, UNICAEN, PSL Research University, EPHE, INSERM, U1077, CHU de Caen Normandie, Caen, France; cDepartment of Neuroradiology,
Rouen University Hospital, Rouen, France; dDepartment of Cardiology, Rouen University Hospital, Rouen, France
ABSTRACT

ARTICLE HISTORY

The delay between cardiac arrest and brain MRI is usually extremely different in the few cerebral
imaging studies assessing the affected brain areas. We report an unusual case of loss of psychic selfactivation appeared immediately after a cardiac arrest in a middle age patient. The first brain MRI, one
month after the vascular event, did not show the classical lesions typically reported, such as lesion of
the caudate nucleus or the globus pallidus. Two years later, although the cognitive performances of our
patient were improved, a second brain MRI demonstrated bilateral pallidal lesions, suggesting a
possible mechanism with delayed hypoxic lesions.

Received 31 December 2018
Accepted 9 April 2019

Introduction
Despite many prior neuroimaging studies after cardiac arrest,
a clear link has not been established between imaging findings
and cognitive outcomes. Part of the problem lies in the variable
delays of imaging after cardiac arrest, ranging from 1 day to 10
months in various studies. Another problem is the paucity of
studies; only four cases of serial MRIs after cardiac arrest have
been described. (Falini et al., 1998; Kano et al., 2006; Konaka,
Miyashita, & Naritomi, 2007). One patient performed four brain
MRI between 2 days and 7 weeks after cardiac arrest (Falini et al.,
1998) and the three other patients performed two brain MRI
between 1 and 17 days (Kano et al., 2006; Konaka et al., 2007).
Three out of these four cases demonstrated delayed development of post-ischemic changes, but the last brain MRI of the
fourth patient without lesion was performed only 8 days after
the cardiac event. Moreover, only three studies have evaluated
the brain lesions underlying the neuropsychological deficits, with
MRI scans performed after cardiac arrest, from 1 to 47 days (Roine,
Raininko, Erkinjuntti, Ylikoski, & Kaste, 1993), from 6 to 22 months
(Grubb et al., 2000), and from 4 to 62 months (Horstmann et al.,
2010), respectively. No correlation between focal damages on
MRI and cognitive performances was found in these three studies. The most common explanation of this discrepancy lies on an
extensive brain damage, leading to the combination of several
cognitive deficits, including impairment of the memory and the
executive functions (Horstmann et al., 2010; Lim, Alexander,
LaFleche, Schnyer, & Verfaellie, 2004). Actually, correlations
between global cerebral atrophy and memory impairment were
found in accordance with this hypothesis (Grubb et al., 2000;
Horstmann et al., 2010). However, it remains unclear why focal
lesions observed after cardiac arrest do not lead to selective

Cardiac arrest; loss of
psychic self-activation;
delayed brain lesions; brain
MRI; cognition

cognitive deficits linked to the topography of these lesions.
Here, we report the case of a man who suffers from loss of psychic
self-activation, a cognitive state similar to abulia with mental
emptiness. These symptoms appeared immediately after
a cardiac arrest, without focal lesion explaining the cognitive
deficit one month after the vascular event, but with delayed
bilateral pallidal lesions two years later.

Clinical report
A 49-year-old man, with no medical history, suffered an out-ofhospital cardiac arrest. His neighbor initiated cardiopulmonary
resuscitation after less than 5 min. The medical team found
ventricular fibrillation, persistent after administration of three
external countershocks and 7 mg of adrenalin. Restoration of
spontaneous circulation was obtained after a venoarterial extracorporeal membrane oxygenation (ECMO) support, one another
external countershock and 1 mg of adrenalin. The low-flow was
estimated to 90 min. Biological analysis, including hemoglobin
and toxic panel, was normal. Angiography revealed a 50% stenosis in the marginal artery. He was supported with ECMO for 7
days and was treated for septic shock due to aspiration pneumonia during 10 days. The first neurologic examination 3 days
later showed delirium – with temporo-spatial disorientation and
fluctuating level of arousal – and a transient mild right hemiparesis, without aphasic symptoms or any other deficit. Arousal
improved during the next few days, but severe apragmatism
and memory impairment were immediately noticed as soon as
the patient was conversational. Brain CT-scan performed at this
time was normal. Four months after the cardiac arrest, while he
recovered enough to clearly understand our explanations, he

CONTACT Olivier Martinaud
martinaud-o@chu-caen.fr
*Present address: Normandie Univ, UNICAEN, Caen University Hospital, Department of Neurology, 14,000 Caen, France.
‡
Present address: Department of Neurology, University Hospital of Toulouse, Toulouse, France.
© 2019 Informa UK Limited, trading as Taylor & Francis Group

KEYWORDS

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O. MARTINAUD ET AL.

gave his written consent to participate in this study (ClinicalTrials.
gov ID: NCT01304576), which was approved by an independent
ethics committee.
During the follow-up, the spontaneous speech was coherent but less fluent. He said he had no thoughts about anything and showed affective indifference towards his family. He
never expressed any anxiety or significant depressive affect.
The only compulsive activity involved food ingestion, but
without any interest in this activity. Although he was very
active in his professional and familial life before the cardiac
arrest, he could spend hours seating without speaking or
taking any initiative. His wife described a major inertia, needing her to start actions for him, such as washing and dressing.

Methods
Our patient underwent a series of standardized cognitive tests,
administered by the same neuropsychologist (DP), over three
sessions, 40 days after cardiac arrest, 5 months and 2 years
later (see Table 1 for details).
A clinical brain 1.5T MRI (Avanto, VB17 software version,
Siemens healthineer, Erlagen, Germany) was performed 30 days
after cardiac arrest, using a standardized procedure, including 3D
T2 Flair weighted imaging (slice thickness 1 mm, TR 5000 ms, TE
355 ms), axial gradient echo sequences imaging (4 mm, TR 945
ms, TE 19.1 ms), axial tensor imaging (4 mm, TR 7900 ms, TE 108
ms), and axial T1 weighted imaging (4 mm, TR 539 ms, TE 12 ms).
A second brain MRI with the same machine was performed 2
years later according to the same acquisition parameters, at the
exception of the gradient echo sequences replaced by T2 star
weighted angiography (SWAN).

Results
Neuropsychological results are summarized in Table 1. Scores
were pathological below the 5th percentile. Cognitive tests
demonstrated verbal episodic memory deficit with a significant
improvement during the two years follow-up period: Cued
recalls were better, demonstrating a real enhancement of the
cue efficiency. Cognitive executive deficit was obvious over the
three sessions, affecting reasoning, flexibility, inhibition and generation capacities, as revealed by the WCST, the TMT, the Stroop
test and verbal fluencies, respectively. A slight improvement was
noticed, especially for the WCST and the TMT. According to the
Apathy Inventory filled by himself and by his wife, he was more
aware of his difficulties at the last session of tests.
First brain MRI showed a circumscribed flair high-signal intensity localized in the anterior part of the left putamen (Figure 1(a))
but no other lesion to explain the major inertia. Diffusion tensor
imaging did not find any acute abnormalities. Although axial
gradient echo sequences showed a symmetrical bilateral pallidal
low-signal intensity (Figure 1(c)), CT-scan demonstrated no argument for recent, especially hemorrhagic, lesions. Two years later,
a symmetrical bilateral pallidal flair high-signal intensity was
clearly apparent (Figure 1(b)), while the SWAN low-signal intensity appeared to be more extensive, involving the whole lenticular nuclei (Figure 1(d)). The hypothesis of neurodegeneration
with brain iron accumulation (NBIA) led to a complete blood
metabolic
assessment
without
any
argument
for

neuroferritinopathy or aceruloplasminemia: plasma iron concentration, plasma ferritin level and serum ceruloplasmin were
normal.

Discussion
We report the brain MRI results in a 49-year-old man 30 days
and 2 years after cardiac arrest and the detailed analysis of his
cognitive abilities over two years. To summarize, our patient
suffered from a typical loss of psychic self-activation (Laplane,
1990), with an improved but persistent deficit over the time.
Surprisingly, neuroimaging did not support any explanation
for this syndrome in the first place, but only later during the
follow-up, with the late appearance of the bilateral pallidal
lesions. According to this result, two questions need to be
resolved. First, what are the classical lesions observed in case
of loss of psychic self-activation, or similar syndromes? Second,
is it possible that a mechanism of delayed hypoxic lesions
could explain this discrepancy?
Loss of psychic self-activation is sometimes compared to pure
psychic akinesia, abulia or athymormia (Habib, 2004). This behavioral impairment shares common features with apathy, such as
a lack of motivation, but is mainly characterized by feelings of
mental emptiness (Laplane, 1990). Bilateral pallidal lesions are
demonstrated in most cases (Kaphan et al., 2014), although
bithalamic infarction (Engelborghs, Marien, Pickut, Verstraeten,
& De Deyn, 2000) and bilateral infarct in the caudate nuclei
(Rodier, Tranchant, Mohr, & Warter, 1994) have been reported.
Interestingly, isolated lesions of the putamen had never been
associated with this syndrome. In a metanalysis of 240 cases with
basal ganglia lesions, 20 patients with isolated putaminal lesions
did not suffer from any behavioural disorder, although 11 out of
43 patients with isolated lesions of the caudate nucleus and 4 out
of 17 patients with isolated lesions of the globus pallidus demonstrated abulia (Bahtia & Marsden, 1994). In a recent review of
neuroimaging studies regarding anatomical correlates of apathy,
basal ganglia lesions involved caudate nucleus, nucleus accumbens, ventral pallidum, and medial thalamic nuclei, but not the
putamen (Le Heron, Apps, & Husain, 2017). In our patient, it
seems unlikely that initial putaminal lesion could explain symptoms, while a correlation with the bilateral pallidal lesions 2 years
later seems more accurate. Then, our case raises the question
about delayed hypoxic lesions depending on the cardiac arrest.
Cognitive deficits after cardiac arrest result from damage to
grey matter regions vulnerable to hypoxia, such as the hippocampus (Horstmann et al., 2010), but also basal ganglia (Choi et al.,
2010) and white-matter regions (Van der Eerden et al., 2014).
Cortical, subcortical and white-matter changes in MRI studies at
the acute stage of anoxic-ischemic encephalopathy may appear
within 7 days of brain insult (Chalela, Wolf, Maldjian, & Kasner,
2001). Interestingly for our purpose, experimental studies demonstrated delayed excitotoxicity in selectively vulnerable neurons
leading to the delayed development of pathological changes
(Lin, 2013). Delayed post-hypoxic leukoencephalopathy is a rare
condition, characterized by delayed cognitive deterioration after
an average symptom-free period of 2 weeks following hypoxemia,
and delayed extensive bilateral MRI white-matter abnormalities
(Lin, 2013). A possible mechanism may relate to the arrest of the
replacement of myelin-related proteins, which half-life range

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3

Table 1. Results of the standardized neuropsychological assessment.
Cognitive function
Global efficiency
Praxis
Verbal memory

Working memory
Cognitive Executive functions

Behavioral executive deficit – DBI (intensity)

Apathy
Mood disorder

Test
MMSE
Praxis evaluation battery
Rey copy
Immediate recall
FCSRT Sum of 3 free recall
FCSRT Sum of 3 total recall
FCSRT Differed free recall
FCSRT Differed total recall
Digit span (forward/backward)
Spatial span (forward/backward)
WCST Number of categories produced
WCST Number of errors and perseverative errors
TMT Part A (sec.)
TMT Part B (sec.)
TMT Total number of errors
Stroop Naming time (sec.)
Stroop Reading time (sec.)
Stroop Interference time (sec.)
Stroop Total number of errors
Literal verbal fluency
Categorical verbal fluency
Reduction of activities
Irritability
Hyperactivity
Lack of anticipation
Perseverations
Lack of interest
Euphoria
Disorders of sexual conduct
Anosognosia
Confabulations
Disorders of social conduct
Environmental dependency
Apathy inventory (patient/wife)
HARS
MADRS

Max
30
8
36
16
48
48
16
16
NA
NA
6
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
12
12
12
12
12
12
12
12
12
12
12
12
36
56
36

Score
(40 days)
19*
7
ND
0
ND
ND
ND
ND
4/4
4/4
ND
ND
52
failed
NA
138*
68*
>240*
NA
1*
3*
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
0/ND
0
4

Score
(5 months)
24
7
28
14
2*
19*
0*
4*
8/8
5/4
3*
41*
28
87
0
87*
53*
180*
0
5*
12*
8*
6*
2
8*
4*
8*
4*
0
8*
0
6*
6*
6/15
0
1

Score
(2 years)
28
8
32
14
8*
30*
6*
13*
7/3*
5/4
5
25*
24
77
0
86*
48
152*
0
8*
8*
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
32/32
0
11

MMSE = Mini Mental State Examination; FCSRT = French adaptation of the Free and Cued Selective Recall Reminding Test; WAIS-III = Wechsler Adult Intelligence
Scale – 3rd edition; WCST = Wisconsin Card Sorting Test; TMT = Trail Making Test; sec. = seconds; DBI = Dysexecutive Behavior Inventory (intensity score), HARS =
Hamilton Anxiety Rating Scale; MADRS = Montgomery and Asberg Depression Rating Scale; * = pathologic (<5th percentile); NA = not applicable; ND = not done.

between 19 and 22 days (Meyer, 2013). However, there is occasional bilateral globus pallidus necrosis attributed to prolonged
hypoxemia, especially after anemia or intoxication, for example,
carbon monoxide intoxication (Prockop & Chichkova, 2007). In this
condition, the asymptomatic period was observed up to 240 days
(Prockop & Chichkova, 2007). The main explanation lies in the
vulnerability of poor vascularization and watershed areas between
two sources of blood supply, which is the case of the globus
pallidus (Prockop & Chichkova, 2007). Moreover, delayed damage
appearing after cardiac arrest may be related to a secondary
ischemic injury (Lin, 2013). In our patient, an asymptomatic cognitive period could be masked by resuscitation procedures. The long
period of low-flow and hypotension may explain the consecutive
bilateral pallidal lesions. Considering the SWAN signal abnormalities demonstrated by the second brain MRI, we cannot exclude
a predisposing factor, potentially responsible for the unusual evolution of cognitive symptoms and their neural correlates. It remains
unclear why these lesions were not apparent on the brain MRI one
month later, although the cognitive deficit was apparent earlier.
One possible explanation could be that the initial small abnormalities on gradient echo sequences match with hemorrhagic conversion, despite a normal first brain CT scan, and that a secondary

process involving glial reaction or fibrosis led to the Flair signal
abnormalities on the second brain MRI.
Several limitations have to be mentioned. The first one is
the lack of neuroimaging between one month and two years
(as well as prior to one month). So, it is not possible to
determine the exact time of appearance of the pallidal lesions,
during this time period. Second, gradient echo and SWAN
sequences are not comparable enough to analyze the evolution of hemorrhagic lesions. Finally, our study is a single subject case report and suffered from limitations inherent to this
kind of study.
Our case provides evidence for delayed basal ganglia lesions
despite acute cognitive impairment, even one month after cardiac
arrest. Serial MRI data in patients suffering from cardiac arrest, but
also other various neurologic injuries such as concussion or anoxic
brain injuries, may be useful to clarify the pathophysiology of
anoxic mechanisms and the neuropsychological correlates.

Disclosure statement
No potential conflict of interest was reported by the authors.

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O. MARTINAUD ET AL.

Figure 1. Axial cerebral MRI: [To view this figure in color, please see the online version of this journal].
(a) performed at 30 days and showing a circumscribed high-signal intensity localized in the anterior part of the left putamen (white arrows); (b) performed 2 years later and showing
a symmetrical bilateral pallidal high-signal intensity (black arrows), in addition to the lesion in the left putamen; (c) gradient echo sequences performed at 30 days and showing small
symmetrical bilateral pallidal low-signal intensity (white arrows); (d) susceptibility weighted imaging performed 2 years later and showing increasing symmetrical bilateral low-signal
intensity involving the all lenticular nucleus on both sides (black arrows).L = left; R = right

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