FULL-LENGTH ORIGINAL RESEARCH
Clinical, neuropsychological, and metabolic characteristics
of transient epileptic amnesia syndrome
*Amel Mosbah, †Eve Tramoni, ‡§Eric Guedj, *Sandrine Aubert, *G
eraldine Daquin, †§¶Mathieu
Ceccaldi, †§¶Olivier F
elician, and *§¶#Fabrice Bartolomei
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
SUMMARY
Dr. Amel Mosbah was
a fellow in epileptology
in Marseille, France,
and is currently a
neurologist in Guelma,
Algeria.
Objective: Transient epileptic amnesia (TEA) is a recently individualized syndrome
occurring in adult patients that includes epileptic seizures with amnestic features and
interictal memory disturbances.
Methods: We investigated the clinical, neuropsychological, and 18F-FDG positron
emission tomography (18F-FDG-PET) features of 30 consecutive cases of TEA in our
center.
Results: The mean age of onset of amnestic seizures was 59 years. Pure acute amnesia
was the only epileptic manifestation in 17% of cases. Interictal electroencephalography
(EEG) abnormalities were present in 57% on awake recording and in most patients in
whom sleep EEG was performed (96%). Nine of 30 patients showed anterograde memory deficit and six of 30 exhibited mild executive functioning impairment. On the autobiographical memory interview (AMI), patients showed a significant deficit for the
recent period of the episodic subscale. Outcome under treatment was favorable in the
majority of cases. A significant improvement was noted on recollection of autobiographical memory. 18F-FDG-PET (22 cases) showed positive correlations between left
mesial temporal metabolism levels and anterograde and retrograde memory scores.
Significance: TEA is an emerging epileptic syndrome that likely remains misidentified
and misdiagnosed. Neurometabolic data support a dysfunction of a hippocampal-neocortical network sustaining episodic memory.
KEY WORDS: Amnesia, Epilepsy, Episodic memory, EEG, FDG-PET, Accelerated
forgetting.
core manifestations.9,10Accordingly, TEA refers to the following: (1) a history of recurrent witnessed episodes of transient amnesia; (2) cognitive functions other than memory
judged to be intact during typical episodes by a reliable witness; (3) evidence for a diagnosis of epilepsy provided by
epileptiform abnormalities on electroencephalography
(EEG), concurrent onset of other clinical features of epilepsy (lip-smacking, olfactory hallucinations), and/or clear
response to anticonvulsant therapy or by a combination of
these three factors.
Although this epileptic syndrome is becoming increasingly recognized,10–14 large homogeneous series that contribute to delineating its main characteristics remain
scarce,10 and its individualization as an epileptic syndrome is therefore discussed.10 Consequently, TEA is
not uniformly acknowledged as a distinct neurologic
condition, and epileptic amnestic attacks probably remain
Partial seizures may manifest as episodes of transient
amnesia, sometimes as the sole epileptic manifestation.1–8
Several terminologies have been used to designate these
epileptic amnestic episodes, among which “transient epileptic amnesia” (TEA) has become the most popular.3 Introduced in 1993, this concept was further expanded to qualify
a syndrome with ictal and interictal memory disturbances as
Accepted January 14, 2014.
*Henri Gastaut/ Hospital, Marseille, France; †Neurology and Neuropsychology Department, Timone Hospital, Marseille, France; ‡Biophysics and
Nuclear Medicine Department, Timone Hospital, Marseille, France;
§School of Medicine, Aix Marseille University, Marseille, France;
¶INSERM, U1106, Brain Dynamic Institute, Marseille, France; and #Clinical Neurophysiology Department, Timone Hospital, Marseille, France
Address correspondence to Fabrice Bartolomei, H^opital Henri Gastaut/
Centre Saint Paul, 300 Bd Sainte Marguerite, 13009 Marseille, France.
E-mail: [email protected]
Wiley Periodicals, Inc.
© 2014 International League Against Epilepsy
1
2
A. Mosbah et al.
underestimated or misidentified as other transient memory disorders.
The aim of the present study was thus to increase current
knowledge on TEA in light of 30 new consecutive cases
diagnosed in our center. We provide a detailed account of
the clinical, neurophysiologic, and neuropsychological
characteristics of the patients along with brain metabolism
data using 18F-FDG positron emission tomography
(18F-FDG-PET) neuroimaging.
Patients and Methods
Patients
This is a retrospective study investigating patients
recruited at two institutions (Timone Hospital and Henri
Gastaut Hospital) in Marseille, France, during the 2007–
2012 period and fulfilling diagnostic criteria for TEA.9 All
the patients were initially seen by one neurologist in one of
the institutions (OF, FB, SA). Two patients have been
included in a previous neuropsychological study.15 Clinical
characteristics of attacks, context of occurrence, possible
triggering factors, and cognitive complaints were carefully
assessed. All patients underwent a full neurologic examination, waking EEG, and neuropsychological assessment. In
addition, sleep EEG and 18F-FDG-PET were performed in
24 and 22 patients of 30, respectively.
The detailed methodology is indicated in Data S1.
Neuropsychological assessment
Each patient underwent a full neuropsychological evaluation, which included a battery of tests assessing anterograde
verbal and visual memory, and retrograde memory for personal events.
Anterograde memory was evaluated using the logical
memory from Wechsler Memory Scale III (WMS-III;
immediate and 30-min delayed recall); the Rey-Osterrieth
Complex Figure (ROCF) test (immediate and 30 min
delayed recall); and the RL-RI 16, a French adaptation of
the Free and Cued Selective Reminding Test (immediate
and 30 min delayed recall). Autobiographical memory was
tested with the autobiographical memory interview
(AMI).16 Autobiographical memory for the last 5 years and
the last 12 months was assessed using a semi-structured
questionnaire (TEMPau task).17,18 In addition, long-term
consolidation was examined in a subset of patients referred
to as accelerated long-term forgetting (ALF) subgroup,
who exhibited the following: (1) normal performance on
standard anterograde memory tests; (2) autobiographical
memory deficit; and (3) subjective complaint of accelerated
forgetting. Sixteen ALF patients (mean age 62.81, (standard
deviation) 9.14) were individualized, and performances
were compared to those obtained from a group of 14 healthy
age-matched controls (mean age 64.28 4.5). The experimental protocol was established according to a previous
study from our group that showed dissociation of long-term
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
consolidation between context-rich and context-free (single
item) memory in patients with temporal lobe epilepsy
(TLE).15 Context-rich memory tasks consisted of two tests
—the logical memory subtest of the WMS-III19 and the
ROCF—composed of several isolated elements (words,
drawings) embedded within a context (words are linked
together within a narrative context, parts of the figure are
linked together within a spatial context). Context-free memory tasks included three single-item recognition memory
tests (for details of procedures, please refer Tramoni
et al.15). Recognition was then tested at 1 h and 6-week
delays in a two forced-choice procedure. Performance of
TEA patients was compared with that obtained by control
subjects using the nonparametric Mann-Whitney U test.
Interictal 18F-FDG-PET study
Interictal brain metabolism was studied in 22 of 30
patients (mean age 63.2 8.0 years), according to the same
protocol for 22 age-matched healthy controls(mean age
62.5 10.7 years). PET scan was performed using an integrated PET/computerized tomography (CT) camera (Discovery ST; GE Healthcare, Waukesha, WI, U.S.A.) using
150 MBq of 18F-FDG that was injected intravenously in an
awake and resting state, with eyes closed, in a quiet environment. Whole-brain statistical analysis was performed at
voxel-level using SPM8 software (Welcome Department of
Cognitive Neurology, University College, London, United
Kingdom). Significant regions of hypometabolism in the
patients were sought in comparison to healthy subjects.
Results
Clinical and EEG data
The clinical characteristics of the patients are indicated in
Table S1.
This series included 18 men (60%). The mean age of onset
of amnestic attacks was 59 years (range 43–77 years),
whereas the mean age at the time of diagnosis was 62 years
(i.e., diagnostic delay of 3 years on average, several weeks to
13 years). The first consultation was motivated by memory
complaints in 16 patients (53%), and only 7 patients (23%)
were referred directly for investigation of epilepsy. Most
patients had no history of neurologic disorder prior to the
onset of amnestic attacks. In fifteen patients (50%), a negative
emotional life event (illness, death of a relative, retirement,
and so on) had occurred soon before the beginning of symptoms. Ten patients (33%) had a past or current history of
depression. Nine patients (30%) had an autoimmune disorder
or biologic abnormalities (Table S1). A history of seizures
was found in a first-degree relative in three patients (10%),
one of them having been diagnosed as TEA.
Amnestic attacks and seizures
Seven patients (23%) experienced attacks that lasted
<5 min, 11 patients (37%) had attacks from 5 to 10 min in
3
Transient Epileptic Amnesia
duration, and 4 patients (13%) from 30 to 60 min. For the
remaining eight patients (27%), attacks could exceed 1 h.
Regarding the frequency of seizure, 13 patients (43%) experienced from 1 to 10 attacks per year, 13 patients (43%)
experienced 1–10 attacks per month, and 3 patients (10%)
experienced 1–10 attacks per week. Only one patient
reported attacks that occurred several times a day. In all
cases, attacks occurred during the daytime, but in five
patients (17%) they also occurred at night. Attacks on awakening were present in 23% of cases (seven patients). Pure
acute amnesia was the sole epileptic manifestation in five
cases (17%). During these episodes, patients typically
exhibited an appropriate behavior while pursuing their
ongoing activity and, afterwards they had little or no recollection of the episode. They were occasionally perplexed
and anxious (11 patients, 37%), with repetitive questioning
(six patients, 20%) or confused, having incoherent speech,
and time and/or space disorientation (13 patients, 43%).
Afterwards, 10 patients (33%) could provide a partial
account of the episode, whereas for the remaining 20
patients (67%), amnesia of the episode was complete.
Twenty-four patients (80%) reported additional epileptic
phenomena such as autonomic changes (seven patients),
fear and strong anxiety (seven patients), rising epigastric
sensation (seven patients), myoclonic jerks (six patients),
deja vu (five patients), oral alimentary automatisms (four
patients), language disturbance (three patients), prolonged
state of unconsciousness (two patients), olfactory hallucinations (two patients), and hyperthermia (one patient). Secondary generalized tonic–clonic seizures occurred in three
patients (10%).
Interictal EEG abnormalities were present in 17 patients
(57%) on awake recording and in most patients who performed sleep EEG (23/24: 96%). Activation of epileptiform
activity during sleep was found in 20 patients (83%). Fully
normal sleep EEG was observed in only one patient.
Interictal epileptiform features were various and included
focal spikes, sharp waves, spike-waves, or theta activity.
Abnormal activity was recorded predominantly by temporal
electrodes: bilaterally in 16 patients (53%), right-sided in 7
(23%), and left sided in 6 (20%).
In one patient, a seizure was recorded during video-EEG
monitoring. EEG showed ictal rhythmic theta discharges
alternating between left and right temporal derivations.
Interictal memory disturbances
Standard neuropsychological assessment
Neuropsychological assessment was completed in all 30
patients with TEA (Table 1). In comparison to normative
data, group analysis demonstrated no significant deficit on
any aspect of the battery. Nevertheless, important betweensubject variability was noted, as 9 of 30 patients showed
anterograde memory deficit, whereas 6 of 30 exhibited mild
executive functioning impairment.
Table 1. Neuropsychological profile of patients with
TEA (n = 30)
Neuropsychological measure
Retrograde memory scores (AMI)
Semantic subscale
Childhood (21) (cutoff = 11)
Adulthood (21) (cutoff = 14)
Recent period (21) (cutoff = 17)
Episodic subscale
Childhood (9) (cutoff = 3)
Adulthood (9) (cutoff = 3)
Recent period (9) (cutoff = 5)
WMS-III story recall subtesta
Immediate
Delayed
Rey figure delayed recall (36)
RL-RI16
Free delayed recall (16)
Total (free + cued) delayed recall (16)
Language/semantic memory scores
Picture naming (80)
Pyramid and palm tree test (52)
WAIS-III information subtesta
Executive function scores
Trail making test A (time in seconds)
Trail making test B (time in seconds)
Letter fluency (words/2 min)
Category fluency (words/2 min)
WCST categories completed (6)
WCST total errors
Stroop interference procedure (time in s)
WAIS-III digit span subtesta
Visuospatial perception score
Rey figure copy (36)
Benton face perception (54)
Benton line orientation (30)
Praxis (29)
Mean scores of
TEA patients (SD)
17.29 (3.3)
18.2 (2.3)
20 (1.4)
5.4 (2.4)
5.1 (2.2)
5.7 (2.5)
11.0 (2.86)
10.9 (2.86)
19.6 (6.88)
9.5 (3.6)
14.6 (2.76)
79.5 (1.05)
51.4 (0.7)
12.1 (3.44)
46.3 (18.3)
118.0 (59.19)
20.8 (8.76)
31.2 (10.27)
5.4 (1.25)
6.4 (5.63)
74.7 (22.23)
9.4 (2.99)
23.6 (4.01)
46.2 (4.02)
34.2 (2.88)
28.6 (0.4)
Numbers in brackets in the first column refer to maximum scores.
Scaled scores: am = 10 3.
Autobiographical memory
Table 1 shows the mean scores according to period of
life of patients at the AMI. On the semantic subscale,
only one patient scored below cutoff for each time period.
This is in sharp contrast to performance on the episodic
subscale, with five patients scoring below cutoff for
childhood and adulthood periods and 11 patients for the
recent period.
Figure 1A indicates the mean scores according to period of life for patients compared with normative data at
the TEMPau task. Results demonstrated a significant loss
covering the last 5 years (24/30 patients had
z-score < 1.14) and the 12 last months (13/30 patients
had z-score < 1.14). For the recent period, the recollected episodes had occurred mainly in the several weeks
prior to assessment, in agreement with the patients’
reports.
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
4
A. Mosbah et al.
A
C
B
D
Figure 1.
(A) Mean scores (SD) by period of life obtained in patients and controls40 at the TEMPau task. (B–D) Performances of ALF patients
(n = 16) and controls (n = 14) at recognition of single items (B), memory (C) and complex figure (D) (1 h and 6-week delays).
Epilepsia ILAE
Long-term consolidation in the ALF subgroup
Performances of ALF patients and controls at recognizing
single items and elements that compose stories and the
ROCF are shown in Figure 1B–D (1 h and 6-week delays).
No significant difference was found between the two groups
in recognition of single items at 1 h (p = 0.185) and at
6-week delays (p = 0.481; Fig. 1B).
Although no significant difference was found between
the two groups in recognizing stories (p = 0.085) and the
ROCF (p = 0.481) at the 1-h time point, a group effect was
found at the 6-week time point (p < 0.01; Fig. 1C,D).
Antiepileptic medication and clinical outcome
The mean duration of follow-up was 2.8 years (range
3 months to 12 years; Table S1). Antiepileptic drugs were
introduced after the completion of the first neuropsychological evaluation and always after imaging and EEG (including sleep EEG) investigations. Antiepileptic drugs were
used in 28 patients (93%), usually based on monotherapy
(26 patients, 93%), but six patients required a combination
of two drugs. Lamotrigine was the most used drug (96%).
Outcome under treatment was considered to be favorable in
the majority of cases for whom follow-up data were available (26 cases, follow-up [FU] > 6 months). Seizure
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
freedom was observed in 19 (73%) of 26 cases, whereas a
significant reduction in seizure frequency (>50%) was
observed in the remaining cases (27%).
With regard to memory complaints, 12 patients were evaluated 1 year after treatment initiation. All patients reported a
subjective improvement in their memory abilities. Nevertheless, statistical analysis yielded no significant improvement
when comparing standard neuropsychological measures
obtained before and after treatment. However, a significant
improvement was noted in the recollection of autobiographical memory for the last 5-year and last 12-month periods
(p = 0.01; nonparametric Wilcoxon test; Fig. 2).
Neuroimaging data
Magnetic resonance imaging
In most cases, magnetic resonance imaging (MRI)
revealed no morphologic change (21 cases, 70%) or nonspecific abnormalities (Table S1).
18F-FDG-PET
In comparison with healthy subjects, patients with TEA
showed significant hypometabolism (22 cases, 75.86%)
within bilateral middle frontal gyri (BA6), and within left
5
Transient Epileptic Amnesia
medial, superior, precentral, and paracentral gyri (BA6,
BA31; p < 0.05, corrected; Table 2 and Fig. 3A). With use
of medial temporal mask, additional hypometabolism was
found within the right posterior parahippocampus (BA36)
and left uncus (BA28; p < 0.005, uncorrected; Table 2 and
Fig. 3B,C).
To explore further the neural basis of memory disturbances, we performed additional correlation analyses
between cognitive scores and the five significant clusters of
decreased metabolism. Only medial temporal clusters were
found to correlate with cognitive measures. In particular, we
observed positive correlations between the left uncus
metabolism level and the following:
- standard anterograde memory scores: immediate
(p = 0.01) and delayed recall (p = 0.02) of the ROCF,
delayed recall of the RL-RI16 (p = 0.005),
Figure 2.
Evolution of TEMPau scores (mean, SD) before and during followup under antiepileptic drugs treatment.
Epilepsia ILAE
- long-term anterograde memory scores: 6 week-delay
word recognition (p = 0.016),
- retrograde memory scores: total AMI (p = 0.035) and
episodic AMI scores (p = 0.016).
We also observed positive correlations between the right
parahippocampal metabolism and place recognition (1 h
delay; p < 0.01) and story recognition (6-week delay;
p < 0.05).
Discussion
Electroclinical presentation
To date, only one large series of TEA, which included 50
patients, has been published.10 As reported previously, TEA
occurs in middle-age individuals, usually between 50 and
60 years of age,9,10,14 with a male predominance.9,10
The etiology underlying TEA remains poorly understood.
An autoimmune context was found in a particularly high
proportion of our patient series (30%). Although a chance
association between unrelated conditions cannot be
excluded, this observation raises interesting issues about
potential pathophysiologic mechanisms.
Amnestic attacks were the main ictal manifestations.
They occurred on waking in only 23% of our patient series. This contrasts with the frequent occurrence of transient amnesia upon waking previously reported in TEA
(74% of cases in the series of Butler et al.).10 Only 23%
of the patients of this current series were referred to an
epileptologist after the first epileptic event. The diagnosis
of epilepsy remains particularly difficult when pure acute
amnesia is the sole manifestation of seizure. This
occurred in 17% of our cases. During typical amnestic
seizure, there is no confusion or altered consciousness.9
These manifestations share several characteristics with
other transient amnestic states, such as transient global
amnesia (TGA), including the inability to form new
memories (anterograde amnesia) along with variable
Table 2. PET hypometabolism in patients with TLE, in comparison to healthy subjects
Analysis
Cluster
p(FWE-cor)
Whole-brain
0.045
482
0.000
1,588
0.004
875
0.255
117
0.426
35
MTL mask
Cluster
k
Peak
p(FDR-cor)
Peak
T
Peak
p(unc)
0.040
0.041
0.040
0.040
0.040
0.040
0.040
0.040
0.284
0.284
0.284
5.22
4.32
5.03
4.88
4.85
4.84
4.54
4.42
3.23
2.86
3.04
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.001
0.003
0.002
Tailairach coordinates
x
y
z
36
34
51
44
36
4
2
14
28
36
22
5
10
0
4
3
19
14
14
39
36
5
50
53
39
48
48
43
60
53
5
12
20
Localization
Right middle frontal gyrus (BA6)
Right middle frontal gyrus (BA6)
Left precentral gyrus (BA6)
Left middle frontal gyrus (BA6)
Left middle frontal gyrus (BA6)
Left paracentral lobule (BA31)
Left medial frontal gyrus (BA6)
Left superior frontal gyrus (BA6)
Right parahippocampal gyrus (BA36)
Right parahippocampal gyrus (BA36)
Left uncus (BA28)
Results from SPM8 are listed in decreasing order of peak T-score value within each cluster
Cor, corrected; unc, uncorrected; FWE, family-wise error; FDR, false discovery rate.
k value represents the number of significant voxels in the particular cluster. x, y, and z are the Tailairach coordinates (mm).
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
6
A. Mosbah et al.
B
A
C
Figure 3.
Anatomic localization of area of hypometabolism in patients, in comparison to healthy subjects. In comparison to healthy subjects,
patients with TEA showed significant hypometabolism within bilateral middle frontal gyri (BA6), and within left medial, superior, precentral, and paracentral gyri (BA6, BA31; p < 0.05, corrected) (A). Additional hypometabolism was found using medial temporal mask within
the left uncus (BA28) (B) and right posterior parahippocampus (BA36) (C).
Epilepsia ILAE
amnesia for recent events (retrograde amnesia). Repetitive questioning is classically less observed in TEA
attacks than in TGA, interpreted as a consequence of partial rather than global anterograde amnesia. This feature
has been reported, however, in about 50% of patients
of the series of Butler et al.10 and was present in 20%
of our cases.
The diagnosis of epileptic seizures is dramatically facilitated when TLE seizure symptoms are also present, such as
deja vu, automatisms, epigastric and olfactory auras. They
were found in >80% of our patients but were not systematically associated with amnestic episodes.
Interictal EEG abnormalities usually reported in TEA
include background slowing and epileptiform discharges,
involving one or both hemispheres, over temporal or frontotemporal electrodes.10,14 However, awake EEG revealed no
abnormal activity in up to 31% of patients in the series of
Butler et al.10 and 43% of the current study. Sleep EEG
recording was particularly useful in this context showing
epileptiform abnormalities in about 96% of our patient
series.
Interictal memory disturbances
Interictal memory impairment was the main manifestation for seeking medical attention in about half of our
patients. This observation is consistent with those of previous reports in which memory complaints preceded the
full-blown syndrome by several years.20,21 Most of our
patients performed within normal range on standardized
memory measures, as mentioned in previous reports.9,10
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
The combination of accelerated long-term forgetting
(ALF) and remote autobiographical memory loss constitute the most characteristic features of interictal memory
deficit in TEA.4,22–26 This pattern of ALF and autobiographical memory loss has also been described in other
types of temporal lobe epilepsy (TLE).15,27–30 Several
pathophysiologic factors could contribute to the occurrence of ALF, including the role of seizures, of interictal
EEG abnormalities, and associated structural lesions.23
However, in the current study, this typical association
(ALF and autobiographical memory loss) was observed in
only 16 of 30 patients. Retrograde memory loss typically
involves the episodic component of autobiographical memory, whereas semantic knowledge of life events is impeded
to a lesser extent. In some patients, the childhood and most
recent periods were less affected, conferring a peculiar
U-shape profile to the memory loss.15,21,25
ALF, which is the excessively rapid loss of newly
acquired memories over a period of days or weeks, has also
been documented in previous studies that focus on patients
with TEA. ALF may not be global but material-specific, that
is, selective to certain material kinds such as episodic memory. In a recent study, we documented this hypothesis and
demonstrated dissociated long-term consolidation of
contextually bound experiences (including episodic memory, impaired) and context-free information (semantic
knowledge and single item, preserved).15 The present study
replicates these findings in the subgroup of patients (16/30;
“ALF subgroup”) showing intact recognition of single items
at 6-week delay, whereas recognition of complex material
7
Transient Epileptic Amnesia
such as stories and ROCF at the same time point was
impaired.
Treatment responsiveness
Most of our patients experienced a complete resolution of
amnesic attacks or a markedly reduced frequency (as
reported in previous studies).9,10,14,31,32 Subjective memory
improvement is often reported after treatment initiation,9,10,14 as in the current study. However, direct comparison between pretreatment and posttreatment memory
performance has been undertaken on rare occasions. In a
recent study focusing on three patients with TEA, cognitive
functions were assessed before and 6 months after initiation
of antiepileptic therapy. A persistent decline in remote autobiographical memory despite full resolution of amnestic seizures was demonstrated.33 Here, we found no significant
improvement on standard neuropsychological measures
obtained before treatment and 1 year following treatment
initiation. Although ALF was not formally reassessed at the
1-year time-point, recollection of autobiographical events
was found to improve. Of interest, autobiographical memory improvement was significant only for the most recent
period, suggesting that reduced ALF may have, at least
partly, contributed to this recovery.
Neuroanatomic correlates
Although the precise anatomic substrates of TEA remain
to be established, several lines of evidence suggest a strong
implication of the medial temporal lobe (MTL). In addition,
mild metabolic hippocampal changes have been reported in
a group study combining 18F- FDG-PET and magnetic resonance spectroscopy imaging.15 In a volumetric study, there
was mild volume reduction in both hippocampal bodies.34
These authors also found a positive correlation between hippocampal volume and performance on visual memory performance but no correlation with ALF or autobiographical
memory scores.34 This leads to the suggestion that ALF and
autobiographical memory impairment could result from a
diffuse anatomic dysfunction rather than from focal MTL
damage. Our PET findings do not support this view, as correlation analysis showed that medial temporal clusters and
the parahippocampal cortex (PHC) correlated not only with
verbal and visual anterograde memory performance but also
with long-term anterograde memory (6-week delay word
and story recognition) and retrograde memory (total AMI
and episodic AMI) scores. This result is in agreement with a
recent study that has investigated patients with TEA using
a functional MRI (fMRI) anterograde memory paradigm. In
comparison with controls, patients showed reduced activation of the posterior parahippocampal gyrus (pPHG) and a
reduced effective connectivity between the right pPHG and
the right middle temporal gyrus.35
However, dysfunction may encompass medial temporal
regions as suggested by the present PET study, which demonstrated clusters of hypometabolism within prefrontal
regions in comparison with controls. These data are coherent with the known architecture of the episodic memory network. fMRI studies have demonstrated that, in addition to
temporal and retrosplenial/cingulate cortices, prefrontal
regions are associated with autobiographical recollection.36,37 In addition to recollection, prefrontal cortices may
also participate in consolidation processes via the early tagging of information to ensure the progressive hippocampaldriven rewiring of cortical networks that support remote
memory storage.38
Taken together, interictal memory impairment in TEA is
probably sustained by neural dysfunction that impedes the
hippocampal-neocortical interplay necessary to form and
stabilize new memory traces, but also to recollect remote
experiences.39
Conclusion
The present series largely confirms previous reports
including seizure occurrence in middle-age subjects that
comprise amnestic features and other TLE symptoms.
Impaired remote autobiographical memory and ALF, which
were frequently the main cause of seeking medical attention, were also noted. Additional features include the frequent occurrence of depression and association with
autoimmune disorders, raising interesting issues regarding
putative pathophysiologic mechanisms. Furthermore, neurometabolic data support a dysfunction of a hippocampalneocortical network sustaining episodic memory.
Acknowledgments
We thank Dr Martine Gavaret, Dr Agnes Trebuchon, and Dr Lejla Koric
for clinical assessment of some of the included patients. We thank Dr Russell Hewett for the English-language revision of the manuscript and helpful
remarks.
Disclosure
None of the authors has any conflict of interest to disclose. We confirm
that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
References
1. Gallassi R, Morreale A, Lorusso S, et al. Epileptic transient amnesia.
Ital J Neurol Sci 1988;(Suppl. 9):37–39.
2. Hodges JR, Warlow CP. Syndromes of transient amnesia: towards a
classification. A study of 153 cases. J Neurol Neurosurg Psychiatry
1990;53:834–843.
3. Kapur N. Transient epileptic amnesia–a clinical update and a
reformulation. J Neurol Neurosurg Psychiatry 1993;56:1184–1190.
4. Kopelman MD, Panayiotopoulos CP, Lewis P. Transient epileptic
amnesia differentiated from psychogenic “fugue”: neuropsychological,
EEG, and PET findings. J Neurol Neurosurg Psychiatry
1994;57:1002–1004.
5. Serafetinides EA. Transient epileptic amnesia–a clinical update and a
reformulation. J Neurol Neurosurg Psychiatry 1994;57:1549.
6. Tharp BR. Transient global amnesia: manifestation of medial temporal
lobe epilepsy. Clin Electroencephalogr 1979;10:54–56.
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
8
A. Mosbah et al.
7. Tassinari CA, Ciarmatori C, Alesi C, et al. Transient global amnesia as
a postictal state from recurrent partial seizures. Epilepsia
1991;32:882–885.
8. Palmini AL, Gloor P, Jones-Gotman M. Pure amnestic seizures in
temporal lobe epilepsy. Definition, clinical symptomatology and
functional anatomical considerations. Brain 1992;115(Pt 3):749–769.
9. Zeman AZ, Boniface SJ, Hodges JR. Transient epileptic amnesia: a
description of the clinical and neuropsychological features in 10 cases
and a review of the literature. J Neurol Neurosurg Psychiatry
1998;64:435–443.
10. Butler CR, Graham KS, Hodges JR, et al. The syndrome of transient
epileptic amnesia. Ann Neurol 2007;61:587–598.
11. Melo TP, Ferro JM, Paiva T. Are brief or recurrent transient global
amnesias of epileptic origin? J Neurol Neurosurg Psychiatry
1994;57:622–625.
12. Rabinowicz AL, Starkstein SE, Leiguarda RC, et al. Transient
epileptic amnesia in dementia: a treatable unrecognized cause of
episodic amnestic wandering. Alzheimer Dis Assoc Disord
2000;14:231–233.
13. Mendes MH. Transient epileptic amnesia: an under-diagnosed
phenomenon? Three more cases. Seizure 2002;11:238–242.
14. Gallassi R. Epileptic amnesic syndrome: an update and further
considerations. Epilepsia 2006;47(Suppl. 2):103–105.
15. Tramoni E, Felician O, Barbeau EJ, et al. Long-term consolidation of
declarative memory: insight from temporal lobe epilepsy. Brain
2011;134:816–831.
16. Kopelman MD, Wilson BA, Baddeley AD. The autobiographical
memory interview: a new assessment of autobiographical and personal
semantic memory in amnesic patients. J Clin Exp Neuropsychol
1989;11:724–744.
17. Piolino P, Desgranges B, Eustache F. Episodic autobiographical
memories over the course of time: cognitive, neuropsychological and
neuroimaging findings. Neuropsychologia 2009;47:2314–2329.
18. Guillery B, Piolino P, Desgranges B, et al. [The assessment of episodic
memory: theory and practice]. Therapie 2000;55:445–453.
19. Wechsler D. Echelle d’Intelligence de Wechsler pour Adulte III
(WAIS-III). Paris: Les Editions du Centre de Psychologie appliquee;
2000.
20. Hornberger M, Mohamed A, Miller L, et al. Focal retrograde amnesia:
extending the clinical syndrome of transient epileptic amnesia. J Clin
Neurosci 2010;17:1319–1321.
21. Felician O, Tramoni E, Barbeau E, et al. [Isolated autobiographical
amnesia: a neurological basis?] Rev Neurol (Paris) 2009;165:449–459.
22. Muhlert N, Milton F, Butler CR, et al. Accelerated forgetting of reallife events in Transient Epileptic Amnesia. Neuropsychologia
2010;48:3235–3244.
23. Butler CR, Zeman AZ. Recent insights into the impairment of memory
in epilepsy: transient epileptic amnesia, accelerated long-term
forgetting and remote memory impairment. Brain 2008;131:2243–
2263.
24. Manes F, Hodges JR, Graham KS, et al. Focal autobiographical
amnesia in association with transient epileptic amnesia. Brain
2001;124:499–509.
25. Manes F, Graham KS, Zeman A, et al. Autobiographical amnesia and
accelerated forgetting in transient epileptic amnesia. J Neurol
Neurosurg Psychiatry 2005;76:1387–1391.
Epilepsia, **(*):1–8, 2014
doi: 10.1111/epi.12565
26. Milton F, Muhlert N, Pindus DM, et al. Remote memory deficits in
transient epileptic amnesia. Brain 2010;133:1368–1379.
27. Blake RV, Wroe SJ, Breen EK, et al. Accelerated forgetting in patients
with epilepsy: evidence for an impairment in memory consolidation.
Brain 2000;123(Pt 3):472–483.
28. O’Connor M, Sieggreen MA, Ahern G, et al. Accelerated forgetting in
association with temporal lobe epilepsy and paraneoplastic
encephalitis. Brain Cogn 1997;35:71–84.
29. Narayanan J, Duncan R, Greene J, et al. Accelerated long-term
forgetting in temporal lobe epilepsy: verbal, nonverbal and
autobiographical memory. Epilepsy Behav 2012;25:622–630.
30. Wilkinson H, Holdstock JS, Baker G, et al. Long-term accelerated
forgetting of verbal and non-verbal information in temporal lobe
epilepsy. Cortex 2012;48:317–332.
31. Pritchard PB III, Holmstrom VL, Roitzsch JC, et al. Epileptic amnesic
attacks: benefit from antiepileptic drugs. Neurology 1985;35:1188–1189.
32. Razavi M, Barrash J, Paradiso S. A longitudinal study of transient
epileptic amnesia. Cogn Behav Neurol 2010;23:142–145.
33. Ioannidis P, Balamoutsos G, Karabela O, et al. Transient epileptic
amnesia in a memory clinic setting: a report of three cases. Epilepsy
Behav 2011;20:414–417.
34. Butler CR, Bhaduri A, Acosta-Cabronero J, et al. Transient epileptic
amnesia: regional brain atrophy and its relationship to memory
deficits. Brain 2009;132:357–368.
35. Milton F, Butler CR, Benattayallah A, et al. The neural basis of
autobiographical memory deficits in transient epileptic amnesia.
Neuropsychologia 2012;50:3528–3541.
36. Svoboda E, McKinnon MC, Levine B. The functional neuroanatomy
of autobiographical memory: a meta-analysis. Neuropsychologia
2006;44:2189–2208.
37. Cabeza R, St Jacques P. Functional neuroimaging of autobiographical
memory. Trends Cogn Sci 2007;11:219–227.
38. Lesburgueres E, Gobbo OL, Alaux-Cantin S, et al. Early tagging of
cortical networks is required for the formation of enduring associative
memory. Science 2011;331:924–928.
39. Moscovitch M, Nadel L. Consolidation and the hippocampal complex
revisited: in defense of the multiple-trace model. Curr Opin Neurobiol
1998;8:297–300.
40. Piolino P, Giffard-Quillon G, Desgranges B, et al. Re-experiencing old
memories via hippocampus: a PET study of autobiographical memory.
Neuroimage 2004;22:1371–1383.
Supporting Information
Additional Supporting Information may be found in the
online version of this article:
Data S1. Neuropsychological testing and Interictal
F18-FDG-PET study (detailed methodology).
Table S1. Clinical data in patients with TEA (n = 30).
Table S2. EEG data in patients with TEA (n = 30). WE,
waking EEG.