495201
research-article2013
EEGXXX10.1177/1550059413495201Clinical EEG and NeuroscienceLapenta et al
Article
Transient Epileptic Amnesia: Clinical
Report of a Cohort of Patients
Clinical EEG and Neuroscience
2014, Vol. 45(3) 179­–183
© EEG and Clinical Neuroscience
Society (ECNS) 2013
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DOI: 10.1177/1550059413495201
eeg.sagepub.com
Leonardo Lapenta1, Valerio Brunetti1, Anna Losurdo1, Elisa Testani1,
Nadia Mariagrazia Giannantoni1, Davide Quaranta1,
Vincenzo Di Lazzaro2, and Giacomo Della Marca1
Abstract
Transient epileptic amnesia is a seizure disorder, usually with onset in the middle-elderly and good response to low dosages
of antiepileptic drugs. We describe the clinical, electroencephalography (EEG), and neuroimaging features of 11 patients with
a temporal lobe epilepsy characterized by amnesic seizures as the sole or the main symptom. We outline the relevance of a
detailed clinical history to recognize amnesic seizures and to avoid the more frequent misdiagnoses. Moreover, the response to
monotherapy was usually good, although the epileptic disorder was symptomatic of acquired lesions in the majority of patients.
Keywords
epilepsy, transient amnesia, temporal lobe epilepsy, symptomatic epilepsy, differential diagnosis
Received April 3, 2013; revised May 3, 2013; accepted June 3, 2013
Introduction
Episodes of transient amnesia may be a seizure disorder, mainly
originating from temporal lobes.1
Despite the wide range of differential diagnoses (such as
transient global amnesia [TGA], closed head injury, psychogenic amnesia, transient ischemic attack [TIA], migraine, and
drug effects)2 that frequently lead to an underdetection of these
phenomena, recurrent acute episodes of memory dysfunction
may be the sole or the main feature of epileptic seizures.
Recently, transient epileptic amnesia (TEA) has been proposed
as a distinctive epileptic syndrome with defined diagnostic criteria.2 However, the definition and the classification of this epileptic disorder are still debated; different studies2-4 have
reported the clinical and neurophysiological features of these
patients to outline the clinical syndrome.
On the basis of the reported features, we describe the clinical, EEG, and neuroimaging characteristics of 11 patients with
TEA and their response to antiepileptic treatment.
Methods and Subjects
We enrolled 11 patients (7 men and 4 women, age range =
35-79 years; mean age = 59.7 years) with episodes of TEA.
These were defined as witnessed epileptic seizures, characterized
by brief, recurrent episodes of amnesia (anterograde, retrograde, or both) with sparing of other cognitive functions.2-4 The
evidence of a diagnosis of epilepsy was provided by (1) wake
or sleep EEG, (2) co-occurrence of other clinical features of
epilepsy, and (3) a clear-cut response to antiepileptic therapy.
For each patient, EEG and ambulatory 24-hour EEG (A-EEG),
magnetic resonance imaging (MRI), and pharmacological
treatment were analyzed; moreover, detailed clinical and epileptological history regarding ictal, interictal, and peri-ictal
features were collected (for details see Tables 1 and 2). All
patients underwent a structured psychiatric interview. Standard
neuropsychological tests were used to assess anterograde and
short memory (copy and 30-minute delayed recall of the Rey–
Osterreith complex figure, the Rey 15-Item Memory Test, the
Rey Word Recognition Test, constructive praxis (figures copy),
general intelligence (Raven’s progressive matrices), selective
attention (the Stroop test), and language (semantic and phonological word production).
Characteristics of the Population
Four patients satisfied all the 3 proposed criteria, 7 patients satisfied criteria 1 and 3. The age at onset of amnesic seizures
ranged from 35 to 78 years (mean = 54.9 years). Eight patients
referred to our Neurological Department for “amnesic episodes” or “memory disturbances,” whereas 3 patients presented
1
Institute of Neurology, Catholic University, Rome, Italy
Institute of Neurology, Campus Biomedico University, Rome, Italy
2
Corresponding Author:
Leonardo Lapenta, Department of Neurosciences, Catholic University,
Policlinico Universitario “A. Gemelli” L.go A. Gemelli, 8, 00168 Rome, Italy.
Email: [email protected]
Full-color figures are available online at http://eeg.sagepub.com
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Clinical EEG and Neuroscience 45(3)
Table 1. General characteristics of the patients and EEG, MRI and memory tests findings.
Patient
No.
Gender
Age Age (Years)
(Years) at Onset
Cause of
First Medical
Consultation
EEG Findings
1
Male
75
62
Brief loss of
Left temporal spikes and
consciousness 4-5 Hz slow waves
2
Female
64
62
TGA-like
3
Male
46
35
Nocturnal
generalized
seizure
4
M
60
58
TGA-like
5
Female
47
40
6
Male
60
58
Generalized
seizure
TGA-like
7
8
9
Male
Male
Female
42
35
79
36
29
78
TGA-like
TGA-like
TGA-like
10
Female
75
73
TGA-like
11
Male
74
73
TGA-like
MRI Findings
Memory Tests
(Abnormal Scores)
Posttraumatic left
Verbal and spatial span,
temporal horn
recency effect, Stroop
meningoencephalocele
test
Asynchronous bitemporal Bilateral mesial temporal
none
sharp waves
lobe gliosis
5-6 Hz bilateral
posttraumatic bilateral
Verbal and spatial span,
frontotemporal slow
basal–frontal gliosis,
recency effect
and sharp waves
right hippocampal
sclerosis
Right frontotemporal
Posttraumatic right
Verbal and spatial span,
sharp waves and spikes
frontal horn gliosis
recency effect
Right frontotemporal
Right temporal–polar
None
sharp waves and spikes
low grade glioma
Asynchronous
Normal
None
bitemporal sharp
waves and spikes
Normal
Normal
None
Normal
Normal
None
Right frontotemporal
Posttraumatic right basal/
None
spikes
orbital frontal gliosis
Asynchronous
Right cerebellar and basal
None
bitemporal spikes and
ganglia postischemic
sharp waves
gliosis
Postsurgical right
None
Left frontotemporal
sharp waves and spikes
occipital gliosis (AVM)
Abbreviations: EEG, electeoencephalogram; MRI, magnetic resonance imaging; AVM, arteriovenous malformation; TGA, transient global amnesia.
Table 2. Clinical characteristics, semiology and treatment of the amnesic seizures.
Patient
No.
1
2
3
4
5
6
7
8
9
10
11
Seizures Duration Ictal Semiology of Amnesia
3 min up to 2 h
2 min up to 3 h
4 min
2-10 min
5-10 min
10 min
3-5 min
2-3 min
5-30 min
2 min up to 48 h
5 min up to 3 h
Anterograde–retrograde
Anterograde
Anterograde
Anterograde–retrograde
Anterograde–retrograde
Anterograde
Anterograde–retrograde
Anterograde–retrograde
Anterograde–retrograde
Anterograde–retrograde
Anterograde–retrograde
Treatment
No. of
Amnesic
Episodes
Time From
The Last
Episode
(Months)
CBZ 800 mg/d
CBZ 800 mg/d
OXC 600 mg/d, CLZ 4 mg/d
VPA 600 mg/d
LEV 1000 mg/d
LEV 1000 mg/d
LEV 750 mg/d
LEV 1000 mg/d
LEV 1000 mg/d
CBZ 200 mg/d
LEV 1000 mg/d
>30
7
48
3
9
3
11
9
8
9
15
37
39
2
33
25
20
6
9
24
11
8
Peri-ictal Features
Slight abdominal discomfort
None
None
None
None
Olfactory hallucinations
None
None
None
Slight confusion
Oral automatisms
Abbreviations: CBZ, carbamazepine; CLZ, clobazam; LEV, levetiracetam; OXC, oxcarbazepine; VPA, valproate.
episodes of loss of consciousness or generalized tonic–clonic
seizures, in one case during sleep. Amnesic attacks lasted from
2 minutes to 48 hours. Except for the first episode, which was
prolonged in 3 patients (up to 48 hours in one case), the duration ranged between 2 and 10 minutes (mean 4.4 minutes). In 4
of 11 patients the amnesic seizures were accompanied by other
peri-ictal signs or symptoms, in particular olfactory hallucinations and/or epigastric rising, oral automatisms, abdominal discomfort, and slight confusion. In the remaining 7 patients,
seizures were only characterized by anterograde amnesia or
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Lapenta et al
Figure 2. Ambulatory EEG (upper panel): low-voltage spikes over
the left temporal region during the non–rapid eye movement sleep
(N2 phase); right temporal sharp waves and spikes with spreading
over the frontocentral regions (lower panel).
Figure 1. Brain magnetic resonance images: (A) posttraumatic
bilateral basal–frontal gliosis in a patient with drug-resistant
amnesic seizures; (B) posttraumatic left temporal horn
meningoencephalocele; (C) right hippocampal sclerosis; and (D)
posttraumatic right frontal horn gliosis.
both anterograde and retrograde amnesia. MRI findings were
normal in 3 patients; 5 patients had mesial temporal lobe signal
abnormalities (Table 1, Figure 1). Seven patients underwent an
MRI study within 4 days from an amnesic episode; none of
them showed diffusion weighted image abnormalities indicating acute focal cytotoxic edema. EEG and A-EEG demonstrated epileptic abnormalities over the frontotemporal regions
in 7 patients (2 left-sided, 2 right-sided, and 3 bilateral asynchronous), whereas 2 patients presented focal sharp waves over
the same regions (Figure 2); 2 of 9 patients had normal EEG.
Ten patients were successfully treated with relatively low dosages of antiepileptic drugs, whereas 1 patient had a drug-resistant epilepsy (Table 2). One patient was described in a previous
article.5 Neuropsychological assessments demonstrated alterations in memory in 3 patients, in particular in recognition memory and recall with slight decrease of the recency effect;
moreover, these patients showed a similar subtle delay in the
Stroop test. The remaining 8 patients showed no alterations
(Table 1).
Discussion
Few recent studies2-4 have reported that transient amnesic episodes may represent the main or the sole feature of epileptic
seizures, especially of temporal lobe origin, probably because
of the involvement of the mesial regions by the seizure
activity.1 On the basis of the increasing number of reports of
patients with similar clinical features, TEA has been proposed
as a distinctive epileptic entity.2-4 In this study, we collected
and analyzed the clinical, neuroradiological, and EEG characteristics of 11 consecutive patients with TEA and their response
to pharmacological treatment. As previously stated,4 the majority of these patients (8/11) referred to our department for acute
memory impairment, sometimes of prolonged duration. Most
of these patients were misdiagnosed at the first medical consultation as affected by TGA. Usually, the diagnosis of epilepsy as
the cause of amnesic episodes is not considered by clinicians.2,3
TGA, TIA, and psychogenic amnesia are the conditions most
often requiring differentiation from TEA.1,4 Moreover, other
possible causes of transient amnesia (such as closed head
injury, migraine, and drug effects)2,3,6 should be considered. On
a clinical ground, the evaluation of the patients during the
amnesic episodes may help in the diagnosis, but the short duration does not often allow medical examination in the acute
phase. However, although the clinical core of the ictal manifestation in our patients (ie, anterograde/retrograde amnesia) was
not easily recognizable as of epileptic origin, a targeted interview with patients’ relatives and/or with medical staff may provide a diagnostic clue. Indeed, the possible occurrence of
additional slight clinical signs or symptoms (in our cases olfactory hallucinations, abdominal “discomfort,” oral automatisms,
and “confusional” features) may indicate an epileptic origin of
the episodes.
Interestingly, the cause of the first medical consultation was
a prolonged amnesic episode in 3 patients (from 3 hours up to
48 hours). From a speculative point of view, these episodes
could be retrospectively considered as a nonconvulsive status
epilepticus because they showed the same semiological features of the shorter attacks; alternatively, the prolonged amnesia may represent a postictal state. Indeed, it is well known that
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Clinical EEG and Neuroscience 45(3)
both seizures and postictal dysfunction can be prolonged, especially in older patients.2 However, in the previous history of
these patients no amnesic episodes were reported nor brief episodes of impairment of consciousness.
As concerns the anamnestic interview with the patients or the
relatives, it is possible that episodes of transient epileptic amnesia may be underestimated because of the amnesic “nature” of
the disorder, especially if characterized by both anterograde/
retrograde amnesia. However, for the same reasons, it can be
difficult to distinguish when the amnesic episode represents the
ictal clinical phenomenon or, by contrast, when it represents the
postictal state of a seizure not recognized by the relatives or
“forgotten” by the patients. In our view, the amnesic postictal
states, if identified, should not be considered as episodes of
transient epileptic amnesia, especially when associated with
impairment of consciousness although they represent the predominant clinical core of the episodes. Indeed, it is well known
that seizures, especially of temporal lobe origin, are followed by
amnesic or dysmnesic postictal states. A clear distinction
between ictal and postictal clinical symptoms, especially in
association with the EEG findings, may help to define these
patients as affected by a “syndrome” rather than by epilepsy.
The concurrent onset of other features of epilepsy may represent
another confounding factor; however, on the basis of the proposed diagnostic criteria, we considered these patients as
affected by amnesic seizures when the episodes, although associated with other features of epilepsy, were clearly characterized
by the sparing of other cognitive functions except the memory.
In partial contrast to other reports,2-4 3 patients had their first
medical consultation for episodes of loss of consciousness of
probable epileptic origin (generalized tonic–clonic seizures
and recurrent brief episodes of unresponsiveness sometimes
associated with slight abdominal discomfort); also in these
cases, the collection of the past history has allowed us to identify previous brief episodes with a pure amnesic core. In these
patients, no medical evaluation was performed before the onset
of the episodes of loss of consciousness.
To corroborate the diagnosis of amnesic seizures, it is worth
noting the key role of neurophysiological assessment (EEG and
A-EEG). In our patients, epileptic abnormalities were consistently over the frontotemporal regions, in 3 cases were bilateral
and asynchronous; except for 1 patient in whom epileptic discharges were evident in “routine” examination, in all other
cases A-EEG revealed epileptic abnormalities in non–rapid eye
movement sleep (mainly stage N2) whereas the “routine” EEG
was unremarkable (Figure 2). Although isolated, this report
outlined the importance of studying sleep EEG in patients with
episodes of transient amnesia of unknown origin. A significant
point may be EEG examination in the acute phase; however,
these patients are generally referred to the emergency department
after symptoms and it is often not possible to perform these
assessments. Moreover, as with most of our patients, the misdiagnosis of TGA did not lead to EEG examination, and focused
diagnostic workup on cerebrovascular diseases. Difficulties in
the diagnosis of epileptic amnesia are reflected in the relatively
rare EEG-documented cases in the literature.7
In previous reports, a symptomatic etiology was a rare finding2-4,8 in patients with epileptic amnesia, whereas it represents
the majority in our cases (8 of 11). Brain MRI showed acquired
lesions localized in the frontotemporal lobes or, in one case, in
the occipital lobe close to medial temporal structures (for
details, see Figure 1). One patient had postischemic right cerebellar and basal ganglia gliosis in the context of a chronic cerebrovascular disease. MRI performed within a few days from an
amnesic episode did not show signal abnormalities; in particular, the hippocampal diffusion weighted image hyperintensity,
which is considered a hallmark of TGA,9 was never detected in
our population. MRI lesions associated with localized EEG
abnormalities and with the seizures semiology indirectly suggest the correlation between the lesions and the epilepsy.
However, as previously stated by other authors,1-3 despite the
symptomatic etiology, our patients were easily and successfully treated with relatively low dosages of antiepileptic drugs,
except for one patient with a drug-resistant epilepsy. These features seem to confirm reported findings in the literature2,3,9 and
lead to considering TEA as a “typical” elderly epilepsy, characterized by a favorable response to treatment with low dosages
of monotherapy.
No patient had psychiatric disturbances. The neuropsychological assessment demonstrated subtle deficits in memory of
three patients, in particular in recognition and recall, and additional slight deficits were reported in the selective attention by
the Stroop test. Of these, 3 patients, 2 (patients 1 and 3) had
hippocampal MRI abnormalities, and 1 (patient 4) had a posttraumatic right frontal horn gliosis. Two of them (patients 1 and
3) reported the highest number of events in our population. The
remaining patients showed no abnormalities in memory nor in
the other tested fields, as previously stated in other works.2 The
relatively low prevalence of persistent memory impairment in
our cohort, as compared with literature,6 could be because of
the early diagnosis and treatment and, consequently, to the low
number of reported seizures. There is an emerging literature
focused on 2 “novel” memory complaints (ie, accelerated longterm forgetting and remote memory impairment) described by
patients with TEA.10-12 Unfortunately, we have not used these
specific tests to assess our patients. Although recent works provide evidence of accelerated long-term forgetting in patients
with extratemporal epilepsy,12 further studies are required to
clarify if remote memory impairment may represent a feature
of patients with TEA or, more widely, with temporal lobe
epilepsy.
In conclusion, TEA represents a form of temporal lobe epilepsy, usually with onset in the middle-elderly age, with good
response to relatively low dosages of antiepileptic drugs.
Although the reported TEA patients were mainly affected by
probable cryptogenic, symptomatic, temporal lobe epilepsy,2,3,8
the majority of our patients (8/11) showed symptomatic etiology. Moreover, we outlined the relevance of clinical history to
recognize TEA, especially if ictal EEG was not available. Since
TEA carries a risk of persistent memory impairment that can be
mistaken for dementia, early diagnosis and treatment are
strongly required.6 Further work is warranted to clarify if ictal
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Lapenta et al
and postictal amnesic states are actually part of the same condition and to understand if these features may represent a distinctive epileptic syndrome.
Acknowledgments
The authors convey their special thanks to Catello Vollono, Valentina
Gnoni, Chiara Di Blasi, Salvatore Mazza for their invaluable
assistance.
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the
research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
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