Seizure 23 (2014) 918–920
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Letter to the Editor Can the syndrome of transient epileptic amnesia be the first feature of Alzheimer’s disease?
Keywords: Transient epileptic amnesia Subjective cognitive impairment Temporal lobe epilepsy Alzheimer’s disease
1. Case report Transient epileptic amnesia (TEA) is a specific type of temporal lobe seizure involving the hippocampus and the parahippocampal gyrus,1 which can be recognized with now published criteria.2 The etiology of TEA is still under debate and probably not unique. Apart from rare patients showing structural lesions on brain MRI,2 microvascular brain load and/or immune-mediated neuronal aggression have been proposed as alternative causes. A neurodegenerative process is also possible, as suggested by decreased hippocampal volume and ongoing memory complaints despite seizure freedom in many treated subjects.1 Thus, late onset Alzheimer’s disease (LOAD) logically appears as a potential cause of TEA. Indeed, we present a case of TEA that secondarily evolved into AD 16 years after seizures onset. The patient was right-handed and had 9 years of education. She had no remarkable medical history. Her mother had been diagnosed with LOAD at the age of 70. The patient was 64 when she came in 2009 to our Memory Clinic for cognitive complaints developing since her first transient antero-retrograde amnesia (in 1994) that lasted about 10 h and started with a preceding aura (ascending thoraco-abdominal pain with diffuse heat sensation and nausea) while witnesses described contact loss for 2 min, bilateral arm dystonia and oral automatisms (tongue smacking). Transient global amnesia (TGA) was diagnosed because screening blood tests, brain CT scan and EEG were all within the normal range. In 1994, her MMSE score was 30/30, even though she was complaining of abnormal long term forgetting and autobiographical difficulties (she did not remember her wedding or several vacations during the previous 10 years). Another antero-retrograde amnesia occurred 5 years later (1999), which lasted 2 h and was preceded by the same aura and a sudden fall. Witnesses again described partial contact loss during amnesia. CT-scan and EEG were still normal as was the cardiovascular work-up. Thereafter, the patient became depressed and the subjective cognitive impairment worsened but her MMSE score remained at 30/30: there was no further memory examination. In 2000, another amnestic episode happened and lasted 12 h. Six years after, the http://dx.doi.org/10.1016/j.seizure.2014.07.008 1059-1311/ß 2014 Published by Elsevier Ltd on behalf of British Epilepsy Association.
Fig. 1. Evolution of brain atrophy in 5 years. (A) Normal brain MRI (coronal T1weighted sequence) in October 2009; (B) same sequence showing bilateral hippocampal and subcortical atrophy 3 years later (October 2012); (C) further progression of the same pattern of atrophy 5 years later (April 2014).
Letter to the Editor / Seizure 23 (2014) 918–920
patient still had cognitive complaints and also mentioned hyposmia: she underwent specific tests in 2006, which returned normal results (MMSE score = 28/30; preserved memory, visuoconstruction, language and executive functions). In 2009, memory problems had even more worsened: her MMSE score was 24/30 accompanied by memory impairment (storage deficit) on the Free and Cued Selective Recall Reminding Test whereas other functions were normal. The patient also described monthly stereotyped ‘‘syncope-like’’ attacks occurring since the early 2000s and consisting in ascending aura, tachycardia, fading of perceptions, dizziness and incipient unconsciousness lasting 1–5 min (average 2 min), sometimes followed by temporo-spatial disorientation and anterograde amnesia for 20–60 min. We therefore suspected temporal lobe epilepsy (TLE): brain MRI (Fig. 1) and video-EEG were normal but treatment with lamotrigine (200 mg daily) provided a clear-cut response on the amnestic and ‘‘syncope-like’’ events, since there was no recurrence during the following 5 years. Nevertheless, the patient did not feel any improvement in her cognitive difficulties. In 2010, a lumbar puncture yielded results supporting AD neuropathology, with Ab42 = 193 pg/ml (N = 500– 1500); P-Tau = 72 pg/ml (N = 0–60); T-Tau = 473 pg/ml (N = 100– 450); IATI (Innotest Abeta tau index) = 0.24 (N > 1.2). Moreover, other CSF analyses were negative (blood cell count, IgG index, antineuron antibodies, oligo-clonal bands, Lyme and syphilis serologies). Rivastigmine (9.5 mg daily) provided a clear subjective alleviation of memory problems with slight objective improvement on MMSE (25/30). MRI and MMSE changes in the following 5 years are shown in Figs. 1 and 2, respectively. The diagnosis of AD is consistent with the initial memory profile of the patient (storage deficits) and her positive CSF biomarkers. Furthermore, she has now converted to dementia with hippocampal atrophy (Fig. 1), and she presented decreased MMSE scores on the past 5 years (Fig. 2). On the other hand, the
919
diagnosis of TLE is also probable despite the normality of repetitive EEGs in view of several arguments. First, the amnestic episodes were TEA and not TGA according to their frequency (>20 when taking into account the ‘‘syncope-like’’ events followed by transient amnesia), their semiology (preceding aura, loss of contact, arm dystonia, oral automatisms) and their response to lamotrigine. In fact, the diagnostic criteria for TEA are fulfilled here.2 Second, other ictal events (ascending aura, nausea, chest pain, duration < 3 min) were compatible with TLE and were likewise responsive to lamotrigine. Considering the diagnosis of AD and TLE, the negativity of the medical workup (including standard blood tests, antineuron antibodies, brain MRI and CSF analysis) and the chronological sequence of events (Fig. 2), it is possible that TLE was the first symptom of AD in this case. But we cannot be entirely sure since AD is a common disease in older patients whilst TEA is a quite rare syndrome: their association in the present case could only be coincidental rather than truly causal. Yet, our report is in accordance with mice models showing that amyloid cascade leads to early epileptogenic excitatory remodeling in the hippocampus and to subsequent inhibitory compensatory responses contributing to memory impairment.3 From this point of view, the treatment with lamotrigine and rivastigmine may have contributed to the long-term stabilization of the MMSE of our patient (Fig. 2). Moreover, a recently published work on the natural history of sporadic AD has shown an increasing Ab burden in the brain from 15 to 25 years before cognitive symptoms. Taken together, all these data suggest that amyloid deposition is likely to have begun in our patient at the time of her first seizure (TEA).4 In conclusion, it is plausibe that incipient AD accounts for some TEAs shortly followed by memory complaints whereas brain imaging and routine cognitive testing are inconclusive at this stage. Further studies are needed to determine which patients are
Fig. 2. Evolution of MMSE score from 1994 to 2014. A, B, C, transient epileptic amnesia misdiagnosed as TGA in 1994, 1999 and 2000 respectively.
920
Letter to the Editor / Seizure 23 (2014) 918–920
concerned. But TEA should no longer be regarded as a benign clinical condition: patients should not be reassured too hastily.
b
Author’s contribution
Centre Me´moire, de Ressources et de Recherche d’Alsace (StrasbourgColmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
B. Cretin wrote the manuscript; N. Philippi, F. Sellal, L. Dibitonto, C. Martin and F. Blanc revised and corrected the first drafts of this article.
Franc¸ois Sellala,b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France b Service de Neurologie, Hospices Civils de Colmar, France a
Conflict of interest statement
Laure Dibitontoa,b,c,d Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
None.
a
Funding None. Acknowledgments The authors thank Dr Maria Paoli Valenti-Hirsch and Constanza Dalvit for their help in the reading and interpretation of the patient’s EEGs. We also thank Nick Barton for having corrected the first draft of this article. References
Catherine Martin-Hunyadia Centre Me´moire, de Ressources et de Recherche d’Alsace (StrasbourgColmar), France
a
Frederic Blanca,b,c,d Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
a
1. Butler C, van Erpe W, Bhaduri A, Hammers A, Heckemann R, Zeman A. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia. Epilepsy Behav 2013;28:363–9. 2. Zeman A, Boniface S, Hodges J. Transient epileptic amnesia: a description of the clinical and neuropsychological features in ten cases and a review of the literature. J Neurol Neurosurg Psychiatry 1998;64:435–43. 3. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 2009;66(April (4)):435–40. 4. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group Amyloid b deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013;12(April (4)):357–67.
Benjamin Cretina,b,c,d,* Nathalie Philippia,b,c,d a Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France
*Corresponding author at: CMRR d’Alsace, De´partement de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Poˆle Teˆte et Cou, 1 Avenue Molie`re, 67200 Strasbourg, France. Tel.: +33 3 88 12 86 32; fax: +33 3 88 12 86 36 E-mail addresses: [email protected], [email protected] (B. Cretin).
1 May 2014
Contents lists available at ScienceDirect
Seizure journal homepage: www.elsevier.com/locate/yseiz
Letter to the Editor Can the syndrome of transient epileptic amnesia be the first feature of Alzheimer’s disease?
Keywords: Transient epileptic amnesia Subjective cognitive impairment Temporal lobe epilepsy Alzheimer’s disease
1. Case report Transient epileptic amnesia (TEA) is a specific type of temporal lobe seizure involving the hippocampus and the parahippocampal gyrus,1 which can be recognized with now published criteria.2 The etiology of TEA is still under debate and probably not unique. Apart from rare patients showing structural lesions on brain MRI,2 microvascular brain load and/or immune-mediated neuronal aggression have been proposed as alternative causes. A neurodegenerative process is also possible, as suggested by decreased hippocampal volume and ongoing memory complaints despite seizure freedom in many treated subjects.1 Thus, late onset Alzheimer’s disease (LOAD) logically appears as a potential cause of TEA. Indeed, we present a case of TEA that secondarily evolved into AD 16 years after seizures onset. The patient was right-handed and had 9 years of education. She had no remarkable medical history. Her mother had been diagnosed with LOAD at the age of 70. The patient was 64 when she came in 2009 to our Memory Clinic for cognitive complaints developing since her first transient antero-retrograde amnesia (in 1994) that lasted about 10 h and started with a preceding aura (ascending thoraco-abdominal pain with diffuse heat sensation and nausea) while witnesses described contact loss for 2 min, bilateral arm dystonia and oral automatisms (tongue smacking). Transient global amnesia (TGA) was diagnosed because screening blood tests, brain CT scan and EEG were all within the normal range. In 1994, her MMSE score was 30/30, even though she was complaining of abnormal long term forgetting and autobiographical difficulties (she did not remember her wedding or several vacations during the previous 10 years). Another antero-retrograde amnesia occurred 5 years later (1999), which lasted 2 h and was preceded by the same aura and a sudden fall. Witnesses again described partial contact loss during amnesia. CT-scan and EEG were still normal as was the cardiovascular work-up. Thereafter, the patient became depressed and the subjective cognitive impairment worsened but her MMSE score remained at 30/30: there was no further memory examination. In 2000, another amnestic episode happened and lasted 12 h. Six years after, the http://dx.doi.org/10.1016/j.seizure.2014.07.008 1059-1311/ß 2014 Published by Elsevier Ltd on behalf of British Epilepsy Association.
Fig. 1. Evolution of brain atrophy in 5 years. (A) Normal brain MRI (coronal T1weighted sequence) in October 2009; (B) same sequence showing bilateral hippocampal and subcortical atrophy 3 years later (October 2012); (C) further progression of the same pattern of atrophy 5 years later (April 2014).
Letter to the Editor / Seizure 23 (2014) 918–920
patient still had cognitive complaints and also mentioned hyposmia: she underwent specific tests in 2006, which returned normal results (MMSE score = 28/30; preserved memory, visuoconstruction, language and executive functions). In 2009, memory problems had even more worsened: her MMSE score was 24/30 accompanied by memory impairment (storage deficit) on the Free and Cued Selective Recall Reminding Test whereas other functions were normal. The patient also described monthly stereotyped ‘‘syncope-like’’ attacks occurring since the early 2000s and consisting in ascending aura, tachycardia, fading of perceptions, dizziness and incipient unconsciousness lasting 1–5 min (average 2 min), sometimes followed by temporo-spatial disorientation and anterograde amnesia for 20–60 min. We therefore suspected temporal lobe epilepsy (TLE): brain MRI (Fig. 1) and video-EEG were normal but treatment with lamotrigine (200 mg daily) provided a clear-cut response on the amnestic and ‘‘syncope-like’’ events, since there was no recurrence during the following 5 years. Nevertheless, the patient did not feel any improvement in her cognitive difficulties. In 2010, a lumbar puncture yielded results supporting AD neuropathology, with Ab42 = 193 pg/ml (N = 500– 1500); P-Tau = 72 pg/ml (N = 0–60); T-Tau = 473 pg/ml (N = 100– 450); IATI (Innotest Abeta tau index) = 0.24 (N > 1.2). Moreover, other CSF analyses were negative (blood cell count, IgG index, antineuron antibodies, oligo-clonal bands, Lyme and syphilis serologies). Rivastigmine (9.5 mg daily) provided a clear subjective alleviation of memory problems with slight objective improvement on MMSE (25/30). MRI and MMSE changes in the following 5 years are shown in Figs. 1 and 2, respectively. The diagnosis of AD is consistent with the initial memory profile of the patient (storage deficits) and her positive CSF biomarkers. Furthermore, she has now converted to dementia with hippocampal atrophy (Fig. 1), and she presented decreased MMSE scores on the past 5 years (Fig. 2). On the other hand, the
919
diagnosis of TLE is also probable despite the normality of repetitive EEGs in view of several arguments. First, the amnestic episodes were TEA and not TGA according to their frequency (>20 when taking into account the ‘‘syncope-like’’ events followed by transient amnesia), their semiology (preceding aura, loss of contact, arm dystonia, oral automatisms) and their response to lamotrigine. In fact, the diagnostic criteria for TEA are fulfilled here.2 Second, other ictal events (ascending aura, nausea, chest pain, duration < 3 min) were compatible with TLE and were likewise responsive to lamotrigine. Considering the diagnosis of AD and TLE, the negativity of the medical workup (including standard blood tests, antineuron antibodies, brain MRI and CSF analysis) and the chronological sequence of events (Fig. 2), it is possible that TLE was the first symptom of AD in this case. But we cannot be entirely sure since AD is a common disease in older patients whilst TEA is a quite rare syndrome: their association in the present case could only be coincidental rather than truly causal. Yet, our report is in accordance with mice models showing that amyloid cascade leads to early epileptogenic excitatory remodeling in the hippocampus and to subsequent inhibitory compensatory responses contributing to memory impairment.3 From this point of view, the treatment with lamotrigine and rivastigmine may have contributed to the long-term stabilization of the MMSE of our patient (Fig. 2). Moreover, a recently published work on the natural history of sporadic AD has shown an increasing Ab burden in the brain from 15 to 25 years before cognitive symptoms. Taken together, all these data suggest that amyloid deposition is likely to have begun in our patient at the time of her first seizure (TEA).4 In conclusion, it is plausibe that incipient AD accounts for some TEAs shortly followed by memory complaints whereas brain imaging and routine cognitive testing are inconclusive at this stage. Further studies are needed to determine which patients are
Fig. 2. Evolution of MMSE score from 1994 to 2014. A, B, C, transient epileptic amnesia misdiagnosed as TGA in 1994, 1999 and 2000 respectively.
920
Letter to the Editor / Seizure 23 (2014) 918–920
concerned. But TEA should no longer be regarded as a benign clinical condition: patients should not be reassured too hastily.
b
Author’s contribution
Centre Me´moire, de Ressources et de Recherche d’Alsace (StrasbourgColmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
B. Cretin wrote the manuscript; N. Philippi, F. Sellal, L. Dibitonto, C. Martin and F. Blanc revised and corrected the first drafts of this article.
Franc¸ois Sellala,b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France b Service de Neurologie, Hospices Civils de Colmar, France a
Conflict of interest statement
Laure Dibitontoa,b,c,d Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
None.
a
Funding None. Acknowledgments The authors thank Dr Maria Paoli Valenti-Hirsch and Constanza Dalvit for their help in the reading and interpretation of the patient’s EEGs. We also thank Nick Barton for having corrected the first draft of this article. References
Catherine Martin-Hunyadia Centre Me´moire, de Ressources et de Recherche d’Alsace (StrasbourgColmar), France
a
Frederic Blanca,b,c,d Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France b Centre Me´moire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universite´ de Strasbourg, France d Centre de Compe´tences des de´mences rares des Hoˆpitaux Universitaires de Strasbourg, France
a
1. Butler C, van Erpe W, Bhaduri A, Hammers A, Heckemann R, Zeman A. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia. Epilepsy Behav 2013;28:363–9. 2. Zeman A, Boniface S, Hodges J. Transient epileptic amnesia: a description of the clinical and neuropsychological features in ten cases and a review of the literature. J Neurol Neurosurg Psychiatry 1998;64:435–43. 3. Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 2009;66(April (4)):435–40. 4. Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group Amyloid b deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013;12(April (4)):357–67.
Benjamin Cretina,b,c,d,* Nathalie Philippia,b,c,d a Unite´ de Neuropsychologie, Service de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Strasbourg, France
*Corresponding author at: CMRR d’Alsace, De´partement de Neurologie des Hoˆpitaux Universitaires de Strasbourg, Poˆle Teˆte et Cou, 1 Avenue Molie`re, 67200 Strasbourg, France. Tel.: +33 3 88 12 86 32; fax: +33 3 88 12 86 36 E-mail addresses: [email protected], [email protected] (B. Cretin).
1 May 2014
