521
Journal of Alzheimer’s Disease 45 (2015) 521–526 DOI 10.3233/JAD-141953 IOS Press
Left Temporal Lobe Epilepsy Revealing Left Posterior Cortical Atrophy Due to Alzheimer’s Disease Benjamin Cretina,b,c,d , Laure Di Bitontoa,b,d , Frederic Blanca,b,c,d and Eloi Magnine,f,g,∗ a Unit´ e
de Neuropsychologie, Service de Neurologie des Hˆopitaux Universitaires de Strasbourg, Strasbourg, France b Centre M´ emoire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universit´ e de Strasbourg, France d Centre de Comp´ etences des d´emences rares des Hˆopitaux Universitaires de Strasbourg/Service de Neurologie, Hospices Civils de Colmar, France e Centre M´ emoire Ressousrces et Recherche (CMRR), CHU Besan¸con, Besan¸con, France f Service de Neurologie, CHU Besan¸ con, Besan¸con, France g Centre Leenaards de la M´ emoire, CHUV, Lausanne, Suisse
Accepted 12 December 2014
Abstract. Seizures can be an early symptom of Alzheimer’s disease (AD) and can precede cognitive decline. Early epilepsy in AD can mimic transient epileptic amnesic syndrome (TEAS) or epileptic amnesic syndrome. We report the case of a patient who started a cerebrospinal fluid (CSF)-proven AD with partial seizures and TEAS that secondarily became a cortical posterior atrophy syndrome. CSF biomarkers showed a high amyloid production, amyloidopathy, and high level of total tau and p-Tau. This observation adds data to the complex AD-early epilepsy interactions and illustrates that atypical AD can cause a TEAS. Possible red flags for an underlying neurodegenerative process in TEAS are discussed. Keywords: Alzheimer’s disease, mild cognitive impairment, posterior cortical atrophy, temporal lobe epilepsy, transient epileptic amnesic syndrome
INTRODUCTION Alzheimer’s disease (AD) induces a risk for epilepsy with increasing dementia severity or with younger age of AD onset [1]. Seizures can be partial as well as generalized and are considered as a rather late phenomenon in the course of the disease [2]. However, temporal lobe epilepsy (TLE) is sometimes present at an earlier stage [3] and can even be the first symptom of AD pathology [4, 5]. Good seizure ∗ Correspondence to: Eloi Magnin, MD, PhD, Department of Neurology, University Hospital of Besancon, 25000 Besancon, France. Tel.: +33381668098; Fax: +33381668470; E-mail: [email protected].
control and tolerability can be obtained with lamotrigine, levetiracetam, or valproate [3]. However, pharmacorestistant epilepsy or status epilepticus have been reported in some AD patients [4, 5]. Cases are scarce in the literature and the precise pathophysiology of AD-related epileptogenesis is currently unknown. We report the case of a patient who initially presented with left TLE and secondary cognitive disorders: she was first misdiagnosed with “transient epileptic amnesic and aphasic syndrome” that later evolved to a left posterior cortical atrophy (PCA). Cerebrospinal fluid (CSF) biomarkers showed an AD profile and high brain amyloid burden.
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
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CASE REPORT The patient was a 55-year-old right-handed woman, with a post-graduate educational level. She had previous medical history of ethanol and tobacco consumption, mild dyslipidemia, and arterial hypertension. No previous history of head trauma was reported. Family history reported dementia at the age of 80 in her mother. She was initially admitted for two tonic-clonicgeneralized seizures. Partial seizures began 6 years before this episode with monthly stereotyped ictal symptoms of “d´ej`a-vu”, language disorders, and ascending clonic jerks of the right arm followed by post-ictal transient sensorial aphasia, right hemiparesis, temporo-spatial disorientation, and amnesia (sometimes lasting for several days). Witnesses also described occasional episodes of unresponsiveness. 6 months prior to her admission, she presented cognitive disorders with topographical difficulties, accelerated long term forgetfulness, autobiographical memory disturbances, and word finding difficulties. However, basic and instrumental activities of daily living (ADL and IADL) were preserved due to efficient compensatory strategies. She also reported right hypoacousia with tinnitus of unknown origin after otological workup. Her interictal neurological status was normal. Screening cognitive tests were in the normal range (Table 1). First brain MRI showed slight left subcortical and parietal atrophy (Fig. 1B-D), while EEG (20 minutes) showed left hemisphere theta slow wave background activity combined with rare sharp-waves (Fig. 1H). No alpha rhythm was detectable. A treatment with topiramate (200 mg daily) was initiated but seizure frequency increased three months later, requiring add-on therapy with carbamazepine (600 mg/d) and clobazam (20 mg/d). Interictal neurological examination remained normal during this period. After four months, her status rapidly worsened: seizure frequency increased, in spite of good treatment adherence, and a permanent right lateral homonymous hemianopia occurred. Ophthalmological workup (including fundus) was normal except for the campimetry that confirmed right lateral homonymous hemianopia. A second MRI did not show any new abnormalities or atrophy progression. Standard blood tests, THPA-VDRL, HIV, and Lyme serology were negative. The lumbar puncture was normal (including 14–3–3 protein); no antineuron, antinuclear, anti-thyroperoxydase, and anti-phospholipides antibodies were found. EEG showed theta slow wave background activity on the left temporal lobe and
delta slow wave background activity on the ipsilateral occipital lobe (Fig. 1I). No alpha rhythm was recorded. Total body FDG-PET scanning showed a left occipital lobe hypometabolism (Fig. 1E, F). No abnormal FDG uptake was observed on the whole-body sequences. One year later, partial complex seizures were still ongoing. Phenobarbital and lacosamide led to seizure alleviation even though one isolated episode of prolonged transient amnesia occurred according to caregivers. Physical examination had meanwhile worsened with slight extrapyramidal signs (axial hypokinesia, hypertonia, and resting tremor predominating on the right arm), right astereognosia with agraphesthesia and hyposmia. Right lateral homonymous hemianopia was still observed. FPCIT SPECT did not show dopaminergic denervation while HMPAO-SPECT confirmed previous left posterior combined with left cingular hypoperfusions and showed, after a follow-up of one year and a half, the occurrence of a contralateral temporal hypoperfusion (Fig. 1G). EEG (20 minutes) revealed delta and triphasic waves on the whole left hemisphere (Fig. 1J). No alpha rhythm was recorded. Serum acanthocytes and muscle and skin biopsies were normal. Neuropsychological testing (Table 1) confirmed the suspicion of a neurodegenerative disease by showing cognitive decline with decreased MiniMental State Examination score, moderate executive dysfunctioning, visuo-constructive apraxia (Fig. 1A), right ideomotor apraxia, attention deficits and psychomotor slowing, and linguistic disorders (anomia, impaired verbal fluency tests, single word repetition preserved, and a length-dependent deficit observed in sentence repetition). No semantic or agrammatic disorder was observed. ADL and IADL were nevertheless preserved except for driving abilities. Another lumbar puncture was carried out. Biomarkers analysis ((Innotest, Innogenetics®, Gent, Belgium) were performed by a laboratory using national standardized procedures for CSF analysis and interpretation with quality control [6, 7]. Increased phosphorylated tau (110 ng/l; 0 < N 9) 14∗ (N = 16)
score.
probable underlying AD pathology. Amyloid imaging was not performed. APOE genotype status was not performed. This case fulfilled the PCA criteria [10–12] based on: 1) the insidious onset with progressive decline; 2) with neurovisual disorders (visuospatial and visuoconstructive deficit, not explained by an ophthalmological pathology); 3) apraxia; 4) memory was preserved; and 5) structural and functional neuroimaging examinations showed asymmetric posterior cortical abnormalities. Hemianopia has been sometimes reported in PCA when primary occipital cortex was involved [13, 14]. The linguistic pattern and the left parieto-temporal abnormalities suggested a logopenic syndrome that can occur in PCA [15, 16]. The moderate parkinsonism was unusual; however, it occurred secondarily during the follow-up.
DISCUSSION Seizures were the first symptoms of AD in this case. When considering clinical and EEG data, left TLE [17] with transient epileptic amnesic syndrome (TEAS) [18, 19] was highly probable. The ictal symptoms (“d´ej`a-vu” followed by sensory aphasia) as well as the post-ictal state (persisting aphasia, temporo-spatial disorientation, occasional prolonged transient amnesia
with normal memory performances during interictal phase) and the interictal signs (unilateral hypoacousia, tinnitus, and hemianopia) sustained this hypothesis [17–19]. However, unusual features suggested that TEAS was not isolated. EEG and neuroimaging abnormalities are usually limited to the temporal lobes in TEAS [20]. The location of the neuronal network involved in epilepsy was, however, larger than the temporal lobe because dysarthria and right arm myoclonus also occurred secondarily and were followed by postictal transient right hemiparesis and posterior aphasia. The first EEG and FDG-PET confirmed this hypothesis, by showing extended slow wave background activity with occurrence of rare sharp waves on the left hemisphere and left occipital hypometabolism, respectively. This network was most probably located over the left temporo-parieto-occipital region [18–20]. In our case, the partial seizures began 5 years and progressively increased before cognitive decline thereby suggesting that epilepsy had induced the observed neuropsychological deficits. During the evolution, TEAS can become epileptic amnesic syndrome (EAS) with permanent cognitive deficits (usually isolated memory disorders) assessed by neuropsychological examination [21, 22]. Those patients indeed frequently match the definition of single domain amnestic mild cognitive impairment [21–23]. A good seizure control is usually obtained with a monotherapy, especially with
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B
A
D
E
H
C
F
I
G
J
Fig. 1. Rey-Osterrieth complex figure copy that was not improved by planification cueing showed visuospatial impairment (A); initial MRI showed slight biparietal atrophy (B), left subcortical atrophy (C), and moderate left hippocampal atrophy (D), on axial T2 FLAIR-weighted sequence; initial FDG-PET showed left occipital and left medial temporal hypometabolism (E) not explained by atrophy on the brain CT-scan (F); after a follow-up of one year and a half, HMPAO-SPECT showed bitemporal and left parieto-occipital and cingular hypoperfusion (G); initial EEG showed no alpha rhythm (H), left theta slow wave background activity (C3-Cz) combined with rare sharp-waves (C3-01 and T3-01) (I); one year later, EEG showed delta background activity and triphasic waves on the whole left hemisphere (J).
lamotrigine, in TEAS [19]. Anticonvulsants usually lead to cognitive improvement (and sometimes to normalization) in EAS [21, 22]. In our case, the refractory seizures (quadritherapy to improve seizure frequency of 75%) and the subsequent cognitive decline with language disorders, parietal and occipital syndrome (with no memory impairment) were also contradictory with
TEAS and EAS. Therefore, a neurodegenerative process was suspected. The etiological link between AD and this progressive partial epilepsy was sustained by several arguments: 1) the medical workup did not reveal any other explanatory disease; 2) the symptoms and signs continuously accumulated on a 3-year period with
B. Cretin et al. / Temporal Epilepsy Revealing PCA Due to AD
ongoing parietal involvement; 3) the atrophy on MRI and the AD CSF biomarkers profile with high amyloid burden [8, 24] suggest an AD pathology; 4) the amyloidopathy is proven as an epileptogenic factor in high amyloid producing transgenic animal models [25, 26]; 5) amyloidosis starts 15 to 20 years before cognitive decline as shown with PET-amyloid studies in sporadic AD [27]; 6) the temporal lobe AD epileptogenesis is probably also a tau dependent phenomenon [28] as tau pathology usually starts in temporal lobes; 7) AD is associated with a decrease of alpha rhythm spectrum on EEG recording [29]; and 8) several clinical reports illustrate that partial seizures can be an early feature of AD with ictal signs (dej`a-vu, amnesia, and sometimes aphasia) and EEG recordings (fronto-central and temporal epileptiform activity) suggest temporal cortex involvement [3–5, 23]. This prodromal AD was also atypical because of the lack of an amnestic profile on cognitive testing. The clinical characteristics (hemianopia, agraphesthesia, astereognosia, visuoconstructive disorders and apraxia, language disorders), neuroimaging findings (left parieto-occipital abnormalities) and the electrophysiological markers (EEG abnormalities) suggested an early involvement of the left parieto-temporooccipital cortex occurred. The clinical picture is therefore suggestive of posterior cortical atrophy [10–12]. Temporal involvement, suggested by TLE and mild medial temporal atrophy, is not inconsistent with PCA in which neuropathlogical studies reported hippocampal neurofibrillary tangles [12]. A mild parkinsonism secondarily occurred and can thus have been misdiagnosed as a corticobasal degeneration [30]. Klaffke et al. reported eight probable corticobasal degeneration patients that all presented abnormal FP-CIT imaging [31]. In our patient, no dopaminergic depletion was observed on FP-CIT imaging and parietal atrophy was bilaterally present on MRI. Moreover, temporal involvement [32] and seizures are rare in neuropathology-proven corticobasal degeneration [33]. Moreover, CSF biomarkers suggested an underlying AD pathology, which is the more frequent neuropathology in PCA [12]. Seizures in PCA or corticobasal syndrome could possibly be a marker of underlying AD neuropathology. Our observation encourages clinicians to be careful when diagnosing a possible TEAS or EAS. This syndrome can evolve into a neurodegenerative disorder, particularly when one of the following red-flags are present: 1) abnormal neurological examination; 2) non-episodic memory impairment on cognitive evaluation; 3) cognitive complaints starting before or a long
525
time after seizures onset; and 4) progressive cognitive decline in spite of the use of anticonvulsants [23]. This report confirms the relevance of these atypical features and also adds to TEAS and EAS electrophysiological “red-flags” (extratemporal epileptiform and/or slow wave background activity and/or decrease of the alpha rhythm spectrum) and neuroimaging “red flags” (extratemporal atrophy and/or hypometabolism). In conclusion, our case confirms the small literature on seizures-AD interactions during the early stages of the disease [3, 23] even in atypical onset such as PCA and illustrates the complex interaction between amyloidopathy and such late-onset epileptogenesis [25, 26]. Moreover, our patient had seizures before cognitive decline, thereby mimicking a possible TEAS. The links between this late-onset epileptic syndrome, the amyloid brain load, and an incipient AD need to be clarified [23]. Further works are needed to better understand the mechanisms underlying early epilepsy and AD. DISCLOSURE STATEMENT Authors’ disclosures available online (http://j-alz. com/manuscript-disclosures/14-1953r2). REFERENCES [1]
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Journal of Alzheimer’s Disease 45 (2015) 521–526 DOI 10.3233/JAD-141953 IOS Press
Left Temporal Lobe Epilepsy Revealing Left Posterior Cortical Atrophy Due to Alzheimer’s Disease Benjamin Cretina,b,c,d , Laure Di Bitontoa,b,d , Frederic Blanca,b,c,d and Eloi Magnine,f,g,∗ a Unit´ e
de Neuropsychologie, Service de Neurologie des Hˆopitaux Universitaires de Strasbourg, Strasbourg, France b Centre M´ emoire, de Ressources et de Recherche d’Alsace (Strasbourg-Colmar), France c Laboratoire ICube, CNRS-Universit´ e de Strasbourg, France d Centre de Comp´ etences des d´emences rares des Hˆopitaux Universitaires de Strasbourg/Service de Neurologie, Hospices Civils de Colmar, France e Centre M´ emoire Ressousrces et Recherche (CMRR), CHU Besan¸con, Besan¸con, France f Service de Neurologie, CHU Besan¸ con, Besan¸con, France g Centre Leenaards de la M´ emoire, CHUV, Lausanne, Suisse
Accepted 12 December 2014
Abstract. Seizures can be an early symptom of Alzheimer’s disease (AD) and can precede cognitive decline. Early epilepsy in AD can mimic transient epileptic amnesic syndrome (TEAS) or epileptic amnesic syndrome. We report the case of a patient who started a cerebrospinal fluid (CSF)-proven AD with partial seizures and TEAS that secondarily became a cortical posterior atrophy syndrome. CSF biomarkers showed a high amyloid production, amyloidopathy, and high level of total tau and p-Tau. This observation adds data to the complex AD-early epilepsy interactions and illustrates that atypical AD can cause a TEAS. Possible red flags for an underlying neurodegenerative process in TEAS are discussed. Keywords: Alzheimer’s disease, mild cognitive impairment, posterior cortical atrophy, temporal lobe epilepsy, transient epileptic amnesic syndrome
INTRODUCTION Alzheimer’s disease (AD) induces a risk for epilepsy with increasing dementia severity or with younger age of AD onset [1]. Seizures can be partial as well as generalized and are considered as a rather late phenomenon in the course of the disease [2]. However, temporal lobe epilepsy (TLE) is sometimes present at an earlier stage [3] and can even be the first symptom of AD pathology [4, 5]. Good seizure ∗ Correspondence to: Eloi Magnin, MD, PhD, Department of Neurology, University Hospital of Besancon, 25000 Besancon, France. Tel.: +33381668098; Fax: +33381668470; E-mail: [email protected].
control and tolerability can be obtained with lamotrigine, levetiracetam, or valproate [3]. However, pharmacorestistant epilepsy or status epilepticus have been reported in some AD patients [4, 5]. Cases are scarce in the literature and the precise pathophysiology of AD-related epileptogenesis is currently unknown. We report the case of a patient who initially presented with left TLE and secondary cognitive disorders: she was first misdiagnosed with “transient epileptic amnesic and aphasic syndrome” that later evolved to a left posterior cortical atrophy (PCA). Cerebrospinal fluid (CSF) biomarkers showed an AD profile and high brain amyloid burden.
ISSN 1387-2877/15/$35.00 © 2015 – IOS Press and the authors. All rights reserved
522
B. Cretin et al. / Temporal Epilepsy Revealing PCA Due to AD
CASE REPORT The patient was a 55-year-old right-handed woman, with a post-graduate educational level. She had previous medical history of ethanol and tobacco consumption, mild dyslipidemia, and arterial hypertension. No previous history of head trauma was reported. Family history reported dementia at the age of 80 in her mother. She was initially admitted for two tonic-clonicgeneralized seizures. Partial seizures began 6 years before this episode with monthly stereotyped ictal symptoms of “d´ej`a-vu”, language disorders, and ascending clonic jerks of the right arm followed by post-ictal transient sensorial aphasia, right hemiparesis, temporo-spatial disorientation, and amnesia (sometimes lasting for several days). Witnesses also described occasional episodes of unresponsiveness. 6 months prior to her admission, she presented cognitive disorders with topographical difficulties, accelerated long term forgetfulness, autobiographical memory disturbances, and word finding difficulties. However, basic and instrumental activities of daily living (ADL and IADL) were preserved due to efficient compensatory strategies. She also reported right hypoacousia with tinnitus of unknown origin after otological workup. Her interictal neurological status was normal. Screening cognitive tests were in the normal range (Table 1). First brain MRI showed slight left subcortical and parietal atrophy (Fig. 1B-D), while EEG (20 minutes) showed left hemisphere theta slow wave background activity combined with rare sharp-waves (Fig. 1H). No alpha rhythm was detectable. A treatment with topiramate (200 mg daily) was initiated but seizure frequency increased three months later, requiring add-on therapy with carbamazepine (600 mg/d) and clobazam (20 mg/d). Interictal neurological examination remained normal during this period. After four months, her status rapidly worsened: seizure frequency increased, in spite of good treatment adherence, and a permanent right lateral homonymous hemianopia occurred. Ophthalmological workup (including fundus) was normal except for the campimetry that confirmed right lateral homonymous hemianopia. A second MRI did not show any new abnormalities or atrophy progression. Standard blood tests, THPA-VDRL, HIV, and Lyme serology were negative. The lumbar puncture was normal (including 14–3–3 protein); no antineuron, antinuclear, anti-thyroperoxydase, and anti-phospholipides antibodies were found. EEG showed theta slow wave background activity on the left temporal lobe and
delta slow wave background activity on the ipsilateral occipital lobe (Fig. 1I). No alpha rhythm was recorded. Total body FDG-PET scanning showed a left occipital lobe hypometabolism (Fig. 1E, F). No abnormal FDG uptake was observed on the whole-body sequences. One year later, partial complex seizures were still ongoing. Phenobarbital and lacosamide led to seizure alleviation even though one isolated episode of prolonged transient amnesia occurred according to caregivers. Physical examination had meanwhile worsened with slight extrapyramidal signs (axial hypokinesia, hypertonia, and resting tremor predominating on the right arm), right astereognosia with agraphesthesia and hyposmia. Right lateral homonymous hemianopia was still observed. FPCIT SPECT did not show dopaminergic denervation while HMPAO-SPECT confirmed previous left posterior combined with left cingular hypoperfusions and showed, after a follow-up of one year and a half, the occurrence of a contralateral temporal hypoperfusion (Fig. 1G). EEG (20 minutes) revealed delta and triphasic waves on the whole left hemisphere (Fig. 1J). No alpha rhythm was recorded. Serum acanthocytes and muscle and skin biopsies were normal. Neuropsychological testing (Table 1) confirmed the suspicion of a neurodegenerative disease by showing cognitive decline with decreased MiniMental State Examination score, moderate executive dysfunctioning, visuo-constructive apraxia (Fig. 1A), right ideomotor apraxia, attention deficits and psychomotor slowing, and linguistic disorders (anomia, impaired verbal fluency tests, single word repetition preserved, and a length-dependent deficit observed in sentence repetition). No semantic or agrammatic disorder was observed. ADL and IADL were nevertheless preserved except for driving abilities. Another lumbar puncture was carried out. Biomarkers analysis ((Innotest, Innogenetics®, Gent, Belgium) were performed by a laboratory using national standardized procedures for CSF analysis and interpretation with quality control [6, 7]. Increased phosphorylated tau (110 ng/l; 0 < N 9) 14∗ (N = 16)
score.
probable underlying AD pathology. Amyloid imaging was not performed. APOE genotype status was not performed. This case fulfilled the PCA criteria [10–12] based on: 1) the insidious onset with progressive decline; 2) with neurovisual disorders (visuospatial and visuoconstructive deficit, not explained by an ophthalmological pathology); 3) apraxia; 4) memory was preserved; and 5) structural and functional neuroimaging examinations showed asymmetric posterior cortical abnormalities. Hemianopia has been sometimes reported in PCA when primary occipital cortex was involved [13, 14]. The linguistic pattern and the left parieto-temporal abnormalities suggested a logopenic syndrome that can occur in PCA [15, 16]. The moderate parkinsonism was unusual; however, it occurred secondarily during the follow-up.
DISCUSSION Seizures were the first symptoms of AD in this case. When considering clinical and EEG data, left TLE [17] with transient epileptic amnesic syndrome (TEAS) [18, 19] was highly probable. The ictal symptoms (“d´ej`a-vu” followed by sensory aphasia) as well as the post-ictal state (persisting aphasia, temporo-spatial disorientation, occasional prolonged transient amnesia
with normal memory performances during interictal phase) and the interictal signs (unilateral hypoacousia, tinnitus, and hemianopia) sustained this hypothesis [17–19]. However, unusual features suggested that TEAS was not isolated. EEG and neuroimaging abnormalities are usually limited to the temporal lobes in TEAS [20]. The location of the neuronal network involved in epilepsy was, however, larger than the temporal lobe because dysarthria and right arm myoclonus also occurred secondarily and were followed by postictal transient right hemiparesis and posterior aphasia. The first EEG and FDG-PET confirmed this hypothesis, by showing extended slow wave background activity with occurrence of rare sharp waves on the left hemisphere and left occipital hypometabolism, respectively. This network was most probably located over the left temporo-parieto-occipital region [18–20]. In our case, the partial seizures began 5 years and progressively increased before cognitive decline thereby suggesting that epilepsy had induced the observed neuropsychological deficits. During the evolution, TEAS can become epileptic amnesic syndrome (EAS) with permanent cognitive deficits (usually isolated memory disorders) assessed by neuropsychological examination [21, 22]. Those patients indeed frequently match the definition of single domain amnestic mild cognitive impairment [21–23]. A good seizure control is usually obtained with a monotherapy, especially with
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B
A
D
E
H
C
F
I
G
J
Fig. 1. Rey-Osterrieth complex figure copy that was not improved by planification cueing showed visuospatial impairment (A); initial MRI showed slight biparietal atrophy (B), left subcortical atrophy (C), and moderate left hippocampal atrophy (D), on axial T2 FLAIR-weighted sequence; initial FDG-PET showed left occipital and left medial temporal hypometabolism (E) not explained by atrophy on the brain CT-scan (F); after a follow-up of one year and a half, HMPAO-SPECT showed bitemporal and left parieto-occipital and cingular hypoperfusion (G); initial EEG showed no alpha rhythm (H), left theta slow wave background activity (C3-Cz) combined with rare sharp-waves (C3-01 and T3-01) (I); one year later, EEG showed delta background activity and triphasic waves on the whole left hemisphere (J).
lamotrigine, in TEAS [19]. Anticonvulsants usually lead to cognitive improvement (and sometimes to normalization) in EAS [21, 22]. In our case, the refractory seizures (quadritherapy to improve seizure frequency of 75%) and the subsequent cognitive decline with language disorders, parietal and occipital syndrome (with no memory impairment) were also contradictory with
TEAS and EAS. Therefore, a neurodegenerative process was suspected. The etiological link between AD and this progressive partial epilepsy was sustained by several arguments: 1) the medical workup did not reveal any other explanatory disease; 2) the symptoms and signs continuously accumulated on a 3-year period with
B. Cretin et al. / Temporal Epilepsy Revealing PCA Due to AD
ongoing parietal involvement; 3) the atrophy on MRI and the AD CSF biomarkers profile with high amyloid burden [8, 24] suggest an AD pathology; 4) the amyloidopathy is proven as an epileptogenic factor in high amyloid producing transgenic animal models [25, 26]; 5) amyloidosis starts 15 to 20 years before cognitive decline as shown with PET-amyloid studies in sporadic AD [27]; 6) the temporal lobe AD epileptogenesis is probably also a tau dependent phenomenon [28] as tau pathology usually starts in temporal lobes; 7) AD is associated with a decrease of alpha rhythm spectrum on EEG recording [29]; and 8) several clinical reports illustrate that partial seizures can be an early feature of AD with ictal signs (dej`a-vu, amnesia, and sometimes aphasia) and EEG recordings (fronto-central and temporal epileptiform activity) suggest temporal cortex involvement [3–5, 23]. This prodromal AD was also atypical because of the lack of an amnestic profile on cognitive testing. The clinical characteristics (hemianopia, agraphesthesia, astereognosia, visuoconstructive disorders and apraxia, language disorders), neuroimaging findings (left parieto-occipital abnormalities) and the electrophysiological markers (EEG abnormalities) suggested an early involvement of the left parieto-temporooccipital cortex occurred. The clinical picture is therefore suggestive of posterior cortical atrophy [10–12]. Temporal involvement, suggested by TLE and mild medial temporal atrophy, is not inconsistent with PCA in which neuropathlogical studies reported hippocampal neurofibrillary tangles [12]. A mild parkinsonism secondarily occurred and can thus have been misdiagnosed as a corticobasal degeneration [30]. Klaffke et al. reported eight probable corticobasal degeneration patients that all presented abnormal FP-CIT imaging [31]. In our patient, no dopaminergic depletion was observed on FP-CIT imaging and parietal atrophy was bilaterally present on MRI. Moreover, temporal involvement [32] and seizures are rare in neuropathology-proven corticobasal degeneration [33]. Moreover, CSF biomarkers suggested an underlying AD pathology, which is the more frequent neuropathology in PCA [12]. Seizures in PCA or corticobasal syndrome could possibly be a marker of underlying AD neuropathology. Our observation encourages clinicians to be careful when diagnosing a possible TEAS or EAS. This syndrome can evolve into a neurodegenerative disorder, particularly when one of the following red-flags are present: 1) abnormal neurological examination; 2) non-episodic memory impairment on cognitive evaluation; 3) cognitive complaints starting before or a long
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time after seizures onset; and 4) progressive cognitive decline in spite of the use of anticonvulsants [23]. This report confirms the relevance of these atypical features and also adds to TEAS and EAS electrophysiological “red-flags” (extratemporal epileptiform and/or slow wave background activity and/or decrease of the alpha rhythm spectrum) and neuroimaging “red flags” (extratemporal atrophy and/or hypometabolism). In conclusion, our case confirms the small literature on seizures-AD interactions during the early stages of the disease [3, 23] even in atypical onset such as PCA and illustrates the complex interaction between amyloidopathy and such late-onset epileptogenesis [25, 26]. Moreover, our patient had seizures before cognitive decline, thereby mimicking a possible TEAS. The links between this late-onset epileptic syndrome, the amyloid brain load, and an incipient AD need to be clarified [23]. Further works are needed to better understand the mechanisms underlying early epilepsy and AD. DISCLOSURE STATEMENT Authors’ disclosures available online (http://j-alz. com/manuscript-disclosures/14-1953r2). REFERENCES [1]
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