Epilepsy & Behavior 20 (2011) 410–413
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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h
Case Report
Complex transient epileptic amnesia Ryan D. Walsh a, Robert E. Wharen Jr. b, William O. Tatum IV a,⁎ a b
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, USA
a r t i c l e
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Article history: Received 17 November 2010 Revised 17 December 2010 Accepted 17 December 2010 Available online 22 January 2011 Keywords: Dementia Epilepsy surgery Epileptic pseudodementia Invasive electroencephalography Temporal lobe epilepsy Todd phenomenon Transient epileptic amnesia
a b s t r a c t Transient epileptic amnesia is a rare but probably underrecognized form of temporal lobe epilepsy, which typically manifests as episodic isolated memory loss. Consequently, transient epileptic amnesia may be readily misdiagnosed as a nonepileptic memory dysfunction in older individuals. When appropriately recognized, it has been described as a treatment-responsive syndrome amenable to antiepileptic drugs. We describe a patient with drug-resistant transient epileptic amnesia treated with unilateral temporal lobectomy. Prolonged postictal slowing in the mesial temporal structures was evident on invasive electroencephalography 5 hours after the occurrence of a brief focal seizure. These findings support the theory of a Todd phenomenon as the underlying pathophysiological mechanism in transient epileptic amnesia. © 2010 Elsevier Inc. All rights reserved.
1. Introduction Temporal lobe seizures that manifest characteristic semiology are easily recognized as epilepsy [1]. Transient epileptic amnesia (TEA) is a rare, recently identified form of temporal lobe epilepsy (TLE) characterized by focal seizures manifesting as recurrent transient episodes of isolated memory loss [2]. If seizures are subtle and occur without such features as aura, postictal state, or awareness of the event, the diagnosis of epilepsy can be elusive [3]. TEA may be underrecognized and mistreated as a degenerative memory disorder [3,4]. Memory difficulties are a common complaint in elderly patients [5]. TEA is typically an epilepsy syndrome that responds favorably to antiepileptic drugs (AEDs). TLE in adulthood is frequently associated with drugresistant focal seizures [1]. We describe a patient with TEA who was initially misdiagnosed with Alzheimer's disease; the patient's condition improved after left temporal lobectomy.
2. Report of a case A 59-year-old right-handed man with obstructive sleep apnea, hyperlipidemia, and chronic back pain presented with a 4-year history of memory complaints. He previously was employed as a systems analyst until he developed “short-term memory problems,” which caused a decline in his job performance and led to early retirement. ⁎ Corresponding author. Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. E-mail address:
[email protected] (W.O. Tatum). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.12.026
There was no contributory family history. He was married and college educated and did not smoke or drink alcohol. Results of a neurological examination were normal, as were his complete blood cell count, metabolic profile, thyroid panel, vitamin B12 and folate levels, and syphilis serology. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) were normal. Neuropsychological testing suggested impairments in selective attention and immediate and delayed memory. A positron emission tomography (PET) scan of the brain was reported as demonstrating bilateral temporal-parietal hypometabolism. He received a diagnosis of Alzheimer's disease and was treated with donepezil without symptomatic improvement. One year later, the patient experienced a generalized tonic–clonic seizure (GTCS). No risk factors for seizures were evident. Two years later he was initiated on phenytoin after experiencing two more GTCs in close succession. Despite adequate serum concentrations of phenytoin, he experienced a series of seven more GTCs. Video/EEG monitoring was performed and demonstrated left temporal spikes during sleep. Seven focal seizures were captured (six during sleep) in 72 hours. Seizures were very subtle and characterized as brief arousal from sleep. During the only waking seizure, he experienced a subtle stare followed by postictal memory loss not identified by his wife even as she was sitting next to him. All seizures were associated with unawareness of the event. Gadolinium-enhanced MRI of the brain using an epilepsy protocol demonstrated subtle left posterior hippocampal formation atrophy without corresponding signal change. A repeated fluorodeoxyglucosePET brain scan was normal, and ictal single-photon-emission computed tomography revealed mild left temporal hyperperfusion.
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Fig. 1. Head CT scan without contrast demonstrating placement of invasive EEG electrodes. (A) Left subtemporal strips. (B) Left temporal lobe depth electrode and posterior temporal 4 × 4 grid. (C) More superiorly, posterior temporal 4 × 4 grid.
Routine neuropsychological testing demonstrated a normal neuropsychological profile with complaints of subjective memory dysfunction of the amnestic type. On a Wada test (an intracarotid methohexital procedure), the patient recognized 5 of 10 pictured objects on left injection and 9 of 10 objects on right injection. On a repeated study, he recognized 9 of 10 objects on left injection and 10 of 10 objects on right injection. Generalized tonic–clonic seizures were infrequent but continued despite use of several AEDs and were associated with continued memory fluctuation, most notable after awakening in the morning. He subsequently underwent presurgical evaluation with left hemispheric invasive EEG using two laterally placed depth electrodes, two subtemporal strips, and a posterior temporal 4 × 4 grid (Fig. 1). Three focal seizures were captured originating in the left inferior (neocortical) temporal subdural strip before depth involvement (Fig. 2). The clinical manifestations were subtle and manifested as retrograde loss of recall of his cat's name and anterograde amnesia for conversations immediately after the events. The patient underwent a left inferior lateral temporal neocorticectomy with hippocampal sparing. At the 6-month follow-up, he was free of amnesic episodes and disabling seizures. Language function postoperatively contained intermittent word-finding difficulties, although his episodic memory dysfunction stabilized and resolved. 3. Discussion Transient epileptic amnesia is probably underrecognized as an epileptic syndrome because of the subtle manifestations of the seizures that often lead to a substantial delay in diagnosis [4]. The attacks may be associated with other symptoms or signs that are suggestive of focal seizures, including olfactory and gustatory hallucinations, oroalimentary automatisms, and overt periods of unresponsiveness [4]. Often, as in our patient with subtle attacks, these features are absent, making the diagnosis of focal seizures associated with temporal lobe epilepsy more difficult and elusive. TEA has been postulated to result from recurrent focal seizures that produce a physiological Todd paralysis of the mesial temporal structures with resultant impaired memory function caused by an enduring postictal state [6]. Case reports have demonstrated prolonged anterograde memory loss for days to months after recovery from acute attacks [4,7]. The commonly discrete nature of the amnesic attacks of TEA and otherwise intact neurological function during the attacks cause an erroneous diagnosis of recurrent transient global amnesia in many patients with TEA. In some patients with TEA, discrete episodes of amnesia may be less apparent and the interictal memory dysfunction may predominate, often resulting in a misdiagnosis of dementia [3,8,9], as in our patient.
The memory dysfunction in TEA is complex and is reflected by the prominence of interictal memory complaints. Up to 70% of patients may demonstrate remote autobiographical memory dysfunction, suggesting retrograde amnesia in addition to milder personal and public semantic memory loss [10,11]. Our patient had recurrent difficulties with memory loss, especially with names, during episodes of TEA. In previous reports, nearly 50% of patients noted symptoms of accelerated forgetfulness [4,12,13]. Accelerated long-term forgetting in patients with TEA appears to be maximal at 24 hours, making routine neuropsychological assessments relatively insensitive for detecting memory impairment, given that measures of declarative memory reflect briefer intervals [14]. In our patient, anterograde memory function appeared to be normal during routine neurological examination and on neuropsychological testing. However, his inability to “think” and “function as a computer operator” during his normal daily routine forced him to retire early from work. Moreover, patients with TEA may complain of remote memory dysfunction in addition to recent episodic loss of recall [13]. Patients with TEA have previously been identified in dementia clinics, and the diagnosis of TEA made only after prolonged EEG monitoring demonstrates electrographic seizures [3]. Furthermore, interictal epileptiform discharges may not be present on routine EEG [4]. Discrete episodes of transient memory impairment, which occur with TEA, represent the ictal phenomenon associated with focal seizures with or without impaired awareness (the latter seen in our patient). However, the pathophysiology that underlies the memory complaints is more complex. In addition to a prolonged physiological Todd “paralysis” of the mesial temporal structures, there may be other potential contributing mechanisms, including structural and functional components [14,15]. Although subtle hippocampal volume loss has been demonstrated in patients with TEA, the degree of atrophy does not appear to correlate with the degree of accelerated long-term forgetting or autobiographical memory impairment [10]. Additional evidence against a primary structural abnormality underlying chronic memory complaints is the fact that most patients improve after the initiation of AEDs, and improvement appears to be sustained [15]. These observations would not be as likely to occur if a structural basis was the principal cause. Interictal memory impairments may also be the result of subclinical seizures or frequent interictal epileptiform discharges involving the hippocampus and mesial temporal lobes [11]. As noted in our patient, TEA may be related to sleep in nearly three-quarters of cases. Persistent memory problems and accelerated forgetfulness might result from nocturnal “subclinical” or subtle focal seizures that disrupt ongoing memory consolidation processes due to dysfunctional hippocampal neural networks [2,16]. Nocturnal TEA may impair remote memory consolidation, a process that involves the active reprocessing of new memories and seems to occur most
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R.D. Walsh et al. / Epilepsy & Behavior 20 (2011) 410–413
effectively during sleep [17]. Explicit encoding involves a functional network between the prefrontal cortex, thalamus, and hippocampus. Activation of this neuronal network appears to be crucial in forming memories that are amenable to sleep-dependent memory consolidation [17,18]. Normal function may therefore be interrupted in TLEs and TEA, resulting in impaired consolidation and subsequent memory complaints. A robust response to AED monotherapy is considered a characteristic feature of TEA, with nearly all patients typically experiencing complete resolution or markedly reduced frequency of amnesic attacks [3,4,8,19]. Mesial TLE with hippocampal onset accounts for at least 80% of all temporal lobe seizures [20]. However, mesial TLE is a heterogeneous syndrome attributable to various pathologies, with up to one third of patients demonstrating drug resistance [21]. Because of his younger age and the association of TEA with convulsions, our patient's presentation reinforces the heterogeneous spectrum of TEA. Although initially treated as Alzheimer's disease, his disease had a clinical course that may have been slightly different because of the neocortical proximity to the hippocampus proper. Our case supports the previous suspicion that the interictal memory dysfunction seen in patients with TEA largely reflects the effects incurred by prolonged postictal slowing involving the medial temporal lobe structures. The inferior temporal neocortical onset seen in our patient may have resulted in earlier clinical recognition of TEA because of the presence of rare generalized seizures, in contrast to the delays in diagnosis described in prior reports [3,4,8]. Nevertheless, neocortical TLE has been reported to occur in patients with TEA [22]. Although the syndrome of TEA may typically present as drugresponsive TLE, drug-resistant TEA may also occur and be amenable to epilepsy surgery. Conflict of interest statement The authors have no conflicts of interest to disclose.
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Fig. 2. (A) Invasive EEG showing seizure onset after spread from IT4 (top arrow) to ST1 and ST2 (bottom arrow). Note the lack of involvement in the depth electrodes. (B) Postictal slowing seen in the IT and intermittently in the depth electrodes (large oval) as well as ST electrodes (small oval) 5 hours after the seizure. AD, anterior depth; FT, frontotemporal; IT, inferior temporal; LT, lateral temporal; PD, posterior depth; ST, superior temporal.
