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Post-ictal hyperfamiliarity syndrome in focal epilepsy
Epilepsy & Behavior 13 (2008) 567–569
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Case Report
Post-ictal hyperfamiliarity syndrome in focal epilepsy Krzysztof Bujarski *, Michael R. Sperling Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 9th and Walnut Sts., Suite 200, Philadelphia, PA 19107, USA
a r t i c l e
i n f o
Article history: Received 5 May 2008 Revised 4 June 2008 Accepted 5 June 2008 Available online 29 July 2008 Keywords: Hyperfamiliarity syndrome Delusion of misidentification Capgras delusion Epilepsy
a b s t r a c t The recognition of familiar faces entails sequential cognitive processing. Initial encoding of face-specific information is followed by semantic association with previously learned information, which results in a subjective feeling of familiarity. We describe here a 32-year-old woman who post-ictally developed a sense of familiarity for previously unknown people and faces in the context of bilateral temporal seizures. We postulate that the delusion resulted from modality-specific indiscriminate association of all face-specific information with the affective label of familiarity. During this delusion, the step of semantic association was not required to generate the feeling of familiarity, which resulted in every face being labeled as familiar. Ó 2008 Elsevier Inc. All rights reserved.
1. Introduction Evidence gained from human lesional and functional neuroimaging studies suggests that the recognition of familiar faces requires several distinct steps of sequential cognitive processing. Initial decoding of face-specific information is accomplished by the visual association networks of the fusiform face area in the ventral occipitotemporal region of both hemispheres [1,2]. Subsequent association of this face-specific information with previously learned face information, a step required for recognition called semantic association, is accomplished by predominantly the right temporal neocortical regions, right hippocampal and parahippocampal gyri, and both frontal lobes [3]. The third step of cognitive processing of facial recognition requires the association of affective content with the face or person that has been recognized. To experience contextually appropriate feelings such as affection, hostility, and familiarity, connections to the limbic system must be maintained [4]. Abnormal processing of face-specific information may result in a variety of clinical syndromes such as prosopagnosia and delusions of misidentification (DOMs). DOMs are a group of related neurocognitive disorders distinguished by a delusional belief in the identity of oneself, other people, or places. Neurocognitive models of DOMs center on abnormal association of person-specific information, such as the face, with the limbic system. For example, in Capgras delusion, patients believe that members of their family have been replaced by impostors. These patients have normal processing of face-specific information, normal semantic association,
* Corresponding author. Fax: +215 955 0606. E-mail address: [email protected] (K. Bujarski). 1525-5050/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2008.06.003
but are unable to generate the appropriate feeling of familiarity because of limbic disconnection [5]. The syndrome of hyperfamiliarity is a DOM in which abnormal cognitive processing leads to inappropriate feelings of familiarity. Patients have a firm belief that they have met or recognize people they have never previously encountered. The syndrome was originally described by Emil Kraepelin in the 1890s in a patient who was recovering from typhus [6]. Subsequently, it has been described only twice, following destructive lesions of the left cingulate region and the left occipitotemporal region [7,8].
2. Case history A 32-year-old right-handed woman developed complex partial seizures during which she was unresponsive and experienced occasional posturing of the right or left upper extremity. Seizures had started 6 months prior to the evaluation and initially occurred several times per week. The patient was admitted for inpatient video/EEG monitoring because of increasing seizure frequency. During the hospitalization, multiple complex partial seizures were observed. The postictal period was marked by a return to baseline mental state within several minutes of seizure termination, with the distinct exception of a strong feeling of familiarity for people the patient had never met before. The patient insisted that doctors, nurses, MRI technicians, and ancillary staff who interacted with her during the hospitalization were familiar, although she could not determine where she had met them before. The patient denied other delusions, feelings of paranoia, or hallucinations. Cognitive evaluation during the postictal period revealed only mild deficits with attention and concentration. For instance, the
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K. Bujarski, M.R. Sperling / Epilepsy & Behavior 13 (2008) 567–569
months backward task took 25 seconds; the normal time is less then 15 seconds. Verbal fluency, categorical fluency, and digit span were normal. She made no sequencing errors and did not have impulsive responses. Verbal and design recognition memory was normal at 30 minutes for three words and three shapes. Visuospatial function, as tested with the Ray–Osterrieth Complex Figure copy, was normal. Specific tests for facial identification were administered. The patient identified 10 famous faces correctly, she recognized six pictures of facial emotion correctly, and she was able to discriminate correctly between faces with subtle differences in facial features (Benton Facial Recognition). The patient was shown pictures of 20 random faces that she had not seen before and reported that 18 seemed familiar. She likewise was shown pictures of streets and buildings that she had never seen before and reported that these did not look familiar. Two days after control of seizure activity, the patient was again shown pictures of random faces and reported that they no longer seemed familiar. MRI revealed a slight decrease in the volume of the right hippocampus without signal change. No other abnormalities were identified. Eighteen complex partial seizures were observed during a period of 36 hours. Seizures consisted of oral automatisms and unresponsive staring lasting 30–50 seconds and occurred every 45 minutes–3 hours. The EEG showed that seizures arose independently from either the left or right anterior temporal lobes beginning with a 4-Hz rhythmic discharge that evolved in frequency and spread to involve the rest of the ipsilateral hemisphere. No generalized convulsions or seizures spreading to the contralateral hemisphere were present. In addition, frequent T1 and T2 sharp waves were present. Ictal SPECT revealed increased perfusion in the left mesial frontal lobe. Interictal SPECT 2 weeks following the seizure activity was normal (Fig. 1). 3. Discussion The delusion of familiarity resulted from a modality-specific disturbance in facial processing. The patient had normal visuospatial function and normal perception of facial features; that is, she did not have a prosopagnosia. In addition, the feeling of familiarity was elicited not by looking at pictures of objects and places, but strictly by viewing faces. The patient was likewise not psychotic and had no other fixed delusions or hallucinations. We postulate that this delusion resulted from nonselective ‘‘labeling” of all facial percepts with the subjective feeling of familiarity; that is, the necessary step of correct semantic association was not required to elicit the feeling of familiarity. This delusion is in direct contrast to Capgras delusion, which occurs when correct semantic association
fails to generate the appropriate feeling of familiarity as a result of sensory–limbic disconnection [4]. In addition, this delusion was distinct from the frequently reported ictal experience of déjà vu in that the feeling of familiarity was specific for faces only. The delusion likely resulted from postictal dysfunction of a specific region of the cortex localized to the site of seizure onset, akin to Todd’s paralysis. As seizures were controlled, the postictal state resolved and functional integrity of the region of cortex was regained. The interictal and ictal scalp EEGs suggest bilateral temporal localization, MRI localized to the right hippocampus, and ictal SPECT revealed hypoperfusion of the left mesial frontal region. Exact anatomical localization is therefore not feasible in this patient, though the limbic system is implicated. Dual models of human memory propose that recognition and familiarity are distinct cognitive processes [9]. Recognition refers to the ability to recall a specific fact about a subject, whereas familiarity refers to the sense that something has been previously experienced. The common experience of ‘‘Where do I know this person from?” crystallizes the essence of such dual models. Evidence for distinct anatomic localization of recognition and familiarity is based on studies of patients who have destructive lesions of bilateral mesial temporal lobes. Such patients may have severely impaired recognition but may be able to experience contextually appropriate sense of familiarity [10]. In addition, functional MRI evidence suggests that recognition and familiarity may be supported by distinct neural networks [11]. Recognition tasks recruit more mesial temporal structures, whereas familiarity tasks are dependent more on extra-hippocampal temporal and mesial frontal regions. The extreme dissociation of recognition and familiarity seen in this patient lends support to the dual-model theory of recognition memory. The aberrant cognitive processing seen in this patient is also supportive of Bear’s hypothesis of sensory–limbic hyperconnection, which has been postulated to be the neural mechanism for the emergence of behavioral syndromes associated with epilepsy [12]. Bear postulated that as a result of ongoing seizure activity, abnormal sensory–limbic neural association pathways form that incorrectly appropriate emotional significance to normal and everyday sensory experiences. The hypothesis has been used to explain elements of temporal lobe epilepsy personality, such as deepening of emotions and chronic interictal psychosis. In addition, it has been postulated to be the mechanism underlying neuroendocrine disturbances seen in epilepsy [13]. The existence of sensory–limbic hyperconnectivity has not been confirmed experimentally. An animal model, which would be analogous to the sensory–limbic disconnection model that established the Kluver–Bucy syndrome, does not exist. Physiological studies
Fig. 1. (A) Ictal SPECT scan demonstrates a strong region of hyperperfusion in the left cingulate region. (B) SPECT obtained 10 days following seizure control is normal.
K. Bujarski, M.R. Sperling / Epilepsy & Behavior 13 (2008) 567–569
similar to those done by Ramachandran et al. in Capgras delusion and Damasio et al. in prosopagnosia that would measure skin conductance to emotional stimuli have not been done in patients with chronic epilepsy [5,14]. Lastly, the lack of clear association between specific interictal behavioral disturbances (interictal personality) and epilepsy subtypes has cast some doubt on the organic basis of interictal behavior, and rather, a multifactorial explanation for these syndromes has been favored [15]. Nevertheless, the delusion of hyperfamiliarity in this patient with epilepsy lends support to the fact that aberrant sensory–limbic processing may be responsible for certain behaviors associated with seizures. References [1] Sergent J, Ohta S, MacDonald B. Functional neuroanatomy of face and object processing: a positron emission tomography study. Brain 1992;115(Pt. 1):15–36. [2] Kanwisher N, McDermott J, Chun MM. The fusiform face area: a module in human extrastriate cortex specialized for face perception. J Neurosci 1997;17:4302–11. [3] Leveroni CL, Seidenberg M, Mayer AR, et al. Neural systems underlying the recognition of familiar and newly learned faces. J Neurosci 2000;20:878–86. [4] Bauer RM. Autonomic recognition of names and faces in prosopagnosia: a neuropsychological application of the Guilty Knowledge Test. Neuropsychologia 1984;22:457–69.
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[5] Hirstein W, Ramachandran VS. Capgras syndrome: a novel probe for understanding the neural representation of the identity and familiarity of persons. Proc R Soc London 1997;264:437–44. [6] Murai T, Kubota Y, Sengoku A. Unknown people believed to be known, the ‘‘assozii Erinnerungs–falschungen” by Kraepelin. Psychopathology 2000;33:52–4. [7] Nente F, Carrillo-Mezo R, Mendez MF, Ramirez J. Pathological hyperfamiliarity for others from a left anterior cingulate lesion. J Neuropsychiatry Clin Sci 2007;19:345–6. [8] Vuilleumier P, Mohr C, Valenza N, Wetzel C, Landis T. Hyperfamiliarity for unknown face after left lateral temporooccipital venous infarction: a double dissociation study with prosopagnosia. Brain 2003;126:889–907. [9] Yonelinas AP. The nature of recollection and familiarity: a review of 30 years of research. J Mem Lang 2002;46:441–517. [10] Mayes AR, Meudell PR, Pickering A. Is organic amnesia caused by a selective deficit in remembering contextual information? Cortex 1985;21:167–202. [11] Yonelinas AP, Otten LJ, Kendra N, Michael DR. Separating the brain regions involved in recollection and familiarity in recognition memory. J Neurosci 2005;25:3002–8. [12] Bear DM. Temporal lobe epilepsy: a syndrome of sensory–limbic hyperconnection. Cortex 1979;15:357–84. [13] Herzog AG. Psychoneuroendocrine aspects of temporolimbic epilepsy. Psychosomatics 1999;40:109–16. [14] Tranel D, Damasio AR. Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics. Science 1985;228:1453–4. [15] Swinkels WA, van Emde Boas W, Kuyk J, van Dyck R, Spinhoven P. Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE. Epilepsia 2006;47:2092–103.
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Case Report
Post-ictal hyperfamiliarity syndrome in focal epilepsy Krzysztof Bujarski *, Michael R. Sperling Jefferson Comprehensive Epilepsy Center, Department of Neurology, Thomas Jefferson University, Jefferson Hospital for Neuroscience, 9th and Walnut Sts., Suite 200, Philadelphia, PA 19107, USA
a r t i c l e
i n f o
Article history: Received 5 May 2008 Revised 4 June 2008 Accepted 5 June 2008 Available online 29 July 2008 Keywords: Hyperfamiliarity syndrome Delusion of misidentification Capgras delusion Epilepsy
a b s t r a c t The recognition of familiar faces entails sequential cognitive processing. Initial encoding of face-specific information is followed by semantic association with previously learned information, which results in a subjective feeling of familiarity. We describe here a 32-year-old woman who post-ictally developed a sense of familiarity for previously unknown people and faces in the context of bilateral temporal seizures. We postulate that the delusion resulted from modality-specific indiscriminate association of all face-specific information with the affective label of familiarity. During this delusion, the step of semantic association was not required to generate the feeling of familiarity, which resulted in every face being labeled as familiar. Ó 2008 Elsevier Inc. All rights reserved.
1. Introduction Evidence gained from human lesional and functional neuroimaging studies suggests that the recognition of familiar faces requires several distinct steps of sequential cognitive processing. Initial decoding of face-specific information is accomplished by the visual association networks of the fusiform face area in the ventral occipitotemporal region of both hemispheres [1,2]. Subsequent association of this face-specific information with previously learned face information, a step required for recognition called semantic association, is accomplished by predominantly the right temporal neocortical regions, right hippocampal and parahippocampal gyri, and both frontal lobes [3]. The third step of cognitive processing of facial recognition requires the association of affective content with the face or person that has been recognized. To experience contextually appropriate feelings such as affection, hostility, and familiarity, connections to the limbic system must be maintained [4]. Abnormal processing of face-specific information may result in a variety of clinical syndromes such as prosopagnosia and delusions of misidentification (DOMs). DOMs are a group of related neurocognitive disorders distinguished by a delusional belief in the identity of oneself, other people, or places. Neurocognitive models of DOMs center on abnormal association of person-specific information, such as the face, with the limbic system. For example, in Capgras delusion, patients believe that members of their family have been replaced by impostors. These patients have normal processing of face-specific information, normal semantic association,
* Corresponding author. Fax: +215 955 0606. E-mail address: [email protected] (K. Bujarski). 1525-5050/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2008.06.003
but are unable to generate the appropriate feeling of familiarity because of limbic disconnection [5]. The syndrome of hyperfamiliarity is a DOM in which abnormal cognitive processing leads to inappropriate feelings of familiarity. Patients have a firm belief that they have met or recognize people they have never previously encountered. The syndrome was originally described by Emil Kraepelin in the 1890s in a patient who was recovering from typhus [6]. Subsequently, it has been described only twice, following destructive lesions of the left cingulate region and the left occipitotemporal region [7,8].
2. Case history A 32-year-old right-handed woman developed complex partial seizures during which she was unresponsive and experienced occasional posturing of the right or left upper extremity. Seizures had started 6 months prior to the evaluation and initially occurred several times per week. The patient was admitted for inpatient video/EEG monitoring because of increasing seizure frequency. During the hospitalization, multiple complex partial seizures were observed. The postictal period was marked by a return to baseline mental state within several minutes of seizure termination, with the distinct exception of a strong feeling of familiarity for people the patient had never met before. The patient insisted that doctors, nurses, MRI technicians, and ancillary staff who interacted with her during the hospitalization were familiar, although she could not determine where she had met them before. The patient denied other delusions, feelings of paranoia, or hallucinations. Cognitive evaluation during the postictal period revealed only mild deficits with attention and concentration. For instance, the
568
K. Bujarski, M.R. Sperling / Epilepsy & Behavior 13 (2008) 567–569
months backward task took 25 seconds; the normal time is less then 15 seconds. Verbal fluency, categorical fluency, and digit span were normal. She made no sequencing errors and did not have impulsive responses. Verbal and design recognition memory was normal at 30 minutes for three words and three shapes. Visuospatial function, as tested with the Ray–Osterrieth Complex Figure copy, was normal. Specific tests for facial identification were administered. The patient identified 10 famous faces correctly, she recognized six pictures of facial emotion correctly, and she was able to discriminate correctly between faces with subtle differences in facial features (Benton Facial Recognition). The patient was shown pictures of 20 random faces that she had not seen before and reported that 18 seemed familiar. She likewise was shown pictures of streets and buildings that she had never seen before and reported that these did not look familiar. Two days after control of seizure activity, the patient was again shown pictures of random faces and reported that they no longer seemed familiar. MRI revealed a slight decrease in the volume of the right hippocampus without signal change. No other abnormalities were identified. Eighteen complex partial seizures were observed during a period of 36 hours. Seizures consisted of oral automatisms and unresponsive staring lasting 30–50 seconds and occurred every 45 minutes–3 hours. The EEG showed that seizures arose independently from either the left or right anterior temporal lobes beginning with a 4-Hz rhythmic discharge that evolved in frequency and spread to involve the rest of the ipsilateral hemisphere. No generalized convulsions or seizures spreading to the contralateral hemisphere were present. In addition, frequent T1 and T2 sharp waves were present. Ictal SPECT revealed increased perfusion in the left mesial frontal lobe. Interictal SPECT 2 weeks following the seizure activity was normal (Fig. 1). 3. Discussion The delusion of familiarity resulted from a modality-specific disturbance in facial processing. The patient had normal visuospatial function and normal perception of facial features; that is, she did not have a prosopagnosia. In addition, the feeling of familiarity was elicited not by looking at pictures of objects and places, but strictly by viewing faces. The patient was likewise not psychotic and had no other fixed delusions or hallucinations. We postulate that this delusion resulted from nonselective ‘‘labeling” of all facial percepts with the subjective feeling of familiarity; that is, the necessary step of correct semantic association was not required to elicit the feeling of familiarity. This delusion is in direct contrast to Capgras delusion, which occurs when correct semantic association
fails to generate the appropriate feeling of familiarity as a result of sensory–limbic disconnection [4]. In addition, this delusion was distinct from the frequently reported ictal experience of déjà vu in that the feeling of familiarity was specific for faces only. The delusion likely resulted from postictal dysfunction of a specific region of the cortex localized to the site of seizure onset, akin to Todd’s paralysis. As seizures were controlled, the postictal state resolved and functional integrity of the region of cortex was regained. The interictal and ictal scalp EEGs suggest bilateral temporal localization, MRI localized to the right hippocampus, and ictal SPECT revealed hypoperfusion of the left mesial frontal region. Exact anatomical localization is therefore not feasible in this patient, though the limbic system is implicated. Dual models of human memory propose that recognition and familiarity are distinct cognitive processes [9]. Recognition refers to the ability to recall a specific fact about a subject, whereas familiarity refers to the sense that something has been previously experienced. The common experience of ‘‘Where do I know this person from?” crystallizes the essence of such dual models. Evidence for distinct anatomic localization of recognition and familiarity is based on studies of patients who have destructive lesions of bilateral mesial temporal lobes. Such patients may have severely impaired recognition but may be able to experience contextually appropriate sense of familiarity [10]. In addition, functional MRI evidence suggests that recognition and familiarity may be supported by distinct neural networks [11]. Recognition tasks recruit more mesial temporal structures, whereas familiarity tasks are dependent more on extra-hippocampal temporal and mesial frontal regions. The extreme dissociation of recognition and familiarity seen in this patient lends support to the dual-model theory of recognition memory. The aberrant cognitive processing seen in this patient is also supportive of Bear’s hypothesis of sensory–limbic hyperconnection, which has been postulated to be the neural mechanism for the emergence of behavioral syndromes associated with epilepsy [12]. Bear postulated that as a result of ongoing seizure activity, abnormal sensory–limbic neural association pathways form that incorrectly appropriate emotional significance to normal and everyday sensory experiences. The hypothesis has been used to explain elements of temporal lobe epilepsy personality, such as deepening of emotions and chronic interictal psychosis. In addition, it has been postulated to be the mechanism underlying neuroendocrine disturbances seen in epilepsy [13]. The existence of sensory–limbic hyperconnectivity has not been confirmed experimentally. An animal model, which would be analogous to the sensory–limbic disconnection model that established the Kluver–Bucy syndrome, does not exist. Physiological studies
Fig. 1. (A) Ictal SPECT scan demonstrates a strong region of hyperperfusion in the left cingulate region. (B) SPECT obtained 10 days following seizure control is normal.
K. Bujarski, M.R. Sperling / Epilepsy & Behavior 13 (2008) 567–569
similar to those done by Ramachandran et al. in Capgras delusion and Damasio et al. in prosopagnosia that would measure skin conductance to emotional stimuli have not been done in patients with chronic epilepsy [5,14]. Lastly, the lack of clear association between specific interictal behavioral disturbances (interictal personality) and epilepsy subtypes has cast some doubt on the organic basis of interictal behavior, and rather, a multifactorial explanation for these syndromes has been favored [15]. Nevertheless, the delusion of hyperfamiliarity in this patient with epilepsy lends support to the fact that aberrant sensory–limbic processing may be responsible for certain behaviors associated with seizures. References [1] Sergent J, Ohta S, MacDonald B. Functional neuroanatomy of face and object processing: a positron emission tomography study. Brain 1992;115(Pt. 1):15–36. [2] Kanwisher N, McDermott J, Chun MM. The fusiform face area: a module in human extrastriate cortex specialized for face perception. J Neurosci 1997;17:4302–11. [3] Leveroni CL, Seidenberg M, Mayer AR, et al. Neural systems underlying the recognition of familiar and newly learned faces. J Neurosci 2000;20:878–86. [4] Bauer RM. Autonomic recognition of names and faces in prosopagnosia: a neuropsychological application of the Guilty Knowledge Test. Neuropsychologia 1984;22:457–69.
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[5] Hirstein W, Ramachandran VS. Capgras syndrome: a novel probe for understanding the neural representation of the identity and familiarity of persons. Proc R Soc London 1997;264:437–44. [6] Murai T, Kubota Y, Sengoku A. Unknown people believed to be known, the ‘‘assozii Erinnerungs–falschungen” by Kraepelin. Psychopathology 2000;33:52–4. [7] Nente F, Carrillo-Mezo R, Mendez MF, Ramirez J. Pathological hyperfamiliarity for others from a left anterior cingulate lesion. J Neuropsychiatry Clin Sci 2007;19:345–6. [8] Vuilleumier P, Mohr C, Valenza N, Wetzel C, Landis T. Hyperfamiliarity for unknown face after left lateral temporooccipital venous infarction: a double dissociation study with prosopagnosia. Brain 2003;126:889–907. [9] Yonelinas AP. The nature of recollection and familiarity: a review of 30 years of research. J Mem Lang 2002;46:441–517. [10] Mayes AR, Meudell PR, Pickering A. Is organic amnesia caused by a selective deficit in remembering contextual information? Cortex 1985;21:167–202. [11] Yonelinas AP, Otten LJ, Kendra N, Michael DR. Separating the brain regions involved in recollection and familiarity in recognition memory. J Neurosci 2005;25:3002–8. [12] Bear DM. Temporal lobe epilepsy: a syndrome of sensory–limbic hyperconnection. Cortex 1979;15:357–84. [13] Herzog AG. Psychoneuroendocrine aspects of temporolimbic epilepsy. Psychosomatics 1999;40:109–16. [14] Tranel D, Damasio AR. Knowledge without awareness: an autonomic index of facial recognition by prosopagnosics. Science 1985;228:1453–4. [15] Swinkels WA, van Emde Boas W, Kuyk J, van Dyck R, Spinhoven P. Interictal depression, anxiety, personality traits, and psychological dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE. Epilepsia 2006;47:2092–103.