- Email: [email protected]
Seizure-free after surgery in a patient with non-lesional startle epilepsy: A case report
Epilepsy & Behavior 25 (2012) 700–703
Contents lists available at SciVerse ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Case Report
Seizure-free after surgery in a patient with non-lesional startle epilepsy: A case report Yan-Ping Sun a, b, Hong-Wei Zhu c,⁎, Shou-Wen Zhang d, Zhao-Yang Huang a, Li-Ping Li a, Liang Qiao c, Wei Du c, Yu-Ping Wang a,⁎⁎ a
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China Department of Neurology, the Affiliated Hospital of the Medical College of Qingdao University, Shandong Province, China Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China d Department of Neurosurgery, Jiangong Hospital, Beijing, China b c
a r t i c l e
i n f o
Article history: Received 21 July 2012 Revised 31 August 2012 Accepted 2 September 2012 Available online 7 November 2012 Keywords: Startle epilepsy Supplementary sensorimotor area Electrocorticograph
a b s t r a c t We present the case of a patient with startle epilepsy provoked by auditory, somatosensory and visual stimuli during video-electrocorticography (ECoG) recording. Ictal ECoG of all types of seizures triggered by the three kinds of stimuli showed that seizure onset originated from the left supplementary sensorimotor area (SSMA). The patient has been seizure‐free after the cortex around the left SSMA only had been resected. Therefore, we speculate that left SSMA is the epileptogenic zone of startle epilepsy in this patient and perhaps the primary cortex to modulate the startle reflex in healthy persons. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Startle epilepsy was described by Gowers in 1901 [1]. It was considered as one of the reflex epilepsy syndromes by the International League Against Epilepsy (ILAE) in 2001. It is triggered by sudden and unexpected stimuli (auditory, somatosensory, and, rarely, visual). The patient with startle epilepsy is often at high risk of severe trauma during seizures [1,2]. Onset of the seizures is during childhood or adolescence [3]. The ictal onset zone in startle epilepsy has been attributed to the primary motor cortex, premotor cortex, parietal lobe, peri‐insular auditory cortex and the SSMA [4–6]. It was reported that most cases of startle epilepsy were associated with structural lesions found on MRI [6–8]. We present a patient with MRI-negative startle seizures who has been seizure‐free after left SSMA resection.
2. Case report The patient was a 17‐year-old male. Family history showed that the father of his grandfather suffered from epilepsy. The patient was diagnosed with epilepsy 5 years earlier; he suffered from both startle‐induced and spontaneous seizures. About 90% of the attacks were triggered by sudden stimuli. He experienced 1 to 3 spontaneous
⁎ Corresponding author. ⁎⁎ Corresponding author. Fax: +86 10 83157841. E-mail addresses: [email protected] (H.-W. Zhu), [email protected] (Y.-P. Wang). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yebeh.2012.09.001
seizures per day usually before he woke up in the morning despite high-dose treatment with sodium valproate, levetiracetam and clonazepam simultaneously. Before he was admitted to the hospital, he had rarely suffered from spontaneous seizures after taking phenobarbital, carbamazepine and sodium valproate simultaneously. However, he experienced more than 10 startle‐induced seizures per day, occasionally accompanied by dropping to the ground. He presented to our Epilepsy Monitoring Center for evaluation of epilepsy surgery. Neurologic examination was normal. Brain MRI (General Electric Medical Systems, Signa 3 T), including axial and sagittal T1, T2, axial and coronal FLAIR sequences, was also normal. Interictal F18-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed hypometabolism in right anterolateral temporal, left mesial temporal and bilateral parietal lobes. Interictal magnetoencephalography (MEG) revealed clusters of magnetic spike sources localized in bilateral parietal and right temporal lobes; no epileptiform activity was found in the regions of the SSMAs. During scalp-EEG monitoring, there were four seizures induced by sudden noise and one seizure induced by turning off the lights in the ward. Semiology of the seizures was characterized by spasm or tonic posturing of bilateral limbs simultaneously and tonic posture in right limbs which lasted longer compared to the left limbs in two seizures. Interictal EEG showed frequent spikes in bilateral frontal, central and parietal regions especially arising from FZ, CZ and PZ. There were few spikes in bilateral temporal regions. Ictal EEG onset was obscured by an artifact. Because of the lack of sufficient lateralizing evidence from clinical seizure semiology and scalp-EEG, we placed bilateral subdural electrodes symmetrically by boring four holes in the patient's skull (Fig. 1). Two strip electrodes (8 contacts in each strip) were positioned within each cerebral longitudinal fissure.
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
701
Fig. 1. Approximate location of the electrodes over the left hemisphere. A. Strip electrodes in the longitudinal fissure (the red electrodes imply the onset area); B. Grid electrodes on the lobes of lateral convexity.
The patient was implanted with three grid electrodes over the dorsolateral frontal, parietal and temporal lobes bilaterally. Interictal ECoG revealed epileptiform activity localized in bilateral SSMA, parietal and temporal lobes, especially in left SSMA. We used acoustic, visual and somatosensory stimuli to induce more than 30 seizures during ECoG monitoring after phenobarbital withdrawal. There were no spontaneous seizures in the course of ECoG recording. There were different types of startle‐provoked epileptic seizures during monitoring, including tonic (symmetrical, unsymmetrical or only on the right side) and spasm (symmetrical or unsymmetrical or only on the right side) seizures lasting for 1 to 10 s accompanied by fear, palpitations and speech arrest. If the seizures lasted for more
than 2 s, they were characterized by sudden generalized tonic extension of all limbs which evolved into asymmetrical tonic-clonic movements. During ECoG recording, the tonic or spasm seizures which occurred only in the right limbs were induced by minor intentional stimuli. They were not recorded during scalp-EEG monitoring. Ictal ECoG of all types of seizures triggered by acoustic, visual and tactile stimuli showed a sharp or a slow wave in bilateral SSMAs followed by high‐amplitude fast activity which originated from the left SSMA (Fig. 2). During sleep, the same stimuli, which could trigger seizures easily when the patient was awake, did not induce seizures. If we warned him shortly before the presentation of the arousal-eliciting stimuli, seizures were usually not provoked or the seizures were minimal.
Fig. 2. Ictal ECoG of startle seizures (black arrows indicate start of stimuli). LL (RL) indicates left (right) interhemispheric strips; LF (RF) represents the ECoG recorded from left (right) frontal lobes; LP (RP) represents the ECoG recorded from left (right) parietal lobes; LT (RT) represents the ECoG that was recorded from left (right) temporal lobes. A. represents the ictal ECoG recording provoked by noise (red arrow indicates the beginning of change of ECoG); B. represents the ictal ECoG provoked by 90‐Hz flash recorded from bilateral posterior interhemispheric strips.
702
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
Fig. 3. Postoperative sagittal (A) and coronal (B) MRI scans (General Electric Medical Systems, Signa 3 T) showing the extent of resection.
Some stimuli induced ECoG changes from the SSMAs bilaterally without clinical symptoms. Cortical electrical stimulation around the left SSMA before resection did not elicit startle seizures, but movement of right limbs when stimulated by 4 to 8 mA (milliampere) electric current was observed. It was decided to resect the left SSMA cortex under awake anesthesia and intraoperative cortical electrical stimulation to establish the functional border (Fig. 3). Postoperative pathological report of the removed tissue revealed focal cortical dysplasia (FCD Type Ia). Muscle strength of the right limbs was reduced to 4/5 postoperatively and recovered completely in two weeks. The patient has been seizure‐free, including startle‐induced seizures and spontaneous seizures, for 12 months postoperatively (Engel Class I). 3. Discussion Startle epilepsy is a rare form of reflex epilepsy characterized by seizures triggered by unexpected stimuli. The majority of cases described in the literature were associated with brain structural lesions found on MRI. Only 3 of more than 100 reported startle epilepsy cases have had resective surgery; furthermore, those three patients had lesions on brain MRI scan, and the resected areas were extensive [4,7–10]. To our knowledge, the case presented here is perhaps the first case of startle epilepsy with negative MRI scan (but histologically proven FCD) documented with subdural electrodes who has been seizure‐free after an operation. Focal cortical dysplasia variants may escape visual MRI inspection [11]. Most patients with startle epilepsy are sensitive to one or two sensory modalities [7,8]. This patient is the first reported case in which seizures were induced by acoustic, visual and somatosensory stimuli during monitoring. Ictal ECoG of all seizures triggered by the three kinds of stimuli showed that the onset area originated from left SSMA. The patient has been seizure‐free after resection of left SSMA after we demonstrated that the left SSMA was the epileptogenic zone. Manifestations of startle epilepsy, including in this patient, are similar to the physiologic startle response but with lower threshold for trigger and asymmetry [12]. Startle reflex originates from the caudal brainstem [12]. The nucleus reticularis pontis caudalis (RPC) seems particularly important [12]. The RPC is subject to a highly differentiated control: other brainstem nuclei (cochlear root nucleus, locus coeruleus, etc.), the limbic system, and even cortical areas modulate the RPC through release of various neurotransmitters [13,14]. It is thought that the emotional state just before a startling stimulus and the level of arousal affect the size of the auditory startle reflex [12]. If we warned the patient that a subsequent arousing stimulus would be presented, a seizure would usually not be triggered. During sleep, seizures could not be elicited by stimuli that provoked seizures during daytime. The
feeling of fear and palpitations during the occurrence of seizures in this patient were in accordance with a normal reflex in a healthy person. The ECoG change over bilateral SSMAs could be seen after startling stimuli even without seizures. Therefore, it is thought that the SSMAs are the primary cortical region that is able to modulate the startle reflex. The pathophysiologic mechanism of startle epilepsy remains unclear. It is thought that startle epilepsy may be generated when the epileptogenic zone overlaps the cortex modulating the startle reflex. For this patient, the startle stimuli may be amplified in the SSMAs to provoke a startle-induced seizure or disappeared in the SSMAs without abnormal reaction. We believed that other cortices which were not covered by the electrodes, such as the cingulate gyrus and precuneus, were involved in startle seizures [6,10,15]. Based on a study using ictal EEG-fMRI and SPECT coregistered to MRI (SPECT/SISCOM), it was proposed that startle seizures resulted from the interaction of all those regions—mainly from parietofrontal networks—that include the motor/premotor cortex, precuneus and SSMA [6]. Therefore, it was thought that in the pathway of startle response, the information was communicated through those areas to the SSMAs. We speculate that the SSMA is the hub for the startle epilepsy network and the major cortical region in which the startle reflex is modulated. Localized magnetic spike sources in the SSMA in patients with MRI-negative startle epilepsy were found in MEG recordings interictally [5,10]; however, in contrast, our MEG recordings did not show any epileptiform activity in the SSMA. Perhaps, this can be explained by studying the interictal ECoG of this patient. The interictal epileptiform activity can be seen in only two electrodes (center-to-center electrode distance was 1 cm) over the SSMA. Therefore, the area of interictal epileptiform discharges was about 2 cm2. Generally, epileptiform discharges in the convex cortical surface of the brain need to extend to 3 cm2 for MEG to detect a projected extracranial magnetic field [16]. Furthermore, the SSMA is deeply inside the interhemispheric fissure, and MEG is considered to be less sensitive to deep sources [17,18]. We showed in this successfully-treated case that surgical treatment for startle epilepsy is possible and reasonable since startle epilepsy is typically intractable and seizures may be frequent [2,7,8].
Statement We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. We state that human studies have been approved by Xuanwu Hospital Ethics Committee and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. This work is original.
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
Acknowledgments We gratefully acknowledge a grant (no. 30770744) from the National Nature Science Foundation of China that supported this work. We thank Professor G. van Luijtelaar (Radboud University Nijmegen, Netherlands) for revising the manuscript. References [1] Sáenz-Lope E, Herranz FJ, Masdeu JC. Startle epilepsy: a clinical study. Ann Neurol 1984;16:78-81. [2] Yang Z, Liu X, Qin J, et al. Clinical and electrophysiological characteristics of startle epilepsy in childhood. Clin Neurophysiol 2010;121:658-64. [3] Xue LY, Ritaccio AL. Reflex seizures and reflex epilepsy. Am J Electroneurodiagnostic Technol 2006;46:39-48. [4] Serles W, Leutmezer F, Pataraia E, et al. A case of startle epilepsy and SSMA seizures documented with subdural recordings. Epilepsia 1999;40:1031-5. [5] Saeki K, Saito Y, Sugai K, et al. Startle epilepsy associated with gait-induced seizures: pathomechanism analysis using EEG, MEG, and PET studies. Epilepsia 2009;50: 1274-9. [6] Fernández S, Donaire A, Maestro I, et al. Functional neuroimaging in startle epilepsy: involvement of a mesial frontoparietal network. Epilepsia 2011;52:1725-32. [7] Manford MRA, Fish DR, Shorvon SD. Startle provoked epileptic seizures: features in 19 patients. J Neurol Neurosurg Psychiatry 1996;61:151-6.
703
[8] Tibussek D, Wohlrab G, Boltshauser E, Schmitt B. Proven startle-provoked epileptic seizures in childhood: semiologic and electrophysiologic variability. Epilepsia 2006;47:1050-8. [9] Oguni H, Hayashi K, Usui N, Osawa M, Shimizu H. Startle epilepsy with infantile hemiplegia: report of two cases improved by surgery. Epilepsia 1998;39: 93-8. [10] García-Morales I, Maestú F, Pérez-Jiménez MA, et al. A clinical and magnetoencephalography study of MRI-negative startle-epilepsy. Epilepsy Behav 2009;16: 166-71. [11] Mühlebner A, Coras R, Kobow K, et al. Neuropathologic measurements in focal cortical dysplasias: validation of the ILAE 2011 classification system and diagnostic implications for MRI. Acta Neuropathol 2012;123:259-72. [12] Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol 2006;5:513-24. [13] Koch M. The neurobiology of startle. Prog Neurobiol 1999;59:107-28. [14] Von Coelln R, Thomas B, Savitt JM, et al. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc Natl Acad Sci U S A 2004;101:10744-9. [15] Pissiota A, Frans O, Michelgård A, et al. Amygdala and anterior cingulated cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci 2003;18:1325-31. [16] Oishi M, Otsubo H, Kameyama S, et al. Epileptic spikes: magnetoencephalography versus simultaneous electrocorticography. Epilepsia 2002;43:1390-5. [17] Baumgartner C, Pataraia E, Lindinger G, Deecke L. Neuromagnetic recordings in temporal lobe epilepsy. J Clin Neurophysiol 2000;17:177-89. [18] Knowlton RC, Laxer KD, Aminoff MJ, Roberts TP, Wong ST, Rowley HA. Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy. Ann Neurol 1997;42:622-31.
Contents lists available at SciVerse ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Case Report
Seizure-free after surgery in a patient with non-lesional startle epilepsy: A case report Yan-Ping Sun a, b, Hong-Wei Zhu c,⁎, Shou-Wen Zhang d, Zhao-Yang Huang a, Li-Ping Li a, Liang Qiao c, Wei Du c, Yu-Ping Wang a,⁎⁎ a
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China Department of Neurology, the Affiliated Hospital of the Medical College of Qingdao University, Shandong Province, China Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China d Department of Neurosurgery, Jiangong Hospital, Beijing, China b c
a r t i c l e
i n f o
Article history: Received 21 July 2012 Revised 31 August 2012 Accepted 2 September 2012 Available online 7 November 2012 Keywords: Startle epilepsy Supplementary sensorimotor area Electrocorticograph
a b s t r a c t We present the case of a patient with startle epilepsy provoked by auditory, somatosensory and visual stimuli during video-electrocorticography (ECoG) recording. Ictal ECoG of all types of seizures triggered by the three kinds of stimuli showed that seizure onset originated from the left supplementary sensorimotor area (SSMA). The patient has been seizure‐free after the cortex around the left SSMA only had been resected. Therefore, we speculate that left SSMA is the epileptogenic zone of startle epilepsy in this patient and perhaps the primary cortex to modulate the startle reflex in healthy persons. © 2012 Elsevier Inc. All rights reserved.
1. Introduction Startle epilepsy was described by Gowers in 1901 [1]. It was considered as one of the reflex epilepsy syndromes by the International League Against Epilepsy (ILAE) in 2001. It is triggered by sudden and unexpected stimuli (auditory, somatosensory, and, rarely, visual). The patient with startle epilepsy is often at high risk of severe trauma during seizures [1,2]. Onset of the seizures is during childhood or adolescence [3]. The ictal onset zone in startle epilepsy has been attributed to the primary motor cortex, premotor cortex, parietal lobe, peri‐insular auditory cortex and the SSMA [4–6]. It was reported that most cases of startle epilepsy were associated with structural lesions found on MRI [6–8]. We present a patient with MRI-negative startle seizures who has been seizure‐free after left SSMA resection.
2. Case report The patient was a 17‐year-old male. Family history showed that the father of his grandfather suffered from epilepsy. The patient was diagnosed with epilepsy 5 years earlier; he suffered from both startle‐induced and spontaneous seizures. About 90% of the attacks were triggered by sudden stimuli. He experienced 1 to 3 spontaneous
⁎ Corresponding author. ⁎⁎ Corresponding author. Fax: +86 10 83157841. E-mail addresses: [email protected] (H.-W. Zhu), [email protected] (Y.-P. Wang). 1525-5050/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yebeh.2012.09.001
seizures per day usually before he woke up in the morning despite high-dose treatment with sodium valproate, levetiracetam and clonazepam simultaneously. Before he was admitted to the hospital, he had rarely suffered from spontaneous seizures after taking phenobarbital, carbamazepine and sodium valproate simultaneously. However, he experienced more than 10 startle‐induced seizures per day, occasionally accompanied by dropping to the ground. He presented to our Epilepsy Monitoring Center for evaluation of epilepsy surgery. Neurologic examination was normal. Brain MRI (General Electric Medical Systems, Signa 3 T), including axial and sagittal T1, T2, axial and coronal FLAIR sequences, was also normal. Interictal F18-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed hypometabolism in right anterolateral temporal, left mesial temporal and bilateral parietal lobes. Interictal magnetoencephalography (MEG) revealed clusters of magnetic spike sources localized in bilateral parietal and right temporal lobes; no epileptiform activity was found in the regions of the SSMAs. During scalp-EEG monitoring, there were four seizures induced by sudden noise and one seizure induced by turning off the lights in the ward. Semiology of the seizures was characterized by spasm or tonic posturing of bilateral limbs simultaneously and tonic posture in right limbs which lasted longer compared to the left limbs in two seizures. Interictal EEG showed frequent spikes in bilateral frontal, central and parietal regions especially arising from FZ, CZ and PZ. There were few spikes in bilateral temporal regions. Ictal EEG onset was obscured by an artifact. Because of the lack of sufficient lateralizing evidence from clinical seizure semiology and scalp-EEG, we placed bilateral subdural electrodes symmetrically by boring four holes in the patient's skull (Fig. 1). Two strip electrodes (8 contacts in each strip) were positioned within each cerebral longitudinal fissure.
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
701
Fig. 1. Approximate location of the electrodes over the left hemisphere. A. Strip electrodes in the longitudinal fissure (the red electrodes imply the onset area); B. Grid electrodes on the lobes of lateral convexity.
The patient was implanted with three grid electrodes over the dorsolateral frontal, parietal and temporal lobes bilaterally. Interictal ECoG revealed epileptiform activity localized in bilateral SSMA, parietal and temporal lobes, especially in left SSMA. We used acoustic, visual and somatosensory stimuli to induce more than 30 seizures during ECoG monitoring after phenobarbital withdrawal. There were no spontaneous seizures in the course of ECoG recording. There were different types of startle‐provoked epileptic seizures during monitoring, including tonic (symmetrical, unsymmetrical or only on the right side) and spasm (symmetrical or unsymmetrical or only on the right side) seizures lasting for 1 to 10 s accompanied by fear, palpitations and speech arrest. If the seizures lasted for more
than 2 s, they were characterized by sudden generalized tonic extension of all limbs which evolved into asymmetrical tonic-clonic movements. During ECoG recording, the tonic or spasm seizures which occurred only in the right limbs were induced by minor intentional stimuli. They were not recorded during scalp-EEG monitoring. Ictal ECoG of all types of seizures triggered by acoustic, visual and tactile stimuli showed a sharp or a slow wave in bilateral SSMAs followed by high‐amplitude fast activity which originated from the left SSMA (Fig. 2). During sleep, the same stimuli, which could trigger seizures easily when the patient was awake, did not induce seizures. If we warned him shortly before the presentation of the arousal-eliciting stimuli, seizures were usually not provoked or the seizures were minimal.
Fig. 2. Ictal ECoG of startle seizures (black arrows indicate start of stimuli). LL (RL) indicates left (right) interhemispheric strips; LF (RF) represents the ECoG recorded from left (right) frontal lobes; LP (RP) represents the ECoG recorded from left (right) parietal lobes; LT (RT) represents the ECoG that was recorded from left (right) temporal lobes. A. represents the ictal ECoG recording provoked by noise (red arrow indicates the beginning of change of ECoG); B. represents the ictal ECoG provoked by 90‐Hz flash recorded from bilateral posterior interhemispheric strips.
702
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
Fig. 3. Postoperative sagittal (A) and coronal (B) MRI scans (General Electric Medical Systems, Signa 3 T) showing the extent of resection.
Some stimuli induced ECoG changes from the SSMAs bilaterally without clinical symptoms. Cortical electrical stimulation around the left SSMA before resection did not elicit startle seizures, but movement of right limbs when stimulated by 4 to 8 mA (milliampere) electric current was observed. It was decided to resect the left SSMA cortex under awake anesthesia and intraoperative cortical electrical stimulation to establish the functional border (Fig. 3). Postoperative pathological report of the removed tissue revealed focal cortical dysplasia (FCD Type Ia). Muscle strength of the right limbs was reduced to 4/5 postoperatively and recovered completely in two weeks. The patient has been seizure‐free, including startle‐induced seizures and spontaneous seizures, for 12 months postoperatively (Engel Class I). 3. Discussion Startle epilepsy is a rare form of reflex epilepsy characterized by seizures triggered by unexpected stimuli. The majority of cases described in the literature were associated with brain structural lesions found on MRI. Only 3 of more than 100 reported startle epilepsy cases have had resective surgery; furthermore, those three patients had lesions on brain MRI scan, and the resected areas were extensive [4,7–10]. To our knowledge, the case presented here is perhaps the first case of startle epilepsy with negative MRI scan (but histologically proven FCD) documented with subdural electrodes who has been seizure‐free after an operation. Focal cortical dysplasia variants may escape visual MRI inspection [11]. Most patients with startle epilepsy are sensitive to one or two sensory modalities [7,8]. This patient is the first reported case in which seizures were induced by acoustic, visual and somatosensory stimuli during monitoring. Ictal ECoG of all seizures triggered by the three kinds of stimuli showed that the onset area originated from left SSMA. The patient has been seizure‐free after resection of left SSMA after we demonstrated that the left SSMA was the epileptogenic zone. Manifestations of startle epilepsy, including in this patient, are similar to the physiologic startle response but with lower threshold for trigger and asymmetry [12]. Startle reflex originates from the caudal brainstem [12]. The nucleus reticularis pontis caudalis (RPC) seems particularly important [12]. The RPC is subject to a highly differentiated control: other brainstem nuclei (cochlear root nucleus, locus coeruleus, etc.), the limbic system, and even cortical areas modulate the RPC through release of various neurotransmitters [13,14]. It is thought that the emotional state just before a startling stimulus and the level of arousal affect the size of the auditory startle reflex [12]. If we warned the patient that a subsequent arousing stimulus would be presented, a seizure would usually not be triggered. During sleep, seizures could not be elicited by stimuli that provoked seizures during daytime. The
feeling of fear and palpitations during the occurrence of seizures in this patient were in accordance with a normal reflex in a healthy person. The ECoG change over bilateral SSMAs could be seen after startling stimuli even without seizures. Therefore, it is thought that the SSMAs are the primary cortical region that is able to modulate the startle reflex. The pathophysiologic mechanism of startle epilepsy remains unclear. It is thought that startle epilepsy may be generated when the epileptogenic zone overlaps the cortex modulating the startle reflex. For this patient, the startle stimuli may be amplified in the SSMAs to provoke a startle-induced seizure or disappeared in the SSMAs without abnormal reaction. We believed that other cortices which were not covered by the electrodes, such as the cingulate gyrus and precuneus, were involved in startle seizures [6,10,15]. Based on a study using ictal EEG-fMRI and SPECT coregistered to MRI (SPECT/SISCOM), it was proposed that startle seizures resulted from the interaction of all those regions—mainly from parietofrontal networks—that include the motor/premotor cortex, precuneus and SSMA [6]. Therefore, it was thought that in the pathway of startle response, the information was communicated through those areas to the SSMAs. We speculate that the SSMA is the hub for the startle epilepsy network and the major cortical region in which the startle reflex is modulated. Localized magnetic spike sources in the SSMA in patients with MRI-negative startle epilepsy were found in MEG recordings interictally [5,10]; however, in contrast, our MEG recordings did not show any epileptiform activity in the SSMA. Perhaps, this can be explained by studying the interictal ECoG of this patient. The interictal epileptiform activity can be seen in only two electrodes (center-to-center electrode distance was 1 cm) over the SSMA. Therefore, the area of interictal epileptiform discharges was about 2 cm2. Generally, epileptiform discharges in the convex cortical surface of the brain need to extend to 3 cm2 for MEG to detect a projected extracranial magnetic field [16]. Furthermore, the SSMA is deeply inside the interhemispheric fissure, and MEG is considered to be less sensitive to deep sources [17,18]. We showed in this successfully-treated case that surgical treatment for startle epilepsy is possible and reasonable since startle epilepsy is typically intractable and seizures may be frequent [2,7,8].
Statement We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. We state that human studies have been approved by Xuanwu Hospital Ethics Committee and have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. This work is original.
Y.-P. Sun et al. / Epilepsy & Behavior 25 (2012) 700–703
Acknowledgments We gratefully acknowledge a grant (no. 30770744) from the National Nature Science Foundation of China that supported this work. We thank Professor G. van Luijtelaar (Radboud University Nijmegen, Netherlands) for revising the manuscript. References [1] Sáenz-Lope E, Herranz FJ, Masdeu JC. Startle epilepsy: a clinical study. Ann Neurol 1984;16:78-81. [2] Yang Z, Liu X, Qin J, et al. Clinical and electrophysiological characteristics of startle epilepsy in childhood. Clin Neurophysiol 2010;121:658-64. [3] Xue LY, Ritaccio AL. Reflex seizures and reflex epilepsy. Am J Electroneurodiagnostic Technol 2006;46:39-48. [4] Serles W, Leutmezer F, Pataraia E, et al. A case of startle epilepsy and SSMA seizures documented with subdural recordings. Epilepsia 1999;40:1031-5. [5] Saeki K, Saito Y, Sugai K, et al. Startle epilepsy associated with gait-induced seizures: pathomechanism analysis using EEG, MEG, and PET studies. Epilepsia 2009;50: 1274-9. [6] Fernández S, Donaire A, Maestro I, et al. Functional neuroimaging in startle epilepsy: involvement of a mesial frontoparietal network. Epilepsia 2011;52:1725-32. [7] Manford MRA, Fish DR, Shorvon SD. Startle provoked epileptic seizures: features in 19 patients. J Neurol Neurosurg Psychiatry 1996;61:151-6.
703
[8] Tibussek D, Wohlrab G, Boltshauser E, Schmitt B. Proven startle-provoked epileptic seizures in childhood: semiologic and electrophysiologic variability. Epilepsia 2006;47:1050-8. [9] Oguni H, Hayashi K, Usui N, Osawa M, Shimizu H. Startle epilepsy with infantile hemiplegia: report of two cases improved by surgery. Epilepsia 1998;39: 93-8. [10] García-Morales I, Maestú F, Pérez-Jiménez MA, et al. A clinical and magnetoencephalography study of MRI-negative startle-epilepsy. Epilepsy Behav 2009;16: 166-71. [11] Mühlebner A, Coras R, Kobow K, et al. Neuropathologic measurements in focal cortical dysplasias: validation of the ILAE 2011 classification system and diagnostic implications for MRI. Acta Neuropathol 2012;123:259-72. [12] Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol 2006;5:513-24. [13] Koch M. The neurobiology of startle. Prog Neurobiol 1999;59:107-28. [14] Von Coelln R, Thomas B, Savitt JM, et al. Loss of locus coeruleus neurons and reduced startle in parkin null mice. Proc Natl Acad Sci U S A 2004;101:10744-9. [15] Pissiota A, Frans O, Michelgård A, et al. Amygdala and anterior cingulated cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci 2003;18:1325-31. [16] Oishi M, Otsubo H, Kameyama S, et al. Epileptic spikes: magnetoencephalography versus simultaneous electrocorticography. Epilepsia 2002;43:1390-5. [17] Baumgartner C, Pataraia E, Lindinger G, Deecke L. Neuromagnetic recordings in temporal lobe epilepsy. J Clin Neurophysiol 2000;17:177-89. [18] Knowlton RC, Laxer KD, Aminoff MJ, Roberts TP, Wong ST, Rowley HA. Magnetoencephalography in partial epilepsy: clinical yield and localization accuracy. Ann Neurol 1997;42:622-31.