Author's Accepted Manuscript
Bizarre semiology and medically intractable seizures Kamilia Nozile-Firth MD*, Elaine Wirrell MD†, Caterina Giannini MD‡
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00043-6 http://dx.doi.org/10.1016/j.spen.2014.04.024 YSPEN490
To appear in: Semin Pediatr Neurol
Cite this article as: Kamilia Nozile-Firth MD*, Elaine Wirrell MD†, Caterina Giannini MD‡, Bizarre semiology and medically intractable seizures, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Bizarre semiology and medically intractable seizures. Author: Kamilia Nozile-Firth, MD,* Elaine Wirrell, MD,† and Caterina Giannini, MD‡
Corresponding Author: Kamilia Nozile-Firth MD Neurology Department Mayo Clinic 200 First St SW Rochester MN 55905 Ph (507) 284-3358 Fax: (507) 266-4752 Email: [email protected]
From *Department of Neurology, Mayo Clinic, Rochester, MN. † Professor of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN. ‡ Professor of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Case Report: A fifteen year-old right-hand dominant young man with medically intractable epilepsy presented to our center to be assessed for surgical candidacy. His seizures began at age five years. Semiology consisted of manual motions where he would grab his groin and rock back and forth. These events were witnessed during the day and lasted for 20 to 30 seconds. Seizure frequency was regular but not more often than twice per day. During the episodes, he seemed aware and there was no post-ictal confusion. Multiple medication trials were tried and he ultimately achieved successful control with carbamazepine monotherapy and remained seizure free for the next 3 years. At eight years of age, there was seizure reoccurrence, but with altered semiology. He experienced a premonitory aura, after which he would locate a safe place to go lie down prior to the start of the seizures. There was hypermotor semiology, which consisted of limb flailing, squealing, and ended with laughter. Compared to prior seizures, the frequency was increased in that he would have seizures 2-3 times per day for a duration of 15 to 20 seconds. Again, there was a quick return to normal baseline cognition immediately after the event with little to no post-ictal phase. The seizures occurred predominantly during the day but did occur during sleep as well. Further therapeutic trials with multiple antiepileptic medications, including carbamazepine, clonazepam, lamotrigine, and gabapentin, failed to adequately control seizures. An EEG was done during one of these episodes which did not show any electroencephalographic discharge. At that point, there was doubt as to whether these were truly seizures and he was referred to psychiatry and treated for a conversion disorder. After six months of unsuccessful psychiatric intervention, he was referred to another neurologist, who diagnosed frontal lobe epilepsy (FLE). The young man had been monitored twice in an Epilepsy Monitoring Unit (EMU) before presenting to our center. EEG results were suggestive of frontal lobe seizures but failed to
show lateralization. A 3-Tesla MRI was done which was reported to be normal. Frequent seizures persisted without any sustained interval of seizure freedom. Anti-epileptic regimen at presentation included lacosamide 250 mg twice daily, oxcarbazepine 1200 mg twice daily, and ezogabine 200 mg three times daily. Ezogabine decreased his frequency of daytime seizures from daily to once every 2 weeks but he continued to have nightly seizures. While he denied any specific aura, his mother reported that he would still be able to get himself to a safe place and in a lying position most of the time. If he were not already lying down, he would fall over, writhe about, flail all of his limbs, squeal and occasionally laugh at the end. There were no lateralizing features such as head or gaze version, nor were there any neurologic signs thereafter. He was able to speak clearly immediately after. These seizures lasted for 15 to 20 seconds, and were still without post-ictal symptoms. He had no loss of bowel or bladder function and did not bite his tongue during these events. There had been a single generalized tonic-clonic seizure, which occurred in the setting of a medication wean, and lasted 4 to 5 minutes. He had never been in status epilepticus. The pregnancy had been unremarkable and he was born at full term by spontaneous vaginal delivery, weighing 9 lbs and 3 ounces. He reached all developmental milestones at the expected age. He had no history of febrile seizure, head trauma, CNS infection, autoimmune/inflammatory, neoplastic or acquired cerebrovascular insult. Socially, he has many friends and enjoys sports. He does, however, have some trouble with math and academic issues secondary to difficulty with focusing and attention. Family history was positive for maternal aunt with febrile seizures as a child. Otherwise there is no history of seizures or neurologic conditions in the family. On examination, the patient was normocephalic with a head circumference of 58.0 cm. No neurocutaneous stigmata were noted. Cardiopulmonary exam was benign. He was alert, oriented, and answered questions appropriately. There was no evidence of speech or
language disturbance. Cranial nerves 2 through 12 were intact. Motor exam was equal and symmetric in upper and lower extremities both proximally and distally. Deep tendon reflexes were normal and symmetric in the biceps, triceps, brachioradialis, patella, and achilles tendons. Plantar responses were flexor. Sensory exam was normal for all modalities. Coordination was normal in both upper and lower extremities. Gait was normal with good stride and arm swing. He was able to walk on his toes, heels, and could tandem walk without difficulty. Romberg was negative. High-resolution cortical surface imaging using a 3 Tesla MRI showed no evidence for focal lesion in either frontal lobe. It suggested relative smallness of the anterior body of right hippocampus without abnormal signal in the hippocampi. The remainder the examination is negative. Follow-up hippocampal volume measurements revealed symmetrically small hippocampal formations, likely reflecting small intracranial volumes. He was admitted to our Epilepsy Monitoring Unit for presurgical workup. Inter-ictal EEG showed left frontal slowing and multifocal epileptiform discharges, maximal over the left frontotemporal region. Eight seizures were recorded. Seven of these were associated with subtle diffuse attenuation of the EEG at onset. Ictal EEG was most prominent over the left frontal region (F3) in only one of the eight seizures. Semiology of all events was consistent, characterized by precipitous onset of hypermotor activity and one event with movement of the right arm and hand toward the groin. Subtraction Ictal SPECT Co-Registered to MRI (SISCOM) analysis demonstrated a notable focus of ictal activity registering to the left frontal lobe anteriorly. PET studies indicated a small area of decreased metabolism in the left anterior frontal lobe. It corresponded in location to the abnormality seen on SISCOM, pointing to an epileptic focus in the left frontal lobe. Following discussions at Epilepsy Surgical conference, the young man was admitted
for subdural electrode placement and monitoring. He underwent left frontal craniotomy and right frontal burr hole, with extensive grid and strip coverage over the left frontal region (centered over F3) as well as insertion of interhemispheric as well as right frontal strips. He had nearly continuous epileptiform discharge recorded over a localized region of the left frontal grid. Ten seizures were recorded, all arising from this same region. He then underwent stimulation of his electrodes to determine regions of eloquent cortex responsible for motor and language function to guide limits of the planned surgical resection (as the left frontal grid covered a portion of the left frontal operculum involved in language). The epileptic focus was located on the left anterior frontal lobe, anterior to the motor stimulated areas. Repeat craniotomy with removal of subdural electrodes as well as left frontal cortical resection with stereotactic guidance was performed without complication. The pathology of the resected region showed a Taylor 2a dysplasia. He has remained seizure-free over the six months from surgery and initiated weaning of ezogabine. He continues to have some difficulties with attention at school. Discussion While temporal lobe epilepsy is the most common focus in adults with intractable focal seizures, frontal lobe epilepsy is most frequent in children. Causes include post-traumatic, inflammatory, infectious, autoimmune, genetic as well as lesional etiologies (neoplasia, vascular malformations or cortical dysplasia). Frontal lobe seizures tend to occur in clusters multiple times per day, generally lasting less than 30 seconds (1). They usually have little to no post-ictal state. There is a tendency for the seizures to occur during sleep. It can be difficult to differentiate nocturnal seizures from parasomnias from history alone, which may warrant overnight monitoring. While seizure auras are common in frontal lobe epilepsy, the sensation is often ill-described and typically does not include epigastric phenomenon as seen in temporal lobe epilepsy. (2)
Frontal lobe seizures are typically hypermotor and may include vocal or gestural automatisms. The literature divides frontal lobe seizures into major subtypes, although there is much overlap between the groups. The subtypes include perirolandic, supplementary sensorimotor area, dorsolateral, orbitofrontal, anterior frontopolar, opercular, cingulate, as well as secondarily generalized types (the latter of which may occur with any of the above named subtypes). (2) In 2000, Kotagal et al studied the lateralizing value of asymmetric tonic limb posturing, or what is also known as the “figure of 4 sign” in 31 patients with focal epilepsy. In patients with supplementary motor seizure subtypes, the figure of 4 sign may have more of a lateralizing where the extended arm is contralateral to the ictal focus. (2, 3) The hypermotor behavior in frontal lobe epilepsy can be quite outlandish and episodes may be mistaken for psychogenic non- epileptic events. Vocalizations, including laughing crying and screaming can be associated but have no localizing value. Reflecting the diverse functions of the frontal cortex, frontal lobe epilepsy can manifest with many different semiologies. Seizure manifestations generally reflect the area of cortex involved, but this may not necessarily the site of origin of the seizure. Originally, these bilateral complex motor seizures were believed to originate from the orbitofrontal, anterior cingulate, or mesial frontal areas (50), but can essentially arise from any region in the frontal lobe.(2) Indeed, the seizure focus ultimately determined in this case presentation did not coincide with the aforementioned (previously-associated) regions. As seen in this case, it is not unusual that imaging and EEG findings are often nonlocalizing and can in fact be misleading with normal or nonspecific findings. (4-7) Large areas of the frontal lobe such as the deep sulci, cingulate cortex, mesial and orbitofrontal areas are inaccessible to scalp electrodes of surface EEG. Abnormalities can also be easily obscured by
motion artifact. Rapid spread of a seizure can lead to false localization of the seizure focus, mimicking primary generalized spike-wave complexes when the discharges become bilaterally synchronous. Up to thirty percent of patients may not have a diagnostic ictal EEG during a frontal lobe seizure.(4) Medically refractory patients may be candidates for resection of their seizure focus. Post-Operative success in patients following frontal resection is generally thought to be lower than with anterior temporal lobectomy. Variability in rates of seizure freedom following surgery in frontal lobe epilepsy exists and seizure outcomes have been shown to vary largely within the first Post-Operative year. (5, 6) More successful outcomes with regards to seizure freedom can be noted in patients with lesional imaging. In their meta-analysis, Englot et al found that overall seizure freedom following frontal lobe resection was found to be 45.1%. (7) In the case of the young man presented, the discovery of cortical dysplasia was not identifiable through the use of structural imaging alone but through functional imaging modalities including radionuclide studies, further aided and verified by FDG PET and electroencephalographic investigations. Cortical dysplasia type I is usually found in the temporal lobe and can include an MRI finding of hippocampal atrophy.(8) Most type 2 cortical dysplasias are evident on MRI with such abnormalities as cortical thickening and blurring of the grey-white junction in both T1 and T2 sequences. (9) In this case, it was more so the functional imaging studies and PET scan that further guided the implantation of subdural EEG grids, ultimately localizing the epileptogenic focus which was surgically resected.
Figure 1. SISCOM analysis demonstrating a focus of ictal activity registering to the left frontal lobe anteriorly.
Figure 2. F-18 FDG PET/CT showing small area of decreased metabolism in the left anterior frontal lobe, corresponding in location to the abnormality seen on previous ictal brain perfusion scan and represents the epileptic focus. Figure 3. The cortex demonstrates loss of the normal cortical lamination and presence of numerous large abnormally shaped dysmorphic neurons, as typical of cortical dysplasia
Taylor type 2a. There was no evidence of balloon cells. [Hematoxylin-Eosin stain (a x40; b x200) and NeuN immunostain (c x200)]
Figure 4. Shown is subdural grid locations over the left frontal convexity. There was also an interhemispheric strip, a posterior grid that extended towards the parietal region, and then another four-strip electrode in the subfrontal region on the left (not shown).
Figure 5. Monitoring revealed nearly continuous spike and wave discharges over the left anterior frontal region. Specifically, these discharges were focused at electrodes LAFG 20, 21, 28, 29, 30. Multiple seizures were recorded with stereotypic semiology & hyper motor activity.
All originated from grid locations number LAFG 20, 21, 28, 29,30 with late spread to LAFG 11, 12, 13 (Figure 6).
References 1.
Rudzinski LA, Shih JJ. The classification of seizures and epilepsy syndromes. Continuum
(Minneap Minn). 2010 Jun;16(3 Epilepsy):15-35. 2.
Bagla R, Skidmore CT. Frontal lobe seizures. Neurologist. [Review]. 2011 May;17(3):125-35.
3.
Kotagal P, Bleasel A, Geller E, Kankirawatana P, Moorjani BI, Rybicki L. Lateralizing value of
asymmetric tonic limb posturing observed in secondarily generalized tonic-clonic seizures. Epilepsia. 2000 Apr;41(4):457-62. 4.
Laskowitz DT, Sperling MR, French JA, O'Connor MJ. The syndrome of frontal lobe epilepsy:
characteristics and surgical management. Neurology. [Research Support, U.S. Gov't, P.H.S.]. 1995 Apr;45(4):780-7. 5.
Kim CH, Chung CK, Lee SK. Longitudinal change in outcome of frontal lobe epilepsy surgery.
Neurosurgery. [Research Support, Non-U.S. Gov't]. 2010 Nov;67(5):1222-9; discussion 9. 6.
Tellez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a
systematic review and meta-analysis. Brain. [Meta-Analysis Research Support, Non-U.S. Gov't Review]. 2005 May;128(Pt 5):1188-98. 7.
Englot DJ, Wang DD, Rolston JD, Shih TT, Chang EF. Rates and predictors of long-term
seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis. J Neurosurg. [Meta-Analysis Review]. 2012 May;116(5):1042-8. 8.
Seo JH, Holland K, Rose D, Rozhkov L, Fujiwara H, Byars A, et al. Multimodality imaging in
the surgical treatment of children with nonlesional epilepsy. Neurology. [Research Support, N.I.H., Extramural]. 2011 Jan 4;76(1):41-8. 9.
Kabat J, Krol P. Focal cortical dysplasia - review. Pol J Radiol. 2012 Apr;77(2):35-43.
Bizarre semiology and medically intractable seizures Kamilia Nozile-Firth MD*, Elaine Wirrell MD†, Caterina Giannini MD‡
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S1071-9091(14)00043-6 http://dx.doi.org/10.1016/j.spen.2014.04.024 YSPEN490
To appear in: Semin Pediatr Neurol
Cite this article as: Kamilia Nozile-Firth MD*, Elaine Wirrell MD†, Caterina Giannini MD‡, Bizarre semiology and medically intractable seizures, Semin Pediatr Neurol , http://dx.doi.org/10.1016/j.spen.2014.04.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Bizarre semiology and medically intractable seizures. Author: Kamilia Nozile-Firth, MD,* Elaine Wirrell, MD,† and Caterina Giannini, MD‡
Corresponding Author: Kamilia Nozile-Firth MD Neurology Department Mayo Clinic 200 First St SW Rochester MN 55905 Ph (507) 284-3358 Fax: (507) 266-4752 Email: [email protected]
From *Department of Neurology, Mayo Clinic, Rochester, MN. † Professor of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN. ‡ Professor of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Case Report: A fifteen year-old right-hand dominant young man with medically intractable epilepsy presented to our center to be assessed for surgical candidacy. His seizures began at age five years. Semiology consisted of manual motions where he would grab his groin and rock back and forth. These events were witnessed during the day and lasted for 20 to 30 seconds. Seizure frequency was regular but not more often than twice per day. During the episodes, he seemed aware and there was no post-ictal confusion. Multiple medication trials were tried and he ultimately achieved successful control with carbamazepine monotherapy and remained seizure free for the next 3 years. At eight years of age, there was seizure reoccurrence, but with altered semiology. He experienced a premonitory aura, after which he would locate a safe place to go lie down prior to the start of the seizures. There was hypermotor semiology, which consisted of limb flailing, squealing, and ended with laughter. Compared to prior seizures, the frequency was increased in that he would have seizures 2-3 times per day for a duration of 15 to 20 seconds. Again, there was a quick return to normal baseline cognition immediately after the event with little to no post-ictal phase. The seizures occurred predominantly during the day but did occur during sleep as well. Further therapeutic trials with multiple antiepileptic medications, including carbamazepine, clonazepam, lamotrigine, and gabapentin, failed to adequately control seizures. An EEG was done during one of these episodes which did not show any electroencephalographic discharge. At that point, there was doubt as to whether these were truly seizures and he was referred to psychiatry and treated for a conversion disorder. After six months of unsuccessful psychiatric intervention, he was referred to another neurologist, who diagnosed frontal lobe epilepsy (FLE). The young man had been monitored twice in an Epilepsy Monitoring Unit (EMU) before presenting to our center. EEG results were suggestive of frontal lobe seizures but failed to
show lateralization. A 3-Tesla MRI was done which was reported to be normal. Frequent seizures persisted without any sustained interval of seizure freedom. Anti-epileptic regimen at presentation included lacosamide 250 mg twice daily, oxcarbazepine 1200 mg twice daily, and ezogabine 200 mg three times daily. Ezogabine decreased his frequency of daytime seizures from daily to once every 2 weeks but he continued to have nightly seizures. While he denied any specific aura, his mother reported that he would still be able to get himself to a safe place and in a lying position most of the time. If he were not already lying down, he would fall over, writhe about, flail all of his limbs, squeal and occasionally laugh at the end. There were no lateralizing features such as head or gaze version, nor were there any neurologic signs thereafter. He was able to speak clearly immediately after. These seizures lasted for 15 to 20 seconds, and were still without post-ictal symptoms. He had no loss of bowel or bladder function and did not bite his tongue during these events. There had been a single generalized tonic-clonic seizure, which occurred in the setting of a medication wean, and lasted 4 to 5 minutes. He had never been in status epilepticus. The pregnancy had been unremarkable and he was born at full term by spontaneous vaginal delivery, weighing 9 lbs and 3 ounces. He reached all developmental milestones at the expected age. He had no history of febrile seizure, head trauma, CNS infection, autoimmune/inflammatory, neoplastic or acquired cerebrovascular insult. Socially, he has many friends and enjoys sports. He does, however, have some trouble with math and academic issues secondary to difficulty with focusing and attention. Family history was positive for maternal aunt with febrile seizures as a child. Otherwise there is no history of seizures or neurologic conditions in the family. On examination, the patient was normocephalic with a head circumference of 58.0 cm. No neurocutaneous stigmata were noted. Cardiopulmonary exam was benign. He was alert, oriented, and answered questions appropriately. There was no evidence of speech or
language disturbance. Cranial nerves 2 through 12 were intact. Motor exam was equal and symmetric in upper and lower extremities both proximally and distally. Deep tendon reflexes were normal and symmetric in the biceps, triceps, brachioradialis, patella, and achilles tendons. Plantar responses were flexor. Sensory exam was normal for all modalities. Coordination was normal in both upper and lower extremities. Gait was normal with good stride and arm swing. He was able to walk on his toes, heels, and could tandem walk without difficulty. Romberg was negative. High-resolution cortical surface imaging using a 3 Tesla MRI showed no evidence for focal lesion in either frontal lobe. It suggested relative smallness of the anterior body of right hippocampus without abnormal signal in the hippocampi. The remainder the examination is negative. Follow-up hippocampal volume measurements revealed symmetrically small hippocampal formations, likely reflecting small intracranial volumes. He was admitted to our Epilepsy Monitoring Unit for presurgical workup. Inter-ictal EEG showed left frontal slowing and multifocal epileptiform discharges, maximal over the left frontotemporal region. Eight seizures were recorded. Seven of these were associated with subtle diffuse attenuation of the EEG at onset. Ictal EEG was most prominent over the left frontal region (F3) in only one of the eight seizures. Semiology of all events was consistent, characterized by precipitous onset of hypermotor activity and one event with movement of the right arm and hand toward the groin. Subtraction Ictal SPECT Co-Registered to MRI (SISCOM) analysis demonstrated a notable focus of ictal activity registering to the left frontal lobe anteriorly. PET studies indicated a small area of decreased metabolism in the left anterior frontal lobe. It corresponded in location to the abnormality seen on SISCOM, pointing to an epileptic focus in the left frontal lobe. Following discussions at Epilepsy Surgical conference, the young man was admitted
for subdural electrode placement and monitoring. He underwent left frontal craniotomy and right frontal burr hole, with extensive grid and strip coverage over the left frontal region (centered over F3) as well as insertion of interhemispheric as well as right frontal strips. He had nearly continuous epileptiform discharge recorded over a localized region of the left frontal grid. Ten seizures were recorded, all arising from this same region. He then underwent stimulation of his electrodes to determine regions of eloquent cortex responsible for motor and language function to guide limits of the planned surgical resection (as the left frontal grid covered a portion of the left frontal operculum involved in language). The epileptic focus was located on the left anterior frontal lobe, anterior to the motor stimulated areas. Repeat craniotomy with removal of subdural electrodes as well as left frontal cortical resection with stereotactic guidance was performed without complication. The pathology of the resected region showed a Taylor 2a dysplasia. He has remained seizure-free over the six months from surgery and initiated weaning of ezogabine. He continues to have some difficulties with attention at school. Discussion While temporal lobe epilepsy is the most common focus in adults with intractable focal seizures, frontal lobe epilepsy is most frequent in children. Causes include post-traumatic, inflammatory, infectious, autoimmune, genetic as well as lesional etiologies (neoplasia, vascular malformations or cortical dysplasia). Frontal lobe seizures tend to occur in clusters multiple times per day, generally lasting less than 30 seconds (1). They usually have little to no post-ictal state. There is a tendency for the seizures to occur during sleep. It can be difficult to differentiate nocturnal seizures from parasomnias from history alone, which may warrant overnight monitoring. While seizure auras are common in frontal lobe epilepsy, the sensation is often ill-described and typically does not include epigastric phenomenon as seen in temporal lobe epilepsy. (2)
Frontal lobe seizures are typically hypermotor and may include vocal or gestural automatisms. The literature divides frontal lobe seizures into major subtypes, although there is much overlap between the groups. The subtypes include perirolandic, supplementary sensorimotor area, dorsolateral, orbitofrontal, anterior frontopolar, opercular, cingulate, as well as secondarily generalized types (the latter of which may occur with any of the above named subtypes). (2) In 2000, Kotagal et al studied the lateralizing value of asymmetric tonic limb posturing, or what is also known as the “figure of 4 sign” in 31 patients with focal epilepsy. In patients with supplementary motor seizure subtypes, the figure of 4 sign may have more of a lateralizing where the extended arm is contralateral to the ictal focus. (2, 3) The hypermotor behavior in frontal lobe epilepsy can be quite outlandish and episodes may be mistaken for psychogenic non- epileptic events. Vocalizations, including laughing crying and screaming can be associated but have no localizing value. Reflecting the diverse functions of the frontal cortex, frontal lobe epilepsy can manifest with many different semiologies. Seizure manifestations generally reflect the area of cortex involved, but this may not necessarily the site of origin of the seizure. Originally, these bilateral complex motor seizures were believed to originate from the orbitofrontal, anterior cingulate, or mesial frontal areas (50), but can essentially arise from any region in the frontal lobe.(2) Indeed, the seizure focus ultimately determined in this case presentation did not coincide with the aforementioned (previously-associated) regions. As seen in this case, it is not unusual that imaging and EEG findings are often nonlocalizing and can in fact be misleading with normal or nonspecific findings. (4-7) Large areas of the frontal lobe such as the deep sulci, cingulate cortex, mesial and orbitofrontal areas are inaccessible to scalp electrodes of surface EEG. Abnormalities can also be easily obscured by
motion artifact. Rapid spread of a seizure can lead to false localization of the seizure focus, mimicking primary generalized spike-wave complexes when the discharges become bilaterally synchronous. Up to thirty percent of patients may not have a diagnostic ictal EEG during a frontal lobe seizure.(4) Medically refractory patients may be candidates for resection of their seizure focus. Post-Operative success in patients following frontal resection is generally thought to be lower than with anterior temporal lobectomy. Variability in rates of seizure freedom following surgery in frontal lobe epilepsy exists and seizure outcomes have been shown to vary largely within the first Post-Operative year. (5, 6) More successful outcomes with regards to seizure freedom can be noted in patients with lesional imaging. In their meta-analysis, Englot et al found that overall seizure freedom following frontal lobe resection was found to be 45.1%. (7) In the case of the young man presented, the discovery of cortical dysplasia was not identifiable through the use of structural imaging alone but through functional imaging modalities including radionuclide studies, further aided and verified by FDG PET and electroencephalographic investigations. Cortical dysplasia type I is usually found in the temporal lobe and can include an MRI finding of hippocampal atrophy.(8) Most type 2 cortical dysplasias are evident on MRI with such abnormalities as cortical thickening and blurring of the grey-white junction in both T1 and T2 sequences. (9) In this case, it was more so the functional imaging studies and PET scan that further guided the implantation of subdural EEG grids, ultimately localizing the epileptogenic focus which was surgically resected.
Figure 1. SISCOM analysis demonstrating a focus of ictal activity registering to the left frontal lobe anteriorly.
Figure 2. F-18 FDG PET/CT showing small area of decreased metabolism in the left anterior frontal lobe, corresponding in location to the abnormality seen on previous ictal brain perfusion scan and represents the epileptic focus. Figure 3. The cortex demonstrates loss of the normal cortical lamination and presence of numerous large abnormally shaped dysmorphic neurons, as typical of cortical dysplasia
Taylor type 2a. There was no evidence of balloon cells. [Hematoxylin-Eosin stain (a x40; b x200) and NeuN immunostain (c x200)]
Figure 4. Shown is subdural grid locations over the left frontal convexity. There was also an interhemispheric strip, a posterior grid that extended towards the parietal region, and then another four-strip electrode in the subfrontal region on the left (not shown).
Figure 5. Monitoring revealed nearly continuous spike and wave discharges over the left anterior frontal region. Specifically, these discharges were focused at electrodes LAFG 20, 21, 28, 29, 30. Multiple seizures were recorded with stereotypic semiology & hyper motor activity.
All originated from grid locations number LAFG 20, 21, 28, 29,30 with late spread to LAFG 11, 12, 13 (Figure 6).
References 1.
Rudzinski LA, Shih JJ. The classification of seizures and epilepsy syndromes. Continuum
(Minneap Minn). 2010 Jun;16(3 Epilepsy):15-35. 2.
Bagla R, Skidmore CT. Frontal lobe seizures. Neurologist. [Review]. 2011 May;17(3):125-35.
3.
Kotagal P, Bleasel A, Geller E, Kankirawatana P, Moorjani BI, Rybicki L. Lateralizing value of
asymmetric tonic limb posturing observed in secondarily generalized tonic-clonic seizures. Epilepsia. 2000 Apr;41(4):457-62. 4.
Laskowitz DT, Sperling MR, French JA, O'Connor MJ. The syndrome of frontal lobe epilepsy:
characteristics and surgical management. Neurology. [Research Support, U.S. Gov't, P.H.S.]. 1995 Apr;45(4):780-7. 5.
Kim CH, Chung CK, Lee SK. Longitudinal change in outcome of frontal lobe epilepsy surgery.
Neurosurgery. [Research Support, Non-U.S. Gov't]. 2010 Nov;67(5):1222-9; discussion 9. 6.
Tellez-Zenteno JF, Dhar R, Wiebe S. Long-term seizure outcomes following epilepsy surgery: a
systematic review and meta-analysis. Brain. [Meta-Analysis Research Support, Non-U.S. Gov't Review]. 2005 May;128(Pt 5):1188-98. 7.
Englot DJ, Wang DD, Rolston JD, Shih TT, Chang EF. Rates and predictors of long-term
seizure freedom after frontal lobe epilepsy surgery: a systematic review and meta-analysis. J Neurosurg. [Meta-Analysis Review]. 2012 May;116(5):1042-8. 8.
Seo JH, Holland K, Rose D, Rozhkov L, Fujiwara H, Byars A, et al. Multimodality imaging in
the surgical treatment of children with nonlesional epilepsy. Neurology. [Research Support, N.I.H., Extramural]. 2011 Jan 4;76(1):41-8. 9.
Kabat J, Krol P. Focal cortical dysplasia - review. Pol J Radiol. 2012 Apr;77(2):35-43.
