Quantitative evaluation of hippocampal gray-white matter boundary blurring in medial temporal lobe epilepsy with hippocampal sclerosis.

INTRODUCTION: The magnetic resonance imaging (MRI) findings of hippocampal sclerosis (HS) include decreased volume, increased signal intensity, and hippocampal gray-white matter boundary blurring (HGWBB). Given that the layered structure is obscure in HS, there have been no reports on the quantitative evaluation of HGWBB and its relationship with the clinical outcome. Thus, this study aims to correlate the extent of HGWBB to its clinical manifestation of HS. METHODS: Fifty-four patients with temporal lobe epilepsy who underwent hippocampal resection were enrolled. To evaluate HGWBB quantitatively, we defined an index by calculating the standard deviation of the intrahippocampal signal on short tau inversion recovery. In addition, we created a prognostic scoring system using four criteria, including hippocampal signal intensity, size of hippocampal cross-sectional area, presence of temporal lobe lesions, and the HGWBB index. RESULTS: The HGWBB index was significantly lower on the affected side than on the unaffected side (p < 0.001). This trend was more prominent in the poor prognosis group than that in the good prognosis group. The prognostic scoring system revealed that when three or more criteria were positive, the prognostic accuracy reached 87.5% sensitivity and 71.7% specificity. CONCLUSION: The HGWBB index is useful for the diagnosis of temporal lobe epilepsy with HS and for predicting seizure outcomes when used with another index of hippocampal volume loss and increased signal intensity.

IVIG in childhood primary angiitis of the central nervous system: A case report.

Aggressive immunosuppressive therapies have been proposed to treat primary angiitis of the central nervous system (PACNS). Here, we report the first successfully stabilized case of childhood, small-vessel PACNS with intravenous immunoglobulin (IVIG) therapy. A 12-year-old boy was admitted to our hospital complaining of recurrent headaches and upper-left homonymous quadrantanopia, since the age of 11 years. Brain computed tomography scans revealed fine calcification in the right temporal and occipital lobes. Brain magnetic resonance imaging scans revealed white matter lesions, with gadolinium enhancement, which waxed, waned, and migrated for 1 year, without immunomodulatory therapies. A cerebrospinal fluid study showed pleocytosis (12 cells per µl). No clinical or serological findings suggested systemic inflammation or vasculitis. Brain angiography was unremarkable. Brain biopsy revealed thickened and hyalinized small vessels, with intramural infiltration of inflammatory cells, which confirmed the diagnosis of small-vessel PACNS. Because the patient developed surgical site infection following biopsy, the administration of monthly IVIG (2 g/kg) was prescribed, instead of immunosuppressive agents. After IVIG therapy, the patient remained stable, except for a single episode of mild radiological exacerbation at 16 months, which occurred when the IVIG interval was expanded. Oral prednisone was added and gradually tapered. At 50 months, his intellectual abilities and motor functions were normal, although he showed residual upper-left homonymous quadrantanopia and post-exercise headache. A temporary headache, associated with the immunoglobulin infusion, was resolved by slowing the infusion rate. PACNS should be treated aggressively to improve prognosis. However, when immunosuppressants are contraindicated, IVIG may be an alternative therapeutic option.

Surgical Technique and Outcome of Extensive Frontal Lobectomy for Treatment of Intracable Non-lesional Frontal Lobe Epilepsy.

Although extensive frontal lobectomy (eFL) is a common surgical procedure for intractable frontal lobe epilepsy (FLE), there have been very few reports regarding surgical techniques for eFL. This article provides step-by-step descriptions of our surgical technique for non-lesional FLE. Sixteen patients undergoing eFL were included in this study. The goals were to maximize gray matter removal, including the orbital gyrus and subcallosal area, and to spare the primary motor and premotor cortexes and anterior perforated substance. The eFL consists of three steps: (1) positioning, craniotomy, and exposure; (2) lateral frontal lobe resection; and (3), resection of the rectus gyrus and orbital gyrus. Resection ahead of bregma allows preservation of motor and premotor area function. To remove the orbital gyrus preserving anterior perforated substance, it is essential to visualize the olfactory trigone beneath the pia. It is important to observe the surface of the contralateral medial frontal lobe for complete removal of the subcallosal area of the frontal lobe. Thirteen patients (81.25%) became seizure-free and three patients (18.75%) continued to have seizures. None of the patients showed any complications. The eFL is a good surgical technique for the treatment of intractable non-lesional FLE. For treatment of epilepsy by eFL, it is important to resect the non-eloquent area of the frontal lobe as much as possible with preservation of the eloquent cortex.

Hippocampal Transection Plus Tumor Resection as a Novel Surgical Treatment for Temporal Lobe Epilepsy Associated with Cerebral Cavernous Malformations.

OBJECTIVE: The optimal surgical treatment for cavernous malformation-related temporal lobe epilepsy (CRTLE) is still controversial because it frequently involves the hippocampus as an epileptogenic zone. Here we describe our unique surgical strategy of performing hippocampal transection (HT) plus tumor resection for CRTLE to solve the question of how to balance postoperative seizure outcomes and neuropsychologic outcomes. METHODS: From 2005 to 2016, 7 cases of HT (3 on dominant side) plus tumor resection were performed for patients with CRTLE. We routinely perform intraoperative electrocorticography just before and after the resection of the tumor with hemosiderin rim. In cases with residual spikes from the hippocampus after the resection, we add HT, considering laterality of the lesion, preoperative memory functions, and magnetic resonance imaging abnormalities in hippocampi. Patient information, including seizure outcomes and preoperative and postoperative (24 months) Wechsler Memory Scale-Revised (WMS-R), were collected. RESULTS: In the mean follow-up of 62.7 months (range 20-119), the postoperative seizure outcome was as follows: Engel class I in 6 cases (85.7%) and II in 1 case (14.3%). Perioperative changes in WMS-R score were as follows: 93.5 preoperatively versus 99.5 postoperatively (P = 0.408) in verbal memory and 90.7 versus 98.0 (P = 0.351) in delayed recall. Overall, no patient presented with more than 25% decline in any of the WMS-R indices postoperatively. CONCLUSIONS: Despite the small sample size and noncontrolled study design, postoperative seizure outcomes were deemed acceptable with favorable memory outcomes, which rather improved postoperatively with marginal statistical significance. In patients with CRTLE, additional HT is a reasonable treatment option.

Microsurgical techniques in temporal lobe epilepsy.

Temporal lobe resection is the most prevalent epilepsy surgery procedure. However, there is no consensus on the best surgical approach to treat temporal lobe epilepsy. Complication rates are low and efficacy is very high regarding seizures after such procedures. However, there is still ample controversy regarding the best surgical approach to warrant maximum seizure control with minimal functional deficits. We describe the most frequently used microsurgical techniques for removal of both the lateral and mesial temporal lobe structures in the treatment of medically intractable temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (corticoamygdalohippocampectomy and selective amygdalohippocampectomy). The choice of surgical technique appears to remain a surgeon's preference for the near future. Meticulous surgical technique and thorough three-dimensional microsurgical knowledge are essentials for obtaining the best results.

Multinodular and vacuolating neuronal tumor affecting amygdala and hippocampus: A quasi-tumor?

Multinodular and vacuolating neuronal tumors (MVNT) have been referred to as distinctive neuronal tumors whose characteristic features include multiple nodules localized in the subcortical white matter. MVNT are composed of vacuolating dysplastic neurons reactive to HuC/HuD. A significant overexpression of alpha-internexin (INA) limited to the stroma of nodules was reported in one tumor. Since genetic analyses have failed to demonstrate any consistent alterations, the nosological position as well as the nature of MVNT, namely, neoplastic or dysplastic, remains unclear. We herein present another example of MVNT involving the amygdala and anterior hippocampus in a 41-year-old man. In addition to the nodular lesions described earlier, we found INA-positive ribbon-like lesions that replaced neuropil and extended along the hippocampal gray matter. We also identified dysplastic neurons infiltrating into the CA4 hilus of the hippocampus. Intense INA expression was present in the stroma as well as the cytoplasmic membrane of dysplastic neurons and their processes. While the invasiveness suggested a neoplasm, a relatively restrictive, either nodular or ribbon-like growth pattern with INA-positive abnormal neuropil suggested a hamartoma. Such quasi-tumors should be accommodated in the World Health Organization classification of tumors of the central nervous system, as are dysembryoplastic neuroepithelial tumor and Lhermitte-Duclos disease.

Abnormal discharges from the temporal neocortex after selective amygdalohippocampectomy and seizure outcomes.

The present study examined the relationship between residual discharges from the temporal neocortex postoperatively and seizure outcomes, in mesial temporal lobe epilepsy (MTLE) patients with hippocampal sclerosis (HS) who were treated with selective amygdalohippocampectomy (SelAH). Abnormal discharges from the temporal neocortex are often observed and remain postoperatively. However, no recommendations have been made regarding whether additional procedures to eliminate these discharges should be performed for seizure relief. We retrospectively analyzed 28 patients with unilateral MTLE and HS, who underwent transsylvian SelAH. The mean follow-up period was 29 months (range: 16-49). In the pre- and postresection states, electrocorticography (ECoG) was recorded for the temporal base and lateral temporal cortex. The extent of resection was not influenced by the results of the preresection ECoG. Even if residual abnormal discharges were identified on the temporal neocortex, no additional procedures were undertaken to eliminate these abnormalities. The postresection spike counts were examined to determine the postresective alterations in spike count, and the frequency of residual spike count. The seizure outcomes were evaluated in all patients using the Engel classification. The postoperative seizure-free rate was 92.9%. No significant correlations were seen between a decreasing spike count and seizure outcomes (p=0.9259), or between the absence of residual spikes and seizure outcomes (p=1.000). Residual spikes at the temporal neocortex do not appear to influence seizure outcomes. Only mesial temporal structures should be removed, and additional procedures to eliminate residual spikes are not required.

Posterior callosotomy using a parietooccipital interhemispheric approach in the semi-prone park-bench position.

A 2-stage corpus callosotomy is accepted as a palliative procedure for patients older than 16 years with, in particular, medically intractable generalized epilepsy and drop attack seizures and is preferable for a lower risk of disconnection syndrome. Although the methods by which a previously performed craniotomy can be reopened for posterior callosotomy have already been reported, posterior corpus callosotomy using a parietooccipital interhemispheric approach with the patient in a semi-prone park-bench position has not been described in the literature. Here, the authors present a surgical technique for posterior callosotomy using a parietooccipital interhemispheric approach with a semi-prone park-bench position as a second surgery. Although this procedure requires an additional skin incision in the parietooccipital region, it makes the 2-stage callosotomy safer and easier to perform because of reduced intracranial adhesion, less bleeding, and an easier approach to the splenium of the corpus callosum.

Surgery for amygdala enlargement with mesial temporal lobe epilepsy: pathological findings and seizure outcome.

OBJECTIVE: Amygdala enlargement (AE) has been suggested to be a subtype of mesial temporal lobe epilepsy (MTLE). However, most reports related to AE have referred to imaging studies, and there have been few reports regarding surgical and pathological findings. The present study was performed to clarify the surgical outcomes and pathology of AE. METHODS: Eighty patients with drug-resistant MTLE were treated surgically at the Tokyo Metropolitan Neurological Hospital between April 2010 and July 2013. Of these patients, 11 were diagnosed as AE based on presurgical MRI. Nine patients with AE underwent selective amygdalohippocampectomy, while the remaining two patients underwent selective amygdalotomy with hippocampal transection. Intraoperative EEG was routinely performed. The histopathology of the resected amygdala tissue was evaluated and compared with the amygdala tissue of patients with hippocampal sclerosis. RESULTS: Pathological findings indicated that 10 of 11 specimens had closely clustering hypertrophic neurons with vacuolisation of the background matrix. Slight gliosis was seen in nine specimens, while the remaining two showed no gliotic changes. Intraoperative EEG showed abnormal sharp waves that seemed to originate not from the amygdala but from the hippocampus in all cases. Ten patients became seizure-free during the postoperative follow-up period. CONCLUSIONS: Histopathologically, clustering hypertrophic neurons and vacuolation with slight gliosis or without gliosis were considered to be pathological characteristics of AE. Amygdalohippocampectomy or hippocampal transection with amygdalotomy is effective for seizure control in patients with AE.

A surgical case of frontal lobe epilepsy due to focal cortical dysplasia accompanied by olfactory nerve enlargement: case report.

A 45-year-old man came to our clinic due to refractory general tonic seizure and an attack of unintended yelling. Magnetic resonance imaging (MRI) demonstrated mild cortical hyperintensity on fluid attenuated inversion recovery (FLAIR) image in the left basal frontal area. Enlargement of the left olfactory nerve was also detected below the affected gyrus. Subtotal resection of the MRI-visible epileptogenic lesion was performed without any neurological deficit. The final pathological diagnosis was focal cortical dysplasia (FCD) type IIa. Seizures and yelling attacks subsided after surgery. Extracerebral abnormalities, including cranial nerve enlargement, are common in patients with hemimegalencephaly. However, such abnormalities are rare with FCD.

Modification of vertical hemispherotomy for refractory epilepsy.

Delalande's vertical hemispherotomy is an innovative evolution of hemispherectomy in minimizing brain resection. We report our modification for this surgical procedure. We modified the original procedure in two aspects for the purpose of less brain resection and confirmation of the complete disconnection. Firstly, all procedures were done via an interhemispheric route instead of a transcortical route. Secondly, we set the anterior disconnection plane as the one that connects the anterior end of the choroidal fissure to the anterior end of the foramen of Monro, instead of the former to the subcallosal area. We applied this modified vertical hemispherotomy to 7 cases. Four cases were children with hemimegalencephaly and other 3 were adults with ulegyric hemisphere. Surgical procedure was completed without complication in all cases. There was no case that required CSF shunting. Seizure outcome was Engel's class I in 6 and class IV in 1. Postoperative MRI revealed complete disconnection of the affected hemisphere in all patients. We reported our modification of vertical hemispherotomy. Although these are minor modifications, they further minimized brain resection and may serve for less invasiveness of procedure and improvement in completeness of disconnection and its confirmation during surgery.

Transsylvian hippocampal transection for mesial temporal lobe epilepsy: surgical indications, procedure, and postoperative seizure and memory outcomes.

OBJECT: Amygdalohippocampectomy is a well-established, standard surgery for medically intractable mesial temporal lobe epilepsy (MTLE). However, in the case of MTLE without hippocampal atrophy or sclerosis, amygdalohippocampectomy is associated with decreased postoperative memory function. Hippocampal transection (HT) has been developed to overcome this problem. In HT the hippocampus is not removed; rather, the longitudinal hippocampal circuits of epileptic activities are disrupted by transection of the pyramidal layer of the hippocampus. The present study describes a less invasive modification of HT (transsylvian HT) and presents the seizure and memory outcomes for this procedure. METHODS: Thirty-seven patients with MTLE (18 men and 19 women; age range 9-63 years; 19 with surgery on the right side and 18 with surgery on the left side; seizure onset from 3 to 34 years) who were treated with transsylvian HT were retrospectively analyzed. All patients had left-side language dominance, and follow-up periods ranged from 12 to 94 months (median 49 months). Seizure outcomes were evaluated for all patients by using the Engel classification. Memory function was evaluated for 22 patients based on 3 indices (verbal memory, nonverbal memory, and delayed recall), with those scores obtained using the Wechsler Memory Scale-Revised. Patients underwent evaluation of the memory function before and after surgery (6 months-1 year). RESULTS: Engel Class I (completely seizure free) was achieved in 25 patients (67.6%). Class II and Class III designation was achieved in 10 (27%) and 2 patients (5.4%), respectively. There were differences in memory outcome between the sides of operation. On the right side, verbal memory significantly increased postoperatively (p = 0.003) but nonverbal memory and delayed recall showed no significant change after the operation (p = 0.718 and p = 0.210, respectively). On the left side, all 3 indices (verbal memory, nonverbal memory, and delayed recall) showed no significant change (p = 0.331, p = 0.458, and p = 0.366, respectively). CONCLUSIONS: Favorable seizure outcome and preservation of verbal memory were achieved with transsylvian HT for the treatment of MTLE without hippocampal atrophy or sclerosis.

Temporal lobe epilepsy with hippocampal sclerosis in acute lymphoblastic leukemia.

Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted.

Efficacy of hippocampal transection for left temporal lobe epilepsy without hippocampal atrophy.

We describe a case of left temporal lobe epilepsy without hippocampal atrophy. A 31-year-old woman presented with typical symptoms of complex partial seizures. Magnetic resonance imaging demonstrated slightly obscure internal structures in the left hippocampus. Scalp electroencephalography revealed interictal epileptiform discharges in the left temporal lobe. A Wada test with propofol determined the language-dominant hemisphere to be the left. Intraoperative electrocorticography revealed active epileptic discharges in the hippocampus and the anterior temporal basal area. The hippocampal epileptic area was treated with multiple transection, which led to the complete cessation of epileptic discharges. After surgery, the Rey Auditory Verbal Learning Test score decreased from 12 to 9. However, it returned to the preoperative level 6months after surgery. We describe this case as a typical example demonstrating the efficacy of hippocampal transection for seizure control and the preservation of verbal memory.

[Surgical technique and neuropsychological outcome of transsylvian hippocampal transection in 26 patients with paradoxical temporal lobe epilepsy].

Considerable research has been conducted to distinguish between mesial temporal lobe epilepsy (MTLE) and non-MTLE, as defined in relation to paradoxical temporal lobe epilepsy (PTLE). Although our previous studies have indicated good memory-related outcome of transsylvian selective amygdalohippocampectomy (TSA) in patients with MTLE, the cause of postoperative decline in verbal memory remains unclear in cases of PTLE. The present study aimed to investigate the effects of transsylvian hippocampal transection (TSHT) sparing the hippocampus and unaffected brain tissue on memory function in cases of PTLE. The study population comprised 26 patients with PTLE syndrome (left, 15; right, 11). All patients underwent comprehensive neuropsychological analysis of their verbal and nonverbal memory, attention, and delayed recall preoperatively, and at 1 month and 1 year after TSHT. Separate repeated-measures multivariate analysis of variance (MANOVA) was performed for memory scores collected at these time points. In the left TSHT group, the IQ scores were maintained even at 1 year postoperatively, whereas in the right TSHT group, the IQ scores improved at 1 month and were maintained at 1 year postoperatively. Although verbal memory decreased immediately after left TSHT, this decline tended to improve to the preoperative level at 1 year postoperatively. In the right TSHT group, verbal memory, nonverbal memory, and delayed recall improved immediately after surgery and the improved was maintained even after 1 year. The results of the present study indicate that TSHT for PTLE is effective in preserving and improving memory function. In particular, TSHT showed significant preservation of verbal memory in patients with left non-hippocampal atrophy.

Memory outcome following transsylvian selective amygdalohippocampectomy in 62 patients with hippocampal sclerosis.

OBJECT: It remains unclear whether selective amygdalohippocampectomy, an operative technique developed for use in epilepsy surgery to spare unaffected brain tissue and thus minimize the cognitive consequences of temporal lobe surgery, actually leads to a better memory outcome. The present study was performed to determine the effects of selective surgery on memory outcome in patients with intractable mesial temporal lobe epilepsy due to hippocampal sclerosis treated using transsylvian selective amygdalohippocampectomy (TSA). METHODS: The study population consisted of 62 patients with left hemisphere language dominance who underwent left-(31 patients) or right-sided (31 patients) TSA. All patients underwent comprehensive neuropsychological testing before and 1 month and 1 year after unilateral TSA. Verbal Memory I, Nonverbal Memory I, Total Memory, Attention, and Delayed Recall were assessed using the Wechsler Memory Scale-Revised, whereas Verbal Memory II was assessed using the Miyake Verbal Retention Test (MVRT), and Nonverbal Memory II was assessed using the Benton Visual Retention Test. Separate repeated-measures multivariate analysis of variance (MANOVA) were performed for these intervals with memory scores. RESULTS: The results of MANOVA indicated that patients who underwent right-sided TSA showed significant improvements in Verbal Memory I (preoperatively vs 1 month postoperatively, p < 0.0001; and preoperatively vs 1 year postoperatively, p = 0.0002), Nonverbal Memory I (preoperatively vs 1 month postoperatively, p = 0.0003; and preoperatively vs 1 year postoperatively, p = 0.006), and Delayed Recall (preoperatively vs 1 month postoperatively, p = 0.028) at both 1-month and 1-year follow-ups. In addition, Verbal Memory II (MVRT) was also significantly improved 1 year after surgery (p = 0.001). In the group of patients who underwent left-sided TSA, both Verbal Memory I and II were maintained at the same level 1 month after surgery, whereas the Verbal Memory I score 1 year after surgery increased with marginal significance (p = 0.074). In addition, Verbal Memory II showed significant improvement 1 year after surgery (p = 0.049). There were no significant changes in Nonverbal Memory I and II, Attention, or Delayed Recall at either the 1-month or 1-year follow-up. CONCLUSIONS: Results of the present study indicated that left-sided TSA for hippocampal sclerosis tends to improve verbal memory function with the preservation of other types of memory function. Moreover, right-sided TSA for hippocampal sclerosis can lead to significant improvement in memory function, with memory improvement observed 1 month after right-sided TSA and persisting 1 year after surgery.

Prediction of seizure outcome following epilepsy surgery: asymmetry of thalamic glucose metabolism and cerebral neural activity in temporal lobe epilepsy.

OBJECTIVE: The objective of this retrospective study is to analyze whether preoperative functional imaging studies using FDG-PET and MEG enable prediction of postoperative seizure outcomes. METHODS: Thirty-six patients with intractable temporal lobe epilepsy were studied. Asymmetry index of tCMRgluc (PET-AI) and the equivalent current dipole intensity of first response of SEF (SEF-AI) were determined preoperatively using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetoencephalography (MEG), respectively. Seizure outcomes were evaluated according to the classification proposed by the International League Against Epilepsy (ILAE) at least 24 months after resection of epileptic focuses. Twelve healthy volunteers were included in this study to determine the normal value. RESULTS: Quantitative analysis revealed mean PET-AI in the patients was 5.4+/-5.2% (significantly different from normal controls); mean SEF-AI was 25.2+/-20.6% (not significantly different). PET-AI was positive (indicative of epileptic focus) in 29 of 36 patients (80.6%), while SEF-AI was positive in 17 of 36 patients (47.2%). Although no significant correlation between PET-AI and SEF-AI was noted (r=0.43), concordant asymmetry in both PET-AI and SEF-AI was significantly associated with better seizure outcome than discordant or paradoxical asymmetry of both factors (p<0.01). CONCLUSIONS: The results suggest that quantitative analysis of tCMRgluc with SEF may be helpful in characterizing the preoperative epileptogenic condition and predicting postoperative seizure outcome in patients with temporal lobe epilepsy, although a constellation of developmental brain abnormalities and environmental factors that together produce epilepsy need to be further explored.