Long-term seizure outcomes in patients with hypothalamic hamartoma treated by stereotactic radiofrequency thermocoagulation.

OBJECTIVE: To investigate long-term seizure outcomes in patients with hypothalamic hamartoma (HH) following stereotactic radiofrequency thermocoagulation (SRT). METHODS: A total of 131 patients with HH who underwent SRT and were followed for at least three years after the last SRT were enrolled. Seizure outcomes were evaluated for gelastic seizures (GS) and other types of seizures (nGS) separately using the International League Against Epilepsy classification. Classes 1 and 2 were considered seizure-free. Kaplan-Meier survival analyses were used to estimate the proportion remaining seizure-free after the first and last SRTs. Risk factors relating to outcomes were analyzed by log-rank tests and a multivariate Cox proportional hazards model. RESULTS: Reoperation was performed in 34 patients (26.2%). Median total follow-up was 61 (range, 36-202) months. Seizure freedom was obtained in 116 patients (88.6%) for GS and 85 of 108 patients (78.7%) for nGS at the last follow-up. Mean GS-free survival times improved from after the first (64.1 [95%CI 57.3-70.9] months) to after the last SRT (80.2 [95%CI 75.7-84.8] months). About 90% of GS recurrences after the first SRT were found within 6 months, though a few patients recurred more than 2 years after the first SRT. On the other hand, mean nGS-free survival times after the first and last SRTs were not different between after the first SRT (84.4 [95%CI 73.0-90.7] months) and after the last SRT (83.1 [95%CI 74.1-92.0] months). There was no factor related to GS outcomes, but the significant factor for nGS-free survival after the last SRT was multiple previous treatments (p=0.01, hazard ratio=15.65, 95%CI 1.79-137.16). SIGNIFICANCE: The last SRT was almost equivalent to achieving complete disconnection of HHs from the hypothalamus according to our strategy. Considering the epileptogenic network, GS outcomes depend on complete disconnection, whereas nGS outcomes are not affected by surgical factors but independency of secondary epileptogenesis.

Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording.

OBJECTIVE: Ablation surgery has become the first line of treatment for hypothalamic hamartomas (HHs). For effective treatment, optimum targeting of ablation is mandatory. The present study aimed to evaluate the correspondence between the electrophysiological features of HHs and morphological targeting by semimicrorecording during stereotactic radiofrequency thermocoagulation (SRT). METHODS: Eighty HH patients who underwent SRT were involved. Semimicrorecording was performed on the first trajectory. The distance from the center of the target at the morphological border (TMB) determined by magnetic resonance imaging, differences in discharge patterns, and area potentials (APs) were measured. RESULTS: The electrophysiological border (EB) between the HH and hypothalamus was detected by semimicrorecording in 73 (91.3%), AP increase (API) in the HH was detected in 31 (38.8%), and spike discharges (SDs) of the HH were detected in 56 patients (70.0%). Semimicrorecording showed significantly different APs among structures passing through the trajectory, except between API and SDs. The median distances from the center of the TMB to the EB, API, SDs, and AP decline were -3.50, -2.49, -1.38, and +2.00 mm, respectively. SIGNIFICANCE: The electrophysiological features of HHs were shown by semimicrorecording during SRT. The EB corresponded to the morphological border. The electrophysiologically active area of HHs was located near the border. Ablation surgery should focus on disconnection at the border between the HH and the hypothalamus to maximize its effectiveness, as well as to reduce complications.

Asymmetric gelastic seizure as a lateralizing sign in patients with hypothalamic hamartoma.

Gelastic seizure (GS) is a cardinal symptom of hypothalamic hamartoma (HH), which is intractable but surgically remediable. Although facial asymmetry with GS has not been extensively discussed, asymmetric GS has been frequently recognized in our large series. We hypothesized that asymmetric GS represents a lateralizing sign caused by the epileptic propagation from the attachment of the HH. To examine this hypothesis, the positive predictive value (PPV) and diagnostic odds ratio (DOR) of asymmetric GS were validated to predict the side of HH attachment. In 103 cases registered to the present analysis, asymmetric GS was recognized in 71 patients and symmetric GS in 32. Asymmetric GS with a lopsided grimace was exclusively observed on the side contralateral to unilateral HH in 39 patients and to the dominant attachment of 23 HHs with bilateral attachment (true positive, n = 62). In contrast, asymmetric GS was exhibited independently on both sides in 4 patients with bilaterally attached HH and on the side ipsilateral to the dominant attachment in the other 4. Symmetric HH attachments were identified in 1 patient (false negative, n = 9). Asymmetric GS was a reliable lateralizing sign with high DOR (6.08) and PPV (78%) to predict the side of epileptic propagation. Furthermore, the present study demonstrated the probability of seizure propagation from bilateral attachment, and this evidence provides a new rationale to the surgical strategy of bilateral disconnection for HH with bilateral attachment.

Variability and Reliability of Paired-Pulse Depression and Cortical Oscillation Induced by Median Nerve Stimulation.

Paired-pulse depression (PPD) has been widely used to investigate the functional profiles of somatosensory cortical inhibition. However, PPD induced by somatosensory stimulation is variable, and the reasons for between- and within-subject PPD variability remains unclear. Therefore, the purpose of this study was to clarify the factors influencing PPD variability induced by somatosensory stimulation. The study participants were 19 healthy volunteers. First, we investigated the relationship between the PPD ratio of each component (N20m, P35m, and P60m) of the somatosensory magnetic field, and the alpha, beta, and gamma band changes in power [event-related desynchronization (ERD) and event-related synchronization (ERS)] induced by median nerve stimulation. Second, because brain-derived neurotrophic factor (BDNF) gene polymorphisms reportedly influence the PPD ratio, we assessed whether BDNF genotype influences PPD ratio variability. Finally, we evaluated the test-retest reliability of PPD and the alpha, beta, and gamma ERD/ERS induced by somatosensory stimulation. Significant positive correlations were observed between the P60m_PPD ratio and beta power change, and the P60m_PPD ratio was significantly smaller for the beta ERD group than for the beta ERS group. P35m_PPD was found to be robust and highly reproducible; however, P60m_PPD reproducibility was poor. In addition, the ICC values for alpha, beta, and gamma ERD/ERS were 0.680, 0.760, and 0.552 respectively. These results suggest that the variability of PPD for the P60m deflection may be influenced by the ERD/ERS magnitude, which is induced by median nerve stimulation.

Predictors of cognitive function in patients with hypothalamic hamartoma following stereotactic radiofrequency thermocoagulation surgery.

OBJECTIVE: To determine the predictors of cognitive function in patients with drug-resistant gelastic seizures (GS) related to hypothalamic hamartoma (HH) before and after stereotactic radiofrequency thermocoagulation surgery (SRT). METHODS: We studied 88 patients with HH who underwent SRT between October 1997 and December 2014. Patients received neuropsychological tests preoperatively and postoperatively. Based on the preoperative measures, patients were categorized as "high-functioning" (full-scale intelligence quotient [FSIQ] ≥70; n = 48) and "low-functioning" group (FSIQ <70; n = 40). Univariate and multivariate linear regression analyses determined the clinical, electroencephalography (EEG), and imaging factors associated with preoperative cognitive function as well as postoperative cognitive change. RESULTS: Eighty-seven patients (98.8%) were followed postoperatively for an average of 3.3 years, and 75 (85.2%) of them achieved GS remission at the last hospital visit. Neuropsychological performance was significantly improved after surgery in both groups. Multivariate linear regression analysis showed that a smaller HH size (p = 0.002) and a smaller number of antiepileptic drugs (p < 0.001) were preoperatively associated with better neuropsychological performance. Multivariate linear regression analysis showed that better postoperative improvement in cognition was associated with a shorter duration of epilepsy (p = 0.03). SIGNIFICANCE: Cognitive impairment related to epileptic encephalopathy may improve following SRT in substantial proportions of HH patients. Reduced improvement in postoperative cognitive function in patients with longer duration of epilepsy warrants further studies to determine if earlier SRT provides a greater chance of postoperative cognitive improvement in patients with HH.

Ca2+ -permeable AMPA receptors associated with epileptogenesis of hypothalamic hamartoma.

Hypothalamic hamartoma (HH), composed of neurons and glia without apparent cytologic abnormalities, is a rare developmental malformation in humans. Patients with HH often have characteristic medically refractory gelastic seizures, and intrinsic epileptogenesis within the lesions has been speculated. Herein we provide evidence to suggest that in HH neurons, Ca2+ permeability through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors is aberrantly elevated. In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues. In HH, however, these activities were clearly abolished by application of Joro Spider Toxin (JSTX), a specific inhibitor of the Ca2+ -permeable AMPA receptor. Consistent with these physiologic findings, the neuronal nuclei showed disappearance of adenosine deaminase acting on RNA 2 (ADAR2) immunoreactivity. Furthermore, examination of glutamate receptor 2 (GluA2) messenger RNA (mRNA) revealed that editing efficiency at the glutamine/arginine site was significantly low. These results suggest that neurons in HH may bear Ca2+ -permeable AMPA receptors due to dislocation of ADAR2.

Inhibitory effect of intensity and interstimulus interval of conditioning stimuli on somatosensory evoked magnetic fields.

Magnetoencephalography (MEG) recordings were performed to investigate the inhibitory effects of conditioning stimuli with various types of interstimulus intervals (ISIs) or intensities on somatosensory evoked magnetic fields (SEFs) using a 306-ch whole-head MEG system. Twenty-three healthy volunteers participated in this study. Electrical stimuli were applied to the right median nerve at the wrist. Six pulse trains with ISIs of 500 ms were presented in Experiment 1. A paired-pulse paradigm with three kinds of conditioning stimulus (CON) intensities, 500 ms before the test stimulus (TS), was applied in Experiment 2. Finally, three CONs 500 or 1000 ms before TS were presented in Experiment 3. Three main SEF deflections (N20m, P35m, and P60m) were observed, and the source activities of P35m and P60m significantly decreased after the 2nd pulse of a six pulse trains. These source activities also significantly decreased with increasing intensity of CON. In addition, these attenuations of source activities were affected by CON-CON or CON-TS intervals. These results indicated that the source activities were modulated by the intensity and ISIs of CONs. Furthermore, P35m after the stimulation were very sensitive to CONs; however, the attenuation of P60m after the stimulation lasted for a longer period than that of P35m. Our findings suggest that the conditioning stimulation had inhibitory effects on subsequent evoked cortical responses for more than 500 ms. Our results also provide important clues about the nature of short-latency somatosensory responses in human studies.

Somatic Mutations in the MTOR gene cause focal cortical dysplasia type IIb.

OBJECTIVE: Focal cortical dysplasia (FCD) type IIb is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, and balloon cells. It has been suggested that FCDs are caused by somatic mutations in cells in the developing brain. Here, we explore the possible involvement of somatic mutations in FCD type IIb. METHODS: We collected a total of 24 blood-brain paired samples with FCD, including 13 individuals with FCD type IIb, 5 with type IIa, and 6 with type I. We performed whole-exome sequencing using paired samples from 9 of the FCD type IIb subjects. Somatic MTOR mutations were identified and further investigated using all 24 paired samples by deep sequencing of the entire gene's coding region. Somatic MTOR mutations were confirmed by droplet digital polymerase chain reaction. The effect of MTOR mutations on mammalian target of rapamycin (mTOR) kinase signaling was evaluated by immunohistochemistry and Western blotting analyses of brain samples and by in vitro transfection experiments. RESULTS: We identified four lesion-specific somatic MTOR mutations in 6 of 13 (46%) individuals with FCD type IIb showing mutant allele rates of 1.11% to 9.31%. Functional analyses showed that phosphorylation of ribosomal protein S6 in FCD type IIb brain tissues with MTOR mutations was clearly elevated, compared to control samples. Transfection of any of the four MTOR mutants into HEK293T cells led to elevated phosphorylation of 4EBP, the direct target of mTOR kinase. INTERPRETATION: We found low-prevalence somatic mutations in MTOR in FCD type IIb, indicating that activating somatic mutations in MTOR cause FCD type IIb.

Effect of muscle contraction strength on gating of somatosensory magnetic fields.

Afferent somatosensory information is modulated before the afferent input arrives at the primary somatosensory cortex during voluntary movement. The aim of the present study was to clarify the effect of muscular contraction strength on somatosensory evoked fields (SEFs) during voluntary movement. In addition, we examined the differences in gating between innervated and non-innervated muscle during contraction. We investigated the changes in gating effect by muscular contraction strength and innervated and non-innervated muscles in human using 306-channel magnetoencephalography. SEFs were recorded following the right median nerve stimulation in a resting condition and during isometric muscular contractions from 10 % electromyographic activity (EMG), 20 and 30 % EMG of the right extensor indicis muscle and abductor pollicis brevis muscle. Our results showed that the equivalent current dipole (ECD) strength for P35m decreased with increasing strength of muscular contraction of the right abductor pollicis brevis muscle. However, changes were observed only at 30 % EMG contraction level of the right extensor indicis muscle, which was not innervated by the median nerve. There were no significant changes in the peak latencies and ECD locations of each component in all conditions. The ECD strength did not differ significantly for N20m and P60m regardless of the strength of muscular contraction and innervation. Therefore, we suggest that the gating of SEF waveforms following peripheral nerve stimulation was affected by the strength of muscular contraction and innervation of the contracting muscle.

Effect of Range and Angular Velocity of Passive Movement on Somatosensory Evoked Magnetic Fields.

To clarify characteristics of each human somatosensory evoked field (SEF) component following passive movement (PM), PM1, PM2, and PM3, using high spatiotemporal resolution 306-channel magnetoencephalography and varying PM range and angular velocity. We recorded SEFs following PM under three conditions [normal range-normal velocity (NN), small range-normal velocity (SN), and small range-slow velocity (SS)] with changing movement range and angular velocity in 12 participants and calculated the amplitude, equivalent current dipole (ECD) location, and the ECD strength for each component. All components were observed in six participants, whereas only PM1 and PM3 in the other six. Clear response deflections at the ipsilateral hemisphere to PM side were observed in seven participants. PM1 amplitude was larger under NN and SN conditions, and mean ECD location for PM1 was at primary motor area. PM3 amplitude was larger under SN condition and mean ECD location for PM3 under SS condition was at primary somatosensory area. PM1 amplitude was dependent on the angular velocity of PM, suggesting that PM1 reflects afferent input from muscle spindle, whereas PM3 amplitude was dependent on the duration. The ECD for PM3 was located in the primary somatosensory cortex, suggesting that PM3 reflects cutaneous input. We confirmed the hypothesis for locally distinct generators and characteristics of each SEF component.

Alternating zones selective to faces and written words in the human ventral occipitotemporal cortex.

Recognition of faces and written words is associated with category-specific brain activation in the ventral occipitotemporal cortex (vOT). However, topological and functional relationships between face-selective and word-selective vOT regions remain unclear. In this study, we collected data from patients with intractable epilepsy who underwent high-density recording of surface field potentials in the vOT. "Faces" and "letterstrings" induced outstanding category-selective responses among the 24 visual categories tested, particularly in high-γ band powers. Strikingly, within-hemispheric analysis revealed alternation of face-selective and letterstring-selective zones within the vOT. Two distinct face-selective zones located anterior and posterior portions of the mid-fusiform sulcus whereas letterstring-selective zones alternated between and outside of these 2 face-selective zones. Further, a classification analysis indicated that activity patterns of these zones mostly represent dedicated categories. Functional connectivity analysis using Granger causality indicated asymmetrically directed causal influences from face-selective to letterstring-selective regions. These results challenge the prevailing view that different categories are represented in distinct contiguous regions in the vOT.

Effect of changes in stimulus site on activation of the posterior parietal cortex.

A previous functional magnetic resonance imaging study elucidated the specific activity of the inferior parietal lobe (IPL) during a two-point discrimination task compared with that during an intensity discrimination task Akatsuka et al. (Neuroimage 40: 852-858, 2008). If the posterior parietal cortex (PPC), including IPL, is responsible for detecting changes in stimulus sites, PPC activity depends on the level of change at stimulus sites. The aim of this study was to clarify whether a particular site exists that could detect changes in stimulus sites using the oddball paradigm. Somatosensory-evoked magnetic fields were recorded in 10 right-handed subjects. Three oddball conditions were performed by all subjects, with the probability of deviant and standard stimuli being 20 and 80 %, respectively, under all three conditions. Deviant stimuli were always presented to the second digit of the hand and standard stimuli were presented to the first (small deviance: SD) and fifth digits (medium deviance: MD) of the hand and the first digit of the toe (large deviance: LD). Inter-stimulus intervals were set at 500 ms. A brain electrical source analysis showed that activities of areas 1 and 3b elicited by the deviant stimuli were not significantly different among the three conditions. In contrast, PPC activity was significantly greater for LD than for SD and MD. PPC activity tended to increase with greater deviance at stimulus sites, but activities of areas 1 and 3b did not differ. These findings suggest that PPC may have a functional role in automatic change detection systems with regard to deviance of stimulus sites.

Characteristic expression of p57/Kip2 in balloon cells in focal cortical dysplasia.

Balloon cells are a pathognomonic cellular feature of various cortical malformations, including focal cortical dysplasia type IIb (FCD IIb), cortical tubers of tuberous sclerosis (TSC) and hemimegalencephaly (HME). In the present study, we investigated the immunohistochemical expression of p57/Kip2, a member of the Cip/Kip family of cyclin-dependent kinase inhibitory proteins, in balloon cells in surgical specimens taken from 26, 17 and six patients with FCD IIb, TSC and HME, respectively. Characteristic dot-like reactivity with a faint, intense, reticular and process-like pattern was confined to the proximal portion of the cytoplasmic processes of the cells. Immunoelectron microscopy revealed the p57/Kip2 reactivity on intermediate filaments in the proximal portion of the processes. The immunohistochemical profile appeared similar to that of CD34; however, a double immunofluorescence study demonstrated that no cells showed reactivity for both p57/Kip2 and CD34. The frequencies of the p57/Kip2-positive cells in FCD IIb and HME were significantly higher than those in TSC, suggesting that the balloon cells may be heterogeneous. These findings suggest some functional significance of the protein on the cytoplasmic processes of balloon cells and appear consistent with the notion that the cells are abnormally differentiated progenitor cells.

Altered activity of the primary visual area during gaze processing in individuals with high-functioning autistic spectrum disorder: a magnetoencephalography study.

BACKGROUND: Individuals with autistic spectrum disorder (ASD) demonstrate an impaired ability to infer the mental states of others from their gaze. Thus, investigating the relationship between ASD and eye gaze processing is crucial for understanding the neural basis of social impairments seen in individuals with ASD. In addition, characteristics of ASD are observed in more comprehensive visual perception tasks. These visual characteristics of ASD have been well-explained in terms of the atypical relationship between high- and low-level gaze processing in ASD. METHOD: We studied neural activity during gaze processing in individuals with ASD using magnetoencephalography, with a focus on the relationship between high- and low-level gaze processing both temporally and spatially. Minimum Current Estimate analysis was applied to perform source analysis of magnetic responses to gaze stimuli. RESULTS: The source analysis showed that later activity in the primary visual area (V1) was affected by gaze direction only in the ASD group. Conversely, the right posterior superior temporal sulcus, which is a brain region that processes gaze as a social signal, in the typically developed group showed a tendency toward greater activation during direct compared with averted gaze processing. CONCLUSION: These results suggest that later activity in V1 relating to gaze processing is altered or possibly enhanced in high-functioning individuals with ASD, which may underpin the social cognitive impairments in these individuals.

Repeated practice of a Go/NoGo visuomotor task induces neuroplastic change in the human posterior parietal cortex: an MEG study.

The posterior parietal cortex (PPC) is strongly related to task performance by evaluating sensory cues and visually guided movements. Sensorimotor processing is improved by task repetition as indicated by reduced response time. We investigated practice-induced changes in PPC visuomotor processing during a Go/NoGo task in humans using 306-channel magnetoencephalography. Eleven healthy adult males were instructed to extend the right index finger when presented with the Go stimulus (a red circle), but not to react to the NoGo stimulus (a green circle or a red square). Magnetic fields over the visual, posterior parietal, and sensorimotor cortices were measured before and after 3 days of task practice. The first peak of the visual-evoked field (VEF) occurred at approximately 80 ms after presentation of either the Go or NoGo stimulus, while a PPC response, with latency to a peak of 175.8 ± 26.7 ms, occurred only after the Go stimulus. No significant change in the first peak of VEF was measured after 3 days of task practice, but there was a significant reduction in the latency to peak PPC activity (160.1 ± 27.6 ms) and in the time from peak PPC activity to electromyogram onset. In all participants, practice resulted in a significant reduction in reaction time. These results demonstrate that practicing a sensorimotor task induces neuroplastic changes in PPC that accelerate sensorimotor processing and reduce motor response times.

Activation of the human premotor cortex during motor preparation in visuomotor tasks.

Functional brain mapping studies in humans suggest that both motor and premotor cortices interact during movement execution. The aim of this study was to investigate whether the premotor cortex also participates in motor planning. We measured movement-related cerebral fields (MRCFs) using magnetoencephalography from the left hemisphere of 12 healthy right-handed participants during two simple visuomotor tasks cued by two visual stimuli S1 and S2. Participants performed a unilateral task in which they always extended the right index finger after S2 presentation regardless of the color of S1 and a bilateral task in which they extended either the right or left index finger after S2 presentation according to the color of S1. Significantly higher MRCF activity was observed during the 500 ms S1 to S2 interval in the bilateral task than in the unilateral task. In the bilateral task trials, the latency of the peak MRCF during the S1 to S2 interval was 343.9 ± 73.5 ms after S1 presentation and that of the peak of movement-evoked field 1 was 33.4 ± 3.9 ms after movement onset in the bilateral task. Equivalent current dipoles at the peak MRCF were significantly medial (9.2 ± 12.1 mm) and anterior (19.8 ± 6.9 mm) to the reference location in the somatosensory cortex (area 3b) established by median nerve stimulation. This location corresponds to the dorsal premotor cortex. These findings suggest that activation of the premotor cortex observed during the interstimulus interval may represent a neurophysiological marker of response selection.

Oligodendroglioma (WHO grade I) in a young epilepsy patient: a specific entity lying within the spectrum of dysembryoplastic neuroepithelial tumor?

We studied a frontal lobe subcortical cystic tumor that had been resected from a 13-year-old girl with a 3-year history of intractable partial seizure. Currently, more than 13 years after surgery, the patient remains recurrence-free and has no neurological deficits. Histological examination showed that the tumor was non-infiltrating and paucicellular with a mucinous matrix, and consisted of fairly uniform small cells with round to oval nuclei. Within the mucinous matrix, the tumor cells were often arranged in pseudorosettes around small blood vessels. Mitotic activity and necrosis were absent, with a Ki-67 labeling index of <1%. Based on the immunohistochemical and ultrastructural findings, the constituent tumor cells were considered to be those of oligodendroglioma, including mini-gemistocytes and gliofibrillary oligodendrocytes. No neuronal elements were identified. Features of cortical dysplasia (FCD Type 1) were evident in the cortex covering the lesion. The surrounding white matter also contained a significant number of ectopic neurons. The entire pathological picture appeared to differ somewhat from that of ordinary oligodendroglioma (WHO grade II). Considering the clinical and pathological features, the present unusual oligodendroglioma appeared to represent a previously undescribed form of oligodendroglioma (WHO grade I) lying within the spectrum of dysembryoplastic neuroepithelial tumor (DNT; WHO grade I). Simultaneously, the present oligodendroglioma also raises the question of whether or not oligodendrocyte-like cells of DNTs truly show neurocytic differentiation.

Incomplete hippocampal inversion in patients with mutations in genes involved in sonic hedgehog signaling.

Sonic hedgehog (Shh) signaling pathways are known to play an important role in the morphological development of the hippocampus in vivo, but their actual roles in humans have not been clarified. Hypothalamic hamartoma (HH) is known to be associated with germline or somatic gene mutations of Shh signaling. We hypothesized that patients with HH and mutations of Shh-related genes also show hippocampal maldevelopment and an abnormal hippocampal infolding angle (HIA). We analyzed 45 patients (age: 1-37 years) with HH who underwent stereotactic radiofrequency thermocoagulation and found Shh-related gene mutations in 20 patients. In addition, 44 pediatric patients without HH (age: 2-25 years) who underwent magnetic resonance imaging (MRI) examinations under the same conditions during the same period were included in this study as a control group. HIA evaluated on MRI was compared between patients with gene mutations and the control group. The median HIA at the cerebral peduncle slice in patients with the gene mutation was 74.36° on the left and 76.11° on the right, and these values were significantly smaller than the corresponding values in the control group (80.46° and 80.56°, respectively, p < 0.01). Thus, mutations of Shh-related genes were correlated to incomplete hippocampal inversion. The HIA, particularly at the cerebral peduncle slice, is a potential indicator of abnormalities of the Shh-signaling pathway.

Clinical patterns and pathophysiology of hypermotor seizures: an ictal SPECT study.

Hypermotor seizures (HMS) can include different forms of hypermotor behaviour due to various mechanisms associated with generation of ictal automatisms. Despite the varied location of seizure onset, similar semiologic features during seizures may exist. Ictal single-photon emission tomography (SPECT) apparently reflects not only the origin of epileptic discharge but also the spread to adjacent cortical areas. Taking this benefit of SPECT studies into account, preoperative SPECT results from 13 patients with HMS who underwent epilepsy surgery were analysed. The radioisotope 99mTc-ECD was injected in all patients within five seconds after seizure onset. Group analysis was performed with statistical parametric mapping (SPM) of paired ictal-interictal SPECTs in order to identify regions of significant ictal hyperperfusion. Hyperperfused regions with a corrected cluster-level significance p-value of < 0.002 were considered significant. Seizure onset at implanted subdural electrodes was defined as the epileptic focus in 12 of 13 patients. Two patterns were recognized: HMS-1 with marked agitation and HMS-2 with mild agitation. Ictal hyperperfusion images revealed significant hyperperfusion in the anterior cingulate cortex, orbito-frontal gyrus, lentiform nucleus, midbrain and pons. These hyperperfused areas represent the symptomatogenic zone which was different from the epileptogenic zone, as confirmed by the favourable outcomes after surgical resection. The present findings suggest that a network, including frontal and possibly extrafrontal brainstem and limbic structures, is involved in the genesis of the complex epileptic manifestations of HMS. Moreover, ictal SPECT analysed by SPM is a useful method for studying the neural networks of different types of seizures.

A Special Approach for Stereotactic Radiofrequency Thermocoagulation of Hypothalamic Hamartomas With Bilateral Attachments to the Hypothalamus: The Transthird Ventricular Approach to the Contralateral Attachment.

BACKGROUND: Disconnection surgery for the treatment of epileptic hypothalamic hamartomas (HHs) is strategically difficult in cases with complex-shaped HHs, especially with bilateral hypothalamic attachments, despite its effectiveness. OBJECTIVE: To evaluate the feasibility of a new approach for stereotactic radiofrequency thermocoagulation (SRT) using penetration of the third ventricle (SRT-TT) aiming to disconnect bilateral hypothalamic attachments in a single-staged, unilateral procedure. METHODS: Ninety patients (median age at surgery, 5.0 years) who had HHs with bilateral hypothalamic attachments and were followed for at least 1 year after their last SRT were retrospectively reviewed. RESULTS: Thirty-three patients underwent SRT-TT as initial surgery. Of the 58 patients after mid-2013 when SRT-TT was introduced, 33 underwent SRT-TT and 12 (20.7%) required reoperation (ReSRT), whereas 20 of 57 patients (35.1%) without SRT-TT underwent reoperation. Reoperation was required in significantly fewer patients after mid-2013 (n = 12 of 58, 20.7%) than before mid-2013 (n = 15 of 32, 46.9%) ( P = .01). Final seizure freedoms were not different between before and after mid-2013 (gelastic seizure freedom, n = 30 [93.8%] vs n = 49 [84.5%] and other types of seizure freedom, n = 21 of 31 [67.7%] vs n = 32 of 38 [84.2%]). Persistent complications were less in SRT-TT than in ReSRT using the bilateral approach, but not significantly. However, hormonal replacement was required significantly more often in ReSRT using the bilateral approach (4 of 9, 44.4%) than in SRT-TT (3 of 32, 9.4%) ( P = .01). CONCLUSION: SRT-TT enabled disconnection of bilateral attachments of HHs in a single-staged procedure, which reduced the additional invasiveness of reoperation. Moreover, SRT-TT reduced damage to the contralateral hypothalamus, with fewer endocrinological complications than the bilateral approach.