Beta resting-state functional connectivity predicts tactile spatial acuity.

Tactile perception is a complex phenomenon that is processed by multiple cortical regions via the primary somatosensory cortex (S1). Although somatosensory gating in the S1 using paired-pulse stimulation can predict tactile performance, the functional relevance of cortico-cortical connections to tactile perception remains unclear. We investigated the mechanisms by which corticocortical and local networks predict tactile spatial acuity in 42 adults using magnetoencephalography (MEG). Resting-state MEG was recorded with the eyes open, whereas evoked responses were assessed using single- and paired-pulse electrical stimulation. Source data were used to estimate the S1-seed resting-state functional connectivity (rs-FC) in the whole brain and the evoked response in the S1. Two-point discrimination threshold was assessed using a custom-made device. The beta rs-FC revealed a negative correlation between the discrimination threshold and S1-superior parietal lobule, S1-inferior parietal lobule, and S1-superior temporal gyrus connection (all P < 0.049); strong connectivity was associated with better performance. Somatosensory gating of N20m was also negatively correlated with the discrimination threshold (P = 0.015), with weak gating associated with better performance. This is the first study to demonstrate that specific beta corticocortical networks functionally support tactile spatial acuity as well as the local inhibitory network.

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.

[Neuroimaging in the Diagnosis of Epilepsy].

Neuroimaging is commonly used for presurgical evaluation in epilepsy surgery. Neuroimaging for epilepsy includes structural and functional neuroimaging. Lesions detected by structural neuroimaging are crucial to determine the indication of epilepsy surgery, as well as to predict seizure outcomes, as patients with MRI-visible lesions are likely to have better seizure outcomes. However, MRI lesions sometimes show very faint findings; therefore, the diagnosis of structural neuroimaging requires sophisticated skills. Moreover, the epilepsy focus should not only involve the MRI-visible lesion, but also the surrounding tissue with abnormal neuronal function. The MRI-lesion, which is almost the same as that epileptogenic lesion, is a part of the epileptogenic zone. Surgical strategy should be conducted by comprehensive evaluation including neuroimaging in addition to other modalities.

Ictal direct current shifts contribute to defining the core ictal focus in epilepsy surgery.

Identifying the minimal and optimal epileptogenic area to resect and cure is the goal of epilepsy surgery. To achieve this, EEG analysis is recognized as the most direct way to detect epileptogenic lesions from spatiotemporal perspectives. Although ictal direct-current shifts (below 1 Hz) and ictal high-frequency oscillations (above 80 Hz) have received increasing attention as good indicators that can add more specific information to the conventionally defined seizure-onset zone, large cohort studies on postoperative outcomes are still lacking. This work aimed to clarify whether this additional information, particularly ictal direct-current shifts which is assumed to reflect extracellular potassium concentration, really improve postoperative outcomes. To assess the usefulness in epilepsy surgery, we collected unique EEG data sets recorded with a longer time constant of 10 s using an alternate current amplifier. Sixty-one patients (15 with mesial temporal lobe epilepsy and 46 with neocortical epilepsy) who had undergone invasive presurgical evaluation for medically refractory seizures at five institutes in Japan were retrospectively enrolled in this study. Among intracranially implanted electrodes, the two core electrodes of both ictal direct-current shifts and ictal high-frequency oscillations were independently identified by board-certified clinicians based on unified methods. The occurrence patterns, such as their onset time, duration, and amplitude (power) were evaluated to extract the features of both ictal direct-current shifts and ictal high-frequency oscillations. Additionally, we examined whether the resection ratio of the core electrodes of ictal direct-current shifts and ictal high-frequency oscillations independently correlated with favourable outcomes. A total of 53 patients with 327 seizures were analyzed for wide-band EEG analysis, and 49 patients were analyzed for outcome analysis. Ictal direct-current shifts were detected in the seizure-onset zone more frequently than ictal high-frequency oscillations among both patients (92% versus 71%) and seizures (86% versus 62%). Additionally, ictal direct-current shifts significantly preceded ictal high-frequency oscillations in patients exhibiting both biomarkers, and ictal direct-current shifts occurred more frequently in neocortical epilepsy patients than in mesial temporal lobe epilepsy patients. Finally, although a low corresponding rate was observed for ictal direct-current shifts and ictal high-frequency oscillations (39%) at the electrode level, complete resection of the core area of ictal direct-current shifts significantly correlated with favourable outcomes, similar to ictal high-frequency oscillation outcomes. Our results provide a proof of concept that the independent significance of ictal direct-current shifts from ictal high-frequency oscillations should be considered as reliable biomarkers to achieve favourable outcomes in epilepsy surgery. Moreover, the different distribution of the core areas of ictal direct-current shifts and ictal high-frequency oscillations may provide new insights into the underlying mechanisms of epilepsy, in which not only neurons but also glial cells may be actively involved via extracellular potassium levels.

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.

Burden of seizures and comorbidities in patients with epilepsy: a survey based on the tertiary hospital-based Epilepsy Syndrome Registry in Japan.

OBJECTIVE: To examine the current medical and psychosocial status of patients with epilepsy, aiming to facilitate appropriate application of the Intractable/Rare Diseases Act of Japan. METHODS: By analysing the cross-sectional data of patients registered in the tertiary hospital-based Epilepsy Syndrome Registry of Japan, we investigated the proportion of patients who met the severity criteria as defined by the Act (seizure frequency of at least once a month, or presence of intellectual/neurological/psychiatric symptoms, or both) and whether there are candidate syndrome/diseases to be added to the existing list in the Act. RESULTS: In total, 2,209 patients were registered. After excluding self-limited/idiopathic epilepsies, 1,851 of 2,110 patients (87.7%) met the severity criteria. The patients were classified into eight main epilepsy syndromes (594 patients), 20 groups based on aetiology (1,078 patients), and three groups without known aetiology (427 patients). Most of the groups classified by syndrome or aetiology had high proportions of patients satisfying the severity criteria (>90%), but some groups had relatively low proportions (<80%) resulting from favourable outcome of surgical therapy. Several small groups with known syndrome/aetiology await detailed analysis based on a sufficiently large enough number of patients registered, some of whom may potentially be added to the list of the Act. SIGNIFICANCE: The registry provides data to examine the usefulness of the severity criteria and list of diseases that are operationally defined by the Act. Most epilepsy patients with various syndromes/diseases and aetiology groups are covered by the Act but some are not, and the list of designated syndromes/diseases should be complemented by further amendments, as suggested by future research.

Surgical Strategy for Directional Deep Brain Stimulation.

Deep brain stimulation (DBS) is a well-established treatment for drug-resistant involuntary movements. However, the conventional quadripole cylindrical lead creates electrical fields in all directions, and the resulting spread to adjacent eloquent structures may induce unintended effects. Novel directional leads have therefore been designed to allow directional stimulation (DS). Directional leads have the advantage of widening the therapeutic window (TW), compensating for slight misplacement of the lead and requiring less electrical power to provide the same effect as a cylindrical lead. Conversely, the increase in the number of contacts from four to eight and the addition of directional elements has made stimulation programming more complex. For these reasons, new treatment strategies are required to allow effective directional DBS. During lead implantation, the directional segment should be placed in a "sweet spot," and the orientation of the directional segment is important for programming. Trial-and-error testing of a large number of contacts is unnecessary, and efficient and systematic execution of the programmed procedure is desirable. Recent improvements in imaging technologies have enabled image-guided programming. In the future, optimal stimulations are expected to be programmed by directional recording of local field potentials.

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.

Current medico-psycho-social conditions of patients with West syndrome in Japan.

OBJECTIVE: To unveil current medical and psychosocial conditions of patients with West syndrome in Japan. METHODS: A cross-sectional analysis was performed in patients with West syndrome registered in the Rare Epilepsy Syndrome Registry (RES-R) of Japan. Furthermore, new-onset patients registered in the RES-R were observed prospectively and their outcomes after one and two years of follow-up were compared with data at onset. RESULTS: For the cross-sectional study, 303 patients with West syndrome were included. Seizures (such as spasms, tonic seizures and focal seizures) occurred daily in 69.3% of the patients at registration. Seizure frequency of less than one per year was observed in cases of unknown etiology (22.6%), genetic etiology (23.8%) and malformation of cortical development (MCD; 19.1%). Neurological findings were absent in 37.0%, but a high rate of abnormality was seen in patients with Aicardi syndrome, hypoxic-ischemic encephalopathy (HIE), genetic etiology and MCD other than focal cortical dysplasia, accompanied by a >50% rate of bedridden patients. Abnormal EEG was found in 96.7%, and CT/MRI was abnormal in 62.7%. Treatments included antiepileptic drug therapy (94.3%), hormonal therapy (72.6%), diet therapy (8.3%) and surgery (15.8%). Intellectual/developmental delay was present in 88.4%, and was more severe in patients with Aicardi syndrome, genetic etiology and HIE. Autism spectrum disorder was found in 13.5%. For the longitudinal study, 27 new-onset West syndrome patients were included. The follow-up study revealed improved seizure status after two years in 66.7%, but worsened developmental status in 55.6%, with overall improvement in 51.9%. SIGNIFICANCE: The study reveals the challenging neurological, physical and developmental aspects, as well as intractable seizures, in patients with West syndrome. More than a half of the children showed developmental delay after onset, even though seizures were reduced during the course of the disease.

The intervention of mechanical tactile stimulation modulates somatosensory evoked magnetic fields and cortical oscillations.

The different cortical activity evoked by a mechanical tactile stimulus depends on tactile stimulus patterns, which demonstrates that simple stimuli (i.e., global synchronous stimulation the stimulus area) activate the primary somatosensory cortex alone, whereas complex stimuli (i.e., stimulation while moving in the stimulus area) activate not only the primary somatosensory cortex but also the primary motor area. Here, we investigated whether the effects of a repetitive mechanical tactile stimulation (MS) on somatosensory evoked magnetic fields (SEFs) and cortical oscillations depend on MS patterns. This single-blinded study included 15 healthy participants. Two types interventions of MS lasting 20 min were used: a repetitive global tactile stimulation (RGS) was used to stimulate the finger by using 24 pins installed on a finger pad, whereas a sequential stepwise displacement tactile stimulation (SSDS) was used to stimulate the finger by moving a row of six pins between the left and right sides on the finger pad. Each parameter was measured pre- and post-intervention. The P50m amplitude of the SEF was increased by RGS and decreased by SSDS. The modulation of P50m was correlated with its amplitude before RGS and with the modulation of beta band oscillation at the resting state after SSDS. This study showed that the effects of a 20-min MS on SEFs and cortical oscillations depend on mechanical tactile stimulus patterns. Moreover, our results offer potential for the modulation of tactile functions and selection of stimulation patterns according to cortical states.

Location of emotional corticobulbar tract in the internal capsule.

Emotional facial paresis (EFP) is a rare neurological symptom with intact volitional facial movement. The exact location of emotional corticobulbar tract remains unclear. EFP was frequently recognized following the surgery of stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma in 84.5% of 58 patients. To examine our hypothesis that EFP might be caused by stereotactic trajectories passing through an area including the internal capsule (IC), topographical locations of trajectories were analyzed and compared between the EFP-positive group (n = 41) and the EFP-negative group (n = 8). In the EFP-positive group, multiple (2 to 5) trajectories focused within the genu of the IC in 31 (75.6%) cases, whereas a single trajectory passed through the genu in 8 (19.5%) cases. In the EFP-negative group, 6 (75.0%) of 8 patients had a single trajectory and only one patient had two trajectories passing through the genu of the IC. The ratio between multiple trajectories and a single trajectory relevant to the genu differed significantly between two groups (p < 0.01). The multiple trajectories focusing in the genu have high risks of EFP, whereas a single trajectory seemed to incidentally cause EFP. The results proved our hypothesis and provided a high probability that the emotional corticobulbar tract passes through the genu rather than anterior or posterior limbs of the IC. The location of the emotional corticobulbar tract is in the genu of the IC.

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.

Repeat stereotactic radiofrequency thermocoagulation in patients with hypothalamic hamartoma and seizure recurrence.

OBJECTIVE: To evaluate the feasibility of repeat stereotactic radiofrequency thermocoagulation (re-SRT) for patients with hypothalamic hamartoma (HH) and to clarify clinical and surgical factors for seizure outcomes. METHODS: Hypothalamic hamartoma patients with gelastic seizures (GSs) who underwent SRT were retrospectively reviewed. Seizure outcomes were evaluated separately for GS and other types of seizures (non-GS). Surgical complications were compared between re-SRT and first SRT. Clinical and surgical factors related to both seizure recurrences after first SRT and final seizure outcomes were analyzed. RESULTS: Participants comprised 150 patients (92 males; median age at surgery, 8 years; range, 1.7-50 years). Of those, 122 (81.3%) had non-GS. Forty-three patients (28.7%) underwent re-SRT. Freedom from GS was achieved by first SRT in 103 patients (68.7%), second SRT in 30/40 (67.5%), third SRT in 3/10 (30.0%), and fourth SRT in 2/3 (66.7%). Finally, 135 patients (90.0%) became GS-free. Ninety patients (73.8%) achieved non-GS freedom, with first SRT in all except one case. Transient complications were more frequent with first SRT (118/150, 78.7%) than re-SRT (35/56, 62.5%), whereas persistent complications were more frequent with re-SRT (7/56, 12.5%) than with first SRT (3/150, 2.0%). Multivariate analyses revealed only younger age at surgery (≤1 year) as related to GS recurrence after first SRT, with no variables affecting final GS outcomes. Meanwhile, seizure type (tonic seizure), intellectual disability, and genetic syndromes were significant factors for both non-GS recurrence and final outcomes. Multiple previous treatments were significantly related to final non-GS outcomes as well. Size and subtype of HH and surgical factors were unrelated to seizure outcomes. SIGNIFICANCE: Repeat stereotactic radiofrequency thermocoagulation provides potential opportunities to achieve freedom from recurrent GS, albeit with increased risks of persistent complications. Non-GS and intellectual disability could offer early surgical indications, and repeated ineffective treatments should be avoided.

Surgical strategy for focal cortical dysplasia based on the analysis of the spike onset and peak zones on magnetoencephalography.

OBJECTIVE: The aim of this study was to elucidate the surgical strategy for focal cortical dysplasia (FCD) based on the interictal analysis on magnetoencephalography (MEG). For this purpose, the correlation between the spike onset zone (Sp-OZ) and the spike peak zone (Sp-PZ) on MEG was evaluated to clarify the differences in the Sp-OZ and its correlation with Sp-PZ in FCD subtypes to develop an appropriate surgical strategy. METHODS: Forty-one FCD patients (n = 17 type I, n = 13 type IIa, and n = 11 type IIb) were included. The Sp-OZ was identified by the summation of gradient magnetic-field topography (GMFT) magnitudes at interictal MEG spike onset, and Sp-PZ was defined as the distribution of the equivalent current dipole (ECD) at spike peak. Correlations between Sp-OZ and Sp-PZ distributions were evaluated and compared with clinical factors and seizure outcomes retrospectively. RESULTS: Good seizure outcomes (Engel class I) were obtained significantly more often in patients with FCD type IIb (10/11, 90.9%) than those with type IIa (4/13, 30.8%; p = 0.003) and type I (6/17, 35.3%; p = 0.004). The Sp-OZ was significantly smaller (1 or 2 gyri) in type IIb (10, 90.9%) than in type IIa (4, 30.8%; p = 0.003) or type I (9, 53.0%; p = 0.036). Concordant correlations between the Sp-OZ and Sp-PZ were significantly more frequent in type IIb (7, 63.6%) than in type IIa (1, 7.7%; p = 0.015) or type I (1, 5.8%; p = 0.004). Complete resection of the Sp-OZ achieved significantly better seizure outcomes (Engel class I: 9/10, 90%) than incomplete resection (11/31, 35.5%) (p = 0.003). In contrast, complete resection of the Sp-PZ showed no significant difference in good seizure outcomes (9/13, 69.2%) compared with incomplete resection (11/28, 39.3%). CONCLUSIONS: The Sp-OZ detected by MEG using GMFT and its correlation with Sp-PZ were related to FCD subtypes. A discordant distribution between Sp-OZ and Sp-PZ in type I and IIa FCD indicated an extensive epileptogenic zone and a complex epileptic network. Type IIb showed a restricted epileptogenic zone with the smaller Sp-OZ and concordance between Sp-OZ and Sp-PZ. Complete resection of the Sp-OZ provided significantly better seizure outcomes than incomplete resection. Complete resection of the Sp-PZ was not related to seizure outcomes. There was a definite difference in the epileptogenic zone among FCD subtypes; hence, an individual surgical strategy taking into account the correlation between the Sp-OZ and Sp-PZ should be considered.

Pathogenic variants of DYNC2H1, KIAA0556, and PTPN11 associated with hypothalamic hamartoma.

OBJECTIVE: Intensive genetic analysis was performed to reveal comprehensive molecular insights into hypothalamic hamartoma (HH). METHODS: Thirty-eight individuals with HH were investigated by whole exome sequencing, target capture-based deep sequencing, or single nucleotide polymorphism (SNP) array using DNA extracted from blood leukocytes or HH samples. RESULTS: We identified a germline variant of KIAA0556, which encodes a ciliary protein, and 2 somatic variants of PTPN11, which forms part of the RAS/mitogen-activated protein kinase (MAPK) pathway, as well as variants in known genes associated with HH. An SNP array identified (among 3 patients) one germline copy-neutral loss of heterozygosity (cnLOH) at 6p22.3-p21.31 and 2 somatic cnLOH; one at 11q12.2-q25 that included DYNC2H1, which encodes a ciliary motor protein, and the other at 17p13.3-p11.2. A germline heterozygous variant and an identical somatic variant of DYNC2H1 arising from cnLOH at 11q12.2-q25 were confirmed in one patient (whose HH tissue, therefore, contains biallelic variants of DYNC2H1). Furthermore, a combination of a germline and a somatic DYNC2H1 variant was detected in another patient. CONCLUSIONS: Overall, our cohort identified germline/somatic alterations in 34% (13/38) of patients with HH. Disruption of the Shh signaling pathway associated with cilia or the RAS/MAPK pathway may lead to the development of HH.

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.

Change-Driven M100 Component in the Bilateral Secondary Somatosensory Cortex: A Magnetoencephalographic Study.

Our previous demonstration that the M100 somatosensory evoked magnetic field (SEF) has a similar temporal profile, dipole orientation and source location whether induced by activation (ON-M100) or deactivation (OFF-M100) of electrical stimulation suggests a common cortical system to detect sensory change. While we have not recorded such change-driven components earlier than M100 using electrical stimulation, clear M50 responses were reported using both ON and OFF mechanical stimulation (Onishi et al. in Clin Neurophysiol 121:588-593, 2010). To examine the significance of M50 and M100 in reflecting the detection of somatosensory changes, we recorded these waveforms in 12 healthy subjects (9 males and 3 females) by magnetoencephalography in response to mechanical stimulation from a piezoelectric actuator. Onset and offset (ON and OFF) stimuli were randomly presented with three preceding steady state (PSS) durations (0.5, 1.5 and 3 s) in one consecutive session. Results revealed that (i) onset and offset somatosensory events elicited clear M50 and M100 components; (ii) M50 and M100 components had distinct origins, with M50 localised to the contralateral primary somatosensory cortex (cS1) and M100 to the bilateral secondary somatosensory cortex (iS2, cS2); and (iii) the amplitude of M50 in cS1 was independent of the PSS durations, whereas that of M100 in S2 was dependent on the PSS durations for both ON and OFF events. These findings suggest that the M50 amplitude in cS1 reflects the number of activated mechanoreceptors during Onset and Offset, whereas the M100 amplitude in S2 reflects change detection based on sensory memory for Onset and Offset stimuli at least in part. We demonstrated that the M50 in cS1 and M100 in S2 plays different roles in the change detection system in somatosensory modality.

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.

Pathophysiological Characteristics Associated With Epileptogenesis in Human Hippocampal Sclerosis.

Mesial temporal lobe epilepsy (MTLE) is the most frequent focal epileptic syndrome in adults, and the majority of seizures originate primarily from the hippocampus. The resected hippocampal tissue often shows severe neuronal loss, a condition referred to as hippocampal sclerosis (HS). In order to understand hippocampal epileptogenesis in MTLE, it seems important to clarify any discrepancies between the clinical and pathological features of affected patients. Here we investigated epileptiform activities ex vivo using living hippocampal tissue taken from patients with MTLE. Flavoprotein fluorescence imaging and local field potential recordings revealed that epileptiform activities developed from the subiculum. Moreover, physiological and morphological experiments revealed possible impairment of K+ clearance in the subiculum affected by HS. Stimulation of mossy fibers induced recurrent trans-synaptic activity in the granule cell layer of the dentate gyrus, suggesting that mossy fiber sprouting in HS also contributes to the epileptogenic mechanism. These results indicate that pathophysiological alterations involving the subiculum and dentate gyrus could be responsible for epileptogenesis in patients with MTLE.

Additional resective surgery after the failure of initial surgery in patients with intractable epilepsy.

Objectives There are three conceivable reasons for the failure of resective surgery for intractable epilepsy: incomplete resection of the epileptogenic zone including or overlapping with eloquent area (group A); incorrect determination of the epileptogenic zone prior to the first surgery (group B); and the development of a new epileptic focus after the first surgery (group C). We examined the relationship between the reason for failure of initial surgery and patient outcomes after repeated surgical resection. Methods The study included 18 patients (5.1%) underwent additional surgery after failure of the initial operation. Post-operative outcomes, complications and other clinical data were collected by retrospective chart review. Results Four patients (22.2%) were assigned to group A, 13 (72.2%) were assigned to group B, and 1 patient was assigned to group C (5.6%). Six patients (40.0%) were seizure-free for 2 or more years after additional surgery. In group B, 11 patients underwent additional resection of the cortex adjacent to the previously resected area and 2 underwent re-operation involving a site distant from the previously resected area; notably, the latter 2 patients did not achieve seizure-free status post-surgery. After the first operation, only one patient (group A) experienced transient paresis; after additional surgery, 10 of 18 patients (56%; 3 group A, 6 group B, and 1 group C) experienced various complications. Discussion Although additional resective surgery provided freedom from seizures in about 40% of the patients, it is important to weigh a high risk of complications against possible benefits when considering additional surgery.