Yosuke Ito

MRI-guided stereotactic radiofrequency thermocoagulation for 100 hypothalamic hamartomas

OBJECT The aim of this study was to elucidate the invasiveness, effectiveness, and feasibility of MRI-guided stereotactic radiofrequency thermocoagulation (SRT) for hypothalamic hamartoma (HH). METHODS The authors examined the clinical records of 100 consecutive patients (66 male and 34 female) with intractable gelastic seizures (GS) caused by HH, who underwent SRT as a sole surgical treatment between 1997 and 2013. The median duration of follow-up was 3 years (range 1-17 years). Seventy cases involved pediatric patients. Ninety percent of patients also had other types of seizures (non-GS). The maximum diameter of the HHs ranged from 5 to 80 mm (median 15 mm), and 15 of the tumors were giant HHs with a diameter of 30 mm or more. Comorbidities included precocious puberty (33.0%), behavioral disorder (49.0%), and mental retardation (50.0%). RESULTS A total of 140 SRT procedures were performed. There was no adaptive restriction for the giant or the subtype of HH, regardless of any prior history of surgical treatment or comorbidities. Patients in this case series exhibited delayed precocious puberty (9.0%), pituitary dysfunction (2.0%), and weight gain (7.0%), besides the transient hypothalamic symptoms after SRT. Freedom from GS was achieved in 86.0% of patients, freedom from other types of seizures in 78.9%, and freedom from all seizures in 71.0%. Repeat surgeries were not effective for non-GS. Seizure freedom led to disappearance of behavioral disorders and to intellectual improvement. CONCLUSIONS The present SRT procedure is a minimally invasive and highly effective surgical procedure without adaptive limitations. SRT involves only a single surgical procedure appropriate for all forms of epileptogenic HH and should be considered in patients with an early history of GS.

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.

Ephaptic transmission is the origin of the abnormal muscle response seen in hemifacial spasm.

OBJECTIVE In patients with hemifacial spasm, stimulation of a branch of the affected facial nerve elicits an abnormal response in the muscles innervated by another branch. We tested the hypothesis that this anomaly results from lateral spread of impulses from one motor axon to another at the site of the nerve compression by the offending artery. METHODS In a preoperative study of 21 patients, we delivered a series of stimuli, in short increments, successively distally along the temporal branch of the facial nerve to record abnormal muscle responses from the orbicularis oculi and mentalis muscles. In intraoperative monitoring of 10 patients during microvascular decompression, we monitored propagating nerve action potentials with a handheld electrode placed on the facial nerve 3mm distal to the vascular compression site. RESULTS With incremental shifts of stimulating points distally, the latency of abnormal muscle responses increased by 0.3±0.1ms/cm. This finding implicates the antidromic motor impulse as the trigger for lateral spread. The nerve action potentials recorded during surgery comprised the initial antidromic signal followed by one or more additional peaks. The latter immediately abated, together with abnormal muscle responses, after microvascular decompression. Thus, the secondary peaks must represent the orthodromic impulses generated by ephaptic transmission. An average inter-peak interval of 1.1ms between the first and secondary peaks is consistent with the estimated conduction time from the stimulation point to the site of vascular compression but not to the facial nucleus and return. CONCLUSION An abnormal muscle response results from lateral spread of impulses between motor axons at the site of vascular compression rather than at the facial nucleus. SIGNIFICANCE This study establishes the mechanism of lateral spread responsible for abnormal muscle responses and contributes to the understanding of pathophysiology underlying hemifacial spasm.

Features of amygdala in patients with mesial temporal lobe epilepsy and hippocampal sclerosis: An MRI volumetric and histopathological study

OBJECTIVE It is well-known that there is a correlation between the neuropathological grade of hippocampal sclerosis (HS) and neuroradiological atrophy of the hippocampus in mesial temporal lobe epilepsy (mTLE) patients. However, there is no strict definition or criterion regarding neuron loss and atrophy of the amygdala neighboring the hippocampus. We examined the relationship between HS and neuronal loss in the amygdala. MATERIALS AND METHODS Nineteen mTLE patients with neuropathological proof of HS were assigned to Group A, while seven mTLE patients without HS were assigned to Group B. We used FreeSurfer software to measure amygdala volume automatically based on pre-operation magnetic resonance images. Neurons observed using Klüver-Barrera (KB) staining in resected amygdala tissue were counted. and the extent of immunostaining with stress marker antibodies was semiquantitatively evaluated. RESULTS There was no significant difference in amygdala volume between the two groups (Group A: 1.41±0.24; Group B: 1.41±0.29cm3; p=0.98), nor in the neuron cellularity of resected amygdala specimens (Group A: 3.98±0.97; Group B: 3.67±0.67 10×-4 number of neurons/μm2; p=0.40). However, the HSP70 level, representing acute stress against epilepsy, in Group A patients was significantly larger than that in Group B. There was no significant difference in the level of Bcl-2, which is known as a protein that inhibits cell death, between the two groups. CONCLUSIONS Neuronal loss and volume loss in the amygdala may not necessarily follow hippocampal sclerosis. From the analysis of stress proteins, epileptic attacks are as likely to damage the amygdala as the hippocampus but do not lead to neuronal death in the amygdala.

Analysis of ictal magnetoencephalography using gradient magnetic-field topography (GMFT) in patients with neocortical epilepsy

OBJECTIVE We aimed to validate the usefulness of gradient magnetic-field topography (GMFT) for analysis of ictal magnetoencephalography (MEG) in patients with neocortical epilepsy. METHODS We identified 13 patients presenting with an ictal event during preoperative MEG. We applied equivalent current dipole (ECD) estimation and GMFT to detect and localize the ictal MEG onset, and compared these methods with the ictal onset zone (IOZ) derived from chronic intracranial electroencephalography. The surgical resection areas and outcomes were also evaluated. RESULTS GMFT detected and localized the ictal MEG onset in all patients, whereas ECD estimation showed localized ECDs in only 2. The delineation of GMFT was concordant with the IOZ at the gyral-unit level in 10 of 12 patients (83.3%). The detectability and precision of delineation of ictal MEG activity by GMFT were significantly superior to those of ECD (p<0.05 and p<0.01, respectively). Complete resection of the IOZ in the concordant group provided seizure freedom in 3 patients, whereas seizures remained in 9 patients who had incomplete resections. CONCLUSIONS Because of its higher spatial resolution, GMFT of ictal MEG is superior to conventional ECD estimation in patients with neocortical epilepsy. SIGNIFICANCE Ictal MEG study is a useful tool to estimate the seizure onset in patients with neocortical epilepsy.

Spatiotemporal Accuracy of Gradient Magnetic-Field Topography (GMFT) Confirmed by Simultaneous Magnetoencephalography and Intracranial Electroencephalography Recordings in Patients with Intractable Epilepsy

Gradient magnetic-field topography (GMFT) is one method for analyzing magnetoencephalography (MEG) and representing the spatiotemporal dynamics of activity on the brain surface. In contrast to spatial filters, GMFT does not include a process reconstructing sources by mixing sensor signals with adequate weighting. Consequently, noisy sensors have localized and limited effects on the results, and GMFT can handle MEG recordings with low signal-to-noise ratio. This property is derived from the principle of the planar-type gradiometer, which obtains maximum gradient magnetic-field signals just above the electrical current source. We assumed that this characteristic allows GMFT to represent even faint changes in brain activities that cannot be achieved with conventional equivalent current dipole analysis or spatial filters. GMFT is thus hypothesized to represent brain surface activities from onset to propagation of epileptic discharges. This study aimed to validate the spatiotemporal accuracy of GMFT by analyzing epileptic activities using simultaneous MEG and intracranial electroencephalography (iEEG) recordings. Participants in this study comprised 12 patients with intractable epilepsy. Epileptic spikes simultaneously detected on both MEG and iEEG were analyzed by GMFT and voltage topography (VT), respectively. Discrepancies in spatial distribution between GMFT and VT were evaluated for each epileptic spike. On the lateral cortices, areas of GMFT activity onset were almost concordant with VT activities arising at the gyral unit level (concordance rate, 66.7–100%). Median time lag between GMFT and VT at onset in each patient was 11.0–42.0 ms. On the temporal base, VT represented basal activities, whereas GMFT failed but instead represented propagated activities of the lateral temporal cortices. Activities limited to within the basal temporal or deep brain region were not reflected on GMFT. In conclusion, GMFT appears to accurately represent brain activities of the lateral cortices at the gyral unit level. The slight time lag between GMFT and VT is likely attributable to differences in the detection principles underlying MEG and iEEG. GMFT has great potential for investigating the spatiotemporal dynamics of lateral brain surface activities.

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

Abstract 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.

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

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).