Progressive myoclonic epilepsy as an expanding phenotype of NGLY1-associated congenital deglycosylation disorder: A case report and review of the literature.

INTRODUCTION: NGLY1-associated congenital disorder of deglycosylation (CDDG1: OMIM #615273) is a rare autosomal recessive disorder caused by a functional impairment of endoplasmic reticulum in degradation of glycoproteins. Neurocognitive dysfunctions have been documented in patients with CDDG1; however, deteriorating phenotypes of affected individuals remain elusive. CASE PRESENTATION: A Japanese boy with delayed psychomotor development showed ataxic movements from age 5 years and myoclonic seizures from age 12 years. Appetite loss, motor and cognitive decline became evident at age 12 years. Electrophysiological studies identified paroxysmal discharges on myoclonic seizure and a giant somatosensory evoked potential. Perampanel was effective for controlling myoclonic seizures. Exome sequencing revealed that the patient carried compound heterozygous variants in NGLY1, NM_018297.4: c.857G > A and c.-17_12del, which were inherited from mother and father, respectively. A literature review confirmed that myoclonic seizures were observed in 28.5% of patients with epilepsy. No other patients had progressive myoclonic epilepsy or cognitive decline in association with loss-of-function variations in NGLY1. CONCLUSION: Our data provides evidence that a group of patients with CDDG1 manifest slowly progressive myoclonic epilepsy and cognitive decline during the long-term clinical course.

A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1.

We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep-onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA-DRB1*15:01-DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1.

Mandibular and chin electrodes as a supplemental recording for detection of epileptiform discharges in mesial temporal lobe epilepsy.

Background: We previously demonstrated the usefulness of periorbital electrodes in supplemental recording to detect epileptiform discharges in patients with mesial temporal lobe epilepsy (MTLE). However, eye movement may disturb periorbital electrode recording. To overcome this, we developed mandibular (MA) and chin (CH) electrodes and examined whether these electrodes could detect hippocampal epileptiform discharges. Methods: This study included a patient with MTLE, who underwent insertion of bilateral hippocampal depth electrodes and video-electroencephalographic (EEG) monitoring with simultaneous recordings of extra- and intracranial EEG as part of a presurgical evaluation. We examined 100 consecutive interictal epileptiform discharges (IEDs) recorded from the hippocampus and two ictal discharges. We compared these IEDs from intracranial electrodes with those from extracranial electrodes such as MA and CH electrodes in addition to F7/8 and A1/2 of international EEG 10-20 system, T1/2 of Silverman, and periorbital electrodes. We analyzed the number, rate of laterality concordance, and mean amplitude of IEDs detected in extracranial EEG monitoring and characteristics of IEDs on the MA and CH electrodes. Results: The MA and CH electrodes had nearly the same detection rate of hippocampal IEDs from other extracranial electrodes without contamination by eye movement. Three IEDs, not detected by A1/2 and T1/2, could be detected using the MA and CH electrodes. In two ictal events, the MA and CH electrodes detected the ictal discharges from the hippocampal onset as well as other extracranial electrodes. Conclusion: The MA and CH electrodes could detect hippocampal epileptiform discharges as well as A1/A2, T1/T2, and peri-orbital electrodes. These electrodes could serve as supplementary recording tools for detecting epileptiform discharges in MTLE.

Detection of ictal and periictal hyperperfusion with subtraction of ictal-interictal 1.5-Tesla pulsed arterial spin labeling images co-registered to conventional magnetic resonance images (SIACOM).

Background: Our recent report showed that 1.5-T pulsed arterial spin labeling (ASL) magnetic resonance (MR) perfusion imaging (1.5-T Pulsed ASL [PASL]), which is widely available in the field of neuroemergency, is useful for detecting ictal hyperperfusion. However, the visualization of intravascular ASL signals, namely, arterial transit artifact (ATA), is more remarkable than that of 3-T pseudocontinuous ASL and is easily confused with focal hyperperfusion. To eliminate ATA and enhance the detectability of (peri) ictal hyperperfusion, we developed the subtraction of ictal-interictal 1.5-T PASL images co-registered to conventional MR images (SIACOM). Methods: We retrospectively analyzed the SIACOM findings in four patients who underwent ASL during both (peri) ictal and interictal states and examined the detectability for (peri) ictal hyperperfusion. Results: In all patients, the ATA of the major arteries was almost eliminated from the subtraction image of the ictal-interictal ASL. In patients 1 and 2 with focal epilepsy, SIACOM revealed a tight anatomical relationship between the epileptogenic lesion and the hyperperfusion area compared with the original ASL image. In patient 3 with situation-related seizures, SIACOM detected minute hyperperfusion at the site coinciding with the abnormal electroencephalogram area. SIACOM of patient 4 with generalized epilepsy diagnosed ATA of the right middle cerebral artery, which was initially thought to be focal hyperperfusion on the original ASL image. Conclusion: Although it is necessary to examine several patients, SIACOM can eliminate most of the depiction of ATA and clearly demonstrate the pathophysiology of each epileptic seizure.

High-echoic line tracing of transthoracic echocardiography accurately assesses right ventricular enlargement in adult patients with atrial septal defect.

Accurate measurement of right ventricular (RV) size using transthoracic echocardiography (TTE) is important for evaluating the severity of congenital heart diseases. The RV end-diastolic area index (RVEDAi) determined using TTE is used to assess RV dilatation; however, the tracing line of the RVEDAi has not been clearly defined by the guidelines. This study aimed to determine the exact tracing method for RVEDAi using TTE. We retrospectively studied 107 patients with atrial septal defects who underwent cardiac magnetic resonance imaging (CMR) and TTE. We measured the RVEDAi according to isoechoic and high-echoic lines, and compared it with the RVEDAi measured using CMR. The isoechoic line was defined as the isoechoic endocardial border of the RV free wall, whereas the high-echoic line was defined as the high-echoic endocardial border of the RV free wall more outside than the isoechoic line. RVEDAi measured using high-echoic line (high-RVEDAi) was more accurately related to RVEDAi measured using CMR than that measured using isoechoic line (iso-RVEDAi). The difference in the high-RVEDAi was 0.3 cm2/m2, and the limit of agreement (LOA) was - 3.7 to 4.3 cm2/m2. With regard to inter-observer variability, high-RVEDAi was superior to iso-RVEDAi. High-RVEDAi had greater agreement with CMR-RVEDAi than with iso-RVEDAi. High-RVEDAi can become the standard measurement of RV size using two-dimensional TTE.

Reflection of the Ictal Electrocorticographic Discharges Confined to the Medial Temporal Lobe to the Scalp-Recorded Electroencephalogram.

Objective: Previous reports on the simultaneous recording of electroencephalography (EEG) and electrocorticography (ECoG) have demonstrated that, in patients with temporal lobe epilepsy (TLE), ictal ECoG discharges with an amplitude as high as 1000 µV originating from the medial temporal lobe could not be recorded on EEG. In contrast, ictal EEG discharges were recorded after ictal ECoG discharges propagated to the lateral temporal lobe. Here, we report a case of TLE in which the ictal EEG discharges, corresponding to ictal ECoG discharges confined to the medial temporal lobe, were recorded. Case report: In the present case, ictal EEG discharges were hardly recognized when the amplitude of the ECoG discharges was less than 1500 µV. During the evolution and burst suppression phase, corresponding to highly synchronized ECoG discharges with amplitudes greater than 1500 to 2000 µV, rhythmic negative waves with the same frequency were clearly recorded both on the lateral temporal lobe and scalp. The amplitude of the lateral temporal ECoG was approximately one-tenth of that of the medial temporal ECoG. The amplitude of the scalp EEG was approximately one-tenth of that of the lateral temporal ECoG. Conclusions: Highly synchronized ictal ECoG discharges with high amplitude of greater than 1500 to 2000 µV in the medial temporal lobe could be recorded on the scalp as ictal EEG discharges via volume conduction.

The effect of interictal epileptic discharges and following spindles on motor sequence learning in epilepsy patients.

Purpose: Interictal epileptic discharges (IEDs) are known to affect cognitive function in patients with epilepsy, but the mechanism has not been elucidated. Sleep spindles appearing in synchronization with IEDs were recently demonstrated to impair memory consolidation in rat, but this has not been investigated in humans. On the other hand, the increase of sleep spindles at night after learning is positively correlated with amplified learning effects during sleep for motor sequence learning. In this study, we examined the effects of IEDs and IED-coupled spindles on motor sequence learning in patients with epilepsy, and clarified their pathological significance. Materials and methods: Patients undergoing long-term video-electroencephalography (LT-VEEG) at our hospital from June 2019 to November 2021 and age-matched healthy subjects were recruited. Motor sequence learning consisting of a finger-tapping task was performed before bedtime and the next morning, and the improvement rate of performance was defined as the sleep-dependent learning effect. We searched for factors associated with the changes in learning effect observed between the periods of when antiseizure medications (ASMs) were withdrawn for LT-VEEG and when they were returned to usual doses after LT-VEEG. Results: Excluding six patients who had epileptic seizures at night after learning, nine patients and 11 healthy subjects were included in the study. In the patient group, there was no significant learning effect when ASMs were withdrawn. The changes in learning effect of the patient group during ASM withdrawal were not correlated with changes in sleep duration or IED density; however, they were significantly negatively correlated with changes in IED-coupled spindle density. Conclusion: We found that the increase of IED-coupled spindles correlated with the decrease of sleep-dependent learning effects of procedural memory. Pathological IED-coupled sleep spindles could hinder memory consolidation, that is dependent on physiological sleep spindles, resulting in cognitive dysfunction in patients with epilepsy.

Stereo-electroencephalography evidence of an eccentrically located seizure-onset zone around a polymorphous low-grade neuroepithelial tumor of the young: illustrative case.

BACKGROUND: Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a newly identified low-grade brain tumor with frequent epileptic presentation. Despite the facilitated use of invasive electroencephalography owing to the growing availability of stereo-electroencephalography (SEEG), intracranial features of tumor-related seizures are still scarcely described. This report provides the first description of SEEG-recorded seizures in PLNTY to provide an insight into its surgical strategy. OBSERVATIONS: Spontaneous clinical seizures were recorded with SEEG in a young adult patient with drug-resistant epilepsy associated with a PLNTY in the left lateral temporal cortex. The seizure onset was characterized by low-voltage fast activity (LVFA) and showed eccentric localization with respect to the tumor: LVFA was localized in the anterior portion of the tumor and spread toward the adjacent polar cortex. The language risks associated with the resection of the posterior temporal cortex could thus be minimized. LESSONS: PLNTY can show a focal and eccentric seizure-onset zone around the tumor. The present findings serve to improve the functional and seizure outcomes using the staged invasive approach in PLNTY.

Postoperative striatal degeneration: a hitherto unrecognized impact of frontal disconnection surgery for drug-resistant epilepsy. Illustrative cases.

BACKGROUND: Frontal disconnection surgery is a useful surgical option for patients with frontal epilepsy whose seizure onset zones are exceedingly large and thus are not amenable to conventional resective surgery. While it has the advantage of avoiding sequelae stemming from a large resection cavity, the impact of radical anatomofunctional disconnection of such a vast frontal region is not fully understood. OBSERVATIONS: The authors have identified secondary degeneration in the striatum ipsilateral to the frontal disconnection surgery in two adult patients who had otherwise favorable postoperative outcomes following the surgery. On serial postoperative magnetic resonance imaging, the striatum showed transient restricted diffusion in the caudate head and rostral putamen around several weeks postoperatively and subsequent atrophy in the caudate head. The affected striatal regions (i.e., the anterior portion of the striatum) were congruent with the known fronto-striatal connectivity corresponding to the disconnected frontal regions anterior to the primary and supplementary motor areas. Both patients achieved 1-year seizure freedom without apparent disability related to the surgery. LESSONS: The benign postoperative course despite the marked degenerative changes in the ipsilateral striatum supports the feasibility of the frontal disconnection surgery in otherwise inoperable patients with broad frontal epileptogenicity.

Atrophy of the hippocampal CA1 subfield relates to long-term forgetting in focal epilepsy.

OBJECTIVE: The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy. METHODS: We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10 min, and 1 week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses. RESULTS: Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10 min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (ß = 7.76; Bonferroni-corrected p = 0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate. SIGNIFICANCE: Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Shadowboxing-induced reflex seizures in a patient with focal epilepsy.

Exercise-induced reflex seizures are a rare form of reflex seizures that are exclusively induced by a specific type of exercise. Many patients with exercise-induced reflex seizures exhibit drug-resistance, and are therefore advised to avoid the triggering exercise. Here, we describe a focal epilepsy patient with shadowboxing-induced reflex seizures. His semiology included focal aware seizures with speech and behavioral arrest that evolved to head version to the right, preceded by cephalic aura. We identified a specific motion that induced these seizures during shadowboxing using video-electroencephalographic recording, and the patient was able to continue boxing by avoiding this motion. We speculate that a broad brain network may be the pathological substrate of his exercise-induced reflex seizures. Identification of the specific motion that induces exercise-induced reflex seizures is useful for not only understanding the underlying pathophysiology, but also for minimizing the therapeutic restriction of the exercise.

Implications and limitations of magnetic resonance perfusion imaging with 1.5-Tesla pulsed arterial spin labeling in detecting ictal hyperperfusion during non-convulsive status epileptics.

Background: Recent our reports showed that 3-T pseudocontinuous arterial spin labeling (3-T pCASL) magnetic resonance perfusion imaging with dual post labeling delay (PLD) of 1.5 and 2.5 s clearly demonstrated the hemodynamics of ictal hyperperfusion associated with non-convulsive status epilepticus (NCSE). We aimed to examine the utility of 1.5-T pulsed arterial spin labeling (1.5-T PASL), which is more widely available for daily clinical use, for detecting ictal hyperperfusion. Methods: We retrospectively analyzed the findings of 1.5-T PASL with dual PLD of 1.5 s and 2.0 s in six patients and compared the findings with ictal electroencephalographic (EEG) findings. Results: In patients 1 and 2, we observed the repeated occurrence of ictal discharges (RID) on EEG. In patient 1, with PLDs of 1.5 s and 2.0 s, ictal ASL hyperperfusion was observed at the site that matched the RID localization. In patient 2, the RID amplitude was extremely low, with no ictal ASL hyperperfusion. In patient 3 with lateralized periodic discharges (LPD), we observed ictal ASL hyperperfusion at the site of maximal LPD amplitude, which was apparent at a PLD of 2.0 s but not 1.5 sec. Among three patients with rhythmic delta activity (RDA) of frequencies <2.5 Hz (Patients 4-6), we observed obvious and slight increases in ASL signals in patients 4 and 5 with NCSE, respectively. However, there was no apparent change in ASL signals in patient 6 with possible NCSE. Conclusion: The detection of ictal hyperperfusion on 1.5-T PASL might depend on the electrophysiological intensity of the epileptic ictus, which seemed to be more prominent on 1.5-T PASL than on 3-T pCASL. The 1.5-T PASL with dual PLDs showed the hemodynamics of ictal hyperperfusion in patients with RID and LPD. However, it may not be visualized in patients with extremely low amplitude RID or RDA (frequencies <2.5 Hz).

Simultaneous Electroencephalographic and Electocorticographic Recordings of Lateralized Periodic Discharges in Temporal Lobe Epilepsy.

OBJECTIVE: Lateralized periodic discharges (LPDs), which constitute an abnormal electroencephalographic (EEG) pattern, are most often observed in critically ill patients with acute pathological conditions, and are less frequently observed in chronic conditions such as focal epilepsies, including temporal lobe epilepsy (TLE). Here we aim to explore the pathophysiological mechanism of LPD in TLE. METHODS: We retrospectively selected 3 patients with drug-resistant TLE who simultaneously underwent EEG and electrocorticography (ECoG) and demonstrated LPDs. We analyzed the correlation between the EEG and ECoG findings. RESULTS: In patients 1 and 2, LPDs were recorded in the temporal region of the scalp during the interictal periods, when repeated spikes followed by slow waves (spike-and-wave complexes; SWs) and periodic discharges (PDs) with amplitudes of >600 to 800 µV appeared in the lateral temporal lobe over a cortical area of >10 cm2. In patient 3, when the ictal discharges persisted and were confined to the medial temporal lobe, repeated SWs were provoked on the lateral temporal lobe. When repeated SWs with amplitudes of >800 µV appeared in an area of the lateral temporal lobe of >10 cm2, the corresponding EEG discharges appeared on the temporal scalp. CONCLUSIONS: LPDs in patients with TLE originate from repeated SWs and PDs of the lateral temporal lobe, which might represent a highly irritable state of the lateral temporal cortex during both interictal and ictal periods.

Comparison of Acute Withdrawal and Slow Taper of Antiseizure Medications during Video Electroencephalographic Monitoring: Efficacy for Shortening of Hospital Stay.

Antiepileptic medications (ASMs) are withdrawn at the epilepsy monitoring unit to facilitate seizure recordings. The effect of rapid tapering of ASMs on the length of hospital stay has not been well documented. We compared the mean length of hospital stay between patients who underwent acute ASM withdrawal and slow dose tapering during long-term video electroencephalography (EEG) monitoring. We retrospectively investigated 57 consecutive patients admitted to the epilepsy monitoring unit regarding the mean length of hospital stay in the acute ASM withdrawal group (n = 30) and slow-taper group (n = 27). In the acute-withdrawal group, all ASMs were discontinued once the patients were admitted. In the slow-taper group, the doses of ASMs were gradually reduced by 15-30% daily. We also evaluated the safety of the acute-withdrawal and slow-taper protocols. The mean lengths of hospital stay were 3.8 ± 1.92 and 5.2 ± 0.69 days in the acute-withdrawal and slow-taper groups, respectively (p < 0.005). No severe adverse events, including status epilepticus, were observed. Acute ASM withdrawal has the advantage of significantly reducing the length of hospital stay over slow tapering, without any severe adverse effects.

Bilateral Representation of Sensorimotor Responses in Benign Adult Familial Myoclonus Epilepsy: An MEG Study.

Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30-50 ms and 30-100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus.

Characteristics of olfactory dysfunction in patients with temporal lobe epilepsy.

OBJECTIVE: To determine the characteristics of olfactory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS: Odor identification was assessed using the odor stick identification test for Japanese (OSIT-J, full score 12 points) in 65 patients with TLE and in 74 controls. RESULTS: The mean OSIT-J score was significantly lower in patients with TLE (mean ±â€¯SD = 8.1 ±â€¯2.8; median = 9) than in the control subjects (mean ±â€¯SD = 10.6 ±â€¯1.1; median = 11) (P < 0.005). Olfactory dysfunction (hyposmia/anosmia) was associated with bilateral seizure foci and older age of onset in TLE. Patients who underwent temporal lobectomy for hippocampal sclerosis did not show significant decline after long-term recovery. The Indian ink part of OSIT-J was useful for the detection of olfactory deficits in patients with TLE (sensitivity = 47%, specificity = 93%). Patients with TLE tended to have preserved olfactory ability for stimulating odors and for familiar odors of daily life. SIGNIFICANCE: We observed characteristic odor identification deficits for individual odors used in OSIT-J. Our study findings provide deeper insight into the underlying mechanism of olfactory function in patients with TLE and may be beneficial in the clinical management of these patients.

Endonasal endoscopic surgery for temporal lobe epilepsy associated with sphenoidal encephalocele.

BACKGROUND: Temporal lobe epilepsy (TLE) associated with temporal lobe encephalocele is rare, and the precise epileptogenic mechanisms and surgical strategies for such cases are still unknown. Although the previous studies have reported good seizure outcomes following chronic subdural electrode recording through invasive craniotomy, only few studies have reported successful epilepsy surgery through endoscopic endonasal lesionectomy. CASE DESCRIPTION: An 18-year-old man developed generalized convulsions at the age of 15 years. Despite treatment with optimal doses of antiepileptic drugs, episodes of speech and reading difficulties were observed 2-3 times per week. Long-term video electroencephalogram (EEG) revealed ictal activities starting from the left anterior temporal region. Magnetic resonance imaging revealed a temporal lobe encephalocele in the left lateral fossa of the sphenoidal sinus (sphenoidal encephalocele). Through the endoscopic endonasal approach, the tip of the encephalocele was exposed. A depth electrode was inserted into the encephalocele, which showed frequent spikes superimposed with high-frequency oscillations (HFOs) suggesting intrinsic epileptogenicity. The encephalocele was resected 8 mm from the tip. Twelve months postoperatively, the patient had no recurrence of seizures on tapering of the medication. CONCLUSION: TLE associated with sphenoidal encephalocele could be controlled with endoscopic endonasal lesionectomy, after confirming the high epileptogenicity with analysis of HFOs of intraoperative EEG recorded using an intralesional depth electrode.

Rapidly spreading seizures arise from large-scale functional brain networks in focal epilepsy.

It remains unclear whether epileptogenic networks in focal epilepsy develop on physiological networks. This work aimed to explore the association between the rapid spread of ictal fast activity (IFA), a proposed biomarker for epileptogenic networks, and the functional connectivity or networks of healthy subjects. We reviewed 45 patients with focal epilepsy who underwent electrocorticographic (ECoG) recordings to identify the patients showing the rapid spread of IFA. IFA power was quantified as normalized beta-gamma band power. Using published resting-state functional magnetic resonance imaging databases, we estimated resting-state functional connectivity of healthy subjects (RSFC-HS) and resting-state networks of healthy subjects (RSNs-HS) at the locations corresponding to the patients' electrodes. We predicted the IFA power of each electrode based on RSFC-HS between electrode locations (RSFC-HS-based prediction) using a recently developed method, termed activity flow mapping. RSNs-HS were identified using seed-based and atlas-based methods. We compared IFA power with RSFC-HS-based prediction or RSNs-HS using non-parametric correlation coefficients. RSFC and seed-based RSNs of each patient (RSFC-PT and seed-based RSNs-PT) were also estimated using interictal ECoG data and compared with IFA power in the same way as RSFC-HS and seed-based RSNs-HS. Spatial autocorrelation-preserving randomization tests were performed for significance testing. Nine patients met the inclusion criteria. None of the patients had reflex seizures. Six patients showed pathological evidence of a structural etiology. In total, we analyzed 49 seizures (2-13 seizures per patient). We observed significant correlations between IFA power and RSFC-HS-based prediction, seed-based RSNs-HS, or atlas-based RSNs-HS in 28 (57.1%), 21 (42.9%), and 28 (57.1%) seizures, respectively. Thirty-two (65.3%) seizures showed a significant correlation with either seed-based or atlas-based RSNs-HS, but this ratio varied across patients: 27 (93.1%) of 29 seizures in six patients correlated with either of them. Among atlas-based RSNs-HS, correlated RSNs-HS with IFA power included the default mode, control, dorsal attention, somatomotor, and temporal-parietal networks. We could not obtain RSFC-PT and RSNs-PT in one patient due to frequent interictal epileptiform discharges. In the remaining eight patients, most of the seizures showed significant correlations between IFA power and RSFC-PT-based prediction or seed-based RSNs-PT. Our study provides evidence that the rapid spread of IFA in focal epilepsy can arise from physiological RSNs. This finding suggests an overlap between epileptogenic and functional networks, which may explain why functional networks in patients with focal epilepsy frequently disrupt.