IgG4-related pachyleptomeningitis with inflammatory pseudotumor.

•We report the first case of IgG4-related pachyleptomeningitis.•Our case showed also an inflammatory pseudotumor on the side ipsilateral to the pachyleptomeningitis.•The pachyleptomeningitis is probably due to inflammation from the dural pseudotumor spreading along the adjacent meninges.

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.

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.

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.

Good seizure outcome after focal resection surgery for super-refractory status epilepticus: Report of two cases.

Background: There is scarce evidence regarding focal resection surgery for super-refractory status epilepticus (SRSE), which is resistant to general anesthetic treatment over 24 h. We report two patients with SRSE, in whom good seizure outcomes were obtained following focal resection surgery. Case Description: Patient 1: A 58-year-old man who underwent left anterior temporal lobectomy with hippocampectomy at the age of 38 years after being diagnosed left medial temporal lobe epilepsy. After 19 years of surgery with no epileptic attacks, the patient developed SRSE. Electroencephalogram (EEG) demonstrated persistence of lateralized periodic discharges in the left frontotemporal region. On the 20th day after SRSE onset, resection of the frontal lobe and temporal lobe posterior to the resection cavity was performed. Patient 2: A 62-year-old man underwent craniotomy for anaplastic astrocytoma in the left frontal lobe at the age of 34 years. Since the age of 60 years, he developed SRSE 3 times over 1 and 1/12 years. On EEG, repeated ictal discharges were observed at the medial part of the left frontal region during the three SRSEs. Corresponding to the ictal EEG findings, high signals on diffusion-weighted magnetic resonance images and focal hypermetabolism on fluorodeoxyglucose-positron emission tomography were observed around the supplementary motor area, medial to the resection cavity. Resection surgery of the area was performed during the interictal period. Conclusion: Good seizure outcome was obtained in the two cases which provide additional support for the recent concept of focal resection surgery as an indication for SRSE.

Long-Term Effect of Acetylcholinesterase Inhibitors on the Dorsal Attention Network of Alzheimer's Disease Patients: A Pilot Study Using Resting-State Functional Magnetic Resonance Imaging.

Background: Alzheimer's disease (AD) is the most common condition of all neurodegenerative diseases and is characterized by various cognitive dysfunctions. Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed the physiological dynamics of functionally connected brain networks, which are called resting-state networks (RSNs). Associations between impairments of RSNs and various neuropsychiatric diseases, such as AD, have been reported. Acetylcholinesterase inhibitors (AChEIs) have been used as a pharmacological treatment for mild-to-moderate moderate AD, and short-term improvements in cognitive functions and RSNs in restricted areas have been reported. Objective: We aimed to characterize AChEI-related RSN changes by acquiring two sets of rs-fMRI data separated by approximately 3 to 6 months. Methods: Seventeen patients with AD and nine healthy subjects participated in this study. Independent component analysis was performed on the rs-fMRI data of AChEI-responsive and non-responsive AD patients, stratified according to change in Mini-Mental State Examination (MMSE) scores after 3 to 6 months of AChEI therapy. In addition, a region of interest-based analysis of the rs-fMRI data before therapy was performed to explore the functional connectivity (FC) changes associated with AchEI therapy. Results: Responders showed a significantly greater increase in MMSE scores, especially for orientation for time, than that of non-responders following AChEI therapy. A subtraction map of MMSE score differences (responders minus non-responders) in the independent component analysis revealed higher FC of the dorsal attention network in responders compared with that in non-responders. Moreover, in the region of interest analysis of untreated status data, the dorsal attention network showed significant negative FC with the right planum temporale, which belongs to the ventral attention network, proportional to MMSE score change. Conclusion: The negative correlation of the FC of the dorsal attention network and right planum temporale before AChEI therapy and MMSE score change may be a biomarker of the therapeutic effect of AChEIs for AD.

Data-point-wise spatiotemporal mapping of human ventral visual areas: Use of spatial frequency/luminance-modulated chromatic faces.

Visual information involving facial identity and expression is crucial for social communication. Although the influence of facial features such as spatial frequency (SF) and luminance on face processing in visual areas has been studied extensively using grayscale stimuli, the combined effects of other features in this process have not been characterized. To determine the combined effects of different SFs and color, we created chromatic stimuli with low, high or no SF components, which bring distinct SF and color information into the ventral stream simultaneously. To obtain neural activity data with high spatiotemporal resolution we recorded face-selective responses (M170) using magnetoencephalography. We used a permutation test procedure with threshold-free cluster enhancement to assess statistical significance while resolving problems related to multiple comparisons and arbitrariness found in traditional statistical methods. We found that time windows with statistically significant threshold levels were distributed differently among the stimulus conditions. Face stimuli containing any SF components evoked M170 in the fusiform gyrus (FG), whereas a significant emotional effect on M170 was only observed with the original images. Low SF faces elicited larger activation of the FG and the inferior occipital gyrus than the original images, suggesting an interaction between low and high SF information processing. Interestingly, chromatic face stimuli without SF first activated color-selective regions and then the FG, indicating that facial color was processed according to a hierarchy in the ventral stream. These findings suggest complex effects of SFs in the presence of color information, reflected in M170, and unveil the detailed spatiotemporal dynamics of face processing in the human brain.

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.

Neuromagnetic correlates of hemispheric specialization for face and word recognition.

The adult human brain appears to have specialized and independent neural systems for the visual processing of faces and words: greater selectivity for faces in the right hemisphere (RH) while greater selectivity for words in the left hemisphere (LH). Nevertheless, the nature of functional differences between the hemispheres is still largely unknown. To elucidate the hemispheric specialization for face and word recognition, event-related magnetic fields (ERFs) were recorded in young adults while they passively viewed faces and words presented either in the right visual field or in the left visual field. If the neural correlates of face recognition and word recognition reflect the same lateralization profile, then the lateralization of the magnetic source of the M170 component should follow a similar profile, with a greater M170 response for faces in the RH and a greater M170 response for words in the LH. We observed the expected finding of a larger M170 in the LH for words. Unexpectedly, a larger M170 response in the RH for faces was not found. Thus, the hemispheric organization of face recognition is different from that of word recognition in terms of specificity.

A novel method for extracting interictal epileptiform discharges in multi-channel MEG: Use of fractional type of blind source separation.

OBJECTIVE: Visual inspection of interictal epileptiform discharges (IEDs) in multi-channel MEG requires a time-consuming evaluation process and often leads to inconsistent results due to variability of IED waveforms. Here, we propose a novel extraction method for IEDs using a T/k type of blind source separation (BSST/k). METHODS: We applied BSST/k with seven patients with focal epilepsy to test the accuracy of identification of IEDs. We conducted comparisons of the results of BSS components with those obtained by visual inspection in sensor-space analysis. RESULTS: BSST/k provided better signal estimation of IEDs compared with sensor-space analysis. Importantly, BSST/k was able to uncover IEDs that could not be detected by visual inspection. Furthermore, IED components were clearly extracted while preserving spike and wave morphology. Variable IED waveforms were decomposed into one dominant component. CONCLUSIONS: BSST/k was able to visualize the spreading signals over multiple channels into a single component from a single epileptogenic zone. BSST/k can be applied to focal epilepsy with a simple parameter setting. SIGNIFICANCE: Our novel method was able to highlight IEDs with increased accuracy for identification of IEDs from multi-channel MEG data.

Prestimulus cortical EEG oscillations can predict the excitability of the primary motor cortex.

BACKGROUND: The motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) vary considerably at rest, but the mechanism underlying this amplitude variation is largely unknown. We hypothesized that prestimulus EEG oscillations modulate the subsequent MEPs in a state-dependent manner. OBJECTIVE: We studied the relationship between prestimulus alpha/beta oscillations and MEPs during eyes open (EO)/closed (EC) conditions, and then modulated TMS intensity in the EO condition. Furthermore, we developed an EEG-triggered TMS system ("informed open-loop") to verify our hypothesis. METHODS: TMS was applied to the left motor cortex. We first compared EEG power differences between high- and low-amplitude MEP epochs in the EO and EC conditions when using a high TMS intensity. Next, we evaluated the effects of varying TMS intensities (high vs. low) on the EEG-MEP relationship. Finally, we used EEG-triggered TMS to determine whether prestimulus EEG oscillations predicted MEP amplitudes. RESULTS: Prestimulus higher-power alpha/low-beta bands produced larger MEPs only in the high-intensity EO condition. A positive relationship between EEG power and MEP amplitude was observed at C3 and left frontal electrodes. This relationship was obscured when using the lower TMS intensity but was observed in the high-intensity condition at the C3 electrode. EEG-triggered TMS demonstrated that higher alpha power predicted higher MEP amplitudes, but beta power at around 20 Hz did not. CONCLUSIONS: A causal relationship between alpha/low-beta oscillations and MEP amplitudes at rest requires high TMS intensity delivered when eyes are open. This association may allow us to develop a new informed open-loop TMS protocol.

Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures.

OBJECTIVES: The objectives of this study were to determine how hemispheric laterality of seizure activity influences periictal heart rate variability (HRV) and investigate the ability of HRV parameters to discriminate right- and left-sided seizures. METHODS: Long-term video electroencephalogram-electrocardiogram recordings of 54 focal seizures in 25 patients with focal epilepsy were reviewed. Using linear mixed models, we examined the effect of seizure laterality on linear (standard deviation of R-R intervals [SDNN], root mean square of successive differences [RMSSD], low frequency [LF] and high frequency [HF] power of HRV, and LF/HF) and nonlinear (standard deviation [SD]1, SD2, and SD2/SD1 derived from Poincaré plots) periictal HRV parameters, the magnitude of heart rate (HR) changes, and the onset time of increased HR. Receiver operating characteristics (ROC) were used to determine the ability of these parameters to discriminate between right- and left-sided seizures. RESULTS: Postictal SDNN, RMSSD, LF, HF, SD1, and SD2 were higher in right- than left-sided seizures. Root mean square of successive difference and HF were decreased after left- but not right-sided seizures. Standard deviation of R-R intervals, LF, and SD1 were increased after right- but not left-sided seizures. Increased ictal HR was earlier and larger in right- than left-sided seizures. Postictal HF showed the greatest area under the ROC curve (AUC) (0.87) for discriminating right- and left-sided seizures. CONCLUSIONS: Our data suggest that postictal parasympathetic activity is higher, whereas ictal HR increase is greater, in right- than left-sided seizures. Involvement of the right hemisphere may be associated with postictal autonomic instability. Postictal HRV parameters may provide useful information on hemispheric laterality of seizure activity.

Grand Total EEG Score Can Differentiate Parkinson's Disease From Parkinson-Related Disorders.

Background: Semi-quantitative electroencephalogram (EEG) analysis is easy to perform and has been used to differentiate dementias, as well as idiopathic and vascular Parkinson's disease. Purpose: To study whether a semi-quantitative EEG analysis can aid in distinguishing idiopathic Parkinson's disease (IPD) from atypical parkinsonian disorders (APDs), and furthermore, whether it can help to distinguish between APDs. Materials and Methods: A comprehensive retrospective review of charts was performed to include patients with parkinsonian disorders who had at least one EEG recording available. A modified grand total EEG (GTE) score evaluating the posterior background activity, and diffuse and focal slow wave activities was used in further analyses. Results: We analyzed data from 76 patients with a final diagnosis of either IPD, probable corticobasal degeneration (CBD), multiple system atrophy (MSA), or progressive supra-nuclear palsy (PSP). IPD patients had the lowest mean GTE score, followed those with CBD or MSA, while PSP patients scored the highest. However, none of these differences were statistically significant. A GTE score of ≤9 distinguished IPD patients from those with APD (p < 0.01) with a sensitivity of 100% and a specificity of 33.3%. Conclusion: The modified GTE score can distinguish patients with IPD from those with CBD, PSP or MSA at a cut-off score of 9 with excellent sensitivity but poor specificity. However, this score is not able to distinguish a particular form of APD from other forms of the disorder.

Monaural 40-Hz auditory steady-state magnetic responses can be useful for identifying epileptic focus in mesial temporal lobe epilepsy.

OBJECTIVE: Patients with mesial temporal lobe epilepsy (mTLE) often exhibit central auditory processing (CAP) dysfunction. Monaural 40-Hz auditory steady-state magnetic responses (ASSRs) were recorded to explore the pathophysiology of mTLE. METHODS: Eighteen left mTLE patients, 11 right mTLE patients and 16 healthy controls (HCs) were examined. Monaural clicks were presented at a rate of 40 Hz. Phase-locking factor (PLF) and power values were analyzed within bilateral Heschl's gyri. RESULTS: Monaural 40-Hz ASSR demonstrated temporal frequency dynamics in both PLF and power data. Symmetrical hemispheric contralaterality was revealed in HCs. However, predominant contralaterality was absent in mTLE patients. Specifically, right mTLE patients exhibited a lack of contralaterality in response to left ear but not right ear stimulation, and vice versa in left mTLE patients. CONCLUSION: This is the first study to use monaural 40-Hz ASSR with unilateral mTLE patients to clarify the relationship between CAP and epileptic focus. CAP dysfunction was characterized by a lack of contralaterality corresponding to epileptic focus. SIGNIFICANCE: Monaural 40-Hz ASSR can provide useful information for localizing epileptic focus in mTLE patients.