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Background: Epilepsy is a widespread neurologic disorder and almost one-third of patients suffer from drug-resistant epilepsy (DRE). Neuromodulation targeting the centromediannucleus of the thalamus (CM) has been showing promising results for patients with generalized DRE who are not surgical candidates. Recently, the effect of CM- deep brain stimulation (DBS) in DRE patients was investigated in the Electrical Stimulation of Thalamus for Epilepsy of Lennox–Gastaut phenotype (ESTEL) trial, a monocentric randomized-controlled study. The same authors described a ‘cold-spot’ and a ‘sweet-spot’, which are defined as the volume of stimulation in the thalamus yielding the least and the best clinical response, respectively. However, it remains unclear which structural connections may contribute to the anti-seizure effect of the stimulation. Objective: We investigated the differences in structural connectivity among CM, the sweet-spot and the cold-spot. Furthermore, we tried to validate our results in a cohort of DRE patients who underwent CM-DBS or CM-RNS (responsive neurostimulation). We hypothesized that the sweet-spot would share similar structural connectivity with responder patients. Methods: By using the software FMRIB Software Library (FSL), probabilistic tractography was performed on 100 subjects from the Human Connectome Project to calculate the probability of connectivity of the whole CM, the sweet-spot and the cold-spot to 45 cortical and subcortical areas. Results among the three seeds were compared with multivariate analysis of variance (MANOVA). Similarly, the structural connectivity of volumes of tissue activated (VTAs) from eight DRE patients was investigated. Patients were divided into responders and non-responders based on the degree of reduction in seizure frequency, and the mean probabilities of connectivity were similarly compared between the two groups. Results: The sweet-spot demonstrated a significantly higher probability of connectivity (p < 0.001) with the precentral gyrus, superior frontal gyrus, and the cerebellum than the whole CM and the cold-spot. Responder patients displayed a higher probability of connectivity with both ipsilateral (p = 0.011) and contralateral cerebellum (p = 0.04) than the non-responders. Conclusion: Cerebellar connections seem to contribute to the beneficial effects of CM-neuromodulation in patients with drug-resistant generalized epilepsy.

Speech decoding from non-invasive EEG signals can achieve relatively high accuracy (70–80%) for strictly delimited classification tasks, but for more complex tasks non-invasive speech decoding typically yields a 20–50% classification accuracy. However, decoder generalization, or how well algorithms perform objectively across datasets, is complicated by the small size and heterogeneity of existing EEG datasets. Furthermore, the limited availability of open access code hampers a comparison between methods. This study explores the application of a novel non-linear method for signal processing, delay differential analysis (DDA), to speech decoding. We provide a systematic evaluation of its performance on two public imagined speech decoding datasets relative to all publicly available deep learning methods. The results support DDA as a compelling alternative or complementary approach to deep learning methods for speech decoding. DDA is a fast and efficient time-domain open-source method that fits data using only few strong features and does not require extensive preprocessing.

IntroductionHypothalamic hamartomas (HHs) are deep-seated congenital lesions that typically lead to pharmacoresistant epilepsy and a catastrophic encephalopathic syndrome characterised by severe neuropsychological impairment and decline in quality of life. A variety of surgical approaches and technologies are available for the treatment of HH-related pharmacoresistant epilepsy. There remains, however, a paucity of literature directly comparing their relative efficacy and safety. This protocol aims to facilitate a systematic review and meta-analysis that will characterise and compare the probability of seizure freedom and relevant postoperative complications across different surgical techniques performed for the treatment of HH-related pharmacoresistant epilepsy.Methods and analysisThis protocol was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Individual Participant Data guidelines. Three major databases, PubMed, Embase and Scopus, will be systematically searched from database inception and without language restrictions for relevant articles using our predefined search strategy. Title–abstract and full text screening using inclusion and exclusion criteria created a priori will be performed by two independent reviewers to identify eligible articles. Conflicts will be resolved via discussion with a third team member. Following data extraction of both study-level and individual patient data (IPD), a study-level and IPD meta-analysis will be performed. Study-level analysis will focus on assessing the degree of heterogeneity in the data and quantifying overall seizure outcomes for each surgical technique. The IPD analysis will use multivariable regression to determine perioperative predictors of seizure freedom and complications that can guide patient and technique selection.Ethics and disseminationThis work will not require ethics approval as it will be solely based on previously published and available data. The results of this review will be shared via conference presentation and submission to peer-reviewed neurosurgical journals.PROSPERO registrationCRD42022378876.

Brain tumors are the most common solid malignancy and leading cause of cancer-related deaths in infants. Current epidemiological data is limited by low numbers of reported cases. This study used a population-based approach with analysis of contemporary and historical survival curves to provide up-to-date prognostication. Observational cohort analysis was performed using the Surveillance, Epidemiology and End Results (SEER) database. Infants with brain tumors diagnosed from 1973 to 2013 were categorized by the most common tumor types (diffuse astrocytic and oligodendroglioma, choroid plexus, embryonal, ependymal, medulloblastoma and pilocytic astrocytoma). The 1, 5 and 10 year survival was stratified by decade, with trends in management and outcomes analyzed. We identified 2996 affected infants satisfying inclusion criteria. All tumor types, except embryonal and choroid plexus, demonstrated improving survival with time. Infants with embryonal tumors showed a decline in survival from the 1970s to 1990s (p = 0.009), whereas infants with choroid plexus tumors had no change in survival. Infants with ependymal tumors experienced the greatest improvement in survival from 1980s to 1990s and 1990s to 2000s (p = 0.0001, p = 0.01), with 5-year survival probability improving from 28% (95% CI 15-42%) in the 1980s to 77% (95% CI 69-83%) the 2000s. The use of radiation declined from 1970 to 2000 for all tumors; however, radiation treatment for embryonal and ependymal subtypes increased after 2000. While overall survival for infants with brain tumors has improved from the 1970s onwards, not every tumor type has seen a statistically significant change. Given changes in management and survival, prognostication of infants with brain tumor should be updated.

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery. Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions. We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion. One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes. To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable. Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2-8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1-24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4-7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8-13.5, p = 0.002) were associated with a good postoperative seizure outcome. Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.

Fascioliasis is an important parasitic disease which affects productivity of ruminants, and imposes significant economic losses. Benzimidazoles are effective in the treatment of fascioliasis; however, there are several reports on benzimidazoles resistant flukes. Combinational therapy is an approach to delay the emergence of resistant flukes. The present study aimed to compare the efficacy of triclabendazole (TBZ) and combination of triclabendazole and levamisole (TBZ + LVM) in the treatment of sheep naturally infected with Fasciola sp. For this purpose, 40 ewes infected with Fasciola sp. in three groups received TBZ, and TBZ + LVM, or remained untreated as CON. Fecal egg count (FEC), fecal egg count reduction (FECR), liver enzymes activity, albumin, globulin, and total protein levels were measured on day 0, 7, 14, and 28 post treatments. Obtained results showed that treatment with TBZ and TBZ + LVM resulted in significant reduction in FEC ( P  < 0.05), and FECR reached to values of higher than 90% on 28 day post treatment. The FEC for TBZ + LMV on day 7 and 14 were 12.25 ± 3.82 and 3.08 ± 1.03, respectively which was significantly lower in comparison to TBZ and CON ( P  < 0.05). Efficacy of TBZ + LMV was higher than TBZ on day 7 and 14 post treatment; however, no significant difference was observed on 28 day. The liver enzyme activities on days 7 and 14 were lower in the TBZ + LVM sheep in comparison to the TBZ and CON. Treatment with TBZ or TBZ + LVM resulted in an increase in albumin and a decrease in globulin. Over all, the present study clarified the importance of combinational therapy, and demonstrated that combination of TBZ + LVM resulted in higher efficacy and earlier improvement of liver conditions in sheep naturally infected with Fasciola sp.

To estimate the effectiveness of anterior cervical discectomy with arthroplasty (ACDA) compared to anterior cervical discectomy with fusion (ACDF) for patient-important outcomes for single-level cervical spondylosis. Electronic databases (MEDLINE, EMBASE, Cochrane Register for Randomized Controlled Trials, BIOSIS and LILACS), archives of spine meetings and bibliographies of relevant articles. We included RCTs of ACDF versus ACDA in adult patients with single-level cervical spondylosis reporting at least one of the following outcomes: functionality, neurological success, neck pain, arm pain, quality of life, surgery for adjacent level degeneration (ALD), reoperation and dysphonia/dysphagia. We used no language restrictions. We performed title and abstract screening and full text screening independently and in duplicate. We used random-effects model to pool data using mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes. We used GRADE to evaluate the quality of evidence for each outcome. Of 2804 citations, 9 articles reporting on 9 trials (1778 participants) were eligible. ACDA is associated with a clinically significant lower incidence of neurologic failure (RR = 0.53, 95% CI = 0.37-0.75, p = 0.0004) and improvement in the Neck pain visual analogue scale (VAS) (MD = 6.56, 95% CI = 3.22-9.90, p = 0.0001; Minimal clinically important difference (MCID) = 2.5. ACDA is associated with a statistically but not clinically significant improvement in Arm pain VAS and SF-36 physical component summary. ACDA is associated with non-statistically significant higher improvement in the Neck Disability Index Score and lower incidence of ALD requiring surgery, reoperation, and dysphagia/dysphonia. There is no strong evidence to support the routine use of ACDA over ACDF in single-level cervical spondylosis. Current trials lack long-term data required to assess safety as well as surgery for ALD. We suggest that ACDA in patients with single level cervical spondylosis is an option although its benefits and indication over ACDF remain in question.

Electroencephalography (EEG) holds promise for brain-computer interface (BCI) devices as a non-invasive measure of neural activity. With increased attention to EEG-based BCI systems, publicly available datasets incorporating the complex stimuli found in naturalistic speech are necessary to establish a common standard of performance within the BCI community. Effective solutions must overcome noise in the EEG signal and remain reliable across sessions and stimuli that reflect types of real-world linguistic complexity without overfitting to a dataset or task. We present two validated datasets (N=8 and N=16) for classification at the phoneme and word level and by the articulatory properties of phonemes. EEG signals were recorded from 64 channels while subjects listened to and repeated six consonants and five vowels. Individual phonemes were combined in different phonetic environments to produce coarticulated variation in 40 consonant-vowel pairs, 20 real words, and 20 pseudowords. Phoneme pairs and words were presented during a control condition and during transcranial magnetic stimulation (TMS) to assess whether stimulation would augment the EEG signal associated with specific articulatory processes.

PurposeDesmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are classified together as grade I neuronal and mixed neuronal-glial tumor of the central nervous system by the World Health Organization (WHO). These tumors are rare and have not been well characterized in terms of clinical outcomes. We aimed to identify clinical predictors of mortality and tumor recurrence/progression by performing an individual patient data meta-analysis (IPDMA) of the literature.MethodsA systematic literature review from 1970 to 2020 was performed, and individualized clinical data for patients diagnosed with DIA/DIG were extracted. Aggregated data were excluded from collection. Outcome measures of interest were mortality and tumor recurrence/progression, as well as time-to-event (TTE) for each of these. Participants without information on these outcome measures were excluded. Cox regression survival analyses were performed to determine predictors of mortality and tumor recurrence / progression.ResultsWe identified 98 articles and extracted individual patient data from 188 patients. The cohort consisted of 58.9% males with a median age of 7 months. The majority (68.1%) were DIGs, while 24.5% were DIAs and 7.5% were non-specific desmoplastic infantile tumors; DIAs presented more commonly in deep locations (p = 0.001), with leptomeningeal metastasis (p = 0.001), and was associated with decreased probability of gross total resection (GTR; p = 0.001). Gender, age, and tumor pathology were not statistically significant predictors of either mortality or tumor recurrence/progression. On multivariate survival analysis, GTR was a predictor of survival (HR = 0.058; p = 0.007) while leptomeningeal metastasis at presentation was a predictor of mortality (HR = 3.27; p = 0.025). Deep tumor location (HR = 2.93; p = 0.001) and chemotherapy administration (HR = 2.02; p = 0.017) were associated with tumor recurrence/progression.ConclusionOur IPDMA of DIA/DIG cases reported in the literature revealed that GTR was a predictor of survival while leptomeningeal metastasis at presentation was associated with mortality. Deep tumor location and chemotherapy were associated with tumor recurrence / progression.

Transcranial magnetic stimulation (TMS) has been widely used to study the mechanisms that underlie motor output. Yet, the extent to which TMS acts upon the cortical neurons implicated in volitional motor commands and the focal limitations of TMS remain subject to debate. Previous research links TMS to improved subject performance in behavioral tasks, including a bias in phoneme discrimination. Our study replicates this result, which implies a causal relationship between electro-magnetic stimulation and psychomotor activity, and tests whether TMS-facilitated psychomotor activity recorded via electroencephalography (EEG) may thus serve as a superior input for neural decoding. First, we illustrate that site-specific TMS elicits a double dissociation in discrimination ability for two phoneme categories. Next, we perform a classification analysis on the EEG signals recorded during TMS and find a dissociation between the stimulation site and decoding accuracy that parallels the behavioral results. We observe weak to moderate evidence for the alternative hypothesis in a Bayesian analysis of group means, with more robust results upon stimulation to a brain region governing multiple phoneme features. Overall, task accuracy was a significant predictor of decoding accuracy for phoneme categories (F(1,135) = 11.51, p < 0.0009) and individual phonemes (F(1,119) = 13.56, p < 0.0003), providing new evidence for a causal link between TMS, neural function, and behavior.