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Unlabelled: We report a 10-year-old boy with familial Wiskott-Aldrich syndrome (WAS) who underwent successful bone marrow transplantation (BMT) at the age of 9 months. With the exception of auto-immune haemolytic anaemia due to warm antibodies lasting 15 months there had not been any complication after BMT. Ten years later the patient presented with diarrhoea, hyperpigmentation of skin and oral mucosa, fatigue and polyuria. Diagnosis of Addison disease was confirmed by typical electrolyte imbalance and absent cortisol response to adrenocorticotrophic hormone. Adrenal antibodies were positive. On therapy with oral gluco- and mineralocorticoids, the symptoms disappeared and electrolytes normalized. To our knowledge auto-immuno endocrinopathy after BMT for WAS has not yet been reported.Conclusion: This is the first report of auto-immune adrenal insufficiency after BMT for WAS. The aetiopathogenesis of this condition remains unknown since auto-immune diseases as toxic side-effects of the ablative treatment before BMT have not yet been reported, and a relapse of WAS and cotransplantation of auto-immune adrenal insufficiency have been ruled out. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this systematic review is to present a comprehensive summary of existing research on the use of 3D printing in spinal surgery., Methods: The researchers conducted a thorough search of four digital databases (PubMed, Web of Science, Scopus, and Embase) to identify relevant studies published between January 1999 and December 2022. The review focused on various aspects, including the types of objects printed, clinical applications, clinical outcomes, time and cost considerations, 3D printing materials, location of 3D printing, and technologies utilized. Out of the 1620 studies initially identified and the 17 added by manual search, 105 met the inclusion criteria for this review, collectively involving 2088 patients whose surgeries involved 3D printed objects., Results: The studies presented a variety of 3D printed devices, such as anatomical models, intraoperative navigational templates, and customized implants. The most widely used type of objects are drill guides (53%) and anatomical models (25%) which can also be used for simulating the surgery. Custom made implants are much less frequently used (16% of papers). These devices significantly improved clinical outcomes, particularly enhancing the accuracy of pedicle screw placement. Most studies (88%) reported reduced operation times, although two noted longer times due to procedural complexities. A variety of 3DP technologies and materials were used, with STL, FDM, and SLS common for models and guides, and titanium for implants via EBM, SLM, and DMLS. Materialise software (Mimics, 3-Matic, Magics) was frequently utilized. While most studies mentioned outsourced production, in-house printing was implied in several cases, indicating a trend towards localized 3D printing in spine surgery., Conclusions: 3D printing in spine surgery, a rapidly growing area of research, is predominantly used for creating drill guides for screw insertion, anatomical models, and innovative implants, enhancing clinical outcomes and reducing operative time. While cost-efficiency remains uncertain due to insufficient data, some 3D printing applications, like pedicle screw drill guides, are already widely accepted and routinely used in hospitals., Competing Interests: Declarations. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Background Context: Following total sacrectomy, lumbopelvic reconstruction is essential to restore continuity between the lumbar spine and pelvis. However, to achieve long-term clinical stability, bony fusion between the lumbar spine and the pelvic ring is crucial. Reduction of the lumbopelvic distance can promote successful bony fusion. Although many lumbopelvic reconstruction techniques (LPRTs) have been previously analyzed, the biomechanical effect of lumbopelvic distance reduction (LPDR) has not been investigated yet., Purpose: To evaluate and compare the biomechanical characteristics of four different LPRTs while considering the effect of LPDR., Study Design/setting: A comparative finite element (FE) study., Methods: The FE models following total sacrectomy were developed to analyze four different LPRTs, with and without LPDR. The closed-loop reconstruction (CLR), the sacral-rod reconstruction (SRR), the four-rod reconstruction (FRR), and the improved compound reconstruction (ICR) techniques were analyzed in flexion, extension, lateral bending, and axial rotation. Lumbopelvic stability was assessed through the shift-down displacement and the relative sagittal rotation of L5, while implant safety was evaluated based on the stress state at the bone-implant interface and within the rods., Results: Regardless of LPDR, both the shift-down displacement and relative sagittal rotation of L5 consistently ranked the LPRTs as ICR

Background Context: Oblique lumbar interbody fusion (OLIF) can provide an ideal minimally invasive solution for achieving spinal fusion in an older, more frail population where decreased bone quality can be a limiting factor. Stabilization can be achieved with bilateral pedicle screws (BPS), which require additional incisions and longer operative time. Alternatively, a novel self-anchoring stand-alone lateral plate system (SSA) can be used, where no additional incisions are required. Based on the relevant literature, BPS constructs provide greater primary biomechanical stability compared to lateral plate constructs, including SSA. This difference is further increased by osteoporosis. Screw augmentation in spinal fusion surgeries is commonly used; however, in the case of OLIF, it is a fairly new concept, lacking a consensus-based guideline., Purpose: This comparative finite element (FE) study aimed to investigate the effect of PMMA screw augmentation on the primary stability of a stand-alone implant construct versus posterior stabilization in OLIF with osteoporotic bone quality., Study Design: The biomechanical effect of screw augmentation was studied inside an in-silico environment using computer-aided FE analysis., Methods: A previously validated and published L2-L4 FE model with normal and osteoporotic bone material properties was used. Geometries based on the OLIF implants (BPS, SSA) were created and placed inside the L3-L4 motion segment with increasing volumes (1-6 cm 3 ) of PMMA augmentation. A follower load of 400 N and 10 Nm bending moment (in the three anatomical planes) were applied to the surgical FE models with different bone material properties. The operated L3-L4 segmental range of motion (ROM), the inserted cage's maximal caudal displacements, and L4 cranial bony endplate principal stress values were measured., Results: The nonaugmented values for the BPS construct were generally lower compared to SSA, and the difference was increased by osteoporosis. In osteoporotic bone, PMMA augmentation gradually decreased the investigated parameters and the difference between the two constructs as well. Between 3 cm 3 and 4 cm 3 of injected PMMA volume per screw, the difference between augmented SSA and standard BPS became comparable., Conclusions: Based on this study, augmentation can enhance the primary stability of the constructs and decrease the difference between them. Considering leakage as a possible complication, between 3 cm 3 and 4 cm 3 of injected PMMA per screw can be an adequate amount for SSA augmentation. However, further in silico, and possibly in vitro and clinical testing is required to thoroughly understand the investigated biomechanical aspects., Clinical Significance: This study sheds light on the possible biomechanical advantage offered by augmented OLIF implants and provides a theoretical augmentation amount for the SSA construct. Based on the findings, the concept of an SSA device with PMMA augmentation capability is desirable., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation (SPES) are widely used to assess effective connectivity between cortical areas and are also implemented in the presurgical evaluation of epileptic patients. Nevertheless, the cortical generators underlying the various components of CCEPs in humans have not yet been elucidated. Our aim was to describe the laminar pattern arising under SPES evoked CCEP components (P1, N1, P2, N2, P3) and to evaluate the similarities between N2 and the downstate of sleep slow waves. We used intra-cortical laminar microelectrodes (LMEs) to record CCEPs evoked by 10 mA bipolar 0.5 Hz electric pulses in seven patients with medically intractable epilepsy implanted with subdural grids. Based on the laminar profile of CCEPs, the latency of components is not layer-dependent, however their rate of appearance varies across cortical depth and stimulation distance, while the seizure onset zone does not seem to affect the emergence of components. Early neural excitation primarily engages middle and deep layers, propagating to the superficial layers, followed by mainly superficial inhibition, concluding in a sleep slow wave-like inhibition and excitation sequence., (© 2024. The Author(s).)

Objective: To evaluate and compare the biomechanical efficacy of six iliosacral screw fixation techniques for treating unilateral AO Type B2 (Denis Type II) sacral fractures using literature-based and QCT-based bone material properties in finite element (FE) models., Methods: Two FE models of the intact pelvis were constructed: the literature-based model (LBM) with bone material properties taken from the literature, and the patient-specific model (PSM) with QCT-derived bone material properties. Unilateral transforaminal sacral fracture was modelled to assess different fixation techniques: iliosacral screw (ISS) at the first sacral vertebra (S1) (ISS1), ISS at the second sacral vertebra (S2) (ISS2), ISS at S1 and S2 (ISS12), transverse iliosacral screws (TISS) at S1 (TISS1), TISS at S2 (TISS2), and TISS at S1 and S2 (TISS12). A 600 N vertical load with both acetabula fixed was applied. Vertical stiffness (VS), relative interfragmentary displacement (RID), and the von Mises stress values in the screws and fracture interface were analysed., Results: The lowest and highest normalised VS was given by ISS1 and TISS12 techniques for LBM and PSM, with 137 % and 149 %, and 375 % and 472 %, respectively. In comparison with the LBM, the patient-specific bone modelling increased the maximum screw stress values by 19.3, 16.3, 27.8, 2.3, 24.4 and 7.8 % for ISS1, ISS2, ISS12, TISS1, TISS2 and TISS12, respectively. The maximum RID values were between 0.10 mm and 0.47 mm for all fixation techniques in both models. The maximum von Mises stress results on the fracture interface show a substantial difference between the two models, as PSM (mean ± SD of 15.76 ± 8.26 MPa) gave lower stress values for all fixation techniques than LBM (mean ± SD of 28.95 ± 6.91 MPa)., Conclusion: The differences in stress distribution underline the importance of considering locally defined bone material properties when investigating internal mechanical parameters. Based on the results, all techniques demonstrated clinically sufficient stability, with TISS12 being superior from a biomechanical standpoint. Both LBM and PSM models indicated a consistent trend in ranking the fixation techniques based on stability. However, long-term clinical trials are recommended to confirm the findings of the study., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Describing intracortical laminar organization of interictal epileptiform discharges (IED) and high frequency oscillations (HFOs), also known as ripples. Defining the frequency limits of slow and fast ripples. We recorded potential gradients with laminar multielectrode arrays (LME) for current source density (CSD) and multi-unit activity (MUA) analysis of interictal epileptiform discharges IEDs and HFOs in the neocortex and mesial temporal lobe of focal epilepsy patients. IEDs were observed in 20/29, while ripples only in 9/29 patients. Ripples were all detected within the seizure onset zone (SOZ). Compared to hippocampal HFOs, neocortical ripples proved to be longer, lower in frequency and amplitude, and presented non-uniform cycles. A subset of ripples (≈ 50%) co-occurred with IEDs, while IEDs were shown to contain variable high-frequency activity, even below HFO detection threshold. The limit between slow and fast ripples was defined at 150 Hz, while IEDs' high frequency components form clusters separated at 185 Hz. CSD analysis of IEDs and ripples revealed an alternating sink-source pair in the supragranular cortical layers, although fast ripple CSD appeared lower and engaged a wider cortical domain than slow ripples MUA analysis suggested a possible role of infragranularly located neural populations in ripple and IED generation. Laminar distribution of peak frequencies derived from HFOs and IEDs, respectively, showed that supragranular layers were dominated by slower (< 150 Hz) components. Our findings suggest that cortical slow ripples are generated primarily in upper layers while fast ripples and associated MUA in deeper layers. The dissociation of macro- and microdomains suggests that microelectrode recordings may be more selective for SOZ-linked ripples. We found a complex interplay between neural activity in the neocortical laminae during ripple and IED formation. We observed a potential leading role of cortical neurons in deeper layers, suggesting a refined utilization of LMEs in SOZ localization., (© 2023. The Author(s).)

Standing radiographs play an important role in the characterization of spinal sagittal alignment, as they depict the spine under physiologic loading conditions. However, there is no commonly available method to apply the lumbar lordosis of standing radiographs to supine CT-based virtual 3D models of the lumbar spine. We aimed to develop a method for the sagittal rigid-body registration of vertebrae to standing radiographs, using the exact geometry reconstructed from CT-data. In a cohort of 50 patients with monosegmental spinal degeneration, segmentation and registration of the lumbar vertebrae and sacrum were performed by two independent investigators. Intersegmental angles and lumbar lordosis were measured both in CT scans and radiographs. Vertebrae were registered using the X-ray module of Materialise Mimics software. Postregistrational midsagittal sections were constructed of the sagittal midplane sections of the registered 3D lumbar spine geometries. Mean Hausdorff distance was measured between corresponding registered vertebral geometries. The registration process minimized the difference between the X-rays' and postregistrational midsagittal sections' lordoses. Intra- and inter-rater reliability was excellent based on angle and mean Hausdorff distance measurements. We propose an accessible, accurate, and reproducible method for creating patient-specific 3D geometries of the lumbar spine that accurately represent spinal sagittal alignment in the standing position., (© 2022. The Author(s).)

Neurological emergencies, such as acute stroke, are especially challenging during the current Coronavirus disease-2019 (COVID-19) pandemic. Symptoms as aphasia or dysarthria are severely impacting cooperation and communication with patients. During physical examination, both the patient and the medical team are fitted routinely with surgical masks to minimize potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, such a practice can lead to concealment of particularly relevant physical signs. We report a case series of four acute stroke patients who were transferred for endovascular mechanical thrombectomy to our institute after intravenous thrombolysis was initiated at primary stroke centers. Upon arrival, after removing their masks, we observed oral angioedema, as a reaction to thrombolytic agent alteplase. Symptoms remained obscured by face masks through patient care at the referring stroke unit and during transportation, nevertheless they resolved after treatment. Most probably, there are a number of similar cases encountered at emergency departments and acute stroke units. To improve patient safety, a compromise between ensuring protection against the novel coronavirus and facilitating detection of potentially life-threatening physical signs must be found.

Background: Distal radius fractures are very common in paediatric patients. Severely displaced fractures may require surgical intervention. The gold standard surgical method is percutaneous K-wire osteosynthesis followed by immobilisation. Metal implants can be removed with a second intervention; however, these extra procedures can cause further complications. Several studies confirm the benefits of bioabsorbable implants for paediatric patients. The aim of this retrospective study was to compare the complication rates of displaced distal metaphyseal radius (AO 23r-M/3.1) and forearm (AO 23-M/3.1) fractures in children operated on with K-wires versus a novel technique with bioresorbable implants., Methods: We retrospectively reviewed 94 patients in three paediatric trauma centres who underwent operations due to severely displaced distal forearm or metaphyseal radial fractures between January 2019 and January 2020. The mean age was 8.23 (ranging from 5-12). 30 patients (bioresorbable group, BR-group) were treated with biodegradable PLGA implants (Bioretec®, ActivaPin®), 40 patients with one or two stainless steel Kirschner-wires (K-wires, Sanatmetal®) which were buried under the skin (KW I-group) and 24 children with K-wires left outside the skin. (KWII. Group). We examined the number of minor and major complications as well as the need for repeated interventions. Follow-up was at least one and half year., Results: There was no significant difference between the complication rates at the two KW groups (p = 0.241; Cramer's V = 0.211), while the complication rate of the BR group was significantly lower. (p = 0.049; Cramer's V = 0.293 and p = 0.002; Cramer's V = 0.418 respectively). No later than half a year after the injury, no difference was observed between the functional outcomes of the patients in each group. One and a half years after the injury, no signs of growth disturbance were found in any of the children. No second surgical intervention was required in the BR group., Conclusions: Surgeries with bioresorbable intramedullary implants may have fewer complications than K- wire osteosynthesis in the treatment of severely displaced distal forearm fractures. The benefits are most pronounced in the first six weeks after surgery, reducing the number of outpatient visits and increasing the child's sense of comfort. As no second intervention is required, this can lead to significant cost savings. After half a year, there is no difference in the outcomes between the different surgical treatment strategies., (© 2022. The Author(s).)

Knowledge about the activity of single neurons is essential in understanding the mechanisms of synchrony generation, and particularly interesting if related to pathological conditions. The generation of interictal spikes-the hypersynchronous events between seizures-is linked to hyperexcitability and to bursting behaviour of neurons in animal models. To explore its cellular mechanisms in humans we investigated the activity of clustered single neurons in a human in vitro model generating both physiological and epileptiform synchronous events. We show that non-epileptic synchronous events resulted from the finely balanced firing of excitatory and inhibitory cells, which was shifted towards an enhanced excitability in epileptic tissue. In contrast, interictal-like spikes were characterised by an asymmetric overall neuronal discharge initiated by excitatory neurons with the presumptive leading role of bursting pyramidal cells, and possibly terminated by inhibitory interneurons. We found that the overall burstiness of human neocortical neurons is not necessarily related to epilepsy, but the bursting behaviour of excitatory cells comprising both intrinsic and synaptically driven bursting is clearly linked to the generation of epileptiform synchrony., (© 2022. The Author(s).)

Data dimensionality informs us about data complexity and sets limit on the structure of successful signal processing pipelines. In this work we revisit and improve the manifold adaptive Farahmand-Szepesvári-Audibert (FSA) dimension estimator, making it one of the best nearest neighbor-based dimension estimators available. We compute the probability density function of local FSA estimates, if the local manifold density is uniform. Based on the probability density function, we propose to use the median of local estimates as a basic global measure of intrinsic dimensionality, and we demonstrate the advantages of this asymptotically unbiased estimator over the previously proposed statistics: the mode and the mean. Additionally, from the probability density function, we derive the maximum likelihood formula for global intrinsic dimensionality, if i.i.d. holds. We tackle edge and finite-sample effects with an exponential correction formula, calibrated on hypercube datasets. We compare the performance of the corrected median-FSA estimator with kNN estimators: maximum likelihood (Levina-Bickel), the 2NN and two implementations of DANCo (R and MATLAB). We show that corrected median-FSA estimator beats the maximum likelihood estimator and it is on equal footing with DANCo for standard synthetic benchmarks according to mean percentage error and error rate metrics. With the median-FSA algorithm, we reveal diverse changes in the neural dynamics while resting state and during epileptic seizures. We identify brain areas with lower-dimensional dynamics that are possible causal sources and candidates for being seizure onset zones., Competing Interests: The authors declare there are no competing interests. Zoltán Somogyvári is employed by Neuromicrosystems Ltd., (©2022 Benkő et al.)

Inhibitory neurons innervating the perisomatic region of cortical excitatory principal cells are known to control the emergence of several physiological and pathological synchronous events, including epileptic interictal spikes. In humans, little is known about their role in synchrony generation, although their changes in epilepsy have been thoroughly investigated. This paper demonstraits how parvalbumin (PV)- and type 1 cannabinoid receptor (CB1R)-positive perisomatic interneurons innervate pyramidal cell bodies, and their role in synchronous population events spontaneously emerging in the human epileptic and non-epileptic neocortex, in vitro. Quantitative electron microscopy showed that the overall, PV+ and CB1R+ somatic inhibitory inputs remained unchanged in focal cortical epilepsy. On the contrary, the size of PV-stained synapses increased, and their number decreased in epileptic samples, in synchrony generating regions. Pharmacology demonstrated-in conjunction with the electron microscopy-that although both perisomatic cell types participate, PV+ cells have stronger influence on the generation of population activity in epileptic samples. The somatic inhibitory input of neocortical pyramidal cells remained almost intact in epilepsy, but the larger and consequently more efficient somatic synapses might account for a higher synchrony in this neuron population. This, together with epileptic hyperexcitability, might make a cortical region predisposed to generate or participate in hypersynchronous events.

Purpose: Percutaneous cement discoplasty (PCD) is a minimally invasive surgical option to treat patients who suffer from the consequences of advanced disc degeneration. As the current two-dimensional methods can inappropriately measure the difference in the complex 3D anatomy of the spinal segment, our aim was to develop and apply a volumetric method to measure the geometrical change in the surgically treated segments., Methods: Prospective clinical and radiological data of 10 patients who underwent single- or multilevel PCD was collected. Pre- and postoperative CT scan-based 3D reconstructions were performed. The injected PMMA (Polymethylmethacrylate) induced lifting of the cranial vertebra and the following volumetric change was measured by subtraction of the geometry of the spinal canal from a pre- and postoperatively predefined cylinder. The associations of the PMMA geometry and the volumetric change of the spinal canal with clinical outcome were determined., Results: Change in the spinal canal volume (ΔV) due to the surgery proved to be significant (mean ΔV = 2266.5 ± 1172.2 mm 3 , n = 16; p = 0.0004). A significant, positive correlation was found between ΔV, the volume and the surface of the injected PMMA. A strong, significant association between pain intensity (low back and leg pain) and the magnitude of the volumetric increase of the spinal canal was shown (ρ = 0.772, p = 0.009 for LBP and ρ = 0.693, p = 0.026 for LP)., Conclusion: The developed method is accurate, reproducible and applicable for the analysis of any other spinal surgical method. The volume and surface area of the injected PMMA have a predictive power on the extent of the indirect spinal canal decompression. The larger the ΔV the higher clinical benefit was achieved with the PCD procedure., The Translational Potential of This Article: The developed method has the potential to be integrated into clinical software's to evaluate the efficacy of different surgical procedures based on indirect decompression effect such as PCD, anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), oblique lumbar interbody fusion (OLIF), extreme lateral interbody fusion (XLIF). The intraoperative use of the method will allow the surgeon to respond if the decompression does not reach the desired level., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors.)

Összefoglaló. Bevezetés és célkitűzés: A terápiarezisztens fokális epilepsziák sebészeti kezelése elterjedten használt kezelési lehetőség. Célunk az epilepsziasebészet-hatékonyság változásának vizsgálata egy évtizednyi távlatból a budapesti centrumban. Módszerek: Az Országos Klinikai Idegtudományi Intézetben reszektív epilepsziasebészeti beavatkozásokon átesett fokális epilepsziás betegek adatai kerültek feldolgozásra. A vizsgált 10 év beteganyagát két periódusra osztottuk a műtét időpontja szerint (2006-2010 és 2011-2016). Vizsgálati szempontjaink: demográfiai adatok, az epilepszia kezdete és típusa, mágnesesrezonancia-lelet, preoperatív rohamfrekvencia, műtéttípus és szövettani lelet. Az epileptológiai kimenetelt az Engel-klasszifikáció alapján értékeltük. Eredmények: Epilepsziasebészeti beavatkozás 187 betegen történt, akik közül 137-nél került sor reszekciós műtétre. A betegek 65%-ában temporalis, 18%-ában frontalis, míg 7%-ában olyan multilobaris epilepszia igazolódott, mely a temporalis vagy a frontalis lebenyt érintette. Teljes rohammentességet (Engel I/A) az 1. évben 68%-ban, a 2. évben 64%-ban, míg az 5. évben 63%-ban mértünk. A két intervallum összehasonlításakor az 1 éves rohammentesség aránya 60%-ról (temporalis: 67%, extratemporalis: 50%) 73%-ra (temporalis: 79%, extratemporalis: 62%) javult a második periódusban. Az etiológia szempontjából a hippocampalis sclerosis aránya 28%-ról 14%-ra csökkent, a fokális corticalis dysplasiák aránya 22%-ról 31%-ra növekedett. Következtetés: A sebészeti kezelés fokális epilepsziák esetén - alapos előzetes kivizsgálást követően - általában biztonságos és a legnagyobb arányban sikeres beavatkozás. A legkedvezőbb kimenetel temporalis lokalizációban érhető el. A hatékonyság az évek során egyre javuló tendenciát mutatott az egyre nehezebb sebészeti esetek ellenére. Ez magyarázható a sebészeti technikák fejlődésével, illetve a jobb, műtét előtti elektrofiziológiai és képalkotó technikákkal, amelyek bevezetésével pontosabb lokalizáció adható. Orv Hetil. 2021; 162(6): 219-226., Introduction and Objective: The surgical treatment of medically intractable focal epilepsies is a well established practice. Our aim was to examine the efficacy of epilepsy surgery within a decade long period in our centre in Budapest., Methods: Data of drug-resistant patients with resective epilepsy surgery in the National Institute of Clinical Neurosciences were evaluated. The examined 10-year period was divided based on the year of the operation in two parts (2006-2010 and 2011-2016). The following data were collected: demography, beginning and type of epilepsy, magnetic resonance, preoperative seizure frequency, type of surgery and histology. Epileptological outcome was based on modified Engel's classification., Results: Out of 187 surgeries, we identified 137 patients with resective intervention: 65% temporal lobe, 18% frontal, and 7% multilobar epilepsy. Seizure-freedom (Engel I/A) was 68% in the first postoperative year, 64% in the second, and 63% in the fifth year. In the first period, 1-year seizure freedom was 60% (temporal: 67% extratemporal: 50%), while in the second period it was 73% (temporal 79%, extratemporal 62%). Hippocampal sclerosis ratio dropped from 28% to 14%, while focal cortical dysplasia ratio increased from 22% to 31%., Conclusion: Surgical treatment in focal epilepsy - after thorough presurgical evaluation - is generally safe and successful. The most favorable outcome is in temporal localization. The efficacy tended to improve over time despite of the more challenging cases. This can be explained with the development of surgical techniques and improvement of presurgical localization. Orv Hetil. 2021; 162(6): 219-226.

Sleep spindles are functionally important NREM sleep EEG oscillations which are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IMEs within cortical layers was confirmed using postsurgical histological reconstructions. Many spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. ECoG spindles were in contrast usually accompanied by IME spindles. Neither IME nor ECoG spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and patients. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Revision surgery of a previous lumbosacral non-union is highly challenging, especially in case of complications, such as a broken screw at the first sacral level (S1). Here, we propose the implementation of a new method based on the CT scan of a clinical case using 3D reconstruction, combined with finite element analysis (FEA), computer-assisted design (CAD), and 3D-printing technology to provide accurate surgical navigation to aid the surgeon in performing the optimal surgical technique by inserting a pedicle screw at the S1 level. Materials and Methods: A step-by-step approach was developed and performed as follows: (1) Quantitative CT based patient-specific FE model of the sacrum was created. (2) The CAD model of the pedicle screw was inserted into the sacrum model in a bicortical convergent and a monocortical divergent position, by overcoming the geometrical difficulty caused by the broken screw. (3) Static FEAs (Abaqus, Dassault Systemes) were performed using 500 N tensile load applied to the screw head. (4) A template with two screw guiding structures for the sacrum was designed and manufactured using CAD design and 3D-printing technologies, and investment casting. (5) The proposed surgical technique was performed on the patient-specific physical model created with the FDM printing technology. The patient-specific model was CT scanned and a comparison with the virtual plan was performed to evaluate the template accuracy Results: FEA results proved that the modified bicortical convergent insertion is stiffer (6,617.23 N/mm) compared to monocortical divergent placement (2,989.07 N/mm). The final template was created via investment casting from cobalt-chrome. The template design concept was shown to be accurate (grade A, Gertzbein-Robbins scale) based on the comparison of the simulated surgery using the patient-specific physical model and the 3D virtual surgical plan. Conclusion: Compared to the conventional surgical navigation techniques, the presented method allows the consideration of the patient-specific biomechanical parameters; is more affordable, and the intraoperative X-ray exposure can be reduced. This new patient- and condition-specific approach may be widely used in revision spine surgeries or in challenging primary cases after its further clinical validation., Competing Interests: MB was employed by the company DO3D Innovations Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Eltes, Bartos, Hajnal, Pokorni, Kiss, Lacroix, Varga and Lazary.)

We investigated the functional network reorganization caused by low-frequency electrical stimulation (LFES) of human brain cortical surface. Intracranial EEG data from subdural grid positions were analyzed in 16 pre-surgery epileptic patients. LFES was performed by injecting current pulses (10 mA, 0.2 ms pulse width, 0.5 Hz, 25 trials) into all adjacent electrode contacts. Dynamic functional connectivity analysis was carried out on two frequency bands (low: 1-4 Hz; high: 10-40 Hz) to investigate the early, high frequency and late, low frequency responses elicited by the stimulation. The centralization increased in early compared to late responses, suggesting a more prominent role of direct neural links between primarily activated areas and distant brain regions. Injecting the current into the seizure onset zone (SOZ) evoked a more integrated functional topology during the early (N1) period of the response, whereas during the late (N2) period - regardless of the stimulation site - the connectedness of the SOZ was elevated compared to the non-SOZ tissue. The abnormal behavior of the epileptic sub-network during both part of the responses supports the idea of the pathogenic role of impaired inhibition and excitation mechanisms in epilepsy.

Interneurons operating with glycine neurotransmitter are involved in the regulation of pain transmission in the dorsal horn of the spinal cord. In addition to interneurons, glycine release also occurs from glial cells neighboring glutamatergic synapses in the spinal cord. Neuronal and glial release of glycine is controlled by glycine transporters (GlyTs). Inhibitors of the two isoforms of GlyTs, the astrocytic type-1 (GlyT-1) and the neuronal type-2 (GlyT-2), decrease pain sensation evoked by injuries of peripheral sensory neurons or inflammation. The function of dorsal horn glycinergic interneurons has been suggested to be reduced in neuropathic pain, which can be reversed by GlyT-2 inhibitors (Org-25543, ALX1393). Several lines of evidence also support that peripheral nerve damage or inflammation may shift glutamatergic neurochemical transmission from N-methyl-D aspartate (NMDA) NR1/NR2A receptor- to NR1/NR2B receptor-mediated events (subunit switch). This pathological overactivation of NR1/NR2B receptors can be reduced by GlyT-1 inhibitors (NFPS, Org-25935), which decrease excessive glycine release from astroglial cells or by selective antagonists of NR2B subunits (ifenprodil, Ro 25-6981). Although several experiments suggest that GlyT inhibitors may represent a novel strategy in the control of neuropathic pain, proving this concept in human beings is hampered by lack of clinically applicable GlyT inhibitors. We also suggest that drugs inhibiting both GlyT-1 and GlyT-2 non-selectively and reversibly, may favorably target neuropathic pain. In this paper we overview inhibitors of the two isoforms of GlyTs as well as the effects of these drugs in experimental models of neuropathic pain. In addition, the possible mechanisms of action of the GlyT inhibitors, i.e. how they affect the neurochemical and pain transmission in the spinal cord, are also discussed. The growing evidence for the possible therapeutic intervention of neuropathic pain by GlyT inhibitors further urges development of drugable compounds, which may beneficially restore impaired pain transmission in various neuropathic conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Targeted stimulation can be used to modulate the activity of brain networks. Previously we demonstrated that direct electrical stimulation produces predictable poststimulation changes in brain excitability. However, understanding the neural dynamics during stimulation and its relationship to poststimulation effects is limited but critical for treatment optimization. Here, we applied 10 Hz direct electrical stimulation across several cortical regions in 14 human subjects (6 males) implanted with intracranial electrodes for seizure monitoring. The stimulation train was characterized by a consistent increase in high gamma (70-170 Hz) power. Immediately post-train, low-frequency (1-8 Hz) power increased, resulting in an evoked response that was highly correlated with the neural response during stimulation. Using two measures of network connectivity, corticocortical evoked potentials (indexing effective connectivity), and theta coherence (indexing functional connectivity), we found a stronger response to stimulation in regions that were highly connected to the stimulation site. In these regions, repeated cycles of stimulation trains and rest progressively altered the stimulation response. Finally, after just 2 min (∼10%) of repetitive stimulation, we were able to predict poststimulation connectivity changes with high discriminability. Together, this work reveals a relationship between stimulation dynamics and poststimulation connectivity changes in humans. Thus, measuring neural activity during stimulation can inform future plasticity-inducing protocols. SIGNIFICANCE STATEMENT Brain stimulation tools have the potential to revolutionize the treatment of neuropsychiatric disorders. Despite the widespread use of brain stimulation techniques such as transcranial magnetic stimulation, the therapeutic efficacy of these technologies remains suboptimal. This is in part because of a lack of understanding of the dynamic neural changes that occur during stimulation. In this study, we provide the first detailed characterization of neural activity during plasticity induction through intracranial electrode stimulation and recording in 14 medication-resistant epilepsy patients. These results fill a missing gap in our understanding of stimulation-induced plasticity in humans. In the longer-term, these data will also guide our translational efforts toward non-invasive, personalized, closed-loop neuromodulation therapy for neurological and psychiatric disorders in humans., (Copyright © 2019 the authors.)

Introduction: In some surgical wards residents start to do laparoscopic operations using both hands, while in other places they only use their dominant hand, and only start to use both hands later. There are no data at the moment about which method is more effective., Methods: We divided 20 students with no laparoscopic experience into 2 groups: one group practised one hand at a time (1K), the other group used both hands (2K) during the 5 days. On the last day both groups had to do every exercise with one hand and two hands as well, then they had to do 3 new exercises, which needed both hands. We measured the time taken, and gave points for the videos taken inside the training box based on OSATS. For statistical analysis we used t-tests, p < 0.05 being significant., Results: On the first day, there was no significant difference between the 1K and 2K groups considering the time taken (518/500 s) and the OSATS points (87/84; 54/55 points). Both groups improved in the mean time and points (1K: 52%, 77% 2K: 50%, 70%) as well, but there was no significant difference between them. In the case of new exercises on the last day, there was no difference between mean time (1K: 425 s, 2K: 411 s) and points (53/59 and 56/52), but there was a significant difference considering the points given for bimanuality., Conclusion: Based on our study, we cannot exactly state that the bimanuality needed for expert laparoscopic surgery would be easier to learn with immediately practising with both hands.

Medication-overuse headache affects 1 to 2 percent of the population. Any kind of painkiller, if taken regularly at least 10 days per month can cause medication-overuse headache, and therefore the possibility of this headache has to be raised whenever a patient with a preexistent headache notices a significant increase in headache frequency during a period of frequent painkiller consumption. Medication-overuse headache is most prevalent in females between 40 and 50 years of age. Its main risk factors are smokig, obesity, depression, and anxiety. The pathomechanism of medication-overuse headache is complex, with a probable genetic propensity and other biological (neurochemical and neurophysiological), as well as psychological and behavioural factors (such as anticipatory anxiety, catastrophisation of pain and consequentially a compulsive painkiller use) contributing to its genesis. The prerequisite of successful treatment is the withdrawal of the overused substance, other necessary elements of the therapy include the treatment of withdrawal symptoms including rebound headache, the introduction of an effective preventative therapy, taking into consideration the highly prevalent comorbid disorders as well, and the education and psychological support of patients. As the relapse rate can be as high as 30 to 40% regardless of effective treatment, the prevention of medication-overuse headache is of paramount importance, and the role of general practitioners can hardly be overstated.

Background: Migraine affects more than 10% of the Hungarian population, causes significant disability and severely affects patients' generic and condition-specific quality of life. Despite these facts, a significant proportion of patients is not diagnosed and not treated adequately. Headache centres can provide care for only a fraction of all patients. The task of primary care providers would be greatly simplified by a reliable self-administered migraine screening questionnaire., Objective: To develop a short and reliable questionnaire as a migraine screening tool., Methods: Outpatients at the Headache Service, Department of Neurology, Semmelweis University completed a self-administered questionnaire which contained 9 yes/no questions about their headaches' characteristics. The number of 'yes' answers (the patients' total score) was evaluated in connection with the diagnosis based on the International Headache Society criteria. We calculated the sensitivity, specificity, positive and negative predictive value as well as the misclassification rate for each total score value and used these to establish the final cutoff value of the questionnaire. 306 patients (242 females, mean age 39.1 ± 13.3 years) were enrolled. The diagnosis was migraine in 244., Results: Completing the questionnaire did not pose any difficulty for the patients. At a cutoff value of 5 points the questionnaire's sensitivity was 0.96 and specificity was 0.61. The positive predictive value was 0.91 and the negative pre- dictive value was 0.81. The misclassification rate was 0.11., Discussion: Our results show that the questionnaire may help the diagnosis of migraine. In order to use it in medical practice, its further evaluation is necessary on a large representative sample of the Hungarian population.

Background and Purpose: Medication overuse headache (MOH) is a common form of disabling headache presenting in as much as 30% of the patients seen in headache subspecialty practice. Quality of life (QOL) is frequently used as a secondary endpoint in headache trials. In MOH, previous trials of QOL focused mostly on generic QOL. We report the results of a pilot study that examined the feasibility of using a new QOL questionnaire, the 23-item Comprehensive Headache-related Quality of life Questionnaire (CHQQ), as an indicator of treatment response in MOH., Patients and Methods: Fifteen patients (13 women and two men; mean age: 39.7 +/- 12.5 years) suffering from MOH were enrolled in a complex treatment programme consisting of acute medication withdrawal, preventive pharmacological treatment, structured advice and lifestyle intervention. The clinical data were collected using a detailed headache diary. CHQQ was completed before and after the treatment programme., Results: MOH patients had low QOL values at baseline which was comparable to the QOL of episodic migraine patients. The treatment programme resulted in significant reductions of the number of headache days and attacks, headache severity and analgesic consumption. The dimensions and total score of CHQQ showed a significant increase after the treatment period. Seventeen of CHQQ's 23 individual items also improved significantly., Conclusion: In this study the new headache-specific quality of life instrument CHQQ was able to demonstrate significant improvements after adequate treatment of MOH. This result indicates that the CHQQ may be an adequate tool for assessing quality of life in headache treatment trials.

Aim: To study clinically relevant aspects of sleep behaviour in preterm children in comparison to term children., Methods: Longitudinal sleep behaviour data were collected prospectively by structured interviews in 130 preterm and 75 control term children from birth to age 10 y., Results: No significant differences in sleep duration (time in bed per 24 h), bedsharing, night wakings, bedtime resistance and sleep-onset difficulties were found between preterm and term children., Conclusion: Sleep behaviour does not differ between preterm and term children from birth to age 10 y, indicating that prematurity or neonatal intensive care experience does not significantly affect sleep in the first 10 y of life.

Objective: Maternal cigarette smoking, alcohol use, and other factors confound studies of in utero cocaine exposure. Our goal was to determine whether in utero cocaine exposure is associated with an abnormal neurologic examination in infants, while controlling for concomitant cigarette smoke exposure and other confounding variables., Design: Healthy newborns with birth weights > or =2000 g were prospectively enrolled into a race-matched study of cocaine-exposed and cocaine-unexposed infants. Urine and meconium samples were analyzed for illicit drugs, the cocaine metabolite, benzoylecgonine, and the nicotine metabolite, cotinine. A detailed neurological examination was performed at approximately 6 weeks of age by an examiner blinded to history., Results: At 6 weeks of age, 40 cocaine-exposed infants and 56 cocaine-unexposed infants were examined. Tone abnormalities were the only neurologic abnormalities discovered, predominantly generalized hypertonia. Logistic models found that maternal urine cotinine levels were predictive of an abnormal neurologic examination, whereas cocaine exposure or benzoylecgonine levels were not. No interaction was found between maternal cigarette smoking and cocaine exposure. Race, ethanol exposure, prenatal care, homelessness, and head circumference were not predictive of an abnormal tone examination. The odds ratio for an abnormal examination was 2.9 (95% confidence interval: 1.04-8.25), if the maternal urine cotinine level was >200 ng/mL., Conclusion: Our findings suggest that maternal cigarette smoking may be the major predictor of tone abnormalities reported in cocaine-exposed infants.

Evaluation is presented of whether or not a detailed neuromotor examination at 3 months of age could predict later neurologic abnormalities among term infants with perinatal depression. In a prospective cohort, infants were neurologically evaluated at 3 and 12 months. Infants were scored from 0 to 5 according to a new neuromotor scoring system. The neuromotor score at 3 months (NMS-3) was compared with the NMS at 12 months (NMS-12). Seventy-four infants were enrolled in the study; nine were lost to follow-up, and five died before reaching 1 year. Sixty infants were examined (neurologic abnormalities = 52%, normal = 48% at 1 year). The NMS-3 correlated strongly with the NMS-12 and the results of the 12-month neurologic examination. All infants with a NMS-3 of 5 had neurologic abnormalities at 1 year. Infants with neonatal seizures had a significantly increased risk of developmental abnormalities at 1 year. Eighteen infants exhibited transient abnormalities. Using a simple scoring system, the results of the early neurologic examinations correlated strongly with outcome among term infants with perinatal depression. A subgroup of infants had transient abnormalities. These findings suggest that in term high-risk infants, the 1-year neurologic outcome can be predicted at 3 months of age using these parameters.