bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood neurofilament light chain as a surrogate marker for dystonia
Authors: Wu Meng‐Chen , Chang Yung‐Yee , Lan Min‐Yu , Chen Ying‐Fa , Tai Chun‐Hwei , Chen Szu‐Ju , Lin Chin‐Hsien 
Published: July 2023

AbstractBackground and purposeDystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia.MethodWe enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single‐molecule array.ResultsPlasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole‐exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores.ConclusionPlasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.
TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features
Authors: Zhao Bi , Jiang Qirui , Lin Junyu , Wei Qianqian , Li Chunyu , Hou Yanbing , Cao Bei , Zhang Lingyu , Ou Ruwei , Liu Kuncheng , Yang Tianmi , Xiao Yi , Shang Huifang 
Published: July 2023

AbstractBackground and purposeHaploinsufficiency of TANK‐binding kinase 1 (TBK1) loss‐of‐function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians.MethodsGenetic analysis was performed on 2011 Chinese ALS patients. Software was used to predict the deleteriousness of missense variants in TBK1. In addition, PubMed, Embase and Web of Science were searched for related literature.ResultsTwenty‐six TBK1 variants were identified in 33 of 2011 ALS patients, including six novel LoF variants (0.3%) and 20 rare missense variants, 12 of which were predicted to be deleterious (0.6%). In addition to TBK1 variants, 11 patients had other ALS‐related gene variants. Forty‐two previous studies found that the frequency of TBK1 variants was 1.81% in ALS/FTD patients. The frequency of TBK1 LoF variants in ALS was 0.5% (Asians 0.4%; Caucasian 0.6%) and that of missense variants was 0.8% (Asians 1.0%; Caucasian 0.8%). ALS patients with TBK1 LoF variants affecting the kinase domain had a significantly younger age of onset than patients carrying LoF variants affecting the coiled coil domains CCD1 and CCD2. FTD has a frequency of 10% in Caucasian ALS patients with TBK1 LoF variants, which was not found in our cohort.ConclusionOur study expanded the genotypic spectrum of ALS patients with TBK1 variants and found that the clinical manifestations of TBK1 carriers are diverse.
Sham‐controlled randomized multicentre trial of transcranial direct current stimulation for prolonged disorders of consciousness
Authors: Thibaut Aurore , Fregni Felipe , Estraneo Anna , Fiorenza Salvatore , Noe Enrique , Llorens Roberto , Ferri Joan , Formisano Rita , Morone Giovanni , Bender Andreas , Rosenfelder Martin , Lamberti Gianfranco , Kodratyeva Ekaterina , Kondratyev Sergey , Legostaeva Liudmila , Suponeva Natalia , Krewer Carmen , Müller Friedemann , Dardenne Nadia , Jedidi Haroun , Laureys Steven , Gosseries Olivia , Lejeune Nicolas , Martens Géraldine ,   the IBIA DOC‐SIG
Published: July 2023

AbstractBackground and purposeTranscranial direct current stimulation (tDCS) has been shown to improve signs of consciousness in a subset of patients with disorders of consciousness (DoC). However, no multicentre study confirmed its efficacy when applied during rehabilitation. In this randomized controlled double‐blind study, the effects of tDCS whilst patients were in rehabilitation were tested at the group level and according to their diagnosis and aetiology to better target DoC patients who might repond to tDCS.MethodsPatients received 2 mA tDCS or sham applied over the left prefrontal cortex for 4 weeks. Behavioural assessments were performed weekly and up to 3 months’ follow‐up. Analyses were conducted at the group and subgroup levels based on the diagnosis (minimally conscious state [MCS] and unresponsive wakefulness syndrome) and the aetiology (traumatic or non‐traumatic). Interim analyses were planned to continue or stop the trial.ResultsThe trial was stopped for futility when 62 patients from 10 centres were enrolled (44 ± 14 years, 37 ± 24.5 weeks post‐injury, 18 women, 32 MCS, 39 non‐traumatic). Whilst, at the group level, no treatment effect was found, the subgroup analyses at 3 months’ follow‐up revealed a significant improvement for patients in MCS and with traumatic aetiology.ConclusionsTranscranial direct current stimulation during rehabilitation does not seem to enhance patients' recovery. However, diagnosis and aetiology appear to be important factors leading to a response to the treatment. These findings bring novel insights into possible cortical plasticity changes in DoC patients given these differential results according to the subgroups of patients.
Everolimus precision therapy for the GATOR1‐related epilepsies: A case series
Authors: Moloney Patrick B. , Kearney Hugh , Benson Katherine A. , Costello Daniel J. , Cavalleri Gianpiero L. , Gorman Kathleen M. , Lynch Bryan J. , Delanty Norman 
Published: July 2023

AbstractBackgroundPathogenic variants in the GAP activity towards RAGs 1 (GATOR1) complex genes (DEPDC5, NPRL2, NPRL3) cause focal epilepsy through hyperactivation of the mechanistic target of rapamycin pathway. We report our experience using everolimus in patients with refractory GATOR1‐related epilepsy.MethodsWe performed an open‐label observational study of everolimus for drug‐resistant epilepsy caused by variants in DEPDC5, NPRL2 and NPRL3. Everolimus was titrated to a target serum concentration (5–15 ng/mL). The primary outcome measure was change in mean monthly seizure frequency compared with baseline.ResultsFive patients were treated with everolimus. All had highly active (median baseline seizure frequency, 18/month) and refractory focal epilepsy (failed 5–16 prior anti‐seizure medications). Four had DEPDC5 variants (three loss‐of‐function, one missense) and one had a NPRL3 splice‐site variant. All patients with DEPDC5 loss‐of‐function variants had significantly reduced seizures (74.3%–86.1%), although one stopped everolimus after 12 months due to psychiatric symptoms. Everolimus was less effective in the patient with a DEPDC5 missense variant (43.9% seizure frequency reduction). The patient with NPRL3‐related epilepsy had seizure worsening. The most common adverse event was stomatitis.ConclusionsOur study provides the first human data on the potential benefit of everolimus precision therapy for epilepsy caused by DEPDC5 loss‐of‐function variants. Further studies are needed to support our findings.
Trends in the neurological emergency room, focusing on persons with seizures
Authors: Welte Tamara M. , Ernst Sebastian , Stritzelberger Jenny , Gollwitzer Stephanie , Lang Johannes D. , Reindl Caroline , Sprügel Maximilian I. , Olmes David , Schwab Stefan , Blinzler Christian , Hamer Hajo M. 
Published: July 2023

AbstractBackground and purposePrevious studies in neurological emergency rooms (nERs) have reported many non‐acute, self‐presenting patients, patients with delayed presentation of stroke, and frequent visits of persons with seizures (PWS). The aim of this study was to evaluate trends during the last decade, with special focus on PWS.MethodsWe retrospectively analyzed patients who presented to our specialized nER during the course of 5 months in 2017 and 2019, and included information on admission/referral, hospitalization, discharge diagnosis, and diagnostic tests/treatment in the nER.ResultsA total of 2791 patients (46.6% male, mean age 57 ± 21 years) were included. The most common diagnoses were cerebrovascular events (26.3%), headache (14.1%), and seizures (10.5%). Most patients presented with symptoms lasting >48 h (41.3%). The PWS group included the largest proportion of patients presenting within 4.5 h of symptom onset (171/293, 58.4%), whereas only 37.1% of stroke patients presented within this time frame (273/735). Self‐presentation was the most common admission pathway (31.1%), followed by emergency service referral (30.4%, including the majority of PWS: 197/293, 67.2%). Despite known diagnosis of epilepsy in 49.2%, PWS more often underwent accessory diagnostic testing including cerebral imaging, compared to the overall cohort (accessory diagnostics 93.9% vs. 85.4%; cerebral imaging 70.1% vs. 64.1%). Electroencephalography in the nER was only performed in 20/111 patients (18.0%) with a first seizure. Nearly half of the patients (46.7%) were discharged home after nER work‐up, including most self‐presenters (632/869, 72.7%) and headache patients (377/393, 88.3%), as well as 37.2% (109/293) of PWS.ConclusionAfter 10 years, nER overuse remains a problem. Stroke patients still do not present early enough, whereas PWS, even those with known epilepsy, often seek acute and extensive assessment, indicating gaps in pre‐hospital management and possible over‐assessment.
Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications
Authors: Bethamcharla Raviteja , Abou‐Al‐Shaar Hussam , Maarbjerg Stine , Chang Yue‐Fang , Gacka Caroline N. , Sekula Raymond F. 
Published: July 2023

AbstractBackground and purposePatients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG).MethodsWe performed a retrospective single‐center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale.ResultsForty‐five patients underwent a total of 66 PGRs of the TG. At short‐term follow‐up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow‐up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb‐V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications.ConclusionIn patients with these anatomical subtypes of TN there was a high rate of short‐term pain relief for the first 1–2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.
Machine learning using multimodal clinical, electroencephalographic, and magnetic resonance imaging data can predict incident depression in adults with epilepsy: A pilot study
Authors: Delgado‐García Guillermo , Engbers Jordan D. T. , Wiebe Samuel , Mouches Pauline , Amador Kimberly , Forkert Nils D. , White James , Sajobi Tolulope , Klein Karl Martin , Josephson Colin B. ,   the Calgary Comprehensive Epilepsy Program Collaborators
Published: July 2023

AbstractObjectiveThis study was undertaken to develop a multimodal machine learning (ML) approach for predicting incident depression in adults with epilepsy.MethodsWe randomly selected 200 patients from the Calgary Comprehensive Epilepsy Program registry and linked their registry‐based clinical data to their first‐available clinical electroencephalogram (EEG) and magnetic resonance imaging (MRI) study. We excluded patients with a clinical or Neurological Disorders Depression Inventory for Epilepsy (NDDI‐E)‐based diagnosis of major depression at baseline. The NDDI‐E was used to detect incident depression over a median of 2.4 years of follow‐up (interquartile range [IQR] = 1.5–3.3 years). A ReliefF algorithm was applied to clinical as well as quantitative EEG and MRI parameters for feature selection. Six ML algorithms were trained and tested using stratified threefold cross‐validation. Multiple metrics were used to assess model performances.ResultsOf 200 patients, 150 had EEG and MRI data of sufficient quality for ML, of whom 59 were excluded due to prevalent depression. Therefore, 91 patients (41 women) were included, with a median age of 29 (IQR = 22–44) years. A total of 42 features were selected by ReliefF, none of which was a quantitative MRI or EEG variable. All models had a sensitivity > 80%, and five of six had an F1 score ≥ .72. A multilayer perceptron model had the highest F1 score (median = .74, IQR = .71–.78) and sensitivity (84.3%). Median area under the receiver operating characteristic curve and normalized Matthews correlation coefficient were .70 (IQR = .64–.78) and .57 (IQR = .50–.65), respectively.SignificanceMultimodal ML using baseline features can predict incident depression in this population. Our pilot models demonstrated high accuracy for depression prediction. However, overall performance and calibration can be improved. This model has promise for identifying those at risk for incident depression during follow‐up, although efforts to refine it in larger populations along with external validation are required.
Antiseizure medication selection and retention for adult onset focal epilepsy in a Swedish health service region: A population‐based cohort study
Authors: Larsson David , Mroué Deala , Andrén Kerstin , Zelano Johan 
Published: July 2023

AbstractObjectiveHistorically, approximately half of those with newly diagnosed epilepsy have responded to and tolerated the first antiseizure medication (ASM), but there are few contemporary real‐world data. Third‐generation ASMs have improved tolerability and are increasingly used according to prescription data. We aimed to describe current ASM selection and retention in adult onset focal epilepsy in western Sweden.MethodsA multicenter retrospective cohort study was performed at five public neurology care providers in western Sweden (nearly complete coverage in the area). We reviewed 2607 medical charts and included patients diagnosed with nongeneralized epilepsy after January 1, 2020 who had a seizure onset after age 25 years (presumed focal onset) and were started on ASM monotherapy.ResultsA total of 542 patients (median age at seizure onset = 68 years, interquartile range = 52–77) were included. Most patients received levetiracetam (62%) or lamotrigine (35%), with levetiracetam being more common among men and those with structural causes or short epilepsy duration. During follow‐up (median = 471.5 days), 463 patients (85%) remained on the first ASM. Fifty‐nine (18%) patients discontinued levetiracetam, and 18 (10%) ended treatment with lamotrigine (p = .010), most commonly because of side effects. In a multivariable Cox regression model, the discontinuation risk was higher for levetiracetam than lamotrigine (adjusted hazard ratio = 2.01, 95% confidence interval = 1.16–3.51).SignificanceLevetiracetam and lamotrigine were the dominating first ASMs for adult onset focal epilepsy in our region, indicating good awareness of problems with enzyme induction or teratogenicity of older drugs. The most striking finding is the high retention rates, perhaps reflecting a shift toward an older epilepsy population, higher tolerability of newer ASMs, or suboptimal follow‐up. The finding that treatment retention differed among patients receiving levetiracetam and lamotrigine aligns with the recent SANAD II results. It suggests lamotrigine may be underutilized in our region and that education efforts are needed to ensure it is considered the first choice more often.
First seizure from sleep: Clinical features and prognosis
Authors: Lawn Nicholas D. , Pang Elaine W. , Lee Judy , Dunne John W. 
Published: July 2023

AbstractObjectivesPatients with a first‐ever unprovoked seizure commonly have subsequent seizures and identifying predictors of recurrence has important management implications. Both prior brain insult and epileptiform abnormalities on electroencephalography (EEG) are established predictors of seizure recurrence. Some studies suggest that a first‐ever seizure from sleep has a higher likelihood of recurrence. However, with relatively small numbers and inconsistent definitions, more data are required.MethodsProspective cohort study of adults with first‐ever unprovoked seizure seen by a hospital‐based first seizure service between 2000 and 2015. Clinical features and outcomes of first‐ever seizure from sleep and while awake were compared.ResultsFirst‐ever unprovoked seizure occurred during sleep in 298 of 1312 patients (23%), in whom the 1‐year cumulative risk of recurrence was 56.9% (95% confidence interval [CI] 51.3–62.6) compared to 44.2% (95% CI 41.1–47.3, p < .0001) for patients with first‐ever seizure while awake. First‐ever seizure from sleep was an independent predictor of seizure recurrence, with a hazard ratio [HR] of 1.44 (95% CI 1.23–1.69), similar to epileptiform abnormalities on EEG (HR 1.48, 95% CI 1.24–1.76) and remote symptomatic etiology (HR 1.47, 95% CI 1.27–1.71). HR for recurrence in patients without either epileptiform abnormalities or remote symptomatic etiology was 1.97 (95% CI 1.60–2.44) for a sleep seizure compared to an awake seizure. For first seizure from sleep, 76% of second seizures also arose from sleep (p < .0001), with 65% of third seizures (p < .0001) also from sleep. Seizures from sleep were less likely to be associated with injury other than orolingual trauma, both with the presenting seizure (9.4% vs 30.6%, p < .0001) and first recurrence (7.5% vs 16.3%, p = .001).SignificanceFirst‐ever unprovoked seizures from sleep are more likely to recur, independent of other risk factors, with recurrences also usually from sleep, and with a lower risk of seizure‐related injury. These findings may inform treatment decisions and counseling after first‐ever seizure.
The effect of sealing process on the textural and sensory properties and protein profile of cooked meat
Authors: Kilic Sare , Oz Emel , Turhan Sadettin , Amarowickz Ryszard , Toldra Fidel , Brennan Charles , Oz Fatih 
Published: July 2023

SummaryThis work aimed to determine the effect of sealing process at different internal temperatures on the cooking loss, lipid oxidation, textural, and sensory properties, as well as the protein profile of cooked meat. For this aim, four different groups were formed. The control group was not sealed, while the other three groups were sealed until their internal temperature reached 20, 30, and 40 °C. Then, all samples were baked until their internal endpoint temperature reached 71 °C to ensure food safety. The lowest cooking loss (11.57%) was detected in the control group, and increased sealing core temperature resulted in an increase in cooking loss. The sealing did not show a significant effect (P > 0.05) on the TBARS value. On the other hand, myofibrillar and sarcoplasmic protein profile were influenced by sealing. Myofibrillar protein profile showed that protein denaturation rate was higher in groups sealed at the internal temperature of 30 and 40 °C. The sealing process affected only the hardness value among the textural properties examined. With the sealing process, the hardness value of the meat significantly (P < 0.05) reduced and the lowest hardness value was determined in the sample sealed at the internal temperature of 20 °C. Sealing positively affected the overall acceptability score of the samples, and the samples sealed until their internal temperatures reached 30 and 40 °C had higher overall acceptability scores.
Histology‐based classifier to distinguish early mycosis fungoides from atopic dermatitis
Authors: Roenneberg Sophie , Braun Stephan Alexander , Garzorz‐Stark Natalie , Stark Sebastian Paul , Muresan Ana‐Maria , Schmidle Paul , Biedermann Tilo , Guenova Emmanuella , Eyerich Kilian 
Published: July 2023

AbstractBackgroundHistopathological differentiation of early mycosis fungoides (MF) from benign chronic inflammatory dermatoses remains difficult and often impossible, despite the inclusion of all available diagnostic parameters.ObjectiveTo identify the most impactful histological criteria for a predictive diagnostic model to discriminate MF from atopic dermatitis (AD).MethodsIn this multicentre study, two cohorts of patients with either unequivocal AD or MF were evaluated by two independent dermatopathologists. Based on 32 histological attributes, a hypothesis‐free prediction model was developed and validated on an independent patient's cohort.ResultsA reduced set of two histological features (presence of atypical lymphocytes in either epidermis or dermis) was trained. In an independent validation cohort, this model showed high predictive power (95% sensitivity and 100% specificity) to differentiate MF from AD and robustness against inter‐individual investigator differences.Limitations.The study investigated a limited number of cases and the classifier is based on subjectively evaluated histological criteria.ConclusionAiming at distinguishing early MF from AD, the proposed binary classifier performed well in an independent cohort and across observers. Combining this histological classifier with immunohistochemical and/or molecular techniques (such as clonality analysis or molecular classifiers) could further promote differentiation of early MF and AD.