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Epileptic Disorders : International... Jul 2024Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined...
OBJECTIVE
Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease.
METHODS
Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done.
RESULTS
Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox-Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations.
SIGNIFICANCE
Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE.
PubMed: 38953904
DOI: 10.1002/epd2.20261 -
Investigative Ophthalmology & Visual... Jul 2024To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
PURPOSE
To investigate the correlation between apparent diffusion coefficient (ADC) histograms and high-risk clinicopathologic features related to uveal melanoma (UM) prognosis.
METHODS
This retrospective study included 53 patients with UM who underwent diffusion-weighted imaging (DWI) between August 2015 and March 2024. Axial DWI was performed with a single-shot spin-echo echo-planar imaging sequence. ADC histogram parameters of ADCmean, ADC50%, interquartile range (IQR), skewness, kurtosis, and entropy were obtained from DWI. The relationships between histogram parameters and high-risk clinicopathological characteristics including tumor size, preoperative retinal detachment, histological subtypes, Ki-67 index, and chromosome status, were analyzed by Spearman correlation analysis, Mann-Whitney U test, or Kruskal-Wallis test.
RESULTS
A total of 53 patients (mean ± SD age, 55 ± 15 years; 22 men) were evaluated. The largest basal diameter (LBD) was correlated with kurtosis (r = 0.311, P = 0.024). Tumor prominence (TP) was correlated with entropy (r = 0.581, P < 0.001) and kurtosis (r = 0.273, P = 0.048). Additionally, significant correlations were identified between the Ki-67 index and ADCmean (r = -0.444, P = 0.005), ADC50% (r = -0.487, P = 0.002), and skewness (r = 0.394, P = 0.014). Finally, entropy was correlated with monosomy 3 (r = 0.541, P = 0.017).
CONCLUSIONS
The ADC histograms provided valuable insights into high-risk clinicopathologic features of UM and hold promise in the early prediction of UM prognosis.
Topics: Humans; Uveal Neoplasms; Male; Female; Middle Aged; Melanoma; Retrospective Studies; Prognosis; Diffusion Magnetic Resonance Imaging; Adult; Aged; Echo-Planar Imaging
PubMed: 38953846
DOI: 10.1167/iovs.65.8.3 -
Journal of Bronchology & Interventional... Jul 2024Cone beam computed tomography (CBCT)-guided bronchoscopic sampling of peripheral pulmonary lesions (PPLs) is associated with superior diagnostic outcomes. However, the...
BACKGROUND
Cone beam computed tomography (CBCT)-guided bronchoscopic sampling of peripheral pulmonary lesions (PPLs) is associated with superior diagnostic outcomes. However, the added value of a robotic-assisted bronchoscopy platform in CBCT-guided diagnostic procedures is unknown.
METHODS
We performed a retrospective review of 100 consecutive PPLs sampled using conventional flexible bronchoscopy under CBCT guidance (FB-CBCT) and 100 consecutive PPLs sampled using an electromagnetic navigation-guided robotic-assisted bronchoscopy platform under CBCT guidance (RB-CBCT). Patient demographics, PPL features, procedural characteristics, and procedural outcomes were compared between the 2 cohorts.
RESULTS
Patient and PPL characteristics were similar between the FB-CBCT and RB-CBCT cohorts, and there were no significant differences in diagnostic yield (88% vs. 90% for RB-CBCT, P=0.822) or incidence of complications between the 2 groups. As compared with FB-CBCT cases, RB-CBCT cases were significantly shorter (median 58 min vs. 92 min, P<0.0001) and used significantly less diagnostic radiation (median dose area product 5114 µGy•m2 vs. 8755 µGy•m2, P<0.0001).
CONCLUSION
CBCT-guided bronchoscopy with or without a robotic-assisted bronchoscopy platform is a safe and effective method for sampling PPLs, although the integration of a robotic-assisted platform was associated with significantly shorter procedure times and significantly less radiation exposure.
Topics: Humans; Bronchoscopy; Male; Retrospective Studies; Female; Cone-Beam Computed Tomography; Middle Aged; Aged; Lung Neoplasms; Adult; Robotic Surgical Procedures; Aged, 80 and over; Robotics; Lung
PubMed: 38953732
DOI: 10.1097/LBR.0000000000000971 -
Operative Neurosurgery (Hagerstown, Md.) Jul 2024The trans-sinus transglabellar and bifrontal approaches offer direct access to the anterior cranial fossa. However, these approaches present potential drawbacks. We...
BACKGROUND AND OBJECTIVES
The trans-sinus transglabellar and bifrontal approaches offer direct access to the anterior cranial fossa. However, these approaches present potential drawbacks. We propose the biportal endoscopic transfrontal sinus (BETS) approach, adapting endoscopic endonasal approach (EEA) techniques for minimally invasive access to the anterior fossa, reducing tissue manipulation, venous sacrifice, and brain retraction.
METHODS
Six formalin specimens were used. BETS approach involves 2 incisions over the medial aspect of both eyebrows from the supraorbital notch to the medial end of the eyebrow. A unilateral pedicled pericranial flap is harvested. A craniotomy through the anterior table of the frontal sinus (FS) and a separate craniotomy through the posterior table are performed. Two variants of the approach (preservative vs cranialization) are described for opening and reconstruction of the FS based on the desired pathology to access. Bone flap replacement can be performed with titanium plates and filling of the external table defect with bone cement.
RESULTS
Like in EEA, this approach provides access for endoscope and multiple working instruments to be used simultaneously. The approach allows wide access to the anterior cranial fossa, subfrontal, and interhemispheric corridors, all the way up to the suprachiasmatic corridor and through the lamina terminalis to the third ventricle. BETS provides direct access to the anterior fossa, minimizing the level of frontal lobe retraction and providing potentially less tissue disruption and improved cosmesis. Cerebrospinal fluid fistula risk remains one of the major concerns as the narrow corridor limits achieving a watertight closure which can be mitigated with a pedicled flap. Mucocele risk is minimized with full cranialization or reconstruction of the FS.
CONCLUSION
The BETS approach is a minimally invasive approach that translates the concepts of EEA to the FS. It allows excellent access to the anterior cranial fossa structures with minimal frontal lobe retraction.
PubMed: 38953666
DOI: 10.1227/ons.0000000000001249 -
Operative Neurosurgery (Hagerstown, Md.) Jul 2024The surgical management of rostral disc herniations at L5-S1 poses challenges for conventional endoscopic approaches, particularly in patients who have had previous...
Full Endoscopic Transpedicular Discectomy for a Rostrally Migrated L5-S1 Disc Herniation in the Setting of Previous Lumbar Surgery: A Case Report With Intraoperative Video.
BACKGROUND AND IMPORTANCE
The surgical management of rostral disc herniations at L5-S1 poses challenges for conventional endoscopic approaches, particularly in patients who have had previous lumbar surgery. We present a full endoscopic transpedicular discectomy (FETD), whereby a pediculotomy is created to pass an endoscope through the pedicle for intracanal access. This addresses anatomic obstacles and potential complications associated with other endoscopic and minimally invasive or open techniques. To date, this is the only article to highlight this approach with a case report and intraoperative video.
CLINICAL PRESENTATION
A 76-year-old man with a history of L3-S1 laminectomy presented with left leg pain and a near-complete left foot drop. An MRI revealed a left paracentral rostrally migrated disc herniation arising from L5-S1 with impingement of the exiting left L5 nerve root at the inferomedial aspect of the pedicle of L5. The patient consented to the FETD procedure. Using sequential reamers of increasing diameter and a high-speed burr, a superolateral to inferomedial pediculotomy was performed. This approach allowed us to target the pathology at the point of maximum compression without traversing the prior operative field. A transforaminal endoscopic approach was not possible with the iliac crest obstructing rostral angulation. The disc was successfully removed without any intraoperative complications, and after surgery, the patient's radiculopathy resolved without any radiographic evidence of instability.
CONCLUSION
FETD is a unique approach that demonstrates the versatility of endoscopic spine surgery, offering advantages over conventional approaches particularly for rostral disc herniations at L5-S1 in the setting of prior lumbar surgery.
PubMed: 38953650
DOI: 10.1227/ons.0000000000001237 -
Journal of Neuroscience Research Jul 2024Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of... (Meta-Analysis)
Meta-Analysis Review
Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.
Topics: Huntington Disease; Humans; Gray Matter; Neuroimaging; Brain; Magnetic Resonance Imaging
PubMed: 38953592
DOI: 10.1002/jnr.25366 -
General Physiology and Biophysics Jul 2024Alzheimer's disease is currently not curable. Almost all attempts to identify disease-modifying drugs failed and the causes of disease etiology are not well understood....
Alzheimer's disease is currently not curable. Almost all attempts to identify disease-modifying drugs failed and the causes of disease etiology are not well understood. Neurofibrillary tangles composed of pathological tau protein belong to the main hallmarks of this disease. Identification of novel physiological and pathological tau interacting proteins may lead to a better understanding of Alzheimer's disease pathology and tau physiology and therefore we performed a screening of the brain library by a yeast two-hybrid system intending to identify new tau interaction partners. We identified CHORDC1 (cysteine and histidine-rich domain-containing protein 1) as a novel tau interaction partner by this approach. The CHORDC1-tau interaction was validated by co-immunoprecipitation from rat brain tissues and by in vitro co-localization in the cellular model expressing full-length human tau protein. We believe that our results can be useful for researchers studying tau protein in health and disease.
Topics: tau Proteins; Rats; Animals; Humans; Protein Binding; Brain; Protein Interaction Mapping; Two-Hybrid System Techniques
PubMed: 38953578
DOI: 10.4149/gpb_2024019 -
General Physiology and Biophysics Jul 2024Vascular endothelial growth factor A (VEGFA) is an important regulator for non-small cell lung cancer (NSCLC). Our study aimed to reveal its upstream pathway to provide...
Vascular endothelial growth factor A (VEGFA) is an important regulator for non-small cell lung cancer (NSCLC). Our study aimed to reveal its upstream pathway to provide new ideas for developing the therapeutic targets of NSCLC. The mRNA and protein levels of VEGFA, ubiquitin-specific peptidase 35 (USP35), and FUS were determined by quantitative real-time PCR and Western blot. Cell proliferation, apoptosis, invasion and angiogenesis were detected using CCK8 assay, EdU assay, flow cytometry, transwell assay and tube formation assay. The interaction between USP35 and VEGFA was assessed by Co-IP assay and ubiquitination assay. Animal experiments were performed to assess USP35 and VEGFA roles in vivo. VEGFA had elevated expression in NSCLC tissues and cells. Interferences of VEGFA inhibited NSCLC cell proliferation, invasion, angiogenesis, and increased apoptosis. USP35 could stabilize VEGFA protein level by deubiquitination, and USP35 knockdown suppressed NSCLC cell growth, invasion and angiogenesis via reducing VEGFA expression. FUS interacted with USP35 to promote its mRNA stability, thereby positively regulating VEGFA expression. Also, USP35 silencing could reduce NSCLC tumorigenesis by downregulating VEGFA. FUS-stabilized USP35 facilitated NSCLC cell growth, invasion and angiogenesis through deubiquitinating VEGFA, providing a novel idea for NSCLC treatment.
Topics: Humans; Vascular Endothelial Growth Factor A; RNA-Binding Protein FUS; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Cell Proliferation; Neovascularization, Pathologic; Neoplasm Invasiveness; Ubiquitination; Cell Line, Tumor; Mice; Animals; Ubiquitin-Specific Proteases; Mice, Nude; Angiogenesis
PubMed: 38953570
DOI: 10.4149/gpb_2024010 -
BJU International Jul 2024To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical...
OBJECTIVES
To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR).
PATIENTS AND METHODS
We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design.
RESULTS
In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design.
CONCLUSIONS
The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.
PubMed: 38953550
DOI: 10.1111/bju.16445 -
Journal of Biochemical and Molecular... Jul 2024Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and...
Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aβ1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kβ), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aβ1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.
Topics: Animals; Polyunsaturated Alkamides; Benzodioxoles; Curcumin; Piperidines; Alkaloids; Rats; Cyclophosphamide; Male; Brain Injuries; Rats, Wistar; Brain; Oxidative Stress; Neuroprotective Agents
PubMed: 38953502
DOI: 10.1002/jbt.23760