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1.
Dev Neurobiol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830696

ABSTRACT

Formation of the corpus callosum (CC), anterior commissure (AC), and postoptic commissure (POC), connecting the left and right cerebral hemispheres, is crucial for cerebral functioning. Collapsin response mediator protein 2 (CRMP2) has been suggested to be associated with the mechanisms governing this formation, based on knockout studies in mice and knockdown/knockout studies in zebrafish. Previously, we reported two cases of non-synonymous CRMP2 variants with S14R and R565C substitutions. Among the, the R565C substitution (p.R565C) was caused by the novel CRMP2 mutation c.1693C > T, and the patient presented with intellectual disability accompanied by CC hypoplasia. In this study, we demonstrate that crmp2 mRNA could rescue AC and POC formation in crmp2-knockdown zebrafish, whereas the mRNA with the R566C mutation could not. Zebrafish CRMP2 R566C corresponds to human CRMP2 R565C. Further experiments with transfected cultured cells indicated that CRMP2 with the R566C mutation could not bind to kinesin light chain 1 (KLC1). Knockdown of klc1a in zebrafish resulted in defective AC and POC formation, revealing a genetic interaction with crmp2. These findings suggest that the CRMP2 R566C mutant fails to bind to KLC1, preventing axonal elongation and leading to defective AC and POC formation in zebrafish and CC formation defects in humans. Our study highlights the importance of the interaction between CRMP2 and KLC1 in the formation of the forebrain commissures, revealing a novel mechanism associated with CRMP2 mutations underlying human neurodevelopmental abnormalities.

2.
Cancers (Basel) ; 16(10)2024 May 12.
Article in English | MEDLINE | ID: mdl-38791929

ABSTRACT

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

3.
Otolaryngol Head Neck Surg ; 171(1): 172-179, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38639320

ABSTRACT

OBJECTIVES: To assess the value of carbon dioxide transoral laser microsurgery (CO2 TOLMS) for early-stage glottic cancer with special regard to involvement of the anterior commissure (AC). STUDY DESIGN: Single-center retrospective cohort study. SETTING: Grade-A tertiary hospital. METHODS: A retrospective analysis of patients with early-stage (Tis-T2) glottic cancer who underwent CO2 TOLMS. All patients had at least 2 years of follow-up. The univariate and multivariate survival analyses were used to identify the risk factors for recurrence and the Kaplan-Meier method was used to analyze OS and DSS rates. RESULTS: A total of 102 patients were included in the study. Eleven patients (10.78%) had recurrence. The univariate analysis showed that the recurrence was associated with the AC classification, T staging, tumor size, and tobacco use (P < .05). However, on multivariate analysis, the AC classification was the only independent risk factor for recurrence (P < .001, HR = 3.179). AC classification were distributed as follows: 59 (57.84%) AC0, 29 (28.43%) AC1, 8 (7.84%) AC2, and 6 (5.88%) AC3, 2-year/5-year OS and DSS rates were progressively reduced in the AC0, AC1, AC2, and AC3 groups (P < .001). At the same T staging, the OS rates incrementally decreased as the level of involvement of the AC became higher (P = .004). CONCLUSION: CO2 TOLMS is an effective treatment for early-stage glottic cancer. AC involvement is an independent risk factors for recurrence and poor prognosis. The AC classification system may be better at grading the prognosis of patients with early-stage glottic cancer and has prognostic value independent of T staging.


Subject(s)
Glottis , Laryngeal Neoplasms , Laser Therapy , Microsurgery , Neoplasm Staging , Humans , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/mortality , Male , Glottis/surgery , Glottis/pathology , Retrospective Studies , Female , Microsurgery/methods , Middle Aged , Laser Therapy/methods , Aged , Treatment Outcome , Neoplasm Recurrence, Local , Adult , Lasers, Gas/therapeutic use , Aged, 80 and over
4.
Indian J Otolaryngol Head Neck Surg ; 76(1): 490-494, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38440588

ABSTRACT

Introduction: The proper visualisation of the larynx is required for the diagnostic assessment and therapeutic intervention. The most significant challenges for surgeon is to visualise the anterior commissure of the glottis region. The aim of this study is to record the preoperative laryngoscore in patients posted for endolaryngeal surgery and to assess preoperative predictors for intraoperative difficult laryngeal exposure by correlating with preoperative laryngoscore. Design: Prospective, Cross-sectional, Observational study. Setting: Department of Otorhinolaryngology in a tertiary care teaching facility. Subjects: 150 patients were included with an endolaryngeal disease who were planned for surgery with age > 18yrs. Methodology: In 150 subjects preoperative laryngoscore was calculated, which comprised 11 parameters including thyromental distance, mandibular prognathism, macroglossia, micrognathia, trismus, inter incisor gap, degree of neck flexion-extension, history of prior open-neck surgery or radiotherapy, upper jaw dental status, modified Mallampati score and body mass index in order to produce a total score out of a possible maximum score of 17. According to the anterior commissure visualisation all patients were categorised into five classes, ranging from class 0 to class IV during surgery. The laryngoscore parameters were assessed and compared statistically with five classes of intraoperative anterior commissure visualisation. Result: Out of 150 patients 70 (46.6%) were having 3-4 laryngoscore, followed by 45 (30%) patients with 5-6 laryngoscore. Total 123 (82%) patient had class 0,1 and 2 intraoperative anterior commissure visualisation while 27 (18%) had class 3 and 4 visualisation. If laryngoscore was either less or equal to 5, 90% of the patients had excellent laryngeal exposure whereas only 10% of the patients had challenging laryngeal exposure. At univariate analysis, thyromental distance, degree of neck flexion/extension, and modified Mallampati classification were found statistically significant for difficulty of anterior commissure visualisation independently. Conclusion: A sound, easy and valid preoperative laryngoscore may be significantly helpful in identifying intraoperative difficult laryngeal exposure. This may prevent inadequacy of surgery, abandon of surgery, intra operative complication, and medico-legal cases for laryngologist.

5.
Eur Arch Otorhinolaryngol ; 281(5): 2597-2608, 2024 May.
Article in English | MEDLINE | ID: mdl-38424299

ABSTRACT

PURPOSE: The involvement of the anterior commissure (AC) is regarded to be a risk factor for poor results after transoral laser microsurgery (TLM) for early glottic cancer. The objective of this study was to determine how AC-related clinical and radiological factors affected oncological outcomes in a cohort of patients with T1 stage early glottic carcinoma involving the anterior commissure who were treated with TLM with negative surgical margins. METHODS: Retrospective analysis was performed on clinical, radiological, and follow-up data of patients consecutively treated with TLM at a tertiary academic center between November 2011 and August 2021 for T1 glottic squamous cell carcinoma involving the anterior commissure. Recurrence-free survival (RFS), local control with laser alone (LCL), laryngeal preservation (LP), and overall survival (OS) rates (Kaplan-Meier) were the primary outcome metrics. RESULTS: In our series, 5-year OS probability was 75.1%, RFS was 64.8%, LCL was 73.8%, and LP was 83.4%. OS and RFS were higher in patients with early stages of AC pattern than in patients with advanced stage (p = 0.004, p = 0.034, respectively). Vertical extension ratio was found to be associated with OS and RFS (p = 0.023, p = 0.001, respectively), and thyroid cartilage interlaminar angle with LCL by multiple Cox regression analysis (p = 0.041). CONCLUSION: TLM remains a valuable treatment option for AC involvement. AC3 type involvement and elevated vertical extension ratio were associated with negative prognosis. There have been signs that thyroid cartilage with a narrow angle increases recurrence. Alternative modalities should be kept in mind in the treatment decision of these cases.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Laryngeal Neoplasms , Laser Therapy , Tongue Neoplasms , Humans , Laryngeal Neoplasms/diagnostic imaging , Laryngeal Neoplasms/surgery , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Retrospective Studies , Microsurgery/methods , Glottis/diagnostic imaging , Glottis/surgery , Glottis/pathology , Tongue Neoplasms/surgery , Laser Therapy/methods , Head and Neck Neoplasms/pathology , Treatment Outcome , Neoplasm Staging , Neoplasm Recurrence, Local/pathology
6.
Neurobiol Dis ; 193: 106455, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38408685

ABSTRACT

White matter (WM) tract formation and axonal pathfinding are major processes in brain development allowing to establish precise connections between targeted structures. Disruptions in axon pathfinding and connectivity impairments will lead to neural circuitry abnormalities, often associated with various neurodevelopmental disorders (NDDs). Among several neuroimaging methodologies, Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) technique that has the advantage of visualizing in 3D the WM tractography of the whole brain non-invasively. DTI is particularly valuable in unpinning structural tract connectivity defects of neural networks in NDDs. In this study, we used 3D DTI to unveil brain-specific tract defects in two mouse models lacking the Nr2f1 gene, which mutations in patients have been proven to cause an emerging NDD, called Bosch-Boonstra-Schaaf Optic Atrophy (BBSOAS). We aimed to investigate the impact of the lack of cortical Nr2f1 function on WM morphometry and tract microstructure quantifications. We found in both mutant mice partial loss of fibers and severe misrouting of the two major cortical commissural tracts, the corpus callosum, and the anterior commissure, as well as the two major hippocampal efferent tracts, the post-commissural fornix, and the ventral hippocampal commissure. DTI tract malformations were supported by 2D histology, 3D fluorescent imaging, and behavioral analyses. We propose that these interhemispheric connectivity impairments are consistent in explaining some cognitive defects described in BBSOAS patients, particularly altered information processing between the two brain hemispheres. Finally, our results highlight 3DDTI as a relevant neuroimaging modality that can provide appropriate morphometric biomarkers for further diagnosis of BBSOAS patients.


Subject(s)
Optic Atrophy , White Matter , Humans , Mice , Animals , Diffusion Tensor Imaging , White Matter/diagnostic imaging , White Matter/pathology , Brain , Magnetic Resonance Imaging , Optic Atrophy/pathology
7.
Int J Mol Sci ; 25(3)2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38338755

ABSTRACT

In marsupials, upper-layer cortical neurons derived from the progenitors of the subventricular zone of the lateral ventricle (SVZ) mature morphologically and send their axons to form interhemispheric connections through the anterior commissure. In contrast, eutherians have evolved a new extra callosal pathway, the corpus callosum, that interconnects both hemispheres. In this study, we aimed to examine neurogenesis during the formation of cortical upper layers, including their morphological maturation in a marsupial species, namely the opossum (Monodelphis domestica). Furthermore, we studied how the axons of upper layers neurons pass through the anterior commissure of the opossum, which connects neocortical areas. We showed that upper-layer II/III neurons were generated within at least seven days in the opossum neocortex. Surprisingly, these neurons expressed special AT-rich sequence binding protein 2 (Satb2) and neuropilin 1 interacting protein (Nrp1), which are proteins known to be essential for the formation of the corpus callosum in eutherians. This indicates that extrinsic, but not intrinsic, cues could be key players in guiding the axons of newly generated cortical neurons in the opossum. Although oligodendrocyte precursor cells were present in the neocortex and anterior commissure, newly generated upper-layer neurons sent unmyelinated axons to the anterior commissure. We also found numerous GFAP-expressing progenitor cells in both brain structures, the neocortex and the anterior commissure. However, at P12-P17 in the opossums, a small population of astrocytes was observed only in the midline area of the anterior commissure. We postulate that in the opossum, midline astrocytes allow neocortical axons to be guided to cross the midline, as this structure resembles the glial wedge required by fibers to cross the midline area of the corpus callosum in the rodent.


Subject(s)
Monodelphis , Neocortex , Animals , Astrocytes , Axon Guidance , Neurons , Corpus Callosum , Axons/physiology , Eutheria
9.
Bioinformation ; 19(11): 1063-1066, 2023.
Article in English | MEDLINE | ID: mdl-38046518

ABSTRACT

Corpus callosum is one of the major association fibre of brain performs an integral role of integration and communication of information between the two hemispheres. 50 formalin fixed cerebral hemispheres (25 right and 25 left) were used for the study. The longitudinal and vertical length of brain, longitudinal length and height of corpus callosum, distance of corpus callosum from various landmarks such as frontal and occipital pole, anterior commissure, lamina terminalis, and highest point on parietal pole and width of different parts of corpus callosum and height were measured. Results were analysed statistically. The results showed positive correlation between the longitudinal dimension of brain and all other parameters. Morphometric variation in size and its relation to nearby structures are seen in many neurological and psychiatric conditions such as Alzheimer's disease, Schizophrenia and bipolar disorders. Hence the present study can be used as reference by neurologist, neurosurgeons and psychiatrists.

10.
Acta Otolaryngol ; 143(9): 823-828, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37837405

ABSTRACT

BACKGROUND: The current treatment options for T1b glottic carcinoma often lead to poor treatment outcomes or voice quality. OBJECTIVES: This study evaluates the therapeutic efficacy of horizontal middle partial laryngectomy with cricothyroidopexy (HMPL-CTP) for stage T1b glottic carcinoma. MATERIAL AND METHODS: A retrospective analysis was conducted on 73 patients with T1b glottic carcinoma. The patients were categorized into three groups: Group A (n = 22) underwent transoral laser microsurgery (TLMS), Group B (n = 21) received frontolateral vertical partial laryngectomy (FVPL), and Group C (n = 30) underwent HMPL-CTP. The study analyzed the 5-year overall survival rate (OS), recurrence rate, phonatory status, and incidence of laryngeal stenosis. RESULTS: Voice quality scores varied significantly in the three groups, while the 5-year OS were similar. The local recurrence rate is higher in Group A than in the other two groups. The laryngeal stenosis rate in Group B is higher than in Groups A and C. Adhesions in the anterior commissure were observed in 18 cases in Group A and nine cases in Group C. CONCLUSIONS AND SIGNIFICANCE: HMPL-CTP demonstrates efficacy as a treatment for stage T1b glottic carcinoma, offering favorable preservation of laryngeal function and minimal complications.


Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , Laryngostenosis , Humans , Laryngectomy , Glottis/surgery , Glottis/pathology , Laryngostenosis/surgery , Retrospective Studies
11.
Brain Sci ; 13(4)2023 Apr 11.
Article in English | MEDLINE | ID: mdl-37190612

ABSTRACT

Little is known empirically about connectivity and communication between the two hemispheres of the brain in the first year of life, and what theoretical opinion exists appears to be at variance with the meager extant anatomical evidence. To shed initial light on the question of interhemispheric connectivity and communication, this study investigated brain correlates of interhemispheric transmission of information in young human infants. We analyzed EEG data from 12 4-month-olds undergoing a face-related oddball ERP protocol. The activity in the contralateral hemisphere differed between odd-same and odd-difference trials, with the odd-different response being weaker than the response during odd-same trials. The infants' contralateral hemisphere "recognized" the odd familiar stimulus and "discriminated" the odd-different one. These findings demonstrate connectivity and communication between the two hemispheres of the brain in the first year of life and lead to a better understanding of the functional integrity of the developing human infant brain.

12.
BMC Neurol ; 23(1): 190, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37173644

ABSTRACT

BACKGROUND: Intracranial hemorrhage accounts for 10-20% of stroke etiologies annually. Basal ganglia is the most common site for intracranial hemorrhage accounting for 50% of all cases. Bilateral spontaneous basal ganglia hemorrhages (BGH) are rare with few reported cases. CASE PRESENTATION: We report an unusual case of a 69-year-old female who presented with a spontaneous bilateral basal ganglia hemorrhage secondary to a right BGH with contralateral extension through the anterior commissure (AC) utilizing the Canal of Gratiolet. Clinical course and imaging findings are discussed. CONCLUSIONS: To our knowledge, this is the first case to specifically detail the extension of spontaneous hemorrhage across the AC via the Canal of Gratiolet, and imaging findings provide a novel depiction of AC anatomy and fiber distribution in a clinical context. These findings may explain the mechanism behind this rare clinical entity.


Subject(s)
Basal Ganglia Hemorrhage , Stroke , Female , Humans , Aged , Basal Ganglia Hemorrhage/complications , Basal Ganglia Hemorrhage/diagnostic imaging , Basal Ganglia/diagnostic imaging , Stroke/complications , Intracranial Hemorrhages/complications , Intracranial Hemorrhages/diagnostic imaging
13.
Folia Phoniatr Logop ; 75(5): 324-333, 2023.
Article in English | MEDLINE | ID: mdl-37004509

ABSTRACT

INTRODUCTION: The conventional rigid-90° and rigid-70° laryngostroboscopy has been so far considered the gold standard in assessing the vibratory behavior of the vocal folds and the glottal closure configuration during phonation. Meanwhile, this rigid laryngostroboscopy is more and more replaced by flexible chip-on-tip systems. The aim of this study was to evaluate the influence of these different endoscopic techniques on glottal closure configuration and on visibility of the complete focal fold length including anterior commissure during phonation. METHODS: Twenty-one euphonic subjects were enrolled (mean age 34.6 ± 9.5; m = 10, f = 11). They were examined with the three laryngoscopic techniques (conventional rigid-90°, rigid-70°, and flexible chip-on-tip laryngoscopy during low and high voice pitch with soft and loud voice intensity). For evaluating the degree of glottal closure, a modified classification of Södersten et al. was applied and the visibility of the anterior commissure was evaluated. The correlation of the three endoscopic techniques was assessed with Cohen and Fleiss' kappa. RESULTS: In even low loud phonation, the rigid-90° and rigid-70° endoscopies revealed a complete closure of the glottis in only 47.6% of subjects but with flexible endoscopy in 81%. The complete vocal fold length with anterior commissure was best visible with flexible endoscopy in 90.5% in low-soft and high-soft phonation. The rigid-90° endoscopy showed a slight agreement in comparison with the flexible endoscopy in regard to the types of vocal fold closure with a Cohen's kappa coefficient k = 0.199. The rigid-90° endoscopy showed an almost perfect agreement with k = 0.84 when compared to the rigid-70° endoscopy. The flexible endoscopy compared to the rigid-70° endoscopy showed a fair agreement with k = 0.346. CONCLUSION: We found mainly corresponding results in both rigid-90° and rigid-70° endoscopic techniques which can be explained by the same transoral approach with the tongue pulled out, whereas the flexible transnasal endoscopy mainly gives a better view on the anterior commissure. The influence of transorally or transnasally guided endoscopic techniques needs to be considered in interpretation of laryngostroboscopic parameters like vocal fold closure and supraglottal hyperactivity.


Subject(s)
Laryngoscopy , Voice Quality , Humans , Adult , Laryngoscopy/methods , Vocal Cords , Glottis , Phonation , Tongue
14.
Biomolecules ; 13(2)2023 02 01.
Article in English | MEDLINE | ID: mdl-36830639

ABSTRACT

α-Synucleinopathies are spreading neurodegenerative disorders characterized by the intracellular accumulation of insoluble aggregates populated by α-Synuclein (α-Syn) fibrils. In Parkinson's disease (PD) and dementia with Lewy bodies, intraneuronal α-Syn aggregates are referred to as Lewy bodies in the somata and as Lewy neurites in the neuronal processes. In multiple system atrophy (MSA) α-Syn aggregates are also found within mature oligodendrocytes (OLs) where they form Glial Cytoplasmic Inclusions (GCIs). However, the origin of GCIs remains enigmatic: (i) mature OLs do not express α-Syn, precluding the seeding and the buildup of inclusions and (ii) the artificial overexpression of α-Syn in OLs of transgenic mice results in a burden of soluble phosphorylated α-Syn but fails to form α-Syn fibrils. In contrast, mass spectrometry of α-Syn fibrillar aggregates from MSA patients points to the neuronal origin of the proteins intimately associated with the fibrils within the GCIs. This suggests that GCIs are preassembled in neurons and only secondarily incorporated into OLs. Interestingly, we recently isolated a synthetic human α-Syn fibril strain (1B fibrils) capable of seeding a type of neuronal inclusion observed early and specifically during MSA. Our goal was thus to investigate whether the neuronal α-Syn pathology seeded by 1B fibrils could eventually be transmitted to OLs to form GCIs in vivo. After confirming that mature OLs did not express α-Syn to detectable levels in the adult mouse brain, a series of mice received unilateral intra-striatal injections of 1B fibrils. The resulting α-Syn pathology was visualized using phospho-S129 α-Syn immunoreactivity (pSyn). We found that even though 1B fibrils were injected unilaterally, many pSyn-positive neuronal somas were present in layer V of the contralateral perirhinal cortex after 6 weeks. This suggested a fast retrograde spread of the pathology along the axons of crossing cortico-striatal neurons. We thus scrutinized the posterior limb of the anterior commissure, i.e., the myelinated interhemispheric tract containing the axons of these neurons: we indeed observed numerous pSyn-positive linear Lewy Neurites oriented parallel to the commissural axis, corresponding to axonal segments filled with aggregated α-Syn, with no obvious signs of OL α-Syn pathology at this stage. After 6 months however, the commissural Lewy neurites were no longer parallel but fragmented, curled up, sometimes squeezed in-between two consecutive OLs in interfascicular strands, or even engulfed inside OL perikarya, thus forming GCIs. We conclude that the 1B fibril strain can rapidly induce an α-Syn pathology typical of MSA in mice, in which the appearance of GCIs results from the pruning of diseased axonal segments containing aggregated α-Syn.


Subject(s)
Multiple System Atrophy , Synucleinopathies , Humans , Mice , Animals , alpha-Synuclein/metabolism , Multiple System Atrophy/pathology , Lewy Bodies/metabolism , Inclusion Bodies/metabolism , Synucleinopathies/metabolism , Oligodendroglia/metabolism , Neurites/metabolism , Mice, Transgenic , Brain/metabolism
15.
Front Neurosci ; 17: 1100121, 2023.
Article in English | MEDLINE | ID: mdl-36793543

ABSTRACT

Over the last decade, a large variety of alterations of the Contactin Associated Protein 2 (CNTNAP2) gene, encoding Caspr2, have been identified in several neuronal disorders, including neurodevelopmental disorders and peripheral neuropathies. Some of these alterations are homozygous but most are heterozygous, and one of the current challenges is to estimate to what extent they could affect the functions of Caspr2 and contribute to the development of these pathologies. Notably, it is not known whether the disruption of a single CNTNAP2 allele could be sufficient to perturb the functions of Caspr2. To get insights into this issue, we questioned whether Cntnap2 heterozygosity and Cntnap2 null homozygosity in mice could both impact, either similarly or differentially, some specific functions of Caspr2 during development and in adulthood. We focused on yet poorly explored functions of Caspr2 in axon development and myelination, and performed a morphological study from embryonic day E17.5 to adulthood of two major brain interhemispheric myelinated tracts, the anterior commissure (AC) and the corpus callosum (CC), comparing wild-type (WT), Cntnap2 -/- and Cntnap2 +/- mice. We also looked for myelinated fiber abnormalities in the sciatic nerves of mutant mice. Our work revealed that Caspr2 controls the morphology of the CC and AC throughout development, axon diameter at early developmental stages, cortical neuron intrinsic excitability at the onset of myelination, and axon diameter and myelin thickness at later developmental stages. Changes in axon diameter, myelin thickness and node of Ranvier morphology were also detected in the sciatic nerves of the mutant mice. Importantly, most of the parameters analyzed were affected in Cntnap2 +/- mice, either specifically, more severely, or oppositely as compared to Cntnap2 -/- mice. In addition, Cntnap2 +/- mice, but not Cntnap2 -/- mice, showed motor/coordination deficits in the grid-walking test. Thus, our observations show that both Cntnap2 heterozygosity and Cntnap2 null homozygosity impact axon and central and peripheral myelinated fiber development, but in a differential manner. This is a first step indicating that CNTNAP2 alterations could lead to a multiplicity of phenotypes in humans, and raising the need to evaluate the impact of Cntnap2 heterozygosity on the other neurodevelopmental functions of Caspr2.

16.
J Voice ; 37(5): 801.e9-801.e15, 2023 Sep.
Article in English | MEDLINE | ID: mdl-34175169

ABSTRACT

PURPOSE: Awareness of variations in laryngeal anatomy among different age and gender groups is crucial during laryngeal framework surgery. The aim of this study is to demonstrate the relationship between gender and laryngeal radiologic morphometrics among different age groups and the applicability of important anatomical landmarks of laryngeal surgery. METHODS: Laryngeal images of 180 adult patients older than 18 years of age were obtained by computed tomography and assessed. A total of 11 measurements of important laryngeal landmarks were taken from the patients' computed tomography images. Results were subgrouped according to gender and age, and these groups were compared for each measurement. RESULTS: The majority of laryngeal measurements obtained in the study were higher in males than females, with the exception of the interlaminar angle. The mean interlaminar angle value was 88.27°± 14.99 for males and 103.04°± 14.81 for females (P <0.005). The distance from the anterior commissure to the inferior border of the thyroid cartilage was 10.46 ± 2.5 mm for males and 7.72 ± 1.9 mm for females. The anterior commissure locates slightly higher than the midpoint of the distance from the thyroid notch to the thyroid inferior border. The shortest distance between the muscular process of the arytenoid cartilage and the thyroid cartilage was found to be 9.60 ± 3.47 mm for males and 7.72 ± 2.33 mm for females (P <0.001). CONCLUSION: Observation of obvious diversities in the size and distance of the important laryngeal structures between the gender groups is an important factor to be considered for successful laryngeal framework surgery. Also, using the midpoint of the thyroid cartilage as a landmark for anterior commissure is a practical method during surgery, especially for thyroplasty.


Subject(s)
Laryngoplasty , Larynx , Male , Adult , Female , Humans , Larynx/diagnostic imaging , Larynx/surgery , Larynx/anatomy & histology , Thyroid Cartilage/diagnostic imaging , Thyroid Cartilage/surgery , Arytenoid Cartilage/anatomy & histology , Tomography, X-Ray Computed
17.
Auris Nasus Larynx ; 50(3): 415-422, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36163067

ABSTRACT

OBJECTIVE: Anterior commissure (AC) involvement is an unfavorable factor for transoral laser microsurgery (TLM) treatment of early glottic carcinoma (EGC). This study aimed to evaluate the therapeutic efficacy of TLM treatment for EGC with AC involvement. METHODS: From 2008 to 2017, 177 patients with T1-T2 EGC with AC involvement were retrospectively included and divided into the TLM group (n=115) receiving CO2 laser TLM and the control group undergoing open surgery (n=62). The survival outcomes, postoperative complications, laryngeal preservation rate, recurrence and the phonological results were compared between groups. RESULT: The TLM group had significantly reduced hospital stay, hospitalization costs, and intraoperative blood loss as compared with the control group. The tracheotomy rate was significantly higher in the control group (96.8% vs. 0%). The 5-year overall survival (OS) was 89.6% and 85.5% in the TLM group and control group, respectively. Log-rank test showed no difference in survival rate between the two groups. There was no significant difference in laryngeal preservation rate and overall recurrence rate between groups. In postoperative vocal function evaluation, there were significant differences in the overall grade (G), the roughness (R), the breathiness (B), Voice Handicap Index-10 (VHI-10), Jitter, Shimmer, noise/harmonic ratio (NHR), maximum phonation time (MPT), phonation threshold pressure (PTP) between the two groups. CONCLUSION: For EGC with AC involvement, TLM has similar survival outcomes with the open surgery, but has better postoperative voice outcomes. Meanwhile, TLM can effectively reduce intraoperative blood loss, hospitalization time, hospitalization costs and postoperative complications.


Subject(s)
Carcinoma , Laryngeal Neoplasms , Laser Therapy , Lasers, Gas , Humans , Microsurgery/methods , Carbon Dioxide , Treatment Outcome , Retrospective Studies , Blood Loss, Surgical , Glottis/surgery , Glottis/pathology , Laryngeal Neoplasms/pathology , Laser Therapy/methods , Lasers, Gas/therapeutic use , Carcinoma/pathology
18.
JTCVS Tech ; 15: 73-77, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36276680

ABSTRACT

Objectives: Mitral valve repair for extensive commissural prolapse is complex; several methods have been reported with variable results. To restore the leaflet area, we introduced an innovative and effective method rather than a simple folding technique through reconstructing a neocommissure with a "collar-like" plasty technique. Methods: From 2016 to 2021, 62 patients with mitral valve extensive commissural prolapse that received the "collar-like" plasty technique were included. Results: The mean age was 51.7 ± 13.8 years, and 38 (61%) were female. Postplasty transesophageal echocardiography showed the mean transvalvular pressure gradients were 3.8 ± 1.2 mm Hg, end diastolic peak flow velocity was 1.1 ± 0.3 m/s, and coaptation height was 7.9 ± 1.1 mm. During the follow-up period of 3 to 6 months, no deaths or cardiovascular-/valvular plasty-related adverse events occurred. All patients regained their heart function and returned to normal physical activities. Conclusions: The "collar-like" plasty technique can be safely performed for patients with extensive commissural prolapse. Echocardiography revealed that the technique can restore the leaflet area of low transvalvular pressure and flow velocity.

19.
Am J Otolaryngol ; 43(6): 103551, 2022.
Article in English | MEDLINE | ID: mdl-36029621

ABSTRACT

BACKGROUND: The oncologic outcomes between transoral laser microsurgery (TLM) and open partial laryngectomy (OPL) using comprehensive analysis in one clinical center is rare. The purpose of this study was to evaluate the oncologic outcomes of TLM in patients with early stage glottic carcinoma, and to compare the results with OPL. SUBJECTS AND METHODS: Records of 425 glottic carcinoma patients with T1 - T2 stage treated with TLM, vertical partial laryngectomy (VPL), and cricohyoidoepiglottopexy (CHEP) from 2005 to 2010 were retrospectively analyzed. The overall survival (OS), disease-specific survival (DSS), and laryngeal function preservation (LFP) of these three treatments were assessed. RESULTS: One hundred and twenty-two patients were treated with TLM. Regarding OPL, 167 patients underwent VPL, and 136 patients underwent CHEP. The mean age was 59.7 years, with men accounting for 97.2 % of all cases. The OS, DSS, and LFP rates of patients with anterior commissure (AC) involvement undergoing TLM were worse than those of patients without AC involvement, but these differences were not statistically significant. The 5-year OS, DSS, and LFP of patients undergoing TLM were 88.4 %, 89.9 %, and 83.5 %, respectively, and the oncologic outcomes of patients undergoing TLM, VPL, and CHEP were not statistically different. CONCLUSION: Glottic carcinoma patients with early stage treated with TLM experience satisfactory oncologic outcomes. No compelling difference in oncologic outcomes among three treatments of TLM, VPL and CHEP, as well as VPL and CHEP can be alternatives to patients who are not suitable for receiving TLM.


Subject(s)
Carcinoma, Squamous Cell , Laryngeal Neoplasms , Laser Therapy , Male , Humans , Middle Aged , Laryngectomy/methods , Glottis/surgery , Glottis/pathology , Microsurgery/methods , Retrospective Studies , Carcinoma, Squamous Cell/pathology , Treatment Outcome , Laryngeal Neoplasms/pathology , Laser Therapy/methods , Lasers , Neoplasm Staging
20.
Dev Neurobiol ; 82(6): 533-544, 2022 09.
Article in English | MEDLINE | ID: mdl-35929227

ABSTRACT

Axonal connections between the two sides of the brain are essential for processing sensorimotor functions, especially in animals with bilateral symmetry. The anterior commissure and postoptic commissure are two crucial axonal projections that develop early in the zebrafish central nervous system. In this study, we characterized the function of collapsin response mediator protein 2 (CRMP2) and CRMP4 in patterning the development of the anterior and postoptic commissures by analyzing morpholino-knockdown zebrafish morphants and CRISPR/Cas9-edited gene-knockout mutants. We observed a loss of commissural structures or a significant reduction in axon bundles connecting the two hemispheres, but the defects could be largely recovered by co-injecting CRMP2 or CRMP4 mRNA. Loss of both CRMP2 and CRMP4 function resulted in a synergistic increase in the number of commissural defects. To elucidate the mechanism by which CRMP2 and CRMP4 provide guidance cues for the development of the anterior and postoptic commissures, we included neuropilin 1a (Nrp1a) morphants and double morphants (CRMP2/Nrp1a and CRMP4/Nrp1a) for analysis. Our experimental results indicated that CRMP2 and CRMP4 might mediate their activities through the common semaphorin 3/Nrp1a signaling pathway.


Subject(s)
Semaphorins , Zebrafish , Animals , Morpholinos/metabolism , Morpholinos/pharmacology , Neuropilins/metabolism , Prosencephalon/metabolism , RNA, Messenger/metabolism , Semaphorin-3A/metabolism , Semaphorins/genetics , Semaphorins/metabolism , Zebrafish/metabolism
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