Selective Neurectomy for Postfacial Paralysis Synkinesis: A Systematic Review.

Facial synkinesis is characterized by unintentional contractions of facial musculature secondary to aberrant facial nerve healing. The associated impairment in facial functioning results in a significant decrease in patients' quality of life. The mainstay treatment for postfacial paralysis synkinesis (PFPS) is chemodenervation and physiotherapy, which requires long-term maintenance neurotoxin injections. This can lead to treatment resistance. Selective neurectomy of the distal branches of the facial nerve has been suggested as an effective surgical treatment of PFPS. This study aims to provide a comprehensive systematic review evaluating the efficacy of selective neurectomy for patients presenting with PFPS. Ovid MEDLINE, Ovid Embase, PubMed, Web of Science, and CINAHL were searched from inception until July 2022. Studies that investigated postoperative outcomes of pediatric and/or adult patients who underwent selective neurectomy as a treatment for PFPS were included. The database search identified 1,967 studies, and 11 were ultimately included based on inclusion and exclusion criteria. These 11 studies represented 363 patients. Studies reported on outcomes following selective neurectomy with or without adjuvant therapies for patients with PFPS. The main outcome categories identified were clinician-reported outcomes and patient-reported outcomes. The studies that used clinician-reported outcomes found an improvement in both synkinesis and facial nerve paralysis (FNP) outcomes following selective neurectomy according to their respective grading systems. Three studies looked at patient-reported outcomes and found increased patient-reported quality of life and satisfaction following selective neurectomy. The most reported complications were upper lip contracture, uneven cheek surface, lagophthalmos, and temporary oral incompetence. Selective neurectomy has demonstrated stable or improved synkinesis, FNP, and quality of life outcomes in patients with PFPS. This approach should be considered for patients with PFPS, particularly for patients with refractory symptoms or those who are unable to undergo continued medical management.

Health Inequity and Time From Pediatric Stroke Onset to Arrival.

BACKGROUND: Time from stroke onset to hospital arrival determines treatment and impacts outcome. Structural, socioeconomic, and environmental factors are associated with health inequity and onset-to-arrival in adult stroke. We aimed to assess the association between health inequity and onset-to-arrival in a pediatric comprehensive stroke center. METHODS: A retrospective observational study was conducted on a consecutive cohort of children (>28 days-18 years) diagnosed with acute arterial ischemic stroke (AIS) between 2004 and 2019. Neighborhood-level material deprivation was derived from residential postal codes and used as a proxy measure for health inequity. Patients were stratified by level of neighborhood-level material deprivation, and onset-to-arrival was categorized into 3 groups: <6, 6 to 24, and >24 hours. Association between neighborhood-level material deprivation and onset-to-arrival was assessed in multivariable ordinal logistic regression analyses adjusting for sociodemographic and clinical factors. RESULTS: Two hundred and twenty-nine children were included (61% male; median age [interquartile range] at stroke diagnosis 5.8-years [1.1-11.3]). Over the 16-year study period, there was an increase in proportion of children diagnosed with AIS living in the most deprived neighborhoods and arriving at the emergency room within 6 hours (P=0.01). Among Asian patients, a higher proportion lived in the most deprived neighborhoods (P=0.02) and level of material deprivation was associated with AIS risk factors (P=0.001). CONCLUSIONS: Our study suggests an increase in pediatric stroke in deprived neighborhoods and certain communities, and earlier arrival times to the emergency room over time. However, whether these changes are due to an increase in incidence of childhood AIS or increased awareness and diagnosis is yet to be determined. The association between AIS risk factors and material deprivation highlights the intersectionality of clinical factors and social determinants of health. Finally, whether material deprivation impacts onset-to-arrival is likely complex and requires further examination.

Third Nerve Palsy Due to Intracranial Aneurysms and Recovery after Endovascular Coiling.

INTRODUCTION: The modality of treatment of third nerve palsy (TNP) associated with intracranial aneurysms remains controversial. While treatment varies with the location of the aneurysm, microsurgical clipping of PComm aneurysms has generally been the traditional choice, with endovascular coiling emerging as a reasonable alternative. METHODS: Patients with TNP due to an intracranial aneurysm who subsequently underwent treatment at a mid-sized Canadian neurosurgical center over a 15-year period (2003-2018) were examined. RESULTS: A total of 616 intracranial aneurysms in 538 patients were treated; the majority underwent endovascular coiling with only 24 patients treated with surgical clipping. Only 37 patients (6.9%) presented with either a partial or complete TNP and underwent endovascular embolization; of these, 17 presented with a SAH secondary to intracranial aneurysm rupture. Aneurysms associated with TNP included PComm (64.9%), terminal ICA (29.7%), proximal MCA (2.7%), and basilar tip (2.7%) aneurysms. In general, smaller aneurysms and earlier treatment were provided for patients for ruptured aneurysms with a shorter mean interval to TNP recovery. In the endovascularly treated cohort initially presenting with TNP, seven presented with a complete TNP and the remaining were partial TNPs. TNP resolved completely in 20 patients (55.1%) and partially in 10 patients (27.0%). Neither time to coiling nor SAH at presentation were significantly associated with the recovery status of TNP. CONCLUSION: Endovascular coil embolization is a viable treatment modality for patients presenting with an associated cranial nerve palsy.

Paralysie du troisième nerf en raison d'un anévrisme intracrânien et rétablissement après la pose d'une bobine endovasculaire. INTRODUCTION: Les modalités de traitement de la paralysie du troisième nerf (PTN) associée aux anévrismes intracrâniens demeurent controversées. Bien que les traitements varient selon l'emplacement de l'anévrisme, le clippage (ou clipping) microchirurgical des anévrismes affectant les artères communicantes postérieures (ACP) est généralement apparu comme le choix le plus courant, la pose d'une bobine endovasculaire (endovascular coiling) ayant aussi émergé comme une option raisonnable. MÉTHODES: Nous nous sommes penchés sur les cas de patients atteints de PTN en raison d'un anévrisme intracrânien qui ont ensuite bénéficié d'un traitement dans un centre neurochirurgical canadien de taille moyenne, et ce, sur une période de 15 ans (2003 à 2018). RÉSULTATS: Au total, 616 anévrismes intracrâniens ayant affecté 538 patients ont été traités. La majorité d'entre eux ont bénéficié de la pose d'une bobine endovasculaire alors que seulement 24 patients ont été traités par clippage microchirurgical. Fait à noter, seuls 37 patients (6,9 %) ont donné à voir une PTN partielle ou totale et ont bénéficié d'une embolisation endovasculaire. De ce nombre, 17 ont donné à voir une hémorragie sous-arachnoïdienne (HSA) consécutive à une rupture d'anévrisme intracrânien. Les anévrismes associés à la PTN ont inclus les ACP (64,9 %), l'artère carotide interne terminale (29,7%), l'artère cérébrale moyenne proximale (2,7 %) et la pointe (tip) de l'artère basilaire (2,7 %). En général, un traitement plus précoce a été proposé aux patients victimes de plus petites ruptures d'anévrisme associées à des délais moyens de rétablissement plus courts à la suite d'une PTN. Dans la cohorte de patients ayant donné à voir des signes de PTN et ayant bénéficié d'un traitement endovasculaire, 7 d'entre eux étaient atteints d'une PTN complète alors que les autres étaient atteints d'une PTN partielle. Les signes de PTN ont fini par disparaître complètement chez 20 patients (55,1 %) et partiellement chez 10 autres (27,0 %). Ni les délais dans la pose d'une bobine endovasculaire ni des signes de HSA au moment de consulter n'ont été notablement associés au processus de rétablissement à la suite d'une PTN. CONCLUSION: En somme, il ressort que l'embolisation endovasculaire au moyen de bobines est une modalité de traitement viable pour les patients présentant une paralysie des nerfs crâniens.

NHS-Ester Tandem Labeling in One Pot Enables 48-Plex Quantitative Proteomics.

Stable-isotope labeling strategies are extensively used for multiplex quantitative proteomics. Hybrid-isotope labeling strategies that combine the use of isotopic mass difference labeling and isobaric tags can greatly increase sample multiplexity. In this work, we present a novel hybrid-isotope labeling approach that we termed NHS-ester tandem labeling in one pot (NETLOP). We first optimized 16-plex isobaric TMTpro labeling of lysine residues followed by 2-plex or 3-plex isotopic mTRAQ labeling of peptide N-termini, both of which with commercially available NHS-ester reactive reagents. We then demonstrated the utility of the NETLOP approach by labeling HeLa cell samples and performing proof-of-principle quantitative 32-plex and 48-plex proteomic analyses, each in a single LC-MS/MS experiment. Compared to current hybrid-isotope labeling methods, our NETLOP approach requires no sample cleanup between different labeling steps to minimize sample loss, induces no retention time shifts that compromise quantification accuracy, can be adapted to other NHS-ester isotopic labeling reagents to further increase multiplexity, and is compatible with samples from any origin in a wide array of biological and clinical proteomics applications.

NanoTPOT: Enhanced Sample Preparation for Quantitative Nanoproteomic Analysis.

With the ever-growing need for protein-level understanding in pathological research, proteomics researchers thrive to examine detailed proteome dynamics using crucial, yet often limited, primary and clinical samples. Aside from mass spectrometer instrumentation advancement, a single-tube-based high-throughput sample processing workflow is imperative to ensure sensitive, quantitative, and reproducible protein analysis for these increasingly sophisticated studies. Leveraging the benefits of an acid-cleavable detergent, RapiGest SF Surfactant (Waters Corporation), we developed and optimized a nanoproteomic workflow that we termed Nanogram TMT Processing in One Tube (NanoTPOT). Through the assessment of proteolytic digestion, tandem mass tag (TMT) labeling, online and offline fractionation strategies, our optimized workflow effectively eliminated the need for sample desalting and enabled compatible sample processing for mass spectrometry analysis. We further applied the NanoTPOT workflow to examine cellular response to stress caused by dithiothreitol in HeLa cells, where we identified and quantified 6935 and 5474 proteins in TMT 10-plex experiments with one microgram of lysate protein and 2000 sorted HeLa cells (roughly half microgram lysate protein) in each channel, respectively. Our workflow has been proven to be an effective alternative for current nanoproteomic sample processing to minimize sample loss in biological and clinical applications.

Salvage Therapy for Childhood Medulloblastoma: A Single Center Experience.

INTRODUCTION: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. METHODS: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. RESULTS: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. CONCLUSION: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.

Traitement de sauvetage dans le cas du médulloblastome chez l'enfant : une expérience menée au sein d'un établissement hospitalier. Introduction: Les enfants chez qui l'on a diagnostiqué un médulloblastome réfractaire à un traitement initial ou qui sont victimes d'une récidive présentent d'habitude des pronostics de guérison vraiment défavorables. Bien qu'il existe des traitements basés sur des essais cliniques de phases I et II, ces traitements ont tendance à produire des taux notables de morbidité et de mortalité. Méthodes: Nous avons ainsi mené à l'Université McMaster une analyse rétrospective des dossiers d'enfants chez qui l'on avait diagnostiqué entre 2002 et 2015 une récidive de médulloblastome. Résultats: La réapparition de cette maladie chez 10 patients a provoqué un phénomène de diffusion leptoméningée, trois d'entre eux étant victimes d'une récidive locale. Sur ces 10 jeunes patients, la maladie a progressé de façon importante : ces enfants ont alors été transférés aux soins palliatifs. Quant aux autres 10 enfants, ils ont subi un certain type de traitement de sauvetage (des résections chirurgicales, de la radiothérapie, de la chimiothérapie), que ce soit de façon exclusive ou en variant les combinaisons possibles. Sur les 13 enfants réfractaires à un traitement initial ou victimes d'une récidive, 4 sont toujours en vie, leur suivi médian ayant été de 38,5 mois (75,5 mois). Sur les 8 patients pour qui on a pu obtenir des données moléculaires, aucun de ceux qui étaient atteints d'un médulloblastome du sous-type Wnt n'a connu de récidive. Conclusion: Les médulloblastomes qui réapparaissent après une période de guérison complète présentent un pronostic de guérison défavorable. Leur taux de survie globale est en effet de 18,2 % au cours d'une période de 5 ans, et ce, même après avoir bénéficié d'un traitement de sauvetage. Ajoutons aussi que le type de traitement initial reçu, la disponibilité des traitements ainsi que la tolérance à l'égard des traitements de sauvetage proposés a entraîné une grande hétérogénéité dans le traitement de ces jeunes patients victimes d'une récidive.

A Review of Recent Advances in Endovascular Therapy for Intracranial Aneurysms.

Despite the advances in neuro-interventional techniques and expertise to treat intracranial aneurysms (IAs), there remains a subset of IAs that are considered to be a significant treatment challenge. Working closely with the neuro-interventional community, bioengineers have harnessed their knowledge of anatomy, physiology, biophysics, and new materials to develop novel therapeutic adjuncts for the successful endovascular treatment of simple and complex IAs. This review describes the biological challenges, the landscape of neuro-interventional management of IAs, and the factors pertinent to which therapeutic modality is recommended. Finally, recent technological advances that have emerged over the last decade are discussed, taking the reader through the devices' objectives, utility, and safety profiles. The goal of this review is to (i) provide physicians treating IAs with the pertinent information to facilitate evidence-based clinical decision thereby minimizing morbidity and mortality and (ii) facilitate professionals in the biomedical engineering field with the clinical background and summarize current endovascular IA treatment options available, with the intent to inspire future IA device development and innovation.