RESUMO
Animals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self-generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) 8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses with twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models.
Assuntos
Cerebelo , Movimento , Animais , Ratos , Feminino , Masculino , Movimento/fisiologia , Cerebelo/fisiologia , Animais Recém-Nascidos , Núcleos Cerebelares/fisiologia , Ratos Sprague-Dawley , Ratos Long-Evans , Potenciais de Ação/fisiologiaRESUMO
Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium.
Assuntos
Encéfalo , Neurônios GABAérgicos , Glutationa Peroxidase GPX1 , Glutationa Peroxidase , Hipotireoidismo , Estresse Oxidativo , Animais , Feminino , Gravidez , Hipotireoidismo/metabolismo , Camundongos , Encéfalo/metabolismo , Encéfalo/embriologia , Neurônios GABAérgicos/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/genética , Metimazol , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Movimento Celular , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Masculino , Placenta/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
PURPOSE OF REVIEW: To review relevant advances in the past half-decade in the treatment of primary brain tumors via modification of blood-brain barrier (BBB) permeability. RECENT FINDINGS: BBB disruption is becoming increasingly common in the treatment of primary brain tumors. Use of mannitol in BBB disruption for targeted delivery of chemotherapeutics via superselective intra-arterial cerebral infusion (SIACI) is the most utilized strategy to modify the BBB. Mannitol is used in conjunction with chemotherapeutics, oligonucleotides, and other active agents. Convection-enhanced delivery has become an attractive option for therapeutic delivery while bypassing the BBB. Other technologic innovations include laser interstitial thermal therapy (LITT) and focused ultrasound (FUS) which have emerged as prime modalities to directly target tumors and cause significant local BBB disruption. In the past 5 years, interest has significantly increased in studying modalities to disrupt the BBB in primary brain tumors to enhance treatment responses and improve clinical outcomes.
Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Humanos , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Manitol/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológicoRESUMO
In 2017, Hurricane Harvey flooded more than 300,000 buildings causing an estimated $125 billion in damages and resulting in 68 deaths (National Hurricane Center). This actual or threatened loss of life and physical harm led many to report negative effects on mental well-being and greater mental illness. However, many individuals have been able to experience similar adverse events without a significant negative impact on their mental health and well-being. Positive thinking factors such as hope, optimism, and self-efficacy have been proposed as protective factors in the face of difficult life events. Hope, optimism, and self-efficacy are related but distinct constructs that have often been studied separately, but whose unique impact on well-being and mental illness is less clear, especially in the context of a natural hazard. The current study uses structural equation modeling to measure the unique contribution of hope, optimism, and hurricane-coping self-efficacy on mental well-being and mental illness in a community sample of 300 subjects who experienced Hurricane Harvey, recruited from Mechanical Turk.
Assuntos
Tempestades Ciclônicas , Saúde Mental , Humanos , Autoeficácia , Otimismo , Adaptação PsicológicaRESUMO
Hope is a cognitive trait that predicts both resilience to and recovery from anxiety and stress-related disorders. The present study examines the prospective associations of hope with subsequent anxiety, stress, and well-being during the COVID-19 pandemic. Perceived emotional control, a transdiagnostic vulnerability factor, was also examined as a potential mediator of these relationships. American adults (N = 822) were recruited during the COVID-19 pandemic using Amazon mTURK and structural equation modeling was used to examine how trait hope predicted outcomes approximately one month later. Higher hope was associated with greater well-being and perceived emotional control, as well as lower levels of anxiety and COVID-19 perceived stress. Results also indicated an indirect effect of hope with all outcomes via perceived emotional control. These findings suggest that hope may associated with resilience to the chronic stressors associated with the COVID-19 pandemic.
Assuntos
Ansiedade/psicologia , COVID-19/psicologia , Esperança , Estresse Psicológico/psicologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Adulto JovemRESUMO
Natural disasters can lead to mental health problems, such as posttraumatic stress disorder (PTSD). Higher levels of loss and/or disruption and prior trauma exposure constitute risk factors for mental illness, whereas protective factors, including hope and resilience, support positive functioning. The present cross-sectional study used structural equation modeling to examine the relative influence of resilience and hope on mental health and well-being 1-3 months after Hurricane Harvey made landfall in August 2017, among a sample of 829 adults in the Greater Houston, Texas area. Resilience was more strongly associated with reduced PTSD symptoms, ß = -.31, 95% CI [-.42, -.21], than was hope, ß = -.17, 95% CI [-;.30, -.04], whereas hope was more strongly associated with components of well-being, ßs = .47-.63. Hope was positively associated with posttraumatic growth, ß = .30, 95% CI [.19, .41], whereas resilience was negatively associated with posttraumatic growth, ß = -.24, 95% CI [-.35, -.12]. These associations remained consistent after considering risk factors, although more variance in trauma-related outcomes was risk factors were included in the model. The present results suggest that considering the influence of both risk and resilience factors provides an enhanced picture of postdisaster mental health.
Assuntos
Tempestades Ciclônicas , Esperança , Saúde Mental , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Proteção , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Inquéritos e Questionários , TexasRESUMO
BACKGROUND: Hair-sparing techniques in cranial neurosurgery have gained traction in recent years and previous studies have shown no difference in infection rates, yet limited data exists evaluating the specific closure techniques utilized during hair-sparing craniotomies. Therefore, it was the intention of this study to evaluate the rate of surgical site infections (SSIs) and perioperative complications associated with using an absorbable intradermal barbed suture for skin closure in hair-sparing supratentorial craniotomies for tumor in order to prove non-inferiority to traditional methods. METHODS: A retrospective review of supratentorial craniotomies for tumor by a single surgeon from 2011 to 2017 was performed. All perioperative adverse events and wound complications, defined as a postoperative infection, wound dehiscence, or CSF leak, were compared between three different groups: (1) hair shaving craniotomies + transdermal polypropylene suture/staples for scalp closure, (2) hair-sparing craniotomies + transdermal polypropylene suture/staples for scalp closure, and (3) hair-sparing craniotomies + absorbable intradermal barbed suture for scalp closure. RESULTS: Two hundred sixty-three patients underwent hair shaving + transdermal polypropylene suture/staples, 83 underwent hair sparing + transdermal polypropylene suture/staples, and 100 underwent hair sparing + absorbable intradermal barbed suture. Overall, 2.9% of patients experienced a perioperative complication and 4.3% developed a wound complication. In multivariable analysis, the use of a barbed suture for scalp closure and hair-sparing techniques was not predictive of any complication or 30-day readmission. Furthermore, the absorbable intradermal barbed suture cohort had the lowest overall rate of wound complications (4%). CONCLUSIONS: Hair-sparing techniques using absorbable intradermal barbed suture for scalp closure are safe and do not result in higher rates of infection, readmission, or reoperation when compared with traditional methods.
Assuntos
Craniotomia/métodos , Cabelo , Procedimentos Neurocirúrgicos/métodos , Neoplasias Supratentoriais/cirurgia , Técnicas de Sutura , Craniotomia/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos Retrospectivos , Couro Cabeludo , Infecção da Ferida Cirúrgica/epidemiologia , Suturas , Técnicas de Fechamento de FerimentosRESUMO
BACKGROUND: People living with dementia in care homes are regularly admitted to hospital. The transition between hospitals and care homes is an area of documented poor care leading to adverse outcomes including costly re-hospitalisation. This review aims to understand the experiences and outcomes of care for people living with dementia who undergo this transition from the perspectives of key stakeholders; people living with dementia, their families and health care professionals. METHODS: A systematic search was conducted on the CINAHL, ASSIA, EMBASE, MEDLINE, PsychINFO, and Scopus databases without any date restrictions. We hand searched reference lists of included papers. Papers were included if they focused on people living with dementia moving from hospital to a short or long term care setting in the community including sub-acute, rehabilitation, skilled nursing facilities or care homes. Titles, abstracts and full texts were screened. Two authors independently evaluated study quality using a checklist. Themes were identified and discussed to reach consensus. RESULTS: In total, nine papers reporting eight studies met the inclusion criteria for the systematic review. A total of 257 stakeholders participated; 37 people living with dementia, 95 family members, and 125 health and social care professionals. Studies took place in Australia, Canada, United Kingdom (UK), and the United States of America (US). Four themes were identified as factors influencing the experience and outcomes of the transition from the perspectives of stakeholders; preparing for transition; quality of communication; the quality of care; family engagement and roles. CONCLUSION: This systematic review presents a compelling case for the need for robust evidence to guide best practice in this important area of multi-disciplinary clinical practice. The evidence suggests this transition is challenging for all stakeholders and that people with dementia have specific needs which need attention during this period. TRIAL REGISTRATION: PROSPERO Registration Number: CRD42017082041 .
Assuntos
Serviços de Saúde Comunitária/tendências , Demência/terapia , Pessoal de Saúde/tendências , Hospitalização/tendências , Transferência de Pacientes/tendências , Participação dos Interessados , Serviços de Saúde Comunitária/métodos , Atenção à Saúde/métodos , Atenção à Saúde/tendências , Demência/epidemiologia , Família , Humanos , Assistência de Longa Duração/métodos , Assistência de Longa Duração/tendências , Transferência de Pacientes/métodosRESUMO
BACKGROUND: In transsphenoidal endoscopic endonasal surgery (TEES), watertight separation of the sinonasal cavity and intracranial compartment is the primary goal of closure. However, even when meticulous closure technique is implemented, cerebrospinal fluid (CSF) leaks, dural scarring, and meningitis may result. Particularly when intraoperative CSF leak occurs, materials that facilitate the creation of a watertight seal that inhibits disease transition and minimizes inflammatory response after durotomy are sought. Dehydrated amniotic membrane (DAM) allograft appears to confer these attributes as studies have shown it augments epithelialization, facilitates wound healing, and minimizes and impedes bacterial growth. We detail the use of DAM allograft to augment sellar closures after TEES. METHODS: We conducted a feasibility study, retrospectively reviewing our institution's database of TEES for resection of pituitary adenomas in which DAM was utilized to supplement sellar closure. RESULTS: One hundred twenty transsphenoidal surgery cases with DAM were used during sellar closure, with a 49.2% intraoperative CSF leak rate. Of this cohort, two patients experienced postoperative CSF leak (1.7%), and no patients developed meningitis. CSF leak rate for TEES-naïve patients was 0.9%. CONCLUSIONS: This feasibility study demonstrates that dehydrated amniotic membrane allograft can be safely utilized as an adjunct during sellar closures for TEES for pituitary adenoma resection with very low rates of CSF leak and meningitis.
Assuntos
Adenoma/cirurgia , Âmnio/transplante , Neuroendoscopia/métodos , Neoplasias Hipofisárias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Técnicas de Fechamento de Ferimentos , Adulto JovemRESUMO
Recurrent treatment-refractory brain metastases can be treated with modern adjuvant therapies such as laser interstitial thermal therapy (LITT). Since previously radiated lesions may be indolent (treatment effect) or recurrent tumor, histological confirmation may be helpful. The authors present the utility of contemporaneous biopsy and LITT using intraoperative O-arm navigation in a patient who presented with multiple refractory metastases. The authors demonstrate the utility of O-arm navigation to confirm intraoperative biopsy and LITT placement. Concurrent stereotactic biopsy and LITT may be a safe and efficacious method for both the diagnosis and treatment of deep lesions that are unamenable to standard adjuvant treatment modalities. The video can be found here: https://youtu.be/SUY-qiahMyo .
Assuntos
Neoplasias Encefálicas/cirurgia , Terapia a Laser/métodos , Recidiva Local de Neoplasia/cirurgia , Neuronavegação/métodos , Termografia/métodos , Adulto , Biópsia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagemRESUMO
BACKGROUND: Unpaid, informal carers or caregivers play an important role in supporting people living with dementia but the role can be challenging and carers themselves may benefit from support. Alzheimer's, dementia or memory cafés are one such form of support . These cafés are usually provided in the voluntary sector and are a place where people with dementia and those supporting them, usually family carers, can meet with others in similar situations. METHODS: Using semi-structured interviews, this qualitative study explored the experiences of 11 carers from five dementia cafés in and around London, England. RESULTS: Thematic analysis resulted in the identification of four key themes. Cafés provide a relaxed, welcoming atmosphere where carers can go where they feel supported and accepted. Café attendance often brought a sense of normality to these carers' lives. Carers and those they care for look forward to going and often enjoy both the activities provided and socialising with others. Other highlighted benefits included peer support from other carers, information provision and support from the volunteer café coordinators. Despite diversity in how the cafés were run and in the activities offered, there were many reported similarities amongst carers in the value ascribed to attending the cafés. CONCLUSIONS: Dementia cafés appear to be a valuable, perhaps unique form of support for carers giving them brief respite from their caring role. Future research incorporating mixed methods is needed to understand the perspectives of those living with dementia.
Assuntos
Cuidadores/psicologia , Cuidadores/normas , Demência/psicologia , Demência/terapia , Pesquisa Qualitativa , Apoio Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Aconselhamento/métodos , Inglaterra/epidemiologia , Feminino , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Dementia in younger people, known as young (YOD) or early onset dementia (EOD), can pose significant challenges. YOD is often diagnosed in those in paid employment who have relatively young children, leading to different challenges to those for older people. It is therefore very important to provide support tailored to their specific needs. This systematic review aimed to synthesize the literature investigating the impact of psychosocial interventions for people with YOD and their family carers. METHOD: Eight electronic databases were searched and three key journals were also hand searched. Narrative synthesis of the selected articles was undertaken. RESULTS: Of the 498 records identified, 495 were ineligible after application of the exclusion criteria. The final sample included three studies, all of which were employment-based. Two were qualitative and one used mixed methods. Study quality was mixed. People with YOD and their carers reported benefits from participating in work-based interventions designed for those with YOD, including improved self-esteem and sense of purpose. Social contact was highlighted. Despite cognitive decline, maintenance in well-being was also reported. Carers described benefits for people with YOD, which extended outside the intervention, e.g. enhanced sleep and mood. The impact of the interventions on carers was not assessed. CONCLUSIONS: This review suggests work-based interventions providing supported, meaningful work outside the home can be beneficial. However, the dearth of studies, the lack of focus on family carers and their mixed quality demonstrate the need for better quality, mixed methods research with larger sample sizes.
Assuntos
Cuidadores/psicologia , Demência/enfermagem , Qualidade de Vida/psicologia , Idade de Início , Demência/diagnóstico , Humanos , Apoio SocialRESUMO
The proteins encoded by the classical HLA class I and class II genes in the major histocompatibility complex (MHC) are highly polymorphic and are essential in self versus non-self immune recognition. HLA variation is a crucial determinant of transplant rejection and susceptibility to a large number of infectious and autoimmune diseases. Yet identification of causal variants is problematic owing to linkage disequilibrium that extends across multiple HLA and non-HLA genes in the MHC. We therefore set out to characterize the linkage disequilibrium patterns between the highly polymorphic HLA genes and background variation by typing the classical HLA genes and >7,500 common SNPs and deletion-insertion polymorphisms across four population samples. The analysis provides informative tag SNPs that capture much of the common variation in the MHC region and that could be used in disease association studies, and it provides new insight into the evolutionary dynamics and ancestral origins of the HLA loci and their haplotypes.
Assuntos
Genética Médica , Antígenos HLA/genética , Haplótipos/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Antígenos de Histocompatibilidade/genética , Humanos , Polimorfismo Genético , Grupos Raciais/genéticaRESUMO
Animals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self-generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) P8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses to twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models.
RESUMO
This meta-analytic review is an update to the first meta-analysis of battering interventions (Babcock et al., 2004) and includes 59 studies that evaluated treatment efficacy for domestically violent men and women. The outcome literature of controlled quasi-experimental and experimental studies was reviewed to test the relative impact of Duluth, cognitive-behavioral therapy (CBT), and novel types of treatment on subsequent recidivism of violence. The first model examines studies comparing interventions to no treatment control conditions. The second model compares novel interventions to treatment as usual (i.e., the Duluth curriculum). Study design and type of treatment were tested as moderators in both models. Consistent with previous meta-analyses, effect sizes were in the small range, smaller in true experiments as compared to quasi-experimental designs when recidivism was based on partner or police reports. However, new experiments comparing novel treatments to the Duluth curriculum reveal effect sizes comparable to when comparing novel interventions to an untreated comparison group. Novel interventions, including Acceptance and Commitment Therapy and Circles of Peace had the largest effect sizes when put head-to-head with Duluth control groups. Future research directions include testing moderators and mechanisms of change of the battering interventions that work. Implications for evidence-based practice in criminal justice include broader implementation and continued testing of these novel interventions with demonstrated efficacy in stopping intimate partner violence.
Assuntos
Violência por Parceiro Íntimo , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Feminino , Masculino , Resultado do Tratamento , Terapia Cognitivo-Comportamental/métodosRESUMO
Aim: Atypical teratoid rhabdoid tumor (ATRT) is a rare and highly aggressive primary CNS neoplasm, predominantly observed in children. The use of autologous stem cell transplantation (ASCT) in pediatric ATRT has shown promise; however, its utility in adult ATRT remains unclear. Patients & methods: This study presents the case of an adult patient with ATRT who is in remission after ASCT and reviews the literature on ASCT in adults with ATRT. Four cases of ATRT in adults who underwent ASCT were identified, with pertinent data summarized. Results: All five patients survived longer than the historical average survival rate, four of whom had no clinical or radiographic evidence of disease at the final follow-up. Conclusion: Based on limited data, there may be a role for ASCT in the treatment of adults with ATRT.
[Box: see text].
Assuntos
Tumor Rabdoide , Teratoma , Transplante Autólogo , Humanos , Tumor Rabdoide/terapia , Tumor Rabdoide/patologia , Tumor Rabdoide/cirurgia , Adulto , Teratoma/terapia , Teratoma/patologia , Teratoma/cirurgia , Transplante de Células-Tronco/métodos , Masculino , Feminino , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgiaRESUMO
Glioblastoma (GBM) poses a significant challenge in oncology and stands as the most aggressive form of brain cancer. A primary contributor to its relentless nature is the stem-like cancer cells, called glioblastoma stem cells (GSCs). GSCs have the capacity for self-renewal and tumorigenesis, leading to frequent GBM recurrences and complicating treatment modalities. While natural killer (NK) cells exhibit potential in targeting and eliminating stem-like cancer cells, their efficacy within the GBM microenvironment is limited due to constrained infiltration and function. To address this limitation, novel investigations focusing on boosting NK cell activity against GSCs are imperative. This study presents two streamlined image-based assays assessing NK cell migration and cytotoxicity towards GSCs. It details protocols and explores the strengths and limitations of these methods. These assays could aid in identifying novel targets to enhance NK cell activity towards GSCs, facilitating the development of NK cell-based immunotherapy for improved GBM treatment.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Células Matadoras Naturais , Células-Tronco Neoplásicas , Células Matadoras Naturais/imunologia , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Movimento Celular/imunologia , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , Imunoterapia/métodosRESUMO
OBJECTIVE: As presented in Part 1 of this series, thalamic gliomas (TGs) are deep-seated, difficult-to-access tumors surrounded by vital neurovascular structures. Given their high operative morbidity, TGs have historically been considered inoperable lesions. Although maximal safe resection (MSR) has become the treatment standard for lobar and even deep-seated mediobasal temporal and insular gliomas, the eloquent location of TGs has precluded this management strategy, with biopsy and adjuvant treatment being the mainstay. The authors hypothesized that MSR can be achieved with low morbidity and mortality for TGs, thus resulting in improved outcomes. METHODS: A retrospective single-center study was performed on all TG patients from 2006 to 2020. Clinical, imaging, and pathology reports were obtained. Univariate and multivariate analyses were performed to determine prognostic variables. Case examples illustrate various approaches and the rationale for staging resections of more complex TGs. RESULTS: A total of 42 patients (26 males, 16 females), among them 12 pediatric (29%) cases, were included. Their mean age was 36.0 ± 21.4 (median 30, range 3-73) years. The median maximal tumor diameter was 45 (range 19-70) mm. Eighteen patients (43%) had a prior stereotactic needle tumor biopsy, with the ultimate diagnosis changed for 7 patients (39%) following microsurgical resection. The most common surgical approaches were transtemporal (29%), anterior interhemispheric transcallosal (29%), and superior parietal lobule (25%). Overall, the combined subtotal and gross-total resection rate was 95% (n = 40). Low-grade gliomas (LGGs; grades I and II) comprised one-third of the group, whereas half of the patients had glioblastoma multiforme. There were no operative mortalities. Although temporary postoperative motor deficits were observed in 12 patients (28.6%), all improved during the early postoperative period except 1 (2.4%), who had mild residual hemiparesis. Two patients required CSF diversion for hydrocephalus. The 2-year overall survival rate was 90% for LGG patients and 15% for high-grade glioma (HGG) patients. Multivariate analysis revealed that histological grade, age, and extent of resection were independent prognostic factors associated with survival. CONCLUSIONS: Management of TGs is challenging, with resection avoided by many, if not most, neurosurgeons, especially for HGGs. The results reported here demonstrate improved outcomes with resection, particularly in younger LGG patients. The authors therefore advocate for MSR for a select cohort of TG patients using carefully planned surgical approaches, contemporary intraoperative adjuncts, and meticulous microsurgical techniques.
RESUMO
OBJECTIVE: The selection of appropriate microsurgical approaches to treat thalamic pathologies is currently largely subjective. The objective of this study was to provide a structured cartography map for surgical navigation to treat gliomas involving different surfaces of the thalamus. METHODS: Fifteen formalin-fixed, silicone-injected cadavers (30 sides) were dissected, and 10 adult brain specimens (20 sides) were used to illustrate thalamic microsurgical anatomy using the Klingler fiber dissection technique. Exposures and trajectories for the six most common microsurgical approaches were depicted using MR data from healthy subjects converted into surface-rendered 3D virtual brain models. Additionally, thalamic surfaces exposed with all six approaches were color mapped on the virtual 3D model and compared side-by-side in 360° views with previously reported microsurgical approaches. These 3D models were then used in conjunction with topographic data to guide cadaveric dissection steps. RESULTS: There are two general surgical routes to thalamic lesions: the subarachnoid transcisternal and transcortical routes. The transcisternal route consists of the following three approaches: 1) anterior interhemispheric transcallosal approach, which exposes the anterior and superior thalamus; 2) posterior interhemispheric transcallosal approach, which exposes the posterosuperior thalamus; and 3) supracerebellar infratentorial approach, which exposes the posteromedial cisternal thalamus and can be extended laterally to approach the posterolateral thalamus by cutting the tentorium. The three transcortical approaches are the 1) superior parietal lobule approach, which exposes the posterosuperior thalamus and is particularly advantageous in the setting of hydrocephalus; 2) transtemporal gyrus approach, which exposes the inferolateral thalamus; and 3) transsylvian transinsular approach, which exposes the lateral thalamus (slightly more superiorly and posteriorly) and is advantageous for pathologies extending laterally into the peduncle, lenticular nucleus, or insula. CONCLUSIONS: Microsurgical approaches to thalamic gliomas continue to be challenging. Nonetheless, safe and effective cisternal, ventricular, and cortical corridors can be developed with thoughtful planning, anatomical understanding, and knowledge of the advantages, risks, and limitations of each approach. In some cases, it is wise to combine these approaches with staged procedures, as the authors demonstrate in Part 2. In Part 1 of this two-part series, they discuss thalamic microsurgical anatomy and illustrate the trajectory and exposures of all six approaches to guide decision-making. Part 2 discusses their thalamic glioma microsurgical case series, which utilizes these microsurgical approaches.