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Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.
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Bulbo Raquídeo , Médula Espinal , Sistema Nervioso Simpático , Animales , Masculino , Ratones , Locomoción/fisiología , Bulbo Raquídeo/fisiología , Ratones Endogámicos C57BL , Neuronas Motoras/fisiología , Neuronas/fisiología , Sueño REM/fisiología , Médula Espinal/fisiología , Sistema Nervioso Simpático/fisiología , Conducta Animal , Recuento de Células , Músculo EsqueléticoRESUMEN
Locomotion is a complex behavior required for animal survival. Vertebrate locomotion depends on spinal interneurons termed the central pattern generator (CPG), which generates activity responsible for the alternation of flexor and extensor muscles and the left and right side of the body. It is unknown whether multiple or a single neuronal type is responsible for the control of mammalian locomotion. Here, we show that ventral spinocerebellar tract neurons (VSCTs) drive generation and maintenance of locomotor behavior in neonatal and adult mice. Using mouse genetics, physiological, anatomical, and behavioral assays, we demonstrate that VSCTs exhibit rhythmogenic properties and neuronal circuit connectivity consistent with their essential role in the locomotor CPG. Importantly, optogenetic activation and chemogenetic silencing reveals that VSCTs are necessary and sufficient for locomotion. These findings identify VSCTs as critical components for mammalian locomotion and provide a paradigm shift in our understanding of neural control of complex behaviors.
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Locomoción/fisiología , Mamíferos/fisiología , Neuronas Motoras/citología , Tractos Espinocerebelares/citología , Animales , Axones/fisiología , Fenómenos Electrofisiológicos , Uniones Comunicantes/metabolismo , Silenciador del Gen , Ácido Glutámico/metabolismo , Proteínas Fluorescentes Verdes/metabolismo , Proteínas de Homeodominio/metabolismo , Interneuronas/fisiología , Vértebras Lumbares/metabolismo , Ratones , Propiocepción , Natación , Sinapsis/fisiología , Factores de Transcripción/metabolismoRESUMEN
Spinal serotonin enables neuro-motor recovery (i.e., plasticity) in patients with debilitating paralysis. While there exists time of day fluctuations in serotonin-dependent spinal plasticity, it is unknown, in humans, whether this is due to dynamic changes in spinal serotonin levels or downstream signaling processes. The primary objective of this study was to determine if time of day variations in spinal serotonin levels exists in humans. To assess this, intrathecal drains were placed in seven adults with cerebrospinal fluid (CSF) collected at diurnal (05:00 to 07:00) and nocturnal (17:00 to 19:00) intervals. High performance liquid chromatography with mass spectrometry was used to quantify CSF serotonin levels with comparisons being made using univariate analysis. From the 7 adult patients, 21 distinct CSF samples were collected: 9 during the diurnal interval and 12 during nocturnal. Diurnal CSF samples demonstrated an average serotonin level of 216.6 ± $ \pm $ 67.7 nM. Nocturnal CSF samples demonstrated an average serotonin level of 206.7 ± $ \pm $ 75.8 nM. There was no significant difference between diurnal and nocturnal CSF serotonin levels (p = .762). Within this small cohort of spine healthy adults, there were no differences in diurnal versus nocturnal spinal serotonin levels. These observations exclude spinal serotonin levels as the etiology for time of day fluctuations in serotonin-dependent spinal plasticity expression.
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Ritmo Circadiano , Serotonina , Humanos , Serotonina/líquido cefalorraquídeo , Masculino , Adulto , Femenino , Ritmo Circadiano/fisiología , Persona de Mediana Edad , Médula Espinal/metabolismo , Cromatografía Líquida de Alta Presión , AncianoRESUMEN
PURPOSE: Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined. METHODS: We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas. RESULTS: Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14). CONCLUSION: Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.
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Adenoma Hipofisario Secretor de ACTH , Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/terapia , Neoplasias Hipofisarias/patología , Recurrencia Local de Neoplasia , Adenoma/terapia , Adenoma/patología , Adenoma Hipofisario Secretor de ACTH/patología , Hipófisis/patologíaRESUMEN
BACKGROUND: Intramedullary abscesses are rare infections of the spinal cord. Intramedullary abscesses often have a complex presentation, making a high index of suspicion essential for prompt diagnosis and management. CASE PRESENTATION: We present two cases of intramedullary abscesses referred to and ultimately managed at our institution. Delayed diagnosis occurred in both instances due to the rarity of intramedullary abscesses and their propensity to mimic other pathologies. For both patients, prompt surgical management and the rapid institution of broad-spectrum antibiotics were critical in preventing further neurological decline. CONCLUSIONS: Although rare, it is critical to consider intramedullary abscesses on the differential for any MRI lesions that are hyperintense on T2 and peripherally enhancing on T1 post-contrast sequences, as even short delays in treatment can lead to severe neurological damage.
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Enfermedades de la Médula Espinal , Streptococcus anginosus , Absceso/diagnóstico , Humanos , Imagen por Resonancia Magnética , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/tratamiento farmacológicoRESUMEN
Background Suboccipital craniectomy (SOC) in conjunction with dura opening and duraplasty for posterior fossa decompression is an effective treatment for symptomatic Chiari 1 malformations (CM1), primarily carried out in the pediatric population. However, dural opening and reconstruction are associated with an increased risk of complications, and their necessity in the adult population has not yet been robustly demonstrated. Given differences in clinical presentation and disease severity between the pediatric and adult patients, we aimed to identify if SOC alone with intraoperative ultrasound confirmation of adequate restoration of pulsatile motion of cerebellar tonsil is sufficient to treat symptomatic CM1 while mitigating surgical risks. Methods We identified a retrospective, institutional cohort of adult patients who underwent SOC for Chiari decompression between 2014 and 2023. Demographic, clinical, and radiographic features were extracted for each patient. Clinical outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) and Motor-Sensory-Sphincter signs score (Clinical Sign Score (CSS)). Radiographic outcomes assessed cerebellar ectopia and associated syrinx characteristics. Results A total of 15 patients were identified, with an average follow-up period of three years. Eight patients underwent SOC with duraplasty, whereas seven patients underwent SOC only without duraplasty. Both groups of patients were of similar age at surgery and had similar nature and duration of symptoms prior to surgery. On pre-operative radiographic evaluation, both groups of patients had similar lengths of cerebellar ectopia (9.9±11.0 mm to 11.1±5.7 mm, p=0.591), and associated syrinxes (75% vs. 42.9%, p=0.205). Intraoperatively, both groups had similar estimated blood losses, though the length of surgery was significantly shorter when durotomy was spared (202±58.3 minutes to 116.3±47.8 minutes, p=0.011). The length of ICU stay was also significantly longer in the durotomy group (1.1±0.6 days to 0.0 days, p<0.001). Neither group reported any post-operative complications. On follow-up, both groups demonstrated similar reductions in cerebellar ectopia and syrinx characteristics. Clinically, the CCOS and CSS scores were similar between the two cohorts at follow-up, with no repeat surgery required in either group. Conclusion Our cohort suggests that for adult CM1 patients, SOC decompression alone without dural reconstruction might lead to comparable clinical and radiographic outcomes to SOC decompression with durotomy/duraplasty, especially if intraoperative ultrasound confirms good cerebrospinal fluid (CSF) flow after SOC. Notably, sparing durotomy and duraplasty is also associated with decreased operative time and decreased ICU stay.
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BACKGROUND AND OBJECTIVES: Aneurysms in the cavernous segment of the internal carotid artery (ICA) often present in an indolent fashion with limited morbidity. However, their growth progression and possible rupture over time remains poorly defined, thereby limiting optimization of serial follow-up. Thus, we aim to describe the progression of cavernous ICA aneurysms over time, as well as the patient and aneurysm characteristics associated with possible growth and rupture status. METHODS: We identified a consecutive cohort of 157 patients from 2007 to 2021 with cavernous ICA aneurysms. Patient demographic data, possible risk factors, presenting symptoms, radiographic features of aneurysms, size progression, rupture status, and concomitant noncavernous aneurysm rupture data were manually extracted. RESULTS: One hundred and fifty-seven patients (mean age at diagnosis 57.2 ± 15.6 years; 85.4% females) with 174 cavernous carotid aneurysms (CCAs) were followed for an average of 7.1 ± 4.8 years. 76.4% of aneurysms were identified incidentally, with predominantly ocular palsies as the presenting symptoms in remaining primary cases. Most aneurysms were small, and of the 168 aneurysms that were followed, 98.2% did not demonstrate appreciable growth. Of the aneurysms that grew, it took an average of 6.0 years to grow 1.6 ± 0.2 mm. Demographic data, hypertension, and smoking status were not associated with aneurysm growth. Most radiographic features also were not associated with growth, except long-axis diameter, which had an odds ratio of 1.4 (CI: 1.2, 1.8) on multivariable analysis. Presenting clinical symptoms were not associated with growth. No CCAs ruptured during follow-up. CONCLUSION: Cavernous ICA aneurysms in our series demonstrate no rupture and limited growth over years of clinical follow-up. No radiographic or patient risk factors were associated with growth except initial aneurysm size. Hence, small CCAs may not require close follow-up over time.
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OBJECTIVE: The expected post-operative changes in radiographic alignment over time remain poorly defined in patients surgically treated for degenerative scoliosis without instrument failure. Here we aim to describe the optimal natural progression of radiographic degenerative scoliosis at multiple timepoints in patients treated with a transforaminal lumbar interbody fusion (TLIF). METHODS: We identified an initial retrospective cohort of 114 patients treated with a TLIF for degenerative scoliosis between 2018 and 2022, with 39 patients ultimately meeting the imaging inclusion criteria. Patients who completed a primary or revision procedure with no evidence of instrument failure, proximal junctional kyphosis, or proximal junctional failure at last follow-up were included. Radiographic measurements of spinopelvic alignment were manually extracted from X-Ray scoliosis films. RESULTS: Thirty-nine patients (mean age 62.6 ± 8.7, mean follow-up 2.9 years), of which 23 underwent a primary TLIF (Primary) and 16 a revision procedure (Revision), were analyzed. Patients in the Primary group experienced a durable improvement in Thoracolumbar Cobb angle (-25° ± 15°), Thoracic Kyphosis (10° ± 13°), and Pelvic Incidence/lumbar lordosis mismatch (PI/LL) (-19° ± 19°) through the first year of follow-up. In the Revision group, at one year follow-up, all measures of spinopelvic alignment except PI/LL mismatch had reverted to pre-operative levels. Thoracolumbar Cobb angle decreased to a significantly greater degree in the Primary group compared to the Revision group. CONCLUSION: Primary TLIF operations without instrument failure consistently improve radiographic outcomes in three key measures through the first year. For revision procedures, there appears to be modest radiographic benefit at follow-up.
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Cifosis , Lordosis , Escoliosis , Fusión Vertebral , Animales , Humanos , Persona de Mediana Edad , Anciano , Escoliosis/diagnóstico por imagen , Escoliosis/cirugía , Escoliosis/etiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Fusión Vertebral/métodos , Lordosis/diagnóstico por imagen , Lordosis/cirugía , Lordosis/etiología , Cifosis/cirugíaRESUMEN
A 48-year-old male with progressive congestive myelopathy had a craniocvervical DAVF treated with surgical clipping using ICG to confirm solitary inflow.
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Malformaciones Vasculares del Sistema Nervioso Central , Enfermedades de la Médula Espinal , Masculino , Humanos , Persona de Mediana Edad , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/cirugía , Procedimientos Neuroquirúrgicos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/cirugíaRESUMEN
BACKGROUND: Spinal cord hypoperfusion undermines clinical recovery in acute traumatic spinal cord injuries. New guidelines suggest cerebrospinal fluid (CSF) drainage is an important strategy for preventing spinal cord hypoperfusion in the acute post-injury phase. METHODS: This study included participants presenting to a single level 1 trauma center between 2018 and 2022 with cervical or thoracic traumatic spinal cord injury severity grade A-C, as evaluated by the American spinal injury association impairment scale (AIS). The primary objective of this study was to compare the efficacy of two CSF drainage protocols in preventing spinal cord hypoperfusion; 1) draining CSF only when spinal cord perfusion pressure (SCPP) drops below 65 mmHg (i.e. reactive) versus 2) empiric CSF drainage of 5-10 mL every hour. Intrathecal pressure, spinal cord perfusion pressure (SCPP), mean arterial pressure (MAP), and vasopressor utilization were compared using univariate T-test statistical analysis. RESULTS: While there was no difference in the incidence of sub-optimal SCPP (<65 mmHg; p = 0.1658), reactively drained participants were more likely to exhibit critical hypoperfusion (<50 mmHg; p = 0.0030) despite also having lower average intrathecal pressures (p < 0.001). There were no differences in average SCPP, mean arterial pressure (MAP), or vasopressor utilization between the two groups (p > 0.05). CONCLUSIONS: Empiric (vs reactive) CSF drainage resulted in fewer incidences of critical spinal cord hypoperfusion for patients with acute traumatic spinal cord injuries.
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Drenaje , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/terapia , Femenino , Masculino , Adulto , Persona de Mediana Edad , Drenaje/métodos , Estudios Retrospectivos , Presión del Líquido Cefalorraquídeo/fisiología , Anciano , Adulto JovenRESUMEN
Background Expandable interbody cages, while popular in minimally invasive fusions due to their slim profile and increased ease of insertion, have not been widely explored in open surgery. The benefits of expandable cages may also extend to open fusions through their potential to achieve a greater restoration of lumbar lordosis while minimizing intraoperative complications. To highlight these benefits, we present a case series of adult spinal deformity (ASD) patients treated with an open transforaminal lumbar interbody fusion (TLIF) using expandable cages and compare outcomes to those of patients treated with static cages from the literature. Methods A retrospective cohort study of patients who underwent a deformity correction procedure and TLIF with expandable interbody cages at Brigham and Women's Hospital between 2018 and 2022 was conducted. Patient demographics, complications, and pre- and postoperative radiographic parameters of spinopelvic alignment were collected. A literature search was completed to identify studies employing static cages. T-tests were performed to compare postoperative changes in radiographic parameters by cage type. Results Forty-five patients (mean age of 62.6 years) with an average of 2.1 cages placed met the inclusion criteria. Patients experienced five intraoperative complications and 23 neurologic deficits (from minor to major), while nine patients required a revision operation. Lumbar lordosis increased by 9.8° ± 14.5° (p < 0.0001), the sagittal vertical axis (SVA) decreased by 25.5 mm ± 56.7 mm (p = 0.0048), and pelvic incidence-lumbar lordosis mismatch decreased by 13.3° ± 17.5° (p < 0.0001) with the use of expandable cages. Expandable cages yielded similar changes in lumbar lordosis to 15° and 8° cages but improved the lumbar lordosis generated from rectangular and 4° cages. When compared to static cages, expandable cages mildly reduced intraoperative complications. Conclusions Expandable interbody cages are an effective means of restoring spinopelvic alignment in ASD that have the potential to improve patient outcomes in open fusions compared to standard static cages. Especially when compared to rectangular and 4° static cages, expandable cages provide a clear benefit in the correction of lumbar lordosis. The impact of open spinal fusions with expandable cages on outcomes should continue to be explored in other cohorts.
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OBJECTIVE: We present an institutional case series of patients treated for colorectal carcinoma (CRC) spinal metastases to investigate the outcomes between no treatment, radiation, surgery, and surgery/radiation. METHODS: A retrospective cohort of patients with CRC spinal metastases presenting to affiliated institutions between 2001 and 2021 wereidentified. Information related to patient demographics, treatment modality, treatment outcomes, symptom improvement, and survival was collected by chart review. Overall survival (OS) was compared between treatments by log-rank significance testing. A literature review was conducted to identify other cases series of CRC patients with spinal metastases. RESULTS: Eighty-nine patients (mean age 58.5) with CRC spinal metastases across a mean of 3.3 levels met inclusion criteria: 14 (15.7%) received no treatment, 11 (12.4%) received surgery alone, 37 (41.6%) received radiation alone, and 27 (30.3%) received both radiation and surgery. Patients treated with combination therapy had the longest median OS of 24.7 months (range 0.6-85.9), which did not significantly differ from the median OS of 8.9 months (range 0.2-42.6) observed in patients who received no treatment (P = 0.075). Combination therapy provided objectively longer survival time in comparison to other treatment modalities but failed to reach statistical significance. The majority of patients that received treatment (n = 51/75, 68.0%) experienced some degree of symptomatic or functional improvement. CONCLUSIONS: Therapeutic intervention has the potential to improve the quality of life in patients with CRC spinal metastases. We demonstrate that surgery and radiation are useful options for these patients, despite their lack of objective improvement in OS.
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Neoplasias Colorrectales , Neoplasias de la Columna Vertebral , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/terapia , Neoplasias de la Columna Vertebral/secundario , Calidad de Vida , Resultado del Tratamiento , Neoplasias Colorrectales/cirugíaRESUMEN
BACKGROUND: Surgical intervention is a critical tool to address adult spinal deformity (ASD). Given the evolution of spinal surgical techniques, we sought to characterize developments in ASD correction and barriers impacting clinical outcomes. METHODS: We conducted a literature review utilizing PubMed, Embase, Web of Science, and Google Scholar to examine advances in ASD surgical correction and ongoing challenges from patient and clinician perspectives. ASD procedures were examined across pre-, intra-, and post-operative phases. RESULTS: Several factors influence the effectiveness of ASD correction. Standardized radiographic parameters and three-dimensional modeling have been used to guide operative planning. Complex minimally invasive procedures, targeted corrections, and staged procedures can tailor surgical approaches while minimizing operative time. Further, improvements in osteotomy technique, intraoperative navigation, and enhanced hardware have increased patient safety. However, challenges remain. Variability in patient selection and deformity undercorrection have resulted in heterogenous clinical responses. Surgical complications, including blood loss, infection, hardware failure, proximal junction kyphosis/failure, and pseudarthroses, pose barriers. Although minimally invasive approaches are being utilized more often, clinical validation is needed. CONCLUSIONS: The growing prevalence of ASD requires surgical solutions that can lead to sustained symptom resolution. Leveraging computational and imaging advances will be necessary as we seek to provide comprehensive treatment plans for patients.
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Discogenic back pain, a subset of chronic back pain, is caused by intervertebral disc (IVD) degeneration, and imparts a notable socioeconomic health burden on the population. However, degeneration by itself does not necessarily imply discogenic pain. In this review, we highlight the existing literature on the pathophysiology of discogenic back pain, focusing on the biomechanical and biochemical steps that lead to pain in the setting of IVD degeneration. Though the pathophysiology is incompletely characterized, the current evidence favors a framework where degeneration leads to IVD inflammation, and subsequent immune milieu recruitment. Chronic inflammation serves as a basis of penetrating neovascularization and neoinnervation into the IVD. Hence, nociceptive sensitization emerges, which manifests as discogenic back pain. Recent studies also highlight the complimentary roles of low virulence infections and central nervous system (CNS) metabolic state alteration. Targeted therapies that seek to disrupt inflammation, angiogenesis, and neurogenic pathways are being investigated. Regenerative therapy in the form of gene therapy and cell-based therapy are also being explored.
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Under what circumstances, is it ethical to perform tumor surgery on a brain-dead individual? The neurosurgeons at Brigham and Women's Hospital were recently faced with such a question when asked to operate on a 28-year-old man who was pronounced brain-dead secondary to a severe brain-stem injury. His advanced directives clearly documented a desire for organ donation. During his transplant work-up, cranial imaging suggested a possible cerebellar mass of unknown etiology that was concerning for metastatic disease. Despite negative full body imaging, the neurosurgical team was asked to perform an open biopsy of the intracranial lesion to rule out occult systemic cancer. This case invites many nuanced questions related to the decisions surgeons and the broader medical community must make in the face of pursuing viable organs for the many in need. What is the moral standing and personhood eligibility of brain-dead individuals? What is the scope of medical interventions and procedures that surgeons are ethically bound to carry out? How ought the desire for increased medical intervention to try to save organs be balanced with practical limitations given limited medical resources?
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The neuroimmunology of traumatic brain injury (TBI) has recently gained recognition as a crucial element in the secondary pathophysiological consequences that occur following neurotrauma. Both immune cells residing within the central nervous system (CNS) and those migrating from the periphery play significant roles in the development of secondary brain injury. However, the precise mechanisms governing communication between innate and adaptive immune cells remain incompletely understood, partly due to a limited utilization of relevant experimental models and techniques. Therefore, in this discussion, we outline current methodologies that can aid in the exploration of TBI neuroimmunology, with a particular emphasis on the interactions between resident neuroglial cells and recruited lymphocytes. These techniques encompass adoptive cell transfer, intra-CNS injection(s), selective cellular depletion, genetic manipulation, molecular neuroimaging, as well as in vitro co-culture systems and the utilization of organoid models. By incorporating key elements of both innate and adaptive immunity, these methods facilitate the examination of clinically relevant interactions. In addition to these preclinical approaches, we also detail an emerging avenue of research that seeks to leverage human biofluids. This approach enables the investigation of how resident and infiltrating immune cells modulate neuroglial responses after TBI. Considering the growing significance of neuroinflammation in TBI, the introduction and application of advanced methodologies will be pivotal in advancing translational research in this field.
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This chapter will provide an introduction into motoneuron anatomy, electrophysiological properties, firing patterns focusing on development and also describing several pathological conditions that affect mononeurons. It starts with a historical retrospective describing the early landmark work into motoneurons. The next section lays out the various types of motoneurons (alpha, beta, and gamma) and their subclasses (fast-twitch fatigable, fast-twitch fatigue-resistant, and slow-twitch fatigue resistant), highlighting the functional relevance of this classification scheme. The third section describes the development of motoneurons' passive and active electrophysiological properties. This section also defines the major terms one uses in describing how a neuron functions electrophysiologically. The electrophysiological aspects of a neuron is critical to understanding how it behaves within a circuit and contributes to behavior since the firing of an action potential is how neurons communicate with each other and with muscles. The electrophysiological changes of motoneurons over development underlies how their function changes over the lifetime of an organism. After describing the properties of individual motoneurons, the chapter then turns to revealing how motoneurons interact within complex neural circuits, with other motoneurons as well as sensory neurons, and how these circuits change over development. Finally, this chapter ends with highlighting some recent advances made in motoneuron pathology, focusing on spinal muscular atrophy, amyotrophic lateral sclerosis, and axotomy.
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Esclerosis Amiotrófica Lateral , Atrofia Muscular Espinal , Esclerosis Amiotrófica Lateral/patología , Humanos , Neuronas Motoras , Músculos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To examine complication rates and radiographic outcomes in patients undergoing surgery for adult spinal deformity (ASD) by a junior surgeon. METHODS: A study was conducted of a retrospective cohort of patients who underwent an open posterior interbody fusion of the thoracic and/or lumbar regions by a single surgeon for ASD between 2018 and 2022. Patient characteristics, complications, and common radiographic parameters of spinopelvic alignment were collated. RESULTS: A total of 112 patients with an average of 4.2 comorbidities underwent surgical correction of ASD. Thirty-seven patients (33.0%) experienced 52 major complications and 50 patients (44.6%) experienced 66 minor complications. Twenty-three patients (20.5%) required a revision operation. Both sagittal vertical axis (P < 10-14) and pelvic incidence-lumbar lordosis mismatch (P < 10-7) significantly improved postoperatively. Number of levels (P < 0.05), operative time >650 minutes (P < 0.01), estimated blood loss >1500 mL (P < 0.01), length of intensive care unit stay >1 day (P < 0.05), and hospitalization length >5 days (P < 0.05) all significantly increased the risk of a major complication. No patient factors significantly increased the risk of minor complications or revision surgery. CONCLUSIONS: Observed complication and revision rates in this cohort were consistent with rates reported in the literature. No preoperative patient risk factors significantly increased risk of complications or need for revision, suggesting that no patient population is at increased risk undergoing surgery by a junior surgeon. The relatively high rate of complications observed in this cohort may be a result of high baseline morbidity.
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Lordosis , Fusión Vertebral , Cirujanos , Adulto , Humanos , Fusión Vertebral/efectos adversos , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Lordosis/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Hypercoagulability with thrombosis and associated inflammation has been well-documented in COVID-19, and catastrophic cerebral venous sinus thromboses (CVSTs) have been described. Another COVID-19-related complication is bacterial superinfection, including sinusitis. Here, the authors reported three cases of COVID-19-associated sinusitis, meningitis, and CVST and summarized the literature about septic intracranial thrombotic events as a cause of headache and fever in COVID-19. OBSERVATIONS: The authors described three adolescent patients with no pertinent past medical history and no prior COVID-19 vaccinations who presented with subacute headaches, photosensitivity, nausea, and vomiting after testing positive for COVID-19. Imaging showed subdural collections, CVST, cerebral edema, and severe sinus disease. Two patients had decline in mental status and progression of neurological symptoms. In all three, emergency cranial and sinonasal washouts uncovered pus that grew polymicrobial cultures. After receiving broad-spectrum antimicrobials and various additional treatments, including two of three patients receiving anticoagulation, all patients eventually became neurologically intact with varying ongoing sequelae. LESSONS: These cases demonstrated similar original presentations among previously healthy adolescents with COVID-19 infections, concurrent sinusitis precipitating CVST, and subdural empyemas. Better recognition and understanding of the multisystem results of severe acute respiratory syndrome coronavirus 2 and the complicated sequelae allows for proper treatment.
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Neuronal diversification is a fundamental step in the construction of functional neural circuits, but how neurons generated from single progenitor domains acquire diverse subtype identities remains poorly understood. Here we developed an embryonic stem cell (ESC)-based system to model subtype diversification of V1 interneurons, a class of spinal neurons comprising four clades collectively containing dozens of molecularly distinct neuronal subtypes. We demonstrate that V1 subtype diversity can be modified by extrinsic signals. Inhibition of Notch and activation of retinoid signaling results in a switch to MafA clade identity and enriches differentiation of Renshaw cells, a specialized MafA subtype that mediates recurrent inhibition of spinal motor neurons. We show that Renshaw cells are intrinsically programmed to migrate to species-specific laminae upon transplantation and to form subtype-specific synapses with motor neurons. Our results demonstrate that stem cell-derived neuronal subtypes can be used to investigate mechanisms underlying neuronal subtype specification and circuit assembly.