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1.
Interv Neuroradiol ; : 15910199241250078, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38711176

RESUMEN

BACKGROUND: Middle meningeal artery (MMA) embolization for subdural hematomas (SDH) and dural arteriovenous fistulas (dAVFs) has gained momentum in the neuroendovascular space. However, there is variability in the technique for safe and effective embolization. The aim of this report is to describe the technical feasibility and clinical performance of using Zoom™ 45 catheter for MMA access to facilitate embolization. METHODS: We analyzed all cases of MMA embolization in which the Zoom™ 45 catheter was used and performed in our institution from February 2021 to March 2023 for SDH and dAVFs. RESULTS: A total of 32 patients were included. Mean age was 64.0 ± 18.0 years, 75.0% (4/32) were male, and 56.7% (17/30), were black. The technical success was achieved in 93.8% (30/32) of cases, with selective embolization utilizing microcatheter directly into frontal and parietal branches for most patients (96.9%, 31/32). Identification of dangerous collaterals, such as lacrimal and petrous branches, prior to embolization, was achieved in most patients (96.9%, 31/32). Bilateral MMA embolization was done in 50.0% (16/32) of patients. The transradial approach and transfemoral approach were used in 53.1% (17/32) and 46.9% (15/32) of patients, respectively. The most common embolization material was n-butyl cyanoacrylate (84.4%, 27/32). There were no access site complications or complications related to the MMA embolization procedures and used devices. CONCLUSIONS: The use of Zoom™ 45 Catheter seems to be technically feasible, safe, and effective for facilitating MMA access for embolization in the context of SDH and dAVFs.

2.
Neurosurg Focus ; 56(5): E5, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38691856

RESUMEN

OBJECTIVE: The authors of this study aimed to investigate independent prognostic factors of survival with a particular focus on comparing the safety and efficacy of endoscopic endonasal versus open approaches in the surgical management of skull base chordoma. METHODS: A retrospective National Cancer Database review of skull base chordoma patients was performed to capture resection cases from 2010 to 2020, evaluating overall survival (OS), early postoperative mortality, readmission rates, and hospital length of stay (LOS) between surgical approaches and the independent prognostication of death utilizing Cox multivariate regression analysis. RESULTS: Among the 736 patients included in the cohort, 456 patients (62.0%) and 280 patients (38.0%) underwent endoscopic endonasal and open resection, respectively. These values represent a rate of change over the study period of +4.1 versus -0.14 cases per year, respectively. Gross-total resection was achieved in 32.5% of cases. A positive margin status was found in 51.8% of cases. There was no association between extent of resection and surgical approach (p = 0.257). There was no difference in OS (p = 0.562), 30- and 90-day mortality (p = 0.209 and 0.126, respectively), and 30-day readmission (p = 0.438) between the two surgical groups. The mean LOS was reduced by 2.1 days in the endoscopic cohort (p = 0.013) compared with the open approach cohort. Finally, multivariate analysis revealed a tumor size ≥ 4 cm (HR 4.03, p = 0.005) and public insurance (HR 2.76, p = 0.004) as negative predictors of survival and treatment at an academic center (HR 0.36, p = 0.043) as a positive prognosticator of survival. CONCLUSIONS: The endoscopic endonasal approach has been increasingly utilized over time and touts noninferiority with respect to safety and efficacy with a marked improvement in LOS, which carries substantial implications for both healthcare costs and enhanced patient recovery. Future prospective studies are necessary to further delineate trends and surgical outcomes for skull base chordoma.


Asunto(s)
Cordoma , Bases de Datos Factuales , Neoplasias de la Base del Cráneo , Humanos , Cordoma/cirugía , Neoplasias de la Base del Cráneo/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Tiempo de Internación/estadística & datos numéricos , Neuroendoscopía/métodos , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos/métodos , Readmisión del Paciente/estadística & datos numéricos
3.
J Clin Med ; 13(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38610689

RESUMEN

Originally pioneered in adults, endoscopic endonasal approaches for skull base pathology are being increasingly applied as a minimally invasive alternative for young children. Intrinsic anatomic differences between these patient populations have sparked discussions on the feasibility, safety, and efficacy of these techniques in pediatric patients. This work aims to serve as a primer for clinicians engaged in the rapidly evolving field of pediatric endoscopic skull base surgery. A succinct overview of relevant embryology, sinonasal anatomy, and diagnostic workup is presented to emphasize key differences and unique technical considerations. Additional discussions regarding select skull base lesions, reconstructive paradigms, potential surgical complications, and postoperative care are also highlighted in the setting of multidisciplinary teams.

4.
J Stroke Cerebrovasc Dis ; 33(7): 107699, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38552890

RESUMEN

BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. METHODS: We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. RESULTS: One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. CONCLUSIONS: Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

5.
Am J Rhinol Allergy ; : 19458924241242198, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38544422

RESUMEN

BACKGROUND: The concept of "time toxicity" has emerged to address the impact of time spent in the healthcare system; however, little work has examined the phenomenon in the field of otolaryngology. OBJECTIVE: To validate the use of Evaluation and Management (E/M) current procedural terminology codes as a method to assess time burden and to pilot this tool to characterize the time toxicity of office visits associated with a diagnosis of pituitary adenoma between 2016 and 2019. METHODS: A retrospective cohort study of outpatient office visits quantified differences between timestamps documenting visit length and their associated E/M code visit length. The IBM MarketScan database was queried to identify patients with a diagnosis of pituitary adenoma in 2016 and to analyze their new and return claims between 2016 and 2019. One-way ANOVA and two-sample t-tests were used to examine claim quantity, time in office, and yearly visit time. RESULTS: In the validation study, estimated visit time via E/M codes and actual visit time were statistically different (P < 0.01), with E/M codes underestimating actual time spent in 79.0% of visits. In the MarketScan analysis, in 2016, 2099 patients received a primary diagnosis of pituitary adenoma. There were 8490 additional-related claims for this cohort from 2016 to 2019. The plurality of new office visits were with endocrinologists (n = 857; 29.3%). Total time spent in office decreased yearly, from a mean of 113 min (2016) to 69 min (2019) (P < 0.001). CONCLUSIONS: E/M codes underestimate the length of outpatient visits; therefore, time toxicity experienced by pituitary patients may be greater than reported. Further studies are needed to develop additional assessment tools for time toxicity and promote increased efficiency of care for patients with pituitary adenomas.

6.
J Neurointerv Surg ; 16(3): 266-271, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-37236781

RESUMEN

BACKGROUND: The transradial approach (TRA) for neurointerventional procedures is increasingly being used given its technical feasibility and safety. However, catheter trackability and device deliverability are reported barriers to TRA adoption. METHODS: This is the first report describing the technical feasibility and performance of using the Zoom RDL Radial Access System (Imperative Care, Inc., Campbell, CA) in 29 patients who underwent neurointerventional procedures from October 2022 to January 2023 in a single-center institution. RESULTS: Mean age of the study population was 61.9±17.2 years, 79.3% were male (23/29), and 62.1% were black (18/29). The most common procedures were stroke thrombectomy (31.0%, 9/29) and aneurysm embolization (27.6%, 8/29). All the stroke thrombectomy procedures were successfully performed; first-pass effect rate (mTICI≥2 c in one pass) was achieved in 66.7% (6/9) of cases. We used TRA in 86.2% of cases (25/29), including distal radial/snuffbox access in 31.0% (9/29) of cases. The radial diameter was >2 mm for all cases. An intermediate/aspiration catheter was used in 89.7% (26/29) of cases. Access success was achieved in 89.7% of cases (26/29); two cases required conversion from TRA to transfemoral approach (6.9%) and one case required conversion to a different guide catheter (3.4%). There were no access site complications or other Zoom RDL-related complications. One intracerebral hemorrhage, and one procedure-related thrombus were observed. CONCLUSIONS: The use of Zoom RDL Radial Access System is technically feasible and effective for complex neurointerventional procedures with low complication rates.


Asunto(s)
Embolización Terapéutica , Accidente Cerebrovascular , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , Arteria Radial/diagnóstico por imagen , Arteria Radial/cirugía , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Catéteres , Estudios Retrospectivos , Resultado del Tratamiento
7.
Cancers (Basel) ; 15(24)2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38136345

RESUMEN

This systematic review aims to characterize ongoing clinical trials and therapeutic treatment options for chordoma, a rare notochordal remnant tumor that primarily affects the cranial base, mobile spine, and sacrum. While radical surgical resection remains the cornerstone for chordoma management, unique technical challenges posed by its proximity to critical neurovascular structures confer a tendency towards disease recurrence which often requires additional treatment modalities. In an attempt to better understand the current treatment landscape, a systematic review was designed to identify clinical trials directed at chordoma. A total of 108 chordoma trials were identified from four clinical trial databases; fifty-one trials were included in the final analysis, of which only 14 were designated as completed (27.5%). Aggregate data suggests most chordoma interventions are repurposed from other neoplasms that share common molecular pathways, with a recent emphasis on combination therapeutics within and across drug classes. Naturally, the publication and dissemination of clinical trial results remain a concern (n = 4, 28.6%), highlighting the need for enhanced reporting and transparency measures. Active clinical trial efforts are quite promising, with a renewed focus on novel biotherapeutic targets and deciphering the natural history, as well as survivorship of this complex disease.

8.
J Neurol Surg B Skull Base ; 84(5): 444-451, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37671297

RESUMEN

Introduction Trigeminal schwannomas (TS) are rare skull base tumors that have been associated with significant neuropathic sequalae for patients. The authors aim to evaluate the clinical features, treatment outcomes, and neuropathic sequelae following endoscopic endonasal approach (EEA) for TS. Methods The study involves a retrospective review of patients who underwent EEA for resection of TS at a single academic institution between 2004 and 2020. Radiographic and clinical data were recorded and analyzed. Results A total of 16 patients were abstracted, with a mean age at the time of surgery of 44 years with a slight female (1.83:1) predominance. Primary preoperative symptomatology included facial pain/neuralgia ( n = 5, 31.3%), facial hypoesthesia ( n = 4, 25.0%), and headache ( n = 4, 25.0%). Following TS resection, patients were found to have facial hypoesthesia ( n = 11, 68.8%), neuropathic keratopathy ( n = 4, 25.0%), and mastication musculature atrophy ( n = 3, 18.8%). Patients with preoperative facial pain/neuralgia ( n = 5, 31.3%) were significantly more likely to try adjunctive pain therapies ( p = 0.018) as well as seek pain consultation ( p = 0.018). Patients with preoperative migraines ( n = 2, 12.5%) were significantly more likely to trial adjunctive pain therapies ( p = 0.025) and undergo evaluation with pain specialists ( p = 0.025). Finally, patients with preoperative pharmacologic agent utilization were significantly more likely to trial adjunctive pain therapies ( p = 0.036) and pursue pain consultation ( p = 0.036). Conclusion Some degree of trigeminal dysfunction may be more common than previously reported following EEA for TS resection. Factors that appear to play a role in the development of trigeminal dysfunction include pre-existing pain syndromes such as facial pain/neuralgia or headache and preoperative medication utilization.

9.
Oper Neurosurg (Hagerstown) ; 24(6): e458-e462, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36912518

RESUMEN

BACKGROUND AND IMPORTANCE: Medial orbital access through a transcaruncular corridor has yet to be fully characterized as a potential approach to intradural lesions within the skull base. Transorbital approaches present unique potential in the management of complex neurological pathologies and require subspecialty collaboration across multiple disciplines. CLINICAL PRESENTATION: A 62-year-old man presented with progressive confusion and mild left-sided weakness. He was found to have a right frontal lobe mass with significant vasogenic edema. A comprehensive systemic workup was otherwise unremarkable. A multidisciplinary skull base tumor board conference recommended a medial transorbital approach through transcaruncular corridor, which was performed by neurosurgery and oculoplastics services. Postoperative imaging demonstrated gross total resection of the right frontal lobe mass. Histopathologic evaluation was consistent with amelanotic melanoma with BRAF (V600E) mutation. At his last follow-up visit, 3 months after surgery, the patient did not experience any visual symptoms and had an excellent cosmetic outcome after surgery. CONCLUSION: The transcaruncular corridor through a medial transorbital approach provides a safe and reliable access to the anterior cranial fossa.


Asunto(s)
Neoplasias de la Base del Cráneo , Base del Cráneo , Masculino , Humanos , Persona de Mediana Edad , Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/cirugía , Procedimientos Neuroquirúrgicos/métodos , Fosa Craneal Anterior , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/cirugía
10.
Otolaryngol Clin North Am ; 55(3): 633-647, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35490042

RESUMEN

Pediatric headache is a common medical complaint managed across multiple subspecialties with a myriad of unique factors (clinical presentation and disease phenotype) that make accurate diagnosis particularly elusive. A thorough understanding of the stepwise approach to headache disorders in children is essential to ensure appropriate evaluation, timely diagnosis, and efficacious treatment. This work aims to review key components of a comprehensive headache assessment as well as discuss primary and secondary headache disorders observed in children, with a particular focus on clinical pearls and "red flag" symptoms necessitating ancillary diagnostic testing.


Asunto(s)
Cefalea , Adolescente , Niño , Diagnóstico Diferencial , Cefalea/diagnóstico , Cefalea/etiología , Humanos
11.
Surg Neurol Int ; 12: 327, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34345468

RESUMEN

BACKGROUND: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids is a rare disorder that presents with subacute brainstem symptoms such as ataxia, facial paresthesias, and episodic diplopia, thought to be due to a T-cell medicated perivascular inflammatory process. A supratentorial variant, Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS), has been described in only three patients. CASE DESCRIPTION: A 71-year-old male presented with word-finding difficulties, confusion, and left leg weakness. Radiographic workup demonstrated multiple supratentorial ring-enhancing lesions. PET/CT demonstrated hypermetabolism and susceptibility-weighted imaging demonstrated a hemorrhagic component. Frozen pathology revealed a predominately T-cell and monocyte inflammatory infiltrate. He demonstrated interval improvement to dexamethasone therapy, but then demonstrated worsening of his symptoms following discontinuation. CONCLUSION: Given his dramatic response to corticosteroids, he was diagnosed with SLIPPERS. SLIPPERS is an underrecognized diagnostic entity to consider in patients with ring-enhancing lesions and can present with hypermetabolic lesions on PET/CT.

13.
Neurosurgery ; 88(5): 961-970, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33475732

RESUMEN

BACKGROUND: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. OBJECTIVE: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. METHODS: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. RESULTS: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. CONCLUSION: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.


Asunto(s)
Hemorragia Cerebral , Procedimientos Quirúrgicos Mínimamente Invasivos , Terapia Trombolítica , Tiempo de Tratamiento , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/cirugía , Craneotomía , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Terapia Trombolítica/mortalidad , Terapia Trombolítica/estadística & datos numéricos , Resultado del Tratamiento
14.
Neurocrit Care ; 34(3): 918-926, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33025542

RESUMEN

BACKGROUND: This study investigates the presence of cerebrovascular injuries in a large sample of civilian penetrating brain injury (PBI) patients, determining the prevalence, radiographic characteristics, and impact on short-term outcome. METHODS: We retrospectively reviewed patients with PBI admitted to our institution over a 2-year period. Computed tomography head scans, computer tomography angiograms and venograms of the intracranial vessels were evaluated to determine the wound trajectory, intracranial injury characteristics, and presence of arterial (AI) and venous sinus (VSI) injuries. Demographics, clinical presentation, and treatment were also reviewed. Discharge disposition was used as surrogate of short-term outcome. RESULTS: Seventy-two patients were included in the study. The mechanism of injury was gunshot wounds in 71 patients and stab wound in one. Forty-one of the 72 patients (60%) had at least one vascular injury. Twenty-six out of 72 patients suffered an AI (36%), mostly pseudoaneurysms and occlusions, involving the anterior and middle cerebral arteries. Of the 72 patients included, 45 had dedicated computed tomography venograms, and of those 22 had VSI (49%), mainly manifesting as superior sagittal sinus occlusion. In a multivariable regression model, intraventricular hemorrhage at presentation was associated with AI (OR 9.9, p = 0.004). The same was not true for VSI. CONCLUSION: Acute traumatic cerebrovascular injury is a prevalent complication in civilian PBI, frequently involving both the arterial and venous sinus systems. Although some radiographic features might be associated with presence of vascular injury, assessment of the intracranial vasculature in the acute phase of all PBI is essential for early diagnosis. Treatment of vascular injury remains variable depending on local practice.


Asunto(s)
Traumatismos Penetrantes de la Cabeza , Heridas por Arma de Fuego , Traumatismos Penetrantes de la Cabeza/diagnóstico por imagen , Traumatismos Penetrantes de la Cabeza/epidemiología , Humanos , Estudios Retrospectivos , Sobrevivientes , Tomografía Computarizada por Rayos X , Heridas por Arma de Fuego/complicaciones , Heridas por Arma de Fuego/diagnóstico por imagen , Heridas por Arma de Fuego/epidemiología
15.
Oper Neurosurg (Hagerstown) ; 20(1): 98-108, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33313847

RESUMEN

BACKGROUND: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. OBJECTIVE: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. METHODS: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. RESULTS: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. CONCLUSIONS: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.


Asunto(s)
Fibrinolíticos , Activador de Tejido Plasminógeno , Hemorragia Cerebral , Fibrinolíticos/uso terapéutico , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico
16.
J Exp Med ; 217(10)2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32648916

RESUMEN

Cerebral cavernous malformations (CCMs) form following loss of the CCM protein complex in brain endothelial cells due to increased endothelial MEKK3 signaling and KLF2/4 transcription factor expression, but the downstream events that drive lesion formation remain undefined. Recent studies have revealed that CCM lesions expand by incorporating neighboring wild-type endothelial cells, indicative of a cell nonautonomous mechanism. Here we find that endothelial loss of ADAMTS5 reduced CCM formation in the neonatal mouse model. Conversely, endothelial gain of ADAMTS5 conferred early lesion genesis in the absence of increased KLF2/4 expression and synergized with KRIT1 loss of function to create large malformations. Lowering versican expression reduced CCM burden, indicating that versican is the relevant ADAMTS5 substrate and that lesion formation requires proteolysis but not loss of this extracellular matrix protein. These findings identify endothelial secretion of ADAMTS5 and cleavage of versican as downstream mechanisms of CCM pathogenesis and provide a basis for the participation of wild-type endothelial cells in lesion formation.


Asunto(s)
Proteína ADAMTS5/metabolismo , Hemangioma Cavernoso del Sistema Nervioso Central/etiología , Versicanos/metabolismo , Proteína ADAMTS1/metabolismo , Proteína ADAMTS4/metabolismo , Animales , Modelos Animales de Enfermedad , Endotelio Vascular/metabolismo , Femenino , Estudios de Asociación Genética , Hemangioma Cavernoso del Sistema Nervioso Central/embriología , Hemangioma Cavernoso del Sistema Nervioso Central/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Proteolisis , Sustancia Blanca/metabolismo
17.
Geroscience ; 42(5): 1351-1363, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32556941

RESUMEN

Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: padj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: padj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain. Graphical abstract.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Transcriptoma , Anciano , Envejecimiento/genética , Encéfalo/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Humanos , Plasma , Factor A de Crecimiento Endotelial Vascular/genética
18.
Nat Commun ; 11(1): 2659, 2020 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-32461638

RESUMEN

Cavernous angiomas (CA) are common vascular anomalies causing brain hemorrhage. Based on mouse studies, roles of gram-negative bacteria and altered intestinal homeostasis have been implicated in CA pathogenesis, and pilot study had suggested potential microbiome differences between non-CA and CA individuals based on 16S rRNA gene sequencing. We here assess microbiome differences in a larger cohort of human subjects with and without CA, and among subjects with different clinical features, and conduct more definitive microbial analyses using metagenomic shotgun sequencing. Relative abundance of distinct bacterial species in CA patients is shown, consistent with postulated permissive microbiome driving CA lesion genesis via lipopolysaccharide signaling, in humans as in mice. Other microbiome differences are related to CA clinical behavior. Weighted combinations of microbiome signatures and plasma inflammatory biomarkers enhance associations with disease severity and hemorrhage. This is the first demonstration of a sensitive and specific diagnostic microbiome in a human neurovascular disease.


Asunto(s)
Microbioma Gastrointestinal/genética , Hemangioma Cavernoso/complicaciones , Adolescente , Adulto , Biomarcadores/sangre , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/microbiología , ADN Bacteriano/genética , Heces/microbiología , Femenino , Hemangioma Cavernoso/diagnóstico , Humanos , Intestinos/microbiología , Intestinos/patología , Masculino , Metagenómica , Persona de Mediana Edad , Proyectos Piloto , ARN Ribosómico 16S/genética , Adulto Joven
19.
World Neurosurg ; 139: 215-218, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32304887

RESUMEN

BACKGROUND: The American Stroke Association and the European Stroke Organization have established guidelines on cerebral venous thrombosis (CVT); however, questions remain when an individual case does not fall within the inclusion criteria on which these guidelines are based. This is relevant when considering the use of anticoagulation in cases of CVT regarding whether or not associated hemorrhage is present and whether the hemorrhage is currently expanding. CASE DESCRIPTION: A 16-year-old right-handed female G2P2 (gravidity 2 [2 pregnancies] and parity 2 [2 live births after at least 24 weeks) presented 8 days postpartum with complaints of slurred speech, right facial droop, and right upper extremity numbness that had progressed over the course of 4 hours before presentation. On imaging the patient had a CVT with associated hemorrhage progressing in size at serial 6-hour stability computed tomography scans for 24 hours post arrival. At 24 hours the patient went into disseminated intravascular coagulation and demonstrated signs of herniation. The patient underwent an emergency hemicraniectomy along with a right frontal external ventricular drain for intracranial pressure monitoring. Most recently, the patient had a Glasgow Coma Scale score of 15 and had a modified Rankin Scale score of 4 and was ultimately discovered to have antiphospholipid syndrome. CONCLUSIONS: This case of CVT demonstrates the need for critically reading guidelines, as in this case the time to anticoagulation treatment was shorter than in cases included in guideline construction and repeated computed tomography examination demonstrated expansion suggesting it is unsuitable for immediate anticoagulation. Certain cases may fall outside of the study parameters on which guidelines are constructed, and clinicians should be aware of these exceptions.


Asunto(s)
Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/diagnóstico , Venas Cerebrales/diagnóstico por imagen , Craniectomía Descompresiva/métodos , Coagulación Intravascular Diseminada/diagnóstico , Hemorragias Intracraneales/diagnóstico por imagen , Trombosis Intracraneal/diagnóstico por imagen , Trombosis Intracraneal/terapia , Trastornos Puerperales/diagnóstico por imagen , Trastornos Puerperales/terapia , Adolescente , Síndrome Antifosfolípido/complicaciones , Angiografía por Tomografía Computarizada , Progresión de la Enfermedad , Coagulación Intravascular Diseminada/etiología , Coagulación Intravascular Diseminada/terapia , Femenino , Humanos , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/terapia , Trombosis Intracraneal/etiología , Guías de Práctica Clínica como Asunto , Trastornos Puerperales/etiología , Tomografía Computarizada por Rayos X , Ventriculostomía
20.
J Neurosurg ; 134(3): 1147-1154, 2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32244216

RESUMEN

OBJECTIVE: The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease. METHODS: One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board-approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed. RESULTS: There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC. CONCLUSIONS: Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.


Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Niño , Preescolar , Estudios de Cohortes , Manejo de la Enfermedad , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/terapia , Humanos , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/cirugía , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Adulto Joven
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