RESUMEN
BACKGROUND: Surgery for lesions of the posterior fossa is associated with significant postoperative pain in pediatric patients related to extensive manipulation of the suboccipital musculature and bone. In this study, we assess the preliminary safety, effect on neuromonitoring, and analgesic efficacy of applying a cervical paraspinal interfascial plane block in pediatric patients undergoing posterior fossa surgery. METHODS: In this prospective case series, we enrolled five patients aged 2-18 years undergoing surgery for symptomatic Chiari type I malformation. An ultrasound-guided cervical cervicis plane (CCeP) block was performed prior to the incision. A local anesthetic agent (bupivacaine) and a steroid adjuvant (dexamethasone) were injected into the fascial planes between the cervical semispinalis capitis and cervical semispinalis cervicis muscles at the level of the planned suboccipital decompression and C1 laminectomy. Motor-evoked and somatosensory-evoked potentials were monitored before and after the block. Patients were assessed for complications from the local injection in the intraoperative period and for pain in the postoperative period. RESULTS: No adverse events were noted intraoperatively, and there were no changes in neuromonitoring signals. Pain scores were low in the immediate postoperative period, and rescue medications were minimal. No complaints of incisional pain or need for narcotics were noted at the time of the 3-month postsurgical follow-up. CONCLUSIONS: In this study, we demonstrate the preliminary safety and analgesic efficacy of a novel application of a CCeP block to pediatric patients undergoing suboccipital surgery. Larger studies are needed to further validate the use of this block in children.
RESUMEN
BACKGROUND: Traumatic brain injury (TBI) poses a significant health burden, particularly among pediatric populations, leading to long-term cognitive, physical, and psychosocial impairments. Timely transfer to specialized trauma centers is crucial for optimal management, yet the influence of socioeconomic factors, such as the Area Deprivation Index (ADI), on transfer patterns remains understudied. METHODS: A retrospective study was conducted on pediatric TBI patients presenting to a Level I Pediatric Trauma Center between January 2012 and July 2023. Transfer status, distance, mode of transport, and clinical outcomes were analyzed in relation to ADI. Statistical analyses were performed using Student t-test and analysis of variance. RESULTS: Of 359 patients, 53.5% were transferred from outside hospitals, with higher ADI scores observed in transfer patients (P<0.01). Air transport was associated with greater distances traveled and higher ADI compared to ground ambulance (P<0.01). Despite similarities in injury severity, intensive care unit admission rates differed between transfer modes, with no significant impact on mortality. CONCLUSIONS: High ADI patients were more likely to be transferred, suggesting disparities in access to specialized care. Differences in transfer modes highlight the influence of socioeconomic factors on logistical aspects. While transfer did not independently impact outcomes, disparities in intensive care unit admission rates were observed, possibly influenced by injury severity. Integrating socioeconomic data into clinical decision-making processes can inform targeted interventions to optimize care delivery and improve outcomes for all pediatric TBI patients. Prospective, multicenter studies are warranted to further elucidate these relationships.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Transferencia de Pacientes , Factores Socioeconómicos , Humanos , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/epidemiología , Masculino , Femenino , Niño , Estudios Retrospectivos , Transferencia de Pacientes/estadística & datos numéricos , Adolescente , Preescolar , Disparidades en Atención de Salud , Centros Traumatológicos , Lactante , Resultado del Tratamiento , Disparidades Socioeconómicas en SaludRESUMEN
PURPOSE: Brain Injury Guidelines (BIG) have been established to guide management related to TBI in adults. Here, BIG criteria were applied to pediatric TBI patients to evaluate reliability, safety, and resource utilization. METHODS: A retrospective study was performed on all pediatric TBI patients aged 18 years or younger from January 2012 to July 2023 at a Level 1 Pediatric Trauma Center. The severity of TBI (BIG 1/2/3) was rated by review of initial cranial imaging by two independent observers. Inter-observer reliability was assessed. Predictions based on BIG criteria regarding repeat cranial imaging, ICU admission, and neurosurgical consultation were compared with observations from the cohort. Outcome data was collected, including neurosurgical intervention and mortality rate. RESULTS: Three hundred fifty-nine patients were included with mean age of 5.3 years. Injury severity included 44 BIG 1 (12.2%), 170 BIG 2 (47.4%), and 145 BIG 3 injuries (40.4%). Inter-rater reliability was 96.4%. Neurosurgical consultation was obtained in all patients, though only predicted by guidelines in 40.4%. Repeat imaging was obtained in 166 BIG 1/2 patients, with an average of 1.3 CT scans and 0.8 MRIs/rapid MRIs per patient. ICU was utilized in 104 (77.6%) patients not recommended per BIG criteria. Ultimately, 37 patients, all BIG 3, required neurosurgical intervention; no neurosurgical interventions were required in those classified as BIG 1/2. CONCLUSIONS: BIG criteria can be applied to pediatric TBI with high inter-observer reliability and without formal neurosurgical training. Retrospective application of BIG predicted fewer imaging studies, ICU admissions, and neurosurgical consults without overlooking patients requiring neurosurgical intervention.
Asunto(s)
Centros Traumatológicos , Humanos , Niño , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Adolescente , Lactante , Reproducibilidad de los Resultados , Lesiones Encefálicas/diagnóstico por imagen , Guías de Práctica Clínica como Asunto , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/terapiaRESUMEN
PURPOSE: Stereoelectroencephalography (SEEG) is a diagnostic surgery that implants electrodes to identify areas of epileptic onset in patients with drug-resistant epilepsy (DRE). SEEG is effective in identifying the epileptic zone; however, placement of electrodes in very young children has been considered contraindicated due to skull thinness. The goal of this study was to evaluate if SEEG is safe and accurate in young children with thin skulls. METHODS: Four children under the age of two years old with DRE underwent SEEG to locate the region of seizure onset. Presurgical planning and placement of electrodes were performed using ROSA One Brain. Preoperative electrode plans were merged with postoperative CT scans to determine accuracy. Euclidean distance between the planned and actual trajectories was calculated using a 3D coordinate system at both the entry and target points for each electrode. RESULTS: Sixty-three electrodes were placed among four patients. Mean skull thickness at electrode entry sites was 2.34 mm. The mean difference between the planned and actual entry points was 1.12 mm, and the mean difference between the planned and actual target points was 1.73 mm. No significant correlation was observed between planned and actual target points and skull thickness (Pearson R = - 0.170). No perioperative or postoperative complications were observed. CONCLUSIONS: This study demonstrates that SEEG can be safe and accurate in children under two years of age despite thin skulls. SEEG should be considered for young children with DRE, and age and skull thickness are not definite contraindications to the surgery.
Asunto(s)
Epilepsia Refractaria , Epilepsia , Niño , Humanos , Lactante , Preescolar , Estudios de Factibilidad , Electroencefalografía , Electrodos Implantados , Técnicas Estereotáxicas , Epilepsia Refractaria/cirugía , Epilepsia/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Middle meningeal artery (MMA) embolization has been increasingly applied in adult populations for the treatment of chronic subdural hematomas (cSDH). There is a paucity of literature on the indications, safety, and outcomes of MMA embolization in the pediatric population. SUMMARY: A systematic literature review on pediatric patients undergoing MMA embolization was performed. We also report the case of successful bilateral MMA embolization for persistent subdural hematomas following resection of a juvenile pilocytic astrocytoma. Persistent bilateral subdural hematomas following resection of a large brain tumor resolved following MMA embolization in a 13-year-old male. Indications for MMA embolization in the pediatric literature included cSDH (6/13, 46.2%), treatment or preoperative embolization of arteriovenous fistula or arteriovenous malformation (3/13, 23.1%), preoperative embolization for tumor resection (1/13, 7.7%), or treatment of acute epidural hematoma (1/13, 7.7%). Embolic agents included microspheres or microparticles (2/13, 15.4%), Onyx (3/13, 23.1%), NBCA (3/13, 23.1%), or coils (4/13, 30.8%). KEY MESSAGES: Whereas MMA embolization has primarily been applied in the adult population for subdural hematoma in the setting of cardiac disease and anticoagulant use, we present a novel application of MMA embolization in the management of persistent subdural hematoma following resection of a large space-occupying lesion. A systematic review of MMA embolization in pediatric patients currently shows efficacy; a multi-institutional study is warranted to further refine indications, timing, and safety of the procedure.
Asunto(s)
Embolización Terapéutica , Hematoma Epidural Craneal , Hematoma Subdural Crónico , Masculino , Adulto , Humanos , Niño , Adolescente , Arterias Meníngeas/diagnóstico por imagen , Embolización Terapéutica/métodos , Hematoma Subdural Crónico/cirugía , Hematoma Epidural Craneal/terapiaRESUMEN
BACKGROUND: Nerve transfer is a surgical technique in which a redundant or expendable fascicle is transferred or coapted to an injured nerve distal to the site of injury for the purpose of reinnervation. Successful nerve transfer is dependent on correct intraoperative identification of donor and recipient nerves. OBSERVATIONS: An 8-year-old male was recommended for ulnar nerve fascicle to biceps branch of musculocutaneous nerve transfer to restore elbow flexion weakness after a demyelinating spinal cord injury. The biceps branch was identified approximately midway along the upper arm. Proximal musculocutaneous nerve stimulation induced hand movement and electromyography activity in the median nerve muscles. Neurolysis of the thickened proximal structure revealed fusion of the musculocutaneous and median nerves. Because of the proximity of the median and musculocutaneous nerves, median rather than ulnar nerve fascicles were used as donors for transfer. LESSONS: The authors provide the first reported intraoperative finding of an anatomical variant in which the musculocutaneous nerve and median nerve were fused in the upper arm, confirmed through intraoperative electrical stimulation. Surgeons should be aware of this rare anatomical variant to ensure correct nerve identification when performing nerve transfers in the proximal upper extremity.
RESUMEN
BACKGROUND Genitofemoral neuralgia is a pain syndrome that involves injury to the genitofemoral nerve and is frequently iatrogenic. We report intraoperative nerve localization using ultrasound, nerve stimulation, and the cremasteric reflex in the surgical treatment of genitofemoral neuralgia. CASE REPORT A 49-year-old man with a history of extracorporeal membrane oxygenation with cannulation sites in bilateral inguinal regions presented with right groin numbness and pain following decannulation. His symptoms corresponded to the distribution of the genitofemoral nerve. He had a Tinel's sign over the midpoint of his inguinal incision. A nerve block resulted in temporary resolution of his symptoms. Due to the presence of a pacemaker, peripheral nerve neuromodulation was contraindicated. He underwent external neurolysis and neurectomy of the right genitofemoral nerve. Following direct stimulation and ultrasound for localization, the nerve was further localized intraoperatively using nerve stimulation with monitoring for the presence of the cremasteric reflex. At his 1-month postoperative visit, his right medial thigh pain had resolved and his right testicular pain 50% improved; his residual pain continued to improve at last evaluation 3 months after surgery. CONCLUSIONS We report the successful use of nerve stimulation and the cremasteric reflex to aid in identification of the genitofemoral nerve intraoperatively for the treatment of genitofemoral neuralgia.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Bloqueo Nervioso , Neuralgia , Masculino , Humanos , Persona de Mediana Edad , Neuralgia/cirugía , Muslo , HipoestesiaRESUMEN
Background: Brachial plexus region tumors are rare. In this study, we reviewed our experience with resection of tumors involving or adjacent to the brachial plexus to identify patterns in presentation and outcome. Methods: We report a retrospective case series of brachial plexus tumors operated on by a single surgeon at a single institution over 15 years. Outcome data were recorded from the most recent follow-up office visit. Findings were compared to a prior internal series and comparable series in the literature. Results: From 2001 to 2016, 103 consecutive brachial plexus tumors in 98 patients met inclusion criteria. Ninety percent of patients presented with a palpable mass, and 81% had deficits in sensation, motor function, or both. Mean follow-up time was 10 months. Serious complications were infrequent. For patients with a preoperative motor deficit, the rate of postoperative motor decline was 10%. For patients without a preoperative motor deficit, the rate of postoperative motor decline was 35%, which decreased to 27% at 6 months. There were no differences in motor outcome based on extent of resection, tumor pathology, or age. Conclusion: We present one of the largest recent series of tumors of the brachial plexus region. Although the rate of worsened postoperative motor function was higher in those without preoperative weakness, the motor deficit improves over time and is no worse than antigravity strength in the majority of cases. Our findings help guide patient counseling in regard to postoperative motor function.
RESUMEN
OBJECTIVE: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Decompressive hemicraniectomy (DHC) is a treatment option for severe pediatric TBI (pTBI) not amenable to medical management of intracranial pressure. Posttraumatic hydrocephalus (PTH) is a known sequela of DHC that may lead to further injury and decreased capacity for recovery if not identified and treated. The goal of this study was to characterize risk factors for PTH after DHC in patients with pTBI by using the Kids' Inpatient Database (KID). METHODS: The records collected in the KID from 2016 to 2019 were queried for patients with TBI using International Classification of Diseases, 10th Revision codes. Data defining demographics, complications, procedures, and outcomes were extracted. Multivariate regression was used to identify risk factors associated with PTH. The authors also investigated length of stay and hospital charges. RESULTS: Of 68,793 patients with pTBI, 848 (1.2%) patients underwent DHC. Prolonged mechanical ventilation (PMV) was required in 475 (56.0%) patients with pTBI undergoing DHC. Three hundred (35.4%) patients received an external ventricular drain (EVD) prior to DHC. PTH was seen in 105 (12.4%), and 50 (5.9%) received a ventriculoperitoneal shunt. DHC before hospital day 2 was negatively associated with PTH (OR 0.464, 95% CI 0.267-0.804; p = 0.006), whereas PMV (OR 2.204, 95% CI 1.344-3.615; p = 0.002) and EVD placement prior to DHC (OR 6.362, 95% CI 3.667-11.037; p < 0.001) were positively associated with PTH. PMV (OR 7.919, 95% CI 2.793-22.454; p < 0.001), TBI with subdural hematoma (OR 2.606, 95% CI 1.119-6.072; p = 0.026), and EVD placement prior to DHC (OR 4.575, 95% CI 2.253-9.291; p < 0.001) were independent predictors of ventriculoperitoneal shunt insertion. The mean length of stay and total hospital charges were significantly increased in patients with PMV and in those with PTH. CONCLUSIONS: PMV, presence of subdural hematoma, and EVD placement prior to DHC are risk factors for PTH in patients with pTBI who underwent DHC. Higher healthcare resource utilization was seen in patients with PTH. Identifying risk factors for PTH may improve early diagnosis and efficient resource utilization.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Craniectomía Descompresiva , Hidrocefalia , Humanos , Niño , Lesiones Traumáticas del Encéfalo/complicaciones , Hidrocefalia/cirugía , Factores de Riesgo , Derivación Ventriculoperitoneal/efectos adversos , Hematoma Subdural/etiología , Craniectomía Descompresiva/efectos adversos , Estudios Retrospectivos , Complicaciones Posoperatorias/etiologíaRESUMEN
We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.
Asunto(s)
COVID-19 , Trastornos Cerebrovasculares , Humanos , Trastornos Cerebrovasculares/epidemiología , Trastornos Cerebrovasculares/diagnóstico , COVID-19/complicaciones , COVID-19/epidemiología , Prueba de COVID-19 , Factores de Riesgo , SARS-CoV-2RESUMEN
BACKGROUND: Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Environment may play a role in the type, severity, and outcome of pediatric TBI (pTBI). Our objective was to characterize the impact of poor socioeconomic status (PSES) on the incidence, treatment, and outcomes of pTBI patients. METHODS: The Kids' Inpatient Database (KID) was queried from 2016 to 2019 for with TBI using International Classification of Disease, 10th revision (ICD 10) codes. Data defining demographics, complications, procedures, and outcomes was extracted. PSES was defined as Medicaid insurance and Q1 median income category. RESULTS: 26,417 patients had pTBI. 11,040 (41.8 %) of pTBI patients were on Medicaid insurance. 13,119 and 8165 (30.9 %) were in Q1 median income category. Land transport caused the majority of pTBI (41 %). Patients on Medicaid or Q1 median income were more likely to experience assault (OR 2.927, CI 95 % 2.455-3.491, p < 0.001 OR 2.033, CI 95 % 1.722-2.4000 p < 0.001 respectively). On propensity matched analysis, PSES was associated with increased mortality (OR 1.667, 95 % CI 1.322-2.100, p < 0.01), length of stay (LOS) (OR 1.369, 95 % CI 1.201-1.559, p < 0.01), and major complicated trauma (OR 1.354 95 % CI 1.090-1.682 p = 0.007). Total hospital charges were higher in pTBI patients on Medicaid ($112,101.52, +/- $203,716.35) versus non-Medicaid ($109,064.37 +/- $212,057.98) (p < 0.001). CONCLUSION: PSES is correlated with increased mortality, complications, and longer LOS. Healthcare coverage and clinical training should take these disparities into account to provide improved care and optimize healthcare resource utilization. LEVEL OF EVIDENCE: Level IV, Retrospective Database.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Niño , Bases de Datos Factuales , Humanos , Tiempo de Internación , Medicaid , Estudios Retrospectivos , Clase Social , Estados Unidos/epidemiologíaAsunto(s)
Edema Encefálico/etiología , COVID-19/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Antibacterianos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Edema Encefálico/diagnóstico por imagen , Edema Encefálico/patología , COVID-19/etiología , COVID-19/patología , Niño , Diagnóstico Diferencial , Quimioterapia Combinada , Electroencefalografía , Encefalitis/diagnóstico , Resultado Fatal , Humanos , Hidroxicloroquina/uso terapéutico , Hipertensión Intracraneal/etiología , Masculino , Evaluación de Síntomas , Síndrome de Respuesta Inflamatoria Sistémica/tratamiento farmacológico , Síndrome de Respuesta Inflamatoria Sistémica/patología , Tomografía Computarizada por Rayos X , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Optic pathway gliomas (OPGs) are low-grade tumors of the white matter of the visual system with a highly variable clinical course. The aim of the study was to generate a magnetic resonance imaging (MRI)-based predictive model of OPG tumor progression using advanced image analysis and machine learning techniques. METHODS: We performed a retrospective case-control study of OPG patients managed between 2009 and 2015 at an academic children's hospital. Progression was defined as radiographic tumor growth or vision decline. To generate the model, optic nerves were manually highlighted and optic radiations (ORs) were segmented using diffusion tractography tools. For each patient, intensity distributions were obtained from within the segmented regions on all imaging sequences, including derivatives of diffusion tensor imaging (DTI). A machine learning algorithm determined the combination of features most predictive of progression. RESULTS: Nineteen OPG patients with progression were matched to 19 OPG patients without progression. The mean time between most recent follow-up and most recently analyzed MRI was 3.5 ± 1.7 years. Eighty-three MRI studies and 532 extracted features were included. The predictive model achieved an accuracy of 86%, sensitivity of 89%, and specificity of 81%. Fractional anisotropy of the ORs was among the most predictive features (area under the curve 0.83, P < 0.05). CONCLUSIONS: Our findings show that image analysis and machine learning can be applied to OPGs to generate a MRI-based predictive model with high accuracy. As OPGs grow along the visual pathway, the most predictive features relate to white matter changes as detected by DTI, especially within ORs.
RESUMEN
Hemispheric disconnection in the form of hemispherectomy or hemispherotomy is the most effective way of treating intractable hemispheric epilepsy. Anatomical hemispherectomy approaches have largely been abandoned in most cases due to a higher risk of superficial hemosiderosis, intraoperative blood loss, hydrocephalus, prolonged hospital stay, and mortality compared to the variety of tissue-sparing hemispherotomy techniques. Disconnective hemispherotomy approaches utilize the lateral ventricle as a key component of the surgical corridor. Without a lateral ventricle, disconnective surgery becomes significantly challenging, typically leading to a hemispherectomy. The authors present the case of a patient with severe hemispheric dysplasia without a lateral ventricle on the pathologic side and detail a novel surgical technique for a prone, occipital interhemispheric, tissue-sparing, purely disconnective aventricular hemispherotomy with an excellent surgical outcome.
RESUMEN
BACKGROUND: The effect of modifications in fetal myelomeningocele (fMMC) closure techniques has not been extensively studied. OBJECTIVE: To study the effect of a modified closure technique on fMMC postnatal patient outcomes: hydrocephalus, hindbrain herniation, and cyst development. METHODS: We performed single-center retrospective study of a subset of post-MOMS (Management of Myelomeningocele Study) trial patients who underwent fMMC closure. After January 2015, the fetal myofascial closure technique was modified. Needlepoint monopolar cautery was used to raise dural lined myofascial flaps to create a more robust closure. Outcomes between the pre- and postmodification groups were compared with regard to hindbrain herniation, hydrocephalus, and cyst development. Families who transitioned care to local institutions were contacted via telephone for outcome information. RESULTS: From January 2011 to May 2016, data were reviewed from 119 fMMC closure patients. Patients without full follow-up data were excluded from the final analysis. Cerebrospinal fluid diversion was seen in 32 of 74 patients with the standard technique compared to 14 of 45 with the modified closure and was significantly decreased in postmodification when compared to that of the MOMS trial (P = .01). Hindbrain herniation resolution was significantly decreased in both the pre- and postmodification groups compared to that of the MOMS trial (P < .01). Prior to January 2015 with standard closure, 23 cysts required resection whereas no cysts required resection in the modified repair group (P < .01). CONCLUSION: Modified myofascial closure for fMMC closure is safe and feasible. The new approach reflects a decreased rate of cyst development requiring surgical resection, and a trend for improved rates of hindbrain herniation and hydrocephalus.
Asunto(s)
Meningomielocele/diagnóstico por imagen , Meningomielocele/cirugía , Ultrasonografía Prenatal/métodos , Femenino , Feto , Humanos , Lactante , Embarazo , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Angiografía Cerebral , Hemorragia Cerebral/diagnóstico por imagen , Malformaciones Arteriovenosas Intracraneales/diagnóstico por imagen , Microcirugia , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/cirugía , Craneotomía , Hemostasis Quirúrgica , Humanos , Malformaciones Arteriovenosas Intracraneales/fisiopatología , Malformaciones Arteriovenosas Intracraneales/cirugía , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Glioblastoma, the most frequent primary malignant brain neoplasm, is genetically diverse and classified into four transcriptomic subtypes, i. e., classical, mesenchymal, proneural, and neural. Currently, detection of transcriptomic subtype is based on ex vivo analysis of tissue that does not capture the spatial tumor heterogeneity. In view of accumulative evidence of in vivo imaging signatures summarizing molecular features of cancer, this study seeks robust non-invasive radiographic markers of transcriptomic classification of glioblastoma, based solely on routine clinically-acquired imaging sequences. A pre-operative retrospective cohort of 112 pathology-proven de novo glioblastoma patients, having multi-parametric MRI (T1, T1-Gd, T2, T2-FLAIR), collected from the Hospital of the University of Pennsylvania were included. Following tumor segmentation into distinct radiographic sub-regions, diverse imaging features were extracted and support vector machines were employed to multivariately integrate these features and derive an imaging signature of transcriptomic subtype. Extracted features included intensity distributions, volume, morphology, statistics, tumors' anatomical location, and texture descriptors for each tumor sub-region. The derived signature was evaluated against the transcriptomic subtype of surgically-resected tissue specimens, using a 5-fold cross-validation method and a receiver-operating-characteristics analysis. The proposed model was 71% accurate in distinguishing among the four transcriptomic subtypes. The accuracy (sensitivity/specificity) for distinguishing each subtype (classical, mesenchymal, proneural, neural) from the rest was equal to 88.4% (71.4/92.3), 75.9% (83.9/72.8), 82.1% (73.1/84.9), and 75.9% (79.4/74.4), respectively. The findings were also replicated in The Cancer Genomic Atlas glioblastoma dataset. The obtained imaging signature for the classical subtype was dominated by associations with features related to edge sharpness, whereas for the mesenchymal subtype had more pronounced presence of higher T2 and T2-FLAIR signal in edema, and higher volume of enhancing tumor and edema. The proneural and neural subtypes were characterized by the lower T1-Gd signal in enhancing tumor and higher T2-FLAIR signal in edema, respectively. Our results indicate that quantitative multivariate analysis of features extracted from clinically-acquired MRI may provide a radiographic biomarker of the transcriptomic profile of glioblastoma. Importantly our findings can be influential in surgical decision-making, treatment planning, and assessment of inoperable tumors.
RESUMEN
Background: Epidermal growth factor receptor variant III (EGFRvIII) is a driver mutation and potential therapeutic target in glioblastoma. Non-invasive in vivo EGFRvIII determination, using clinically acquired multiparametric MRI sequences, could assist in assessing spatial heterogeneity related to EGFRvIII, currently not captured via single-specimen analyses. We hypothesize that integration of subtle, yet distinctive, quantitative imaging/radiomic patterns using machine learning may lead to non-invasively determining molecular characteristics, and particularly the EGFRvIII mutation. Methods: We integrated diverse imaging features, including the tumor's spatial distribution pattern, via support vector machines, to construct an imaging signature of EGFRvIII. This signature was evaluated in independent discovery (n = 75) and replication (n = 54) cohorts of de novo glioblastoma, and compared with the EGFRvIII status obtained through an assay based on next-generation sequencing. Results: The cross-validated accuracy of the EGFRvIII signature in classifying the mutation status in individual patients of the independent discovery and replication cohorts was 85.3% (specificity = 86.3%, sensitivity = 83.3%, area under the curve [AUC] = 0.85) and 87% (specificity = 90%, sensitivity = 78.6%, AUC = 0.86), respectively. The signature was consistent with EGFRvIII+ tumors having increased neovascularization and cell density, as well as a distinctive spatial pattern involving relatively more frontal and parietal regions compared with EGFRvIII- tumors. Conclusions: An imaging signature of EGFRvIII was found, revealing a complex, yet distinct macroscopic glioblastoma phenotype. By non-invasively capturing the tumor in its entirety, the proposed methodology can assist in evaluating the tumor's spatial heterogeneity, hence overcoming common spatial sampling limitations of tissue-based analyses. This signature can preoperatively stratify patients for EGFRvIII-targeted therapies, and potentially monitor dynamic mutational changes during treatment.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Imagen de Difusión Tensora/métodos , Receptores ErbB/genética , Glioblastoma/genética , Imagen por Resonancia Magnética/métodos , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto JovenRESUMEN
Importance: Which children with fetal ventriculomegaly, or enlargement of the cerebral ventricles in utero, will develop hydrocephalus requiring treatment after birth is unclear. Objective: To determine whether extraction of multiple imaging features from fetal magnetic resonance imaging (MRI) and integration using machine learning techniques can predict which patients require postnatal cerebrospinal fluid (CSF) diversion after birth. Design, Setting, and Patients: This retrospective case-control study used an institutional database of 253 patients with fetal ventriculomegaly from January 1, 2008, through December 31, 2014, to generate a predictive model. Data were analyzed from January 1, 2008, through December 31, 2015. All 25 patients who required postnatal CSF diversion were selected and matched by gestational age with 25 patients with fetal ventriculomegaly who did not require CSF diversion (discovery cohort). The model was applied to a sample of 24 consecutive patients with fetal ventriculomegaly who underwent evaluation at a separate institution (replication cohort) from January 1, 1998, through December 31, 2007. Data were analyzed from January 1, 1998, through December 31, 2009. Exposures: To generate the model, linear measurements, area, volume, and morphologic features were extracted from the fetal MRI, and a machine learning algorithm analyzed multiple features simultaneously to find the combination that was most predictive of the need for postnatal CSF diversion. Main Outcomes and Measures: Accuracy, sensitivity, and specificity of the model in correctly classifying patients requiring postnatal CSF diversion. Results: A total of 74 patients (41 girls [55%] and 33 boys [45%]; mean [SD] gestational age, 27.0 [5.6] months) were included from both cohorts. In the discovery cohort, median time to CSF diversion was 6 days (interquartile range [IQR], 2-51 days), and patients with fetal ventriculomegaly who did not develop symptoms were followed up for a median of 29 months (IQR, 9-46 months). The model correctly classified patients who required CSF diversion with 82% accuracy, 80% sensitivity, and 84% specificity. In the replication cohort, the model achieved 91% accuracy, 75% sensitivity, and 95% specificity. Conclusion and Relevance: Image analysis and machine learning can be applied to fetal MRI findings to predict the need for postnatal CSF diversion. The model provides prognostic information that may guide clinical management and select candidates for potential fetal surgical intervention.