RESUMEN
Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity and unique brain functions in rodents1,2 and are dysregulated in multiple human neurological disorders3-5. Little is known about the molecular characteristics of adult human hippocampal imGCs, and even their existence is under debate1,6-8. Here we performed single-nucleus RNA sequencing aided by a validated machine learning-based analytic approach to identify imGCs and quantify their abundance in the human hippocampus at different stages across the lifespan. We identified common molecular hallmarks of human imGCs across the lifespan and observed age-dependent transcriptional dynamics in human imGCs that suggest changes in cellular functionality, niche interactions and disease relevance, that differ from those in mice9. We also found a decreased number of imGCs with altered gene expression in Alzheimer's disease. Finally, we demonstrated the capacity for neurogenesis in the adult human hippocampus with the presence of rare dentate granule cell fate-specific proliferating neural progenitors and with cultured surgical specimens. Together, our findings suggest the presence of a substantial number of imGCs in the adult human hippocampus via low-frequency de novo generation and protracted maturation, and our study reveals their molecular properties across the lifespan and in Alzheimer's disease.
Asunto(s)
Envejecimiento , Hipocampo , Longevidad , Neurogénesis , Neuronas , Adulto , Envejecimiento/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Proliferación Celular , Giro Dentado/citología , Giro Dentado/patología , Perfilación de la Expresión Génica , Hipocampo/citología , Hipocampo/patología , Humanos , Longevidad/genética , Aprendizaje Automático , Ratones , Células-Madre Neurales/citología , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Neurogénesis/genética , Neuronas/citología , Neuronas/metabolismo , Neuronas/patología , Reproducibilidad de los Resultados , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Transcripción GenéticaRESUMEN
Heterozygous pathogenic variants in DNM1 cause developmental and epileptic encephalopathy (DEE) as a result of a dominant-negative mechanism impeding vesicular fission. Thus far, pathogenic variants in DNM1 have been studied with a canonical transcript that includes the alternatively spliced exon 10b. However, after performing RNA sequencing in 39 pediatric brain samples, we find the primary transcript expressed in the brain includes the downstream exon 10a instead. Using this information, we evaluated genotype-phenotype correlations of variants affecting exon 10a and identified a cohort of eleven previously unreported individuals. Eight individuals harbor a recurrent de novo splice site variant, c.1197-8G>A (GenBank: NM_001288739.1), which affects exon 10a and leads to DEE consistent with the classical DNM1 phenotype. We find this splice site variant leads to disease through an unexpected dominant-negative mechanism. Functional testing reveals an in-frame upstream splice acceptor causing insertion of two amino acids predicted to impair oligomerization-dependent activity. This is supported by neuropathological samples showing accumulation of enlarged synaptic vesicles adherent to the plasma membrane consistent with impaired vesicular fission. Two additional individuals with missense variants affecting exon 10a, p.Arg399Trp and p.Gly401Asp, had a similar DEE phenotype. In contrast, one individual with a missense variant affecting exon 10b, p.Pro405Leu, which is less expressed in the brain, had a correspondingly less severe presentation. Thus, we implicate variants affecting exon 10a as causing the severe DEE typically associated with DNM1-related disorders. We highlight the importance of considering relevant isoforms for disease-causing variants as well as the possibility of splice site variants acting through a dominant-negative mechanism.
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Encefalopatías , Dinaminas , Síndromes Epilépticos , Humanos , Encefalopatías/genética , Causalidad , Dinaminas/genética , Exones/genética , Heterocigoto , Mutación/genética , Síndromes Epilépticos/genéticaRESUMEN
PURPOSE: Polymorphous low-grade neuroepithelial tumors of the young (PLNTY) represent a rare pediatric-type tumor that most commonly presents as medically refractory epilepsy. PLNTY has only recently been recognized as a distinct clinical entity, having been first described in 2016 and added to the World Health Organization classification of CNS tumors in 2021. Molecular studies have determined that PLNTY is uniformly driven by aberrant MAPK pathway activation, with most tumors carrying either a BRAF V600E mutation or activating FGFR2 or FGFR3 fusion protein. Although it is known that these driver mutations are mutually exclusive, little is known about differences in clinical presentation or treatment outcomes between PLNTY cases driven by these distinct mutations. METHODS: We performed a systematic review and cumulative analysis of PLNTY cases to assess whether or not PLNTY tumors carrying the BRAF V600E mutation exhibit different clinical behaviors. By searching the literature for all cases of PLNTY wherein BRAF V600E status was characterized, we compiled a dataset of 62 unique patient instances. Using a logistic regression-based approach, we assessed a primary outcome of what factors of a clinical presentation were associated with BRAF V600E mutations and a secondary outcome of what factors predicted total seizure freedom post-surgical resection. RESULTS: PLNTY cases carrying BRAF V600E mutations in the literature were strongly positively associated with adult patients (p = 0.0055, OR = 6.556; 95% Conf. Int. = 1.737-24.742). BRAF V600E status was also positively associated with tumor involvement of the temporal lobe (p = 0.0046, OR = 11.036; 95% Conf. Int. = 2.100-58.006). Male sex was also positively associated with BRAF V600E status, but the result did not quite achieve statistical significance (p = 0.0731). BRAF V600E status was not found to be associated with post-operative seizure freedom. CONCLUSIONS: These findings indicate that BRAF V600E-positive PLNTY exhibit characteristic clinical presentations but are not necessarily different in treatment responsiveness. Non-BRAF V600E tumors are more commonly associated with young patients.
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Neoplasias Encefálicas , Neoplasias Neuroepiteliales , Proteínas Proto-Oncogénicas B-raf , Niño , Humanos , Masculino , Neoplasias Encefálicas/patología , Mutación , Neoplasias Neuroepiteliales/genética , Proteínas Proto-Oncogénicas B-raf/genética , Convulsiones/complicacionesRESUMEN
Conjoined twins who are classified as craniopagus (joined at the cranium) have a rare congenital anomaly. Despite advances in surgical techniques and critical care, the rate of complications and death is still high among twins with total fusion in which the superior sagittal sinus is shared. Here, we describe total-fusion craniopagus twins who at 10 months of age underwent successful surgical separation performed by a multidisciplinary team. Computer-aided design and modeling with a three-dimensional printer, custom-designed cranial distraction and constriction devices, and intraoperative navigation techniques were used. These techniques allowed for separation of the twins at an early age and harnessed the regenerative capacity of their young brains.
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Osteogénesis por Distracción , Cráneo/cirugía , Gemelos Siameses/cirugía , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Angiografía Cerebral , Femenino , Humanos , Lactante , Procedimientos de Cirugía Plástica/métodos , Cráneo/diagnóstico por imagen , Seno Sagital Superior/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Stereoelectroencephalography (SEEG) is a widely used technique for localizing seizure onset zones prior to resection. However, its use has traditionally been avoided in children under 2 years of age because of concerns regarding pin fixation in the immature skull, intraoperative and postoperative electrode bolt security, and stereotactic registration accuracy. In this retrospective study, the authors describe their experience using SEEG in patients younger than 2 years of age, with a focus on the procedure's safety, feasibility, and accuracy as well as surgical outcomes. METHODS: A retrospective review of children under 2 years of age who had undergone SEEG while at Children's Hospital of Philadelphia between November 2017 and July 2021 was performed. Data on clinical characteristics, surgical procedure, imaging results, electrode accuracy measurements, and postoperative outcomes were examined. RESULTS: Five patients younger than 2 years of age underwent SEEG during the study period (median age 20 months, range 17-23 months). The mean age at seizure onset was 9 months. Developmental delay was present in all patients, and epilepsy-associated genetic diagnoses included tuberous sclerosis (n = 1), KAT6B (n = 1), and NPRL3 (n = 1). Cortical lesions included tubers from tuberous sclerosis (n = 1), mesial temporal sclerosis (n = 1), and cortical dysplasia (n = 3). The mean number of placed electrodes was 11 (range 6-20 electrodes). Bilateral electrodes were placed in 1 patient. Seizure onset zones were identified in all cases. There were no SEEG-related complications, including skull fracture, electrode misplacement, hemorrhage, infection, cerebrospinal fluid leakage, electrode pullout, neurological deficit, or death. The mean target point error for all electrodes was 1.0 mm. All patients proceeded to resective surgery, with a mean follow-up of 21 months (range 8-53 months). All patients attained a favorable epilepsy outcome, including Engel class IA (n = 2), IC (n = 1), ID (n = 1), and IIA (n = 1). CONCLUSIONS: SEEG can be safely, accurately, and effectively utilized in children under age 2 with good postoperative outcomes using standard SEEG equipment. With minimal modification, this procedure is feasible in those with immature skulls and guides the epilepsy team's decision-making for early and optimal treatment of refractory epilepsy through effective localization of seizure onset zones.
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Epilepsia Refractaria , Epilepsia , Esclerosis Tuberosa , Niño , Preescolar , Epilepsia Refractaria/cirugía , Electrodos Implantados , Electroencefalografía/métodos , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Proteínas Activadoras de GTPasa , Histona Acetiltransferasas , Humanos , Lactante , Estudios Retrospectivos , Convulsiones/cirugía , Técnicas Estereotáxicas , Esclerosis Tuberosa/cirugíaRESUMEN
OBJECTIVE: To demonstrate that a novel noninvasive index of intracranial pressure (ICP) derived from diffuse optics-based techniques is associated with intracranial hypertension. STUDY DESIGN: We compared noninvasive and invasive ICP measurements in infants with hydrocephalus. Infants born term and preterm were eligible for inclusion if clinically determined to require cerebrospinal fluid (CSF) diversion. Ventricular size was assessed preoperatively via ultrasound measurement of the fronto-occipital (FOR) and frontotemporal (FTHR) horn ratios. Invasive ICP was obtained at the time of surgical intervention with a manometer. Intracranial hypertension was defined as invasive ICP ≥15 mmHg. Diffuse optical measurements of cerebral perfusion, oxygen extraction, and noninvasive ICP were performed preoperatively, intraoperatively, and postoperatively. Optical and ultrasound measures were compared with invasive ICP measurements, and their change in values after CSF diversion were obtained. RESULTS: We included 39 infants, 23 with intracranial hypertension. No group difference in ventricular size was found by FOR (P = .93) or FTHR (P = .76). Infants with intracranial hypertension had significantly higher noninvasive ICP (P = .02) and oxygen extraction fraction (OEF) (P = .01) compared with infants without intracranial hypertension. Increased cerebral blood flow (P = .005) and improved OEF (P < .001) after CSF diversion were observed only in infants with intracranial hypertension. CONCLUSIONS: Noninvasive diffuse optical measures (including a noninvasive ICP index) were associated with intracranial hypertension. The findings suggest that impaired perfusion from intracranial hypertension was independent of ventricular size. Hemodynamic evidence of the benefits of CSF diversion was seen in infants with intracranial hypertension. Noninvasive optical techniques hold promise for aiding the assessment of CSF diversion timing.
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Circulación Cerebrovascular/fisiología , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/fisiopatología , Hipertensión Intracraneal/diagnóstico , Derivaciones del Líquido Cefalorraquídeo , Estudios de Factibilidad , Femenino , Humanos , Hidrocefalia/cirugía , Recién Nacido , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/fisiopatología , Presión Intracraneal/fisiología , Masculino , Imagen Óptica , Proyectos Piloto , Reproducibilidad de los Resultados , Análisis EspectralRESUMEN
PURPOSE: Several variations of functional disconnection surgery have been described for the treatment of lateralized, hemispheric, drug-resistant epilepsy in children. The purpose of this study is to investigate the existing literature regarding patient selection, approach, and outcomes after hemispherotomy. METHODS: A systematic review of the English literature through February 2019 was performed in accordance with the PRISMA statement. The articles were classified by level of evidence and summarized in an evidentiary table. Seizure outcomes, functional outcomes, surgical techniques, complications, and patient selection were critically analyzed. RESULTS: A total of 173 papers were reviewed, of which 37 met criteria of inclusion and exclusion. Thirteen studies were classified as level III evidence, the remaining reached level IV. Vertical and lateral hemispherotomy achieve similar rates of seizure freedom and functional outcomes, though parasagittal and interhemispheric approaches may have shorter operative times and less blood loss. Etiology, bilateral MRI abnormalities, and nonlateralizing EEG did not predict worse seizure or functional outcomes. CONCLUSIONS: Both vertical and lateral hemispherotomy approaches result in durable, reproducible benefits to epilepsy severity and functional status in appropriately selected pediatric patients.
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Epilepsia Refractaria , Epilepsia , Hemisferectomía , Niño , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Humanos , Convulsiones/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVE: Interictal spikes are a characteristic feature of invasive electroencephalography (EEG) recordings in children with refractory epilepsy. Spikes frequently co-occur across multiple brain regions with discernable latencies, suggesting that spikes can propagate through distributed neural networks. The purpose of this study was to examine the long-term reproducibility of spike propagation patterns over hours to days of interictal recording. METHODS: Twelve children (mean age 13.1 years) were retrospectively studied. A mean ± standard deviation (SD) of 47.2 ± 40.1 hours of interictal EEG recordings were examined per patient (range 17.5-166.5 hours). Interictal recordings were divided into 30-minute segments. Networks were extracted based on the frequency of spike coactivation between pairs of electrodes. For each 30-minute segment, electrodes were assigned a "Degree Preference (DP)" based on the tendency to appear upstream or downstream within propagation sequences. The consistency of DPs across segments ("DP-Stability") was quantified using the Spearman rank correlation. RESULTS: Regions exhibited highly stable preferences to appear upstream, intermediate, or downstream in spike propagation sequences. Across networks, the mean ± SD DP-Stability was 0.88 ± 0.07, indicating that propagation patterns observed in 30-minute segments were representative of the patterns observed in the full interictal window. At the group level, regions involved in seizure generation appeared more upstream in spike propagation sequences. SIGNIFICANCE: Interictal spike propagation is a highly reproducible output of epileptic networks. These findings shed new light on the spatiotemporal dynamics that may constrain the network mechanisms of refractory epilepsy.
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Epilepsia Refractaria/fisiopatología , Electroencefalografía , Red Nerviosa/fisiopatología , Adolescente , Niño , Epilepsia Refractaria/terapia , Terapia por Estimulación Eléctrica , Electrodos Implantados , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Estudios Retrospectivos , Espacio SubduralRESUMEN
PURPOSE: Children with myelomeningocele (MMC) are at increased risk of developing neuromuscular scoliosis and spinal cord re-tethering (Childs Nerv Syst 12:748-754, 1996; Neurosurg Focus 16:2, 2004; Neurosurg Focus 29:1, 2010). Some centers perform prophylactic untethering on asymptomatic MMC patients prior to scoliosis surgery because of concern that additional traction on the cord may place the patient at greater risk of neurologic deterioration peri-operatively. However, prophylactic untethering may not be justified if it carries increased surgical risks. The purpose of this study was to determine if prophylactic untethering is necessary in asymptomatic children with MMC undergoing scoliosis surgery. METHODS: A multidisciplinary, retrospective cohort study from seven children's hospitals was performed including asymptomatic children with MMC < 21 years old, managed with or without prophylactic untethering prior to scoliosis surgery. Patients were divided into three groups for analysis: (1) untethering at the time of scoliosis surgery (concomitant untethering), (2) untethering within 3 months of scoliosis surgery (prior untethering), and (3) no prophylactic untethering. Baseline data, intra-operative reports, and 90-day post-operative outcomes were analyzed to assess for differences in neurologic outcomes, surgical complications, and overall length of stay. RESULTS: A total of 208 patients were included for analysis (mean age 9.4 years, 52% girls). No patient in any of the groups exhibited worsened motor or sensory function at 90 days post-operatively. However, comparing the prophylactic untethering groups with the group that was not untethered, there was an increased risk of surgical site infection (SSI) (31.3% concomitant, 28.6% prior untethering vs. 12.3% no untethering; p = 0.0104), return to the OR (43.8% concomitant, 23.8% prior untethering vs. 17.4% no untethering; p = 0.0047), need for blood transfusion (51.6% concomitant, 57.1% prior untethering vs. 33.8% no untethering; p = 0.04), and increased mean length of stay (LOS) (13.4 days concomitant, 10.6 days prior untethering vs. 6.8 days no untethering; p < 0.0001). In multivariable logistic regression analysis, prophylactic untethering was independently associated with increased adjusted relative risks of surgical site infection (aRR = 2.65, 95% CI 1.17-5.02), unplanned re-operation (aRR = 2.17, 95% CI 1.02-4.65), and any complication (aRR = 2.25, 95% CI 1.07-4.74). CONCLUSION: In this study, asymptomatic children with myelomeningocele who underwent scoliosis surgery developed no neurologic injuries regardless of prophylactic untethering. However, those who underwent prophylactic untethering were more likely to experience SSIs, return to the OR, need a blood transfusion, and have increased LOS than children not undergoing untethering. Based on these data, prophylactic untethering in asymptomatic MMC patients prior to scoliosis surgery does not provide any neurological benefit and is associated with increased surgical risks.
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Transfusión Sanguínea/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Meningomielocele/cirugía , Procedimientos Quirúrgicos Profilácticos , Escoliosis/cirugía , Enfermedades de la Médula Espinal/cirugía , Infección de la Herida Quirúrgica/epidemiología , Adolescente , Enfermedades Asintomáticas , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Meningomielocele/complicaciones , Análisis Multivariante , Defectos del Tubo Neural/cirugía , Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias/epidemiología , Reoperación/estadística & datos numéricos , Escoliosis/etiología , Enfermedades de la Médula Espinal/etiologíaRESUMEN
INTRODUCTION: Syrinx has been reported in 25-85 % of children with Chiari malformation type I (CMI), and it is most commonly cervical in location. As a result, cervical MRI is routinely included in an evaluation for CMI. Isolated thoracic syrinx without involvement of the cervical cord in this population is uncommon but clinically important because its presence may influence the decision to operate, surgical techniques employed, or interpretation of follow-up imaging. The purpose of this study was to determine the incidence of isolated thoracic syrinx in a large group of children evaluated for CMI. METHODS: We retrospectively reviewed all patients under 21 years of age who were evaluated for CMI at Columbia University/Morgan Stanley Children's Hospital of New York from 1998 to 2013. All patients underwent MRI of the entire spine as part of the CMI evaluation, regardless of whether surgery was planned. The proportion of patients exhibiting isolated thoracic syrinx was determined. Presenting signs, symptoms, and imaging findings were then studied in an attempt to identify any clinical features associated with isolated thoracic syrinx. RESULTS: We identified 266 patients evaluated over the study period. One-hundred thirty-two patients (50 %) presented with a syrinx, and 12 patients (4.5 % of all patients evaluated and 9.1 % of all patients with a syrinx) had an isolated thoracic syrinx. Demographic variables, clinical presentation, and extent of tonsillar ectopia showed great heterogeneity in this group, and no factor was consistently associated with isolated thoracic syrinx. CONCLUSIONS: Isolated thoracic syrinx is an uncommon but clinically significant finding in children with CMI. Our data demonstrate that the presence of a CMI-related thoracic syrinx cannot be reliably predicted clinically and is therefore likely to be missed in patients who do not undergo complete spinal cord imaging. MRI of the entire spinal cord should be considered for all children undergoing initial evaluation for CMI.
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Malformación de Arnold-Chiari/complicaciones , Siringomielia/complicaciones , Siringomielia/epidemiología , Vértebras Torácicas/patología , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Imagen por Resonancia Magnética , Masculino , Estudios RetrospectivosRESUMEN
Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) as a primary treatment for hydrocephalus is gaining popularity in North America, particularly among the infant population. Unfortunately, despite considerable experience with ETV/CPC at several centers, treatment failures still exist. Early reports have suggested that greater than 90 % cauterization of the choroid plexus is associated with improved clinical outcomes. However, individual patient anatomy and smaller overall ventricular size can limit the amount of choroid plexus cauterization that is technically possible through a single frontal burr hole. Furthermore, the degree of cauterization achieved by surgeons using this technique is difficult to quantify objectively. In this report, we describe the case of an infant who failed initial ETV/CPC but then had successful resolution of hydrocephalus after additional choroid plexus cauterization performed through bilateral occipital burr holes. The child remains shunt-free over a year after treatment, suggesting that this three-pronged CPC approach (the "bowling ball" technique) may be successful in some young children with persistent hydrocephalus after ETV/CPC from a single frontal burr hole.
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Cauterización/métodos , Plexo Coroideo/cirugía , Hidrocefalia/cirugía , Tercer Ventrículo/cirugía , Ventriculostomía/métodos , Adolescente , Plexo Coroideo/diagnóstico por imagen , Femenino , Humanos , Hidrocefalia/diagnóstico por imagen , Imagen por Resonancia Magnética , Tercer Ventrículo/diagnóstico por imagenRESUMEN
BACKGROUND: Ommaya reservoirs are ventricular access devices used primarily for the administration of intrathecal antineoplastic chemotherapy. In patients with low or normal ventricular volume, stereotaxy can improve accuracy of catheter placement with minimal morbidity. Frameless stereotaxy has become an increasingly popular alternative to frame-based stereotaxy. Relative rates of successful catheter placement between these two techniques are not described in the literature. OBJECTIVES: To compare a large series of frameless to frame-based stereotactic catheter placements for Ommaya reservoirs, with an aim to compare accuracy and complication rate between the two procedures. METHODS: A consecutive series of 41 frame-based and 68 frameless Ommaya reservoir placement procedures performed at our institution from 1998 to 2013 was reviewed. Patient demographics, operative accuracy and complication rates for the two techniques were compared. RESULTS: Characteristics of the two groups were similar in diagnoses, age and other related factors. Comparison of frameless to frame-based stereotactic Ommaya catheter placement did not show significant differences in accuracy of placement, overall morbidity or mortality, or in any subcategory of complications. CONCLUSIONS: These findings suggest that frameless stereotactic Ommaya reservoir placement is as safe and accurate as the frame-based technique.
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Sistemas de Liberación de Medicamentos/métodos , Neuronavegación/métodos , Técnicas Estereotáxicas/instrumentación , Sistemas de Liberación de Medicamentos/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronavegación/instrumentaciónRESUMEN
Modern glioma surgery has evolved around the central tenet of safely maximizing resection. Recent surgical adjuncts have focused on increasing the maximum extent of resection while minimizing risk to functional brain. Technologies such as cortical and subcortical stimulation mapping, intraoperative magnetic resonance imaging, functional neuronavigation, navigable intraoperative ultrasound, neuroendoscopy, and fluorescence-guided resection have been developed to augment the identification of tumor while preserving brain anatomy and function. However, whether these technologies offer additional long-term benefits to glioma patients remains to be determined. Here we review advances over the past decade in operative technologies that have offered the most promising benefits for glioblastoma patients.
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Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Cirugía Asistida por Computador/métodos , Encéfalo/patología , Encéfalo/cirugía , Neoplasias Encefálicas/patología , Glioblastoma/patología , HumanosRESUMEN
OBJECT: Pediatric patients with sickle cell anemia (SCA) carry a significant risk of developing moyamoya syndrome (MMS) and brain ischemia. The authors sought to review the safety and efficacy of pial synangiosis in the treatment of MMS in children with SCA by performing a comprehensive review of all previously reported cases in the literature. METHODS: The authors retrospectively reviewed the clinical and radiographic records in 17 pediatric patients with SCA treated at the Morgan Stanley Children's Hospital of New York (MSCHONY) who developed radiological evidence of MMS and underwent pial synangiosis between 1996 and 2012. The authors then added any additional reported cases of pial synangiosis for this population in the literature for a combined analysis of clinical and radiographic outcomes. RESULTS: The combined data consisted of 48 pial synangiosis procedures performed in 30 patients. Of these, 27 patients (90%) presented with seizure, stroke, or transient ischemic attack, whereas 3 (10%) were referred after transcranial Doppler screening. At the time of surgery, the median age was 12 years. Thirteen patients (43%) suffered an ischemic stroke while on chronic transfusion therapy. Long-term follow-up imaging (MR angiography or catheter angiography) at a mean of 25 months postoperatively was available in 39 (81%) treated hemispheres. In 34 (87%) of those hemispheres there were demonstrable collateral vessels on imaging. There were 4 neurological events in 1590 cumulative months of follow-up, or 1 event per 33 patient-years. In the patients in whom complete data were available (MSCHONY series, n = 17), the postoperative stroke rate was reduced more than 6-fold from the preoperative rate (p = 0.0003). CONCLUSIONS: Pial synangiosis in patients with SCA, MMS, and brain ischemia appears to be a safe and effective treatment option. Transcranial Doppler and/or MRI screening in asymptomatic patients with SCA is recommended for the diagnosis of MMS.
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Anemia de Células Falciformes/complicaciones , Venas Cerebrales/cirugía , Enfermedad de Moyamoya/cirugía , Procedimientos Neuroquirúrgicos/métodos , Adolescente , Anemia de Células Falciformes/fisiopatología , Isquemia Encefálica/cirugía , Angiografía Cerebral , Niño , Estudios de Cohortes , Femenino , Humanos , Ataque Isquémico Transitorio/etiología , Ataque Isquémico Transitorio/cirugía , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Enfermedad de Moyamoya/diagnóstico por imagen , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/cirugía , Resultado del Tratamiento , Adulto JovenRESUMEN
While recent technological advancements are reshaping the landscape of surgical epilepsy management, the established techniques of resective and disconnective surgeries guided by electrographic monitoring remain the workhorse interventions for the management of refractory seizures and have the highest likelihood of achieving complete seizure resolution. Here we discuss examples of recent developments in surgical approaches and techniques for resective and disconnective surgeries with discussion of their indications and potential advantages.
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Procedimientos Neuroquirúrgicos , Niño , Humanos , Epilepsia Refractaria/cirugía , Electroencefalografía , Epilepsia/cirugía , Procedimientos Neuroquirúrgicos/métodosRESUMEN
The transpalpebral approach provides a minimally invasive corridor to the anterior skull base and temporal lobe. It has been described for anterior circulation aneurysms and skull base tumors as well as more recently for resection of epileptogenic pathology in the adult population. We describe our experience using this approach in a 13-year-old adolescent boy suffering from epilepsy secondary to concomitant left temporal focal cortical dysplasia and pleomorphic xanthoastrocytoma extending throughout the amygdala with excellent results.1-5 To the best of our knowledge, this is the first published case using the transpalpebral approach for this pathology, as well for epilepsy in the pediatric population. The patient consented to the procedure and to the publication of his image.
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BACKGROUND: Tonic and atonic "drop attack" seizures are a classic and morbid semiology in Lennox-Gastaut syndrome, resulting in frequent injuries and emergency room visits, in addition to neurocognitive sequelae. Recent years have seen a growing interest in less invasive techniques for performing the classic surgical treatment for drop attacks in Lennox-Gastaut syndrome, that is, corpus callosotomy. OBSERVATIONS: A 5-year-old boy with Lennox-Gastaut syndrome presented for surgical evaluation. He experienced up to 20 daily tonic seizures despite multiple antiseizure medications. Preoperative imaging revealed highly abnormal anatomy with severe ventriculomegaly and thinning of the cortex and corpus callosum. Open microsurgery or an interhemispheric bimanual endoscopic approach to corpus callosotomy posed a risk for ventricular collapse and subdural hematoma, and the corpus callosum was too thin for laser ablation. A fully endoscopic transventricular "inside-out" complete corpus callosotomy was performed through a 7-mm burr hole via a single working channel without intraoperative complications. The patient continues to experience daily seizures but with a reduced frequency and intensity and a family-reported increased quality of life. LESSONS: In cases of drug-resistant tonic and atonic seizures associated with ventriculomegaly, a fully endoscopic transventricular complete corpus callosotomy can be performed safely, potentially limiting the risk of ventricular collapse and subdural bleeding. https://thejns.org/doi/10.3171/CASE24160.
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Trans-sylvian peri-insular hemispherotomy represents a functional hemispherectomy with minimal brain removal used for treatment of refractory hemispheric epilepsy.1 Exposure for this procedure is achieved by craniotomy. Refinement in the hemispherotomy technique, including trends toward minimizing cortical resection, has contributed to a substantial drop in complication rates.2 We present a refinement of this technique, allowing for complete hemispheric disconnection through a single burr hole. In this instance, this technique was applied in the case of a 4-year-old girl who presented with medically refractory epilepsy, which had developed on the first day of life due to a perinatal incomplete left middle cerebral artery stroke. Postoperatively, the patient experienced no worsening of her preexisting right-sided hemiparesis and remains seizure-free 18 months postoperatively, now off medication. While the trans-sylvian peri-insular hemispherotomy represents an established surgical technique, this is the first report of this procedure performed in a minimally invasive fashion through a single burr hole. Beyond the minimal incision and small aperture in the skull, seldom appreciated nuances of hemispheric disconnection are described and demonstrated, including amygdala disconnection, hippocampal tail disconnection directly into splenium disconnection, concomitant intermediate disconnection and callosotomy, and frontobasal disconnection landmarks. Consent was obtained from the patient's parents for the surgical procedure, use of outcome videos, and for publication of this video and associated materials. The participants and patient's parents consented to publication of their images and that of the patient.
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OBJECTIVE: Intracranial complications of acute bacterial sinusitis are rare pathologies that occur in children, and are associated with significant neurological morbidity and mortality. There is a subjective concern among neurosurgeons that the incidence of this rare disease has increased since the onset of the novel COVID-19 pandemic. The primary objective of this study was to review the presentation and management of patients admitted at the authors' institution with intracranial extension of sinusitis, to better understand the local disease burden relative to the COVID-19 pandemic. METHODS: This is a single-center retrospective observational cohort study. The patients underwent neurosurgical intervention for intracranial extension of sinusitis between January 1, 2007, and March 1, 2023. The historical cohort was defined as those patients who presented prior to March 2020. Clinical covariates such as surgical and microbiological data were collected and analyzed. RESULTS: A total of 78 patients (55 historical, 23 new) were included; they had a median age of 11.7 years and a male predominance of 69.2%. There was a significant increase in the annual rate of neurosurgical intervention for suppurative intracranial extension of acute bacterial sinusitis after the onset of the COVID-19 pandemic, with an average of 4.2 cases per year prior to March 2020 compared to 7.7 cases per year after that date (p = 0.013). This increase was largely driven by the unprecedented case volume of 13 cases in 2022. Patients in the new cohort were older (p = 0.009) and more likely to have Pott's puffy tumor/frontal bone osteomyelitis (p = 0.003) at the time of presentation than patients in the historical cohort. Patients in the new cohort had lower rates of readmission within 30 days of discharge than those in the historical cohort (p = 0.047). In both cohorts, patients with seizure on presentation were more likely to have neurological sequelae at last follow-up (p = 0.004), which occurred at a median of 2.9 months after discharge. CONCLUSIONS: Clinicians encountering pediatric patients presenting with persistent symptoms of acute bacterial sinusitis must have a high index of suspicion for suppurative intracranial extension. Prompt neuroimaging and subsequent neurosurgical intervention are critical to ensure timely diagnosis and treatment. The results in this study show a significant increase in the number of neurosurgical interventions for suppurative intracranial extension of sinusitis per year after the onset of the COVID-19 pandemic. Further research is needed to understand the underlying pathophysiology of this clinical phenomenon.
RESUMEN
BACKGROUND CONTEXT: Intraoperative neurophysiological monitoring (IONM) is used to reduce the risk of spinal cord injury during pediatric spinal deformity surgery. Significant reduction and/or loss of IONM signals without immediate recovery may lead the surgeon to acutely abort the case. The timing of when monitorable signals return remains largely unknown. PURPOSE: The goal of this study was to investigate the correlation between IONM signal loss, clinical examination, and subsequent normalization of IONM signals after aborted pediatric spinal deformity surgery to help determine when it is safe to return to the operating room. STUDY DESIGN/SETTING: This is a multicenter, multidisciplinary, retrospective study of pediatric patients (<18 years old) undergoing spinal deformity surgery whose surgery was aborted due to a significant reduction or loss of IONM potentials. PATIENT SAMPLE: Sixty-six patients less than 18 years old who underwent spinal deformity surgery that was aborted due to IONM signal loss were enrolled into the study. OUTCOME MEASURES: IONM data, operative reports, and clinical examinations were investigated to determine the relationship between IONM loss, clinical examination, recovery of IONM signals, and clinical outcome. METHODS: Information regarding patient demographics, deformity type, clinical history, neurologic and ambulation status, operative details, IONM information (eg, quality of loss [SSEPs, MEPs], laterality, any recovery of signals, etc.), intraoperative wake-up test, postoperative neurologic exam, postoperative imaging, and time to return to the operating were all collected. All factors were analyzed and compared with univariate and multivariate analysis using appropriate statistical analysis. RESULTS: Sixty-six patients were enrolled with a median age of 13 years [IQR 11-14], and the most common sex was female (42/66, 63.6%). Most patients had idiopathic scoliosis (33/66, 50%). The most common causes of IONM loss were screw placement (27/66, 40.9%) followed by rod correction (19/66, 28.8%). All patients had either complete bilateral (39/66, 59.0%), partial bilateral (10/66, 15.2%) or unilateral (17/66, 25.8%) MEP loss leading to termination of the case. Overall, when patients were returned to the operating room 2 weeks postoperatively, nearly 75% (40/55) had monitorable IONM signals. Univariate analysis demonstrated that bilateral SSEP loss (p=.019), bilateral SSEP and MEP loss (p=.022) and delayed clinical neurologic recovery (p=.008) were significantly associated with having unmonitorable IONM signals at repeat surgery. Multivariate regression analysis demonstrated that delayed clinical neurologic recovery (> 72 hours) was significantly associated with unmonitorable IONM signals when returned to the operating room (p=.006). All patients ultimately made a full neurologic recovery. CONCLUSIONS: In children whose spinal deformity surgery was aborted due to intraoperative IONM loss, there was a strong correlation between combined intraoperative SSEP/MEP loss, the magnitude of IONM loss, the timing of clinical recovery, and the time of electrophysiological IONM recovery. The highest likelihood of having a prolonged postoperative neurological deficit and undetectable IONM signals upon return to the OR occurs with bilateral complete loss of SSEPs and MEPs.