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Raphia K. Rahman, Neil Majmundar, Hira Ghani, Ali San, Monika Koirala, Avi A. Gajjar, Amy Pappert, and Catherine A. Mazzola

OBJECTIVE

Neurocutaneous melanocytosis (NCM), also referred to as neurocutaneous melanosis, is a rare neurocutaneous disorder characterized by excess melanocytic proliferation in the skin, leptomeninges, and cranial parenchyma. NCM most often presents in pediatric patients within the first 2 years of life and is associated with high mortality due to proliferation of melanocytes in the brain. Prognosis is poor, as patients typically die within 3 years of symptom onset. Due to the rarity of NCM, there are no specific guidelines for management. The aims of this systematic review were to investigate approaches toward diagnosis and examine modern neurosurgical management of NCM.

METHODS

A systematic review was performed using the PubMed database between April and December 2021 to identify relevant articles using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search criteria were created and checked independently among the authors. Inclusion criteria specified unique studies and case reports of NCM patients in which relevant neurosurgical management was considered and/or applied. Exclusion criteria included studies that did not report associated neurological diagnoses and neuroimaging findings, clinical reports without novel observations, and those unavailable in the English language. All articles that met the study inclusion criteria were included and analyzed.

RESULTS

A total of 26 extracted articles met inclusion criteria and were used for quantitative analysis, yielding a cumulative of 74 patients with NCM. These included 21 case reports, 1 case series, 2 retrospective cohort studies, 1 prospective cohort study, and 1 review. The mean patient age was 16.66 years (range 0.25–67 years), and most were male (76%). Seizures were the most frequently reported symptom (55%, 41/74 cases). Neurological diagnoses associated with NCM included epilepsy (45%, 33/74 cases), hydrocephalus (24%, 18/74 cases), Dandy-Walker malformation (24%, 18/74 cases), and primary CNS melanocytic tumors (23%, 17/74 cases). The most common surgical technique was CSF shunting (43%, 24/56 operations), with tethered cord release (4%, 2/56 operations) being the least frequently performed.

CONCLUSIONS

Current management of NCM includes CSF shunting to reduce intracranial pressure, surgery, chemotherapy, radiotherapy, immunotherapy, and palliative care. Neurosurgical intervention can aid in the diagnosis of NCM through tissue biopsy and resection of lesions with surgical decompression. Further evidence is required to establish the clinical outcomes of this rare entity and to describe the diverse spectrum of intracranial and intraspinal abnormalities present.

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Shane Shahrestani, Nolan J. Brown, Ben A. Strickland, Joshua Bakhsheshian, Seyed Mohammadreza Ghodsi, Tasha Nasrollahi, Michela Borrelli, Julian Gendreau, Jacob J. Ruzevick, and Gabriel Zada

OBJECTIVE

Frailty embodies a state of increased medical vulnerability that is most often secondary to age-associated decline. Recent literature has highlighted the role of frailty and its association with significantly higher rates of morbidity and mortality in patients with CNS neoplasms. There is a paucity of research regarding the effects of frailty as it relates to neurocutaneous disorders, namely, neurofibromatosis type 1 (NF1). In this study, the authors evaluated the role of frailty in patients with NF1 and compared its predictive usefulness against the Elixhauser Comorbidity Index (ECI).

METHODS

Publicly available 2016–2017 data from the Nationwide Readmissions Database was used to identify patients with a diagnosis of NF1 who underwent neurosurgical resection of an intracranial tumor. Patient frailty was queried using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. ECI scores were collected in patients for quantitative measurement of comorbidities. Propensity score matching was performed for age, sex, ECI, insurance type, and median income by zip code, which yielded 60 frail and 60 nonfrail patients. Receiver operating characteristic (ROC) curves were created for complications, including mortality, nonroutine discharge, financial costs, length of stay (LOS), and readmissions while using comorbidity indices as predictor values. The area under the curve (AUC) of each ROC served as a proxy for model performance.

RESULTS

After propensity matching of the groups, frail patients had an increased mean ± SD hospital cost ($85,441.67 ± $59,201.09) compared with nonfrail patients ($49,321.77 ± $50,705.80) (p = 0.010). Similar trends were also found in LOS between frail (23.1 ± 14.2 days) and nonfrail (10.7 ± 10.5 days) patients (p = 0.0020). For each complication of interest, ROC curves revealed that frailty scores, ECI scores, and a combination of frailty+ECI were similarly accurate predictors of variables (p > 0.05). Frailty+ECI (AUC 0.929) outperformed using only ECI for the variable of increased LOS (AUC 0.833) (p = 0.013). When considering 1-year readmission, frailty (AUC 0.642) was outperformed by both models using ECI (AUC 0.725, p = 0.039) and frailty+ECI (AUC 0.734, p = 0.038).

CONCLUSIONS

These findings suggest that frailty and ECI are useful in predicting key complications, including mortality, nonroutine discharge, readmission, LOS, and higher costs in NF1 patients undergoing intracranial tumor resection. Consideration of a patient’s frailty status is pertinent to guide appropriate inpatient management as well as resource allocation and discharge planning.

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Jeffrey Z. Nie, Constantine L. Karras, S. Joy Trybula, Pavlos Texakalidis, and Tord D. Alden

OBJECTIVE

Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem neurocutaneous disorder associated with cortical tubers, brain lesions seen in nearly all patients with TSC, which are frequently epileptogenic. Seizures are often the earliest clinical manifestation of TSC, leading to epilepsy in over 70% of patients. Medical management with antiepileptic drugs constitutes early therapy, but over 50% develop medically refractory epilepsy, necessitating surgical evaluation and treatment. The objective of this study was to summarize the literature and report seizure outcomes following surgical treatment for TSC-associated epilepsy.

METHODS

A systematic literature review was performed in accordance with the PRISMA guidelines. The PubMed and Embase databases were searched for journal articles reporting seizure outcomes following epilepsy surgery in TSC patients. Included studies were placed into one of two groups based on the surgical technique used. Excellent and worthwhile seizure reductions were defined for each group as outcomes and extracted from each study.

RESULTS

A total of 46 studies were included. Forty of these studies reported seizure outcomes following any combination of resection, disconnection, and ablation on a collective 1157 patients. Excellent and worthwhile seizure reductions were achieved in 59% (683/1157) and 85% (450/528) of patients, respectively. Six of these studies reported seizure outcomes following treatment with neuromodulation. Excellent and worthwhile seizure reductions were achieved in 34% (24/70) and 76% (53/70) of patients, respectively.

CONCLUSIONS

Surgery effectively controls seizures in select patients with TSC-associated epilepsy, but outcomes vary. Further understanding of TSC-associated epilepsy, improving localization strategies, and emerging surgical techniques represent promising avenues for improving surgical outcomes.

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Min Jae Kim, Brian Y. Hwang, David Mampre, Serban Negoita, Yohannes Tsehay, Haris I. Sair, Joon Y. Kang, and William S. Anderson

OBJECTIVE

Piriform cortex (PC) is one of the critical structures in the epileptogenesis of mesial temporal lobe epilepsy (mTLE), but its role is poorly understood. The authors examined the utility of apparent diffusion coefficient (ADC; an MR-based marker of tissue pathology) of the PC as a predictor of seizure outcome in patients with mTLE undergoing MR-guided laser interstitial thermal therapy (MRgLITT).

METHODS

A total of 33 patients diagnosed with mTLE who underwent MRgLITT at the authors’ institution were included in the study. The 6-month postoperative seizure outcomes were classified using the International League Against Epilepsy (ILAE) system as good (complete seizure freedom, ILAE class I) and poor (seizure present, ILAE classes II–VI). The PC and ablation volumes were manually segmented from both the preoperative and intraoperative MRI sequences, respectively. The mean ADC intensities of 1) preablation PC; 2) total ablation volume; 3) ablated portion of PC; and 4) postablation residual PC were calculated and compared between good and poor outcome groups. Additionally, the preoperative PC volumes and proportion of PC volume ablated were examined and compared between the subjects in the two outcome groups.

RESULTS

The mean age at surgery was 36.5 ± 3.0 years, and the mean follow-up duration was 1.9 ± 0.2 years. Thirteen patients (39.4%) had a good outcome. The proportion of PC ablated was significantly associated with seizure outcome (10.16 vs 3.30, p < 0.05). After accounting for the variability in diffusion tensor imaging acquisition parameters, patients with good outcome had a significantly higher mean ADC of the preablation PC (0.3770 vs −0.0108, p < 0.05) and the postoperative residual PC (0.4197 vs 0.0309, p < 0.05) regions compared to those with poor outcomes. No significant differences in ADC of the ablated portion of PC were observed (0.2758 vs −0.4628, p = 0.12) after performing multivariate analysis.

CONCLUSIONS

A higher proportion of PC ablated was associated with complete seizure freedom. Preoperative and postoperative residual ADC measures of PC were significantly higher in the good seizure outcome group in patients with mTLE who underwent MRgLITT, suggesting that ADC analysis can assist with postablation outcome prediction and patient stratification.

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Christopher S. Graffeo, Michael J. Link, and Michael T. Lawton

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Ehsan Dowlati, Kory B. Dylan Pasko, Esteban A. Molina, Daniel R. Felbaum, R. Bryan Mason, Jeffrey C. Mai, M. Nathan Nair, Edward F. Aulisi, and Rocco A. Armonda

OBJECTIVE

It has not been well-elucidated whether there are advantages to preserving bone flaps in abdominal subcutaneous (SQ) tissue after decompressive hemicraniectomy (DHC), compared to discarding bone flaps. The authors aimed to compare perioperative outcomes and costs for patients undergoing autologous cranioplasty (AC) after DHC with the bone flap preserved in abdominal SQ tissue, and for patients undergoing synthetic cranioplasty (SC).

METHODS

A retrospective review was performed of all patients undergoing DHC procedures between January 2017 and July 2021 at two tertiary care institutions. Patients were divided into two groups: those with flaps preserved in SQ tissue (SQ group), and those with the flap discarded (discarded group). Additional analysis was performed between patients undergoing AC versus SC. Primary end points included postoperative and surgical site complications. Secondary endpoints included operative costs, length of stay, and blood loss.

RESULTS

A total of 248 patients who underwent DHC were included in the study, with 155 patients (62.5%) in the SQ group and 93 (37.5%) in the discarded group. Patients in the discarded group were more likely to have a diagnosis of severe TBI (57.0%), while the most prevalent diagnosis in the SQ group was malignant stroke (35.5%, p < 0.05). There were 8 (5.2%) abdominal surgical site infections and 9 (5.8%) abdominal hematomas. The AC group had a significantly higher reoperation rate (23.2% vs 12.9%, p = 0.046), with 11% attributable to abdominal reoperations. The average cost of a reoperation for an abdominal complication was $40,408.75 ± $2273. When comparing the AC group to the SC group after cranioplasty, there were no significant differences in complications or surgical site infections. There were 6 cases of significant bone resorption requiring cement supplementation or discarding of the bone flap. Increased mean operative charges were found for the SC group compared to the AC group ($72,362 vs $59,726, p < 0.001).

CONCLUSIONS

Autologous bone flaps may offer a cost-effective option compared to synthetic flaps. However, when preserved in abdominal SQ tissue, they pose the risk of resorption over time as well as abdominal surgical site complications with increased reoperation rates. Further studies and methodologies such as cryopreservation of the bone flap may be beneficial to reduce costs and eliminate complications associated with abdominal SQ storage.

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Christoph Bettag, Abdelhalim Hussein, Bawarjan Schatlo, Alonso Barrantes-Freer, Tammam Abboud, Veit Rohde, and Dorothee Mielke

OBJECTIVE

Fluorescence-guided resection of cerebral metastases has been proposed as an approach to visualize residual tumor tissue and maximize the extent of resection. Critics have argued that tumor cells at the resection margins might be overlooked under microscopic visualization because of technical limitations. Therefore, an endoscope, which is capable of inducing fluorescence, has been applied with the aim of improving exposure of fluorescent tumor tissue. In this retrospective analysis, authors assessed the utility of endoscope assistance in 5-aminolevulinic acid (5-ALA) fluorescence–guided resection of brain metastases.

METHODS

Between June 2013 and December 2016, a standard 20-mg/kg dose of 5-ALA was administered 4 hours prior to surgery in 26 patients with suspected single brain metastases. After standard neuronavigated microsurgical tumor resection, a microscope capable of inducing fluorescence was used to examine tumor margins. The authors classified the remaining fluorescence into 3 grades (0 = none, 1 = weak, and 2 = strong). Endoscopic assistance was employed if no or only weak fluorescence was visualized at the resection margins under the microscope. Endoscopically identified fluorescent tissue at the margins was resected and evaluated separately via histological examination to prove or disprove tumor infiltration.

RESULTS

Under the microscope, weakly fluorescent tissue was seen at the margins of the resection cavity in 15/26 (57.7%) patients. In contrast, endoscopic inspection revealed strongly fluorescent tissue in 22/26 (84.6%) metastases. In 11/26 (42.3%) metastases no fluorescence at the tumor margins was detected by the microscope; however, strong fluorescence was visualized under the endoscope in 7 (63.6%) of these 11 metastases. In the 15 metastases with microscopically weak fluorescence, strong fluorescence was seen when using the endoscope. Neither microscopic nor endoscopic fluorescence was found in 4/26 (15.4%) cases. In the 26 patients, 96 histological specimens were obtained from the margins of the resection cavity. Findings from these specimens were in conjunction with the histopathological findings, allowing identification of metastatic infiltration with a sensitivity of 95.5% and a specificity of 75% using endoscope assistance.

CONCLUSIONS

Fluorescence-guided endoscope assistance may overcome the technical limitations of the conventional microscopic exposure of 5-ALA–fluorescent metastases and thereby increase visualization of fluorescent tumor tissue at the margins of the resection cavity with high sensitivity and acceptable specificity.

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Joseph H. Garcia, Ramin A. Morshed, Jason Chung, Miguel A. Millares Chavez, Vivek Sudhakar, Satvir Saggi, Lauro N. Avalos, Aaron Gallagher, Jacob S. Young, Mariza Daras, Michael W. McDermott, Paul A. Garcia, Edward F. Chang, and Manish K. Aghi

OBJECTIVE

Epileptic seizures are a common and potentially devastating complication of metastatic brain tumors. Although tumor-related seizures have been described in previous case series, most studies have focused on primary brain tumors and have not differentiated between different types of cerebral metastases. The authors analyzed a large surgical cohort of patients with brain metastases to examine risk factors associated with preoperative and postoperative seizures and to better understand the seizure risk factors of metastatic brain tumors.

METHODS

Patients who underwent resection of a brain metastasis at the University of California, San Francisco (UCSF), were retrospectively reviewed. Patients included in the study were ≥ 18 years of age, required resection of a brain metastasis, and were treated at UCSF. Primary cancers included melanoma, non–small cell lung adenocarcinoma, breast adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, renal cell carcinoma, urothelial carcinoma, ovarian carcinoma, cervical squamous cell carcinoma, and endometrial adenocarcinoma. Patients were evaluated for primary cancer type and seizure occurrence, as well as need for use of antiepileptic drugs preoperatively, at time of discharge, and at 6 months postoperatively. Additionally, Engel classification scores were assigned to those patients who initially presented with seizures preoperatively. Univariate and multivariate regression analyses were used to assess the association of tumor type with preoperative seizures.

RESULTS

Data were retrospectively analyzed for 348 consecutive patients who underwent surgical treatment of brain metastases between 1998 and 2019. The cohort had a mean age of 60 years at the time of surgery and was 59% female. The mean and median follow-up durations after the date of surgery for the cohort were 22 months and 10.8 months, respectively. In univariate analysis, frontal lobe location (p = 0.05), melanoma (p = 0.02), KRAS mutation in lung carcinoma (p = 0.04), intratumoral hemorrhage (p = 0.04), and prior radiotherapy (p = 0.04) were associated with seizure presentation. Postoperative checkpoint inhibitor use (p = 0.002), prior radiotherapy (p = 0.05), older age (p = 0.002), distant CNS progression (p = 0.004), and parietal lobe tumor location (p = 0.002) were associated with seizures at 6 months postoperatively. The final multivariate model confirmed the independent effects of tumor location in the frontal lobe and presence of intratumoral hemorrhage as predictors of preoperative seizures, and checkpoint inhibitor use and parietal lobe location were identified as significant predictors of seizures at 6 months postoperatively.

CONCLUSIONS

Within this surgical cohort of patients with brain metastases, seizures were seen in almost a quarter of patients preoperatively. Frontal lobe metastases and hemorrhagic tumors were associated with higher risk of preoperative seizures, whereas checkpoint inhibitor use and parietal lobe tumors appeared to be associated with seizures at 6 months postoperatively. Future research should focus on the effect of metastatic lesion–targeting therapeutic interventions on seizure control in these patients.

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Visish M. Srinivasan, Katherine Karahalios, Kavelin Rumalla, Nathan A. Shlobin, Redi Rahmani, Lea Scherschinski, Dimitri Benner, Joshua S. Catapano, Mohamed A. Labib, Christopher S. Graffeo, and Michael T. Lawton

OBJECTIVE

Giant cerebral cavernous malformations (GCCMs) are rare vascular malformations. Unlike for tumors and aneurysms, there is no clear definition of a "giant" cavernous malformation (CM). As a result of variable definitions, working descriptions and outcome data of patients with GCCM are unclear. A new definition of GCCM related to surgical outcomes is needed.

METHODS

An institutional database was searched for all patients who underwent resection of CMs > 1 cm in diameter. Patient information, surgical technique, and clinical and radiographic outcomes were assessed. A systematic review was performed to augment an earlier published review.

RESULTS

In the authors’ institutional cohort of 183 patients with a large CM, 179 with preoperative and postoperative modified Rankin Scale (mRS) scores were analyzed. A maximum CM diameter of ≥ 3 cm was associated with greater risk of severe postoperative decline (≥ 2-point increase in mRS score). After adjustment for age and deep versus superficial location, size ≥ 3 cm was strongly predictive of severe postoperative decline (OR 4.5, 95% CI 1.2–16.9). A model with CM size and deep versus superficial location was developed to predict severe postoperative decline (area under the receiver operating characteristic curve 0.79). Thirteen more patients with GCCMs have been reported in the literature since the most recent systematic review, including some patients who were treated earlier and not discussed in the previous review.

CONCLUSIONS

The authors propose that cerebral CMs with a diameter ≥ 3 cm be defined as GCCMs on the basis of the inflection point for functional and neurological outcomes. This definition is in line with the definitions for other giant lesions. It is less exclusive than earlier definitions but captures the rarity of these lesions (approximately 1% incidence) and variation in outcomes. GCCMs remain operable with potentially favorable outcomes. The term "giant" is not meant to deter or contraindicate surgery.