Laser interstitial thermal therapy for first-line treatment of insular glioma.

OBJECTIVE: Insular gliomas pose a significant surgical challenge due to the complex surrounding functional and vascular anatomy. The authors report their experience using a novel framework for the treatment of insular gliomas with laser interstitial thermal therapy (LITT) and provide representative case examples emphasizing indications, rationale, and technical pearls. METHODS: A prospectively gathered institutional database was used to identify patients with newly diagnosed insular gliomas who underwent LITT between 2015 and 2023. The proposed framework of insular glioma management is guided by tumor size and extent of extra-insular tumor involvement. Patients with tumors localized to the insula (insula-only) were treated with single-session or staged LITT. Patients with insular tumors with frontotemporal involvement (insular+) were treated with insular LITT and standard frontotemporal resection of extra-insular tumor. Clinical and volumetric lesional characteristics were analyzed, with particular emphasis on extent of cytoreductive treatment and safety. RESULTS: Of the 261 patients treated at the authors' institution with LITT between 2015 and 2023, 33 LITT procedures were identified involving 22 unique patients with treatment-naive insular gliomas. Of the 22 patients, 12 had insular-only tumors and were treated with LITT alone, while 10 patients had insular+ lesions and were treated with LITT and resection. The median tumor volume for insular-only tumors was 13.4 cm3 (IQR 10.6, 26.3 cm3), with a median extent of treatment of 100% (IQR 92.1%, 100%). Insular+ lesions were significantly larger, with a median volume of 81.2 cm3 (IQR 51.9, 97 cm3) and median extent of treatment of 96.6% (IQR 93.7%, 100%). All patients with insular-only tumors were discharged the day after ablation, while insular+ patients had significantly longer hospital stays, with 50% staying more than 3 days. Overall, 8% of insular-only patients had permanent neurological deficits compared with 33% of insular+ patients. Two patients' tumors progressed during follow-up: one patient with WHO grade 4 astrocytoma and the other with diffuse glioma not otherwise specified. Patients with grade 4 tumors had the highest rate of permanent neurological deficit (43%) and a larger decline in postoperative Karnofsky Performance Status score (p = 0.046). CONCLUSIONS: The authors present their experience using a novel insular glioma treatment paradigm that incorporates LITT into the broader framework of insular glioma surgery. Their findings suggest that insular LITT is feasible and may allow for high rates of cytoreduction while potentially ameliorating the risks of conventional insular glioma surgery.

Laser interstitial thermal therapy for deep-seated perivascular brain tumors is not associated with distal ischemia.

PURPOSE: Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment option for brain tumors with a risk of vascular injury from catheter placement or thermal energy. This may be of concern with deep-seated tumors that have surrounding end-artery perforators and critical microvasculature. The purpose of this study was to assess the risk of distal ischemia following LITT for deep-seated perivascular brain tumors. METHODS: A retrospective review of a multi-institution database was used to identify patients who underwent LITT between 2013 and 2022 for tumors located within the insula, thalamus, basal ganglia, and anterior perforated substance. Demographic, clinical and volumetric tumor characteristics were collected. The primary outcome was radiographic evidence of distal ischemia on post-ablation magnetic resonance imaging (MRI). RESULTS: 61 LITT ablations for deep-seated perivascular brain tumors were performed. Of the tumors treated, 24 (39%) were low-grade gliomas, 32 (52%) were high-grade gliomas, and 5 (8%) were metastatic. The principal location included 31 (51%) insular, 14 (23%) thalamic, 13 (21%) basal ganglia, and 3 (5%) anterior perforated substance tumors. The average tumor size was 19.6 cm3 with a mean ablation volume of 11.1 cm3. The median extent of ablation was 92% (IQR 30%, 100%). Two patients developed symptomatic intracerebral hemorrhage after LITT. No patient had radiographic evidence of distal ischemia on post-operative diffusion weighted imaging. CONCLUSION: We demonstrate that LITT for deep-seated perivascular brain tumors has minimal ischemic risks and is a feasible cytoreductive treatment option for otherwise difficult to access intracranial tumors.

Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas.

Recurrence of meningiomas is unpredictable by current invasive methods based on surgically removed specimens. Identification of patients likely to recur using noninvasive approaches could inform treatment strategy, whether intervention or monitoring. In this study, we analyze the DNA methylation levels in blood (serum and plasma) and tissue samples from 155 meningioma patients, compared to other central nervous system tumor and non-tumor entities. We discover DNA methylation markers unique to meningiomas and use artificial intelligence to create accurate and universal models for identifying and predicting meningioma recurrence, using either blood or tissue samples. Here we show that liquid biopsy is a potential noninvasive and reliable tool for diagnosing and predicting outcomes in meningioma patients. This approach can improve personalized management strategies for these patients.

Sinonasal Packing is Not a Requisite for Successful Cerebrospinal Fluid Leak Repair.

Background Numerous methods have been described to repair nasal cerebrospinal fluid (CSF) leaks. Most studies have focused on optimizing CSF leak repair success, leading to closure rates of 90 to 95%. Objective This study aimed to determine if excellent reconstruction rates could be achieved without using sinonasal packing. Methods A prospective case series of 73 consecutive patients with various CSF leak etiologies and skull base defects was conducted to evaluate reconstruction success without sinonasal packing. The primary outcome measure was postoperative CSF leak. Secondary outcome measures were postoperative epistaxis requiring intervention in operating room or emergency department, infectious sinusitis, and 22-item sinonasal outcome test (SNOT-22) changes. Results Mean age was 54.5 years and 64% were female. Multilayered reconstructions were performed in 55.3% of cases, with collagen or bone epidural inlay grafts, and nasal mucosal grafts or nasoseptal flaps for onlay layers. Onlay-only reconstructions with mucosal grafts or nasoseptal flaps were performed in 44.7% of cases. Tissue sealants were used in all cases, and lumbar drains were used in 40.8% of cases. There were two initial failures (97.4% initial success), but both resolved with lumbar drains alone (no revision surgeries). There were no instances of postoperative epistaxis requiring intervention in the operating room or emergency department. Infectious sinusitis occurred in 2.7% of patients in the first 3 months postoperatively. SNOT-22 did not change significantly from preoperatively to first postoperative visits, then improved over time. Conclusion Nasal CSF leaks from various etiologies and defect sites were successfully repaired without using sinonasal packing, and patients experienced minimal sinonasal morbidity.

Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.

BACKGROUND: Laser interstitial thermal therapy (LITT) for glioblastoma (GBM) has been reserved for poor surgical candidates and deep "inoperable" lesions. We present the first reported series of LITT for surgically accessible recurrent GBM (rGBM) that would otherwise be treated with surgical resection. OBJECTIVE: To evaluate the use of LITT for unifocal, lobar, first-time rGBM compared with a similar surgical cohort. METHODS: A retrospective institutional database was used to identify patients with unifocal, lobar, first-time rGBM who underwent LITT or resection between 2013 and 2020. Clinical and volumetric lesional characteristics were compared between cohorts. Subgroup analysis of patients with lesions ≤20 cm 3 was also completed. Primary outcomes were overall survival and progression-free survival. RESULTS: Of the 744 patients with rGBM treated from 2013 to 2020, a LITT cohort of 17 patients were compared with 23 similar surgical patients. There were no differences in baseline characteristics, although lesions were larger in the surgical cohort (7.54 vs 4.37 cm 3 , P = .017). Despite differences in lesion size, both cohorts had similar extents of ablation/resection (90.7% vs 95.1%, P = .739). Overall survival (14.1 vs 13.8 months, P = .578) and progression-free survival (3.7 vs 3.3 months, P = 0. 495) were similar. LITT patients had significantly shorter hospital stays (2.2 vs 3.0 days, P = .004). Subgroup analysis of patients with lesions ≤20 cm 3 showed similar outcomes, with LITT allowing for significantly shorter hospital stays. CONCLUSION: We found no difference in survival outcomes or morbidity between LITT and repeat surgery for surgically accessible rGBM while LITT resulted in shorter hospital stays and more efficient postoperative care.

Hypertrophic olivary degeneration and palatal myoclonus from a Streptococcus intermedius infection of the brain: illustrative case.

BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare condition that can occur after disruption of the Guillain-Mollaret triangle. Clinically, HOD can present with palatal myoclonus with or without oculopalatal tremor, which sometimes results in symptomatic dysphagia and/or speech abnormalities. This condition is commonly associated with vascular lesions, with only three prior reported cases of HOD resulting from intracranial abscess. OBSERVATIONS: An otherwise healthy patient developed multiple intracranial abscesses. Biopsy showed gram-positive cocci; however, culture findings were negative. Polymerase chain reaction (PCR) identified Streptococcus intermedius. The patient demonstrated palatal myoclonus and vertical nystagmus, which resulted in persistent mild dysphagia and altered speech intonation. After appropriate antimicrobial therapy with resolution of the enhancing lesions, symptoms persisted. Follow-up imaging demonstrated progressive hypertrophy of the right olive with persistent disruption of the right-sided rubro-olivo fiber pathways. LESSONS: Although HOD classically occurs after vascular insult, it can also be seen as a postinfectious sequela. Despite eradication of the infection, palatal myoclonus and oculopalatal tremor may have a persistent impact on quality of life due to impaired speech and swallowing. This case emphasizes the utility of universal PCR in detecting fastidious organisms as well as diffusion tensor imaging for characterization of disrupted fiber pathways.

Clinically useful tumor fluorescence greater than 24 hours after 5-aminolevulinic acid administration.

Background: 5-aminolevulinic acid (5-ALA) is a valuable surgical adjuvant used for the resection of glioblastoma multiforme (GBM). Since Food and Drug Administration approval in 2017, 5-ALA has been used in over 37,000 cases. The current recommendation for peak efficacy and intraoperative fluorescence is within 4 h after administration. This narrow time window imposes a perioperative time constraint which may complicate or preclude the use of 5-ALA in GBM surgery. Case Description: This case report describes the prolonged activity of 5-ALA in a 66-year-old patient with a newly diagnosed GBM lesion within the left supramarginal gyrus. An awake craniotomy with language and sensorimotor mapping was planned along with 5-ALA fluorescence guidance. Shortly, after receiving the preoperative 5-ALA dose, the patient developed a fever. Surgery was postponed for an infectious disease workup which proved negative. The patient was taken to surgery the following day, 36 h after 5-ALA administration. Despite the delay, intraoperative fluorescence within the tumor remained and was sufficient to guide resection. Postoperative imaging confirmed a gross total resection of the tumor. Conclusion: The use of 5-ALA as an intraoperative adjuvant may still be effective for patients beyond the recommended 4-h window after initial administration. Reconsideration of current use of 5-ALA is warranted.

Detection of tumor-specific DNA methylation markers in the blood of patients with pituitary neuroendocrine tumors.

BACKGROUND: DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect methylome alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system (CNS) tumors but not across PitNETs. The aim of the study was to use the liquid biopsy (LB) approach to detect PitNET-specific methylation signatures to differentiate these tumors from other sellar diseases. METHODS: We profiled the cfDNA methylome (EPIC array) of 59 serum and 41 plasma LB specimens from patients with PitNETs and other CNS diseases (sellar tumors and other pituitary non-neoplastic diseases, lower-grade gliomas, and skull-base meningiomas) or nontumor conditions, grouped as non-PitNET. RESULTS: Our results indicated that despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylomes captured epigenetic features reported in PitNET tissue and provided information about cell-type composition. Using LB-derived PitNETs-specific signatures as input to develop machine-learning predictive models, we generated scores that distinguished PitNETs from non-PitNETs conditions, including sellar tumor and non-neoplastic pituitary diseases, with accuracies above ~93% in independent cohort sets. CONCLUSIONS: Our results underpin the potential application of methylation-based LB profiling as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the prognostication and management of patients with PitNETs.

Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs.

BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion. OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia. METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period. RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P < .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105). CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns.

Fluorescence-Guided High-Grade Glioma Surgery More Than Four Hours After 5-Aminolevulinic Acid Administration.

Background: Fluorescence-guided surgery (FGS) using 5-aminolevulic acid (5-ALA) is a widely used strategy for delineating tumor tissue from surrounding brain intraoperatively during high-grade glioma (HGG) resection. 5-ALA reaches peak plasma levels ~4 h after oral administration and is currently approved by the FDA for use 2-4 h prior to induction to anesthesia. Objective: To demonstrate that there is adequate intraoperative fluorescence in cases undergoing surgery more than 4 h after 5-ALA administration and compare survival and radiological recurrence to previous data. Methods: Retrospective analysis of HGG patients undergoing FGS more than 4 h after 5-ALA administration was performed at two institutions. Clinical, operative, and radiographic pre- and post-operative characteristics are presented. Results: Sixteen patients were identified, 6 of them female (37.5%), with mean (SD) age of 59.3 ± 11.5 years. Preoperative mean modified Rankin score (mRS) was 2 ± 1. All patients were dosed with 20 mg/kg 5-ALA the morning of surgery. Mean time to anesthesia induction was 425 ± 334 min. All cases had adequate intraoperative fluorescence. Eloquent cortex was involved in 12 cases (75%), and 13 cases (81.3%) had residual contrast enhancement on postoperative MRI. Mean progression-free survival was 5 ± 3 months. In the study period, 6 patients died (37.5%), mean mRS was 2.3 ± 1.3, Karnofsky score 71.9 ± 22.1, and NIHSS 3.9 ± 2.4. Conclusion: Here we demonstrate that 5-ALA-guided HGG resection can be performed safely more than 4 h after administration, with clinical results largely similar to previous reports. Relaxation of timing restrictions could improve procedure workflow in busy neurosurgical centers, without additional risk to patients.

Minimally Invasive Surgery Strategies: Changing the Treatment of Spine Tumors.

Innovation in surgical technique and contemporary spinal instrumentation paired with intraoperative navigation/imaging concepts allows for safer and less-invasive surgical approaches. The combination of stereotactic body radiotherapy, contemporary surgical adjuncts, and less-invasive techniques serves to minimize blood loss, soft tissue injury, and length of hospital stay without compromising surgical efficacy, potentially enabling patients to begin adjuvant treatment sooner.

Adapting to Space Limitations During Prone Real-Time Magnetic Resonance Imaging-Guided Stereotaxic Laser Ablation: Technical Pearls.

BACKGROUND: New techniques of intraoperative magnetic resonance imaging (MRI)-guided stereotaxy enable minimally invasive approaches to intracranial pathology. Laser interstitial thermal therapy (LITT), convection-enhanced drug delivery, and stereotactic biopsy can be performed with a real-time confirmation of location and the ability to adjust for intracranial shift during the procedure. However, these procedures are constrained by patient positioning and the need for trajectories that avoid collision between stereotactic elements and the small MRI bore. To our knowledge, this is the first report to outline the technical details of safe intraoperative MRI (iMRI)-guided stereotaxy, performed with prone positioning. OBJECTIVE: To present technical pearls to guide the safe conduction of iMRI-guided stereotaxy and LITT while in the prone position. METHODS: The details of the positioning and trajectories for a series of patients who underwent Clearpoint® (MRI Interventions Inc) frameless real-time MRI-guided stereotaxis using a posterior approach were reviewed. RESULTS: In this series, 5 patients underwent selective amygdalohippocampectomy, and 2 underwent tumor biopsy/ablation while in the prone position without any complications. CONCLUSION: Prone iMRI procedures can be performed safely even in a 60-cm MRI bore.

Trends in the Abscopal Effect After Radiation to Spinal Metastases: A Systematic Review.

While the abscopal effect has been previously described, the phenomenon has been poorly defined in the case of spinal metastases. This article is unique in that we present the first systematic review of the abscopal effect after radiation therapy to metastatic spinal cancer, especially since the spinal column represents one of the most common metastatic locations. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) resources, a systematic review identified relevant studies via a computer-aided search of MEDLINE and Embase. Ten publications that met the inclusion and exclusion criteria from the PRISMA flow diagram described a total of 13 patients, 76.9% of whom demonstrated image findings of the abscopal effect. In summary, important trends in the nine patients who experienced the abscopal effect in this review include higher doses of radiation and treatment with immunomodulators, both of which may help guide treatment paradigms for spinal metastases superimposed on diffuse metastatic disease. These trends, however, still warrant further investigations with experimental and clinical studies for a mechanistic understanding of the abscopal effect.

Delirium and topographical disorientation associated with glioblastoma multiforme tumour progression into the isthmus of the cingulate gyrus.

Since there is no cure for glioblastoma multiforme (GBM), the goal of treatment becomes prolonging the survival through cytoreduction while minimising neurological deficits. In this case report, laser interstitial thermal therapy (LITT) was used once the tumour progressed into the isthmus of the cingulate gyrus. One year after temporal lobectomy, disorders of memory, emotion, personality and navigation, likely related to limbic system involvement along with hallucinations and fluctuating cognition occurred as the tumour progressed. After ablation of the posterior cingulum, worsening of topographical disorientation was observed.Per literature review, delirium has been noted in patients with strokes involving the right-sided temporo-parieto-occipital junction, and topographical disorientation has been associated with lesions of the right posterior cingulum. Alternative causes of these deficits were ruled out, leaving structural changes as the primary explanation. This is the first report of the neurological deficits associated with tumour progression and vasogenic oedema in this region.

Reoperation for Recurrent Glioblastoma Multiforme.

The role of reoperation for glioblastoma multiforme (GBM) recurrence is currently unknown. However, multiple studies have indicated that survival and quality of life are improved with a repeat operation at the time of disease recurrence. Prognosis is likely interdependent on several factors, including age, functional status, initial resection status, disease location, and surgical efficacy. However, there are significant data indicating no survival benefit for reoperation. This comprehensive literature review considering the controversial question of whether to operate for progressive or recurrent GBM seeks to evaluate the current available evidence and report on its conclusions.

Complications of ventricular entry during craniotomy for brain tumor resection.

OBJECTIVE Recent studies have demonstrated that periventricular tumor location is associated with poorer survival and that tumor location near the ventricle limits the extent of resection. This finding may relate to the perception that ventricular entry leads to further complications and thus surgeons may choose to perform less aggressive resection in these areas. However, there is little support for this view in the literature. This study seeks to determine whether ventricular entry is associated with more complications during craniotomy for brain tumor resection. METHODS A retrospective analysis of patients who underwent craniotomy for tumor resection at Henry Ford Hospital between January 2010 and November 2012 was conducted. A total of 183 cases were reviewed with attention to operative entry into the ventricular system, postoperative use of an external ventricular drain (EVD), subdural hematoma, hydrocephalus, and symptomatic intraventricular hemorrhage (IVH). RESULTS Patients in whom the ventricles were entered had significantly higher rates of any complication (46% vs 21%). Complications included development of subdural hygroma, subdural hematoma, intraventricular hemorrhage, subgaleal collection, wound infection, urinary tract infection/deep venous thrombosis, hydrocephalus, and ventriculoperitoneal (VP) shunt placement. Specifically, these patients had significantly higher rates of EVD placement (23% vs 1%, p < 0.001), hydrocephalus (6% vs 0%, p = 0.03), IVH (14% vs 0%, p < 0.001), infection (15% vs 5%, p = 0.04), and subgaleal collection (20% vs 4%, p < 0.001). It was also observed that VP shunt placement was only seen in cases of ventricular entry (11% vs 0%, p = 0.001) with 3 of 4 of these patients having a large ventricular entry (defined here as entry greater than a pinhole [< 3 mm] entry). Furthermore, in a subset of glioblastoma patients with and without ventricular entry, Kaplan-Meier estimates for survival demonstrated a median survival time of 329 days for ventricular entry compared with 522 days for patients with no ventricular entry (HR 1.13, 95% CI 0.65-1.96; p = 0.67). CONCLUSIONS There are more complications associated with ventricular entry during brain tumor resection than in nonviolated ventricular systems. Better strategies for management of periventricular tumor resection should be actively sought to improve resection and survival for these patients.

Surgical Management of Dural Arteriovenous Fistula After Craniotomy: Case Report and Review of Literature.

BACKGROUND: Development of dural arteriovenous fistula (dAVF) with cortical venous drainage at the site of previous craniotomy is a rare manifestation of nontraumatic subarachnoid hemorrhage (SAH). The authors present a case of postcraniotomy dAVF formation and discuss plausible underlying mechanisms of fistula formation and treatment options as well as review the literature. CASE DESCRIPTION: A 62-year-old man, who had undergone craniotomy 2 decades previously, presented with SAH. Workup revealed a low-flow dAVF with leptomeningeal venous drainage at the posterior margin of the craniotomy. Surgical resection of fistula was undertaken that resulted in cure. CONCLUSIONS: Spontaneous SAH in patients with a previous history of an intracranial procedure (e.g., craniotomy, ventriculostomy) should prompt detailed imaging evaluation. In the absence of vascular disease, meticulous review of the angiogram must be undertaken to rule out dAVF at the procedure site and it should be treated definitively.

Further evidence for a pain pathway involving the cingulate gyrus: a case of chronic cluster headache cured by glioblastoma.

The authors report a case of a 49-year-old man with long-standing, chronic cluster headache (CH) refractory to medical therapy and occipital nerve stimulation that resolved a few weeks prior to the diagnosis of glioblastoma involving primarily the right cingulate gyrus. An attempt to explore the underlying role of the cingulate cortex in pain modulation by appraising the current literature is presented. This report suggests that the cingulate gyri could be a potential target for neuromodulation in patients with medically refractory chronic CH.