Focal drug-resistant temporal lobe epilepsy associated with an ipsilateral anterior choroidal artery aneurysm: illustrative case.

BACKGROUND: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus. OBSERVATIONS: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively. LESSONS: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

Endoscopic endonasal transclival approach for a ventral brainstem epidermoid cyst: illustrative case.

BACKGROUND: Intracranial epidermoid cysts are benign, slow-growing malformations that most commonly arise at the skull base. Maximizing resection of the cyst contents and the capsule reduces long-term recurrence but can be made difficult by cyst wall adherence to critical neurovascular structures. Expanded endonasal approaches (EEAs) offer an alternative to traditional open transcranial approaches for accessible epidermoid cysts. In this case report, the authors demonstrate a transclival EEA for a large, ventral brainstem epidermoid cyst. OBSERVATIONS: A 41-year-old woman who presented with progressive headaches, diplopia, malaise, and fatigue was found to have a 4.7-cm midline, ventral brainstem epidermoid cyst. She underwent an expanded endonasal transclival approach that exposed the brainstem from the level of the dorsum sella to the tip of the basion. A near-total resection was completed with removal of all cyst contents and most of the capsular wall. Reconstruction was completed with Duragen, an autologous fat graft, and a nasoseptal flap. Postoperatively, she had a partial left cranial nerve VI palsy that remained stable 8 weeks after surgery. LESSONS: The expanded endoscopic transclival approach can facilitate effective resection of midline, ventral epidermoid cysts.

Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

Increasing the intensity of tumor treating fields (TTF) within a tumor bed improves clinical efficacy, but reaching sufficiently high field intensities to achieve growth arrest remains challenging due in part to the insulating nature of the cranium. Using MRI-derived finite element models (FEMs) and simulations, we optimized an exhaustive set of intracranial electrode locations to obtain maximum TTF intensities in three clinically challenging high-grade glioma (HGG) cases (i.e., thalamic, left temporal, brainstem). Electric field strengths were converted into therapeutic enhancement ratios (TER) to evaluate the predicted impact of stimulation on tumor growth. Concurrently, conventional transcranial configurations were simulated/optimized for comparison. Optimized intracranial TTF were able to achieve field strengths that have previously been shown capable of inducing complete growth arrest, in 98-100% of the tumor volumes using only 0.54-0.64 A current. The reconceptualization of TTF as a targeted, intracranial therapy has the potential to provide a meaningful survival benefit to patients with HGG and other brain tumors, including those in surgically challenging, deep, or anatomically eloquent locations which may preclude surgical resection. Accordingly, such an approach may ultimately represent a paradigm shift in the use of TTFs for the treatment of brain cancer.

A national stratification of the global macroeconomic burden of central nervous system cancer.

OBJECTIVE: Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. METHODS: Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. RESULTS: The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. CONCLUSIONS: Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.

Magnetic Resonance Image Guided Focused Ultrasound Thalamotomy. A Single Center Experience With 160 Procedures.

INTRODUCTION: MRgFUS thalamotomy has gained popularity as an FDA approved, non-invasive treatment for patients with Essential Tremor and tremor predominant Parkinson's Disease. We present our initial clinical experience with 160 consecutive cases of MRgFUS thalamotomy and describe the clinical outcomes with long term follow-up. METHODS: A retrospective chart review of all patients who underwent MRgFUS thalamotomy at our institution was performed. CRST Part A tremor scores were obtained pre-operatively and at each follow-up visit along with an assessment of side effects (SE). All patients had a post-operative MRI within 24 h to determine the location, size, and extent of the MRgFUS lesion. RESULTS: One hundred and sixty unilateral MRgFUS Thalamotomies (Left, n = 128; Right, n = 32) were performed for medically refractory essential Tremor (n = 150) or tremor predominant Parkinson's disease (n = 10). Mean age at surgery was 75 Years (range: 48-93) and the mean skull density ratio (SDR) was 0.48 (range: 0.32-0.75; median: 0.46). In ET patients, both rest and postural tremor was abolished acutely and remained so at follow-up whereas intention tremor was reduced acutely by 93% below baseline, 87% at 3 months, 83.0% at 1-year, and 78% at 2 years. On post-operative day 1, the most common SE's included imbalance (57%), sensory disturbances (25%), and dysmetria (11%). All adverse events were rated as mild on the Clavien-Dindo Scale and improved over time. At 2-years follow-up, imbalance was seen in 18%, sensory disturbance in 10% and dysmetria in 8% patients. Mean clinical follow-up for all patients was 14 months (range: 1-48 months). CONCLUSION: MRgFUS thalamotomy is a safe and effective procedure for long term improvement of unilateral tremor symptoms, with the most common side-effects being imbalance and sensory disturbance.

Two-trajectory laser amygdalohippocampotomy: Anatomic modeling and initial seizure outcomes.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS: We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS: The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p < .05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, whereas one-laser trajectories could not. Five patients with at least 1 year of follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year of follow-up (mean = 6.6 months) are on track for Engel class I outcomes. SIGNIFICANCE: Our anatomic analyses and initial clinical results suggest that LITT amygdalohippocampotomy performed via two-laser trajectories may promote excellent seizure outcomes. Future studies are required to validate the long-term clinical efficacy and safety of this approach.

Case Report: Frontoparietal Metastasis From a Primary Fallopian Tube Carcinoma.

Background: Metastatic brain tumors typically arise from primary malignancies of the lung, kidney, breast, skin, and colorectum. Brain metastases originating from malignancies of the female genital tract are extremely rare. We present a case of fallopian tube brain metastasis and in so doing review the pertinent literature. Case Description: We describe a 59-year-old patient with a history of fallopian tube carcinoma who presented with an incidentally identified left frontal brain mass. MRI demonstrated an enhancing lesion in the left centrum semiovale with a second enhancing lesion noted in the cerebellar vermis. She underwent a left parietal craniotomy for resection of the dominant and clinically symptomatic lesion. Immunohistochemical stains were positive for PAX8 and p53, confirming fallopian tube origin. Conclusions: Fallopian tube cancer brain metastasis is extremely uncommon. We highlight the treatment and surgical resection of this patient's BRCA1 metastatic fallopian lesion and systematically review the literature regarding the pathogenesis, diagnosis, treatment, and histologic characteristics of the previously identified fallopian tube metastases to the central nervous system. The optimal course of treatment for brain metastasis of fallopian tube carcinoma has not been clearly defined due in part to the rarity of this condition. Consistent with BRCA1 neoplasms involving the breast and ovaries, the BRCA1 status of the patient's primary tumor likely increased the risk of central nervous system dissemination. This highlights a potential benefit of early screening of individuals with metastatic gynecologic malignancies associated with BRCA1 in the absence of any neurological symptoms.

The diagnosis and management of primary and iatrogenic soft tissue sarcomas of the sella.

PURPOSE: Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS of the sella to define the clinical course of this entity. METHODS: This study employed a multi-institutional retrospective case review, literature review, and nationwide analysis using the National Cancer Database (NCDB). RESULTS: We report five patients who were diagnosed at three institutions with malignant STS of the sella. All patients presented with symptoms related to mass effect in the sellar region. All tumors extended to the suprasellar space, with the majority displaying extension into the cavernous sinus. All patients underwent an operation via a transsphenoidal approach with a goal of maximal safe tumor resection in four patients and biopsy for 1 patient. Histopathologic evaluation demonstrated STS in all patients. Post-operative adjuvant radiotherapy and chemotherapy were given to 2 and 1 out of 4 patients with known post-operative clinical course, respectively. The 1-year and 5-year overall survival rates were 100% (5/5) and 25% (1/4). Twenty-two additional reports of primary, non-iatrogenic STS of the sella were identified in the literature. Including the three cases from our series, treatment included resection in all cases, and adjuvant radiotherapy and chemotherapy were utilized in 50% (12/24) and 17% (4/24) of cases, respectively. The national prevalence of malignant STS is estimated to be 0.01% among all pituitary and sellar tumors within the NCDB. CONCLUSIONS: We report the prevalence and survival rates of STS of the sella. Multimodal therapy, including maximal safe resection, chemotherapy, and radiotherapy are necessary to optimize outcomes for this uncommon pathology.

Central Nervous System-Invading Eccrine Gland Carcinoma: A Clinicopathologic Case Series and Literature Review.

BACKGROUND: Eccrine carcinoma involvement of the central nervous system (CNS) is exceedingly rare. The prognosis and response to treatment of this pathology remain poorly characterized. METHODS: A retrospective case series and literature review were conducted. RESULTS: CNS-invading eccrine carcinoma was diagnosed in 3 patients (2 male and 1 female; age range, 60-79 years), including 2 cases of brain metastases and 1 case of brain-invading skull metastasis with subsequent spinal metastasis. The interval from primary tumor to CNS invasion was 18-51 months. All patients received multimodal therapy following diagnosis of CNS involvement. One patient who harbored a NOTCH1 mutation demonstrated a durable oncologic response after treatment with the immune checkpoint inhibitor pembrolizumab and lived 39 months after CNS invasion. The other 2 patients were discharged to hospice care within 1 month after the diagnosis of eccrine carcinoma brain metastasis. Including this case series, 23 cases of eccrine carcinoma invasion or metastasis to the CNS have been reported, with survival after diagnosis of CNS involvement ranging from a few weeks to 4 years. CONCLUSIONS: We present 3 cases of eccrine carcinoma metastatic to the CNS, including the first reported case to our knowledge of eccrine carcinoma treated with immunotherapy. This case, harboring a NOTCH1 mutation, demonstrated the longest durable oncologic response reported in this rare disease. Genomic and molecular testing may play increasingly important roles in the evaluation of these metastases.

Unilateral Thalamic Deep Brain Stimulation Versus Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: The predominant neurosurgical approach to medication-refractory essential tremor is thalamic deep brain stimulation (DBS). The emergence of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has reawakened the debate surrounding the use of DBS versus thalamotomy for this indication. Herein, we aimed to provide a contemporary comparison between DBS and MRgFUS. METHODS: Two controlled trials that evaluated DBS and MRgFUS for the unilateral treatment of refractory essential tremor were compared. Clinical outcomes extracted included postural tremor score in the treated upper extremity, quality of life (QoL), and incidence of adverse events (AE). RESULTS: Baseline patient characteristics were comparable in the 2 studies, except that DBS patients were younger and had more severe baseline tremor. Both DBS- and MRgFUS-treated patients had significant tremor improvement that was sustained for 1-year posttreatment, and significant improvement in QoL. The MRgFUS cohort had higher rates of persistent neurologic AE, whereas the DBS group had higher rates of surgery- and hardware-related AEs, including intracranial hemorrhage. CONCLUSIONS: In context of prior literature, both DBS and MRgFUS significantly improve tremor control and QoL. The 2 approaches are predominantly differentiated by their AE-profile. Additional head-to-head comparison on matched clinical populations are required to more accurately compare clinical efficacy and long-term outcomes.

Evaluation of Endoscopic Strip Craniectomy and Orthotic Therapy for Bilateral Coronal Craniosynostosis.

BACKGROUND: Bilateral coronal craniosynostosis is the premature fusion of both coronal sutures. Traditionally, this condition is treated by frontal-orbital advancement (FOA). Endoscopic strip craniectomy with cranial orthotic therapy, which has gained popularity in treating single suture craniosynostosis, has recently been adapted for the treatment of bicoronal synostosis. There have been few studies documenting the outcomes of this treatment. The objective of this study is to compare the morphological outcomes of endoscopic strip craniectomy and FOA in patients with bicoronal synostosis. METHODS: A retrospective case series was done on 24 patients with bilateral coronal synostosis treated with endoscopic strip craniectomy or FOA at 2 institutions. Patients with preoperative and 1-year postoperative computed tomography scans were included. Multiple measures of cranial shape and size were assessed: cephalic index, turricephaly index, basofrontal angle, circumference Z-score, and cranial vault volume Z-score. RESULTS: The 2 groups were similar statistically in terms of morphology at preoperative scan. There were no statistical differences between the FOA group and endoscopic group at postoperative scan in any of the morphologic outcomes measured. Cranial vault volume Z-scores increased postoperatively in both the endoscopic (P < 0.001) and FOA (P = 0.034) groups. CONCLUSIONS: One year after repair there were no significant morphological difference between patients with bicoronal synostosis treated with the endoscopic approach and those treated by FOA.

Focused ultrasound in neurosurgery: a historical perspective.

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.