Deep Brain Stimulation for Chronic Cluster Headaches: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic cluster headache (CCH) is a severe and debilitating sub-type of trigeminal autonomic cephalalgia that can be resistant to medical management and associated with significant impairment in quality of life. Studies of deep brain stimulation (DBS) for CCH have provided promising results but have not been assessed in a comprehensive systematic review/meta-analysis. OBJECTIVE: The objective was to perform a systematic literature review and meta-analysis of patients with CCH treated with DBS to provide insight on safety and efficacy. METHODS: A systematic review and meta-analysis were performed according to PRISMA 2020 guidelines. 16 studies were included in final analysis. A random-effects model was used to meta-analyze data. RESULTS: Sixteen studies reported 108 cases for data extraction and analysis. DBS was feasible in >99% of cases and was performed either awake or asleep. Meta-analysis revealed that the mean difference in headache attack frequency and headache intensity after DBS were statistically significant (p < 0.0001). Utilization of microelectrode recording was associated with statistically significant improvement in headache intensity postoperatively (p = 0.006). The average overall follow-up period was 45.4 months and ranged from 1 to 144 months. Death occurred in <1%. The rate of major complications was 16.67%. CONCLUSIONS: DBS for CCHs is a feasible surgical technique with a reasonable safety profile that can be successfully performed either awake or asleep. In carefully selected patients, approximately 70% of patients achieve excellent control of their headaches.

CT Perfusion collateral index in assessment of collaterals in acute ischemic stroke with delayed presentation: Comparison to single phase CTA.

BACKGROUND & PURPOSE: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients. METHODS: ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS. RESULTS: A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003). CONCLUSION: CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Low Rate of Intrathecal Baclofen Pump Catheter-Related Complications: Long-Term Study in Over 100 Adult Patients Associated With Reinforced Catheter.

OBJECTIVES: Intrathecal baclofen (ITB) is a cost-effective therapy for patients with severe spasticity. The most common complications are catheter-related complications (CRCs) including kinking/occlusion, blockage, migration, fracture, disconnection, and CSF leak. Our objective was to determine the CRC rate in a large cohort of adults with newly implanted ITB pump systems with polymer reinforced silicone catheters. MATERIALS AND METHODS: This is a retrospective study of a prospectively maintained database consisting of patients who had undergone implantation of ITB pump systems with Ascenda (Medtronic, Minneapolis) catheters from 2013 to 2020. Over this seven-year period, 141 patients underwent ITB pump system implantations; 126 of which had a minimum of one-year follow-up. RESULTS: The 126 patients with a minimum of one year follow-up (average 43 month; range 12-89), had an average age of 51 years (63% male). Severe spasticity was due to spinal cord injury (38%), traumatic brain injury (15%), cerebral palsy (13%), multiple sclerosis (11%), stroke (10%), and other (13%). Nine (7.1%) CRCs occurred in 7 (5.6%) patients (median 6 mo. post-implant): 5 intrathecal catheter occlusions (range 3-52 months post-implant), two fractures in one patient (6 months), one disconnection at the catheter pump interface (2 months), and one due to kinking at 84 months No migrations occurred. CONCLUSIONS: Reported CRCs have been high for ITB pump systems. Ours is the first large cohort, long-term study of CRCs related to reinforced catheters; additionally, our low CRC rate compares favorably to previously published data. Thus, implantation of reinforced catheters may be associated with a low CRC rate.

Management and survival trends for adult patients with malignant gliomas in the setting of multiple primary tumors: a population based analysis.

INTRODUCTION: The impact of multiple primary tumors, in the setting of malignant glioma (MG), has not been heavily explored. METHODS: We extracted demographics and clinical data from the SEER-18 registry for adult patients with MGs. The cases were separated based on the sequence of MG diagnosis relative to the other primary tumors: Group (A) One primary only or first primary of multiple primaries and Group (B) second primary or subsequent primary tumor. Incidences, frequencies, and glioma-related survivals were analyzed. RESULTS: Group B constituted 12.8% of new MG. The incidences of group B, relative to those of all new MG, range from 0.14 to 0.18. Compared to group A, group B exhibited an older age. Moreover, group B exhibited a higher proportion of females, Caucasians, smaller tumors, non-operative cases, and those receiving radiation (p < 0.05); the proportion with GTR remained comparable. Multiple groupings (oral cavity, digestive system, respiratory system, skin, breast, genital systems, urinary system, lymphoma) exhibited lower glioma-related observed survival (p < 0.05) compared to Group A. An active diagnosis of "leukemia" appears to confer longer glioma-related survival while a history of "breast" or "digestive system" malignancies portends a shorter glioma-related survival. CONCLUSION: For newly diagnosed MG, a high proportion does have history of extra-CNS primary tumors. Generally, these patients appear to have worse glioma-related observed survival compare to those with malignant glioma as the only primary or the first of multiple primary tumors. Knowledge regarding epidemiology, clinical factors, and observed survival can help guide clinical management/consultation for this subset of patients.

Stereotactic laser ablation of amygdala and hippocampus using a Leksell stereotactic frame.

Approximately one-third of patients with epilepsy are resistant to medical therapy, particularly in those with mesial temporal lobe epilepsy. While there are several surgical modalities, efforts have been focused on developing safer and minimally invasive techniques. In this video, the authors present the case of a 45-year-old woman with a 2-year history of refractory left mesial temporal lobe epilepsy who underwent MRI-guided laser ablation of amygdala and hippocampus. There were no perioperative complications. The video can be found here: https://youtu.be/XFHt2jTdE_4 .

Molecular Markers of Therapy-Resistant Glioblastoma and Potential Strategy to Combat Resistance.

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. With its overall dismal prognosis (the median survival is 14 months), GBMs demonstrate a resounding resilience against all current treatment modalities. The absence of a major progress in the treatment of GBM maybe a result of our poor understanding of both GBM tumor biology and the mechanisms underlying the acquirement of treatment resistance in recurrent GBMs. A comprehensive understanding of these markers is mandatory for the development of treatments against therapy-resistant GBMs. This review also provides an overview of a novel marker called acid ceramidase and its implication in the development of radioresistant GBMs. Multiple signaling pathways were found altered in radioresistant GBMs. Given these global alterations of multiple signaling pathways found in radioresistant GBMs, an effective treatment for radioresistant GBMs may require a cocktail containing multiple agents targeting multiple cancer-inducing pathways in order to have a chance to make a substantial impact on improving the overall GBM survival.

Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion.

BACKGROUND AND PURPOSE: Endovascular recanalization treatment for acute ischemic stroke is a complex, time-sensitive intervention. Trip-and-treat is an interhospital service delivery model that has not previously been evaluated in the literature and consists of a shared mobile interventional stroke team that travels to primary stroke centers to provide on-site interventional capability. We compared treatment times between the trip-and-treat model and the traditional drip-and-ship model. METHODS: We performed a retrospective analysis on 86 consecutive eligible patients with acute ischemic stroke secondary to large vessel occlusion who received endovascular treatment at 4 hospitals in Manhattan. Patients were divided into 2 cohorts: trip-and-treat (n=39) and drip-and-ship (n=47). The primary outcome was initial door-to-puncture time, defined as the time between arrival at any hospital and arterial puncture. We also recorded and analyzed the times of last known well, IV-tPA (intravenous tissue-type plasminogen activator) administration, transfer, and reperfusion. RESULTS: Mean initial door-to-puncture time was 143 minutes for trip-and-treat and 222 minutes for drip-and-ship (P<0.0001). Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (P=0.0887), initial door-to-recanalization was nonetheless 79 minutes faster for trip-and-treat (P<0.0001). There was a trend in improved admission-to-discharge change in National Institutes of Health Stroke Scale for trip-and-treat compared with drip-and-ship (P=0.0704). CONCLUSIONS: Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.

Endovascular management of fusiform aneurysms in the posterior circulation: the era of flow diversion.

Fusiform aneurysms are uncommon compared with their saccular counterparts, yet they remain very challenging to treat and are associated with high rates of rebleeding and morbidity. Lack of a true aneurysm neck renders simple clip reconstruction or coil embolization usually impossible, and more advanced techniques are required, including bypass, stent-assisted coiling, and, more recently, flow diversion. In this article, the authors review posterior circulation fusiform aneurysms, including pathogenesis, natural history, and endovascular treatment, including the role of flow diversion. In addition, the authors propose an algorithm for treatment based on their practice.

Deep brain stimulation of the ventralis intermedius nucleus for the treatment of essential tremor.

A 59-year-old woman with a 30-year history of essential tremor refractory to medical therapy underwent staged deep brain stimulation of the ventralis intermedius nucleus of the thalamus (VIM). Left-sided lead placement was performed first. Once in the operating room, microelectrode recording (MER) was performed to confirm the appropriate trajectory and identify the VIM border with the ventralis caudalis nucleus. MER was repeated after repositioning 2 mm anteriorly to reduce the likelihood of stimulation-induced paresthesias. Physical examination prior to permanent lead placement demonstrated micro-lesion effect, suggesting optimal trajectory. After implantation of the permanent lead, physical examination showed excellent results. The video can be found here: https://youtu.be/nn3KRdmRCZ4 .

A step-down unit transfer protocol for low-risk aneurysmal subarachnoid hemorrhage.

OBJECTIVE Patients who have experienced subarachnoid hemorrhage (SAH) often receive care in the setting of the ICU. However, SAH patients may not all require extended ICU admission. The authors established a protocol on January 1, 2015, to transfer select, low-risk patients to a step-down unit (SDU) to streamline care for SAH patients. This study describes the results of the implemented protocol. METHODS In this retrospective chart review, patients presenting with SAH between January 2011 and September 2016 were reviewed for inclusion. The control group consisted of patients admitted prior to establishment of the SDU transfer protocol, while the intervention group consisted of patients admitted afterward. RESULTS Of the patients in the intervention group, 79.2% (57/72) were transferred to the SDU during their admission. Of these transferred patients, 29.8% (17/57) required return to the neurosurgical ICU (NSICU). There were no instances of morbidity or mortality directly related to care in the SDU. Patients in the intervention group had a mean reduced NSICU length of stay, by 1.95 days, which trended toward significance, and a longer average hospitalization, by 2.7 days, which also trended toward significance. In-hospital mortality and 90-day readmission rate were not statistically different between the groups. In addition, early transfer timing prior to 7 days was associated with neither a higher return rate to the NSICU nor higher 90-day readmission rate. CONCLUSIONS In this retrospective study, the authors demonstrated that the transfer protocol was safe, feasible, and effective in reducing the ICU length of stay and was independent of transfer timing. Confirmation of these results is needed in a large, multicenter study.

Novel and emerging technologies for endovascular thrombectomy.

Endovascular thrombectomy device improvements in recent years have served a pivotal role in improving the success and safety of the thrombectomy procedure. As the intervention gains widespread use, developers have focused on maximizing the reperfusion rates and reducing procedural complications associated with these devices. This has led to a boom in device development. This review will cover novel and emerging technologies developed for endovascular thrombectomy.

Radiation-induced brain injury: low-hanging fruit for neuroregeneration.

Brain radiation is a fundamental tool in neurooncology to improve local tumor control, but it leads to profound and progressive impairments in cognitive function. Increased attention to quality of life in neurooncology has accelerated efforts to understand and ameliorate radiation-induced cognitive sequelae. Such progress has coincided with a new understanding of the role of CNS progenitor cell populations in normal cognition and in their potential utility for the treatment of neurological diseases. The irradiated brain exhibits a host of biochemical and cellular derangements, including loss of endogenous neurogenesis, demyelination, and ablation of endogenous oligodendrocyte progenitor cells. These changes, in combination with a state of chronic neuroinflammation, underlie impairments in memory, attention, executive function, and acquisition of motor and language skills. Animal models of radiation-induced brain injury have demonstrated a robust capacity of both neural stem cells and oligodendrocyte progenitor cells to restore cognitive function after brain irradiation, likely through a combination of cell replacement and trophic effects. Oligodendrocyte progenitor cells exhibit a remarkable capacity to migrate, integrate, and functionally remyelinate damaged white matter tracts in a variety of preclinical models. The authors here critically address the opportunities and challenges in translating regenerative cell therapies from rodents to humans. Although valiant attempts to translate neuroprotective therapies in recent decades have almost uniformly failed, the authors make the case that harnessing human radiation-induced brain injury as a scientific tool represents a unique opportunity to both successfully translate a neuroregenerative therapy and to acquire tools to facilitate future restorative therapies for human traumatic and degenerative diseases of the central nervous system.

Stereotactic radiosurgery for facial nerve schwannomas: A preliminary assessment and review of the literature.

OBJECTIVE: Facial nerve schwannomas (FNS) are rare tumors, and their appropriate management remains the subject of considerable debate. This report details the results of a series of patients with FNS treated with stereotactic radiosurgery (SRS) at the University of Virginia. METHODS: We performed a retrospective review of the clinical and imaging outcomes of 5 patients who underwent Gamma Knife RS (GKRS) for small-to-medium-sized (<5 mL) FNS at our institution. The study population consisted of 3 males and 2 females with a median age of 35 years. All patients presented with varying degrees of facial palsy and/or hearing dysfunction. Tumor volumes at GKRS ranged from 0.1 to 5 (median=0.8) mL. The median maximum radiosurgical dose and tumor margin dose were 24 Gy and 12 Gy, respectively. RESULTS: After a median follow-up period of 12 (range, 6-36) months, three tumors were radiographically smaller and two remained stable. Facial function improved in three patients, remained stable in one patient, and slightly declined from House-Brackmann grade I to II in one patient. Hearing function was preserved in three patients and deteriorated in two patients, one from Gardner-Robertson grade I to II and the other from serviceable hearing grade II to III. CONCLUSION: SRS appears to offer a reasonable rate of facial nerve preservation and tumor control for patients with small-to-medium-sized FNS. Considering the published outcomes achieved with resection, RS may be the preferred first-line treatment for these tumors.

Etiology, prognosis, and management of secondary pituitary abscesses forming in underlying pituitary adenomas.

Pituitary abscesses occurring in pre-existing pituitary pathology like Rathke's cleft cyst or adenomas (secondary pituitary abscesses) are rare and of unclear etiology. While surgery and antibiotics have been effective in some cases reported to date, leading to the suggestion that secondary pituitary abscesses are mostly indolent, we investigated the hypothesis that infected adenomas, given their propensity to invade the paranasal sinuses and subarachnoid space, could carry a worse prognosis than uninfected adenomas or secondary abscesses forming in other pituitary pathologies. We identified infected adenomas from our center through retrospective review. Given the rarity of this diagnosis at any single center, we also reviewed published cases of secondary pituitary abscesses occurring in pituitary adenomas to look for common features. Twenty-three cases (19 from the literature and four from our center) of infected adenomas were identified. The mean age at presentation was 46 years, with 65 % male. The most common presenting symptoms were visual disturbances (83 %) and headache (65 %), followed by infectious signs like fever (39 %) and meningitis (26 %). The sphenoidal sinus was the most common site of extrasellar invasion. While good outcome occurred in 74 % of patients, and most achieved vision improvement, the mortality was 26 %. Patients with infected pituitary adenomas commonly present with visual disturbances and headache, with symptoms of infection also occurring. Surgery and antibiotics are indicated for these lesions. While the infection is more indolent than other intracranial abscesses, it is associated with high mortality even after prompt operation and antibiotic treatment.

Targeting MET for glioma therapy.

Glioblastoma multiforme is the most common and most lethal of all primary brain tumors. Even with the standard therapy, life expectancy is still poor, with an average survival of approximately 14 months following initial diagnosis. Hence, there is an urgent need for novel treatment strategies that inhibit proliferation and angiogenesis in high-grade gliomas. One such strategy consists of inhibiting receptor tyrosine kinases, including MET and/or its ligand hepatocyte growth factor (HGF). Because of their widespread involvement in human cancer, HGF and MET have emerged as promising therapeutic targets, and some inhibitory agents that target them have already entered clinical trials. In this paper, the authors highlight recent evidence implicating HGF/MET pathway deregulation in glioblastoma multiforme, discuss therapeutic approaches to inhibit HGF/MET signaling, and summarize ongoing clinical trials targeting this pathway.

Awake craniotomy for supratentorial tumors or epileptogenic lesions in pediatric patients: a 16-year retrospective cohort study.

OBJECTIVE: Awake craniotomy with intraoperative mapping is the widely accepted procedure for adult patients undergoing supratentorial tumor or epileptogenic focus resection near eloquent cortex. In children, awake craniotomies are notably less common due to concerns for compliance and emotional or psychological repercussions. Despite this, successfully tolerated awake craniotomies have been reported in patients as young as 8 years of age, with success rates comparable to those of adults. The authors sought to describe their experience with pediatric awake craniotomies, including insight regarding feasibility and outcomes. METHODS: A retrospective review was completed for all pediatric (age < 18 years) patients at Children's Wisconsin for whom an awake craniotomy was attempted from January 2004 until March 2020. Institutional review board approval was granted. RESULTS: Candidate patients had intact verbal ability, cognitive profile, and no considerable anxiety concerns during neuropsychology assessment. Nine patients presented with seizure. Five patients were diagnosed with tumor and secondary epilepsy, 3 with tumor only, and 3 with epilepsy only. All patients who underwent preoperative functional MRI successfully completed and tolerated testing paradigms. A total of 12 awake craniotomies were attempted in 11 patients, with 1 procedure aborted due to intraoperative bleeding. One patient had a repeat procedure. The mean patient age was 15.5 years (range 11.5-17.9 years). All patients returned to or maintained baseline motor and speech functions by the latest follow-up (range 14-130 months). Temporary deficits included transient speech errors, mild decline in visuospatial reasoning, leg numbness, and expected hemiparesis. Of the 8 patients with a diagnosis of epilepsy prior to surgery, 7 patients achieved Engel class I designation at the 1-year follow-up, 6 of whom remained in class I at the latest follow-up. CONCLUSIONS: This study analyzes one of the largest cohorts of pediatric patients who underwent awake craniotomy for maximal safe resection of tumor or epileptogenic lesions. For candidate patients, awake craniotomy is safe, feasible, and effective in carefully selected children.

Dorsal third ventricular cysts revisited.

INTRODUCTION: We have previously argued that the clinical entity of dorsal third ventricular cyst in association with agenesis of the corpus callosum is a developmentally, radiologically, and clinically distinct and separate entity from the dorsal cyst of alobar holoprosencephaly. PATIENTS AND METHODS: Herein, we describe seven patients who underwent treatment of their dorsal third ventricular cyst with fluid diversion and shunting and report their long-term follow-up. The authors reviewed the literature and discrepancies identified in differentiating dorsal third ventricular cysts and holoprosencephaly. RESULTS: Postoperative scans showed evidence of cyst decompression and stabilization of head circumference. Two patients required shunt revision surgery for delayed malfunction while the remainder has had no revision surgery since initial placement. CONCLUSIONS: Given the good clinical outcome in comparison to alobar holoprosencephaly patients, we recommend fluid diversion in this population of patients.

Dabigatran, intracranial hemorrhage, and the neurosurgeon.

Dabigatran etexilate (Pradaxa) is a novel oral anticoagulant that has gained FDA approval for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In randomized trials, the incidence of hemorrhagic events has been demonstrated to be lower in patients treated with dabigatran compared with the traditional anticoagulant warfarin. However, dabigatran does not have reliable laboratory tests to measure levels of anticoagulation and there is no pharmacological antidote. These drawbacks are challenging in the setting of intracerebral hemorrhage. In this article, the authors provide background information on dabigatran, review the existing anecdotal experiences with treating intracerebral hemorrhage related to dabigatran therapy, present a case study of intracranial hemorrhage in a patient being treated with dabigatran, and suggest clinical management strategies. The development of reversal agents is urgently needed given the growing number of patients treated with this medication.

Association between biomechanical parameters and concussion in helmeted collisions in American football: a review of the literature.

OBJECT: The authors' goal was to better define the relationship between biomechanical parameters of a helmeted collision and the likelihood of concussion. METHODS: The English-language literature was reviewed in search of scholarly articles describing the rotational and translational accelerations observed during all monitored impact conditions that resulted in concussion at all levels of American football. RESULTS: High school players who suffer concussion experience an average of 93.9g of translational acceleration (TA) and 6505.2 rad/s(2) of rotational acceleration (RA). College athletes experience an average of 118.4g of TA and 5311.6 rad/s(2) of RA. While approximately 3% of collisions are associated with TAs greater than the mean TA associated with concussion, only about 0.02% of collisions actually result in a concussion. Associated variables that determine whether a player who experiences a severe collision also experiences a concussion remain hypothetical at present. CONCLUSIONS: The ability to reliably predict the incidence of concussion based purely on biomechanical data remains elusive. This study provides novel, important information that helps to quantify the relative insignificance of biomechanical parameters in prediction of concussion risk. Further research will be necessary to better define other factors that predispose to concussion.

Lead toxicity due to retained intracranial bullet fragments: illustrative case.

BACKGROUND: Lead toxicity (plumbism) secondary to retained lead bullet fragments is a rare complication in patients with gunshot wounds. To the authors' knowledge, there has been no definitive case reported of lead toxicity due to retained intracranial bullet fragments. OBSERVATIONS: The authors reported the case of a 23-year-old man who presented after being found down. Computed tomography scanning of the head revealed bullet fragments within the calvaria adjacent to the left transverse sinus. During follow-up, he developed symptoms of plumbism with paresthesias in his bilateral hands and thighs, abdominal cramping, labile mood, and intermittent psychosis. Plumbism was confirmed with sequentially elevated blood lead levels (BLLs). The patient opted for surgical removal of the bullet fragments, which led to reduction in BLLs and resolution of his symptoms. LESSONS: Although rare, lead toxicity from retained intracranial bullet fragments should be considered in patients who have suffered a gunshot wound to the head and have symptoms of lead toxicity with elevated BLLs. For safe and accessible intracranial bullet fragments in patients with plumbism, surgical intervention may be indicated.