Geographic access to pediatric neurosurgeons in the USA: an analysis of sociodemographic factors.

PURPOSE: Geographic access to physicians has been shown to be unevenly distributed in the USA, with those in closer proximity having superior outcomes. The purpose of this study was to describe how geographic access to pediatric neurosurgeons varies across socioeconomic and demographic factors. METHODS: Actively practicing neurosurgeons were identified by matching several registries and membership logs. This data was used to find their primary practice locations and the distance the average person in a county must travel to visit a surgeon. Counties were categorized into "surgeon deserts" and "surgeon clusters," which were counties where providers were significantly further or closer to its residents, respectively, compared to the national average. These groups were also compared for differences in population characteristics using data obtained from the 2020 American Community Survey. RESULTS: A total of 439 pediatric neurosurgeons were identified. The average person in a surgeon desert and cluster was found to be 189.2 ± 78.1 miles and 39.7 ± 19.6 miles away from the nearest pediatric neurosurgeon, respectively. Multivariate analyses showed that higher Rural-Urban Continuum (RUC) codes (p < 0.001), and higher percentages of American Indian (p < 0.001) and Hispanic (p < 0.001) residents were independently associated with counties where the average person traveled significantly further to surgeons. CONCLUSION: Patients residing in counties with greater RUC codes and higher percentages of American Indian and Hispanic residents on average need to travel significantly greater distances to access pediatric neurosurgeons.

A Comparison of Clinical Outcomes for Subependymal Giant Cell Astrocytomas Treated with Laser Interstitial Thermal Therapy, Open Surgical Resection, and mTOR Inhibitors.

INTRODUCTION: Subependymal giant cell astrocytoma (SEGA) is the most common CNS tumor in patients with tuberous sclerosis complex (TSC). Although these are benign, their proximity to the foramen of Monroe frequently causes obstructive hydrocephalus, a potentially fatal complication. Open surgical resection has been the mainstay of treatment; however, this can cause significant morbidity. The development of mTOR inhibitors has changed the treatment landscape, but there are limitations to their use. Laser interstitial thermal therapy (LITT) is an emerging treatment modality that has shown promise in treatment of a variety of intracranial lesions, including SEGAs. We present a single institution, retrospective study of patients treated for SEGAs with LITT, open resection, mTOR inhibitors, or a combination of these modalities. The primary study outcome was tumor volume at most recent follow-up compared with volume at treatment initiation. The secondary outcome was clinical complications associated with treatment modality. METHODS: Retrospective chart review was performed to identify patients with SEGAs treated at our institution from 2010 to 2021. Demographics, treatment information, and complications were collected from the medical record. Tumor volumes were calculated from imaging obtained at initiation of treatment and at most recent follow-up. Kruskal-Wallis nonparametric testing was used to assess differences in tumor volume and follow-up duration between groups. RESULTS: Four patients underwent LITT (3 with LITT only), three underwent open surgical resection, and four were treated with mTOR inhibitors only. Mean percent tumor volume reduction for each group was 48.6 ± 13.8, 90.7 ± 39.8, and 67.1 ± 17.2%, respectively. No statistically significant difference was identified comparing percent tumor volume reduction between the three groups (p = 0.0513). Additionally, there was no statistically significant difference in follow-up duration between groups (p = 0.223). Only 1 patient in our series required permanent CSF diversion and 4 discontinued or decreased the dose of mTOR inhibitor due to either cost or side effects. CONCLUSIONS: Our study suggests that LITT could be considered as a treatment option for SEGAs as it was effective in reducing tumor volume with very few complications. This modality is less invasive than open resection and may be an alternative for patients who are not candidates for mTOR inhibitors. We recommend an updated paradigm for SEGA treatment which includes LITT in select cases after consideration of patient-specific factors.

Neuropsychological outcomes following supratotal resection for high-grade glioma: a review.

PURPOSE: Supratotal resection (SpTR) of high-grade glioma (HGG), in which surgical removal of the tumor is extended outside the margins of the preoperative radiographic abnormality, has been suggested to improve overall survival (OS) and progression free survival (PFS) in patients harboring tumors of non-eloquent cortex when compared to gross total resection (GTR). While current literature demonstrates these findings without an increase in post-operative complications or neurological deficits, there remains a paucity of data examining the neuropsychological outcomes of SpTR for HGG. As quality of life dramatically influences survival rates in these patients, it is crucial for neurosurgeons, neuro-oncologists, and neuropsychiatrists to understand the behavioral and cognitive outcomes following SpTR, such that optimal treatment strategies can be tailored for each patient. METHODS: We performed a comprehensive review of the available literature regarding survival, neuropsychological, and quality of life (QOL) outcomes following SpTR for HGG. We also review neuropsychological and QOL outcomes following GTR for HGG to serve as a framework for better understanding potential implications of SpTR. RESULTS: While results are limited following SpTR for HGG, available data suggests similar outcomes to those seen in patients undergoing GTR of HGG, as well as low-grade glioma. These include a short-term decline in neuropsychological functioning post-surgically with a return to baseline across most neurocognitive domains occurring within several months. Memory and attention remain relatively diminished at long term follow-up. CONCLUSIONS: Limited data exist examining postoperative cognitive and behavioral outcomes following SpTR for HGG. While the available data suggests a return to baseline for many neurocognitive domains, attention and memory deficits may persist. However, sample sizes are relatively small and have not been examined in the context of QOL and OS/PFS. More rigorous pre- and post-surgical neuropsychological assessment will help shed light on the long-term cognitive and behavioral effects of SpTR in the setting of HGG and inform clinical care and counseling when SpTR is considered.

Laser interstitial thermal therapy for gyrus rectus cortical dysplasia in a child: a technical note.

Laser interstitial thermal therapy (LITT) has become a popular tool in the treatment of tumors and epilepsy. While most commonly used for the treatment of mesial temporal lobe epilepsy, it can be used as a minimally invasive option for the treatment of any seizure focus but has very rarely been discussed in the setting of cortical dysplasia. Here, we discuss the case of a 5-year-old girl with medically refractory epilepsy secondary to a right medial orbital gyrus and gyrus rectus cortical dysplasia successfully treated with LITT. After confirmation of seizure focus using stereo electroencephalography (SEEG), the patient underwent thermal ablation of the focus through an eyebrow incision with use of a single laser fiber. She has been seizure-free 6 months postoperatively, only on one anti-seizure medication, with normal EEG. The use of LITT in this case was successful because of the cylindrical shape of the cortical dysplasia, making it easily accessible via a single laser fiber in the absence of a yet to develop fontal sinus. While open resection would have also been appropriate, the use of LITT provided a minimally invasive alternative approach that allowed for an excellent outcome with limited risks.

Robot-assisted stereoelectroencephalography electrode placement in twenty-three pediatric patients: a high-resolution analysis of individual lead placement time and accuracy at a single institution.

PURPOSE: We describe a detailed evaluation of predictors associated with individual lead placement efficiency and accuracy for 261 stereoelectroencephalography (sEEG) electrodes placed for epilepsy monitoring in twenty-three children at our institution. METHODS: Intra- and post-operative data was used to generate a linear mixed model to investigate predictors associated with three outcomes (lead placement time, lead entry error, lead target error) while accounting for correlated observations from the same patients. Lead placement time was measured using electronic time-stamp records stored by the ROSA software for each individual electrode; entry and target site accuracy was measured using postoperative stereotactic CT images fused with preoperative electrode trajectory planning images on the ROSA computer software. Predictors were selected from a list of variables that included patient demographics, laterality of leads, anatomic location of lead, skull thickness, bolt cap device used, and lead sequence number. RESULTS: Twenty-three patients (11 female, 48%) of mean age 11.7 (± 6.1) years underwent placement of intracranial sEEG electrodes (median 11 electrodes) at our institution over a period of 1 year. There were no associated infections, hemorrhages, or other adverse events, and successful seizure capture was obtained in all monitored patients. The mean placement time for individual electrodes across all patients was 6.56 (± 3.5) min; mean target accuracy was 4.5 (± 3.5) mm. Lesional electrodes were associated with 25.7% (95% CI: 6.7-40.9%, p = 0.02) smaller target point errors. Larger skull thickness was associated with larger error: for every 1-mm increase in skull thickness, there was a 4.3% (95% CI: 1.2-7.5%, p = 0.007) increase in target error. Bilateral lead placement was associated with 26.0% (95% CI: 9.9-44.5%, p = 0.002) longer lead placement time. The relationship between placement time and lead sequence number was nonlinear: it decreased consistently for the first 4 electrodes, and became less pronounced thereafter. CONCLUSIONS: Variation in sEEG electrode placement efficiency and accuracy can be explained by phenomena both within and outside of operator control. It is important to keep in mind the factors that can lead to better or worse lead placement efficiency and/or accuracy in order to maximize patient safety while maintaining the standard of care.

Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.

Dysregulation of leptin signaling in Alzheimer disease: evidence for neuronal leptin resistance.

Leptin signaling has received considerable attention in the Alzheimer disease (AD) field. Within the past decade, the peptide hormone has been demonstrated to attenuate tau hyperphosphorylation in neuronal cells and to be modulated by amyloid-ß. Moreover, a role in neuroprotection and neurogenesis within the hippocampus has been shown in animal models. To further characterize the association between leptin signaling and vulnerable regions in AD, we assessed the profile of leptin and the leptin receptor in AD and control patients. We analyzed leptin levels in CSF, and the concentration and localization of leptin and leptin receptor in the hippocampus. Significant elevations in leptin levels in both CSF and hippocampal tissue of AD patients, compared with age-matched control cases, indicate a physiological up-regulation of leptin in AD. However, the level of leptin receptor mRNA decreased in AD brain and the leptin receptor protein was localized to neurofibrillary tangles, suggesting a severe discontinuity in the leptin signaling pathway. Collectively, our results suggest that leptin resistance in the hippocampus may play a role in the characteristic changes associated with the disease. These findings are the first to demonstrate such dysregulated leptin-signaling circuitry and provide novel insights into the possible role of aberrant leptin signaling in AD. In this study, increased leptin was found in CSF and hippocampus in Alzheimer disease indicating its physiological up-regulation, yet leptin receptor mRNA was decreased and leptin receptor protein was localized to neurofibrillary tangles, suggesting a discontinuity in the leptin signaling pathway. The lack of leptin signaling within degenerating neurons may represent a novel neuronal leptin resistance in Alzheimer disease.

Focal motor weakness and recovery following chronic subdural hematoma evacuation.

OBJECTIVE: The incidence of chronic subdural hematomas (cSDHs) is expected to climb precipitously in the coming decades because of the aging populous. Neurological weakness is one of the most common presenting neurological symptoms of cSDH. Yet, the recovery rates of motor strength recovery are seldom documented, as neurological outcomes have predominantly focused on broader functional assessment scores or mortality. In this study, the authors performed one of the first detailed analyses on functional motor weakness and recovery in patients who underwent cSDH evacuation. METHODS: Patients who underwent evacuation of a cSDH at a tertiary academic medical center between November 2013 and December 2021 were retrospectively identified using ICD-9 and ICD-10 billing codes. The presence of focal motor weakness was subcategorized by location as upper extremity (UE) or lower extremity (LE). Postoperative improvement, worsening, or resolution of weakness was recorded at the time of discharge. Statistical analysis included univariate and backward stepwise multivariable logistic regression modeling. RESULTS: A total of 311 patients were included in the analysis. Patients were significantly more likely to experience UE weakness than LE weakness (29% vs 18%, p < 0.001). Forty-one percent (43/104) had both UE and LE weakness present. Risk factors for the development of focal motor weakness at the time of presentation were older age (OR 1.02, p = 0.03), increased cSDH size (OR 1.04, p = 0.02), and the presence of a unilateral cSDH (OR 2.32, p = 0.008). The majority of patients (68%, 71/104) experienced motor strength improvement following cSDH evacuation, with 58% (60/104) having complete resolution of weakness. Multivariable logistic regression analysis revealed that longer symptom duration was associated with lower rates of improvement (OR 0.96, p = 0.024). Older age was also associated with reduced resolution of weakness (OR 0.96, p = 0.02). CONCLUSIONS: This study represents one of the first in-depth analyses investigating the rates of motor strength weakness and recovery following cSDH evacuation. Nearly two-thirds of all patients had complete resolution of their weakness by the time of discharge, and more than three-quarters had partial improvement. Risk factors for impaired neurological recovery were longer symptom duration prior to treatment and older age.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

Asleep Speech Mapping Using Orofacial Muscles as Surrogates for Motor Speech in Patients Who Cannot Tolerate Awake Surgery: A Case Series.

Background Bi-polar electrical cortical stimulation during awake craniotomy has been the gold standard for mapping eloquent cortex to preserve speech. Unfortunately, not all patients can tolerate awake surgery. Monopolar hi-frequency electrical stimulation can be conducted while a patient is under general anesthesia. Utilizing this technique and targeting the orofacial muscles as surrogates for motor speech may provide a limited alternative to awake cortical mapping in patients unable to undergo surgery awake. Objective To evaluate the utility of asleep motor speech mapping during dominant hemisphere craniotomy for lesion resection in patients who cannot tolerate awake surgery. Methods We describe a series of seven patients who underwent craniotomy for resection of intra-axial lesion in eloquent cortex for whom a novel "asleep speech" cortical stimulation paradigm was used for motor speech preservation. Results Compound muscle action potentials (CMAPs) from orofacial muscles involved in motor speech were recorded during direct cortical stimulation of eloquent cortex prior to and during lesion resection. Planned resections proceeded in all cases with no adverse neuromonitoring events. Speech was preserved in all patients. Conclusions To preserve motor speech functionality in patients unable to tolerate awake speech mapping, we employed a technique in which asleep neurophysiological mapping is specifically applied to motor cortex controlling the orofacial muscles of phonation and articulation. Further study is necessary regarding the safety and efficacy of this technique for motor speech preservation when awake surgery cannot be performed.

Multiple Brain Abscesses Due to Nocardia otitidiscaviarum: Case Report and Treatment Implications.

Nocardia infections typically present in immunocompromised hosts. Brain abscesses caused by species such as Nocardia  asteroides, farcinica, and abscessus are well-documented in the literature. We present a rare case of an immunocompetent patient with multiple brain abscesses due to Nocardia otitidiscaviarum requiring a decompressive fronto-temporoparietal craniectomy due to symptomatic intracranial hypertension. The patient was treated with intrathecal amikacin in addition to standard antibiotics with the resolution of the disease and good neurologic outcome. This is one of few case reports overall involving this species within the brain, and the second to report favorable outcomes. This case describes implications for treatment and adds to sparse literature regarding this particular pathogen.

Large Adult Spinal Diffuse Midline Histone H3 Lysine27-to-Methionine-Mutant Glioma With Intramedullary and Extramedullary Components Presenting With Progressive Hydrocephalus: A Case Report Highlighting Unique Imaging Findings and Treatment.

Diffuse midline glioma with histone H3 lysine27-to-methionine mutation (H3 K27M mutation) is a rare, aggressive tumor that is designated as World Health Organization (WHO) grade IV regardless of histologic features. Preoperative diagnosis remains challenging due to limited evidence regarding distinctive clinical and imaging characteristics. We describe the case of a young woman who presented with progressively worsening headaches due to communicating hydrocephalus. MR imaging with contrast of the cervical and thoracic spine revealed diffuse leptomeningeal enhancement with focal areas of intramedullary and subarachnoid T2 hyperintensity and enhancement, suggestive of a potential infectious process. Intraoperatively, no epidural pathology was identified, and with the differential diagnosis remaining broad, a second procedure was conducted involving intradural exploration and biopsy of a lesion. This was then identified as a diffuse midline glioma with H3 K27M mutation. The nonfocal clinical presentation in the setting of communicating hydrocephalus as well as the significant exophytic tumor growth and imaging findings made the initial diagnosis unique and challenging. This case, therefore, emphasizes the rare presentation of this tumor, and the need for further understanding of the clinical and imaging characteristics of this disease as well as the need for effective therapeutics.

Pathological implications of cell cycle re-entry in Alzheimer disease.

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Improved seizure burden and cognitive performance in a child treated with responsive neurostimulation (RNS) following febrile infection related epilepsy syndrome (FIRES).

Responsive neurostimulation (RNS) is an emerging therapy for patients with refractory focal epilepsy who are not candidates for surgical resection, with limited published experience in the pediatric population. We report a case of refractory multifocal epilepsy following febrile infection related epilepsy syndrome (FIRES) in which surgical resection was not feasible due to multifocal independent seizures and risk of cognitive deficit, and RNS was pursued. Relevant RNS data and neuropsychological testing results were reviewed. By eight months after implantation, decreased frequency and severity of clinical seizures were noted, and RNS data revealed decreased "long episodes," reduced spread of electrographic seizures, and fewer detections. Neuropsychological assessment, though potentially confounded by stimulant medication, revealed significant improvement in multiple cognitive domains, particularly working memory and processing speed, at six months. These findings illustrate success in detecting and aborting seizures, and additionally suggest a neuromodulatory effect of RNS stimulation. Our case demonstrates feasibility, efficacy and safety of RNS in a pediatric patient with FIRES, with evidence to also suggest cognitive improvement.

Robotic Surgical Assistant Rehearsal: Combining 3-Dimensional-Printing Technology With Preoperative Stereotactic Planning for Placement of Stereoencephalography Electrodes.

BACKGROUND: The use of frameless stereotactic robotic technology has rapidly expanded since the Food and Drug Administration's approval of the Robotic Surgical Assistant (ROSA) in 2012. Although the use of the ROSA robot has greatly augmented stereotactic placement of intracerebral stereoelectroencephalography (sEEG) for the purposes of epileptogenic focus identification, the preoperative planning stages remain limited to computer software. OBJECTIVE: To describe the use of a 3-dimensionally (3D)-printed patient model in the preoperative planning of ROSA-assisted depth electrode placement for epilepsy monitoring in a pediatric patient. METHODS: An anatomically accurate 3D model was created and registered in a preoperative rehearsal session using the ROSA platform. After standard software-based electrode trajectory planning, sEEG electrodes were sequentially placed in the 3D model. RESULTS: Utilization of the 3D-printed model enabled workflow optimization and increased staff familiarity with the logistics of the robotic technology as it relates to depth electrode placement. The rehearsal maneuvers enabled optimization of patient head positioning as well as identification of physical conflicts between 2 electrodes. This permitted revision of trajectory planning in anticipation of the actual case, thereby improving patient safety and decreasing operative time. CONCLUSION: Use of a 3D-printed patient model enhanced presurgical positioning and trajectory planning in the placement of stereotactic sEEG electrodes for epilepsy monitoring in a pediatric patient. The ROSA rehearsal decreased operative time and increased efficiency of electrode placement.

Robotic Surgical Assistant (ROSA™) Rehearsal: Using 3-Dimensional Printing Technology to Facilitate the Introduction of Stereotactic Robotic Neurosurgical Equipment.

BACKGROUND: The use of frameless stereotactic robotic technology has rapidly expanded since the Food and Drug Administration's approval of the Robotic Surgical Assistant (ROSA™) in 2012. Although the safety and accuracy of the ROSA platform has been well-established, the introduction of complex robotic technology into an existing surgical practice poses technical and logistical challenges particular to a given institution. OBJECTIVES: To better facilitate the integration of new surgical equipment into the armamentarium of a thriving pediatric neurosurgery practice by describing the use of a three-dimensional (3D)-printed patient model with in situ 3D-printed tumor for presurgical positioning and trajectory optimization in the stereotactic biopsy of a pontine lesion in a pediatric patient. METHODS: A 3D model was created with an added silicone mock tumor at the anatomical position of the lesion. In a preoperative rehearsal session, the patient model was pinned and registered using the ROSA platform, and a mock biopsy was performed targeting the in Situ silicone tumor. RESULTS: Utilization of the 3D-printed model enabled workflow optimization and increased staff familiarity with the logistics of the robotic technology. Biopsy trajectory successfully reached intralesional tissue on the 3D-printed model. The rehearsal maneuvers decreased operative and intubation time for the patient and improved operative staff familiarity with the robotic setup. CONCLUSION: Use of a 3D-printed patient model enhanced presurgical positioning and trajectory planning in the biopsy of a difficult to reach pontine lesion in a pediatric patient. The ROSA rehearsal decreased operative time and increased staff familiarity with a new complex surgical equipment.

Intracranial Bypass of Posterior Inferior Cerebellar Artery Aneurysms: Indications, Technical Aspects, and Clinical Outcomes.

BACKGROUND: For some posterior inferior cerebellar artery (PICA) aneurysms, there is no constructive endovascular or direct surgical clipping option. Intracranial bypass is an alternative to a deconstructive technique. OBJECTIVE: To evaluate the clinical features, surgical techniques, and outcome of PICA aneurysms treated with bypass and obliteration of the diseased segment. METHODS: Retrospective review of PICA aneurysms treated via intracranial bypass was performed. Outcome measurements included postoperative stroke, cranial nerve deficits, gastrostomy/tracheostomy requirement, bypass patency, modified Rankin scale (mRS) at discharge, and mRS at 6 mo. RESULTS: Seven patients with PICA aneurysms treated with intracranial bypass were identified. Five had fusiform aneurysms (4 ruptured, 1 unruptured), 1 had a giant partially thrombosed saccular aneurysm (unruptured), and 1 had a dissecting traumatic aneurysm (ruptured). Two aneurysms were at the anteromedullary segment, 4 at the lateral medullary segment, and 1 at the tonsillomedullary segment. Three patients underwent PICA-to-PICA side to side anastomoses, 2 PICA-to-PICA reanastomosis, 1 vertebral artery-to-PICA bypass, and 1 occipital artery-PICA bypass. Six out of 7 aneurysms were obliterated surgically and 1 with additional endovascular occlusion after the bypass. All bypasses were patent intraoperatively; 2 were later demonstrated occluded without radiological signs or symptoms of stroke. No patients had new cranial nerve deficit postoperatively. With the exception of 1 death due to pulmonary emboli 3 mo postoperatively, all others remain at a mRS ≤ 2. CONCLUSION: Constructive bypass and aneurysm obliteration remains a viable alternative for treatment of PICA aneurysms not amenable to direct surgical clipping or to a vessel-preserving endovascular option.

The Recent Revolution in the Design and Manufacture of Cranial Implants: Modern Advancements and Future Directions.

Large format (i.e., >25 cm) cranioplasty is a challenging procedure not only from a cosmesis standpoint, but also in terms of ensuring that the patient's brain will be well-protected from direct trauma. Until recently, when a patient's own cranial flap was unavailable, these goals were unattainable. Recent advances in implant computer-aided design and 3-dimensional (3-D) printing are leveraging other advances in regenerative medicine. It is now possible to 3-D-print patient-specific implants from a variety of polymer, ceramic, or metal components. A skull template may be used to design the external shape of an implant that will become well integrated in the skull, while also providing beneficial distribution of mechanical force in the event of trauma. Furthermore, an internal pore geometry can be utilized to facilitate the seeding of banked allograft cells. Implants may be cultured in a bioreactor along with recombinant growth factors to produce implants coated with bone progenitor cells and extracellular matrix that appear to the body as a graft, albeit a tissue-engineered graft. The growth factors would be left behind in the bioreactor and the graft would resorb as new host bone invades the space and is remodeled into strong bone. As we describe in this review, such advancements will lead to optimal replacement of cranial defects that are both patient-specific and regenerative.

Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass.

Considerable debate and controversy surround the cause(s) of Alzheimer's disease (AD). To date, several theories have gained notoriety, however none is universally accepted. In this review, we provide evidence for the oxidative stress-induced AD cascade that posits aged mitochondria as the critical origin of neurodegeneration in AD.

Nanoparticle delivery of transition-metal chelators to the brain: Oxidative stress will never see it coming!

The pathological lesions typical of Alzheimer disease (AD) are sites of significant and abnormal metal accumulation. Metal chelation therapy, therefore, provides a very attractive therapeutic measure for the neuronal deterioration of AD, though its institution suffers fundamental deficiencies. Namely, chelating agents, which bind to and remove excess transition metals from the body, must penetrate the blood-brain barrier to instill any real effect on the oxidative damages caused by the presence of the metals in the brain. Despite many advances in chelation administration, however, this vital requirement remains therapeutically out of reach: the most effective chelators-i.e., those that have high affinity and specificity for transition metals like iron and copper-are bulky and hydrophilic, making it difficult to reach their physiological place of action. Moreover, small, lipophilic chelators, which can pass through the brain's defensive wall, essentially suffer from their over-effectiveness. That is, they induce toxicity on proliferating cells by removing transition metals from vital RNA enzymes. Fortunately, research has provided a loophole. Nanoparticles, tiny, artificial or natural organic polymers, are capable of transporting metal chelating agents across the blood-brain barrier regardless of their size and hydrophilicity. The compounds can thereby sufficiently ameliorate the oxidative toxicity of excess metals in an AD brain without inducing any such toxicity themselves. We here discuss the current status of nanoparticle delivery systems as they relate to AD chelation therapy and elaborate on their mechanism of action. An exciting future for AD treatment lies ahead.