Threshold for Tonic Motor Effects from Random Waveform in a Rat Experimental Model of Frontal Cortex Stimulation.

BACKGROUND: Brain stimulation is utilized to treat a variety of neurological disorders. Clinical brain stimulation technologies currently utilize charge-balanced pulse stimulation. The brain may better respond to other stimulation waveforms. This study was designed to evaluate the motor threshold of the brain to stimulation with various waveforms. METHODS: Three stimulation waveforms were utilized on rats with surgically implanted brain electrodes: pulses, square waves, and random waveform. The peak-to-peak stimulation voltage was increased in a step-wise manner until motor signs were elicited. RESULTS: The random waveform had the highest motor threshold with brain stimulation compared to the other waveforms. Random waveform stimulation reached maximum voltage without motor side effects while stimulating through both 1 and 8 electrodes. In contrast, the stimulation thresholds for motor side effects of the other two waveforms were on average less than half of the maximum voltage and lower for stimulation through 8 electrodes than stimulation through 1 electrode (p < 0.0005). CONCLUSION: The random waveform was better tolerated than the other waveforms and may allow for the use of higher stimulation voltage without side effects.

Iatrogenic pseudoaneurysm rupture of the anterior cerebral artery after placement of an external ventricular drain, treated with clip-wrapping: a case report and review of the literature.

External ventricular drains (EVDs) are often placed emergently for patients with hydrocephalus, which carries a risk of hemorrhage. Rarely, rupture of a pseudoaneurysm originating from an EVD placement precipitates such a hemorrhage. An EVD was placed in a patient with a ruptured left posterior communicating artery aneurysm who later underwent endovascular coil embolization. On post-bleed day 20, a distal right anterior cerebral artery pseudoaneurysm along the EVD tract ruptured, which was successfully treated via clip-wrapping. Although EVD-associated pseudoaneurysms are rare, they have a high propensity for rupture. Early treatment of these lesions should be considered to prevent neurologic deterioration.

ZEB1 expression is increased in IDH1-mutant lower-grade gliomas.

Transcription factors that induce epithelial-mesenchymal transition (EMT) promote invasion, chemoresistance and a stem-cell phenotype in epithelial tumors, but their roles in central nervous system tumors are not well-understood. We hypothesized these transcription factors have a functional impact in grades II-III gliomas. Using the National Cancer Institute (NCI) Repository for Molecular Brain Neoplasia Data (REMBRANDT) and the Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) data, we determined the impact of EMT-promoting transcription factors (EMT-TFs) on overall survival in grades II-III gliomas, compared their expression across common genetic subtypes and subsequently validated these findings in a set of 31 tumors using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. Increased expression of the gene coding for the transcriptional repressor Zinc Finger E box-binding Homeobox 1 (ZEB1) was associated with a significant increase in overall survival (OS) on Kaplan-Meier analysis. Genetic subtype analysis revealed that ZEB1 expression was relatively increased in IDH1/2-mutant gliomas, and IDH1/2-mutant gliomas expressed significantly lower levels of many ZEB1 transcriptional targets. Similarly, IDH1/2-mutant tumors expressed significantly higher levels of targets of microRNA 200C (MIR200C), a key regulator of ZEB1. In a validation study, ZEB1 mRNA was significantly increased in IDH1-mutant grades II-III gliomas, and ZEB1 protein expression was more pronounced in these tumors. Our findings demonstrate a novel relationship between IDH1/2 mutations and expression of ZEB1 and its transcriptional targets. Therapy targeting ZEB1-associated pathways may represent a novel therapeutic avenue for this class of tumors.

Subtemporal Transcollateral Sulcus Approach for Temporal Horn Tumors: 2-Dimensional Operative Video and Description of the Technique.

INTRODUCTION: Purely temporal intraventricular tumors are uncommon. Given their deep location, access to these brain tumors can be challenging in terms of preserving brain tissue. The subtemporal approach spares the lateral temporal cortex and is a less traumatic corridor to reach intraventricular temporal tumors. OBJECTIVE: To describe and assess the feasibility of the subtemporal transcollateral approach for the removal of a temporal horn tumor. METHODS: We describe the subtemporal transcollateral sulcus operative technique detailed step-by-step and depicted through both video and illustrations to surgically resect a left intraventricular temporal mass in a 44-year-old woman who presented with worsening memory deficits. The surgery was performed under general anesthesia and with the use of a microscope and neuronavigation. RESULTS: The patient did not suffer from any postoperative complications. Her vision was intact, and her memory deficit was unchanged. A brain MRI showed complete removal of the tumor. The pathological examination revealed a World Health Organization grade I meningioma. CONCLUSION: The subtemporal transsulcal approach seems to be an efficient and safe way to access intraventricular lesions within the temporal horn while avoiding any disruption of the optic radiations and temporal language areas.

Occipital Artery-Posterior Inferior Cerebellar Artery (PICA) Bypass for the Treatment of a Ruptured Fusiform Aneurysm of the Left PICA: 2-Dimensional Operative Video.

Posterior inferior cerebellar artery (PICA) aneurysms are usually complex to treat because of their deep location, frequent entanglement with the lower cranial nerves, the presence of perforating arteries to the brainstem, and their often dissecting or fusiform morphology.1 These aneurysms can require revascularization of the PICA.2 The length and size of the occipital artery (OA) make it an excellent donor.3,4 Video 1 shows the technical nuances of an OA-PICA bypass for the treatment of a ruptured fusiform aneurysm of the left PICA. The patient is a 34-year-old male presenting with an abrupt headache and confusion (Hunt and Hess grade III and World Federation Neurology Surgeons grade II). Computed tomography of the brain revealed hydrocephalus and subarachnoid hemorrhage (Fisher IV) and digital subtraction angiography revealed a fusiform aneurysm on the tonsillomedullary segment of the left PICA. Given the dissecting nature of this aneurysm and the fact that it was ruptured, we felt it would be safer to be prepared to perform revascularization and to secure the aneurysm using an open surgical approach.5 There were no complications associated with this procedure. The patient remained neurologically intact, and imaging showed good flow through the bypass and no evidence of stroke. OA-PICA bypass is a useful strategy to treat ruptured fusiform PICA aneurysms since it avoids sacrificing the PICA and the use of dual-antiplatelet therapy. This video is one of the few videos published on OA-PICA bypass.6,7 It explains the technical aspects, open and endovascular alternatives, and rationale for this procedure.

Pharmacy postgraduate education transformation: pharmacist preferences for microcredentials.

OBJECTIVES: To explore micro-credentialing for postgraduate study in pharmacy practice. METHODS: An online survey of practicing or intern pharmacists in New Zealand was designed to identify learner preferences for education, determine interest and demand for microcredentials and elicit preferred 'willingness-to-pay' thresholds. KEY FINDINGS: A total of 430 responses were obtained. A stacked microcredential programme was preferred by 88% over traditional courses. Interest, skill development and career development were the top-ranked aspects. Participants favoured the lowest cost option ($300 NZD per microcredential). CONCLUSIONS: Pharmacists in New Zealand are supportive of microcredentials for postgraduate study as an alternative to traditional programmes.

Race\ethnicity and outcome after traumatic brain injury at a single, diverse center.

BACKGROUND: Many factors may predict mortality and disability after traumatic brain injury (TBI), including age and injury severity. However, the role of race\ethnicity has typically been studied tangentially or in homogeneous settings. We investigated whether race\ethnicity was associated with medical outcomes at a single, diverse center. METHODS: We retrospectively identified patients with TBI older than 17 years with blunt injuries admitted to a Level I trauma center from 2001 to 2004. Glasgow Outcome Scale (GOS) was used to determine outcome at discharge. We performed multivariable logistic regression on two measures of outcome by dichotomizing Glasgow Outcome Scale scores. RESULTS: We identified 357 patients with TBI from five categories: whites (46.2%), Asians (19.9%), Hispanics (17.9%), blacks (10.9%), and other\unknown (5.0%). Without adjusting for other factors, Asians experienced higher mortality (odds ratio [OR] = 2.25, p = 0.01) compared with whites but not degree of disability. After adjusting for age and Injury Severity Score, a weaker trend remained for higher mortality in Asians (OR = 1.38, p = 0.35), and after excluding cases of assault, the finding was again significant (OR = 2.00, p = 0.04). We also confirmed the recently reported OR of higher mortality among blacks (OR = 1.30). Hispanics seemed to do slightly better at discharge. CONCLUSIONS: The question of whether and how race plays a role in TBI is controversial. At a single, diverse center, we found that mortality is associated with race, age, and Injury Severity Score. Future clinical studies will benefit from detailed genotypic and phenotypic data and should balance larger sample sizes with ethnic diversity.

Contralateral Interhemispheric Transfalcine Approach for Intra-Axial Medial Occipital Lesion: 2-Dimensional Operative Video.

Safe access to intra-axial mesial cortical lesions is challenging. When approached through standard transcortical approaches, normal white matter tracts such as the superior longitudinal fasciculus, corona radiata, and optic radiations may be violated en route to the lesion. Conversely, use of ipsilateral interhemispheric approaches necessitates retraction and manipulation of edematous and friable perilesional tissue. The contralateral interhemispheric transfalcine (CIHTF) approach may circumvent these challenges. The CIHTF approach uses a gravity-created window between the ipsilateral hemisphere and the falx and allows direct access contralaterally by opening the falx. We demonstrate the CIHTF approach for an intra-axial, medial occipital/precuneus lesion in a 69-yr-old man presenting with left homonymous hemianopia. MRI revealed a heterogeneously enhancing intra-axial lesion in the right mesial occipital lobe. After the patient gave voluntary informed consent, a CIHTF approach was planned, with the patient positioned laterally, right side up (IRB approval was unnecessary). A lumber drain facilitated gravity autoretraction of the ipsilateral lobe. Within the created trajectory, the falx was opened with use of a nerve hook attached to monopolar electrocautery. The contralateral lesion was visualized and removed piecemeal with the assistance of fluorescence imaging. Postoperative MRI showed complete removal. The patient reported a significant vision improvement. The diagnosis was metastatic adenocarcinoma from the lung; subsequent radiosurgery was recommended. MRI at the 8-mo follow-up revealed no recurrence of the lesion. The CIHTF approach is feasible for a mesial intra-axial lesion because it offers gravity autoretraction, a large working angle, and avoidance of parenchymal swelling. Used with permission from Barrow Neurological Institute.

Quantitative Endoscopic Comparison of Contralateral Interhemispheric Transprecuneus and Supracerebellar Transtentorial Transcollateral Sulcus Approaches to the Atrium.

OBJECTIVE: The contralateral interhemispheric transprecuneus approach (CITP) and the supracerebellar transtentorial transcollateral sulcus approach (STTC) are 2 novel approaches to access the atrium of the lateral ventricle. We quantitatively compared the 2 approaches. METHODS: Both approaches were performed in 6 sides of fixed and color-injected cadaver heads. We predefined the 6 targets in the atrium for measurement and standardization of the approaches. Using a navigation system, we quantitatively measured the working distance, cortical transgression, angle of attack, area of exposure, and surgical freedom. RESULTS: The distances from the craniotomy edge to the posterior pole of the choroid plexus of the CITP (mean ± standard deviation, 67 ± 5.3 mm) and STTC (mean, 57 ± 4.0 mm) differed significantly (P < 0.01). Cortical transgression with the CITP (mean, 27 ± 2.8 mm) was significantly greater than that with the STTC (mean, 21 ± 6.7 mm; P = 0.03). The CITP showed a significantly wider rostrocaudal angle of attack than that with the STTC (P = 0.01). The STTC showed a significantly wider mediolateral angle (P < 0.01). No significant difference was found for surgical freedom of any target except for point E, for which the CITP was larger. The exposure area did not differ significantly between the 2 approaches (P = 0.07). CONCLUSIONS: Both approaches were feasible for accessing the atrium. The STTC provided a shorter working distance and wider mediolateral angle, CITP provided a wider rostrocaudal angle of attack and better exposure and maneuverability to the anterior and superior atrium. In contrast, the STTC was more favorable for the inferior and posterior regions.

Minimally invasive approaches to aneurysms of the anterior circulation: selection criteria and clinical outcomes.

Over the last few decades, cerebrovascular surgery has gravitated towards a minimally invasive philosophy without compromising the foundational principles of patient safety and surgical efficacy. Enhanced radiosurveillance modalities and increased average life expectancy have resulted in an increased reported incidence of intracranial aneurysms. Although endovascular therapies have gained popularity in the recent years, microsurgical clipping continues to be of value in the management of these aneurysms owing to its superior occlusion rates, applicability to complex aneurysms and reduced retreatment rates. The concept of keyhole transcranial procedures has advanced the field significantly leading to decreased postoperative neurological morbidity and quicker recovery. The main keyhole neurosurgical approaches include the supraorbital craniotomy (SOC), lateral supraorbital craniotomy (LSOC), mini-pterional craniotomy (MPTC), mini-orbitozygomatic craniotomy and the mini anterior interhemispheric approach (MAIA). As these minimally invasive approaches can have an inherent limitation of a narrow viewing angle and low regional illumination, the use of endoscopic assistance in such procedures is being popularized. Neuroendoscopy can aid in the visualization of hidden neurovascular structures and inspection of the parent arterial segment without undue retraction of the lesion. This review focuses on the historical progression of the surgical management of intracranial aneurysms, the technical details of various minimally invasive approaches, patient selection and clinical outcomes of the anterior circulation aneurysms and useful tenets to avoid complications during these procedures. Meticulous preoperative planning to understand the patient's vascular anatomy, the orientation and relationship of the aneurysm to adjacent structures, use of neuronavigation guidance and endoscopic assistance if needed can lead to an optimal surgical outcome while minimizing neurological morbidity and mortality.

Extraventricular neurocytomas.

Extraventricular neurocytomas (EVNs) are rare neoplasms with many similar morphologic features compared with central neurocytomas. EVNs have been reported in a variety of locations and mainly occur within the cerebral hemispheres. These lesions display wide variability in morphologic features, cellularity, and proliferation rates. In addition, given their aggressive biological nature and tendencies to affect eloquent areas, EVNs are associated with a poorer prognosis. The epidemiology of these rare tumors is not definitively known, and effective treatment strategies have not been developed. This article reviews these tumors, including their epidemiology, clinical presentation, locations, radiological findings, treatment options, and prognosis.

Association of cerebellopontine angle atypical teratoid/rhabdoid tumors with acute facial nerve palsy in infants.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS tumors found almost exclusively in childhood. Although essentially universally fatal when incompletely resected, prompt diagnosis followed by early chemoradiation can improve outcomes. An AT/RT can occur extraaxially at the cerebellopontine angle (CPA) and cause acute cranial nerve deficits as the presenting sign. The authors report a series of 3 children who presented with isolated acute facial nerve palsies and in whom subsequent diagnosis of a CPA AT/RT was made. The authors propose that in young children whose presenting symptom is an acute facial nerve palsy with a CPA tumor, AT/RT should be highly suspected.