Retraction: Ghali MGZ, et al. Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons. Journal of Integrative Neuroscience. 2020; 19: 521-560.

No abstract present.

Multiple and mirror intracranial aneurysms: study of prevalence and associated risk factors.

OBJECTIVE: Multiple intracranial aneurysms (MIA) account for 30% of all intracranial aneurysms, while mirror aneurysms, a subgroup of MIA, are present in 5% of all patients with cerebral aneurysms. We investigated the risk factors associated with the presence of multiple and mirror intracranial aneurysms. METHODS: 1404 patients, 314 males (22.4%) and 1090 female (77.6%) were enrolled for this study. Diagnosis was performed with a digital subtraction angiography (DSA). Multiplicity was defined as the presence of two or more aneurysms and mirror aneurysms as one pair of aneurysms involving bilateral corresponding arteries. Patients were followed-up from September 2009 till August 2018. Individuals' characteristics such as sex, age, smoking, hypertension and use of contraceptives were evaluated. RESULTS: Five hundred and twelve patients (36.4%) were diagnosed with MIA, approximately 4%/year. We observed 203 pairs of mirror aneurysms, accounting for 406 aneurysms (13% of the population). There was an increased frequency of females with multiple (p < 0.001, OR = 1.883, 95% CI = 1.386-2.560) and mirror aneurysms (p < 0.001, OR = 2.828, 95% CI = 1.725-4.636). Smoking was associated with multiplicity (p< 0.001, OR = 1.458, 95% CI = 1.160-1.833), as well as advanced age (p < 0.001, OR = 1.938, 95% CI = 1.438-2.611), but there was no significant relation with presence of mirror aneurysms. We observed higher frequency of baby aneurysms (<3mm) in the group of patients with MIA, while giant aneurysms (>25 mm) were most found in patients with only one aneurysm (p < 0.001). No differences between patients who used contraceptives against patients who did not use were found (p = 0.600). CONCLUSIONS: Gender and smoking, known risk factors to the development of a single intracranial aneurysm, are proportionally increased in patients with MIA. Hypertension and oral contraceptives were not associated with multiplicity.

Surgical selection and outcomes among elderly patients with brain arteriovenous malformations.

OBJECTIVE: Studies of resection of brain arteriovenous malformations (AVMs) in the elderly population are scarce. This study examined factors influencing patient selection and surgical outcome among elderly patients. METHODS: Patients 65 years of age and older who underwent resection of an unruptured or ruptured brain AVM treated by two surgeons at two centers were identified. Patient demographic characteristics, AVM characteristics, clinical presentation, and outcomes measured using the modified Rankin Scale (mRS) were analyzed. For subgroup analyses, patients were dichotomized into two age groups (group 1, 65-69 years old; group 2, ≥ 70 years old). RESULTS: Overall, 112 patients were included in this study (group 1, n = 61; group 2, n = 51). Most of the patients presented with hemorrhage (71%), a small nidus (< 3 cm, 79%), and a low Spetzler-Martin (SM) grade (grade I or II, 63%) and were favorable surgical candidates according to the supplemented SM grade (supplemented SM grade < 7, 79%). A smaller AVM nidus was statistically significantly more likely to be present in patients with infratentorial AVMs (p = 0.006) and with a compact AVM nidus structure (p = 0.02). A larger AVM nidus was more likely to be treated with preoperative embolization (p < 0.001). Overall outcome was favorable (mRS scores 0-3) in 71% of the patients and was statistically independent from age group or AVM grading. Patients with ruptured AVMs at presentation had significantly better preoperative mRS scores (p < 0.001) and more favorable mRS scores at the last follow-up (p = 0.04) than patients with unruptured AVMs. CONCLUSIONS: Outcomes were favorable after AVM resection in both groups of patients. Elderly patients with brain AVMs treated microsurgically were notable for small nidus size, AVM rupture, and low SM grades. Microsurgical resection is an important treatment modality for elderly patients with AVMs, and supplemented SM grading is a useful tool for the selection of patients who are most likely to achieve good neurological outcomes after resection. ABBREVIATIONS: AVM = arteriovenous malformation; BNI = Barrow Neurological Institute; LY = Lawton-Young; mRS = modified Rankin Scale; SM = Spetzler-Martin; supp-SM = supplemented SM; UCSF = University of California, San Francisco.

Mechanisms underlying the generation of autonomorespiratory coupling amongst the respiratory central pattern generator, sympathetic oscillators, and cardiovagal premotoneurons.

The respiratory rhythm and pattern and sympathetic and parasympathetic outflows are generated by distinct, though overlapping, propriobulbar arrays of neuronal microcircuit oscillators constituting networks utilizing mutual excitatory and inhibitory neuronal interactions, residing principally within the metencephalon and myelencephalon, and modulated by synaptic influences from the cerebrum, thalamus, hypothalamus, cerebellum, and mesencephalon and ascending influences deriving from peripheral stimuli relayed by cranial nerve afferent axons. Though the respiratory and cardiovascular regulatory effector mechanisms utilize distinct generators, there exists significant overlap and interconnectivity amongst and between these oscillators and pathways, evidenced reciprocally by breathing modulation of sympathetic oscillations and sympathetic modulation of neural breathing. These coupling mechanisms are well-demonstrated coordinately in sympathetic- and respiratory-related central neuronal and efferent neurogram recordings and quantified by the findings of cross-correlation, spectra, and coherence analyses, combined with empirical interventions including lesioning and pharmacological agonist and antagonist microinjection studies, baroloading, barounloading, and hypoxic and/or hypercapnic peripheral and/or central chemoreceptor stimulation. Sympathetic and parasympathetic central neuronal and efferent neural discharge recordings evidence classic fast rhythms produced by propriobulbar neuronal networks located within the medullary division of the lateral tegmental field, coherent with cardiac sympathetic nerve discharge. These neural efferent nerve discharges coordinately evidence slow synchronous oscillations, constituted by Traube Hering (i.e., high frequency), Mayer wave (i.e., medium or low frequency), and vasogenic autorhythmicity (i.e., very low frequency) wave spectral bands. These oscillations contribute to coupling neural breathing, sympathetic oscillations, and parasympathetic cardiovagal premotoneuronal activity. The mechanisms underlying the origins of and coupling amongst, these waves remains to be unresolved.

Impact of removed tumor volume and location on patient outcome in glioblastoma.

Glioblastoma is an aggressive primary brain tumor with devastatingly poor prognosis. Multiple studies have shown the benefit of wider extent of resection (EOR) on patient overall survival (OS) and worsened survival with larger preoperative tumor volumes. However, the concomitant impact of postoperative tumor volume and eloquent location on OS has yet to be fully evaluated. We performed a retrospective chart review of adult patients treated for glioblastoma from January 2006 through December 2011. Adherence to standardized postoperative chemoradiation protocols was used as an inclusion criterion. Detailed volumetric and location analysis was performed on immediate preoperative and immediate postoperative magnetic resonance imaging. Cox proportional hazard modeling approach was employed to explore the modifying effects of EOR and eloquent location after adjusting for various confounders and associated characteristics, such as preoperative tumor volume and demographics. Of the 471 screened patients, 141 were excluded because they did not meet all inclusion criteria. The mean (±SD) age of the remaining 330 patients (60.6% male) was 58.9 ± 12.9 years; the mean preoperative and postoperative Karnofsky performance scores (KPSs) were 76.2 ± 10.3 and 80.0 ± 16.6, respectively. Preoperative tumor volume averaged 33.2 ± 29.0 ml, postoperative residual was 4.0 ± 8.1 ml, and average EOR was 88.6 ± 17.6%. The observed average follow-up was 17.6 ± 15.7 months, and mean OS was 16.7 ± 14.4 months. Survival analysis showed significantly shorter survival for patients with lesions in periventricular (16.8 ± 1.7 vs. 21.5 ± 1.4 mo, p = 0.03), deep nuclei/basal ganglia (11.6 ± 1.7 vs. 20.6 ± 1.2, p = 0.002), and multifocal (12.0 ± 1.4 vs. 21.3 ± 1.3 months, p = 0.0001) locations, but no significant influence on survival was seen for eloquent cortex sites (p = 0.14, range 0.07-0.9 for all individual locations). OS significantly improved with EOR in univariate analysis, averaging 22.3, 19.7, and 13.2 months for >90, 80-90, and 70-80% resection, respectively. Survival was 22.8, 19.0, and 12.7 months for 0, 0-5, and 5-10 ml postoperative residual, respectively. A hazard model showed that larger preoperative tumor volume [hazard ratio (HR) 1.05, 95% CI 1.02-1.07], greater age (HR 1.02, 95% CI 1.01-1.03), multifocality (HR 1.44, 95% CI 1.01-2.04), and deep nuclei/basal ganglia (HR 2.05, CI 1.27-3.3) were the most predictive of poor survival after adjusting for KPS and tumor location. There was a negligible but significant interaction between EOR and preoperative tumor volume (HR 0.9995, 95% CI 0.9993-0.9998), but EOR alone did not correlate with OS after adjusting for other factors. The interaction between EOR and preoperative tumor volume represented tumor volume removed during surgery. In conclusion, EOR alone was not an important predictor of outcome during GBM treatment once preoperative tumor volume, age, and deep nuclei/basal ganglia location were factored. Instead, the interaction between EOR and preoperative volume, representing reduced disease burden, was an important predictor of reducing OS. Removal of tumor from eloquent cortex did not impact postoperative KPS. These results suggest aggressive surgical treatment to reduce postoperative residual while maintaining postoperative KPS may aid patient survival outcomes for a given tumor size and location.

Motor cortex arteriovenous malformation.

Supratentorial arteriovenous malformations in eloquent territories can be difficult to resect. This video presents the treatment of a patient with a symptomatic 3-cm arteriovenous malformation in the left motor strip. At the authors' institution, per the surgeon's discretion, preoperative angiography is performed to evaluate the need for preoperative embolization. Multimodality treatment reduced the microsurgical risk by allowing early occlusion of a draining vein, by decreasing overall intraoperative hemorrhage, and by allowing minimal pial dissection in the deep aspect of the arteriovenous malformation that abutted the corticospinal tract. The choice of embolysate was an additional nuance of the embolization. The video can be found here: https://youtu.be/HWZ0RjgPEXg .

The anterior interhemispheric approach to a third ventricular cavernous malformation.

The anterior interhemispheric approach is a workhorse for treatment of lesions in the third ventricle. In this case, we demonstrate the utility of this approach for resecting a complex third ventricular cavernous malformation. We discuss patient positioning, optimal location of the craniotomy, and surgical resection techniques for safe removal of these lesions. We also demonstrate the importance of gravity retraction using the falx to prevent injury to the dominant frontal lobe. The video can be found here: https://youtu.be/38woc28er7M .

The supracerebellar infratentorial approach to the dorsal midbrain.

The supracerebellar infratentorial approach provides access to the dorsal midbrain, pineal region, and tentorial incisura. This approach can be used with the patient in a sitting, prone, park-bench, or supine position. For a patient with a supple neck and favorable anatomy, we prefer the supine position. The ipsilateral shoulder is elevated, the head turned to the contralateral side, the chin is tucked, and the neck extended toward the floor to open the craniocervical angle for added working room. Care must be taken to place the craniotomy laterally to make use of the ascending angle of the tentorium for ease of access to deep-seated lesions. The video can be found here: https://youtu.be/BZh6ljmE23k .

Endoscope-assisted supracerebellar transtentorial approach to the posterior medial temporal lobe for resection of cavernous malformation.

The mesial temporal lobe can be approached via a pterional or orbitozygomatic craniotomy, the subtemporal approach, or transcortically. Alternatively, the entire mesial temporal lobe can be accessed using a lateral supracerebellar transtentorial (SCTT) approach. Here we describe the technical nuances of patient positioning, craniotomy, supracerebellar dissection, and tentorial disconnection to traverse the tentorial incisura to arrive at the posterior mesial temporal lobe for a cavernous malformation. The SCTT approach is especially useful for lesions in the dominant temporal lobe where an anterolateral approach may endanger language centers or the vein of Labbé. The video can be found here: https://youtu.be/D8mIR5yeiVw .

Prospective evaluation of the utility of intraoperative confocal laser endomicroscopy in patients with brain neoplasms using fluorescein sodium: experience with 74 cases.

OBJECTIVE: This study evaluated the utility, specificity, and sensitivity of intraoperative confocal laser endomicroscopy (CLE) to provide diagnostic information during resection of human brain tumors. METHODS: CLE imaging was used in the resection of intracranial neoplasms in 74 consecutive patients (31 male; mean age 47.5 years; sequential 10-month study period). Intraoperative in vivo and ex vivo CLE was performed after intravenous injection of fluorescein sodium (FNa). Tissue samples from CLE imaging-matched areas were acquired for comparison with routine histological analysis (frozen and permanent sections). CLE images were classified as diagnostic or nondiagnostic. The specificities and sensitivities of CLE and frozen sections for gliomas and meningiomas were calculated using permanent histological sections as the standard. RESULTS: CLE images were obtained for each patient. The mean duration of intraoperative CLE system use was 15.7 minutes (range 3-73 minutes). A total of 20,734 CLE images were correlated with 267 biopsy specimens (mean number of images/biopsy location, in vivo 84, ex vivo 70). CLE images were diagnostic for 45.98% in vivo and 52.97% ex vivo specimens. After initiation of CLE, an average of 14 in vivo images and 7 ex vivo images were acquired before identification of a first diagnostic image. CLE specificity and sensitivity were, respectively, 94% and 91% for gliomas and 93% and 97% for meningiomas. CONCLUSIONS: CLE with FNa provided intraoperative histological information during brain tumor removal. Specificities and sensitivities of CLE for gliomas and meningiomas were comparable to those for frozen sections. These data suggest that CLE could allow the interactive identification of tumor areas, substantially improving intraoperative decisions during the resection of brain tumors.

Developmental venous anomaly, capillary telangiectasia, cavernous malformation, and arteriovenous malformation: spectrum of a common pathological entity?

Vascular malformations of the central nervous system are thought to originate from abnormal developmental processes during embryogenesis. Reports have cited the dynamic nature of these lesions and their "maturation" into other types of malformations. Herein we report on three patients with vascular malformations who exhibited dynamic alterations with stepwise progression of their lesions. These cases lend support to the hypothesis that these malformations may constitute the spectrum of a single disease caused by alterations in a common developmental program and that accumulating injury (e.g., by radiation) may allow one malformation type to mature into another. This concept warrants further investigation.

Surgical management of skull base tumors.

AIM: To present a review of the contemporary surgical management of skull base tumors. BACKGROUND: Over the last two decades, the treatment of skull base tumors has evolved from observation, to partial resection combined with other therapy modalities, to gross total resection and no adjuvant treatment with good surgical results and excellent clinical outcomes. MATERIALS AND METHODS: The literature review of current surgical strategies and management of skull base tumors was performed and complemented with the experience of Barrow Neurological Institute. RESULTS: Skull base tumors include meningiomas, pituitary tumors, sellar/parasellar tumors, vestibular and trigeminal schwannomas, esthesioneuroblastomas, chordomas, chondrosarcomas, and metastases. Surgical approaches include the modified orbitozygomatic, pterional, middle fossa, retrosigmoid, far lateral craniotomy, midline suboccipital craniotomy, and a combination of these approaches. The selection of an appropriate surgical approach depends on the characteristics of the patient and the tumor, as well as the experience of the neurosurgeon. CONCLUSION: Modern microsurgical techniques, diagnostic imaging, intraoperative neuronavigation, and endoscopic technology have remarkably changed the concept of skull base surgery. These refinements have extended the boundaries of tumor resection with minimal morbidity.

Normal perfusion pressure breakthrough theory: a reappraisal after 35 years.

The intrinsic ability of the brain to maintain constant cerebral blood flow (CBF) is known as cerebral pressure autoregulation. This ability protects the brain against cerebral ischemia and hyperemia within a certain range of blood pressures. The normal perfusion pressure breakthrough (NPPB) theory described by Spetzler in 1978 was adopted to explain the edema and hemorrhage that sometimes occur after resection of brain arteriovenous malformations (AVMs). The underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial. Over the last three decades, advances in neuroimaging, CBF, and cerebral perfusion pressure (CPP) measurement have both favored and contradicted the NBBP theory. At the same time, other theories have been proposed, including the occlusive hyperemia theory. We believe that both theories are related and complementary and that they both explain changes in hemodynamics after AVM resection. The purpose of this work is to review the current status of the NBBP theory 35 years after its original description.

Update on transient cardiac standstill in cerebrovascular surgery.

Transient cardiac standstill is a complementary procedure used with microsurgery to treat patients with particularly complex aneurysms, such as large or giant cerebral aneurysms. These procedures allow the aneurysms to be decompressed while maintaining a bloodless field and increased surgical exposure. Deep hypothermia combined with circulatory arrest provides cerebroprotection with optimal surgical conditions. However, its disadvantage is the relatively high risk of the procedure, which requires extensive expertise and infrastructure. Thus, its use is typically limited to patients with complex posterior circulation aneurysms. Adenosine-induced transient asystole is an easily applied technique in a variety of clinical situations. Its use requires minimal advanced preparation and no complex logistical coordination with other subspecialties. However, patient-specific dose-response relationships must be determined by exposure, so the relationship may not be known in an emergent situation. Persistent hypotension is a potentially major complication. Rapid ventricular pacing (RVP) has recently been reintroduced into cerebrovascular surgery. It is more predictable than adenosine in response time and, thus, can be used during unanticipated complications, such as aneurysmal rupture. It also induces a shorter period of hypotension compared with adenosine. However, RVP is more invasive and more complex from an anesthesia standpoint. Vascular neurosurgeons should be familiar with these techniques and know their applications and limitations.

Microsurgical management of a large ICA bifurcation aneurysm.

A 70-year-old man with progressive visual disturbances, left superior quadrantanopsia, and right-sided papilledema underwent imaging that demonstrated a right internal carotid artery (ICA) terminus aneurysm with third-ventricle mass effect and ipsilateral optic nerve and chiasm compression. We performed a right modified orbitozygomatic craniotomy, with proximal control and dissection of the aneurysm and small perforator arteries. Temporary ICA and anterior cerebral artery (ACA) clips allowed placement of a large curved permanent clip, reconstructing the ICA bifurcation and maintaining adequate patency of the ACA and middle cerebral artery. Complete aneurysm obliteration was confirmed by intraoperative indocyanine green angiography and postoperative CT angiography. The video can be found here: http://youtu.be/5WEEgmA-g2A.

Surgical clipping of a ruptured posterior inferior cerebellar artery aneurysm.

Posterior circulation aneurysms are commonly treated with endovascular techniques. In select cases, microsurgery remains an essential tool for treating these lesions. We present a case of a ruptured posterior inferior cerebellar artery (PICA) aneurysm approached via a craniotomy. Given the labyrinth of neurovascular bundles present in the posterior fossa, surgical exposure of PICA aneurysms can be challenging. This video demonstrates the steps of the craniotomy, subarachnoid dissection, mobilization of the vertebral artery and lower cranial nerves, and clipping of the aneurysm. The video can be found here: http://youtu.be/fQSxQj7oL0U .

Surgical clipping of a large left middle cerebral artery aneurysm.

Middle cerebral artery aneurysms, especially those with complex morphology, are considered excellent aneurysms for surgical clipping, given the challenges that exist with current endovascular techniques. We present a case of a large, complex, left middle cerebral artery aneurysm treated with microsurgical clipping. This video highlights critical steps in obtaining proximal and distal control as well as subarachnoid dissection necessary to prepare the aneurysm for final clipping. The video can be found here: http://youtu.be/RlKH2Km9z5Y .

Microsurgical clipping of an unruptured basilar apex aneurysm.

Unruptured posterior circulation aneurysms pose a treatment challenge. Although data supports the use of endovascular technique for select ruptured cases, in unruptured cases, there may be clinical equipoise. Furthermore, wide-necked basilar apex aneurysms commonly require the use of stents and placement of patients on dual therapy. We present a case of a healthy 50-year-old woman with an incidental basilar tip aneurysm treated via an orbitozygomatic craniotomy. This video highlights the steps of dynamic retraction, which is retraction without placement of permanent rigid retraction system, and the added maneuverability afforded by the use of the mouthpiece on the microscope. The video can be found here: http://youtu.be/jVfC6CCXdZY .

Repair of intraoperative aneurysm neck tear utilizing the cotton-clipping technique.

Intraoperative rupture of an intracranial aneurysm is a potentially devastating but controllable complication. The authors have successfully used the previously described cotton-clip technique to repair tears at the necks of aneurysms. (1-4) A tear on the neck of the aneurysm is covered with a piece of cotton and held in place with a suction device. The cotton is then clipped onto the tear with an aneurysm clip, using the cotton as a bolster. This simple, effective method has been useful in repairing a partial avulsion of the neck of an aneurysm. (1 , 3) The video can be found here: http://youtu.be/nT86RYVQWpc .

Microsurgical resection of cervical spinal arteriovenous malformation: the pial resection technique.

We present the case of a 26-year-old female patient who had two episodes of sudden, left, upper and lower extremity paresthesias and weakness, which resolved completely after 5 months. After recovery, she presented for evaluation. Imaging demonstrated a C3-C6 intra- and extra-axial arteriovenous malformation (AVM) with spinal cord compression and edema. A spinal angiogram showed arterial feeders arising from both vertebral arteries and from the right ascending pharyngeal artery. The AVM had been partially embolized after her first bleeding episode. She underwent C3-C6 laminoplasty and microsurgical resection of the AVM. After locating the main arterial feeders and draining veins, the malformation was resected using the pial resection technique. A postoperative spinal angiogram demonstrated gross total resection. Video used with permission from Barrow Neurological Institute. The video can be found here: http://youtu.be/JbbIwCTUsuI.