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.

Telovelar surgical approach.

Surgical access to lesions in the fourth ventricle may be achieved utilizing transvermian or transtelovelar trajectories. We performed a search of the PubMed database for studies describing the microsurgical details and evaluating the clinical utility of the telovelar surgical approach. The telovelar approach has proven to be a safe, effective, and versatile alternative to the transvermian approach. The operative strategy utilizes midline suboccipital craniotomy without or with C1 laminectomy, followed by cerebellar hemispheric and tonsillar retraction, and wide durotomy. Access is generously provided to the fourth ventricle from calamus scriptorius to Sylvian aqueduct and foramen Luschkae bilaterally. Anatomic dissection studies evaluating and comparing the relative benefits of the operative exposure offered by these approaches have demonstrated improved access to the lateral recess gained by the telovelar trajectory and facilitated exposure of rostral reaches of the fourth ventricle by the vermian trajectory. In general, operative exposure may be significantly improved with tonsillar retraction or resection, bilateral telovelar opening, and performing C1 laminectomy in order to improve access to the rostral fourth ventricle, which may be variably combined depending on location of pathology. Cerebellar mutism, a high incidence of which occurs with vermian approaches, is not commonly observed with use of the telovelar trajectory, though injury to the dentate nuclei may precipitate this syndrome. Deficits incurred with the vermian approach may include cerebellar mutism, dysequilibrium, truncal ataxia, posterior fossa syndrome, cranial nucleopathies and nerve palsies, and vascular injury to the posterior inferior cerebellar artery. The telovelar surgical approach has proven a safe and useful alternative to the transvermian trajectory. A significantly lower incidence of cerebellar mutism and cerebellogenic deficits represents the principal advantage of the telovelar approach. Further studies are necessary in order to prospectively evaluate and compare extents of resection, morbidity, and mortality utilizing the telovelar versus vermian approaches for microsurgically resecting fourth ventricular tumors.

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.

Mechanisms Contributing to the Generation of Mayer Waves.

Mayer waves may synchronize overlapping propriobulbar interneuronal microcircuits constituting the respiratory rhythm and pattern generator, sympathetic oscillators, and cardiac vagal preganglionic neurons. Initially described by Sir Sigmund Mayer in the year 1876 in the arterial pressure waveform of anesthetized rabbits, authors have since extensively observed these oscillations in recordings of hemodynamic variables, including arterial pressure waveform, peripheral resistance, and blood flow. Authors would later reveal the presence of these oscillations in sympathetic neural efferent discharge and brainstem and spinal zones corresponding with sympathetic oscillators. Mayer wave central tendency proves highly consistent within, though the specific frequency band varies extensively across, species. Striking resemblance of the Mayer wave central tendency to the species-specific baroreflex resonant frequency has led the majority of investigators to comfortably presume, and generate computational models premised upon, a baroreflex origin of these oscillations. Empirical interrogation of this conjecture has generated variable results and derivative interpretations. Sinoaortic denervation and effector sympathectomy variably reduces or abolishes spectral power contained within the Mayer wave frequency band. Refractorines of Mayer wave generation to barodeafferentation lends credence to the hypothesis these waves are chiefly generated by brainstem propriobulbar and spinal cord propriospinal interneuronal microcircuit oscillators and likely modulated by the baroreflex. The presence of these waves in unitary discharge of medullary lateral tegmental field and rostral ventrolateral medullary neurons (contemporaneously exhibiting fast sympathetic rhythms [2-6 and 10 Hz bands]) in spectral variability in vagotomized pentobarbital-anesthetized and unanesthetized midcollicular (i.e., intercollicular) decerebrate cats supports genesis of Mayer waves by supraspinal sympathetic microcircuit oscillators. Persistence of these waves following high cervical transection in vagotomized unanesthetized midcollicular decerebrate cats would seem to suggest spinal sympathetic microcircuit oscillators generate these waves. The widespread presence of Mayer waves in brainstem sympathetic-related and non-sympathetic-related cells would seem to betray a general tendency of neurons to oscillate at this frequency. We have thus presented an extensive and, hopefully cohesive, discourse evaluating, and evolving the interpretive consideration of, evidence seeking to illumine our understanding of origins of, and insight into mechanisms contributing to, the genesis of Mayer waves. We have predicated our arguments and conjectures in the substance and matter of empirical data, though we have occasionally waxed philosophical beyond these traditional confines in suggesting interpretations exceeding these limits. We believe our synthesis and interpretation of the relevant literature will fruitfully inspire future studies from the perspective of a more intimate appreciation and conceptualization of network mechanisms generating oscillatory variability in neuronal and neural outputs. Our evaluation of Mayer waves informs a novel set of disciplines we term quantum neurophysics extendable to describing subatomic reality. Beyond informing our appreciation of mechanisms generating sympathetic oscillations, Mayer waves may constitute an intrinsic property of neurons extant throughout the cerebrum, brainstem, and spinal cord or reflect an emergent property of interactions between arteriogenic and neuronal oscillations.

ß-Adrenergic receptor structure and function: molecular insights guiding the development of novel therapeutic strategies to treat malignancy.

ß adrenergic receptors mediate effects via activation of G proteins, transactivation of membrane growth factor receptors, or ß adrenergic receptor-ß arrestin-facilitated scaffold-mediated signaling. Agonist occupancy of the ß adrenergic receptor induces desensitization by promoting ß adrenergic receptor kinase phosphorylation of the carboxyl terminal domain, facilitating binding of the amino terminal of the ß arrestin, which sterically inhibits interactions between ß adrenergic receptors and G proteins and induces clathrin-coated pit-mediated receptor endocytosis. Scaffold formation promoted by ß arrestin binding to the ß adrenergic receptor activates extracellular regulated kinase 1/2 in a manner which elicits cytosolic retention of, and prevents promotion of nuclear transcriptional activity by, mitogen-activated protein kinase. The ß adrenergic receptor kinase also interacts with a yet to be determined microsomal membrane protein via high-affinity electrostatic interactions. We evaluate ß adrenergic receptor structure, function, and downstream signaling and ß arrestin-mediated desensitization, receptor endocytosis, and scaffold-facilitated signal transduction in order to illumine therapeutic strategies designed to modulate these pathways. We trust these approaches may arm us with the capacity to selectively modulate signal transduction pathways regulating cellular proliferation, immunogenicity, angiogenesis, and invasive and metastatic potential implicated in cancer initiation, promotion, and progression.

Microsurgical techniques for achieving gross total resection of ependymomas of the fourth ventricle.

Ependymomas arising from the ventricular surface present a major challenge to achieving a complete operative extirpation when located in the fourth ventricle given the presence of significant adherence to the floor of the same. Overzealous dissection and removal of a tumor from this zone may precipitate potentially catastrophic neurological deficits attributable to cranial nucleopathies and cranial neuropathies. Consequently, the classic neurosurgical teaching has advised attempted gross total resection, leaving adherent residual in the floor of the fourth ventricle, in order to prevent the development of major cranial nucleopathies and cranial neuropathies. Following surgical tumoral extirpation, residual tumor is adjuvantly stereotactically irradiated. Authors have consequently developed novel neurophysiologically guided microsurgical techniques designed to remove adherent tumor from the fourth ventricular floor. These strategies have successfully and consistently facilitated gross total resection and improved clinical outcomes in patients harboring ependymomas of the fourth ventricle. We discuss and evaluate the innovation in microsurgical strategies developed to achieve complete operative extirpation of tumoral adherence to the floor of the fourth ventricle.

Mechanisms contributing to the genesis of hypoglossal preinspiratory discharge.

Preinspiratory discharge manifests in the neuronal recordings of the pre-Bötzinger complex, parafacial respiratory group, retrotrapezoid nucleus, and Kölliker-Fuse nucleus, as well as the efferent neural discharge of respiratory-related nerves innervating upper airway musculature. This neural component of triphasic eupnea contemporaneously contributes to the genesis of native and originate respiratory rhythmic activity, as well as the preinspiratory component of efferent neural respiratory discharges. In the course of our investigations evaluating hypoglossal discharge in response to asphyxia, we noted a curious pattern of neural respiratory recovery following postasphyxia resuscitation in hypoglossal, vagal, and phrenic neurograms in unanesthetized decerebrate rats. Specifically, we observed a gradual return of a pseudobiphasic eupnea characterized by initial transition bursts followed by robust eupneic bursts with dynamics inclusive of a gradually and progressively increasing duration of the hypoglossal eupneic bursts and duration and amplitude of the preinspiratory component of these bursts, as well as progressively lengthening expiratory interval between these bursts in the phrenic nerve discharge. This was followed by conversion to regular triphasic eupnea. We discuss our extrapolations based on these findings regarding eupneic respiratory central pattern generation and mechanisms contributing to the genesis of preinspiratory activity in hypoglossal discharge.

Posterior reversible encephalopathy syndrome in pediatric patients: pathophysiology, diagnosis, and management.

Posterior reversible encephalopathy syndrome (PRES) is well-described in adults, but has been reported with relative rarity in children, usually occurring in the context of chemotherapy for acute leukemia. Pathogenesis involves perturbed cerebral autoregulation leading to vasogenic edema predominantly affecting the parieto-occipital white matter, though involvement of the frontal and temporal lobes, as well as posterior fossa, is also described. We review the literature on the pathophysiology, diagnosis, and management of PRES in pediatric patients.

Neuroleukemiosis: Diagnosis and management.

An exceedingly rare manifestation of leukemia, termed neuroleukemiosis, involves peripheral nerve infiltration by leukemic cells. Patients with neuroleukemiosis typically present with a peripheral neuropathy and/or chloromatous masses. The diagnosis is supported by, and established with, electrophysiologic testing, imaging, histopathology, and immunophenotyping. We present the case of 21 year old male with multiply relapsed M4 type of acute myelogenous leukemia (AML) who presented with extremity pain and was subsequently found to have multiple cervical, thoracic, and lumbosacral nerve root masses. A diagnosis of neuroleukemiosis was established via CT-guided biopsy and immunophenotyping. The patient's neuroleukemiosis responded well to chemotherapy, donor lymphocyte infusions, and spinal irradiation. The literature is reviewed regarding this interesting and rare clinical condition.

Vein of Galen Malformations: The Texas Children's Hospital Experience in the Modern Endovascular Era.

BACKGROUND: Vein of Galen malformations (VOGM) comprise nearly a third of pediatric cerebrovascular anomalies, with potentially devastating neurological and systemic complications. Advances in endovascular therapies have dramatically improved outcomes compared to historical surgical treatments, and neurosurgeons are an essential component of the multidisciplinary critical care team. OBJECTIVE: To retrospectively review pediatric patients with VOGM treated at Texas Children's Hospital (TCH), a quaternary referral center, over 15 yr, and present lessons learned in treating children with modern endovascular techniques. METHODS: Charts from TCH were retrospectively reviewed for the past 15 yr. Patients with diagnosis including "Vein of Galen," "Vein of Galen malformation," "Vein of Galen aneurysmal malformation," or any abbreviations (ie, VOG, VOGM, VOGAM) were reviewed. Presentation, imaging, treatment specifics, and clinical outcomes were reported. RESULTS: There were 18 patients with VOGM managed at TCH from 2002 to 2018 with a total of 29 embolizations. Seventeen were performed with a single embolisate (NBCA or Onyx), and 12 with a combination. A dual lumen balloon catheter was used as an adjunct in 3 embolizations. Complications occurred in 5 embolizations (24%), including hemorrhage, embolisate migration, and femoral vessel occlusion. Surviving patients were followed for a mean of 38 mo, with 12 having normal or near-normal neurological development. CONCLUSION: VOGM can present with a myriad of neurological and systemic symptoms, potentially in extremis. Neurosurgical involvement in these cases is critical, as urgent treatment can be lifesaving. Patients may require multiple treatment sessions using a variety of endovascular tools and techniques.

Microsurgical technique for concurrent cervical corpectomy and ventral phrenic nerve access in the rat.

The phrenic nerve is useful to record as a motor output in studies investigating neural control of respiration. It may be accessed via dorsal or ventral microsurgical approaches. Since such studies frequently involve concurrent access to the spinal cord, the two approaches may be alternatively used, each with its own set of advantages and disadvantages. The dorsal approach permits easier exposure of the spinal cord via laminectomy, but, compared to the ventral approach, phrenic nerve access proves more challenging, and concurrent surgical access to the full complement of respiratory-related nerves (i.e., glossopharyngeal, vagus, recurrent laryngeal, hypoglossal nerves) and cervical sympathetic nerve in the neck is limited. The ventral approach achieves more direct access to the phrenic and respiratory-related nerves, but ventral access to the spinal cord via corpectomy requires much greater diligence and vigilance. Ventral spinal cord access, however, facilitates neuronal (e.g., phrenic motoneuron and interneuron) recordings in the ventral horn of the spinal cord, given greater proximity to the ventral compared to the dorsal surface of the spinal cord providing more leeway in recording pipette insertion point and trajectory. Additionally, ventral access to the cervical spinal cord proves useful across a broad range of studies investigating normal spinal cord physiology as well as spinal cord injury. We detail the microsurgical technique of concurrent ventral phrenic nerve dissection and cervical corpectomy in adult rats.

Outcomes after coverage of lenticulostriate vessels by flow diverters: a multicenter experience.

OBJECTIVE: With the increasing use of flow diversion as treatment for intracranial aneurysms, there is a concomitant increased vigilance in monitoring complications. The low porosity of flow diverters is concerning when the origins of vessels are covered, whether large circle of Willis branches or critical perforators. In this study, the authors report their experience with flow diverter coverage of the lenticulostriate vessels and evaluate their safety and outcomes. METHODS: The authors retrospectively reviewed 5 institutional databases of all flow diversion cases from August 2012 to June 2018. Information regarding patient presentation, aneurysm location, treatment, and outcomes were recorded. Patients who were treated with flow diverters placed in the proximal middle cerebral artery (MCA), proximal anterior cerebral artery, or distal internal carotid artery leading to coverage of the medial and lateral lenticulostriate vessels were included. Clinical outcomes according to the modified Rankin Scale were reviewed. Univariate and multivariate analyses were performed to establish risk factors for lenticulostriate infarct. RESULTS: Fifty-two patients were included in the analysis. Postprocedure cross-sectional images were available in 30 patients. Two patients experienced transient occlusion of the MCA during the procedure; one was asymptomatic, and the other had a clinical and radiographic ipsilateral internal capsule stroke. Five patients had transient symptoms without radiographic infarct in the lenticulostriate territory. Two patients experienced in-stent thrombosis, leading to clinical MCA infarcts (one in the ipsilateral caudate) after discontinuing antiplatelet therapy. Discontinuation of dual antiplatelet therapy prior to 6 months was the only variable that was significantly correlated with stroke outcome (p < 0.01, OR 0.3, 95% CI 0-0.43), and this significance persisted when controlled for other risk factors, including age, smoking status, and aneurysm location. CONCLUSIONS: The use and versatility of flow diversion is increasing, and safety data are continuing to accumulate. Here, the authors provide early data on the safety of covering lenticulostriate vessels with flow diverters. The authors concluded that the coverage of these perforators does not routinely lead to clinically significant ischemia when dual antiplatelet therapy is continued for 6 months. Further evaluation is needed in larger cohorts and with imaging follow-up as experience develops in using these devices in more distal circulation.

Synchronous Primary Central Nervous System and Pulmonary Lymphoma in a 7-Year-Old Female with Unspecified T-Cell Immunodeficiency.

Primary central nervous system lymphoma (PCNSL) is rare in children with immunocompromise as an important risk factor. A 7-year-old girl with unspecified T-cell immunodeficiency presented with left-sided weakness and was found to have a right-sided frontal lobe mass on imaging. The mass was resected; histopathology and molecular studies evidenced diffuse large B-cell lymphoma. Prior chest imaging had revealed left upper lobe mass, and repeat chest imaging revealed multiple pulmonary nodules, initially concerning for metastasis. Video-assisted thoracoscopic surgical wedge resection of the lung mass was performed; the molecular profile was distinct from the PCNSL, suggesting synchronous de novo lymphomagenesis of brain and pulmonary primaries.

Idiopathic thoracic spinal cord herniation.

Idiopathic spinal cord herniation represents an uncommon and unique diagnostic entity, most commonly affecting middle-aged individuals, with a nearly twofold female predilection. It most characteristically affects the mid-thoracic spine, with the herniation occurring ventrally or ventrolaterally. Clinical presentation is typically a slowly-progressive myelopathy, with Brown-Séquard syndrome occurring more frequently than spastic paraparesis. Diagnosis is made by imaging, with high-resolution or phase-contrast MR sequences and/or CT myelography. Treatment should be individualized, with options including conservative management with routine follow-up and surgical intervention. We review the literature on this interesting topic and report on, and present our technique for, operative reduction and repair of idiopathic spinal cord herniation in a 66 year-old woman.

Multimodal Treatment of Intracranial Aneurysms in Children: Clinical Case Series and Review of the Literature.

BACKGROUND: The management of intracranial aneurysms in the pediatric population presents unique challenges. Cases are rare and tend to be of higher complexity compared with aneurysms in adults. Outcomes in long-term follow-up are not well-characterized. Here we present illustrative case examples to demonstrate key concepts in managing these lesions in the context of the modern neurovascular era. METHODS: Four institutional databases of neurovascular procedures from 2012 to 2017 were reviewed. Patients <18 years old who underwent treatment for intracranial aneurysms were included. Patient characteristics, aneurysm details, treatment information, and angiographic and clinical outcomes were recorded. RESULTS: Ten cases of intracranial aneurysms in 9 children were identified. Management included direct clipping, trapping and bypass, endovascular coil embolization, endovascular vessel sacrifice, and flow diversion. CONCLUSIONS: The management of intracranial aneurysms in pediatric patients requires special considerations, from the diagnostic phase to treatment methods and follow-up regimen. These are ideally considered by a multidisciplinary team, with expertise from pediatric neurosurgeons, cerebrovascular neurosurgeons, and neurointerventionalists.

Overt and Subclinical Baroreflex Dysfunction After Bilateral Carotid Body Tumor Resection: Pathophysiology, Diagnosis, and Implications for Management.

BACKGROUND: Carotid body paragangliomas are rare, usually benign, tumors arising from glomus cells of the carotid body. Bilateral involvement is present in ∼5% of sporadic cases and up to one third of familial cases. In most patients undergoing bilateral resection of carotid body tumors, a condition known as baroreflex failure syndrome (BFS) develops after resection of the second tumor characterized by headache, anxiety, emotional lability, orthostatic lightheadedness, hypertension, and tachycardia. This condition is believed to result from damage to the carotid baroreceptor apparatus. Patients without overt cardiovascular abnormalities may have subclinical baroreceptor dysfunction evident only on specific testing, measuring heart rate and sympathetic nerve responses to baroloading (e.g., phenylephrine) and barounloading (e.g., Valsalva maneuver). Given the high incidence of BFS in patients undergoing bilateral resection of carotid body tumors, it is suggested that operation is limited to unilateral resection of the dominant/symptomatic lesion and nonsurgical intervention (i.e., embolization, radiotherapy) on the contralateral side. Alternatively, refinement of surgical technique to prevent injury to elements of the baroreceptor apparatus may prevent this complication of bilateral tumor resection. METHODS AND RESULTS: We present a case of a 16-year-old girl with bilateral jugular vagale and carotid body tumors who developed hypertension after surgical resection of her left jugular vagale tumor and worsening of hypertension concurrent with progression, requiring intensity-modulated radiation therapy and a resection for significant progression of her left jugular vagale tumor. Additional case studies and series of bilateral carotid body tumors and BFS were identified through a comprehensive literature search in the PubMed database. CONCLUSIONS: Our case shows the generalizability of BFS to patients with tumors involving the vagal baroafferent fibers.