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.

Structure and function of the perivascular fluid compartment and vertebral venous plexus: Illumining a novel theory on mechanisms underlying the pathogenesis of Alzheimer's, cerebral small vessel, and neurodegenerative diseases.

Blood dynamically and richly supplies the cerebral tissue via microvessels invested in pia matter perforating the cerebral substance. Arteries penetrating the cerebral substance derive an investment from one or two successive layers of pia mater, luminally apposed to the pial-glial basal lamina of the microvasculature and abluminally apposed to a series of aquaporin IV-studded astrocytic end feet constituting the soi-disant glia limitans. The full investment of successive layers forms the variably continuous walls of the periarteriolar, pericapillary, and perivenular divisions of the perivascular fluid compartment. The pia matter disappears at the distal periarteriolar division of the perivascular fluid compartment. Plasma from arteriolar blood sequentially transudates into the periarteriolar division of the perivascular fluid compartment and subarachnoid cisterns in precession to trickling into the neural interstitium. Fluid from the neural interstitium successively propagates into the venules through the subarachnoid cisterns and perivenular division of the perivascular fluid compartment. Fluid fluent within the perivascular fluid compartment flows gegen the net direction of arteriovenular flow. Microvessel oscillations at the central tendency of the cerebral vasomotion generate corresponding oscillations of within the surrounding perivascular fluid compartment, interposed betwixt the abluminal surface of the vessels and internal surface of the pia mater. The precise microanatomy of this most fascinating among designable spaces has eluded the efforts of various investigators to interrogate its structure, though most authors non-consensusly concur the investing layers effectively and functionally segregate the perivascular and subarachnoid fluid compartments. Enlargement of the perivascular fluid compartment in a variety of neurological disorders, including senile dementia of the Alzheimer's type and cerebral small vessel disease, may alternately or coordinately constitute a correlative marker of disease severity and a possible cause implicated in the mechanistic pathogenesis of these conditions. Venular pressures modulating oscillatory dynamic flow within the perivascular fluid compartment may similarly contribute to the development of a variety among neurological disorders. An intimate understanding of subtle features typifying microanatomy and microphysiology of the investing structures and spaces of the cerebral microvasculature may powerfully inform mechanistic pathophysiology mediating a variety of neurovascular ischemic, neuroinfectious, neuroautoimmune, and neurodegenerative diseases.

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.

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.

Galenic Pial Arteriovenous Fistulas in Adults.

BACKGROUND: Vein of Galen aneurysmal malformations (VOGMs) are pial arteriovenous fistulas possessing Galenic venous drainage most commonly presenting during the neonatal period and infancy, with initial discovery during adulthood quite rare. OBJECTIVES AND METHODS: We conducted a literature survey of the PubMed database in order to identify Galenic pial arteriovenous fistulas (GPAVFs) with major manifestation or initial presentation during adulthood. Inclusionary criteria included pial AVFs with Galenic drainage with major manifestation or initial presentation at, or older than, 18 years. Exclusionary criteria included exclusive pediatric onset of symptomatology attributable to GPAVFs without a new onset major presentation during adulthood, exclusive or major dural arterial supply, arteriovenous malformations with Galenic drainage, developmental venous anomalies with Galenic drainage, isolated varices or anomalies of the vein of Galen, and any lesions with uncertainty regarding true GPAVF nature. RESULTS: Our search generated 1589 articles. Excluding duplicates, 26 cases met criteria for evaluation. Mean age was 34.1 +/- 2.53 years. Clinical presentations of GPAVFs among adults included headache, intracranial hemorrhage, seizures, and focal neurologic deficits. Management strategies included observation (n = 5), emergent ventriculostomy or Torkildsen shunt (n = 3), cerebrospinal fluid diversion via ventriculoperitoneal shunting (n = 4), microsurgical obliteration or thrombectomy (n = 4), transarterial and/or transvenous embolotherapeutic obliteration (n = 7), and concurrent embolotherapy and radiosurgical irradiation (n = 1). CONCLUSIONS: GPAVFs in adults often present with symptomatology of mild severity and may be effectively managed conservatively, though occasionally present catastrophically or may be treated via cerebrospinal fluid diversion, microsurgical obliteration, or endovascular embolization. Severity sufficient to require emergent intervention portended a poor outcome.

Topographic Classification of the Thalamus Surfaces Related to Microneurosurgery: A White Matter Fiber Microdissection Study.

OBJECTIVE: To describe the topographic anatomy of surgically accessible surfaces of the human thalamus as a guide to surgical exploration of this sensitive area. METHODS: Using the operating microscope, we applied the fiber microdissection technique to study 10 brain specimens. Step-by-step dissections in superior-inferior, medial-lateral, and posterior-anterior directions were conducted to expose the surfaces and nuclei of the thalamus and to investigate the relevant anatomic relationships and visible connections. RESULTS: There were 4 distinct free surfaces of the thalamus identified: lateral ventricle surface, velar surface, cisternal surface, and third ventricle surface. Each is described with reference to recognizable anatomic landmarks and to the underlying thalamic nuclei. The neural structures most commonly encountered during the surgical approach to each individual surface are highlighted and described. CONCLUSIONS: Observations from this study supplement current knowledge, advancing the capabilities to define the exact topographic location of thalamic lesions. This improved understanding of anatomy is valuable when designing the most appropriate and least traumatic surgical approach to thalamic lesions. These proposed surface divisions, based on recognizable anatomic landmarks, can provide more reliable surgical orientation.

Microsurgical anatomy of the hypoglossal nerve.

The aim of the present study was to review the surgical anatomy of the hypoglossal nerve (HN), to reveal its relationships on its course and to provide some landmarks to its identification. Ten cadaveric head dissections (20 sides) were performed using microsurgical techniques. The anatomical relationships between the HN and other nerves, muscles, arteries and veins were carefully recorded, and some measurements were made between the HN and related structures. Thus, various landmarks were determined for the easy identification of the HN. In addition, the hypoglossal triangle, which containes major vascular structures, is described. The HN is divided into three main parts: cisternal, intracanalicular and extracranial. The HN arises from the medulla as a line of rootlets situated along the anterior margin of the lower two-thirds of the olive in the preolivary sulcus. It is the newly described 'hypoglossal' triangle in the anterior neck that is bordered by the descending hypoglossus laterally, transverse hypoglossus inferiorly and inferior border of the stylohyoid muscle superiorly. In our specimens, we determined that the HN was 3-7 mm (mean 5 mm) inferior to the digastric tendon, as well as mostly superficial. The occipital artery arose from the posterior surface of the external carotid artery (ECA) 6-9 mm (mean 7 mm) above the carotid bifurcation. There is also an important 'cross' between the occipital artery and the HN. In all cadavers, this crossing point was 7-9 mm (mean 8 mm) superior to the emergence of the occipital artery from the ECA. In conclusion, understanding the detailed anatomy of the HN and using landmarks to identify the nerve are crucial for surgery in the region.

Genetic pathways to glioblastoma: a population-based study.

We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (<50 years) to 1.6 months (>80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16(INK4a) deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.

Surgical anatomy of supratentorial midline lesions.

OBJECT: In this paper the authors correlate the surgical aspects of deep median and paramedian supratentorial lesions with the connective fiber systems of the white matter of the brain. METHODS: The cerebral hemispheres of 10 cadaveric brains were dissected in a mediolateral direction by using the fiber dissection technique, corresponding to the surgical approach. CONCLUSIONS: This study illuminates the delicacy of the intertwined and stratified fiber laminae of the white matter, and establishes that these structures can be preserved at surgical exploration in patients.

Evaluating the importance of the tentorial angle in the paramedian supracerebellar-transtentorial approach for selective amygdalohippocampectomy.

OBJECTIVE: A challenging step of the paramedian supracerebellar-transtentorial approach is to expose the anterior portion of the mediobasal-temporal region (MTR), a step that seems most affected by the steepness of the tentorium. The objective of this study was to define magnetic resonance imaging measurements that can predict the level of challenge in exposing the anterior portion of the MTR. METHODS: Cranial magnetic resonance imaging studies of 100 healthy individuals were examined. The tentorial and occipital angles were measured, and the amount of brain tissue that remained hidden on the microscopic view in front of the petrous apex was indirectly estimated. These measurements were statistically compared with the cephalic index of each person. RESULTS: The mean values for the tentorial and occipital angles were 42° (range 25°-53°) and 98° (range 69°-122°), respectively. The results proved that the higher the tentorial angle, the higher the occipital angle and the greater the amount of hidden brain tissue. Of 100 persons, 3 (3%) were found to be dolichocephalic, 23 (23%) were mesocephalic, and 74 (74%) were brachycephalic. Statistical analysis proved that individuals with a dolichocephalic cranial shape have lower tentorial and occipital angles. CONCLUSIONS: The results provide strong evidence proving that the lesser the tentorial and occipital angles, the easier the exposure of the anterior portion of the MTR during the paramedian supracerebellar-transtentorial approach. The tendency of the cranial shape toward dolichocephaly seems to have the same practical value in choosing the approach. It is easier to expose the anterior portion of the MTR in these individuals.

Atypical extraventricular neurocytoma with oligodendroglioma-like spread and an unusual pattern of chromosome 1p and 19q loss.

An insular cortex tumor in a 54-year-old woman showed unequivocal neurocytic features, including open nuclei, distinct nucleoli, and strong synaptophysin immunoreactivity. Ultrastructurally, there were neuritic-type processes with microtubules and hillock-like attachments, and there were dense-core granules. Atypical features were mitotic activity, prominent vasculature, and small foci of necrosis. Peripherally, there was oligodendroglia-like histology with single-cell infiltration of white matter and perineuronal spread in cortex. Fluorescence in situ hybridization analysis with chromosome 1 and 19 probes showed 3 copies of 1q and 2 copies of 1p and showed 2 copies of 19q and 4 copies of 19p. This yielded a 1p-19q loss of heterozygosity pattern similar to that seen in oligodendrogliomas, although the actual chromosomal abnormality is distinct. This tumor, best classified as an atypical neurocytoma with oligodendroglia-like spread, supports suggestions of a close histogenic relationship between oligodendroglial and neurocytic tumors. This case also illustrates the limitations of relying exclusively on loss of heterozygosity analysis for tumor classification.

New laboratory model for neurosurgical training that simulates live surgery.

OBJECT: Laboratory training models are essential for developing and refining surgical skills, especially for microsurgery. The closer to live surgery the model is, the greater the benefit. In this paper the authors introduce a cadaver model with unique characteristics: dynamic filling of the cerebral vasculature with colored liquid and clear fluid filling of the arachnoid cisterns. This model is distinctive and has great practical value for training in a wide range of surgical procedures. METHODS: Cadaveric heads were prepared for surgical procedures in the following manner: the carotid arteries (CAs) and vertebral arteries (VAs) in the neck were cannulated, as were the internal jugular veins (JVs) on both sides. Two tubes were introduced into the spinal canal and each one was advanced into one of the cerebellopontine angle cisterns. A CA, VA, or both were then connected to a reservoir containing light red fluid and a pressure of 80 to 120 mm Hg and a pulse rate of 60 beats/minute were established using a pump. The JV on the side currently being dissected was connected to a reservoir containing dark red fluid and kept at a pressure between 20 and 40 mm Hg. The remaining vessels were clamped in the neck. The cisternal tubes were connected to a reservoir of clear fluid that was regulated by an adjustable flow. Nine trainees have tested this model on eight specimens by practicing a variety of surgical procedures and maneuvers, including craniotomies; hemostasis; cisternal and vascular dissection; vascular anastomosis and repair; establishment of arterial bypasses; aneurysm creation, dissection, and clipping; management of an aneurysm rupture; intraparenchymal resection such as amygdalohippocampectomy; ventricular endoscopy and third ventriculostomy; cavernous sinus and skull base approaches; and resection of artificial tumors in the basal cisterns. CONCLUSIONS: This model mimics the normal human anatomy and dynamic vascular filling found in real surgery and presents it from the training perspective, allowing a wide range of skill development and repeated practice. It provides an alternative model to laboratory animals. It is inexpensive and readily available, and has great value for the acquisition and refinement of surgical skills that are not only specific to neurosurgery, but are applicable to other surgical disciplines.

A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma.

OBJECT: The incidence of pilocytic astrocytomas and the rate of patient survival were analyzed in a population-based study in the canton of Zürich, Switzerland. METHODS: Between 1980 and 1994, 987 astrocytic and oligodendroglial tumors were diagnosed, of which 55 (5.5%) were pilocytic astrocytomas. The incidence rate, adjusted to the World Standard Population, was 4.8 per 1 million per year. The mean age at clinical diagnosis was 19.6 +/- 12.7 years, and the male/female ratio was 1.12. The most frequent tumor sites were the cerebellum (40%), followed by supratentorial locations (35%), the optic pathway and hypothalamus (11%), and the brainstem (9%). The mean follow-up period was 12 years. Observed survival rates were 100% at 5 years and 95.8% at 10 years after diagnosis (relative survival rate at 10 years: 96.8%). Seven patients (13%) received postoperative radiotherapy, but this did not significantly affect survival. In all patients the tumors were histologically classified as WHO Grade I, except in two patients who had anaplastic pilocytic astrocytoma (Grade III), one of whom died after 7 years, whereas the other was still alive after 10 years. CONCLUSIONS: This population-based study shows that, because of the benign biological behavior of pilocytic astrocytomas and advances in microneurosurgery, the survival rates for patients with these tumors are excellent, regardless of postoperative radiotherapy.

De novo cerebellar medulloblastoma in a 26-year recurrence-free case of temporal glioblastoma multiforme. Case report.

The authors describe a patient who survived 26 years after resection of a right temporal glioblastoma multiforme (GBM) without signs of tumor recurrence. Preoperative emergency angiography demonstrated a hypovascular mass localized in the right temporal lobe with right-to-left shift of the vascular structures. At surgery, the tumor had cystic and solid components localized in the lateral occipitotemporal gyrus, reaching the posterolateral wall of the inferior horn of the right lateral ventricle and extending to the trigone and posterior horn. The initial pathological diagnosis of a GBM was reviewed and confirmed throughout the follow-up period. Twenty-six years after surgery and subsequent radiosurgery, the patient underwent resection of a medulloblastoma localized in the right cerebellum as well as stereotactic biopsy sampling of tissue at the original GBM site. Neither radiological nor histological evidence of recurrence of the GBM could be documented. The intraoperative, histological, and radiological findings are described.

New alternative to animal models for surgical training.

Laboratory training models are essential for developing and refining surgical skills, especially in microsurgery. A perfect training model is the one that can provide the same situation during surgery, in the same anatomy; the closer to live surgery the model is, the greater the benefit. The lack of an accurate vascular model has sometimes necessitated the use of live models when bleeding, and vascular liquid filling is desired for optional learning. We developed a new model utilising human cadavers that can replace the use of live anaesthetised animals for surgical training. The vessels in a cadaveric specimen were connected to artificial blood reservoirs. The arterial side was connected to a pump to provide pulsating pressure inside the arteries, while the venous side was kept under static pressure that applied to the reservoir. This method provides a condition that simulates live surgery in terms of bleeding, pulsation and liquid filling of the vascular tree. It is an excellent alternative model and can be applied to the whole cadaver or to a particular cadaveric specimen (head, arm, leg) or to an isolated organ. It is distinctive and of a great practical value for training in a wide range of surgical procedures, Utilising this technique could forever eliminate the use of live anaesthetised animals for surgical training. The model and device are patent pending application no. 10/339,053.

The selective amygdalohippocampectomy for intractable temporal limbic seizures.

OBJECT: The proximal (anterior) transsylvian approach through a pterional craniotomy was developed by the senior author (M.G.Y.) in 1967 for the microsurgical treatment of saccular aneurysms of the circle of Willis, frontoorbital and temporobasal arteriovenous malformations, cavernomas, and extrinsic and intrinsic tumors. The acquired positive surgical experiences on this large series enabled the senior author, in 1973, to apply this approach for the selective amygdalohippocampectomy in patients with intractable mesial temporal lobe epilepsy. METHODS: The proximal (anterior) transsylvian-transamygdala approach to the mesial temporal structures permits the selective two-thirds resection of the amygdala and hippocampus-parahippocampus in an anteroinferior to posteroinferior exploration axis along the base of the semicircular temporal horn. This strategy ensures preservation of the overlying neopallial temporal convolutions such as the T1, T2, T3, and T4 gyri as well as the related subcortical connective fiber systems and other essential components of the temporal white matter. The application of rigid brain self-retaining retractor systems was strictly avoided during the entire procedure. Computer-assisted navigation was never used. On routine postoperative CT scanning and MR imaging studies, infarction was not observed in any patient. The availability of tractography technology has proven that the connective fiber system around the resected mesial temporal area remains intact. RESULTS: The surgical outcome and results on neoplastic and vascular lesions of the mesiobasal temporal region have been presented in Volumes II, IIIB, and IVB of Microneurosurgery. The surgical outcomes and results in 102 patients with mesial temporal seizures who underwent surgery performed by the senior author in Zürich have been previously published. In this paper, 73 patients who underwent surgery between 1994 and September 2006 in Little Rock, Arkansas, are presented, and 13 other patients are excluded who underwent surgery after September 2006. Altogether, among 188 patients who underwent surgery, there was no surgical mortality or morbidity, and no neurological deficits, new neurocognitive dysfunction, or impairments of the preoperative incapacities. CONCLUSIONS: The surgical outcome in terms of seizures was rewarding in the majority of patients, particularly in those who exhibited the following irregularities on preoperative investigations: regular local dysfunctions on electroencephalography, dysmorphic changes in the mesiobasal temporal parenchyma on MR imaging studies, and hypometabolism in the anterior third of the temporal lobe on PET studies.

Failure of a Torkildsen shunt after functioning for 50 years.

Mechanical obstruction is a severe complication of ventricular catheter use. Its incidence was shown to be high in the 1960s and 1970s, with up to 41% of the catheters becoming obstructed within 10 years after surgery. The authors present what is to their knowledge the first reported case of a patient with failure of a Torkildsen shunt after 50 years of functioning. A 60-year-old woman presented with increasing gait ataxia, decline in cognitive functions (including short-term memory loss), and slight urinary incontinence. The diagnosis of hydrocephalus and thus malfunction of the Torkildsen shunt implanted 50 years previously was confirmed by MR images, which revealed a prominent triventricular hydrocephalus. The patient subsequently underwent endoscopic third ventriculostomy (ETV), the current surgical treatment of choice, resulting in total resolution of her neurological symptoms and amelioration of cerebral tissue distension. Decrease in ventricle dilation and success of the ETV were confirmed on postoperative follow-up MR images.