William T. Couldwell

Variations on the standard transsphenoidal approach to the sellar region, with emphasis on the extended approaches and parasellar approaches: surgical experience in 105 cases.

OBJECTIVE:The traditional boundaries of the transsphenoidal approach may be expanded to include the region from the cribriform plate of the anterior cranial base to the inferior clivus in the anteroposterior plane, and laterally to expose the cavernous cranial nerves and the optic canal. We review our combined experience with these variations on the transsphenoidal approach to various lesions of the sellar and parasellar region. METHODS:From 1982 to 2003, we used the extended and parasellar transsphenoidal approaches in 105 patients presenting with a variety of lesions of the parasellar region. This study specifically reviews the breadth of pathological lesions operated and the complications associated with the approaches. RESULTS:Variations of the standard transsphenoidal approach have been used in the following series: 30 cases of pituitary adenomas extending laterally to involve the cavernous sinus, 27 craniopharyngiomas, 11 tuberculum/diaphragma sellae meningiomas, 10 sphenoid sinus mucoceles, 18 clivus chordomas, 4 cases of carcinoma of the sphenoid sinus, 2 cases of breast carcinoma metastatic to the sella, and 3 cases of monostotic fibrous dysplasia involving the clivus. There was no mortality in the series. Permanent neurological complications included one case of monocular blindness, one case of permanent diabetes insipidus, and two permanent cavernous cranial neuropathies. There were four cases of internal carotid artery hemorrhage, one of which required ligation of the cervical internal carotid artery and resulted in hemiparesis. The incidence of postoperative cerebrospinal fluid fistulae was 6% (6 of 105 cases). CONCLUSION:These modifications of the standard transsphenoidal approach are useful for lesions within the boundaries noted above, they offer excellent alternatives to transcranial approaches for these lesions, and they avoid prolonged exposure time and brain retraction. Technical details are discussed and illustrative cases presented.

Use of the h index in neurosurgery. Clinical article.

OBJECT Assessing academic productivity through simple quantification may overlook key information, and the use of statistical enumeration of academic output is growing. The h index, which incorporates both the total number of publications and the citations of those publications, has been recently proposed as an objective measure of academic productivity. The authors used several tools to calculate the h index for academic neurosurgeons to provide a basis for evaluating publishing by physicians. METHODS The h index of randomly selected academic neurosurgeons from a sample of one-third of the academic programs in the US was calculated using data from Google Scholar and from the Scopus database. The mean h index for each academic rank was determined. The h indices were also correlated with various other factors (such as time spent practicing neurosurgery, authorship position) to identify how these factors influenced the h index. The h indices were then compared with other citation statistics to evaluate the robustness of this metric. Finally, h indices were also calculated for a sampling of physicians in other medical specialties for comparison. RESULTS As expected, the h index increased with academic rank and there was a statistically significant difference between each rank. A weighting based on position of authorship did not affect h indices. The h index was positively correlated with time since American Board of Neurological Surgery certification, and it was also correlated with other citation metrics. A comparison among medical specialties supports the assertion that h index values may not be comparable between fields, even closely related specialties. CONCLUSIONS The h index appears to be a robust statistic for comparing academic output of neurosurgeons. Within the field of academic neurosurgery, clear differences of h indices between academic ranks exist. On average, an increase of the h index by 5 appears to correspond to the next highest academic rank, with the exception of chairperson. The h index can be used as a tool, along with other evaluations, to evaluate an individuals productivity in the academic advancement process within the field of neurosurgery but should not be used for comparisons across medical specialties.

Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro.

Direct measurement of protein kinase C (PKC) activity in vitro revealed a significant increase in the activity of the enzyme in all human malignant glioma lines examined and the rat C6 tumor in comparison with control nonneoplastic astrocyte and mixed glial cultures. The total and particulate PKC activity in these cell types correlated strongly [r = 0.98 (P less than 0.001) and 0.94 (P = 0.002), respectively] with the maximal growth rates as measured by 3H-thymidine incorporation in each of the samples. An alteration in the growth rate of an individual glioma line (A172) by varying the serum concentration in the growth medium produced comparative changes in the measured PKC activity. The addition of the phorbol ester phorbol-12-myristate-13-acetate to this tumor line under high serum conditions produced down-regulation of the enzyme, which was accompanied by a corresponding reduction in thymidine incorporation. The administration of the PKC inhibitor staurosporine produced a dose-related decrease in the basal proliferation rate of glioma lines A172 and C6, as measured by 3H-thymidine uptake and confirmed by flow cytometry, indicating that the high intrinsic PKC activity is amenable to pharmacological manipulation. Cytofluorometric deoxyribonucleic acid cell cycle analysis of the tumors treated with PKC modulators demonstrated that reduced proliferation rates were caused by an inhibition of entrance into the deoxyribonucleic acid synthesis (S) phase (decrease in proliferative index), supporting the evidence that these modulators are not slowing the tumor growth in a nonspecific cytotoxic manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein Kinase C Activity Correlates with the Growth Rate of Malignant Gliomas: Part II. Effects of Glioma Mitogens and Modulators of Protein Kinase C

The proliferation rates of gliomas may be modulated by the protein kinase C (PKC) signal transduction system. The present study was undertaken to further examine the role of PKC system in growth regulation of gliomas in vitro by measurement of PKC activity over various phases of tumor growth and by assessing its potential role as a signal transduction system induced by serum mitogens and the known glioma mitogens epidermal growth factor and fibroblast growth factor. All human glioma lines examined, and the rat glioma C6, displayed high PKC activity relative to nonmalignant glial cells, which correlated with their proliferation rates over their respective growth phase. Frozen surgical human malignant glioma specimens also displayed high PKC activity. The relatively selective PKC inhibitor staurosporine (SP) reduced PKC activity and corresponding growth rates in a dose-related manner. Stimulation of PKC with phorbol esters under different concentrations of serum in the growth medium indicated that the high PKC activity, which correlated with their rapid growth rates, is highly susceptible to down-regulation by these agents. Epidermal growth factor and fibroblast growth factor increased both PKC activity and the growth rate of glioma line A172; addition of SP reduced the growth rate to levels observed in SP-treated control tumors, indicating that PKC may be a common signal transduction system induced by these mitogens. These results implicate PKC as an important signal transduction system regulating glioma growth, and offers a potential target for tumor inhibition.

Transsphenoidal and Transcranial Surgery for Pituitary Adenomas

This paper reviews the progress made over the first century of pituitary surgery. The goals of surgery for pituitary tumors are to eliminate tumor mass effect and perform as complete a removal as possible, retain pituitary function, and normalize any hormonal hypersecretion. Since the initial transsphenoidal approach performed in Austria by Schloffer, the transsphenoidal approach has become the preferred surgical approach to most pituitary tumors. The history and development of the transsphenoidal approach to the sella is discussed, as are the contemporary techniques of microscopic and endoscopic pituitary surgery. The continued evolution of the variations and extension of the transsphenoidal approach to other lesions are reviewed. The indications and use of a transcranial approach to remove pituitary tumors are discussed. More recently, stereotactic radiosurgery (SRS) has become an important adjuvant management technique in the management of difficult pituitary adenomas, especially with cavernous sinus invasion.

Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications.

Neurofibromatosis 1 (NF1) is a common autosomal dominant disease characterized by complex and multicellular neurofibroma tumors. Significant advances have been made in the research of the cellular, genetic, and molecular biology of NF1. The NF1 gene was identified by positional cloning. The functions of its protein product, neurofibromin, in RAS signaling and in other signal transduction pathways are being elucidated, and the important roles of loss of heterozygosity and haploinsufficiency in tumorigenesis are better understood. The Schwann cell was discovered to be the cell of origin for neurofibromas, but understanding of a more complicated interplay of multiple cell types in tumorigenesis, specifically recruited heterogenous cell types such as mast cells and fibroblasts, has important implications for surgical therapy of these tumors. This review summarizes the most recent NF1 and neurofibroma literature describing the pathogenesis and treatment of nerve sheath tumors. Understanding the biological underpinnings of tumorigenesis in NF1 has implications for future surgical and medical management of neurofibromas.

Ruptured intracranial dermoid cysts: clinical, radiographic, and surgical features.

OBJECTIVE Intracranial dermoid cysts are pathologically characterized by a thick, stratified squamous epithelium cyst wall containing dermal elements. Rupture into the subarachnoid spaces and ventricles is extremely rare. We review the clinical, radiographic, and surgical features of eight ruptured dermoid cysts. METHODS We retrospectively evaluated five surgically treated patients with pathologically proven ruptured dermoid cysts. Clinic notes, operative reports, and neuroimaging, including initial computed tomographic and magnetic resonance imaging scans, were reviewed. Imaging was also available on three outside patients reviewed by members of our radiology department. RESULTS The most common presentations were headaches (57%) and seizures (42%), followed by hydrocephalus (29%) from intraventricular rupture. These lesions were consistently hypodense on computed tomographic scans and hyperintense on T1-weighted images with minimal to no enhancement after gadolinium administration. Disseminated fat droplets were present in the subarachnoid space in both cerebral hemispheres in all patients, and five patients had intraventricular rupture with fat-fluid levels in the ventricles. Gross to near-total resection of the primary lesion was achieved in all five surgically treated patients treated at our institution. Four patients had remnant tumor capsules adherent to neurovascular structures that were unresectable. Repeat resection was performed for one recurrence; there were no further recurrences during a follow-up period of 2 to 134 months (mean, 65.6 mo). Two patients with preoperative hydrocephalus eventually required ventriculoperitoneal shunting. CONCLUSION Ruptured intracranial dermoid cysts represent 0.18% of all central nervous system tumors surgically treated in our institution during a 12-year period. The presence of disseminated fat droplets in the subarachnoid space or ventricles on neuroimaging is diagnostic for a ruptured dermoid cyst. Gross total removal is achievable; however, residual tumor capsules adherent to neurovascular structures should be left behind to minimize complications.

Neuron-Specific Enolase Is Increased After Single Seizures During Inpatient Video/EEG Monitoring

Neuron‐specific enolase (NSE) is a marker of brain injury after acute neurologic insults. We report changes in serum NSE (s‐NSE) in 25 patients (15 with epilepsy and 10 patients with nonepileptic events) during continuous inpatient video/EEG monitoring. s‐NSE was significantly increased as compared with baseline and normal controls after the first ictal event in the epileptic group, especially in patients with secondarily generalized tonic‐clonic seizures (p = 0.01), but s‐NSE was not increased in patients with nonepileptic events. These preliminary data indicate that s‐NSE may be increased after complex partial seizures‐and generalized tonic‐clonic seizures (GTCS).

Zones of approach for craniofacial resection: minimizing facial incisions for resection of anterior cranial base and paranasal sinus tumors.

OBJECTIVEAnterior cranial base tumors are surgically resected with combined craniofacial approaches that frequently involve disfiguring facial incisions and facial osteotomies. The authors outline three operative zones of the anterior cranial base and paranasal sinuses in which tumors can be resected with three standard surgical approaches that minimize transfacial incisions and extensive facial osteotomies. METHODSThe zones were defined by performing dissections on 10 cadaveric heads and by evaluating radiographic images of patients with anterior cranial base tumors. The three approaches performed on each cadaver were transbasal, transmaxillary, and extended transsphenoidal. RESULTSThree zones of approach were defined for accessing tumors of the anterior cranial base, nasal cavity, and paranasal sinuses. Zone 1 is exposed by the transbasal approach, which is limited anteriorly by the supraorbital rim, posteriorly by the optic chiasm and clivus, inferiorly by the palate, and laterally by the medial orbital walls. This approach allows access to the entire anterior cranial base, nasal cavity, and the majority of maxillary sinuses. The limitation imposed by the orbits results in a blind spot in the superolateral extent of the maxillary sinus. Zone 2 is exposed by a sublabial maxillotomy approach and accesses the entire maxillary sinus, including the superolateral blind spot and the ipsilateral anterior cavernous sinus. However, access to the anterior cranial base is limited. Zone 3 is exposed by the transsphenoidal approach. This approach accesses the midline structures but is limited by the lateral nasal walls and intracavernous carotid arteries. An extended transsphenoidal approach allows further exposure to the anterior cranial base, clivus, or cavernous sinuses. The use of the endoscope facilitates tumor resection in the nasal cavity and paranasal sinuses. CONCLUSIONThe operative zones outlined offer minimally invasive craniofacial approaches to accessing lesions of the anterior cranial base and paranasal sinuses, obviating facial incisions and facial osteotomies. Case illustrations demonstrating the approach selection paradigm are presented.

Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage

Cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage that has become refractory to maximal medical management can be treated with selective intra-arterial papaverine infusions. Papaverine is a potent vasodilator of the proximal, intermediate, and distal cerebral arteries and can improve cerebral blood flow (CBF). When infused intra-arterially using endovascular microcatheter techniques, papaverine can effectively increase angiographic vessel diameter, decrease prolonged cerebral circulation time, and improve cerebral oxygenation. However, one of the major disadvantages of papaverine is its transient nature, which can result in recurrent and/or persistent angiographic and clinical vasospasm that may require multiple repeated infusions, despite a successful response to the initial treatment. Intra-arterial papaverine can be used alone or in combination with balloon angioplasty. This article reviews the mechanism of action, technique of administration, effects on CBF, clinical results, and complications of intra-arterial papaverine for the treatment of cerebral vasospasm.