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Antônio A F. De Salles and Iñaki Manchola

✓ Arteriovenous malformations (AVM's) are congenital tangles of vessels that have a high blood flow through a low-resistance nidus. The vessels in the nidus may lack normal vasoreactivity in response to changes in PaCO2 or perfusion pressure (autoregulation). Arteriovenous malformation hemodynamics have been assessed based on the response of AVM feeding arteries to hypocapnia.

Twenty-five AVM patients, aged 34 ± 11 years (mean ± standard deviation), were admitted to the Massachusetts General Hospital for proton-beam radiation therapy. Fourteen healthy volunteers aged 30 ± 7 years served as control subjects. Angiograms with calibrated markers permitting magnification correction were available for all patients. The limits of the middle cerebral artery, as determined by transcranial Doppler ultrasonography, were compared to measurements made on the angiograms. Hyperventilation was induced at a rate set by a metronome. Fixed bilateral Doppler probes allowed almost simultaneous sampling of two vessels. Volunteer control subjects were hyperventilated in two steps. The two PaCO2 step decreases were significant (mean resting PaCO2 40.6 ± 3.5 mm Hg, Step 1 level 29.4 ± 3.5 mm Hg and Step 2 level 23.8 ± 3.5 mm Hg; p < 0.01). These decreases induced a significant decrease in mean flow velocity (Vm) and an increase in the pulsatility index (p < 0.001). Mean carbon dioxide reactivity (%ΔVm/ΔPaCO2) was 2.74 ± 1.0 for Step 1 and 1.44 ± 1.8 for Step 2 (p < 0.003). The mean PaCO2 decrease in patients was from 39.5 ± 4.0 mm Hg to 27.0 ± 3.5 mm Hg. Carbon dioxide reactivity was 0.92 ± 1.12 for feeding vessels and 2.59 ± 1.78 for nonfeeding vessels (p < 0.001).

Transcranial Doppler ultrasound and angiographic depth measurements correlated well. Hyperventilation induced significantly more hemodynamic changes in control and nonfeeding middle cerebral arteries than in feeding vessels. Impaired CO2 reactivity may help to identify AVM feeding vessels as well as the relative magnitude of the flow provided to the malformation.

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Leonardo Frighetto, Antonio A. F. De Salles, Eric Behnke, Zachary A. Smith and Dennis Chute

✓ Interactive image-guided neuronavigation was used to obtain biopsy specimens of cavernous sinus (CS) tumors via the foramen ovale. In this study the authors demonstrated a minimally invasive approach in the management of these lesions.

In four patients, whose ages ranged from 29 to 89 years (mean 61.2 years) and who harbored undefined lesions invading the CS, neuronavigation was used to perform frameless stereotactic fine-needle biopsy sampling through the foramen ovale. The biopsy site was confirmed on postoperative computerized tomography scanning.

The frameless technique was accurate in displaying a real-time trajectory of the biopsy needle throughout the procedure. The lesions within the CS were approached precisely and safely. Diagnostic tissue was obtained in all cases and treatment was administered with the aid of stereotactic radiosurgery or fractionated stereotactic radiotherapy. The patients were discharged after an overnight stay with no complications.

Neuronavigation is a precise and useful tool for image-guided biopsy sampling of CS tumors via the foramen ovale.

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Aaron A. Cohen-Gadol, Edward R. Laws, Dennis D. Spencer and Antonio A. F. De Salles

✓ The evolution of transsphenoidal surgery represents a special chapter in the progress of neurosurgery. Although Cushing initially advocated a transsphenoidal approach to pituitary tumors, he became disenchanted with this approach, ultimately favoring the subfrontal or “transfrontal” route late in his career. Other neurosurgeons followed Cushing's example, and the fate of transsphenoidal surgery entered a dark era in 1929. A review of Cushing's patients' records reveals that his abandonment of the transsphenoidal route was primarily related to the limitations of this approach in providing effective resection of large pituitary lesions—the symptomatic tumor recurrence rate after this procedure was substantial. Furthermore, given the preoperative uncertainty about the suprasellar extension of pituitary tumors prior to modern neuroimaging, the transfrontal route assured Cushing an adequate decompression of the optic chiasm. By 1927, Cushing's mastery of intracranial surgery was accompanied by the use of electrosurgical methods that enabled him to remove sellar lesions through the transfrontal route safely and with timely and effective restoration of visual loss. Transsphenoidal surgery remained relatively dormant, awaiting the efforts and enthusiasm of Norman Dott who bridged the gap between Cushing and Gerard Guiot, the surgeon who revitalized transsphenoidal adenomectomy for future generations of pituitary surgeons.

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Alessandra Gorgulho, Antonio A. F. De Salles, Leonardo Frighetto and Eric Behnke

Object. The goal of this study was to analyze the incidence of intracranial bleeding in patients who underwent procedures guided by microelectrode recording (MER) rather than by macroelectrode stimulation alone.

Methods. Between March 1994 and July 2001, 178 patients underwent 248 functional neurosurgical procedures performed by the same team at the University of California at Los Angeles. The procedures included pallidotomy (122 patients), thalamotomy (19 patients), and implantation of deep brain stimulation electrodes in the subthalamic nucleus (36 patients), globus pallidus internus (17 patients), and ventralis intermedius nucleus (54 patients). One hundred forty-four procedures involved macroelectrode stimulation and 104 involved MER. Groups were analyzed according to the presence of arterial hypertension, MER or macroelectrode stimulation use, and occurrence of hemorrhage. Nineteen patients with arterial hypertension underwent 28 surgical procedures.

Five cases of hemorrhage (2.02%) occurred. One patient presented with hemiparesis and dysphasia but no surgery was required. The incidence of hemorrhage in patients in whom MER was performed was 2.9%, whereas the incidence in patients in whom MER was not used was 1.4% (p = 0.6529). Bleeding occurred in 10.71% of patients with hypertension and 0.91% of those who were nonhypertensive (p = 0.0111). Among the 104 patients in whom MER was performed, 12 had hypertension. Bleeding occurred in two (16.67%) of these 12 patients. An increased incidence of bleeding in hypertensive patients who underwent MER (p = 0.034) was noticed when compared with nonhypertensive patients who underwent MER. A higher number of electrode passes through the parenchyma was observed when MER was used (p = 0.0001). A positive trend between the occurrence of hemorrhage and multiple passes was noticed.

Conclusions. Based on the data the authors suggest that a higher incidence of hemorrhage occurs in hypertensive patients, and a higher incidence as well in hypertensive patients who underwent MER rather than macroeletrode stimulation. Special attention should be given to MER use in hypertensive patients and particular attention should be made to multiple passes.

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Antonio A. F. De Salles, William P. Melega, Goran Laćan, Lisa J. Steele and Timothy D. Solberg

Object. Radiosurgery for functional neurosurgery performed using a linear accelerator (LINAC) has not been extensively characterized in preclinical studies. In the present study, the properties of a newly designed 3-mm-diameter collimator were evaluated in a dedicated LINAC, which produced lesions in the basal ganglia of vervet monkeys. Lesion formation was determined in vivo in three animals by examining magnetic resonance (MR) images to show the dosedelivery precision of targeting and the geometry and extent of the lesions. Postmortem immunohistochemical studies were conducted to determine the extent of lesion-induced radiobiological effects.

Methods. In three male vervet monkeys, the subthalamic nucleus (STN; one animal) and the pars compacta of the lateral substantia nigra (SN; two animals) were targeted by a Novalis Shaped Beam Surgery System that included a 3-mm collimator and delivered a maximum dose of 150 Gy. Magnetic resonance images obtained 4, 5, and 9 months posttreatment were reviewed, and the animals were killed so that immunohistological characterizations could be made.

Conclusions. The generation of precise radiosurgical lesions by a 3-mm collimator was validated in studies that targeted the basal ganglia of the vervet monkey. The extent of the lesions created in all animals remained restricted in diameter (< 3 mm) throughout the duration of the studies, as assessed by reviewing MR images. Histological studies showed that the lesions were contained within the STN and SN target areas and that there were persistent increases in glial fibrillary acidic protein immunoreactivity. Increases in immunoreactivity for tyrosine hydroxylase, the serotonin transporter, and the GluR1 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate glutamate receptor in penumbral regions of the lesion were suggestive of compensatory neuronal adaptations. This radiosurgical approach may be of particular interest for the induction of lesions of the STN and SN in studies of experimental parkinsonism, as well as for the development of potential radiosurgical treatments for Parkinson disease.

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Jae Y. Lim, Antonio A. F. de Salles, Jeff Bronstein, Donna L. Masterman and Jeffrey L. Saver

✓ The authors report on a series of patients with idiopathic Parkinson's disease (IPD) who underwent stereotactic radiofrequency (RF) pallidotomies, three of whom suffered delayed postoperative strokes. These three belonged to a group consisting of 42 patients with medically intractable IPD in whom 50 pallidotomies were performed. All three patients had significant previous vascular disease and were in a high-risk group for cerebral infarction. A postoperative magnetic resonance (MR) image was obtained immediately after the pallidotomy was performed to document the placement of the RF lesion and to rule out any hematoma. The delayed strokes occurred on postoperative Days 10, 51, and 117 in patients with previous vascular disease (Group 1, 11 patients). No strokes occurred in the group with the vascular disease risk factor (Group 2, 11 patients) or in the group with no risk factors for vascular disease (Group 3, 20 patients). This observation is statistically significant (p < 0.05). The T2-weighted MR images showed the lesions as high-intensity signals extending to the posterior limb of the internal capsule ipsilateral to the pallidotomy site. The poststroke T1-weighted images obtained in two patients showed persistent contrast enhancement of the RF lesion and no enhancement around the stroke lesion. Clinically and radiographically, these discrete new lesions represent delayed infarctions, suggesting that RF lesioning can induce delayed injury in adjacent tissue. Patients with previously identified vasculopathy may be at risk for delayed capsular infarction following RF pallidotomy.

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Daniel A. N. Barbosa, Ricardo de Oliveira-Souza, Felipe Monte Santo, Ana Carolina de Oliveira Faria, Alessandra A. Gorgulho and Antonio A. F. De Salles

The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets.

Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts.

This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

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Carlos A. Mattozo, Antonio A. F. De Salles, Ivan A. Klement, Alessandra Gorgulho, David McArthur, Judith M. Ford, Nzhde Agazaryan, Daniel F. Kelly and Michael T. Selch


The authors analyzed the results of stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for the treatment of recurrent meningiomas that were described at initial resection as showing aggressive, atypical, or malignant features (nonbenign).


Twenty-five patients who underwent SRS and/or SRT for nonbenign meningiomas between December 1992 and August 2004 were included. Thirteen of these patients underwent treatment for multiple primary or recurrent lesions. In all, 52 tumors were treated. All histological sections were reviewed and reclassified according to World Health Organization (WHO) 2000 guidelines as benign (Grade I), atypical (Grade II), or anaplastic (Grade III) meningiomas. The median follow-up period was 42 months.

Seventeen (68%) of the cases were reclassified as follows: WHO Grade I (five cases), Grade II (11 cases), and Grade III (one case). Malignant progression occurred in eight cases (32%) during the follow-up period; these cases were considered as a separate group. The 3-year progression-free survival (PFS) rates for the Grades I, II, and III, and malignant progression groups were 100, 83, 0, and 11%, respectively (p < 0.001). In the Grade II group, the 3-year PFS rates for patients treated with SRS and SRT were 100 and 33%, respectively (p = 0.1). After initial treatment, 22 new tumors required treatment using SRS or SRT; 17 (77%) of them occurred inside the original resection cavity. Symptomatic edema developed in one patient (4%).


Stereotactic radiation treatment provided effective local control of “aggressive” Grade I and Grade II meningiomas, whereas Grade III lesions were associated with poor outcome. The outcome of cases in the malignant progression group was intermediate between that of the Grade II and Grade III groups, with the lesions showing a tendency toward malignancy.