Alessandra Gorgulho

Probabilities of Radiation Myelopathy Specific to Stereotactic Body Radiation Therapy to Guide Safe Practice

PURPOSE Dose-volume histogram (DVH) results for 9 cases of post spine stereotactic body radiation therapy (SBRT) radiation myelopathy (RM) are reported and compared with a cohort of 66 spine SBRT patients without RM. METHODS AND MATERIALS DVH data were centrally analyzed according to the thecal sac point maximum (Pmax) volume, 0.1- to 1-cc volumes in increments of 0.1 cc, and to the 2 cc volume. 2-Gy biologically equivalent doses (nBED) were calculated using an α/β = 2 Gy (units = Gy(2/2)). For the 2 cohorts, the nBED means and distributions were compared using the t test and Mann-Whitney test, respectively. Significance (P<.05) was defined as concordance of both tests at each specified volume. A logistic regression model was developed to estimate the probability of RM using the dose distribution for a given volume. RESULTS Significant differences in both the means and distributions at the Pmax and up to the 0.8-cc volume were observed. Concordant significance was greatest for the Pmax volume. At the Pmax volume the fit of the logistic regression model, summarized by the area under the curve, was 0.87. A risk of RM of 5% or less was observed when limiting the thecal sac Pmax volume doses to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. CONCLUSION We report the first logistic regression model yielding estimates for the probability of human RM specific to SBRT.

Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas

Objective  Giant pituitary adenomas (≥40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro‐endocrine team with multimodality treatment of these tumours in three specialized institutions.

Avoiding the ventricle : a simple step to improve accuracy of anatomical targeting during deep brain stimulation

OBJECT The authors examined the accuracy of anatomical targeting during electrode implantation for deep brain stimulation in functional neurosurgical procedures. Special attention was focused on the impact that ventricular involvement of the electrode trajectory had on targeting accuracy. METHODS The targeting error during electrode placement was assessed in 162 electrodes implanted in 109 patients at 2 centers. The targeting error was calculated as the shortest distance from the intended stereotactic coordinates to the final electrode trajectory as defined on postoperative stereotactic imaging. The trajectory of these electrodes in relation to the lateral ventricles was also analyzed on postoperative images. RESULTS The trajectory of 68 electrodes involved the ventricle. The targeting error for all electrodes was calculated: the mean +/- SD and the 95% CI of the mean was 1.5 +/- 1.0 and 0.1 mm, respectively. The same calculations for targeting error for electrode trajectories that did not involve the ventricle were 1.2 +/- 0.7 and 0.1 mm. A significantly larger targeting error was seen in trajectories that involved the ventricle (1.9 +/- 1.1 and 0.3 mm; p < 0.001). Thirty electrodes (19%) required multiple passes before final electrode implantation on the basis of physiological and/or clinical observations. There was a significant association between an increased requirement for multiple brain passes and ventricular involvement in the trajectory (p < 0.01). CONCLUSIONS Planning an electrode trajectory that avoids the ventricles is a simple precaution that significantly improves the accuracy of anatomical targeting during electrode placement for deep brain stimulation. Avoidance of the ventricles appears to reduce the need for multiple passes through the brain to reach the desired target as defined by clinical and physiological observations.

Modulation of food intake following deep brain stimulation of the ventromedial hypothalamus in the vervet monkey: Laboratory investigation

OBJECT Deep brain stimulation (DBS) has become an effective therapy for an increasing number of brain disorders. Recently demonstrated DBS of the posterior hypothalamus as a safe treatment for chronic intractable cluster headaches has drawn attention to this target, which is involved in the regulation of diverse autonomic functions and feeding behavior through complex integrative mechanisms. In this study, the authors assessed the feasibility of ventromedial hypothalamus (VMH) DBS in freely moving vervet monkeys to modulate food intake as a model for the potential treatment of eating disorders. METHODS Deep brain stimulation electrodes were bilaterally implanted into the VMH of 2 adult male vervet monkeys by using the stereotactic techniques utilized in DBS in humans. Stimulators were implanted subcutaneously on the upper back, allowing ready access to program stimulation parameters while the animal remained conscious and freely moving. In anesthetized animals, intraoperatively and 6-10 weeks postsurgery, VMH DBS parameters were selected according to minimal cardiovascular and autonomic nervous system responses. Thereafter, conscious animals were subjected to 2 cycles of VMH DBS for periods of 8 and 3 days, and food intake and behavior were monitored. Animals were then killed for histological verification of probe placement. RESULTS During VMH DBS, total food consumption increased. The 3-month bilateral implant of electrodes and subsequent periods of high-frequency VMH stimulation did not result in significant adverse behavioral effects. CONCLUSIONS This is the first study in which techniques of hypothalamic DBS in humans have been applied in freely moving nonhuman primates. Future studies can now be conducted to determine whether VMH DBS can change hypothalamic responsivity to endocrine signals associated with adiposity for long-term modulation of food intake.

Stereotactic body radiotherapy is an effective treatment in reirradiating spinal metastases: current status and practical considerations for safe practice.

Spinal metastases are a relatively common manifestation in advanced cancer patients. Low-dose conventional radiotherapy has long been the mainstay of treatment under the assumption that patients have a limited life expectancy in the order of 3–6 months. However, with new developments in systemic therapies, patients are surviving longer than expected. As the spinal retreatment rates, secondary to conventional radiation, can approach 20–50%, retreatments are likely to be more frequent. Rather than a second course of even lower-dose conventional radiation, spine stereotactic body radiotherapy (SBRT) has been developed predominantly to overcome the limitations of conventional reirradiation. Spine SBRT permits a second course of high-dose radiation aimed at local tumor control while sparing the spinal cord, and other surrounding normal tissues, of a toxic dose. The focus of this review is to provide an overview of reirradiation spine SBRT, and address key issues surrounding safe and effective practice.

Hypothalamic Deep Brain Stimulation Reduces Weight Gain in an Obesity-Animal Model

Prior studies of appetite regulatory networks, primarily in rodents, have established that targeted electrical stimulation of ventromedial hypothalamus (VMH) can alter food intake patterns and metabolic homeostasis. Consideration of this method for weight modulation in humans with severe overeating disorders and morbid obesity can be further advanced by modeling procedures and assessing endpoints that can provide preclinical data on efficacy and safety. In this study we adapted human deep brain stimulation (DBS) stereotactic methods and instrumentation to demonstrate in a large animal model the modulation of weight gain with VMH-DBS. Female Göttingen minipigs were used because of their dietary habits, physiologic characteristics, and brain structures that resemble those of primates. Further, these animals become obese on extra-feeding regimens. DBS electrodes were first bilaterally implanted into the VMH of the animals (n = 8) which were then maintained on a restricted food regimen for 1 mo following the surgery. The daily amount of food was then doubled for the next 2 mo in all animals to produce obesity associated with extra calorie intake, with half of the animals (n = 4) concurrently receiving continuous low frequency (50 Hz) VMH-DBS. Adverse motoric or behavioral effects were not observed subsequent to the surgical procedure or during the DBS period. Throughout this 2 mo DBS period, all animals consumed the doubled amount of daily food. However, the animals that had received VMH-DBS showed a cumulative weight gain (6.1±0.4 kg; mean ± SEM) that was lower than the nonstimulated VMH-DBS animals (9.4±1.3 kg; p<0.05), suggestive of a DBS-associated increase in metabolic rate. These results in a porcine obesity model demonstrate the efficacy and behavioral safety of a low frequency VMH-DBS application as a potential clinical strategy for modulation of body weight.

Endonasal microscopic removal of clival chordomas

INTRODUCTION Clival chordomas have traditionally been removed using a variety of anterior and lateral skull base approaches. Herein, we evaluate the outcomes of patients who underwent an extended endonasal transsphenoidal removal of a clival chordoma. METHOD All consecutive patients with a clival chordoma treated using an endonasal microscope approach were identified. In 8 cases, frameless surgical navigation was used, and in 4 cases, endoscopic assistance was used. Patients treated with prior radiotherapy were excluded. RESULT Over 5 years, 18 procedures were performed on 14 patients (7 females; mean age, 47 years). Patients were followed from 3 to 58 months (median, 20 months). Mean tumor diameter was 32 +/- 17 mm; 7 (50%) patients had intradural extension. Postoperative MRIs after the initial operation showed gross total, near-total (>90%), and subtotal resection in 43%, 43%, and 14% of patients, respectively. Use of the endoscope was associated with gross total or near-total tumor removal in 4 of 4 cases. Tumor regrowth occurred in 2 (14%) cases 10 and 12 months after the initial surgery and before radiotherapy. Two patients had multiple operations, in one as a planned staged operation, and in the other, 3 additional debulkings were performed despite an initial gross total removal. Nine patients, all with CS invasion, had subsequent stereotactic radiation. Of 10 patients with cranial neuropathy, 80% improved or resolved including 75% and 67% of sixth and fifth CN palsies, respectively. Complications included one each of adrenal insufficiency and chemical meningitis. There were no CSF leaks or new neurological deficits. CONCLUSION In this small series with relatively short follow-up, endonasal microscopic removal of clival chordomas proved safe and elfective with gross total or near-total removal in 86% of patients and improvement of cranial neuropathy in 80% of patients. Endoscopy for aiding tumor removal and assessing completeness of resection, as well as surgical navigation, are recommended for all cases.

White matter connectivity of human hypothalamus.

The macroscopic extrinsic white matter connectivity and the internal structure of the hypothalamus are still incompletely defined in humans. We investigated whether in-vivo diffusion tensor imaging tractography provides evidence of systematization according to hypothalamic compartmentalization. Six defined hypothalamic macroscopic compartments, preoptic, supraoptic, anteroventral, anterodorsal, lateral and posterior, were probed, within the right and left hemispheres of 14 subjects. Important new insights into the macroscopic structure of hypothalamus and white matter connections were found; the preoptic, anteroventral, lateral and posterior compartments are strongly connected to the cortex. The anteroventral connects particularly to the prefrontal cortex while the preoptic compartment connects mainly to the deep anterior brain. The anterodorsal connects mainly to the medial thalamus and the midline gray matter. There is a rightward frontal trend of hemispheric connectivity for the preoptic, anteroventral and lateral compartments. These findings may aid new neuromodulation applications and understanding in brain connectomics.

Diffusion tensor imaging and colored fractional anisotropy mapping of the ventralis intermedius nucleus of the thalamus.

BACKGROUND The ventralis intermedius (VIM) nucleus of the thalamus is the primary surgical target for treatment of tremor. Most centers rely on indirect targeting based on atlas-defined coordinates rather than patient-specific anatomy, making intraoperative physiological mapping critical. Detailed identification of this target based on patient-specific anatomic features can help optimize the surgical treatment of tremor. OBJECTIVE To study colored fractional anisotropic images and diffusion tensor imaging (DTI) tractography to identify characteristic magnetic resonance appearances of the VIM nucleus. METHODS Four patients undergoing stereotactic surgery for essential tremor (ET) were retrospectively studied with analysis of magnetic resonance imaging-based colored fractional anisotropy (FA) images and fiber tractography. All were scanned with a 1.5-T magnetic resonance imaging unit, and all sequences were obtained before frame placement. Because the goal of this study was to identify the DTI characteristics of physiologically defined VIM nucleus, we selected and studied patients who had undergone DTI and had efficacious tremor control with intraoperative microlesioning effect and tremor reduction with less than 2.0-V stimulation. RESULTS Analysis of color FA maps, which graphically illustrate fiber directionality, revealed consistent anatomic patterns. The region of the VIM nucleus can be seen as an intermediate region where there is a characteristic transition of color. Presumptive VIM nucleus interconnectivity with sensorimotor cortex and cerebellum was identified via the internal capsule and the superior cerebellar peduncle, respectively. FA maps could also be used to distinguish segments of gray matter, white matter, and gray-white matter boundaries. CONCLUSION Analysis of DTI and FA maps on widely available 1.5-T magnetic resonance imaging yields clear identification of various structures key to neurosurgical targeting. Prospective evaluation of integrating DTI into neurosurgical planning may be warranted. ABBREVIATIONS DBS: deep brain stimulation DTI: diffusion tensor imaging FA: fractional anisotropy PILC: posterior limb of the internal capsule VIM: ventralis intermedius

The role of modern imaging modalities on deep brain stimulation targeting for mental illness

INTRODUCTION The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. METHODS Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. RESULTS Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. CONCLUSIONS Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.