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Marco Cenzato, Francesco DiMeco, Marco Fontanella, Davide Locatelli, and Franco Servadei

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Marco Losa, Micol Valle, Pietro Mortini, Alberto Franzin, Camillo Ferrari da Passano, Marco Cenzato, Stefania Bianchi, Piero Picozzi, and Massimo Giovanelli

Object. Radiation therapy diminishes the risk of recurrence of incompletely removed nonfunctioning pituitary adenoma (NPA). The authors evaluated the efficacy and safety of gamma knife surgery (GKS) in patients with residual NPA following surgical debulking of the tumor.

Methods. Fifty-four patients, 26 men and 28 women, ranging in age from 29 to 72 years underwent gamma knife treatment. Baseline and follow-up studies involved magnetic resonance imaging, hormone evaluation, and neuroophthalmological examination 6 and 12 months after GKS and at yearly intervals thereafter. The mean follow up after GKS was 41.1 ± 3.1 months. Two of 52 patients undergoing follow up had a recurrence 40 and 49 months after GKS. In both of these patients the treated lesion had reduced in size, but a new lesion appeared in the contralateral side of the sella turcica. The recurrence-free interval at 5 years was 88.2% (95% confidence interval 72.6–100%). Tumor volume decreased from a baseline value of 2.3 ± 0.2 to 1.7 ± 0.2 cm3 at the last follow up (p < 0.001). Twenty-two patients (42.3%) had a 20% or greater reduction in tumor volume. The administered radiation dose had been significantly higher in patients who experienced tumor reduction. Visual function and motility did not deteriorate in any patient. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 12.5, 8.6, and 2.3%, respectively, of assessable patients at risk.

Conclusions. Gamma knife surgery was effective in controlling the growth of residual NPA after previously performed maximal surgical debulking. The major advantage of GKS compared with fractionated radiotherapy seems to be a lower risk of side effects, especially a lower risk of hypopituitarism.

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Marco Cenzato, Alberto Debernardi, Roberto Stefini, Giuseppe D'Aliberti, Maurizio Piparo, Giuseppe Talamonti, Matteo Coppini, and Pietro Versari

The aim of this study is to review the clinical outcome of patients treated for spinal dural arteriovenous malformations and investigate the presence of pretreatment indicators of outcome after short- and midterm follow-up. The authors retrospectively reviewed the records of 65 consecutive patients treated either surgically or endovascularly in 3 neurosurgery departments between 1989 and 2009. After treatment, 80% of patients reported improvement of at least 1 symptom. Motor symptoms improved more than sensory disorders, pain, or sphincter impairment. Spinal dural arteriovenous fistulas at the thoracic level, and in particular at the lower level, responded better than those in other spinal areas. Spinal dural arteriovenous fistula is a rare pathology with a malignant course that should be treated aggressively. This study appears to confirm that neurological status before treatment, anatomical location of the fistula, and symptoms at presentation are all factors that can predict outcome. Early diagnosis of spinal dural arteriovenous malformations in the lower thoracic area in patients with an Aminoff scale score < 3 was associated with the most favorable outcome.

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Roberto Stefini, Emanuela Catenacci, Simone Piva, Silvano Sozzani, Alessandra Valerio, Riccardo Bergomi, Marco Cenzato, Pietro Mortini, and Nicola Latronico


The clinical outcome of patients with severe head injuries is still critically dependent on their secondary injuries. Although hypoxia and hypotension appear to mediate a substantial proportion of secondary injuries, many studies associate secondary brain injury with neuroinflammatory responses. Chemokines have been detected in the cerebrospinal fluid but not in the brain tissue of patients with head trauma. This study was performed to determine if chemokines were expressed in pericontusional brain tissue in patients with moderate or severe head trauma who underwent surgical evacuation of their brain contusions.


Twelve patients with posttraumatic cerebral contusion requiring a surgical evacuation were studied. A 20- to 40-mg sample of white matter was removed from the surgical cavity in the pericontusional area. Two patients undergoing elective surgery for clip ligation of an unruptured aneurysm were used as controls. The median interval from trauma to biopsy procedure was 44 hours (range 3–360 hours). Total RNA was isolated from these samples and a ribonuclease protection assay was performed to measure the mRNA levels of several chemokines: CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, and XCL1.


The CCL2, a monocyte chemoattractant produced by activated astrocytes, was the most strongly expressed chemokine, followed by CXCL8, CCL3, and CCL4. The chemokines CXCL10 and CCL5 were expressed at very low levels, and XCL1 was not detected.


Chemokine activation occurs early after moderate or severe head trauma and is maintained for several days after trauma. This event may contribute to neuroinflammatory exacerbation of posttraumatic brain damage in the pericontusional brain tissue.

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Marco Cenzato, Davide Colistra, Giorgia Iacopino, Christian Raftopoulos, Ulrich Sure, Marcos Tatagiba, Robert F. Spetzler, Alexander N. Konovalov, Andriy Smolanka, Volodymir Smolanka, Roberto Stefini, Carlo Bortolotti, Paolo Ferroli, Giampietro Pinna, Angelo Franzini, Philipp Dammann, Georgios Naros, Davide Boeris, Paolo Mantovani, Domenico Lizio, Mariangela Piano, and Enrica Fava


In this paper, the authors aimed to illustrate how Holmes tremor (HT) can occur as a delayed complication after brainstem cavernoma resection despite strict adherence to the safe entry zones (SEZs).


After operating on 2 patients with brainstem cavernoma at the Great Metropolitan Hospital Niguarda in Milan and noticing a similar pathological pattern postoperatively, the authors asked 10 different neurosurgery centers around the world to identify similar cases, and a total of 20 were gathered from among 1274 cases of brainstem cavernomas. They evaluated the tremor, cavernoma location, surgical approach, and SEZ for every case. For the 2 cases at their center, they also performed electromyographic and accelerometric recordings of the tremor and evaluated the post-operative tractographic representation of the neuronal pathways involved in the tremorigenesis. After gathering data on all 1274 brainstem cavernomas, they performed a statistical analysis to determine if the location of the cavernoma is a potential predicting factor for the onset of HT.


From the analysis of all 20 cases with HT, it emerged that this highly debilitating tremor can occur as a delayed complication in patients whose postoperative clinical course has been excellent and in whom surgical access has strictly adhered to the SEZs. Three of the patients were subsequently effectively treated with deep brain stimulation (DBS), which resulted in complete or almost complete tremor regression. From the statistical analysis of all 1274 brainstem cavernomas, it was determined that a cavernoma location in the midbrain was significantly associated with the onset of HT (p < 0.0005).


Despite strict adherence to SEZs, the use of intraoperative neurophysiological monitoring, and the immediate success of a resective surgery, HT, a severe neurological disorder, can occur as a delayed complication after resection of brainstem cavernomas. A cavernoma location in the midbrain is a significant predictive factor for the onset of HT. Further anatomical and neurophysiological studies will be necessary to find clues to prevent this complication.

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Philipp Dammann, Adib A. Abla, Rustam Al-Shahi Salman, Hugo Andrade-Barazarte, Vladimir Benes, Marco Cenzato, E. Sander Connolly Jr., Jan F. Cornelius, William T. Couldwell, Rafael G. Sola, Santiago Gomez-Paz, Erik Hauck, Juha Hernesniemi, Juri Kivelev, Giuseppe Lanzino, R. Loch Macdonald, Jacques J. Morcos, Christopher S. Ogilvy, Hans-Jakob Steiger, Gary K. Steinberg, Alejandro N. Santos, Laurèl Rauschenbach, Marvin Darkwah Oppong, Börge Schmidt, Robert F. Spetzler, Karl Schaller, Michael T. Lawton, and Ulrich Sure


Indication for surgery in brainstem cavernous malformations (BSCMs) is based on many case series, few comparative studies, and no randomized controlled trials. The objective of this study was to seek consensus about surgical management aspects of BSCM.


A total of 29 experts were invited to participate in a multistep Delphi consensus process on the surgical treatment of BSCM.


Twenty-two (76%) of 29 experts participated in the consensus. Qualitative analysis (content analysis) of an initial open-ended question survey resulted in 99 statements regarding surgical treatment of BSCM. By using a multistep survey with 100% participation in each round, consensus was reached on 52 (53%) of 99 statements. These were grouped into 4 categories: 1) definitions and reporting standards (7/14, 50%); 2) general and patient-related aspects (11/16, 69%); 3) anatomical-, timing of surgery–, and BSCM-related aspects (22/37, 59%); and 4) clinical situation–based decision-making (12/32, 38%). Among other things, a consensus was reached for surgical timing, handling of associated developmental venous anomalies, handling of postoperative BSCM remnants, assessment of specific anatomical BSCM localizations, and treatment decisions in typical clinical BSCM scenarios.


A summary of typical clinical scenarios and a catalog of various BSCM- and patient-related aspects that influence the surgical treatment decision have been defined, rated, and interpreted.