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Carlo Serra, Lelio Guida, Victor E. Staartjes, Niklaus Krayenbühl and Uğur Türe

The authors report on and discuss the historical evolution of the 3 intellectual and scientific domains essential for the current understanding of the function of the human thalamus: 1) the identification of the thalamus as a distinct anatomical and functional entity, 2) the subdivision of thalamic gray matter into functionally homogeneous units (the thalamic nuclei) and relative disputes about nuclei nomenclature, and 3) experimental physiology and its limitations.

Galen was allegedly the first to identify the thalamus. The etymology of the term remains unknown although it is hypothesized that Galen may have wanted to recall the thalamus of Odysseus. Burdach was the first to clearly and systematically define the thalamus and its macroscopic anatomy, which paved the way to understanding its internal microarchitecture. This structure in turn was studied in both nonhuman primates (Friedemann) and humans (Vogt and Vogt), leading to several discrepancies in the findings because of interspecies differences. As a consequence, two main nomenclatures developed, generating sometimes inconsistent (or nonreproducible) anatomo-functional correlations. Recently, considerable effort has been aimed at producing a unified nomenclature, based mainly on functional data, which is indispensable for future developments. The development of knowledge about macro- and microscopic anatomy has allowed a shift from the first galenic speculations about thalamic function (the “thalamus opticorum nervorum”) to more detailed insights into the sensory and motor function of the thalamus in the 19th and 20th centuries. This progress is mostly the result of lesion and tracing studies. Direct evidence of the in vivo function of the human thalamus, however, originates from awake stereotactic procedures only.

Our current knowledge about the function of the human thalamus is the result of a long process that occurred over several centuries and has been inextricably intermingled with the increasing accumulation of data about thalamic macro- and microscopic anatomy. Although the thalamic anatomy can currently be considered well understood, further studies are still needed to gain a deeper insight into the function of the human thalamus in vivo.

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Carlo Serra, Jan-Karl Burkhardt, Giuseppe Esposito, Oliver Bozinov, Athina Pangalu, Antonios Valavanis, David Holzmann, Christoph Schmid and Luca Regli

OBJECTIVE

The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas.

METHODS

Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI.

RESULTS

The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5–47 mm) and 5.23 cm3 (range 0.09–22.14 cm3), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm3). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05).

CONCLUSIONS

The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

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Kevin Akeret, David Bellut, Hans-Jürgen Huppertz, Georgia Ramantani, Kristina König, Carlo Serra, Luca Regli and Niklaus Krayenbühl

OBJECTIVE

Surgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)–associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy.

METHODS

The authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome.

RESULTS

The neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis.

CONCLUSIONS

Morphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.

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Alberto Franzin, Giorgio Spatola, Carlo Serra, Piero Picozzi, Marzia Medone, Davide Milani, Paola Castellazzi and Pietro Mortini

Object

Due to technological advances in neuroradiology in recent years, incidental diagnoses of vestibular schwannomas (VSs) have increased. The aim of this study was to evaluate the hearing function after treatment with Gamma Knife surgery (GKS) for VSs in patients adequately selected with “good” or “useful” hearing before treatment and to assess the possible predictive factors for hearing function preservation.

Methods

Of all patients treated in the authors' hospital between 2001 and 2007, they retrospectively studied 50 patients with a unilateral VS in whom there was serviceable hearing (Gardner-Robertson [GR] Class I or II). Additional inclusion criteria were: no Type 2 neurofibromatosis, no previous treatment, and at least 6 months' follow-up of neuroradiological and audiological data. The median patient age was 54 years (range 24–78 years). The median tumor volume was 0.73 ml (range 0.03–6.6 ml), and the median radiation dose to the tumor margin was 13 Gy (range 12–16 Gy) with an isodose of 50%.

Results

Patient age, tumor volume, and presenting symptoms were found to correlate with hearing function. At a median of 36 months after radiosurgery, tumor growth control was 96% and no patient required any other additional treatment. Serviceable hearing was preserved in 34 patients (68%): 21 (62%) with GR Class I hearing and 13 (38%) with GR Class II hearing. The remaining 16 patients had poor hearing function:15 with GR Class III and 1 with GR Class IV hearing function. In 19 (58%) of 33 patients with GR Class I function before GKS the same class was maintained posttreatment; 29 (88%) maintained functional hearing (GR Class I or II). In all patients with an intracanalicular lesion, functional hearing was maintained. Significant prognostic factors for maintaining serviceable hearing were GR Class I function before treatment, symptoms at presentation, patient age younger than 54 years, and Koos Stage T1 disease.

Conclusions

The results of the study show that the probability of preserving functional hearing in patients undergoing GKS treatment for unilateral VSs is very high. Patients with GR Class I, age younger than 54 years, with presenting symptoms other than hearing loss, and a Koos Stage T1 tumor have better prognosis. The prescribed dose of 13 Gy appears to represent an excellent compromise between controlling the disease and preserving auditory function.

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Victor E. Staartjes, Carlo Serra, Giovanni Muscas, Nicolai Maldaner, Kevin Akeret, Christiaan H. B. van Niftrik, Jorn Fierstra, David Holzmann and Luca Regli

OBJECTIVE

Gross-total resection (GTR) is often the primary surgical goal in transsphenoidal surgery for pituitary adenoma. Existing classifications are effective at predicting GTR but are often hampered by limited discriminatory ability in moderate cases and by poor interrater agreement. Deep learning, a subset of machine learning, has recently established itself as highly effective in forecasting medical outcomes. In this pilot study, the authors aimed to evaluate the utility of using deep learning to predict GTR after transsphenoidal surgery for pituitary adenoma.

METHODS

Data from a prospective registry were used. The authors trained a deep neural network to predict GTR from 16 preoperatively available radiological and procedural variables. Class imbalance adjustment, cross-validation, and random dropout were applied to prevent overfitting and ensure robustness of the predictive model. The authors subsequently compared the deep learning model to a conventional logistic regression model and to the Knosp classification as a gold standard.

RESULTS

Overall, 140 patients who underwent endoscopic transsphenoidal surgery were included. GTR was achieved in 95 patients (68%), with a mean extent of resection of 96.8% ± 10.6%. Intraoperative high-field MRI was used in 116 (83%) procedures. The deep learning model achieved excellent area under the curve (AUC; 0.96), accuracy (91%), sensitivity (94%), and specificity (89%). This represents an improvement in comparison with the Knosp classification (AUC: 0.87, accuracy: 81%, sensitivity: 92%, specificity: 70%) and a statistically significant improvement in comparison with logistic regression (AUC: 0.86, accuracy: 82%, sensitivity: 81%, specificity: 83%) (all p < 0.001).

CONCLUSIONS

In this pilot study, the authors demonstrated the utility of applying deep learning to preoperatively predict the likelihood of GTR with excellent performance. Further training and validation in a prospective multicentric cohort will enable the development of an easy-to-use interface for use in clinical practice.

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Alberto Franzin, Alberto Vimercati, Piero Picozzi, Carlo Serra, Silvia Snider, Lorenzo Gioia, Camillo Ferrari da Passano, Angelo Bolognesi and Massimo Giovanelli

Object

Treatment options for patients with brain metastasis include tumor resection, whole-brain radiation therapy, and radiosurgery. A single treatment is not useful in cases of multiple tumors, of which at least 1 is a cystic tumor. The purpose of this study was to assess the role of stereotactic drainage and Gamma Knife surgery (GKS) in the treatment of cystic brain metastasis.

Methods

Between January 2001 and November 2005, 680 consecutive patients with brain metastases underwent GKS at our hospital, 30 of whom were included in this study (18 males and 12 females, mean age 60.6 ± 11 years, range 38–75 years). Inclusion criteria were: 1) no prior whole-brain radiation therapy or resection procedure; 2) a maximum of 4 lesions on preoperative MR imaging; 3) at least 1 cystic lesion; 4) a Karnofsky Performance Scale score ≥ 70; and 5) histological diagnosis of a malignant tumor.

Results

Non–small cell lung carcinoma was the primary cancer in most patients (19 patients [63.3%]). A single metastasis was present in 13 patients (43.3%). There was a total of 81 tumors, 33 of which were cystic. Ten patients (33.3%) were in recursive partitioning analysis Class I, and 20 (66.6%) were in Class II. Before drainage the mean tumor volume was 21.8 ml (range 3.8–68 ml); before GKS the mean tumor volume was 10.1 ml (range 1.2–32 ml). The mean prescription dose to the tumor margin was 19.5 Gy (range 12–25 Gy). Overall median patient survival was 15 months. The 1- and 2-year survival rates were 54.7% (95% confidence interval 45.3–64.1%) and 34.2% (95% confidence interval 23.1–45.3%). Local tumor control was achieved in 91.3% of the patients.

Conclusions

The results of this study support the use of a multiple stereotactic approach in cases of multiple and cystic brain metastasis.

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Alberto Franzin, Alberto Vimercati, Marzia Medone, Carlo Serra, Stefania Bianchi Marzoli, Maddalena Forti, Lorenzo Gioia, Micol Valle and Piero Picozzi

Object

Treatment options for patients with cavernous sinus meningiomas (CSMs) include microsurgical tumor resection, radiotherapy, and radiosurgery. Gamma Knife surgery (GKS) is increasingly being used because it is associated with lower mortality and morbidity rates than microsurgery. The purpose of this study was to assess the role of GKS in the treatment of CSM and to thoroughly analyze the clinical response to GKS.

Methods

Between January 2001 and December 2005, 123 patients (25 men and 98 women; mean age 62.6 ± 11 years, range 31–86 years) who underwent treatment for CSMs were included in this study. Of these, 41 patients underwent microsurgery before GKS, whereas the remaining 82 had GKS as a first-line therapy after a diagnosis was made based on magnetic resonance imaging findings. Dysfunction in cranial nerves (CNs) II, III, IV, V, and VI was noted in 74 patients at the time of GKS. The mean tumor volume was 7.99 cm3 (0.7–30.5 cm3). The mean prescription dose to the tumor margin was 13.8 ± 1.1 Gy (range 10–20 Gy).

Results

The overall tumor control rate was 98.4% with a median follow-up of 36 months. The actuarial tumor control rate at 5 years was 90.5%. A reduction in tumor volume was observed in 53 patients (43.1%), whereas in 68 patients (55.3%) no volumetric variation was recorded. Of the 74 patients who presented with CN deficits, improvement was noted in 23 (31.1%).

Conclusions

Gamma Knife surgery is a useful treatment for CSM both as a first- or second-line therapy. It is a safe and effective treatment for tumors located close to the optic pathways.

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Victor E. Staartjes, Costanza M. Zattra, Kevin Akeret, Nicolai Maldaner, Giovanni Muscas, Christiaan Hendrik Bas van Niftrik, Jorn Fierstra, Luca Regli and Carlo Serra

OBJECTIVE

Although rates of postoperative morbidity and mortality have become relatively low in patients undergoing transnasal transsphenoidal surgery (TSS) for pituitary adenoma, cerebrospinal fluid (CSF) fistulas remain a major driver of postoperative morbidity. Persistent CSF fistulas harbor the potential for headache and meningitis. The aim of this study was to investigate whether neural network–based models can reliably identify patients at high risk for intraoperative CSF leakage.

METHODS

From a prospective registry, patients who underwent endoscopic TSS for pituitary adenoma were identified. Risk factors for intraoperative CSF leaks were identified using conventional statistical methods. Subsequently, the authors built a prediction model for intraoperative CSF leaks based on deep learning.

RESULTS

Intraoperative CSF leaks occurred in 45 (29%) of 154 patients. No risk factors for CSF leaks were identified using conventional statistical methods. The deep neural network–based prediction model classified 88% of patients in the test set correctly, with an area under the curve of 0.84. Sensitivity (83%) and specificity (89%) were high. The positive predictive value was 71%, negative predictive value was 94%, and F1 score was 0.77. High suprasellar Hardy grade, prior surgery, and older age contributed most to the predictions.

CONCLUSIONS

The authors trained and internally validated a robust deep neural network–based prediction model that identifies patients at high risk for intraoperative CSF. Machine learning algorithms may predict outcomes and adverse events that were previously nearly unpredictable, thus enabling safer and improved patient care and better patient counseling.