Clival Metastases: Single-Center Retrospective Case Series and Literature Review.

Background/Objectives: Clivus metastases from distant neoplasms are uncommon occurrences both in clinical practice and the neurosurgical literature. Surgical management is debated, particularly about the role of surgery and the preferable approach. The aim of this study was to report our surgical experience and review the concerning literature. Methods: Our institutional registry was retrospectively reviewed, and patients who underwent surgical treatment for clival metastasis from 1998 to 2023 were included. A PRISMA systematic review of the literature was performed. Results: Four patients were enrolled, and all of them underwent an endoscopic endonasal approach (EEA). Three presented with cranial nerve (CN) VI palsy. The aim of surgery was biopsy in all cases. No complications were reported. Mean overall survival (OS) was 6 ± 1 months. The systematic review retrieved 27 papers reporting 39 patients who underwent the surgical treatment of clivus metastases. Most of them (79.5%) presented with CN palsies, and EEA was the preferred approach in 92.3% of the cases, to perform a biopsy in most patients (59%). Two hemorrhagic complications (5.1%) were reported, and the mean OS was 9.4 ± 5.6 months. Conclusions: Clival metastases are uncommonly observed, in most cases, during advanced stages of oncological disease. The aim of surgery should be the confirmation of diagnosis and symptomatic relief, balancing the risk-benefit ratio in a multidisciplinary context. EEA is the approach of choice, and it should be carried out in experienced tertiary skull base centers.

Combined Endoscopic Transorbital and Transmaxillary-Pterygoid Approach for a Recurrent Spheno-Orbital Meningioma: 2-Dimensional Operative Video.

Spheno-orbital meningiomas are challenging invasive tumors, involving different cranial regions, requiring multiple surgical approaches and often with an unfavorable biological behavior characterized by multiple recurrences and possible escape from standard treatments.1 We present a case of a 57-year-old woman, already undergone a transcranial approach, an endoscopic transorbital surgery, and a radiosurgical treatment for a spheno-orbital meningioma. She presented a further tumoral recurrence, involving the orbit and the infratemporal and pterygopalatine fossa, and we proposed a combined fully endoscopic multistaged approach. The patient consented to the procedure and to the publication of his/her image. We adopted the endoscopic transorbital and the endoscopic transmaxillary-pterygoid corridors for the different portions of the tumor, followed by radiation therapy with carbon ions, achieving a large tumor resection with no progression at 12-month follow-up and without complications or neurological sequelae. This treatment strategy gave us the possibility to fully manage the tumoral extension with 2 innovative minimally invasive surgical procedures, which resulted well-tolerated and favored the prompt patient recovery and quality-of-life preservation, leaving the meningioma remnant to the external radiation therapy.2-6 Our case emphasizes the possibilities given by the endoscopic approaches to manage at 360° the multiregional extensions of a spheno-orbital meningioma, demonstrating how such direct and extracranial corridors could allow the surgeon to remove these tumors, with no brain retraction or manipulation and limited functional or neurological sequelae.7,8.

Development and external validation of clinical prediction models for pituitary surgery.

Introduction: Gross total resection (GTR), Biochemical Remission (BR) and restitution of a priorly disrupted hypothalamus pituitary axis (new improvement, IMP) are important factors in pituitary adenoma (PA) resection surgery. Prediction of these metrics using simple and preoperatively available data might help improve patient care and contribute to a more personalized medicine. Research question: This study aims to develop machine learning models predicting GTR, BR, and IMP in PA resection surgery, using preoperatively available data. Material and methods: With data from patients undergoing endoscopic transsphenoidal surgery for PAs machine learning models for prediction of GTR, BR and IMP were developed and externally validated. Development was carried out on a registry from Bologna, Italy while external validation was conducted using patient data from Zurich, Switzerland. Results: The model development cohort consisted of 1203 patients. GTR was achieved in 207 (17.2%, 945 (78.6%) missing), BR in 173 (14.4%, 992 (82.5%) missing) and IMP in 208 (17.3%, 167 (13.9%) missing) cases. In the external validation cohort 206 patients were included and GTR was achieved in 121 (58.7%, 32 (15.5%) missing), BR in 46 (22.3%, 145 (70.4%) missing) and IMP in 42 (20.4%, 7 (3.4%) missing) cases. The AUC at external validation amounted to 0.72 (95% CI: 0.63-0.80) for GTR, 0.69 (0.52-0.83) for BR, as well as 0.82 (0.76-0.89) for IMP. Discussion and conclusion: All models showed adequate generalizability, performing similarly in training and external validation, confirming the possible potentials of machine learning in helping to adapt surgical therapy to the individual patient.

Endoscopic Endonasal Transplanum-Transtuberculum Approach for Pituitary Adenomas/PitNET: 25 Years of Experience.

The role of the endoscopic transplanum-transtuberculum approach (ETTA) in the treatment of pituitary adenomas/PitNETs (PAs) is sparsely analyzed in the literature, and its use is still debated in the current practice. The aim of this study was to report our experience with this approach. Our institutional registry was retrospectively reviewed, and patients who underwent ETTA for a PA from 1998 to 2022 were included. Fifty-seven cases were enrolled over a time span of 25 years, corresponding to 2.4% of our entire PA caseload. Radical resection was achieved in 57.9% of cases, with re-do surgery (p = 0.033) and vessel encasement/engulfment (p < 0.001) as predictors of partial resection. CSF leak incidence stood at 8.8%, with higher BMI (p = 0.038) as its only significant predictor. Partial or full improvement of the visual field deficits was achieved in 73.5% of cases. No surgical mortality was observed. According to our results, ETTA for the treatment of PAs is characterized by a satisfactory surgical outcome but with greater morbidity than the conventional endoscopic approach. Therefore, it should be reserved for the few selected cases otherwise unsuitable for the endoscopic trans-sphenoidal route, representing a valid alternative and an effective complementary route for the transcranial approach for these challenging PAs.

Endoscopic Transorbital Approach for Spheno-Orbital Tumors: Case Series and Systematic Review of Literature.

BACKGROUND: Transorbital neuroendoscopic surgery (TONES) comprises a group of approaches with indications expanding from orbital tumors to more complex skull base lesions. We analyzed the role of the endoscopic transorbital approach (eTOA) for spheno-orbital tumors, reporting the results of our clinical series and of a systematic review of the literature. MATERIALS AND METHODS: All patients operated on from 2016 to 2022 at our institution for a spheno-orbital tumor through an eTOA were included in a clinical series, and a systematic review of the literature was performed. RESULTS: Our series consisted of 22 patients (16 females, mean age 57 ± 13 years). Gross tumor removal was achieved in 8 patients (36.4%) after the eTOA and in 11 (50.0%) after a multistaged strategy combining the eTOA with the endoscopic endonasal approach. Complications included 1 chronic subdural hematoma and 1 permanent extrinsic ocular muscle deficit. Patients were discharged after 2.4 ± 1.3 days. The most common histotype was meningioma (86.4%). Proptosis improved in all cases, visual deficit in 66.6%, and diplopia in 76.9%. These results were confirmed by the review of the 127 cases reported in the literature. CONCLUSIONS: Despite its recent introduction, a significant number of spheno-orbital lesions treated with an eTOA are being reported. Its main advantages are favorable patient outcome and optimal cosmetic results, with minimal morbidity and quick recovery. This approach can be combined with other surgical routes or adjuvant therapies for complex tumors. However, it is a technically demanding procedure, requiring specific skills in endoscopic surgery, that should be reserved to dedicated centers.

Clinical characterization of non-ketotic hyperglycemia-related seizures: A systematic review and individual participant data meta-analysis.

New-onset epileptic seizures and status epilepticus (SE) are the most frequent neurological manifestations of non-ketotic hyperglycemia (NKH), an acute complication of diabetes mellitus (DM). Treatment consists of the correction of the underlying metabolic disorder, whereas anti-seizure medications (ASMs) may even worsen seizures. Evidence on NKH-related seizures is currently restricted to case reports and small case-series. We conducted a systematic review of the PubMed, Embase, and Cochrane Library databases to provide a comprehensive description of NKH-related seizures. Statistical analyses were performed to explore possible associations of glycemic and osmolarity levels with clinical variables. We selected 130 publications and 332 patients (186 males, mean age: 61.1 years). DM was newly-diagnosed in 40%. Mean glycemia and osmolarity levels at presentation were 529.7 mg/dL and 309.6 mmol/mol, respectively; 22.6% showed other neurological symptoms besides seizures. Focal motor seizures were the prominent seizure type (49.4%); non-motor focal seizures (23.2%) most commonly manifested as visual symptoms. Reflex seizures occurred in 10.5%. Brain MRI in 48.7% of cases showed focal T2 subcortical hypodensity and/or overlying cortical T2 hyperintensity with DWI restriction. ASMs were administered in 54.2% of cases, achieving seizure control in just 18.3%. Higher osmolarity levels were associated with newly-diagnosed DM (p = 0.002) and other symptoms at presentation (p < 0.001). Glycemic values were higher in patients with focal aware seizures with motor onset compared to those with focal seizures without motor onset (p = 0.0046) or focal seizures with impaired awareness (p = 0.0306). Lower glycemic values were associated with reflex seizures (p = 0.036) and ASM administration (p < 0.001). NKH-related seizures should be suspected in adults with new-onset clustering focal seizures arising from the motor or posterior cortices, even in the absence of a history of DM. Typical focal changes on brain MRI, while not pathognomonic, can drive the clinical diagnosis. Statistical associations suggest a key role of hyperglycemia in the excitability of higher-energy-demanding cortical areas.

Endoscopic endonasal approach for loco-regional recurrent clivus chordomas.

•EEA represents an ideal approach for loco-regional recurrent CCs.•EEA is well tolerated, with preservation of patients QoL.•EEA can be considered for patients with perspectives of adjuvant therapies.•Otherwise, EEA can be considered only in selected cases with a palliative aim.

Role of endoscopic endonasal approach for craniopharyngiomas extending into the third ventricle in adults.

•EAA is an innovative, promising, safe and effective approach for 3VCPs.•Key of success is surgeon learning curve in endoscopy and patients selection.•With correct indications, EEA gives GTR and morbidity rate similar to other routes.•Clinical, tumoral and anatomical features should be considered for EEA selection.

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Machine learning-based clinical outcome prediction in surgery for acromegaly.

PURPOSE: Biochemical remission (BR), gross total resection (GTR), and intraoperative cerebrospinal fluid (CSF) leaks are important metrics in transsphenoidal surgery for acromegaly, and prediction of their likelihood using machine learning would be clinically advantageous. We aim to develop and externally validate clinical prediction models for outcomes after transsphenoidal surgery for acromegaly. METHODS: Using data from two registries, we develop and externally validate machine learning models for GTR, BR, and CSF leaks after endoscopic transsphenoidal surgery in acromegalic patients. For the model development a registry from Bologna, Italy was used. External validation was then performed using data from Zurich, Switzerland. Gender, age, prior surgery, as well as Hardy and Knosp classification were used as input features. Discrimination and calibration metrics were assessed. RESULTS: The derivation cohort consisted of 307 patients (43.3% male; mean [SD] age, 47.2 [12.7] years). GTR was achieved in 226 (73.6%) and BR in 245 (79.8%) patients. In the external validation cohort with 46 patients, 31 (75.6%) achieved GTR and 31 (77.5%) achieved BR. Area under the curve (AUC) at external validation was 0.75 (95% confidence interval: 0.59-0.88) for GTR, 0.63 (0.40-0.82) for BR, as well as 0.77 (0.62-0.91) for intraoperative CSF leaks. While prior surgery was the most important variable for prediction of GTR, age, and Hardy grading contributed most to the predictions of BR and CSF leaks, respectively. CONCLUSIONS: Gross total resection, biochemical remission, and CSF leaks remain hard to predict, but machine learning offers potential in helping to tailor surgical therapy. We demonstrate the feasibility of developing and externally validating clinical prediction models for these outcomes after surgery for acromegaly and lay the groundwork for development of a multicenter model with more robust generalization.

A practical algorithm to predict postsurgical recurrence and progression of pituitary neuroendocrine tumours (PitNET)s.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNET)s can be aggressive, thus presenting local invasion, postsurgical recurrence and/or resistance to treatment, responsible for significant morbidity. The study aimed at identifying prognostic factors of postsurgical outcome using data-driven classification of patients. DESIGN: Retrospective observational study. METHODS: Clinicopathological and radiological data of patients with PitNET treated via endoscopic endonasal surgery were collected. Tumour recurrence/progression and progression-free survival were assessed by classification tree analysis (CTA) and Kaplan-Meier curves, respectively. Histological subtype, cavernous/sphenoid sinus invasion, mitosis, Ki-67, p53, Trouillas' grading, degree of tumour exeresis and postsurgery disease activity were also evaluated. RESULTS: A total of 1066 (466 gonadotroph, 287 somatotroph, 148 lactotroph, 157 corticotroph and 8 thyrotroph) tumours were included; 21.7% invaded the cavernous/sphenoid sinus. Based on Trouillas' classification, 64.3% were grade 1a, 14.2% 1b, 16.1% 2a, and 5.4% 2b; 18.3% had >2/10 HPF mitoses, 24.9% had Ki-67 ≥3%; 15.8% were positive for p53. Exeresis was radical in 81.2% of the cases. Median follow-up was 59.2 months. At last evaluation, 79.4% of the patients were cured; 20.6% had disease persistence, controlled by medical treatment in 18.3% of them. Disease recurrence/progression was recorded in 10.9% of the cases. CTA identified 5 distinct patient subgroups with different risk of disease recurrence/progression. Grade 2 of the Trouillas' grading, >2/10 HPF mitoses, Ki-67 ≥3%, p53 protein expression (P < .001), tumour invasion (P = .002) and ACTH-subtype (P = .003) were identified as risk factors of disease recurrence/progression. CONCLUSIONS: The combined evaluation of Trouillas' grading, proliferation indexes and immunohistochemistry appears promising in the prediction of surgical outcome in PitNET.

Outcome of Endoscopic Endonasal Surgery in Pediatric Craniopharyngiomas.

BACKGROUND: In the last years, few reports have shown the feasibility of the endoscopic endonasal approach (EEA) for craniopharyngiomas in pediatric patients. For these tumors, recent studies have suggested less aggressive surgery, favoring the preservation of the patient's quality of life. OBJECTIVE: The aim of this study was to assess the outcome of the EEA in a large series with specific attention on the long-term functional sequelae. MATERIALS: All consecutive pediatric craniopharyngiomas operated on through this approach since 2000 were included in the study. Preoperative and postoperative operative clinical, radiologic, and pathologic features were retrieved from patient records (mean follow-up, 72 ± 67 months). RESULTS: The series included 25 patients (12 female; mean age, 8.9 ± 4.1 years). Most of the tumors presented with a supradiaphragmatic extension (88%). Removal was radical in 23 patients (92%). Complications consisted of 6 cerebrospinal fluid leaks (24%). One patient (4%) died of postoperative respiratory complications. Most patients (92%) developed panhypopituitarism and visual disturbances normalized or improved in 6 patients (43%). At follow-up, 9 patients (36%) were overweight/obese (6 were already overweight before surgery). The tumor recurrence rate was 19%. CONCLUSIONS: EEA can be an effective approach for midline craniopharyngiomas in children older than 3 years. It gives a satisfactory exposure of the suprasellar region and an adequate assessment of the brain-tumor interface. Its main limitations are age-related anatomic features of nasal/paranasal sinuses and the risk of cerebrospinal fluid leak.

Clival chordomas: considerations after 16 years of endoscopic endonasal surgery.

OBJECTIVE In the past decade, the role of the endoscopic endonasal approach (EEA) has relevantly evolved for skull base tumors. In this study, the authors review their surgical experience with using an EEA in the treatment of clival chordomas, which are deep and infiltrative skull base lesions, and they highlight the advantages and limitations of this ventral approach. METHODS All consecutive cases of chordoma treated with an EEA between 1998 and 2015 at a single institution are included in this study. Preoperative assessment consisted of neuroimaging (MRI and CT with angiography sequences) and endocrinological, neurological, and ophthalmological evaluations, which were repeated 3 months after surgery and annually thereafter. Postoperative adjuvant therapies were considered. RESULTS Sixty-five patients (male/female ratio 1:0.9) were included in this study. The median age was 48 years (range 9-80 years). Gross-total resection (GTR) was achieved in 47 cases (58.7%). On univariate analysis, primary procedures (p = 0.001), location in the superior or middle third of the clivus (p = 0.043), extradural location (p = 0.035), and histology of conventional chordomas (p = 0.013) were associated with a higher rate of GTR. The complication rate was 15.1%, and there were no perioperative deaths. Most complications did not result in permanent sequelae and included 2 CSF leaks (2.5%), 5 transient cranial nerve VI palsies (6.2%), and 2 internal carotid artery injuries (2.5%), which were treated with coil occlusion of the internal carotid artery without neurological deficits. Three patients (3.8%) presented with complications resulting in permanent neurological deficits due to a postoperative hematoma (1.2%) causing a hemiparesis, and 2 permanent ophthalmoplegias (2.5%). Seventeen patients (26.2%) have died of tumor progression over the course of follow-up (median 52 months, range 7-159 months). Based on Kaplan-Meier analysis, the survival rate was 77% at 5 years and 57% at 10 years. On multivariate analysis, the extent of tumor removal (p = 0.001) and the absence of previous treatments (p = 0.001) proved to be correlated with a longer survival rate. CONCLUSIONS The EEA was associated with a high rate of tumor removal and symptom control, with low morbidity and preservation of a good quality of life. These results allow for a satisfactory overall survival rate, particularly after GTR and for primary surgery. Considering these results, the authors believe that an EEA can be a helpful tool in chordoma surgery, achieving a good balance between as much tumor removal as possible and the preservation of an acceptable patient quality of life.

Acromegaly is associated with increased cancer risk: a survey in Italy.

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68, P < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58, P = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34, P < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87, P < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.

Endoscopic Endonasal Surgery for Pituitary Apoplexy: Evidence On a 75-Case Series From a Tertiary Care Center.

BACKGROUND: The optimal management of pituitary apoplexy (PA) remains debated. The aim of this study was to assess the outcome of the transsphenoidal approach for PA in a large surgical experience. MATERIALS: Each consecutive case of PA consecutively operated by endoscopic endonasal approach from our tertiary care center, from 1998 to 2015, was included in this series. RESULTS: Seventy-five patients (47 male; mean age 52.4 ± 16.2 years) were included. Mean follow-up was 69.3 ± 46.7 months. On admission, all patients presented with abrupt severe headache (100%), associated with anterior hypopituitarism in 51 patients (68%), visual disturbances in 55 (73.4%), ophthalmoplegia in 38 (50.7%), and a remarkable reduction of consciousness in 2 (2.6%). Apoplexy proved to be ischemic in 35 patients (46.7%) and hemorrhagic in 40 (53.3%). Patients with hemorrhagic necrosis presented more often with major suprasellar expansion (P = 0.012) Radical removal was achieved in 60 cases (80%). Surgical morbidity consisted in one case of postoperative cerebrospinal fluid leak (1.3%). Anterior hypopituitarism worsened in 15 cases (20%), and diabetes insipidus occurred in 4 cases (5.3%). Ophthalmoplegia improved/normalized in 71% and visual symptoms in 85.5% of the patients, with better results achieved in ischemic forms (P = 0.043). The 2 comatose patients regained normal consciousness. CONCLUSIONS: The endoscopic endonasal approach represents a valid, effective, and safe technique in the management of PA. Favorable outcomes can be achieved by referring patients to dedicated pituitary centers with a multidisciplinary team. Further studies are still needed to define criteria for surgical indication and to identify outcome predictors.

The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3.

The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.

Postoperative outcome of body core temperature rhythm and sleep-wake cycle in third ventricle craniopharyngiomas.

OBJECTIVE One of the more serious risks in the treatment of third ventricle craniopharyngiomas is represented by hypothalamic damage. Recently, many papers have reported the expansion of the indications for the endoscopic endonasal approach (EEA) to be used for these tumors as well. The aim of this study was to assess the outcome of sleep-wake cycle and body core temperature (BCT), both depending on hypothalamic control, in patients affected by craniopharyngiomas involving the third ventricle that were surgically treated via an EEA. METHODS All consecutive adult patients with craniopharyngiomas that were treated at one center via an EEA between 2014 and 2016 were prospectively included. Each patient underwent neuroradiological, endocrinological, and ophthalmological evaluation; 24-hour monitoring of the BCT rhythm; and the sleep-wake cycle before surgery and at follow-up of at least 6 months. RESULTS Ten patients were included in the study (male/female ratio 4:6, mean age 48.6 years, SD 15.9 years). Gross-total resection was achieved in 8 cases. Preoperative BCT rhythm was pathological in 6 patients. After surgery, these disturbances resolved in 2 cases, improved in another 3, and remained the same in 1 patient; also, 1 case of de novo onset was observed. Before surgery the sleep-wake cycle was pathological in 8 cases, and it was restored in 4 patients at follow-up. After surgery the number of patients reporting diurnal naps increased from 7 to 9. CONCLUSIONS The outcome of the sleep-wake cycle and BCT analyzed after EEA in this study is promising. Despite the short duration of the authors' experience, they consider these results encouraging; additional series are needed to confirm the preliminary findings.