Correction to: Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study.

The members of the PERNO Study Group were not individually captured in the metadata of the original publication. They are included in the metadata of this publication.

Which elderly newly diagnosed glioblastoma patients can benefit from radiotherapy and temozolomide? A PERNO prospective study.

The role of temozolomide concurrent with and adjuvant to radiotherapy (RT/TMZ) in elderly patients with glioblastoma (GBM) remains unclear. We evaluated the outcome of patients >70 years in the context of the Project of Emilia-Romagna Region in Neuro-Oncology (PERNO), the first Italian prospective observational population-based study in neuro-oncology. For this analysis the criteria for selecting patients enrolled in the PERNO study were: age >70 years; PS 0-3; histologically confirmed GBM; postoperative radiotherapy (RT) after surgery with or without concomitant temozolomide (TMZ) or postsurgical TMZ alone. Between January 2009 and December 2010, 76 GBM elderly patients were identified in the prospective PERNO study. Twenty-three patients did not receive any treatment after surgery, and 53 patients received postsurgical treatments (25 patients received RT alone and 28 patients RT/TMZ). Median survival was 11.1 months (95 % CI 8.8-13.5), adding temozolomide concomitant and adjuvant to radiotherapy it was 11.6 months (95 % CI 8.6-14.6), and 9.3 months (95 % CI 8.1-10.6) in patients treated with RT alone (P = 0.164). However, patients with MGMT methylated treated with RT/TMZ obtained a better survival (17.2 months, 95 % CI 11.5-22.9) (P = 0.042). No difference in terms of survival were observed if patients with MGMT unmethylated tumor received RT alone, or RT/TMZ or, in MGMT methylated tumor, if patients received radiotherapy alone. In elderly patients RT/TMZ represent a widely used approach but it is effective with methylated MGMT tumors only.

How to avoid trivial mistakes during IPG replacement in patients treated with DBS for movement disorders: technical note from 13-years experience.

PURPOSE: Recent data suggest how adverse events occur more frequently after Implantable Pulse Generator (IPG) replacement than during the deep electrode positioning in patients treated with Deep Brain Stimulation (DBS). For instance, erroneous extension adjustment to change in laterality and inaccurate lead connection represent problems, which strongly affect patients' outcome. We analyzed our data after 13 years of IPG replacement. MATERIALS AND METHODS: We treated 107 patients (83 PD and 24 Dystonia) with DBS in 13 years. The Dual Channel IPGs replaced during this period were 91. 25 patients needed more than one replacement, especially among the dystonic population. During surgery, we temporarily marked in all the cases the right extension lead before the disconnection from the exhausted IPG. Good impedances were intraoperatively checked in all the cases. RESULTS: Our surgical technique allowed us to avoid any erroneous change in laterality or abnormal impedances due to a suboptimal connection to the IPG. The mean duration of the operation was 25 min and a quick postoperative restart of DBS was possible in all the cases. Stability of symptoms after IPG replacement was achieved in all the patients, with an accurate clinical management within the first 48-72 postoperative hours. CONCLUSION: Our surgical and postoperative management demonstrates how to avoid some important adverse events with some easy steps, without any discomfort for the patients in terms of duration of surgery or longer hospitalization. Thus, stability of symptoms after the IPG replacement may be easily guaranteed during the first postoperative period.

Transpars approach for L5-S1 foraminal and extra-foraminal lumbar disc herniations: technical note.

BACKGROUND: The short pars and the narrowed surgical corridor for far lateral L5S1 herniation make the transpars approach challenging. The aim of this study is to determine the feasibility, efficacy, and safety of the transpars microscopic approach for the treatment of L5-S1 foraminal and extraforaminal lumbar disc herniation. METHODS: From 2015 to 2019, patients with L5-S1 far lateral lumbar disc herniation were prospectively recruited. Drug intake, working days lost, NRS-leg, NRS-back, nerve-root palsy, Oswestry disability-index, Macnab criteria were recorded before surgery and at follow-up. Patients were seen at 1-6-12 months after surgery. Lumbar dynamic X-rays were performed at 6-12 months after surgery and again at 2-4 years after surgery. Key-steps of surgery are described. RESULTS: Fourteen patients were enrolled. NRS-leg and NRS-back scores significantly improved (from 7.93 to 1.43 and from 3.2 to 0.6, respectively; P<0.0001). Oswestry Score significantly decreased (from 63.14 to 19.36 at 12 months; P<0.0001). L5 Root palsy improved in all cases (from 3.72/5 to 5/5; P<0.0001). At 12-months, excellent or good outcome (Macnab criteria) was achieved in 12 (85.7%) and 2 (14.3%) patients, respectively. All patients who were not retired returned to work within 30 days after surgery. No recurrence, instability or re-operations occurred. CONCLUSIONS: The trans pars microscopic approach is feasible, safe, and effective for L5-S1 foraminal and extraforaminal disc herniation. During surgery, the key-point is the oblique working angle, directed caudally, parallel to L5 pedicle. The iliac crest does not seem to constitute an obstacle.

Is the resection of gliomas in Wernicke's area reliable? : Wernicke's area resection.

Wernicke's area was, for a long time, considered a non-removable area and patients affected by low-grade gliomas (LGGs) or high-grade gliomas (HGGs) in this region were considered inoperable. Several studies have demonstrated a large functional reshaping of language networks in patients affected by gliomas or acute stroke involving Wernicke's territories, and the complete resection of this region invaded by LGG has recently been reported. We report our experience in the removal of Wernicke's territories invaded by gliomas. Four patients underwent awake surgery, with neuropsychological and neurophysiological monitoring and direct cortico-subcortical bipolar stimulation, for resection of LGG (one case) and HGGs (three cases) invading Wernicke's territories. Resection rates were evaluated by means of magnetic resonance imaging (MRI) and computed tomography (CT) perfusion for LGG and HGGs, respectively. HGGs were totally resected and LGG was partially resected (67%), according to functional limits. No patients reported neurological deficit. The patient affected by LGG underwent postoperative chemotherapy. Two of the patients harbouring HGGs died 21 and 23 months after surgery and postoperative adjuvant treatment, respectively. The third one is still alive and progression-free 21 months after surgery. Awake surgery is a reliable and effective technique for resection of gliomas invading Wernicke's territories without postoperative permanent deficit. LGGs in this region can safely be removed, according to the functional subcortical boundaries, allowing postoperative adjuvant treatment, functional reshaping and multi-step surgery. HGGs, instead, can be completely removed without deficits and sometimes beyond the contrast enhancement area, allowing the best possible oncological prognosis for the patients.

Functional outcome of patients with unstable single-level/two-level lumbar stenosis treated with decompression plus divergent screws (cortical bone trajectory) or percutaneous convergent pedicle screws.

BACKGROUND: The aim of this prospective comparative study was to assess the functional outcome in two groups of patients suffering from spinal lumbar instability and treated by decompression and stabilization with posterior lumbar interbody fusion using percutaneous pedicle screws (PCT) or a novel technique of divergent pedicle screws insertion using a cortical bone divergent trajectory (CBT). Functional outcome after surgery has been evaluated using Numeric Rating Scale (NRS), Modified Rankin Scale (MRS), Smiley-Webster Scale, and Oswestry Disability Index (ODI). METHODS: Seventy-two consecutive patients were treated at our department from February 2013 to February 2018 for one-two levels unstable stenosis with one-year follow-up. Forty-one patients were treated with percutaneous screws and thirty-one patients were treated with divergent cortical bone trajectory screws. Functional outcome and complications were analyzed with logistic regression analysis. No funding was received for this research. RESULTS: Pain significantly improved in both groups. Charlson Comorbidity Index (CCI≥3) was the only variable associated with increased risk of complications (OR=5.73, P=0.04). Patients with BMI≥27.4 (median value) and patients with percutaneous screws had an increased risk of a worse Smiley-Webster Score (OR=3.675; P=0.029 and OR=3.747; P=0.05, respectively). Patients with BMI≥27.4, patients with percutaneous screws and patients with more comorbidities (CCI≥3) showed a higher risk of presenting severe/crippling Oswestry Disability Index Score (OR=6; P=0.027, OR=10.747; P=0.04 and OR=6.310; P=0.043, respectively). CONCLUSIONS: Cortical bone trajectory screws technique could represent a valid alternative to the traditional percutaneous pedicle screws technique in posterior lumbar interbody fusion.

Remodulation of neurosurgical activities in an Italian region (Emilia-Romagna) under COVID-19 emergency: maintaining the standard of care during the crisis.

BACKGROUND: The impact of COVID-19 outbreak in the neurosurgical practice has been dramatic, imposing several limitations. The aim of this study is to present how the neurosurgical departments of Emilia-Romagna, a northern Italian region, have re-set their organization to maintain the higher standard of care as possible. METHODS: All operative room and outpatient activities performed during the COVID-19 emergency in the neurosurgical department of Emilia-Romagna have been collected and compared to the means of the same timeframe in 2018 and 2019. RESULTS: In 2020, 205 surgical procedures and 466 outpatient consultations have been performed, representing respectively 28.8% and 26.4% of the previous biennium. The most of OR procedures had been emergencies/urgencies and oncological patients (113 and 66 vs. 164.5 and 84.5, respectively, of the previous biennium), while elective surgeries decrease up to -97.1%, as for spinal nerves and endoscopic skull base procedures. The patients phone contacts and telemedicine evaluations of their examinations have permitted to reduce the hospital access for outpatients of 75.6%, but these modalities have, also, permitted to follow-up a large number of cases. CONCLUSIONS: The outbreak of COVID-19 has imposed several limits to our current practice, however this should not represent an excuse to reduce the standard of care. In our experience, the net integration of different local centers has permitted for each of them to effectively cope the crisis, managing the local cases requiring a prompt surgery and keeping the care continuity with already discharged patients.

Pituitary apoplexy and COVID-19 vaccination: a case report and literature review.

A 50-year-old man was admitted to our hospital for vomit, nausea, diplopia, and headache resistant to analgesic drugs. Symptoms started the day after his third COVID-19 mRNA vaccine (Moderna) whereas SARS-CoV-2 nasal swab was negative. Pituitary MRI showed recent bleeding in macroadenoma, consistent with pituitary apoplexy. Adverse Drug Reaction was reported to AIFA (Italian Medicines Agency).A stress dexamethasone dose was administered due to the risk of adrenal insufficiency and to reduce oedema. Biochemistry showed secondary hypogonadism; inflammatory markers were elevated as well as white blood cells count, fibrinogen and D-dimer. Pituitary tumour transsphenoidal resection was performed and pathology report was consistent with pituitary adenoma with focal haemorrhage and necrosis; we found immunohistochemical evidence for SARS-CoV-2 proteins next to pituitary capillaries, in the presence of an evident lymphocyte infiltrate.Few cases of pituitary apoplexy after COVID-19 vaccination and infection have been reported. Several hypotheses have been suggested to explain this clinical picture, including cross-reactivity between SARS-CoV-2 and pituitary proteins, COVID-19-associated coagulopathy, infection-driven acutely increased pituitary blood demand, anti-Platelet Factor 4/heparin antibodies development after vaccine administration. Ours is the first case of SARS-CoV-2 evidence in pituitary tissue, suggesting that endothelial infection of pituitary capillaries could be present before vaccination, possibly due to a previous asymptomatic SARS-CoV-2 infection. Our case underlines that SARS-CoV-2 can associate with apoplexy by penetrating the central nervous system, even in cases of negative nasal swab. Patients with pituitary tumours may develop pituitary apoplexy after exposure to SARS-CoV-2, therefore clinicians should be aware of this risk.

Surgical Treatment of Diffuse Idiopathic Skeletal Hyperostosis (DISH) Involving the Cervical Spine: Technical Nuances and Outcome of a Multicenter Experience.

STUDY DESIGN: Retrospective multicenter. OBJECTIVES: diffuse idiopathic skeletal hyperostosis (DISH) involving the cervical spine is a rare condition determining disabling aero-digestive symptoms. We analyzed impact of preoperative settings and intraoperative techniques on outcome of patients undergoing surgery for DISH. METHODS: Patients with DISH needing for anterior cervical osteophytectomy were collected. Swallow studies and endoscopy supported imaging in targeting bone decompression. Patients characteristics, clinico-radiological presentation, outcome and surgical strategies were recorded. Impact on clinical outcome of duration and time to surgery and different surgical techniques was evaluated through ANOVA. RESULTS: 24 patients underwent surgery. No correlation was noted between specific spinal levels affected by DISH and severity of pre-operative dysphagia. A trend toward a full clinical improvement was noted preferring the chisel (P = 0.12) to the burr (P = 0.65), and whenever C2-C3 was decompressed, whether hyperostosis included that level (P = 0.15). Use of curved chisel reduced the surgical times (P = 0.02) and, together with the nasogastric tube, the risk of complications, while bone removal involving 3 levels or more (P = 0.04) and shorter waiting times for surgery (P < 0.001) positively influenced a complete swallowing recovery. Early decompressions were preferred, resulting in 66.6% of patients reporting disappearance of symptoms within 7 days. One and two recurrences respectively at clinical and radiological follow-up were registered 18-30 months after surgery. CONCLUSION: The "age of DISH" counts more than patients' age with timeliness of decompression being crucial in determining clinical outcome even with a preoperative mild dysphagia. Targeted bone resections could be reasonable in elderly patients, while in younger ones more extended decompressions should be preferred.

Impact of COVID-19 on surgical activities and personnel: lessons for the future.

BACKGROUND: COVID-19 pandemic has impacted professional, economic and social activities. In the surgical field, it has brought changes to operating activities, the organization of workforces, the protection measures for patients and personnel against possible intraoperative transmissions as well as training young surgeons. This study intends to assess the extent of this impact in our institution. METHODS: The patients operated on in nine Operating Units (OUs) in the period February 1 - March 31, 2020, with follow-ups on April 30, 2020, were evaluated both retrospectively and prospectively. Organizational, clinical and impact parameters on staff were evaluated. RESULTS: Of the 833 consecutive admitted patients, 742 were operated on, 705 of whom were recruited for the study. Compared to the same period in 2019 there was a decrease in the number of operations (742 compared to 1187), similar use of intensive care unit (ICU), a diagnostic activity only for symptomatic patients, heterogeneity in organizational behaviors, an impact on staff who highlighted concerns about getting sick or passing the infection on to others (87.64%) or their family members (75.14%). CONCLUSIONS: The present study made it possible to detect the need to make significant changes in the clinical, organizational and teaching fields, for which some operational proposals are suggested.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Do antiplatelet and anticoagulant drugs modify outcome of patients treated for chronic subdural hematoma? Still a controversial issue.

BACKGROUND: Anticoagulants (ACs) and antiplatelet aggregation agents (AAAs) seem to be correlated to a higher incidence of chronic subdural hematoma (CSDH) but whether or not they contribute to its recurrence is debated. Few data are available on clinical outcomes and indications for the management of this therapy are not so well defined. We investigated the role of ACs and AAAs in modifying patients' clinical outcomes treated for CSDH, especially for re-bleedings. METHODS: This retrospective study, enrolled patients treated for CSDH. Patients characteristics were recorded including drugs used (antiplatelet/anticoagulant) and clinical conditions (Modified Rankin Scale [mRS]) upon admission. Patients underwent surgery (burrhole vs. minicraniectomy) with subdural drainage positioning. Clinical/radiological follow-ups were performed at one and six months. Chi-square/Fisher's Exact test were used to compare variables and stepwise backward logistic regression analysis was used for defining their impact on complications, risk of re-bleeding and reoperation. RESULTS: Overall, 230 patients (45 on ACs, 76 on AAAs and nine on both) were enrolled. Higher mRS scores were significantly associated with a higher risk of general complications (OR=3.78, 95% CI: 1.66-8.62, P=0.002), higher risk of rebleeding (OR =15.82, 95% CI: 4.33-57.90, P<0.001) and re-operation (OR=11.39, 95% CI: 3.35-37.56, P<0.0001). No statistically significant association was found between AAAs or ACs and complications or re-bleedings or risk of reoperation. CONCLUSIONS: AAAs and ACs alone do not seem to worsen the clinical outcome or increase re-bleedings. mRS may be a predicting factor, since patients with higher scores showed a worse outcome and an increased risk of re-bleeding, general complications and reoperation.

Pallidal stimulation for segmental dystonia: long term follow up of 11 consecutive patients.

Pallidal stimulation is a convincing and valid alternative for primary generalized dystonia refractory to medical therapy or botulinum toxin. However, the clinical outcome reported in literature is variable most likely because of heterogeneity DBS techniques employed and /or to clinical dystonic pattern of the patients who undergo surgery. In this study, we report the long term follow up of a homogeneous group of eleven subjects affected by segmental dystonia who were treated with bilateral stimulation of the Globus Pallidus pars interna (GPi) from the years 2000 to 2008. All the patients were evaluated, before surgery and at 6-12-24-36 months after the treatment, in accordance with the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS). Our study indicates that DBS promotes an early and significant improvement at 6 months with an even and a better outcome later on. The analysis of specific sub items of the BFMDRS revealed an earlier and striking benefit not only as far as segmental motor function of the limbs but also for the complex cranial functions like face, (eyes and mouth), speech and swallowing, differently from results reported in primary generalized dystonia. Deep Brain Stimulation of GPi should be considered a valid indication for both generalized and segmental dystonia when other therapies appear ineffective.

Standard of care, controversies, and innovations in the medical treatment of severe traumatic brain injury.

Severe traumatic brain injury (STBI) is characterized by a primary injury which cannot be reversed and a secondary injury that can be prevented or reversed. Management of STBI patients in intensive care mainly aims at preventing the secondary injury. Treatment aims to: reducing ICP pressure (that can result in an ischemic insult); avoiding hypotension, hyperthermia, or hypoxemia; maintaining a normal electrolytes homeostasis; treating the autonomic dysfunction syndrome, coagulopathies, acute kidney injury and maintaining an adequate nutrition. Many treatment protocols are already well established, while many others are still debated. Moreover, new frontiers in STBI management are represented by the neurovascular regeneration and neurorestoration which are showing very promising results even if most of them still need a clinical validation. In this paper we review standard of care, controversies and innovations in the medical treatment of STBI.

The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase Methylation Status in Glioblastoma Patients: The Female Power.

BACKGROUND: Clinical and molecular factors are essential to define the prognosis in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of surgical resection are the most relevant prognostic factors. Our investigation of the role of gender in predicting prognosis shows a slight survival advantage for female patients. METHODS: We performed a prospective evaluation of the Project of Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors in patients with GBM who received standard treatment. RESULTS: A total of 169 patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively. MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival was longer in the methylated females compared with the methylated males (P = 0.028) but was not significantly different between the unmethylated females and the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT methylation status considered together (methylated females vs. methylated males; hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017), age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI, 0.948-0.982; P < 0.001) were significantly correlated with survival. CONCLUSIONS: Survival was consistently longer among MGMT methylated females compared with males. Gender can be considered as a further prognostic factor.