Eosinophilic granuloma of the calvarium: is conservative management a valid option? Illustrative case and systematic review of the literature.

INTRODUCTION: Eosinophilic granuloma (EG) is the most common form of Langerhans cell histiocytosis, presenting as a single osteolytic lesion of the calvarium. Its diagnosis is based on typical clinical and radiological features. While surgical resection has been the standard treatment for EG, growing evidence favors watchful waiting, as unifocal calvarial lesions appear to frequently undergo spontaneous remission. However, histopathological confirmations of this hypothesis are still very limited. METHODS: Methods. Here, we report a case of EG with typical clinical and radiological features which, due to intervening circumstances, was resected in a delayed fashion. Moreover, we perform a systematic review of the literature on conservative management of EG. RESULTS: In our case, histological examination showed ongoing bone regeneration with no traces of the disease. Through our literature review, we found 47 cases of calvarial EG managed with watchful waiting. No active intervention was required in 43 cases (91%). Four patients (9%) received surgery or chemotherapy due to the persistence/progression of symptoms or family request. Three reports other than ours documented spontaneous disease remission in surgically resected EG upon histopathological examination. CONCLUSION: Our report provides further evidence that watchful waiting can be a reasonable option in the management of single calvarial EG.

Selective cell cycle arrest in glioblastoma cell lines by quantum molecular resonance alone or in combination with temozolomide.

BACKGROUND: Glioblastoma is the most aggressive form of brain cancer, characterised by high proliferation rates and cell invasiveness. Despite advances in surgery and radio-chemotherapy, patients continue to have poor prognoses, with a survival rate of 14-15 months. Thus, new therapeutic strategies are needed. Non-ionising electromagnetic fields represent an emerging option given the potential advantages of safety, low toxicity and the possibility to be combined with other therapies. METHODS: Here, the anticancer activity of quantum molecular resonance (QMR) was investigated. For this purpose, three glioblastoma cell lines were tested, and the QMR effect was evaluated on cancer cell proliferation rate and aggressiveness. To clarify the QMR mechanism of action, the proteomic asset after stimulation was delineated. Mesenchymal stromal cells and astrocytes were used as healthy controls. RESULTS: QMR affected cancer cell proliferation, inducing a significant arrest of cell cycle progression and reducing cancer tumorigenicity. These parameters were not altered in healthy control cells. Proteomic analysis suggested that QMR acts not only on DNA replication but also on the machinery involved in the mitotic spindle assembly and chromosome segregation. Moreover, in a combined therapy assessment, QMR significantly enhanced temozolomide efficacy. CONCLUSIONS: QMR technology appears to be a promising tool for glioblastoma treatment.

The role of the craniotomy size in the surgical evacuation of acute subdural hematomas in elderly patients: a retrospective multicentric study.

BACKGROUND: Elderly patients operated for an acute subdural hematoma (ASDH) frequently have a poor outcome, with a high frequency of death, vegetative status, or severe disability (Glasgow Outcome Score, GOS, 1-3). Minicraniotomy has been proposed as a minimally invasive surgical treatment to reduce the impact of surgery in the elderly population. The present study aimed to compare the influence of the size of the craniotomy on the functional outcome in patients undergoing surgical treatment for ASDH. METHODS: We selected patients ≥70 years old admitted to 5 Italian tertiary referral neurosurgical for the treatment of a post-traumatic ASDH between January 1st 2016 and December 31st 2019. We collected demographic data, clinical data (GCS, GOS, Charlson Comorbidity Index-CCI, antiplatelet/anticoagulant therapy, neurological deficits, seizure, pupillary size, length of stay), surgical data (craniotomy size, dividing the patients into 3 groups based on the corresponding tertile, and surgery duration), radiological data (ASDH side and thickness, midline shift, other post-traumatic lesions, extent of ASDH evacuation) and we assessed the functional outcome at hospital discharge and 6-month follow-up considering GOS=1-3 as a poor outcome. ANOVA and Chi-squared tests and logistic regression models were used to assess differences in and associations between clinicalradiological characteristics and functional outcomes. RESULTS: We included 136 patients (76 males) with a mean age of 78±6 years. Forty-five patients underwent a small craniotomy, 47 a medium size, and 44 a large craniotomy. Among the different craniotomy size groups, there were no differences in gender, anticoagulant/antithrombotic therapy, CCI, side of ASDH, ASDH thickness, preoperative GCS, focal deficits, seizures, and presence of other posttraumatic lesions. Patients undergoing small craniotomies were older than patients undergoing medium-large craniotomies; ASDH treated with medium size craniotomy were thinner than the others; patients undergoing large craniotomies showed greater midline shift and a higher rate of anisocoria. The three groups did not differ for functional outcome and postoperative midline shift, but the length of surgery and the rate of >50% of ASDH evacuation were lower in the small craniotomy group. CONCLUSIONS: A small craniotomy was not inferior to larger craniotomies in determining functional outcomes in the treatment of ASDH in the elderly.

Imaging features and ultraearly hematoma growth in intracerebral hemorrhage associated with COVID-19.

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.

Pneumocephalus in subthalamic deep brain stimulation for Parkinson's disease: a comparison of two different surgical techniques considering factors conditioning brain shift and target precision.

BACKGROUND: Precise placement of electrodes in deep brain stimulation (DBS) may be influenced by brain shift caused by cerebrospinal fluid leaking or air inflow. We compared accuracy and treatment outcomes between a standard technique and one aiming at reducing brain shift. METHODS: We retrospectively reviewed 46 patients (92 targets) treated with bilateral subthalamic-DBS for Parkinson's disease. The patients were divided into two groups: group A surgery was performed in supine position with standard burr hole, dural opening, fibrin glue and gelfoam plugging. Group B patients were operated in a semi-sitting position with direct dural puncture to reduce CSF loss. We analysed target deviation on head CT performed immediately after surgery and at 1 month merged with preoperative MRI planning. We recorded pneumocephalus volume, brain atrophy and target correction by intraoperative neurophysiology (ION). RESULTS: In group A, the mean pneumocephalus volume was 10.55 cm3, mean brain volume 1116 cm3, mean target deviation 1.09 mm and ION corrected 70% of targets. In group B, mean pneumocephalus was 7.60 cm3 (p = 0.3048), mean brain volume 1132 cm3 (p = 0.6526), mean target deviation 0.64 mm (p = 0.0074) and ION corrected 50% of targets (p = 0.4886). Most leads' deviations realigned to the planned target after pneumocephalus reabsorbtion suggesting a deviation caused by displacement of anatomical structures due to brain shift. Definitive lead position was always decided with ION. CONCLUSIONS: The modified DBS technique significantly reduced errors of electrode placement, though such difference was clinically irrelevant. ION corrected a high amount of trajectories in both groups (70% vs 50%). The choice of either strategy is acceptable.

Neurosurgery in times of a pandemic: a survey of neurosurgical services during the COVID-19 outbreak in the Veneto region in Italy.

OBJECTIVE: The purpose of this study was to analyze the effect of the coronavirus disease 2019 (COVID-19) outbreak and of the subsequent lockdown on the neurosurgical services of the Veneto region in Italy compared to the previous 4 years. METHODS: A survey was conducted in all 6 neurosurgical departments in the Veneto region to collect data about surgical, inpatient care and endovascular procedures during the month of March for each year from 2016 to 2020. Safety measures to avoid infection from SARS-CoV-2 and any COVID-19 cases reported among neurosurgical patients or staff members were considered. RESULTS: The mean number of neurosurgical admissions for the month of March over the 2016-2019 period was 663, whereas in March 2020 admissions decreased by 42%. Emergency admissions decreased by 23%. The average number of neurosurgical procedures was 697, and declined by 30% (range -10% to -51% in individual centers). Emergency procedures decreased in the same period by 23%. Subarachnoid hemorrhage and spontaneous intracerebral hemorrhage both decreased in Veneto-by 25% and 22%, respectively. Coiling for unruptured aneurysm, coiling for ruptured aneurysm, and surgery for ruptured aneurysm or arteriovenous malformation diminished by 49%, 27%, and 78%, respectively. Endovascular procedures for acute ischemic stroke (AIS) increased by 33% in 2020 (28 procedures in total). There was a slight decrease (8%) in brain tumor surgeries. Neurosurgical admissions decreased by 25% and 35% for head trauma and spinal trauma, respectively, while surgical procedures for head trauma diminished by 19% and procedures for spinal trauma declined by 26%. Admissions and surgical treatments for degenerative spine were halved. Eleven healthcare workers and 8 patients were infected in the acute phase of the pandemic. CONCLUSIONS: This multicenter study describes the effects of a COVID-19 outbreak on neurosurgical activities in a vast region in Italy. Remodulation of neurosurgical activities has resulted in a significant reduction of elective and emergency surgeries compared to previous years. Most likely this is a combined result of cancellation of elective and postponable surgeries, increase of conservative management, increase in social restrictions, and in patients' fear of accessing hospitals. Curiously, only endovascular procedures for AIS have increased, possibly due to reduced physical activity or increased thrombosis in SARS-CoV-2. The confounding effect of thrombectomy increase over time cannot be excluded. No conclusion can be drawn on AIS incidence. Active monitoring with nasopharyngeal swabs, wearing face masks, and using separate pathways for infected patients reduce the risk of infection.

Acute subdural hematoma in the elderly: outcome analysis in a retrospective multicentric series of 213 patients.

OBJECTIVE: The objective of this study was to analyze the risk factors associated with the outcome of acute subdural hematoma (ASDH) in elderly patients treated either surgically or nonsurgically. METHODS: The authors performed a retrospective multicentric analysis of clinical and radiological data on patients aged ≥ 70 years who had been consecutively admitted to the neurosurgical department of 5 Italian hospitals for the management of posttraumatic ASDH in a 3-year period. Outcome was measured according to the Glasgow Outcome Scale (GOS) at discharge and at 6 months' follow-up. A GOS score of 1-3 was defined as a poor outcome and a GOS score of 4-5 as a good outcome. Univariate and multivariate statistics were used to determine outcome predictors in the entire study population and in the surgical group. RESULTS: Overall, 213 patients were admitted during the 3-year study period. Outcome was poor in 135 (63%) patients, as 65 (31%) died during their admission, 33 (15%) were in a vegetative state, and 37 (17%) had severe disability at discharge. Surgical patients had worse clinical and radiological findings on arrival or during their admission than the patients undergoing conservative treatment. Surgery was performed in 147 (69%) patients, and 114 (78%) of them had a poor outcome. In stratifying patients by their Glasgow Coma Scale (GCS) score, the authors found that surgery reduced mortality but not the frequency of a poor outcome in the patients with a moderate to severe GCS score. The GCS score and midline shift were the most significant predictors of outcome. Antiplatelet drugs were associated with better outcomes; however, patients taking such medications had a better GCS score and better radiological findings, which could have influenced the former finding. Patients with fixed pupils never had a good outcome. Age and Charlson Comorbidity Index were not associated with outcome. CONCLUSIONS: Traumatic ASDH in the elderly is a severe condition, with the GCS score and midline shift the stronger outcome predictors, while age per se and comorbidities were not associated with outcome. Antithrombotic drugs do not seem to negatively influence pretreatment status or posttreatment outcome. Surgery was performed in patients with a worse clinical and radiological status, reducing the rate of death but not the frequency of a poor outcome.

Techniques for pneumocephalus and brain shift reduction in DBS surgery: a review of the literature.

Deep brain stimulation has become an established therapeutic choice to manage the symptoms of medically refractory Parkinson's disease. Its efficacy is highly dependent on the accuracy of electrodes' positioning in the correct anatomical target. During DBS procedure, the opening of the dura mater induces the displacement of neural structures. This effect mainly depends on the loss of the physiological negative intracranial pressure, air inflow, and loss of cerebrospinal fluid. Several studies concentrated on correcting surgical techniques for DBS electrodes' positioning in order to reduce pneumocephalus which may result in therapeutic failure. The authors focused in particular on reducing the brain air window and maintaining the pressure gradient between intra- and extracranial compartments. A significant reduction of pneumocephalus and brain shift was obtained by excluding the opening of the subarachnoid space, by covering the dura mater opening with tissue sealant and by reducing the intracranial pressure in general anesthesia. Smaller burr hole diameters were not statistically relevant for reducing air inflow and displacement of anatomical targets. The review of the literature showed that conserving a physiological intra-extracranial pressure gradient plays a fundamental role in avoiding pneumocephalus and consequent displacement of brain structures, which improves surgical accuracy and DBS long-term results.

Complete embolization of jugular paragangliomas by direct puncture. Technical note.

Objective: Intra-arterial embolization of jugular paragangliomas is an established endovascular technique. Intratumoral embolization by direct puncture has been proposed, prior to surgical treatment or radiosurgery to reduce the risk of cranial nerve deficits. Methods: We examined the technical aspects of two patients with jugular paragangliomas embolized with liquid embolic agent by direct puncture of the lesion, as sole treatment. Results: Two patients with jugular paragangliomas presented with lower cranial nerve deficits. The first patient showed an extended lesion (55-mm) and was treated with partial intra-arterial embolization plus direct puncture and injection of Squid 18 and a second staged embolization by direct puncture and filling of the remainder of the lesion. The second patient with a smaller jugular paraganglioma (33-mm) was treated by single embolization by direct puncture of the tumor and injection of Squid 12 and Squid 18 obtaining complete filling of the lesion. No procedural complications were observed. Both patients showed no residual and initial improvement of the neurological deficits. Conclusion: The intratumoral embolization by direct puncture of jugular paragangliomas, under accurate radiological control is a safe procedure, and complete exclusion of the lesion can be obtained in selected cases. A staged particle embolization of the lesion by direct puncture can be proposed for large lesions. Only further studies with larger series and long-term follow-up will be able to define, if this strategy can be curative avoiding additional surgical or radio-surgical treatment.

Supplementary Tests in Idiopathic Normal Pressure Hydrocephalus: A Single-Center Experience with a Combined Lumbar Infusion Test and Tap Test.

BACKGROUND: The lumbar infusion test (LIT) and tap test (TT) have previously been described for the diagnosis and selection of appropriate surgical candidates in idiopathic normal pressure hydrocephalus (iNPH). METHODS: We retrospectively reviewed 81 consecutive patients with a clinical diagnosis of iNPH selected for supplementary testing. Clinical evaluation was scored with the Japanese Grading Scale for Normal Pressure Hydrocephalus, the Global Deterioration Score, and the modified Rankin Scale (mRS). The test protocol included a cerebrospinal fluid pressure monitoring (PMi), an LIT, and a TT. Patients were selected for surgery if outflow resistance was ≥14 mm Hg/mL/minute or if a clinical improvement was recorded after TT. RESULTS: Sixty-eight patients were selected for ventriculoperitoneal shunting; 72.8% had a positive PMi or LIT, 74.1% had a positive TT, and 63.0% were positive to both tests. Complications were all transient. Clinical evaluation at 12 months after shunting showed a global improvement in 60 patients (88.2%). Overall, 75.0% of patients had no significant disability (mRS score, 1 and 2), 20.6% had an mRS score of 3 or 4, and 4.4% had severe disability after surgery. The positive predictive value of PMi/LIT, TT, or both combined was similar (89.8, 90.0, and 88.2%); however, 21.7% of patients who improved after surgery were selected with either a positive LIT or TT alone. CONCLUSIONS: LIT and TT are complementary and they can easily be combined in sequence with a low complication rate and high probability of selecting patients with iNPH who may benefit from ventriculoperitoneal shunt surgery.

Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma.

PURPOSE: We evaluated the relationship between 11C-methionine PET (11C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. METHODS: A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative 11C-METH PET were analysed. Semiquantitative evaluation of the 11C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). RESULTS: In all patients, the tumour was identified on 11C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. CONCLUSION: 11C-METH PET parameters are significantly correlated with histological grade and IDH1 mutation status in patients with glioma. Grade, pathological classification, molecular biomarkers, SUVmax and SUVratio were prognostic factors for PFS in this cohort of patients. The trial was registered with ClinicalTrials.gov (registration: NCT02518061).

Implantation of Stereoelectroencephalography Electrodes: A Systematic Review.

BACKGROUND: Stereoelectroencephalography (SEEG) was developed by Talairach and Bancaud in Paris in the late 1950s. Subsequently, the Talairach methodology was adopted at a number of additional centers in Europe and Canada. Technical aspects remained essentially unchanged for the following 30 years. Only in the last two decades, because of advancements in image-guided surgery systems, robotics, and computer-aided planning, use of SEEG has become more widespread, and reports describing these new developments have been published. OBJECTIVES: This systematic review was designed to assess published reports of SEEG surgical techniques and safety profile. DATA SOURCES: An electronic search was performed of Medline, Embase, and Scopus databases. In addition, the content pages of several standard epilepsy surgery textbooks were searched. Full-text English studies describing SEEG surgical technique or pertinent epidemiological data were included. Conference abstracts, reviews, posters, editorials, comments, and letters were excluded. RESULTS: Three hundred fifty-nine of 2,903 potentially eligible studies published by 32 centers were reviewed. Thirty-one of these primarily discussed the surgical technique. Thirty-five major complications (including 4 fatalities) were reported among 4,000 patients (0.8%) implanted with 33,000 electrodes. LIMITATIONS: The number of SEEG patients is likely to be underestimated because only a few groups have exhaustively reported their experience. Moreover, it is possible that a number of teams performing SEEG have not published studies on the topic. CONCLUSIONS: Rigorous SEEG, thanks to its basic principles and updated technologies, is a safe and accurate method to define the epileptogenic zone by means of stereotactically implanted intracerebral electrodes.

Monopolar high-frequency language mapping: can it help in the surgical management of gliomas? A comparative clinical study.

OBJECT Intraoperative language mapping is traditionally performed with low-frequency bipolar stimulation (LFBS). High-frequency train-of-five stimulation delivered by a monopolar probe (HFMS) is an alternative technique for motor mapping, with a lower reported seizure incidence. The application of HFMS in language mapping is still limited. Authors of this study assessed the efficacy and safety of HFMS for language mapping during awake surgery, exploring its clinical impact compared with that of LFBS. METHODS Fifty-nine patients underwent awake surgery with neuropsychological testing, and LFBS and HFMS were compared. Frequency, type, and site of evoked interference were recorded. Language was scored preoperatively and 1 week and 3 months after surgery. Extent of resection was calculated as well. RESULTS High-frequency monopolar stimulation induced a language disturbance when the repetition rate was set at 3 Hz. Interference with counting (p = 0.17) and naming (p = 0.228) did not vary between HFMS and LFBS. These results held true when preoperative tumor volume, lesion site, histology, and recurrent surgery were considered. Intraoperative responses (1603) in all patients were compared. The error rate for both modalities differed from baseline values (p < 0.001) but not with one another (p = 0.06). Low-frequency bipolar stimulation sensitivity (0.458) and precision (0.665) were slightly higher than the HFMS counterparts (0.367 and 0.582, respectively). The error rate across the 3 types of language errors (articulatory, anomia, paraphasia) did not differ between the 2 stimulation methods (p = 0.279). CONCLUSIONS With proper setting adjustments, HFMS is a safe and effective technique for language mapping.

Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways.

BACKGROUND: Resection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context. METHODS: In 591 tumors involving the corticospinal tract, the use of HF and LF was tailored to the clinical context defined by patient clinical history and tumor features (by imaging). The effect was evaluated on the feasibility of mapping, the impact on immediate and permanent morbidity, the extent of resection, and the number of patients treated. RESULTS: By integrating the choice of the probe and the stimulation protocol with patient clinical history and tumor characteristics, the best probe-frequency match was identified for the different sets of clinical conditions. This integrative approach allows increasing the extent of resection and patient functional integrity, and greatly expands the number of patients who could benefit from surgery. CONCLUSIONS: The integration of stimulation modalities with clinical context enhances the extent and safety of resection and expands the population of patients who could benefit from surgical treatment.

Surgical brain metastases: management and outcome related to prognostic indexes: a critical review of a ten-year series.

Brain metastasis are the most common neoplastic lesions of the nervous system. Many cancer patients are diagnosed on the basis of a first clinical presentation of cancer on the basis of a single or multiple brain lesions. Brain metastases are manifestations of primary disease progression and often determine a poor prognosis. Not all patients with a brain metastases undergo surgery: many are submitted to alternative or palliative treatments. Management of patients with brain metastases is still controversial, and many studies have been developed to determine which is the best therapy. Furthermore, management of patients operated for a brain metastasis is often difficult. Chemotherapy, stereotactic radiosurgery, panencephalic radiation therapy, and surgery, in combination or alone, are the means most commonly used. We report our experience in the management of a ten-year series of surgical brain metastasis and discuss our results in the preoperative and postoperative management of this complex condition.