A peculiar case of pure intraventricular glioblastoma.

Glioblastoma (formerly named glioblastoma multiforme) is the most common primary central nervous system tumor, representing 45% of all cases and 15% of all intracranial neoplasms [1]. Its typical radiologic findings and localization make it often a lesion easy to diagnose. In MRI it usually appears as an irregularly shaped cystic lesion with ring contrast enhancement in T1-weighted images, localized in subcortical white matter and deep gray matter nuclei of the cerebral hemispheres. It involves more frequently the frontotemporal region followed by parietal lobes [1]. Few articles in literature described cases of intraventricular glioblastomas, defining those as secondary ventricular tumors because of their probable origin primarily from cerebral tissue with consequent transependymal development [2, 3]. Atypical presentations of these tumors make it more difficult to clearly differentiate them from other lesions more commonly located in the ventricular system. We describe a case with a unique radiological presentation: an intraventricular glioblastoma lying entirely within the ventricular walls, involving all the ventricular system, without mass effect or nodular parenchymal lesions.

Glioneuronal and Neuronal Tumors of the Central Nervous System.

Glioneuronal and neuronal tumors (GNTs) are rare neoplasms composed of neural and glial elements frequently located in the temporal lobe. Epilepsy is the main symptom and diagnosis mostly occurs before adulthood. The great majority of GNTs are WHO grade I tumors, but anaplastic transformations and forms exist. Their common association with focal cortical dysplasia is well recognized and should be taken into consideration during neurophysiological presurgical and surgical planning since the aim of surgery should be the removal of the tumor and of the entire epileptogenic zone according to anatomo-electrophysiological findings. Surgery still remains the cornerstone of symptomatic GNT, while radiotherapy, chemotherapy, and new target therapies are generally reserved for anaplastic, unresectable, or evolving tumors. Furthermore, since many GNTs show overlapping clinical and neuroradiological features, the definition of specific histopathological, genetic, and molecular characteristics is crucial. Epileptological, oncological, neurosurgical, and pathological issues of these tumors make a multidisciplinary management mandatory.

Open-aqueduct LOVA, LIAS, iNPH: a comparative clinical-radiological study exploring the "grey zone" between different forms of chronic adulthood hydrocephalus.

PURPOSE: The definition of chronic adult hydrocephalus encompasses different pathological entities with overlapping characteristics, including long-standing overt ventriculomegaly in adults (LOVA), late-onset idiopathic aqueductal stenosis (LIAS) and idiopathic normal pressure hydrocephalus (iNPH). The aim of our study was to identify preoperative clinical and radiological features peculiar of these diseases providing some pathophysiology inferences on these forms of hydrocephalus. METHODS: Clinical and radiological preoperative records, type of surgical treatment and clinical outcome of patients with chronic adult hydrocephalus who were surgically treated between 2013 and 2019 were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the contribution of each variable to the differential diagnosis. RESULTS: In total, 105 patients were included: 18 with LOVA, 23 with LIAS and 64 with iNPH. On multivariate analysis, an enlarged cisterna magna and a more severe ventriculomegaly were associated with the diagnosis of LOVA, while an older age and DESH with iNPH. LIAS patients tend to have an higher prevalence of raised ICP symptoms. Based on that, a clinical and radiological scoring system was developed to distinguish between iNPH and no iNPH cases. A precise cut-off value with a sensitivity of 95.1% and a specificity of 90.6% was identified. CONCLUSIONS: LOVA, LIAS and iNPH are different forms of chronic adulthood hydrocephalus and present different and peculiar clinical and radiological features, with an impact on the treatment and outcome prediction. The implementation of a clinical-radiological score for differential diagnosis may help the differentiation. Further studies are warranted.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Coexistence of meningoencephalocele and hippocampal sclerosis: a new type of dual pathology.

Both temporal lobe meningoencephalocele (TE) and hippocampal sclerosis (HS) are causes of drug-resistant temporal lobe epilepsy. Spontaneous TE constitutes a rare but well-known and increasingly recognised cause of refractory epilepsy. It is well known that HS may be associated with another neocortical lesion (dual pathology). Here we report for the first time a new type of dual pathology; namely, the coexistence of temporal pole meningoencephalocele and HS.

Focal cortical dysplasias in temporal lobe epilepsy surgery: Challenge in defining unusual variants according to the last ILAE classification.

OBJECTIVE: Focal cortical dysplasias (FCDs) represent a common architectural cortical disorder underlying pharmacoresistant focal epilepsy. The recent ILAE classification defines different types of FCDs based on their histopathological features, MRI imaging, and presumed pathogenesis; however, their clinical features and their prognostic significance are still incompletely defined. In addition, the combination of different histopathological abnormalities can represent "unusual" subtypes that can be difficult to classify. The aim of our study was to analyze the incidence and the significance of these "unusual" subtypes of FCDs in drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: We retrospectively analyzed 133 patients consecutively submitted to tailored anteromesial temporal lobe resection for pharmacoresistant MTLE. Seizure onset, seizure duration, age at surgery, and postoperative seizure outcome were evaluated in relation to the different neuropathological groups defined according to the new ILAE classification. RESULTS: Focal cortical dysplasias were found in 80 out of 133 patients. Six patients were affected by isolated FCD type I, 12 patients by FCD type II, and 44 patients by FCD type III. Furthermore, we found 18 "atypical" cases (20.5% of all FCD cases and 26.6% of FCDs associated with a principal lesion): 10 cases of associated FCD type II-hippocampal sclerosis (HS) and 8 cases associated with FCD II-epilepsy-associated tumors (EATs). CONCLUSION: Our results indicate that "unusual" subtypes of FCDs, in particular associated FCD type II, are not uncommon findings, suggesting that they deserve a classification recognition. Similarities in seizure outcome and immunohistochemical and molecular evidences, shared by FCD type II+EATs and EATs, suggest a common pathogenic link. The choice to create a specific unifying class or, on the contrary, to also include "associated FCD type II" in the definition of the new unifying class FCD type III should be further discussed.

The persistent crucial role of the left hemisphere for language in left-handers with a left low grade glioma: a stimulation mapping study.

BACKGROUND: Left-handers have a more bilateral language representation than right-handers. Therefore, in left-handers with a low-grade glioma (LGG) in the left hemisphere (LH), one could hypothesize that the right hemisphere (RH) might allow language compensation, at least partly, with no or only a minor persistent role of the LH in speech. However, although LGG induces language reorganization in right-handed patients, little is known in left-handers. Here, we report the first series of left-handers who underwent awake surgery for a left LGG using intraoperative mapping, in order to investigate whether there was still an involvement of LH in language. METHOD: Ten consecutive left-handed patients were operated for a left LGG (three frontal, four paralimbic, one parietal, one temporal, one parieto-temporal tumor) using an awake procedure with intraoperative electrical language mapping. RESULTS: Intraoperative language disorders were elicited in all cases but one by electrostimulation in the LH. Cortical language sites were detected in nine cases. Subcortical stimulation also demonstrated the crucial role of left white matter pathways in language, including the inferior occipital-frontal fascicle, arcuate fascicle, lateral segment of the superior longitudinal fascicle and fibers from the ventral premotor cortex. Moreover, stimulation of deep gray nuclei generated language disturbances in four patients. These nine patients experienced transient postoperative language worsening, supporting the persistent critical role of LH in speech. In only one patient, no language deficit was evoked intraoperatively and postoperatively. The ten patients returned to a normal life. Total or subtotal resection was achieved in all cases but one. CONCLUSIONS: Our results suggest that, even though the RH may participate in language compensation, the LH in left-handers still plays a crucial role, despite a left slow-growing LGG. Thus, we propose to routinely consider awake surgery for left LGG removal in left-handers patients, to optimize the extent of resection while preserving language.

Surgical and radiosurgical treatment of hypothalamic hamartoma: The Italian experience between 2011 and 2021.

OBJECTIVE: To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques. METHODS: We collected pseudo-anonymized patient's data with at least 12 months of follow-up. Surgical outcome was defined according to Engel classification of seizure outcome. Univariate analysis was performed to assess the risk of post-operative seizures, categorized in dichotomous variable as favorable and unfavorable; explanatory variables were considered. Mann-Whitney or Chi-squared test were used to assess the presence of an association between variables (p < 0.05). RESULTS: Full presurgical and postoperative data about 42 patients from 6 epilepsy surgery centers were gathered. Engel class I was reached in the 65.8% and 66.6% of patients with gelastic and non-gelastic seizures, respectively. Other than daily non-gelastic seizures were associated with seizure freedom (p = 0.01), and the radiological type presented a trend toward significance (p = 0.12). SIGNIFICANCE: Endoscopic disconnection and laser interstitial thermal therapy are effective in the treatment of HH-related epilepsy, with a tolerable safety profile. Both gelastic and non-gelastic seizures can be treated, also in patients with a long history of seizures. PLAIN LANGUAGE SUMMARY: This study collected data about 42 patients with HH-related epilepsies. Endoscopic disconnection and laser therapy are both effective and safe in the treatment of hypothalamic hamartoma-related epilepsies.

Isolated entrapment of the lateral ventricle after neuroendoscopic resection of colloid cysts: single - center experience and management.

BACKGROUND: A minimally invasive option of colloid cyst surgical treatment is endoscopic resection, well validated in various reports and clinical practice. A rare complication of the surgical treatment, previously reported only once in literature, is the entrapment of the lateral ventricle. In this study we aim to outline our experience in the management of this occurrence, hypothesizing possible etiopathogenetic causes. METHODS: Among patients who underwent neuroendoscopic resection for a colloid cysts at our Institution between 2013 and 2022, cases who developed a postoperative lateral ventricle entrapment were retrospectively reviewed and included. Clinical history, imaging and treatment were reported. RESULTS: Among 34 patients treated for a colloid cysts, two (5.9 %) patients developed an ipsilateral ventricular entrapment with dilation from two to five months after the resection. Both patients were substantially asymptomatic and neurologically intact, and therefore treated conservatively. One case underwent complete spontaneous radiological resolution one month later, and the other one has remained neurological asymptomatic at follow-up. CONCLUSIONS: Isolated asymptomatic ventricular entrapment with significant dilation after endoscopic colloid cyst resection is a rare occurrence which can be plausibly caused by scar tissue at the level of the foramen of Monro. Because they can have an indolent course with spontaneous resolution, conservative treatment is a viable option, with strict radiological and clinical follow - up. Given the rarity of the occurrence, further studies with larger cohorts are warranted to confirm the etiopathogenetic hypothesis and validate the clinical management.

A case of clinical worsening after stereo-electroencephalographic-guided radiofrequency thermocoagulation in a patient with polymicrogyria.

Radiofrequency thermocoagulation (RF-TC) is a wide-used procedure for drug-resistant epilepsy. The technique is considered safe with an overall risk of 1.1% of permanent complications, mainly focal neurological deficits. We report the case of a patient with drug-resistant epilepsy who complained of immediate seizure worsening and an unexpected event seven months following RF-TC. A 35-year-old male with drug-resistant epilepsy from the age of 18 years underwent stereoelectroencephalography (SEEG) implantation for a right peri-silvian polymicrogyria. He was excluded from surgery due to extent of the epileptogenic zone and the risk of visual field deficits. RF-TC was attempted to ablate the most epileptogenic zone identified by SEEG. After RF-TC, the patient reported an increase in seizure severity/frequency and experienced episodes of postictal psychosis. Off-label cannabidiol treatment led to improved seizure control and resolution of postictal psychosis. Patients with polymicrogyria (PwP) may present with a disruption of normal anatomy and the co-existence between epileptogenic zone and eloquent cortex within the malformation. RF-TC should be considered in PwP when they are excluded from surgery for prognostic and palliative purposes. However, given the complex interplay between pathological and electrophysiological networks in these patients, the remote possibility of clinical exacerbation after RF-TC should also be taken into account.

Intraoperative Ultrasonography in Endoscopic Approaches for Orbital Lesions: A Single-Center Case Series.

BACKGROUND: Recently, endoscopic approaches for orbital lesions have been proposed. Their results seem promising; however, orbital surgery remains challenging with possible significant morbidity, mostly because of orbital structures manipulation. Ultrasonography is an innovative intraoperative imaging technique that can assist the surgeon in these approaches. OBJECTIVE: To assess the role of intraoperative ultrasound (IOUS) in endoscopic orbital surgery. METHODS: All consecutive patients with orbital tumors operated in our institution through an endoscopic approach with IOUS have been prospectively collected from 2019 to May 2021. RESULTS: Fifteen patients were included. Based on tumor location, evaluated on preoperative MRI, the endoscopic endonasal approach was preferred in 7 tumors in medial quadrants while the endoscopic transpalpebral in 8 lateral ones. During surgery, IOUS allowed us to identify the tumors and the most relevant anatomic structures in all cases. Time spent for IOUS preparation before the first scan was 8 ± 6 minutes on average, and each intraoperative scan took approximately 30 to 120 seconds. Gross tumor removal was achieved in 8 patients, subtotal in 3, while in 4 patients, surgery was limited to a biopsy. No surgical complications were observed. CONCLUSION: IOUS has allowed us to localize the lesion and to identify the straighter surgical corridor and assess the tumor resection, effectively helping the surgeon and potentially reducing operative complications. This tool provides a real-time image, not affected by the orbital structures shift, which can be dynamically assessed multiple times during surgery. However, it is hampered by the need of specific training and possible artifacts.

Idiopathic Aqueductal Stenosis: Late Neurocognitive Outcome in ETV Operated Adult Patients.

Objective: The aim of the present study is to evaluate a neurocognitive outcome in patients affected by late-onset idiopathic aqueductal stenosis (LIAS) who underwent endoscopic third ventriculostomy (ETV). Materials and Methods: A prospective study was conducted between January 2015 and December 2017 in a series of 10 consecutive adult patients referred to the Neurosurgery Department of IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. All the adult patients admitted with absence of CSF flow through the aqueduct in phase-contrast (PC)-MRI sequences or a turbulence void signal in T2-weighted images in midsagittal thin-slice MR sequences underwent a specific neuroradiological, neurological, and neurocognitive assessment pre- and postoperatively. Results: All patients affected by gait and sphincter disturbances improved after ETV. Attentive and executive functions as well as visuo-spatial memory and verbal executive functions improved in several patients. Similarly, the affective and behavioral scales improved in almost 50% of the patients. No major complications have been recorded, and no patients required a second surgery for shunt placement. Conclusion: Endoscopic third ventriculostomy represents a safe and effective surgical procedure for the treatment of LIAS. In addition to neurological improvement, we demonstrated also postoperative neurocognitive improvement mainly in attentive and executive functions, visuo-spatial memory, verbal executive functions, and behavioral and affective domains.

What Can Resting-State fMRI Data Analysis Explain about the Functional Brain Connectivity in Glioma Patients?

Resting-state functional MRI has been increasingly implemented in imaging protocols for the study of functional connectivity in glioma patients as a sequence able to capture the activity of brain networks and to investigate their properties without requiring the patients' cooperation. The present review aims at describing the most recent results obtained through the analysis of resting-state fMRI data in different contexts of interest for brain gliomas: the identification and localization of functional networks, the characterization of altered functional connectivity, and the evaluation of functional plasticity in relation to the resection of the glioma. An analysis of the literature showed that significant and promising results could be achieved through this technique in all the aspects under investigation. Nevertheless, there is room for improvement, especially in terms of stability and generalizability of the outcomes. Further research should be conducted on homogeneous samples of glioma patients and at fixed time points to reduce the considerable variability in the results obtained across and within studies. Future works should also aim at establishing robust metrics for the assessment of the disruption of functional connectivity and its recovery at the single-subject level.

Neuroplasticity Mechanisms in Frontal Brain Gliomas: A Preliminary Study.

Background: Pathological brain processes may induce adaptive cortical reorganization, however, the mechanisms underlying neuroplasticity that occurs in the presence of lesions in eloquent areas are not fully explained. The aim of this study was to evaluate functional compensatory cortical activations in patients with frontal brain gliomas during a phonemic fluency task and to explore correlations with cognitive performance, white matter tracts microstructural alterations, and tumor histopathological and molecular characterization. Methods: Fifteen patients with frontal glioma were preoperatively investigated with an MRI study on a 3T scanner and a subgroup underwent an extensive neuropsychological assessment. The hemispheric laterality index (LI) was calculated through phonemic fluency task functional MRI (fMRI) activations in the frontal, parietal, and temporal lobe parcellations. Diffusion-weighted images were acquired for all patients and for a group of 24 matched healthy volunteers. Arcuate Fasciculus (AF) and Frontal Aslant Tract (FAT) tractography was performed using constrained spherical deconvolution diffusivity modeling and probabilistic fiber tracking. All patients were operated on with a resective aim and underwent adjuvant therapies, depending on the final diagnosis. Results: All patients during the phonemic fluency task fMRI showed left hemispheric dominance in temporal and parietal regions. Regarding frontal regions (i.e., frontal operculum) we found right hemispheric dominance that increases when considering only those patients with tumors located on the left side. These latter activations positively correlate with verbal and visuo-spatial short-term memory, and executive functions. No correlations were found between the left frontal operculum and cognitive performance. Furthermore, patients with IDH-1 mutation and without TERT mutation, showed higher rightward frontal operculum fMRI activations and better cognitive performance in tests measuring general cognitive abilities, semantic fluency, verbal short-term memory, and executive functions. As for white matter tracts, we found left and right AF and FAT microstructural alterations in patients with, respectively, left-sided and right-side glioma compared to controls. Conclusions: Compensatory cortical activation of the corresponding region in the non-dominant hemisphere and its association with better cognitive performance and more favorable histopathological and molecular tumor characteristics shed light on the neuroplasticity mechanisms that occur in the presence of a tumor, helping to predict the rate of post-operative deficit, with the final goal of improving patients'quality of life.

Oligodendroglial hamartoma: a potential source of misdiagnosis for oligodendroglioma.

Various subtypes of intracerebral hamartomas, associated with seizure disorders, have long been described. We describe a cerebral hamartoma placed in the left frontal lobe, associated with drug-resistant epilepsy, composed exclusively of mature oligodendroglial cells. The patient was a 27-year-old right-handed male presenting with severe epileptic encephalopathy and symptoms of behavior dysfunction (disinhibition, rage attacks) associated with a left frontal lesion. Magnetic resonance imaging revealed a small area iso-hypointense compared to the gray matter in T1-weighted sequences not enhancing after gadolinium contrast injection in the left frontal site. On histology, a cortical lesion composed of large aggregates of oligodendroglial cells, with round central nuclei and clear perinuclear halos, was observed. Neither mitotic figures nor necrosis were present. Reactivity for Ki67 and P53 was not found. The lesion was well demarcated from the adjacent brain parenchyma and perineuronal satellitosis was not observed in the cortex. In conclusion, albeit extremely rare, recognition of oligodendroglial hamartoma and its distinction from other epileptogenic lesions as dysembryoplastic neuroepithelial tumor or above all oligodendroglioma have important therapeutic and prognostic implications.

Ultrasound assisted awake epilepsy surgery for type IIB focal cortical dysplasia in eloquent areas.

Focal cortical dysplasia (FCD) type IIb is a frequent cause of pharmacoresistant epilepsy. However, intraoperative identification of the pathological tissue still remains a challenge despite the use of neuronavigation, particularly when it lies in eloquent areas. We here report a case of intraoperative identification of a right frontal FCD type IIB through ultrasound assisted neuronavigation during awake surgery in a patient with drug-resistant epilepsy. Intraoperative ultrasound may have a role in focal cortical dysplasia localization optimizing its resection. In selected patient submitted to epilepsy surgery the integration of disposable technologies (i.e. brain neuronavigation, fMRI and iUS) with awake surgery could improve FCD identification preventing unacceptable neurological morbidity.

Low-grade tumour over the left temporal neocortex and ictal asystole: network and surgical implications.

We describe a patient with focal epilepsy characterized by ictal asystole episodes and low-grade tumour over the left temporal neocortex. Non-invasive pre-surgical evaluation showed an epileptogenic zone extended beyond the low-grade tumour. This extension was confirmed by intraoperative electrocorticography. One-stage surgery with anterior temporal lobe resection was performed. The patient was seizure-free after one year of follow-up. Detailed electroclinical and therapeutic reasoning with hypotheses defining epileptogenic and symptomatogenic networks are discussed.