Clinical implications of the 2022 WHO classification on the multidisciplinary management of PitNETS patients.

The review explores the 2022 update to the World Health Organization (WHO) classification of pituitary adenomas, now referred to as pituitary neuroendocrine tumors (PitNETs), and his possible impact on the clinical management of PitNET patients. The review highlights the differences and the evolution from the 2017 to 2022 version, with the current classification considering the lineage of the tumor cells, cell type, hormones produced, and other auxiliary characteristics for a comprehensive histological classification. The revision in terminology reflects a broader perspective on neuroendocrine neoplasia. The new approach based on transcription factors, hormone expression and other biomarkers has allowed a major revision of the nomenclature and a more accurate classification of pituitary adenomas. Furthermore, in some cases this approach is also assuming a prognostic value, useful in clinical practice. However, despite this elaborate classification and stratification, the review points out the lack of a robust grading or staging system and suggests the need for further research and validation of diagnostic methods. Despite these limitations, the revised classification presents a significant step towards understanding and managing PitNETs patients.

A Toluene-induced Infundibulo-neurohypophysitis: A New Cause of Hypophysitis Secondary to Toxic Exposure.

BACKGROUND: Hypophysitis is a rare inflammatory disorder of the pituitary gland. Symptoms and signs of hypophysitis can be various, and its recognition may be challenging. Arginine vasopressin deficiency (AVP-D) due to exposure to a variety of drugs and toxic substances is rare, but some cases have been reported. Only 2 cases of AVP-D following toxic exposure to toluene, an aromatic hydrocarbon, have been reported in the literature. To our knowledge, our case represents the first description of an infundibulo neurohypophysitis (INH), manifested with AVP-D, secondary to inhalation of toluene. CASE REPORT: A 59-year-old man with an unremarkable medical history was referred to our department for headache, polyuria, and polydipsia after the inhalation of spray film containing toluene. The blood tests revealed a hyperosmolar plasma hypernatremia with normal kidney function. A desmopressin test was performed, with an improvement in water balances, blood electrolytes, and diuresis contraction. A pituitary MRI detected the absence of a normal hyperintense signal of the neuro-pituitary in the T1-weighted images. In consideration of the clinical signs and radiological imaging suggestive of INH, a therapy with desmopressin and corticosteroids was instituted, with gradual improvement of polyuria and resolution of the radiological features of INH. CONCLUSION: The exceptional finding of INH, manifested with AVP-D, following toluene inhalation could represent a new secondary cause of hypophysitis. The possibility that drugs or toxic substances never reported before could induce INH should not be excluded since the study on hypophysitis is relatively recent but emerging, predictably destined to increase exponentially in the coming years.

Diffusion tensor imaging in detecting gliomas sub-regions of infiltration, local and remote recurrences: a systematic review.

Given that glioma cells tend to infiltrate and migrate along WM tracts, leading to demyelination and axonal injuries, Diffusion Tensor Imaging (DTI) emerged as a promising tool for identifying major "high-risk areas" of recurrence within the peritumoral brain zone (PBZ) or at a distance throughout the adjacents white matter tracts. Of our systematic review is to answer the following research question: In patients with brain tumor, is DTI able to recognizes within the peri-tumoral brain zone (PBZ) areas more prone to local (near the surgical cavity) or remote recurrence compared to the conventional imaging techniques?. We conducted a comprehensive literature search to identify relevant studies in line with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. 15 papers were deemed compatible with our research question and included. To enhance the paper's readability, we have categorized our findings into two distinct groups: the first delves into the role of DTI in detecting PBZ sub-regions of infiltration and local recurrences (n = 8), while the second group explores the feasibility of DTI in detecting white matter tract infiltration and remote recurrences (n = 7). DTI values and, within a broader framework, radiomics investigations can provide precise, voxel-by-voxel insights into the state of PBZ and recurrences. Better defining the regions at risk for potential recurrence within the PBZ and along WM bundles will allow targeted therapy.

Topography and Radiological Variables as Ancillary Parameters for Evaluating Tissue Adherence, Hypothalamic-Pituitary Dysfunction, and Recurrence in Craniopharyngioma: An Integrated Multidisciplinary Overview.

Craniopharyngiomas continue to present a challenge in clinical practice due to their heterogeneity and unpredictable adherence to vital neurovascular structures, particularly the hypothalamus. This results in different degrees of hypothalamus-pituitary axis dysfunction and a lack of uniform consensus and treatment guidelines regarding optimal management. MRI and CT are complementary techniques in the preoperative diagnostic phase, enabling the precise definition of craniopharyngioma size, shape, and consistency, as well as guiding classification into histopathological subtypes and topographical categories. Meanwhile, MRI plays a crucial role in the immediate postoperative period and follow-up stages by identifying treatment-related changes and residual tumors. This pictorial essay aims to provide an overview of the role of imaging in identifying variables indicative of the adherence degree to the hypothalamus, hypothalamic-pituitary dysfunction, the extent of surgical excision, and prognosis. For a more comprehensive assessment, we choose to distinguish the following two scenarios: (1) the initial diagnosis phase, where we primarily discuss the role of radiological variables predictive of adhesions to the surrounding neurovascular structures and axis dysfunction which may influence the choice of surgical resection; (2) the early post-treatment follow-up phase, where we discuss the interpretation of treatment-related changes that impact outcomes.

"False friends" in Language Subcortical Mapping: A Systematic Literature Review.

BACKGROUND: Subcortical brain mapping in awake glioma surgery might optimize the extent of resection while minimizing neurological morbidity, but it requires a correct interpretation of responses evoked during surgery. To define, with a systematic review: 1) a comprehensive 'map' of the principal white matter bundles involved in awake surgery on language-related networks, describing the most employed tests and the expected responses; 2) In linguistics, a false friend is a word in a different language that looks or sounds like a word in given language but differs significantly in meaning. Similarly, our aim is to give the surgeons a comprehensive review of potentially misleading responses, namely "false friends", in subcortical language mapping. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Standardized data extraction was conducted. RESULTS: Out of a total of 224 initial papers, 67 were included for analysis. Expected responses, common tests, and potential "false friends" were recorded for each of the following white matter bundles: frontal aslant tract, superior and inferior longitudinal fascicles, arcuate fascicle, inferior fronto-occipital fascicle, uncinate fascicle. Practical examples are discussed to underline the risk of intraoperative fallouts ("false friends") that might lead to an early interruption (false positive) or a risky surgical removal (false negative). CONCLUSIONS: This paper represents a critical review of the present status of subcortical awake mapping and underlines practical "false-friend" in mapping critical crossroads in language-related networks.

Neuroradiological manifestations in hospitalized patients with COVID-19: An Italian national multicenter study on behalf of AINR (Associazione Italiana di Neuroradiologia) and SIRM (Società Italiana di Radiologia Medica).

PURPOSE: This multicentric study aims to characterize and assess the occurrence of neuroradiological findings among patients with SARS-CoV-2 infection during the first Italian wave of the pandemic outbreak. MATERIALS AND METHODS: Patients' data were collected between May 2020 and June 2020. Clinical and laboratory data, chest imaging, brain CT, and MRI imaging were included. Acquired data were centralized and analyzed in two hospitals: ASST Spedali Civili, Brescia, and IRRCS San Raffaele Research Hospital, Milan, Italy. COVID-19 patients were classified into two different subgroups, vascular and nonvascular. The vascular pattern was further divided into ischemic and hemorrhagic stroke groups. RESULTS: Four hundred and fifteen patients from 20 different Italian Centers were enrolled in the study. The most frequent symptom was focal neurological deficit, found in 143 patients (34.5%). The most frequent neuroradiological finding was ischemic stroke in 122 (29.4%) patients. Forty-four (10.6%) patients presented a cerebral hemorrhage. Forty-seven patients had non-stroke neuroimaging lesions (11.3%). The most common was PRES-like syndrome (28%), SWI hypointensities (22%), and encephalitis (19%). The stroke group had higher CAD risk (37.5% vs 20%, p = .016) and higher D-dimer levels (1875 ng/mL vs 451 ng/mL, p < .001) compared to the negative group. CONCLUSION: Our study describes the biggest cohort study in Italy on brain imaging of COVID-19 patients and confirms that COVID-19 patients are at risk of strokes, possibly due to a pro-thrombotic microenvironment. Moreover, apart from stroke, the other neuroradiological patterns described align with the ones reported worldwide.

Posterior Cranial Fossa Surgery with a 3 Dimensional Exoscope: A Single-Center Survey-Based Analysis and a Literature Review.

OBJECTIVE: The potential advantages of exoscopy have been discussed theoretically for a long time. Such a concept holds significance, especially in the specific setting of the posterior cranial fossa (PCF), characterized by complex anatomy and long and narrow surgical corridors with relatively extreme working angles. We aimed to: 1) analyze the institutional preliminary case-based data on the use of the Robotic 3D Exoscope AEOS Aesculap in three different PCF approaches: retrosigmoid (RSA), midline suboccipital (MSA), and supracerebellar infratentorial via feedbacks was collected using a 20-point questionnaire, and 2) perform a comprehensive review of the literature concerning the use of EX in PCF surgery. RESULTS: A total of 38 patients with neurosurgical pathologies underwent a neurosurgical procedure using the EX (Robotic 3D exoscope AEOS Aesculap) at our institution between January and March 2022. 21 surgeons were involved in the abovementioned PCF surgeries and answered the questionnaire. The main perceived advantages were in terms of ergonomics (67%), magnification (52%), and visualization of extreme angles. The main reported disadvantage was color vision (16, 76%), followed by manual mobility (24%). Concerning the review, the search of the literature yielded a total of 177 results. Upon full-text review, 17 articles were included, including 153 patients. CONCLUSIONS: In conclusion, our study provides a comprehensive evaluation of the advantages and challenges associated with using the exoscope in posterior fossa surgery, setting a precedent as the first to report on a questionnaire-based analysis of exoscope utilization in this specific domain.

H3K27-Altered Diffuse Glioma of the Spinal Cord in Adult Patients: A Qualitative Systematic Review and Peculiarity of Radiological Findings.

Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.

The FKBP51s Splice Isoform Predicts Unfavorable Prognosis in Patients with Glioblastoma.

The primary treatment for glioblastoma (GBM) is removing the tumor mass as defined by MRI. However, MRI has limited diagnostic and predictive value. Tumor-associated macrophages (TAM) are abundant in GBM tumor microenvironment (TME) and are found in peripheral blood (PB). FKBP51 expression, with its canonical and spliced isoforms, is constitutive in immune cells and aberrant in GBM. Spliced FKBP51s supports M2 polarization. To find an immunologic signature that combined with MRI could advance in diagnosis, we immunophenotyped the macrophages of TME and PB from 37 patients with GBM using FKBP51s and classical M1-M2 markers. We also determined the tumor levels of FKBP51s, PD-L1, and HLA-DR. Tumors expressing FKBP51s showed an increase in various M2 phenotypes and regulatory T cells in PB, indicating immunosuppression. Tumors expressing FKBP51s also activated STAT3 and were associated with reduced survival. Correlative studies with MRI and tumor/macrophages cocultures allowed to interpret TAMs. Tumor volume correlated with M1 infiltration of TME. Cocultures with spheroids produced M1 polarization, suggesting that M1 macrophages may infiltrate alongside cancer stem cells. Cocultures of adherent cells developed the M2 phenotype CD163/FKBP51s expressing pSTAT6, a transcription factor enabling migration and invasion. In patients with recurrences, increased counts of CD163/FKBP51s monocyte/macrophages in PB correlated with callosal infiltration and were accompanied by a concomitant decrease in TME-infiltrating M1 macrophages. PB PD-L1/FKBP51s connoted necrotic tumors. In conclusion, FKBP51s identifies a GBM subtype that significantly impairs the immune system. Moreover, FKBP51s marks PB macrophages associated with MRI features of glioma malignancy that can aid in patient monitoring. SIGNIFICANCE: Our research suggests that by combining imaging with analysis of monocyte/macrophage subsets in patients with GBM, we can enhance our understanding of the disease and assist in its treatment. We discovered a similarity in the macrophage composition between the TME and PB, and through association with imaging, we could interpret macrophages. In addition, we identified a predictive biomarker that drew more attention to immune suppression of patients with GBM.

Head CT Scans in the Emergency Department during the COVID-19 Pandemic: Use or Overuse?

BACKGROUND: The COVID-19 pandemic seemed to mainly involve the respiratory system, but it was realized that it could affect any organ, including the CNS. The pandemic has followed a wave-like trend, with its peaks being due to the COVID-19 different variants and the introduction of the vaccine, which led to an apparent reduction in hospitalizations but also brought about perplexities related to its adverse effects. The aim of this study was to analyze the changes in the use of head CT/contrast CT and their impacts on the onset of cerebrovascular disease in our emergency department during the COVID-19 period and the vaccine rollout. METHODS: Patients ≥ 18 years old admitted to our emergency department from January 2018 to September 2021 were enrolled. The patients were divided into three groups. The COVID-19 period included patients who visited our emergency department from 1 March 2020 to 31 January 2021; the vaccine period was considered to range from 1 February 2021 to 30 September 2021. The patients who visited the emergency department from 1 January 2018 to 31 January 2020 were considered the controls. RESULTS: We found an increase in head CT/contrast CT requests during the COVID-19 period and increase in head contrast CT during the vaccine period, without an increase in the incidence of cerebrovascular disease. CONCLUSIONS: The uncertainty regarding the possible thrombotic events associated with COVID-19 and its vaccine increased the relative use of head CT/contrast CT by about 20% compared to the control period.

Trouillas's Grading and Post-Surgical Tumor Residue Assessment in Pituitary Adenomas: The Importance of the Multidisciplinary Approach.

BACKGROUND: We aim to assess the role of a multidisciplinary approach in pituitary adenomas (PitNETs) classification, evaluate criteria concordance, and compare intraoperative assessments with post-operative MRIs for tumor remnants. METHODS: Clinical, radiological, histological, and intra- and post-operative data of the treated PitNETs were extracted from prospectively created records. PitNETs were graded according to Trouillas, and the evaluation of the tumor remnants was recorded. RESULTS: Of 362 PitNETs, 306 underwent surgery, with Trouillas grading assigned to 296. Eight-nine radiologically non-invasive PitNETs progressed to grades 1b (27), 2a (42), or 2b (20) due to proliferative or surgical invasiveness criteria. Twenty-six radiologically invasive tumors were graded 2b due to proliferative criteria. Surgical resection details and post-surgical MRI findings revealed that residual tumors were more common in grades 2a and 2b. During surgery, small tumor remnants were documented in 14 patients which were not visible on post-surgical MRI. Post-surgical MRIs identified remnants in 19 PitNETs not seen during surgery, located in lateral recesses of the sella (4), retrosellar (2), or suprasellar regions (7), along the medial wall of the cavernous sinus (6). CONCLUSIONS: The Pituitary Board allows for the correct grading of PitNETs to be obtained and an accurate identification of high-risk patients who should undergo closer surveillance due to tumor remnants.

The Pathogenic RET Val804Met Variant in Acromegaly: A New Clinical Phenotype?

Several genetic investigations were conducted to identify germline and somatic mutations in somatotropinomas, a subtype of pituitary tumors. To our knowledge, we report the first acromegaly patient carrying a RET pathogenic variant: c.2410G>A (rs79658334), p.Val804Met. Alongside the fact that the patient's father and daughter carried the same variant, we investigated the clinical significance of this variant in the context of somatotropinomas and other endocrine tumors, reviewing the RET mutations' oncogenic mechanisms. The aim was to search for new targets to precisely manage and treat acromegaly. Our case describes a new phenotype associated with the RET pathogenic variant, represented by aggressive acromegaly, and suggests consideration for RET mutation screening if NGS for well-established PitNET-associated gene mutations renders negative.

Giant Congenital Hemangioma of the Skull: Prenatal Diagnosis and Multimodal Endovascular and Surgical Management.

Introduction: calvarial capillary hemangiomas are vascular tumors rarely seen in newborns. Differential diagnosis may be not straightforward on imaging studies and the management depends on patient and lesion characteristics. Case report: we present the case of a large congenital intracranial extra-axial lesion detected by routine prenatal US screening, a giant calvarial congenital hemangioma, treated with a multimodal strategy. Neonatal MR showed a hemorrhagic solid lesion, causing compression of brain tissue. Conservative treatment was attempted, but a one-month follow-up MR showed growth of the lesion with increased mass effect. Pre-operative endovascular embolization and surgical resection were performed. The pathology was consistent with intraosseous capillary hemangioma. The post-operative course was uneventful. At the 8-month follow-up, the patient had no clinical deficits and MR showed complete resection of the lesion. At the 13-month follow-up, the patient was asymptomatic, showing normal neurological examination and psychophysical development. Conclusions: although wait-and-see policy is feasible for small and asymptomatic lesions, radical resection is indicated when the mass is large, thus causing severe mass effect on the brain. Hypervascularization of the tumor may be responsible for hemorrhagic complications and severe anemia. On these grounds, endovascular treatment is feasible and effective to reduce hemorrhagic complications.

Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.