Characterization of purinergic signaling in tumor-infiltrating lymphocytes from lower- and high-grade gliomas.

Malignant gliomas are highly heterogeneous glia-derived tumors that present an aggressive and invasive nature, with a dismal prognosis. The multi-dimensional interactions between glioma cells and other tumor microenvironment (TME) non-tumoral components constitute a challenge to finding successful treatment strategies. Several molecules, such as extracellular purines, participate in signaling events and support the immunosuppressive TME of glioma patients. The purinergic signaling and the ectoenzymes network involved in the metabolism of these extracellular nucleotides are still unexplored in the glioma TME, especially in lower-grade gliomas (LGG). Also, differences between IDH-mutant (IDH-Mut) versus wild-type (IDH-WT) gliomas are still unknown in this context. For the first time, to our knowledge, this study characterizes the TME of LGG, high-grade gliomas (HGG) IDH-Mut, and HGG IDH-WT patients regarding purinergic ectoenzymes and P1 receptors, focusing on tumor-infiltrating lymphocytes. Here, we show that ectoenzymes from both canonical and non-canonical pathways are increased in the TME when compared to the peripheral blood. We hypothesize this enhancement supports extracellular adenosine generation, hence increasing TME immunosuppression.

The Infratrigeminal Suprafloccular Approach to Intrapontine Lesions: An Anatomical Overview and Relevance for the Approach to Intrapontine Lesions.

Background and objectives Brainstem lesions have long been considered complex pathologies that may lead to permanent deficits or life-threatening complications, posing significant challenges for surgical removal. Among these lesions, intrapontine lesions are particularly challenging in the field of neurosurgery. However, with advancements in microsurgical anatomy knowledge and technology, these lesions have become more amenable to surgical treatment. In this study, the authors examine an infratrigeminal suprafloccular approach, which has been shown to be a safe surgical route, resulting in fewer postoperative complications, while evaluating the anatomical nuances of the approach and route. Methods Twenty cadaveric brainstem specimens were analyzed to assess the anatomy, focusing on the lateral aspect of the pons as a potential safe entry zone for intrapontine lesions. The authors consistently analyzed twenty brainstem specimens, carefully examining the pontine microsurgical anatomy. A triangular area of entrance was measured, with three sides or walls (X, Y, and Z) aiming to identify the safe zone that would spare the distinct pontine nuclei, ascending sensory pathways, corticospinal, corticonuclear, and corticopontine tracts of the brainstem. An illustrative case was adapted to the described safe entry zone for corroboration purposes. Results The authors measured three distinct lines on the lateral surface of the pons, named X, Y, and Z, forming a triangle in shape. Line X extended from the midpoint anteroposteriorly of the flocculus of the cerebellum to the apparent trigeminal exit in the lateral aspect of the pons. Line Y ran from the trigeminal exit in the pons to the apparent exit of the facial-vestibulocochlear complex in the far lateral aspect of the pontomedullary sulcus in the cerebellopontine fissure. Line Z represented the measurement from the vestibulocochlear complex to the midpoint anteroposteriorly of the flocculus of the cerebellum. The mean measurements were as follows: X = 14.41mm (range: 10mm to 20mm), Y = 13.1mm (range: 10mm to 21mm), and Z = 3mm (range: 2mm to 5mm). The mean surface area of the analyzed specimens within the triangle (formed by X, Y, and Z) was 20.1mm² (range: 10mm² to 40mm²). This area was identified as a safe zone for the entry of microsurgical approaches to intrapontine lesions, involving less retraction of the anterior pons and potentially sparing critical structures, such as the corticospinal tracts, pontine perforating arteries, tegmentum pontis, cranial nerve nuclei, substantia reticulata dorsally, and transverse pontine fibers. Microsurgical anatomical findings, combined with intraoperative monitoring in an illustrative case, consistently demonstrated that this entry area predicted less functional instability of the analyzed tracts and resulted in fewer postoperative complications. Conclusion Deep-seated pontine lesions present a complex range of pathologies with a high potential for devastating outcomes, particularly those involving hemorrhage. This study identifies and describes a presumed safe entry zone that allows for the creation of a surgical corridor for biopsy or microsurgical resection of these lesions, reducing morbidity in a previously considered impenetrable region.

SMART Syndrome Identification and Successful Treatment.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare late complication of brain irradiation. Patients commonly present recurrent attacks of headaches, seizures, and paroxysmal focal neurological deficits including aphasia, negligence, or hemianopsia. We report a 41-year-old male patient admitted to our emergency room with a reduced level of consciousness and global aphasia. One month prior to admission, he started with frequent headache attacks of moderate intensity and paroxysmal behavioral alterations, advancing to confusion, gait instability, language impairment, and somnolence. He had a history of medulloblastoma treated with surgical resection followed by craniospinal irradiation 21 years before symptom onset. After excluding more frequent causes for the patient's symptoms along with a suggestive image pattern, we started treatment for SMART syndrome with high-dose corticosteroid and calcium channel blocker verapamil. The patient gradually improved his level of consciousness and recovered from aphasia and gait instability without new seizures or neuropsychiatric symptoms. Follow-up brain magnetic resonance imaging showed resolution of the typical findings. This case displays a successful clinical evolution of a patient treated for SMART syndrome in which identification of previous radiation treatment, exclusion of other etiologies, and prompt treatment institution were key for effectively tackling this disease.