ABSTRACT:Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.
Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma, which uncommonly presents with optic nerve infiltration (ONI). ONI has been reported mostly in relapse cases of PCNSL and is rarely the sole manifestation of the disease at the time of diagnosis. We report a case of a 69year-old female who presented with progressive visual impairment with relative afferent pupillary defect (RAPD) on examination. Orbital and cranial magnetic resonance imaging (MRI) revealed bilateral optic nerve sheath contrast enhancement with an incidental finding of a right frontal lobe mass. Routine cerebrospinal fluid analysis and cytology were unremarkable. Excision biopsy of the frontal lobe mass yielded the diagnosis of a diffuse B-cell lymphoma. Intraocular lymphoma was excluded on ophthalmologic workup. Whole body positron emission tomography scan did not reveal extracranial involvement establishing the diagnosis of PCNSL. Chemotherapy was initiated with rituximab, methotrexate, procarbazine, and vincristine as induction regimen and cytarabine as consolidation therapy. On follow-up, the visual acuity of both eyes significantly improved with the resolution of RAPD. Repeat cranial MRI did not show a recurrence of the lymphomatous process.To the best of the authors' knowledge, ONI as the initial presentation at the time of PCNSL diagnosis has only been reported three times. The present case's unusual presentation highlights the need to consider PCNSL as a differential diagnosis in patients who present with visual deterioration and optic nerve involvement. Prompt evaluation and treatment of PCNSL are essential for improving the visual outcomes of patients.
Background In addition to poor survival rates, individuals with glioblastoma (GB) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients; and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance. Methods This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4-weeks; i.e., baseline) and 3-, 6-, 12-, and 18- months later, or until tumor progression. Here, we present baseline data. Forty-five GBM patients (mean age = 55) completed objective neurocognitive tests, and self-report measures of neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms. Results Compared to normative samples, GBM patients scored significantly lower on all neurocognitive tests, with 34 (76%) patients exhibiting neurocognitive impairment. Specifically, 53% exhibited impairment in memory retention, 51% in executive function, 42% in immediate recall, 41% in verbal fluency, and 24% in attention. There were high rates of clinically elevated sleep disturbance (70%), fatigue (57%), depressive symptoms (16%), and neurobehavioral symptoms (27%). A multivariate regression analysis revealed that depressive symptoms are significantly associated with neurocognitive impairment. Conclusions GBM patients are vulnerable to adverse outcomes including neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance and depressive symptoms shortly after diagnosis, prior to completing chemoradiation. Those with increased depressive symptoms are more likely to demonstrate neurocognitive impairment, highlighting the need for early identification and treatment of depression in this population.
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