The 2016 revision of the WHO Classification of Central Nervous System Tumours: retrospective application to a cohort of diffuse gliomas.

The classification of central nervous system tumours has more recently been shaped by a focus on molecular pathology rather than histopathology. We re-classified 82 glial tumours according to the molecular-genetic criteria of the 2016 revision of the World Health Organization (WHO) Classification of Tumours of the Central Nervous System. Initial diagnoses and grading were based on the morphological criteria of the 2007 WHO scheme. Because of the impression of an oligodendroglial component on initial histological assessment, each tumour was tested for co-deletion of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH-1 and 2) genes. Additionally, expression of proteins encoded by alpha-thalassemia X-linked mental retardation (ATRX) and TP53 genes was assessed by immunohistochemistry. We found that all but two tumours could be assigned to a specific category in the 2016 revision. The most common change in diagnosis was from oligoastrocytoma to specifically astrocytoma or oligodendroglioma. Analysis of progression free survival (PFS) for WHO grade II and III tumours showed that the objective criteria of the 2016 revision separated diffuse gliomas into three distinct molecular categories: chromosome 1p/19q co-deleted/IDH mutant, intact 1p/19q/IDH mutant and IDH wild type. No significant difference in PFS was found when comparing IDH mutant grade II and III tumours suggesting that IDH status is more informative than tumour grade. The segregation into distinct molecular sub-types that is achieved by the 2016 revision provides an objective evidence base for managing patients with grade II and III diffuse gliomas based on prognosis.

Binaural interactions develop in the auditory brainstem of children who are deaf: effects of place and level of bilateral electrical stimulation.

Bilateral cochlear implants (CIs) might promote development of binaural hearing required to localize sound sources and hear speech in noise for children who are deaf. These hearing skills improve in children implanted bilaterally but remain poorer than normal. We thus questioned whether the deaf and immature human auditory system is able to integrate input delivered from bilateral CIs. Using electrophysiological measures of brainstem activity that include the Binaural Difference (BD), a measure of binaural processing, we showed that a period of unilateral deprivation before bilateral CI use prolonged response latencies but that amplitudes were not significantly affected. Tonotopic organization was retained to some extent as evidenced by an elimination of the BD with large mismatches in place of stimulation between the two CIs. Smaller place mismatches did not affect BD latency or amplitude, indicating that the tonotopic organization of the auditory brainstem is underdeveloped and/or not well used by CI stimulation. Finally, BD amplitudes decreased when the intensity of bilateral stimulation became weighted to one side and this corresponded to a perceptual shift of sound away from midline toward the side of increased intensity. In summary, bilateral CI stimulation is processed by the developing human auditory brainstem leading to perceptual changes in sound location and potentially improving hearing for children who are deaf.

Life after surgical resection of a low-grade glioma: A prospective cross-sectional study evaluating health-related quality of life.

Health related quality of life (HRQoL) has become an important consideration in LGG patients. We report the largest prospective, longitudinal, cross-sectional cohort study of HRQoL in LGG patients, aiming to identify actionable determinants of HRQoL. Post-operative LGG adults at a large tertiary center underwent HRQoL assessment using the EORTC QLQ-C30 questionnaire administered at follow-up visits and by mail. Scores at 12 month intervals were compared with those from a normative reference population. Spearman's Rho was used to evaluate correlation of subdomain and symptom scores with global HRQoL and change over time. There were 167 participants and 366 questionnaires analysed. Patients reported reduced global HRQoL at nearly every 12 month interval with significant impairments at 12, 72, 108, and 120+ months postoperative. They also reported a significant impairment in each functional subdomain at 12 months, which persisted to varying degrees over 120 months, as did significant fatigue and insomnia. Role, emotional, and social subdomains, as well as fatigue, were significantly associated with global HRQoL at the first 12 month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. LGG patients report considerable, sustained impairments in HRQoL after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and insomnia. These are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that with intervention, may improve HRQoL for our LGG patients. This is the largest prospective longitudinal study of HRQoL in postoperative LGG patients yet reported and is ongoing. It identifies several determinants of impaired HRQoL with available management options and interventions that have the potential to significantly improve HRQoL in these patients.

Life after surgical resection of a meningioma: a prospective cross-sectional study evaluating health-related quality of life.

Background: Few studies have evaluated the health-related quality of life (HRQoL) of patients with meningiomas. Here, we report the largest prospective, longitudinal cross-sectional cohort study of HRQoL in meningiomas to date, in order to identify possible actionable determinants of global HRQoL. Methods: Adults who had undergone resection of a grade I intracranial meningioma and were in routine follow-up at a single large tertiary center underwent HRQoL assessment using the QLQ-C30 questionnaire administered opportunistically at follow-up visits. Averaged transformed QLQ-C30 scores at 12-month intervals were compared with scores from a normative reference population, with reference to known minimal clinically meaningful difference (CMD) in scores. To evaluate for possible determinants of changes in global HRQoL, global HRQoL scores were correlated (Spearman's Rho) with subdomain and symptom scores and with interval time from surgical resection. Results: A total of 291 postoperative patients with histologically confirmed and surgically treated grade I meningiomas consented to participation and a total of 455 questionnaires were included for analysis. Patients with meningiomas reported reduced global HRQoL at nearly every 12-month interval with clinically and statistically significant impairments at 12, 48, 108, and 120 months postoperative compared with the normative population (P < 0.05). Meningioma patients at the 12-month interval also reported a reduction of each subdomain of HRQoL assessment (P < 0.05); however, a CMD was only seen in cognitive functioning. Physical, emotional, cognitive, and social subdomains, as well as fatigue and sleep/insomnia, were significantly associated with global HRQoL at the first 12-month interval. Overall, there was no significant correlation between time from surgery and global HRQoL or the subdomain functional or symptom sections of the QLQ-C30. Conclusions: Meningioma patients report considerable limitations in HRQoL for more than 120 months after surgery, particularly in cognitive, emotional, and social function, as well as suffering significant fatigue and sleep impairment compared with a normative reference population. The majority of these reported functional impairments and symptoms are strongly associated with global HRQoL and thus can be considered determinants of global HRQoL that if treated, have the potential to improve HRQoL for our meningioma patients. This hypothesis requires future study of targeted interventions to determine their efficacy.