Surveillance tools for detection of recurrent nasopharyngeal carcinoma: An evidence-based review and recommendations.

Objective: Nasopharyngeal carcinomas (NPC) are tumors arising from epithelium of the nasopharynx. The 5-year survival rate of primary NPC is 80% with significant risks of recurrence. The objective here is to provide an evidence-based systemic review of the diagnostic value of different modalities in detecting local, regional, and distal recurrent NPC, as well as the associated costs with these modalities. Methods: MEDLINE, EMBASE, and the Cochrane review database were queried. Two hundred and twenty-three abstracts were generated using the inclusion criteria: patients >18 years of age; histopathological reference standard; and modalities pertaining to imaging or microbiology. Results: Twenty-four manuscripts fulfilled the inclusion criteria and 5 surveillance tools identified: endoscopy, MR, FDG-PET, Tc-99m MIBI and 201TI SPECT, and EBV DNA. Conclusions: For local surveillance, endoscopy is the gold standard recommendation, with increased efficacy if Narrow Band Imaging or contact endoscopy are utilized. MRI and FDG-PET is also recommended to help with local to distal spread; however, Tc-99m MIBI and 201TI SPECT are options as well. EBV DNA is recommended as a cheap and accessible adjunct surveillance tool if an available as an option.

Treatment and outcomes of nasopharyngeal carcinoma in a unique non-endemic population.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is common in Southeast Asia. Due to the influx of immigrants from this region, the incidence in British Columbia is increasing. Current literature from non-endemic populations encompasses heterogeneous cohorts. This study examines NPC in a North American population, with a high incidence, to understand the population's characteristics, treatment outcomes and recurrence patterns. METHODS AND MATERIALS: A retrospective analysis of patients treated for primary and recurrent NPC over 15-years. Regression analyses were used to identify predictors of disease recurrence and death. A subgroup analysis of the locoregional recurrence cohort was conducted. Five-year survival outcomes were determined. RESULTS: 601 patients were included. Asian ethnicity comprised 77% and the majority had non-keratinizing carcinoma (81%). In total, 19.3% of patients experienced recurrence: 58% local, 22% regional and 20% distant. Five-year overall survival was 70%. Smoking, advancing T-stage, poorer performance status and advanced overall stage were all associated with worse overall survival (p < 0.05). Asian ethnicity improved overall survival but not recurrence free survival. Similar features in addition to non-keratinizing histology were associated with increased locoregional recurrence (p < 0.05). Competing risk analysis indicated radiotherapy alone had a higher recurrence relative to chemoradiotherapy (HR 1.91, CI 1.17-3.09, p = 0.01). CONCLUSIONS: We report the largest study evaluating treatment and outcomes of NPC in a non-endemic population. This unique population falls between described endemic and non-endemic populations. Non-keratinizing pathology and primary radiotherapy did not affect survival; however, both had a propensity for recurrence. Finally, patients experienced more locoregional and less distant recurrence, supporting that this cohort may be amenable to curative salvage therapy.

Misleading Focal Clinical, Neurophysiologic, and Imaging Features in 2 Children With Generalized Epilepsy Who Underwent Invasive Electroencephalographic (EEG) Monitoring.

Children and adults with genetic generalized epilepsy may have focal clinical seizure symptoms as well as electroencephalographic (EEG) findings. This may pose a diagnostic challenge to clinicians, especially when concomitant focal neuroimaging findings exist and the epilepsy is medically refractory. We sought to highlight the challenges that clinicians may face through the description of 2 children with suspected genetic generalized epilepsy who had both focal seizure symptoms and EEG/neuroimaging findings and underwent invasive EEG monitoring. Ultimately, invasive monitoring failed to demonstrate a focal origin for the seizures in both cases, and instead confirmed the presence of genetic generalized epilepsy. We demonstrate that ≥3-Hz generalized monomorphic spike and waves are less likely to represent secondary bilateral synchrony, that focal neuroimaging findings may not always be causal and that repeated hyperventilation is an essential activation procedure for genetic generalized epilepsy.

Altered beta-band functional connectivity may be related to 'performance slowing' in good outcome aneurysmal subarachnoid patients.

Recent evidence suggests that good neurological outcome in subarachnoid hemorrhage (SAH) does not equate to good neuropsychological and cognitive outcome. These individuals continue to face cognitive difficulties in tasks involving mental flexibility, short-term memory and attention, resulting in decreased independence in daily living and reduced ability to return to work. In the current study, we examined the functional connectivity profiles using magnetoencephalography (MEG) in SAH patients, versus controls, during a visual short-term memory, 1-back, task. Our results found that a global measure of MEG-based phase synchrony in the beta band (15-30 Hz), derived from a time window during correct recognition, significantly differentiated the controls from the patients. During correct recognition, the connectivity patterns in the controls were characterized by inter-hemispheric parieto-frontal connections, involving the posterior parietal cortex, while patients appeared to recruit an entirely different network of regions, involving the anterior frontal and temporal regions. Reduced beta-band synchrony during recognition was associated with overall poorer performance, demonstrated as lower accuracy and slower reaction times in patients, but not in controls. This differentiation between groups suggests an important and distinct role of beta-band phase synchronization, perhaps for memory retrieval, associated with good performance. Performance slowing, short-term memory and attention deficits in these patients may be attributed to the impaired beta-band connectivity among prefrontal regions and the posterior parietal cortex.

Disconnected neuromagnetic networks in children born very preterm: Disconnected MEG networks in preterm children.

Many children born very preterm (≤32 weeks) experience significant cognitive difficulties, but the biological basis of such problems has not yet been determined. Functional MRI studies have implicated altered functional connectivity; however, little is known regarding the spatiotemporal organization of brain networks in this population. We provide the first examination of resting-state neuromagnetic connectivity mapped in brain space in school age children born very preterm. Thirty-four subjects (age range 7-12 years old), consisting of 17 very preterm-born children and 17 full-term born children were included. Very preterm-born children exhibited global decreases in inter-regional synchrony in all analysed frequency ranges, from theta (4-7 Hz) to high gamma (80-150 Hz; p < 0.01, corrected). These reductions were expressed in spatially and frequency specific brain networks (p < 0.0005, corrected). Our results demonstrate that mapping connectivity with high spatiotemporal resolution offers new insights into altered organization of neurophysiological networks which may contribute to the cognitive difficulties in this vulnerable population.

Desynchronization of fronto-temporal networks during working memory processing in autism.

BACKGROUND: Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). METHODS: We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. RESULTS: We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps < 0.04 corrected) previously associated with challenging high-level conditions (i.e. the left insula and the anterior cingulate cortex (ACC)) and memory encoding and/or recognition (i.e. the right middle temporal gyrus and the right fusiform gyrus). Additionally, we found that reduced connectivity processes related to the right fusiform were correlated with the severity of symptoms in children with ASD, suggesting that such atypicalities could be directly related to the behavioural deficits observed. DISCUSSION: This study provides new evidence of atypical long-range synchronization in children with ASD in fronto-temporal areas that crucially contribute to challenging WM tasks, but also emotion regulation and social cognition processes. Thus, these results support the network disorder hypothesis of ASD and argue for a specific pathophysiological contribution of brain processes related to working memory and executive functions on the symptomatology of autism.

Reduced beta band connectivity during number estimation in autism.

Recent evidence suggests that disruption of integrative processes in sensation and perception may play a critical role in cognitive and behavioural atypicalities characteristic of ASD. In line with this, ASD is associated with altered structural and functional brain connectivity and atypical patterns of inter-regional communication which have been proposed to contribute to cognitive difficulties prevalent in this group. The present MEG study used atlas-guided source space analysis of inter-regional phase synchronization in ASD participants, as well as matched typically developing controls, during a dot number estimation task. This task included stimuli with globally integrated forms (animal shapes) as well as randomly-shaped stimuli which lacked a coherent global pattern. Early task-dependent increases in inter-regional phase synchrony in theta, alpha and beta frequency bands were observed. Reduced long-range beta-band phase synchronization was found in participants with ASD at 70-145 ms during presentation of globally coherent dot patterns. This early reduction in task-dependent inter-regional connectivity encompassed numerous areas including occipital, parietal, temporal, and frontal lobe regions. These results provide the first evidence for inter-regional phase synchronization during numerosity estimation, as well as its alteration in ASD, and suggest that problems with communication among brain areas may contribute to difficulties with integrative processes relevant to extraction of meaningful 'Gestalt' features in this population.

Reduced beta connectivity during emotional face processing in adolescents with autism.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social cognition. The biological basis of deficits in social cognition in ASD, and their difficulty in processing emotional face information in particular, remains unclear. Atypical communication within and between brain regions has been reported in ASD. Interregional phase-locking is a neurophysiological mechanism mediating communication among brain areas and is understood to support cognitive functions. In the present study we investigated interregional magnetoencephalographic phase synchronization during the perception of emotional faces in adolescents with ASD. METHODS: A total of 22 adolescents with ASD (18 males, mean age =14.2 ± 1.15 years, 22 right-handed) with mild to no cognitive delay and 17 healthy controls (14 males, mean age =14.4 ± 0.33 years, 16 right-handed) performed an implicit emotional processing task requiring perception of happy, angry and neutral faces while we recorded neuromagnetic signals. The faces were presented rapidly (80 ms duration) to the left or right of a central fixation cross and participants responded to a scrambled pattern that was presented concurrently on the opposite side of the fixation point. Task-dependent interregional phase-locking was calculated among source-resolved brain regions. RESULTS: Task-dependent increases in interregional beta synchronization were observed. Beta-band interregional phase-locking in adolescents with ASD was reduced, relative to controls, during the perception of angry faces in a distributed network involving the right fusiform gyrus and insula. No significant group differences were found for happy or neutral faces, or other analyzed frequency ranges. Significant reductions in task-dependent beta connectivity strength, clustering and eigenvector centrality (all P <0.001) in the right insula were found in adolescents with ASD, relative to controls. CONCLUSIONS: Reduced beta synchronization may reflect inadequate recruitment of task-relevant networks during emotional face processing in ASD. The right insula, specifically, was a hub of reduced functional connectivity and may play a prominent role in the inability to effectively extract emotional information from faces. These findings suggest that functional disconnection in brain networks mediating emotional processes may contribute to deficits in social cognition in this population.

Atypical resting synchrony in autism spectrum disorder.

Autism spectrum disorder (ASD) is increasingly understood to be associated with aberrant functional brain connectivity. Few studies, however, have described such atypical neural synchrony among specific brain regions. Here, we used magnetoencephalography (MEG) to characterize alterations in functional connectivity in adolescents with ASD through source space analysis of phase synchrony. Resting-state MEG data were collected from 16 adolescents with ASD and 15 age- and sex-matched typically developing (TD) adolescents. Atlas-guided reconstruction of neural activity at various cortical and subcortical regions was performed and inter-regional phase synchrony was calculated in physiologically relevant frequency bands. Using a multilevel approach, we characterized atypical resting-state synchrony within specific anatomically defined networks as well as altered network topologies at both regional and whole-network scales. Adolescents with ASD demonstrated frequency-dependent alterations in inter-regional functional connectivity. Hyperconnectivity was observed among the frontal, temporal, and subcortical regions in beta and gamma frequency ranges. In contrast, parietal and occipital regions were hypoconnected to widespread brain regions in theta and alpha bands in ASD. Furthermore, we isolated a hyperconnected network in the gamma band in adolescents with ASD which encompassed orbitofrontal, subcortical, and temporal regions implicated in social cognition. Results from graph analyses confirmed that frequency-dependent alterations of network topologies exist at both global and local levels. We present the first source-space investigation of oscillatory phase synchrony in resting-state MEG in ASD. This work provides evidence of atypical connectivity at physiologically relevant time scales and indicates that alterations of functional connectivity in adolescents with ASD are frequency dependent and region dependent.

Oscillations, networks, and their development: MEG connectivity changes with age.

Magnetoencephalographic (MEG) investigations of inter-regional amplitude correlations have yielded new insights into the organization and neurophysiology of resting-state networks (RSNs) first identified using fMRI. Inter-regional MEG amplitude correlations in adult RSNs have been shown to be most prominent in alpha and beta frequency ranges and to express strong congruence with RSN topologies found using fMRI. Despite such advances, little is known about how oscillatory connectivity in RSNs develops throughout childhood and adolescence. This study used a novel fMRI-guided MEG approach to investigate the maturation of resting-state amplitude correlations in physiologically relevant frequency ranges within and among six RSNs in 59 participants, aged 6-34 years. We report age-related increases in inter-regional amplitude correlations that were largest in alpha and beta frequency bands. In contrast to fMRI reports, these changes were observed both within and between the various RSNs analyzed. Our results provide the first evidence of developmental changes in spontaneous neurophysiological connectivity in source-resolved RSNs, which indicate increasing integration within and among intrinsic functional brain networks throughout childhood, adolescence, and early adulthood.