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Balance, falls risk, and related disability in untreated vestibular schwannoma patients.

ABSTRACT: Background Many vestibular schwannoma (VS) patients complain of balance dysfunction; however, validated standardized assessments are lacking. The relative contribution of imbalance and factors like anxiety to disability is unknown. Because imbalance significantly affects quality of life in this group and vestibular rehabilitation may improve outcomes, determining the severity of balance dysfunction is important to understand long-term rehabilitation needs. Aim To assess functional balance (Vertigo Symptom Scale-Vertigo [VSS-VER] and Functional Gait Assessment [FGA]) and the relative contribution of symptom severity (VSS-VER), ambulant posture (FGA), and anxiety symptoms (Vertigo Symptom Scale-Anxiety [VSS-SA]) to disability in untreated patients. Methods Patients not exposed to surgery completed the VSS, Vertigo Handicap Questionnaire (VHQ), and FGA. VSS scores were compared with migrainous vertigo (MV) patients, a mixed neuro-otological group, and healthy controls. Results A correlation was found between decreased FGA and increasing age (r = - 0.35; p < 0.01), female sex (r = 0.42; p = 0.001), increasing handicap (r = - 0.55; p < 0.001), and symptom severity (r = - 0.52; p < 0.001). In 12 of 21 patients (57%) > 60 years of age the FGA score was ≤ 22 suggesting increased falls risk. VSS-VER scores were higher than in healthy controls (p < 0.001) but lower than MV (p < 0.001) and mixed neuro-otology controls (p < 0.001). VSS-SA scores in VS patients with balance symptoms were higher than normal controls (p < 0.05) and correlated with handicap (r = 0.59; p < 0.001) and symptom severity (r = 0.74; p < 0.001). After controlling for age and sex, the VSS-VER, VSS-SA, and FGA explained 47% of the variation in VHQ scores. Conclusion Older VS patients are at significant risk of falls. Balance symptoms are more severe than in healthy controls but less than other neuro-otological patients. Balance symptom severity, anxiety symptoms, and ambulant posture were significant contributors to disability and should be the focus of vestibular rehabilitation strategies.

SUBMITTER: Saman Y

PROVIDER: S-EPMC4176536 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Project description:Bilateral vestibular schwannoma is the hallmark of NF2-related schwannomatosis, a rare tumour predisposition syndrome associated with a lifetime of surgical interventions, radiotherapy and off-label use of the anti-angiogenic drug bevacizumab. Unilateral vestibular schwannoma develops sporadically in non-NF2-related schwannomatosis patients for which there are no drug treatment options available. Tumour-infiltrating immune cells such as macrophages and T-cells correlate with increased vestibular schwannoma growth, which is suggested to be similar in sporadic and NF2-related schwannomatosis tumours. However, differences between NF2-related schwannomatosis and the more common sporadic disease include NF2-related schwannomatosis patients presenting an increased number of tumours, multiple tumour types and younger age at diagnosis. A comparison of the tumour microenvironment in sporadic and NF2-related schwannomatosis tumours is therefore required to underpin the development of immunotherapeutic targets, identify the possibility of extrapolating ex vivo data from sporadic vestibular schwannoma to NF2-related schwannomatosis and help inform clinical trial design with the feasibility of co-recruiting sporadic and NF2-related schwannomatosis patients. This study drew together bulk transcriptomic data from three published Affymetrix microarray datasets to compare the gene expression profiles of sporadic and NF2-related schwannomatosis vestibular schwannoma and subsequently deconvolved to predict the abundances of distinct tumour immune microenvironment populations. Data were validated using quantitative PCR and Hyperion imaging mass cytometry. Comparative bioinformatic analyses revealed close similarities in NF2-related schwannomatosis and sporadic vestibular schwannoma tumours across the three datasets. Significant inflammatory markers and signalling pathways were closely matched in NF2-related schwannomatosis and sporadic vestibular schwannoma, relating to the proliferation of macrophages, angiogenesis and inflammation. Bulk transcriptomic and imaging mass cytometry data identified macrophages as the most abundant immune population in vestibular schwannoma, comprising one-third of the cell mass in both NF2-related schwannomatosis and sporadic tumours. Importantly, there were no robust significant differences in signalling pathways, gene expression, cell type abundance or imaging mass cytometry staining between NF2-related schwannomatosis and sporadic vestibular schwannoma. These data indicate strong similarities in the tumour immune microenvironment of NF2-related schwannomatosis and sporadic vestibular schwannoma.

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Balance, falls risk, and related disability in untreated vestibular schwannoma patients.

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