Perspectives of adults with neurofibromatosis regarding the design of psychosocial trials: Results from an anonymous online survey.

BACKGROUND/AIMS: Individuals with neurofibromatosis, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2)-related schwannomatosis (SWN), and other forms of SWN, often experience disease manifestations and mental health difficulties for which psychosocial interventions may help. An anonymous online survey of adults with neurofibromatosis assessed their physical, social, and emotional well-being and preferences about psychosocial interventions to inform clinical trial design. METHODS: Neurofibromatosis clinical researchers and patient representatives from the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration developed the survey. Eligibility criteria included age ≥ 18 years, self-reported diagnosis of NF1, NF2, or SWN, and ability to read and understand English. The online survey was distributed internationally by the Neurofibromatosis Registry and other neurofibromatosis foundations from June to August 2020. RESULTS: Surveys were completed by 630 adults (18-81 years of age; M = 45.5) with NF1 (78%), NF2 (14%), and SWN (8%) who were mostly White, not Hispanic/Latino, female, and from the United States. The majority (91%) reported that their neurofibromatosis symptoms had at least some impact on daily life. In the total sample, 51% endorsed a mental health diagnosis, and 27% without a diagnosis believed they had an undiagnosed mental health condition. Participants indicated that neurofibromatosis affected their emotional (44%), physical (38%), and social (35%) functioning to a high degree. Few reported ever having participated in a drug (6%) or psychosocial (7%) clinical trial, yet 68% reported they "probably" or "definitely" would want to participate in a psychosocial trial if it targeted a relevant concern. Top treatment targets were anxiety, healthier lifestyle, and daily stress. Top barriers to participating in psychosocial trials were distance to clinic, costs, and time commitment. Respondents preferred interventions delivered by clinicians via individual sessions or a combination of group and individual sessions, with limited in-person and mostly remote participation. There were no significant group differences by neurofibromatosis type in willingness to participate in psychosocial trials (p = 0.27). Regarding interest in intervention targets, adults with SWN were more likely to prefer psychosocial trials for pain support compared to those with NF1 (p < 0.001) and NF2 (p < 0.001). CONCLUSION: This study conducted the largest survey assessing physical symptoms, mental health needs, and preferences for psychosocial trials in adults with neurofibromatosis. Results indicate a high prevalence of disease manifestations, psychosocial difficulties, and untreated mental health problems in adults with neurofibromatosis and a high degree of willingness to participate in psychosocial clinical trials. Patient preferences should be considered when designing and implementing psychosocial interventions to develop the most feasible and meaningful studies.

Current Recommendations for Patient-Reported Outcome Measures Assessing Domains of Quality of Life in Neurofibromatosis Clinical Trials.

OBJECTIVE: To review and recommend patient-reported outcome (PRO) measures assessing multidimensional domains of quality of life (QoL) to use as clinical endpoints in medical and psychosocial trials for children and adults with neurofibromatosis (NF) type 1, NF2, and schwannomatosis. METHODS: The PRO working group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration used systematic methods to review, rate, and recommend existing self-report and parent-report PRO measures of generic and disease-specific QoL for NF clinical trials. Recommendations were based on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility. RESULTS: The highest-rated generic measures were (1) the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales for NF clinical trials for children or for children through adults, (2) the Functional Assessment of Cancer Therapy-General for adult medical trials, and (3) the World Health Organization Quality of Life-BREF for adult psychosocial trials. The highest-rated disease-specific measures were (1) the PedsQL NF1 Module for NF1 trials, (2) the NF2 Impact on Quality of Life Scale for NF2 trials, and (3) the Penn Acoustic Neuroma Quality of Life Scale for NF2 trials targeting vestibular schwannomas. To date, there are no disease-specific tools assessing multidimensional domains of QoL for schwannomatosis. CONCLUSIONS: The REiNS Collaboration currently recommends these generic and disease-specific PRO measures to assess multidimensional domains of QoL for NF clinical trials. Additional research is needed to further evaluate the use of these measures in both medical and psychosocial trials.

Recommendations for Social Skills End Points for Clinical Trials in Neurofibromatosis Type 1.

OBJECTIVE: To review parent-report social skills measures to identify and recommend consensus outcomes for use in clinical trials of social deficit in children and adolescents (ages 6-18 years) with neurofibromatosis type 1 (NF1). METHODS: Searches were conducted via PubMed and ClinicalTrials.gov to identity social skills outcome measures with English language versions used in clinical trials in the past 5 years with populations with known social skills deficits, including attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD). Measures were rated by the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Neurocognitive Committee on patient characteristics, use in published studies, domains assessed, availability of standard scores, psychometric properties, and feasibility to determine their appropriateness for use in NF1 clinical trials. RESULTS: Two measures were ultimately recommended by the committee: the Social Responsiveness Scale-2 (SRS-2) and the Social Skills Improvement System-Rating Scale (SSIS-RS). CONCLUSIONS: Each of the 2 measures assesses different aspects of social functioning. The SSIS-RS is appropriate for studies focused on broader social functioning; the SRS-2 is best for studies targeting problematic social behaviors associated with ASD. Researchers will need to consider the goals of their study when choosing a measure, and specific recommendations for their use are provided.

Acute Neurologic Deterioration in Mobile Spinal Schwannoma.

BACKGROUND: Spinal schwannomas are commonly presented with minor symptoms, including radicular pain, sensory deficits, and minor neurologic deficit. Acute neurologic deterioration is uncommon. CASE DESCRIPTION: In this study, a case of cauda equina schwannoma presented with acute neurologic deficit after movement of spinal schwannoma is presented. CONCLUSIONS: It is noted that movement of spinal schwannoma and resultant acute neurologic deterioration should be considered during the follow-up.

A missing piece? Neuropsychiatric functioning in untreated patients with tumors within the cerebellopontine angle.

PURPOSE: To date, little is known about neuropsychiatric symptoms in patients with tumors within the cerebellopontine angle (CPA). These, however, might be of clinical relevance. Aim of this study was thus to assess possible impairment in cognition, elevation in mood symptoms, and fatigue in this specific patient group. METHODS: Forty-five patients with an untreated CPA tumor (27 vestibularis schwannoma, 18 meningioma) were tested within a cross-sectional observational study in a single institution prior to neurosurgical treatment. Patients were administered a multifaceted battery comprising of widely-used tests for assessment of neuropsychiatric functioning. RESULTS: The majority of the included patients (69%) showed neurocognitive impairment, most frequently in the areas of attention and visuo-motor speed (e.g., alertness) (62%) as well as visuo-construction (44%). Impaired structural integrity of the brain stem was accompanied by more serious neurocognitive deficits. About one-third of the sample reported clinically relevant depression and/or anxiety and an even higher proportion (48%) described high levels of fatigue. Cognitive and affective symptoms as well as fatigue contributed significantly to patients' Quality of Life, indicating the clinical relevance of neuropsychiatric symptoms in patients with CPA tumors. CONCLUSIONS: Although patients with untreated CPA tumors often suffer from devastating and prominent physical symptoms, neuropsychiatric problems are also frequent. Including these aspects in the routine clinical assessment and initiating treatment accordingly might thus improve clinical management of the patients and improve Quality of Life.

Health literacy assessment in adults with neurofibromatosis: electronic and short-form measurement using FCCHL and Health LiTT.

Determining health literacy level is an important prerequisite for effective patient education. We assessed multiple dimensions of health literacy and sociodemographic predictors of health literacy in patients with neurofibromatosis. In 86 individuals with a confirmed diagnosis of neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), or schwannomatosis, we assessed health literacy status using two HL tools-the adapted functional, communicative, and critical health literacy scale (adapted FCCHL) and health literacy assessment using talking touchscreen technology (Health LiTT). Factor analyses of the adapted FCCHL in NF patients showed factor structure and psychometric properties similar to pilot work in other patient populations. As a group, patients with NF had moderate scores on the Health LiTT and moderate to high scores on the adapted FCCHL, with the highest score on the functional health literacy subscale. Patients with NF1, those with lower education and those with learning disabilities had lower scores on Health LiTT; in multivariate analysis, learning disability and education remained significant predictors of HealthLiTT scores. Only lower education was associated with lower adapted FCCHL scores. Results suggest utilizing health literacy tools in NF patients is feasible and could provide physicians with valuable information to tailor health communication to subpopulations with lower health literacy levels.

First use of patient reported outcomes measurement information system (PROMIS) measures in adults with neurofibromatosis.

The patient reported outcomes measurement information system (PROMIS) provides clinicians and researchers access to reliable, validated measures of physical, mental, and social well-being. The use of PROMIS can facilitate comparisons among clinical subpopulations and with the U.S. general population. We report on the first study using PROMIS measures in patients with neurofibromatosis (NF). Eighty-six adult patients (mean age = 44; 55% female; 87% white; 50% NF1, 41% NF2 and 9% schwannomatosis) completed a battery of PROMIS computerized adaptive tests (CATs). Across all PROMIS instruments, mean scores for each CAT were between 48.97 and 52.60, which is within ±0.5 SD of the U.S. general population norms. However, scores were distributed across a broad range for each PROMIS measure (±3 SDs). Clinically meaningful scores (defined >1 SD impairment) were observed in 20% (pain interference), 17% (pain behavior), 16% (physical function), 16% (anxiety), 16% (depression), 15% (satisfaction with social roles), 13% (fatigue), 6% (anger), and 5% (satisfaction with discretionary social activities) of the sample. All PROMIS measures were highly interrelated in bivariate analysis (P ≤ .001). There were no differences in PROMIS scores by disease type (NF1, NF2 and schwannomatosis), or self reported learning disabilities, or compared with the US population. Scores suggest a broad continuum of symptoms and functioning in patients with NF that is not affected by NF type, as well as interrelation among the physical and psychosocial domains as measured by PROMIS. PROMIS measures may be useful in clinical practice to monitor changes in symptoms and functioning over time, as well as in clinical trials to determine patient reported changes during drug and psychosocial clinical trials.

Improved patient quality of life following intradural extramedullary spinal tumor resection.

OBJECTIVE Resection significantly improves the clinical symptoms and functional outcomes of patients with intradural extramedullary tumors. However, patient quality of life following resection has not been adequately investigated. The aim in this retrospective analysis of prospectively collected quality of life outcomes is to analyze the efficacy of resection of intradural extramedullary spinal tumors in terms of quality of life markers. METHODS A retrospective review of a single institutional neurosurgical administrative database was conducted to analyze clinical data. The Oswestry Disability Index (ODI), visual analog scale (VAS) for pain, and the EQ-5D-3 L descriptive system were used to analyze quality of life preoperatively, less than 1 month postoperatively, 1-3 months postoperatively, 3-12 months postoperatively, and more than 12 months postoperatively. RESULTS The ODI scores increased perioperatively at the < 1-month follow-up from 36 preoperatively to 47. Relative to preoperative values, the ODI score decreased significantly at 1-3, 3-12, and > 12 months to 23, 17, and 20, respectively. VAS scores significantly decreased from 6.1 to 3.5, 2.4, 2.0, and 2.9 at the < 1-month, 1- to 3-, 3- to 12-, and > 12-month follow-ups, respectively. EQ-5D mobility significantly worsened at the < 1-month follow-up but improved at the 3- to 12-and > 12-month follow-ups. EQ-5D self-care significantly worsened at the < 1-month follow-up but significantly improved by the 3- to 12-month follow-up. EQ-5D usual activities improved at the 1- to 3-, 3- to 12-, and > 12-month follow-ups. EQ-5D pain and discomfort significantly improved at all follow-up points. EQ-5D anxiety and depression significantly improved at 1- to 3-month and 3- to 12-month follow-ups. CONCLUSIONS Resection of intradural extramedullary spine tumors appears to significantly improve patient quality of life by decreasing patient disability and pain and by improving each of the EQ-5D domains.

Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis.

Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis share a predisposition to develop multiple nerve sheath tumors. Previous studies have demonstrated that patients with NF1 and NF2 have reduced quality of life (QOL), but no studies have examined the relationship between whole-body tumor burden and QOL in these patients. We administered a QOL questionnaire (the SF-36) and a visual analog pain scale (VAS) to a previously described cohort of adult neurofibromatosis patients undergoing whole-body MRI. One-sample t-tests were used to compare norm-based SF-36 scores to weighted population means. Spearman correlation coefficients and multiple linear regression analyses controlling for demographic and disease-specific clinical variable were used to relate whole-body tumor volume to QOL scales. Two hundred forty-five patients (142 NF1, 53 NF2, 50 schwannomatosis) completed the study. Subjects showed deficits in selected subscales of the SF-36 compared to adjusted general population means. In bivariate analysis, increased tumor volume was significantly associated with pain in schwannomatosis patients, as measured by the SF-36 bodily pain subscale (rho = -0.287, P = 0.04) and VAS (rho = 0.34, P = 0.02). Regression models for NF2 patients showed a positive relationship between tumor burden and increased pain, as measured by the SF-36 (P = 0.008). Patients with NF1, NF2, and schwannomatosis suffer from reduced QOL, although only pain shows a clear relationship to patient's overall tumor burden. These findings suggest that internal tumor volume is not a primary contributor to QOL and emphasize the need for comprehensive treatment approaches that go beyond tumor-focused therapies such as surgery by including psychosocial interventions.

Emotional functioning of patients with neurofibromatosis tumor suppressor syndrome.

PURPOSE: Although patients with neurofibromatosis are predisposed to multiple nerve sheath tumors that can develop anywhere in the body and cause significant morbidity (e.g., hearing loss; pain), little research has examined emotional correlates of neurofibromatosis. The purpose of this study was to examine emotional functioning among adult patients with neurofibromatosis. METHODS: A total of 248 patients with neurofibromatosis (neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis) who received care at a specialized clinic completed validated measures to assess symptoms of depression and anxiety, level of perceived stress, and self-esteem. RESULTS: Patients with neurofibromatosis reported significantly more symptoms of depression and anxiety, higher levels of perceived stress, and lower levels of self-esteem as compared with general population norms. No significant differences were found among patients with neurofibromatosis 1, neurofibromatosis 2, and schwannomatosis, and emotional functioning was not significantly associated with disease severity. However, increased symptoms of depression and anxiety, higher levels of perceived stress, and lower levels of self-esteem were associated with a higher frequency of self-reported medical visits in the past year (P values ≤0.05). CONCLUSION: Neurofibromatosis appears to be associated with reduced emotional functioning. Although further research is needed, these findings suggest a role for a multidisciplinary treatment approach to address emotional distress among adult patients with neurofibromatosis.

Pathological laughter in trigeminal schwannoma: case report and review of the literature.

Pathological laughter is an uncommon manifestation of neurosurgical diseases. Very few cases of trigeminal schwannoma have been reported in the literature presenting with pathological laughter as a predominant symptom. We are reporting on a case of multi-compartmental trigeminal schwannoma presenting as pathological laughter and discuss a review of the literature. A 23-year-old lady presented with pathological laughter, along with symptoms pertaining to other cranial nerves and cerebellar dysfunction. Magnetic resonance imaging (MRI) of the brain was suggestive of a dumbbell-shaped mass in the middle and posterior cranial fossa on the left side, causing significant compression of the pons. She was investigated and operated for multi-compartmental trigeminal schwannoma. Following surgery, abnormal laughter disappeared immediately and no recurrence of symptoms was -present for a follow-up of 16 months. This case supports the role of the brainstem, especially the pons, in the control of laughter and, perhaps, of the medial temporal lobe too.

Trigeminal schwannoma associated with pathological laughter and crying.

A 46 year old man with trigeminal schwannoma displayed symptoms of ataxia with pathological laughter and crying. The tumour developed in the cerebellopontine angle, compressing the pontomesencephalic structures backward, extending in the posterior parasellar region and Meckel's cave. No recurrence of laughter and crying attacks were noted after total removal of the tumour. Theories of mechanism of pathological laughter and crying reported in the literature are reviewed.