Quality of life in patients with neurofibromatosis type 1 and 2 in Canada.
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ABSTRACT:
SUBMITTER: Hamoy-Jimenez G
PROVIDER: S-EPMC7317053 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis study examined the association between neurological symptoms and quality of life (QoL) in patients with neurofibromatosis type 2 (NF2) using a national database of all patients who newly claimed for medical expense subsidies in Japan from 2015 to 2019.MethodsThe Japanese Ministry of Health, Labour and Welfare provided access to the "National Database of Designated Intractable Diseases of Japan" containing the "Medical Certificates of Designated Intractable Diseases" of all patients with NF2. The database included information on five items of QoL: "mobility," "self-care," "usual activities," "pain/discomfort," and "anxiety/depression." To examine the association between the presence/absence of neurological symptoms and QoL, multivariable logistic regression analyses were performed, adjusted for potential confounders.ResultsData from 187 patients (97 females and 90 males; mean (standard deviation) age, 43.1 (17.9) years) were analyzed. Overall, 31% to 55% of patients were recorded as having moderate/severe impairment of QoL. Spinal dysfunction was significantly associated with deterioration of all components of QoL, whereas speech dysfunction and hemiparesis were specifically associated with physical health-related components of QoL. Spinal dysfunction, facial nerve palsy, and age 25-64 years were significantly associated with "anxiety/depression."ConclusionsIn the present epidemiological study using a national database of NF2 in Japan, spinal dysfunction was significantly associated with deterioration of all components of QoL, including subjective and mental health-related components of QoL, whereas speech dysfunction and hemiparesis were specifically associated with physical health-related components of QoL.
| S-EPMC11362668 | biostudies-literature
Project description:BackgroundNeurofibromatosis type 1 (NF1) is a genetic disorder that affects multiple systems in the body, often leading to physical disfigurements and a wide range of clinical symptoms. This study aims to investigate the relationship between NF1 severity and visibility and the quality of life (QoL) in children.MethodsThe Pediatric Quality of Life Inventory (PedsQL) and a modified version of the Ablon scale were used to assess QoL and NF1 severity and visibility, respectively. Self-reported and parent-reported QoL scores were compared, and the associations between NF1 severity/visibility and QoL were explored.ResultsThirty-eight pediatric NF1 patients and their parents were enrolled. QoL scores did not differ significantly between patient self-reports and parent reports. However, correlational analyses revealed that higher NF1 severity was associated with lower physical QoL in patients, and greater NF1 visibility was linked to lower physical and social QoL. For parents, higher NF1 severity correlated with lower school functioning, whereas NF1 visibility did not show a significant correlation with QoL.ConclusionThe severity and visibility of NF1 have distinct impacts on various aspects of QoL in children, highlighting the need for tailored interventions that address both physical and psychological challenges. These findings underscore the importance of comprehensive care approaches in managing NF1 in pediatric populations.
| S-EPMC11352328 | biostudies-literature
Project description:Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder resulting from germline mutations in the NF1 gene, which encodes neurofibromin. Patients experience a variety of symptoms, but pain in the context of NF1 remains largely underrecognized. Here, we characterize nociceptive signaling and pain behaviors in a miniswine harboring a disruptive NF1 mutation (exon 42 deletion). We present the first characterization of pain-related behaviors in a pig model of NF1, identifying unchanged agitation scores, lower tactile thresholds (allodynia), and decreased response latencies to thermal laser stimulation (hyperalgesia) in NF1 (females only) pigs. Male NF1 pigs with tumors showed reduced sleep quality and increased resting, 2 health-related quality-of-life symptoms found to be comorbid in people with NF1 pain. We explore these phenotypes in relationship to suppression of the increased activity of the N-type voltage-gated calcium (CaV2.2) channel by pharmacological antagonism of phosphorylation of a regulatory protein-the collapsin response mediator protein 2 (CRMP2), a known interactor of neurofibromin, and by targeting the interface between the α subunit of CaV2.2 and the accessory β-subunits with small molecules. Our data support the use of NF1 pigs as a large animal model for studying NF1-associated pain and for understanding the pathophysiology of NF1. Our findings demonstrate the translational potential of 2 small molecules in reversing ion channel remodeling seen in NF1. Interfering with CaV2.2, a clinically validated target for pain management, might also be a promising therapeutic strategy for NF1-related pain management.
| S-EPMC6800626 | biostudies-literature
Project description:Neurofibromatosis type 1 (NF1), or von Recklinghausen disease, is an autosomal dominant disease that presents with various symptoms, including café-au-lait spots and neurofibromas. NF1 patients occasionally suffer from renal artery vasculopathy, which impairs renal function, while results of a previous report suggested that male NF1 patients have a low creatinine level in peripheral blood. The assessment of renal function in NF1 patients remains inadequate. In this study, renal function in NF1 was assessed. We recruited 308 patients consisting of 149 NF1 patients (77 males and 72 females) and 159 control patients (102 males and 57 females). Creatinine, blood urea nitrogen and haemoglobin A1c in peripheral blood as well as protein, occult blood and sugar in urine were examined. In addition, the estimated glomerular filtration rate was calculated. The mean age and body mass index did not differ significantly between the NF1 patients and controls for both sexes. For both sexes, i) the mean creatinine value was significantly lower in the NF1 patients than in the controls; ii) the mean blood urea nitrogen value did not differ significantly between the NF1 patients and controls; iii) the mean blood urea nitrogen-to-creatinine ratio was significantly higher in the NF1 patients than in the controls; iv) the mean estimated glomerular filtration rate was significantly higher in the NF1 patients than in the controls; and v) the mean haemoglobin A1c value was significantly lower in the NF1 patients than in the controls. In conclusion, NF1 patients may have improved renal function. The clinical significances should be further examined.
| S-EPMC9168021 | biostudies-literature
Project description:BackgroundPlexiform neurofibromas (PN) are complex, benign nerve-sheath tumours that occur in 30-50% of patients with neurofibromatosis type 1 (NF1), a rare, genetic disorder. PN are associated with substantial, heterogeneous morbidities that impact health-related quality of life (HRQoL), including affecting motor function and causing pain, though HRQoL and work productivity data are scarce. This UK cross-sectional study explored HRQoL and work productivity in adult patients with NF1 PN and caregivers of paediatric patients.MethodsAdult patients and caregivers of paediatric patients self-enrolled in an online survey (March-April 2021). Outcomes included EQ-5D-5L, PROMIS® GH and INF1-QOL (adult patients only), and EQ-5D-5L, CarerQol and WPAI (caregivers only). Utilities were estimated from EQ-5D-5L responses using the UK crosswalk value set. Linear regression models explored univariable associations between adult patient characteristics and HRQoL.ResultsMean (± standard deviation) EQ-5D utility in adult patients with NF1 PN was 0.65 (± 0.29; n = 35; age-/sex-matched norm: 0.89 [± 0.04]). Moderate-extreme pain/discomfort and anxiety/depression were reported by 14/35 (40.0%) and 18/35 (51.4%) patients, respectively. Mean PROMIS® GH physical and mental health scores were 43.6 (± 9.19) and 41.7 (± 11.5; n = 35; matched norm: 50.0 [± 10.0]). Mean INF1-QOL score was 11.03 (± 6.02; n = 33). Chronic itching, at least one symptom, at least one comorbidity, PN location at extremities (arms/legs) and pain were associated with worse HRQoL scores. Mean caregiver EQ-5D utility was 0.72 (± 0.24; n = 8; age-/sex-matched norm: 0.88 [± 0.03]). Moderate pain/discomfort and moderate-severe anxiety/depression were reported by 4/8 (50.0%) and 2/8 (25.0%) caregivers, respectively. Mean CarerQol score was 69.3 (± 13.9; n = 8). Mean WPAI regular activity productivity loss was 36.3% (± 31.6%; n = 8).ConclusionsNF1 PN worsens adult patient and caregiver HRQoL compared to the general population, notably affecting pain and discomfort, anxiety and depression and caregiver productivity.
| S-EPMC10666383 | biostudies-literature
Project description:Profound hearing loss is a serious complication of neurofibromatosis type 2, a genetic condition associated with bilateral vestibular schwannomas, benign tumors that arise from the eighth cranial nerve. There is no medical treatment for such tumors.We determined the expression pattern of vascular endothelial growth factor (VEGF) and three of its receptors, VEGFR-2, neuropilin-1, and neuropilin-2, in paraffin-embedded samples from 21 vestibular schwannomas associated with neurofibromatosis type 2 and from 22 sporadic schwannomas. Ten consecutive patients with neurofibromatosis type 2 and progressive vestibular schwannomas who were not candidates for standard treatment were treated with bevacizumab, an anti-VEGF monoclonal antibody. An imaging response was defined as a decrease of at least 20% in tumor volume, as compared with baseline. A hearing response was defined as a significant increase in the word-recognition score, as compared with baseline.VEGF was expressed in 100% of vestibular schwannomas and VEGFR-2 in 32% of tumor vessels on immunohistochemical analysis. Before treatment, the median annual volumetric growth rate for 10 index tumors was 62%. After bevacizumab treatment in the 10 patients, tumors shrank in 9 patients, and 6 patients had an imaging response, which was maintained in 4 patients during 11 to 16 months of follow-up. The median best response to treatment was a volumetric reduction of 26%. Three patients were not eligible for a hearing response; of the remaining seven patients, four had a hearing response, two had stable hearing, and one had progressive hearing loss. There were 21 adverse events of grade 1 or 2.VEGF blockade with bevacizumab improved hearing in some, but not all, patients with neurofibromatosis type 2 and was associated with a reduction in the volume of most growing vestibular schwannomas.
| S-EPMC4816642 | biostudies-literature
Project description:Genetic analysis of Neurofibromatosis type 1 (NF1) may facilitate the identification of patients in early phases of the disease. Here, we present an overview of our diagnostic research spanning the last 11 years, with a focus on the description of 225 NF1 mutations, 126 of which are novel, found in a series of 607 patients (513 unrelated) in Italy. Between 2003 and 2013, 443 unrelated patients were profiled by denaturing high pressure liquid chromatography (DHPLC) analysis of 60 amplicons derived from genomic NF1 DNA and subsequent sequencing of heterozygotic PCR products. In addition, a subset of patients was studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications, large deletions or microdeletions present at the locus. Over the last year, 70 unrelated patients were investigated by MLPA and sequencing of 22 amplicons spanning the entire NF1 cDNA. Mutations were found in 70% of the 293 patients studied by DHPLC, thereby fulfilling the NIH criterion for the clinical diagnosis of NF1 (detection rate: 70%); furthermore, 87% of the patients studied by RNA sequencing were genetically characterized. Mutations were also found in 36 of the 159 patients not fulfilling the NIH clinical criteria. We confirmed a higher incidence of intellectual disability in patients harboring microdeletion type 1 and observed a correlation between a mild phenotype and the small deletion c.2970_2972delAAT or the missense alteration in amino acid residue 1809 (p.Arg1809Cys). These data support the use of RNA-based methods for genetic analysis and provide novel information for improving the management of symptoms in oligosymptomatic patients.
| S-EPMC4694136 | biostudies-literature
Project description:Neurofibromatosis type I (NF1) predisposes patients to various neoplasias, including gastrointestinal stromal tumors (GISTs). Little is known about the risk of developing GISTs for NF1 patients or the clinicopathologic features and prognosis of NF1-GIST.We conducted a multi-detector computed tomography screen for adult NF1 patients between 2003 and 2012. Clinicopathologic data of sporadic GISTs from patients who underwent surgery between 2001 and 2010 were retrospectively collected from 32 hospitals in Japan.CT screening identified 6 GIST patients from the 95 NF1 patients screened, suggesting that the prevalence rate of GISTs was approximately 6.3/100 in NF1 patients. All 6 NF1 patients exhibited hyperplasia of the interstitial cells of Cajal in the adjoining small intestine. NF1-GISTs may account for 1.1-1.3 % of primary sporadic GISTs and present as multiple tumors in the small intestine, with low mitotic activity and no KIT or PDGFRA mutations. The risk of recurrence and mortality is very similar between NF1 and non-NF1 patients after surgical resection of GISTs.NF1 patients may be predisposed to developing small intestinal GISTs, which may appear as multiple GISTs without KIT and PDGFRA mutations. The prognosis of patients with NF1-GISTs is similar to patients with conventional GISTs.
| S-EPMC4880630 | biostudies-literature
Project description:The narrow therapeutic index and large interpatient variability in sirolimus pharmacokinetics (PK) make therapeutic drug monitoring necessary. Factors responsible for PK variability are not well understood, and published PK studies do not include pediatric patients with neurofibromatosis type 1 (NF1). The objectives of this study were to estimate sirolimus clearance in a cohort of children with NF1 using data collected in a concentration-guided trial, to evaluate the effect of treatment duration on clearance and dose requirements, and to evaluate the association of sirolimus clearance with patient-specific factors, including age, weight, body surface area (BSA), race, and sex.Sirolimus concentration-time data were collected from an ongoing prospective trial in children with NF1. An iterative 2-stage Bayesian method was used for the PK parameter analyses.Data from 44 patients with NF1 were included in the analyses. Mean age was 8.4 years (SD 4.5, range 3-18), and mean weight was 29.8 kg (SD 16.7, range 12-85.8). Mean sirolimus clearance was 11.8 L/h (SD 4.6, range 2.2-24.1), and the mean dose to obtain a target trough concentration of 10-15 ng/mL was 2.0 mg/m administered twice daily (SD 0.72, range 0.77-3.85). A nonlinear relationship between age and clearance was observed. Total body weight and BSA were strong predictors of sirolimus clearance (r = 0.67 and 0.65, respectively).Sirolimus clearance in children with NF1 is comparable with that in pediatric transplant patients. Clearance was most associated with body size parameters (BSA and total body weight) in children with NF1. When normalized for size, an age effect on clearance was observed in the youngest patients, most likely because of the maturational changes in drug absorption and metabolism. A mean dose of 2.0 mg/m twice a day was required for attainment of target trough concentrations of 10-15 ng/mL in children greater than 3 years of age who have NF1. The updated model will allow PK-guided individualized dosing of sirolimus in patients with NF1.
| S-EPMC3660960 | biostudies-other
Project description:The objective of this study was to investigate the association between ethnicity and health related quality of life (HRQoL) in patients with type 2 diabetes.The EuroQol EQ-5D measure was administered to 1,978 patients with type 2 diabetes in the UK Asian Diabetes Study (UKADS): 1,486 of south Asian origin (Indian, Pakistani, Bangladeshi or other south Asian) and 492 of white European origin. Multivariate regression using ordinary least square (OLS), Tobit, fractional logit and Censored Least Absolutes Deviations estimators was used to estimate the impact of ethnicity on both visual analogue scale (VAS) and utility scores for the EuroQol EQ-5D.Mean EQ-5D VAS and utility scores were lower among south Asians with diabetes compared to the white European population; the unadjusted effect on the mean EQ-5D VAS score was -7.82 (Standard error [SE]?=?1.06, p?<?0.01) and on the EQ-5D utility score was -0.06 (SE?=?0.02, p?<?0.01) (OLS estimator). After controlling for socio-demographic and clinical confounders, the adjusted effect on the EQ-5D VAS score was -9.35 (SE?=?2.46, p?<?0.01) and on the EQ-5D utility score was 0.06 (SE?=?0.04), although the latter was not statistically significant.There was a large and statistically significant association between south Asian ethnicity and lower EQ-5D VAS scores. In contrast, there was no significant difference in EQ-5D utility scores between the south Asian and white European sub-groups. Further research is needed to explain the differences in effects on subjective EQ-5D VAS scores and population-weighted EQ-5D utility scores in this context.
| S-EPMC4060842 | biostudies-other