NF1 Group Research Articles

63 Comparison of Measures for Identification of Social Difficulties in Early Childhood for Children with Neurofibromatosis Type 1

Objective:Social functioning patterns vary across measures in children with neurofibromatosis type 1 (NF1; Glad et al., 2021) with broad psychosocial screening measures having shown no impairment (Klein-Tasman et al., 2014; Martin et al., 2012; Sangster et al., 2011) while a more specific social functioning measure indicated poorer social skills (Barton & North, 2004; Huijbregts & de Sonneville, 2011; Loitfelder et al., 2015). The current aims were to characterize caregiver-reported social skills using three different measures and determine which measure appears to best capture social difficulties for young children with NF1.Participants and Methods:Fifty children with NF1 (31 males; M=3.96, SD=1.05) and 20 unaffected siblings (11 males; M=4.34, SD=0.88) in early childhood (ages 3-6) were rated by a caregiver on one social functioning measure (the Social Skills scale on the Social Skills Rating System (SSRS)) and two broader functioning measures that include assessment of social functioning (the Social Skills scale on the Behavior Assessment System for Children-Second Edition (BASC-2), Social Interaction and Communication domain on the Scales of Independent Behavior-Revised (SIB-R)).Results:For children with NF1, the SSRS mean standard score was significantly lower than the BASC-2 and SIB-R (f=-5.11, p<.001; f=-4.63, p<.001) while there was no significant difference between the BASC-2 and SIB-R. No significant differences emerged between measures for unaffected siblings. No significant group differences in mean standard score were found for the SSRS, BASC-2 or SIB-R. Fisher’s exact tests revealed the NF1 group had significantly more frequent difficulties than unaffected siblings on the BASC-2 (p=.017) but not on the SSRS or SIB-R. For both groups, Cochran’s Q tests determined a significant difference in the proportion of identified social difficulties across measures (NF1: X2(2)=16.33, p<.001; Siblings: X2(2)=9.25, p=.01). Follow up McNemar’s tests demonstrated significantly more difficulties reported on the SSRS compared to the BASC-2 for both groups (NF1: p<.001; Siblings: p=.016). Significantly more frequent difficulties were also reported on the SSRS compared to the SIB-R for the NF1 group (p=.002) but not for the unaffected siblings group. No difference in the frequency of difficulties was evident between the BASC-2 and SIB-R for either group.Conclusions:Social skills difficulties appear to be best captured using the SSRS in young children, particularly for children with NF1 as this measure resulted in the lowest mean score and the greatest frequency of difficulties observed within the NF1 group. However, it is notable that group differences in comparison to unaffected siblings were not observed in mean score or frequency of difficulties, such that these young children with NF1 are not showing marked social challenges but rather, social difficulties may be mild when present at this age. Nevertheless, using a measure that specifically targets social functioning, rather than a measure where social functioning is merely a component of a broad measure, appears beneficial to capturing social difficulty. Using measures that best capture social difficulties will contribute to early identification and assessment of intervention effectiveness. Further work with additional age ranges and longitudinal trajectory is needed.

Aberrant oscillatory activity in neurofibromatosis type 1: an EEG study of resting state and working memory

BackgroundNeurofibromatosis type 1 (NF1) is a genetic neurodevelopmental disorder commonly associated with impaired cognitive function. Despite the well-explored functional roles of neural oscillations in neurotypical populations, only a limited number of studies have investigated oscillatory activity in the NF1 population.MethodsWe compared oscillatory spectral power and theta phase coherence in a paediatric sample with NF1 (N = 16; mean age: 13.03 years; female: n = 7) to an age/sex-matched typically developing control group (N = 16; mean age: 13.34 years; female: n = 7) using electroencephalography measured during rest and during working memory task performance.ResultsRelative to typically developing children, the NF1 group displayed higher resting state slow wave power and a lower peak alpha frequency. Moreover, higher theta power and frontoparietal theta phase coherence were observed in the NF1 group during working memory task performance, but these differences disappeared when controlling for baseline (resting state) activity.ConclusionsOverall, results suggest that NF1 is characterised by aberrant resting state oscillatory activity that may contribute towards the cognitive impairments experienced in this population.Trial registrationClinicalTrials.gov, NCT03310996 (first posted: October 16, 2017).

Head circumference and anthropometric changes and their relation to plexiform and skin neurofibromas in sporadic and familial neurofibromatosis 1 Brazilian adults: a cross-sectional study

BackgroundNeurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and plexiform neurofibroma (Pnf), café-au-lait spots, and freckle-like lesions are common in NF1, but many other manifestations can occur. We aimed to evaluate head circumference, height, weight, body mass index (BMI), head circumference-to-height ratio (HCHR) and waist–hip ratio (WHR) in adult NF1 Brazilian individuals versus a paired control group and investigate their correlation with the presence of clinically visible Pnfs, and number of “skin neurofibromas” (Snf), which include both cutaneous and subcutaneous neurofibromas.MethodsA case–control study was conducted with 168 individuals, 84 with NF1 and 84 without NF1, paired by sex and age. Head circumference and anthropometric measurements, Snf quantification, evaluation of clinically visible Pnf and familial inheritance were accessed.ResultsPrevalence of macrocephaly was significantly higher in NF1 women. Height and weight were significantly lower in both males and females with NF1. HCHR was higher in the NF1 group than in the control group for both sexes. BMI was significantly lower in men with NF1. Waist and hip circumferences were significantly reduced in NF compared with the controls, but the mean WHR was significantly lower only in NF1 women. No correlation was found between the Snf and head circumference and anthropometric measurements, sex or family history. The presence and larger size of clinically visible plexiform neurofibromas were associated with normal stature (p = 0.037 and p = 0.003, respectively).ConclusionsNF1 individuals have increased prevalence of macrocephaly, short stature, low BMI, and reduced abdominal fat. There is no relation between head circumference and anthropometric data with family history, or neurofibromas.

New insights into pathogenesis of congenital pseudarthrosis of tibia in children using periosteum proteomics analysis.

The exact etiology and pathogenesis of congenital pseudarthrosis of tibia (CPT) are not clear. Quantitative proteomics analysis plays a vital role in disease pathology research. Tandem mass tag (TMT)-based proteomics techniques were employed to identify and analyze the differentially expressed proteins (DEP) in the tibia periosteum tissues of CPT patients. The samples were divided into three groups: CPT with NF1 group, CPT without NF1 group (non-NF1-CPT), and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 were used as the thresholds to screen DEPs. Subsequently, bioinformatics resources such as online tools DAVID and String were used to generate gene ontology (GO) annotation, KEGG pathways enrichment, and protein-protein interaction (PPI) network for these DEPs. The results show that a total of 347 proteins were differentially expressed in NF1-CPT groups, 212 of which were upregulated and 135 were downregulated. There were more DEPs in non-NF1-CPT groups; we identified 467 DEPs, including 281 upregulated and 186 downregulated. Among them, NF1-CPT groups and non-NF1-CPT groups shared 231 DEPs, and the remaining 230 DEPs showed the same expression trend in the two disease groups, with 117 upregulated and 113 downregulated. In particular, 116 proteins were altered only in NF1-CPT groups (94 were upregulated and 22 were downregulated), whereas 236 proteins were altered only in non-NF1-CPT groups (164 were upregulated and 72 were downregulated). Finally, compared with non-NF1-CPT groups, 47 proteins changed 1.5-fold and P-value < 0.05 in NF1-CPT groups. To sum up, we found that common DEPS in periosteum of NF1-CPT and non-NF1-CPT groups are mainly involved in cell matrix assembly, cell adhesion, AKT-PI3K signal pathway activation, and vascular agglutination, which indicate that these are the pathological characteristics of CPT. The osteogenic ability is weak, the osteoclastic ability is strong, the vascular lumen is narrow, the invasive growth and the proliferation of fibroblasts are enhanced in CPT patients.

Steady-state visual evoked potentials in children with neurofibromatosis type 1: associations with behavioral rating scales and impact of psychostimulant medication

BackgroundNeurofibromatosis type 1 (NF1) is a genetic disorder often associated with cognitive dysfunctions, including a high occurrence of deficits in visuoperceptual skills. The neural underpinnings of these visuoperceptual deficits are not fully understood. We used steady-state visual evoked potentials (SSVEPs) to investigate possible alterations in the synchronization of neural activity in the occipital cortex of children with NF1.MethodsSSVEPs were measured using electroencephalography and compared between children with NF1 (n = 28) and neurotypical controls (n = 28) aged between 4 and 13 years old. SSVEPs were recorded during visual stimulation with coloured icons flickering at three different frequencies (6 Hz, 10 Hz, and 15 Hz) and analyzed in terms of signal-to-noise ratios. A mixed design ANCOVA was performed to compare SSVEP responses between groups at the three stimulation frequencies. Pearson’s correlations with levels of intellectual functioning as well as with symptoms of ADHD, ASD and emotional/behavioral problems were performed. The impact of psychostimulant medication on the SSVEP responses was analyzed in a subset of the NF1 group (n = 8) with paired t-tests.ResultsWe observed reduced signal-to-noise ratios of the SSVEP responses in children with NF1. The SSVEP responses were negatively correlated with symptoms of inattention and with symptoms of emotional/behavioral problems in the NF1 group. The SSVEP response generated by the lowest stimulation frequency (i.e., 6 Hz) was rescued with the intake of psychostimulant medication.ConclusionsImpaired processing of rhythmic visual stimulation was evidenced in children with NF1 through measures of SSVEP responses. Those responses seem to be more reduced in children with NF1 who exhibit more symptoms of inattention and emotional/behavioral problems in their daily life. SSVEPs are potentially sensitive electrophysiological markers that could be included in future studies investigating the impact of medication on brain activity and cognitive functioning in children with NF1.

Early Developmental Trajectories in Infants With Neurofibromatosis 1.

ObjectiveTo examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties.Study designInfants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent–infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time.ResultsNo group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent–infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups.ConclusionCognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes.

Perspectives on adapting a mobile application for pain self-management in neurofibromatosis type 1: results of online focus group discussions with individuals living with neurofibromatosis type 1 and pain management experts

ObjectiveNeurofibromatosis type 1 (NF1) is a genetic disorder in which chronic pain commonly occurs. The study sought to understand the needs of individuals with NF1 and pain management experts when...

Autism Symptoms in Children and Young Adults With Fragile X Syndrome, Angelman Syndrome, Tuberous Sclerosis Complex, and Neurofibromatosis Type 1: A Cross-Syndrome Comparison.

ObjectiveThe etiology of autism spectrum disorder (ASD) remains unclear, due to genetic heterogeneity and heterogeneity in symptoms across individuals. This study compares ASD symptomatology between monogenetic syndromes with a high ASD prevalence, in order to reveal syndrome specific vulnerabilities and to clarify how genetic variations affect ASD symptom presentation.MethodsWe assessed ASD symptom severity in children and young adults (aged 0-28 years) with Fragile X Syndrome (FXS, n = 60), Angelman Syndrome (AS, n = 91), Neurofibromatosis Type 1 (NF1, n = 279) and Tuberous Sclerosis Complex (TSC, n = 110), using the Autism Diagnostic Observation Schedule and Social Responsiveness Scale. Assessments were part of routine clinical care at the ENCORE expertise center in Rotterdam, the Netherlands. First, we compared the syndrome groups on the ASD classification prevalence and ASD severity scores. Then, we compared individuals in our syndrome groups with an ASD classification to a non-syndromic ASD group (nsASD, n = 335), on both ASD severity scores and ASD symptom profiles. Severity scores were compared using MANCOVAs with IQ and gender as covariates.ResultsOverall, ASD severity scores were highest for the FXS group and lowest for the NF1 group. Compared to nsASD, individuals with an ASD classification in our syndrome groups showed less problems on the instruments' social domains. We found a relative strength in the AS group on the social cognition, communication and motivation domains and a relative challenge in creativity; a relative strength of the NF1 group on the restricted interests and repetitive behavior scale; and a relative challenge in the FXS and TSC groups on the restricted interests and repetitive behavior domain.ConclusionThe syndrome-specific strengths and challenges we found provide a frame of reference to evaluate an individual's symptoms relative to the larger syndromic population and to guide treatment decisions. Our findings support the need for personalized care and a dimensional, symptom-based diagnostic approach, in contrast to a dichotomous ASD diagnosis used as a prerequisite for access to healthcare services. Similarities in ASD symptom profiles between AS and FXS, and between NF1 and TSC may reflect similarities in their neurobiology. Deep phenotyping studies are required to link neurobiological markers to ASD symptomatology.

Neuroanatomical correlates of working memory performance in Neurofibromatosis 1.

IntroductionNeurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive impairments, particularly with deficits in working memory. Prior research indicates that brain structure is affected in NF1, but it is unclear how these changes relate to aspects of cognition.Methods29 adolescents aged 11-17 years were compared to age and sex-matched controls. NF1 subjects were assessed using detailed multimodal measurements of working memory at baseline followed by a 3T MR scan. A voxel-based morphometry approach was used to estimate the total and regional gray matter(GM) volumetric differences between the NF1 and control groups. The working memory metrics were subjected to a principal component analysis (PCA) approach.ResultsThe NF1 groups showed increased gray matter volumes in the thalamus, corpus striatum, dorsal midbrain and cerebellum bilaterally in the NF1 group as compared to controls. Principal component analysis on the working memory metrics in the NF1 group yielded three independent factors reflecting high memory load, low memory load and auditory working memory. Correlation analyses revealed that increased volume of posterior cingulate cortex, a key component of the default mode network (DMN) was significantly associated with poorer performance on low working memory load tasks.ConclusionThese results are consistent with prior work showing larger subcortical brain volumes in the NF1 cohort. The strong association between posterior cingulate cortex volume and performance on low memory load conditions supports hypotheses of deficient DMN structural development, which in turn may contribute to the cognitive impairments in NF1.

Congenital abnormalities of the retinal vasculature in neurofibromatosis type I

The aim of this cross-sectional study was to investigate congenital abnormalities of the retinal vasculature (CARVs) in patients with neurofibromatosis type I (NF-1). Forty-eight patients (96 eyes) with NF-1 diagnosed according to the National Institutes of Health (NIH) criteria and 48 healthy controls were included in this study. Standard fundus photographs were obtained for each subject to evaluate the presence and frequency of CARVs. The sensitivity, specificity, and diagnostic accuracy of different cut-off numbers of CARVs were compared with those of the NIH criteria. Forty-four (91.7%) patients in the NF-1 group demonstrated either supranumeraty optic disc vessels or triple branching of the retinal vasculature, and 22 patients (45.8%) demonstrated both findings. The frequencies of these two CARVs were significantly different between the two groups (p < 0.00001). A cut-off value of either one for supranumerary optic disc vessels or triple branching showed the highest accuracy along with sensitivity and specificity of 91.7% and 87.5%. CARVs such as supranumerary optic disc vessels or triple branching were frequently observed in NF-1 patients, and their occurrence was unrelated to the age of patients. Thus, these CARVs could be added as new ophthalmologic manifestions for NF-1 and may potentially enable early diagnosis of NF-1.

Does spinal deformity correction of non-dystrophic scoliosis in neurofibromatosis type I with one-stage posterior pedicle screw technique produce outcomes similar to adolescent idiopathic scoliosis?

Background ContextThe efficacy of one-stage posterior pedicle screw instrument used in the treatment of non-dystrophic scoliosis in neurofibromatosis type I (NF-1) is unknown. Also, there is no study that has directly compared the results of spinal deformity correction between non-dystrophic scoliosis in NF-1 and adolescent idiopathic scoliosis (AIS). PurposeThe objectives of this study were to study the efficacy of a one-stage posterior pedicle screw instrument used in the treatment of non-dystrophic scoliosis in NF-1 and to compare non-dystrophic scoliosis in NF-1 with matched AIS to illustrate the differences. Study DesignThis is a retrospective case control study. Patient SampleFifteen patients with non-dystrophic scoliosis in NF-1 and 15 patients with AIS underwent a one-stage posterior surgery with the pedicle screw system. Outcome MeasuresPreoperative and postoperative whole-spine radiographs were used to determine coronal and sagittal Cobb angles. Also, the distance between the C7 plumb line and the center sacral vertical line and the sagittal vertebral axis was measured to assess spinal balance. The Scoliosis Research Society (SRS)-22 questionnaire was used to evaluate functional outcomes. MethodsWe matched 15 patients with non-dystrophic scoliosis in NF-1 with patients with AIS (ratio, 1:1) for age, sex, and degree of major deformity. The overall mean age was 13.4±2.0 and 14.0±2.1 years, respectively. The NF-1 group consisted of 10 boys and 5 girls, and the AIS group consisted of 9 boys and 6 girls. The mean follow-up was 37.6±3.9 and 33.5±5.0 months, respectively. The AIS group underwent end vertebra (EV) or EV+1 fusion. The NF-1 group underwent EV+1, 2, or 3 fusion. Both coronal and sagittal Cobb angles, trunk balance, operative time, blood loss, fusion levels, length of stay, and scores on the SRS-22 questionnaire were compared between the two groups. The study was supported by the National Natural Science Foundation of China (Grant No. 81401760). There were no study-specific conflict of interest-associated biases. ResultsThe preoperative main curve magnitude was similar between the two groups; however, the flexibility of the NF-1 group tended to be less than that of the AIS group. The rate of correction of the main curve obtained surgically (79.8% compared with 81.1%) was similar in the NF-1 and AIS groups. There were no significant differences in the loss of correction between the two groups (p>.05). Also, there were no significant differences between the groups in operative time, blood loss, fusion levels, screw number, length of stay, trunk balance, and scores on the SRS-22. There were no serious complications related to surgery in both groups. ConclusionsDespite the differences in preoperative flexibilities and fusion strategies, non-dystrophic scoliosis in NF-1 can be treated with a satisfied correction rate and progression rate similar to comparable AIS by using the one-stage posterior pedicle screw technique. Dural ectasia or thin pedicles in non-dystrophic scoliosis could make pedicle screw placement challenging.

Motor impairment in children with Neurofibromatosis type 1: Effect of the comorbidity with language disorders

BackgroundThere is a body of evidence demonstrating comorbidity of motor and cognitive deficit in «idiopathic» developmental disorders. These associations are also found in developmental disorders secondary to monogenic disorders as in Neurofibromatosis type 1 for which the principal complication during childhood is learning disabilities. The comparison of motor impairment between developmental disorders either idiopathic or secondary as in NF1 could help us to better understand the cause of the combined language/motor deficit in these populations. AimThe aim of this current study was to investigate motor impairment in children with NF1 for which oral language had been specified and then to compare the motors skills of the NF1 group to motor performance of children with Specific Language Disorder (SLD). MethodTwo groups of 49 children between 5 and 12years old were included and compared, the NF1 group and the SLD (Specific Language Disorder) group. Each child completed evaluation involving cognitive, language and motor assessment. ResultsIn NF1 group, motor impairment was more frequent and more severe and concerned specifically balance rather than manual dexterity or ball skills, compared to a group of children with SLD. This motor impairment was independent of language status in the NF1 group. ConclusionsThese results as well as other studies on the same topic could suggest that in NF1 children, fine motor skills impairment would be dependent on the existence of comorbidity with language disorders. Also, that gross motor skills impairment, and more precisely the balance deficit would be characteristic of NF1. This issue encourages studies of procedural learning that can involve the fronto-striatal or the fronto-cerebellar loops according to the type of motor tasks and the stage of learning.

Surgical Outcomes of the Nondystrophic Scoliosis Secondary to Neurofibromatosis Type I versus Curve-Matched Adolescent Idiopathic Scoliosis

Introduction Patients with nondystrophic scoliosis caused by NF-1 mostly require surgery. Although the radiographic findings in patients with nondystrophic scoliosis secondary to NF-1 are similar to those in patients with idiopathic scoliosis, evidence-based surgical guidelines, and long-term results are not as established as those for patients with AIS. The objective of this study is to compare the surgical outcomes of nondystrophic scoliosis secondary to neurofibromatosis type I (NF-1) and curve-matched adolescent idiopathic scoliosis (AIS) to identify the feasibility of treating nondystrophic NF-1 using the same principals as AIS and seek for potential surgical improvement. Patients and Methods A total of 19 adolescent patients with nondystrophic scoliosis secondary to NF-1 and 19 curve-matched patients with AIS were recruited into the study. Preoperative immediately and 6-month postoperative, and follow-up radiological data were reviewed and analyzed. The mean age of patients with NF-1 was 14.4 ± 1.3 years compared with 15.7 ± 3.1 years of patients with AIS. The main curves were 70.1 ± 14.4 and 75.9 ± 11.3 degrees for the patients with NF-1 and AIS, respectively. The minor curves were 37.4 ± 14.2 and 39.5 ± 13.4 degrees for the patients with NF-1 and AIS, respectively. The mean follow-up durations were 33.8 months (range, 24–60 months) and 31.6 months (range, 24–41 months) for the NF-1 and AIS groups, respectively. Results After surgery, the nondystrophic NF-1 group had less main curve correction (62.3 ± 15.5 vs. 68.9 ± 13.2%, p &lt; 0.001), less apical vertebral translation (AVT) correction (−20.3 vs. −22.9 mm, p = 0.019), and less trunk shift (TS) correction (−7.8 vs. −16.0 mm, p &lt; 0.001). On the sagittal plane, significantly more correction of sagittal vertical axis (SVA) (−19.3 vs. −10.0 mm, p = 0.041) was noted in the nondystrophic NF-1 group. A significant trend to worse was observed in NF-1 group during the follow-up period. At the final follow-up, significantly more loss of correction (5.4 vs. −0.8 degrees, p = 0.013) of the main curve was observed in the nondystrophic NF-1 group. Conclusion Current results suggest that satisfactory short-term surgical outcomes can be achieved in both NF-1 patients with non-dystrophic scoliosis and patients with AIS while sharing the same management strategy. However, the long-term result of nondystrophic scoliosis in patients with NF-1 is not identical to that of patients with AIS. Despite all this, it is fair to suggest that applying the surgical strategy of AIS in treating nondystrophic scoliosis secondary to NF-1 should be acknowledged.

Neurofibromatosis type 1 and chronic neurological conditions in the United States: an administrative claims analysis.

PurposeNeurofibromatosis Type 1 (NF1) has been linked to several neurological conditions including: epilepsy, Parkinson's disease, headache, multiple sclerosis, and sleep disturbances, predominantly through case reports and series that lack comparison groups. Our objective was to assess whether specific neurological conditions occur more frequently in individuals with NF1 vs. those without NF1.MethodsWe used the 2006-2010 MarketScan Commercial Claims and Encounters database to examine associations between neurological conditions and NF1. The NF1 group was identified through ≥2 ICD-9-CM NF codes (237.70, 237.71) occurring ≥30 days apart or one inpatient NF code. A non-NF1 comparison group was frequency-matched to the NF1 group on age and enrollment length at a 10:1 ratio. Unconditional logistic regression was employed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NF and neurological conditions.ResultsCompared to the non-NF1 group (n=85,790), the NF1 group (n=8,579) had a significantly higher odds of health insurance claims for epilepsy (OR=7.3; 95% CI 6.4-8.3), Parkinson's disease (OR=3.1; 95% CI 1.3-7.5), headache (OR=2.9, 95% CI 2.6-3.1), multiple sclerosis (OR=1.9, 95% CI 1.2-2.9), and sleep disturbances/disorder (OR=1.4, 95% CI 1.2-3.6).ConclusionThis large study provides strong evidence for positive associations between several neurological conditions and NF1.

Reactivity to visual signals in neurofibromatosis type 1: Is everything ok?

Deficits in multiple aspects of attention are a hallmark of the cognitive impairments found with neurofibromatosis type I (NF1). Given, however, that some attention components are hierarchically organized, it is possible that sustained attention, flexibility, and resistance to interference deficits observed in NF1 may be because of weakened lower order attention components. This study investigated the state of these low-level components in NF1. Twenty participants with NF1 (ages 7-13) and 20 matched controls participated in a visual task. They were required to locate a target as quickly and as accurately as possible and to ignore a potential distractor that could appear either before, at the same time, or after the target. Response times (RTs) were collected, and indices of alerting (i.e., reactivity to warning signals), distraction, and interruption (i.e., reactivity to signals appearing during attentive processing) were computed. The amplitude of the indices differed between the groups, F(2, 76) = 3.1, p < .05. No difference was found with alerting (p > .85) or distraction (p > .84), but the interruption index was higher in the NF1 group than the controls (p < .043). Elementary components on which more complex attention processes are based are not all ok in NF1. It is suggested that overreactivity to and longer inspection of visual signals occurring outside the current focus of attention characterizes NF1 and that this might be partially responsible for focus of attention instability and lower interference resistance in NF1.

Representações sociais de pacientes e familiares sobre neurofibromatose tipo 1

Type 1 Neurofibromatosis (NF1) is a disease with diverse manifestations. Few studies have addressed the psychological aspects associated with it from the perspective of those who have NF1 or their relatives. In this study 46 subjects were interviewed, 28 people with NF1 (Group P) and 18 relatives (Group F) seeking to identify the understanding of the day-to-day reality experienced by these two groups and possible distinctions between them, based on the social representations of each group. Data analysis was conducted using Classic Content Analysis. The respondents' answers were organized into categories and subcategories based on their meanings. The results revealed that the quantitative distribution of the categories had similar frequencies for both groups. However, important qualitative differences were observed in terms of the meanings of the answers. Difficulty in obtaining information about NF1 along with few references about social support networks by people with the disease or their family members contributed to the identification of a veil of social invisibility around NF1. These aspects highlight the need for greater investment in research and intervention related to NF1 in order to expand the social coping conditions for those afflicted with the disease.

Lower extremity strength and hopping and jumping ground reaction forces in children with neurofibromatosis type 1

The purpose of this study was to (1) extend the research findings of decreased muscular force production in grip strength to the lower extremity strength of children with NF1 and (2) to determine if there was a relationship between isometric strength and functional activities in children with NF1. Force production was assessed using a hand held dynamometer (HHD) and a functional task (hopping and jumping) on a force plate. Data from twenty-six children with NF1 were compared to data from 48 typically developing children of similar sex, weight and height. Children with NF1 demonstrated statistically significant lower force production with HHD (p<0.01) during hip extension, but similar force production for knee extension and ankle plantar flexion compared to the control group. A relationship existed between the ground reaction forces at take-off from both hopping and jumping and the force generated from knee extensor strength in the NF1 group. The addition of a functional task to hand held dynamometry is useful for determining a relationship between common clinical measures and functional activities.

The pulmonary dysfunction patterns in scoliosis associated with neurofibromatosis type I

To investigate the pulmonary dysfunction patterns in patients of scoliosis associated with neurofibromatosis type I (NF1) and to identify factors affecting the pulmonary function in patients with scoliosis associated with NF1. Preoperative pulmonary function tests (PFTs) were evaluated in 100 patients with scoliosis [NF1 group, 36 cases; idiopathic scoliosis (IS) group, 64 cases] from January 2003 to June 2009. According to location of apical vertebra and dystrophic change in patients with NF1, the parameters of pulmonary function [vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximal mid-expiratory flow (MMEF), maximal voluntary ventilation (MVV)] were compared between NF1 group and IS group, and between the subgroups of NF1. The correlation between pulmonary function parameters and radiographic parameters of scoliosis was analyzed. The VC, FVC, FEV1, MMEF, MVV in NF1 group and IS group were of no significant difference (P > 0.05). In NF1 patients, the pulmonary dysfunction was more severe in thoracic subgroup than non-thoracic subgroup (P < 0.05), while there was no difference between dystrophic scoliosis and non-dystrophic scoliosis (P > 0.05). The location of apical vertebra and the severity of scoliosis correlated significantly with the pulmonary dysfunction in NF1 group. The pattern of pulmonary dysfunction in scoliosis associated with NF1 is similar with IS. Pulmonary dysfunction is more severe in thoracic scoliosis. The location of apical vertebra and the severity of scoliosis are the risk factors influencing the pulmonary dysfunction.

FOCAL AREAS OF HIGH-SIGNAL INTENSITY ON BRAIN T2-WEIGHTED MAGNETIC RESONANCE IMAGING SCANS ARE SIGNIFICANT FOR THE DIAGNOSIS OF NEUROFIBROMATOSIS VON RECKLINGHAUSEN TYPE 1

INTRODUCTION: Neurofibromatosis von Recklinghausen type 1 (NF1) is characterized by the following National Institutes of Health (NIH) diagnostic criteria: café au lait spots, freckling, neurofibromas, Lisch nodules, optic glioma, distinct osseous lesions, and first-degree relative with NF1. Focal areas of high-signal intensity (FASI) in white matter and deep gray matter are typical brain MRI findings in children with NF1. OBJECTIVE: This study evaluated the frequency of FASI and the possibility of using FASI as a diagnostic criterion. METHODS: In a group of 160 children, the diagnosis of NF1 was confirmed in keeping with the NIH criteria. All children had MRI examination of the brain. The MRI findings of FASI in the children with NF1 were compared both with the brain MRI findings of the control group of 160 children with different diagnoses and with frequencies of the NIH diagnostic criteria. RESULTS: In 137 (86%) patients with NF1, ≥1 FASI were found. The difference between frequency of FASI in the NF1 group and in the control group (14 [9%]) is highly significant. The frequencies of the diagnostic criteria were as follows: café au lait spots: 157 (98%); freckling: 123 (77%); neurofibromas: 112 (70%); NF1 relatives: 89 (56%); Lisch nodules: 71 (44%); optic glioma: 45 (28%); and osseous lesions: 15 (9%; only partial examination of the group). CONCLUSIONS: The findings of FASI in T2-weighted images of the brain MRI are significantly frequent in children with NF1. Frequency of FASI is comparable with frequency of NIH diagnostic criteria. FASI could be proposed as an additional or new criterion for the NF1, mainly in childhood.

Multicenter Study of Wound Healing in Neurofibromatosis and Neurofibroma

Based on clinical experience, the senior author has become convinced that wounds produced to correct the deformities of patients with neurofibromatosis (NF-1) have produced remarkably good scars, the interesting feature being that progression to keloid or hypertrophic scar is rare. The other point noted was that this situation did not change, no matter the patient's race or skin color. There have been few reports describing or discussing this hypothesis. The purpose of this study was to investigate whether wounds produced in the patients with NF-1 produce keloid or hypertrophic scars. The patients with solitary neurofibroma were also included in this study; these were compared with the NF-1 group. This was conducted as a multicenter study. Patients with neurofibromatosis/solitary neurofibroma, who were operated on from 1990 to 2000, were evaluated by reviewing their medical charts and photographs retrospectively. The patients were treated in centers from five different countries. The analysis was undertaken based on the following points: 1) age and sex at surgery; 2) race of the patients; 3) past and family histories of hypertrophic scar and keloid; 4) surgical site(s); 5) diagnosis, NF1 or solitary neurofibroma; 6) surgical complications; 7) number of reoperations to manage the complications; 8) adjuvant therapy for the tumor; 9) depth of the tumors; and 10) incidence of malignant degeneration. A total of 101 cases with neurofibromatosis or solitary neurofibroma was analyzed. The age at surgery ranged from 1 year 6 months to 74 years; sex ratio was 47 males and 54 females. The racial distribution of the patients was 13 white, 13 black, 3 Hispanic, and 58 Asian. There was no past or family history of hypertrophic scar or keloid. The surgical sites were head and neck in 70 cases, trunk in 20 cases, upper extremities in 22 cases, and lower extremities in 20 cases. The clinical diagnosis was NF-1 in 57 cases, solitary neurofibroma in 35 cases, plexiform neurofibroma in four cases, and no distinct clinical diagnosis in five cases. There were no other types of neurofibromatosis. Hematoma and white wide scar were the main postoperative complications found in six cases of NF-1. Infection was also noted in four cases. However, no patient developed hypertrophic scar or keloid in the neurofibromatosis group, whereas two cases showed hypertrophic scar in the solitary neurofibroma group. The outcome showed that the patients with NF-1 and plexiform neurofibroma, no matter the racial group, produce good scars without keloid or hypertrophic changes, whereas solitary neurofibroma has a potential to cause hypertrophic scar.