Quality of life of patients with neurofibromatosis 1 – physical disability does not necessarily result in inferior mental health.

doi:10.21203/rs.3.rs-2373244/v1

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Quality of life of patients with neurofibromatosis 1 – physical disability does not necessarily result in inferior mental health.

https://doi.org/10.21203/rs.3.rs-2373244/v1

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Introduction

Neurofibromatosis 1 (NF1) is a chronic neurocutaneous disease with tremendous impact on quality of life (QoL). We have performed an analysis of disease severity, mental and physical QoL and compared the different severity classes of patients with neurofibromatosis 1 (NF1).

Patients and methods

We performed a prospective analysis of 89 patients with NF-1 which are included in the period of 1/2016 - 3/2018. Local records served as data source including demographic data, employment status, level of education, and marital status were evaluated. All patients received 36-Item Short Form Health Survey (SF-36). Additionally, numerical pain rating scale (NPS) Patients were stratified according to different severity of NF-1 and different visibility and severity of disease.

Results:

Out of 89 patients, severity grad 4 was identified in 42 (47.2%), moderate in 17 (19.1%), mild in 23 (25.8%) and minimal in 7 (7.9%) cases. According to visibility scale, severe grade 3 was found in 28 (31.5%), moderate grade 2 in 26 (29.2%) and mild grade in 35 (39.3%) cases. All SF-36 related data except for pain showed significantly lower values, if compared to the standard German population (p<0.001, physical component summary p=0.045). Sex, marital status and level of education showed no significant differences. Employment was significantly associated with better mental and physical status (p=0.028 and p=0.01 respectively) and age >40 was significantly associated with lower physical (p=0.027) but not mental component (p=0.362). According to the numerical pain rating scale, 7-10 were noted in 9 cases (10,1%), 5-6 in 10 patients (11.2%), 1-4 in 26 patients (29.2%) and no pain in 44 cases (49.4%). Physical component showed significant difference between different NPS grades (p<0.001) but no significance in mental component summery (p=0.06). Finally, we found no significant difference between different severity grades and visibility grades in mental component summery.

Conclusion:

The severity grade and visibility grade of patients with NF-1 does not necessarily results in decreased mental components and physical limitations in comparison with lower grades, so that symptomatic treatment should be considered even in patients with severe disability, since these still may have comparable QoL to less severe disabled patients with NF-1. Employment was associated with better QoL according to our results.

NF1

Quality of life

SF-36

severity

visibility

Neurofibromatosis is a heterogeneous neuro-cutaneous disease, including neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis.^1,2 The most common is NF1 (1:2700 births), characterized by many typical features such as café-au-lait macules (CALM), freckling, Lisch nodules, cutaneous and plexiform neurofibromas, optic gliomas, bone deformities and in addition associated with learning difficulties and deficits in attention (ADHD) with different impact on quality of life (QoL).^1–3 The plexiform neurofibromas bear the risk not only for malignant transformation resulting in malignant peripheral nerve sheath tumors (MPNST) but also for visible deformities which may influence QoL .⁴ Patients with NF1 have a higher risk to develop several other tumor diseases like gastrointestinal tumors or breast cancer, which are limiting the life expectancy.^5,6 These patients need repetitive surgeries and commonly develop different neurological impairments due to tumor progression, so that decision making for an aggressive treatment is difficult and the severity grade may influence the final choice.

Health related QoL defines the physical, psychological and social well-being of patients and describes the complex and multifactorial conditions and factors which influence the patient’s life.⁷ The aim of this study is to identify the different aspects of QoL in patients with NF1 and to report predictors of QoL in this population. Although earlier studies described an association between neurofibromatosis and a lower QoL, our knowledge about the factors which influence the QoL of this group is low ^1,3. Furthermore, we have analyzed the influence of employment, age, marital status and level of education on QoL.

Study design

We conducted a prospective, descriptive, observational study between 2016 and 2018 on 89 patients. The patients were consecutively enrolled in the study. The study was approved by the local ethics committee (N 51/16) and performed according to international Declaration of Helsinki. Informed consent was signed by each participant.^3,8

Collected data

A standardized, generic survey for health-related quality of life was chosen to ensure reproducibility and comparability in this topic. All patients who attended the specialized NF outpatient department and signed informed consent were included in the study. The advantage of local NF outpatient department is the interdisciplinary participation of neurologist, neurosurgeon, dermatologist, pediatrician and an expert in the field of genetics. All patients underwent a neurological examination and received the 36-Item Short Form Health Survey (SF-36) and numerical pain rating scale.^9,10 The local records were analyzed for demographic data and patients were stratified according to severity and visibility grades as proposed by Huson et al and Ablon et al.^3,8

Demographic data including age, sex, marital status and employment were analyzed. Two age groups with cut of > 40 years were evaluated. The cut off value was based on assumption that it is the middle of life episode, typically with grounded family.

Statistical analysis:

Data were initially analyzed by descriptive methods. Mean and standard deviation were reported for continuous variables and absolute and relative frequencies for the qualitative parameters. Explorative tests between interesting subgroups were selected by the underlying parameters (ANOVA as well as T-test). Non-parametric tests were performed in the presence of non-Gaussian distribution of values (Mann-Whitney Test, Kruskal-Vallis-test). The significance level was defined as p < 0.05. SPSS® statistical software (IBM Company, SPSS Inc. Chicago Illinois) was used to analyze the collected data.

Demographic and general data

Detailed demographic data including severity and visibility scores and further NF-1 characteristics are summarized in Table 1. Females were more common in our cohort. Most of patients have a ob and slightly more patients are married or are living with a partner. Half of the patients have a familial form of the NF1 (Table 1).

Table 1

Patients´characteristics.
Sex	Male	N = 33 (37.1%)	P = 0.015
	Female	N = 56 (62.9%)
Age	Mean (SD)	38,67 ± 16,12
Inheritance	Familial	42 (47.2%)	P = 0.596
	Sporadic	47 (52.8%)
Partner/Marital status	Single	42 (47.2%)	P = 0.596
	Partner/married	47 (52.8%)
Level of education	None	9 (10.1%)	P < 0.001
	Elementary school	36 (40.4%)
	Middle school	24 (27%)
	High school	20 (22.5%)
Employment	Employed	76 (78.4%)	P < 0.001
	Unemployed	13 (21.6%)
Disease severity	Minimal (Grade 1)	7 (7.9%)	P < 0.001
	Mild (Grade 2)	23 (25.8%)
	Moderate (Grade 3)	17 (19.1%)
	Severe (Grade 4)	42 (47.2%)
Visibility scale	Mild (Grade 1)	35 (39.3%)	P = 0.471
	Moderate (Grade 2)	26 (29.2%)
	Severe (Grade 3)	28 (31.5%)

Regarding the Level of education, it´s visible that 10.1% of the patients are without any graduation, which is more than twice as much as in the general German population (4.7%).

Severe grades were noted in nearly half of the patients (N = 42, 47.1%) in our study which is typically associated with more surgeries and frequent hospitalizations.

Quality of Life:

Evaluating SF-36, all domains showed significantly lower values if compared to the normal population (Table 2).

Table 2

Results of short-form 36 health survey for patients with neurofibromatosis type 1 compared with German standard population.
	NF1, Mean ± SD (n = 89)	German Standard Population, Mean ± SD (n = 2773)	p
Physical component summary	48,34 ± 10,61	50,21 ± 10,24	0,045
Mental component summary	42,85 ± 7,60	51,54 ± 8,14	< 0,001
Physical functioning	82,36 ± 23,25	96,61 ± 10,04	< 0,001
Role: physical	70,51 ± 40,69	96,89 ± 13,88	< 0,001
Bodily pain	71,54 ± 30,18	94,60 ± 14,99	< 0,001
General health	61,60 ± 24,16	79,89 ± 13,66	< 0,001
Vitality	54,78 ± 19,67	71,90 ± 14,31	< 0,001
Social functioning	53,79 ± 10,56	94,87 ± 12,33	< 0,001
Role: emotional	76,40 ± 38,99	96,89 ± 14,13	< 0,001
Mental health	63,46 ± 14,51	79,16 ± 13,11	< 0,001

Sex, marital status and level of education showed no significant differences in regard to QoL (Table 3). Employment was significantly associated with better mental and physical status according to SF.36 (Table 3) and age > 40 was significantly associated with lower physical but not mental component (Table 3).

Table 3

Comparison of physical and mental component summary according to patients´characteristics.
	Level of education	Mean ± SD	P value
Physical component summary	None	46,59 ± 8,06	0,474
	Elementary school	48,87 ± 10,26
	Middle school	46,77 ± 11,64
	High school	50,04 ± 11,30
Mental component summary	None	45,55 ± 5,27	0,693
	Elementary school	42,57 ± 8,68
	Middle school	42,13 ± 6,72
	High school	42,85 ± 7,60
	Employment	Mean ± SD	P value
Physical component summary	Employed	49,54 ± 10,17	0,010
	Unemployed	41,30 ± 10,77
Mental component summary	Employed	43,62 ± 7,22	0,028
	Unemployed	38,40 ± 8,50
	Partner/marital status	Mean ± SD	P value
Physical component summary	Single	47,84 ± 11,69	0,863
	Partnered/married	48,78 ± 9,64
Mental component summary	Single	41,84 ± 8,74	0,375
	Partnered/married	43,76 ± 6,36
	Age (years)	Mean ± SD	P value
Physical component summary	≤ 40	50,08 ± 11,38	0,027
	> 40	46,47 ± 9,49
Mental component summary	≤ 40	43,53 ± 7,62	0,362
	> 40	42,13 ± 7,59
	Sex	Mean ± SD	P value
Physical component summary	Male	47,00 ± 11,93	0,530
Physical component summary	Female	49,12 ± 9,77	0,530
Mental component summary	Male	43,61 ± 7,88	0,316
Mental component summary	Female	42,41 ± 7,46	0,316

According to numerical pain rating scale, 7–10 were noted in 9 cases (10,1%), 5–6 in 10 patients (11.2%), 1–4 in 26 patients (29.2%) and no pain in 44 cases (49.4%). Physical component showed significant difference between different NPS grades (p < 0.001, Table 4) but no significant difference in mental component summery (p = 0.06).

Table 4

Comparison of physical and mental component summery between different grades of disease severity.
	Numerical rating scale	Mean ± SD	P value
Physical component summary	0	54,30 ± 7,21	< 0,001
	1–4	46,89 ± 8,70
	5–6	41,28 ± 6,79
	7–10	31,21 ± 8,65
Mental component summary	0	42,25 ± 7,81	0,064
	1–4 (n = 26)	45,93 ± 6,16
	5–6 (n = 10)	40,96 ± 8,01
	7–10 (n = 9)	39,03 ± 7,91
	Visibility scale	Mean ± SD	P value
Physical component summary	Grade 1	53,30 ± 8,04	< 0,001
	Grade 2	47,69 ± 10,69
	Grade 3	42,73 ± 10,71
Mental component summary	Grade 1	42,63 ± 7,31	0,840
	Grade 2	42,83 ± 6,98
	Grade 3	43,16 ± 7,60
	Disease severity	Mean ± SD	P value
Physical component summary	Grade 1 (n = 7)	54,90 ± 7,92	0,006
	Grade 2 (n = 23)	52,02 ± 10,21
	Grade 3 (n = 17)	43,00 ± 10,78
	Grade 4 (n = 42)	47,38 ± 10,16
Mental component summary	Grade 1 (n = 7)	46,18 ± 2,96	0,678
	Grade 2 (n = 23)	41,04 ± 8,82
	Grade 3 (n = 17)	42,92 ± 5,88
	Grade 4 (n = 42)	43,27 ± 7,96

We have found no significant difference between different severity grades and visibility grades in mental component summery (Table 4). As expected, physical components were significantly worse in more severe cases (Fig. 1) and in patients with higher visibility grades.

The QoL is one of the most relevant outcome parameters in patients with chronic diseases.^11–13 Generally, all patients in our study showed reduced QoL based on SF-36. This aspect displays the tremendous impact of NF-1 on QoL which is similar to former studies.^14,15

Regarding the visible aspects of this neurocutaneous disease, it is astonishing, that in contrast to previous studies, we found no difference in mental differences among different severity groups. Chren et al and Krueger et al showed in contrast, that disorders that affect the skin result in negative emotional and psychological outcomes.^16,17 Kodra et al have found similar results in NF 1 where the changing of the appearance because of the skin abnormalities ends in an inferior QoL.⁷ Smith et al reported that the female sex is especially affected by cosmetic burdens of the NF1.¹⁸ Similarly, Hummervoll et al. noticed that females had tremendously worse QoL in contrast to men.¹⁹ This is in discrepancy to our results which showed no significant difference between males and females. Similar to our results, Crawford et al haven´t found gender differences nor even an influence of visibly changes of the QoL in the Australian population.²⁰ The participants of our study may cope better with the change of the appearance or have a better body image than we have expected. Many participants cope with the visible aspects of the NF1 by concealing the skin with special clothing or avoiding activities like swimming.² Similarly to our study, a Canadian publication also showed no significant differences in the body image scores of women compared to men.²¹

In previous studies it is noticed, that because of the visible aspects of NF1, forming relationships and finding a partner is more difficult.²² We haven´t found a relevant difference compared to the standard population in our study.²²

It is known that the attractiveness is positively influencing the state of employment, so it is to be expected, that the skin abnormalities of the NF1 leads to a higher number of unemployment, but in contract to former studies, the participants of our study have a normal level of employment.^23,24 The level of education is lower, which is correlating with the type of employment. So, many participants in our study are simple workers in factories or working as unskilled people, where the visual aspects are not so important and mentioned.

Learning difficulties are a well-known aspect in NF1 and are often the reason for painful school experiences, including social assaults and unhappiness, leading to school refusers and a drop out of trainings.^8,22 The results of these learning difficulties are often a lack of self-confidence, missed career choices and employment opportunities. In our cohort, the level of education is lower compared to the German population.²⁵ Especially the number of people without any graduation is higher and the number of participants having a university degree is much lower. These results are in line with former studies.²⁶ Other studies describe that older adults (born before 1970) have worse school experiences than younger ones, this may be explained by a greater awareness of NF1 and leads to a necessity of an early support and the treatment of the learning difficulties and the lack of concentration.²⁷

Pain is an important factor related to QoL, so we used except of the SF-36 questionnaire and the patient history, the NRS to correlate the severity of the pain with the QoL. Nearly half of the population described no pain, but the physical component showed significant difference with increasing NRS. In our study, participants reported mostly back pain or headaches, which are typical findings in NF1, on the one hand attributed to the typical bodily findings in the NF1 like scoliosis and poor postures, but on the other hand it can be a sign of psychological disorders like depression and a insufficient disease processing.^28,29 It´s important to investigate and treat the physical restrictions in the early childhood to avoid later problems. Emphasis should be given on psychological therapies such as acceptance and commitment therapies, learning resilience and coping.^1,14,27

Regarding the influence of the age, many studies show a lower QoL in younger patients with NF1, consistent with the results in other chronic diseases.^30,31 We have not included children in our study, but we mentioned, that the age > 40years is significantly associated with a lower physical component. Probably, possible bone abnormalities like scoliosis, plexiform neurofibromas and a higher risk of developing malignant tumors as well as associated surgeries can explain the higher physical problems of this group. Contrary to our expectations, the mental component wasn´t affected. Probably, the coping strategies are better and the life and family planning is completed. In addition, there are not enough investigations to report the differences between adults and children with NF1 (even separated by children and parents reports) or long-term follow-ups, regarding the development of this population over the years.

The detailed analysis revealed that the severity grade does not reflect inferior mental status even if physical functioning is worse. In former studies, the principal concerns of the participants were the cosmetic neurofibromas followed by learning difficulties and across all age groups and gender the fear of disease progression. We haven´t expected, that the measured severity of the disease by the scale of Huson is not the criteria for the individual perception of this disease. Some participants seem to cope better with their chronic disease and their acceptance of their body seems to be much better. Especially the impact of psychosocial factors, due to the lack of treatment methods and the limitations of medication in NF1 should be considered to have the opportunity to develop resiliency strategies.¹⁵

Based on our finding and experience, an early investigation of the children in specialized centers, the initiation of specialized individual therapies and altogether a better awareness of the NF1 is essential.

Study limitations

Due to the relatively low and heterogenic cohort, it is not possible to generalize our results. This aspect might have influenced our results negatively. Detailed analysis of QoL is challenging and including many factors which are difficult to summarize and quantify.

The severity grade and visibility grade of patients with NF-1 does not necessarily results in decreased mental components and handicap in comparison with lower grades, Employment was associated with better QoL according to our results, so it is important to support this group of patients to protect their jobs and even if the level of education was not significant for the QoL, it is important to support the younger patients with NF1 to minimize learning disabilities and to acquire a graduation and thereby an employment.

Ethical approval:

Ethikkommission der Universität Ulm (N51/16)

Consent to Participate: available

Fundings: No

Authors´contributions:

U.B. and A.P. wrote the main manuscript text. L.S. did the evaluation. All authors reviewed the manuscript.

Availabbility of supporting data: on demand

Competing interests: No

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No competing interests reported.

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Quality of life of patients with neurofibromatosis 1 – physical disability does not necessarily result in inferior mental health.

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Abstract

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Introduction

Patients and Methods

Statistical analysis:

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

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