Rachel Poulain

Céline Cappe

Magali Batty

Social impairment in the autistic spectrum: real-life versus online perceived social skills

Keywords: Autistic traits, Perceived social skills, online communication

Objectives:

While socio-communicative difficulties are identified as a core diagnostic criterion for Autism Spectrum Disorder (ASD), there is growing evidence that social difficulties could be context-dependent and could be overcome by the use of online communication. Beyond the spectrum, the symptoms of ASD can be met in the general population at a milder scale, leading researchers to extend their work to subjects with high autistic traits, also called the broader autism phenotype. The present study explored online versus real life social skills in the general population according to the level of autistic traits.

Method:

Seventy-one adults without ASD (from 18 to 55 years old) reporting using social networks completed a questionnaire assessing their real-life and online social skills. Their autistic traits were assessed using the autistic quotient (AQ).

Results:

Results showed a direct influence of the level of autistic traits on real-life and online social skills: participants having high autistic traits demonstrated a lower level of real-life social skills (r=-0.26, p<.05) and conversely higher online social skills (r=0.28, p<.05), suggesting that social difficulties might be context-dependent.

Conclusions:

While further studies are needed in a population with ASD, our results report preliminary evidence of the potential benefit of online social interactions within the autistic spectrum. Further studies in ASD could consider the potential for using an electronic mediator within social remediations.

When meeting a person with Autism Spectrum Disorder (ASD), one typically notices differences in their social behavior: an unusual eye gaze (which may be reduced or overextended), and when present, atypical speech with a lack of nonverbal gestures and facial expressions, as well as an unusual voice rhythm that sounds slightly stilted [START_REF] Asperger | Die "Autistischen Psychopathen" im Kindesalter[END_REF][START_REF] Attwood | Asperger's syndrome[END_REF][START_REF] Kanner | Autistic disturbances of affective contact[END_REF]. Socio-communicative difficulties are indeed considered as a major dysfunctional element in ASD and constitute the first axis of diagnosis, the second being repetitive and restricted behaviors [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders (DSM-5)[END_REF]. Research has provided evidence that individuals closely related to individuals with ASD display autistic characteristics, albeit to a milder extent [START_REF] Piven | Personality characteristics of the parents of autistic individuals[END_REF]. This discovery has catalyzed the emergence of the "broader autism phenotype" (Constantino & Todd, 2003, p. 529) as a conceptual framework. Furthermore, these distinct characteristics are not limited to family members but are also observable within the broader population (for a review, [START_REF] Ruzich | Measuring autistic traits in the general population : A systematic review of the Autism-Spectrum Quotient (AQ) in a nonclinical population sample of 6,900 typical adult males and females[END_REF]. In order to assess the degree of autistic traits in any individual adult, psychometric tools were developed, such as the "Autism spectrum Quotient" (AQ; Baron-Cohen et al., 2001, p. 6). The impaired responses to social information typically observed in ASD are also found in people without ASD but with high autistic traits. More precisely, many social difficulties in common between ASD subjects and subjects with high autistic traits have been highlighted and concern, for example, difficulties in the attribution of mental states (e.g., [START_REF] Baksh | The Edinburgh Social Cognition Test (ESCoT) : Examining the effects of age on a new measure of theory of mind and social norm understanding[END_REF][START_REF] Stewart | Theory of mind performance in younger and older adults with elevated autistic traits[END_REF], a gaze orientation preference towards blurred images rather than faces (e.g., [START_REF] Bayliss | Gaze and arrow cueing of attention reveals individual differences along the autism spectrum as a function of target context[END_REF], socio-communicative difficulties and social reciprocity (e.g., [START_REF] Bezemer | The Predictive Value of the AQ and the SRS-A in the Diagnosis of ASD in Adults in Clinical Practice[END_REF][START_REF] Constantino | Reciprocal social behavior in children with and without pervasive developmental disorders[END_REF] as well as cerebral hypoactivity in social contact [START_REF] Voos | Autistic traits are associated with diminished neural response to affective touch[END_REF].

The internet is a vehicle of communication used by a large number of people. In the general population, various studies have found that internet use fosters and facilitates social interaction by decreasing social isolation and loneliness, as well as increasing social connectivity (e.g., [START_REF] Adams | Growing Together : Personal Relationships across the Life Span[END_REF][START_REF] Bradley | Assistive technology, computers and Internet may decrease sense of isolation for homebound elderly and disabled persons[END_REF][START_REF] Ellison | The benefits of Facebook « friends: » Social capital and college students' use of online social network sites[END_REF][START_REF] Erickson | Internet use and psychological wellness during late adulthood[END_REF][START_REF] Subrahmanyam | Online and offline social networks : Use of social networking sites by emerging adults[END_REF][START_REF] White | Surfing the Net in Later Life : A Review of the Literature and Pilot Study of Computer Use and Quality of Life[END_REF]. Some studies of the last decade suggested a preference among ASD people for communicating online [START_REF] Gillespie-Lynch | Intersections between the autism spectrum and the internet : Perceived benefits and preferred functions of computer-mediated communication[END_REF][START_REF] Van Der Aa | Computer-mediated communication in adults with high-functioning autism spectrum disorders and controls[END_REF][START_REF] Westerberg | An Internet Based Intervention for Adults With Autism Spectrum Disorder-A Qualitative Study of Participants Experiences[END_REF]. The review by [START_REF] Hassrick | Benefits and Risks : A Systematic Review of Information and Communication Technology Use by Autistic People[END_REF] highlighted that online communication offers multiple opportunities for ASD regarding the learning of social rules, the creation of relationships based on social media, and the enhancement of mental health by reducing anxiety and feelings of loneliness. More precisely, the primary reason for the preference for online interactions among individuals with ASD, is believed to be the slower pace of the online environment. This preference can be attributed to reduced information processing demands [START_REF] Van Der Aa | Computer-mediated communication in adults with high-functioning autism spectrum disorders and controls[END_REF]. Additionally, written computer-mediated communication has the potential to alleviate social stress associated with social conventions such as body language, eye contact, and tone of voice, which can be particularly distressing for individuals with ASD [START_REF] Westerberg | An Internet Based Intervention for Adults With Autism Spectrum Disorder-A Qualitative Study of Participants Experiences[END_REF]. Consequently, ASD subjects reported higher satisfaction with their online social life than with their social life and life in general [START_REF] Van Der Aa | Computer-mediated communication in adults with high-functioning autism spectrum disorders and controls[END_REF], a feeling of greater understanding and control over communication, and the opportunity to express their true selves in computer-mediated communication [START_REF] Gillespie-Lynch | Intersections between the autism spectrum and the internet : Perceived benefits and preferred functions of computer-mediated communication[END_REF]. Moreover, heightened depressive symptoms, reduced overall life satisfaction, and diminished self-esteem have been consistently linked to experiences of loneliness in individuals with ASD [START_REF] Mazurek | Loneliness, friendship, and well-being in adults with autism spectrum disorders[END_REF]. Interestingly, [START_REF] Mazurek | Loneliness, friendship, and well-being in adults with autism spectrum disorders[END_REF] showed that the intensity of loneliness tends to wane in the presence of a more substantial number and higher-quality of friendships. Therefore, considering the potential of online communication to facilitate satisfying social interactions in ASD, online communication tools could significantly enhance their mental well-being. However, so far, no studies have investigated online social skills in the autistic spectrum, while an easy-to-administer tool has recently been developed to specifically assess communicative and online socio-emotional skills [START_REF] Mantzouranis | Assessing Online and Offline Adolescent Social Skills : Development and Validation of the Real and Electronic Communication Skills Questionnaire[END_REF]. The purpose of this study was to examine global social skills both online and in real life according to autistic traits, in order to better characterize social functioning in everyday life situations within the autistic spectrum.

Method

Participants

In the present study, seventy-one participants (8 males) from the general population participated (Mean age=35.23;SD=11.46;. G*Power software was used to test the power analysis of our sample size. We rejected the null hypothesis if we observed a sample correlation coefficient outside the interval [-0.2287052, 0.2287052]. The total sample size required to ensure a power (1 -β) > 0.80 was 74. Therefore, the inclusion of seventy-one participants in the current study can be considered correct. All participants reported using social networks to communication in everyday life. They had normal or corrected-to-normal vision and had no history of neurological or psychiatric illness. No information about ethnic background, socio-economic status or sexual orientation was available. Note that the use of the Real and Electronic Communication Skills questionnaire (RECS) did not reveal any gender effect in the original study [START_REF] Mantzouranis | Assessing Online and Offline Adolescent Social Skills : Development and Validation of the Real and Electronic Communication Skills Questionnaire[END_REF], conversely to the AQ [START_REF] Baron-Cohen | The autism-spectrum quotient (AQ) : Evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians[END_REF].

Procedure

The participants were recruited through calls for volunteers that were posted on social networks and university websites. These recruitment methods allowed for a broad reach and potential engagement of individuals active on social media platforms. Participants completed surveys that were conducted in French using an online survey tool in the following order: AQ-RCS-ECS.

Measures

Autistic traits and social profile

The Autism-Spectrum Quotient (AQ) is a validated 50-items self-report questionnaire for identifying the degree to which an adult presents autistic traits. The instrument measures five dimensions (10 items each): Social skill (e.g., "I find it hard to make new friends"), Attention switching (e.g., "I frequently get so strongly absorbed in one thing that I lose sight of other things"), Attention to detail (e.g., "I often notice small sounds when others do not"), Communication (e.g., "I enjoy social chit-chat") and Imagination (e.g., "I find making up stories easy") (Baron-Cohen et al., 2001, p. 15-16). Each response is scored 0 or 1, a higher score indicates higher levels of autistic behavior. Previous studies found a high internal consistency for the overall AQ score with a Cronbach's alpha between .72 and .79 [START_REF] Hoekstra | Factor Structure, Reliability and Criterion Validity of the Autism-Spectrum Quotient (AQ) : A Study in Dutch Population and Patient Groups[END_REF][START_REF] Ruzich | Measuring autistic traits in the general population : A systematic review of the Autism-Spectrum Quotient (AQ) in a nonclinical population sample of 6,900 typical adult males and females[END_REF][START_REF] Stevenson | Psychometric Properties of the Autism-Spectrum Quotient for Assessing Low and High Levels of Autistic Traits in College Students[END_REF]. Autism-Spectrum Quotient global score was used as an indicator of autistic traits. Furthermore, [START_REF] Baron-Cohen | The autism-spectrum quotient (AQ) : Evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians[END_REF] suggested that a score exceeding 32 on the AQ can be used as a valuable threshold for discerning individuals exhibiting clinically significant levels of autistic traits. However, it is worth noting that none of the participants in our study reached such a high score on the AQ global scale. We used the French version of the AQ [START_REF] Kempenaers | The assessment of autistic traits with the Autism Spectrum Quotient : Contribution of the French version to its construct validity[END_REF].

In order to obtain an assessment of the social abilities of the participants, a validated questionnaire in French, the Real and Electronic Communication Skills questionnaire (RECS; [START_REF] Mantzouranis | Assessing Online and Offline Adolescent Social Skills : Development and Validation of the Real and Electronic Communication Skills Questionnaire[END_REF] was administered. This instrument includes two self-reported questionnaires, one assessing social abilities in real life (Real Communication Skills; RCS) and the other assessing online social abilities (Electronic Communication Skills; ECS). Each of these questionnaires includes 18 items that are scored with a 5-point Likert scale and are composed of four dimensions: Sociability (e.g., RCS: "I really like meeting new people"; ECS: "I really like to increase my circle of friends online"), Disclosure (e.g., RCS: "I sometimes cry in front of others"; ECS: "When I chat online with a close friend, I can easily tell him things that make me feel ashamed"), Emotion Decoding (e.g., RCS: "When someone is sad, I see it immediately, even if they try to hide it"; ECS: "When I am online, I can easily identify the emotions of other Internet users") and Assertiveness. (e.g., RCS: "In general, my friends see me as someone who knows how to assert themselves"; ECS: "If I disagree with someone online, I say so") (Mantzouranis et al., 2019, p. 25-26). [START_REF] Mantzouranis | Assessing Online and Offline Adolescent Social Skills : Development and Validation of the Real and Electronic Communication Skills Questionnaire[END_REF] found a high internal consistency for the RCS and ECS scores with a Cronbach's alpha of .75 and .78, respectively, and a high scale reliability with a McDonald's omega of .81 and .84, respectively and confirm the external validity using the subscales of the Social Skills Inventory (Riggio, 1992).

Data Analyses

The normality of the data was tested using the Shapiro-Wilk test on the global score of the AQ, the RCS, and the ECS questionnaires. In order to examine the relationship between autistic traits and the social abilities of participants, Pearson's correlations were applied on the total and subscale scores for the AQ and the RCS, as well as for the AQ and the ECS. The relation between the online social skills (ECS) and real-life social skills (RCS) was also examined using similar tests. The effect of autistic traits on social abilities assessed with real-life situations has been commonly highlighted in non-ASD individuals; High autistic traits are associated with greater social difficulties (e.g., [START_REF] Stewart | Lexical effects on speech perception in individuals with "autistic" traits[END_REF][START_REF] Voos | Autistic traits are associated with diminished neural response to affective touch[END_REF]. However, the correlational analyses do not provide a sense of the relationship between variables. In this context, a Structural Equation Model (SEM) was used to test the influence of autistic traits (AQ) on online social skills (ECS). SEM is a multivariate statistical analysis technique that is used to analyze structural relationships by using path models that mathematically represent the causal influences on the variables of interest. In addition, an ANOVA analysis was calculated to further compare the models testing the direct and indirect effect of AQ on ECS.

Results

The global score of the AQ ranged from 7 to 32 with a mean of 17.91 (SD=6.04), which is in line with previous results in the general population reporting a mean of 16.08 (SD=5.53) with a range from 2 to 31 (e.g., Mayer et al., 2016). The mean score of the RCS was 61.09 (SD=7.66) with a range from 45 to 75. The ECS ranged from 33 to 71 and presented a mean of 47.26 (SD=7.61). Due to the novelty of the RCS, no descriptive results are available in the literature. Consequently, we were not able to compare our data with reference data. The means, standard deviations and ranges of total scores, and dimensions of the questionnaires are presented in Table 1. Because the global scores of the RCS and ECS questionnaires did not follow a normal distribution (W = 0.963 p < 0.05), the questionnaires scores (global score and dimensions of the AQ, the RCS and the ECS) were transformed into a z-score for the statistical analyses.

The results of Pearson's correlation between total scores and dimensions of the questionnaires are presented in Table 2. In general, the results demonstrated a significant negative correlation between autistic traits (AQ) and social skills in real life (RCS), with higher levels of autistic traits related to lower social abilities in real life (see Fig. 1A). This is to be expected since the social dimensions of the AQ are based on real-life social scenes. In contrast, the autistic traits (AQ) correlated positively with online social skills (ECS), meaning that the more the participants had autistic traits, the more they reported online social skills (see Fig. 1B). Note that the correlations between the RCS and the ECS with the AQ do not concern the same dimensions of the questionnaires. Specifically, the correlation between the AQ and RCS was primarily driven by negative relationships between the dimensions assessing social skills on the questionnaires. The more social difficulties participants expressed (Social skills, AQ), the fewer social skills (Sociability, RCS) they reported. Similarly, the more they perceived difficulty communicating (Communication, AQ), the less they were able to socialize (Sociability, RCS). Other dimensions drove the positive correlation between the AQ and the ECS. The more subjects expressed difficulties imagining (Imagination, AQ), the more ease they reported in online social interactions (ECS total). In addition, the more difficulties subjects had in sustaining a conversation (Communication, AQ), the more intimate information they shared with others (disclosure, ECS). No significant correlation was found between real-life and online social skills. The application of a structural equation model showed significant regression coefficients between autistic traits and real-life social skills (-0.26, p<.05), between autistic traits and online social skills (0.28, p<.05), and between real-life social skills and online social skills (0.27, p<.01, see Fig. 1C). The significance of the indirect effect (the influence of AQ on ECS mediated by RCS) was tested using bootstrapping procedures. Unstandardized indirect effects were computed for each of 1 000 bootstrapped samples, and the 95% confidence interval was computed by determining the indirect effects at the 2.5th and 97.5th percentiles. The bootstrapped unstandardized indirect effect was -0.08 and the 95% confidence interval ranged from -1.13 to 0 (p = .052). Thus, autistic traits significantly influenced perceived online social skills and real-life ones. In addition, the influence of autistic traits on online social skills was not mediated by real-life social skills.

In addition, an ANOVA was computed to compare the models with and without the indirect effect and revealed a significant enhancement when the indirect effect was removed (F(1,35) = 3.2, p > .05), suggesting that the best model is the simple one that test the direct effect of the AQ on the ECS.

Discussion

Within the autistic spectrum (ASD and autistic traits), social difficulties have commonly been explored using questionnaires or experimental paradigms focusing on real-life social situations. No study has yet explored social skills in an electronic context (i.e., online). However, such an investigation is crucial to characterize social functioning in everyday life situations to better understand socio-communicative difficulties, which are central within the autistic spectrum. We assessed the autistic traits of participants from the general population and highlighted that participants with high autistic traits presented lower social skills in real life and higher online social skills than participants with low autistic traits. These results, which reveal accentuated difficulties in real-life social interactions and facilities in online ones, suggest that the social difficulties commonly reported in the autistic spectrum could be context-dependent. Our results provide crucial preliminary evidence of the positive social capital that participants with high autistic traits gain by participating in online social interactions and may constitute an interesting avenue for the development of strengths-based interventions in ASD. Furthermore, identifying the factors responsible for the perception of higher online social skills could inform us on how to modify the environment to promote social interactions in the autistic spectrum.

Online communication: A way to foster social connection?

The results showed that autistic traits were associated with more perceived social skills when communicating online and, on the contrary, difficulties when communicating in real life. Previous research has already indicated that non-ASD individuals who exhibit self-reported social avoidance behaviors, such as aloofness, tend to experience a decrease in mental wellbeing [START_REF] Stimpson | The Association Between Autistic Traits and Mental Well-Being[END_REF]. Furthermore, this association was partially explained by the level of social support perceived by the individuals. Another study by [START_REF] Stice | Social Connectedness and Loneliness Mediate the Association Between Autistic Traits and Internalizing Symptoms Among Young Adults[END_REF] revealed that individuals with high autistic traits reported lower levels of social connectedness, which subsequently contributed to increased feelings of loneliness. As a result, these heightened feelings of loneliness were associated with elevated levels of anxiety and depressive symptoms. Considering our findings, online communication could have several social benefits for individuals having high autistic traits and consequently positively impact their mental wellbeing. The review by [START_REF] Hassrick | Benefits and Risks : A Systematic Review of Information and Communication Technology Use by Autistic People[END_REF] shed light on the multifaceted advantages of online communication in ASD. Their findings suggested benefits encompassing social skills development and cultivating positive social capital. Moreover, the study elucidated the potential of online communication as a tool for bolstering mental health outcomes in this population. Even if these results suggest the positive potential of online communication in enhancing the well-being and social integration of individuals with ASD, we cannot exclude that in our study, perception of enhanced social skills based on self-report questionnaires may reveal a higher comfort with online communication rather than a real improvement in social competencies. Further studies could explore the extension of previous results in ASD on individuals with high autistic traits by using more objective tools in assessing social abilities when using online communication and evaluating the impact on mental health. Additionally, investigating the underlying factors contributing to the increased sociability online would be particularly intriguing.

Online communication: A socially explicit and structured environment?

A tentative explanation of the lower level of real-life social skills and, conversely, higher online perceived social skills in participants having high autistic traits could be linked to the socially explicit and structured characteristics of online communication. In face-to-face conversations, people with ASD often have difficulties interpreting non-verbal communication cues (body language, tone of voice, etc.), which are critical to understanding the speaker's intent [START_REF] Apa | Diagnostic and Statistical Manual of Mental Disorders (DSM-5)[END_REF]. In addition, people with ASD may feel the need to have more time than non-ASD subjects to interpret a conversation and formulate a response [START_REF] Haigh | Processing Speed is Impaired in Adults with Autism Spectrum Disorder, and Relates to Social Communication Abilities[END_REF]. Instead, online interactions offer stable cues over time, visual signs of organization, and a presentation accompanying the written text that helps the user decipher the speaker's intentions, such as font features, punctuation, emoticons, etc., and allow participants to respond at their own pace. In this sense, online interactions potentially offer people with ASD the opportunity to communicate more comfortably and benefit from more easily interpretable cues (e.g., emoticons are always the same, whereas in real life, everyone expresses their emotions differently). Such a socially explicit online environment could also explain the link found in the present study between online social skills and difficulties in imagining. Participants with the most difficulty imagining may benefit more from supports that facilitate the representation of fictional scenes (pictures, videos, emoticons, descriptions, etc.). It would have been be helpful to ask our subjects about their use of social networks, both in terms of frequency of use and content viewed to better understand the origin of such ease in online social communication.

Moreover, one of the specificities of online social communication is the highly structured communicative environment: since the design of social networks is stable, the appearance of conversations is similar from one person to another. Communicating online allows us to choose the people with whom to interact and who share common interests with us. All these elements are markedly reduced in real life, where interactions take place in different contexts, with a changing environment and are more random and unexpected. One of the particularities of ASD is the axis of high-intensity restricted interests as well as the excessive adherence to regular patterns (e.g. setting up routines or rituals) and the marked preference for predictable information (APA, 2013). Thus, it is possible that the regular and predictable environment of online communication as well as control over conversational topics and choices with whom to engage/respond foster engagement in social interactions in the autistic spectrum. In addition, such control of the social content could be at the origin of the internet addictions commonly highlighted in ASD (e.g., [START_REF] Murray | Autism, Problematic Internet Use and Gaming Disorder : A Systematic Review[END_REF] and in people without ASD but with high autistic traits (e.g., [START_REF] Finkenauer | Brief Report : Examining the Link Between Autistic Traits and Compulsive Internet Use in a Non-Clinical Sample[END_REF].

Online communication: a controlled sensory flow? A higher sensory sensitivity has been well characterized all along the autistic spectrum (e.g., [START_REF] Markram | The Intense World Theory -A Unifying Theory of the Neurobiology of Autism[END_REF][START_REF] Mayer | The Relationship Between Autistic Traits and Atypical Sensory Functioning in Neurotypical and ASD Adults : A Spectrum Approach[END_REF][START_REF] Takayama | Standardization of the Japanese version of the Glasgow Sensory Questionnaire (GSQ)[END_REF] and the sensory profile is commonly associated with the severity of symptoms or the degree of autistic traits [START_REF] Horder | Autistic Traits and Abnormal Sensory Experiences in Adults[END_REF][START_REF] Mayer | The Relationship Between Autistic Traits and Atypical Sensory Functioning in Neurotypical and ASD Adults : A Spectrum Approach[END_REF]. Thus, using electronic devices to communicate could reduce sensory inputs and increase social skills. More precisely, the intensity of sensory inputs is directly and instantly modular when using electronic tools (such as the auditory dB level or the light intensity), which is not the case in real-life contexts. In addition, this sensory sensitivity could lead to a saturation of the perceptual load in real life, generating social difficulties. Specifically, a recent study found a decrease in the severity of social difficulties in ASD when the number of surrounding items of information is diminished [START_REF] Haskins | Reduced social attention in autism is magnified by perceptual load in naturalistic environments[END_REF]. In this vein, since the amount of information is severely diminished online and focuses on the relevant information to be processed (e.g., the main information from a conversation with another person), this may favor adapted social behaviors.

Higher self-disclosure in online communication

Correlation analysis showed that the facilitation of online social skills concerned more particularly the states of self-disclosure in subjects with communication difficulties. The more subjects exhibited high autistic traits, the more they opened up about their intimacy with others. Self-disclosure behaviors are particularly implicated in developing or maintaining intimate relationships [START_REF] Brehm | Intimate relationships[END_REF]. The online environment could represent a defined and restricted place where ASD subjects or subjects with high autistic traits could direct interactions with their most intimate relatives, motivating self-disclosure behaviors. Nevertheless, despite the fact that revealing information about self can help people as they attempt to maintain close relationships with others, some authors [START_REF] Miell | Strategies in Developing Friendships[END_REF] suggest that self-disclosure could generate problems for individuals and relationships. Individuals must learn to regulate their disclosures to avoid inappropriate self-disclosure in conversation with a stranger or to control revealing feelings with close friends that can be "cruel and destroy trust" [START_REF] Hargie | The handbook of communication skills[END_REF]. Notably, because self-disclosure behaviors are linked to communication difficulties, it would be interesting to explore how and with whom subjects engage in self-disclosure behaviors within the autistic spectrum. Such an investigation would allow us to understand better whether online use promotes or hinders the appropriate use of self-disclosure in individuals with high communication difficulties.

Side effects of online communication

Finally, although online communication could have favorable effects on social communication, it is nevertheless crucial to mention the limits of using such a tool. Indeed, even if online communication offers several opportunities to create social connection, it also contains several risks, including cyberbullying and unwanted sexual solicitation, particularly in adolescents, with victimization rates being as high as 53% in some studies (for a review, [START_REF] Valkenburg | Online communication among adolescents : An integrated model of its attraction, opportunities, and risks[END_REF]. Within ASD, the study of [START_REF] Triantafyllopoulou | Social Media and Cyber-Bullying in Autistic Adults[END_REF] revealed a noteworthy association between elevated levels of social media usage and an amplified risk of cyber-victimization. Conversely, higher self-esteem exhibited positive correlations with feelings of belonging within online communities, while displaying negative correlations with feelings of being ignored on social network sites and chat rooms.

Limitations and Future Research

Our study has several limitations. Most importantly, the results of this study may not be generalizable to the overall autistic spectrum due to several factors, including the recruitment of participants without an ASD diagnosis, the overrepresentation of females, and the exclusion of individuals with intellectual delay. These limitations raise important considerations regarding the interpretation and applicability of the findings.

Firstly, our study focuses on the general population and not on ASD. While individuals with high autistic traits may share some similarities in social particularities with those diagnosed with ASD, it is essential to recognize that autistic traits are subclinical and do not interfere with quality of life. Since similarities have commonly been found between subjects with elevated autistic traits and ASD subjects, we might expect to replicate our results in a clinical population (e.g., [START_REF] Bezemer | The Predictive Value of the AQ and the SRS-A in the Diagnosis of ASD in Adults in Clinical Practice[END_REF][START_REF] Constantino | Reciprocal social behavior in children with and without pervasive developmental disorders[END_REF][START_REF] Voos | Autistic traits are associated with diminished neural response to affective touch[END_REF]. Furthermore, the concept of autistic traits should be interpreted cautiously because, although consensual, it remains hypothetical as no empirical evidence has confirmed the extension of autistic characteristics in the general population [START_REF] Sasson | Studies of autistic traits in the general population are not studies of autism[END_REF]. Questionnaires assessing autistic traits do not require clinical judgment, are not designed as diagnostic evaluations, rely on self-evaluation, and contain elements often interpreted differently by individuals with and without ASD [START_REF] Gernsbacher | Specificity, contexts, and reference groups matter when assessing autistic traits[END_REF]. More specially, while self-report measures provide valuable insights into individuals' perceptions of their social abilities, they may be subject to biases, such as social desirability or limited self-awareness [START_REF] Arnold | Social Desirability Response Bias in Self-Report Choice Situations[END_REF]. Additionally, the absence of direct assessment limits the objective evaluation of participants' social skills in real-life and online contexts. A more comprehensive assessment approach that includes direct observations or behavioral measures would have provided a more robust understanding of social skills in the autistic spectrum.

Secondly, the overrepresentation of females in our study sample is another factor that limits the generalizability of the results. Autism has traditionally been recognized as a condition that affects males more frequently than females [START_REF] Zeidan | Global prevalence of autism : A systematic review update[END_REF]. By recruiting a predominantly female sample, the study may have inadvertently skewed the findings and failed to capture the full range of social skills difficulties experienced by males on the autistic spectrum. Note that a gender effect on AQ in non-ASD subjects has been demonstrated and shows higher scores for men [START_REF] Baron-Cohen | The autism-spectrum quotient (AQ) : Evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians[END_REF]. Such a difference in score could be linked to the use of compensation strategies (referred to as camouflaging strategies) by women, making their social difficulties invisible although present [START_REF] Hull | Putting on My Best Normal" : Social Camouflaging in Adults with Autism Spectrum Conditions[END_REF][START_REF] Hull | The Female Autism Phenotype and Camouflaging : A Narrative Review[END_REF]. Such strategies have also been proposed as the origin of the high male prevalence of ASD, with a male-to-female ratio of 3:1 [START_REF] Hull | Putting on My Best Normal" : Social Camouflaging in Adults with Autism Spectrum Conditions[END_REF][START_REF] Hull | The Female Autism Phenotype and Camouflaging : A Narrative Review[END_REF][START_REF] Loomes | What Is the Male-to-Female Ratio in Autism Spectrum Disorder? A Systematic Review and Meta-Analysis[END_REF]. Thus, because our study primarily included females, it may not adequately capture the experiences and characteristics of males and highlight the need for further studies to include a more genderbalanced sample.

Fig. 1 .

 1 Fig. 1. Relation between autistic traits and social skills. Correlation between (A) the autistic traits (AQ) and the social skills in real life (RCS) and (B) the autistic traits (AQ) and online social skills (ECS). (C) Tested model regarding the relationship between autistic traits, and online and real-life social skills. Data were normalized by computing the z-score. *p < .05; **p < .01

Table 1

 1 Means, SDs and ranges of the questionnaires

		AQ total (0-50)	Social skills (0-10)	Att. Switch. (0-10)	Att. to detail (0-10)	Comm. (0-10)	Imag. (0-10)
	Mean (SD)	17.91 (6.04)	3.16 (2.43)	4.2 (1.79)	5.41 (2.39)	2.65 (1.52)	2.65 (1.52)
	Range	7-32	0-10	1-9	0-10	0-6	0-7
		ECS total (0-90)	Sociability (0-25)	Disclosure (0-25)	Emo. Decod. (0-25)	Assertiv. (0-15)
	Mean (SD)	47.26 (7.61)	9.12 (3.6)	11.75 (3.5)	17.03 (3.25)	9.37 (2.48)
	Range	33-71	5-25	5-23	10-25	3-14
		RCS total (0-90)	Sociability (0-25)	Disclosure (0-25)	Emo. Decod. (0-25)	Assertiv. (0-15)
	Mean (SD)	61.09 (7.66)	13.93 (4.03)	15.58 (4.47)	20.57 (2.45)	11.02 (2.07)
	Range	45-75	5-25	6-24	13-25	6-15

Table 2

 2 Pearson correlation matrix between the questionnaires

		AQ total	Social skills	Att. Switch.	Att. to detail	Comm.	Imag.
	RCS total	-0.26*
		[-0.47, -0.028]

  Authors have no conflicts of interest to disclose. The study conformed with the Code of Ethics of the World Medical Associations (Declaration of Helsinki) and was approved by the local research ethics committee (Comité de Protection des Personnes Sud Mediterranée III, Avis N° 2020-A03056-33). Authors contribution : Rachel Poulain: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Software; Writing-Original draft; Writing-Review & editing. Céline Cappe: Conceptualization; Investigation; Project administration; Supervision; Validation; Visualization; Writing-Review & editing. Magali Batty: Conceptualization; Investigation; Methodology; Project administration; Supervision; Validation; Visualization; Writing-Review & editing. Data from the present study are not available. All authors approved the final submitted version. The authors wish to thank all participants in this research. This research did not receive any specific grant from funding agencies in the public, commercial, or not -for -profit sectors.


Elodie Piche
email: piche.e@chu-nice.fr

Frédéric Chorin

Raphaël Zory

Patricia Duarte Freitas

Olivier Guerin

Pauline Gerus

Piche Elodie

Chorin Frédéric

Zory Raphaël

De Souza Barbosa

Guerin Olivier

Gerus Pauline

Affiliations

Metabolic cost and co-contraction during walking at different speeds in young and old adults

Keywords: ageing, co-contraction, energy cost, gait biomechanics, EMG-driven model

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

Aging is associated with a decline in mobility and balance, which may lead to falls and a loss of independent function [START_REF] Bigland-Ritchie | Changes in muscle contractile properties and neural control during human muscular fatigue[END_REF]. To increase postural stability, older adults are likely to develop compensatory strategies especially during locomotion tasks. Muscle co-activation, which is the concurrent activation of agonist and antagonist muscles that cross a joint, is one strategy to enhance joint stability [START_REF] Nagai | Effect of the muscle coactivation during quiet standing on dynamic postural control in older adults[END_REF]. Estimation of co-activation during gait with surface electromyographic analysis (sEMG) has demonstrated that older adults have higher muscle co-activation, particularly in antagonist muscles, than their younger counterparts [START_REF] Pincivero | Quadriceps-hamstring EMG activity during functional, closed kinetic chain exercise to fatigue[END_REF][START_REF] Lee | Age-related differences in muscle coactivation during locomotion and their relationship with gait speed: a pilot study[END_REF][START_REF] Larsen | Comparison of ground reaction forces and antagonist muscle coactivation during stair walking with ageing[END_REF][START_REF] Hortobágyi | Interaction between age and gait velocity in the amplitude and timing of antagonist muscle coactivation[END_REF]. However, the age-related increase in antagonist muscle co-activation would in turn require each agonist muscle to produce additional force, recruiting a greater portion of muscle mass and, thus, consume more metabolic energy, to offset the opposing force of the antagonist muscle. This process could be a contributor to the higher metabolic cost (NCw) in old adults compared to their younger counterparts [START_REF] Mian | Metabolic cost, mechanical work, and efficiency during walking in young and older men[END_REF][START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF].

Results of studies of the association between co-activation and NCw are contradictory and offer a limited understanding. For example, Ortega et al [START_REF] Ortega | Effects of aging on mechanical efficiency and muscle activation during level and uphill walking[END_REF] showed a low correlation (r=0. [START_REF] Lo | Functional implications of muscle co-contraction during gait in advanced age[END_REF] between NCw and co-activation while other studies [START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF][START_REF] Moore | Relationship between metabolic cost and muscular coactivation across running speeds[END_REF][START_REF] Marques | Association between energy cost of walking, muscle activation, and biomechanical parameters in older female fallers and non-fallers[END_REF] have found higher correlations (r=0.5-0.69). Also, Marques et al. [START_REF] Marques | Association between energy cost of walking, muscle activation, and biomechanical parameters in older female fallers and non-fallers[END_REF] highlighted that NCw is only correlated with co-activation at the knee joint, whereas Peterson et al. [START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF] emphasized a correlation at the ankle joint. Mian et al. [START_REF] Mian | Metabolic cost, mechanical work, and efficiency during walking in young and older men[END_REF] explained that their results were highly dependent on the method used to determine co-activation and found that their method, which normalizes EMG with a maximal voluntary contraction (MVC), could be inadequate when applied in older adults. Indeed, this population may have trouble consistently reaching MVC, leading to a miscalculation in coactivation. Moreover, Souissi et al. 2017 [START_REF] Souissi | Comparison of methodologies to assess muscle cocontraction during gait[END_REF] show that co-activation methods tend to misestimate the simultaneous action of agonist and antagonist contractions, which can lead to an underestimation of energy cost and erroneous clinical conclusions during pathological gait analysis. New methods based on EMGdriven models have been developed and may provide a more reliable description of muscle action than coactivation methods. First, Co-Activation methods are based on one agonist and one antagonist muscles when the CCI includes several agonist and antagonist muscles. This can be particularly important at the ankle joint where three muscles represent the plantar flexor muscles group and one muscle for the dorsiflexor muscle group. In addition, the normalized EMG used to compute the Co-Activation leads to equivalent contribution of agonist and antagonist. It is important to note that the maximal muscle moment production which is fourfold stronger in the plantar flexors than in the dorsiflexor cannot be included when normalized EMG or normalized moment [START_REF] Knarr | Comparison of electromyography and joint moment as indicators of co-contraction[END_REF] are used. Finally, the EMG data does not include the nonneural factors that influence muscle moment [START_REF] Knarr | Comparison of electromyography and joint moment as indicators of co-contraction[END_REF] such as the contraction mode (eccentric vs concentric) that lead to different muscle force. These new methods could significantly help to determine the most prominent factor in the prediction of metabolic cost, which is still a challenging task. Indeed, previous studies, most using co-activation methods, have only demonstrated a correlation between co-activation and metabolic cost without explaining which joints (knee, ankle or hip) or other parameters contribute the most.

The use of a more reliable method to estimate co-contraction could provide a further understanding of this relationship.

The aim of this study was, thus, to compare knee and ankle co-contraction index (CCI) levels between young and old adults and to identify their contributions to metabolic cost (NCw) with a new consistent method. The detailed hypotheses are (1) older adults exhibit higher NCw than young adults, (2) older adults have higher levels of co-contraction in the knee and ankle than young adults across a range of walking speeds, and (3) higher levels of co-contraction are associated with higher NCw in both older and young individuals.

MATERIALS AND METHODS

PARTICIPANTS

9 healthy subjects (25.2 +/-3.3 years) were included in the Young Group (YG) and 9 older subjects (68.7 +/-5.9 years) constituted the Old Participants' group (OG) (Table 1). Approval of the study protocol was obtained (n° 2015-A01188-41). Inclusion criteria were the ability to walk independently without walking aids, no use of antispastic medications and no orthopedic surgery in the last 6 months. Prior to enrollment in the study, all participants provided written informed consent.

[Please insert Table 1]

EXPERIMENTAL PROTOCOL

Participants were asked to walk on a Bertec instrumented treadmill (Bertec, Columbus, OH, USA) where kinematics, kinetics, surface electromyography (EMG) and oxygen consumption were recorded.

Before acquisition, practice sessions were performed to familiarize participants with the procedure. Then, five trials were recorded at different speeds (OG: 0.6 m/s, 0.8m/s, 1 m/s, 1.2 m/s and 1.4 m/s and YG: 1 m/s, 1.2 m/s, 1.4 m/s, 1.6 m/s and 1.8 m/s) for 2 min each, in a random order. Only the last 30 s was analyzed. The five speeds were selected to provide a broad range of walking speed encompassing the preferred walking speeds of both older and young adults [START_REF] Bohannon | Comfortable and maximum walking speed of adults aged 20-79 years: Reference values and determinants[END_REF]. The procedure was based on the statement that older adults have lower PWS than their younger counterparts [START_REF] Chung | The change of gait parameters during walking at different percentage of preferred walking speed for healthy adults aged 20-60 years[END_REF].

The whole-body segmental motion was recorded at 100 Hz using 9 optoelectronic cameras (Prime 13, Optitrack, NaturalPoint, USA) based on a full-body marker set [START_REF] Besier | Repeatability of gait data using a functional hip joint centre and a mean helical knee axis[END_REF]. Ground reaction forces were recorded from two force plates integrated in the treadmill. Skin surface electrodes (EMG) were placed longitudinally on different muscle bellies with respect to their muscle fiber direction following SENIAM conventions [START_REF] Hermie | Development of recommendations for SEMG sensors and sensor placement procedures[END_REF] and were recorded at 1000 Hz using a Bagnoli 16-channel bipolar surface electrode system (Delsys, Boston, USA). Finally, oxygen uptake (V02) was recorded by a COSMED K5 portable gas exchange system (COSMED, Rome, Italy) in breath-by-breath mode [START_REF] Guidetti | Validity, reliability and minimum detectable change of COSMED K5 portable gas exchange system in breath-by-breath mode[END_REF][START_REF] Kalron | Physical activity in mild multiple sclerosis: contribution of perceived fatigue, energy cost, and speed of walking[END_REF].

ESTIMATION OF AGONIST/ANTAGONIST MUSCLE MOMENT

Muscle forces at the ankle and knee joints were estimated using an EMG-driven approach with two degrees of freedom, which has been described in detail elsewhere [START_REF] Buchanan | Neuromusculoskeletal modeling: Estimation of muscle forces and joint moments and movements from measurements of neural command[END_REF]. OpenSim (version 3.1, SimTK, Stanford, USA) was used to create the anatomical model based on a full-body model [START_REF] Hamner | Muscle contributions to propulsion and support during running, 14[END_REF] including eight muscle-tendon units: biceps femoris long-head (BicFemLH), semi-tendinosus (SeTend), gastrocnemius medialis (GasMed), soleus (Sol), rectus femoris (RecFem), vastus lateralis (VasLat), vastus medialis (VasMed) and tibialis anterior (TibAnt). Muscle activation patterns were derived from the raw EMG data after band-pass filtering (30-400 Hz), full-wave rectification, low-pass filtering (4th order, 6 Hz cut-off frequency), and normalization by the maximal value of the muscle concerned. The transformation from normalized EMG to muscle activation was obtained by including second-order dynamics, electromechanical delay and a nonlinear relationship between EMG and muscle activation [START_REF] Manal | A one-parameter neural activation to muscle activation model: Estimating isometric joint moments from electromyograms[END_REF]. EMG-driven model was calibrated on the left side in knee and ankle joint by minimizing the difference between knee and ankle joint moments. Moments at hip, knee and ankle joints were calculated by multiplying each individual muscle forces of the relative joint by the muscle-tendon moment arms and summed to obtain the total moment of the joint. Then the CCI was computed as: * * 100 [START_REF] Lo | Functional implications of muscle co-contraction during gait in advanced age[END_REF] The antagonist moment (M(t) antagonist) was defined as the moment of lowest absolute value and the agonist moment (M(t) agonist) as the highest absolute value. The moment of the muscle group was computed as the sum of all the muscle moments.

METABOLIC COST CALCULATION

VO2 and VCO2 (ml/min) were averaged over the final 30 s of each trial, when they were stabilized.

As the respiratory exchange ratio (QR) was always below 1 during the walking trial, confirming that aerobic metabolism was the main metabolic pathway, an energetic equivalent of 20.1 J/mL 02 (EEQ) [START_REF] Mian | Metabolic cost, mechanical work, and efficiency during walking in young and older men[END_REF] was used to convert to Joules. The resting metabolic rate was subtracted from the gross metabolic rate (GMR) and divided by walking speed to determine net metabolic cost (NCw).

The equation is as follows:

[24] [START_REF] Gupta | The Metabolic Cost of Walking in healthy young and older adults -A Systematic Review and Meta Analysis[END_REF].

where EEQ is the Energetic Equivalent of the oxygen consumed (VO2(J/min)), GMR is the gross metabolic rate (energy expenditure measured during the trial in ml/kg/min) and RMR the resting metabolic rate (J/kg/min).

DATA ANALYSIS AND STATISTICAL CALCULATIONS

Mean values and standard deviations (SD) were calculated for each variable. The distribution of the data was checked using the Shapiro-Wilk normality test. A two-way (2*3, group * speed) ANOVA with repeated measures was used to determine the effects of age and walking speed on metabolic cost and CCI. Significant ANOVA results were followed by post hoc comparisons using Tukey's HSD test except for NCw that failed the normality test where a Dunn post-hoc was used. A Tukey p-correction was applied for multiple association. Concerning NCw, a one-tailed Welch test was used to test the difference between YG and OG at each speed. Cohen's d coefficient was used to measure the effect size. Pearson's r correlation coefficient was used to test the bivariate association between the dependent variable (i.e., NCw) and the covariate factors (CCI) for the entire sample (n= 18) at different speeds (1m/s ; 1.2 m/s ; 1.4 m/s) and in YG and OG separately. Then, a multiple regression model was built with backward selection to determine the overall fit of the model and the relative contribution of each of the predictors (CCI) to the total variance explained (NCw). The criterion for statistical significance was set at p< 0.05. Statistical analysis was performed using JASP (JASP Team (2020). JASP (Version 0.14.1)).

RESULTS

Older adults exhibit significantly higher NCw (M= 3.5 J/kg/m ; SD=1) than young adults (M=2.8 J/kg/m ; SD=0.4) with an average across speeds of 25% (Table 2, Figure 1) confirming the first hypothesis. No significant difference in NCw between speed were found " ! 0.409, ' 0.368, + 0.014 (Table 2) but it reflects a curvilinear response (Figure 1).

Concerning CCI at knee and ankle joint, no significant higher level of CCI at ankle joint were found in OG compared to YG (Table 2, Figure 2). However, at the knee joint (Knee_CCI, Knee_CCI_stance and Knee_CCI_swing),significant higher values were found for OG (Table 2, Figure 2). The walking speed where the difference in CCI between groups is significative is for 1m/s (Figure 2).

[Please insert Table 2] [Please insert Figure 1]

[Please insert Figure 2]
In YG+OG, all the CCI except for Ankle_CCI_swing and Knee_CCI_swing were moderately correlated with NCw [r= 0.251-0.304] (Table 3). Higher level of CCI are associated with higher NCw only in OG (r=0.475, p=0.012 ; r=0.493, p=0.009 respectively for Ankle_CCI and Ankle_CCI_stance) while in YG no significant correlation between NCw and CCI variables (Table 3).

A multiple linear regression model was built with the 6 CCI variables to quantify their contribution to NCw in YG+OG and YG and OG separately. They are preliminary results regarding the number of parameters [START_REF] Hortobágyi | Interaction between age and gait velocity in the amplitude and timing of antagonist muscle coactivation[END_REF] and the number of participants (9 when divided into groups). Regarding YG + OG, the model was significant and explained 29.6% of the variability of NCw (F (5.48) = 4.027, p=0.004). Ankle_CCI and Ankle_CCI_stance were found as the main contributors in NCw with a slope coefficient of 0.188 and -0.139, respectively (p<0.05) (Table 4). The positive slope coefficient for Ankle_CCI means that NCw increase with Ankle_CCI. Conversely, an increase in NCw is associated with a decrease in Ankle_CCI_stance. The model in YG is also significant and very similar to YG+OG with 62.3% of the variability of NCw explained (F (5.21) = 6.946, p<0.001). The main contributors are Ankle_CCI and Ankle_CCI_stance with a slope coefficient of 0.138 and -0.126 respectively (p=0.003) (Table 4). Finally, the model for OG is significant with only 2 variables that explained 33.2% of the variability of NCw (F (2.24) = 5.972, p = 0.008).

[Please insert Table 3] [Please insert Table 4]

DISCUSSION

The aim of this study was to compare knee and ankle CCI levels between young and old adults and to identify their contributions to metabolic cost using a new consistent method. NCw was significantly higher in OG for each speed, confirming the hypothesis. The hypothesis was also confirmed for Knee_CCI, Knee_CCI_swing and Knee_CCI_stance where it is significantly higher in OG. While we hypothesized that both ankle and knee CCI could play a role in NCw, results highlighted that NCw was largely explained by ankle_CCI, with a positive relationship between them.

The NCw average was 2.77± 0.43 J/kg/m in YG and 3.5 ± 1 J/kg/m in OG. A meta-analysis established that the average NCw in YG was 2.4 ± 0.4 J/kg/m while it was 2.8 ± 0.5 J/kg/m in OG [START_REF] Gupta | The Metabolic Cost of Walking in healthy young and older adults -A Systematic Review and Meta Analysis[END_REF]. It should be noted that walking on a treadmill leads to a higher metabolic cost than walking overground [START_REF] Parvataneni | Kinematic, kinetic and metabolic parameters of treadmill versus overground walking in healthy older adults[END_REF] which could contribute to our slightly higher values. The preferred walking speed was around 1 m/s for OG and 1.2 m/s for YG which is also in the range of habitual walking speeds in community-dwelling older adults (1.0-1.3 m/s) as for young adults (1.3-1.5 m/s) [START_REF] Himann | Age-related changes in speed of walking[END_REF]. Our results confirmed the significantly higher NCw in older adults compared to their younger counterparts with an average difference across all speeds of 25%.

This is similar to the 23% increase seen in a similar study (M= 71 years) [START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF] and slightly lower than the 31% increase in NCw seen in a previous study (M= 74 years) [START_REF] Mian | Metabolic cost, mechanical work, and efficiency during walking in young and older men[END_REF]. Thus, the decline of aerobic capacity with aging and the concurrent increase in NCw likely contribute to a reduced ability to maintain the activities of daily living, and potentially increase fatigue and fall risk. It is therefore important to determine the underlying contributing factors to the higher NCw in OG.

Significantly higher CCI values were found in OG for all the gait phases (entire gait cycle, swing, and stance phase) at the knee joint but not at the ankle joint. This result was the same as previous work [START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF][START_REF] Macaluso | Contractile muscle volume and agonist-antagonist coactivation account for differences in torque between young and older women[END_REF],

where the authors found that co-activation for biceps femoris/ vastus lateralis (knee joint) was 35% to 60% higher in the elderly, and no significant difference between groups for tibialis anterior/Gastrocnemius lateralis (ankle joint). Also, for the knee joint, the greatest difference between groups was during the stance phase. During initial stance, the quadriceps muscles display a burst of activation as they stabilize the pelvis and the thigh to reduce the displacement of the center of mass in the sagittal plane. During terminal stance, when the anterior acceleration of the center of mass occurs, these muscles exhibit a second burst of activation, again to stabilize the lumbopelvic and thigh regions [START_REF] Liu | Muscles that support the body also modulate forward progression during walking[END_REF]. We theorize that older adults increased co-contraction of knee muscles during stance to a greater extent than young adults to maintain stabilization of the ankle and hip, as a consequence of lower knee extensor strength. In general, increased muscle coactivation during locomotion is most commonly described as a compensatory mechanism to increase joint stiffness and thereby enhance stability [START_REF] Hortobágyi | Interaction between age and gait velocity in the amplitude and timing of antagonist muscle coactivation[END_REF]. Previous studies found similar results [START_REF] Hortobágyi | Interaction between age and gait velocity in the amplitude and timing of antagonist muscle coactivation[END_REF][START_REF] Hortobágyi | Association between muscle activation and metabolic cost of walking in young and old adults[END_REF] [31] concluding that old adults may not be able to control the amount of muscle co-contraction according to performance speed. Instead of increasing muscle co-contraction, they may stiffen their joints and lessen the movement in a more challenging task [START_REF] Iwamoto | Differences of muscle co-contraction of the ankle joint between young and elderly adults during dynamic postural control at different speeds[END_REF]. Perhaps, in old adults, the level of co-activation reached a ceiling and could not further increase. Such insensitivity could limit the functional level of joint stiffness at ankle and knee joint during gait.

Although our results were in agreement with prior research that showed older adults walk with a higher metabolic cost and use greater co-activation, CCI at ankle and knee joint and NCw were only moderately correlated (r = 0.296, r = 0. Previous studies also found that ankle joint co-activation was positively correlated with NCw in old adults (r=0.23-0.52, p < 0.05), while no correlation appeared in young adults [START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF][START_REF] Marques | Association between energy cost of walking, muscle activation, and biomechanical parameters in older female fallers and non-fallers[END_REF]. These results do not offer a window on the relative contributions and degree of involvement of the ankle and knee joint co-contraction in NCw. However, multiple regression revealed Ankle_CCI as the most contributive value on NCw (β = 0.08-0.188, p<0.008), whether the analysis was made on separate or mixed groups. The soleus muscles has one of the largest physiological cross-sectional areas in the lower limb and, thus, may contribute greatly to changes in metabolic cost. Finally, from a purely mechanical point of view, muscle co-contraction is an inefficient use of muscle forces, does not contribute to the useful work output of muscles, and requires higher metabolic cost.

Two reasons why the results of the various studies may differ is that different methods were used to calculate co-activation and different antagonist muscle pairs were evaluated. Indeed, while CCI were obtained from the estimation of muscle moments using the EMG-driven model in Lo et al. [START_REF] Lo | Functional implications of muscle co-contraction during gait in advanced age[END_REF], other studies calculate the co-activation index derived from EMG data [START_REF] Lee | Age-related differences in muscle coactivation during locomotion and their relationship with gait speed: a pilot study[END_REF][START_REF] Peterson | Effects of age and walking speed on coactivation and cost of walking in healthy adults[END_REF]. Methods derived from EMG data have been found to underestimate the simultaneous action of agonist and antagonist contraction while CCI from EMG-driven models may provide a more reliable description of muscle action [START_REF] Souissi | Comparison of methodologies to assess muscle cocontraction during gait[END_REF]. Also, different combinations of muscles can be considered to compose the joint. While Marques et al. [START_REF] Marques | Association between energy cost of walking, muscle activation, and biomechanical parameters in older female fallers and non-fallers[END_REF] defined the ankle joint with rectus femoris/biceps femoris, Lee et al. [START_REF] Lee | Age-related differences in muscle coactivation during locomotion and their relationship with gait speed: a pilot study[END_REF] preferred to use the vastus medialis oblique and biceps femoris. As each muscle plays different roles during walking, if the combination of muscle pairs is not exactly similar, slight differences could be found in CCI calculation and therefore comparisons between studies should be made carefully.

One limitation of the present study is its sole focus on the role of muscle activation in NCw instead of using a multifactorial approach. There are several other age-related adaptations, including differences in gait kinematics or proximal redistribution of lower extremity joint torque, and NCw may be affected to some degree by all of these factors. To fully understand why NCw is elevated in older adults, it is important to explore in more detail each factor and its effect on NCw. Silder et al [START_REF] Silder | Predicting the metabolic cost of incline walking from muscle activity and walking mechanics[END_REF] used a multifactorial approach and their linear regression model explained 96% of the variance in NCw, while our best model only explained 62.3%. However, caution should be made to the multiple linear results as the analysis was overfitted. Indeed, the rule of thumb is usually 2 subject per variable (SPV) [START_REF] Austin | The number of subjects per variable required in linear regression analyses[END_REF] and when groups are divided into 2 parts (9 participants per group) with 6 variables as input of the model, the SPV is not greater than 1.5. When the number of SPV is low, Austin et al [START_REF] Austin | The number of subjects per variable required in linear regression analyses[END_REF] suggest to take the adjusted R2 over the conventional R2 for quantifying the proportion of variance explained by the model which was applied in this study. However, as a result of overfitting, these preliminary results may be poorly reproducible in other samples [START_REF] Austin | The number of subjects per variable required in linear regression analyses[END_REF]. Also, it is unclear how the use of a treadmill has affected gait and whether our results would be reproducible in gait tasks other than on a treadmill. To minimize its potential impact, we used 6 minutes of familiarization, which, according to Meyer et al [START_REF] Meyer | Familiarization with treadmill walking: How much is enough?[END_REF], was sufficient to assure the reliability of lumbar, hip and knee kinematics. It might also be suggested that older adults feel more apprehensive on a treadmill, particularly when asked to walk at speeds faster than they are habitually accustomed to, resulting in an artificially elevated NCw. It is not clear the degree to which this influenced the relation between cocontraction and metabolic cost.

PERSPECTIVES

The present study has demonstrated a higher metabolic cost in old compared to their younger counterparts. This is closely related to the age-related decrease efficiency of the muscle itself, which would then require more metabolic energy to perform a given amount of mechanical work. The findings of the study also highlight that older adults had higher knee co-contraction compared to young adults while ankle co-contraction was found to be the most important contributor to the higher metabolic cost in old adults. This is very interesting as ankle co-contraction has been shown to be associated with an increased fall risk in older adults [START_REF] Nelson-Wong | Increased fall risk is associated with elevated co-contraction about the ankle during static balance challenges in older adults[END_REF]. By providing a better understanding of how muscle co-contraction contributes to the greater metabolic cost of walking in older adults, the results of this study may help scientists and clinicians to further develop strategies aimed at neuromuscular rehabilitation and improving muscle efficiency as a means of improving mobility and independence among older adults.

Figures

Figure 1 :

 1 Figure 1: The NCw-speed relationship, comparison of the metabolic cost between old (solid squares) and young (open circles) with standard deviation. * p<0.05 for difference between OG and YG.

Figure 2 :

 2 Figure 2: Knee and Ankle CCI during the entire gait cycle (a-b), in swing (c-d) and stance phase (e-f) at different speeds (1 m/s, 1.2 m/s and 1.4 m/s) in YG (open circles) and OG (solid squares). *p<0.05 for significant ANOVA results (group*speed).

  273, p<0.05 respectively) with the strongest positive correlation for Knee_CCI_stance (r = 0.304, p= 0.025) in YG+OG similarly to Peterson et al. (r=0.39-0.46) [8]. When collapsed across age groups, no bivariate correlation was found in YG while Ankle_CCI and Ankle_CCI_stance were correlated with NCw in OG (r=0.475, p=0.012; r=0.493, p=0.009, respectively).

Table 1 :

 1 Participant's characteristic

		Tables
		Young (YG) (n=9)	Old (OG) (n=9)	P values
	Age (years)	25.2 +/-3.3	68.7 +/-5.9	<0.001*
	Height (cm)	172.3 +/-5.2	162.8 +/-8.5	0.011*
	Weight (kgs)	66.3 +/-6.2	66.4 +/-12.7	0.982
	BMI (kg/m2)	22.3+/-1.3	25 +/-4	0.072
	Resting metabolic rate	122.4 +/-21.2	91.1 +/-17.2	0.003*
	(J/kg/min)
	Values are mean +/-SD. The p-values were from two-tailed unpaired t-tests between the groups.
	For all tests, the alternative hypothesis specifies that OG is greater than YG. * means significant
	difference (p<0.05)

Table 2 :

 2

	Parameters	YG	OG	Model	F	p	Effect size d
				group	18.33 <0.001 **	0.267
	Knee_CCI (%)	52.1 +/-13	65.5 +/-9.3	speed	0.69	0.506	0.02
				Group*speed 0.526	0.594	0.015
				group	0.16	0.691	0.003
	Ankle_CCI (%)	32 +/-13	33.2 +/-8.8	speed	0.315	0.731	0.013
				Group*speed 0.026	0.974	0.001
				group	5.545	0.023 *	0.101
	Knee_CCI_swing (%)	49.3 +/-19.9	59.8 +/-11.9	speed	0.312	0.734	0.011
				Group*speed 0.429	0.654	0.016
				group	2.897	0.095	0.056
	Ankle_CCI_swing (%)	80.1 +/-7	76.1 +/-9.7	speed	0.067	0.935	0.003
				Group*speed 0.344	0.711	0.013
				group	16.854 <0.001 **	0.249
	Knee_CCI_stance (%) 52.6 +/-15.1	66.6 +/-9.3	speed	0.864	0.428	0.026
				Group*speed 0.580	0.58	0.016

Mean +/-SD for each parameters (average across speed) in YG and OG and ANOVA outputs (group, speed, group*speed). * p<0.05, ** p<0.001. a : non parametric

Table 3 :

 3 Correlation matrix and bivariate association between NCw and CCI parameters in YG, OG and YG+OG.

	Significant results are in bold
		YG		OG		YG+OG
		r	p	r	p	r	p
	NCw -Knee CCI	-0.176	0.379	0.331	0.091	0.296	0.03*
	NCw -Ankle CCI	0.022	0.914	0.475	0.012*	0.273	0.046*
	NCw-	0.201	0.314	0.205	0.306	0.251	0.067
	Knee_CCI_SWING
	NCw-	-0.136	0.498	-0.018	0.929	-0.082	0.556
	Ankle_CCI_SWING
	NCw-	-0.104	0.607	0.354	0.07	0.304	0.025*
	Knee_CCI_STANCE
	NCw-	-0.052	0.796	0.493	0.009*	0.271	0.048*
	Ankle_CCI_STANCE

Note: * p<0.05, r = Pearson's correlationTable 4 :

 4 Multiple linear regression model (backward) in YG, OG and YG+OG. The most predictive parameters are in bold.Note : β = magnitude of the slope of the relationship ; p = probability of whether or not β is significantly different from 0 (* indicates values that were statistically significant)

	Model		β	t	p
		Knee_CCI	-0.015	-1.763	0.092
		Ankle_CCI	0.138	3.360	0.003*
	YG	Ankle_CCI_stance	-0.126	-3.421	0.003*
		Knee_CCI_swing	0.014	2.073	0.051
		Ankle_CCI_swing	-0.064	-3.320	0.003*
	OG	Ankle_CCI	0.08	3.454	0.002*
		Ankle_CCI_swing	-0.039	-1.96	0.062
		Ankle_CCI	0.188	2.761	0.008*
		Knee_CCI_stance	0.031	2.137	0.038*
	YG + OG	Ankle_CCI_stance	-0.139	-2.117	0.04*
		Knee_CCI_swing	-0.030	-2.111	0.04*
		Ankle_CCI_swing	-0.069	-3.546	<0.001*


MBBS William I Haynes
email: william.haynes@inserm.fr

PhD Marie De Boutray

MD Thibault Kennel

MD Julien Boetto

Osteocutaneous radial forearm free Flap for anterior cranial base reconstruction: technical note

Keywords: Anterior skull base, anterior cranial fossa, free flap, radial forearm free flap, reconstructive surgery

The reconstruction of anterior skull base defects after carcinologic surgery is challenging. Large defects can require the use of autologous free tissue transfer. Currently, most reconstructions use soft-tissue flaps. We describe the use of an osteo-cutaneous radial forearm free flap to reconstruct a large defect secondary to a malignant paraganglioma extending into the anterior cranial fossa and both orbits. The surgical resection required endonasal and transcranial approaches. We reconstructed the defect with a free osteocutaneous radial forearm flap. We laid the bone flap across the defect, resting on the orbital roof on each side, and sutured the soft component to the edge of the dura. The pedicle was funnelled from the craniotomy to a

INTRODUCTION

The anterior skull base has a crucial role in isolating the intracranial intradural space from the sino-nasal tract and upper airways. Surgery for malignant tumours in this area can result in complex defects connecting the orbital, nasal and/or intracranial spaces. Consequently, tumour removal needs to be followed by a reconstruction of the anterior skull base. In addition, the opening of the dura mater requires this reconstruction to be watertight to avoid the leakage of cerebrospinal fluid (CSF) and subsequent complications (meningitis, brain abscesses, osteomyelitis). Thus, the reconstructive strategy is central to the planning of carcinologic surgery of the anterior skull base [START_REF] Wang | Free-Flap Reconstruction of Skull Base and Orbital Defects[END_REF][START_REF] Pusic | Microvascular reconstruction of the skull base: a clinical approach to surgical defect classification and flap selection[END_REF].

While small defects can be managed with local allogenic or xenogenic grafts, extensive defects concerning soft tissue, osseous and dural structures require alternative techniques such as vascularized tissue transplants. Defects deriving from an endoscopic endonasal approach are generally closed with mucosal vascularized flaps (e.g. nasoseptal flap) [START_REF] Hara | Cranial Base Repair Using Suturing Technique Combined with a Mucosal Flap for Cerebrospinal Fluid Leakage During Endoscopic Endonasal Surgery[END_REF][START_REF] Liu | Surgical nuances for nasoseptal flap reconstruction of cranial base defects with high-flow cerebrospinal fluid leaks after endoscopic skull base surgery[END_REF][START_REF] Hadad | A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle nasoseptal flap[END_REF]. However, these local flaps can be insufficient in the case of very large defects (frequent with transcranial approaches) or when the nasal mucosa is unavailable (e.g. tumour invasion). In the latter case, the use of a galea periosteum flap with or without a bone graft is possible [START_REF] Kryzanski | Low complication rates of cranial and craniofacial approaches to midline anterior skull base lesions[END_REF][START_REF] Noone | Pericranial flap for closure of paramedian anterior skull base defects[END_REF][START_REF] Jones | Reconstruction of the cranial base following tumour resection[END_REF]. In the former, vascularised flaps seem most appropriate [START_REF] Pusic | Microvascular reconstruction of the skull base: a clinical approach to surgical defect classification and flap selection[END_REF]. In case of recurrences, the use of a pedicled temporal muscle flap or a free vascular supplied tissue (mainly the radial forearm free flap (RFFF) or the anterolateral thigh flap (ALT)) is the last strategy.

Here, we report the surgical technique to reconstruct the defect from a suspected malignant paraganglioma of the anterior skull base with an osteocutaneous RFFF.

Haynes 4

CASE DESCRIPTION

A 66-year-old patient was referred to the emergency department with left exophthalmia and a rapid left visual impairment in the context of deterioration in general condition and weight loss.

Further interrogation revealed anosmia and cacosmia. The computerised tomography (CT-scan) at the emergency department showed a voluminous ethmoidal lesion which extended into both orbital cavities and upwards through the anterior skull base towards the frontal lobes. Magnetic resonance images (MRI) were in favour of an esthesioneuroblastoma or carcinoma (Figure1A-H). Biopsies were performed using an endonasal endoscopic approach. The diagnosis at this stage was uncertain with an aspecific morphology, and immunohistochemistry positive for neuroendocrine markers (chromogranine A and synaptophysin), PS100, SOX10 and CD56. The lesion had a high KI67 index (40%). The pathology team concluded to a possible malignant paraganglioma. Whole body CT-scan and Octreoscan did not show secondary lesions. The case was discussed at the head and neck oncology meeting, where we decided on a surgical resection followed by adjuvant radiotherapy. An osteocutaneous RFFF with anastomoses to the facial artery and veins was selected for the reconstruction of the defect.

SURGICAL TECHNIQUE

Tumour removal: The surgery was performed by a multidisciplinary surgical team (neurosurgeon, ENT-surgeon and maxillofacial surgeon). A lumbar drain was inserted. The first stage was the resection of the tumour through a combined endonasal endoscopic (Figure 2A) and transcranial open approach (Figure 2B), using standard techniques for anterior skull base tumour resection. The dura mater appeared pathological and was excised over approximately 19 cm 2 . Resection of the intra-orbital portions of the lesion was performed from the bifrontal craniotomy approach (Figure 2B).

Flap preparation: In the meantime, the maxillofacial surgeons prepared the left osteocutaneous RFFF with a long pedicle (one artery and two veins), using standard technique: 1. removal of a Haynes 5 5x4cm skin paddle at the distal part of the forearm, centered on the radial pedicle; 2. dissection of the pedicle along the radial periosteum over 6cm; 3 preparation of a 6cm radius sample (anterior cortical bone) stopping 4cm from the bone's distal extremity. 4.dissection of the radial pedicle up to the elbow and associated sampling of the cephalic vein for superficial venous drainage.

Receiving site preparation: A left cervicotomy was made to expose the facial artery and its satellite veins. A superior sulcal incision and small bone window in the anterior wall of the maxillary sinus was performed.

Flap positioning: The pedicle was funnelled from the craniotomy, through the maxillary sinus, the maxillectomy, and inside the cheek, to the cervicotomy using a Delbet drain folded on itself (FIGURE 2C). The micro-anastomoses were performed on the facial artery and two satellite veins, with good clinical and ultrasound permeability. The flap was inserted through the craniotomy with concomitant endoscopic guidance, soft component first (facing downwards).

The flap was sutured to the edge of the dural defect, from the craniotomy side, with endoscopic endonasal support (FIGURE 2D). The bone flap was then set to lie across the skull base defect, resting laterally part on each orbital roof (FIGURE 2E). The dural reconstruction was strengthened by a pericranial flap, biological fibrin glue and a dural substitute (Tachosil, TAKEDA, Tokyo, Japan) (FIGURE 2F). The craniotomy was closed using standard technique.

The radial donor site was closed using a transitional artificial matrix (INTEGRA, Integra Life Science Corporation, Plainsboro, New Jersey) before a secondary skin graft performed three weeks afterwards.

POSTOPERATIVE COURSE

The initial post-operative period was spent in intensive care to minimise intracranial pressure and airway pressure that could compromise the flap or its sutures. The lumbar drain was Haynes 6 removed 3 days after surgery. The post-operative MRI showed a centimetric residue in the right orbit, reason why the patient was reoperated using an endoscopic endonasal approach to achieve a total macroscopic removal of the tumour,. This tumour residue was accessed without displacing the flap. The total macroscopic resection was confirmed by the postoperative MRI, with a good flap position (Figure 3A-C).

The patient was extubated at day 7 after the first surgery. Unfortunately, a compressive pneumocephalus after a respiratory effort led to a deterioration of his neurological status and readmittance into the intensive care unit. An endoscopic endonasal examination of the flap revealed a rupture in the centre of the soft tissue flap, unlike the classic suture dehiscence for pharyngeal flaps. This required a thrid intervention to suture the defect from the transcranial approach. Local evolution was afterwards satisfactory, with good healing of the flap. The patient was discharged from hospital with no neurological deficit and a KPS score of 80, and received adjuvant radiotherapy without any other post-operative complication at 9 months.

DISCUSSION

In our institution, anterior skull base defects are usually patched with adipose tissue grafts, synthetic material or nasopharyngeal mucosal flaps. However, we deemed these techniques insufficient given the anticipated size of the soft and hard tissue defect (19 cm 2 , Figure 1E-G), and the risk of a secondary CSF leakage or brain prolapse. The extensive invasion of the nasal fossa made it impossible to use a nasal mucosal flap. In this context a free flap with a bony and soft tissue component seemed optimal to provide adequate support, airtightness and rapid closing. An additional requirement was to have a long vascular pedicle in order to make the vascular anastomoses onto cervical vessels. Indeed, the patient's temporal arteries were skinny and sclerotic, and thus inadequate as recipient vessels. The temporal muscles were hypotrophic and would not have been able to cover the entire defect.

Haynes 7

Consequently, we chose a combined endoscopic endonasal, and transcranial approach for the resection, followed by a reconstruction using an osteocutaneous RFFF. Additional support for this choice was a pre-existing loss of function of the left superior limb due to post-traumatic bicipital retraction.

The RFFF is one of the classic flaps to reconstruct anterior skull base defects, alongside the ALT and rectus abdomini flaps [START_REF] Wang | Free-Flap Reconstruction of Skull Base and Orbital Defects[END_REF][START_REF] Vargo | Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction[END_REF][START_REF] Ungar | Anterior Median Skull Base Reconstruction Using a Vascularized Free Flap: Rationale, Patient Selection and Outcome[END_REF]. Most often, the RFFF is used in its classic adipofascial form, with [START_REF] Jsfernandes | Evaluation of reconstructive techniques for anterior and middle skull base defects following tumor ablation[END_REF][START_REF] Biron | Radial forearm free flap with titanium mesh sandwich reconstruction in complex anterior skull base defects[END_REF][START_REF] Yano | The Flap Sandwich Technique for a Safe and Aesthetic Skull Base Reconstruction[END_REF] or without [START_REF] Wang | Free-Flap Reconstruction of Skull Base and Orbital Defects[END_REF][START_REF] Ungar | Anterior Median Skull Base Reconstruction Using a Vascularized Free Flap: Rationale, Patient Selection and Outcome[END_REF][START_REF] Llorente | Outcomes following Microvascular Free Tissue Transfer in Reconstructing Skull Base Defects[END_REF][START_REF] Duchateau | Reconstruction of the median anterior skull base with an intracranial free radial forearm flap after recurrent resection of Haynes 10 tumour[END_REF][START_REF] Aksu | Microvascular Tissue Transfers for Midfacial and Anterior Cranial Base Reconstruction[END_REF][START_REF] Pangrazi | Adipofascial Radial Forearm Free Flap for Anterior Skull Base Reconstruction in Complicated Forebrain Oncological Surgery[END_REF][START_REF] Schwartz | Use of the radial forearm microvascular free-flap graft for cranial base reconstruction[END_REF][START_REF] Weber | Role of free tissue transfer in skull base reconstruction[END_REF] support from a titanium mesh depending on the size of the defect. The size of the skull base defect in our patient dictated the use of a rigid support system, because a lack of support was at risk of a brain prolapse or suture dehiscence from gravity traction, as has been established for defects extending beyond the cribriform plate to the orbital roof [START_REF] Vargo | Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction[END_REF][START_REF] Yano | A new concept for classifying skull base defects for reconstructive surgery[END_REF]. However, using a titanium implant seemed problematic given the anticipated course of post-operative radiotherapy. Indeed, radiation therapy increases the number of wound dehiscence and decreases the quality of scar tissue, leading to exposure and chronic infection of foreign implants in this location [START_REF] Jsfernandes | Evaluation of reconstructive techniques for anterior and middle skull base defects following tumor ablation[END_REF][START_REF] Yano | The Flap Sandwich Technique for a Safe and Aesthetic Skull Base Reconstruction[END_REF][START_REF] Jeducic | The Versatile Extended Pericranial Flap for Closure of Skull Base Defects[END_REF]. Therefore, we wanted to use a free flap with an osseous component in order to provide a vascularised rigid support.

Amongst the standard flaps for anterior skull base reconstruction, only the radial forearm flap provided that opportunity. This radial forearm flap is also considered more versatile in its molding to the recipient cavity [START_REF] Besteiro | Free flap reconstruction of tumors involving the cranial base[END_REF].

Our main complication was a compressive pneumocephalus. A careful analysis of the radiologic images and an endoscopic endonasal examination of the flap revealed the appearance of a central defect in the soft tissue part, unlike classic wound dehiscence [START_REF] Weber | Role of free tissue transfer in skull base reconstruction[END_REF][START_REF] Neligan | Flap selection in cranial base reconstruction[END_REF].

It probably came from an inadvertent introduction of nasopharyngeal suction in intensive care. This complication highlights that the gastric tube should be inserted under direct endoscopic vision at the end of the procedure by the surgical team. Moreover, post-operative instructions should be carefully checked and written by the surgical team (No intranasal or pharyngeal procedures such as suction or tube replacement without endoscopic supervision, systematic Haynes 8 post-operative antibiotic therapy for 48h, supine position with a 30° head raise, no patient mobilization during the first two days, no anti-platelet therapy during the first days) Despite the fact that no CSF leak occurred during the post-operative course, the compressive pneumocephalus did not resolve spontaneously and led to a second, transcranial, intervention in order to suture the defect. This complication is standard in the literature [START_REF] Vargo | Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction[END_REF][START_REF] Chepeha | Radial Forearm Free Tissue Transfer Reduces Complications in Salvage Skull Base Surgery[END_REF],

where pneumocephalus and CSF leak are the most frequent, if still rare (Pneumocephalus: 2 for 69 patients in the literature [START_REF] Vargo | Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction[END_REF][START_REF] Llorente | Outcomes following Microvascular Free Tissue Transfer in Reconstructing Skull Base Defects[END_REF][START_REF] Schwartz | Use of the radial forearm microvascular free-flap graft for cranial base reconstruction[END_REF][START_REF] Chepeha | Radial Forearm Free Tissue Transfer Reduces Complications in Salvage Skull Base Surgery[END_REF][START_REF] Weber | Radial forearm free tissue transfer in the management of persistent cerebrospinal fluid leaks[END_REF]). Vascular failures remain exceptional. The occurrence of such complications is not correlated to the size of the defect [START_REF] Vargo | Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction[END_REF]. To prevent a CSF leak, we used a combined approach to ensure the watertightness of the reconstruction, adding a local pericranial flap and fibrin glue to the free flap [START_REF] Chepeha | Radial Forearm Free Tissue Transfer Reduces Complications in Salvage Skull Base Surgery[END_REF][START_REF] Yeo | Successful Reconstruction of Irradiated Anterior Skull Base Defect Using the Dual Flap Technique Involving Local Pericranial Flap and Radial Forearm Free Flap[END_REF][START_REF] Califano | Anterior cranial base reconstruction using free tissue transfer: changing trends[END_REF].

CONCLUSION

The use of an osteocutaneous radial forearm free flap needs to be considered for large bony defects of the skull base when no other option is available and when a rigid support system is needed, specifically for cases with potential post-operative radiation. However, this procedure adds significant morbidity to the surgical procedure, is associated with frequent post-operative complications, and should be performed by a multidisciplinary team.

Figure 1 :

 1 Figure 1: Pre-operative images of the lesion. (A) and (B): coronal T2 weighted sequences and (C) and (D) axial T1 weighted images after injection of gadolinium showing an extensive mass extending into the ethmoid, both orbits and the anterior cranial fossa. (E-H): CT scan images showing the bony defect and the defect surface calculation. (E) sagittal image along the orange plane in G, (F) axial image along the purple plane in E&G, and (G) coronal image along the blue plane in E, (H) same section as G with a bone window.

Figure 2 :

 2 Figure 2: Intraoperative images of the procedure. (A) Sub frontal endoscopic view of the posterior edge of the defect at the level of the planum sphenoidale and the left optic nerve penetration trough the optic canal. The orbit and the maxillary sinus are also visualized. MS: Maxillary sinus. ON: Optic nerve. Or: Orbit. PlSD: planum sphenoidale dura. (B) Superior view

Figure 3 :

 3 Figure 3: Post-operative images. (A) CT scan: 3D vascular reconstruction of the pedicle (white arrows) running from the facial vessels (bottom arrow) through the jugal space, and entering the

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.