Diagnostic properties of sensitivity changes in patients with maxillofacial fractures: a systematic review

Aim: Verify the accuracy of objective assessments compared to subjective tests in detecting changes in somatosensory perception in individuals affected by maxillofacial trauma. Methods: The review (PROSPERO n ° CRD42019125546) used the databases: MEDLINE, Cochrane, EMBASE, LILACS and other bibliographic resources. Prospective and retrospective studies that used objective and subjective methods of assessing facial sensitivity in maxillofacial fractures were included. There was no restriction on language or publication date. Risk of bias was assessed using the QUADAS-2. Data extraction and analysis were performed using a form developed for the study. Results: 21 studies were included. The clinical objective examination mainly includes assessments of: tactile sensitivity (95.24%) and nociceptive sensitivity (57.14%).The subjective assessment was based on the patient’s report, spontaneously (61.90%), guided by structured questionnaires (33.33%) and/or using scales (9.52%) to measure the degree of impairment. In risk of bias assessment,


Introduction
Trauma involving the skull and face are among the leading causes of morbidity and mortality, especially in the young population 1 . It is estimated that, globally, there are 7.5 million new cases of facial fractures with 1.8 million people living with their comorbidities 2 tional, and sports accidents 1,3 . In general, besides bone fractures, individuals have other injuries that can limit their functional capacity 3 .
Among these traumas, maxillofacial traumas, as well as their repair procedures, cause bone dislocations that can result in lesions in the peripheral nerve, which are responsible for facial sensation and perception. Thus, compression, sectioning, or stretching of the branches of the trigeminal nerve (V1, V2, and V3) and the nerves of the cervical plexus (C1 and C2) 4 may result in somatosensory changes that impact functionality, quality of life, and well-being of individuals. It may impair the functions of chewing, breathing, swallowing, sucking, and speaking 5 . The diagnosis of these changes is based on clinical and instrumental assessment, which considers the patient's report, the use of subjective questionnaires and quantitative neurosensory tests 5,6 . standard to determine the diagnosis, as it considers aspects of somatosensory perception more comprehensively. In it, individuals are submitted to a qualitative assessment of changes in sensory perception 5,6 . It considers parameters such as the presence or absence of change and the description of the change sensation 5 .
The objective assessment of sensory changes, represented by quantitative tests, is based into parameters that assess the patient's perception according to the different somatosensory modalities explored. It determines the profile of the detection of thermal, painful, touch, and proprioceptive stimuli, using instruments to identify perception and quantitative measurement of perceptual thresholds 6 . The objective assessment of facial sensitivity uses different techniques. They can be classified according to the type of fiber being stimulated. It may be nociceptive sensation) 6 .
Thus, the present study aims to conduct a systematic review of the literature to verify the accuracy of objective tests compared to subjective tests of facial sensitivity in detecting changes in somatosensory perception in individuals affected by maxillofacial trauma.

Materials and methods
This review was conducted based on the guidelines proposed by the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy reported follow-ing the PRISMA 7 recommendations and registered in PROSPERO under number CRD42019125546. Studies that used objective and subjective methods of assessing facial sensitivity in patients with maxillofacial trauma were included.

Criteria for including studies in this review
Types of studies Studies that used objective and subjective methods to assess facial sensitivity to detect peripheral somatosensory changes resulting from maxillofacial trauma were included. Prospective and retrospective studies were considered, provided they had both exams.

Participants
Studies with an assessment of patients with sensory changes in the peripheral nervous system originating from trauma or postoperative traumatic maxillofacial injuries. Participants underwent at least one of the modalities of objective assessment and at least one modality of subjective sensitivity assessment.

Index test
Changes in facial sensitivity must have been assessed objectively using quantitative tests or scales.

Reference standard
All patients must have been subjected to a subjective assessment of changes in sensory perception considering the following parameters: presence or absence of change or description of the sensation.

Target conditions
Changes in the peripheral sensory perception of the face.
The search was carried out in the MEDLINE, Cochrane, EMBASE, Scopus, and LILACS databases of articles published until March 2019, using the following terms and their correlates: "facial fractures," "zygomatic-orbital fracture," "mandibular fractures," and "somatosensory disorders." The search strategy for each database is available in Appendix 1. The search was complemented by the manual review of ProQuest, dissertations, theses, and reference lists. There was no restriction on language or publication date. The authors of the selected studies were contacted to

Data collection and analysis Selection of studies
The studies were initially analyzed by title and abstracts by two independent evaluators (KWS and ECR), including studies that met the eligibility criteria. A third evaluator (DCGMV) judged doubts regarding the inclusion to obtain consensus. Those eligible in this stage were read in full for a final decision on their inclusion. Those selected were registered on a form regarding inclusion or exclusion in the study at each step of the selection process, as well as the respective reasons.

Data extraction and management
for this analysis. First, data on the characteristics of the studies and their population were tabulated. Data were also extracted regarding the objective and subjective assessment methods used, as well as a description of the facial sensitivity assessment techniques performed.

Assessment of methodological quality
The studies were assessed regarding quality using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) 8 by two independent evaluators (KWS and ECR) and, in case of disagreement, a third evaluator (DCGMV) was consulted. Divided into four domains (patient selection, index test, reference standard, and flow and timing) the QUADAS-2 tool analyzes the methodological quality of the included studies, judging the risk of bias and applicability 8 .

Study selection
Out of the 7782 titles and abstracts analyzed from the search strategies, 135 met the eligibility criteria for reading the full manuscript. The authors of four articles 9-12 were contacted for more information on the methodology used in their studies, but they were excluded due to a lack of responses. Thus, for quality analysis, 21 studies 13-33 were included. The PRISMA flow diagram ( Figure 1) provides, according to the different phases of the systematic review, the registration of the identified, included and excluded studies, and the reasons for the exclusions.

Study characteristics
The characteristics of the studies included are described in Table 1. The studies were predominantly observational (85.71%), with a sample composed of individuals aged between 11 and 83 years, mostly males. Individuals from 11 years old were included when they presented the same type of intervention used in adults 34 . Despite the liter-vidual's age and sex 4 , the studies included in this review do not show differences in results in the assessments regarding the age and sex variables.
Among the causes of trauma, from the most recurring to the least common are: work accidents, and domestic accidents. The most frequent type of fracture was the middle third of the face (52.38%), involving the regions of the zygoma, maxilla, and orbit; mandibular fractures (38.10%), including the regions of the body, angle, branch, with open reduction (76.19%), with intra-oral (37.5%), extra-oral (37.5%), or combined to stabilize the fracture, and others also bring conservative treatment (14.28%) as an option for trauma management.    Figure 2 gathers the results of the quality analysis, which is described below.

Index Test
As for the risk of bias concerning the objective sensitivity test, 20 (95.24%) studies 13-21,23-33 had high risk, and 1 (4.76%) study 22 had low risk. The high rate of bias was due to the lack of blinding to subjective assessment by the examiner to perform the objective tests. The non-independent assessment may have distorted the execution or interpretation of the objective test. Also, there was no adequate description of the interpretation of the tests, without description of diagnostic thresholds. As for applicability, all studies were considered adequate, as they contemplate the review proposal.

Reference Standard
3 (14.29%) studies 22,29,33 had high risk and 18 (85.71%) studies 13-21,23-27,29-32 low risk. It was considered a low-risk criterion when the reference test was conducted according to the patient's report, without adaptation of the terms by the researchers. As for applicability, 19 (90.48%) studies 13-21,23-32 showed good applicability, and 2 (9.52%) studies 22,33 showed flaws in their applicability. In one of the studies, there was an interpretation of the perceptual responses by the authors 33 , which may distort the data obtained. In another, the assessment procedures were not adequately described 22 .  Flow and timing application interval between the reference test and the index test is not a variable that can interfere with the test results. All patients in the studies were submitted to the index and reference tests and included in the data analysis.

Assessments
The characteristics of the facial sensitivity assessment are described in Table 2.

Procedures and measurements
As for subjective assessment, it is always performed before the objective clinical examination, from touching the affected region, using materials, or the gloved hand. The subjective assessment was carried out based on the patient's report, spontaneously (61.90%) or guided by structured questionnaires (33.33%), or using scales created for the respective studies (9.52%). When assessments based on the reports are used, they could take place from unstructured conversations between the researcher and the patient or contain questions with yes or no answers. The questions were related to changes in sensitivity, numbness, burning and tingling sensation, thermal sensitivity, pain, functional changes (mainly during feeding, such as bites on the lips and escape of food from the oral cavity) and interference in the individual's daily life and quality of life. Some studies guide the comparison of sensory differences on the injured side with a region of the face with uninvolved innervation or a sensitive region of another part of the body. The use of scales sugrepresented visually by numbers, where zero corresponds to the absence of sensory complaints, and ten/hundred corresponds to severe sensory changes. For the subjective assessment to be reliable, the patient's report must be considered. For this, the evaluator must investigate the sensory complaint, asking the patient to explain and describe the altered sensation.
As for the objective assessment, studies advise that patients should be examined in a quiet room, with their eyes closed and in a comfortable position, preferably with a headrest. For each type of assessment, procedures are cited for carrying out the different measurements proposed. The studies bring the following measurements and procedures/techniques for assessing touch and nociceptive sensation: • Light touch/static light touch (61.90%) -assessment of detection of light touch (MARSTOCK nerve test, Marburg, Germany) 14 , (esthesiometer) 15 • Vibratory sensation (4.76%) -assessment of the detection of vibration and determination of the threshold of the disappearance of the stimulus (rapidly-adapting Vibrometer and 256-cps tuning fork 29 ; • Thermal discrimination (9.52%) -detection of temperature differences and determination of cold or hot stimuli. Cotton-tipped applicator saturated with a spray freeze of -50°C temperature 17 , and Ethyl chloride vapor was sprayed onto a spherical dental cotton bud (cold sensation) (diameter: 5 mm) 26 ; • Painful stimuli/pinprick (33.33%) -assessment of painful stimulus detection: 17 and 27-gauge needle 25 ; • Pain detection threshold (14.29%) -a gradual measurement of the detection of painful stimuli, of an ascending and descending character to determine the threshold (aid in the determination of hypoalgesia): Neurometer CPT (Neurotron Inc) 15 and Non-invasive electrocutaneous stimulation 19 ; • Sensory assessment/ sensory changes: • Thermography 25 (4.76%); • Assessment of nerve function latency and amplitude: Trigeminal somatosensory evoked potential 30 (4.76%).
• Details on how to conduct facial sensitivity assessment procedures described in the articles are listed in Appendix 2.
It was not possible to carry out a meta-analysis because the studies did not have of nomenclature, procedures, and equipment used in the sensitivity objective assessment procedures.

DISCUSSION
In this study, we found a varied number of procedures used to assess each sensory modality. Considering the high incidence of traumatic events that cover the facial region 1-3,14,16,17,25 and the occurrence of sensitivity changes resulting from these episodes 9,10,13-33 , it is necessary to have tests that assess these changes accurately.
Bearing in mind that the subjective procedures were considered as reference tests in questionnaires with questions aimed at guiding the patient's report and/or scales to patient are found, and the results are subject to inappropriate analyzes, distortion of the report, and inadequate diagnoses of the change. Also, there is qualitative heterogeneity in the scales used by the authors, who create scales for the punctual assessment using variations of the visual analog scale 14,16 . Based on this, what is effective in most studies is the realization of a questionnaire with structured questions 13,17,20,27,30,33 and the consideration of the patient's report as a marker of change 15,18,19,[21][22][23][24][25][26]28,29,31,32 to guide the use of objective tests.
The objective assessment of facial sensitivity must be seen as a complement to the subjective assessment, and it must involve a large number of procedures that sitivity (pain and temperature). Most of the articles used the touch assessment as being 13,15,16,20,21,25,26,30,32 or not 14,17,18,[22][23][24][27][28][29][30]33 associated with nociceptive assessment. About touch assessment, the method used in most studies is the detection of light touch stimulus, usually associated with the mechanical detection threshold, with cutaneous sensitivity thresholds. The method allows a gradual assessment of impairment and nervous recovery over time, in cases where there is a follow-up after the intervention 14,15,17,27,28,30 . The nociceptive assessment, on the other hand, - 13,15,[17][18][19]21,25,26,31,32 , eventually being accompanied by the sensation of temperature 17,26,31 . Regarding these modalities, when researching the sensation of pain, studies use the prick test 13,17,18,21,25,26,32 , and when researching the sensation of temperature, they determine if the patient differentiates cold and hot stimuli 17,26 . A limiting factor of these assessments refers tests, using heterogeneous equipment, which results in several protocols.

Chart 1. Questions to guide the patient's report
Questions to guide the patient's report: patient's report, since changes, even if slight, may be present despite the patient not reporting complaints. In the objective assessment, it is necessary to perform procedures of the touch and nociceptive modalities, to stimulate different receptors stimuli; and Meissner corpuscles and , which are involved in the transduction of nerve signals. The nociceptive modality (perception of pain and 4 . Thus, in the case of touch stimulation, it is recommended, due to the frequency of use in the articles included and the ease of application, the Light touch/static light touch test and, consequently, the Mechanical detection threshold, which can also be per-These tests will allow the stimulation of corpuscular receptors and stimulation of 4 . For nociceptive stimulation, the use of the prick test or thermal stimulation is recommended. However, it is emphasized that for proper stimulation and central transmission of painful stimuli, cutaneous thresholds must be between 23g and 51g, and if thermal stimulation is used, temperatures below 0°C or above 47°C 4 .
The tests are carried out with the patient with eyes closed, informing the applicator from which point the stimulation is perceived.
In conclusion, The instruments for investigating facial sensitivity used in the clinic in cases of maxillofacial trauma involve, for subjective assessment: the patient's report guided by structured questions; and for objective assessment: predominantly the evaluation of touch and nociceptive sensitivity, the latter also comprising thermal evaluation. From this, it is proposed a standardization to investigate changes in improvement of surgical techniques and to a safe return about the long-term results of the patient's sensory situation 14 .

Limitations
It was not possible to carry out a meta-analysis of this systematic review because tingency tables. Also, they showed high qualitative heterogeneity in the aspects of nomenclature, procedures, and equipment used in the sensitivity objective assessment procedures. For this, more studies should investigate the validity of the tests used in practice, to favor the use of effective diagnostic procedures, since the accuracy analysis of the tests was not possible due to the low availability of data in the studies.

Zygomatic Fractures[MeSH Terms]) OR Zygomatic bone fracture) OR Zygomatic Fracture) OR Zygomatico-orbital fracture) OR Zygoma Fractures) OR Zygomatic complex fractures) OR Blow-Out Fractures) OR Orbital Fractures[MeSH Terms]) OR Orbital Fractur*) OR Orbitozygomatic complex) OR Orbitozygomatic fractur*
6.641 Static light touch and mechanical detection threshold Examinations were started on the uninjured side on unilateral fractures. The filaments were applied perpendicular to the face in a descending order of magnitude to assess the threshold at which sensation disappeared. Procedure was repeated four times. Semmes-Weinstein monofilament (estesiometer) 11,13,23,24,25 Static light touch and mechanical detection threshold Monofilament is placed perpendicular to the skin and pressed until the filament begins to deform. The monofilament gently touched the skin and patients were asked about sensibility. Each measurement was repeated 3/4 times and filament was applied for 1.5 seconds, held for 1.5 seconds, and released for 1.5 seconds. If the patients were able to feel the monofilament minor caliper, testing ceased. If they were unable, the test followed until the patient could feel the monofilament touching the skin. Neurometer CPT (Neurotron Inc) 11 Current perception threshold (identify and evaluate nerve fiber damage -sense of pressure, temperature and pain)

Jaw Fracture[MeSH Terms]) OR Jaw Fractur*) OR Mandibular Fractures[MeSH Terms]) OR Mandibular Injuries[MeSH Terms]) OR Mandibular Injur*) OR Mandib* fractur*) OR Mandibular condyle fracture) OR Angle fracture) OR Multiple mandibular fractures) OR Mandibular trauma) OR
Fixing an electrode to the test site using the attached tape. Two different current intensities were passed from the electrode to the patient, who was then asked to say which current the patient believed was stronger. Minimum perceivable current was measured when an electrical stimulation at 2,000, 250, or 5 Hz was applied. The measurements were taken 3 times at each frequency. 0.7-mm-gauge needle (BD Precision GlideTM) 13 Static light touch (SLT) and brush directional stroke (BDS) SLT: The needle gently touched the skin, and the point that the patient feel sensibility was noted. BDS: It was applied in a 1-cm stroke in each point. The examiner decided if move it from right to left or from left to right in each interval, and the patient was asked about the direction of the movement. A needle held the between thumb and index finger 13 Pinprick discrimination The intensity was applied sufficiently so the patient would feel pain or to draw as small drop of blood at the puncture side. Cotton-tipped applicator saturated with a spray freeze of −50 C temperature 13

Thermal discrimination
The patients were asked about cold or normal/not cold feeling immediately upon application of each respective applicator.
Non-invasive electrocutaneous stimulation 15 Pain detection threshold (PDT) Is performed applying noninvasive electrocutaneous stimulation of the dry skin in the region by active 2 mm diame e elec de a d a i e elec de fi ed b a ie ha d h mb a d f efi ge . PDT a a e ed using ascending method of limits. The stimulating current was gradually increased by fixed rate until the subject indicated first pain sensation. Three PDTs were evaluated. Pressure-Specified Sensory Device (PSSD) 18,25 One-point static discrimination, two-point static discrimination and moving-touch discrimination The small blue PSSD is hand held by the person doing the testing, and the two small metal probes are touched gently to the skin area being tested. The cutaneous pressure thresholds for one-point static and moving-touch discrimination were recorded in grams per square millimeter, and the pressures required for two-point static and moving-touch discrimination were recorded as the pressure for a given interprong distance (in millimeters). Cotton roll 22 light touch sensation Not described 27 gauge needle 22 Pain test Not described Dental cotton swab 22 Directional test Not described Thermography 22 Sensory changes Each subject was asked not to eat, drink, or smoke for an hour before the examination. All cosmetics were washed off and the skin surface allowed to dry in the air. Hair was held off the face with hair grips. No sources of radiation were allowed in this environment and sunlight was excluded. All air convection sources were minimized and only two operators were allowed into the room while the examination was in progress. Once stabilized, baseline measurements were recorded for the frontal and left and right profiles of each patient in a sitting position at a focal distance of one metre perpendicular to the region of interest. MacKinnon-Dellon Disk-Crimínator® (North Coast Medicai, Inc.) or Aesthesiometer 2 point 23,25,26 static two-point discrimination and moving two-point discrimination Series with either ascending or descending increments with a successively longer or shorter pin distance in the device, during which the subject reported on a present or absent sensation of two separate points of stimulation. A test series was terminated after a response reversal, i.e. when a particular type of response (positive/negative) on a stimulus increment was followed by two responses of the opposite type on successive increments. Each of the tests consisted of four alternating series.
-The initial two point testing distance was 24 mm, proceeding in stages down to 2mm. The stimulus was randomly alternated between one and two points. If the patient correctly perceived the changes, the distance was decreased. This testing pattern was continued until the patient answered incorrectly, at which time the observer returned to the next higher distance. In the two-point limit, two of three correct answers were required for this distance to be chosen as the end-point.
Ethyl chloride vapour was sprayed onto a spherical dental cotton bud (diameter: 5 mm) 23

Cold sensation
After ice crystals had been formed, the bud was placed on the test site for at most 1 s. The drop in temperature varied within a range from 22 to 24~ at the interface between cotton bud and skin.
Vibrometer 26 vibratory threshold Using a fixed-frequency (120Hz) variable amplitude instrument. The vibrating portion of the instrument was applied to the test area, and the voltage was gradually increased until the patient was first able to perceive vibration. The threshold is converted into microns (amplitude) of displacement. Trigeminal somatosensory evoked potential (TSEP) 27 Sensory assessment The recording electrode was placed contralateral to the side of stimulation 2cm posterior to C3 and C4 at the coronal suture. A reference electrode was placed at mid frontal site and the array was earthed by ground electrode placed around neck. The electrical stimulator provided stimuli at a rate of 2 sec and each stimulus lasted for 0.1 sec. The stimulus intensity was adjusted by gradual increasing up to the level where minimal lower eye lid twitch could be observed. In order to achieve pure sensory stimulation with maximum activation of the nerve fibers and minimum electrical artifact, the Infra-Orbital Nerve (ION) stimulation was performed at the ION foramen using the stimulator electrode of TSEP. TSEP was at least repeated twice to confirm the reproducibility and reliability of the response;