Evaluation of Femoral Anteversion and Femoral Neck-Shaft Angles in Cerebral Palsy and a Review of the Literature

Mehmet ALBAYRAK; Gazi ZORER

doi:10.4274/nkmj.galenos.2022.40427

ABSTRACT

Aim:

Cerebral palsy (CP) is a chronic, sensorimotor disease as a result of damage in the brain that has not completed its development. In this study, we evaluated femoral anteversion (FA) and femoral neck-shaft (FNS) angles in pediatric patients with CP and studied whether there was a difference between the healthy population and patient group according to involvement subtypes or Gross Motor Functional Classification System (GMFCS).

Materials and Methods:

Thirty patients (20 females, 10 males; mean age 10 years 8 months; range 4 to 14 years) diagnosed with spastic CP, who had undergone surgery, were evaluated retrospectively. Of thirty patients, eleven were quadriplegic, ten were diplegic and nine were hemiplegic. Fifty-one hips of 30 patients were investigated in the study. According to the GMFCS, there were nine patients at level II, eight at level III, six at level IV, and seven at level V. X-rays and computed tomograhy images of the patient and control group were evaluated by radiological files of the hospital. FA and FNS angles of all patients were measured and the obtained values were compared.

Results:

The FNS angle (p<0.05) and the FA angle (p<0.05) were significantly larger in the patient group than in the control group. The FNS angle (p<0.05) and the FA angle (p<0.05) were significantly larger in the quadriplegic group than in the diplegic and hemiplegic groups. The FNS angle (p<0.05) and FA angle (p<0.05) were significantly larger in GMFCS level IV/V patients than in GMFCS level II/III patients.

Conclusion:

FA and FNS angles are increased in CP compared to normal population due to the spasticity in some muscles acting on the hip and the resulting imbalance in muscle strength. In quadriplegics, angles are significantly higher compared to diplegics and hemiplegics, GMFCS level IV/V had higher angle values compared to GMFCS II/III.

Keywords:

Cerebral palsy, femoral anteversion angle, femoral neck-shaft angle

INTRODUCTION

Cerebral palsy (CP) is proposed as a group of permanent disorders of the development of movement and posture, causing activity limitation, whereas the disturbances in fetal or infant brain are non-progressive. In CP, the spinal cord and muscles are structurally and biochemically normal so called all of the pathology is attributed to brain. The abnormality of the brain results in motor impairment¹.

The prevalence of CP is 2 in 1000 live births and the most common type of involvement is spastic diplegia constituting 80% of the patients². The lesion in the brain creates problems in muscle tone and coordination. Over time, secondary disorders in the form of joint contractures develop due to unbalanced distribution of muscle strength in the musculoskeletal system^1-3.

Spasticity, which is an increase in the physiological tension of the muscle to passive movements, is caused by lesions in the cerebral cortex. Although the lesion in the brain does not show progression, adaptive changes secondary to spasticity occur over time in the musculoskeletal system⁴.

Although muscle spasticity and contractures need physical therapy or surgical treatments like tendon lenghtenings and contracture releases for treatment, femoral anteversion (FA) and femur neck-shaft angle (FNS) increment of which are commonly seen in CP patients, leading to joint luxations or gait imbalance need purely surgical corrections for treatment^1,5. Being aware of these angular changes, which can be detected by various measurement methods and corrected surgically, is extremely important in terms of the course of disease and determining the degree of planned surgical corrections to prevent hip instability and as well as hip joint luxation⁴.

The Gross Motor Functional Classification System (GMFCS) is the most reliable classification system of CP patients according to capacity of mobility and independent movement and have been described for various bands⁶.

The aim of this retrospective study is to evaluate FA and FNS angles of CP patients by comparing a healthy control group and also comparing the same angles within the patient group according to GMFCS levels.

GİRİŞ

Serebral palsi (SP), aktivite sınırlamasına neden olan hareket ve postür gelişimindeki bir grup kalıcı bozukluklar olarak tanımlanırken, fetal veya bebek beynindeki rahatsızlıklar ilerleyici değildir. SP’de omurilik ve kaslar yapısal ve biyokimyasal olarak normaldir, yani patolojinin tamamı beyin ile ilişkilidir. Beynin anormalliği motor bozulmaya neden olur¹.

SP prevalansı 1000 canlı doğumda 2’dir ve en sık görülen tutulum tipi hastaların %80’ini oluşturan spastik diplejidir². Beyindeki lezyon, kas tonusu ve koordinasyonunda problemler yaratır. Zamanla kas-iskelet sisteminde kas gücünün dengesiz dağılımına bağlı olarak eklem kontraktürleri şeklinde sekonder bozukluklar gelişir^1-3.

Pasif hareketlere karşı kasın fizyolojik gerginliğinin artması olan spastisite, serebral korteksteki lezyonlardan kaynaklanır. Beyindeki lezyon ilerleme göstermese de kas-iskelet sisteminde zamanla spastisiteye bağlı adaptif değişiklikler meydana gelir⁴.

Kas spastisitesi ve kontraktürlerinin tedavisi için fizik tedavi veya cerrahi tedaviler gerekmesine rağmen, SP hastalarında yaygın olarak görülen femoral anteversiyon (FA) ve femur boyun şaft açısı (FNS) artışları eklem çıkıklarına veya yürüme dengesizliğine yol açar ve tedavi için tamamen cerrahi düzeltmeler gerekir^1,5. Çeşitli ölçüm yöntemleriyle saptanabilen ve cerrahi olarak düzeltilebilen bu açısal değişikliklerin farkında olmak, hastalığın seyri ve kalça instabilitesi ve kalça eklemi çıkıklarının önlenmesi için planlanan cerrahi düzeltmelerin derecesinin belirlenmesi açısından son derece önemlidir⁴.

Kaba Motor Fonksiyonel Sınıflandırma Sistemi (GMFCS), SP hastalarının mobilite ve bağımsız hareket kapasitesine göre en güvenilir sınıflandırma sistemidir ve çeşitli gruplar için tanımlanmıştır⁶.

Bu retrospektif çalışmanın amacı, SP hastalarının FA ve FNS açılarını sağlıklı bir kontrol grubu ile karşılaştırarak ve aynı açıları hasta grubu içinde GMFCS seviyelerine göre karşılaştırarak değerlendirmektir.

MATERIALS AND METHODS

Files of sixty patients (32 females, 28 males; mean age 11 years 2 months; range 4 to 22 years) with a diagnosis of spastic CP who had already been operated for surgical correction of FA and FNS angles between February 2000 and July 2004 were retrospectively evaluated after the approval of the Tekirdağ Namık Kemal University of Ethics Committee (protocol number: 2021.115.04.10, date: 27.04.2021).

In order to make the evaluation as objective as possible, patients who had no visual and cooperative problems, no significant mental retardation, and no extrapyramidal system involvement were chosen. Furthermore, patients using medications affecting motor functions (e.g. baclofen, botulinum toxin, and benzodiazepine) were not included in the study. At the end, thirty patients (20 females, 10 males; mean age 10 years 8 months; range 4 to 14 years), who met the criteria and had both X-rays and computed tomography (CT) images that had already been taken as a matter of fact before their surgeries to plan the correction amount, were included in the study. A control group was formed with 30 age-matched patients (18 females, 12 males; mean age 10 years 3 months; range 4 to 16 years) having no history of CP and being admitted to the emergency department of the hospital because of polytrauma and having undergone AP pelvic X-ray and whole body CT during evaluation. Their pelvic X-rays and CT views were investigated through radiological files of the hospital.

According to involvement subtypes, eleven were quadriplegic, ten were diplegic and nine were hemiplegic. While both hips of diplegic and quadriplegic patients were included in the study, only the involved hips of the hemiplegic patients were added. As a sum, 51 hips of 30 patients were investigated in the study.

According to the GMFCS, there were nine patients at level II, eight at level III, six atlevel IV, and seven at level V.

Twenty two of the patients in the study group were born before 36^th gestational week, 4 had prenatal complications, and the other 4 patients had complications in 3 months and further after birth. So called prematurity was the most seen etiologic factor in the patient group.

On the AP pelvic X-rays, a straight line was drawn from the midline of the femoral neck by accepting the midline according to two reference points. The femoral anatomical axis was also drawn and the angle at the medial side of the two lines was measured with a goniometer, providing the FNS angle (Figure 1)⁷.

In order to measure the FA angle, the longitudinal axis of the femoral neck was drawn in the scan where the femoral neck appeared longest in the hip (Figure 2) in CT scans. Then, the bicondylar axis was drawn in the femoral condylar region (Figure 3). The angle of the bicondylar axis with the longitudinal axis of the femoral neck was measured⁸. This angle provided the FA value.

Data related to the study and control groups are given in Table 1 and Table 2, respectively.

For all comparisons, only the involved sides of hemiplegic patients were included in the study group (11 quadriplegic patients-22 hips, 10 diplegic patients-20 hips, 9 hemiplegic patients-9 hips; a total of 30 patients-51 hips).

Patients in the study and control groups were compared using the parameters listed below.

1. Homogeneity of variables in the study and control groups,

2. Age distribution between the study and control groups,

3. FNS and FA angle values between the study and control groups,

4. Comparison of FNS and FA angle values in the study group based on CP involvement types,

5. Comparison of FNS and FA angle values in the study group based on GMFCS types.

Statistical Analysis

To evaluate the number of the patients in the study group, G*power programme was used. The sample size was evaluated by large effect size (d=0.8) and the mean error level of α=0.05 and at the end of analysis, it was evident that at least 52 people had to be involved in the study, 26 for the study group and another 26 for the control group. For this reason, the sample size of the research was determined to be at least 52. Within the scope of data analysis, independent samples t-test, which is one of the parametric tests, was used while comparing the experimental and control groups according to variables. Before analyzing, Q-Q plot and P-P plots were examined for the assumption of normality, and it was seen that the normality assumption was met. For the assumption of homogeneity of variances, the Levene’s test value was examined and it was found that the variances were not homogeneous.

For this reason, the results of the Wald test were used to calculate the t value.

The analyses were carried out in the PASW statistics 18 (2009; SPSS Inc. Chicago, IL, ABD) program and the level of significance was determined as α=0.05.

RESULTS

All variables in the study and control groups were found to be homogeneous (p<0.05). There was no significant difference between the study and control groups in terms of age distribution (p>0.05). The FNS angle (p<0.05) and the FA angle (p<0.05) were significantly larger in the patient group than in the control group. The FNS angle (p<0.05) and the FA angle (p<0.05) were significantly larger in the quadriplegic group than in the diplegic and hemiplegic groups. The FNS angle (p<0.05) and FA angle (p<0.05) were significantly larger in the GMFCS level IV/V patients than in the GMFCS level II/III patients.

All of the variables and standard deviations are seen in Table 3.

DISCUSSION

Adduction, flexion and internal rotation deformities are the most commonly seen deformities in the hips of CP patients¹. The type of deformity in CP patients varies depending on the type of involvement as well as the severity and distribution of spasticity. Since spasticity is more severe in quadriplegic and diplegic patients compared to hemiplegic patients, deformities may also be more severe in these patients⁹. In our study, we also revealed that quadriplegic ones had more bony deformities than the others in the patient group.

At birth, every infant, even CP patients, have a FA angle of about 40 degrees¹⁰. During the development process, in a healthy child, FA and its angle gradually decrease in accordance with the Wolf’s law due to the extensive tension of the muscle forces to the proximal femur and the plasticity of the skeletal system in the child until the age of 16 years, and decrease to the physiological level of 15 degrees in adults¹⁰. Whereas in CP patients, FA angle remains the same and high as a value. The main reason for the increase in FA angle in patients with CP is increased spasticity in the iliopsoas muscle⁷. Another responsible factor is the partially or completely diminished strength of the gluteal muscles adhering to the apophysis of the trochanter major^11-14. In our study, we also concluded that FA angle was higher in the patient group compared to the healthy control group.

Although FNS angles of healthy children and children with CP are similar in the first years of life, the angles of children with CP barely change or even increase while the angles of healthy children decrease as they progress towards adult age¹⁰. Miller et al.⁹ declared that increase of FNS angle was associated with the shortening of the femoral neck due to an increase in FA. We also declared that FNS angles were higher in the study group compared to the control group.

FA and FA angle can be measured with a numerous methods including physical examination^5,15,16, biplanar radiology X-ray^17,18, fluoroscopy¹⁰, ultrasonography⁹, 2 or 3-dimensional CT^15,19-21, and magnetic resonance imaging²².

There are some methodological interactions for the evaluation or validation of FA angle. Chung et al.²³ revealed that physical examination combined with AP pelvic X-ray was enough for FA angle evaluation and this diminished the need for CT and excess radiation.

Miller et al.²⁴ revealed that ultrasonography of the hip performed in internal rotation position gave better results than CT. In an experimental investigation on femora models, Riccio et al.²⁵ found that 3D reconstruction of CT was necessary and gave more accurate results about FA angles independent of FNS angles.

Davids et al.²¹ revealed that the most important was the position of the patient during CT scanning. If the position is inaccurate then even 3D reconstruction will give false results vice versa 2D CT is enough for correct results.

In case of FNS angles, Kay et al.²⁶ revealed in a cadaveric study that positioning of the extremity in 15 degrees of internal rotation would give the most accurate information about FNS angle.

Davids et al.¹⁵ reported that trochanteric prominence angle test and 3D CT scans gave similar increasing of FA and FNS angle results in CP patients so there was no need for CT to evaluate these patients.

In contrast to all these, Scorcelletti et al.⁸ have revealed that there is not a reliable evaluation method for FA and FNS angles and CT gives high doses of radiation to patients so must not be used.

There is still a debate in the literature about the accurate measurement technique of FA and FNS in CP patients and a consensus could not been achieved yet. In our study, we used 2 dimensional CT for the measurement of FA angles and plain pelvic X-rays for FNS angle measurements.

Yamaguchi et al.¹⁴ revealed that in non-ambulatory patients, FNS and FA were found in higher values than in ambulatory patients.

Bobroff et al.¹⁰ stated that FA angle was higher in ambulatory CP patients compared to non-ambulatory ones but in contrast, FNS was smaller as an angle value in ambulatory ones compared to non-ambulatories, and they concluded this with fluoroscopy method.

In a biplanar radiographic study, Laplaza and Root¹⁷concluded that there was not any difference between ambulatory and non-ambulatory CP patients in means of FA angles but they also reported that FNS angle was higher in non-ambulatory ones.

Gose et al.²⁷ found with 3D CT that FA angle change was controversial but FNS angle was higher in non-ambulatory ones and they also revealed that in quadriplegic and GMFCS IV-V levels, FNS and FA angles were higher compared to diplegics and GMFCS II-III respectively.

Massaad et al.²⁸ revealed that FA and FNS angle increased in CP patients compared to a healthy control group and they concluded this with low dose biplanar X-ray technique.

Robin et al.⁵ concluded that FA angles were higher in GMFCS I-II patients than in healthy control group but were lower than GMFCS III to V group and they also concluded that FNS angles increased as GMFCS level increased.

Laplaza et al.⁷ reported that GMCSF level was the main factor affecting FA and FNS angles so called when level increased the angles also increased.

In our study, we found that FA and FNS angles were both higher in non-ambulatory group of CP patients compared to ambulatory ones by means as GMFCS level increased both of the angles also increased and we also concluded that FA and FNS angles were higher in quadriplegics compared to diplegics and hemiplegics.

Study Limitations

This article has some limitations. The age variability in a large range is a limitation. Another limitation is that measurement of FNS angle on AP X-ray alone is not sufficient, these measurements cause errors especially in the hips with increased FA. Actually, this measurement on the AP X-ray gives the projected angle, while the true angle is obtained from the intersection points of the projected FNS angle in AP pelvic and lateral hip X-rays taken at 90 degrees of hip flexion and 20 degrees of hip abduction on corrected tables²⁹.

TARTIŞMA

Addüksiyon, fleksiyon ve iç rotasyon deformiteleri SP’li hastaların kalçalarında en sık görülen deformitelerdir¹. SP hastalarında deformitenin tipi tutulumun tipine ve de spastisitenin şiddetine ve dağılımına göre değişir. Kuadriplejik ve diplejik hastalarda spastisite hemiplejik hastalara göre daha şiddetli olduğu için bu hastalarda deformiteler daha şiddetli olabilir⁹. Biz de çalışmamızda hasta grubunda kuadriplejik olanların diğerlerine göre daha fazla kemik deformitesi olduğunu ortaya koyduk.

Doğumda her bebek, hatta SP hastaları bile yaklaşık 40 derecelik bir FA açısına sahiptir¹⁰. Gelişim sürecinde sağlıklı bir çocukta FA ve açısı, Wolf yasasına göre, çocukta 16 yaşına kadar proksimal femura kas kuvvetlerinin aşırı gerilmesi ve iskelet sisteminin plastisitesi nedeniyle giderek azalır ve yetişkinlerde 15 dereceye kadar fizyolojik seviyeye düşer¹⁰. SP’li hastalarda ise FA açısı aynı kalır veya bir değer olarak yükselir. SP’li hastalarda FA açısındaki artışın temel nedeni iliopsoas kasındaki artmış spastisitedir⁷. Diğer bir sorumlu faktör, trokanter majör apofizine yapışan gluteal kasların kısmen veya tamamen azalmış gücüdür^11-14. Çalışmamızda da hasta grubunda FA açısının sağlıklı kontrol grubuna göre daha yüksek olduğu sonucuna vardık.

Sağlıklı çocukların ve SP’li çocukların FNS açılarının yaşamın ilk yıllarında benzer olmasına rağmen, SP’li çocukların açıları çok az değişir, hatta artarken, sağlıklı çocukların açıları erişkin yaşa doğru ilerledikçe azalır¹⁰. Miller ve ark.⁹ FNS açısındaki artışın, FA’daki artışa bağlı olarak femur boynunun kısalması ile ilişkili olduğunu bildirmişlerdir. Ayrıca çalışma grubunda kontrol grubuna göre FNS açılarının daha yüksek olduğunu belirledik.

FA ve FA açısı, fizik muayene^5,15,16, biplanar radyoloji röntgeni^17,18, floroskopi¹⁰, ultrasonografi⁹, 2 veya 3 boyutlu bilgisayarlı tomografi (BT)^15,19-21 ve manyetik rezonans görüntüleme²² gibi birçok yöntemle ölçülebilir.

FA açısının değerlendirilmesi veya doğrulanması için bazı metodolojik etkileşimler vardır. Chung ve ark.²³ AP pelvik röntgeni ile birlikte fizik muayenenin FA açısı değerlendirmesi için yeterli olduğunu ve bunun BT ihtiyacını ve aşırı radyasyon maruziyetini azalttığını ortaya koydu.

Miller ve ark.²⁴ iç rotasyon pozisyonunda yapılan kalça ultrasonografisinin BT’den daha iyi sonuçlar verdiğini ortaya koymuştur. Femur modelleri üzerine deneysel bir araştırmada, Riccio ve ark.²⁵ BT’nin 3D rekonstrüksiyonunun gerekli olduğunu ve FNS açılarından bağımsız olarak FA açıları hakkında daha doğru sonuçlar verdiğini ortaya koymuşlardır.

Davids ve ark.²¹ en önemlisinin hastanın BT taraması sırasındaki pozisyonu olduğunu belirtmişlerdir. Eğer pozisyon yanlışsa, 3D rekonstrüksiyon bile yanlış sonuçlar verecektir, ya da 2D BT ise doğru sonuçlar için yeterlidir.

FNS açıları durumunda, Kay ve ark.²⁶ bir kadavra çalışmasında, ekstremitenin 15 derecelik iç rotasyonda konumlandırılmasının FNS açısı hakkında en doğru bilgiyi vereceğini ortaya koymuşlardır.

Davids ve ark.¹⁵ trokanterik prominans açısı testi ve 3D BT taramalarının SP hastalarında FA ve FNS açı sonuçlarında benzer artış sağladığını ve bu nedenle bu hastaları değerlendirmek için BT’ye gerek olmadığını bildirmişlerdir.

Tüm bunların aksine, Scorcelletti ve ark.⁸ FA ve FNS açıları için güvenilir bir değerlendirme yöntemi olmadığını ve BT’nin hastalara yüksek dozda radyasyon verdiğini ve kullanılmaması gerektiğini ortaya koymuşlardır.

SP’li hastalarda FA ve FNS’nin doğru ölçüm tekniği konusunda literatürde halen bir tartışma bulunmaktadır ve henüz bir fikir birliğine varılamamıştır. Çalışmamızda FA açılarının ölçümü için 2 boyutlu BT, FNS açı ölçümleri için düz pelvik X ışınları kullanıldı.

Yamaguchi¹⁴ FNS ve FA’nın ambulatuvar olmayan hastalarda ambulatuvar hastalara göre daha yüksek değerlerde bulunduğunu ortaya koymuşlardır.

Bobroff ve ark.¹⁰ ambulatuvar SP’li hastalarda FA açısının ambulatuvar olmayanlara göre daha yüksek olduğunu, ancak bunun aksine ambulatuvar olanlarda FNS’nin açı değeri olarak ambulatuvar olmayanlara göre daha küçük olduğunu belirtmişler ve bunu floroskopi yöntemi ile sonuçlandırmışlardır.

Biplanar bir radyografik çalışmada, Laplaza ve Root¹⁷ FA açıları açısından ambulatuvar ve ambulatuvar olmayan SP’li hastalar arasında fark olmadığı sonucuna varmışlardır, ancak FNS açısının ambulatuvar olmayanlarda daha yüksek olduğunu da bildirmişlerdir.

Gose ve ark.²⁷ 3D BT ile FA açı değişikliğinin tartışmalı olduğunu ancak ambulatuvar olmayanlarda FNS açısının daha yüksek olduğunu bulmuşlar ve ayrıca kuadriplejik ve GMFCS IV-V seviyelerinde, FNS ve FA açılarının sırasıyla diplejiklere ve GMFCS II-III’e göre daha yüksek olduğunu ortaya koymuşlardır.

Massaad ve ark.²⁸ sağlıklı kontrol grubuna göre SP’li hastalarda FA ve FNS açısının arttığını ortaya koymuşlar ve bu sonuca düşük doz biplanar X-ray tekniği ile varmışlardır.

Robin ve ark.⁵ GMFCS I-II hastalarında FA açılarının sağlıklı kontrol grubuna göre daha yüksek, ancak GMFCS III ila V grubuna göre daha düşük olduğu sonucuna varmışlardır ve ayrıca GMFCS seviyesi arttıkça FNS açılarının arttığını ortaya koymuşlardır.

Laplaza ve ark.⁷ GMCSF düzeyinin FA ve FNS açılarını etkileyen ana faktör olduğunu, yani seviye arttıkça açıların da arttığını bildirmişlerdir.

Çalışmamızda, GMFCS düzeyi arttıkça her iki açının da arttığını tespit ederek, ambulatuvar olmayan SP hastalarında hem FA hem de FNS açılarının ambulatuvar hastalara göre daha yüksek olduğunu saptadık ve ayrıca diplejikler ve hemiplejiklere kıyasla kuadriplejiklerde FA ve FNS açılarının daha yüksek olduğu sonucuna ulaştık.

Çalışmanın Kısıtlılıkları

Bu makalenin bazı kısıtlılıkları vardır. Geniş bir aralıktaki yaş değişkenliği bir kısıtlılıktır. Diğer bir kısıtlılık ise AP röntgeninde FNS açısının ölçülmesinin tek başına yeterli olmaması, bu ölçümlerin özellikle FA artmış kalçalarda hatalara neden olmasıdır. Aslında AP röntgeni üzerindeki bu ölçüm, öngörülen açıyı verirken, 90 derece kalça fleksiyonu ve 20 derecelik kalça abdüksiyonunda çekilen AP pelvik ve lateral kalça röntgenlerinde öngörülen FNS açısının kesişme noktalarından gerçek açı elde edilir²⁹.

CONCLUSION

CP patients are coming in front of orthopedic surgeons with increasing in number by the development and wellness of newborn intensive care units so called they care premature newborns much better compared to past. As the number of CP patients increases, their evaluation and surgeries also increase both in number and in importance.

FA and FNS angles are important for well-being of the hips of CP patients. FA and FNS angles increase in this patient group and this will bring their hips in danger for instability and luxation. If there is any suspicion of a change in FA and FNS angles in the clinical examinations performed during the periodic visits of patients with CP, these angles should be examined. If FA increase causing apparent toeing-in gait pattern in patients or FA and FNS increase showing tendency of subluxation is detected, soft tissue and osseous surgical interventions should not be avoided in order to prevent further hip pathologies. The progression of coxa valga is more critical and grave in quadriplegics and GMFCS IV/V group.

Ethics

Ethics Committee Approval: The study were approved by the Tekirdağ Namık Kemal University of Local Ethics Committee (protocol number: 2021.115.04.10, date: 27.04.2021).

Informed Consent: Retrospective study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: G.Z., Concept: M.A., G.Z., Design: M.A., Data Collection or Processing: M.A., Analysis or Interpretation: M.A., Literature Search: M.A., Writing: M.A.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.

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