Sciatic Nerve Variants and the Piriformis Muscle: A Systematic Review and Meta-Analysis

The present systematic review and meta-analysis provides a comprehensive assessment of the sciatic nerve (SN) variants relative to the piriformis muscle (PM) and compares those variants’ prevalence among different geographical populations with respect to gender and laterality. A database search was conducted to identify cadaveric studies pertinent to SN variants relative to the PM. A total of 44 articles were included. The typical morphological pattern (type A, with the SN passing undivided below the PM) was found to be the most common variant, with 90% pooled prevalence. SN variants were more common among East Asians, with a 31% pooled prevalence of total variants. No significant differences were established with respect to gender and laterality. In greater than 10% of the population, the SN coursed through or above piriformis. Patients’ epidemiological characteristics may predispose them to certain variants. The common peroneal nerve (CPN) is more susceptible to injury during a total hip arthroplasty or a hip arthroscopy where anomalies are encountered. As anatomical variants are commonly associated with piriformis syndrome, they should always be considered during diagnosis and treatment.


Introduction And Background
The sciatic nerve (SN), the longest and widest nerve of the human body, is formed from the L4-S3 ventral roots and normally exits the pelvis, via a single trunk, through the great sciatic foramen below the piriformis muscle (PM). The SN courses in the posterior thigh compartment and divides into the tibial and the common peroneal trunk at the popliteal fossa. The tibial and common peroneal nerves (TN and CPN) are surrounded by a common epineural sheath into the SN main trunk. However, tibial and peroneal fascicular groups are separated by a connective tissue, known as the Compton-Cruveilheir septum [1]. The SN innervates the muscles of the posterior thigh compartment and all the lower leg and foot compartments.
The separate (autonomous) development of the SN tibial and peroneal divisions could explain the source of SN variants during embryonic development [2]. The possible relationships between the SN and PM were first categorized by Beaton and Anson [3] into the following six morphological types ( Figure 1): Type A: typical pattern with the SN passing below the PM, undivided Type B: the CPN exits through the PM and TN exits below the PM Type C: the CPN exits above the PM and TN and below the PM Type D: the SN exits through the PM, as a single trunk Type E: the CPN exits above the PM and TN through the PM, and Type F: the SN passes undivided above the PM Clinical awareness of SN variants is of high importance, as they constitute a common etiology of piriformis syndrome (a condition characterized by the SN entrapment from PM). Common symptoms include buttock pain and sciatica, which are aggravated by sitting [4]. An awareness of SN variants is crucial when performing a total hip arthroplasty, particularly via a posterior approach, SN blockade, or PM imagingguided injections. Accurate knowledge of the typical SN anatomy and its variants could prevent a plethora of complications during procedures in the area and could aid in the diagnosis of various pathologies.
The current systematic review and meta-analysis of the literature provides an evidence-based assessment of SN variants in relation to the PM, by highlighting the variants' prevalence among different populations, 1 2 3 4 4 taking into account gender and laterality as well.

Search Strategy
The current systematic review and meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [5]. A literature search of the databases PubMed, Scopus, SciELO, and Web of Science was conducted from their inception up to May 2020 to find studies about SN variants relative to the PM. The search terms used were as follows: "sciatic nerve", "nervus ischiadicus", "Ischiadic Nerve", "Ischiatic Nerve", "anatomy", "variation" and "anomalies" with "AND" and "OR" as Boolean terms.

Inclusion Criteria and Study Selection
Only cadaveric studies were included. Case reports, letters to the editors, conference abstracts, and articles involving clinical or imaging studies were excluded. In compliance with the search strategy, two independent investigators screened and assessed the retrieved articles for eligibility. Any duplicates or obviously irrelevant studies were excluded. If eligibility could not be confirmed by the title or the abstract, the full text was retrieved. Reference lists of the related articles were hand-searched for any additional eligible studies in a further effort not to miss out on any relevant publications. Any disagreement regarding eligibility was resolved by a discussion between the two investigators and, if necessary, a third investigator was consulted.

Data Extraction
A dedicated data extraction form was developed for recording all relevant details, involving publication details [author(s) and year of publication], sample size, SN variants relative to the PM, gender, and laterality when recorded. In cases of nonexisting data, the authors were contacted for further clarification if possible. The classification system used was the one introduced by Beaton and Anson [3]. We exclusively analyzed our data according to types A-D, as E and F types were described as hypothetical by Beaton and Anson and most of the subsequent studies did not subcategorize their groups according to them.

Statistical Analysis
Collected data were statistically analyzed using MetaXL version 5.3 (EpiGear International, Queensland, Australia). Heterogeneity assessment was performed by using the I2 statistic and x 2 test. I 2 statistic of >50% and/or a p-value of <0.1 for Cochran's Q were deemed indicators of significant heterogeneity among studies.
Using the random-effects model, the weighted average and confidence intervals (95% CI) were calculated.

Results and discussion
From the initial search, a total of 5,520 records were retrieved. Manual searching of reference lists yielded 21 additional articles. After exclusion of duplicates (211), articles not in English, and those irrelevant to the objectives of the present systematic review (5,210), 120 publications were retrieved in full text. Forty-four articles were deemed suitable for inclusion. The literature review selection process is summarized in Figure  2.

Study Characteristics
Study characteristics of the included articles are summarized in Table 1. A total of 44 studies (8,257 samples) were included in the systematic review and meta-analysis [3,. Included studies were published from 1893 up to 2016, were written in the English language (or at least included an abstract written in English), and involved a population origin of wide geographical distribution. Geographic subgroup analysis was based on population characteristics, the geographic location, and the number of studies derived from each country.

Discussion
The present systematic review and meta-analysis provides a comprehensive and evidence-based assessment of SN variants in relation to PM. Although typical (type A) morphological pattern was the most common one (90% prevalence), its presence widely varied (64.5-100%) among the selected studies. The variant type B had 8% prevalence, followed by types C and D with 2% and 1% prevalence, respectively. Type B had a significantly higher prevalence in East Asia (24% prevalence) compared to Europe (9%), the USA (4%), and Africa (3%). Concerning gender impact, females appeared to have a higher, but not significant, prevalence of SN variants compared to males. Type B variant was twice as prevalent in females (13% prevalence) compared to males (6%). This finding could be explained by the SN's close proximity to female reproductive organs. Thus, patients' epidemiological characteristics may predispose them to certain variants. Analysis based on laterality revealed symmetry in typical SN anatomy (62% prevalence), as well as in variant patterns' occurrence (16% prevalence).
An awareness of SN variants is essential to avoid iatrogenic nerve injury [41][42][43][44]48]. The two most common mechanisms of nerve injury, intraoperatively, are stretching and direct injury (compression or laceration) [41][42][43]. The SN is subject to traction forces during total hip arthroplasty, especially when performed via a posterior approach [29,30]. Therefore, SN variants relative to the PM increase the intraoperative risk of injury, either due to improper Hohmann retractor placement or by direct injury when a PM tenotomy is required [45]. The CPN is more susceptible to injury by traction when the variant types B and C are encountered, either during hip dislocation or when the lengthening of the extremity occurs [45]. The SN may also be injured after traumatic posterior hip dislocation [45], and in such cases, the coexistence of variants in the area increases the risk of injury.
Hip arthroscopy and specifically the posterolateral portal placement (as close as 11 mm to the SN) may injure the SN due to its close proximity. Type B variant may put the SN at an increased risk of injury during hip arthroscopy. Moreover, knowledge of SN variants is necessary when the SN blockade is conducted. There is a high probability of anesthetizing only the CPN or the TN when an SN high bifurcation is present, as in types B and C [39].
The piriformis syndrome is characterized by sciatic clinical manifestations caused by extrapelvic SN compression at the hip. An incidence of 6% of piriformis syndrome has been reported in patients suffering from sciatica [23,34]. Typical clinical manifestations include buttock pain with or without radiation to the ipsilateral posterior thigh and the occasional extension below the knee [4]. Pain is exacerbated by flexion, adduction, and internal rotation of the hip. Aberrations of the SN course may contribute to its compression.
Pećina has suggested that type B variant (CPN course through the PM) is more commonly associated with piriformis syndrome, and especially when the CPN passes between PM tendinous parts [16]. The clinician should consider the SN variants when treating a patient with sciatica and especially when dealing intraoperatively with a piriformis syndrome [24,26].
Multiple imaging modalities are available for SN variant identification. Among them, MRI remains the gold standard. Magnetic resonance neurography can reliably and effectively identify the presence of an SN variant or even SN compression in piriformis syndrome [32,33].

Study limitations
This study has some limitations. Many studies we looked into had modified the classification system proposed by Beaton and Anson or had included variants that were stated as "non-classified". High heterogeneity was observed among the studies, which could not be explained by geographic or gender differences alone.

Conclusions
Based on our findings, type A (a single SN trunk coursing below the PM) is the most common morphological type and is considered as the typical pattern. SN variants are fairly common, particularly among East Asians. Clinicians should always bear in mind those variants when performing hip interventions, nerve blockade in the area, and during diagnosis and treatment of piriformis syndrome. Future clinical investigations are necessary to further evaluate SN atypical course clinical implications in relation to the PM.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.