INTRODUCTION
Far-out syndrome (FOS), initially identified by Wiltse et al. [1] in 1984, involves the compression of the L5 nerve between the transverse process of L5 and the ala of the sacrum. Because the nerve compression occurs outside the intervertebral foramen, specifically at or beyond the nerve root exit points, the location is often referred to as the extraforaminal or the "far lateral" area, at the L5–S1 spine level (i.e., the lumbosacral junction/transition area). FOS can result from degenerative disc disease/herniation, or stenosis, and it can be associated with Bertolotti syndrome, a congenital structural anomaly involving partial or complete fusion of the lowest lumbar vertebra to the sacrum [2,3]. The presence of an abnormal articulation can also contribute to similar symptoms [4].
This condition typically manifests as L5 spinal nerve radiculopathy, and because it is uncommon diagnosis is frequently delayed, and treatment can be challenging [5]. The prevalence of FOS, though not thoroughly documented, is believed to contribute to a considerable percentage of lower back pain cases, particularly in aging populations where degenerative changes can exacerbate foraminal and extraforaminal stenosis [6].
Diagnosing FOS is complicated by overlapping symptoms with other lumbosacral disorders, and the complex anatomical structures at the L5–S1 junction [7]. Advanced radiographic techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance myelography (MRM), as well as electrophysiological studies have been are proposed as effective diagnostic approaches. However, their actual sensitivity and accuracy still need to be rigorously evaluated and compared [8-10].
Treatment of FOS has evolved markedly over the past 4 decades [11-14]. The traditional Wiltse approach (open decompression performed far laterally that may include removal of the lower half of the pedicle and the entire transverse process) has evolved into innovative techniques such as microscopic and full endoscopic decompressive surgeries, including an ultra-minimally invasive endoscopic approach, and these developments appear to improve patient outcomes [11,13,14]. However, there remains ongoing debate in the medical community as to which procedure provides the most benefit, a question that is complicated by variability in patient anatomy, disease characteristics, and outcomes [12]. Nevertheless, surgical decompression is considered the definitive treatment for most patients [11].
Given the complexities and limitations of previous research, alongside the evolving understanding of FOS and its treatments, a comprehensive review is essential. The purpose of this report is to critically assess the diagnostic approaches, challenges, evolution of treatments, and current treatment modalities of FOS. Our aim is to compile key evidence and propose directions for future research, with the goals of enhancing understanding and treatments of FOS, thereby optimizing diagnostic and therapeutic strategies to improve the quality of life for individuals affected by this condition.
METHOD
1. Literature Search and Selection
We conducted a comprehensive literature search for articles about FOS. The search was performed using PubMed and Cochrane CENTRAL database, and identified all English language articles published from the inception of the database until May 7, 2024. The search terms used were tailored to encompass these issues: FOS disease overview, diagnostic approaches including CT and MRI, and electromyography, and treatments from open decompression, and newer methods such as endoscopic techniques and navigation-assisted surgery.
2. Inclusion and Exclusion Criteria
Only peer-reviewed articles were considered for inclusion. Conference abstracts, editorials, and other non-peer-reviewed materials were excluded to maintain the quality and reliability of the information reviewed.
3. Review Process
All records retrieved were initially screened by title and abstract for relevance with respect to the review objectives. The full texts of potentially relevant articles were then independently assessed for eligibility by multiple coauthors of this article. Discrepancies between reviewers regarding article inclusion were resolved through discussion and consensus.
RESULTS
The search strategy employed specific keywords to retrieve relevant records. The search terms and the number of records initially retrieved were: "Far-out syndrome" identified 29 articles, "far lateral disc herniation" identified 63 articles, "Bertolotti's syndrome" identified 57 articles, "L5 extraforaminal entrapment" identified 22 articles, and "L5 extraforaminal stenosis" identified 59 articles. After screening of the identified articles, a total of 32 articles were included in this review.
1. Diagnosis
Diagnosis of FOS can be divided into radiographic methods (MRI, CT), and electrophysiologic methods. Of these methods, 3-dimentional (3D) MRM appears to have the best sensitivity and specificity for diagnosing FOS [9,15].
Kojima et al. [9] examined the results of 270 patients that received MRM. Swelling of the dorsal root ganglion (DRG) was seen in patients with intraforaminal and extraforaminal stenosis, and a DRG diameter width ≥ 6.5 mm was shown to be diagnostic for foraminal stenosis. A lumbosacral transitional vertebra is when the last lumbar vertebra has elongation of the transverse process, and exhibits varying degrees of fusion to the first sacral segment, and the reported prevalence is 4% to 30% [15]. The condition is consistent with FOS and Bertolotti syndrome. Byun et al. [15] showed that indentation or swelling of the L5 nerve root on 3D MRM was diagnostic of symptomatic extraforaminal stenosis. In another study, Kim et al. [16] reported that 3D Proset MR images findings were significantly associated with symptoms and surgical results in patients with foraminal and extraforaminal stenosis at L5–S1. Notably, 2-dimensional (2D) MRI has been shown to not be reliable for diagnosing extraforaminal stenosis in the lumbosacral transition: Takahashi et al. [17] showed that more than half of extraforaminal stenosis was missed with 2D MRI.
Moon et al. [18] examined the role of CT in diagnosing FOS. Their results showed that asymmetric enlargement of the anterior primary division (APD) of the L5 spinal root on CT scan is associated with foraminal or extraforaminal entrapment of the L5 spinal root at the lumbosacral junction. Studies comparing MRI and CT for diagnosis of FOS have given somewhat varied results, although discrepancies may be due to different radiographic methods and patient selection. For example, Lee et al. [10] reported that CT and MRM exhibited similar sensitivity with respect to APD swelling on CT and DRG swelling on MRM. On the other hand, although Kim et al. [19] reported agreement between 3T MRM and CT discography (disco-CT) for diagnosing far later disc herniation, they concluded that 3T MRM is an appropriate diagnostic method compared to disco-CT.
Some electrophysiological methods have been shown to be very useful for diagnosing L5 nerve root entrapment. The sensory nerve action potential (SNAP) is decreased in amplitude when there is entrapment at or distal to the DRG [11]. Ando et al. [8] showed measurement of SNAP had a sensitivity of 91% and specificity of 86% for diagnosis of L5–S1 foraminal stenosis. In another study using electrophysiological parameters, Iwasaki et al. [20] showed that decreased distal motor latency potential were significantly associated with extraforaminal stenosis at L5–S1.
Additionally, we noted that some studies highlight the utility of diagnostic transforaminal epidural steroid injections (TESIs) in accurately identifying the specific nerve root causing pain, guiding treatment strategies, and aiding patient selection for invasive surgical interventions. This technique is discussed in relation to lumbar radiculopathy, facet arthropathy, and discogenic pain [21,22]. The procedure involves administering an anesthetic or corticosteroid into the suspected nerve root, allowing clinicians to determine if the nerve is the source of pain based on the patient's response. Lewandrowski [22] found that diagnostic TESI effectively identifies patients who would benefit from endoscopic decompression surgery, with a high accuracy in correctly identifying both true and noncases. Despite these evidences, no literature has specifically focused on their use for diagnosing or differentiating FOS, limiting our further discussion in the present review.
2. Treatment Approaches
Treatments for FOS have evolved since the condition was first described. We will review treatments beginning with open surgical decompression, and continue chronologically to the latest innovations consisting of intraoperative CT navigation.
1) Open surgical decompression
Gokyar and Tonga [23] reported the results of 132 patients treated with an intertransverse extraforaminal approach. The mean visual analogue scale (VAS) pain scored decreased from 8 preoperatively to 2 at 1 month after surgery, and with a mean follow-up of 43 months the long-term satisfaction rate according to MacNab criteria were 74% excellent-good, 20% moderate, and 6% poor. There were no serious complications; however, the authors cautioned that because of the anatomy of the region surgeons should become proficient in the method by training with an experienced surgeon before they use the method on their own. Though only a single case report, Haines et al. [24] reported good results treating FOS with indirect decompression with anterior column support via lateral lumbar interbody fusion. Notably, the authors pointed out that disc fragment excision was not necessary.
Two studies were identified in which a microendoscope or a surgical microscope were used. Matsumoto et al. [13] reported good results using a microendoscope or a surgical microscope to partially resect the sacral ala, the L-5 transverse process, and the L5–S1 facet joint along the L-5 spinal nerve. Twenty-eight patients were included, and all patients reported relief of leg pain immediately after surgery. The mean Japanese Orthopaedic Association (JOA) low-back pain score was 11 before surgery and 24 at the final follow-up examination. No serious complications were reported. Siu and Lin [14] reported a modified direct tubular lumbar microdiscectomy in which the retractor was docked caudally directly over the disc space with the aid of a microscope. The study consisted of 19 patients, and significant improvements in the Oswestry Disability Index (ODI), VAS leg pain score, VAS back pain score, and 36-item Short Form health survey (SF-36) physical functioning and SF-36 bodily pain scores were noted.
2) Minimally invasive decompression (microscopy, endoscopy)
The first report by Sasaki et al. [25] published in 2014 described mid-term surgical outcomes of microscopic posterior decompression for FOS. Although the reported only included 8 patients, in all patients FOS was confirmed by MRI or CT. In brief, a 4- to 5-cm incision was made just above the far-out area, the far-out area was exposed using Wilte intermuscular approach, and the nerve root was decompressed with partial resection of the transverse process and the sacral ala and removal of the iliolumbar ligament. All patients reported reduced pain immediately after surgery, and at follow-up there were improvements in JOA and VAS leg pain scores. In a similar report, Ikuta et al. [12] retrospectively reviewed the records of 25 patients who underwent minimally invasive transtubular endoscopy for decompression of L5 lumbosacral extraforaminal lesions. All patients had a follow-up of at least 1 year, and JOA score improved significantly from a mean of 14 at baseline to 23 at the 1-year follow-up. Notably, all patients resumed their normal activities within 1 month after surgery.
In 2019, Ren et al. [26] reported result of percutaneous endoscopic lumbar discectomy (PELD), minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) combined with contralateral translaminar screw, and MIS-TLIF combined with bilateral pedicle screws. The data of 74 middle-aged and elderly patients were analyzed, and while there were differences in the operation time and costs of the 3 methods, all methods provided similar results for the treatment of FOS. Full endoscopic spine surgery (FESS) and unilateral biportal endoscopy (UBE) have also proven effective for FOS. Specifically, FESS enables targeted decompression through a small incision with minimal tissue disruption, offering faster recovery and significant pain relief. Compared to PELD and MIS-TLIF, FESS is particularly advantageous in patients with complex anatomy, effectively addressing extraforaminal stenosis at the lumbosacral junction while minimizing surgical trauma [27,28].
In 2023, Connolly et al. [29] compared outcomes and costs following open vs. endoscopic far lateral discectomy. There were 92 patients that received open surgery, and 52 that received endoscopic surgery. Similar outcomes were observed with the 2 methods; however, patients who underwent an open procedure had longer hospital stays, longer surgery time, longer duration of follow-up, and less favorable discharge dispositions. Laskay et al. [30] reported a novel minimally invasive far lateral lumbar discectomy technique that minimized the amount of bone drilling necessary for nerve root decompression, and thus reducing the level of postoperative pain and the risk of spinal instability. The study retrospectively reviewed the records of 48 patients who underwent the procedure, and 43 patients had improvement in their symptoms; 6 patients had immediate symptom resolution after surgery and 27 complete resolution an average of 2.6 months after surgery.
UBE is a recently developed, novel minimally invasive technique for the treatment of lumbar spinal stenosis and lumbar disc herniations [31]. Uniportal endoscopy has been successfully used prior to the development of UBE for lumbar discectomy and decompressive laminectomy; however, UBE provides some advantages. UBE is a percutaneous full endoscopic technique that is performed through 2 separate small surgical wounds on either side of the spinous process to achieve precise decompression with reduced soft tissue damage. The procedure is performed with continuous high-pressure normal saline irrigation and a high-definition arthroscope, which allows for very precise decompression in a clear and magnified surgical field, leading to shorter recovery times and fewer complications compared to traditional open surgeries [31]. While there are many articles describing UBE for spinal decompression, our search only identified 4 articles related to FOS (Table 1), primarily technical notes and small case series. Park et al. [32] provided a detailed description of their use of UBE for the treatment of FOS, and mentioned they have achieved good results for the treatment of FOS after much experience performing UBE for other types of spinal decompression. Similarly, Ha et al. [5] described their method of performing UBE for FOS, and reported a good outcome in the case of a 44-year-old male with symptoms of right leg pain and numbness. MRI preoperatively showed extraforaminal stenosis due to disc herniation at L5–S1. The procedure was performed without complications, and leg pain had improved by 1 week after surgery.
Heo et al. [27] reported a series of 16 patients with FOS treated with UBE. The mean leg VAS pain score and ODI were significantly improved after surgery and notably concomitant extraforaminal disc herniation was significantly associated with a favorable outcome. Similarly, Park et al. [33] reported the results of 35 patients who underwent UBE for L5–S1 extraforaminal stenosis between March 2018 and February 2019. There were significant decreases in VAS back pain score, VAS leg pain score, and ODI postoperatively as compared to the preoperative values. No serious complications were observed.
While minimally invasive decompression techniques have shown significant success in treating FOS, the choice between decompression alone and decompression combined with fixation remains a subject of debate. Studies have demonstrated that decompression alone can effectively relieve symptoms in carefully selected patients with stable spines, reducing surgical time and associated risks [13,34]. In contrast, decompression with fixation may provide better outcomes for patients with instability or severe degenerative changes, but it is associated with longer recovery times and increased costs.
3) Intraoperative CT navigational assistance
Radiographic navigational assistance has been developed for many different surgical procedures, and navigational assistance using CT is the most recent innovation for the treatment of FOS. Ran et al. [35] described the outcomes of percutaneous lumbar transforaminal endoscopic discectomy with intraoperative CT navigation for the treatment of FOS. Thirty patients who received the procedure between 2016 and 2020 were included in the analysis. The procedure was performed without complications in all patients, and postoperatively there were significant improvements in VAS leg pain score, ODI, JOA score, and Eg-5D-5 L value. Stavrinou et al. [36] reported similar results of 10 patients who underwent extraforaminal decompression of the L5 nerve root using CT navigation for transmuscular transtubular decompression. In a unique report, Soliman et al. [37] combined CT navigation and electrophysiological monitoring for far later lumbar microdiscectomy. The electrophysiological monitoring allowed precise 3-dimensional anatomical localization and identification of the exiting nerve. Although the report only included 5 patients, all patients achieved good outcomes.
3. Strengths and Limitations
A strength of this study is that it is the first to comprehensively review diagnostic and treatment methods of FOS, a relatively rare condition that can be difficult to treat due to the complex anatomy. It is limited by that the evidence on recently applied interventions, such as UBE and navigation, is relatively scarce. A further limitation is that it is a literature review, not a systematic review and meta-analysis of published studies to quantitatively assess outcomes between different diagnostic tools or treatments. Lastly, we did not include 'grey literature,' such as conference abstracts, in this review. It is possible that these materials could have provided valuable insights but were not reviewed.
CONCLUSIONS
FOS is a somewhat challenging condition to diagnose and treat. Our results suggest that MRI is the best method for diagnosing FOS. While open surgery is effective for treating FOS, recently developed minimally invasive methods offer good outcomes with fewer complications and faster recovery. Microscopic or endoscopic minimally invasive decompression procedures currently appear to be the method of choice for the treatment of FOS. New methods, such as UBE and CT-assisted navigation, require further evaluation regarding outcomes and cost-effectiveness. Although we are expecting positive results, there is currently little literature describing their usefulness.
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