Adjacent Segment Disease Associated with Klippel-Feil Syndrome: A New Classification System with Corresponding Therapeutic Options

Klippel-Feil Syndrome (KFS) is a relatively rare disorder that was initially described by Maurice Klippel and Andre Feil in 1912.¹ Its prevalence has not been studied in a large series; however, it may occur in every 40,000 newborns with a slight predominance of females.^{1, 2, 3, 4} It occurs due to the failure or incomplete and inappropriate segmentation of somites that occurs during embryogenesis between 3 to 8 gestational weeks. In other words, there is a failure of normal segmentation or formation of the cervical somites.^{1, 5, 6}

The vast majority of KFS cases are sporadic, but there are several genetic types of KFS.^{7, 8, 9} KFS and ocular anomalies associated with Wildervanck syndrome may have X-linked inheritance.¹⁰ Congenital fusion of the cervical vertebrae may be a possible risk factor for the occurrence of degenerative cervical myelopathy (DCM).⁶

Conventionally, KFS is described as having the clinical triad of a short neck, low posterior hairline, and restriction of neck motion, which may be attributed to the fusion of cervical vertebrae.^1,3,5 However, many patients do not typically display the conventional triad of KFS.

The vertebral column is comprised of fibrocartilagenous intervertebral discs and ossified vertebral units. Congenital malformations of the vertebral column involve kyphosis, scoliosis, spina bifida, and KFS.¹¹ Klippel-Feil Syndrome can occur in a wide variety of phenotypes, its impact on the quality of life depends on the number of segmentary involvement which accompanies the deformity. ^{1, 3, 4}

In general, cervical spinal deformity increases with the increasing number of segments involved and these patients are more likely to present with concomitant congenital problems.⁶ Patients with KFS are under risk for acceleration of degenerative changes and hypermobility in segments adjacent to the spinal fusion.⁶

The relationship between KFS and degenerative cervical myelopathy (DCM) has not been well defined, despite reports of segmental hypermobility and predisposition to KFS patients' degenerative changes in the cervical region. Since the patients with spinal fusion may be at risk for adjacent segment disease, there is a need for investigation of KFS patients for the tendency to develop neurological sequelae due to the degeneration of the neighboring segment.⁴

In this study, we aimed to share our experience with 22 patients who were treated for adjacent segment disease (ASD) associated with KFS. We describe the clinical and radiological findings together with our treatment outcomes and we propose “Yilmaz-Yucesoy Classification System” as a novel grading system for KFS with ASD based on our data along with a brief review of current literature.

A total of 22 KFS patients (10 males, 12 females) with ASD met the eligibility criteria for the current study. The average age of our series was 56.09 (range 41 to 67) years. The anatomical locations of the lesions, clinical data of the patients, and treatment modalities are presented in Table 1.

The combined imaging modalities were employed to confirm the diagnosis of KFS and patients were initially graded according to the Samartzis Classification System (Table 2).¹² The distribution of the patients according to the Samartzis Classification was as follows: 18 patients (81.80 %) were Type 1, 3 cases (13.63%) were Type 2, and 1 patient (4.54 %) was Type 3.

The operative technique was selected concerning our novel “Yilmaz-Yucesoy Classification System” (Table 3). Accordingly, 1 patient (4.54 %) had non-surgical treatment (Yilmaz-Yucesoy Grade 1), 6 patients (27.27 %) received anterior cervical arthroplasty (Yilmaz-Yucesoy Grade 2) (Figure 1), 7 cases (31.81 %) received anterior cervical discectomy or corpectomy and fusion with cervical cage and plate (Yilmaz-Yucesoy Grade 3) (Figure 2). These latter patients did not have cervical spinal instability but had spinal stenosis at more than 1 level. They needed at least 2 level discectomy or corpectomy due to the ossification of posterior longitudinal ligament or osteophyte formation. Eight patients (36.36 %) with cervical spinal instability were performed anterior cervical discectomy or corpectomy and fusion with cervical cage and plate (Yilmaz-Yucesoy Grade 4) (Figure 3).

Figure 1A, B, C.X-ray, computerized tomography, and magnetic resonance imaging views of a Yilmaz-Yucesoy Classification System Grade 2 patient.

Figure 2.Computerized tomography, and magnetic resonance imaging views of a Yilmaz-Yucesoy Classification System Grade 3 patient who underwent anterior cervical discectomy and fusion with cervical cage and plate.

Figure 3.Computerized tomography scans of a Yilmaz-Yucesoy Classification System Grade 4 patient who underwent anterior cervical discectomy and fusion with cervical cage and plate.

Spinal cord intensity changes were found in seventeen (77.27 %) patients in the MRI. The preoperative and postoperative condition of the patients was assessed with the modified Japanese Orthopaedic Association Scale (mJOA).¹³ Preoperative average mJOA scores were 14.5±1.4 and postoperative third month mJOA scores 16.2±1.6. In our series, no perioperative mortality was reported and no complications occurred during operations and early postoperative period. The mean follow-up period was 40 months (range: 12 months to 12 years). A satisfactory degree of recovery was observed in all patients.

This study was performed to present our clinical experience with a series of KFS patients with concomitant ASD. Based on our clinical, diagnostic, and therapeutic data, we propose a new classification system that can be used to recognize the patients accurately and to tailor the appropriate treatment strategy in order to optimize the treatment outcomes.

Evaluation of KFS patients necessitates a complete and detailed physical examination. This disorder can be accompanied by various pathologies such as Sprengel’s Deformity, Duane Syndrome, renal agenesis, Wildervanck Syndrome, renal, vascular, and cardiac malformations. Notably, nearly half of KFS patients may suffer from concurrent scoliosis and atlantoaxial instability.¹ The radiological assessment of the cervical spine in KFS patients consists of plain radiographs, CT, and MRI. Plain radiographs on flexion and extension may exhibit details of spinal stability and mobility.¹ A wasp-waist sign may be present on radiographs and flexion/extension X-ray may illustrate the status of spinal stability and movement in a clinically stable patient.¹ No specific etiologic factors have yet been identified for KFS.⁴

Possible multisystemic involvement and syndromic presentation must be remembered in KFS patients with ASD. Therefore, a multidisciplinary approach and close collaboration between various branches are crucial in the evaluation of these patients and particularly candidates for surgical treatment.¹ Patients with persistent neurological pain, myelopathy, abrupt and recent onset of muscular weakness, and documented spinal instability are possible candidates for surgical treatment. In addition to spinal instability, deformities are important during the decision making for surgical treatment. Cervical fusion may occur from either anterior or posterior approaches subsequent to evaluation. Anterior approach can involve either cervical fusion or corpectomy with the placement of synthetic or bone grafts. Cervical total disc arthroplasty can be considered as a surgical alternative that may be beneficial for the quality of life and prevention of ASD especially in the adult population with degenerative changes. On the other hand, posterior approaches can be employed including decompression and fusion by means of different instrumentation procedures. Selected cases with severe deformities may be treated with a combined anterior-posterior approach. Healing osteomyelitis or discitis, previous fusion without instrumentation, ankylosing spondylitis, and juvenile idiopathic arthritis must be considered in the differential diagnosis.^{6, 14}

Congenital fusion of cervical vertebrae, such as KFS, is a possible risk factor for the development of degenerative cervical myelopathy (DCM).⁶ Klippel-Feil Syndrome occurs due to the failure or incomplete segmentation of somites early during the gestational development of the spinal column.^{6, 15}

KFS can present in a wide phenotype spectrum and its impact on the quality of life is associated with the severity of the condition, accompanying deformity, and the possibility for compression of spinal cord and myelopathy. Typically, the cervical spinal deformity increases in parallel with the number of levels involved.⁶ Congenital defects that may influence visceral, musculoskeletal, otolaryngological, and neurological systems may be observed in these patients.³ It has been postulated that KFS patients are vulnerable to accelerated degenerative changes and hypermobility at segments adjacent to the spinal fusion.⁶

Patients with KFS are prone to the development of cervical joint degeneration. Even though the mechanism for this association is still obscure, the increased biomechanical stress on nonfused segments may be contributory.⁸

The exclusion of patients with idiopathic cervical fusion (ICF) of vertebrae who did not demonstrate the typical “wasp-waist sign” associated with KFS was based on the assumption that none of these subjects displayed any signs of degenerative changes at the fused level. It must be remembered that ICF may constitute a distinct clinical entity rather than simply representing a broader spectrum of phenotypes associated with KFS.⁶ In addition, ICF, which refers to congenital fusions that do not exhibit any shreds of evidence for degenerative fusion, have not been previously reported.

The relationship between KFS and DCM has not been completely elucidated but there are reports indicating segmental hypermobility and a tendency for degenerative changes in the cervical spine of patients with KFS.^{1, 3} The recognition that patients with the surgical fusion of vertebrae may be at risk for ASD further supports that patients with KFS should be investigated for an increased risk to develop neurologic sequelae linked with degenerative changes.⁴

Limited mobility, usually due to bone and soft tissue restrictions associated with KFS, may lead to excessive movement and shear stress in unfused segments that may appear clinically as degenerative disc disease later in life.⁵ 

Operative management strategies have included arthrodesis and stabilization of the cervical spine. Other surgical treatment options have been attempted, including cervical disc replacement, in order to restore physiological movement and take action on further loss of motion and development of adjacent segment disease.⁵ The relatively high prevalence of KFS in surgical series and their more obvious MRI findings remind that these patients are more vulnerable for the development of cervical spondylotic myelopathy.⁴

The literature has noted that up to half of KFS cases may not present with typical findings such as “wasp-waist sign” and the reason behind such assertions remains speculative.¹⁶

The strengths of the current study involve data integrity and adequate duration of follow-up. However, limitations such as retrospective design, data restricted to the experience of a single-center, and possible confounding effects of ethnic, genetic, and socioenvironmental factors must be remembered during extrapolation of our data to larger populations.

In conclusion, recognition and classification of KFS patients with ASD is critical for the establishment of diagnosis accurately and tailoring the individualized treatment strategy without delay. Our preliminary data yielded that the novel “Yilmaz-Yucesoy Classification System” can be useful to categorize these patients and to optimize therapeutic outcomes. However, further multi-centric, prospective, randomized trials on larger series are warranted to confirm and validate our newly proposed classification system.

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