The literature review yielded a total of 18 articles related to kyphosis surgery in MPS I patients (Table 2). Only eight of these papers reported ≥2 patients. Of the 18 articles, individual patient data was extracted from 47 patients (Table 3). The median reported age at surgery was 6.4 years (range 2.4–16.8 years) and the median kyphotic angle prior to surgery was 67° (range 30° - 110°). Twenty-eight patients underwent a combined anterior and posterior surgical approach, 13 patients a posterior only approach, one patient an anterior only approach, in one patient a Vertical Expandable Prosthetic Titanium Rib technique (VEPTR) was used and in 4 patients the approach was not reported. Spinal complications after surgery were an adjacent kyphosis (n = 4) and an adjacent segment listhesis (n = 3) after a median follow-up of 3.5 years (range 1.1–8.3 years). Data on the long-term course of the kyphotic angle or on functional outcomes (i.e. activities of daily living (ADL)) and quality of life were absent in all of the reviewed publications.
Table 2 Summary of included studies regarding kyphosis surgery in MPS I patients Table 3 Individual MPS I patients – kyphosis surgery All of the invited experts participated in at least one round (Table 4). During this Delphi procedure, sixteen statements were developed and full consensus was reached on all statements.
Table 4 Number of participants Delphi Procedure Statement 1
18 participants agreed and 1 stated: “this is not my expertise”
The aim of kyphosis surgery in MPS I patients is correction and prevention of ongoing progression of kyphosis with a satisfactory neurological, biomechanical (i.e. improvement of sagittal balance) and cosmetic outcome for the patient, with maintenance or improvement of activities of daily living.
The immediate goal of surgery is correcting the kyphotic deformity and preventing recurrence and progression of the deformity. The ultimate goal is to maintain the ADL in patients with an asymptomatic kyphosis as performance may deteriorate in the future or, in patients who have clinical symptoms due to their kyphosis, such as back pain, sagittal imbalance or neurological impairment, to improve daily life performance. Furthermore, correction of the kyphosis can lead to an improvement of the patient’s posture, thus improving cosmetic appearance, which may benefit the quality of life of older patients with relatively intact cognition.
As data on long-term outcomes is lacking, future studies are warranted to address these, especially focused on quality of life and daily life performance [21].
More data is available on surgical intervention in non-MPS related kyphosis. Murray et al. reported that in adult patients with Scheuermann kyphosis (average age 35 years, range 25–82) increasing curve magnitude led to more concern about their appearance compared to a healthy control group. Also, patients with the apex at a caudal level seemed to have less self-esteem issues with increasing magnitude of the kyphotic deformity [22]. Quality of life including physical functioning improved after corrective spinal surgery in adult patients with a symptomatic thoracolumbar or lumbar kyphosis secondary to osteoporosis [23]. Patients with Scheuermann kyphosis showed that functional outcome significantly improved 2 to 8 years after surgery. However, long term follow-up (14 to 21 years postoperatively) of the same patient cohort showed no difference in functional outcome compared to the preoperative scores [24]. However, the nature of the MPS disease, the age group, comorbidities and intellectual function strongly limit comparison with Scheuermann kyphosis.
Despite the fact that respiratory improvement after kyphosis correction has been reported in patients with Scheurmann kyphosis and kyphosis due to severe osteoporosis, this was not included in the statement since the panelists agreed that their collective experience with MPS I did not support this.
Statement 2
17 participants agreed and 2 stated: “this is not my expertise”
The timing of surgery depends on the progression and flexibility of the spinal deformity, the presence of symptoms, growth potential and comorbidities.
If indicated, surgery is generally performed between 5 and 13 years of age.
While it was agreed that timing of surgery is not based on age, it was noted that kyphosis surgery at a very young age may have a higher risk of implant failure. Furthermore, at a very young age, HCT complications may adversely affect the health of the patient and their ability to withstand surgery safely. In older patients, cardiac involvement increases the risks of surgery [25, 26]. It was also agreed that kyphosis surgery in older patients may be made more complicated by increasing stiffness of the deformity. As a result, it was concluded that patients are generally operated on between 5 and 13 years of age (Table 2) with the exception of extreme kyphosis and/or neurological signs and symptoms in very young patients or mature patients.
Statement 3
18 participants agreed and 1 stated: “this is not my expertise”
The indication for surgery should be made by a multidisciplinary team, including the spinal surgeon. The spinal surgeon finalizes the decision in consensus with the patient/parents.
Because of the complexities involved in the treatment of patients with MPS I, a multi-disciplinary team (MDT) needs to be involved. Such an MDT will include a metabolic specialist or clinical geneticist (often also acting as the coordinator of the team), an orthopedic and spinal surgeon, a physiotherapist, a rehabilitation specialist, an occupational therapist, a cardiologist, an anesthesiologist, an ear nose and throat specialist and a pulmonologist, all preferably with experience in MPS [17, 27,28,29].
An MPS I patient with a kyphosis is referred to a spinal surgeon who initially decides on the indication for surgery, which will first be discussed with the metabolic specialist and with the patients/parents. Before the final decision is made, the MDT is essential to assess the risk of potential complications and contraindications. The organization of an MDT will differ between centers and countries, and different strategies for consultation and communication can be used effectively. It is essential that a case manager/coordinator is appointed.
Statement 4
17 participants agreed and 2 stated: “this is not my expertise”
Preoperative full spine and brain MRI should be evaluated for spinal cord compression at sites away from the kyphotic deformity, particularly the occipito-cervical junction and the cervico-thoracic junction.
While spinal and brain MRIs are recommended every other year in MPS I patients [27], it is essential to assess the spinal column and brain by MRI prior to kyphosis surgery for the presence and degree of spinal stenosis and cord compression at sites away from the deformity, as well as hydrocephalus. Furthermore, plain lateral cervical X-ray studies, if feasible in voluntary flexion and extension, are necessary to detect the presence of atlantoaxial instability, which is reported in 20% of transplanted Hurler patients [14]. This information is needed to prevent neurological complications during and immediately after surgery.
Statement 5
18 participants agreed and 1 stated: “this is not my expertise”
For patients presenting with back pain, it is essential to first explore the cause of the pain and to try non-operative therapeutic options (e.g. physiotherapy, pain medication and/or a brace). Surgery may be considered after all other options to treat the pain have failed, which is considered a rare event.
Back pain as a single symptom is rarely an indication for surgery. There are a number of possible causes for back pain in MPS I, such as problems related to the intervertebral discs, muscles, ligaments, facet joints and back pain as a result of posture deviations due to hip problems. To provide adequate non-operative treatment it is important to determine the cause. When non-operative management is ineffective and back pain is severe, surgery of spine deformities may be an option.
With increasing life expectancy, due to improvement of supportive care, symptomatic treatment and treatment with HCT, patients may suffer from sagittal imbalance for a considerable time which may lead to an increase in the number of patients presenting with back pain.
Statement 6A
17 participants agreed and 2 stated: “this is not my expertise”
Abnormal clinical neurological signs and symptoms caused by kyphosis (though rare) are an indication for kyphosis surgery. Only a few MPS I patients with neurological signs and symptoms, attributable to a thoracolumbar kyphosis have been reported [13, 30]. Despite its rarity, it is generally agreed that MPS I patients with a thoracolumbar kyphosis and abnormal clinical neurological signs and symptoms should undergo surgery.
Statement 6B
17 participants agreed and 2 stated: “this is not my expertise”
Signs of spinal cord compromise on spinal MRI at the level of the kyphosis and/or detected by electrophysiological studies can be an indication for surgery.
With the purpose of detecting myelopathy at an early stage, an MRI scan of the spine is recommended every other year during follow-up of MPS I patients [27]. Signs of myelopathy on MRI and/or electrophysiological studies can be present without accompanying clinical signs or symptoms, but when progressive or severe, warrant surgical decompression. Since progressive cord myelopathy is difficult to interpret in patients with MPS I, it is preferable that a radiologist with experience in MPS I should evaluate the MRI.
Statement 7
19 participants agreed
A low developmental quotient is not a contra-indication for surgery where a benefit in quality of life can be expected.
Patients with MPS I (both with the Hurler and severe Hurler-Scheie phenotype) often have neurocognitive impairment despite HCT [10, 31].
Intellectual ability is often expressed as developmental quotient (DQ), defined as the developmental age divided by the chronological age multiplied by 100 [32]. There was full agreement that DQ should be taken into account when considering kyphosis surgery, but that a low DQ is not a contra-indication for surgery if a benefit in quality of life is expected by correcting the kyphosis.
Statement 8
18 participants agreed and 1 stated: “this is not my expertise”
Hip range of motion should be taken into account when kyphosis surgery is considered.
Hip dysplasia is present in most Hurler patients, even after successful HCT, and may lead to a restricted hip range of motion [5, 14, 33,34,35]. Since both the hip and spine are involved in maintaining sagittal balance, it is important to consider the contribution of both when discussing kyphosis surgery. Compensatory mechanisms may negatively impact the outcomes of surgery (e.g. in a patient with severe hip contractures, compensatory lordosis of the lumbar spine after kyphosis surgery may lead to sagittal imbalance). In addition, knee flexion and ankle plantarflexion (though to a lesser extent) should also be taken into account since this may also impact spinal alignment.
The optimal timing of hip surgery and kyphosis surgery in a patient needs to be assessed by a hip surgeon and a spinal surgeon, in consultation with the MDT. In general, hip surgery will be performed at a relatively earlier age than spine surgery because this allows reconstructive surgery whereas at an older age a salvage procedure (e.g. a shelf augmentation or Chiari osteotomy) will be the only option [36].
Statement 9
17 participants agreed and 2 stated: “this is not my expertise”
Patient positioning for spinal radiographs should be standardized (preferably standing and unsupported). If this is not feasible for an individual patient the position of the patient should be reported.
To adequately evaluate the spinal deformity, an anteroposterior and a lateral radiograph are required. The radiographs should include the total thoracolumbar spine and the pelvis, with patients preferably in the standing position focused on straight knees and hips. This is important because patients tend to compensate sagittal imbalance by thoracic lordosis, pelvic retroversion and flexion of the knees [17, 37, 38]. Furthermore, it was strongly recommended to report the patient’s position on both the radiograph and the report, since they can become disconnected.
Statement 10
15 participants agreed and 4 stated: “this is not my expertise”
Radiographic assessment of the kyphotic deformity in MPS I should include angular and translational measurements on serial radiographs.
Traditionally the kyphotic angle is measured by the Cobb method [39], however due to dysplasia of the vertebrae, application of this method can be challenging as the contours of the upper endplate of the upper vertebra and of the lower endplate of the lower vertebra are often difficult to assess. It appears that clinicians use approximations applicable to the specific radiographic abnormalities. While this is generally adequate for clinical practice, for research purposes and communication, a standardized protocol stating how to measure the kyphotic angle in patients with MPS I is essential. The same applies for the translational data, i.e. the severity of spondylolisthesis. Vertebral beaking, (sub)luxation of vertebrae and scoliosis are also regularly observed in MPS I in combination with kyphosis, and need to be evaluated on radiographic examination [13, 33]. It is important to evaluate the sagittal balance which is determined by a combination of the position of the spine, hips, knees and to a lesser extent the ankles. Measuring sagittal balance on radiography can be challenging in MPS I patients, as patients need to stand still, unsupported and without bending forward.
Kyphosis surgery should be based on the evaluation of more than 1 radiograph, in order to be able to assess the extent of progression. Radiographs should be routinely performed at a minimum of every other year [27].
Statement 11
18 participants agreed and 1 stated: “this is not my expertise”
Neurological monitoring is mandatory during kyphosis surgery. Surgery should only be carried out in a unit with the capability to carry out appropriate multimodality neurophysiological monitoring including the anterior motor pathway.
To reduce the risk of paralysis, it is important to monitor the function of the spinal cord pre- and peri-operatively. It was agreed that optimal monitoring includes both motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs). MEPs are considered essential since they assess the anterolateral part of the spinal cord [40], which may be stretched during the procedure, potentially resulting in motor impairment. Obtaining MEPs can be difficult or even impossible in young (approx. < 5 years) patients due to neurophysiological immaturity of the cortical pathways. In addition, MEPs are contra-indicated in some patients with seizure disorders [41]. In those cases, medulla stimulation may be used as alternative approach to monitor these tracts [42].
Statement 12
15 participants agreed and 4 stated: “this is not my expertise”
The posterior only approach and the combined (anterior and posterior) approach both have benefits and disadvantages, and the decision regarding which surgical approach to use should be based on the patient’s size and weight and the degree and flexibility of deformity of the spine.
The following advantages of the posterior only approach were raised during this session: it is less invasive and the chest is not opened, there is less morbidity, a shorter procedure, a shorter hospital stay and it is less likely that patients have significant postoperative recovery issues. The reported disadvantages of the posterior only approach were: it leads to less correction of the kyphotic angle, efficient fusion is not achievable, it leads to further destruction of the weak posterior ligamentous complex, there is a risk of a possible future need for anterior surgery and adequate fixation can be difficult in the dysplastic vertebrae. The reported advantages of the combined approach (i.e. both anterior and posterior approaches) are that it leads to better correction and stability. The reported disadvantages of the combined approach include the obvious facts that a two incision approach is more invasive, the diaphragm is taken down, there is a higher risk of pulmonary complications and morbidity, the surgery is technically demanding, the operating time is longer and an ICU admission more likely. Although, the combined approach was regarded as the optimal strategy, several experts from the panel mentioned that nowadays a preference is emerging to the posterior only approach as stronger implant systems have been introduced leading to good posterior column fixation. If satisfactory alignment cannot be achieved by a posterior approach only through posterior osteotomies [43], a subsequent anterior approach should be performed. The decision on the optimal approach in individual patients will be influenced by the patient’s size, weight, degree and flexibility of the deformity and the experience of the surgeon. In case of a large deformity and a stiff and/or large spine, an additional anterior approach may be the best option.
Statement 13
16 participants agreed and 3 stated: “this is not my expertise”
Selection of the number of surgical levels to be fused during kyphosis surgery depends on the degree of deformity, the number of dysplastic segments, the level of the kyphosis, the approach used and expected correction. Instrumenting at minimum 2 levels above and 2 below the dysplastic segments seems to produce adequate alignment. However, despite adequate surgical management, junctional malalignment can be a complication.
The selection of the number of surgical levels depends on several factors, but a minimum of 2 levels above and 2 levels below the dysplastic segments is considered to be sufficient as reported in several publications [17, 44, 45]. When optimal correction cannot be achieved during surgery, another level can be added to improve correction. Unfortunately, there are no long-term follow up data on the outcome related to the levels of fusion and during the meeting several experts reported, that spines initially considered adequately corrected may show kyphotic or junctional failure and malalignment during long term follow up, this was also discussed in the article of Bekmez et al. [43].
Statement 14
18 participants agreed and 1 stated: “this is not my expertise”
Bracing in young children with large flexible deformities may be considered as it may postpone surgery up to an age where vertebral development allows rigid fixation.
There is no consensus whether a brace is effective in the treatment of kyphosis. However, bracing prior to surgery may be considered in young patients with large flexible deformities as it may help to maintain sagittal balance, and may slow down the progression of the deformity and thus delay surgery until patients reach an age where surgery is expected to be technically more successful. Bracing is generally well accepted in young patients.
In patients with back pain due to kyphosis, lightweight flexible braces may be advised to offer comfort.
Statement 15
17 participants agreed and 2 stated: “this is not my expertise”
Bracing post-surgery may be considered for a period of 3 to 6 months as it may protect the arthrodesis and the adjacent segments.
There are several reasons to use bracing in MPS I patients after kyphosis surgery. First, due to the small dysplastic vertebrae of MPS I patients, fixation may be not as strong as fixation in non-MPS I patients. Second, patients with developmental delay may be over-active and/or have problems following instructions. This may jeopardize the surgical construct. However, it should be taken into account that brace compliance in these older patients may be low because of discomfort.
Statement 16
17 participants agreed and 2 stated: “this is not my expertise”
Treatment algorithms based on measurement of the kyphotic angle alone are not sufficient in MPS I patients. Indication should not be based on curve magnitude only, but on the indications as discussed in statement 6.
General indications for spinal surgery in kyphosis with another etiology cannot be applied to MPS I patients. For example, Wenger et al. proposed that patients with a Scheuermann kyphosis > 75°, or a significant kyphosis (> 65°) associated with pain that cannot be alleviated with conservative treatment, should be considered for surgery [46, 47]. Vaccaro et al. report an angle of 30° (as an additional criterion) in patients with a traumatic thoracic kyphosis be used as an indication for surgery [48]. For MPS I it has been reported, that kyphotic deformities exceeding 45 degrees tend to progress [49], and as such should be monitored more closely. In addition, progression exceeding 15 degrees per year has been proposed as an indication for surgery [43].
During the meeting, all experts agreed that no mandatory cut-off value for the Cobb angle can be established for kyphosis surgery in MPS I patients. This decision depends on the presence of abnormal clinical neurological signs and symptoms and MRI and/or electrophysiological signs of spinal cord compromise (statement 6). In addition, it also depends on the deformity progression and flexibility, the presence of symptoms, growth potential and comorbidities (statement 3).