Delayed Onset Post-Operative Neurologic Deficit in a Patient With Mucopolysaccharidosis type VI: A Case Report

Abstract

Background

Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterized by abnormal deposition of glycosaminoglycans (GAGs) in tissues. In type VI MPS, otherwise known as Maroteaux-Lamy syndrome, the defect is in the enzyme N-acetylgalactosamine-4-sulfatase. Thoracolumbar kyphosis results from GAG deposition, leading to incompetence of posterior ligamentous structures as well as poor trunk control. Though neurologic symptoms from canal compression due to deformity and hypertrophy of tissues have been described, occasionally requiring surgical decompression, there has not been a prior report of late onset of symptoms in a previously neurologically intact patient following surgery to correct spine deformity.

Methods

The case reviewed is a 14 year old girl with mucopolysaccharidosis type VI underwent anterior release and posterior instrumentation for correction of severe progressive lumbar kyphosis. Postoperatively she developed delayed onset of profound lower extremity weakness and underwent urgent wide laminectomies and resection of thickened ligamentum flavum. At 1 year follow-up, she had near complete neurologic recovery.

Conclusion

Patients with mucopolysacchari-doses are at significant risk for neurologic compromise both as part of the natural history of the disease, and as a risk of deformity correction. The surgeon must consider the pathologic thickening of tissues surrounding the spinal cord when planning surgery.

Level of Evidence: IV

Introduction

Mucopolysaccharidosis (MPS) type VI, otherwise known as Maroteaux-Lamy syndrome, is one of several known lysosomal storage disorders characterized by accumulation of glycosaminoglycans (GAGs) in lysosomes and abnormal deposition in tissues.¹ In the case of MPS VI, the defect is in the enzyme N-acetylgalactosamine-4-sulfatase (also known as arylsulfatase B, or ASB) which degrades dermatan sulfate.^2,3 Like all MPS diseases except MPS II (which is X-linked), MPS VI is inherited in autosomal recessive fashion.¹ The incidence is estimated between 1 in 238,000 to 1 in 300,000, and makes up about 4.2% of the documented US cases of MPS.^1,4 The clinical presentation is heterogenous, but includes dysmorphic facies, cardiopulmonary disease, stunted growth, and progressive skeletal and joint deformities.¹

Advancements in treatment, including hematopoietic stem cell transplants and enzyme replacement therapy, have dramatically improved life expectancy for MPS patients,^5,6 but these treatments do not prevent most musculoskeletal manifestations, including spine pathology. Thoracolumbar kyphosis results from GAG deposition leading to incompetence of posterior ligamentous structures as well as poor trunk control. This is quite common in MPS I (Hurler syndrome) and occurs in up to 90% of those patients.^5,7 It is also described in MPS II, IV, and VI and many authors have published their experiences with kyphotic deformity and correction in patients with MPS.^5,8-11 Deposition of GAGs in the meninges, PLL, and ligamentum flavum, leads to stenosis of the spinal canal, both in the upper cervical spine and in the thoracolumbar spine at the apex of the gibbous deformity.^7,11 Neurologic symptoms from this compression is known to develop in 12-40% of patients with MPS, and does occasionally require surgical decompression.¹¹

Herein we present a case of a young girl with MPS type VI with no pre-operative neurologic signs or symptoms, who developed delayed neurologic compromise after combined anterior release and posterior spinal fusion for a lumbar kyphotic deformity, treated with return to the operating room for wide laminectomy and decompression.

The patient’s parents did provide consent for data concerning this case to be published as a case report. Our institutional IRB considers case studies of three or fewer patients as exempt, per section 12.G of the Human Subjects Office’s SOP manual.

The Case

A 14-year-old female with history of mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) presented to the senior author (SLW) for evaluation of progressive thoracolumbar kyphosis and worsening back pain. She had a history of prior cervical laminectomy at C1-C3, as well as bilateral carpal tunnel and trigger finger release. Due to severe, symptomatic progressive kyphosis centered at L2-3 (Figure 1), the patient was indicated for anterior release and posterior correction and instrumentation in a single, two-part procedure. She had failed conservative management and bracing was felt unlikely to improve her symptoms and deformity. Preoperative bolster films demonstrated partial correction of the deformity (Figure 2). Anterior releases were planned, not for the purpose of a more aggressive correction, but because in the senior author’s opinion, without releases, there would be increased force on the posterior hardware in pathologic bone. In addition, most of the pre-operative stenosis was anterior on MRI (Figures 3, 4). Multiple level anterior release with meticulous ligation of unilateral segmental vessels has been extensively documented as safe, especially when using neuromonitoring technology.^12,13 Risks, benefits and alternatives were discussed with family and the patient’s parents signed the consent document. There was no pre-operative neurologic deficit.

Figure 1.

Preoperative AP and lateral scoliosis films. Preoperatively there was 38 degrees of lumbar kyphosis with hypoplastic L2. Planned surgery included anterior releases from T12 to L4 with subsequent posterior instrumentation.

Figure 2.

Lateral scoliosis film with a bolster, demonstrating good flexibility with partial correction of the deformity.

Figure 3.

Preoperative sagittal T2 weighted MRI scan demonstrating mild to moderate stenosis near the apex of the gibbous deformity, but no areas of severe stenosis in the thoracolumbar spine.

Figure 4.

Preoperative axial T2 weighted MRI at the apex of the gibbous (T1-2), showing mild to moderate stenosis.

After induction of general anesthesia, the patient was placed in the right lateral decubitus position and neuromonitoring with sensory (SSEP) and motor evoked potentials (MEP) was initiated. After positioning, MEPs were noted to be normal on the left side but distally on the right were negligible to absent at baseline. A standard thoracoabdominal anterior approach was carried out, and anterior releases were performed at disc spaces of each level from T12 to L4. Throughout the anterior procedure, neuromonitoring was unchanged. After uncomplicated anterior release, the patient was flipped prone. MEPs were then detected in all extremities. Pedicle screws were placed bilaterally from T10 to L4. Rods were placed, and kyphosis was reduced using cantilever technique. Throughout reduction, all MEPs remained normal and intraoperative wake-up test demonstrated volitional movement of both lower extremities, so the correction was not felt to be overly aggressive. Satisfied with the correction (Figure 5) and the successful wake-up test, the wound was closed. The patient was transported to the pediatric ICU (PICU) for close monitoring. She was extubated uneventfully the day of surgery and was noted to have full symmetric strength in lower extremities.

Figure 5.

Postoperative supine films with excellent correction of lumbar kyphosis and no hardware complications.

On post-operative day 1 and 2, the patient reported some paresthesias in lower extremities and on exam had trace weakness in tibialis anterior (TA), extensor hallucis longus (EHL), and gastrocsoleus complex (GSC). On post-operative day 3, she exhibited ascending weakness in the right lower extremity with new weakness in hamstrings and flexor hallucis longus (FHL), and profound weakness in TA and EHL. An MRI and CT were obtained (Figures 6-10), showing multiple levels of central stenosis and misposition of one screw at L4 on the left (non-affected side). Over the next 24 hours, she had gradual progression of the weakness in the right lower extremity. Gradual onset and unilateral weakness without hyperreflexia was most consistent with a cauda equina syndrome.

Figure 6.

Sagittal MRI postoperatively is limited by metal artifact, but demonstrates most significant compression at T10-11, L1-2 and L2-3 levels.

Figure 10.

Axial cut of postoperative CT demonstrating misplaced screw at L4 pedicle on the left. Screw with noted inferior and medial breach. This is notably on the contralateral side of the patient’s symptoms.

Figure 7.

Axial cut of postoperative MRI, also limited by metal artifact at T10-11, but demonstrates significant stenosis.

Figure 8.

Most severe level of stenosis on axial MRI cuts postoperatively at L1-2 level.

Figure 9.

Postoperative sagittal CT demonstrating misplaced screw at L4 pedicle on the left. Screw with noted inferior and medial breach. This is notably on the contralateral side of the patient’s symptoms.

In the absence of relevant literature, and after discussion with several experienced colleagues, both within and outside our institution, the decision was made to perform urgent laminectomies with extensive central decompression. The mispositioned L4 screw was replaced, but not thought to play a part in the neurologic symptoms. Wide laminectomies were performed from T9 to L5, and dramatically thickened ligamentum flavum was encountered with buckling of the tissues throughout. The ligamentum was carefully dissected off the dura. After this dissection was completed, the dura was noted to also be thickened and have undulating indentations from the hypertrophied ligamentum flavum (Figure 11), however at this point was completely decompressed posteriorly. As SSEPs were improving during the case, and clinically, the canal was felt to be adequately decompressed, the correction was not reversed. The patient returned to PICU postoperatively and was started on 0.1 mg/kg dexamethasone every 6 hours.

Figure 11:

Representative picture after decompression with extensive laminectomies. Centrally, undulating indentations in the dura can be seen after removal of the thickened ligamentum flavum.

Post-operatively, the patient continued to have profound weakness (0-1/5) in TA, and EHL, with 3/5 strength in hamstrings, GSC, and FHL on the right. She also had weakness to a lesser extent on the left with 1-2/5 in TA and EHL and 4/5 in hamstrings, GSC, and FHL. By her 6-week postoperative appointment, she had about a 15-20% improvement in strength. Over the next 6 months, the patient exhibited gradual but steady improvement. At one-year post op, the patient made almost complete neurologic recovery, with nearly normal strength, 4+/5 in TA, GSC, EHL, FHL on the left, GSC on the right, otherwise 5/5.

Discussion

Spinal stenosis is common in mucopolysaccharidoses, and neurologic compromise is described in the natural history of the disease.^5,11 In this case report we describe, to our knowledge, a previously unreported complication in a patient with MPS VI who developed critical stenosis after correction of thoracolumbar deformity, related to pathologic thickening of the ligamentum and dura. In this case, our patient did have a prior cervical spine decompression due to cervical myelopathy, so her spinal cord was known to be at risk. During the case however, neuro monitoring did not show any changes in motor potentials. Though there were some irregularities in SSEPs, the intraoperative wake-up test was normal, and the case was uncomplicated. Indeed, the patient was not found to have significant neurologic compromise until post-op day 3.

Post-operative neurologic changes are not new in MPS. There is a reported series (Pauchard et al., 2014)¹⁴ of two patients with Hurler syndrome and one patient with Morquio syndrome who experienced similar postoperative neurologic compromise within a week of correction of thoracolumbar kyphosis. One of these was treated expectantly, one with hardware removal and casting, and one (thought to be due to epidural hematoma) was taken back for laminectomy, but unfortunately did not experience neurologic recovery and died from the resulting quadriparesis. The conclusion of these authors was that surgeons must be cognizant of “spinal cord fragility” in patients with MPS.¹⁴ Although MPS type VI is less prevalent, these patients are known to have similarly tenuous neurologic status, which is not improved by enzyme replacement.¹⁵

In conclusion, with modern enzyme replacement therapies, patients with mucopolysaccharidoses can survive many decades. Spinal deformity is common among these patients, and deformity correction is desirable to maintain function and quality of life. The surgeon must be cognizant of the risks of neurologic compromise, and consider pathologic thickening of the meninges, PLL, and ligamentum when performing surgical deformity correction. Caution should be used regarding degree of correction, and sagittal and coronal alignment goals should likely be less aggressive than for healthy patients. If any intraoperative concern is encountered, or large correction needed, prophylactic laminectomy and resection of thickened ligamentum may be considered. These risks should be discussed as part of the informed consent process with families of patients.