Childs Nerv Syst (2006) 22: 249–252 DOI 10.1007/s00381-005-1212-7
E. Al-Shail A. Al-Odaib P. T. Ozand
Received: 3 June 2004 Revised: 28 March 2005 Published online: 20 August 2005 # Springer-Verlag 2005
E. Al-Shail Department of Neurosurgery, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia A. Al-Odaib (*) . P. T. Ozand Department of Genetics, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia e-mail:
[email protected] Tel.: +966-1-4647272 Fax: +966-1-4414839
ORIGINA L PA PER
Early neurosurgical intervention in spondyloepiphyseal dysplasias
Abstract Goals: The aim of this study is to evaluate the benefits of early intervention in two major spondyloepiphyseal dysplasias of Saudi Arabia, namely, multiple sulfatase deficiency (MSD, Austin’s disease) and Morquio’s disease. The MSD is encountered frequently in the Kingdom and poses significant health risk to the child because of cord compression. The clinics of this hospital have several Austin’s patients. Results: This study indicates that early intervention before serious irreversible damage to the cervical cord occurs improves the neurological course of the patient; no patient had a worse outcome. On the other hand,
Introduction Three lysosomal storage diseases that cause spondyloepiphyseal dysplasia are multiple sulfatase deficiency (MSD, Austin’s disease), Morquio’s disease, and Maroteaux– Lamy syndrome. The patient referral to this hospital indicates that the major entity among those is MSD and then Morquio’s disease. All three conditions cause significant and severe abnormalities at the C1–C2 junction, restriction of foramen magnum, atlanto-occipital dislocation, and odontoid hypoplasia. Thereby, there is compression of the cervical cord and, in advanced cases, cervical cord myelopathy. The time of intervention to stabilize the cervical vertebrae is not well studied for Austin’s disease because this is rare outside Saudi Arabia. However, there are several reports for the benefits of such an early approach in
neurosurgical intervention after the neurological symptoms of cord compression occurs was not as rewarding. Conclusion: Morquio’s disease is more common outside the Kingdom. The results in this study also confirm that early intervention in this disease is beneficial. Other surgeons make a similar recommendation for Morquio’s disease. However, their experience with Austin’s disease is not reported due to the rarity of this disease elsewhere. Keywords Odontoid hypoplasia . Cervical cord compression . MSD . Morquio
Morquio’s disease. This study is to review the results obtained in MSD and Morquio’s disease in this hospital.
Patients and methods Nineteen patients with MSD and 16 with Morquio’s disease are included in this study. These are patients who have been followed by neurosurgery for 1–8 years. Although 30 MSD and 20 Morquio’s disease are in the files of the hospital, some patients dropped out of the follow-up, some expired, and some refused surgery. In two patients with Morquio’s disease, bone marrow transplantation was attempted, however, it was not beneficial, and in one patient with MSD, bone marrow transplantation arrested the progression of the disease (results not shown).
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All patients in this study were subjected to a battery of lysosomal enzyme determination in leukocytes and cultured fibroblasts with methods described before [1]. The phenotype of Saudi MSD has been reported by Al Aqeel et al. [2].
Results
Normal Myelopathy Odontoid hypoplasia Cervical cord compression a
The main neurological findings of the 19 MSD and 16 Morquio’s disease patients that are included in this study are shown in Table 1. Approximately 58% of the patients with MSD showed developmental delay or mental retardation; approximately 25% had pyramidal tract signs, either in the form of spasticity, hypotonia, or pathological neurological reflexes (Table 1). Among Morquio’s disease in 6%, there was developmental delay. In 44%, there were pyramidal tract signs as spasticity, hypotonia, or pathological neurological reflexes. These findings include those patients before they have undergone cervical stabilization. Magnetic resonance imaging (MRI) of cervical cord and brain was available in most patients. The findings paralleled the clinical observations. Cervical myelopathy was detected in 21 and 50% of the MSD and Morquio’s disease patients, respectively (Table 2). The central white matter disease, as mild or severe, was encountered in all MSD patients, whereas it was never seen among patients with Morquio’s disease (Table 2). Although in MSD, cervicocranial instability was seen among 37%, this figure was 63% in Morquio’s disease. However, cervical cord compression at C1–C2 level in MSD and Morquio’s was 42 and 75%, respectively (Table 2). This table brings forth the importance of recognition of cervical cord abnormalities both in MSD and in Morquio’s disease and justifies neurosurgical intervention.
Neurosurgical intervention The neurosurgical intervention included C1 laminectomy and posterior occiput-C2 fixation with wire or cable fusion and bone graft. However, we felt this did not have any Table 1 Clinical findings
Sex (F/M) Age Follow-up Mental status (N/MR) Spasticity Hypotonia Babinski or ankle clonus
Table 2 MRI findings of cervical spinal cord
MSD (n=19)
Morquio (n=16)
10/9 28 months 45 months 7/12 8 1 5
7/9 6 years 5 years Normal 7 5 7
N Normal, MR mental retardation
MSD (n=18)a
Morquio (n=16)
12 4 14 8
12 8 15 12
MRI was not conducted in one MSD patient
significant effect on the final outcome because all patients were followed up till bony fusion is achieved. We felt that to validate our surgical outcome, we needed to correlate it with the clinical and radiological findings. Among patients with Austin disease, seven were found to have craniocervical instability (C-C inst). All these patients had neurological symptoms, except one male patient in whom the C-C inst was discovered on routine work up; however, he was found to have odontoid hypoplasia. The follow-up and outcome of patients is summarized in Table 3. Only one patient had delayed surgery without any improvement, four patients offered surgery, but refused. The average follow-up period was 75 months during which 14 patients deteriorated, and among them 4 died. The remaining three continued to be stable. Two patients offered bone marrow transplant, one died following the transplantation. The 16 patients with Morquio’s syndrome were divided into two groups, 13 symptomatic and 3 asymptomatic. All patients had MRI of the craniocervical junction. Among the symptomatic group (five male and eight female with an average age onset of 39.88 months), nine patients had craniocervical instability. All the 13 patients had odontoid hypoplasia, 10 had cord compression, which varied from mild to moderate, 8 had myelopathy. Only five patients had early surgery, no delayed surgery was performed; two patients offered surgery, but declined (Table 3). Only one among the asymptomatic group had craniocervical instability. However, two of them had odontoid hypoplasia and cord compression. Only one treated with halo-vest stabilization, and another patient declined from surgery. The average follow-up was 88.5 months, during which the majority of the symptomatic group eight patients worsened, four stabilized, one improved. Among the asymptomatic group, two patients worsened and one remained stable. Only one died at 16 years of age. Two patients were treated with bone marrow transplantation that has been stable clinically (Table 3).
Discussion Spondyloepiphyseal dysplasias cause instability at the atlanto-occipital junction. They may lead to cervical myelopathy, cervical cord compression, and even cervical cord transection. As such, they are neurosurgical emergen-
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Table 3 Neurological symptoms and surgical interventions (number of patients)
Preoperatively asymptomatic surgery No Austin’s disease
0 0 8 Morquio’s disease 1 0 2
Preoperatively symptomatic surgery
Neurological examination and follow-up
Early
Delayed
No
Early
Delayed
0 0 0 0 0 0
0 0 0 0 0 0
3 0 7 0 0 8
0 0 0 4 1 0
0 0 1 0 0 0
cies. Three storage diseases Maroteaux–Lamy syndrome (MPS VI), multiple sulfatase deficiency (MSD or Austin’s disease), and Morquio’s disease (MPS IV) are among such disorders. The MPS VI and MSD are not detailed for their cervical cord pathology because of the rarity of these disorders in the West. On the other hand, several detailed studies for MPS IV have been published. In Saudi Arabia, MSD is the commonest among three, and our experience has been published [2]. This study is to present our view for early surgical intervention in MSD and MPS IVA. More than 50 patients with MSD or Austin’s disease exist (Mc. Kusick number 272200). Despite this relatively large number, it is a rare disease in the world. This is a very common storage disease in Saudi Arabia with more than 30 patients reported. The clinical findings in the Saudi variant were reported [2]. It is a syndrome that combines the features of metachromatic leukodystrophy (MLD) with those of a mucopolysaccharidosis (MPS). The features of these two diseases vary among various groups. The phenotype and pathology of MSD represents an overlap between a leukodystrophy and MPS. The phenotype shows a pattern apparently depending on the degree of enzyme deficiency encountered among seven different sulfatases [3, 4]. In Saudi Arabia, the MPS features, such as MPS VI and MPS IVA, are more prominent than those of MLD. The defective gene and its product are unknown. There is evidence that a cysteine residue at the active center that is conserved in all sulfatases fails to be converted into 2-amino3-oxopropionic acid [5]. At least seven sulfatase activities are deficient in varying proportions among the reported cases and causes diagnostic confusion [4]. Only one patient, a Saudi Arabian, has been studied for the cervical instability. This was a 30-month-old boy with MSD and features of cervical cord compression due to thickened posterior arch of atlas
Stable Improved Deteriorated Stable Improved Deteriorated
and hydrocephalus due to meningeal thickening and a narrow foramen magnum. He also had hydrocephalus [6]. The cervical instability in Morquio’s disease poses difficulties in laryngoscopy for anesthesia; a cord dissection can occur which has been reported elsewhere as well as in this Institution. Several groups reviewed this [7, 8]. For this purpose, fiberendoscopic nasotracheal intubation or a curved endoscopic intubation laryngoscope with angulated distal tip has been recommended. MPS IV is a clinical disorder quite different from other MPS conditions. The management issue revolves around the prevention of cervical myelopathy [9]. These authors mention that the timing of occipito-cervical fusion and the selection patients for this procedure do not have set rules. They recommended a prophylactic surgery, although no evidence exists that all untreated patients will invariably develop cervical myelopathy. However, the report by Ransford et al. [10] suggests prophylactic surgery. In their series of 17 patients with Morquio’s syndrome, those patients with recent onset myelopathic symptoms made some recovery. But severely myelopathic patients showed little or no recovery. Their conclusion was prophylactic occipito-cervical fusion in these patients because the cartilagineous dens is not strong enough to ensure atlanto-occipital articulation (AOA) mechanical stability. As can be seen from the aforementioned discussion, there is a general tendency to provide presymptomatic neurosurgical intervention in MPS IVA. Our experience also supports this point of view. One way to look at MSD is as a cross between MPS IVA and MLD. The MSD has many features of MPS IVA including the AOA instability. What has been advised for MPS IVA should also hold true for MSD. Therefore, we also recommend early preventive AOA stabilization in MSD.
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3. Macaulay RJ, Lowry NJ, Casey RE (1998) Pathologic findings of multiple sulfatase deficiency reflect the pattern of enzyme deficiencies. Pediatr Neurol 19:372–376
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