Purpose

Patients with ankylosing spondylitis (AS) are vulnerable to cervical spine injury following relatively minor trauma. The authors present a retrospective review to determine the characteristics, treatment and outcome following cervical spine injury in these patients.

Purpose

Patients with ankylosing spondylitis (AS) are vulnerable to cervical spine injury following relatively minor trauma. The authors present a retrospective review to determine the characteristics, treatment and outcome following cervical spine injury in these patients.

Patients with spinal injuries are very vulnerable to early complications or secondary spinal cord injuries before and during transfer, which may delay their rehabilitation. We designed transfer guidelines following concerns raised in a pilot study of the transfer of 16 patients. We then examined the effectiveness of the guidelines in 100 consecutive patients and completed the cycle by re-auditing a further 254 consecutive admissions after incorporating changes from the initial audit.

The transfer guidelines addressed ten areas of clinical concern. We recorded a 50% improvement in airway monitoring and management. There was also improvement in anti-ulcer therapy and thromboprophylaxis (from 50% to 96%). We saw a 50% improvement in the use of appropriate support staff during the transfer.

The re-audit showed that initial improvements were maintained and further improvements were noted in the transfer of relevant documentation and investigations. Improvement was also noted in the use of a vacuum mattress for the transfer of spinal injury patients and subsequently reduced incidence of pressure sores by a statistically significant level, which helped in the early rehabilitation of these patients. The majority of transfers were safe.

The transfer guidelines were easy to use and improved patient care by ensuring that common problems had been addressed before and during transfer. This system reduced the risk of preventable complications during inter-hospital transfer. There may be wider application of similar guidelines to other trauma patients who require inter-hospital transfer, where there is a possibility of preventable secondary injury.

Introduction: Diminished adult stature is a key feature of Hereditary Multiple Exostoses (HME). Current debate on the pathogenesis of skeletal abnormalities in HME centres on whether there are ‘field-change’ effects which might retard bone-growth, or whether exostoses themselves distort normal bone development locally. The latter theory allows for surgical excision of exostoses to improve prospects for local normal bone development whereas the former does not. No study has previously investigated patterns of height disturbance in HME. Such an analysis in a cohort of children and adults with HME may provide evidence for or against either pathogenesis theory, and throw light on the chance of success of lower limb surgery in improving final height.

Methods: Between 1996 and 2000, 172 individuals from 78 families with HME had clinical measurement of standing height and leg length (anterior superior iliac spine to medial malleolus. 71 were skeletally immature (1st and 2nd decades). Surgical intervention in anatomical areas affecting stature (lower limb, pelvis and spine) were recorded. Centile heights were calculated from Tanner Whitehouse charts.

Results: 25/172 (15%) exhibited severe short stature (< 3rd centile height). Overall, Statural retardation was not apparent up to age 10; thereafter progressive diminution in centile height was recorded (figure 1). Before age 10, 25/37 (68%) were over the 50th centile. Beyond this age, 98/35 (73%) were less than the 50th centile (X2=22.42, p< 0.001). 101 patients who had surgery did not achieve a greater stature than those who had not. In the normal population lower limb contribution to height increases with age, whereas in HME it remains static suggesting that the retardation of stature seen between ages 10 and 20 in HME is mainly due to lower limb, not spinal growth retardation. Leg length discrepancy of > 1% of centile height was seen in 35/167 (21%), encompassing all age groups without significant difference.

Discussion: The pattern of height retardation observed in this study is consistent with a progressive linear disturbance which is not apparent in early childhood, but progresses significantly in the second decade. Overt spinal exostoses are rare; and the spine’s contribution to growth retardation in HME appears be far less than that due to the lower limb. Although the genetics of HME allow for a field-change effect as well as a local osteo-chondroma effect, these results reinforce the possibility that solutions to severe short stature in HME may be achieved through lower limb surgery.

To determine whether the spectrum of genetic mutation in Hereditary Multiple Exostoses supports a neoplastic aetiology for this condition.

Historically, experts have been cautious in attributing neoplastic qualities to the osteochondroma. Solomon states ‘[osteochondromas] are not neoplastic in the ordinary sense of the word’; Morton that it ‘is not a tumour but a growth-aberration; Peterson that the ‘osteochondroma is not a true neoplasm’; and Schmale that ‘exostoses are the result of dysplasia of the lateral apect of the growth-plate’. There are, however, several features of osteochondroma behaviour common to other neoplasms which suggest a neoplastic aetiology:

the existence of an autosomal dominant inherited multiple form, in which lesions are histologically identical to the solitary form.

Recent genetic data has supported a fresh look at the neoplastic nature of osteochondromas. EXT1 and EXT2 genes are responsible for Hereditary Multiple Exostoses (HME). EXT1 codes for a protein which alters the synthesis and display of cell-surface heparan sulphate glycosaminoglycans; molecules which affect cellular growth, differentiation, motility and adhesion. Loss-of-function of such a gene may initiate a neoplastic pathogenesis in osteochondromas.

From 1996–1999, 51 families with HME were screened for EXT mutation, with mutations identified in 41 families. EXT mutation was assessed by means of fluorescent single-strand conformational polymorphism (f-SSCP) screening, followed by sequencing analysis.

Results : All missense mutations had previously been reported in the literature. In contrast, only 9 of 34 loss-of function mutations (frame-shift, splice-site and nonsense) had previously been reported.

All frame-shift, splice-site and nonsense mutations are loss-of-function. Missense mutations may result in partial or complete dysfunction if a crucial folding or binding site is involved. Since no missense mutations were new, this suggested their mutation sites are important, and may effectively result in loss-of-function. These data strongly support a tumour suppressor gene function for EXT genes, and a neoplastic pathogenesis for HME.

To identify if disease severity and cancer-risk might depend on genotype in Hereditary Multiple Exostoses (HME).

The discovery that the EXT family of tumour suppressor genes is responsible for Hereditary Multiple Exostoses (HME) now enables correlation of clinical features with genetic defects. Genetic epidemiological studies, such as this, may provide additional data of use to the clinician. In most population-based HME cohorts, the incidence of sarcomatous degeneration has been estimated as 1–5%. This is not high, but occurs at a younger age (on average 2–3 decades younger) than chondrosarcoma in the general population. Genetic stratification might allow a very high-risk subgroup to be identified, within which surveillance for neoplastic change in osteochondromas could be concentrated.

In a pilot study, 29 affected individuals from 17 families with HME were screened for EXT mutation, with mutations identified in 12 families. Pedigrees were obtained and a complete assessment of disease severity made. We have since expanded this cohort; a further 71 affected individuals from 34 families with HME have provided detailed pedigree data and undergone a simple clinical examination to assess number of palpable osteo-chondromas. EXT mutation was assessed by means of fluorescent single-strand conformational polymorphism (f-SSCP) screening, followed by sequencing analysis.

Validation of clinical examination : In those who underwent radiographic examination for clinical purposes, number of palpable osteochondromas correlated strongly with number seen on radiographs at 146 anatomical sites (r= 0.814, p< 0.001), validating the usefulness of clinical examination in a population analysis, and negating the need for a radiographic skeletal survey in individuals at risk from malignant change.

The observation that osteochondromas are more frequent in patients with EXT1 than EXT2 mutations is an important message in genetic counselling. If disease severity and cancer risk is greater in individuals with EXT1 mutation, screening for neoplastic change might be targeted on this group, in which lifetime risk of malignant change in osteochondromas could be increased to between 5% and 10%.