Neurogenic heterotopic ossification: prevalence, risk factors, management and treatment

Introduction: Neurogenic heterotopic ossification (NHO) occurs as a complication of a central nervous system injury and represents the formation of true bone in environments where it is not usually found. It is particularly prevalent among patients with traumatic brain injury (TBI) and traumatic spinal cord injury (TSCI). Once NHO has developed it does not allow for prophylactic drug therapy and surgery, the only effective NHO treatment, carries with it many additional health risks. Thus no "gold standard" exists as regards NHO treatment and new and non-invasive treatment methods are urgently needed to be tested. Extracorporeal shockwave therapy (ESWT) has emerged as one potential treatment method. Objectives of this thesis: 1. To clarify NHO descriptors and clinically significant risk factors associated with NHO in TBI and TSCI patients. 2. To identify the extent of the use of ESWT in the clinical management of NHO in TBI and TSCI patients. 3. To identify the prevalence of NHO in TBI and TSCI patients in specialised and non-specialised units in Australia. 4. To conduct a clinical trial to investigate the effect of ESWT on chronic NHO in patients with TBI. Methods: Narrative and systematic reviews with a meta-analysis were undertaken on NHO descriptors and the use of ESWT in the clinical management of NHO. Retrospective audits of TBI and TSCI patients admitted to a tertiary referral hospital and to specialised units were undertaken to determine the prevalence of NHO. A single case study was carried out using the novel intervention of ESWT on a head injured patient with recurrent NHO; this was followed by a larger series of single case research studies using a similar protocol. Results: The published literature indicates that sites of NHO following TBI and/or TSCI are usually around the major joints, in particular the hip, knee and elbow. In those patients who do develop NHO, it is an extremely debilitating complication with serious consequences on their functional abilities. From the audit undertaken at the specialised units in Australia the prevalence of NHO in TBI patients and TSCI patients was found to be ~4% and 11%, respectively (Reznik et al., 2014). The audit undertaken at the nonspecialised hospital resulted in no records of NHO in TSCI/TBI patients, although six instances of HO (not related to TBI or TSCI) were recorded. (Reznik et al., 2015). The only common risk factors associated with NHO in both TBI and TSCI patients were deep vein thrombosis and/or pulmonary emboli (DVT/PE) (Reznik et al., 2014) with OR of 10.35 and 5.57 for TBI and TSCI, respectively. The remaining risk-factors were found to be discrete to the condition. In particular, spasticity (OR=27.75) followed by a period of intubation >25 days (OR=18.73), urinary tract infection (OR=6.74) and multiple injuries (OR=5.70) were identified as predictors of NHO in TBI patients. Multiple pressure ulcers (OR=5.61) and an AIS impairment score of B (OR= 3.59) were found to be predictors of HO in TSCI patients. Background data suggest that that ESWT may be associated with clinically significant improvement of range of motion (ROM) in the lower extremity joints of patients with HO, although there is limited evidence in the literature to confirm the effects of ESWT in TBI or TSCI patients. The results of a single case study undertaken in a TBI patient with chronic NHO at the hip were a reduction in pain, an increase in range of motion and improvement in gait parameters, suggesting that ESWT may be a non-invasive, low risk intervention for the management of NHO (Reznik et al, 2013a). Subsequently, a series of single case research studies was undertaken at a specialised rehabilitation hospital on 11 TBI patients with chronic NHO at the hip or knee joint, confirming the results achieved from the single case study. Overall the patients showed a significant reduction in pain and an improvement in all ranges of motion, except internal and external rotation of the hip. Overall function as measured by functional reach (FR) or modified functional reach (MFR) also showed improvement. Conclusions and clinical implications: The audit conducted at the non-specialised unit, which presented no records of NHO in TBI/TSCI patients, indicated that the problem may have been related to the coding used for these patients in the hospital. In the audit of the specialised units the prevalence of NHO in TBI patients was found to be less than one third of that found in TSCI patients, with many of the associated risk factors being quite discrete. The results of the series of single case research studies suggest that ESWT may be a non-invasive and effective treatment in the clinical management of NHO following TBI. Further replication of our findings by other groups using our protocol would enhance the evidence for this intervention