INTRODUCTION
Heterotopic ossification (HO) is a benign aberrant formation of lamellar bone in extra-skeletal soft tissues, usually developed around joints (1). More recently, the HO has been observed in about a quarter of brain-injured individuals with prolonged disorders of consciousness (DoC), regardless aetiology and level of consciousness (2). However, to date no specific risk factors for developing HO in such severely disabled patients have been identified.
In this context, the Special Interest Group on acquired brain injury and DoC of the Italian Society of Neurological Rehabilitation advised a multi-center observational study aimed at investigating the occurrence of HO and possible risk factors in a cohort of patients with prolonged DoC (i.e. vegetative state, VS and minimally conscious state, MCS) consecutively admitted to 23 intensive neuro-rehabilitation units qualified for expertise in post-acute care of patients with DoC. 
MATERIALS AND METHODS
Within 1 week from patients’ enrolment, all participating centers collected patients’ demographic and anamnestic information, level of consciousness, by Coma Recovery Scale- Revised (CRS-R) [3], level of functional disability, by the Disability Rating Scale (DRS) [4]; level of clinical complexity as measured by Early Rehabilitation Barthel Index (ERBI) [5]; presence of non-invasive ventilator support; presence (and skeletal region affected) of bone fractures occurred after brain injury. At 3 months after admission and during rehabilitation stay, the presence of HO (diagnosed by standard radiological or sonographic evaluation in presence of clinical evidence of limited range motion and/or evoked pain and/or local inflammatory signs of joints) and joint affected, occurrence of paroxysmal sympathetic hyperactivity and presence (and body region) of spasticity were also gathered. 
RESULTS
278 patients with prolonged DoC (191 males=191; mean age: 56.4 ± 17.5; time post-injury: 46.2 ± 22.3 days; VS=150, MCS=128) due to traumatic (n=83); anoxic (n=56), vascular (n=125) and other (n=14) etiology were included in the analysis.
Thirty-one patients developed HO within 3 months after admission. Presence of HO was significantly higher in patients in VS than in patients in MCS (p=.04) and in patients with traumatic than in patients with vascular, anoxic, or other etiology (p=0.003) Moreover, patients with HO showed higher DRS category (p=.03), and total score (p=.04), and bone fractures at study entry, and had more frequent limb spasticity, than patients without HO. Proportion of patients with HO did not differ from patients without HO for sex, age, time post-injury, CRS-R, and ERBI total scores, presence of non-invasive ventilator support at study entry, and presence of paroxysmal sympathetic hyperactivity during 3 months from neuro-rehabilitation admission (see Tab 1). 
CONCLUSIONS
The present multi-center observational study found that 11,2% of our sample developed HO within 3 months after admission in neuro-rehabilitation setting. The HO occurred more frequently in patients with worse clinical condition, as patients in VS and lower level of consciousness/responsiveness and functional disability and in patients with high occurrence of spasticity (located in the same muscle-skeletal region of HO). Moreover, the HO was significantly more frequent in patients with traumatic aetiology, whereas it rarely occurred in DoC patients with vascular brain injury. However, we did not observe any possible association with risk factors for occurrence of HO previously described in brain-injured patients [6] likely because of higher clinical complexity of patients with DoC.
References
1.	van Kampen PJ et al. J Head Trauma Rehabil 2011; 26: 384-391.
2.	Estraneo  et al. Arch Phys Med Rehabil 2018; 99:2523-2531.
3.	Giacino JT et al. Arch Phys Med Rehabil 2004;85:2020-9
4.	Rappaport. Arch Phys Med Rehabil 1982; 63: 118-123
5.	Schönle. Rehabilitation 1995; 34: 69-73.
6.	 Bargellesi S, et al. Clin Rehabil 2018;32:255-262.

A multi-centric observational study on heterotopic ossification in severely brain-injured patients with Disorders of Consciousness: preliminary data.