Unusual association of diseases/symptoms

CASE REPORT

Intracerebral haemorrhage and hemiplegia with
heterotopic ossification of the affected hip
M M C O’Brien,1 T Murray,2 F Keeling,2 D Williams3
1

Department of Geriatric
Medicine, Beaumont Hospital,
Dublin, Ireland
2
Department of Radiology,
Beaumont Hospital, Dublin,
Ireland
3
Department of Geriatric and
Stroke Medicine, Royal College
of Surgeons in Ireland and
Beaumont Hospital, Dublin,
Ireland
Correspondence to
Dr M M C O’Brien,
drmichelleobrien@gmail.com
Accepted 20 July 2015

SUMMARY
We present the case of a 72-year-old woman who
developed right hemiparesis following a left frontal
intraparenchymal haemorrhage. Three months following
initial presentation, the patient noted poorly localised
right lower quadrant pain. Following extensive
investigations, a diagnosis of heterotopic ossification of
the hip was made. We discuss the aetiology and
pathogenesis of this uncommon entity, and discuss its
relationship to ipsilateral neurological injury. The link
with neurological injury can result in a delayed and
atypical presentation. Early recognition and treatment are
important for those caring for patients with acquired
neurological deficits, and permit improved patient
outcomes.

BACKGROUND
Spontaneous intracerebral haemorrhage is the
second most common cause of stroke and carries a
high morbidity and mortality rate. The incidence of
intracerebral haemorrhage is approximately 16–33
cases per 100 000.1 It is widely acknowledged that
such patients require to be managed in an intensive
care unit whereby the patient’s vitals are monitored
regularly and managed appropriately. Heterotopic
ossification (HO) is a rare phenomenon and has
been documented to occur in patients with hemiplegia. We present a case of HO secondary to spontaneous intracerebral haemorrhage, and describe
the importance of differentiating this benign entity
from other more sinister causes of soft-tissue
calcification.

haemorrhage. Antiepileptic medication with levetiracetam was started.
Two months postinitial presentation the patient
reported poorly localised right iliac fossa pain.
Owing to dysarthria and dysphasia, patient history
was difficult and site of pain was difficult to elicit.
Initial abdominal investigation comprised of a plain
film X-ray of the abdomen and an ultrasound
abdomen, which were unremarkable. A radiograph
of the pelvis was performed, to exclude a pelvic
cause of the poorly-localised right flank pain. The
pelvic radiograph demonstrated calcification extending from the lateral margin of the acetabulum and
proximal femur (figure 1). It was thought that this
may be due to heterotopic bone formation or an
underlying bony lesion. At this point, a wide differential diagnosis was suggested, included exostosis,
osteochondroma, parosteal osteosarcoma and softtissue sarcoma. CT of bilateral hips showed extensive calcification/ossification in the soft tissue and
gluteal musculature adjacent to the right hip joint
(figure 2). It appeared to be separate from the bone
except at the most inferior aspect just inferior to the
lesser trochanter where it was not seen separately
from the surface of the femur. Fluoroscopic bone
biopsy was performed, as the history of pain was
concerning for malignant transformation.
Alkaline phosphatase (AP) results on admission
showed an AP of 60 (ref range; 30–130) which steadily increased over 4 weeks to a peak of 306, remaining at that level for a further month (figure 3). It was

CASE PRESENTATION

To cite: O’Brien MMC,
Murray T, Keeling F, et al.
BMJ Case Rep Published
online: [ please include Day
Month Year] doi:10.1136/
bcr-2015-211467

A 72-year-old woman presented to a tertiary referral
hospital with acute onset dense right-sided hemiparesis. Medical history was significant for type 2 diabetes mellitus, hypertension and depression.
Examination on admission revealed hypertension
(145/95 mm Hg). National Institute of Health Stroke
Score (NIHSS) was 24/34, and Glasgow Coma Scale
(GCS) was 11/15. Non-contrast CT of the brain on
admission demonstrated a left frontal parenchymal
haemorrhage. Medical management was initiated.
Four weeks following acute presentation, paroxysmal
atrial fibrillation was diagnosed. The patient developed bilateral pulmonary emboli with an associated
right heart strain. A temporary inferior vena cava
filter was inserted, and anticoagulation was started
following resolution of the intraparenchymal haemorrhage. New onset of seizure activity ensued some
months postinitial presentation. Repeat imaging
demonstrated a new right frontal lobe subarachnoid

Figure 1 Plain film radiograph demonstrates diffuse
calcification surrounding the right hip. The joint itself is
preserved.

O’Brien MMC, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-211467

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Unusual association of diseases/symptoms

Figure 4 Planar sctintigraphic imaging demonstrates increased
radioisotope within the right hip and surrounding soft-tissue. Further
urinary isotope noted within urinary catheter.
Figure 2 Axial CT demonstrates calcification within the soft tissue
extending from the right acetabulum and ischium medially, to the
proximal femur laterally.
at that time that investigations into the right iliac fossa and hip
pain began. Our patient was treated with analgesia while investigations were undertaken. Slowly over the following 8 weeks, the AP
steadily decreased to a level of 120 and remained in the normal
range.
The biopsy demonstrated disorganised fibrous tissue and bony
fragments within the biopsy, but did not reveal any malignant
cells. 99mTechnetium bone scan was performed. Marked increase
in radioisotope activity was noted at the right hip (figure 4), corresponding with the site of the known soft tissue ossification and
patient symptoms. The remainder of the axial skeleton and the
lower limbs were within normal limits. The characteristic differentiating feature in this case was osseous maturation and development of a peripheral corticated rim on imaging.

INVESTIGATIONS
Plain film radiograph demonstrated diffuse calcification surrounding the right hip. The joint itself was preserved.

CT demonstrated calcification within the soft tissue extending
from the right acetabulum and ischium medially, to the proximal
femur laterally.
Planar sctintigraphic imaging demonstrated increased radioisotope within the right hip and surrounding soft-tissue. Further
urinary isotope was noted within urinary catheter.

DIFFERENTIAL DIAGNOSIS
▸ Heterotopic ossification
▸ Osteochondroma with malignant transformation into a
chondrosarcoma
▸ Exostosis
▸ Parosteal osteosarcoma
▸ Soft-tissue sarcoma

TREATMENT
From a multidisciplinary perspective, this patient was assessed
by the stroke rehabilitation team shortly following admission to
the stroke unit, with input from nursing, physiotherapy, occupational therapy, speech and language therapy and nutritionists.
Rehabilitation continued over the following weeks. On onset of

Figure 3 Alkaline phosphatase (AP)
results increased from normal range on
admission (ref range; 30–130) to a
peak of 306.

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O’Brien MMC, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-211467

Unusual association of diseases/symptoms
the right iliac fossa and right hip pain, analgesia was started and
investigation ensued. Rehabilitation was intermittently halted
due to it causing discomfort to the patient. The patient required
assistance of two people for functional movement, when reassessed 3 months later, the same result was noted. A mild passive
range of movement exercise programme followed.
Reported management plans for patients with HO include;
identifying those at risk and treating prophylactically, surgical
intervention, radiotherapy and physiotherapy.

HO may be more prevalent in acquired neurological deficits
than the quoted 0.5–1.2%, given the diagnostic challenges in
this cohort of patients. There are several common pathological
processes in a hemiplegic limb, notably soft-tissue strain in the
setting of contractures, premorbid arthritis, or altered sensation
due to stroke.15 HO should be considered in the correct clinical
context, and clinicians dealing with this patient cohort should
be aware of this entity.

OUTCOME AND FOLLOW-UP
A conservative management plan was adopted in this case with
regular analgesia and additional pain relief as required. In addition, a gentle passive range of movement exercise programme
was followed. No significant improvement in functional status
was noted.

DISCUSSION
HO is the formation of bone in an abnormal site. Generally,
lamellar bone forms in the soft tissue surrounding a joint.2 It
was first described by Patin in 16923 when working with children diagnosed with myositis ossificans progressive, a rare
genetic disorder characterised by the progressive ossification of
skeletal muscle. Dejerine and Celier4 described a similar entity
in patients with spinal cord injury in the aftermath of World
War I. In 1954, it was first documented by Irving and LeBrun in
patients with hemiplegia.5 HO in post-stroke hemiplegia occurs
in 0.5–1.2%.6 Its diagnosis is often confused with and mimicked
by a number of other conditions including; cellulitis, osteomyelitis, thrombophlebitis, osteosarcoma and osteochondroma.
Presentation of HO can be due to pain, palpable mass, fever,
decreased range of motion, decreased mobility, inflammation,
swelling or effusion. Two forms appear to exist; acquired and
hereditary. The acquired form is the more common and can be
due to trauma or a neurogenic cause. The inherited form is
known as myositis ossificans progressiva.7 HO in the acquired
form has been documented to be caused by head injuries,
stroke, encephalitis, spinal cord injuries, burns or direct muscle
trauma.2 8 The true aetiology of HO remains unknown. Many
hypotheses exist including neuronal control mechanisms9 and
bone morphogenetic protein transforming mesenchymal muscle
cells from fibrous tissue into bone.10 Suggested contributing
factors including prostaglandin E2 (PGE2), osteoblast stimulating factors, hypercalcaemia, hypoxia, changes in sympathetic
nerve activity, prolonged immobilisation, remobilisation and disequilibrium of parathyroid hormone and calcitonin.7
Diagnosis of HO can be aided by AP screening, use of 24 h
prostaglandin E2 (PGE2) urinary excretion, and use of various
imaging modalities.7 AP can increase early in the process before
subsequently decreasing to normal range although this pattern
can vary. Urinary prostaglandin E2 has also been documented as
an early indicator of HO. The radiological modalities used to
diagnose HO include plain film radiography, radioisotope bone
scan, CT and MRI. Treatment options for HO include bisphosphonates, non-steroidal anti-inflammatories, radiation therapy
and surgery.7 A recommended timetable for proposed surgery
to areas affected by HO does exist. In cases with acquired
neurological deficits, 18 months following development of HO
has been suggested.11 Bone scans, AP measurements, patient’s
symptoms and signs are also useful in determining the optimum
surgical timing. There are conflicting viewpoints in the literature
regarding the benefits of range of motion exercise in patients
with HO. It has been suggested that it may contribute to development,12 while others state it is a valuable treatment aid.13 14
O’Brien MMC, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-211467

Learning points
▸ Haemorrhagic stroke can be associated with significant
morbidity and mortality, it is a debilitating condition.
▸ Clinicians should be aware that heterotopic ossification is a
condition, which although rare, can occur in patients with
hemiplegia due to stroke.
▸ Alkaline phosphatase levels, 24 h prostaglandin E2 (PGE2)
urinary excretion levels and imaging modalities may be
utilised to investigate and diagnose heterotopic ossification.
▸ Treatment of heterotopic ossification can include;
bisphosphonates, non-steroidal anti-inflammatories,
radiation therapy, surgery and physiotherapy.

Contributors Contributors to this case include the listed authors who represent the
general medical team and radiology colleagues. Additional contributors include the
multidisciplinary team, laboratory and pathology diagnostic staff. MMCO is
guarantor of this case report.
Competing interests None declared.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.

REFERENCES
1
2
3
4
5

6
7
8
9
10

11
12

13
14
15

Sacco S, Marini C, Toni D, et al. Incidence and 10-year survival of intracerebral
hemorrhage in a population-based registry. Stroke 2009;40:394–9.
Kocaaga Z, Bal S, Gurgan A. Hemiplegia and heterotopic ossification on the
non-paretic extremity: a case report. J Rehabil Med 2007;39:500–2.
Bossche LV, Vanderstraeten G. Heterotopic ossification: a review. J Rehabil Med
2005;37:129–36.
Dejerine A, Ceilier A. Para-osteo-arthropathies des paraplegiques par lesion
medullaire; etude clinique et radiographique. Ann Med 1918;5:497.
Speed J, Banovac K, Sheridan RL, et al. Medscape. Heterotopic Ossification.
Medscape. Updated May 28th 2013. http://emedicine.medscape.com/article/
327648-overview
Varghese G. Heterotopic ossification. Phys Med Rehab Clin North Am
1992;3:407–15.
Shehab D, Elgazzar AH, Collier BD. Heterotopic ossification. J Nucl Med
2002;43:346–53.
Teasell R. Musculoskeletal complications of hemiplegia following stroke. Semin
Arthritis Rheum 1991;20:385–95.
Garland DE. Heterotopic ossification. In: Nickell VL, Botte MJ, eds. Orthopedic
rehabilitation. New York: Livingstone, 1992:452–69.
Urist MR, Nakagawa M, Nakata N, et al. Experimental myositis ossificans: cartilage
and bone formation in muscle in response to diffusible bone matrix-derived
morphogen. Arch Pathol Lab Med 1978;102:312–16.
Garland DE. A clinical perspective on common forms of acquired heterotopic
ossification. Clin Orthop 1991;263:13–29.
Michelsson JE, Ganroth G, Andersson LC. Myositis ossificans following forcible
manipulation of the leg. A rabbit model for the study of heterotopic bone
formation. J Bone Joint Surg Am 1980;62:811–15.
Stover SL, Hataqay CJ, Zeiger HE. Heterotopic ossification in spinal cord injured
patients. Arch Phys Med Regabil 1975;56:199–204.
Wharton GW, Morgan TH. Ankylosis in the paralyzed patients. J Bone Joint Surg
Am 1970;52:105–12.
Hajek VE. Heterotopic ossification in hemiplegia following stroke. Arch Phys Med
Rehabil 1987;68:313–14.

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Unusual association of diseases/symptoms
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O’Brien MMC, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2015-211467