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Neuroradiology Case of the Week

Case 408

May 2009

Gurshawn Singh, MS2, and Rajiv Mangla, MD

Clinical Presentation: Patient is a 6-year-old child who has undergone bone marrow transplant for treatment of osteopetrosis.

Imaging Findings: Diffuse sclerosis of the skull bones on CT with bone in bone appearance classically visualized in the region of the bilateral petrous and basiocciput bones. MRI showed significant prominence of sub-arachnoid spaces which were also bulging outside in the region of the anterior fontanel. Venogram showed narrowing in the region of the sigmoid sinuses. MRI of the orbits showed thin atrophic bilateral optic nerves with prominent CSF sleeves. Findings in the appendicular skeleton also showed classical appearances of bone in bone appearance as seen in osteopetrosis.

Diagnosis: Cranial imaging findings in autosomal recessive (malignant) osteopetrosis

Discussion: Osteopetrosis can present as two different clinical cases, autosomal recessive osteopetrosis and autosomal dominant osteopetrosis. Autosomal recessive osteopetrosis presents in infancy and is diagnosed at very young ages with a malignant phenotype whereas autosomal dominant osteopetrosis usually presents in adulthood and is benign in nature.
     Our patient had autosomal recessive osteopetrosis and initially had an unremarkable delivery and unremarkable examination at 12 weeks. However, vision impairment was of concern, which was confirmed later by examination by the ophthalmologist. Significant bulging of the anterior fontanel was apparent and the child later developed vomiting and irritability. Also remarkable was his poor weight and height gain despite normal head circumference. His height and weight were in the 10th percentile while head circumference was 98th percentile at 12 weeks. At this point, the diagnosis of osteopetrosis and failure to thrive was made.
     Our patient had hydrocephalus causing pressure in the brain, and as a result, a ventriculoparietal shunt was inserted. The child underwent typical treatment for osteopetrosis of bone marrow transplant. Bone marrow transplant is usually performed to increase the presence of osteoclast precursors, so recurrent bone remodeling can occur. Since osteopetrosis is manifested by a decrease in function of osteoclasts, it is important that osteoclast function is established in treatment.
     Osteopetrosis patients present with failure to thrive, bony defects of the skull, delayed dentition, fragile and easily fractured bones, hydrocephalus, deafness, and proptosis. The patient presented had almost all of the common symptoms, along with very convincing radiological findings. Most notably were findings associated with the petrous portion of the temporal bone with a bone in bone appearance, which is characteristic to osteopetrosis. Osteopetrosis is manifested by a failure of osteoclasts to resorb bone with normal osteoblast bone formation, resulting in abnormally dense bone, which can be seen on radiographs as abnormally dense bone with a bone in bone appearance.
     Tonsillar herniation, proptosis, dural venous sinus stenosis, and ventriculomegaly, can be seen in most patients with autosomal recessive osteopetrosis. Atrophy of the optic nerve and narrowing of the optic nerve canal are also usually present. Calvarial thickening is present and maybe responsible for tonsillar herniation, hydrocephaly, and optic nerve sheath dilation. Primarily in osteopetrosis, there will be sclerosis evident in both axial and appendicular skeletons, but endobone presence will be in the localized to the skull.
Normally, the receptor activator of nuclear factor kappa B ligand(RANKL) produced by osteoblasts activates osteoclasts, however genetic defects cause an abnormal increase in osteoprotegrin, a decoy receptor which bind and inhibit RANKL from stimulating osteoclast differentiation and function.
     Carbonic anhydrase II deficiency is usually associated with autosomal recessive osteopetrosis. Patients with this enzyme deficiency in osteopetrosis can develop renal tubular acidosis and cerebral calcification. Fractures, short stature, dental abnormalities, cranial nerve compression, and developmental delays are all manifestations that may occur as a result because of the inability of osteoclasts to create an acid environment for bone resorption. Bone marrow transplant is usually successful in treating the clinical manifestations, except the renal tubular acidosis if present pre-transplant. This patient did not present with renal tubular acidosis so this was not a complication, and all their clinical manifestations were specific to osteoclast dysfunction.
     This patient had the autosomal recessive malignant type of osteopetrosis. This condition is very rare, with incidence of 1 in 300,000 births and fatal if not treated appropriately. Our patient received proper treatment via bone marrow transplant but developed graft versus host disease as a result of the therapy. The osteopetrotic endobone appearance seen in pre-transplant radiographs with high bone radiodensity of the petrous bone were normal 6 months post-transplant, indicating transplant was successful and osteoclast function was established. Osteopetrosis can also lead to hydrocephalus. This is most likely attributed to inadequate space for flow of cerebral spinal fluid, since bone is intruding on that space.

References:

1. Tolar J, Teitelbaum SL, Orchard PJ. Osteopetrosis. N Engl J Med. 2004 Dec 30;351(27):2839-49. [PubMed]
2. Carolino J, Perez JA, Popa A. Osteopetrosis. Am Fam Physician. 1998 Mar 15;57(6):1293-6. [PubMed] http://www.aafp.org/afp/980315ap/carolino.html
3. Bhargava A, Blank, R. Osteopetrosis. eMedicine. September 19, 2007. http://emedicine.medscape.com/article/123968-overview
4. Curé JK, Key LL, Goltra DD, VanTassel P. Cranial MR imaging of osteopetrosis. AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1110-5. [PubMed]