Subdural Hematoma as Clinical Presentation of Osteogenesis Imperfecta Anja Groninger, MD*, Jörg Schaper, MD†, Martina Messing-Juenger, MD‡, Ertan Mayatepek, MD*, and Thorsten Rosenbaum, MD* Osteogenesis imperfecta is an inherited collagenous disease. The mildest form may present with less severe findings, for example blue sclera, but can also lead to significant handicap such as deafness or multiple bone fractures. We describe an 11-month-old female in whom bilateral chronic subdural hematoma was the leading clinical presentation of osteogenesis imperfecta type I. She was hospitalized due to epileptic seizures caused by these bilateral subdural hematomas without preceding trauma. Osteogenesis imperfecta type I was diagnosed on the basis of clinical and radiologic findings. This case demonstrates that nontraumatic chronic subdural hematoma in patients with osteogenesis imperfecta type I may be caused by impaired bone calcification, vascular fragility, and permanent friction between multiple bone fragments of the skull. Osteogenesis imperfecta type I should be considered as an underlying disease in cases of nontraumatic subdural hematoma. A thorough clinical examination is recommended to exclude subtle characteristics of the disease. © 2005 by Elsevier Inc. All rights reserved. Groninger A, Schaper J, Messing-Juenger M, Mayatepek E, Rosenbaum T. Subdural hematoma as clinical presentation of osteogenesis imperfecta. Pediatr Neurol 2005;32:140-142. From the *Department of General Pediatrics, †Institute for Diagnostic Radiology, and ‡Department of Neurosurgery, Heinrich-HeineUniversity, Düsseldorf, Germany. 140 PEDIATRIC NEUROLOGY Vol. 32 No. 2 Introduction Osteogenesis imperfecta is a collagenous disease of autosomal-dominant inheritance or due to spontaneous mutation. The stable collagen I-molecule consists of two ␣1-chains and one ␣2-chain. This important protein exists in bone, tendons, ligaments, skin, sclera, teeth and middle and inner ear. Absent expression of one COL1A1 or COL1A2 allele on chromosome 17 leads to a 50% reduction of collagen synthesis [1]. In osteogenesis imperfecta type I, collagen I is quantitatively reduced but of normal quality. In contrast, more severe forms of the disease additionally manifest structural defects of the protein. Type I osteogenesis imperfecta does not necessarily result in multiple bone fractures, which are in fact typical for the more severe forms of the disease. In the majority of cases, a diagnosis of osteogenesis imperfecta can be established on the basis of clinical criteria. Blue sclera, temporal bone deformity, muscular hypotonia, and hyperflexibility of joints are suggestive of the disease. A caput membranaceum or wormian bones in the skull x-ray in addition to these clinical findings confirm the diagnosis. Collagen or genetic testing can be performed for further confirmation of the clinical diagnosis, but up to 15% of mildly affected individuals might still be tested negative. In osteogenesis imperfecta patients, capillary fragility may be increased whereas platelet retention may be decreased. Some laboratory data also suggest a reduced factor VIII [2]. The combination of vascular, plateletrelated, and plasmatic coagulation defects can lead to easy bleeding as a result of minimal trauma or even without previous trauma [3-5]. This report investigates bilateral chronic subdural hematoma in an 11-month-old female as the leading symptom of osteogenesis imperfecta type I. Case Report The female patient is the first child of healthy parents without consanguinity. There is no family history of osteogenesis imperfecta or easy fracturing. Pregnancy, birth, and further development were uneventful. At the age of 11 months, the female suddenly manifested an altered behavior and subsequently a first seizure. On hospitalization, cranial computed tomograms revealed massive bilateral chronic hematoma without any history of a preceding trauma or fracture. As an emergency Communications should be addressed to: Dr. Groninger; Department of General Pediatrics; Heinrich-Heine-University; Moorenstrasse 5; D-40225 Düsseldorf, Germany. Received February 26, 2004; accepted July 26, 2004. © 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2004.07.011 ● 0887-8994/05/$—see front matter Figure 1. X-ray of the skull revealing wormian bones. Figure 2. Magnetic resonance imaging scan (T1-weighted, axial) depicting bilateral subdural hematoma. procedure the subdural hematoma was unilaterally punctured in a foreign hospital. Afterwards the child was transferred to our clinic in stable condition. The 11-month-old infant was in good clinical condition, with body weight, height, and head circumference in the 90th percentile. She was alert and making efforts to stand alone with some help. However, on clinical examination a mild generalized muscular hypotonia was evident, and the child’s blue sclera were observed. The skull was protruding bitemporally and she had hyperflexible long fingers, as well as toes. Ophthalmologic examination revealed a corneal arcus senilis, one of the typical findings in mild osteogenesis imperfecta. X-rays of the left hand and skull yielded the typical picture of a caput membranaceum (Fig 1) and a marked osteoporosis. Hearing was not affected. Analysis of blood coagulation parameters and bleeding time were found to be normal. Based on these clinical and radiologic findings, the diagnosis of osteogenesis imperfecta type I was made in reference to “NIH Osteoporosis and Related Bone Diseases” guidelines. Given this straightforward clinical diagnosis, further genetic testing was not performed. A magnetic resonance imaging scan 7 days after the neurosurgical intervention (Fig 2) disclosed a progression of the bilateral subdural hematomas. At the same time, her clinical condition deteriorated: She presented with sunken eyes and increased pulse rate so that urgent neurosurgical intervention was necessary. This time the child received a bifrontal drainage which was maintained for 2 days. During the operation, massive amounts of chronic hematoma were discovered, indicating greatly increased intracranial pressure. Although the child quickly recovered after surgery, a pulsating burr hole was observed intermittently. Because of the intermittent nature of these symptoms and the child’s good condition, a subsequent intervention was not undertaken, keeping in mind that each intervention might cause new bleeding. A control cranial computed tomography scan 3 months after discharge indicated a persistent small hematoma without any clinical problems. At the age of 24 months, there were no neurologic deficits and the child was developing well, walking and talking adequately for her age. Discussion Osteogenesis imperfecta type I is characterized by a 10-30% incidence of bleeding diathesis [4,6]. Because of deficient production of collagen 1, an increased vascular fragility, a decreased platelet retention, as well as a deficient collagen-induced platelet aggregation, there is an increased risk of bleeding during surgery or even with only minor trauma [2,5,7]. It can be assumed that the collagen defect causes friable tissues, deficient platelet aggregation, and an inadequate small vessel constriction. Prolonged bleeding despite normal coagulation parameters has been reported in osteogenesis imperfecta patients by several authors [5,8]. Abnormalities of the cerebral artery system have been described [9] and may be another reason for the increased risk of intracerebral bleeding. So far, there is only one report of unilateral subdural hematoma in an infant with osteogenesis imperfecta type I [10]. This child also had a skull protrusion on the affected side. Bilateral chronic subdural hematoma in more severe forms of osteogenesis imperfecta but not in osteogenesis imperfecta type I has been described by other authors [3,11]. In general, chronic subdural hematoma is a rare but important manifestation of the disease. In the absence of Groninger et al: Subdural Hematoma in Osteogenesis Imperfecta 141 fractures as in the present case, it might be one of the first symptoms leading to hospitalization. This fact indicates that in these patients, osteogenesis imperfecta type I might not be recognized for a long time. Affected children may have normal psychomotor development and do not necessarily have bone fractures. However, they fracture easier and hearing loss and—as we could demonstrate—nontraumatic intracranial bleeding may occur. Unrecognized chronic subdural hematoma might subsequently cause psychomotor retardation, epileptic seizures, and even irreversible changes of the underlying brain [12-14]. To prevent this unfavorable outcome, clinical monitoring of these children is indispensable. This need is underlined by the observation that early therapy of subdural hematoma in children with osteogenesis imperfecta type I results in a good prognosis [15]. The present case clearly documents that diagnosis of osteogenesis imperfecta type I in its mildest form of this inherited collagenous disease may be missed in clinical examination. In this patient there was no history of fractures, development was adequate, and body measures were completely normal. Before the episode of an acute seizure, the child had no noticeable neurologic deficits, except for an unrecognized mild muscular hypotonia. Normal neurologic outcome despite chronic subdural hematoma might be explained by the bilateral manifestation which avoided a shift of midline structures and thus prevented more severe symptoms. In addition, the weak bone calcification led to temporal bone deformities, which also reduced further intracranial pressure. In light of the presented case, we suggest that osteogenesis imperfecta deserves consideration in the differential diagnosis of atraumatic subdural hematoma. 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