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Bilateral Subdural Hematomas in an Adult with Osteogenesis Imperfecta
Case Report
Bilateral Subdural Hematomas in an Adult with Osteogenesis Imperfecta Hussam Seif Eddeine, MD, Rima M. Dafer, MD, MPH, Michael J. Schneck, MD, FAAN, ´ Biller, MD, FACP, FAAN, FAHA FAHA, and Jose
Osteogenesis imperfecta (OI) is a rare inherited disorder characterized by disruption of normal collagen formation, brittle bones, and low bone density, predisposing to multiple bone fractures and wide-spectrum symptomatology. Extradural and subdural hematomas and spinal cord injuries have been reported but mainly in children with OI. We cared for a 60-year old woman with OI and bilateral nontraumatic subdural hematomas possibly caused by spontaneous intracranial hypotension. Key Words: Osteogenesis imperfecta—subdural hematoma— spontaneous intracranial hypotension. Ó 2009 by National Stroke Association
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disease affecting the collagen type I. OI leads to disruption of normal collagen formation predisposing to bone fractures, ligamentous laxity, joint hyperflexibility, bluish scleral discoloration, easy bruisability, and teeth abnormality. Unlike OI type I, OI type III is the most severe form, and is commonly associated with multiple bone fractures. Neurologic complications of OI may include macrocephaly, intracranial hemorrhages, hydrocephalus, basilar invagination, spine and skull fractures, and spinal deformity. Epidural and subdural hematomas (SDHs) have been reported in infants and children with this disorder. Intracranial hemorrhages have been attributed to underlying bleeding diathesis, vessel fragility, or bone indentation.
From the Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois. Received November 4, 2008; accepted November 11, 2008. Address correspondence to Rima M. Dafer, MD, MPH, Department of Neurology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, 2700 McGuire, Maywood, IL 60153. E-mail: rdafer@ lumc.edu. 1052-3057/$—see front matter Ó 2009 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2008.11.008
Case Report A 60-year-old woman with OI had sudden onset of severe positional, dull, holocephalic headaches after a prolonged bout of sneezing. Her headaches were exacerbated by Valsalva maneuver, and were followed by a brief syncope. She had received low molecular–weight heparin (enoxaparin) for deep vein thrombosis prophylaxis after knee surgery 2 weeks before clinical presentation. Her history was otherwise remarkable for multiple pelvic, spinal, and long-bone fractures, and bilateral hearing loss. General examination was remarkable for short stature, bluish discoloration of the sclera, tainted teeth, bilateral hearing loss, multiple bruises, kyphosis, and mild limitation of neck flexion. Neurologic examination revealed normal findings. Computerized cranial tomography (CT) showed bilateral subacute-on-chronic SDHs without skull fractures (Fig 1, A). Magnetic resonance imaging (MRI) of the brain with gadolinium confirmed the subacute SDHs. There was also diffuse patchy enhancement of the pachymeninges suggestive of intracranial hypotension syndrome (Fig 1, B and C). Her headaches resolved after 2 days of conservative treatment with hydration, bed rest, and analgesics. However, the patient returned 1 month later, with recurrent intractable postural headaches. A repeated CT scan showed resolution of the previously noted SDHs, with
Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 4 (July-August), 2009: pp 313-315
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H.SEIF EDDEINE ET AL.
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Figure 1. Axial head CT without contrast shows bilateral frontal/parietal/temporal SDH (A). Axial fluid-attenuated inversion recovery MRI shows bilateral subacute SDH (B). Coronal T1 MRI brain also shows diffuse pachymeningeal enhancement (C).
minimal residual pachymeningeal enhancement noted on MRI of the brain. MRI of the whole spine produced normal findings. Radionuclide cisternography demonstrated significant soft-tissue, kidneys, and bladder accumulation of the tracer, consistent with cerebrospinal fluid (CSF) leak, the location of which could not be identified (Fig 2). CT myelogram showed a collection of contrast at the medial aspect of the left psoas muscle adjacent to the L3 vertebral body (Fig 3 a), tracking toward the left L3 nerve root sleeve without evidence of direct communication (Fig 3 b). She was treated with an autologous epidural blood patch, hydration, and intravenous caffeine infusion with minimal improvement. Fortunately, her headaches subsequently resolved completely after a repeated epidural blood patch was performed.
Discussion The incidence of OI has been estimated to be about 1/ 20,000 births. OI has prominent skeletal manifestations with involvement of other structures rich in type I collagen such as joints, eyes, ears, and skin. The disorder is a result of a quantitative or qualitative defect in type I collagen resulting from a mutation in one of the two specific genes coding the alpha 1 and alpha 2 chains of the collagen
Figure 2.
molecules that combine to form type I collagen (COL1A1, COL1A2).1 OI is classified into 8 different types subtypes based on genetic analysis, radiographic and/or histologic findings, and clinical presentations. The main types include the milder types I and IV, the severe and fatal type II of infants, and the type III trait that is commonly associated with multiple bone fractures.2,3 Diagnosis is based on clinical and radiologic findings. Genetic studies are confirmatory. In OI type 1, there is decreased production of collagen type I with normal collagen I molecules, causing mild skeletal abnormalities. Other OI types are a result of production of abnormal polypeptide chains that cannot assemble into a triple helix configuration required for functional collagen molecules. Mutation in one of the two genes (COL1A1, COL1A2) occurs in 90% of the affected subjects.1,2,4-6 Bleeding complications may occur as a result of vessel fragility, deficient collagen-induced platelet aggregation, decreased level of factor VIII, impaired release of platelet factor 3, abnormal platelet aggregation to adenosine diphosphate, and defective aggregation to collagen.7 Intracranial arterial stenosis, arterial rupture moyamoya-like abnormalities, subarachnoid hemorrhage, and vertebral artery fenestration may occur as a result of
Significant soft-tissue, right kidney (black arrow), and bladder (white arrow) accumulation of tracer on radionuclide cisternography.
OSTEOGENESIS IMPERFECTA & SUBDURAL HEMATOMAS
Figure 3. body.
315
CT myelogram, in axial (A) and coronal (B) views, shows collection of contrast (arrow) at medial aspect of left psoas muscle adjacent to L3 vertebral
impaired bone calcification, vascular fragility, and friction between multiple bone fragments of the skull.8,9 SDHs associated with OI have been mainly reported in children.10-13 A fatal SDH has also been reported in an adult man with renal insufficiency while undergoing hemodialysis.14 SDH may also occur as a result of the intracranial hypotension syndrome caused by spontaneous CSF leak. The syndrome of intracranial hypotension is a known complication among subjects with underlying structural weakness of the meninges, especially among those with Marfan syndrome, Ehlers-Danlos syndrome type II, autosomal dominant polycystic kidney disease, and OI.15 To our knowledge, however, this is the first reported case of nontraumatic bilateral SDHs secondary to intracranial hypotension syndrome in an adult patient with OI. The diagnosis of intracranial hypotension syndrome was suspected on the basis of clinical presentation and MRI findings, and was further supported by findings on radionuclide cisternography and CT myelography. Patients with OI associated with nontraumatic SDHs should, therefore, be investigated for a possible CSF leak with resultant intracranial hypotension syndrome as a possible cause.
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References 1. Shapiro JR, Rowe DW. Collagen genes and brittle bones. Ann Intern Med 1983;99:700-704. 2. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101-116. 3. Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran’s pathologic basis of disease. 7th ed. St Louis: Elsevier Health Sciences, 2004:1279-1281. 4. Sillence DO, Barlow KK, Cole WG, et al. Osteogenesis imperfecta type III: Delineation of the phenotype with refer-
13.
14.
15.
ence to genetic heterogeneity. Am J Med Genet 1986; 23:821-832. Sillence DO, Barlow KK, Garber AP, et al. Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity. Am J Med Genet 1984; 17:407-423. Sillence DO, Rimoin DL, Danks DM. Clinical variability in osteogenesis imperfecta–variable expressivity or genetic heterogeneity. Birth Defects Orig Artic Ser 1979; 15(5B):113-129. Hathaway WE, Solomons CC, Ott JE. Platelet function and pyrophosphates in osteogenesis imperfecta. Blood 1972;39:500-509. Albayram S, Kizilkilic O, Yilmaz H, et al. Abnormalities in the cerebral arterial system in osteogenesis imperfecta. AJNR Am J Neuroradiol 2003;24:748-750. Okamura T, Yamamoto M, Ohta K, et al. A case of ruptured cerebral aneurysm associated with fenestrated vertebral artery in osteogenesis imperfecta [Japanese]. No Shinkei Geka 1995;23:451-455. Sasaki-Adams D, Kulkarni A, Rutka J, et al. Neurosurgical implications of osteogenesis imperfecta in children: Report of 4 cases. J Neurosurg Pediatr 2008;1:229-236. Cole WG, Lam TP. Arachnoid cyst and chronic subdural hematoma in a child with osteogenesis imperfecta type III resulting from the substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen. J Med Genet 1996;33:193-196. Tokoro K, Nakajima F, Yamataki A. Infantile chronic subdural hematoma with local protrusion of the skull in a case of osteogenesis imperfecta. Neurosurgery 1988; 22:595-598. Groninger A, Schaper J, Messing-Juenger M, et al. Subdural hematoma as clinical presentation of osteogenesis imperfecta. Pediatr Neurol 2005;32:140-142. Sayre MR, Roberge RJ, Evans TC. Nontraumatic subdural hematoma in a patient with osteogenesis imperfecta and renal failure. Am J Emerg Med 1987;5:298-301. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006; 295:2286-2296.
Bilateral Subdural Hematomas in an Adult with Osteogenesis Imperfecta Hussam Seif Eddeine, MD, Rima M. Dafer, MD, MPH, Michael J. Schneck, MD, FAAN, ´ Biller, MD, FACP, FAAN, FAHA FAHA, and Jose
Osteogenesis imperfecta (OI) is a rare inherited disorder characterized by disruption of normal collagen formation, brittle bones, and low bone density, predisposing to multiple bone fractures and wide-spectrum symptomatology. Extradural and subdural hematomas and spinal cord injuries have been reported but mainly in children with OI. We cared for a 60-year old woman with OI and bilateral nontraumatic subdural hematomas possibly caused by spontaneous intracranial hypotension. Key Words: Osteogenesis imperfecta—subdural hematoma— spontaneous intracranial hypotension. Ó 2009 by National Stroke Association
Osteogenesis imperfecta (OI) is a rare genetic connective tissue disease affecting the collagen type I. OI leads to disruption of normal collagen formation predisposing to bone fractures, ligamentous laxity, joint hyperflexibility, bluish scleral discoloration, easy bruisability, and teeth abnormality. Unlike OI type I, OI type III is the most severe form, and is commonly associated with multiple bone fractures. Neurologic complications of OI may include macrocephaly, intracranial hemorrhages, hydrocephalus, basilar invagination, spine and skull fractures, and spinal deformity. Epidural and subdural hematomas (SDHs) have been reported in infants and children with this disorder. Intracranial hemorrhages have been attributed to underlying bleeding diathesis, vessel fragility, or bone indentation.
From the Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois. Received November 4, 2008; accepted November 11, 2008. Address correspondence to Rima M. Dafer, MD, MPH, Department of Neurology, Loyola University Chicago, Stritch School of Medicine, 2160 S First Ave, 2700 McGuire, Maywood, IL 60153. E-mail: rdafer@ lumc.edu. 1052-3057/$—see front matter Ó 2009 by National Stroke Association doi:10.1016/j.jstrokecerebrovasdis.2008.11.008
Case Report A 60-year-old woman with OI had sudden onset of severe positional, dull, holocephalic headaches after a prolonged bout of sneezing. Her headaches were exacerbated by Valsalva maneuver, and were followed by a brief syncope. She had received low molecular–weight heparin (enoxaparin) for deep vein thrombosis prophylaxis after knee surgery 2 weeks before clinical presentation. Her history was otherwise remarkable for multiple pelvic, spinal, and long-bone fractures, and bilateral hearing loss. General examination was remarkable for short stature, bluish discoloration of the sclera, tainted teeth, bilateral hearing loss, multiple bruises, kyphosis, and mild limitation of neck flexion. Neurologic examination revealed normal findings. Computerized cranial tomography (CT) showed bilateral subacute-on-chronic SDHs without skull fractures (Fig 1, A). Magnetic resonance imaging (MRI) of the brain with gadolinium confirmed the subacute SDHs. There was also diffuse patchy enhancement of the pachymeninges suggestive of intracranial hypotension syndrome (Fig 1, B and C). Her headaches resolved after 2 days of conservative treatment with hydration, bed rest, and analgesics. However, the patient returned 1 month later, with recurrent intractable postural headaches. A repeated CT scan showed resolution of the previously noted SDHs, with
Journal of Stroke and Cerebrovascular Diseases, Vol. 18, No. 4 (July-August), 2009: pp 313-315
313
H.SEIF EDDEINE ET AL.
314
Figure 1. Axial head CT without contrast shows bilateral frontal/parietal/temporal SDH (A). Axial fluid-attenuated inversion recovery MRI shows bilateral subacute SDH (B). Coronal T1 MRI brain also shows diffuse pachymeningeal enhancement (C).
minimal residual pachymeningeal enhancement noted on MRI of the brain. MRI of the whole spine produced normal findings. Radionuclide cisternography demonstrated significant soft-tissue, kidneys, and bladder accumulation of the tracer, consistent with cerebrospinal fluid (CSF) leak, the location of which could not be identified (Fig 2). CT myelogram showed a collection of contrast at the medial aspect of the left psoas muscle adjacent to the L3 vertebral body (Fig 3 a), tracking toward the left L3 nerve root sleeve without evidence of direct communication (Fig 3 b). She was treated with an autologous epidural blood patch, hydration, and intravenous caffeine infusion with minimal improvement. Fortunately, her headaches subsequently resolved completely after a repeated epidural blood patch was performed.
Discussion The incidence of OI has been estimated to be about 1/ 20,000 births. OI has prominent skeletal manifestations with involvement of other structures rich in type I collagen such as joints, eyes, ears, and skin. The disorder is a result of a quantitative or qualitative defect in type I collagen resulting from a mutation in one of the two specific genes coding the alpha 1 and alpha 2 chains of the collagen
Figure 2.
molecules that combine to form type I collagen (COL1A1, COL1A2).1 OI is classified into 8 different types subtypes based on genetic analysis, radiographic and/or histologic findings, and clinical presentations. The main types include the milder types I and IV, the severe and fatal type II of infants, and the type III trait that is commonly associated with multiple bone fractures.2,3 Diagnosis is based on clinical and radiologic findings. Genetic studies are confirmatory. In OI type 1, there is decreased production of collagen type I with normal collagen I molecules, causing mild skeletal abnormalities. Other OI types are a result of production of abnormal polypeptide chains that cannot assemble into a triple helix configuration required for functional collagen molecules. Mutation in one of the two genes (COL1A1, COL1A2) occurs in 90% of the affected subjects.1,2,4-6 Bleeding complications may occur as a result of vessel fragility, deficient collagen-induced platelet aggregation, decreased level of factor VIII, impaired release of platelet factor 3, abnormal platelet aggregation to adenosine diphosphate, and defective aggregation to collagen.7 Intracranial arterial stenosis, arterial rupture moyamoya-like abnormalities, subarachnoid hemorrhage, and vertebral artery fenestration may occur as a result of
Significant soft-tissue, right kidney (black arrow), and bladder (white arrow) accumulation of tracer on radionuclide cisternography.
OSTEOGENESIS IMPERFECTA & SUBDURAL HEMATOMAS
Figure 3. body.
315
CT myelogram, in axial (A) and coronal (B) views, shows collection of contrast (arrow) at medial aspect of left psoas muscle adjacent to L3 vertebral
impaired bone calcification, vascular fragility, and friction between multiple bone fragments of the skull.8,9 SDHs associated with OI have been mainly reported in children.10-13 A fatal SDH has also been reported in an adult man with renal insufficiency while undergoing hemodialysis.14 SDH may also occur as a result of the intracranial hypotension syndrome caused by spontaneous CSF leak. The syndrome of intracranial hypotension is a known complication among subjects with underlying structural weakness of the meninges, especially among those with Marfan syndrome, Ehlers-Danlos syndrome type II, autosomal dominant polycystic kidney disease, and OI.15 To our knowledge, however, this is the first reported case of nontraumatic bilateral SDHs secondary to intracranial hypotension syndrome in an adult patient with OI. The diagnosis of intracranial hypotension syndrome was suspected on the basis of clinical presentation and MRI findings, and was further supported by findings on radionuclide cisternography and CT myelography. Patients with OI associated with nontraumatic SDHs should, therefore, be investigated for a possible CSF leak with resultant intracranial hypotension syndrome as a possible cause.
5.
6.
7.
8.
9.
10.
11.
12.
References 1. Shapiro JR, Rowe DW. Collagen genes and brittle bones. Ann Intern Med 1983;99:700-704. 2. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101-116. 3. Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran’s pathologic basis of disease. 7th ed. St Louis: Elsevier Health Sciences, 2004:1279-1281. 4. Sillence DO, Barlow KK, Cole WG, et al. Osteogenesis imperfecta type III: Delineation of the phenotype with refer-
13.
14.
15.
ence to genetic heterogeneity. Am J Med Genet 1986; 23:821-832. Sillence DO, Barlow KK, Garber AP, et al. Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity. Am J Med Genet 1984; 17:407-423. Sillence DO, Rimoin DL, Danks DM. Clinical variability in osteogenesis imperfecta–variable expressivity or genetic heterogeneity. Birth Defects Orig Artic Ser 1979; 15(5B):113-129. Hathaway WE, Solomons CC, Ott JE. Platelet function and pyrophosphates in osteogenesis imperfecta. Blood 1972;39:500-509. Albayram S, Kizilkilic O, Yilmaz H, et al. Abnormalities in the cerebral arterial system in osteogenesis imperfecta. AJNR Am J Neuroradiol 2003;24:748-750. Okamura T, Yamamoto M, Ohta K, et al. A case of ruptured cerebral aneurysm associated with fenestrated vertebral artery in osteogenesis imperfecta [Japanese]. No Shinkei Geka 1995;23:451-455. Sasaki-Adams D, Kulkarni A, Rutka J, et al. Neurosurgical implications of osteogenesis imperfecta in children: Report of 4 cases. J Neurosurg Pediatr 2008;1:229-236. Cole WG, Lam TP. Arachnoid cyst and chronic subdural hematoma in a child with osteogenesis imperfecta type III resulting from the substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen. J Med Genet 1996;33:193-196. Tokoro K, Nakajima F, Yamataki A. Infantile chronic subdural hematoma with local protrusion of the skull in a case of osteogenesis imperfecta. Neurosurgery 1988; 22:595-598. Groninger A, Schaper J, Messing-Juenger M, et al. Subdural hematoma as clinical presentation of osteogenesis imperfecta. Pediatr Neurol 2005;32:140-142. Sayre MR, Roberge RJ, Evans TC. Nontraumatic subdural hematoma in a patient with osteogenesis imperfecta and renal failure. Am J Emerg Med 1987;5:298-301. Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA 2006; 295:2286-2296.