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Subdural haematoma, non-accidental head injury or . . . ?
doi: 10.1053/ejpn.2001.0500 available online at http://www.idealibrary.com on European Journal of Paediatric Neurology 2001; 5: 175±176
COMMENTARY
Subdural haematoma, non-accidental head injury or . . . ? JOHN H MENKES Professor Emeritus of Neurology and Pediatrics, University of California, Los Angeles, Director Emeritus of Pediatric Neurology, Cedars Sinai Medical Center, USA
The neurologist asked to consult on an infant found to have a subdural haematoma on a neuroimaging study should have a high index of suspicion that the infant was the victim of an inflicted injury. His suspicion will become near certainty when the imaging studies disclose more than one subdural haemorrhage of different chronicity, when radiographs of long bones show a fracture or a diaphyseal periosteal reaction reminiscent of that seen following repeated trauma, and when there are retinal haemorrhages. Yet, other diagnoses must be considered and excluded. Subdural haemorrhages are common in Menkes' disease, and develop with progression of the condition. Two factors are responsible for this complication. Cerebral atrophy is frequent and usually can be demonstrated during the first few months of life. Loss of brain tissue is believed to be due to the reduced activity of the various coppercontaining enzymes, in particular from mitochondrial dysfunction and from vascular lesions. As a result the subdural bridging veins elongate. Dysfunction of copper-dependent lysyl oxidase induces a failure in elastin and collagen crosslinking. Veins become tortuous, have an irregular lumen and a frayed and split intimal lining. These factors predispose to recurrent subdural haemorrhages that develop spontaneously or as a result of relatively minor head trauma.1,2 Multiple and recurrent pathologic fractures of the long bones, the mandible and the skull are common. They were seen in 58% of patients in the series of Baerlocher and Nadal, and result in cortical thickening of the long bones.3 The tortuosity and friability of the retinal vasculature
predispose to retinal haemorrhages that are another albeit less common feature of Menkes' disease. The diagnosis of Menkes' disease is based on a clinical history of developmental arrest or regression, hypotonia, seizures, and the appearance of the infant, in particular the unusual colourless and friable hair. The poor pigmentation is due to defective activation of tyrosinase, a process that is dependent on the copper-transporting P-type ATPase, MNK.4 A number of hair shaft abnormalities are evident under the microscope. Most commonly one sees pill torti, a hair shaft that is flattened and twisted 180 degrees on its own axis. Many other different abnormalities are also present and eyebrows and eyelashes can be affected.5 After the first month of life reduced serum caeruloplasmin and copper confirm the clinical diagnosis. A clinical picture that features subdural haematomas and retinal haemorrhages is inherent to glutaric aciduria type 1 (GA1), an autosomal recessive disease with an estimated population frequency of 1 in 30 000 neonates. The condition is caused by a defect in the gene that codes for glutaryl-CoA dehydrogenase. For reasons that are still poorly explained but in part are probably due to the stretching of bridging veins that attend cerebral atrophy, acute or chronic subdural haematomas and effusions are found in 20±30% of subjects with this condition.6 Haematomas often are induced by relatively minor trauma not only in this condition but also in various other conditions associated with significant cerebral atrophy. Retinal haemorrhages are seen in some 20±30% of subjects with GA1.6, 7 In at least one infant with
Received 20.04.2001. Accepted 28.04.2001. Correspondence: Professor J H Menkes, 9320 Wilshire Blvd, Suite 202, Beverly Hills, CA 90212-3216. e-mail: [email protected]
1090±3798/01/05/0175+2 $35.00
& 2001 European Paediatric Neurology Society
176 GA1 there also was a periosteal reaction suggesting recurrent trauma.7 There are wide phenotypic variations in GA1, and unless urinary organic acid analysis is performed, the diagnosis can easily be overlooked.8 Unlike in other organic acidaemias there often is no metabolic or lactic acidosis, and hypoglycaemia or hyperammonaemia are rarely found. A positive urine organic acid screen should be followed by measurement of plasma total and free carnitine, and determination of glutaryl-CoA dehydrogenase activity.9 When diagnosed early GA1 can be treated with a limited intake of dietary protein and a diet deficient in the amino acids lysine, hydroxylysine and tryptophan.10 Another genetic defect that can present during infancy with a subdural haematoma and retinal haemorrhage is the Hermansky±Pudlak syndrome.11 This rare autosomal recessive disorder is characterized by oculocutaneous albinism, lysosomal ceroid storage, and a lifelong bleeding tendency. The material stored is histochemically similar to that stored in neuronal ceroid lipofuscinosis, and the Hermansky±Pudlak syndrome results from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules and lysosomes.12 Haemorrhagic disease of the newborn is one of the various other bleeding disorders that can induce the combination of subdural haematoma and retinal haemorrhage.13 Less often the underlying cause is a disorder in electrolyte balance, notably hypo- and hypernatraemia. Even though child abuse must be on top of the differential diagnosis for all infants who present with retinal haemorrhages and subdural haematoma, the physician should avoid being swept up by the recent enthusiasm for reporting child abuse cases, and be certain to exclude the various metabolic, genetic and haemorrhagic disorders that can mimic non-accidental trauma.
Commentary: J H Menkes
References 1 Menkes JH. Menkes disease and Wilson disease: two sides of the same copper coin. Part I. Menkes disease. Eur J Paediatr Neurol 1999; 3: 147±158. 2 Howard MA, Bell BA, Uttley D. The pathophysiology of infant subdural haematomas. Br J Neurosurg 1993; 7: 355±365. 3 Baerlocher K, Nadal D. Das Menkes-Syndrom. Ergeb Inn Med Kinderheilk 1988; 57: 77±144. 4 Petris MJ, Strausak D, Mercer JF. The Menkes copper transporter is required for the activation of tyrosinase. Hum Mol Genet 2000; 9: 2845±2851. 5 Powell J, Ferguson DJ, Dawber RP. Is kinky-hair disease a misnomer for Menkes syndrome? Arch Dermatol 2001; 137: 92±93. 6 Hoffmann GF, Athanassopoulos S, Burlina AB et al. Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 1996; 27: 115±123. 7 Hartley LM, Khwaja OS, Verity CM. Glutaric aciduria type 1 and nonaccidental head injury. Pediatrics 2001; 107: 174±176. 8 Superti-Furga A, Hoffmann GF. Glutaric aciduria type 1 (glutaryl-coA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. Eur J Pediatr 1997; 156: 821±828. 9 Morris AAM, Hoffmann GF, Naughten ER., et al. Glutaric aciduria and suspected child abuse. Arch Dis Child 1984; 80: 404±405. 10 Monavari AA, Naughten ER. Prevention of cerebral palsy in glutaric aciduria type 1 by dietary management. Arch Dis Child 2000: 82: 67±70. 11 Russell-Eggitt IM, Thompson DA, Khair K et al. Hermansky±Pudlak syndrome presenting with subdural haematoma and retinal haemorrhages in infancy. J R Soc Med 2000; 93: 591±592. 12 Oh J, Bailin T, Kukai K et al. Positional cloning of a gene for Hermansky±Pudlak syndrome, a disorder of cytoplasmic organelles. Nature Genet 1996; 14: 300±306. 13 Rutty GN, Smith CM, Malia RG. Late-form hemorrhagic disease of the newborn: a fatal case report with illustration of investigations that may assist in avoiding the mistaken diagnosis of child abuse. Am J Forensic Med Pathol 1999; 20: 48±51.
COMMENTARY
Subdural haematoma, non-accidental head injury or . . . ? JOHN H MENKES Professor Emeritus of Neurology and Pediatrics, University of California, Los Angeles, Director Emeritus of Pediatric Neurology, Cedars Sinai Medical Center, USA
The neurologist asked to consult on an infant found to have a subdural haematoma on a neuroimaging study should have a high index of suspicion that the infant was the victim of an inflicted injury. His suspicion will become near certainty when the imaging studies disclose more than one subdural haemorrhage of different chronicity, when radiographs of long bones show a fracture or a diaphyseal periosteal reaction reminiscent of that seen following repeated trauma, and when there are retinal haemorrhages. Yet, other diagnoses must be considered and excluded. Subdural haemorrhages are common in Menkes' disease, and develop with progression of the condition. Two factors are responsible for this complication. Cerebral atrophy is frequent and usually can be demonstrated during the first few months of life. Loss of brain tissue is believed to be due to the reduced activity of the various coppercontaining enzymes, in particular from mitochondrial dysfunction and from vascular lesions. As a result the subdural bridging veins elongate. Dysfunction of copper-dependent lysyl oxidase induces a failure in elastin and collagen crosslinking. Veins become tortuous, have an irregular lumen and a frayed and split intimal lining. These factors predispose to recurrent subdural haemorrhages that develop spontaneously or as a result of relatively minor head trauma.1,2 Multiple and recurrent pathologic fractures of the long bones, the mandible and the skull are common. They were seen in 58% of patients in the series of Baerlocher and Nadal, and result in cortical thickening of the long bones.3 The tortuosity and friability of the retinal vasculature
predispose to retinal haemorrhages that are another albeit less common feature of Menkes' disease. The diagnosis of Menkes' disease is based on a clinical history of developmental arrest or regression, hypotonia, seizures, and the appearance of the infant, in particular the unusual colourless and friable hair. The poor pigmentation is due to defective activation of tyrosinase, a process that is dependent on the copper-transporting P-type ATPase, MNK.4 A number of hair shaft abnormalities are evident under the microscope. Most commonly one sees pill torti, a hair shaft that is flattened and twisted 180 degrees on its own axis. Many other different abnormalities are also present and eyebrows and eyelashes can be affected.5 After the first month of life reduced serum caeruloplasmin and copper confirm the clinical diagnosis. A clinical picture that features subdural haematomas and retinal haemorrhages is inherent to glutaric aciduria type 1 (GA1), an autosomal recessive disease with an estimated population frequency of 1 in 30 000 neonates. The condition is caused by a defect in the gene that codes for glutaryl-CoA dehydrogenase. For reasons that are still poorly explained but in part are probably due to the stretching of bridging veins that attend cerebral atrophy, acute or chronic subdural haematomas and effusions are found in 20±30% of subjects with this condition.6 Haematomas often are induced by relatively minor trauma not only in this condition but also in various other conditions associated with significant cerebral atrophy. Retinal haemorrhages are seen in some 20±30% of subjects with GA1.6, 7 In at least one infant with
Received 20.04.2001. Accepted 28.04.2001. Correspondence: Professor J H Menkes, 9320 Wilshire Blvd, Suite 202, Beverly Hills, CA 90212-3216. e-mail: [email protected]
1090±3798/01/05/0175+2 $35.00
& 2001 European Paediatric Neurology Society
176 GA1 there also was a periosteal reaction suggesting recurrent trauma.7 There are wide phenotypic variations in GA1, and unless urinary organic acid analysis is performed, the diagnosis can easily be overlooked.8 Unlike in other organic acidaemias there often is no metabolic or lactic acidosis, and hypoglycaemia or hyperammonaemia are rarely found. A positive urine organic acid screen should be followed by measurement of plasma total and free carnitine, and determination of glutaryl-CoA dehydrogenase activity.9 When diagnosed early GA1 can be treated with a limited intake of dietary protein and a diet deficient in the amino acids lysine, hydroxylysine and tryptophan.10 Another genetic defect that can present during infancy with a subdural haematoma and retinal haemorrhage is the Hermansky±Pudlak syndrome.11 This rare autosomal recessive disorder is characterized by oculocutaneous albinism, lysosomal ceroid storage, and a lifelong bleeding tendency. The material stored is histochemically similar to that stored in neuronal ceroid lipofuscinosis, and the Hermansky±Pudlak syndrome results from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules and lysosomes.12 Haemorrhagic disease of the newborn is one of the various other bleeding disorders that can induce the combination of subdural haematoma and retinal haemorrhage.13 Less often the underlying cause is a disorder in electrolyte balance, notably hypo- and hypernatraemia. Even though child abuse must be on top of the differential diagnosis for all infants who present with retinal haemorrhages and subdural haematoma, the physician should avoid being swept up by the recent enthusiasm for reporting child abuse cases, and be certain to exclude the various metabolic, genetic and haemorrhagic disorders that can mimic non-accidental trauma.
Commentary: J H Menkes
References 1 Menkes JH. Menkes disease and Wilson disease: two sides of the same copper coin. Part I. Menkes disease. Eur J Paediatr Neurol 1999; 3: 147±158. 2 Howard MA, Bell BA, Uttley D. The pathophysiology of infant subdural haematomas. Br J Neurosurg 1993; 7: 355±365. 3 Baerlocher K, Nadal D. Das Menkes-Syndrom. Ergeb Inn Med Kinderheilk 1988; 57: 77±144. 4 Petris MJ, Strausak D, Mercer JF. The Menkes copper transporter is required for the activation of tyrosinase. Hum Mol Genet 2000; 9: 2845±2851. 5 Powell J, Ferguson DJ, Dawber RP. Is kinky-hair disease a misnomer for Menkes syndrome? Arch Dermatol 2001; 137: 92±93. 6 Hoffmann GF, Athanassopoulos S, Burlina AB et al. Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 1996; 27: 115±123. 7 Hartley LM, Khwaja OS, Verity CM. Glutaric aciduria type 1 and nonaccidental head injury. Pediatrics 2001; 107: 174±176. 8 Superti-Furga A, Hoffmann GF. Glutaric aciduria type 1 (glutaryl-coA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. Eur J Pediatr 1997; 156: 821±828. 9 Morris AAM, Hoffmann GF, Naughten ER., et al. Glutaric aciduria and suspected child abuse. Arch Dis Child 1984; 80: 404±405. 10 Monavari AA, Naughten ER. Prevention of cerebral palsy in glutaric aciduria type 1 by dietary management. Arch Dis Child 2000: 82: 67±70. 11 Russell-Eggitt IM, Thompson DA, Khair K et al. Hermansky±Pudlak syndrome presenting with subdural haematoma and retinal haemorrhages in infancy. J R Soc Med 2000; 93: 591±592. 12 Oh J, Bailin T, Kukai K et al. Positional cloning of a gene for Hermansky±Pudlak syndrome, a disorder of cytoplasmic organelles. Nature Genet 1996; 14: 300±306. 13 Rutty GN, Smith CM, Malia RG. Late-form hemorrhagic disease of the newborn: a fatal case report with illustration of investigations that may assist in avoiding the mistaken diagnosis of child abuse. Am J Forensic Med Pathol 1999; 20: 48±51.