- Email: [email protected]
Stroke presenting under 3 hours in patients younger than 18 years of age
Case Reports / Journal of Clinical Neuroscience 16 (2009) 1481–1482
1481
Stroke presenting under 3 hours in patients younger than 18 years of age Cassandra Szoeke a,b, Christopher Bladin b, Anne Gordon c,d, Mark T. Mackay c,d,* a
Eastern Melbourne Neurosciences, Box Hill Hospital, Melbourne, Victoria, Australia Office of Gender and Health, University of Melbourne, Parkville, Victoria, Australia c Children’s Neuroscience Centre, The Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia d Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia b
a r t i c l e
i n f o
Article history: Received 4 May 2008 Accepted 18 January 2009
Keywords: Stroke Children Adolescent Intervention Thrombolysis
a b s t r a c t We report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one of the most significant obstacles to offering acute thrombolytic therapies in teenagers and children. Feasibility of treatment is further limited by a lack of dosage and safety data in the paediatric population. Improved community awareness and more rapid recognition of stroke may reduce lag time to diagnosis. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction Intravenous tissue plasminogen activator (tPA) has been registered for use in adults with arterial ischaemic stroke presenting in under 3 hours since 2003. The tPA trials in the stroke population have excluded individuals under 18 years and therefore the evidence for using this intervention in the paediatric population is lacking.1 Expert adult stroke centres around Australia now face the dilemma of teenagers for whom the benefits, complications, and dosage of tPA are not known. 2. Case report A previously well 14-year-old girl collapsed on the sidelines of a school volleyball match at 2 pm. She was transferred by wheelchair to the sick bay because she was drowsy and unable to stand. After some delay the school nurse noted a left facial droop at 12.45 pm. The child’s mother was contacted and arrived 5 minutes later. She was advised by the school nurse to see her general practitioner (GP). While in transit by private car there was some improvement and she was able to walk with assistance on arrival at the GP’s surgery at 3.15 pm. The child was briefly assessed by her GP on arrival and then remained under observation. She was reassessed at 4 pm because of a deteriorating conscious state and referred to the Box Hill Hospital Emergency Department (ED). While in transit by private car she developed a dense left hemiplegia at 4.30 pm. She arrived at Box Hill ED at 4.40 pm in a semi-conscious state. She was seen by ED staff and assessed by the Stroke Registrar at 5.10 pm at which time her National Institutes of Health Stroke Scale (NIHSS) score was 16. A stroke protocol urgent CT brain scan was arranged at 5.35 pm, which revealed no abnormality, with CT perfusion scans not being possible because of movement artefact. She therefore went on to have an urgent MRI at 6 pm (diffusion sequences only), which revealed a large area of restricted diffusion in the distribution of the right middle cerebral artery. A diagnosis of ischaemic stroke was finally made at 6.20 pm, more than 4 hours after symptom onset. The patient was transferred to the Royal Children’s Hospital for further investigation and management. After receiving in-patient rehabilitation services, she was transferred for community-based rehabilitation with a * Corresponding author. Tel.: +61 3 93455914; fax: +61 3 93491819. E-mail address: [email protected] (M.T. Mackay).
hospital discharge NIHSS score of 5 and a modified Rankin score of 3. 3. Discussion 3.1. Epidemiology of childhood stroke Arterial ischaemic stroke affects about 2.7 per 100,000 children per year2 and is among the top ten causes of death in children.3 Long-term neurological deficits following childhood arterial stroke occur in 50% to 85% of patients.2,4 Recurrent ischaemic events are reported in 19% to 40% of children.2,4 In contrast to adults, stroke in children is not caused by atherosclerosis. Vasculopathies including post-varicella angiopathy, arterial dissection, Moyamoya and sickle cell disease are major causes of arterial ischaemic stroke, occurring in more than 50% of children.5 Cardioembolic causes account for up to one-quarter of strokes.2,5,6 No cause can be found in about one-third of patients. 3.2. Thrombolysis in paediatric stroke Use of thrombolytic agents in individuals under 18 years was first described in 2000.7 There appears to be increasing use of thrombolytic therapy, with tPA administered to 1.6% of children in a nationwide United States survey8 and to 3.6% of children recruited to the international paediatric stroke registry treated with tPA.9 Almost half were treated beyond 3 hours and cerebral bleeding was encountered in 29% of patients.9 Thrombolysis is not recommended in recent consensus-based treatment guidelines because of lack of safety and efficacy data in the paediatric population.10–12 There are physiological differences in the coagulation systems in children compared to adults with hypoactive fibrinolytic systems13 so tPA doses in adult practice may not apply to the paediatric population. A multicentre study to establish safe and appropriate tPA dosing in the paediatric population is planned in the near future.14 There needs to be greater focus on use of intravenous tPA to improve functional outcome and reduce mortality in the younger population but the most significant obstacle is the lag time to diagnosis. Mean times from symptom onset to presentation to any health professional have been documented at 34 hours with time to imaging of 42 hours in one paediatric study.15 Symptoms are frequently attributed to other problems such as migraine,
1482
Case Reports / Journal of Clinical Neuroscience 16 (2009) 1482–1485
encephalitis, tumors and Todd’s paralysis following seizures.16 For this reason research into the use of imaging to target acute thrombolytic therapy at the retrievable penumbra may be required in line with recent multicentre adult studies.17 Geographically located stroke units within tertiary paediatric centres are not feasible given the small numbers of patients presenting at any one time with stroke. However, the principles of adult stroke units can still be applied to the paediatric population by identifying health professionals with an interest and expertise in various aspects of diagnosis and management. Involvement of neurologists, haematologists, radiologists, emergency physicians, paediatricians, neonatologists, paediatric intensivists, cardiologists, neurosurgeons and the extended allied health team are essential to the coordinated care of children with stroke. There are now consensus-based guidelines with recommendations for standardised diagnostic and treatment protocols.10–12 4. Conclusions With increased awareness of the importance of early presentation to hospital with stroke symptoms from advertising campaigns (e.g. the Australian National Stroke Foundation’s campaign ‘‘FAST = face, arm, speech, time”) and health professional education, the rates of teenagers and young adults presenting acutely to large stroke centres is likely to increase. In the patient described, the young girl was referred directly to the stroke unit by her family GP, familiar with the acute stroke service in his metropolitan area. We should therefore be focusing research attention on the lack of evidence of acute thrombolytic intervention in children and teenagers. Development of paediatric stroke programs and multicentre international collaborations are required to achieve these goals. A consortium of paediatric neurologists and haematologists has been enrolling patients in the International Paediatric Stroke Study (https://app3.ccb.sickkids.ca/cstrokestudy/). This registry aims to increase knowledge about risk factors and mechanisms of stroke and to establish accurate recurrence risks. A multicentre study to
establish safe and appropriate tPA dosing in the paediatric population is planned for the near future.14 References 1. Saver JL, Yafeh B. Confirmation of tPA treatment effect by baseline severityadjusted end point reanalysis of the NINDS-tPA stroke trials. Stroke 2007;38:414–6. 2. deVeber GGroup. TCPISS. Canadian Pediatric Ischaemic Stroke Study Registry: analysis of children with arterial ischaemic stroke. Ann Neurol 2000;48:514. 3. Murphy SL. Deaths: final data for 1998. Natl Vital Stat Rep 2000;48:1–105. 4. Ganesan V, Hogan A, Shack M, et al. Outcome after ischaemic stroke in childhood. Develop Med Child Neurol 2000;42:455–61. 5. Chabrier S, Husson B, Lasjaunias P, et al. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients. J Child Neurol 2000 May;15:290–4. 6. Ganesan V, Prengler M, McShane MA, et al. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol 2003 Feb;53:167–73. 7. Gruber A, Nasel C, Lang W, et al. Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke. Neurology 2000;54:1684–6. 8. Janjua N, Nasar A, Lynch JK, et al. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 2007 Jun;38:1850–4. 9. Amlie-Lefond C. Thrombolysis in children with arterial ischemic stroke: initial results from the International Pediatric Stroke Study (Abstract). Proceedings of the 32nd International Stroke Conference 2007;38:485. 10. Paediatric Stroke Working Group. Stroke in Childhood: Clinical Guidelines for Diagnosis, Management and Rehabilitation. Suffolk, UK: Royal College of Physicians; Lavenham Press; 2004. 11. Monagle P, Chalmers E, Chan A, et al. Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed.). Chest 2008;133(Suppl. 6):887S–968S. 12. Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008;39:2644–91. 13. Andrew M, Vegh P, Johnston M, et al. Maturation of the hemostatic system during childhood. Blood 1992 Oct 15;80:1998–2005. 14. Whelan HT, Cook JD, Amlie-Lefond CM, et al. Practical model-based dose finding in early-phase clinical trials: optimizing tissue plasminogen activator dose for treatment of ischemic stroke in children. Stroke 2008 Sep;39:2627–36. 15. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics 2002;110:924–8. 16. Braun K, Kappelle L, Kirkham F, et al. Diagnostic pitfalls in paediatric ischaemic stroke. Dev Med Child Neurol 2006;48:985–90. 17. Butcher KS, Parsons M, MacGregor L, et al. Refining the perfusion–diffusion mismatch hypothesis. Stroke 2005;36:1153–9.
doi:10.1016/j.jocn.2009.01.014
Transcortical sensory aphasia following a left frontal lobe infarction probably due to anomalously represented language areas E.J. Kim a, M.K. Suh b, B.H. Lee b, K.C. Park c, B.D. Ku d, C.S. Chung b, D.L. Na b,* a
Department of Neurology, Pusan National University School of Medicine and Medical Research Institute, Busan, Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea Department of Neurology, Kyunghee University College of Medicine, Seoul, Korea d Department of Neurology, Kwandong University College of Medicine, Myongji Hospital, Gyeonggi, Korea b c
a r t i c l e
i n f o
Article history: Received 4 April 2008 Accepted 18 January 2009
Keywords: Anomalous language representation Left frontal lobe Transcortical sensory aphasia
a b s t r a c t A 57-year-old right-handed man presented with speech disturbance 1 day prior to his admission. The standardized aphasia test batteries showed transcortical sensory aphasia. MRI revealed a left frontal and insular infarct. Positron emission tomography scans also revealed a glucose hypometabolism in the same region as the infarcted area on MRI. Repeated aphasia testing showed that his aphasia only partially improved. Ó 2009 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +82 2 3410 3591; fax: +82 2 3410 0052. E-mail address: [email protected] (D.L. Na).
1481
Stroke presenting under 3 hours in patients younger than 18 years of age Cassandra Szoeke a,b, Christopher Bladin b, Anne Gordon c,d, Mark T. Mackay c,d,* a
Eastern Melbourne Neurosciences, Box Hill Hospital, Melbourne, Victoria, Australia Office of Gender and Health, University of Melbourne, Parkville, Victoria, Australia c Children’s Neuroscience Centre, The Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia d Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia b
a r t i c l e
i n f o
Article history: Received 4 May 2008 Accepted 18 January 2009
Keywords: Stroke Children Adolescent Intervention Thrombolysis
a b s t r a c t We report a 14-year-old girl with a delayed diagnosis of stroke, highlighting one of the most significant obstacles to offering acute thrombolytic therapies in teenagers and children. Feasibility of treatment is further limited by a lack of dosage and safety data in the paediatric population. Improved community awareness and more rapid recognition of stroke may reduce lag time to diagnosis. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction Intravenous tissue plasminogen activator (tPA) has been registered for use in adults with arterial ischaemic stroke presenting in under 3 hours since 2003. The tPA trials in the stroke population have excluded individuals under 18 years and therefore the evidence for using this intervention in the paediatric population is lacking.1 Expert adult stroke centres around Australia now face the dilemma of teenagers for whom the benefits, complications, and dosage of tPA are not known. 2. Case report A previously well 14-year-old girl collapsed on the sidelines of a school volleyball match at 2 pm. She was transferred by wheelchair to the sick bay because she was drowsy and unable to stand. After some delay the school nurse noted a left facial droop at 12.45 pm. The child’s mother was contacted and arrived 5 minutes later. She was advised by the school nurse to see her general practitioner (GP). While in transit by private car there was some improvement and she was able to walk with assistance on arrival at the GP’s surgery at 3.15 pm. The child was briefly assessed by her GP on arrival and then remained under observation. She was reassessed at 4 pm because of a deteriorating conscious state and referred to the Box Hill Hospital Emergency Department (ED). While in transit by private car she developed a dense left hemiplegia at 4.30 pm. She arrived at Box Hill ED at 4.40 pm in a semi-conscious state. She was seen by ED staff and assessed by the Stroke Registrar at 5.10 pm at which time her National Institutes of Health Stroke Scale (NIHSS) score was 16. A stroke protocol urgent CT brain scan was arranged at 5.35 pm, which revealed no abnormality, with CT perfusion scans not being possible because of movement artefact. She therefore went on to have an urgent MRI at 6 pm (diffusion sequences only), which revealed a large area of restricted diffusion in the distribution of the right middle cerebral artery. A diagnosis of ischaemic stroke was finally made at 6.20 pm, more than 4 hours after symptom onset. The patient was transferred to the Royal Children’s Hospital for further investigation and management. After receiving in-patient rehabilitation services, she was transferred for community-based rehabilitation with a * Corresponding author. Tel.: +61 3 93455914; fax: +61 3 93491819. E-mail address: [email protected] (M.T. Mackay).
hospital discharge NIHSS score of 5 and a modified Rankin score of 3. 3. Discussion 3.1. Epidemiology of childhood stroke Arterial ischaemic stroke affects about 2.7 per 100,000 children per year2 and is among the top ten causes of death in children.3 Long-term neurological deficits following childhood arterial stroke occur in 50% to 85% of patients.2,4 Recurrent ischaemic events are reported in 19% to 40% of children.2,4 In contrast to adults, stroke in children is not caused by atherosclerosis. Vasculopathies including post-varicella angiopathy, arterial dissection, Moyamoya and sickle cell disease are major causes of arterial ischaemic stroke, occurring in more than 50% of children.5 Cardioembolic causes account for up to one-quarter of strokes.2,5,6 No cause can be found in about one-third of patients. 3.2. Thrombolysis in paediatric stroke Use of thrombolytic agents in individuals under 18 years was first described in 2000.7 There appears to be increasing use of thrombolytic therapy, with tPA administered to 1.6% of children in a nationwide United States survey8 and to 3.6% of children recruited to the international paediatric stroke registry treated with tPA.9 Almost half were treated beyond 3 hours and cerebral bleeding was encountered in 29% of patients.9 Thrombolysis is not recommended in recent consensus-based treatment guidelines because of lack of safety and efficacy data in the paediatric population.10–12 There are physiological differences in the coagulation systems in children compared to adults with hypoactive fibrinolytic systems13 so tPA doses in adult practice may not apply to the paediatric population. A multicentre study to establish safe and appropriate tPA dosing in the paediatric population is planned in the near future.14 There needs to be greater focus on use of intravenous tPA to improve functional outcome and reduce mortality in the younger population but the most significant obstacle is the lag time to diagnosis. Mean times from symptom onset to presentation to any health professional have been documented at 34 hours with time to imaging of 42 hours in one paediatric study.15 Symptoms are frequently attributed to other problems such as migraine,
1482
Case Reports / Journal of Clinical Neuroscience 16 (2009) 1482–1485
encephalitis, tumors and Todd’s paralysis following seizures.16 For this reason research into the use of imaging to target acute thrombolytic therapy at the retrievable penumbra may be required in line with recent multicentre adult studies.17 Geographically located stroke units within tertiary paediatric centres are not feasible given the small numbers of patients presenting at any one time with stroke. However, the principles of adult stroke units can still be applied to the paediatric population by identifying health professionals with an interest and expertise in various aspects of diagnosis and management. Involvement of neurologists, haematologists, radiologists, emergency physicians, paediatricians, neonatologists, paediatric intensivists, cardiologists, neurosurgeons and the extended allied health team are essential to the coordinated care of children with stroke. There are now consensus-based guidelines with recommendations for standardised diagnostic and treatment protocols.10–12 4. Conclusions With increased awareness of the importance of early presentation to hospital with stroke symptoms from advertising campaigns (e.g. the Australian National Stroke Foundation’s campaign ‘‘FAST = face, arm, speech, time”) and health professional education, the rates of teenagers and young adults presenting acutely to large stroke centres is likely to increase. In the patient described, the young girl was referred directly to the stroke unit by her family GP, familiar with the acute stroke service in his metropolitan area. We should therefore be focusing research attention on the lack of evidence of acute thrombolytic intervention in children and teenagers. Development of paediatric stroke programs and multicentre international collaborations are required to achieve these goals. A consortium of paediatric neurologists and haematologists has been enrolling patients in the International Paediatric Stroke Study (https://app3.ccb.sickkids.ca/cstrokestudy/). This registry aims to increase knowledge about risk factors and mechanisms of stroke and to establish accurate recurrence risks. A multicentre study to
establish safe and appropriate tPA dosing in the paediatric population is planned for the near future.14 References 1. Saver JL, Yafeh B. Confirmation of tPA treatment effect by baseline severityadjusted end point reanalysis of the NINDS-tPA stroke trials. Stroke 2007;38:414–6. 2. deVeber GGroup. TCPISS. Canadian Pediatric Ischaemic Stroke Study Registry: analysis of children with arterial ischaemic stroke. Ann Neurol 2000;48:514. 3. Murphy SL. Deaths: final data for 1998. Natl Vital Stat Rep 2000;48:1–105. 4. Ganesan V, Hogan A, Shack M, et al. Outcome after ischaemic stroke in childhood. Develop Med Child Neurol 2000;42:455–61. 5. Chabrier S, Husson B, Lasjaunias P, et al. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients. J Child Neurol 2000 May;15:290–4. 6. Ganesan V, Prengler M, McShane MA, et al. Investigation of risk factors in children with arterial ischemic stroke. Ann Neurol 2003 Feb;53:167–73. 7. Gruber A, Nasel C, Lang W, et al. Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke. Neurology 2000;54:1684–6. 8. Janjua N, Nasar A, Lynch JK, et al. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke 2007 Jun;38:1850–4. 9. Amlie-Lefond C. Thrombolysis in children with arterial ischemic stroke: initial results from the International Pediatric Stroke Study (Abstract). Proceedings of the 32nd International Stroke Conference 2007;38:485. 10. Paediatric Stroke Working Group. Stroke in Childhood: Clinical Guidelines for Diagnosis, Management and Rehabilitation. Suffolk, UK: Royal College of Physicians; Lavenham Press; 2004. 11. Monagle P, Chalmers E, Chan A, et al. Antithrombotic Therapy in Neonates and Children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed.). Chest 2008;133(Suppl. 6):887S–968S. 12. Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008;39:2644–91. 13. Andrew M, Vegh P, Johnston M, et al. Maturation of the hemostatic system during childhood. Blood 1992 Oct 15;80:1998–2005. 14. Whelan HT, Cook JD, Amlie-Lefond CM, et al. Practical model-based dose finding in early-phase clinical trials: optimizing tissue plasminogen activator dose for treatment of ischemic stroke in children. Stroke 2008 Sep;39:2627–36. 15. Gabis LV, Yangala R, Lenn NJ. Time lag to diagnosis of stroke in children. Pediatrics 2002;110:924–8. 16. Braun K, Kappelle L, Kirkham F, et al. Diagnostic pitfalls in paediatric ischaemic stroke. Dev Med Child Neurol 2006;48:985–90. 17. Butcher KS, Parsons M, MacGregor L, et al. Refining the perfusion–diffusion mismatch hypothesis. Stroke 2005;36:1153–9.
doi:10.1016/j.jocn.2009.01.014
Transcortical sensory aphasia following a left frontal lobe infarction probably due to anomalously represented language areas E.J. Kim a, M.K. Suh b, B.H. Lee b, K.C. Park c, B.D. Ku d, C.S. Chung b, D.L. Na b,* a
Department of Neurology, Pusan National University School of Medicine and Medical Research Institute, Busan, Korea Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea Department of Neurology, Kyunghee University College of Medicine, Seoul, Korea d Department of Neurology, Kwandong University College of Medicine, Myongji Hospital, Gyeonggi, Korea b c
a r t i c l e
i n f o
Article history: Received 4 April 2008 Accepted 18 January 2009
Keywords: Anomalous language representation Left frontal lobe Transcortical sensory aphasia
a b s t r a c t A 57-year-old right-handed man presented with speech disturbance 1 day prior to his admission. The standardized aphasia test batteries showed transcortical sensory aphasia. MRI revealed a left frontal and insular infarct. Positron emission tomography scans also revealed a glucose hypometabolism in the same region as the infarcted area on MRI. Repeated aphasia testing showed that his aphasia only partially improved. Ó 2009 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +82 2 3410 3591; fax: +82 2 3410 0052. E-mail address: [email protected] (D.L. Na).