Summary of PERINATAL STROKE (PS) AS A POSSIBLE CONTRIBUTOR TO CP

- By Steven Korzeniewski 

Some children with CP apparently had suffered strokes in the perinatal period (just before, during or after birth) . A stroke is when the blood supply to the brain is interrupted by bleeding or clotting in a blood vessel  [i] [ii]   Perinatal stroke is quite rare. Three large surveys from the US and Canada agree that about 1 Perinatal Stroke occurs in every  4,000 live births.[iii] [iv] [v] It has also been estimated that fatal perinatal strokes occur in nearly 1 of every 10,000 live births, accounting for about 1% of deaths in the newborn period.[vi]  Perinatal strokes might account for up to 10% of CP.  

What causes perinatal strokes?  Babies who are very ill with congenital heart disease, or because of very difficult deliveries, or who have sickle cell anemia, may have strokes.[vii] Sometimes,  the placenta may be the source of a blood clot that can lodge in a baby’s brain [viii]  

Recently, scientists have wondered whether certain inherited genes that influence the blood clotting system could play a role in perinatal stroke. [ix]   Examples include the Factor V Leiden gene, [x] [xi]  [xii] and antithrombin-III deficiency. [xiii]  .[xiv] [xv] [xvi]    

Many of the factors that lead to perinatal stroke may also be the same factors that lead some women to lose their babies during their pregnancy (miscarriages).  Some scientists therefore think that when miscarriage occurs, the baby may have suffered a perinatal stroke before it was born. [xvii]  

More research needs to be conducted before scientists completely understand the relationship between perinatal stroke and cerebral palsy . But  the limited amount of information we have does suggest that perinatal stroke is one way that children get cerebral palsy. 

link to references on another page (so references don't intimidate anyone)


[i] Lynch JK, Hirtz DG et al. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 2002;109:116-23.

[ii]  Lynch JK, Nelson KB: Epidemiology of perinatal stroke. Current Opinion in Pediatrics 2003;13:: 499-505. 

[iii] deVeber G. Canadian Pediatric Ischemic Stroke Registry [abstract]. Paediatr Child Health. 2000:A17  

[iv] Perlman JM, Rollins NK, Evans D. Neonatal stroke: clinical characteristics and cerebral blood flow velocity measurements. Pediatr Neurol. 1994;11:281-284  

[v]  National Hospital Discharge Survey  

[vi] Murphy S. Deaths: Final Data for 1998. National Vital Statistics Reports. Hyattsville, MD: National Center for Health Statistics; 2000 

[vii] Ment LR, Duncan CC, Ehrenkranz RA: Perinatal cerebral infarction. Annals of Neurology 1984; 16: 559-568 

[viii] Amato, M., P. Huppi, et al. (1991). "Prenatal Stroke Suggested by Intrauterine Ultrasound and Confirmed by Magnetic-Resonance-Imaging." Neuropediatrics 22(2): 100-102.

[ix]  Ganesan V, McShane MA, Liesner R, Cookson J, Hann I, Kirkham FJ. (1998) Inherited prothrombotic states and ischaemic stroke in childhood. Journal of Neurology, Neurosurgery and Psychiatry 65: 508-11. 

[x]   Harum KH, Hoon AH, Kato GJ et al: Developmental Medicine & Child Neurology 1999, 41: 777-780 

[xi] Zenz W, Bodo Z, Plotho J, Streif W, Male C, Bernert G, Rauter L, Ebetsberger G, Kaltenbrunner K, Kurnik P, et al. (1998) Factor V Leiden and prothrombin gene G 20210 A variant in children with ischemic stroke. Thrombosis and Haemostasis 80: 763-6. 

[xii] Hagstrom JN, Walter J, Bluebond-Langner R, Amatniek JC, Manno CS, High KA. (1998) Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease. Journal of Pediatrics 133: 777-81. 

[xiii] Andrew ME, Monagle P et al. Thromboembolic Disease and Antithrombotic Therapy in Newborns. Hematology 2001; 358-374.

 

[xiv] Debus O, Koch HG, Kurlemann G, Strater R, Vielhaber H, Weber P, Nowak-Göttl U. (1998) Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. Archive of Disease in Childhood. Fetal and Neonatal Edition. 78: 121-4. 

[xv] Mercuri, E., M. Rutherford, et al. (1999). "Early prognostic indicators of outcome in infants with neonatal cerebral infarction: A clinical, electroencephalogram, and magnetic resonance imaging study." Pediatrics 103(1): 39-46. 

[xvi] Nelson KB, Dambrosia JM, Grether JK et al: Neonatal cytokines and coagulation factors in children with cerebral palsy. Annals of Neurology 1998; 44: 665-75. 

[xvii] Ray et al 

[xvii] Debus O, Koch HG, Kurlemann G, Strater R, Vielhaber H, Weber P, Nowak-Göttl U. (1998) Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. Archive of Disease in Childhood. Fetal and Neonatal Edition. 78: 121-4. 

[xvii] Mercuri, E., M. Rutherford, et al. (1999). "Early prognostic indicators of outcome in infants with neonatal cerebral infarction: A clinical, electroencephalogram, and magnetic resonance imaging study." Pediatrics 103(1): 39-46. 

[xvii] Nelson KB, Dambrosia JM, Grether JK et al: Neonatal cytokines and coagulation factors in children with cerebral palsy. Annals of Neurology 1998; 44: 665-75.

 Physisicans, Scientists, and Interested Lay Readers:

PERINATAL STROKE (PS) AS CONTRIBUTOR TO CP- Paneth, N., & Korzeniewski, S.J. 

A growing body of literature suggests a link between inherited thrombophilias, antiphospholipid antibodies and CP, presumably mediated by PS.[16] [17] [18]

PS is a cerebrovascular event occurring between 28 weeks of gestation and 28 days of postnatal age, often involving the middle cerebral artery, and commonly the result of thromboembolism from an intracranial or extracranial vessel, the heart, or the placenta. [1] [2]  

In spite of variations in presentation, diagnosis and imaging across centers, three large surveys from the US and Canada converge on a prevalence estimate for PS of about 1 per 4,000 live births,[3] [4] [5] and it has been estimated that lethal PS occurs in nearly of every 10,000 live births, accounting for about 1% of neonatal mortality.[6]

            Acute neonatal illnesses (especially sepsis, meningitis, varicella, polycythemia and dehydration), congenital heart disease, birth asphyxia, and inherited conditions such as sickle cell anemia, all play a role in PS.[7]   The placenta may be the source of cerebral emboli in some cases.[8]  But recent attention has focused on inherited thrombophilias,[9] such as Factor V Leiden heterozygosity, [10] [11]  [12] and antithrombin-III deficiency [13], since about 2/3 of PS is ischemic in origin. 

Inherited coagulation defects, such as protein-C and -S deficiencies, have been implicated in the 1/3 of PS that is hemorrhagic, and it has also been suggested that methylenetetrahydrofolate reductase deficiency may accelerate vessel wall damage by homocysteine, thereby predisposing to PS.

Maternal antiphospholipid antibodies, including lupus anticoagulant and anticardiolipin, are not rare, and since they are directed against anticoagulant proteins and interfere with normal coagulation, they can also increase the risk for PS.[14]  Many of these genetic polymorphisms and conditions also predispose to increased risk of fetal loss, and it is possible that PS underlies some of these losses.[15] 

 

 


[1] Lynch JK, Hirtz DG et al. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics 2002;109:116-23. 

[2]  Lynch JK, Nelson KB: Epidemiology of perinatal stroke. Current Opinion in Pediatrics 2003;13:: 499-505. 

[3] deVeber G. Canadian Pediatric Ischemic Stroke Registry [abstract]. Paediatr Child Health. 2000:A17  

[4] Perlman JM, Rollins NK, Evans D. Neonatal stroke: clinical characteristics and cerebral blood flow velocity measurements. Pediatr Neurol. 1994;11:281-284

[5]  National Hospital Discharge Survey  

[6] Murphy S. Deaths: Final Data for 1998. National Vital Statistics Reports. Hyattsville, MD: National Center for Health Statistics; 2000 

[7] Ment LR, Duncan CC, Ehrenkranz RA: Perinatal cerebral infarction. Annals of Neurology 1984; 16: 559-568 

[8] Amato, M., P. Huppi, et al. (1991). "Prenatal Stroke Suggested by Intrauterine Ultrasound and Confirmed by Magnetic-Resonance-Imaging." Neuropediatrics 22(2): 100-102. 

[9]  Ganesan V, McShane MA, Liesner R, Cookson J, Hann I, Kirkham FJ. (1998) Inherited prothrombotic states and ischaemic stroke in childhood. Journal of Neurology, Neurosurgery and Psychiatry 65: 508-11. 

[10]   Harum KH, Hoon AH, Kato GJ et al: Developmental Medicine & Child Neurology 1999, 41: 777-780 

[11] Zenz W, Bodo Z, Plotho J, Streif W, Male C, Bernert G, Rauter L, Ebetsberger G, Kaltenbrunner K, Kurnik P, et al. (1998) Factor V Leiden and prothrombin gene G 20210 A variant in children with ischemic stroke. Thrombosis and Haemostasis 80: 763-6. 

[12] Hagstrom JN, Walter J, Bluebond-Langner R, Amatniek JC, Manno CS, High KA. (1998) Prevalence of the factor V Leiden mutation in children and neonates with thromboembolic disease. Journal of Pediatrics 133: 777-81. 

[13] Andrew ME, Monagle P et al. Thromboembolic Disease and Antithrombotic Therapy in Newborns. Hematology 2001; 358-374. 

[14] Arias F, Romero R, Joist H, Kraus FT. (1998) Thrombophilia: a mechanism of disease in women with adverse pregnancy outcome and thrombotic lesions in the placenta. Journal of Maternal-Fetal Medicine 7: 277-86. 

[15] Ray et al 

[16] Debus O, Koch HG, Kurlemann G, Strater R, Vielhaber H, Weber P, Nowak-Göttl U. (1998) Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly. Archive of Disease in Childhood. Fetal and Neonatal Edition. 78: 121-4. 

[17] Mercuri, E., M. Rutherford, et al. (1999). "Early prognostic indicators of outcome in infants with neonatal cerebral infarction: A clinical, electroencephalogram, and magnetic resonance imaging study." Pediatrics 103(1): 39-46. 

[18] Nelson KB, Dambrosia JM, Grether JK et al: Neonatal cytokines and coagulation factors in children with cerebral palsy. Annals of Neurology 1998; 44: 665-75.

 

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