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10 - Central nervous system

Published online by Cambridge University Press:  05 September 2014

By
Waney Squier  and
Férechté Encha-Razavi
Edited by
Marta C. Cohen  and
Irene Scheimberg
Waney Squier
Affiliation:
Oxford University John Radcliffe Hospital
Férechté Encha-Razavi
Affiliation:
Hôpital Necker-Enfants Malades, Paris
Marta C. Cohen
Affiliation:
Sheffield Children’s Hospital
Irene Scheimberg
Affiliation:
Barts and the London NHS Trust, London
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Summary

Introduction

This chapter provides a practical guide to examination of the fetal, infant, and child’s brain. It covers those conditions most likely to be encountered in daily diagnostic practice and indicates practice points and pitfalls. More detailed texts are referred to for further reading.

Autopsy examination and removal of the brain

The parental wishes and their authority to examine the brain are paramount prior to neuropathological examination. This is a sensitive topic and must be broached with parents at a time when they are grieving. A careful and empathetic approach usually results in consent to examine the brain. In order to make the best possible diagnosis, with the opportunity to revisit the diagnosis and to use tissue for later teaching and research, it is necessary to request permission for the brain to be retained after diagnosis has been made. Parents are usually extremely generous if this need is explained, but their wishes should always be fully respected. It is almost always possible to accommodate both the parents’ requirements for tissue return for burial and comprehensive brain examination by expediting fixation (for example by using extra-strength formalin). While not ideal, this may be a worthwhile compromise so that the best possible diagnostic service can be offered while remaining sensitive to parents’ wishes.

Type
Chapter
Information
The Pediatric and Perinatal Autopsy Manual , pp. 173 - 204
Publisher: Cambridge University Press
Print publication year: 2000

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References

Hayes, B. C., Cooley, S., Donnelly, J., et al. The placenta in infants >36 weeks gestation with neonatal encephalopathy: a case control study. Arch Dis Child Fetal Neonatal Ed 2013; 98: F233–9.CrossRefGoogle ScholarPubMed
Volpe, J. J.. Injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol 2009; 8: 110–24.CrossRefGoogle ScholarPubMed
Boyle, J. D. and Boyle, E. M.. Born just a few weeks early: does it matter?Arch Dis Child Fetal Neonatal Ed 2013; 98: F85–8CrossRefGoogle ScholarPubMed
Dror, D. K.. Vitamin D status during pregnancy: maternal, fetal, and postnatal outcomes. Curr Opin Obstet Gynecol 2011; 23: 422–6.CrossRefGoogle ScholarPubMed
McNeely, P. D., Atkinson, J. D., Saigal, G., et al. Subdural hematomas in infants with benign enlargement of the subarachnoid spaces are not pathognomonic for child abuse. AJNR Am J Neuroradiol 2006; 27: 1725–8.Google Scholar
Volpe, J. J.. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol 2012; 72: 156–66.CrossRefGoogle ScholarPubMed
Cowan, F., Rutherford, M., Groenendall, F., et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet 2003; 361: 736–42.CrossRefGoogle ScholarPubMed
Marmarou, A.. A review of progress in understanding the pathophysiology and treatment of brain edema. Neurosurg Focus 2007; 22: E1.CrossRefGoogle ScholarPubMed
Gilles, F. and Nelson, M.. The Developing Human Brain: Growth and Adversities. London, MacKeith Press, 2012.Google Scholar
Squier, M., Chamberlain, P., Zaiwalla, Z., et al. Five cases of brain injury following amniocentesis in mid-term pregnancy. Dev Med Child Neurol 2000; 42: 554–60.CrossRefGoogle ScholarPubMed
Hortobagyi, T., Wise, S., Hunt, N., et al. Traumatic axonal damage in the brain can be detected using beta-APP immunohistochemistry within 35 min after head injury to human adults 1. Neuropathol Appl Neurobiol 2007; 33: 226–37.CrossRefGoogle Scholar
Geddes, J. F., Vowles, G. H., Beer, T. W., and Ellison, D. W.. The diagnosis of diffuse axonal injury: implications for forensic practice. Neuropathol Appl Neurobiol 1997; 23: 339–47.CrossRefGoogle Scholar
Oehmichen, M., Schleiss, D., Pedal, I., et al. Shaken baby syndrome: re-examination of diffuse axonal injury as cause of death. Acta Neuropathol 2008; 116: 317–29.CrossRefGoogle ScholarPubMed
Johnson, M. W., Stoll, L., Rubio, A., et al. Axonal injury in young pediatric head trauma: a comparison study of beta-amyloid precursor protein (beta-APP) immunohistochemical staining in traumatic and nontraumatic deaths. J Forensic Sci 2011; 56: 1198–205.CrossRefGoogle ScholarPubMed
Kinney, H. C., Panigrahy, A., Newburger, J. W., et al. Hypoxic-ischemic brain injury in infants with congenital heart disease dying after cardiac surgery 1. Acta Neuropathol (Berl) 2005; 110: 563–78.CrossRefGoogle Scholar
Buser, J. R., Maire, J., Riddle, A., et al. Arrested preoligodendrocyte maturation contributes to myelination failure in premature infants. Ann Neurol 2012; 71: 93–109.CrossRefGoogle ScholarPubMed
Riddle, A., Dean, J., Buser, J. R., et al. Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury. Ann Neurol 2011; 70: 493–507.CrossRefGoogle ScholarPubMed
Jakovcevski, I., Filipovic, R., Zhicheng, M., et al. Oligodendrocyte development and the onset of myelination in the human fetal brain. Front Neuroanat 2009; 3: 5.CrossRefGoogle ScholarPubMed
Favrais, G., van de Looij, Y., Fleiss, B., et al. Systemic inflammation disrupts the developmental program of white matter. Ann Neurol 2011; 70: 550–65.CrossRefGoogle ScholarPubMed
Banker, B. Q. and Larroche, J. C.. Periventricular leukomalacia of infancy: a form of neonatal anoxic encephalopathy. Arch Neurol 1962; 7: 386–410.CrossRefGoogle ScholarPubMed
Squier, W., Austin, T., Anslow, P., et al. Infant subcortical cystic leucomalacia: a distinct pathological entity resulting from impaired fluid handling. Early Hum Dev 2011; 87: 421–6CrossRefGoogle ScholarPubMed
Cohen, M. C. and Scheimberg, I.. Evidence of occurrence of intradural and subdural hemorrhage in the perinatal and neonatal period in the context of hypoxic ischemic encephalopathy: an observational study from two referral institutions in the United Kingdom. Pediatr Dev Pathol 2009; 12: 169–76.CrossRefGoogle ScholarPubMed
Scheimberg, I., Cohen, M. C., Zapata Vazquez, R. E., et al. Non-traumatic intradural and subdural hemorrhage and hypoxic ischaemic encephalopathy in fetuses, infants and children up to 3 years of age: analysis of two audits of 636 cases from two referral centers in the UK. Pediatr Dev Pathol 2013; 16: 149–59CrossRefGoogle Scholar
Mack, J., Squier, W., and Eastman, J.. Anatomy and development of the meninges: implications for subdural collections and CSF circulation. Pediatr Radiol 2009; 39: 200–10.CrossRefGoogle ScholarPubMed
Squier, W. and Mack, J.The neuropathology of infant subdural haemorrhage. Forensic Sci Int 2009; 187: 6–13.CrossRefGoogle ScholarPubMed
Keeling, J. and Busuttil, A.. Sudden unexpected death in infancy. In: Paediatric Forensic Medicine and Pathology. London, Edward Arnold, 2009, chapter 11.Google Scholar
Rogers, C. B., Itabashi, H. H., Tomiyasu, U., and Heuser, E.. Subdural neomembranes and sudden infant death syndrome. J Forensic Sci 1998; 43: 375–6.CrossRefGoogle ScholarPubMed
Rooks, V. J., Eaton, J. P., Reuss, L., et al. Prevalence and evolution of intracranial hemorrhage in asymptomatic term infants. Am J Neuroradiol 2008; 29: 1082–9.CrossRefGoogle ScholarPubMed
Hobbs, C., Childs, A. M., Wynne, J., et al. Subdural haematoma and effusion in infancy: an epidemiological study. Arch Dis Child 2005; 90: 952–5.CrossRefGoogle Scholar
Larroche, J. C.. Lesions of haemorrhagic type, mainly venous: developmental pathology of the neonate. In: Excerpta Medica. Amsterdam, Excerpta Medica Foundation, 1977, 355–98.Google Scholar
Huang, A. H. and Robertson, R. L.. Spontaneous superficial parenchymal and leptomeningeal hemorrhage in term neonates. Am J Neuroradiol 2004; 25: 469–75.Google ScholarPubMed
Tubbs, R. S., Salter, E. G., Weltons, J., et al. The sphenoparietal sinus. Neurosurg 2007; 60: 9–12.Google ScholarPubMed
Wu, Y. W., Hamrick, S. E., Miller, S., et al. Intraventricular hemorrhage in term neonates caused by sinovenous thrombosis. Ann Neurol 2003; 54: 123–6.CrossRefGoogle ScholarPubMed
Dlamini, N., Billinghurst, L., and Kirkham, F.. Cerebral venous sinus (sinovenous) thrombosis in children. Neurosurg Clin N Am 2010; 21: 511–27.CrossRefGoogle ScholarPubMed
Maguire, J. L., deVeber, G., Parkin, P.. Association between iron-deficiency anemia and stroke in young children. Pediatrics 2007; 120: 1053–7.CrossRefGoogle ScholarPubMed
Guerrini, R., Dubeau, F., Dulac, O., et al. Bilateral parasagittal parietooccipital polymicrogyria and epilepsy. Ann Neurol 1997; 41: 65–73.CrossRefGoogle ScholarPubMed
DeVeber, G., Andrew, M., Adams, C., et al. Cerebral sinovenous thrombosis in children. N Engl J Med 2001; 345: 417–23.CrossRefGoogle ScholarPubMed
Sebire, G., Tabarki, B., Saunders, D., et al. Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain 2005; 128: 477–89.CrossRefGoogle ScholarPubMed
Ramenghi, L. A., Govaert, P., Williams, L., et al. Neonatal cerebral sinovenous thrombosis. Semin Fetal Neonatal Med 2009; 14: 278–83.CrossRefGoogle ScholarPubMed
Berfelo, F. J., Kersbergen, K. J., van Ommen, C., et al. Neonatal cerebral sinovenous thrombosis from symptom to outcome. Stroke 2010; 41: 1382–8.CrossRefGoogle Scholar
Wasay, M. and Azeemuddin, M.. Neuroimaging of cerebral venous thrombosis. J Neuroimaging 2005; 15: 118–28.CrossRefGoogle ScholarPubMed
Eichler, F., Krishnamoorthy, K., and Grant, P.. Magnetic resonance imaging evaluation of possible neonatal sinovenous thrombosis. Pediatr Neurol 2007; 37: 317–23.CrossRefGoogle ScholarPubMed
Krasnokutsky, M. V.. Cerebral venous thrombosis: a potential mimic of primary traumatic brain injury in infants. Am J Roentgenol 2011; 197: W503–7.CrossRefGoogle ScholarPubMed
Drewes, L. R.. Making connexions in the neurovascular unit. J Cereb Blood Flow Metab 2012; 32: 1455–6.CrossRefGoogle Scholar
Abbott, N. J., Patabendige, A. A., Dolman, D., et al. Structure and function of the blood–brain barrier. Neurobiol Dis 2010; 37: 13–25.CrossRefGoogle ScholarPubMed
Hamel, E.. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 2006; 100: 1059–64.CrossRefGoogle ScholarPubMed
Jones, P., Dauger, S., and Peters, M.. Bradycardia during critical care intubation: mechanisms, significance and atropine. Arch Disease Child 2012; 97: 139–44.CrossRefGoogle ScholarPubMed
McCoy, B., King, M., Gill, D., and Twomey, E.. Childhood posterior reversible encephalopathy syndrome. Eur J Paediatr Neurol 2011; 15: 91–4.CrossRefGoogle ScholarPubMed
Probert, R., Saunders, D. E., Ganesan, V.. Reversible cerebral vasoconstriction syndrome: rare or under-recognized in children?Develop Med Child Neurol 2013; 55: 385–9.CrossRefGoogle ScholarPubMed
Weber, M. A., Klein, N. J., Hartley, J., et al. Infection and sudden unexpected death in infancy: a systematic retrospective case review. Lancet 2008; 371: 1848–53.CrossRefGoogle ScholarPubMed
Gaytant, M. A., Rours, G. I., Steegers, E., et al. Congenital cytomegalovirus infection after recurrent infection: case reports and review of the literature. Eur J Pediatr. 2003; 162: 248–53.Google ScholarPubMed
Suri, M.. Genetic basis for acute necrotizing encephalopathy of childhood. Develop Med Child Neurol 2010; 52: 4–5.CrossRefGoogle ScholarPubMed
Hart, M. N. and Earle, K. M.. Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases. J Neurol Neurosurg Psychiatry 1975; 38: 585–91.CrossRefGoogle ScholarPubMed
Young, N. P., Weinshenker, B. G., Parisi, J., et al. Perivenous demyelination: association with clinically defined acute disseminated encephalomyelitis and comparison with pathologically confirmed multiple sclerosis. Brain 2010; 133: 333–48.CrossRefGoogle ScholarPubMed
Lindenberg, R. and Freytag, E.. Morphology of brain lesions from blunt trauma in early infancy. Arch Pathol 1969; 87: 298–305.Google ScholarPubMed
Emerson, M. V., Jakobs, E., and Green, W.. Ocular autopsy and histopathologic features of child abuse. Ophthalmology 2007; 114: 1384–94.CrossRefGoogle ScholarPubMed
Gilles, E. E., McGregor, M. L., and Levy-Clarke, G.. Retinal hemorrhage asymmetry in inflicted head injury: a clue to pathogenesis?J Pediatr 2003; 143: 494–9.CrossRefGoogle ScholarPubMed
Till, K.. Subdural haematoma and effusion in infancy. BMJ 1968; 3: 400–2.CrossRefGoogle ScholarPubMed
Geddes, J. F., Hackshaw, A. K., Vowles, G., et al. Neuropathology of inflicted head injury in children: I. Patterns of brain damage. Brain 2001; 124: 1290–8.CrossRefGoogle ScholarPubMed
Geddes, J. F., Vowles, G. H., Hacksaw, A., et al. Neuropathology of inflicted head injury in children: II. Microscopic brain injury in infants. Brain 2001; 124: 1299–306.CrossRefGoogle ScholarPubMed
Duhaime, A. C., Gennarelli, T. A., Thibault, L., et al. The shaken baby syndrome: a clinical, pathological, and biomechanical study. J Neurosurg 1987; 66: 409–15.CrossRefGoogle ScholarPubMed
Squier, W., Mack, J., Green, A., and Aziz, T.. The pathophysiology of brain swelling associated with subdural hemorrhage: the role of the trigeminovascular system. Childs Nerv Syst 2012; 28: 2005–15.CrossRefGoogle ScholarPubMed
Verity, C. M., Winstone, A. M., Stellitano, L., et al. The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based study. Develop Med Child Neurol 2010; 52: 434–40.CrossRefGoogle ScholarPubMed
Tzoulis, C. and Bindoff, L. A.. Acute mitochondrial encephalopathy reflects neuronal energy failure irrespective of which genome the genetic defect affects. Brain 2012; 135: 3627–34.CrossRefGoogle ScholarPubMed
Matthews, P. M., Nagy, Z., Brown, G., Land, J., and Squier, M.. Isolated capillary proliferation in Leigh’s syndrome. Clin Neuropathol 1994; 13: 139–41.Google ScholarPubMed
Encha-Razavi, F., Gonzalès, M., Laquerrière, A., et al. A practical approach to the examination of the malformed fetal brain: impact on genetic counseling. Pathology 2008; 40: 180–7.CrossRefGoogle Scholar
Thornton, G. K. and Woods, C. G.. Primary microcephaly: do all roads lead to Rome?Trends Genet 2009; 25: 501–10.CrossRefGoogle ScholarPubMed
Yang, Y., Phillips, O. R., Kan, E., et al. Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2012; 36: 798–806.CrossRefGoogle ScholarPubMed
Cohen, M. M. and Sulik, K. K.. Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. J Craniofac Genet Dev Biol 1992; 12: 196–244.Google ScholarPubMed
Lipinski, R. J., Godin, E. A., O’Leary-Moore, S. K., Parnell, S. E., and Sulik, K. K.. Genesis of teratogen-induced holoprosencephaly in mice. Am J Med Genet C 2010; 154C: 29–42.CrossRefGoogle ScholarPubMed
Putoux, A., Thomas, S., Coene, K. L., et al. KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes. Nat Genet. 2011; 43: 601–6.CrossRefGoogle ScholarPubMed
Dobyns, W. B., Stratton, R. F., and Greenberg, F.. Syndromes with lissencephaly. I: Miller–Dieker and Norman–Roberts syndromes and isolated lissencephaly. Am J Med Genet 1984; 18: 509–26.CrossRefGoogle ScholarPubMed
Dobyns, W. B., Kirkpatrick, J. B., Hittner, H. M., Roberts, R. M., and Kretzer, F. L.. Syndromes with lissencephaly. II: Walker–Warburg and cerebro-oculo-muscular syndromes and a new syndrome with type II lissencephaly. Am J Med Genet 1985; 22: 157–95.CrossRefGoogle Scholar
Dobyns, W. B., Gilbert, E. F., and Opitz, J. M.. Further comments on the lissencephaly syndromes. Am J Med Genet. 1985; 22: 197–211.CrossRefGoogle ScholarPubMed
Encha Razavi, F., Larroche, J. C., Roume, J., et al. Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome. Am J Med Genet 1996; 62: 16–22.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Encha-Razavi, F. and Chelly, J.. Pitfalls of the morphologic approach. J Neuropathol Exp Neurol. 2006; 65: 302; author reply 302–3.CrossRefGoogle ScholarPubMed
Viot, G., Sonigo, P., Simon, I., et al. Neocortical neuronal arrangement in LIS1 and DCX lissencephaly may be different. Am J Med Genet A 2004; 126A: 123–8.CrossRefGoogle ScholarPubMed
Forman, M. S., Squier, W., Dobyns, W. B., and Golden, J. A.. Genotypically defined lissencephalies show distinct pathologies. J Neuropathol Exp Neurol. 2005; 64: 847–57.CrossRefGoogle ScholarPubMed
Devisme, L., Bouchet, C., Gonzalès, M., et al. Cobblestone lissencephaly: uropathological subtypes and correlations with genes of dystroglycanopathies. Brain 2012; 135: 469–82.CrossRefGoogle Scholar
Bonneau, D., Toutain, A., Laquerrière, A., et al. X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG): clinical, magnetic resonance imaging, and neuropathological findings. Ann Neurol 2002; 51: 340–9.CrossRefGoogle ScholarPubMed
Fallet-Bianco, C., Loeuillet, L., Poirier, K., et al. Neuropathological phenotype of a distinct form of lissencephaly associated with mutations in TUBA1A. Brain 2008; 131: 2304–20.CrossRefGoogle ScholarPubMed
Vuillaumier-Barrot, S., Bouchet-Séraphin, S. Céline, Chelbi, M., et al. Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly. Am J Hum Genet 2012; 9: 1135–43.CrossRefGoogle Scholar
Michaud, J., Mizrahi, E. M., and Urich, H.. Agenesis of the vermis with fusion of the cerebellar hemispheres, septo-optic dysplasia and associated anomalies: report of a case. Acta Neuropathol 1982; 56: 161–6.CrossRefGoogle ScholarPubMed
Pasquier, L., Marcorelles, P., Loget, P., et al. Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases. Acta Neuropathol 2009; 117: 185–200.CrossRefGoogle ScholarPubMed
Bessières-Grattagliano, B., Foliguet, B., Devisme, L., et al. Refining the clinicopathological pattern of cerebral proliferative glomeruloid vasculopathy (Fowler syndrome): report of 16 fetal cases. Eur J Med Genet 2009; 52: 386–92.CrossRefGoogle ScholarPubMed
Thomas, S., Encha-Razavi, F., Devisme, L., et al. High-throughput sequencing of a 4.1 Mb linkage interval reveals FLVCR2 deletions and mutations in lethal cerebral vasculopathy. Hum Mutat 2010; 31: 1134–41CrossRefGoogle ScholarPubMed
Ostrovskaya, T. I. and Lazjuk, G. I.. Cerebral abnormalities in the Neu–Laxova syndrome. Am J Med Genet 1988; 30: 747–56.CrossRefGoogle ScholarPubMed
Namavar, Y., Barth, P. G., Poll-The, B. T., and Baas, F.. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis 2011; 6: 50.CrossRefGoogle ScholarPubMed
Namavar, Y., Barth, P. G., Kasher, P. R., et al. Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. Brain 2011; 134: 143–56.CrossRefGoogle ScholarPubMed
Mahieu-Caputo, D., Salomon, L. J., Dommergues, M., et al. Arthrogryposis multiplex congenita and cerebellopontine ischemic lesions in sibs: recurrence of prenatal disruptive brain lesions with different patterns of expression?Fetal Diagn Ther 2002; 17: 153–6.CrossRefGoogle Scholar
Harris, M. J. and Juriloff, D. M.. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. Birth Defects Res A Clin Mol Teratol 2010; 88: 653–69.CrossRefGoogle Scholar

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