Neuropathology Specialty Conference
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1 Neuropathology Specialty Conference March 22, 2010 Case 2 Rebecca Folkerth, MD Brigham and Women s Hospital Children s Hospital Harvard Medical School
2 Clinical History 18-gestational-week fetus found on prenatal ultrasound and MR to have: Cystic posterior fossa c/w Dandy-Walker malformation (DWM) Bilateral germinal matrix and intraventricular hemorrhage Hydrocephalus Amniocentesis with FISH for trisomies 13, 18, and 21 were normal Mother was 20-year-old G1P0, healthy
3 Fetal US - Coronal Fetal MR Coronal T2
4 Fetal MR - Parasagittal Fetal MR - Parasagittal
5 View of vermis and IVth ventricle from dorsally and superiorly L cerebellar hemisphere Remnant of vermis Floor IVth vent. Clot in IVth vent., compressing R cerebellar hemisphere
6 View of IVth ventricle from dorsally and inferiorly L cerebellar hemisphere with calcification and old hem. Occipital bone Floor IVth vent Distorted R cerebellum
7 Coronal section of cerebral hemispheres Old and recent hemorrhage, and calcification, in floor of lateral ventricles, which are expanded
8 - Multifocal old and recent hemorrhage - *Focal cortical disruption and cystic degeneration * Sup. vermis Micro * IVth v. Pons
9 Focal cerebellar cortical disruption Focal cystic change in cerebellar cortex
10 Cerebellar cx remnant GFAP
11 Cerebellar cx hemorrhage and mineralization Iron stain
12 Differential Diagnosis Dandy-Walker malformation (DWM; vermian aplasia/hypoplasia), with incidental intrauterine germinal matrix hemorrhage Disruptive lesion involving cerebellum, germinal matrix, and other sites Intrauterine infection (i.e., TORCH) Coagulopathy (e.g., Factor V Leiden deficiency, von Willebrand s disease)
13 Diagnosis Multifocal disruptive hemorrhagic lesions, with: Organizing germinal matrix hemorrhage with intraventricular extension (US grade III) Massive hydrocephalus due to aqueductal obstruction by hemorrhagic debris Acute and chronic ependymitis Organizing hemorrhage with cyst of cerebellar vermis, mimicking D-W Malformation Diffuse petechiae Epidural and subdural hemorrhages, acute and organizing Periventricular leukomalacia Gliosis of thalamus Special stains for toxo, HSV, VZV, CMV - negative
14 Why is this not DWM? DWM is a developmental constellation of: Absence of most or all of cerebellar vermis Cystic dilatation of the fourth ventricle Bowl-shaped expansion of the posterior fossa (indicating chronicity) Association with other CNS midline defects, cardiac and other systemic malformations, which tend to determine the prognosis Hemorrhage, mineralization, etc., are NOT present, and instead indicate disruption of a normally formed brain (= different pathogenesis) (Caveat: cannot absolutely exclude DWM, but not favored)
15 Pathology of typical DWM Note: NO evidence of hemorrhagic disruption
16 Pathogenesis of DWM may involve patterning defects
17 Autopsy in 2 of 3 cases showed organizing hemorrhage in posterior fossa, with tentorial, parenchymal, and subarachnoid hemorrhages Compression and atrophy or necrosis of adjacent structures resulted in cystic changes interpreted on prenatal imaging as developmental lesion (DWM, retrocerebellar dermoid cyst or arachnoid cyst) Presence of blood products in different compartments was key to recognition of disruptive process
18 Clinical implications Possible role of maternal/familial coagulopathy, with subsequent risk for future pregnancies Work-up of mother should be done DWM has very low risk of familial occurrence (<2%); associated anomalies largely determine the prognosis
19 Selected References
20 Acknowledgements Dr. Adre Du Plessis, Neonatal Neurology, Children s Hospital Boston Dr. Catherine Limperopoulos, Neurology and Neuroradiology, Toronto Sick Children s Hospital
21 Key Words Dandy-Walker, cerebellar hypoplasia, germinal matrix hemorrhage, perinatal brain
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