Filamin A–negative hyaline astrocytic inclusions in pediatric patients with intractable epilepsy: report of 2 cases

View More View Less
  • 1 Departments of Pathology and Laboratory Medicine,
  • 2 Neurosurgery,
  • 3 Diagnostic and Interventional Imaging, and
  • 4 Pediatrics, The University of Texas Health Science Center at Houston; and
  • 5 Memorial Hermann Hospital–Texas Medical Center, Houston, Texas

Although rare, hyaline cytoplasmic inclusions isolated to astrocytes of the cerebral cortex have been identified in a spectrum of diseases ranging from intractable epilepsy in pediatric patients with only mild to moderate developmental delays to Aicardi syndrome. These inclusions classically stain positive for filamin A, giving rise to the term “filaminopathies.” The authors report on 2 pediatric patients with intractable epilepsy and developmental delay who uniquely displayed filamin A–negative hyaline astrocytic inclusions in resected brain tissues. Additionally, these inclusions stained positive for S100 and negative for glial fibrillary acidic protein, chromogranin, neurofilament, CD34, vimentin, periodic acid–Schiff (PAS), and Alcian blue. These are the first reported cases of filamin A–negative hyaline astrocytic inclusions, providing a novel variation on a previously reported entity and justification to further investigate the pathogenesis of these inclusions. The authors compare their findings with previously reported cases and review the literature on hyaline astrocytic inclusions in intractable pediatric epilepsy.

ABBREVIATIONS FCD = focal cortical dysplasia; GFAP = glial fibrillary acidic protein; PAS = periodic acid–Schiff; PVH = periventricular heterotopia.

Contributor Notes

Correspondence Meenakshi B. Bhattacharjee: University of Texas Health Science Center at Houston, TX. meenakshi.b.bhattacharjee@uth.tmc.edu.

INCLUDE WHEN CITING Published online March 27, 2020; DOI: 10.3171/2020.1.PEDS19706.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

  • 1

    Alzheimer A. Beiträge zur kenntnis der pathologischen neuroglia und ihrer beziehungen zu den abbauvorgängen im nervengewebe. In: Nissl F, Alzheimer A, eds. Histlogische und Histopathologische Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der Geisteskrankheiten. Vol 3. Jena, Germany: Gustav Fischer Verlag; 1910:401562.

    • Search Google Scholar
    • Export Citation
  • 2

    Miyakawa T, Sumiyoshi S, Deshimaru M, Tatetsu S. Electron microscopic study on a case of idiocy: astrocytes and mental deficiency. Acta Neuropathol. 1970;16(1):2534.

    • Search Google Scholar
    • Export Citation
  • 3

    Abe H, Yagishita S, Itoh K, Hamano S. Novel eosinophilic inclusion in astrocytes. Acta Neuropathol. 1992;83(6):659663.

  • 4

    Minagawa M, Shioda K, Shimizu Y, Isshiki T. Inclusion bodies in cerebral cortical astrocytes: a new change of astrocytes. Acta Neuropathol. 1992;84(1):113116.

    • Search Google Scholar
    • Export Citation
  • 5

    Minamitani M, Tanaka J, Maekawa K. Peculiar eosinophilic inclusions within astrocytes in a patient with malformed brain. Brain Dev. 1994;16(4):309314.

    • Search Google Scholar
    • Export Citation
  • 6

    Horoupian DS, Hattab EM, Heit G. Astrocytic cytoplasmic inclusions within an epileptic focus in an otherwise neurologically intact patient. Hum Pathol. 2003;34(7):714716.

    • Search Google Scholar
    • Export Citation
  • 7

    Adam J, Polivka M, Kaci R, Hyaline astrocytic inclusions in pediatric epilepsy: report of two cases. Clin Neuropathol. 2010;29(4):246253.

    • Search Google Scholar
    • Export Citation
  • 8

    AlAbdulsalam AA, Sabbagh A, AlHameed MH, Hyaline eosinophilic cortical astrocytic inclusions in a child with intractable epilepsy. Int J Clin Exp Pathol. 2016;9(3):40044008.

    • Search Google Scholar
    • Export Citation
  • 9

    Buchino JJ, Nicol KK, Parker JC Jr. Aicardi syndrome: a morphologic description with particular reference to intracytoplasmic inclusions in cortical astrocytes. Pediatr Pathol Lab Med. 1996;16(2):285291.

    • Search Google Scholar
    • Export Citation
  • 10

    Hazrati LN, Kleinschmidt-DeMasters BK, Handler MH, Astrocytic inclusions in epilepsy: expanding the spectrum of filaminopathies. J Neuropathol Exp Neurol. 2008;67(7):669676.

    • Search Google Scholar
    • Export Citation
  • 11

    Hedley-Whyte ET, Goldman JE, Nedergaard M, Hyaline protoplasmic astrocytopathy of neocortex. J Neuropathol Exp Neurol. 2009;68(2):136147.

    • Search Google Scholar
    • Export Citation
  • 12

    Van den Veyver IB, Panichkul PP, Antalffy BA, Presence of filamin in the astrocytic inclusions of Aicardi syndrome. Pediatr Neurol. 2004;30(1):715.

    • Search Google Scholar
    • Export Citation
  • 13

    Visanji NP, Wong JC, Wang SX, A proteomic analysis of pediatric seizure cases associated with astrocytic inclusions. Epilepsia. 2012;53(3):e50e54.

    • Search Google Scholar
    • Export Citation
  • 14

    Wong JC, O’Neill B, Hawkins CE, Child neurology: pediatric seizures with hyaline astrocytic inclusions. Neurology. 2013;81(3):e14e16.

    • Search Google Scholar
    • Export Citation
  • 15

    Spacek J, Nozicka Z. Cytoplasmic inclusions in neocortical astrocytes associated with arteriopathic encephalopathy and dementia. Hum Pathol. 1994;25(12):13661370.

    • Search Google Scholar
    • Export Citation
  • 16

    Rosser T. Aicardi syndrome. Arch Neurol. 2003;60(10):14711473.

  • 17

    Andrews JP, Gummadavelli A, Farooque P, Association of seizure spread with surgical failure in epilepsy. JAMA Neurol. 2019;76(4):462469.

    • Search Google Scholar
    • Export Citation
  • 18

    Tanaka K, Watase K, Manabe T, Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science. 1997;276(5319):16991702.

    • Search Google Scholar
    • Export Citation
  • 19

    Stossel TP, Condeelis J, Cooley L, Filamins as integrators of cell mechanics and signalling. Nat Rev Mol Cell Biol. 2001;2(2):138145.

    • Search Google Scholar
    • Export Citation
  • 20

    Chen MH, Walsh CA. FLNA-related periventricular nodular heterotopia. In: Adam MP, Ardinger HH, Pagon RA, , eds. GeneReviews [Internet]. Seattle: University of Washington; 19932020. https://www.ncbi.nlm.nih.gov/books/NBK1213/. Accessed February 12, 2020.

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 346 346 101
Full Text Views 27 27 4
PDF Downloads 20 20 7
EPUB Downloads 0 0 0