Infantile tauopathies: Hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma

Sarnat, Harvey B.; Flores-Sarnat, Laura

doi:10.1016/j.braindev.2014.08.010

Cited by 73Epilepsy research and treatmentFetal and Pediatric Neurological DisordersTuberous Sclerosis Complex Research

Infantile tauopathies: Hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma

Sarnat, Harvey B., Flores-Sarnat, Laura·2015·Brain and Development

DOI 10.1016/j.braindev.2014.08.010

Open this paper in CoChat — free account

Abstract

Tau is a normal microtubule-associated protein; mutations to phosphorylated or acetylated forms are neurotoxic. In many dementias of adult life tauopathies cause neuronal degeneration. Four developmental disorders of the fetal and infant brain are presented, each of which exhibits up-regulation of tau. Microtubules are cytoskeletal structures that provide the strands of mitotic spindles and specify cellular polarity, growth, lineage, differentiation, migration and axonal transport of molecules. Phosphorylated tau is abnormal in immature as in mature neurons. Several malformations are demonstrated in which upregulated tau may be important in pathogenesis. All produce highly epileptogenic cortical foci. The prototype infantile tauopathy is (1) hemimegalencephaly (HME); normal tau is degraded by a mutant AKT3 or AKT1 gene as the aetiology of focal somatic mosaicism in the periventricular neuroepithelium. HME may be isolated or associated with neurocutaneous syndromes, particularly epidermal naevus syndromes, also due to somatic mutations. Other tauopathies of early life include: (2) tuberous sclerosis complex; (3) focal cortical dysplasia type 2b (FCD2b); and (4) ganglioglioma, a tumor with dysplastic neurons and neoplastic glial cells. Pathological tau in these infantile cases alters cellular growth and architecture, synaptic function and tissue organization, but does not cause neuronal loss. All infantile tauopathies are defined neuropathologically as a tetrad of (1) dysmorphic and megalocytic neurons; (2) activation of the mTOR signaling pathway; (3) post-zygotic somatic mosaicism; and (4) upregulation of phosphorylated tau. HME and FCD2b may be the same disorder with different timing of the somatic mutation in the mitotic cycles of the neuroepithelium. HME and FCD2b may be the same disorder with different timing of the somatic mutation in the mitotic cycles of the neuroepithelium. Tauopathies must be considered in infantile neurological disease and no longer restricted to adult dementias. The mTOR inhibitor everolimus, already demonstrated to be effective in TSC, also may be a potential treatment in other infantile tauopathies.

Integrity signals

Registry

Crossref · 10.1016/j.braindev.2014.08.010

Cites

105 of 105 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

TSC is an infantile tauopathy accumulating phosphorylated tau.
“This is based on prior studies which have shown that TSC is an infantile tauopathy accumulating phosphorylated tau [10].”
From Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation (2022) · cites this paper as [10]
The compact NFTs observed are morphologically most like those seen in primary age-related tauopathy (PART), Alzheimer's disease (AD), and chronic traumatic encephalopathy (CTE), but the topographical distribution and immunostaining characteristics differ from these more common tauopathies.
“The compact NFTs observed are morphologically most like those seen in primary age-related tauopathy (PART) [4], Alzheimer’s disease (AD) [22], and chronic traumatic encephalopathy (CTE) [13, 14], but the topographical distribution and immunostaining characteristics differ from these more common tauopathies in several respects.”
From Tuberous sclerosis complex is associated with a novel human tauopathy (2023) · cites this paper as [22]
Overactivation of other mTOR pathway proteins is linked to tau pathology.
“Interestingly, an overactivation of other mTOR pathway proteins are also linked to tau pathology.22,23”
From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [22]
TSC is considered one of a group of juvenile tauopathies.
“In fact, TSC is considered 1 of a group of juvenile tauopathies.22”
From Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia (2020) · cites this paper as [22]

The clinicopathologic spectrum of focal cortical dysplasias: A consensus classification proposed by an ad hoc Task Force of the ILAE Diagnostic Methods Commission1
Blümcke, I., Thom, M., Aronica, E., Armstrong, D. D., Vinters, H. V., Palmini, A., Jacques, T. S., AVANZINI, G., Barkovich, A. J., Battaglia, G. S., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02777.x · Cited by 1,746 · see citing works
Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34
Slegtenhorst, M. V., Hoogt, R. D., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Ouweland, A. V. D., Halley, D., Young, J., et al. (1997) · Science · doi:10.1126/science.277.5327.805 · Cited by 1,648 · see citing works
Identification and characterization of the tuberous sclerosis gene on chromosome 16
(1993) · Cell · doi:10.1016/0092-8674(93)90618-z · Cited by 1,645 · see citing works
Tuberous sclerosis
Curatolo, P., Bombardieri, R., & Jóźwiak, S. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61279-9 · Cited by 1,106 · see citing works
Focal dysplasia of the cerebral cortex in epilepsy
Taylor, D. C., Falconer, M. A., Bruton, C. J., & Corsellis, J. (1971) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.34.4.369 · Cited by 1,074 · see citing works
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
Krueger, D. A., Caré, M. M., Holland, K. D., Agricola, K. D., Tudor, C., Mangeshkar, P., Wilson, K. A., Byars, A. W., Sahmoud, T., & Franz, D. N. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001671 · Cited by 1,003 · see citing works
Terminology and classification of the cortical dysplasias
Palmini, A., Najm, I., AVANZINI, G., Babb, T. L., Guerrini, R., Foldvary‐Schaefer, N., Jackson, G. D., Lüders, H. O., Prayson, R. A., Spreafico, R., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000114507.30388.7e · Cited by 948 · see citing works
A Mosaic Activating Mutation in AKT1 Associated with the Proteus Syndrome
Lindhurst, M. J., Sapp, J. C., Teer, J. K., Johnston, J. J., Finn, E., Peters, K. F., Turner, J. T., Cannons, J. L., Bick, D. P., Blakemore, L. C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104017 · Cited by 892 · see citing works
Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial
Franz, D. N., Belousova, E., Sparagana, S., Bebin, E. M., Frost, M., Kuperman, R., Witt, O., Kohrman, M. H., Flamini, J. R., Wu, J. Y., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61134-9 · Cited by 794 · see citing works
A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus
Tang, S. J., Reis, G., Kang, H., Gingras, A.-C., Sonenberg, N., & Schuman, E. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012605299 · Cited by 734 · see citing works
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly
Lee, J. H., Huynh, M., Silhavy, J. L., Kim, S., Dixon-Salazar, T., Heiberg, A., Scott, E., Bafna, V., Hill, K. J., Collazo, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2329 · Cited by 703 · see citing works
Mechanisms of tau-induced neurodegeneration
Iqbal, K., Liu, F., Gong, C.-X., Alonso, A. D. C., & Grundke-Iqbal, I. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0486-3 · Cited by 628 · see citing works
Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Johnson, V. E., Stewart, W., & Smith, D. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00513.x · Cited by 620 · see citing works
Rapamycin causes regression of astrocytomas in tuberous sclerosis complex
Franz, D. N., Leonard, J. M., Tudor, C., Chuck, G., Caré, M. M., Sethuraman, G., Dinopoulos, A., Thomas, G., & Crone, K. R. (2006) · Annals of Neurology · doi:10.1002/ana.20784 · Cited by 614 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Control of Dendritic Arborization by the Phosphoinositide-3′-Kinase–Akt–Mammalian Target of Rapamycin Pathway
Jaworski, J., Spangler, S. A., Seeburg, D. P., Hoogenraad, C. C., & Sheng, M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2270-05.2005 · Cited by 576 · see citing works
Dysregulation of mTOR signaling in fragile X syndrome
Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3696-09.2010 · Cited by 557 · see citing works
Somatic activation of AKT3 causes hemispheric developmental brain malformations
Poduri, A., Evrony, G. D., Cai, X., Elhosary, P. C., Beroukhim, R., Lehtinen, M. K., Hills, L. B., Heinzen, E. L., Hill, A., Hill, R. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.010 · Cited by 478 · see citing works
Cerebral Cortical Dysplasia Associated with Pediatric Epilepsy. Review of Neuropathologic Features and Proposal for a Grading System
Mischel, P. S., Nguyen, L. P., & Vinters, H. V. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199503000-00001 · Cited by 450 · see citing works
Gangliogliomas: An Intriguing Tumor Entity Associated With Focal Epilepsies
Blümcke, I., & Wiestler, O. D. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.7.575 · Cited by 377 · see citing works
Supratentorial gangliogliomas: Histopathologic grading and tumor recurrence in 184 patients with a median follow‐up of 8 years
Luyken, C., Blümcke, I., Fimmers, R., Urbach, H., Wiestler, O. D., & Schramm, J. (2004) · Cancer · doi:10.1002/cncr.20332 · Cited by 347 · see citing works
Different features of histopathological subtypes of pediatric focal cortical dysplasia
Kršek, P., Maton, B., Korman, B., Pacheco-Jácome, E., Jayakar, P., Dunoyer, C., Rey, G. J. F. D., Morrison, G., Ragheb, J. R., Vinters, H. V., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21398 · Cited by 303 · see citing works
Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., Xie, S. X., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Brain · doi:10.1093/brain/aws013 · Cited by 281 · see citing works
Morphogenesis and Pattern Formation
Connelly, T. G., Brinkley, L. L., & Carlson, B. M. (1981) · Medical Entomology and Zoology · Cited by 277 · see citing works
mTOR: A pathogenic signaling pathway in developmental brain malformations
Crino, P. B. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.07.008 · Cited by 266 · see citing works
A transient array of parallel microtubules in frog eggs: Potential tracks for a cytoplasmic rotation that specifies the dorso-ventral axis
Elinson, R. P., & Rowning, B. A. (1988) · Developmental Biology · doi:10.1016/0012-1606(88)90281-3 · Cited by 250 · see citing works
Tau Loss Attenuates Neuronal Network Hyperexcitability in Mouse and <i>Drosophila</i> Genetic Models of Epilepsy
Holth, J. K., Bomben, V. C., Reed, J. G., Inoue, T., Younkin, L., Younkin, S. G., Pautler, R. G., Botas, J., & Noebels, J. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3191-12.2013 · Cited by 238 · see citing works
Selective pharmacogenetic inhibition of mammalian target of Rapamycin complex I (mTORC1) blocks long-term synaptic plasticity and memory storage
Stoica, L., Zhu, P. J., Huang, W., Zhou, H., Kozma, S. C., & Costa-Mattioli, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014715108 · Cited by 232 · see citing works
Hemimegalencephaly: Part 1. Genetic, Clinical, and Imaging Aspects
Flores‐Sarnat, L. (2002) · Journal of Child Neurology · doi:10.1177/088307380201700512 · Cited by 227 · see citing works
Self-citation
Interaction of Tau with the Neural Membrane Cortex Is Regulated by Phosphorylation at Sites That Are Modified in Paired Helical Filaments
Maas, T., Eidenmüller, J., & Brandt, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000389200 · Cited by 226 · see citing works
Glial and Neuronal Tau Pathology in Tauopathies: Characterization of Disease-Specific Phenotypes and Tau Pathology Progression
Ferrer, I., López-González, I., Carmona, M., Arregui, L., Dalfó, E., Torrejón-Escribano, B., Diehl, R., & Kovacs, G. G. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000030 · Cited by 217 · see citing works
Survey of Somatic Mutations in Tuberous Sclerosis Complex (TSC) Hamartomas Suggests Different Genetic Mechanisms for Pathogenesis of TSC Lesions
Niida, Y., Stemmer-Rachamimov, A. O., Logrip, M. L., Tapon, D., Perez, R., Kwiatkowski, D. J., Sims, K. B., MacCollin, M., Louis, D. N., & Ramesh, V. (2001) · The American Journal of Human Genetics · doi:10.1086/321972 · Cited by 205 · see citing works
Epileptogenesis in pediatric cortical dysplasia: The dysmature cerebral developmental hypothesis
Cepeda, C., André, V., Levine, M. S., Salamon, N., Miyata, H., Vinters, H. V., & Mathern, G. W. (2006) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2006.05.012 · Cited by 200 · see citing works
Altered mTOR signaling and enhanced CYFIP2 expression levels in subjects with fragile X syndrome
Hoeffer, C. A., Sanchez, E., Hagerman, R. J., Mu, Y., Nguyen, D. V., Wong, H., Whelan, A. M., Zukin, R. S., Klann, E., & Tassone, F. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00768.x · Cited by 198 · see citing works
Dendritic pathology in mental retardation: from molecular genetics to neurobiology
Dierssen, M., & Ramakers, G. J. A. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00224.x · Cited by 190 · see citing works
Focal transmantle dysplasia: A specific malformation of cortical development
Barkovich, A. J., Kuzniecky, R., Bollen, A. W., & Grant, P. E. (1997) · Neurology · doi:10.1212/wnl.49.4.1148 · Cited by 183 · see citing works
Dysembryoplastic Neuroepithelial Tumors Share with Pleomorphic Xanthoastrocytomas and Gangliogliomas BRAFV600E Mutation and Expression
Chappé, C., Padovani, L., Scavarda, D., Forest, F., Nanni‐Metellus, I., Loundou, A., Mercurio, S., Fina, F., Lena, G., Colin, C., et al. (2013) · Brain Pathology · doi:10.1111/bpa.12048 · Cited by 180 · see citing works
Characterization of the Cytosolic Tuberin-Hamartin Complex
Nellist, M. D., van Slegtenhorst, M. A., Goedbloed, M., van den Ouweland, A. M. W., Halley, D. J. J., & van der Sluijs, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35647 · Cited by 176 · see citing works
Mammalian Target of Rapamycin (mTOR) Pathways in Neurological Diseases
Wong, M. (2013) · Biomedical Journal · doi:10.4103/2319-4170.110365 · Cited by 169 · see citing works
Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia
Ljungberg, M. C., Bhattacharjee, M. B., Lu, Y., Armstrong, D. L., Yoshor, D., Swann, J. W., Sheldon, M., & D’Arcangelo, G. (2006) · Annals of Neurology · doi:10.1002/ana.20949 · Cited by 155 · see citing works
Microtubules in Bacteria: Ancient Tubulins Build a Five-Protofilament Homolog of the Eukaryotic Cytoskeleton
Pilhofer, M., Ladinsky, M. S., McDowall, A. W., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1001213 · Cited by 131 · see citing works
Fetal Brain Lesions in Tuberous Sclerosis Complex: TORC1 Activation and Inflammation
Prabowo, A. S., Anink, J. J., Lammens, M. M. Y., Nellist, M. D., van den Ouweland, A. M. W., Adle‐Biassette, H., Sarnat, H. B., Flores‐Sarnat, L., Crino, P. B., & Aronica, E. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00616.x · Cited by 127 · see citing works
Self-citation
Germ-Line Mosaicism in Tuberous Sclerosis: How Common?
Rose, V. M., Au, K. S., Pollom, G., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302322 · Cited by 119 · see citing works
Fetal Brain mTOR Signaling Activation in Tuberous Sclerosis Complex
Tsai, V., Parker, W. E., Orlova, K. A., Baybis, M., Chi, A. W. S., Berg, B. D., Birnbaum, J. F., Estevez, J., Okochi, K., Sarnat, H. B., et al. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhs310 · Cited by 116 · see citing works
Self-citation
Hemimegalencephaly: Part 2. Neuropathology Suggests a Disorder of Cellular Lineage
Flores‐Sarnat, L., Sarnat, H. B., Dávila-Gutiérrez, G., & Álvarez, A. (2003) · Journal of Child Neurology · doi:10.1177/08830738030180111101 · Cited by 109 · see citing works
Self-citation
Developmental brain abnormalities in tuberous sclerosis complex: A comparative tissue analysis of cortical tubers and perituberal cortex
Ruppe, V., Dilsiz, P., Reiss, C. S., Carlson, C., Devinsky, O., Zagzag, D., Weiner, H. L., & Talos, D. M. (2014) · Epilepsia · doi:10.1111/epi.12545 · Cited by 108 · see citing works
Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease
Kang, J., Vanderstichele, H., Trojanowski, J. Q., & Shaw, L. M. J. (2012) · Methods · doi:10.1016/j.ymeth.2012.03.023 · Cited by 107 · see citing works
Cytoskeletal and signaling mechanisms of neurite formation
Sainath, R., & Gallo, G. (2015) · Cell and Tissue Research · doi:10.1007/s00441-014-1955-0 · Cited by 103 · see citing works
Tuberous sclerosis in a 20-week gestation fetus: immunohistochemical study
Park, S., Pepkowitz, S. H., Kerfoot, C. A., Rosa, M. J. D., Poukens, V., Wienecke, R., DeClue, J. E., & Vinters, H. V. (1997) · Acta Neuropathologica · doi:10.1007/s004010050691 · Cited by 98 · see citing works
Focal brain malformations: Seizures, signaling, sequencing
Crino, P. B. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02289.x · Cited by 98 · see citing works
Pediatric Neuroimaging
Wycliffe, N., Holshouser, B. A., Bartnik‐Olson, B., et al. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-37101-8.00012-6 · Cited by 95 · see citing works
Epilepsy Related to Developmental Tumors and Malformations of Cortical Development
Aronica, E., & Crino, P. B. (2014) · Neurotherapeutics · doi:10.1007/s13311-013-0251-0 · Cited by 94 · see citing works
Hyperphosphorylated tau in young and middle-aged subjects
El‐Obeid, A., Soininen, H. S., & Alafuzoff, I. I. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0906-z · Cited by 92 · see citing works
Molecular Neuropathology of Epilepsy-Associated Glioneuronal Malformations
Becker, A. J., Blümcke, I., Urbach, H., Hans, V., & Majores, M. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000199570.19344.33 · Cited by 90 · see citing works
Gene expression profile analysis of epilepsy-associated gangliogliomas
Aronica, E., Boer, K., Becker, A. J., Redeker, S., Spliet, W. G. M., van Rijen, P. C., Wittink, F. R. A., Breit, T. M., Wadman, W. J., Lopes, F. H. D. S., et al. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.10.036 · Cited by 85 · see citing works
Regression of Subependymal Giant Cell Astrocytoma With Rapamycin in Tuberous Sclerosis Complex
Koenig, M. K., Butler, I. J., & Northrup, H. (2008) · Journal of Child Neurology · doi:10.1177/0883073808321764 · Cited by 83 · see citing works
Focal Cortical Dysplasias: clinical implication of neuropathological classification systems
Spreafico, R., & Blümcke, I. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0714-x · Cited by 80 · see citing works
An Increase in Basal BDNF Provokes Hyperactivation of the Akt-Mammalian Target of Rapamycin Pathway and Deregulation of Local Dendritic Translation in a Mouse Model of Down's Syndrome
Troca-Marín, J. A., Alves-Sampaio, A., & Montesinos, M. L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0011-11.2011 · Cited by 79 · see citing works
Good interobserver and intraobserver agreement in the evaluation of the new ILAE classification of focal cortical dysplasias
Coras, R., de Boer, O. J., Armstrong, D. L., et al. (2012) · Epilepsia · doi:10.1111/j.1528-1167.2012.03508.x · Cited by 76 · see citing works
Co‐Localization of TSC1 and TSC2 Gene Products in Tubers of Patients with Tuberous Sclerosis
Johnson, M. W., Emelin, J. K., Park, S., & Vinters, H. V. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00209.x · Cited by 72 · see citing works
Molecular Pathogenesis of Focal Cortical Dysplasia and Hemimegalencephaly
Crino, P. B. (2005) · Journal of Child Neurology · doi:10.1177/08830738050200041101 · Cited by 70 · see citing works
Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex
Perek‐Polnik, M., Jóźwiak, S., Jurkiewicz, E., Perek, D., & Kotulska, K. (2011) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2011.09.006 · Cited by 67 · see citing works
Levels of microtubules during the meiotic maturation of the Xenopus oocyte
Jessus, C., Thibier, C., & Ozon, R. (1987) · Journal of Cell Science · doi:10.1242/jcs.87.5.705 · Cited by 64 · see citing works
Phosphorylated tau/amyloid beta 1-42 ratio in ventricular cerebrospinal fluid reflects outcome in idiopathic normal pressure hydrocephalus
Patel, S. V., Lee, E. B., Xie, S. X., Law, A. C., Jackson, E. M., Arnold, S. E., Clark, C. M., Shaw, L. M. J., Grady, M. S., Trojanowski, J. Q., et al. (2012) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-9-7 · Cited by 62 · see citing works
Aberrant neuronal development in hemimegalencephaly: Immunohistochemical and Golgi studies
Takashima, S., Chan, F., Becker, L. E., et al. (1991) · Pediatric Neurology · doi:10.1016/0887-8994(91)90045-m · Cited by 61 · see citing works
Recent Advances in Epilepsy 5
Palia, S. S. (1993) · Postgraduate Medical Journal · doi:10.1136/pgmj.69.814.666 · Cited by 61 · see citing works
Co-expression of cyclin D1 and phosphorylated ribosomal S6 proteins in hemimegalencephaly
Aronica, E., Boer, K., Baybis, M., Yu, J., & Crino, P. B. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0225-6 · Cited by 59 · see citing works
Cell injury and Premature Neurodegeneration in Focal Malformations of Cortical Development
Iyer, A. M., Prabowo, A. S., Anink, J. J., Spliet, W. G. M., van Rijen, P. C., & Aronica, E. (2013) · Brain Pathology · doi:10.1111/bpa.12060 · Cited by 56 · see citing works
Epilepsy in newborns with tuberous sclerosis complex
Kotulska, K., Jurkiewicz, E., Domańska‐Pakieła, D., et al. (2014) · European Journal of Paediatric Neurology · doi:10.1016/j.ejpn.2014.06.009 · Cited by 55 · see citing works
Original article Hemimegalencephaly: foetal tauopathy with mTOR hyperactivation and neuronal lipidosis
Sarnat, H. B., Flores‐Sarnat, L., Crino, P. B., Hader, W. J., & Bello‐Espinosa, L. E. (2012) · Folia Neuropathologica · doi:10.5114/fn.2012.32363 · Cited by 52 · see citing works
Self-citation
Comparative study of cellular and synaptic abnormalities in brain tissue samples from pediatric tuberous sclerosis complex and cortical dysplasia type II
Cepeda, C., André, V., Yamazaki, I., Hauptman, J. S., Chen, J., Vinters, H. V., Mathern, G. W., & Levine, M. S. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02633.x · Cited by 50 · see citing works
Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex
Yalon, M., Ben‐Sira, L., Constantini, S., & Toren, A. (2010) · Child s Nervous System · doi:10.1007/s00381-010-1222-y · Cited by 50 · see citing works
Epilepsies associated with focal cortical dysplasias (FCDs)
Najm, I., Tassi, L., Sarnat, H. B., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1304-0 · Cited by 49 · see citing works
Self-citation
Tuberous sclerosis
Curatolo, P., & Bombardieri, R. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)87009-6 · Cited by 48 · see citing works
Neuronal and Glial Proteins: Structure, Function, and Clinical Application
Marangos, P. J., Campbell, I. C., & Cohen, R. M. (1988) · Cited by 46 · see citing works
Radial Microcolumnar Cortical Architecture: Maturational Arrest or Cortical Dysplasia?
Sarnat, H. B., & Flores‐Sarnat, L. (2013) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2012.10.001 · Cited by 45 · see citing works
Self-citation
Misfolded tau protein and disease modifying pathways in transgenic rodent models of human tauopathies
Žilka, N., Korenova, M., & Novák, M. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0499-y · Cited by 45 · see citing works
Hemimegalencephaly in Tuberous Sclerosis Complex
Galluzzi, P., Cerase, A., Strambi, M., et al. (2002) · Journal of Child Neurology · doi:10.1177/088307380201700905 · Cited by 44 · see citing works
Epidermal nevus syndrome with hemimegalencephaly: Neuropathological study
Sakuta, R., Aikawa, H., Takashima, S., et al. (1991) · Brain and Development · doi:10.1016/s0387-7604(12)80060-x · Cited by 43 · see citing works
Novel Types of Frontotemporal Lobar Degeneration: Beyond Tau and TDP-43
Mackenzie, I. R., Neumann, M., Cairns, N. J., Muñoz, D. G., & Isaacs, A. M. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9551-1 · Cited by 40 · see citing works
Enhanced expression of microtubule‐associated protein 2 in large neurons of cortical dysplasia
Yamanouchi, H., Zhang, W., Jay, V., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410390109 · Cited by 39 · see citing works
Expression of neurodegenerative disease‐related proteins and caspase‐3 in glioneuronal tumours
Prabowo, A. S., Iyer, A. M., Veersema, T. J., Anink, J. J., Meeteren, A. Y. N. S., Spliet, W. G. M., van Rijen, P. C., Ferrier, C. H., Thom, M., & Aronica, E. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12143 · Cited by 36 · see citing works
Tau‐associated neuropathology in ganglion cell tumours increases with patient age but appears unrelated to ApoE genotype
Brat, D. J., Gearing, M., Goldthwaite, P. T., Wainer, B. H., & Burger, P. C. (2001) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2001.00311.x · Cited by 36 · see citing works
Hemimegalencephaly, a paradigm for somatic postzygotic neurodevelopmental disorders
Baek, S. T., Gibbs, E. M., Gleeson, J. G., & Mathern, G. W. (2013) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32835ef373 · Cited by 35 · see citing works
Tuberous sclerosis-related gene expression in normal and dysplastic brain
Vinters, H. V., Kerfoot, C. A., Catania, M. G., Emelin, J. K., Roper, S. N., & DeClue, J. E. (1998) · Epilepsy Research · doi:10.1016/s0920-1211(98)00036-9 · Cited by 33 · see citing works
Mechanisms of mitosis
McIntosh, J. R. (1984) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(84)90138-5 · Cited by 33 · see citing works
4 Microtubules and Cytoplasmic Reorganization in the Frog Egg
Houliston, E., & Elinson, R. P. (1992) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(08)60440-8 · Cited by 31 · see citing works
Morphogenesis timing of genetically programmed brain malformations in relation to epilepsy
Sarnat, H. B., & Flores‐Sarnat, L. (2014) · Progress in brain research · doi:10.1016/b978-0-444-63326-2.00010-7 · Cited by 31 · see citing works
Self-citation
Everolimus for Tumor Recurrence After Surgical Resection for Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex
Franz, D. N., Agricola, K. D., Tudor, C., & Krueger, D. A. (2012) · Journal of Child Neurology · doi:10.1177/0883073812449904 · Cited by 30 · see citing works
Synaptogenèses et épigenèses cérébrales
Bourgeois, J. (2005) · médecine/sciences · doi:10.1051/medsci/2005214428 · Cited by 29 · see citing works
Tauopathies: One Disease or Many?
Bouchard, M., & Suchowersky, O. (2011) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100012087 · Cited by 27 · see citing works
Longitudinal MR findings in a patient with hemimegalencephaly associated with tuberous sclerosis
Sakuma, H., Iwata, O., & Sasaki, M. (2005) · Brain and Development · doi:10.1016/j.braindev.2004.11.004 · Cited by 26 · see citing works
Transmantle Dysplasia in Tuberous Sclerosis
Vigliano, P., Canavese, C., Bobba, B., et al. (2002) · Journal of Child Neurology · doi:10.1177/08830738020170101601 · Cited by 26 · see citing works
Hemimegalencephaly and tuberous sclerosis complex
Cartwright, M. S., McCarthy, S. C., & Roach, E. S. (2005) · Neurology · doi:10.1212/01.wnl.0000154465.87255.78 · Cited by 26 · see citing works
Hemimegalencephaly--morphological and immunocytochemical study.
Yasha, T. C., Santosh, V., Das, S., et al. (1997) · PubMed · Cited by 26 · see citing works
Synaptogenesis in hemimegalencephaly: the numerical density of asymmetric and symmetric synapses in the cerebral cortex
OʼKusky, J. R., Akers, M.-A., & Vinters, H. V. (1996) · Acta Neuropathologica · doi:10.1007/s004010050503 · Cited by 25 · see citing works
Everolimus (RAD001): First Systemic Treatment for Subependymal Giant Cell Astrocytoma Associated with Tuberous Sclerosis Complex
Jóźwiak, S., Stein, K. F., & Kotulska, K. (2012) · Future Oncology · doi:10.2217/fon.12.146 · Cited by 20 · see citing works
Is intractable epilepsy a tauopathy?
Xi, Z., Wang, X., Shu, X.-F., Chen, G., Xiao, F., Sun, J., & Zhu, X. (2011) · Medical Hypotheses · doi:10.1016/j.mehy.2011.03.003 · Cited by 19 · see citing works
Hemimegalencephaly syndrome
Flores‐Sarnat, L. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)87010-2 · Cited by 18 · see citing works
Self-citation
Looking for novel functions of tau
Ávila, J., de Barreda, E. G., Fuster-Matanzo, A., Simón, D., Llorens-Martı́n, M., Engel, T., Lucas, J. J., Dı́az-Hernández, M., & Hernández, F. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120006 · Cited by 17 · see citing works
Ganglioglioma with neurofibrillary tangles (NFTs): neoplastic NFTs share antigenic determinants with NFTs of Alzheimer's disease
Soffer, D., Umansky, F., & Goldman, J. E. (1995) · Acta Neuropathologica · doi:10.1007/bf00307651 · Cited by 16 · see citing works
Similarity of Balloon Cells in Focal Cortical Dysplasia to Giant Cells in Tuberous Sclerosis
Jóźwiak, J., Kotulska, K., & Jóźwiak, S. (2006) · Epilepsia · doi:10.1111/j.1528-1167.2006.00531_1.x · Cited by 15 · see citing works
Epidermal nevus syndrome.
Koizumi, H., Tsukinaga, I., Kaneko, F., et al. (1987) · The Nishinihon Journal of Dermatology · doi:10.2336/nishinihonhifu.49.655 · Cited by 11 · see citing works
796. The HSV-1 iBAC Amplicon Vector for Functional Genomics Studies into the Genetic Mechanisms of Neurodegenerative Disease
(2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.06.835 · Cited by 2 · see citing works
MICROTUBULES: STRUCTURAL, FUNCTIONAL, AND CLINICAL ASPECTS
Wallin, M. (1988) · Elsevier eBooks · doi:10.1016/b978-0-12-470348-3.50017-3 · Cited by 1 · see citing works

Flagged first, then by citations

Research works printed but not linked: 5

Flores-Sarnat L. Hemimegalencephaly syndrome. In: Handbook of clinical neurology. Sarnat HB, Curatolo P, editors. Malformations of the nervous system, vol. 87. Edinburgh: Elsevier; 2008. p. 153–76. · DOI
Oblak A, Murrell J, Richardson R, Epperson F, Ghetti B. Comparative analysis of neuronal vulnerability of the anterior cingulate cortex in hereditary and sporadic tauopathies. J Neuropathol Exp Neurol 2014;73:597 (abstract).
Yalon, 2011, Regression of subependymal giant cell astrocytomas with RAD001 (Everolimus) in tuberous sclerosis complex, Childs Nerv Syst, 27, 179, 10.1007/s00381-010-1222-y · DOI
Gondim D, Murrell J, Oblak A, Sokol D, Walsh L, Bosh G, et al. Childhood neurodegenerative disease with widespread tauopathy. J Neuropathol Exp Neurol 2014;73:624–5 (abstract).
Iqbal, 2009, Mechanisms of tau-induced neurodegeneration, Acta Neuropathol, 118, 53, 10.1007/s00401-009-0486-3 · DOI · Paper page

Sorted by citations

Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
“…et al., 2014), focal cortical dysplasia IIB (FCDIIb) (Sen et al., 2007; Iyer et al., 2014), and tuberous sclerosis complex (TSC) (Sarnat and Flores-Sarnat, 2015; Liu et al., 2020), as well as animal models of post-traumatic epilepsy (PTE) (Cho et al., 2020; Alyenbaawi et al., 2021), Lafora…”
Background
Widespread genotype-phenotype correlations in intellectual disability
Casanova, E. L., Gerstner, Z., Sharp, J. L., Casanova, M. F., & Feltus, F. A. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00535 · Cited by 31 · see citing works
Association of Cognitive and Behavioral Features Between Adults With Tuberous Sclerosis and Frontotemporal Dementia
Liu, A. J., Staffaroni, A. M., Rojas-Martinez, J. C., Olney, N. T., Alquezar-Burillo, C., Ljubenkov, P. A., La Joie, R., Fong, J. C., Taylor, J., Karydas, A., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4284 · Cited by 18 · see citing works
Tuberous sclerosis complex is a novel, amyloid-independent tauopathy associated with elevated phosphorylated 3R/4R tau aggregation
Liu, A. J., Lusk, J. B., Ervin, J., Burke, J., O’Brien, R., & Wang, S.-H. J. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01330-x · Cited by 15 · see citing works
Tuberous sclerosis complex is associated with a novel human tauopathy
Hwang, J.-H. L., Perloff, O. S., Gaus, S. E., Benitez, C., Alquezar, C., Cosme, C. Q., Nana, A. L., Vatsavayai, S. C., Ramos, E. M., Geschwind, D. H., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-022-02521-5 · Cited by 15 · see citing works
The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases
Lane-Donovan, C., Paredes, M., & Kao, A. W. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102854 · Cited by 3 · see citing works
Amyloid-Independent Elevation of Plasma phosphorylated tau-217 Tracks Neurodegenerative Risk in Tuberous Sclerosis Complex: Implications for mTOR-Targeted Intervention
Baumel, J., Lutz, M., Ding, C., Capal, J., Ritter, D., Krueger, D., Salter, A., Werner, K., & Liu, A. J. (2026) · medRxiv · doi:10.64898/2026.09.09.26362677

Radiologic-pathologic correlation in focal cortical dysplasia and hemimegalencephaly in 18 children
Woo, C. L. F., Chuang, S. H., Becker, L. E., et al. (2001) · Pediatric Neurology · doi:10.1016/s0887-8994(01)00318-6 · Cited by 53 · see citing works
Is focal cortical dysplasia sporadic? Family evidence for genetic susceptibility
Leventer, R. J., Jansen, F. E., Mandelstam, S. A., et al. (2014) · Epilepsia · doi:10.1111/epi.12533 · Cited by 31 · see citing works
Mammalian target of rapamycin pathway mutations cause hemimegalencephaly and focal cortical dysplasia
D’Gama, A. M., Geng, Y., Couto, J. A., Martin, B., Boyle, E. A., LaCoursiere, C. M., Hossain, A. A., Hatem, N. E., Barry, B. J., Kwiatkowski, D. J., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24357 · Cited by 290 · see citing works
Investigating the role of somatic mutations in malformations of brain development
Leventer, R. J., Scerri, T. S., Marsh, A. P. L., Maixner, W. J., MacGregor, D. P., Harvey, A. S., Delatycki, M. B., Amor, D. J., Bahlo, M., & Lockhart, P. J. (2017) · Pathology · doi:10.1016/j.pathol.2016.12.082
[Classification and pathogenesis of cerebral cortical malformations].
Takashima, S., Tsuru, A., & Mizuguchi, M. (1996) · PubMed

Authors: Sarnat, H. B., & Flores-Sarnat, L.
Affiliations: University of Calgary (CA)
Corresponding author: Sarnat, Harvey B.
ORCID: Sarnat, Harvey B.
Venue: Brain and Development
Publisher: Elsevier BV
Published: 2015-06
Volume: 37
Issue: 6
Pages: 553-562
ISSN: 0387-7604 (ISSN-L)
DOI: 10.1016/j.braindev.2014.08.010
OpenAlex: W1989822657
Semantic Scholar: 69044d1f638de472b5a1c0813170f5d2a28edbe6
Cited by: 73
References: 105
Citations by year: 2025: 3 · 2024: 1 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 10 · 2016: 7 · 2015: 6 · 2014: 1 · 2012: 1
FWCI: 5.38
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Brain and Development (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
Keywords: hemimegalencephaly, tuberous sclerosis complex, ganglioglioma, tau phosphorylation, somatic mosaicism, mTOR signaling, everolimus, neurocutaneous syndrome, developmental brain malformations
MeSH terms: Brain, Epilepsy, Humans, Infant, Male, Microtubules, Neurons, Phosphorylation, Tuberous Sclerosis, tau Proteins, Ganglioglioma, Tauopathies, TOR Serine-Threonine Kinases, Malformations of Cortical Development, Group I, Hemimegalencephaly

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Infantile tauopathies: Hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks