Astrocytic inclusions in epilepsy: expanding the spectrum of filaminopathies.
We report the finding of unique astrocytic inclusions in a series of pediatric epilepsy patients, all of whom presented with seizures in their first year of life and had mild-to-moderate developmental delay. All eventually underwent surgical treatment for refractory epilepsy and, on pathological examination, were found to have distinctive, eosinophilic, globular cytoplasmic inclusions confined to cortical astrocytes. These inclusions were almost exclusively juxtanuclear, highly refractile, spared distal subpial, or perivascular astrocytic processes and were strongly and exclusively immunopositive for filamin A, an actin binding protein involved in neuronal migration. Identical inclusions have been identified and characterized in cases of Aicardi syndrome, a rare neurodevelopmental disease. The presence of the same inclusions in the cortex of epilepsy patients, some of whom had concomitant brain anomalies related to migrational problems, prompted us to consider that these patients may lie within a spectrum of disease involving dysfunction of filamin or filamin-interacting proteins. The term "filaminopathy" is tentatively proposed as a distinct pathological entity for this condition in which clinical manifestations range from epilepsy in mildly neurologically impaired patients to severe mental and physical handicap in the Aicardi syndrome. Future studies will be necessary to unravel the exact nature of the filamin A protein or gene aberrations in these patients.
Hazrati
Lili-Naz
LN
Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Kleinschmidt-DeMasters
B K
BK
Handler
Michael H
MH
Smith
Mary Lou
ML
Ochi
Ayako
A
Otsubo
Hiroshi
H
Rutka
James T
JT
Go
Cristina
C
Weiss
Shelly
S
Hawkins
Cynthia E
CE
D001253:Astrocytes / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003285:Contractile Proteins / Q000378:metabolism*; D004827:Epilepsy / Q000473:pathology*; D005260:Female; D064448:Filamins; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000379:methods
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins