TY - JOUR
T1 - Unusual variants of Alexander's disease
AU - Van Der Knaap, Marjo S.
AU - Salomons, Gajja S.
AU - Li, Rong
AU - Franzoni, Emilio
AU - Gutiérrez-Solana, Luiz González
AU - Smit, Leo M.E.
AU - Robinson, Richard
AU - Ferrie, Collin D.
AU - Cree, Bruce
AU - Reddy, Alyssa
AU - Thomas, Neil
AU - Banwell, Brenda
AU - Barkhof, Frederik
AU - Jakobs, Cornelis
AU - Johnson, Anne
AU - Messing, Albee
AU - Brenner, Michael
PY - 2005/3
Y1 - 2005/3
N2 - The purpose of this study was to describe unusual variants of Alexander's disease. We studied 10 patients who did not meet previously established magnetic resonance imaging (MRI) criteria for Alexander's disease, but for whom this diagnosis was considered because of Rosenthal fibers at histological examination or presence of some MRI features suggestive of Alexander's disease. Sequence analysis of the GFAP gene was performed. In eight patients, MRI results showed predominantly posterior fossa lesions, especially multiple tumor-like brainstem lesions. One patient had asymmetrical frontal white matter abnormalities and basal ganglia abnormalities. One patient (Patient 10) developed degeneration of the frontal white matter. In nine patients, a mutation was found that was concluded to be pathogenic, because the mutation was de novo (five patients), a known mutation was found (two patients), or assembly of the glial fibrillary acidic protein was abnormal in cultured cells (two patients). In Patient 10, a DNA variation was found that was also present in the patient's clinically unaffected father and was concluded to be a polymorphism. In conclusion, DNA diagnostics is warranted in patients who display MRI features suggestive of Alexander's disease, even if they do not meet the full set of previously established MRI criteria.
AB - The purpose of this study was to describe unusual variants of Alexander's disease. We studied 10 patients who did not meet previously established magnetic resonance imaging (MRI) criteria for Alexander's disease, but for whom this diagnosis was considered because of Rosenthal fibers at histological examination or presence of some MRI features suggestive of Alexander's disease. Sequence analysis of the GFAP gene was performed. In eight patients, MRI results showed predominantly posterior fossa lesions, especially multiple tumor-like brainstem lesions. One patient had asymmetrical frontal white matter abnormalities and basal ganglia abnormalities. One patient (Patient 10) developed degeneration of the frontal white matter. In nine patients, a mutation was found that was concluded to be pathogenic, because the mutation was de novo (five patients), a known mutation was found (two patients), or assembly of the glial fibrillary acidic protein was abnormal in cultured cells (two patients). In Patient 10, a DNA variation was found that was also present in the patient's clinically unaffected father and was concluded to be a polymorphism. In conclusion, DNA diagnostics is warranted in patients who display MRI features suggestive of Alexander's disease, even if they do not meet the full set of previously established MRI criteria.
UR - http://www.scopus.com/inward/record.url?scp=20044367817&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ana.20381
DO - https://doi.org/10.1002/ana.20381
M3 - Article
C2 - 15732098
SN - 0364-5134
VL - 57
SP - 327
EP - 338
JO - Annals of neurology
JF - Annals of neurology
IS - 3
ER -