Abnormal hippocampal development in children with medulloblastoma treated with risk-adapted irradiation.
OBJECTIVE
Children with medulloblastoma demonstrate post-treatment neurocognitive deficits in a number of areas, including memory performance. However, there is no definitive understanding of the neuropathology underlying these functional deficits. Previous literature has reported that hippocampal integrity is crucial to the acquisition of new episodic memories. Therefore, we hypothesized that longitudinal hippocampal volume measurements are abnormal in patients with medulloblastoma and thereby provide a possible substrate for explaining memory dysfunction.


METHODS
Twenty-five pediatric patients underwent 159 serial MR imaging examinations (mean = six examinations per patient) for up to 5 years after irradiation and chemotherapy treatment for medulloblastoma. Right and left hippocampal volumes were obtained by manually tracing 1.5-mm contiguous coronal sections through the structure. Random coefficient models were used to examine longitudinal change in hippocampal volume as a function of time after diagnosis.


RESULTS
Both right and left hippocampal volumes initially decreased after treatment. This abnormal volume pattern continued until approximately 2-3 years after diagnosis, when hippocampal volumes returned toward a normal positive growth pattern. Volume loss occurred predominately in the posterior regions. Female sex, low parental education, shunt placement, and positive seizure history all had a significant negative impact on hippocampal volume.


CONCLUSIONS
Pediatric medulloblastoma survivors demonstrate an abnormal pattern of hippocampal volume development after treatment. Radiation dose mapping may expand our understanding of region-specific changes in hippocampal volume. Further exploration of the relationships between radiation therapy, memory dysfunction, and hippocampal pathology in this population is warranted.
Nagel
Bonnie J
BJ
Division of Behavioral Medicine, St Jude Children's Research Hospital, Memphis, TN, USA.
Palmer
Shawna L
SL
Reddick
Wilburn E
WE
Glass
John O
JO
Helton
Kathleen J
KJ
Wu
Shengjie
S
Xiong
Xiaoping
X
Kun
Larry E
LE
Gajjar
Amar
A
Mulhern
Raymond K
RK
D000647:Amnesia / Q000175:diagnosis*; D001284:Atrophy; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006624:Hippocampus / Q000528:radiation effects*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D011379:Prognosis; D011832:Radiation Injuries / Q000175:diagnosis*; D011879:Radiotherapy Dosage