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the left or right hippocampus (dose, P ≥ .2), cerebrum
(P ¼ .22), or SVZ (P ≥ .21) and performance on the
vocabulary test.
Visuospatial working memory (Bead Memory).—There
was no relationship between mean radiation dose to
the left or right hippocampus (P ≥ .66), temporal lobes
(P ≥ 0.87), SVZ ( P ≥ 0.18), or cerebrum (P ≥ .25) and
performance on the spatial working memory test.
Discussion
We present a prospective study examining the relation-
ship between radiation dose to NPC-containing niches,
temporal lobes, and cerebrum and neurocognitive func-
tion following RT. We demonstrate a significant associ-
ation between increasing mean RT dose to the
hippocampus and temporal lobes and decline in select
neurocognitive skills following cranial irradiation, but
no association between mean dose to SVZ or cerebrum
and test performance. This is one of the first human
studies to corroborate animal data suggesting a relation-
ship between radiation-induced damage to the hippo-
campus and neurocognitive dysfunction. –
These prospective data are consistent with prior ret-
rospective studies on long-term cancer survivors that
have demonstrated a significant association between ra-
diation dose to the temporal lobes and neurocognitive
dysfunction A prior prospective study found that
patients receiving .43.2 Gy to 13% of the volume of
the left temporal lobe were significantly more likely to
demonstrate a .10% decline in performance in full-
scale IQ An analysis of patients with nasopharyngeal
carcinoma reported significantly lower cognitive func-
tioning scores in patients with a mean dose to the tempo-
ral lobes of .36 Gy
Changes in the development of neuropsychological
skills (especially motor speed, declarative memory, and
visuoperceptual skills) following cranial irradiation
may result from radiation-induced structural damage
to the brain. For example, Nagel et a demonstrated
that the volume of both the right and left hippocampi de-
creased during the first 2–3 years following craniospinal
radiation for medulloblastoma. Diffusion tensor MRI
has been used to detect increased diffusion of water mol-
ecules in the hippocampus of patients receiving RT
Similarly, changes in white matter integrit and
volume occur following cranial irradiation, and
reduced volumes of the cerebellar vermis predict
reduced performance on neuropsychological testing
Future studies will be critical in gaining additional
insight into the mechanism of radiation-induced struc-
tural changes in the brain and its relationship to neuro-
cognitive dysfunction.
Our study did not demonstrate a relationship
between RT dose to the SVZ and neurocognitive func-
tion, a finding that is consistent with a prior study
Improved neurocognitive performance has also been re-
ported in patients with central nervous system germ cell
tumors treated with whole ventricle irradiation com-
pared with craniospinal RT suggesting that the most
critical areas for neurocognitive dysfunction are likely
to reside outside of the SVZ.
There are several limitations to our study. First, al-
though hippocampal and temporal lobe functions are
classically associated with declarative memory and
learning, the most significant relationship between radi-
ation dose to these areas and reduced performance was
on the test of motor speed, which may reflect the sensi-
tivity of tests of motor function to neural dysfunction
outside the frontally mediated motor systems. These
changes to motor function may reflect earlier effects on
more widespread subcortical white matter pathways in-
volved in the development of motor speed. In addition,
the test of motor function is the only timed measure in-
cluded in this battery, and the results may therefore
reflect a difference in processing speed. Performance on
the test of motor speed may also have been impacted
by radiation dose to other structures, such as the cerebel-
lum, which received a mean dose of 29.5 Gy (range
2–50.4 Gy). Although the relatively large percentage
of patients with infratentorial tumors could have con-
founded our results, there was no significant difference
Fig. 5. Performance on Purdue Pegboard 2-Hand test (Z-scores) at 6 mo following completion of RT relative to (A) mean left temporal lobe
radiation dose, P ¼ .033, and (B) mean right temporal lobe radiation dose, P ¼ .015. Standardized scores were used in this analysis to
account for the impact of age on test performance.
Redmond et al.: Radiation to neural progenitor niches and neurocognitive outcomes
366 NEURO-ONCOLOGY † M A R C H 2 0 1 3
at Universitaet Leipzig, Institut fuer Informatik/URZ, Bibliothek on August 25, 2014
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