Elsevier

Neuropsychologia

Volume 47, Issue 1, January 2009, Pages 180-194
Neuropsychologia

Reading impairment in a patient with missing arcuate fasciculus

https://doi.org/10.1016/j.neuropsychologia.2008.08.011Get rights and content

Abstract

We describe the case of a child (“S”) who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominanance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.

Introduction

Cranial irradiation is an effective treatment for primary and metastatic central nervous system tumors (e.g., Jenkin, Danjoux, & Greenberg, 1998; Waber et al., 2001). However, it is well-known that long-term complications of radiation therapy can be severe, especially in children. Of the many types of damage, so-called late-delayed effects (including radiation necrosis) are the most devastating because of their irreversible nature. The pathophysiological mechanisms underlying this damage are an active area of research, and it is clear that the process is complex and involves damage to the endothelial cells of the vascular system and oligodendrocyte/astrocyte (O2-A) progenitor cells [for a review, see Belka, Budach, Kortmann, and Bamberg (2001) and Tofilon and Fike (2000)].

The cognitive consequences of radiation treatment are usually debilitating. In a longitudinal study of the effects of craniospinal irradiation on childhood medulloblastoma, significant reductions in IQ, reading, spelling, and math scores were reported, with reading skills especially affected in young patients (Mulhern et al., 2005). IQ changes are progressive, with a loss of 1.6–8.2 points per year (Fouladi et al., 2004, Mulhern et al., 2005). Other studies have demonstrated similar cognitive changes following radiation combined with chemotherapy (e.g., Fouladi et al., 2004, Mulhern et al., 2005, Reddick et al., 2006). Indeed, significant neuropsychological deficits are found in virtually all long-term survivors of childhood medulloblastoma treated with cranial irradiation (Walter et al., 1999).

Here we describe the case of a child (referred to as “S”) who was treated with whole-brain radiation therapy at age 5 for the recurrence of a malignant tumor in her upper spine and brain. The radiation treatment resulted in clinical remission, but left her with radiation-induced tissue necrosis, especially in the white matter of the brain. She was introduced to us at age 15 due to her extreme difficulties with learning to read. Damage produced as a result of radiation treatment is usually selective to white matter (Valk & Dillon, 1991), so we performed diffusion tensor imaging (DTI) to assess the state of white matter pathways and their connections in her brain. Most major white matter pathways were intact in S, but she was missing much of the superior longitudinal fasciculus (SLF), a major set of connections between lateral–frontal language areas and language regions in the parietal and temporal lobes that include the arcuate fasciculus (AF). We further characterized her cognitive strengths and weaknesses with neuropsychological testing, and confirmed the location of key language regions using functional MRI.

Section snippets

Control group

The control group was originally recruited for a longitudinal study of reading development. The data used here are from the first measurement in that longitudinal study. The group consisted of 54 children (25 males) ages 7–12 (median age 10.1). From this group we created two control groups; the first using the entire group of 54 and the second using only the 28 subjects who were female with basic reading scores greater than 90 (median age 9.7, range 7–12). Although results using either group as

Cognitive functioning of S

S is strongly right-handed as assessed by the EHI [Laterality Index = 82] (Oldfield, 1971). She exhibited generally consistent intellectual abilities over the time she was formally evaluated, with relatively average verbal abilities and well below average visuospatial abilities (see Table 2, Intellectual functioning). Her working memory abilities were well below average. Though the composite WMI from the WISC-IV is slightly different than the older version of the WISC-III's FD, the ability to

Radiation can produce damage to specific pathways

Our results indicate that damage from radiation-induced white matter necrosis can be both diffuse and focal. In previous studies of radiation-induced white matter necrosis, diffuse changes in fractional anisotropy (FA) and mean diffusivity (MD) due to radiation treatment have been shown to correlate with decreasing IQ (Khong et al., 2006; Mabbott, Noseworthy, Bouffet, Rockel, & Laughlin, 2006). In this study, we propose that more specific cognitive deficits may be linked to acute damage to

Conclusions

We have shown that it is possible to quantitatively compare white matter regions in a single subject with DTI data from a group of controls. Such a technique may prove very powerful in a clinical setting, where inferences made on a group level are less helpful than those made for an individual.

Our results demonstrate that in cases of radiation-induced necrosis, diffuse white matter differences evident in T2 and diffusion images may be accompanied by complete loss of specific pathways. The loss

Acknowledgements

First and foremost we thank S for her willingness to share her story with us and her patient cooperation during our testing. S's courage and determination to overcome the challenges that she faced were deeply inspiring. We also thank S's mother for her extensive help in arranging the measurements, compiling medical records, and for her general persistence in seeing the project through. Brian Wandell provided guidance, Adele Behn performed neuropsychological testing, and Arvel Hernandez assisted

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