Cerebral Abnormalities in Adults with Ataxia-Telangiectasia

Abstract

SUMMARY: Ataxia-telangiectasia, an autosomal recessive disorder caused by defect of the ataxia-telangiectasia mutated gene, is characterized by progressive neurologic impairment with cerebellar atrophy, ocular and cutaneous telangiectasia, immunodeficiency, heightened sensitivity to ionizing radiation and susceptibility to developing lymphoreticular malignancy. Supratentorial brain abnormalities have been reported only rarely. In this study, brain MRI was performed in 10 adults with ataxia-telangiectasia having stable neurologic impairment. Intracerebral telangiectasia with multiple punctate hemosiderin deposits were identified in 60% of subjects. These lesions were apparently asymptomatic. They are similar in appearance to radiation-induced telangiectasia and to cryptogenic vascular malformations. Also noted, in the 2 oldest subjects, was extensive white matter T2 hyperintensity, and in 1 of these a space-occupying fluid collection consistent with transudative capillary leak and edema as evidenced by reduced levels of metabolites on MR spectroscopic imaging. Asymptomatic supratentorial vascular abnormalities appear to be common in adults with ataxia-telangiectasia.

Investigating neural connectivity of corticomotor networks in ataxia telangiectasia: improving our understanding of the clinical phenotype

“…These findings were not reflected in structural T2-weighted axial scans ( Figure 3.4, Appendices), indicating the sensitivity and specificity of dMRI for delineating WM degeneration. Our radiological findings in general do not reflect past imaging observations in cerebral pathological conditions in A-T. 158 As seen from clinical observations of our A-T cohort, A-T neuropathology can be heterogeneous in nature among different patients, irrespective of age; [82][83][84] therefore, disease characteristics may differ from cohort to cohort.…”

“…146 Asymptomatic supratentorial vascular abnormalities in the cerebrum have also been reported in a recent study using 10 adult A-T patients, where intracerebral telangiectasia with multiple punctate haemosiderin deposits were identified in 60% of the imaged patients. 158 These more recent findings reflect post-mortem observations of cerebral pathology in A-T 91, 92 with slight pathological differences due to individual patient differences and differences in the progressive stage of disease.…”

“…While cerebellar degeneration is a wellestablished finding in A-T, structural changes in the cerebral motor cortex and spinal cord, particularly in histopathological studies, have been confined mainly to older A-T patients (reviewed in Sahama 15 ) and sparingly in young patients. 88,157 Cerebral abnormalities in structural MRI studies have also been observed largely in adult A-T patients, 145,158,193 however exceptional cases in early A-T have been noted. 157 Our current findings of cerebellar, somatosensory and spinal cord neurodegeneration, and our previous observations of reduced grey matter density in A-T motor regions, 183 provide evidence that the thalamus, precentral gyrus and postcentral gyrus are likely affected in our young A-T patient cohort.…”

“…Lin and colleagues (158) T1/T2 19-34 4/6 Findings: manifest cerebellar atrophy was seen in A-T; supratentorial brain showed no sign of volume loss. Intracerebral telangiectasia with multiple punctate haemosiderin deposits were identified in 60% of subjects.…”

“…84,144,148,150,158 Although this has been useful from a radiological perspective, such morphological studies provide limited information of the association between neurodegeneration and the loss in neural motor network integrity. Diffusion-weighted MRI (dMRI), particularly diffusion tensor imaging (DTI), has been demonstrated to allow a more accurate depiction of brain and brainstem structure integrity than that afforded by standard MRI.…”