Altered regional brain glucose metabolism in Duchenne muscular dystrophy: A pet study

Abstract

The basis for cognitive impairment in Duchenne muscular dystrophy (DMD) is not well understood but may be related to abnormal expression of dystrophin in brain. The aim of this study was to determine whether regional brain glucose metabolism is altered in children with DMD and whether such metabolic disturbances are localized to regions shown to be normally rich in dystrophin expression. Ten boys (mean age, 11.8 years) with DMD and 17 normal adults as a control group (mean age, 27.6 years) underwent 2-deoxy-2[(18)F]fluoro-D-glucose positron emission tomography (PET) and neuropsychological evaluation. The PET data were analyzed by statistical parametric mapping (SPM). The SPM analysis showed five clusters of decreased glucose metabolism in children with DMD, including the medial temporal structures and cerebellum bilaterally and the sensorimotor and lateral temporal cortex on the right side. At the voxel level, significant glucose hypometabolism was found in the right postcentral and middle temporal gyri, uncus, and VIIIB cerebellar lobule, as well as in the left hippocampal gyrus and cerebellar lobule. The neuropsychological profile of the DMD group revealed borderline nonverbal intellectual functioning, impaired manual dexterity bilaterally, borderline cognitive functioning, and internalizing behavioral difficulties. Our findings demonstrate region-specific hypometabolism, as well as cognitive and behavioral deficits in DMD children. As the regions showing hypometabolism on PET include those normally rich in dystrophin expression, it will be important to determine whether the hypometabolic regions also show cytoarchitectural abnormalities related to the lack of dystrophin.

Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy

“…The impact of dystrophin gene mutations on neuronal excitability, cerebral perfusion, and CBF reactivity is only partly elucidated; in boys with DMD, positron emission tomography [33], MR spectroscopy of the brain [34], and, recently, resting state fMRI [35] suggest reduced glucose metabolism in brain tissue [33], as well as a decrease in the motor cortex synchronization of spontaneous activity in patients with DMD versus healthy controls as detected using resting state fMRI of the motor cortex [35]. Further, reduced cerebral blood flow [27] and a global reduction in cerebral gray matter [36] has been reported in boys with DMD.…”

Decreased Gray Matter Concentration and Local Synchronization of Spontaneous Activity in the Motor Cortex in Duchenne Muscular Dystrophy

“…10 MRS studies on mdx mice showed elevated choline-containing compounds in the cerebellum and hippocampus. 11 PET studies have reported an altered metabolism of glucose in the cerebellum 12,13 and the right sensorimotor cortex. 13 A TMS study implicated decreased excitability in the left motor cortex in patients with DMD.…”

“…11 PET studies have reported an altered metabolism of glucose in the cerebellum 12,13 and the right sensorimotor cortex. 13 A TMS study implicated decreased excitability in the left motor cortex in patients with DMD. 14 Brain MR imaging studies did not find prominent structural abnormality in DMD participants 10,12,13 and mdx mice.…”

Duchenne Muscular Dystrophy and Brain Function

“…Bresolin et al (1994) found decreased glucose uptake in the cerebellum in DMD boys using PET imaging. Lee et al (2002) using PET and MRI found four clusters of decreased glucose metabolism in DMD: medial temporal structures and cerebellum bilaterally, the sensorimotor and lateral temporal cortex on the right side (compared to an adult control group). The authors suggest that these findings may reflect local cytoarchitectural changes and abnormalities associated with altered neural development.…”

“…The ratio of choline-containing compounds to N-acetylaspartyl-containing compounds (Cho/NA) was shown to correlate significantly with scores on the Matrix Analogies Test (MAT). The cerebellar and hippocampal focus of the biochemical lesions in DMD are of interest, due to the normally high expression of dystrophin in neurons found in these regions (Bresolin et al 1994;Lee et al 2002;). Both Dorman et al (1988) and Billard et al (1998) noted that the reading deficits seen in DMD patients are similar to those seen in phonological dyslexia (Castles & Coltheart, 1993).…”