Inappropriate intracranial hemodynamics in the natural course of MELAS.

The abnormalities of intracranial hemodynamics associated with strokelike episodes in MELAS are variable depend on the time phase from the onset of strokelike episodes and on the progression of the dementia state. To clarify the regional cerebral blood flows (rCBF) in the natural course of MELAS is very important to understand the pathogenic mechanism of this disorder, either cytopathy, angiopathy or both. We analyzed the serial studies of brain statistical parametric mapping (SPM) 99 single photon emission computed tomography (SPECT) in 5 MELAS patients in maximum 10 years interval, who fulfilled the clinical, pathological and genetic criteria of MELAS, and have an A3243G mutation in the mitochondrial tRNA(Leu(UUR)) gene. SPM is a proven and effective method for the voxel-by-voxel analysis of functional images which show the advantage in its promise of fully automated neurophysiological imaging analysis throughout the whole brain using various statistical analyses. SPECT acquisition was initiated and was reconstructed by iterative algorithm and were processed and analyzed with SPM 99 for Windows software. Statistics were displayed as Z scores (threshold: P < 0.01). The inappropriate intracranial hemodynamics was found not only at the acute but at the interictal phase, and was getting worse as the disease progress. Hypoperfusion in the posterior cingulate cortex was always observed (corrected P < 0.01) in MELAS patients, which is the typical finding reported in Alzheimer's disease. The inappropriate intracranial hemodynamics is a common feature and may be related with mitochondrial angiopathy in the natural course of MELAS.