Do lesional perfusion abnormalities on arterial spin labeling truly contribute to the diagnosis of Leigh syndrome?


Dear Editor, With interest we read the article by Whitehead et al. [1] about lesional perfusion abnormalities on arterial spin labeling (ASL) in eight patients with Leigh syndrome that correlated with disease activity. Necrotic lesions were hypointense and showed hypoperfusion, whereas active lesions with hyperintense diffusion-weighted imaging (DWI) showed hyperperfusion [1]. We have the following comments and concerns. Our main objection is that the investigated cohort of eight patients with Leigh syndrome is not defined with regard to the genetic cause and the phenotypic manifestations. How was the diagnosis of Leigh syndrome established? Was it based only upon the criteria of symmetrical brainstem or cerebral gray matter lesions, lactacidosis and clinical manifestations of a mitochondrial disorder, or was it also based upon muscle biopsy findings, biochemical investigations or genetic studies? Leigh syndrome is genetically extremely heterogeneous [2]. Which genes were mutated in the eight cases? Were only mitochondrial deoxyribonucleic acid (mtDNA)-located genes affected or were nuclear DNA-located genes, of which SURF1, NDUFS18, NDUFV1-2, SDH, and PDHC are the most frequent, also affected [2]? Among those carrying a mutation in an mtDNAlocated gene, were heteroplasmy rates correlatedwith perfusion abnormalities in the symmetrical lesions on ASL? Another disadvantage is the application of propofol as an intravenous anesthetic to carry out the MRI. It is well known that one side effect of propofol is a propofol infusion syndrome and that propofol is mitochondrion-toxic [3]. There are even indications that propofol triggers the development of a propofol infusion syndrome more commonly in patients with an mitochondrial disorder than in those without a mitochondrial disorder. How did propofol influence the cerebral blood flow? Previous studies have shown that propofol may reduce perfusion, particularly of the thalamo-cortical and fronto-parietal networks [4]. Readers should be informed how many of the eight patients had developed stroke-like episodes during the disease course with corresponding stroke-like lesions on cerebral MRI. Stroke-like episodes are a rare phenotypic manifestation of Leigh syndrome [5], and corresponding dynamic, chronic cerebral lesions may interfere with the symmetrical necrotic lesions in Leigh syndrome. Stroke-like lesions are most frequently associatedwith a vasogenic edema onDWI and apparent diffusion coefficient maps, suggesting that ASL results may depend on the presence or absence of a vasogenic edema. ASL may show crossed cerebellar hyperperfusion after a stroke-like episode [4]. Leigh syndrome frequently manifests with seizures, and seizure activity may significantly influence cerebral blood flow. Reduced diffusion in the subcortical regions of the frontal lobes has been found 5 days after onset of a status epilepticus [6]. ASL may show reduced cerebral blood flow already on day 1 of the epileptic state in the same regions [6]. Readers need to be informed about the medication the eight included patients were taking at the time of the examination. How many required antiepileptic treatment, how many cardiac therapy, and how many took vitamins, antioxidants or co-factors? To which degree did these compounds influence ASL? Overall, this interesting study could be improved by provision of data about the diagnosis, additional phenotypic features, and the medication at the time of investigation. Results of ASL may be influenced by drugs, seizures, and presence or absence of a stroke-like lesion. * Josef Finsterer

DOI: 10.1007/s00247-016-3718-4


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@article{Finsterer2016DoLP, title={Do lesional perfusion abnormalities on arterial spin labeling truly contribute to the diagnosis of Leigh syndrome?}, author={Josef Finsterer}, journal={Pediatric Radiology}, year={2016}, volume={47}, pages={124-125} }