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. 2022 Jun;9(6):841-852.
doi: 10.1002/acn3.51564. Epub 2022 May 6.

Visual memory failure presages conversion to MELAS phenotype

Emily B Leaffer  1   2   3 , Darryl C De Vivo  4 , Kristin Engelstad  4 , Robert H Fryer  4 , Yian Gu  5 , Dikoma C Shungu  6 , Michio Hirano  4 , Salvatore DiMauro  4 , Veronica J Hinton  1   2
Affiliations

Visual memory failure presages conversion to MELAS phenotype

Emily B Leaffer et al. Ann Clin Transl Neurol. 2022 Jun.

Abstract

Objective: To examine the correlation between verbal and visual memory function and correlation with brain metabolites (lactate and N-Acetylaspartate, NAA) in individuals with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).

Methods: Memory performance and brain metabolites (ventricular lactate, occipital lactate, and occipital NAA) were examined in 18 MELAS, 58 m.3243A > G carriers, and 20 familial controls. Measures included the Selective Reminding Test (verbal memory), Benton Visuospatial Retention Test (visual memory), and MR Spectroscopy (NAA, Lactate). ANOVA, chi-squared/Fisher's exact tests, paired t-tests, Pearson correlations, and Spearman correlations were used.

Results: When compared to carriers and controls, MELAS patients had the: (1) most impaired memory functions (Visual: p = 0.0003; Verbal: p = 0.02), (2) greatest visual than verbal memory impairment, (3) highest brain lactate levels (p < 0.0001), and (4) lowest brain NAA levels (p = 0.0003). Occipital and ventricular lactate to NAA ratios correlated significantly with visual memory performance (p ≤ 0.001). Higher lactate levels (p ≤ 0.01) and lower NAA levels (p = 0.0009) correlated specifically with greater visual memory dysfunction in MELAS. There was little or no correlation with verbal memory.

Interpretation: Individuals with MELAS are at increased risk for impaired memory. Although verbal and visual memory are both affected, visual memory is preferentially affected and more clearly associated with brain metabolite levels. Preferential involvement of posterior brain regions is a distinctive clinical signature of MELAS. We now report a distinctive cognitive phenotype that targets visual memory more prominently and earlier than verbal memory. We speculate that this finding in carriers presages a conversion to the MELAS phenotype.

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Conflict of interest statement

Dr. Leaffer reports no financial and nonfinancial disclosure or conflict of interest. Dr. De Vivo reports no financial and nonfinancial disclosure or conflict of interest. Ms. Engelstad reports no financial and nonfinancial disclosure or conflict of interest. Dr. Fryer reports no financial and nonfinancial disclosure or conflict of interest. Dr. Gu reports no financial and nonfinancial disclosure or conflict of interest. Dr. Shungu reports no financial and nonfinancial disclosure or conflict of interest. Dr. Hirano reports no financial and nonfinancial disclosure of conflict of interests. Dr. DiMauro reports no financial and nonfinancial disclosure or conflict of interest. Dr. Hinton report no financial and nonfinancial disclosure or conflict of interest.

Figures

Figure 1
Figure 1
Brain metabolites by group.
Figure 2
Figure 2
Relationship between visual memory and brain metabolite ratios.
Figure 3
Figure 3
Relationship between verbal memory and brain metabolite ratios.
See this image and copyright information in PMC

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