New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis.
Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) mutations in the MT-TL1 gene. The pathophysiology of neurological manifestations is still unclear, but neuronal hyperexcitability and neuron-astrocyte uncoupling have been suggested. Glutamatergic neurotransmission is linked to glucose oxidation and mitochondrial metabolism in astrocytes and neurons. Given the relevance of neuron-astrocyte metabolic coupling and astrocyte function regulating energetic metabolism, we aimed to assess glutamate and glutamine CSF levels in MELAS patients. Methods This prospective observational case-control study determined glutamate and glutamine CSF levels in patients with MELAS syndrome and compared them with controls. The plasma and CSF levels of the remaining amino acids and lactate were also determined. Results Nine adult patients with MELAS syndrome (66.7% females mean age 35.8 ± 3.2 years) and 19 controls (63.2% females mean age 42.7 ± 3.8 years) were included. The CSF glutamate levels were significantly higher in patients with MELAS than in controls (18.48 ± 1.34 vs. 5.31 ± 1.09 μmol/L, p < 0.001). Significantly lower glutamine concentrations in patients with MELAS than controls were shown in CSF (336.31 ± 12.92 vs. 407.06 ± 15.74 μmol/L, p = 0.017). Moreover, the CSF levels of alanine, the branched-chain amino acids (BCAAs) and lactate were significantly higher in patients with MELAS. Conclusions Our results suggest the glutamate-glutamine cycle is altered probably due to metabolic imbalance, and as a result, the lactate-alanine and BCAA-glutamate cycles are upregulated. These findings might have therapeutic implications in MELAS syndrome.
Background and Purpose: Mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA mutations. There are no disease-modifying therapies, and treatment remains mainly supportive. It has been shown previously that patients with MELAS syndrome have significantly increased cerebrospinal fluid (CSF) glutamate and significantly decreased CSF glutamine levels compared to controls. Glutamine has many metabolic fates in neurons and astrocytes, and the glutamate-glutamine cycle couples with many metabolic pathways depending on cellular requirements. The aim was to compare CSF glutamate and glutamine levels before and after dietary glutamine supplementation. It is postulated that high-dose oral glutamine supplementation could reduce the increase in glutamate levels.Method: This open-label, single-cohort study determined the safety and changes in glutamate and glutamine levels in CSF after 12 weeks of oral glutamine supplementation.Results: Nine adult patients with MELAS syndrome (66.7% females, mean age 35.8 ± 3.2 years) were included. After glutamine supplementation, CSF glutamate levels were significantly reduced (9.77 ± 1.21 vs. 18.48 ± 1.34 μmol/l, p < 0.001) and CSF glutamine levels were significantly increased (433.66 ± 15.31 vs. 336.31 ± 12.92 μmol/l, p = 0.002). A side effect observed in four of nine patients was a mild sensation of satiety.One patient developed mild and transient elevation of transaminases, and another patient was admitted for an epileptic status without stroke-like episode.Discussion: This study demonstrates that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients.
The MRI Barkhof-Tintoré criteria have proved to be highly specific for predicting conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes (CIS), but lacked an optimal sensitivity. In order to improve the accuracy of early multiple sclerosis diagnosis, new imaging criteria have been proposed by Swanton et al. We aimed to evaluate the accuracy of both MRI criteria for dissemination in space to predict conversion from CIS to clinically definite multiple sclerosis. We studied 79 CIS patients with baseline MRI performed within the first 3 months after onset. The sensitivity and specificity of both MRI criteria to predict conversion to clinically definite multiple sclerosis were analysed. The time to develop clinically definite multiple sclerosis from CIS onset, according to each imaging criteria, was studied by Kaplan-Meier survival curves. The overall conversion rate was 75.7% with a median follow-up of 57 months. Barkhof- Tintoré's criteria showed a sensitivity of 71.9% and a specificity of 77.2%. Swanton's criteria had a sensitivity of 91.2% and a specificity of 68.1%. Both MRI criteria identified CIS patients with higher risk and faster conversion to clinically definite multiple sclerosis. Swanton's criteria are simpler and more sensitive than Barkhof-Tintoré's criteria, with a slight decrease in specificity. These results reinforce their use in multiple sclerosis diagnosis.
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