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Journal of the Neurological Sciences May 2020One of the most frequent cerebral lesions in mitochondrial disorders(MIDs) on imaging is the stroke-like lesion(SLL) clinically manifesting as stroke-like episode (SLE,... (Review)
Review
OBJECTIVES
One of the most frequent cerebral lesions in mitochondrial disorders(MIDs) on imaging is the stroke-like lesion(SLL) clinically manifesting as stroke-like episode (SLE, metabolic stroke). This review aims at discussing recent advances concerning the presentation, diagnosis, and treatment of SLLs.
METHODS
Systematic literature review using appropriate search terms.
RESULTS
SLLs are the hallmark of MELAS but occasionally occur in other MIDs. SLLs are best identified on multimodal, cerebral MRI. SLLs may present as uni-/multilocular, symmetric/asymmetric, cortical/subcortical, supra-/infratentorial condition, initially resembling a cytotoxic edema and later a vasogenic edema, or a variable mix between them. SLLs run through an acute and a chronic stage. The acute stage is characterised by a progressively expanding lesion over days, weeks, or months, showing up as increasing hyperintensity on T2/FLAIR, DWI, and PWI and by hyperperfusion, that does not conform to a vascular territory. ADC maps are initially hypointens to become hyperintens during the course. More rarely, a variable mixture of hyper- and hypointensities may be found. The chronic stage is characterised by hypoperfusion, gadolinium enhancement, and regression of hyperintensities to various endpoints. SLLs originate from an initial cortical lesion due to focal metabolic breakdown, which either remains stable or expands within the cortex or to subcortical areas. Some SLLs show spontaneous reversibility (fleeing cortical lesions) suggesting that neuronal/glial damage does not reach the threshold of irreversible cell death.
CONCLUSIONS
SLLs are a unique feature of various MIDs in particular MELAS. SLLs are dynamic and change their appearance over time. SLLs are accessible to treatment.
Topics: Contrast Media; Gadolinium; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Stroke
PubMed: 32088469
DOI: 10.1016/j.jns.2020.116726 -
Molecular Biology Reports Dec 2020The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by... (Review)
Review
The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by mutations of mitochondria-related genes, notably SUCLG1 and SUCLA2. Here, we presented a 5-year-old boy with clinical features of mitochondrial encephalomyopathy from Iran. Also, a systematic review was performed to explore the involvement of SUCLG1 mutations in published mitochondrial encephalomyopathies cases. Genotyping was performed by implementing whole-exome sequencing. Moreover, quantification of the mtDNA content was performed by real-time qPCR. We identified a novel, homozygote missense variant chr2: 84676796 A > T (hg19) in the SUCLG1 gene. This mutation substitutes Cys with Ser at the 60-position of the SUCLG1 protein. Furthermore, the in-silico analysis revealed that the mutated position in the genome is well conserved in mammalians, that implies mutation in this residue would possibly result in phenotypic consequences. Here, we identified a novel, homozygote missense variant chr2: 84676796 A > T in the SUCLG1 gene. Using a range of experimental and in silico analysis, we found that the mutation might explain the observed phenotype in the family.
Topics: Child, Preschool; DNA, Mitochondrial; Homozygote; Humans; Iran; Male; Mitochondria; Mitochondrial Encephalomyopathies; Mutation, Missense; Succinate-CoA Ligases
PubMed: 33230783
DOI: 10.1007/s11033-020-05999-y -
American Journal of Medical Genetics.... Jan 2023Biallelic pathogenic variants in the TARS2 gene cause combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial...
Biallelic pathogenic variants in the TARS2 gene cause combined oxidative phosphorylation deficiency, subtype 21 (COXPD21, MIM #615918), which is a rare mitochondrial encephalomyopathy (ME) characterized by early-onset severe axial hypotonia, limb hypertonia, delayed psychomotor development, epilepsy, and brain anomalies. Currently, eight COXPD21 patients have been reported in the literature, and 11 pathogenic variants in TARS2 have been identified. Here, we report a 2-year-6-month-old Chinese female who presented with severe dystonia, developmental regression, absent speech, and intractable epilepsy. Laboratory examination showed persistently increased serum lactate. Brain MRI showed that the head of the caudate and partial lenticular nucleus were bilateral symmetrical T2-weighted imaging (T2WI) hyperintense and the corpus callosum was very thin. The clinical characteristics pointed to a ME. Trio-based whole-exome sequencing (WES) was employed to detect the causative variants. WES revealed novel compound heterozygous variants, c.470G>C (p.Thr157Arg) and c.2051C>T (p.Arg684Gln), in TARS2 in our patient that were inherited from the mother and father, respectively. Next, we systematically reviewed the available clinical features of COXPD21 patients and noticed that the reduced fetal movement observed in our patient may be a novel phenotype of COXPD21. These findings expand the mutation spectrum of TARS2 and provide insights into the genotype-phenotype relationship in COXPD21 as well as a foundation for its genetic counseling, diagnosis and treatment.
Topics: Humans; Female; Mitochondrial Encephalomyopathies; East Asian People; Exome Sequencing; Phenotype; Mutation
PubMed: 36218002
DOI: 10.1002/ajmg.a.62988 -
Zeitschrift Fur Rheumatologie Feb 2024The objectives of this study are to analyze the association between anti-mitochondrial antibody (AMA) and cardiac involvement in idiopathic inflammatory myopathy (IIM)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The objectives of this study are to analyze the association between anti-mitochondrial antibody (AMA) and cardiac involvement in idiopathic inflammatory myopathy (IIM) and to evaluate the diagnostic value of AMA for cardiac involvement in IIM patients.
METHODS
We conducted a comprehensive search in PubMed, Web of Science, EMBASE, and the Cochrane Library to identify English-language studies published before November 19, 2021. Stata 12.0 software (Stata Corp., College Station, TX, USA) was used for the statistical analyses. We used the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curve to evaluate the diagnostic value of AMA for cardiac involvement in IIM patients. Statistical heterogeneity of studies was assessed using the I statistic with 95% confidence intervals (95% CIs).
RESULTS
Seven studies were included in the final analyses, with a total of 2308 IIM patients (including 171 AMA-positive and 2137 AMA-negative patients). The pooled sensitivity of AMA for cardiac involvement in IIM patients was 0.29 (95% CI: 0.19-0.43) and specificity was 0.92 (95% CI: 0.88-0.96). The pooled PLR was 3.9 (95% CI: 2.82-5.38), NLR was 0.76 (95% CI: 0.66-0.88), and the diagnostic odds ratio (DOR) was 5 (95% CI: 3-7). The area under the SROC curve was 0.76 (95% CI: 0.72-0.79).
CONCLUSION
The overall diagnostic value of AMA may not be very high for cardiac involvement in IIM patients.
Topics: Humans; ROC Curve; Myositis; Sensitivity and Specificity
PubMed: 35575829
DOI: 10.1007/s00393-022-01216-2 -
Journal of Neuroradiology = Journal de... Sep 2021Major cerebral vessels have been proposed as a target of defective mitochondrial metabolism in patients with mitochondrial encephalopathy, lactic acidosis, and... (Review)
Review
Major cerebral vessels have been proposed as a target of defective mitochondrial metabolism in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS). Cerebral angiographic techniques are not routinely performed in MELAS patients. A systematic literature review was performed to identify studies describing major vessel caliber alterations in MELAS. Twenty-three studies reporting on 46 MELAS patients were included. Alterations in major caliber vessels were present in 59% (27/46) of patients. Dilation occurred in 37% (17/46) of patients, and in 88% (15/17) of them during a stroke-like episode (SLE). Stenosis was reported in 24% (11/46) of patients: 36% (4/11) related to an SLE and 64% (7/11) to dissections or degenerative changes. During an SLE, identification of intracranial vessels dilation or stenosis could be a selection tool for new treatment protocols. Outside SLE, identification of major cerebral vessels dissections and degenerative changes may help to prevent subsequent complications.
Topics: Cerebral Angiography; Humans; MELAS Syndrome; Radionuclide Imaging; Stroke
PubMed: 33596430
DOI: 10.1016/j.neurad.2021.02.002 -
Frontiers in Physiology 2022Blood flow restriction exercise (BFRE) has become a common method to increase skeletal muscle strength and hypertrophy for individuals with a variety of conditions. A...
Blood flow restriction exercise (BFRE) has become a common method to increase skeletal muscle strength and hypertrophy for individuals with a variety of conditions. A substantial literature of BFRE in older adults exists in which significant gains in strength and functional performance have been observed without report of adverse events. Research examining the effects of BFRE in heart disease (HD) and heart failure (HF) appears to be increasing for which reason the Muscle Hypothesis of Chronic Heart Failure (MHCHF) will be used to fully elucidate the effects BFRE may have in patients with HD and HF highlighted in the MHCHF. A comprehensive literature review was performed in PubMed and the Cochrane library through February 2022. Inclusion criteria were: 1) the study was original research conducted in human subjects older than 18 years of age and diagnosed with either HD or HF, 2) study participants performed BFRE, and 3) post-intervention outcome measures of cardiovascular function, physical performance, skeletal muscle function and structure, and/or systemic biomarkers were provided. Exclusion criteria included review articles and articles on viewpoints and opinions of BFRE, book chapters, theses, dissertations, and case study articles. Seven BFRE studies in HD and two BFRE studies in HF were found of which four of the HD and the two HF studies examined a variety of measures reflected within the MHCHF over a period of 8-24 weeks. No adverse events were reported in any of the studies and significant improvements in skeletal muscle strength, endurance, and work as well as cardiorespiratory performance, mitochondrial function, exercise tolerance, functional performance, immune humoral function, and possibly cardiac performance were observed in one or more of the reviewed studies. In view of the above systematic review, BFRE has been performed safely with no report of adverse event in patients with a variety of different types of HD and in patients with HF. The components of the MHCHF that can be potentially improved with BFRE include left ventricular dysfunction, inflammatory markers, inactivity, a catabolic state, skeletal and possibly respiratory muscle myopathy, dyspnea and fatigue, ANS activity, and peripheral blood flow. Furthermore, investigation of feasibility, acceptability, adherence, adverse effects, and symptoms during and after BFRE is needed since very few studies have examined these important issues comprehensively in patients with HD and HF.
PubMed: 35874535
DOI: 10.3389/fphys.2022.924557 -
Orphanet Journal of Rare Diseases Nov 2019Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary...
Evaluation of earlier versus later dietary management in long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein deficiency: a systematic review.
BACKGROUND
Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection.
METHODS
We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another.
RESULTS
We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups.
CONCLUSIONS
There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.
Topics: Cardiomyopathies; Female; Humans; Lipid Metabolism, Inborn Errors; Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase; Male; Mitochondrial Myopathies; Mitochondrial Trifunctional Protein; Nervous System Diseases; Rhabdomyolysis
PubMed: 31730477
DOI: 10.1186/s13023-019-1226-y -
International Journal of Environmental... Jun 2020Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movements with...
Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, inherited disorder characterized by a congenital absence of conjugate horizontal eye movements with progressive scoliosis developing in childhood and adolescence. Mutations in the Roundabout (3) gene located on chromosome 11q23-25 are responsible for the development of horizontal gaze palsy and progressive scoliosis. However, some studies redefined the locus responsible for this pathology to a 9-cM region. This study carried out a systematic review in which 25 documents were analyzed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was made in the following electronic databases from January 1995 to October 2019: PubMed, Scopus, Web of Science, PEDRO, SPORT Discus, and CINAHL. HGPPS requires a multidisciplinary diagnostic approach, in which magnetic resonance imaging might be the first technique to suggest the diagnosis, which should be verified by an analysis of the 3 gene. This is important to allow for adequate ocular follow up, apply supportive therapies to prevent the rapid progression of scoliosis, and lead to appropriate genetic counseling.
Topics: Adolescent; Child; Female; Humans; Male; Mutation; Ocular Motility Disorders; Ophthalmoplegia, Chronic Progressive External; Receptors, Cell Surface; Receptors, Immunologic; Scoliosis
PubMed: 32580277
DOI: 10.3390/ijerph17124467 -
Der Anaesthesist Jul 2020Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare progressive disease with acute neurological episodes caused by a... (Review)
Review
BACKGROUND
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare progressive disease with acute neurological episodes caused by a mitochondriopathy. Due to a defect of oxidative phosphorylation in the respiratory chain, there is impaired mitochondrial energy production with subsequent lactic acidosis, especially in situations with increased stress. Due to the high risk of metabolic derailment MELAS syndrome is a great challenge with respect to the perioperative management of anesthesia.
OBJECTIVE
This article gives a general overview of the special features of anesthesia management in patients with MELAS syndrome. A case report is presented in order to demonstrate how intraoperative parenteral nutrition can possibly be used to counteract the formation of lactic acidosis.
MATERIAL AND METHODS
A systematic review of the literature was performed. As only very few reports on MELAS syndrome are available, a case report was also integrated into this overview article for illustration purposes.
RESULTS AND CONCLUSION
Patients with MELAS syndrome represent a challenging cohort with respect to management of anesthesia and an intensive monitoring of the metabolic status is crucial. In cases of increasing lactate values, the administration of intraoperative parenteral nutrition seems to be a suitable approach to avoid lactic acidosis and to improve the perioperative treatment of patients with MELAS syndrome in the future.
Topics: Adult; Anesthesia; Anesthesia, General; Anesthesiology; Female; Humans; Intraoperative Care; MELAS Syndrome
PubMed: 32424662
DOI: 10.1007/s00101-020-00793-8