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• A critical literature review of case reports on statins-induced side effects in various hereditary myopathies. • Setting criteria to assess case reports of statin myotoxicity in hereditary myopathies. • Identification of myopathies with high risk for statin usage (MELAS and other mitochondrial disorders, myotonic dystrophy type 2, McArdle disease). • Suggesting practical management of hyperlipidemia in hereditary myopathies. Hyperlipidemia is not uncommon in patients with hereditary myopathies who get older and also in several conditions in which it is frequently observed. Thus, using the common cholesterol reducing medications of the stains group could be considered. However, the side effects of these drugs include myalgia, myopathy and rhabdomyolysis typically associated with high serum creatine kinase (CK). Because high CK levels are very frequently found in hereditary myopathies, physicians are reluctant to use statins in such patients. Reviewing the literature about statin side effects in hereditary myopathies does not provide a clear evidence about the true risk of these drugs. This review critically describes the reported cases of statin side effects in several genetic myopathies and suggests some guidelines for conditions that are contra indicated for statin usage (particularly in mitochondrial disorders, metabolic myopathies, myotonic dystrophy type 2). Possible solutions to the dilemma of whether to use statins in hereditary myopathies are discussed (prescribing other cholesterol lowering agents and a carefully monitored treatment initiation of statins). [ABSTRACT FROM AUTHOR]

Abstract Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and nemaline myopathy are two rare genetic conditions. We report the first case reported in world literature with coexistence of both these rare disorders. Case presentation A 11-year-old previously healthy Sri Lankan male child, product of a nonconsanguineous marriage with normal development presented with acute onset short lasting recurring episodes of right-sided eye deviation with impaired consciousness. In between episodes he regained consciousness. Family history revealed a similar presentation in the mother at 36 years of age. Examination was significant for short stature and proximal upper and lower limb weakness. His plasma and cerebrospinal fluid lactate were elevated. Magnetic resonance imaging brain had evidence of an acute infarction in the right occipital territory. Sanger sequencing for common mitochondrial variants of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes confirmed this diagnosis. Whole exome sequencing revealed pathogenic compound heterozygous variants in NEB gene implicating in coexisting nemaline myopathy. Acute presentation was managed with supportive care, antiepileptics, and mitochondrial supplementation. Currently he is stable on daily supplementation of arginine and limb-strengthening physiotherapy. He is being monitored closely clinically and with serum lactate level. Conclusion Genetic diseases are rare. Coexistence of two genetic conditions is even rarer. Genetic confirmation of diagnosis is imperative for prediction of complications, accurate management, and genetic counseling.

Background: Coupling between neuronal activity and blood perfusion is termed neurovascular coupling (NVC), and it provides a potentially new mechanistic perspective into understanding numerous brain diseases. Although abnormal brain activity and blood supply have been separately reported in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS), whether anomalous NVC would be present is unclear. Purpose: To investigate NVC changes and potential neural basis in MELAS by combining resting‐state functional MRI (rs‐fMRI) and arterial spin labeling (ASL). Study Type: Prospective. Subjects: Twenty‐four patients with MELAS (age: 29.8 ± 7.3 years) in the acute stage and 24 healthy controls (HCs, age: 26.4 ± 8.1 years). Additionally, 12 patients in the chronic stage were followed up. Field Strength/Sequence: 3.0 T, resting‐state gradient‐recalled echo‐planar imaging and pseudo‐continuous 3D ASL sequences. Assessment: Amplitude of low‐frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and functional connectivity strength (FCS) were calculated from rs‐fMRI, and cerebral blood flow (CBF) was computed from ASL. Global NVC was assessed by correlation coefficients of CBF‐ALFF, CBF‐fALFF, CBF‐ReHo, and CBF‐FCS. Regional NVC was also evaluated by voxel‐wise and lesion‐wise ratios of CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS. Statistical Tests: Two‐sample t‐test, paired‐sample t‐test, Gaussian random fields correction. A P value <0.05 was considered statistically significant. Results: Compared with HC, MELAS patients in acute stage showed significantly reduced global CBF‐ALFF, CBF‐fALFF, CBF‐ReHo, and CBF‐FCS coupling (P < 0.001). Altered CBF/ALFF, CBF/fALFF, CBF/ReHo, and CBF/FCS ratios were found mainly distributed in the middle cerebral artery territory in MELAS patients. In addition, significantly increased NVC ratios were found in the acute stroke‐like lesions in acute stage (P < 0.001), with a recovery trend in chronic stage. Data Conclusions: This study showed dynamic alterations in NVC in MELAS patients from acute to chronic stage, which may provide a novel insight for understanding the pathogenesis of MELAS. Evidence Level: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

T cells have been shown to maintain a lower percentage (heteroplasmy) of the pathogenic m.3243A>G variant (MT‐TL1, associated with maternally inherited diabetes and deafness [MIDD] and mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes [MELAS]). The mechanism(s) underlying this purifying selection, however, remain unknown. Here we report that purified patient memory CD4+ T cells have lower bulk m.3243A>G heteroplasmy compared to naïve CD4+ T cells. In vitro activation of naïve CD4+ m.3243A>G patient T cells results in lower bulk m.3243A>G heteroplasmy after proliferation. Finally, m.3243A>G patient T cell receptor repertoire sequencing reveals relative oligoclonality compared to controls. These data support a role for T cell activation in peripheral, purifying selection against high m.3243A>G heteroplasmy T cells at the level of the cell, in a likely cell‐autonomous fashion. [ABSTRACT FROM AUTHOR]

Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) and m.3243A>G being the most common phenotype and genotype, respectively. The treatment for MELAS patients is still less effective. Here, we performed transcriptomic and proteomic analysis in muscle tissue of MELAS patients, and discovered that the expression of molecules involved in serine catabolism were significantly upregulated, and serine hydroxymethyltransferase 2 (SHMT2) increased significantly in both the mRNA and protein levels. The SHMT2 protein level was also increased in myoblasts with m.3243A>G mutation, which was transdifferentiated from patients derived fibroblasts, accompanying with the decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio and cell viability. After treating with SHMT2 inhibitor (SHIN1), the NAD+/NADH ratio and cell viability in MELAS myoblasts increased significantly. Taken together, our study indicates that enhanced serine catabolism plays an important role in the pathogenesis of MELAS and that SHIN1 can be a potential small molecule for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Background: Patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) usually present with multisystemic dysfunction with a wide range of clinical manifestations. When the tests for common mitochondrial DNA (mtDNA) point mutations are negative and the mtDNA defects hypothesis remains, urine epithelial cells can be used to screen the mitochondrial genome for unknown mutations to confirm the diagnosis. Case presentation: A 66-year-old Chinese woman presented with symptoms of MELAS and was initially misdiagnosed with acute encephalitis at another institution. Although genetic analysis of blood lymphocyte DNA was negative, brain imaging, including magnetic resonance imaging, magnetic resonance spectroscopy, and clinical and laboratory findings, were all suggestive of MELAS. Finally, the patient was eventually diagnosed with MELAS with the mtDNA 5783G>A mutation in the MT-TC gene with a urinary sediment genetic test. Conclusion: This case report expands the genetic repertoire associated with MELAS syndrome and highlights the importance that full mtDNA sequencing should be warranted beside the analysis of classical variants when a mitochondrial disorder is highly suspected. Furthermore, urine sediment genetic testing has played a crucial role in the diagnosis of MELAS. [ABSTRACT FROM AUTHOR]

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare mitochondrial neurodegenerative disorder characterized by stroke-like episodes, seizure, and lactic acidosis. The diagnosis of MELAS is often challenging due to its variable phenotypic manifestations and rarity of this disease. In this article, we report the case of a 38-year-old woman who presented with repeated seizures and clinical stroke-like symptoms. She had no positive family history, and lactic acidosis was only present in her initial episode. Magnetic resonance imaging (MRI) of the brain was also normal in her first presentation. However, subsequent scans due to new clinical events showed migratory stroke-like lesions that were hyperintense on T2/fluid attenuated inversion recovery (FLAIR) sequence and had restricted diffusion. They did not conform to vascular territories but had a predilection for posterior temporal, occipital and parietal regions. The radiological findings prompted the suspicion of MELAS, which diagnosis was confirmed with genetic testing. Here, we also reviewed the MRI features of MELAS from literature, in particular the diffusion-weighted sequence findings, as debate still exists on whether the apparent diffusion coefficient (ADC) signal should be high or low in these lesions. Our case highlights the importance of recognizing key imaging features of this rare and highly heterogenous disease. In addition to helping with earlier diagnosis, these imaging findings also provide more insight into the underlying pathophysiology of MELAS. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial disease that affects various systems in the body, particularly the brain, nervous system, and muscles. Among these systems, sensorineural hearing loss is a common additional symptom. Methods: A 42-year-old female patient with MELAS who experienced bilateral profound deafness and underwent bilateral sequential cochlear implantation (CIs). Speech recognition and subjective outcomes were evaluated. Results: Following the first CI follow-up, the patient exhibited improved speech recognition ability and decided to undergo the implantation of the second ear just two months after the initial CI surgery. The second CI also demonstrated enhanced speech recognition ability. Subjective outcomes were satisfactory for bilateral CIs. Conclusions: MELAS patients receiving bilateral CIs can attain satisfactory post-CI speech recognition, spatial hearing, and sound qualities. [ABSTRACT FROM AUTHOR]

MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with the stroke-like episodes being its primary manifestation. Arginine supplementation has been used and recommended as a treatment for these acute attacks; however, insufficient evidence exists to support this treatment for MELAS. The mechanisms underlying the effect of arginine on MELAS pathophysiology remain unclear, although it is hypothesized that arginine could increase nitric oxide availability and, consequently, enhance blood supply to the brain. A more comprehensive understanding of these mechanisms is necessary to improve treatment strategies, such as dose and regimen adjustments; identify which patients could benefit the most; and establish potential markers for follow-up. This review aims to analyze the existing evidence concerning the mechanisms through which arginine supplementation impacts MELAS pathophysiology and provide the current scenario and perspectives for future investigations. [ABSTRACT FROM AUTHOR]

The MT‐TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5‐year‐old child with heteroplasmy for this variant who developed neurological regression and stroke‐like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z‐scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke‐like episodes. The use of intravenous arginine during stroke‐like episodes and daily enteral L‐citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1‐methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N‐acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT‐TL2 m.12315G>A to include neurological regression and a MELAS‐like phenotype. Individuals with this variant should undergo in‐depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment. [ABSTRACT FROM AUTHOR]

Objective: Mitochondrial myopathy without extraocular muscles involvement (MiMy) represents a distinct form of mitochondrial disorder predominantly affecting proximal/distal or axial muscles, with its phenotypic, genotypic features, and long-term prognosis poorly understood. Methods: A cross-sectional study conducted at a national diagnostic center for mitochondrial disease involved 47 MiMy patients, from a cohort of 643 mitochondrial disease cases followed up at Qilu Hospital from January 1, 2000, to January 1, 2021. We compared the clinical, pathological, and genetic features of MiMy to progressive external ophthalmoplegia (PEO) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients. Results: MiMy patients demonstrated a more pronounced muscle involvement syndrome, with lower 6MWT scores, higher FSS, and lower BMI compared to PEO and MELAS patients. Serum levels of creatinine kinase (CK), lactate, and growth and differentiation factor 15 (GDF15) were substantially elevated in MiMy patients. Nearly a third (31.9%) displayed signs of subclinical peripheral neuropathy, mostly axonal neuropathy. Muscle biopsies revealed that cytochrome c oxidase strong (COX-s) ragged-red fibers (RRFs) were a typical pathological feature in MiMy patients. Genetic analysis predominantly revealed mtDNA point pathogenic variants (59.6%) and less frequently single (12.8%) or multiple (4.2%) mtDNA deletions. During the follow-up, a majority (76.1%) of MiMy patients experienced stabilization or improvement after therapeutic intervention. Conclusions: This study provides a comprehensive profile of MiMy through a large patient cohort, elucidating its unique clinical, genetic, and pathological features. These findings offer significant insights into the diagnostic and therapeutic management of MiMy, ultimately aiming to ameliorate patient outcomes and enhance the quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To describe examination and findings in a case of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) with particular focus on the ocular sequelae from diabetes. Observations: Neovascular glaucoma is not a common manifestation of MELAS. Conclusions and Importance: We present a rare case of neovascular glaucoma in a patient with MELAS with a history of diabetes, hearing loss, and macular dystrophy. MELAS should be suspected in patients with this constellation of symptoms.

Bu çalışmada şeker fabrikası atığı olan melas ve süt farikası yan ürünü olan peynir altı suyu elma ve portakal kaplamasında kullanılarak üç hafta boyunca depolanmıştır. Depolama süresince kalite değişimleri belirlenmiştir. Kaplamada kullanılan peynir altı suyu ve melasın briks değerleri sırasıyla 30 ve 50, pH’ları ise 1 ve 7.8’dir. Çalışmada kaplanan meyvelerin ağırlık kaybı ve renk değerleri incelenmiştir. Çalışma sonucunda üç haftalık depolama periyodunda elma için melas+su, portakal için ise peynir altı suyunun etkisinin önemli olduğu tespit edilmiştir. Melas+su ile kaplanan elmalarda ağırlık kaybı %3.645 iken kaplanmayan örneklerde %6.327’dir. Peynir altı suyu ile kaplanan portakallarda ağırlık kaybı %17.860 iken kaplanmayan örneklerde ise %27.930’dur. Çalışma ile melasın elmada, peynir altı suyunun da portakalda kaplama materyali olarak kullanılabileceği sonucuna varılmıştır. Özellikle ağırlık kaybı meyvelerin depolanmasında istenmeyen bir durumdur. Meyvelerin kaplanması ile bu durum minimuma indirilebilir. Kullanılan peynir altı suyu ve melas özellikle ağırlık kaybının azaltılmasında etkili olmuştur.

In this study; a new additive material, which we called Molasses Based Fly Ash Compound (MEUKB), was synthesized in laboratory using sugar beet molasses and fly ash. 50/70 penetration bitumen was modified with MEUKB at 2%, 3%, 4%, 5%, 6%, 7% and 8% by weight. Rotational viscosity (RV), Dynamic Shear Rheometer (DSR), Marshall designs and Nicholson stripping tests were applied in order to evaluate the effects of MEUKB on bitumen and bituminous mixture properties. According to the test results, the yield and deformation resistance of the bitumen were determined to be improved by MEUKB. An increase up to 41.7% in rutting resistance of the bitumen was calculated. As a result of the modification of bitumen with 3% MEUKB, the stability of the bituminous mixtures was enhanced up to 10.6%. Moreover, stripping resistance of the aggregate-bitumen mixtures was raised to a level of 85-90%. [ABSTRACT FROM AUTHOR]

The syndrome of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a multi-organ disease that develops mainly in childhood and is a type 1 progressive mitochondrial encephalomyosis. Its clinical features include multiple cerebral infarctions, progressive muscle weakness, peripheral neuropathy such as numbness in the hands and feet, endocrine symptoms, sensorineural hearing loss, intellectual regression, and many other symptoms due to mitochondrial genetic abnormalities. Because of the wide variety of systemic symptoms, it takes time to reach a diagnosis. There is no clear cure, and it is recognized as a disease with a poor prognosis. There are reports of a decrease in general muscle strength, but there have been a few reports of symptoms around the oromaxillofacial area. In this study, a patient with type 1 diabetes mellitus whose jaw position was unstable due to a decrease in the strength of the masticatory muscles thought to be caused by MELAS underwent systemic management in cooperation with internal medicine, tooth extraction under local anesthesia, and then all-jaw oral function management, with a good course. The volume and form of meals improved. The patient received regular oral care after dental treatment, but then refused dental treatment. After that, the patient's general condition rapidly deteriorated, and he died due to multiple organ failure. [ABSTRACT FROM AUTHOR]

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, caused by a single base substitution in mitochondrial DNA (m.3243A>G), is one of the most common maternally inherited mitochondrial diseases accompanied by neuronal damage due to defects in the oxidative phosphorylation system. There is no established treatment. Our previous study reported a superior restoration of mitochondrial function and bioenergetics in mitochondria-deficient cells using highly purified mesenchymal stem cells (RECs). However, whether such exogenous mitochondrial donation occurs in mitochondrial disease models and whether it plays a role in the recovery of pathological neuronal functions is unknown. Here, utilizing induced pluripotent stem cells (iPSC), we differentiated neurons with impaired mitochondrial function from patients with MELAS. MELAS neurons and RECs/mesenchymal stem cells (MSCs) were cultured under contact or non-contact conditions. Both RECs and MSCs can donate mitochondria to MELAS neurons, but RECs are more excellent than MSCs for mitochondrial transfer in both systems. In addition, REC-mediated mitochondrial transfer significantly restored mitochondrial function, including mitochondrial membrane potential, ATP/ROS production, intracellular calcium storage, and oxygen consumption rate. Moreover, mitochondrial function was maintained for at least three weeks. Thus, REC-donated exogenous mitochondria might offer a potential therapeutic strategy for treating neurological dysfunction in MELAS. [ABSTRACT FROM AUTHOR]

The mitochondrial (m.) 3243A>G mutation is known to be associated with various mitochondrial diseases including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS). Their clinical symptoms have been estimated to occur with an increased mitochondrial DNA (mtDNA) heteroplasmy and reduced activity of oxidative phosphorylation (OXPHOS) complexes, but their trends in the central nervous system remain unknown. Six autopsied mutant cases and three disease control cases without the mutation were enrolled in this study. The mutant cases had a disease duration of 1–27 years. Five of six mutant cases were compatible with MELAS. In the mutant cases, cortical lesions including a laminar necrosis were frequently observed in the parietal, lateral temporal, and occipital lobes; less frequently in the frontal lobe including precentral gyrus; and not at all in the medial temporal lobe. The mtDNA heteroplasmy in brain tissue samples of the mutant cases was strikingly high, ranging from 53.8% to 85.2%. The medial temporal lobe was preserved despite an inhospitable environment having high levels of mtDNA heteroplasmy and lactic acid. OXPHOS complex I was widely decreased in the mutant cases. The swelling of smooth muscle cells in the vessels on the leptomeninges, with immunoreactivity (IR) against mitochondria antibody, and a decreased nuclear/cytoplasmic ratio of choroidal epithelial cells were observed in all mutant cases but in none without the mutation. Common neuropathological findings such as cortical laminar necrosis and basal ganglia calcification were not always observed in the mutant cases. A high level of mtDNA heteroplasmy was observed throughout the brain in spite of heterogeneous cortical lesions. A lack of medial temporal lesion, mitochondrial vasculopathy in vessels on the leptomeninges, and an increased cytoplasmic size of epithelial cells in the choroid plexus could be neuropathological hallmarks helpful in the diagnosis of mitochondrial diseases. [ABSTRACT FROM AUTHOR]

MELAS e митохондриално заболяване, съчетаващо енцефало-миопатия, лактатна ацидоза и инсулто-подобни епизоди. Началото му е в първите две десетилетия от живота, с вариабилни клинични симптоми, най-често от страна на нервната система. Клиничната и образната находка при MELAS е топична и не отговаря на даден съдов басейн, по-често е в задната краниална ямка, лезиите могат да са обратими, но често са рецидивиращи и постепенно нарастват в съседство с вече наличните в рамките на седмици до месеци, често придружени от епилептични пристъпи, неврологична дисфункция и корова атрофия. За поставянето на диагнозата е необходимо и установяването на хетероплазмия на мутацията и мултисистемно засягане. В настоящата публикация представяме пациентка (МПС) на 33-годишна възраст с доказана A3243G мутация в митохондриал ния геном с 31,6% хетероплазмия в кръвта и 74% хетероплазмия в епителни клетки от уринен седимент, отговаряща на MELAS синдром. Началните оплаквания са на 22-годишна възраст, като поради погрешна интерпретация на образната находка от МРТ като туморна формация, при нея е проведена резекция вляво темпорално две години след началните оплаквания. От неврологичния статус са налице квадрипирамиден, панцеребеларен, епилептичен и когнитивен синдроми, и двустранно невро сензорно намаление на слуха. Проведена е симптоматична терапия с Levetiracetam, витаминни препарати и нутрицевтици.

MELAS is a systemic hereditary condition that can present as hypertrophic or mixed hypertrophic and dilated phenotype cardiomyopathy in young individuals, although a late-onset form is also described in the literature. Genetic testing is essential for correct diagnosis and appropriate management.

MELAS – an acronym for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes – is a multiorgan disease caused by a mutation in mitochondrial DNA (mtDNA). Its clinical manifestations are highly variable; mainly stroke-like episodes, seizures, recurrent headaches, or muscle weakness. However, gastrointestinal complications such as chronic intestinal pseudo-obstruction (IPO), pancreatitis, gastroparesis and hepatopathy are also common. In this report we describe a young patient with gastrointestinal complication of MELAS which led to superior mesenteric artery syndrome (SMAS). It is rare but not surprising combination and should be considered in cases with significant weight loss and resistance to symptomatic treatment. The optimal energy support is the main pillar of the treatment.

ObjectiveMitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a severe multisystemic disease, although some have a milder phenotype. We aimed to evaluate the clinical spectrum of this disease from MELAS patients to asymptomatic carriers and identify predictors of severity.MethodsWe reviewed 81 patients, who had MELAS or had positive genetics without meeting clinical criteria. Patients who met criteria including lactic acidosis, encephalomyopathy, and stroke-like episodes (SLE) were categorized as MELAS, symptomatic non-MELAS, and asymptomatic. MELAS was further categorized as “standard-onset” if the first stroke-like episode (SLE) occurred before age 40 or “late-onset.”ResultsEighty-one patients were included: 42 MELAS (13 late-onset), 30 symptomatic non-MELAS, and 9 asymptomatic. MELAS patients had lower BMI at onset (mean 18.6 vs. 25.1 asymptomatic and 22.0 symptomatic non-MELAS, p

Background. Friedrich Nietzsche (1844-1900) is one of the most profound modern philosophers. Since childhood, Nietzsche suffered from severe headaches, and at the age of thirty he became blind in his right eye. At the age of 44, Nietzsche experienced a mental collapse, after which he became dependent on others. For a long time, it was thought that neurosyphilis was the diagnosis of Nietzsche's symptoms. However, latest studies suggest other hypotheses. Materials and methods. Nietzsche's letters to his friends, the memories of his family members and friends, and the medical records of his doctors were analysed. On the basis of primary sources, a retrospective medical history of Nietzsche is presented. Furthermore, in accordance with secondary articles on Nietzsche's illnesses, the main hypotheses have been provided along with their advantages and disadvantages. Results. The hypothesis of neurosyphilis becomes obsolete. New diagnoses have been proposed: frontotemporal dementia, intracranial mass, MELAS syndrome, and CADASIL. Conclusions. Despite a detailed analysis of Nietzsche's illnesses, the exact diagnosis remains unclear.

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON). Case presentation: Here we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms. Conclusions: Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders. [ABSTRACT FROM AUTHOR]

The mitochondrial DNA m.3243A>G mutation can affect mitochondrial function and lead to a wide phenotypic spectrum, including mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, diabetes mellitus, hearing impairment, cardiac involvement, epilepsy, migraine, myopathy, and cerebellar ataxia. However, m.3243A>G has been rarely reported in patients with cerebellar ataxia as their predominant manifestation. The aim of this study is to investigate the prevalence and clinical features of m.3243A>G in a Taiwanese cohort of cerebellar ataxia with unknown genetic diagnosis. This retrospective cohort study conducted the mutation analysis of m.3243A>G by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 232 unrelated Han Chinese patients with genetically-undetermined cerebellar ataxia. The clinical presentation and neuroimaging features of patients with m.3243A>G mutation-related cerebellar ataxia were characterized. We identified two patients harboring m.3243A>G mutation. These patients have suffered from apparently sporadic and slowly progressive cerebellar ataxia since age 52 and 35 years, respectively. Both patients had diabetes mellitus and/or hearing impairment. The neuroimaging studies revealed generalized brain atrophy with predominantly cerebellar involvement in both individuals and bilateral basal ganglia calcifications in one of the patients. Mitochondrial m.3243A>G mutation accounted for 0.9% (2/232) of genetically-undetermined cerebellar ataxia in the Han Chinese cohort in Taiwan. These findings highlight the importance of investigating m.3243A>G in patients with genetically-undetermined cerebellar ataxia. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a group of maternally inherited disorders caused by mutations or deletions in mitochondrial genes with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes as the main clinical manifestations. Case presentation: We reported a 20-year-old female patient with MELAS syndrome combined with autoimmune abnormalities. She suffered from an intermittent headache in the right temporal region with no obvious cause, and then, after strenuous exercise in dance class, the headache became aggravated, accompanied by unresponsiveness, blurred vision, and diplopia. Her blood lactate levels were elevated, her antinuclear antibodies were positive, and the antimetabolic glutamate receptors 5 in her serumwere positive. Brain DWI showed a hypertensive signal in the right temporo-parietal-occipital cortex and subcortical area. Brain MRS showed decreased NAA peak and increased Lac peak. Muscle biopsy showed myogenic damage, and the modified Gomori trichrome (MGT) staining showed ragged red fibers (RRF). A genetic study revealed a mitochondrial DNA A3243G mutation. Conclusion: Mitochondrial encephalomyopathy is a rare clinical condition; however, the association with autoimmune diseases is not yet clear and still needs further research and analysis. [ABSTRACT FROM AUTHOR]

In mammalian mitochondria, the processing of primary RNA transcripts involves a coordinated series of cleavage and modification events, leading to the formation of processing intermediates and mature mt-RNAs. RNA19 is an unusually stable unprocessed precursor, physiologically polyadenylated, which includes the 16S mt-rRNA, the mt-tRNALeuUUR and the mt-ND1 mRNA. These peculiarities, together with the alteration of its steady-state levels in cellular models with defects in mitochondrial function, make RNA19 a potentially important molecule for the physiological regulation of mitochondrial molecular processes as well as for the pathogenesis of mitochondrial diseases. In this work, we quantitatively and qualitatively examined RNA19 in MELAS trans-mitochondrial cybrids carrying the mtDNA 3243A>G transition and displaying a profound mitochondrial translation defect. Through a combination of isokinetic sucrose gradient and RT-qPCR experiments, we found that RNA19 accumulated and co-sedimented with the mitoribosomal large subunit (mt-LSU) in mutant cells. Intriguingly, exogenous expression of the isolated LARS2 C-terminal domain (Cterm), which was shown to rescue defective translation in MELAS cybrids, decreased the levels of mt-LSU-associated RNA19 by relegating it to the pool of free unbound RNAs. Overall, the data reported here support a regulatory role for RNA19 in mitochondrial physiopathological processes, designating this RNA precursor as a possible molecular target in view of therapeutic strategy development. [ABSTRACT FROM AUTHOR]

Introduction: Patients with mitochondrial disorders always show neurological deficits. However, the diversity of clinical manifestations, genetic heterogeneity and threshold effect caused by maternal heredity make its diagnosis very challenging. Case presentation: A 30-year-old female presented to our neurology department with a recurrence of symmetrical weakness proximally in the lower extremities. Seven years ago, the patient had a sudden onset of persistent weakness in bilateral proximal lower extremities, along with elevated creatinine kinase (CK) and CK-MB. Given the diagnosis of Guillain-Barre syndrome, she was treated with high-dose glucocorticoid (GC) therapy at the local hospital and recovered. After admission to our hospital, laboratory analysis revealed elevated CK and alpha-hydroxybutyrate dehydrogenase in serum. Electrocardiography showed sinus tachycardia and left high ventricular voltage. Electromyography (EMG) and evoked potential (EP) suggested peripheral neurogenic damage of the upper and lower extremities with myogenic wear. Chronic inflammatory demyelinating polyneuropathy (CIDP) was initially considered, but neurological symptoms were not significantly improved with glucocorticoid shock therapy. An elevated level of lactate was found. The short-tau inversion recovery (STIR) axial magnetic resonance image (MRI) revealed mild hyperintensities, indicating muscle edema. Meanwhile, muscle biopsies suggested pathological changes in mitochondrial disorders (MIDs) and neuronal damage. Further mitochondrial genome analysis revealed a heteroplasmic m3271 T>C mutation in the mitochondrial tRNA-Leu gene (UUR). Collectively, the patient was finally diagnosed with mitochondrial disorder and apparently improved after the corresponding treatment to regulate energy metabolism. Conclusions: To our knowledge, it's the first report about MELAS with 3271 mutation that have only shown peripheral nerve motion impairment. Proximal weakness is also common in CIDP. In the context of this patient's experience, mitochondrial genome analysis provides an auxiliary criterion for differential diagnosis between MIDs and CIDP. In the meantime, we discussed the clinical effect of GCs on MIDs. [ABSTRACT FROM AUTHOR]

Abstract Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a systemic disorder in which multi-organ dysfunction may occur from mitochondrial metabolism failure. Maternally inherited mutations in the MT-TL1 gene are the most frequent causes for this disorder. Clinical manifestations may include stroke-like episodes, epilepsy, dementia, headache and myopathy. Among these, acute visual failure, usually in association with cortical blindness, can occur because of stroke-like episodes affecting the occipital cortex or the visual pathways. Vision loss due to optic neuropathy is otherwise considered a typical manifestation of other mitochondrial diseases such as Leber hereditary optic neuropathy (LHON). Case presentation Here we describe a 55-year-old woman, sister of a previously described patient with MELAS harbouring the m.3243A > G (p.0, MT-TL1) mutation, with otherwise unremarkable medical history, that presented with subacute, painful visual impairment of one eye, accompanied by proximal muscular pain and headache. Over the next weeks, she developed severe and progressive vision loss limited to one eye. Ocular examination confirmed unilateral swelling of the optic nerve head; fluorescein angiography showed segmental perfusion delay in the optic disc and papillary leakage. Neuroimaging, blood and CSF examination and temporal artery biopsy ruled out neuroinflammatory disorders and giant cell arteritis (GCA). Mitochondrial sequencing analysis confirmed the m.3243A > G transition, and excluded the three most common LHON mutations, as well as the m.3376G > A LHON/MELAS overlap syndrome mutation. Based on the constellation of clinical symptoms and signs presented in our patient, including the muscular involvement, and the results of the investigations, the diagnosis of optic neuropathy as a stroke-like event affecting the optic disc was performed. L-arginine and ubidecarenone therapies were started with the aim to improve stroke-like episode symptoms and prevention. The visual defect remained stable with no further progression or outbreak of new symptoms. Conclusions Atypical clinical presentations must be always considered in mitochondrial disorders, even in well-described phenotypes and when mutational load in peripheral tissue is low. Mitotic segregation of mitochondrial DNA (mtDNA) does not allow to know the exact degree of heteroplasmy existent within different tissue, such as retina and optic nerve. Important therapeutic implications arise from a correct diagnosis of atypical presentation of mitochondrial disorders.

MELAS syndrome, characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, represents a devastating mitochondrial disease, with the stroke-like episodes being its primary manifestation. Arginine supplementation has been used and recommended as a treatment for these acute attacks; however, insufficient evidence exists to support this treatment for MELAS. The mechanisms underlying the effect of arginine on MELAS pathophysiology remain unclear, although it is hypothesized that arginine could increase nitric oxide availability and, consequently, enhance blood supply to the brain. A more comprehensive understanding of these mechanisms is necessary to improve treatment strategies, such as dose and regimen adjustments; identify which patients could benefit the most; and establish potential markers for follow-up. This review aims to analyze the existing evidence concerning the mechanisms through which arginine supplementation impacts MELAS pathophysiology and provide the current scenario and perspectives for future investigations.

(1) Introduction: Symptom spectrum can be of great diversity and heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) patients in clinical practice. Here, we report a case of MELAS presenting asymptomatic refractory hypotension with m.3243 A>G mutation. (2) Case representation: A 51-year-old male patient presented with a headache, vertigo, and difficulty in expression and understanding. The magnetic resonance imaging of the brain revealed an acute stroke-like lesion involving the left temporoparietal lobe. A definitive diagnosis of MELAS was given after the genetic test identified the chrM-3243 A>G mutation. The patient suffered recurrent stroke-like episodes in the 1-year follow-up. Notably, refractory hypotension was observed during hospitalizations, and no significant improvement in blood pressure was found after continuous use of vasopressor drugs and fluid infusion therapy. (3) Conclusions: We report a case of refractory hypotension which was unresponsive to fluid infusion therapy found in a patient with MELAS. Our case suggests that comprehensive management should be paid attention to during treatment. A further study on the pathological mechanism of the multisystem symptoms in MELAS would be beneficial to the treatment of patients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The stroke‐like episodes and brain MRI lesions in MELAS usually have a nonischemic pattern, are resolved over time, and have a migrating pattern that helps us distinguish them from ischemic cerebral infarcts. Nevertheless, conditions such as intracardiac thromboses, PFO, and hypercoagulable state may be present concomitantly, leading to mismanagement. Therefore, further investigation and echocardiography are suggested in MELAS patients. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) is the most common maternally‐inherited mitochondrial disorder presenting by stroke‐like episodes, seizures, encephalopathy and muscle weakness. We report the clinical, imaging, echocardiography and muscle biopsy findings of a patient presenting by unique characteristics which have not been reported in previous cases of MELAS. The reported case is a 34 year old man with the history of three times hospitalization due to muscle weakness, encephalopathy, progressive cognitive decline, and gradual visual loss. Muscle biopsy revealed Ragged Red Fibers concomitant with mitochondrial disorders. PFO was found in echocardiography leading to mismanagement of this patient and MR imaging showed ischemic lesions with a progressive pattern. This is the first reported case of MELAS accompanying with PFO. All previous reported cases of MELAS have mentioned a fluctuating characteristic for the ischemic lesions; hence this is the first case of MELAS with the progressive pattern of ischemic lesions. [ABSTRACT FROM AUTHOR]

Objective: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT-TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes. Materials and methods: Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G (MT-TL1; tRNALeu) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively. [ABSTRACT FROM AUTHOR]

Color descriptions depend on both culture and era. An explicit example consists in the Greek term melas which was used at the earliest stage of developing the Greek literature to describe various dark colors, as well as difficult mental states and negative emotions, whereas in the Hellenistic papyrus texts it was used in noun form to describe the writing material and pigment in painting. Analyzing the Hebrew equivalent of šāḥōr has revealed a similarity in terms of perceiving and the nomenclature concerning dark colors also in Jewish environments. The conducted study constitutes an attempt to solve methodological difficulties as well as an attempt to capture the elusive semantics and symbolism of the Greek chromatic system in biblical terms. [ABSTRACT FROM AUTHOR]

• • The mtDNA mutation frequency could be calculated by qPCR using the FAM and VIC probes. • • This method was used to draw a standard curve by applying the angle-degree method. • • The accuracy of the mutation frequency obtained by this method (2.4 ± 1. %) was higher vs. the existing methods. • • This method can also be applied to obtain other mutation frequencies in DNA other than mtDNA, e.g., in the context of diabetes, aging, cancer, and neurodegenerative diseases. We designed a method to examine the mutation frequencies of the A3243G mutation of mitochondrial DNA (mtDNA) in patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. We performed a qPCR assay using the FAM and VIC TaqMan probes, which detect the 3243G (mutated) and 3243A (wild-type) sequences of mtDNA, respectively. The results obtained by "degree" in a series of differential mutation frequencies were used to plot a standard curve of the mutation frequency. The standard curve was then applied for qPCR assays of the desired samples. The standard deviation (%) of the samples calculated using the standard curve for the TaqMan probe was 2.4 ± 1.5%. This method could be used to examine mutation frequencies in the context of diabetes, aging, cancer, and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease. We report here the safe use of remimazolam in a pediatric MELAS patient. Case presentation A 10-year-old girl (118 cm, 16 kg) was scheduled for an open gastrostomy to improve nutrition and epileptic seizure control. We induced and maintained general anesthesia with remimazolam, remifentanil, fentanyl, and rocuronium. We also performed a bilateral subcostal transversus abdominis plane block before the surgery. The surgery finished uneventfully. After we discontinued remimazolam administration, the patient woke up immediately but calmly without flumazenil. Epileptic seizures did not occur during intra- and early post-operative periods. Conclusion Remimazolam enabled us to provide a pediatric MELAS patient with general anesthesia without causing delayed emergence or epileptic seizures.

Abstract Background Genetic mitochondrial diseases represent a significant challenge to human health. These diseases are extraordinarily heterogeneous in clinical presentation and genetic origin, and often involve multi-system disease with severe progressive symptoms. Mitochondrial diseases represent the most common cause of inherited metabolic disorders and one of the most common causes of inherited neurologic diseases, yet no proven therapeutic strategies yet exist. The basic cell and molecular mechanisms underlying the pathogenesis of mitochondrial diseases have not been resolved, hampering efforts to develop therapeutic agents. Main body In recent pre-clinical work, we have shown that pharmacologic agents targeting the immune system can prevent disease in the Ndufs4(KO) model of Leigh syndrome, indicating that the immune system plays a causal role in the pathogenesis of at least this form of mitochondrial disease. Intriguingly, a number of case reports have indicated that immune-targeting therapeutics may be beneficial in the setting of genetic mitochondrial disease. Here, we summarize clinical and pre-clinical evidence suggesting a key role for the immune system in mediating the pathogenesis of at least some forms of genetic mitochondrial disease. Conclusions Significant clinical and pre-clinical evidence indicates a key role for the immune system as a significant in the pathogenesis of at least some forms of genetic mitochondrial disease.

Ribosomopathies are rare congenital disorders associated with defective ribosome biogenesis due to pathogenic variations in genes that encode proteins related to ribosome function and biogenesis. Defects in ribosome biogenesis result in a nucleolar stress response involving the TP53 tumor suppressor protein and impaired protein synthesis leading to a deregulated translational output. Despite the accepted notion that ribosomes are omnipresent and essential for all cells, most ribosomopathies show tissue-specific phenotypes affecting blood cells, hair, spleen, or skin. On the other hand, defects in mitochondrial ribosome biogenesis are associated with a range of clinical manifestations affecting more than one organ. Intriguingly, the deregulated ribosomal function is also a feature in several human malignancies with a selective upregulation or downregulation of specific ribosome components. Here, we highlight the clinical conditions associated with defective ribosome biogenesis in the nucleus and mitochondria with a description of the affected genes and the implicated pathways, along with a note on the treatment strategies currently available for these disorders. • Ribosomopathies are rare congenital disorders associated with defective ribosome biogenesis in the nucleus and mitochondria. • Most ribosomopathies show tissue-specific phenotypes affecting blood cells, hair, spleen, or skin. • Mitochondrial ribosomopathies are associated with heterogeneous clinical manifestations affecting multiple organs. • Clinical diagnosis and developing therapeutic strategies for ribosomopathies are of paramount importance. [ABSTRACT FROM AUTHOR]

• Epileptic seizure is one of the most common symptoms in MELAS and the initial symptom of 69.1% patients was epileptic seizure. • The seizure types of the patients with MELAS are variable, with generalized onset to be the most common type. • Drug-resistant epilepsy in MELAS is demonstrated to be closely related to the earlier age of seizure onset, as well as the higher mRS score and higher resting serum lactic value. This study aimed to characterize the clinical features of epilepsy in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and analyze the clinical determinants for drug-resistant epilepsy in MELAS. A single-center, retrospective study was conducted to investigate the clinical features of epilepsy in patients with MELAS. Collected variables included seizure semiology, electroencephalography (EEG), muscle biopsy, genetic testing, neuroimaging findings, resting serum lactic value and modified Rankin scale (mRS) of patients with MELAS. We also investigated the differences between the adult-onset group and the child-onset group and analyzed the risk factors for drug-resistant epilepsy in MELAS. We studied 97 patients (56 males: 41 females) with confirmed MELAS. Epileptic seizure occurred in 100.0% of patients and the initial symptom of 69.1% patients was epileptic seizure. The average age of disease onset was 21.0 years, ranging from 2 to 60 years. The seizure types of these patients with MELAS were variable, with generalized onset (51.5%) to be the most common type. The EEG changes in the patients with MELAS were mainly slow wave (90.9%) and epileptiform discharge (68.2%). The child-onset group with earlier seizure onset presented significantly higher resting serum lactic value (p = 0.0048) and lower incidence of stroke-like lesion in the brain (p = 0.003), especially in the temporal lobe (p < 0.001), compared with the adult-onset group. Importantly, drug-resistant epilepsy in MELAS was demonstrated to be closely related to the earlier age of seizure onset (p = 0.013), as well as the higher mRS score (p < 0.001) and higher resting serum lactic value (p = 0.009). Early identification of MELAS should be considered among individuals with recurrent epilepsy through clinical screening. Age of seizure onset and resting serum lactic value may predict the development of drug-resistant epilepsy in MELAS. Close observation and appropriate anti-epileptic treatment are indispensable for individuals with MELAS to improve the prognosis. Further studies with larger sample size are required to further evaluate the risk factors of drug-resistant epilepsy in MELAS and provide guidance on treatment of MELAS. [ABSTRACT FROM AUTHOR]

Key Clinical Message The stroke‐like episodes and brain MRI lesions in MELAS usually have a nonischemic pattern, are resolved over time, and have a migrating pattern that helps us distinguish them from ischemic cerebral infarcts. Nevertheless, conditions such as intracardiac thromboses, PFO, and hypercoagulable state may be present concomitantly, leading to mismanagement. Therefore, further investigation and echocardiography are suggested in MELAS patients. Abstract Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS) is the most common maternally‐inherited mitochondrial disorder presenting by stroke‐like episodes, seizures, encephalopathy and muscle weakness. We report the clinical, imaging, echocardiography and muscle biopsy findings of a patient presenting by unique characteristics which have not been reported in previous cases of MELAS. The reported case is a 34 year old man with the history of three times hospitalization due to muscle weakness, encephalopathy, progressive cognitive decline, and gradual visual loss. Muscle biopsy revealed Ragged Red Fibers concomitant with mitochondrial disorders. PFO was found in echocardiography leading to mismanagement of this patient and MR imaging showed ischemic lesions with a progressive pattern. This is the first reported case of MELAS accompanying with PFO. All previous reported cases of MELAS have mentioned a fluctuating characteristic for the ischemic lesions; hence this is the first case of MELAS with the progressive pattern of ischemic lesions.

El síndrome de Melas es una enfermedad de herencia mitocondrial caracterizada por encefalopatía mitocondrial, acidosis láctica y eventos similares a ataque cerebrovascular, secundaria a una mutación en los genes que codifican las proteínas transportadoras de electrones, limitando la producción energética y generando disfunción multiorgánica, que afecta principalmente el sistema músculo esquelético y el sistema nervioso, lo que está en correlación con las características clínicas que presentan los pacientes. El diagnostico se basa en la sospecha clínica, los hallazgos paraclínicos e imagenológicos y la confirmación de la mutación a través del estudio genético. No existe tratamiento específico, se basa únicamente en el manejo sintomático y requiere apoyo multidisciplinario. Presentamos el caso de un paciente con antecedente de Melas, que ingresó por evento cerebrovascular isquémico bioccipital y correlación con hallazgos en neuroimágenes (espectroscopia y tractografía).

Purpose: We present a unique case of foveomacular vitelliform lesions in a patient with metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Observations: After performing large panel next generation sequencing genetic testing, there was no likely alternative genetic etiology for vitelliform maculopathy in this patient. Conclusions and Importance: We present a rare case of a visually asymptomatic pediatric patient with MELAS and vitelliform maculopathy, which may be part of the spectrum of retinal manifestations in MELAS. Pediatric-onset vitelliform maculopathy in MELAS may be under-diagnosed due to its asymptomatic nature. Given the known risk of choroidal neovascularization in vitelliform maculopathy, it is important to identify these patients for proper surveillance.