Stroke-like Episodes Syndrome Research Articles

Clinical, imaging, and pathological characteristics of 35 cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome

Objective: To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. Methods: A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. Results: The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent 1H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. Conclusion: The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.

Unraveling RNA Conformation Dynamics in Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episode Syndrome with Solid-State Nanopores.

This study investigates transfer ribonucleic acid (tRNA) conformational dynamics in the context of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) using solid-state silicon nitride (SiN) nanopore technology. SiN nanopores in thin membranes with specific dimensions exhibit high signal resolution, enabling real-time and single-molecule electronic detection of tRNA conformational changes. We focus on human mitochondrial tRNALeu(UAA) (mt-Leu(UAA)) that decodes Leu codons UUA/UUG (UUR) during protein synthesis on the mt-ribosome. The single A14G substitution in mt-Leu(UAA) is the major cause of MELAS disease. Measurements of current blockades and dwell times reveal distinct conformational dynamics of the wild-type (WT) and the A14G variant of mt-Leu(UAA) in response to the conserved post-transcriptional m1G9 methylation. While the m1G9-modified WT transcript adopts a more stable structure relative to the unmodified transcript, the m1G9-modified MELAS transcript adopts a less stable structure relative to the unmodified transcript. Notably, these differential features were observed at 0.4 M KCl, but not at 3 M KCl, highlighting the importance of experimental settings that are closer to physiological conditions. This work demonstrates the feasibility of the nanopore platform to discern tRNA molecules that differ by a single-nucleotide substitution or by a single methylation event, providing an important step forward to explore changes in the conformational dynamics of other RNA molecules in human diseases.

Visual disturbances in a 12-year-old male patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome

Abstract: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare condition. Here, we present a case of a male patient with a very unique combination of symptoms that started at the age of 12. Transient symptoms manifested after 4 days of high fever and included lethargy, a loss of appetite, and an inability to recognize faces. After that, the patient was symptom-free for 4 years before he was hospitalized again with a working diagnosis of acute disseminated encephalomyelitis. The ophthalmic symptoms at this stage were photophobia and discrete horizontal nystagmus. One year later, the patient had another seizure and during hospitalization, predominantly displayed cerebral symptoms such as dystaxia, dysmetria, generalized muscle hypotrophy, and absent myotonic reflexes. Like before, an ophthalmic examination demonstrated a best-corrected visual acuity of 1.0 and a normal anterior segment. A fundus examination revealed a slightly rarefied retina, along with areas of perifoveal and parapapillary atrophy, in addition to increased vascular tortuosity. Optical coherence tomography scans of the macula and the optic disc depicted a mild thinning of the retinal layers. Visual field testing showed an isopter contraction with a predominant loss of the temporal visual field in both eyes. A genetic serum analysis was positive for mitochondrial mutation m.3243A>G, and a diagnosis of MELAS was confirmed. The treatment included anticonvulsive drugs and dietary precautions. Patients with MELAS syndrome can manifest a wide range of visual disturbances, meaning that a detailed ophthalmic examination is required.

Gastrointestinal Complications of Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome Managed By Parenteral Nutrition.

Gastrointestinal complications of MELAS such as chronic intestinal pseudo-obstruction, pancreatitis and gastroparesis can lead to undernutrition.Superior mesenteric artery syndrome is a rare condition but should be considered in cases with significant weight loss and resistance to symptomatic treatment.Optimal caloric intake and energy support can improve the condition of patients with MELAS.

MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC).

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.

An Acute Metabolic Encephalopathy, Lactic Acidosis and Stroke-like Episodes Syndrome Patients with Hyperperfusion Responsive to Steroid Treatment

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a genetic disorder caused by mutation in mitochondrial DNA. Patients with stroke-like episodes show restrictive lesions in diffusion weighted image, whereas magnetic resonance angiography images show both vasodilation or vasoconstriction. Vasodilation may lead to hyperperfusion and cerebral edema, which may worsen clinical outcome. Here, we report a 25-year-old male patient diagnosed as MELAS, who presented with stroke-like episodes and seizures and showed cerebral edema with vasodilation which was normalized after steroid treatment.

Clinicoradiologic Criteria for the Diagnosis of Stroke-like Episodes in MELAS.

Stroke-like episodes (SLEs) in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome are often misdiagnosed as acute ischemic stroke (AIS). We aimed to determine unique clinical and neuroimaging features for SLEs and formulate diagnostic criteria. We retrospectively identified patients with MELAS admitted for SLEs between January 2012 and December 2021. Clinical features and imaging findings were compared with a cohort of patients who presented with AIS and similar lesion topography. A set of criteria was formulated and then tested by a blinded rater to evaluate diagnostic performance. Eleven MELAS patients with 17 SLE and 21 AISs were included. Patients with SLEs were younger (median 45 [37-60] vs 77 [68-82] years, p < 0.01) and had a lower body mass index (18 ± 2.6 vs 29 ± 4, p < 0.01), more commonly reported hearing loss (91% vs 5%, p < 0.01), and more commonly presented with headache and/or seizures (41% vs 0%, p < 0.01). The earliest neuroimaging test performed at presentation was uniformly a noncontrast CT. Two main patterns of lesion topography with a stereotypical spatiotemporal evolution were identified-an anterior pattern (7/21, 41%) starting at the temporal operculum and spreading to the peripheral frontal cortex and a posterior pattern (10/21, 59%) starting at the cuneus/precuneus and spreading to the lateral occipital and parietal cortex. Other distinguishing features for SLEs vs AIS were cerebellar atrophy (91% vs 19%, p < 0.01), previous cortical lesions with typical SLE distribution (46% vs 9%, p = 0.03), acute lesion tissue hyperemia and venous engorgement on CT angiography (CTA) (45% vs 0%, p < 0.01), and no large vessel occlusion on CTA (0% vs 100%, p < 0.01). Based on these clinicoradiologic features, a set of diagnostic criteria were constructed for possible SLE (sensitivity 100%, specificity 81%, AUC 0.905) and probable SLE (sensitivity 88%, specificity 95%, AUC 0.917). Clinicoradiologic criteria based on simple anamnesis and a CT scan at presentation can accurately diagnose SLE and lead to early administration of appropriate therapy. This study provides Class III evidence that an algorithm using clinical and imaging features can differentiate stroke-like episodes due to MELAS from acute ischemic strokes.

Identification of m.3243A>G mitochondrial DNA mutation in patients with cerebellar ataxia

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.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome: a case report from Nepal.

A 28-year-old male presented with slurring of speech and drowsiness for 7h. He was a diagnosed case of type 2 diabetes mellitus, Wolf-Parkinson-White syndrome, and bilateral hearing loss. The patient had expressive aphasia with impaired fluency, repetition, and naming. After being discharged, he represented with loss of consciousness and involuntary movements of the whole body. MRI and MRS showed extension of hyperintense lesions to parieto-occipital regions from temporal regions not limited by vascular territories. MELAS was considered, which was confirmed by molecular genetic analysis. Coenzyme Q10 was used for MELAS. Insulin, Linagliptin, and levetiracetam were used for diabetes and seizures. Regular follow-up was advised to the patient.MELAS is an important syndrome to consider in any young patient presenting with unexplained stroke disorders. A high index of suspicion is needed in an appropriate clinical setting to avoid misdiagnosis.

A Case of MELAS Syndrome Involving Diabetes Mellitus, Cerebellar Ataxia and Progressive Sensorineural Hearing Loss

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder. MELAS syndrome manifests different clinical symptoms due to mitochondrial heteroplasmy and individual susceptibility and tends to be aggravated by metabolic events. It presents various clinical manifestations including hearing impairment, diabetes mellitus, and stroke like episodes. However, to date, only a few cases of MELAS syndrome accompanied with cerebellar ataxia have been reported in Korea. We hereby present an unusual case of a patient diagnosed with MELAS syndrome involving diabetes mellitus, cerebellar ataxia and sensorineural hearing loss, which were aggravated by metabolic stresses such as pregnancy and hypoglycemic shock.

Embolization of a Transplanted Kidney in MELAS Requires Special Considerations

With interest we read the article by Kim et al. on an 18 year-old female with mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome, who underwent en block kidney transplantation (EBKT) because of renal failure due to glomerulosclerosis [1]. Two months after transplantation the patient experienced urinary tract infection due to hydronephrosis of the left transplanted kidney [1]. Despite all measures to preserve the left kidney, hydronephrosis was classified as intractable and it was decided to sacrifice the culprit kidney and to embolise it which was technically difficult because of kinking, multiple renal arteries, but was lastly successful [1]. The study is excellent, but has limitations that are cause of concerns and should be discussed. The main limitation of the study is that it was not mentioned how MELAS was diagnosed and that the causative mutation responsible for MELAS was not reported. Knowing the underlying genetic defect is crucial as it may allow assessing the prognosis and may facilitate genetic counselling. Since 80% of the MELAS patients carry the mtDNA variant m.3243A&gt;G in MT-TL1, we should know if MELAS in the index patient was due to this common cause of MELAS and whether other first-degree family members also carried this variant. Knowing whether an mtDNA or nDNA located gene was mutated is critical, as the phenotypic expression of mtDNA located genes is strongly dependent on heteroplasmy rates and mtDNA copy number. Knowing the nature of the underlying mutation is also critical for choosing the optimal immunosuppressive treatment after transplantation, as immunosuppressants can be mitochondrion-toxic. Another limitation is that it is unclear whether the index patient had inherited the pathogenic variant from her parents or whether it had occurred de novo. Knowing whether kidney failure due to glomerulosclerosis was inherited is critical as the index patient would transmit the causative mutation if it was inherited but may not inherit the defect to the next generation if the mutation had occurred de novo. We should know why the left kidney was embolized and not explanted. Because recurrent infections were made responsible for hydronephrosis, it cannot be ruled out that the left kidney hosted microbial agents, which could be a permanent source of bacteriemia or viremia. Therefore, we should know the long-term outcome after embolization. Did the index patient still experience recurrent urinary tract infections or was renal function completely restored after embolization? There is not mention, whether the complicated anatomy, multiple angulations, accessory renal arteries were present already immediately after transplantation or whether they developed during the time between transplantation and the development of hydronephrosis. Were the multiple renal arteries already described in the operation report? Knowing the pathophysiology of multiple renal arteries and kinking is crucial for future cases. Hydronephrosis was attributed to ureter obstruction but there is no discussion of its pathophysiology. We should know whether ureter obstruction was due to host-versus graft reaction, due to ureteritis, due to spasms, or due to ureter stones. Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and could improve the status of the study. Complications after kidney transplantation in MELAS patients require special attention and management.

Late-onset mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with mitochondrial DNA 3243A&gt;G mutation masquerading as autoimmune encephalitis: A case report

Here, we present a unique case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome, which initially appeared to be autoimmune encephalitis and was ultimately confirmed as MELAS with the mitochondrial DNA 3243A>G mutation. A 58-year-old female presented with acute-onset speech impediment and auditory hallucinations, symmetrical bitemporal lobe abnormalities, clinical and laboratory findings, and a lack of relevant prodromal history, which suggested diagnosis of autoimmune encephalitis. Further work-up, in conjunction with the patient's medical history, family history, and lactate peak on brain lesions on magnetic resonance imaging, suggested a mitochondrial disorder. Mitochondrial genome analysis revealed the m.3243A>G variant in the MT-TL1 gene, which led to a diagnosis of MELAS syndrome. This case underscores the importance of considering MELAS as a potential cause of autoimmune encephalitis even if patients are over 40 years of age, as the symptoms and signs are atypical for MELAS syndrome.

Comprehensive Diagnostic Criteria for MELAS Syndrome; a Case Study Involving an Elderly Patient With MT-TWm.5541C>T Mutation.

The mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a matrilineal hereditary multisystem disease caused by mutations in the mitochondrial DNA. Although the initial diagnostic criteria correlate with a range of clinical phenotypes, including clinical onset after the age of 40, there is still lack of a unified single diagnostic standard for MELAS. A 71-year-old female patient with recurrent stroke was reported. Magnetic resonance imaging showed a cerebral gyrus-like diffusion weighted imaging high signal lesion in the parietal-occipital lobe and the area of this lesion expanded with disease progression. The MRS result showed significantly inverted Lac/Lip peaks. The nucleic acid sequencing result displayed a MT-TWm.5541C>T mutation, and a 12.86% mutation rate in the blood sample. The patient had a 6-year history of type 2 diabetes. Patients with the MELAS syndrome may present with a variety of clinical manifestations. Our data demonstrated that, for patients with atypical cerebral infarction and suspected MELAS syndrome, gene sequencing and muscle biopsy should be performed in time. This case provides a reference for the diagnostic criteria of MELAS syndrome.

Ischemic optic neuropathy as first presentation in patient with m.3243 A > G MELAS classic mutation

BackgroundMitochondrial 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 presentationHere 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.ConclusionsAtypical 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.

Acute onset of diabetes and rapid cognitive decline in a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome.

Mitochondrial diseases are a group of rare diseases presenting with heterogeneous clinical, biochemical, and genetic disorders caused by mutations in the mitochondrial or nuclear genome. Multiple organs can be affected, particularly those with high energy demand. Diabetes is a common endocrine manifestation of mitochondrial diseases. The onset of mitochondrial diabetes can be latent or acute, and the presenting phenotype can be type 1- or type 2-like. Studies show that diabetes ais associated with latent progression of cognitive decline in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Herein, we report a case of rapid cognitive decline after the acute onset of diabetes in a patient with MELAS syndrome. The patient was a 36-year-old woman who was hospitalized due to hyperglycemic crisis and seizures. She was diagnosed with MELAS syndrome two years previously, and had gradually progressing dementia and hearing loss. However, following the acute onset of diabetes, she developed rapid cognitive decline and loss of ability to perform daily activities. In conclusion, the acute onset of diabetes could be an associated risk factor for rapid cognitive decline in patients with MELAS syndrome. Thus, these patients as well as healthy carriers with related genetic mutations should undergo diabetes education and screening tests. Moreover, clinicians should be aware of the possibility for acute onset of hyperglycemic crisis, particularly in the presence of triggering factors. Diabetes is a common endocrine manifestation of mitochondrial diseases, presenting with a type 1- or type 2-like phenotype depending on the level of insulinopenia. Metformin should be avoided in patients with mitochondrial diseases to prevent metformin-induced lactic acidosis. Mitochondrial diabetes can manifest before or after the onset of MELAS syndrome. In patients with MELAS syndrome, diabetes can initially manifest with a life-threatening severe hyperglycemic crisis and can cause rapid cognitive decline. Diabetes screening tests (e.g. hemoglobin A1c, oral glucose tolerance test, or random blood glucose level measurement) should be performed either systematically or in the presence of symptoms, particularly after triggering events. Genetic testing and counseling should be provided to patients and their families for the purpose of better understanding the inheritance, progression, and possible outcomes of the disease.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome: a case report

ABSTRACT A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome.

Development of a sensitive double TaqMan Probe-based qPCR Angle-Degree method to detect mutation frequencies

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.

Characteristics of stroke-like lesions on cerebral imaging.

<p><strong>Objective</strong> &ndash; Stroke-like lesions (SLLs) are pathognomonic for mitochondrial ence&shy;pha&shy;lopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome but occur in other mitochondrial and non-mitochondrial disorders as well. This mini-review aims at summarising and discussing recent findings to open up future perspectives how to manage this fleeting phenomenon.<br><strong>Results </strong>&ndash;<strong> </strong>Typically, SLLs are dynamic lesions, which increase in size and intensity to regress after a nadir. SLLs are incongruent with a vascular territory, originate frequently from the cortex to spread subcortically, can be monofocal or multifocal, run through an acute (attack) and chronic (remission) stage, and may either completely disappear or end up as laminar cortical necrosis, white matter lesion, subcortical atrophy, cyst, or the toenail sign. On cerebral CT, SLLs are hypodense. SLLs can be best visualized on multimodal MRI showing up as hyperintensity on T2, FLAIR, DWI, and PWI, and as hypointensity on OEF-MRI. On MR-spectroscopy, SLLs typically present with a decreased N-acetyl-aspartate peak and an increased lactate peak. DTI in acute SLLs reveals reduced connectivity, increased global efficiency, and reduced focal efficiency. Tc-HMPAO SPECT of SLLs indicates hyperperfusion and L-iomazenil SPECT reduced tracer uptake. FDG-PET typically shows hypometabolism within a SLL.<br><strong>Conclusion</strong> &ndash; SLLs present with typical findings on various imaging modalities but the combination of cerebral CT, multimodal MRI, MRS, and PET clearly delineate a SLL from other acute or chronic cerebral lesions.&nbsp;</p>.

Traumatic Brain Injury Triggers Neurodegeneration in a Mildly Symptomatic MELAS Patient: Implications on the Detrimental Role of Damaged Mitochondria in Determining Head Trauma Sequalae in the General Population.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited genetic mitochondrial disease with a typical onset in the first two decades of life and a major involvement of central nervous system (CNS). We present the case of a man affected with an oligosymptomatic, genetically determined MELAS syndrome, whose clinical picture dramatically and irreversibly worsened following a mild head injury. We hypothesize that the CNS metabolic stress induced by the brain injury activated an irreversible cascade of events leading to progressive neurodegeneration because damaged mitochondria were unable to restore the balance between energy requirements and availability.

Arginine for the Treatment of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes: A Systematic Review.

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndromeis a mitochondrial disease that lacks a definitive treatment. Lately, there has been an increased interest in the scientific community about the role of arginine in the short and long-term settings of the disease. We aim to conduct a systematic review of the clinical use of arginine in themanagement of MELAS and explore the role of arginine in the pathophysiology of the disease. We used PubMed advanced-strategy searches and only included full-text clinical trials on humans written in the English language. After applying the inclusion/exclusion criteria, four clinical trials were reviewed. We used the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol for this systematic review. We used the Cochrane Collaboration risk-of-bias tool to assess the bias encountered in each study. Overall, IV arginine seems to be effective in improving symptoms during acute attacks of MELAS, while oral arginine supplementation increases endothelial function, preventing further stroke-like episodes.