Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is 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 the management 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.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi-systemic phenotype that predominantly features neurological manifestations--stroke-like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses.
A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed.
Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke-like episodes. Heteroplasmy is higher in a tissue other than blood in most cases.
The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.
Zespół MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) jest chorobą uwarunkowaną genetycznie, związaną z mutacją w mitochondrialnym DNA. Przedstawiamy przypadek pacjentki, u której w trakcie diagnostyki niedoboru wzrostu wysunięto podejrzenie zespołu MELAS. U dziewczynki oprócz niedoboru wzrostu obserwowano inne objawy sugerujące chorobę mitochondrialną, takie jak m.in. hipotonia mięśniowa, bóle głowy, niedowład nerwu VI lewego, zwyrodnienie barwnikowe siatkówki, niedosłuch zmysłowo-nerwowy, zwiększone stężenie kwasu mlekowego. W rezonansie magnetycznym mózgu zobrazowano hiperdensyjne zmiany w istocie białej w obrazach T2- zależnych. Biopsja mięśnia wykazała obraz poszarpanych włókien czerwonych charakterystyczny dla zespołu MELAS. W wykonanych badaniach genetycznych nie wykryto najczęstszych mutacji w genie MT-TL1 i MT-ND5. W toku diagnostyki endokrynologicznej rozpoznano somatotropinową niedoczynność przysadki, rozpoczęto leczenie preparatem hormonu wzrostu (rhGH). Po roku leczenia rhGH na podstawie doustnego testu obciążenia glukozą zdiagnozowano cukrzycę. Ponadto u obecnie 14-letniej dziewczynki obserwuje się opóźnione dojrzewanie płciowe. Test z LH–RH wykazał wartości przedpokwitaniowe. Zaburzenia endokrynologiczne mogą być jedną z pierwszych manifestacji zespołu MELAS. W diagnostyce niedoboru wzrostu należy uwzględniać jego rzadsze przyczyny jak np. choroby mitochondrialne.

暂无摘要。

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.

BACKGROUND: Mitochondrial encephalomyopathy with lactic acidosis and stroke- like episodes (MELAS) syndrome is caused by mitochondrial respiratory chain dysfunction and oxidative phosphorylation disorder. It is a rare clinical metabolic disease involved with multiple systems.
UNASSIGNED: A 22-year-old patient presented with limb convulsion accompanied by loss of consciousness, headache, partial blindness, blurred vision, and so on.
UNASSIGNED: Brain magnetic resonance imaging showed a high-intensity area in bilateral occipital cortex, left parietal lobe and cerebellum on diffusion-weighted imaging. These focus did not distribute as vascular territory. The pathological examination of skeletal muscle revealed several succinate dehydrogenase reactive vessels with overreaction and increased content of lipid droplets in some muscle fibers. Genetic testing showed that the patient carried m.10158T>C mutation.
METHODS: She was provided with traditional arginine hydrochloride therapy and orally medication of coenzyme Q (10 mg).
RESULTS: Mitochondrial DNA of blood and hair follicle of patient carried m.10158T>C mutation LESSONS:: For the suspected patients of MELAS syndrome, if the hot-spot mutation test is negative, more detection sites should be selected.

Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA.
This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are thought to be rarely accompanied by macroangiopathy. We reported a case of MELAS that presented right distal internal carotid arterial (ICA) stenosis and reviewed 12 similar previously reported cases involving intracranial large blood vessels.
METHODS: A 38-year-old man suffered from recurrent stroke-like episodes (SE) such as alternating hemiparesis (right lesion 3 years ago and current left lesion), cortical blindness and seizure for 3 years, and was previously misdiagnosed as cerebral infarction. Magnetic Resonance Angiography (MRA) and Digital Subtraction Angiography (DSA) revealed right distal ICA stenosis and sparse cortex blood vessels, which were related to the previous SE.
METHODS: He was diagnosed by genetic screening (a mitochondrial DNA A3243G point mutation) and presence of high lactic acidosis (4.03 mmol/L), which rose to 7.8 mmol/L after exercise.
METHODS: The patient received Coenzyme Q10, vitamin C, L-arginine for 2 weeks and valproic acid sodium (400 mg bid) to prevent seizures till now.
RESULTS: He is currently less active and intelligent than his peers, with occasional seizures, and needs family care.
CONCLUSIONS: Till date, there are 12 reported cases of MELAS combined with major cerebral arteries abnormalities including stenosis, dissection, occlusion, reversible vasoconstriction, aneurysms, and atherosclerosis. Hence, macroangiopathy in MELAS is not very rare. There is correlation between the affected vessels and the lesions in some cases, but not in others, which may increase the misdiagnosis rate. Hence, mitochondrial diseases cannot be excluded due to concurrent macroangiopathic lesions.

Symmetric, bilateral basal ganglia calcification is rare finding that sometimes occurs asymptomatically. Its prevalence increases with age, and the most affected site is the globus pallidus.
A series of seven cases with clinical and imaging diagnosis of basal ganglia calcification, recorded during the 2012 to 2016 period at the Department of Internal Medicine of the Hospital Civil de Guadalajara \"Fray Antonio Alcalde, is presented. Most common clinical presentation was with altered alertness, headache and seizures. There was one case with movement disorders; there were no cases identified with dementia or tetany.
Ganglia calcification can be associated with age-related neurodegenerative changes, but it can be an initial manifestation of a variety of systemic pathologies, including disorders of the calcium metabolism, intoxication by different agents, and autoimmune and genetic diseases. Correlation of typical imaging findings with clinical manifestations and laboratory results should be established to reach a definitive judgment.
La calcificación bilateral y simétrica de los ganglios basales es un hallazgo infrecuente que a veces no ocasiona síntomas. Su prevalencia aumenta con la edad y el sitio más afectado es el globo pálido.
Se describe una serie de siete casos con diagnóstico clínico y por imagen de calcificación de ganglios basales, atendidos entre 2012 y 2016 en el Servicio de Medicina Interna del Hospital Civil de Guadalajara Fray Antonio Alcalde. Las manifestaciones clínicas más comunes fueron alteración del estado de alerta, cefalea y crisis convulsivas. Se identificó un caso con trastornos del movimiento; no hubo casos con demencia o tetania.
La calcificación de los ganglios puede estar relacionada con cambios neurodegenerativos por la edad, pero puede ser la manifestación inicial de una variedad de patologías sistémicas, incluyendo trastornos del metabolismo del calcio, intoxicación por diversos agentes, enfermedades autoinmunes y genéticas. Se debe hacer la correlación de los hallazgos de imagen típicos con manifestaciones clínicas y resultados de laboratorio para llegar a un dictamen definitivo.

To evaluate the feasibility of microRNAs (miR) in clinical use to fill in the gap of current methodology commonly used to test hearing impairment in MELAS patients.
A literature review was performed using the following keywords, i.e., MELAS, Hearing Loss, Hearing Impairment, Temporal Bone, Otoacustic Emission (OTOAE), Auditory Brain Response (ABR), and microRNA. We reviewed the literature and focused on the aspect of the temporal bone, the results of electrophysiological tests in human clinical studies, and the use of miR for detecting lesions in the cochlea in patients with MELAS.
In patients with MELAS, Spiral Ganglions (SG), stria vascularis (SV), and hair cells are damaged, and these damages affect in different ways various structures of the temporal bone. The function of these cells is typically investigated using OTOAE and ABR, but in patients with MELAS these tests provide inconsistent results, since OTOAE response is absent and ABR is normal. The normal ABR responses are unexpected given the SG loss in the temporal bone. Recent studies in humans and animals have shown that miRs, and in particular miRs 34a, 29b, 76, 96, and 431, can detect damage in the cells of the cochlea with high sensitivity. Studies that focus on the temporal bone aspects have reported that miRs increase is correlated with the death of specific cells of the inner ear. MiR - 9/9* was identified as a biomarker of human brain damage, miRs levels increase might be related to damage in the central auditory pathways and these increased levels could identify the damage with higher sensitivity and several months before than electrophysiological testing.
We suggest that due to their accuracy and sensitivity, miRs might help monitor the progression of SNHL in patients with MELAS.