A case report of late-onset MELAS with paroxysmal sympathetic hyperactivity syndrome / 中华神经科杂志

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome characterized by paroxysmal tachycardia, increased blood pressure, tachypnea, hyperthermia, profuse sweating, abnormal posture or dystonia. It occurs in diseases such as moderate to severe brain injury, cerebral hypoxia, hydrocephalus, brain tumor and encephalitis. At present, the etiology and pathogenesis are still unclear, and it is easy to be misdiagnosed as epilepsy clinically. This article reports a 43-year-old male patient with late-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) confirmed by genetic testing. During hospitalization, he suddenly developed episodic involuntary limb movements, profuse sweating, tachycardia, and arterial hypertension. He was initially diagnosed with symptomatic epilepsy, but long-term electroencephalogram monitoring showed no synchronized discharge, and he was given antiepileptic drugs. The treatment was also ineffective. Brain magnetic resonance imaging revealed a new lesion in the left insular and insular operculum. Dexmedetomidine, baclofen, and gabapentin were given to suppress sympathetic nerve excitability. Drugs were effective, so the diagnosis was corrected to PSH. There is no report of MELAS complicated with PSH in the previous literature. It is speculated that it may be related to the low clinical cognition of PSH. In this case, new lesions in the insula and insular operculum appeared during the onset of PSH, suggesting that may be related to the pathogenesis of PSH.

A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes mimicking migraine attacks with visual aura / 中国医师杂志

Objective:To study the case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) which mimic migraine attacks with visual aura, to analyze the clinical features, and to recognize the nature of headache.Methods:The clinical features, image data and video electroencephalogram (EEG) of a suspected patient with MELAS were analyzed. Genomic DNA of mitochondria was extracted from blood and the next generation sequencing was performed to explore the mutation of genes about MELAS.Results:The patient was adolescent-onset, and presented with migraine-like attacks with visual aura, epileptic seizures, stroke-like episodes and hyperlactemia. Brain images suggested basal ganglia calcification, reversible left occipital cortex infarction and abnormal lactic acid peaks in both occipital cortex. Video EEG suggested abnormal adolescent EEG. Mitochondrial DNA sequencing showed that MT-TL1 gene had m. 3243A>G pathogenic mutation.Conclusions:There are a variety of clinical manifestations in MELAS, and migraine-like attacks with visual aura as initial symptoms may be manifestations of occipital lobe epilepsy. Clinicians should avoid confusing the diagnosis of migraine with visual aura, occipital epilepsy and MELAS, in order to make rational clinical decisions.

Síndrome MELAS en pediatría. Reporte de caso / MELAS Syndrome in pediatrics. Case report

Resumen Introducción. El síndrome de encefalopatía mitocondrial, acidosis láctica y episodios similares a un accidente cerebrovascular (MELAS, por su sigla en inglés) es una de las enfermedades mitocondriales más frecuentes. Estas patologías se caracterizan por ser hereditarias, multisistémicas y progresivas, y por causar un compromiso predominantemente neurológico que provoca discapacidad y mortalidad, por lo que el diagnóstico temprano y la consejería genética son de gran importancia para mejorar el pronóstico de estos pacientes. Presentación del caso. Paciente femenina de cinco años quien fue llevada a consulta al servicio de pediatría por convulsión y ataxia, y en quien se evidenció retraso psicomotor. Aunque los estudios de neuroimagen fueron normales, se observó hiperlactatemia. Se encontró una relación lactato/piruvato >20, por lo que se sospechó enfermedad mitocondrial. Seis meses después, la paciente presentó deterioro neurológico progresivo caracterizado por alteración de la consciencia, mioclonías y hemiparesia. Se realizó tomografía axial computarizada de cráneo y resonancia magnética por espectroscopia que permitieron identificar una lesión isquémica occipital y aumento del lactato cerebral, respectivamente. Para confirmar el diagnóstico de síndrome MELAS, se solicitó estudio de ADN mitocondrial, en el que se observó la mutación m.3243A>G en el gen MT-TL1. La paciente tuvo un rápido deterioro, presentando una involución de las capacidades adquiridas, falleciendo a los cuatro años del inicio de los signos clínicos. Conclusión. Las enfermedades mitocondriales deben ser consideradas en pacientes con antecedentes de epilepsia y otras alteraciones neurológicas como ataxia e involución del neurodesarrollo.

Abstract Introduction: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) syndrome is the most common mitochondrial disease. These diseases are hereditary, multi-systemic and progressive, and lead to a predominant neurological involvement that causes disability and death, so early diagnosis and genetic counseling are of great importance for improving the prognosis of these patients. Case presentation: Five-year-old female patient who was taken to the pediatrics service of the hospital due to epileptic seizure, psychomotor retardation and ataxia. Although in the first medical consultation her neuroimaging studies were normal, hyperlactatemia was identified. In addition, a lactate to pyruvate ratio >20 was observed, so a mitochondrial disease was suspected. Six months later, the patient showed progressive deterioration of her health condition. A cranial CT scan and a magnetic resonance spectroscopy allowed the identification of an ischemic lesion in the occipital lobe and increased cerebral lactate levels, respectively. In order to confirm the MELAS syndrome diagnosis, a mitochondrial DNA study was requested, in which the m.3243A>G mutation was found. Unfortunately, the patient had a rapid deterioration of her health condition, showing a regression of her acquired functions, and died four years after the onset of the clinical signs. Conclusion: Mitochondrial diseases diagnosis should always be considered in patients with a history of epilepsy and other neurological disorders such as ataxia and neurodevelopmental regression.

Dexmedetomidine as a non-triggering anesthetic agent in a patient with MELAS syndrome and systemic sepsis: A case report

BACKGROUND: The selection of anesthetic agents is important in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome patient because serious and unexpected complications can occur after anesthetic exposure.CASE: A 30-year-old man with MELAS syndrome and sepsis underwent colectomy. Propofol was administered by step-wise until target effect-site concentration (Ce) 1.0 µg/ml and stopped for the loss of consciousness and to avoid hemodynamic instability. After the loss of consciousness, total intravenous anesthesia (TIVA) using dexmedetomidine (1.0 µg/ml/h) and remifentanil (1–4 ng/ml of Ce) was performed for the maintenance of anesthesia to avoid malignant hyperthermia and mitochondrial dysfunction. During the surgery, the bispectral index score stayed between 26 and 44, and increased to 97 after the end of anesthesia.CONCLUSIONS: TIVA with dexmedetomidine and remifentanil as non-triggering anesthetic agents in patients with MELAS syndrome and systemic sepsis may have advantages to decrease damages associated with mitochondrial stress and metabolic burden.

Twenty-one-year follow-up of variable onset MELAS syndrome with heteroplasmic nt3243A>G mtDNA mutation: A case report

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder of which m.3243A>G is the most commonly associated mutation, resulting in an inability to meet the energy requirements of various organs. MELAS poses a diagnostic challenge owing to its multiple organ involvement and great clinical variability due to its heteroplasmic nature. We report three cases from a family who were initially misdiagnosed with myasthenia gravis or undiagnosed. Although there is no optimal consensus treatment approach for patients with MELAS because of the disease's heterogeneity, our 21-year-long therapy regimen of l-arginine, l-carnitine, and coenzyme Q10 supplementation combined with dietary management appeared to provide noticeable protection from the symptoms and complications. Prompt early diagnosis is important, as optimal multidisciplinary management and early intervention may improve outcomes.

A clinical and natural history research on mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes / 中华神经科杂志

Objective To summarize the clinical features,natural history and causes of death of mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes (MELAS).Methods We retrospectively evaluated the clinical findings of 64 patients diagnosed as MELAS more than 3 years (death cases excluded) in Huashan Hospital from January 2005 to March 2017 and analyzed the natural course and the causes of death of the disease.Results Among 64 patients,the male-to-female ratio was 1.3 ∶ 1.Median onset age was 20.5 (16.8) years.The peak of incidence age was from 14 to 22 years.The most common features of MELAS in acute phase were seizures (48/64,75.0％),headache (41/64,64.1％),blurred vision (37/64,57.8％),nausea and vomiting (27/64,42.1％),fever (25/64,39.1％),mental and behavioral disorder (24/64,37.5％).Lactate dehydrogenase (31/60,51.6％),resting blood lactic acid (43/58,74.1％) and cerebral spinal fluid lactic acid (9/9) were elevated.Abnormal findings in electroencephalogram (36/40,90.0％),electrocardiogram (37/47,78.7％),electromyography (25/41,61.0％) were detected.In this cohort,20 patients (20/64,31.3％) with MELAS were dead.A Kaplan-Meier survival curve showed the estimated overall median survival time was 12 years.The median survival time of the group onset before sex maturity (≤ 14 years) was 8 years and that in the group onset after sex maturity (＞ 14 years) was 21 years.The causes of death were cardiogenic incidence (4/20,20.0％),pulmonary infection (4/20,20.0％),lactic acidosis (2/20,10.0％) and status epilepticus (2/20,10.0％).Conclusions MELAS is usually presented in young people associated with high mortality rate.The leading causes of death are cardiogenic,pulmonary infection and lactic acidosis.

Clinical, myopathological and genetic research of a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes/Leigh syndrome overlap syndrome caused by m.10158 T>C mutation / 中华神经科杂志

Objective To report the clinical, myopathological and genetic features of a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)/Leigh syndrome (LS) overlap syndrome who carried m.10158 T>C mutation. Methods The patient′s clinical and imaging materials were collected. An open biopsy of right biceps brachii was performed. DNA samples were prepared from the patient and her mother′s blood. Direct sequencing of the complete mitochondrial genome was performed to detect the mtDNA mutation.Western blotting was used to estimate the content of respiratory complexes in the patient′s muscle. Results The patient was a 40-year-old female. She had seizures and lost consciousness for 9 months. Brain MRI findings consisted of asymmetrical lesions in the cerebral cortex of the frontal and temporal lobes, as well as symmetrical lesions bilaterally in the basal ganglia. Muscle biopsy showed typical ragged red fibers. Direct sequencing of the complete mitochondrial genome from blood and muscle of the patient revealed the T-to-C transition at nucleotide position 10158 in the MT-ND3 gene.The mutation rate was 9.31% and 70.0%, respectively.Western blotting demonstrated that the contents of complexes Ⅰ and Ⅳ were significantly lower in the patient′s muscle mitochondria compared with the normal controls (53.1%±1.2% vs 88.6%±1.7%, t=4.08, PC mutation in MT-ND3 gene and DNA test is very important for the diagnosis of the disease.

Acute Auditory Agnosia Resulted from MELAS Syndrome / 听力学及言语疾病杂志

Objective To investigate the clinical features,etiology,diagnosis and treatment of acute auditory agnosia.Methods We studied the clinical manifestation,diagnosis and treatment of acute auditory agnosia in a patient in our hospital.Results A 28 year oldyoung woman visited our department because she suffered from the tinnitus for 7 days and she could not distinguish the semantics for 1 day.There were no other abnormal symptoms in the central and peripheral nervous system on admission.Audiological testing showed normal,language testing showed that the speech discrimination score was zero.MRI showed extensive damage to temporal lope.MR spectroscopy revealed increased lactate and reduced N-acetyl aspartate.Acute auditory agnosia resulted from mitochondrial myopathy was considered.After symptomatic treatment,the symptoms were significantly improved.Molecular genetics examination showed the A3243G mtDNA mutation,further confirmed the diagnosis of mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes (MELAS) syndrome.Conclusion Acute auditory agnosia and acute tinnitus can be the first symptoms in MELAS,thus,MELAS should be suspected in patients with acute auditory agnosia,acute tinnitus,sudden hearing loss in children and youth.Imaging examination plays an important role in the etiological diagnosis of acute auditory agnosia.

Epileptic seizures and electroencephalographic findings in patients of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes / 中国医师进修杂志

Objective To investigate the features of epileptic seizures and eletroencepalogram (EEG)in patients of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Methods Fifty-five patients with MELAS were selected. EEG and head MRI was performed on all patients.The types of epileptic seizure and EEG changes were compared between patients in and outside stroke-like episodes. Results Epileptic seizures occurred in 49 of 55 patients (89.1%) with MELAS, while multitype epileptic seizures were presented in 33 cases(67.3%). The frequency of partial seizures, generalized tonic-clonic seizures, status epilepticus was 47.3%(26/55), 69.1%(38/55), 38.2%(21/55) in stroke-like episodes and12.7%(7/55), 27.3%(15/55), 5.5%(3/55) in nonstroke-like episodes, which had statistical significance (χ2 = 8.023, 10.647, 11.002; P=0.022, 0.016, 0.005, respectively). Abnormal EEGs appeared in all patients.The rates of slow alpha frequency, diffuseδorθwave, epileptic discharges were 7.3%(4/55), 43.6%(24/55) and 25.5%(14/55) in stroke-like episodes and 30.9%(17/55), 58.2%(32/55) and 23.6%(13/55) in nonstroke-like episodes, respectively.Slow alpha frequency was significantly different between patients in and outside stroke-like episodes (χ2=8.933, P=0.019). Conclusions Epileptic seizures with different types are more common during stroke-like episodes in patients with MELAS.While the rates of epileptic discharges are also common outside the stroke-like episodes.

The MRI findings of mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes / 实用放射学杂志

Objective To analyze retrospectively the MR features of MELAS patients,in order to improve the early diagnosis of MELAS.Methods MR data of 1 6 MELAS patients confirmed by clinical diagnose and muscle biopsy were retrospectively analyzed. MR features of plain scan(n=1 6),ASL(n=3),MRA(n=1 5),DWI(n=14)and MRS(n=3)were analyzed.Results MRI data demonstrated brain lesions mainly distributed in posterior cerebral hemisphere extending to subcortical area,which was not consistent with the vascular supply territories.The lesions were observed as low signal on Spin-echo sequence of T1 WI,while high signal on T2 WI, FLAIR and DWI.The focal lesions showed increasing Lac peak on MRS.Fifteen of 16 patients underwent MRA and one showed increased arterial branches in lesion zones.Three patients had ASL scanning demonstrating high irrigation in lesion zones which would wander once relapsed.Meanwhile,old lesions showed encephalatrophy and cerebromalacia.All patients’muscle biopsy pathology showed ragged red muscle fibers.Under electron-microscopic,bioblasts were bigger and more than average level and muscle fibers atrophied.Mitochondrial DNA sequence of 3 patients showed mtDNA A3243G transgenation.Conclusion The DWI,MRS and ASL sequences show good ability in MELAS diagnosis and differential diagnosis.

Clinical features of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes：an analysis of 190 cases / 中华神经科杂志

Objective To summarize the clinical features of Chinese patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes ( MELAS).Methods A total of 190 patients with MELAS who presented to Peking University First Hospital between 1997 and 2015 were recruited.Among 190 patients, 175 were identified carrying mitochondrial DNA mutations, and the remaining 15 patients were diagnosed by muscle biopsy.The clinical features, including predisposing factors of stroke-like episodes, the onset symptoms and frequencies of various manifestations were analyzed and reported.Results In our cohort of MELAS patients, the male-to-female ratio was 1.44∶1.The median age of onset was 14 years ( from 7 months to 45 years).The peak onset ages were 8-12 years.The median onset age of the first stroke-like episode was 16 years ( from 1 to 53 years ).There were 66 ( 46.15%) patients who had predisposing factors before the onset, and fatigue and upper respiratory tract infection were the most common predisposing factors of stroke-like episodes in these patients ( 37.88%, 25/66 and 34.85%, 23/66, respectively).Other predisposing factors included emotional agitation, drinking alcohol, trauma, withdrawal of antiepileptic drugs, being frightened, satiation and hunger.Stroke-like episodes appeared in 70.53%(134/190) patients as an onset symptom and developed in all patients with disease progression.The neurological manifestations included seizure ( 89.42%, 169/189 ) , mental retardation or dementia (82.87%, 150/181), headache (74.30%, 133/179), hemianopia or cortical blindness (67.72%, 107/158), exercise intolerance (50.87%, 88/173), hemiplegia or hemianesthesia (47.44%, 74/156), sensorineural deafness (46.20%, 85/184), aphasia (39.47%, 60/152), behaviour disorder (17.71%, 31/175) and ophthalmoplegia ( 9.60%, 17/177 ).The manifestations of extra-nervous systems included hirsutism (67.57%, 100/148), vomiting (65.58%, 101/154), fever (62.07%, 90/145), short stature (45.32%, 63/139), diarrhea or constipation (43.48%, 70/161), low body mass index (26.62%, 37/139), diabetes mellitus (20.79%, 37/178) and kidney disease (3.16%, 6/190).Conclusions The majority of the patients in this study have the disease onset during childhood.There are more male MELAS patients than females.Most common clinical manifestations are seizure, mental retardation or dementia, headache, cortical blindness, hirsutism, vomiting and fever in this patient group.

A Case of MELAS Syndrome Presenting with Type 1 Diabetes Mellitus / 대한내과학회지

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presents with various clinical features, including seizures, stroke-like episodes, encephalopathy, myopathy, cardiac involvement, and diabetes. However, due to its clinical heterogeneity, the diagnosis of MELAS syndrome is complex and difficult. The present report describes an 18-year-old male who was diagnosed with MELAS syndrome following the onset of type 1 diabetes. The patient had suffered from ataxia, mental retardation, and recurrent headaches for several years; following hospitalization for loss of consciousness, he was treated for cerebellar atrophy and Wolf-Parkinson-White (WPW) syndrome. Although the patient had no history of lactic acidosis, the recent onset of type 1 diabetes and his medical history of encephalopathy and WPW syndrome suggested MELAS syndrome. The diagnosis of MELAS syndrome was confirmed by molecular genetic testing, which revealed a point mutation (A3243G) in the patient's mitochondrial DNA.

Epileptic seizures and electroencephalographic findings in patients with mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes / 中华神经科杂志

Objective To investigate the features of epileptic seizures and eletroencepalogram (EEG) in patients with mitochondrial myopathy encephalopathy,lactic acidosis and stroke-like episodes (MELAS).Methods Forty-four patients with MELAS were diagnosed at the First Hospital of Peking University from November 2007 to August 2013.EEG and head MRI were performed on all patients.The types of epileptic seizure and EEG changes were compared between patients in and outside stroke-like episodes.Results Epileptic seizures occurred in 39 of 44 patients (88.6％) with MELAS,while multitype epileptic seizures were presented in 26 cases (66.7％).In stroke-like episodes,22 patients presented with partial seizures,30 with generalized seizures and 17 with status epilepticus.In nonstroke-like episodes,7 patients presented with partial seizures,14 with generalized seizures and 2 with status epilepticus.The frequency of partial seizures,generalized tonic-clonic seizures,status epilepticus were 47.7％ (21/44),68.2％ (30/44),38.6％ (17/44) in stroke-like episodes and 13.6％ (6/44),27.3％ (12/44),4.5％ (2/44) in nonstroke-like episodes,which have statistical significance (x2 =12.022,14.758,15.103;P =0.001,0.000,0.000,respectively).Abnormal EEGs appeared in all patients.The rates of slow alpha frequency,diffuse δ or θ wave,epileptic discharges were 6.8％ (3/44),43.2％ (19/44),25.0％(11/44) in stroke-like episodes and 31.8％ (14/44),59.1％ (26/44),22.7％ (10/44) in nonstroke-like episodes,respectively.Slow alpha frequency were significantly different between patients in and outside stroke-like episodes (x2 =8.822,P =0.003).Conclusions Epileptic seizures with different types are more common during stroke-like episodes in patients with MELAS.While the rates of epileptic discharges are also common outside the stroke-like episodes.

Dynamic evolution of brain magnetic resonance imaging findings in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome / 中华神经科杂志

Objective To analyze the dynamic evolution of brain MRI in patients with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes (MELAS) syndrome.Methods A retrospective study was performed on 58 MELAS cases with pathologically and (or) molecularly confirmed diagnosis.MRI were repeated within 60 days after the onset of stroke-like episodes (SLE) and the evolution changes of cerebral lesions were accessed.Brain atrophy index (BAI) was calculated in the remission stage from 31 patients with MELAS,and the correlation between BAI,age and disease duration was analyzed.Results The proportion of lesions expansion,migration and shrink within 30 days after the onset of SLE was 64.1％ (25/39),10.2％ (4/39),17.9％ (7/39),respectively,and 13％ (3/23),21.7％ (5/23),56.5％ (13/23),between 30-60 days after the onset of SLE respectively.In the recovery stage of SLE,the BAI in 31 patients with MELAS was 15.2％ ±2.8％.The correlation coefficient between BAI and the age,total disease course and duration of encephalopathy was 0.329 (P =0.043),0.405 (P =0.012) and 0.649 (P =0.000).Conclusions Brain atrophy in the studied MELAS patients gradually develops and strokelike lesions shrink with progression of the disease.However,the migration of lesions is persistent.

Clinical features and misdiagnosis analysis of six children MELAS syndrome patients / 中国医师杂志

Objective To explore clinical features and misdiagnosis reasons in mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes (MELAS) syndrome.Methods The results of clinical data,brain magnetic resonance imaging (MRI),and the course of diagnosis were analyzed in 6 patients with MELAS.Results (1) Clinical features:headache and vomiting were the starting symptoms in 4 of 6 cases,and developmental delay was initial symptoms in 2 of 6 cases.Marasmus occurred in 6 cases,seizure in 5 cases,fever in 3 cases,and hirsutism and visual impairment in 2 cases.(2) Experimental results:blood lactic acid was higher in 6 (4.28 ～ 10.3 mmol/L).(3) Brain MRI:6 patients had abnormal signals in parietal,occipital,temporal lobe,which were not in accordance with vascular distribution.(4) Molecular genetics:All the 6 patients had A3243G gene mutation.(5) Three patients were misdiagnosed for viral encephalitis,and 2 developmental retardation.Conclusions MELAS is characterized with developmental retardation,and repeated encephalitis attack.It is also misdiagnosed because of its variety of clinical features.If patients have high level of lactic acid and multiple MRI signal abnormalities of brain which are not in accordance with vascular distribution,MELAS should be suspected of.Genetic examination and muscle biopsy are especially important in the diagnosis of MELAS.

A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MEALS) Syndrome with Intracardiac Thrombus

Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

Permanent Pacemaker Implantation in a Patient with MELAS Syndrome / 대한내과학회지

A 35-year-old male patient with heart and renal failure and pneumonia was transferred to our department due to recurrent cardiac standstill with syncope. He had been diagnosed as and treated for MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome for the past 3 years. Electrocardiography (ECG) showed the Wolff-Parkinson-White pattern, and an echocardiogram showed hypertrophic cardiomyopathy. He developed syncopal attacks intermittently, and ECG monitoring showed intermittent bradycardia. His Holter monitoring showed several episodes of 5-16 seconds of sinus arrest. We conducted an electrophysiological study to evaluate the arrhythmia. During atrial and ventricular extra-stimuli, cardiac standstill developed several times, and the duration of pauses varied from 2.5 to 5.5 seconds. Abrupt asystolic events also developed accompanying syncopal attacks that were not related to the extra-stimuli. We decided to implant a permanent pacemaker. The patient's syncopal episodes disappeared after implantation of a DDD type pacemaker.

Genetics of Mitochondrial Myopathies

Mitochondrion is an intracellular organelle with its own genome. Its function in cellular metabolism is indispensable that mitochondrial dysfunction gives rise to multisystemic failure. The manifestation is most prominent with tissues of high energy demand such as muscle and nerve. Mitochondrial myopathies occur not only by mutations in mitochondrial genome, but also by defects in nuclear genes or secondarily by toxic insult on mitochondrial replication. Currently curative treatment modality does not exist and symptomatic treatment remains mainstay. Administration of L-arginine holds great promise according to the recent reports. Advances in mitochondrial RNA import might enable a new therapeutic strategy.

Evaluation of vascular autoregulation in mitochondrial myopathy, encephalopathy, lactic acidosis,and stroke-like episodes patients / 中华神经科杂志

Objective To investigate the cerebral vascular autoregulation in patients with mitochondrial encephalomyopathy with lactic acidosis and strokc-like episodes (MELAS) during the remission of stroke-like episodes,including cerebrovascular CO2 reactivity and vascular endothelial function.Methods Twenty-nine MELAS patients confirmed by genetic analysis were recruited in this study. They underwent the examination at least 2 weeks after the onset of last stroke-like episode.Twenty-eight healthy people were collcctcd as healthy controls. Carotid ultrasound and brain magnetic resonance angiogram (MRA) were done to evaluate the cervical and intracranial appearance of large arteries. Evaluation of vascular autoregulation included: (1) the cerebrovascular CO2 reactivity with breath-holding test by transcranial Doppler and calculating breath holding index (BHI),and ( 2 ) flow-mediatcd dilation ( FMD )and nitroglycerin-mediated dilation with ultrasound assessment of humeral artery.Independent-samples t test was done between the results of two groups.Results Carotid ultrasound and cranial MRA revealed no abnormalities in both MELAS patients and healthy controls.The BHI of MELAS patients was significantly decreased than that of normal controls ( 1.36 ± 0.52 vs 1.81 ±0.26,t =- 3.693,P ＜ 0.01 ),and the FMD of MELAS patients was also significantly lower than that of normal controls (11.0％ ±4.8％ vs 15.8％ ±5.8％,t =-3.390,P ＜0.01).Conclusion The function of vascular autoregulation,including cerebrovascular CO2 reactivity and FMD,is impaired in MELAS patients.

Phenotype in 6 patients with mitochondrial DNA G13513A mutation / 中华神经科杂志

Objective To report 6 Chinese patients with mitochondrial encephalomyopathy caused by mitochondrial DNA(mtDNA)G13513A mutation and discuss the mitochondrial phenotype associated with this mutation based on the data of our patient series as well as the reports by others.Methods Direct sequencing of polymerase chain reaction(PCR)products or PCR-RFLP analysis Was performed to screen mtDNA G13513A mutation in 35 cases with mitoehondrial encephalomyopathy.who carried no mtDNA common mutations(1arge 8eale deletion,A3243G,T3271 C,A8344G,or T8993G/C).The clinical features,MRI changes were retrospectively collected and analyzed.Published studies of all patients with mtDNA G13513A mutation were also reviewed.Results Six patients were identified carrying mtDNA G13513A mutation.All patients presented stroke-like episodes with hemianopsia.hemiparesis or hemiparesthesia.Three adult patients presented clinical and radiological features of adult-onset mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes(MELAS),including stroke-like episodes,epilepsy,headache,short stature,sensorineural deafness,multifocal lesions on parietal,occipital and temporal lobes on cranial MRI scans.Three iuvenile.onset patients presented the clinical and brain MRI features of MELAS-Leigh syndrome(LS)overlap syndrome.In addition to the stroke-like episodes,they also showed brain stem lesions with dysarthria,ataxia,and ophthalmopJegia. Brain MRI revealed asymmetrical lesions in the cortex of the oecipital and temporal lobes,as well as symmetrical lesions in the bilateral basal ganglia and brainstem.Muslce biopsy showed ragged redfibem in 5 patients.The infant-onset LS or Leigh-like syndrome with mtDNA G135 13A was described in the English literature.Conclusions mtDNA G13513A mutation is a common pathogenic mutmion for mitochondrial encephalomyopathy,which can result in Leigh syndrome,MELAS-LS overlap syndrome and adult MELAS.The onset of various phenotypes is relatively age-dependent.