Clinical Analysis Of 23 Cases Of Mitochondrial Encephalomyopathy

Background and ObjectiveMitochondrial encephalomyopathy is multiple system disease,which caused by mitochondrial DNA(mt DNA)or nucleus DNA(n DNA)defects,lead to mitochondrial structure and function dysfunction and insufficiency of ATP synthesis.Mitochondrial encephalomyopathy cardinal symptoms are exhaustion after activities and improved after the break,muscle enzyme histochemical staining showed ragged red fiber(RRF).The disease has diverse clinical manifestations,mainly for mental disorders,retardation,paralysis,cortical blindness,seizures,myoclonus,ataxia,short stature,optic nerve atrophy,hearing impairment,exercise intolerance and peripheral neuropathy and a series of clinical manifestations,easily misdiagnosed as cerebral infarction,encephalitis,mental diseases and other diseases.At present,the pathogenesis is unknown,most scholars believe that it is caused by the decoupling of oxidative phosphorylation.The early diagnosis and prognosis of the disease are mostly good.If the diagnosis and treatment is not timely,the sequelae can be left out,and even death can be caused.Since 1962,when Luft first reported a case of mitochondrial myopathy.in 1981,Anderson has determined the full-length sequence of human mt DNA.In 1988 Holt for the first time,mt DNA deletion was found in mitochondrial myopathy patients for the first time.It is confirmed that mt DNA mutation is an important cause of human diseases.So far,the reported cases of this disease have been increasing.However,most of the patients failed to get early diagnosis and active treatment because of their diverse clinical manifestations and clinicians’ lack of understanding of the disease.The purpose of this study is to analyze the onset age,clinical manifestations,magnetic resonance imaging(MRI),case data,gene detection,treatment and prognosis of mitochondrial encephalomyopathy,and provide clinical reference for early diagnosis and treatment.Materials and Methods1.We collected the clinical data of 23 cases of mitochondrial encephalomyopathy diagnosed from October 2015 to December 2017 in Department of Neurology of the First Affiliated Hospital of Zhengzhou University.Inclusion criteria: in accordance with the current clinical diagnosis of mitochondrial encephalomyopathy patients;the clinical manifestations are not typical,but part of imaging data with mitochondrial encephalomyopathy,lactic acid and exercise test with features in patients with mitochondrial encephalomyopathy;the clinical symptoms of suspected mitochondrial myopathy,and diagnosed by gene analysis.Exclusion criteria:(1)gene diagnosis was not consistent with mitochondrial encephalomyopathy;(II)more than 8 dentures,heart stent,fracture plate,claustrophobia,etc.All patients signed the informed consent form,which were approved by the ethics committee of the hospital.2.The clinical manifestations,family history,laboratory and imaging examination,muscle biopsy,gene detection,treatment and prognosis of 23 patients with mitochondrial encephalomyopathy were retrospectively analyzed.All patients underwent routine examination and head MRA and MRI examination,exercise test,blood lactic acid,muscle enzymes,EMG laboratory examination and laboratory;the subjects of muscle biopsy(usually from moderate atrophy of muscles),frozen sections were stained;Diagnostic analysis of mitochondrial DNA in patients according to muscle biopsy results.Results1.This group of patients,12 cases were male and 11 female cases,male: female= 1.1:1.Onset age: minimum 9 years old,maximum 48 years old.2.This group of patients,5 patients with mental and behavioral abnormalities as the initial symptoms(21.7%),5 cases with epilepsy as the first symptom(21.7%),6cases with limb weakness as the first symptom(26.1%),3 cases with sensory abnormalities as the first symptom(13.0%),2 cases with extraocular muscle paralysis as the first symptom(8.7%),2 cases with visual field defect as the first symptom.3.This group of patients,mental disorders accounted for 30.4%,seizures accounted for 34.7%,accounted for 13% of limbs tremor,limb sensory abnormalities accounted for 34.7%,limb weakness accounted for 60.8%,emergence of extraocular muscle paralysis accounted for 86.9%,visual field defect loss accounted for 8.7%,accounted for 21.7% of short stature,stroke-like episodes accounted for 82.6%,impaired hearing accounting for 17.4%,sports intolerance accounted for 82.6%,headache accounted for 21.7%.4.This group of patients,23 patients underwent blood lactic acid exercise test(blood lactic acid were detected before,after exercise immediately and 10 minutes after exercise),patients after exercise immediately and 10 minutes after exercise blood lactate values were higher 5 times than those of normal high limit(2.09mmol/L),18 cases rheumatism immunological examination,abnormal 4 cases(22.2%),23 cases of thyroid function and antibody test,abnormal 5 cases(21.7%),23 cases of homocysteine examination,abnormal 17 cases(73.9%),19 cases of creatine kinase examination,abnormal 11 cases(57.8%).5.This group of patients,12 patients performed limb electromyog-raphy.8 cases(66.7%)with different degrees muscle derived lesions,4 cases(33.3%)with neurogenic lesions.Electrocardiogram was performed in all 23 cases,and 13 cases(56.5%)had different degrees of heart block.In 5 patients,electrical audiometry showed nerve deafness(21.7%),8 patients had abnormal liver function(34.8%),9patients suffered from type two diabetes(39.1%),and 4 patients had impaired visual field(17.4%).6.This group of patients,6 patients performed muscle biopsy,5 cases patients with the typical ragged red fibers(RRF)(83.3%),3 cases SDH staining of myenteric small vessels strongly stained(SSV)(50.0%),3 cases ATP enzyme staining musclefibers were checkerboard like distribution(50.0%),5 cases HE staining of edge basophilic muscle fibers(83.3%).7.This group of patients,23 cases were examined with MRI,21 cases of abnormal(91.3%),7 cases lesions involving the temporal lobe(30.4%),12 cases lesions involving the parietal lobe(52.2%),15 cases lesions involving the occipital lobe(65.2%),1 patients lesions involving the basal ganglia(4.3%),2 cases lesions involving the optic nerve(8.7%);2 cases lesions involving the extraocular muscle(8.7%);9 cases were examined with cranial magnetic resonance spectrum imaging(MRS),7 cases showed abnormal lactate peak(30.4%).8.This group of patients,23 patients underwent mitochondrial gene detection,19 cases with A3243 G point mutation,1 cases wih NDUFS4(c.10G>C)point mutation,2 cases with mt DNA3460 point mutation,1 cases with Mt DNA fragment lost.Conclusion1.The mitochondrial encephalomyopathy is mostly found in young and middle-aged people,and the male is slightly more than the female.2.The mitochondrial encephalomyopathy can involve multiple systems.The clinical manifestations are complex and diverse.The main clinical manifestations are intolerance,mental and behavioral abnormalities,stroke like episodes,seizures,sensory abnormalities,and limb weakness.3.Blood lactic acid exercise test,muscle enzyme,extremities electromyography,cranial magnetic resonance examination,muscle biopsy are important significance in the differential diagnosis of mitochondrial encephalomyopathy.4.The mitochondrial encephalomyopathy head MRI can show long T1 long T2,DWI diffusion limited,flair high signal,and more involved occipital lobe,frontal lobe and parietal cortex,showing "lace sign".It can also involve the optic nerve and the extraocular muscle lesions.5.The typical broken red fibers(RRF)and SDH staining,strong staining of intermuscular small vessels(SSV),muscle fibers distributed on chessboard,and basophilic muscle fibers as the main characteristics of muscle biopsy.