RESUMO
BACKGROUND AND OBJECTIVE: TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d. METHODS: We studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics. RESULTS: We found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features. CONCLUSIONS: By analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.
Assuntos
Miopatias Mitocondriais , Doenças Musculares , Adulto , DNA Mitocondrial/genética , Humanos , Imageamento por Ressonância Magnética , Miopatias Mitocondriais/diagnóstico por imagem , Miopatias Mitocondriais/genética , Músculo Esquelético/diagnóstico por imagem , Doenças Musculares/diagnóstico por imagem , Doenças Musculares/genéticaRESUMO
PURPOSE: To report the first case describing choroidal neovascularization in long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. METHODS: Case report including multimodal imaging discussion. RESULTS: A 21-year-old woman affected by LCHAD deficiency (confirmed by 1528 G>C homozygous mutation) was referred to our department for progressive visual decline in both eyes. Best-corrected visual acuities were 20/40 and 20/1,000 in the right and left eye, respectively. Ultra-widefield imaging, fluorescein angiography, structural optical coherence tomography, and optical coherence tomography angiography revealed the presence of macular and midperipheral chorioretinal atrophy complicated by a choroidal neovascularization in the left eye. CONCLUSION: Ocular changes in LCHAD deficiency are long-term complications and severely affect the quality of life of patients. We report for the first time the evidence that choroidal neovascularization could complicate ocular changes accelerating the progressive vision impairment.
Assuntos
Cardiomiopatias , Neovascularização de Coroide , Erros Inatos do Metabolismo Lipídico , Miopatias Mitocondriais , Proteína Mitocondrial Trifuncional/deficiência , Doenças do Sistema Nervoso , Rabdomiólise , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Neovascularização de Coroide/complicações , Neovascularização de Coroide/diagnóstico por imagem , Feminino , Angiofluoresceinografia , Humanos , Erros Inatos do Metabolismo Lipídico/complicações , Erros Inatos do Metabolismo Lipídico/diagnóstico por imagem , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/diagnóstico por imagem , Imagem Multimodal , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/diagnóstico por imagem , Rabdomiólise/complicações , Rabdomiólise/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto JovemRESUMO
BACKGROUND: Increasing evidence from pathological and biochemical investigations suggests that mitochondrial metabolic impairment and oxidative stress play a crucial role in the pathogenesis of mitochondrial diseases, such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, and various neurodegenerative disorders. Recent advances in molecular imaging technology with positron emission tomography (PET) and functional magnetic resonance imaging (MRI) have accomplished a direct and non-invasive evaluation of the pathophysiological changes in living patients. SCOPE OF REVIEW: In this review, we focus on the latest achievements of molecular imaging for mitochondrial metabolism and oxidative stress in mitochondrial diseases and neurodegenerative disorders. MAJOR CONCLUSIONS: Molecular imaging with PET and MRI exhibited mitochondrial metabolic changes, such as enhanced glucose utilization with lactic acid fermentation, suppressed fatty acid metabolism, decreased TCA-cycle metabolism, impaired respiratory chain activity, and increased oxidative stress, in patients with MELAS syndrome. In addition, PET imaging clearly demonstrated enhanced cerebral oxidative stress in patients with Parkinson's disease or amyotrophic lateral sclerosis. The magnitude of oxidative stress correlated well with clinical severity in patients, indicating that oxidative stress based on mitochondrial dysfunction is associated with the neurodegenerative changes in these diseases. GENERAL SIGNIFICANCE: Molecular imaging is a promising tool to improve our knowledge regarding the pathogenesis of diseases associated with mitochondrial dysfunction and oxidative stress, and this would facilitate the development of potential antioxidants and mitochondrial therapies.
Assuntos
Acidose Láctica/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Síndrome MELAS/diagnóstico por imagem , Mitocôndrias/metabolismo , Miopatias Mitocondriais/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem , Acidose Láctica/metabolismo , Acidose Láctica/patologia , Encefalopatias/metabolismo , Encefalopatias/patologia , Transporte de Elétrons/genética , Ácidos Graxos/metabolismo , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Síndrome MELAS/metabolismo , Síndrome MELAS/patologia , Imageamento por Ressonância Magnética , Mitocôndrias/genética , Mitocôndrias/patologia , Miopatias Mitocondriais/metabolismo , Miopatias Mitocondriais/patologia , Imagem Molecular , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo , Tomografia por Emissão de Pósitrons , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Myopathy associated with anti-mitochondrial antibody (AMA) has recently been characterized as a distinct type of idiopathic inflammatory myopathy. The purpose of this study is to evaluate the pattern of involvement in thigh muscles in AMA myopathy using MRI. METHODS: Six patients with AMA myopathy were identified and their muscle MRI findings evaluated. RESULTS: On thigh muscle MRI, all six patients showed high signal intensity with short-tau inversion recovery that reflected disease activity mostly in the adductor magnus, called a "cuneiform sign." Fatty degeneration was also prominent in the adductor magnus, as well as the semimembranosus muscles. DISCUSSION: These characteristic changes on MRI contrast with those of other inflammatory myopathies. From these observations, we concluded that the localization pattern of the inflammatory changes in muscle MRI can contribute to the diagnosis of AMA myopathy.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico por imagem , Mitocôndrias Musculares/imunologia , Miopatias Mitocondriais/diagnóstico por imagem , Miopatias Mitocondriais/etiologia , Músculo Esquelético/diagnóstico por imagem , Coxa da Perna/diagnóstico por imagem , Tecido Adiposo/patologia , Adulto , Idoso , Atrofia , Feminino , Granuloma/patologia , Humanos , Hipertrofia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Coxa da Perna/patologiaRESUMO
Mitochondrial diseases are a complex and heterogeneous group of genetic disorders that occur as a result of either nuclear DNA or mitochondrial DNA pathogenic variants, leading to a decrease in oxidative phosphorylation and cellular energy (ATP) production. Increasing knowledge about molecular, biochemical, and genetic abnormalities related to mitochondrial dysfunction has expanded the neuroimaging phenotypes of mitochondrial disorders. As a consequence of this growing field, the imaging recognition patterns of mitochondrial cytopathies are continually evolving. In this review, we describe the main neuroimaging characteristics of pediatric mitochondrial diseases, ranging from classical to more recent and challenging features. Due to the increased knowledge about the imaging findings of mitochondrial cytopathies, the pediatric neuroradiologist plays a crucial role in the diagnosis and evaluation of these patients.
Assuntos
Encéfalo/diagnóstico por imagem , Síndrome de Kearns-Sayre/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Miopatias Mitocondriais/diagnóstico por imagem , Neuroimagem/métodos , Encéfalo/patologia , Humanos , Síndrome de Kearns-Sayre/patologia , Miopatias Mitocondriais/patologiaRESUMO
We report the cases of 2 patients who presented to our Myositis Center with myalgias and elevated creatine kinase levels. Muscle biopsy showed pathological features consistent with mitochondrial myopathy. In both cases, a single large deletion in mitochondrial DNA at low-level heteroplasmy was identified by next-generation sequencing in muscle tissue. In 1 case, the deletion was identified in muscle tissue but not blood. In both cases, the deletion was only identified on next-generation sequencing of muscle mitochondrial DNA and missed on array comparative genome hybridization testing. These cases demonstrate that next-generation sequencing of mitochondrial DNA in muscle tissue is the most sensitive method of molecular diagnosis for mitochondrial myopathy due to mitochondrial DNA deletions.
Assuntos
DNA Mitocondrial/genética , Miopatias Mitocondriais/genética , Deleção de Sequência/genética , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagemRESUMO
Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease.
Assuntos
Microscopia Eletrônica de Varredura/métodos , Microscopia Eletrônica de Transmissão/métodos , Mitocôndrias Musculares/ultraestrutura , Miopatias Mitocondriais/patologia , Músculo Esquelético/citologia , Idoso , Biópsia , DNA Mitocondrial/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias Musculares/patologia , Miopatias Mitocondriais/diagnóstico por imagem , Miopatias Mitocondriais/genética , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Mutação , Adulto JovemRESUMO
INTRODUCTION: Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT-ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. METHODS: In this study we report a 30-year-old man with NARP and m.8993T>G in MT-ATP6. RESULTS: Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. CONCLUSIONS: We emphasize the phenotypic variability of the m.8993T>G MT-ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328-333, 2016.
Assuntos
Ataxia/genética , Miopatias Mitocondriais/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Debilidade Muscular/genética , Retinose Pigmentar/genética , Adulto , Ataxia/complicações , Humanos , Imageamento por Ressonância Magnética , Masculino , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/diagnóstico por imagem , Debilidade Muscular/complicações , Mutação/genética , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico por imagem , Nervo Sural/patologia , Nervo Sural/ultraestruturaRESUMO
A 24-year-old man was referred to our hospital emergency department due to a sudden onset of convulsions after drinking. On arrival he presented status epilepticus and was managed by artificial ventilation. He had no brainstem signs or meningeal irritation. Head MRI showed an old infarction-like lesion in the left occipital lobe, but no abnormal signals on diffusion-weighted images. The patient showed acute rhabdomyolysis (CK 18,000â IU/l) and renal failure, and hemodialysis was started. On 18 day after admission, he was transferred to our department with mild proximal limb muscle weakness and bilateral sensorineural hearing impairment. Electroencephalography demonstrated diffuse intermittent slow wave activities. We suspected a mitochondrial disease because of a significant increase in the lactate/pyruvate ratio (24.1) in the spinal fluid, and identified A3243G mutations in mitochondrial DNA (heteroplasmy 20%) in peripheral white blood cells. We diagnosed his illness as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). This is a rare case presenting an acute onset of rhabdomyolysis following alcohol intake related to A3243G mitochondrial mutation without preceding stroke-like episodes.
Assuntos
Síndrome MELAS/complicações , Miopatias Mitocondriais/complicações , Rabdomiólise/etiologia , Humanos , Síndrome MELAS/diagnóstico por imagem , Masculino , Miopatias Mitocondriais/diagnóstico por imagem , Imagem Multimodal , Rabdomiólise/diagnóstico por imagem , Adulto JovemRESUMO
CLINICAL CASE: A five-year-old patient, with a diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium. Best corrected visual acuity was 6/6 in both eyes, and he had a normal electroretinography test. DISCUSSION: We perform a review of the literature and recent findings in relation to this disease through the description of a clinical case in order to improve the knowledge of this uncommon disorder.
Assuntos
Cardiomiopatias , Erros Inatos do Metabolismo Lipídico , Miopatias Mitocondriais , Proteína Mitocondrial Trifuncional/deficiência , Doenças do Sistema Nervoso , Rabdomiólise , Cardiomiopatias/diagnóstico por imagem , Pré-Escolar , Humanos , Erros Inatos do Metabolismo Lipídico/diagnóstico por imagem , Masculino , Miopatias Mitocondriais/diagnóstico por imagem , Doenças do Sistema Nervoso/diagnóstico por imagem , Rabdomiólise/diagnóstico por imagemRESUMO
Left ventricular hypertrabeculation/noncompaction (LVHT/LVNC), characterized by prominent trabeculations and intertrabecular recesses within the left ventricle, is a cardiac abnormality of unclear etiology. Although the left ventricle is the most commonly affected site, a few cases of biventricular involvement have also been reported. We report a 31-year-old woman who presented with mild cardiac symptoms and progressive bilateral limb muscle weakness following exercise which she had also been experiencing for about 5 years. Abnormal serum levels of creatine kinase, lactic acid and pyruvic acid, combined with the results of modified lactate stress test, needle EMG and muscle biopsy indicated that she had mitochondrial myopathy. The transthoracic echocardiography, together with magnetic resonance imaging (MRI), revealed biventricular hypertrabeculation.
Assuntos
Miopatias Mitocondriais/diagnóstico , Disfunção Ventricular/diagnóstico , Adulto , Ecocardiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Miopatias Mitocondriais/sangue , Miopatias Mitocondriais/diagnóstico por imagem , Disfunção Ventricular/sangue , Disfunção Ventricular/diagnóstico por imagemRESUMO
OBJECTIVES: Disappearance of left ventricular hypertrabeculation (LVHT) over time has been occasionally recognized, but absence on echocardiography and autopsy and presence on histological examination after autopsy has not been reported. METHODS: Routine investigations such as chocardiography, cardiac MRI and coronary angiography were applied. Autopsy studies included macroscopic inspection and dissection but also histological work-up. RESULTS: In a 64-year-old male, LVHT was diagnosed at age 51 years during diagnostic work-up for hypertrophic cardiomyopathy. He had a history of mitochondrial myopathy which was diagnosed long before the cardiac problem became evident. Thickening of the left ventricular myocardium increased over years, resulting also in thickening of the trabeculations and the disappearance of the intertrabecular recesses. This is why LVHT was no longer visible on echocardiography shortly before death at age 64 years. The autopsy revealed that macroscopically no LVHT was visible but upon histological work-up the preformed recesses were still visible but had become unfolded. CONCLUSIONS: This case shows that LVHT may disappear due to thickening of the trabeculations but may remain visible on postmortem histological examination in patients with hypertrophic cardiomyopathy from a mitochondrial myopathy.
Assuntos
Miopatias Mitocondriais/patologia , Miocárdio/patologia , Ecocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/diagnóstico por imagemAssuntos
Miocárdio Ventricular não Compactado Isolado/complicações , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/diagnóstico por imagem , Miocárdio/patologia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
It is well known that morphological changes at the cellular level occur in muscle of patients with mitochondrial myopathy (MM), but changes in muscle structure with fat infiltration and gross variation of muscle fiber size with giant fibers, normally encountered in the muscular dystrophies, have typically not been associated with mitochondrial disease. We investigated gross and microscopic muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with MM, and compared findings with those obtained in muscular dystrophy patients and healthy subjects. Changes of muscle architecture, similar to those found in the group of muscular dystrophy patients occurred consistently in patients with a high mutation load for single, largescale deletions of mtDNA, but were absent in all patients with the 3243A-->G mtDNA point mutation. Dystrophic changes of muscle architecture were also present in one MM patient with a unique, sporadic mutation in the mtDNA tRNA(Met) gene. These findings provide evidence that morphological changes in muscle of MM patients are common and may resemble those of muscular dystrophies, but that development of dystrophic-like changes in muscle relate to genotype.
Assuntos
Miopatias Mitocondriais/genética , Miopatias Mitocondriais/patologia , Músculo Esquelético/patologia , Adipócitos/patologia , Deficiência de Citocromo-c Oxidase/patologia , DNA Mitocondrial/genética , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Distrofias Musculares/diagnóstico por imagem , Distrofias Musculares/genética , Distrofias Musculares/patologia , Mutação , RadiografiaRESUMO
OBJECTIVE: To assess the progression of cardiac involvement (CI), defined as 'definite', 'possible' or 'absent', based on history, clinical examination, electrocardiography, 24 h ambulatory electrocardiography and transthoracic echocardiography in patients with myotonic dystrophy (MD), Becker muscular dystrophy (BMD) and mitochondrial myopathy (MMP) over five years. DESIGN: An investigational, follow-up study. SETTING: A neurological and cardiological department in Austria. PATIENTS: Thirteen patients aged 29 to 60 years with MD, five patients aged 23 to 68 years with BMD and 10 patients aged 24 to 73 years with MMP. MAIN OUTCOME MEASURES: Muscular disability score, CI score and sum of abnormality score. RESULTS: Five patients (two with MD, one with BMD, two with MMP) died during the observational period, one died presumably from rhythm abnormalities. One patient refused to join the follow-up. At baseline/five years later, CI was 'definite' in 12/10, four/four and six/three; 'possible' in one/one, one/zero and three/four; and 'absent' in zero/zero, zero/zero and one/zero of the patients with MD, BMD and MMP, respectively. The most frequent abnormal investigations at baseline/five years later were the history (BMD/MD), the electrocardiogram (MD/MD) and the echocardiography (MMP/BMD). The mean number of abnormalities per patient with MD, BMD and MMP at baseline/five years later was 4.5/4.8, 5.6/8.3 and 4.1/3.4, respectively. CONCLUSIONS: CI is a frequent finding in patients with MD, BMD and MMP, but progression of CI within five years is found only in single cases. Patients with MD, BMD or MMP should be cardiologically investigated and treated only if CI becomes symptomatic, or if severe electrocardiographic or echocardiographic abnormalities are present.
Assuntos
Cardiopatias Congênitas/complicações , Miopatias Mitocondriais/complicações , Distrofia Muscular de Duchenne/complicações , Distrofia Miotônica/complicações , Adulto , Idoso , Progressão da Doença , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miopatias Mitocondriais/diagnóstico por imagem , Miopatias Mitocondriais/fisiopatologia , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/fisiopatologia , Distrofia Miotônica/diagnóstico por imagem , Distrofia Miotônica/fisiopatologia , Fatores de Tempo , UltrassonografiaRESUMO
OBJECTIVE: To investigate cerebral metabolism by 2-[18F]fluorodeoxy-d-glucose (FDG) uptake using PET and cerebrovascular reverse capacity by transcranial Doppler sonography (TCD) in different mitochondrial diseases (mitochondrial myopathy; mitochondrial encephalopathy, lactacidosis, and stroke-like episodes [MELAS]; and chronic external ophthalmoplegia). BACKGROUND: Previous studies on individual patients with mitochondriopathies revealed abnormal accumulations of mitochondria in endothelium, smooth muscle cells, and pericytes of blood vessels in different parts of the nervous system (cerebrum, cerebellum, sural nerve) and skeletal muscle. On this basis, some investigators suggested a pathogenic role of vascular involvement in the MELAS syndrome and other encephalopathies. smhd1 DESIGN/METHODS: The authors investigated neuronal metabolism and cerebrovascular involvement with PET in 5 cases and with TCD with acetazolamide stimulation in 15 cases. The patients were divided into three groups: 1) interictal MELAS (n = 4); 2) progressive external ophthalmoplegia (n = 6); and 3) pure mitochondrial myopathy and neuropathy (n = 5). The results were compared with those from matched normal control subjects. The diagnoses were based on clinical phenotype as well as histopathologic and molecular analysis. RESULTS: Cerebral glucose uptake was impaired in all patients, both with and without CNS symptoms, particularly in the occipital and temporal lobes. The vasoreactivity of the small arterioles to acetazolamide did not differ significantly between the patients and healthy control subjects or between the different groups of mitochondrial disorders. CONCLUSIONS: MELAS does not appear to be a functional disturbance of arterioles leading to an ischemic vascular event. The clinical symptoms in MELAS are not the result of a mitochondrial angiopathy but are the consequences of a mitochondrial cytopathy affecting neurons or glia. There is no correlation between the decreased glucose metabolism and the duration of the disease.
Assuntos
Circulação Cerebrovascular , Glucose/metabolismo , Miopatias Mitocondriais/metabolismo , Acetazolamida , Acidose Láctica/diagnóstico por imagem , Acidose Láctica/metabolismo , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Inibidores da Anidrase Carbônica , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Síndrome MELAS/diagnóstico por imagem , Síndrome MELAS/metabolismo , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiologia , Encefalomiopatias Mitocondriais/diagnóstico por imagem , Encefalomiopatias Mitocondriais/metabolismo , Miopatias Mitocondriais/diagnóstico por imagem , Oftalmoplegia Externa Progressiva Crônica/diagnóstico por imagem , Oftalmoplegia Externa Progressiva Crônica/metabolismo , Tomografia Computadorizada de Emissão , Ultrassonografia Doppler TranscranianaRESUMO
A 39-year-old man with cardiomyopathy due to point mutation of mitochondrial DNA(3243) was admitted to our hospital because of exertional dyspnea accompanied by hearing disturbance and diabetes mellitus. Echocardiography revealed asymmetric hypertrophy of the anterolateral and posterior walls and systolic dysfunction of the left ventricle (fractional shortening = 18%). Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern. Iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) myocardial scintigraphy showed decreased accumulation in the anterolateral, posterior, and apical walls. Left ventriculography showed moderately decreased ejection fraction (43%), and left ventricular end-diastolic pressure was mildly elevated (18 mmHg). Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous adenosine triphosphate was impaired in the left anterior descending and left circumflex arteries compared to the right coronary artery. Intracellular accumulations of abnormal mitochondria were detected by histologic examination of the cardiac and skeletal muscles. Evaluation of cardiac function showed that the area of myocardial hypertrophy was nearly consistent with the region of decrease in 123I-BMIPP accumulation and coronary flow reserve.