Can diffusion weighted magnetic resonance imaging help differentiate stroke from stroke-like events in MELAS?

The precise mechanism of neurological symptoms in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is still controversial. The diffusion weighted MR findings at the acute phase of a neurological event in MELAS are described and the pathophysiology of stroke-like lesion in the light of diffusion changes is discussed.Brain MRI was performed 2 days after the sudden onset of cortical blindness in a 25 year old patient with MELAS. Fluid attenuated inversion recovery (FLAIR) images showed multifocal cortical and subcortical hyperintensities located bilaterally in the frontobasal and the temporo-occipital lobes. Diffusion weighted images showed normal to increased apparent diffusion coefficient values in the acute left temporooccipital lesion and increased values in the older stroke-like lesions.These diffusion weighted findings support the metabolic rather than the ischaemic pathophysiological hypothesis for stroke-like episodes occurring in MELAS. Normal or increased apparent diffusion coefficient values within 48 hours of a neurological deficit of abrupt onset should raise the possibility of MELAS, especially if conventional MR images show infarct-like lesions.     

Neuronal hyperexcitability in stroke-like episodes of MELAS syndrome

BACKGROUND: The pathogenesis of stroke-like episodes in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) remains unknown. METHODS: Fourteen stroke-like episodes in six patients with MELAS were studied using clinical, neuroradiologic, and electrophysiologic approaches. In two patients postmortem examination was done. RESULTS: Headache and epileptic seizure were the most common presenting symptoms. In 13 of 14 episodes the cerebral cortex was primarily involved with variable subcortical edema particularly in the temporal, occipital, and parietal cortex. Repeated MRI performed in two episodes revealed progressive spread of the cortical lesion to the surrounding cortex for a few weeks after the onset of symptoms. In 6 of 11 episodes T1-weighted hyperintense cortical signal compatible with cortical laminar necrosis was seen during subacute stage of the episode. Fat-suppression MRI confirmed intracortical gyral hemorrhage in one episode. Petechial gyral microhemorrhages were also pathologically confirmed in the autopsy of another patient. In 9 of 11 episodes focal epileptiform discharges on EEG were noted in the acute brain lesion. In seven of nine episodes focal cortical hyperperfusion was seen in SPECT studies. CONCLUSION: The stroke-like episodes in MELAS may reflect neuronal hyperexcitability, which increases energy demand and creates energy imbalance between energy requirement and adequate availability of adenosine triphosphate due to oxidative phosphorylation defect particularly in the susceptible neuronal population, causing cortical necrosis. The episodic nature of stroke-like episodes is unexplained.     

MELAS型线粒体脑肌病的脑部MRI表现(附三例报道)

目的 总结分析MELAs型线粒体脑肌病的脑部MRI表现.方法 回顾性分析3例MELAS型线粒体脑肌病患者的临床资料和MRI表现.结果 MRI显示MELAS型线粒体脑肌病表现为以颞叶、顶、枕叶为主的皮层及皮层下白质病变,病变多呈双侧非对称性分布,部分患者以累及基底节为主要表现,T2WI和液体衰减翻转恢复序列对病变的显示有独特的作用,DWI、ADC图及增强扫描能够诊断及鉴别诊断线粒体脑肌病及卒中,MRS对其诊断可以起到辅助作用.结论 MELAS型线粒体脑肌病在MRI图像上具有特征性,MRI影像表现结合临床资料对本病多能作出正确的诊断.     

线粒体脑肌病伴高乳酸血症和卒中样发作综合征的影像学特征及动态演变

目的探讨线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)综合征的影像学特点及其动态演变过程。方法收集2011年1月-2016年2月我院经肌肉病理确诊的21例MELAS综合征的资料,对他们的头部CT、MRI、增强MRI、MRA和MRS表现进行回顾性分析。结果 19例患者行头部CT,其中8例显示双侧基底节区对称性钙化。卒中样发作急性期头部磁共振主要表现为T_1WI低信号、T_2WI和FLAIR高信号,DWI高信号或等信号,ADC高信号或低信号;增强MRI未见明显强化或线状强化,MRA未见明显异常,MRS可见N-乙酰天门冬氨酸峰(NAA)下降、乳酸峰(Lac)明显升高。19例(90.5%)病灶累及2个及2个以上脑叶,最常累及的部位是枕叶、颞叶和顶叶。病灶呈层状坏死,分布不符合脑血管的支配区域,动态观察具有"可逆性"、"游走性"和"进展性"。结论 MELAS综合征临床表现复杂,神经影像学具有一定的特征性,具有重要诊断价值。充分认识这些特征,有助于早期诊治、减少误诊。     

Laminar cortical necrosis in adrenal crisis: sequential changes on MRI

We describe the serial magnetic resonance imaging (MRI) findings in a six-year-old girl with congenital adrenal hyperplasia, who presented with seizures and unconsciousness during a hypoadrenal crisis. Initial neuroimaging revealed the presence of brain edema with high signal changes in the fronto-parietal cortex on diffusion-weighted MRI. The brain edema worsened four days into admission, and by day 14 low-density areas were seen over the frontal lobes bilaterally using computed tomography (CT). Follow-up MRI at between one and two months of admission revealed extensive white matter lesions with high intensity on T2-weighted images (T2WI) and fluid-attenuated inversion recovery (FLAIR) images, which extended into deep cortical layers. Additionally, linear lesions with high signal change on T1-weighted imaging developed in the superficial cortical layers, with frontal predominance. This layer appeared isointense on T2WI and high intensity on FLAIR images, suggesting laminar cortical necrosis. Two months later, linear, cavitary lesions appeared in the middle cortical layers between the aforementioned superficial laminar abnormality and deep cortex/white matter lesions. The high-intensity signals in the deep cortical layers remained contiguous with the white matter lesions. This unique type of multi-layered cortical lesion may have resulted from a complex combination of hypoglycemia and hypoxia/ischemia in the setting of adrenal insufficiency.     

Distinguishing ischemic stroke from the stroke-like lesions of MELAS using apparent diffusion coefficient mapping

We report two patients with migraine, acute visual field defects and other neurological symptoms who were found to have high T(2) signal and FLAIR abnormalities on brain MRI in temporal and parieto-occipital regions. In these patients, the apparent diffusion coefficient (ADC) of their lesions was increased, distinguishing these lesions from those of ischemic stroke. Both were ultimately diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We conclude that conventional MRI when used with diffusion-weighted MR imaging may be invaluable in detecting mitochondrial-related CNS dysfunction.     

Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-like Episodes (MELAS) May Respond to Adjunctive Ketogenic Diet

BackgroundMitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome can present management challenges. Refractory seizures and stroke-like episodes leading to disability are common.PatientWe analyzed the clinical, electrophysiologic, and radiologic data of a 22-year-old woman with multiple episodes of generalized and focal status epilepticus and migratory cortical stroke-like lesions who underwent muscle biopsy for mitochondrial genome sequencing.ResultsAlthough initial mitochondrial genetic testing was negative, muscle biopsy demonstrated a mitochondrial DNA disease-causing mutation (m.3260A > G). New antiepileptic medications were added with each episode of focal status epilepticus with only temporary improvement, until a modified ketogenic diet and magnesium were introduced, leading to seizure freedom despite development of a new stroke-like lesion, and subsequent decrease in frequency of stroke-like episodes. We propose a metabolic model in which the ketogenic diet may lead to improvement of the function of respiratory chain complexes.ConclusionsThe ketogenic diet may lead to improvement of mitochondrial dysfunction in MELAS, which in turn may promote better seizure control and less frequent stroke-like episodes.     

Magnetic resonance imaging shows specific abnormalities in the MELAS syndrome

The MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) can be difficult to identify. We report MRI abnormalities that we believe are specific to this disorder in three patients with complete or partial MELAS syndrome. The patients all showed an unusual pattern on T2-weighted MRI with multifocal areas of hyperintense signal confined to the cortex of the cerebrum, cerebellum, and adjacent white matter. Some images suggested selective cortical involvement of deeper layers only. Deep white matter was relatively spared, distinguishing this from usual cerebrovascular disease or the edema after status epilepticus. Specificity of these findings is further suggested by a good correlation of these findings with the previously described unique postmortem brain pathology of MELAS.     

Laminar cortical necrosis in mitochondrial disorders

Objectives

Laminar cortical necrosis, defined as focal or diffuse necrosis of one or more cortical lamina, represents an increasingly recognized neuropathological endpoint of vascular, endocrine, immunologic, metabolic, or toxic conditions, of which mitochondrial disorders (MIDs) are the third most frequent after cerebral ischemia and hypoxia.

Aims

To investigate the prevalence of laminar cortical necrosis in MIDs, types of MIDs associated with laminar cortical necrosis, and the morphological characteristics on imaging and autopsy.

Methods

Medline literature review for the terms “laminar cortical necrosis”, “cortical signal change”, “mitochondrial” and all acronyms of syndromatic MIDs.

Results

Among 139 hits for “laminar cortical necrosis”, 10 articles fulfilled the inclusion criteria (7%). Among the ten hits five were case series and the other five single case reports. The syndromic MID most frequently associated with laminar cortical necrosis is the MELAS syndrome, but was also described in a single patient each with Leigh syndrome, mitochondrial depletion syndrome, and mitochondrial spinocerebellar ataxia. The morphological and pathohistological features of laminar cortical necrosis in MIDs were not at variance from those in non-mitochondrial disorders.

Conclusions

In MIDs laminar cortical necrosis represents the histopathological and imaging endpoint of a stroke-like lesion. Though laminar cortical necrosis may have a wide pathophysiological background the histological and imaging characteristics do not vary between the different underlying conditions.     

Thalamic aphasia associated with mitochondrial encephalopathy,lactic acidosis,and stroke-like episodes: A case report

BackgroundMitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with aphasia is a rare disorder, with the associated aphasia reported as either Wernicke’s or Broca’s. Herein, we report a patient with MELAS complicated by thalamic aphasia.CaseA 15-year-old right-handed girl presented with headache, nausea, right homonymous hemianopsia, and aphasia. She could repeat words said by others, but had word-finding difficulty, paraphasia, and dysgraphia. Brain MRI revealed abnormal signals from the left occipital lobe to the temporal lobe and left thalamus, but Wernicke’s area and Broca’s area were not involved. Additionally, she had short stature, lactic acidosis, bilateral sensorineural hearing loss, and a maternal family history of diabetes and mild deafness. Based on clinical findings and the presence of a mitochondrial A3243G mutation, she was diagnosed with MELAS. With treatment, the brain MRI lesions disappeared and her symptoms improved. Her aphasia was classified as amnesic aphasia because she could repeat words, despite having word-finding difficulty, paraphasia, and dysgraphia. Based on MRI findings of a left thalamic lesion, we diagnosed her with thalamic aphasia.ConclusionThalamic aphasia may be caused by MELAS. Assessment of whether repetition is preserved is important for classifying aphasia.     

Precipitation of stroke-like event by chickenpox in a child with MELAS syndrome

The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA (mtDNA). Herein we report a case of MELAS, whose second stroke-like episode was provoked by chickenpox. A point mutation at nucleotide (nt) 3243 in mtDNA supported the diagnosis of MELAS in this case. History of myopathy, the presence of lesions that did not conform to accepted distributions of vascular territories on cranial magnetic resonance imaging (MRI), normal result of cranial magnetic resonance angiography, hyperintensity on diffusion weighted MRI and apparent diffusion coefficient mapping indicating the presence of vasogenic edema in the fresh stroke-like lesion, and mitochondrial DNA analysis helped to exclude the diagnosis of ischemic cerebral infarction which can also be induced by chickenpox.     

Regional cerebral blood flow and cerebrovascular reactivity during chronic stage of stroke-like episodes in MELAS -- implication of neurovascular cellular mechanism

BACKGROUND: Ischemic vascular hypothesis as a causative role in the pathogenesis of stroke-like episodes in MELAS remains to be debated. METHODS: This study consisted of two parts. Part 1 is a clinicoradiological study during acute stage of 18 consecutive stroke-like episodes in six patients with MELAS. Part 2 is a SPECT study to assess the regional cerebrovascular reactivity (rCVR) to acetazolamide during chronic stage in five patients with MELAS. RESULTS: Headache and epileptic seizure were the most common presenting symptoms. Unique features of acute stroke-like lesions included progressive spread of cortical lesions with vasogenic edema, focal periodic epileptiform discharges, focal hyperperfusion, and cortical laminar necrosis during subacute stage. During chronic stage, SPECT showed hypoperfusion in non-affected occipital cortex in three patients as well as in previously affected regions in four. The rCVR was preserved in three patients, focally impaired in one, and extensively impaired in one, but relatively preserved in the occipital cortex in all patients. CONCLUSIONS: Stroke-like episodes could be non-ischemic neurovascular events initiated by neuronal hyperexcitability. Once neuronal hyperexcitability develops in a focal brain region, epileptic activities depolarize adjacent neurons, leading to a propagation of epileptic activities into the surrounding cortex, and resulting in energy imbalance. The mechanisms for neuronal hyperexcitability remain to be elucidated.     

Neuroimaging characteristics in mitochondrial encephalopathies associated with the m.3243A>G MTTL1 mutation

Stroke-like lesions (SLL) are common radiological findings in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (SLE; MELAS) harboring the m.3243A>G MTTL1 mutation. Imaging patterns in the m.3243A>G mutation carriers with encephalopathies lacking SLE have not been systematically examined to date. The aim of this study was to analyze brain imaging findings in encephalopathies associated with the m.3243A>G mutation irrespective of the presence or absence of SLE. Brain MRI and cranial CT scans from 11 m.3243A>G mutation carriers with encephalopathies were analyzed by two neuroradiologists in consensus. We evaluated stroke-like lesions (SLL), deep grey matter (DGM) changes on T1- and T2-weighted MR images, calcification on CT, brain atrophy, and white matter (WM) changes. SLL were present in all patients showing the full MELAS phenotype with SLE (4/11). Seven patients did not show SLE. DGM changes with T1 hyperintensity and T2 hypointensity were a distinctive finding in most patients (7/11) and present in the majority of m.3243A>G mutation carriers lacking SLE (5/7). DGM changes were also seen in half of our MELAS patients with SLL (2/4), though less pronounced. Brain atrophy was a prominent finding in general and accentuated in the cerebellum. In contrast, WM changes were rather mild and more prevalent and pronounced in MELAS. Our data stress that the distinction between MELAS with SLE and m.3243A>G mutation carriers lacking SLE is rather artificial. In clinical practice, mitochondrial disorders associated with the m.3243A>G mutation should be taken into consideration in encephalopathies with DGM changes, even when SLE and SLL are lacking.     

线粒体基因G13513A突变导致的线粒体脑肌病六例临床表型分析

目的 报告6例mtDNA G13513A点突变引起的线粒体脑肌病患者的临床、影像学特点,总结mtDNA G13513A突变所致的线粒体病的临床表型.方法 对35例mtDNA常见突变(包括大片段缺失及A3243G、T3271C、A8344G、T8993G/C点突变)检查为阴性的线粒体脑肌病患者,用线粒体DNA全长测序和(或)聚合酶链反应-限制性片段长度多态法检测mtDNA G13513A点突变,分析阳性患者的临床特点,复习文献报道的mtDNA G13513A所致线粒体病的病例.结果 35例患者中有6例存在mtDNA G13513A突变.该6例患者均出现偏盲、轻偏瘫或偏身感觉障碍等卒中样发作表现,其中3例成人发病者以卒中样发作为主要症状,伴随癫痫、头痛、身材矮小、神经性耳聋等,头颅MRI显示以顶-枕-颢叶受累为主的大片病灶,符合成人型线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)的临床和影像学特点;3例青少年发病者除卒中样发作外,还有构音障碍、共济失调、眼外肌瘫痪等脑干受累的症状,MRI检查可见枕-颞叶大脑皮质非对称性病灶,以及双侧基底节和脑干的对称性病灶,符合青少年型MELAS-Leigh叠加综合征的临床和影像学特点.肌肉病理检查在5例患者发现不整红边纤维.经复习文献,发现mtDNA G13513A突变患者还存在婴幼儿型Leigh或Leigh样综合征表型.结论 mtDNA G13513A点突变是线粒体脑肌病较常见的致病性突变,主要导致Leigh综合征、MELAS-Leigh叠加综合征或MELAS综合征,其临床表型具有年龄依赖性.

Abstract：

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.     

MELAS综合征和Leigh病患者的影像学观察

目的观察线粒体脑肌病伴乳酸血症和卒中样发作(MELAS)综合征和Leigh病患者的影像学特点。方法对12例MELAS综合征、7例Leigh病和1例MELAS与Leigh病叠加患者的影像学特点进行系统分析。结果 12例MELAS综合征患者脑CT及MRI示病灶多位于枕、颞、顶叶皮质及皮质下,且病灶在左侧占优势;7例leigh病患者病变部位主要在双侧基底节、丘脑及脑干。4例MELAS综合征、4例Leigh病患者、1例叠加的核磁波谱检查示病变区乳酸水平明显增高。DWI仅显示新病灶,FLAIR可观察到所有新旧病灶,较T2像敏感。MELAS可见部分病变侧MRA血管增粗增多,且病情复发时病灶有迁徙,旧病变有萎缩的特点。结论 MELAS和Leigh的影像学特点有显著差异,前者以脑叶皮质及皮质下受累为主,病变范围较大,不符合大脑动脉供血区分布。Leigh患者主要病变部位在脑干、基底节,且病灶发展变化趋势有一定的规律性。FLAIR与DWI是不可缺少的扫描像位。MRS对线粒体脑病和线粒体脑肌病的诊断有重要价值,应作为本病常规扫描序列。     

Deep white matter pathologic features in watershed regions: a novel pattern of central nervous system involvement in MELAS

BACKGROUND: Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome typically manifests in adults younger than 40 years with encephalopathy, stroke-like episodes, and lactic acidosis. Magnetic resonance imaging (MRI) abnormalities typically involve the cortical gray and the adjacent subcortical white matter. OBJECTIVE: To describe a 58-year-old woman diagnosed with MELAS who was initially seen with acute myopathy, cardiac ischemia, psychosis, and MRI changes in a watershed distribution. RESULTS: Initial MRI of the brain showed the characteristic parieto-occipital gray matter lesions involving the adjacent white matter. Follow-up MRI revealed striking deep white matter involvement in a watershed distribution. A cerebral angiogram and thorough hypercoagulable workup results were normal. Electromyography showed acute denervation and myopathy. A muscle biopsy specimen revealed ragged red and cytochrome-c oxidase-negative fibers. Mitochondrial DNA analysis revealed an A3243G mutation. CONCLUSIONS: Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes should be considered in older patients with myopathy, cardiomyopathy, encephalopathy, and unaccountable MRI findings. Watershed pathologic features are a rare pattern of cerebral involvement in MELAS.     

Neuroimaging of stroke-like episodes in MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) shows sudden neurological deficits that are called ‘stroke-like episodes’. With regard to the pathophysiology of stroke-like episodes, so-called mitochondrial angiopathy and cytopathy theories have been proposed, but the subject is still controversial. To clarify this matter and to contribute to the development of a treatment for MELAS, we review here current neuroimaging research and consider the pathophysiology of stroke-like lesions. With regard to diffusion-weighted imaging findings, early reports often showed an elevated apparent diffusion coefficient (ADC) in stroke-like lesions; this was considered to be mainly vasogenic edema in the acute phase and is a different pattern than that in stroke. However, there has recently been an increase in the number of reports of a decrease in ADC; these cases are considered to be cytotoxic edema in the acute phase, which is compatible with stroke. With regard to ¹H-magnetic resonance spectroscopy findings in stroke-like lesions, a decrease in N-acetylaspartate and an increase in lactate have been reported. With regard to single photon emission computed tomography findings for stroke-like lesions in MELAS, an overall trend is hyperperfusion in the acute stage (within 1 month) of stroke-like episodes and hypoperfusion in the chronic stage (several months later). With regard to positron emission tomography, nearly all of these reports are consistent with the mitochondrial cytopathy theory. With regard to neuropathology in MELAS, the most common findings during the chronic stage of stroke-like episodes include foci of necrosis and peculiar vascular changes (abnormalities of mitochondria in small arteries). Concerning the pathology of the acute stage of stroke-like episodes, extensive petechial hemorrhage along the gyri of the cortex corresponding to acute stroke-like lesions has been reported. To clarify the true pathophysiology of stroke-like episodes, we offer three suggestions. First, we must define the precise onset of stroke-like episodes. Second, current studies are limited by the difficulty of imaging just before and just after (within a few minutes) the onset of stroke-like episodes. Third, we hope to establish an experimental animal model. We should conduct a simultaneous multimodal imaging and histological study just before and just after (within a few minutes) the onset of stroke-like episodes in an experimental animal model.     

Vasogenic edema on MELAS: a serial study with diffusion-weighted MR imaging

The authors performed a serial study of a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS) who presented with diffusion-weighted MRI (DWI). DWI demonstrated a higher apparent diffusion coefficient in the lesion than in the control region during the acute stage of stroke. Vasogenic edema is present in stroke-like episodes in MELAS.     

Detection of 14-3-3 protein in the cerebrospinal fluid in mitochondrial encephalopathy with lactic acidosis and stroke-like episodes

We describe a 13-year-old boy with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) who experienced a stroke-like episode resulting in severe mental regression and quadriplegia. We tested 14-3-3 protein in the cerebrospinal fluid (CSF) of the patient four times around a stroke-like episode in a magnetic resonance imaging (MRI) study. Detection of the protein in the CSF was well correlated with the clinical course and range of damage of the brain lesion on MRI. Interestingly, 14-3-3 CSF protein was detected at the beginning of mitochondrial encephalopathy without new MRI abnormalities, suggesting that it is a sensitive brain marker. We conclude that 14-3-3 CSF protein is a useful biological marker of brain disruption in MELAS as well as other neurological disorders.     

An autopsy case of generalized seizures, myoclonus, blindness and deafness

We have reported the clinical and autopsy findings in a case with generalized seizures, myoclonus, blindness and deafness which was accompanied by stroke-like episodes. This case was diagnosed as mitochondrial encephalomyopathy, lactic acidosis & stroke-like episodes (MELAS) from these findings. Solitary and continuous lesions of softening were distributed in both hemispheres, more severely in the frontal and occipital poles. These lesions did not correspond to a vascular supply. The pulvinar, lateral and medial geniculate body of the thalamus, cerebellar vermis and dentate nucleus had small lesions of softening. The cortical lesions occurred mainly in layer 4, and the most prominent lesions among them appeared cystic, involving the subcortical white matter, but nerve cells in layer 1 and 2 were preserved. Proliferation of small blood vessels was seen around the softening areas. Electron microscopy revealed increased mitochondria in endothelial cells of these vessels, abnormal dense bodies in skeletal muscle cells and tightly packed mitochondria in choroid plexus epithelial cells. Immunohistochemical study suggested that vimentin positive cells were seen around lesions and proliferated vessels are different from those seen in the intact tissues.