MELAS with mtDNA 3243A>G mutation presenting as bilateral symmetric occipital and temporal cortices lesions: a case report and literature review

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Stroke-like episode affecting the cortical cortex is the hallmark of MELAS, however, it rarely presents as simultaneously bilateral symmetric cortices lesions. Methods: We reported a case of MELAS in a 46-year-old female patient with bilateral symmetric occipital and internal temporal cortices involvements on brain magnetic resonance imaging (MRI). A literature review of MELAS patients and a retrospective analysis were performed. Results: We reported a case of MELAS in a 46-year-old female patient with cortical blindness and cognitive decline as well as status epilepticus. She had a family history of diabetes. Although she denied a history of diabetes, elevated blood glucose was noted after admission and diabetes was diagnosed. Laboratory examination revealed elevated lactate acid and creatine kinase levels in blood. Cranial computed tomography (CT) image demonstrated basal ganglia calcification, as well as subtle decreased attenuation in bilateral symmetric occipital and internal temporal cortices. Brain magnetic resonance imaging (MRI) demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on fluid-attenuated inversion recovery (FLAIR) images with restricted diffusion on diffusion weighted images (DWI). A genetic test revealed a point mutation in the mtDNA(3243A > G) by blood examination. Literature review showed there were 231 eligible patients with MELAS were identified from 212 published papers. Symmetric cortical involvements were seen in 15(6.5%) patients on brain MRI. Conclusions: MELAS should be considered as a potential diagnosis in the patients with bilateral symmetric stroke-like cortices lesions. MELAS Symmetry Magnetic resonance imaging cortical lesions Figures Figure 1 Figure 2 Figure 3 1. Background Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited multisystem disorder caused by mitochondrial DNA mutation 1 , which is with a broad spectrum of clinical and radiological presentations. Typical features of MELAS on brain imaging include stroke-like areas, basal ganglia calcification and brain atrophy. The imaging findings of most patients with MELAS are asymmetric 2 . To our knowledge, rare patients with MELAS present with symmetrical lesions in cerebral cortex 3 . In this report, we describe the case of a 46-year-old female patient of MELAS presenting a feature of bilateral symmetric occipital and internal temporal cortices lesions. 2. Case presentation A 46-year-old female patient who experienced an acute episode of visual hallucination and blurry vision for the last four days was admitted to our hospital. Initially, she was admitted to another hospital, no abnormalities were found on the ophthalmologic test. Although she denied that she had a history of diabetes, elevated blood glucose was noted after admission and diabetes was diagnosed. There was a history of exercise intolerance since her childhood. The patient had no history of migraine or sensorineural hearing Loss. Developmental milestone was normal. After admission, a physical examination revealed a height of 166cm, a body weight of 50kg, suggesting that there was no obvious short stature. On neurologic examination, her visual acuity was hand motion in both eyes. She also had diminished osteotendinous reflex of the limbs. The rest of the neurological examinations was normal. Blood chemistry analysis at the time of admission revealed elevated fasting blood glucose levels of 18mmol/L, elevated arterial blood lactic acid levels of 2.97mmol/L, elevated creatine kinase levels of 272u/L, elevated high sensitivity C-reactive protein levels of 6.51 mg/L, elevated low density lipoprotein cholesterol levels of 3.91mmol/L, and elevated total cholesterol levels of 5.89mmol/L. Examination of the cerebrospinal fluid (CSF) showed a normal cell count, high total protein level of 59mg/dL, high glucose level of 8.37mmol/L. Her autoimmune encephalitis antibodies and paraneoplastic antibodies in blood and CSF were negative. Herpes simplex virus type 1 was identified by Second-generation sequencing technology (NGS) of the CSF, but only 4 sequencing reads in NGS data was identified. Cranial CT image demonstrated basal ganglia calcification，as well as subtle decreased attenuation in bilateral occipital lobe and internal temporal lobes. (Figure. 1a). The first brain MRI examination demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on T2-weighted images (Figure. 1e), apparent diffusion coefficient (ADC) maps images (Figure. 1c), and FLAIR images (Figure. 1d) with restricted diffusion on DWI sequence (Figure. 1b). Magnetic resonance angiography (MRA) examination was normal (Figure. 1f). Magnetic resonance spectroscopy (MRS) revealed a large double inverted lactate peak (Figure. 1h). Contrast-enhanced MRI of the brain showed no enhancement in the lesions, but dural enhancement (Figure. 1g). The patient's visual impairment progressively worsened after admission, and developed cortical blindness 4 days after admission. 5 days after admission, the patient developed cognitive impairment followed by status epilepticus with decreased blood oxygen. saturation. She was transferred to intensive care unit and performed with tracheal intubation. The electroencephalography (EEG)showed spikes, sharp waves and sharp wave complexes in the right occipital lobe. She was received MRI reexamination of the brain 6 days after admission. DWI sequence revealed gyriform hyperintensities in bilateral occipital lobes and internal temporal lobes, with significantly progressed scope of the lesion (Figure. 2a-2b). ADC maps sequence indicated hypo/hyperintensities corresponding to DWI lesions (Figure. 2c-2d). FLAIR sequence (Figure. 2e-2f) and T2-weighted images (Figure. 2g-2h) showed hyperintensities corresponding to DWI lesions with significantly progressed scope of the lesion. A genetic test revealed a point mutation in the mtDNA(3243A > G) by blood examination (Figure.3). After antiepileptic therapy, her status epilepticus was controlled. she did not consent to a muscle biopsy and was transferred to another hospital for treatment 8 days after admission. 3. Literature review We searched Pubmed databases using “melas”, “mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes” as keywords and the article type filter set to case reports only. Patients without a brain MRI examination and a genetic test were excluded. Only full text articles in English were included. The search was last updated on 28th August 2023. Descriptive statistical analysis was performed with SPSS 25. 4. Results A total of 231 eligible patients with MELAS were identified from 212 papers. Of the 231 eligible patients, 115 (49.8%) were male. The mean age of presentation was 30.6 years (standard deviation, SD=17.6), ranging from 3 to 76 years. Results of cranial CT were available for 58 patients. Of the 58 patients, cranial CT revealed calcifcation in the bilateral basal ganglia in 31 patients (53.4%). Genetic analysis was performed in all cases. The sequencing including mtDNA and nuclear genes revealed a total of 236 variants in 228 patients, and no disease-causing gene mutation in the remaining 3 patients. Of the 228 patients,162(71.7%) carried mtDNA(3243A > G) mutation,8(3.5%) carried mtDNA(13513G>A) mutation,6(2.6%) carried mtDNA(10158T>C) mutation,3(1.3%) carried a double pathogenic mutation. Brain MRI was performed in all 231 eligible patients. Simultaneously bilateral stroke-like lesions involving bilateral cerebral hemispheres were seen in 114(49.4%) eligible patients. Symmetric cortical involvements were seen in 15(6.5%) patients. Of 15 patients, 7(43.8%) involved bilateral symmetric temporal lobes 4-10 ,1(6.7%) involved bilateral symmetric temporo-parietal-occipital lobes 11 , 1(6.7%) involved bilateral symmetric frontal-occipital lobes 12, , 2(13.3%) involved bilateral symmetric frontal -temporo-parietal-occipital lobes 13,14 , 1(6.7%) involved bilateral symmetric frontal -temporo-occipital lobes 15 , 1(6.7%) involved bilateral symmetric frontal-temporo lobes 16 , 1(6.7%) involved bilateral symmetric basal ganglia 17 , 1(6.7%) involved bilateral symmetric precentral gyrus 18 .Non-simultaneous bilateral stroke-like lesions involving bilateral cerebral hemispheres were seen in 27(11.7%) eligible patients. 5. Discussion MELAS is one of probably the most common maternally inherited mitochondrial disease with variable clinical presentations, such as stroke-like episodes, seizures, dementia, muscle weakness, short stature, cerebellar ataxia, migraine, sensorineural hearing loss, diabetes mellitus, peripheral neuropathy, cardiomyopathy, cerebellar signs, progressive external ophthalmoplegia 19 , etc. The mtDNA(3243A > G) mutation located in the tRNALeu (UUR) of the mitochondrial genome accounts for approximately 80% of MELAS cases 20 .Although typical MELAS patients are easy to recognize, the diagnosis of MELAS in some patients are challenging due to the phenotypic heterogeneity. Here we reported a patient presenting with unusual cortical cortex lesion, achieving the final diagnosis with genetic examination. This case also has some manifestations that are atypical of MELAS. First, the age of onset over 40 years old account for only 1-6% of MELAS patients 21 . The patient in our case was 46 years old, which is unusual for MELAS. Second, the absence of headaches, short stature and hearing loss in our patient increased the difficulty of reaching to a right diagnosis in time. Third, identification of herpes simplex virus (HSV) type 1 by NGS of the CSF increased our suspicion of herpes simplex encephalitis. But given a normal CSF cell count and relatively few sequencing reads, the possibility of false-positive test was not excluded. Lakeman et al. found that 6% of patients with negative brain biopsy results for HSV had positive CSF HSV PCR results 22 . Fourth, there is variability in characteristics of ADC maps sequence of MELAS. To our knowledge, most cases indicated hyperintensities on ADC maps sequence in stroke-like lesions, supporting vasogenic edema 23,24,25. However, there were many reports of ADC maps sequence hypointensities in recent years, which might be associated with cytotoxic edem a26,27,28 . In our patient, ADC maps sequence demonstrated hyperintensities on the first MRI. On day 6 after admission, MRI reexamination revealed hypo/hyperintensities mixed, which might suggest the presence of co-existence of vasogenic edema and cytotoxic edema in the affected areas. Fifth, in our case, the affected areas involving cortex and white matter of bilateral occipital lobes and internal temporal lobes in neuroimaging were symmetric. This case has some essential MELAS features including a positive family history of diabetes mellitus which revealed possibly manifestations of mitochondrial diabetes, diagnosed diabetes mellitus after admission, exercise intolerance, elevated lactate acid and creatine kinase levels in blood laboratory examination, basal ganglia calcification on cranial CT, gyriform hyperintensities on DWI, FLAIR, and T2-weighted images, a lactate peak on MRS. Simultaneously bilateral symmetrical cortical lesions are frequently seen in Creutzfeldt–Jakob disease 29 , seizures 30 , diffuse brain ischaemia–hypoxia 31 , hypoglycaemia 32 , autoimmune encephalitis 33 , herpes simplex encephalitis 34 ,reversible posterior leukoencephalopathy 35 , Wernicke encephalopathy 36 , hyperammonemic encephalopathy 37 . carbon monoxide poisoning 38 , etc. Previous studies strengthened the notion that the affected areas of MELAS in neuroimaging were asymmetric 2,39,40 . Bhatia, et al. stated that symmetric cortical involvement could be observed in patients of MELAS, and the symmetrical involvement of the anterior cortex of only the middle-third of the postcentral gyrus and posterior cortex of the middle-third of the postcentral gyrus had specific diagnostic significance 3 . In our literature review, symmetric cortical involvements in brain MRI accounts for 6.5% of MELAS patients approximately. Bilateral symmetric temporal lobe lesions were the most common imaging findings. In our case and literature review, the symmetrical involvement of bilateral occipital lobes and internal temporal lobes was the unusual presentation of MELAS. 6. Conclusions This case and literature review underscores the importance of genetic analysis of mitochondrial disease in patients with bilateral symmetric cortices lesions. although the probability of diagnosis of MELAS is relatively rare. Declarations Ethics approval and consent to participate The patient gived her written consent to this publication and approval for this study was provided by the Research Ethics Committee of Taiyuan Central Hospital Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Funding No funding was received. Competing interests The authors declare that they have no competing interests. Authors’ contributions Liu Qing and Su Yangli collected clinical data and wrote the main manuscript text. Shi Jing, Wang Wenxia, Wen Chao, Zhu Yanping, Chen Xuan and Xing Xiaolian performed a literature review and a retrospective analysis. Wang Zhaoxia reviewed the manuscript. The authours read and approved the final manuscript. Acknowledgements We are grateful to all who participated in this study. References Ciafaloni E, Ricci E, Shanske S, et al. MELAS: clinical features, biochemistry, and molecular genetics[J]. Annals of neurology, 1992;31(4):391-8. El-Hattab AW, Adesina AM, Jones J, et al. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options[J]. 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Radiology case reports, 2022l;17(7):2428-2431. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3910568","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":270038511,"identity":"f667f20e-5a40-49aa-820d-aaa693b7e2c5","order_by":0,"name":"Qing Liu","email":"","orcid":"","institution":"Taiyuan Central Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Liu","suffix":""},{"id":270038512,"identity":"9250c6d5-8adf-4942-a082-dffc0c453ad9","order_by":1,"name":"Zhaoxia Wang","email":"","orcid":"","institution":"Peking University First 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\u003cstrong\u003ed-e \u003c/strong\u003eFLAIR sequence and T2-weighted images showed hyperintensities corresponding to DWI lesions. \u003cstrong\u003ef \u003c/strong\u003eMRA examination was normal. \u003cstrong\u003eg \u003c/strong\u003eContrast-enhanced MRI of the brain showed no enhancement in the lesions, but dural enhancement. \u003cstrong\u003eh \u003c/strong\u003eMRS revealed a large double inverted lactate peak in the bilateral occipital lobe lesions.\u003c/p\u003e","description":"","filename":"Figure.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3910568/v1/c652beeb68d8cedba695ad23.jpg"},{"id":50511444,"identity":"a273c520-15bb-42bf-8b32-55d80e348c2d","added_by":"auto","created_at":"2024-02-01 16:14:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204301,"visible":true,"origin":"","legend":"\u003cp\u003eOn day 6 after admission, MRI reexamination the brain was performed. \u003cstrong\u003ea-b \u003c/strong\u003eDWI sequence revealed symmetric gyriform hyperintensities in bilateral occipital lobes and internal temporal lobes, with significantly progressed scope of the lesion. \u003cstrong\u003ec-d \u003c/strong\u003eADC maps sequence indicated symmetric hypo/hyperintensities corresponding to DWI lesions.\u003cstrong\u003e e-f \u003c/strong\u003eFLAIR sequence images showed symmetric hyperintensities corresponding to DWI lesions with significantly progressed scope of the lesion. \u003cstrong\u003eg-h \u003c/strong\u003eT2-weighted images showed hyperintensities corresponding to DWI lesions with significantly progressed scope of the lesion.\u003c/p\u003e","description":"","filename":"Figure.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3910568/v1/283d3027252fac65c12d49cf.jpg"},{"id":50511442,"identity":"b010ffb2-f119-4e66-b327-6819c1c74cda","added_by":"auto","created_at":"2024-02-01 16:14:39","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":45658,"visible":true,"origin":"","legend":"\u003cp\u003eA genetic test revealed a point mutation in the mtDNA (3243A \u0026gt; G) by blood examination.\u003c/p\u003e","description":"","filename":"Figure.3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3910568/v1/e61f67a6f677295cbe0ddd8a.jpg"},{"id":50522668,"identity":"f87b9c81-8588-4ac9-8f1a-b441d078137c","added_by":"auto","created_at":"2024-02-01 19:52:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":506477,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3910568/v1/6ecf6b94-fb67-4b4f-8ede-053bf0496beb.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"MELAS with mtDNA 3243A\u003eG mutation presenting as bilateral symmetric occipital and temporal cortices lesions: a case report and literature review","fulltext":[{"header":"1. Background","content":"\u003cp\u003eMitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited multisystem disorder caused by mitochondrial DNA mutation\u003csup\u003e1\u003c/sup\u003e, which is with a broad spectrum of clinical and radiological presentations. Typical features of MELAS on brain imaging include stroke-like areas, basal ganglia calcification and brain atrophy. The imaging findings of most patients with MELAS are asymmetric\u003csup\u003e2\u003c/sup\u003e. To our knowledge, rare patients with MELAS present with symmetrical lesions in cerebral cortex \u003csup\u003e3\u003c/sup\u003e. In this report, we describe the case of a 46-year-old female patient of MELAS presenting a feature of bilateral symmetric occipital and internal temporal cortices lesions.\u003c/p\u003e"},{"header":"2. Case presentation","content":"\u003cp\u003eA 46-year-old female patient who experienced an acute episode of visual hallucination and blurry vision for the last four days was admitted to our hospital. Initially, she was admitted to another hospital, no abnormalities were found on the ophthalmologic test.\u003c/p\u003e\n\u003cp\u003eAlthough she denied that she had a history of diabetes, elevated blood glucose was noted after admission and diabetes was diagnosed. There was a history of exercise intolerance since her childhood. The patient had no history of migraine or sensorineural hearing Loss. Developmental milestone was normal.\u003c/p\u003e\n\u003cp\u003eAfter admission, a physical examination revealed a height of 166cm, a body weight of 50kg, suggesting that there was no obvious short stature. On neurologic examination, her visual acuity was hand motion in both eyes. She also had diminished osteotendinous reflex of the limbs. The rest of the neurological examinations was normal.\u003c/p\u003e\n\u003cp\u003eBlood chemistry analysis at the time of admission revealed elevated fasting blood glucose levels of 18mmol/L, elevated arterial blood lactic acid levels of 2.97mmol/L, elevated creatine kinase levels of 272u/L, elevated high sensitivity C-reactive protein levels of 6.51 mg/L, elevated low density lipoprotein cholesterol levels of 3.91mmol/L, and elevated total cholesterol levels of 5.89mmol/L. Examination of the cerebrospinal fluid (CSF) showed a normal cell count, high total protein level of 59mg/dL, high glucose level of 8.37mmol/L. Her autoimmune encephalitis antibodies and paraneoplastic antibodies in blood and CSF were negative. Herpes simplex virus type 1 was identified by Second-generation sequencing technology (NGS) of the CSF, but only 4 sequencing reads in NGS data was identified.\u003c/p\u003e\n\u003cp\u003eCranial CT image demonstrated basal ganglia calcification，as well as subtle decreased attenuation in bilateral occipital lobe and internal temporal lobes. (Figure. 1a). The first brain MRI examination demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on T2-weighted images (Figure. 1e), apparent diffusion coefficient (ADC) maps images (Figure. 1c), and FLAIR images (Figure. 1d) with restricted diffusion on DWI sequence (Figure. 1b). Magnetic resonance angiography (MRA) examination was normal (Figure. 1f). Magnetic resonance spectroscopy (MRS) revealed a large double inverted lactate peak (Figure. 1h). Contrast-enhanced MRI of the brain showed no enhancement in the lesions, but dural enhancement (Figure. 1g).\u003c/p\u003e\n\u003cp\u003eThe patient\u0026apos;s visual impairment progressively worsened after admission, and developed cortical blindness 4 days after admission. 5 days after admission, the patient developed cognitive impairment followed by status epilepticus with decreased blood oxygen. saturation. She was transferred to intensive care unit and performed with tracheal intubation. The electroencephalography (EEG)showed spikes, sharp waves and sharp wave complexes in the right occipital lobe. She was received MRI reexamination of the brain 6 days after admission. DWI sequence revealed gyriform hyperintensities in bilateral occipital lobes and internal temporal lobes, with significantly progressed scope of the lesion (Figure. 2a-2b). ADC maps sequence indicated hypo/hyperintensities corresponding to DWI lesions (Figure. 2c-2d). FLAIR sequence (Figure. 2e-2f) and T2-weighted images (Figure. 2g-2h) showed hyperintensities corresponding to DWI lesions with significantly progressed scope of the lesion. A genetic test revealed a point mutation in the mtDNA(3243A \u0026gt; G) by blood examination (Figure.3). After antiepileptic therapy, her status epilepticus was controlled. she did not consent to a muscle biopsy and was transferred to another hospital for treatment 8 days after admission.\u003c/p\u003e"},{"header":"3. Literature review","content":"\u003cp\u003eWe searched Pubmed databases using \u0026ldquo;melas\u0026rdquo;, \u0026ldquo;mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes\u0026rdquo; as keywords and the article type filter set to case reports only. Patients without a brain MRI examination and a genetic test were excluded. Only full text articles in English were included. The search was last updated on 28th August 2023. Descriptive statistical analysis was performed with SPSS 25.\u003c/p\u003e"},{"header":"4. Results","content":"\u003cp\u003eA total of 231 eligible patients with MELAS were identified from 212 papers. Of the 231 eligible patients, 115 (49.8%) were male. The mean age of presentation was 30.6 years (standard deviation, SD=17.6), ranging from 3 to 76 years. Results of cranial CT were available for 58 patients. Of the 58 patients, cranial CT revealed calcifcation in the bilateral basal ganglia in 31 patients (53.4%). Genetic analysis was performed in all cases. The sequencing including mtDNA and nuclear genes revealed a total of 236 variants in 228 patients, and no disease-causing gene mutation in the remaining 3 patients. Of the 228 patients,162(71.7%) carried mtDNA(3243A \u0026gt; G) mutation,8(3.5%) carried mtDNA(13513G\u0026gt;A) mutation,6(2.6%) carried mtDNA(10158T\u0026gt;C) mutation,3(1.3%) carried a double pathogenic mutation. Brain MRI was performed in all 231 eligible patients. Simultaneously bilateral stroke-like lesions involving bilateral cerebral hemispheres were seen in 114(49.4%) eligible patients. Symmetric cortical involvements were seen in 15(6.5%) patients. Of 15 patients, 7(43.8%) involved bilateral symmetric temporal lobes\u003csup\u003e4-10\u003c/sup\u003e,1(6.7%) involved bilateral symmetric temporo-parietal-occipital lobes\u003csup\u003e11\u003c/sup\u003e, 1(6.7%) involved bilateral symmetric frontal-occipital lobes\u003csup\u003e12,\u003c/sup\u003e , 2(13.3%) involved bilateral symmetric frontal -temporo-parietal-occipital lobes \u003csup\u003e13,14\u003c/sup\u003e, 1(6.7%) involved bilateral symmetric frontal -temporo-occipital lobes\u003csup\u003e15\u003c/sup\u003e, 1(6.7%) involved bilateral symmetric frontal-temporo lobes\u003csup\u003e16\u003c/sup\u003e, 1(6.7%) involved bilateral symmetric basal ganglia\u003csup\u003e17\u003c/sup\u003e, 1(6.7%) involved bilateral symmetric precentral gyrus\u003csup\u003e18\u003c/sup\u003e.Non-simultaneous bilateral stroke-like lesions involving bilateral cerebral hemispheres were seen in 27(11.7%) eligible patients.\u003c/p\u003e"},{"header":"5. Discussion ","content":"\u003cp\u003eMELAS is one of probably the most common maternally inherited mitochondrial disease with variable clinical presentations, such as stroke-like episodes, seizures, dementia, muscle weakness, short stature, cerebellar ataxia, migraine, sensorineural hearing loss, diabetes mellitus, peripheral neuropathy, cardiomyopathy, cerebellar signs, progressive external ophthalmoplegia\u003csup\u003e19\u003c/sup\u003e, etc. The mtDNA(3243A \u0026gt; G) mutation located in the tRNALeu (UUR) of the mitochondrial genome accounts for approximately 80% of MELAS cases\u003csup\u003e20\u003c/sup\u003e.Although typical MELAS patients are easy to recognize, the diagnosis of MELAS in some patients are challenging due to the phenotypic heterogeneity. Here we reported a patient presenting with unusual cortical cortex lesion, achieving the final diagnosis with genetic examination.\u003c/p\u003e\n\u003cp\u003eThis case also has some manifestations that are atypical of MELAS. First, the age of onset over 40 years old account for only 1-6% of MELAS patients\u003csup\u003e21\u003c/sup\u003e. The patient in our case was 46 years old, which is unusual for MELAS. Second, the absence of headaches, short stature and hearing loss in our patient increased the difficulty of reaching to a right diagnosis in time. Third, identification of herpes simplex virus (HSV) type 1 by NGS of the CSF increased our suspicion of herpes simplex encephalitis. But given a normal CSF cell count and relatively few sequencing reads, the possibility of false-positive test was not excluded. Lakeman et al. found that 6% of patients with negative brain biopsy results for HSV had positive CSF HSV PCR results\u003csup\u003e22\u003c/sup\u003e. Fourth, there is variability in characteristics of ADC maps sequence of MELAS. To our knowledge, most cases indicated hyperintensities on ADC maps sequence in stroke-like lesions, supporting vasogenic edema\u003csup\u003e23,24,25.\u003c/sup\u003e However, there were many reports of ADC maps sequence hypointensities in recent years, which might be associated with cytotoxic edem\u003csup\u003ea26,27,28\u003c/sup\u003e. In our patient, ADC maps sequence demonstrated hyperintensities on the first MRI. On day 6 after admission, MRI reexamination revealed hypo/hyperintensities mixed, which might suggest the presence of co-existence of vasogenic edema and cytotoxic edema in the affected areas. Fifth, in our case, the affected areas involving cortex and white matter of bilateral occipital lobes and internal temporal lobes in neuroimaging were symmetric.\u003c/p\u003e\n\u003cp\u003eThis case has some essential MELAS features including a positive family history of diabetes mellitus which revealed possibly manifestations of mitochondrial diabetes, diagnosed diabetes mellitus after admission, exercise intolerance, elevated lactate acid and creatine kinase levels in blood laboratory examination, basal ganglia calcification on cranial CT, gyriform hyperintensities on DWI, FLAIR, and T2-weighted images, a lactate peak on MRS.\u003c/p\u003e\n\u003cp\u003eSimultaneously bilateral symmetrical cortical lesions are frequently seen in Creutzfeldt\u0026ndash;Jakob disease\u003csup\u003e29\u003c/sup\u003e, seizures\u003csup\u003e30\u003c/sup\u003e, diffuse brain ischaemia\u0026ndash;hypoxia\u003csup\u003e31\u003c/sup\u003e, hypoglycaemia\u003csup\u003e32\u003c/sup\u003e, autoimmune encephalitis\u003csup\u003e33\u003c/sup\u003e, herpes simplex encephalitis\u003csup\u003e34\u003c/sup\u003e,reversible posterior leukoencephalopathy\u003csup\u003e35\u003c/sup\u003e, Wernicke encephalopathy\u003csup\u003e36\u003c/sup\u003e, hyperammonemic encephalopathy\u003csup\u003e37\u003c/sup\u003e. carbon monoxide poisoning\u003csup\u003e38\u003c/sup\u003e, etc.\u003c/p\u003e\n\u003cp\u003ePrevious studies strengthened the notion that the affected areas of MELAS in neuroimaging were asymmetric\u003csup\u003e2,39,40\u003c/sup\u003e. Bhatia, et al. stated that symmetric cortical involvement could be observed in patients of MELAS, and the symmetrical involvement of the anterior cortex of only the middle-third of the postcentral gyrus and posterior cortex of the middle-third of the postcentral gyrus had specific diagnostic significance\u003csup\u003e3\u003c/sup\u003e. In our literature review, symmetric cortical involvements in brain MRI accounts for 6.5% of MELAS patients approximately. Bilateral symmetric temporal lobe lesions were the most common imaging findings. In our case and literature review, the symmetrical involvement of bilateral occipital lobes and internal temporal lobes was the unusual presentation of MELAS.\u003c/p\u003e"},{"header":"6. Conclusions","content":"\u003cp\u003eThis case and literature review underscores the importance of genetic analysis of mitochondrial disease in patients with bilateral symmetric cortices lesions. although the probability of diagnosis of MELAS is relatively rare.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient gived her written consent to this publication and approval for this study was provided by the Research Ethics Committee of Taiyuan Central Hospital\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLiu Qing and Su Yangli collected clinical data and wrote the main manuscript text. Shi Jing, Wang Wenxia, Wen Chao, Zhu Yanping, Chen Xuan and Xing Xiaolian performed a literature review and a retrospective analysis. Wang Zhaoxia reviewed the manuscript. The authours read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to all who participated in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCiafaloni E, Ricci E, Shanske S, et al. MELAS: clinical features, biochemistry, and molecular genetics[J]. Annals of neurology, 1992;31(4):391-8.\u003c/li\u003e\n\u003cli\u003eEl-Hattab AW, Adesina AM, Jones J, et al. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options[J]. Molecular genetics and metabolism, 2015; 116 (1-2) :4-12.\u003c/li\u003e\n\u003cli\u003eK D Bhatia, P Krishnan, H Kortman, et al. Acute cortical lesions in MELAS syndrome: manatomic distribution, symmetry, and evolution[J]. 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Brain \u0026amp; development, 2011;33(4):283-8.\u003c/li\u003e\n\u003cli\u003eWen-Gao Zeng, Wan-Min Liao, Jue Hu, Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis: A case report[J]. Radiology case reports, 2022l;17(7):2428-2431.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"MELAS, Symmetry, Magnetic resonance imaging, cortical lesions","lastPublishedDoi":"10.21203/rs.3.rs-3910568/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3910568/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Purpose: \u003c/strong\u003eMitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the most common maternally inherited mitochondrial diseases. Stroke-like episode affecting the cortical cortex is the hallmark of MELAS, however, it rarely presents as simultaneously bilateral symmetric cortices lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe reported a case of MELAS in a 46-year-old female patient with bilateral symmetric occipital and internal temporal cortices involvements on brain magnetic resonance imaging (MRI). A literature review of MELAS patients and a retrospective analysis were performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eWe reported a case of MELAS in a 46-year-old female patient with cortical blindness and cognitive decline as well as status epilepticus. She had a family history of diabetes. Although she denied a history of diabetes, elevated blood glucose was noted after admission and diabetes was diagnosed. Laboratory examination revealed elevated lactate acid and creatine kinase levels in blood. Cranial computed tomography (CT) image demonstrated basal ganglia calcification, as well as subtle decreased attenuation in bilateral symmetric occipital and internal temporal cortices. Brain magnetic resonance imaging (MRI) demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on fluid-attenuated inversion recovery (FLAIR) images with restricted diffusion on diffusion weighted images (DWI). A genetic test revealed a point mutation in the mtDNA(3243A \u0026gt; G) by blood examination. Literature review showed there were 231 eligible patients with MELAS were identified from 212 published papers. Symmetric cortical involvements were seen in 15(6.5%) patients on brain MRI.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eMELAS should be considered as a potential diagnosis in the patients with bilateral symmetric stroke-like cortices lesions.\u003c/p\u003e","manuscriptTitle":"MELAS with mtDNA 3243A\u0026gt;G mutation presenting as bilateral symmetric occipital and temporal cortices lesions: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-01 16:14:34","doi":"10.21203/rs.3.rs-3910568/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3f487def-708a-45d0-9f55-0eef53d99dbb","owner":[],"postedDate":"February 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-01T19:44:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-01 16:14:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3910568","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3910568","identity":"rs-3910568","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}