Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy.  Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30-57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function.

The MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child with heteroplasmy for this variant who developed neurological regression and stroke-like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z-scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke-like episodes. The use of intravenous arginine during stroke-like episodes and daily enteral L-citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1-methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N-acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT-TL2 m.12315G>A to include neurological regression and a MELAS-like phenotype. Individuals with this variant should undergo in-depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations have been administered worldwide, with occasional reports of associated neurological complications. Specifically, the impact of vaccinations on individuals with X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is unclear. Patients with CMTX1 can have stroke-like episodes with posterior reversible encephalopathy syndrome on magnetic resonance imaging (MRI), although this is rare.
METHODS: A 39-year-old man was admitted with episodic aphasia and dysphagia for 2 d. He received SARS-CoV-2 vaccination 39 d before admission. Physical examination showed pes cavus and reduced tendon reflexes. Brain MRI showed bilateral, symmetrical, restricted diffusion with T2 hyperintensities in the cerebral hemispheres. Nerve conduction studies revealed peripheral nerve damage. He was diagnosed with Charcot-Marie-Tooth disease, and a hemizygous mutation in the GJB1 gene on the X chromosome, known to be pathogenic for CMTX1, was identified. Initially, we suspected transient ischemic attack or demyelinating leukoencephalopathy. We initiated treatment with antithrombotic therapy and immunotherapy. At 1.5 mo after discharge, brain MRI showed complete resolution of lesions, with no recurrence.
CONCLUSIONS: SARS-CoV-2 vaccination could be a predisposing factor for CMTX1 and trigger a sudden presentation.

UNASSIGNED: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT-TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes.
UNASSIGNED: Fifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G (MT-TL1; tRNA Leu) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively.
UNASSIGNED: The lesions were most commonly located in the posterior brain, with 37 (37/59, 63%) in the occipital lobe, 32 (32/59, 54%) in the parietal lobe, and 30 (30/59, 51%) in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases.
UNASSIGNED: The imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity.

UNASSIGNED: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common maternally inherited mitochondrial diseases which rarely affects elderly people.
UNASSIGNED: We reported the case of a 61-year-old male patient with MELAS. He was experiencing acute migraine-like headaches as the first symptoms. Laboratory data showed elevated lactate and creatine kinase levels. Brain magnetic resonance imaging (MRI) found a high signal intensity lesion in the left occipital-temporal-parietal lobe on diffusion-weighted imaging (DWI). Magnetic resonance angiography (MRA) revealed reversible vasoconstriction of the middle cerebral arteries and superficial temporal arteries. A muscle biopsy suggested minor muscle damage. A genetic study revealed a mitochondrial DNA A3243G mutation.
UNASSIGNED: Elderly onset of MELAS is rare and easily misdiagnosed as an ischemic stroke. MELAS with the onset of stroke-like episodes should be considered in adult or elderly patients with imaging findings that are atypical for cerebral infarction. The use of multimodal MRI in the clinical diagnosis of MELAS could be extremely beneficial.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is caused by mutations in mitochondrial DNA and is one of the most common syndromes among the mitochondrial diseases. Clinical manifestations typically occur before the age of 40 years. The present study reports a case of MELAS with a mutation in the adenine to guanine conversion at mitochondrial genome 3243 in a 48-year-old woman who was suspected of suffering from recurrent strokes. Finally, the genomic analysis confirmed the diagnosis of MELAS. This case highlights the importance of considering MELAS as a potential cause of recurrent stroke-like events if imaging findings are atypical for cerebral infarction, even among middle-aged patients with vascular risk factors.

Mitochondrial myopathy encephalopathy lactic acidosis and stroke-like episodes (MELAS) is an important cause of stroke-mimicking diseases that predominantly affect patients before 40 years of age. MELAS results from gene mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) responsible for the wide spectrum of clinical symptoms and imaging findings. Neurological manifestations can present with stroke-like episodes (the cardinal features of MELAS), epilepsy, cognitive and mental disorders, or recurrent headaches. Magnetic resonance imaging (MRI) is an important tool for detecting stroke-like lesions, accurate recognition of imaging findings is important in guiding clinical decision making in MELAS patients. With the development of neuroimaging technologies, MRI plays an increasingly important role in course monitoring and efficacy assessment of the disease. In this article, we provide an overview of the neuroimaging features and the application of novel MRI techniques in MELAS syndrome.

This study aimed to evaluate the sensitivity and specificity of the vessel signs, including the Vessel Flow Void Sign (VFVS) and the Hyperintense Vessel Sign (HVS) in Fluid Attenuated Inversion Recovery (FLAIR) images during the differentiation of Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) in Acute Ischemic Stroke (AIS).
Magnetic Resonance Imaging (MRI) scans of 13 MELAS and 20 AIS patients were obtained during the acute stage of the diseases (median time to scan <1 day from symptom onset). To evaluate VFVS and HVS on the FLAIR images, Logistic Regression was used to analyze their correlation with MELAS. Then, a new scale of scoring, involving two aspects (VFVS and HVS) on FLAIR images was established. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of the developed criterion.
FLAIR images from 12 of the 13 MELAS patients exhibited VFVS while none exhibited HVS. Moreover, FLAIR images from 3 of the 20 AIS patients exhibited VFVS while 17 exhibited HVS. Logistic Regression showed that VFVS and the absence of HVS (NoHVS) were independent MELAS predictors. If there were VFVS, the patient scored 2 points, while there were NoHVS, the patient scored 1 point. Patients with >1.5 scores were prone to be MELAS, while patients with <1.5 scores were prone to be AIS. Sensitivity was found to be 92.3%, specificity was 85%, with an AUC of 0.94.
We have established a new scoring criterion, with a high sensitivity and specificity, for differentiating between MELAS and AIS in patients during the acute stage.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the dynamic functional connectivity (dFC) of brain networks in MELAS has not been explored.
To investigate the abnormalities of dFC in patients with MELAS at the acute and chronic stages, and to determine the possible relations between dynamic connectivity alterations and volumes of stroke-like lesions (SLLs).
Prospective.
Twenty-two MELAS patients at the acute stage, 23 MELAS patients at the chronic stage, and 22 healthy controls.
Single-shot gradient-recalled echo planar imaging (EPI) sequence at 3T.
Dynamic FC states were estimated using the sliding window approach and k-means clustering analyses. Combined with graph theory, the topological properties of the dFC network were also accessed.
Permutation test, Pearson correlation coefficient, and false discovery rate correction.
We identified four dFC states and found that MELAS patients (especially at the acute stage) spent more time in a state with weaker connectivity (state 1) and less time in states with stronger connectivity. In addition, volumes of acute SLLs were positively correlated with mean dwell time in state 1 (r = 0.539, P < 0.05) and negatively correlated with the number of transitions (r = -0.520, P < 0.05). Furthermore, MELAS patients at the acute stage exhibited significantly increased global efficiency (P < 0.01) and decreased local efficiency (P < 0.001) compared to the controls and the patients at the chronic stage. Patients at the chronic stage only showed significantly (P < 0.001) decreased local efficiency compared to the controls.
Our findings suggest similar and distinct dFC alterations in MELAS patents at the acute and chronic stages, providing novel insights for understanding the neuropathological mechanisms of MELAS. Level of Evidence 2 Technical Efficacy Stage Stage 2 J. MAGN. RESON. IMAGING 2021;53:427-436.

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) may cause whole-brain functional changes due to mitochondrial dysfunction. Our purpose is to comprehensively evaluate the alterations of spontaneous brain activity in MELAS patients at stroke-like episodes (SLE) attack and remission stages using resting-state functional magnetic resonance imaging. Forty MELAS patients at attack stage (n = 20) and remission stage (n = 20) and 22 healthy controls were enrolled in this study. We suggested that MELAS patients presented decreased spontaneous brain activities beyond the areas of stroke-like lesions (SLLs), with a downward trend from SLE attack stage to remission stage. In addition, the regional spontaneous activity of SLL, an inherent change in MELAS, was less than that in unaffected areas. Furthermore, the fractional amplitude of low frequency fluctuations value in left precuneus may be used as a promising neuroimaging biomarker for monitoring the disease status of MELAS.