Search

母系遗传性糖尿病伴耳聋相关黄斑营养不良一例

儿童持续性部分性癫痫的诊断算法

总结一组持续性部分性癫痫（Epilepsia partialis continua，EPC）患儿的特点，并提出一种整合关键鉴别诊断的诊断算法。对 2002 年—2019 年在三级儿科神经病学中心就诊的 EPC 患儿进行分析。54 例患儿符合 EPC 诊断标准。中位发病年龄为 7 岁（0.6～15 岁），中位随访时间为 4.3 年（0.2～16 年）。其中，诊断为 Rasmussen 脑炎（Rasmussen encephalitis，RE）30 例（56%），线粒体疾病 12 例（22.2%），磁共振成像（MRI）阳性病灶相关局灶性癫痫 6 例（11.1%），诊断不明 5 例（9%）。线粒体疾病患儿更早出现 EPC，EPC 发病年龄每增加一年，诊断线粒体疾病的几率降低 26%（P = 0.02）。EPC 发作前存在发育问题（OR=22，P<0.001），EPC 发作前无癫痫发作（OR=22，P<0.001）， EEG 提示双侧半球慢波（OR 26，P<0.001），以及脑脊液（CSF）蛋白水平升高（OR=16）均预示着线粒体疾病。30 例 RE 患儿中有 18 例（60%）出现 EPC 发作时，MRI 提示明显不对称或一侧半球萎缩，其余患儿出现的中位时间则在 EPC 发作后 6 个月（3～15 个月）。首选诊断检查为头部 MRI。一侧半球萎缩结合临床表现及脑电图改变的偏侧性，提示诊断为 RE。对于初次扫描时不能诊断为 RE，但临床和影像学表现提示 RE 的儿童，建议每 6 个月重复影像学检查以排查进行性一侧半球皮质萎缩，并应考虑脑活检，鞘内炎症的证据（寡克隆带和新蝶呤升高）可为佐证。对于存在双侧半球源性 EPC 的患儿，建议进行快速 DNA 聚合酶 γ（POLG）基因检测，如为阴性，则应提取外周血 DNA 进行 mtDNA 测序及全外显子组测序。线粒体病所致 EPC 患儿表现出与 RE 和结构性癫痫不同的临床特征。这一针对 EPC 患儿的诊断算法有助于进行针对性检查并及时诊断。

Research progress in cell and animal models of Leber hereditary optic neuropathy

Leber hereditary optic neuropathy (LHON) is a blinding disease caused by mutations in mitochondrial DNA. It is a classic disease model for studying mitochondrial abnormalities. Its main mutation sites are m11778G.A, m.3460G.A and m.14484T.C. LHON cell models are mainly produced by lymphoblasts, fibroblasts, cell hybrids and induced pluripotent stem cells, while LHON animal models are mainly mice, which are produced by rotenone and ND4 mutants. Although the research on the LHON model has achieved good results, there are still many difficulties in constructing an ideal experimental model, which severely limit the exploring to the pathogenesis and therapeutic drugs of LHON. A detailed understanding of the application and characteristics of existing models in LHON will help improve experimental design and construct new models.

Analysis of retinal sublayer thickness in Leber hereditary optic neuropathy and G11778A mutation carriers

Objective To analyze the thickness of peripapillary retinal nerve fiber layer (pRNFL) and photoreceptor (PR) sublayer in Leber hereditary optic neuropathy (LHON) and G11778A mutation carriers. MethodsA cross sectional study. From September 2020 to October 2021, 68 LHON patients (136 eyes) (patient group) and 40 G11778A mutation carriers (80 eyes) of LHON patients' families (carrier group) were included in the study. All patients were found to have G11778A mutation by Genetic testing. Forty healthy volunteers with 80 eyes matched to the age and gender of the patient group were recruited as a normal control group. All eyes were examined by optical coherence tomography (OCT). The pRNFL thickness was automatically measured by the built-in software of the OCT device. The total retinal thickness (MT) and the thickness of the outer bundle layer (OPL), outer nuclear layer (ONL), external limiting membrane to retinal pigment epithelium (ELM-RPE) in macular OCT images were measured by Image J software. Linear mixed model was used to analyze and compare the thickness of pRNFL, macular fovea and four layers above the nasal and temporal paracentral retina in patients, carriers and normal controls. The correlation between pRNFL and macular retinal sublayer thickness and the course of disease was also analyzed. ResultsThe thickness of the upper and lower pRNFL, temporal pRNFL and average pRNFL of the patients were smaller than those of the carriers and the normal control group (P＜0.01), and the nasal pRNFL thickness of the patients was smaller than that of the carriers (P＜0.01). Fovea: compared with the normal control group, the thickness of MT and ONT in the patient group was decreased, ONL thickness decreased in carrier group, with the significant different (P＜0.05). Parafovea: compared with normal control group, the thickness of MT and temporal ONL decreased and temporal OPL increased in the patients group, with the significant different (P＜0.05). In the carrier group, the thickness of MT and temporal, nasal ONL decreased, and the thickness of nasal OPL increased, with the significant different (P＜0.05). Compared with the carrier group, the MT thickness of the patient group was decreased, and the nasal ONL and nasal ELM-RPE thickness were increased, with the significant different (P＜0.05). Correlation analysis results showed that the thinning of pRNFL in the superior, nasal, temporal and average (r=－0.22, －0.21, －0.25, －0.22), and the thickening of ELM-RPE in foveo-temporal (r=0.19) were correlated with the course of disease (P＜0.05). ConclusionsThe pRNFL of LHON patients with G11778A mutation becomes thinner and is related to the course of the disease. There were significant differences in the thickness of MT and PR sublayers between patients and carriers compared to the normal control group.