Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.

BACKGROUND: Previous reports revealed that patients with acquired paralytic strabismus caused by central nervous system diseases are primarily affected by the etiology and treatment of the condition. Strabismus correction for these acquired paralytic strabismus should be performed as soon as the primary disease has been stabilized for 6 months in order to archive a favorable surgical outcome.
METHODS: We followed an infrequent case of longer-lasting supranuclear ophthalmoplegia secondary to brain stem cavernoma.
METHODS: A 25-year-old Chinese Han female developed aberrant head posture and ipsilateral conjugate gaze palsies 8 years after the first brainstem hemorrhage caused by pontine cavernoma. The patient was diagnosed with supranuclear ophthalmic palsy and brain stem cavernoma after surgery. A resection-recession procedure along with a rectus muscle transposition was performed. The patient\'s abnormal head position disappeared, with a normal primary position.
CONCLUSIONS: Resection-recession procedures combined with rectus muscle transposition works very well for longer duration large-angle strabismus caused by brain stem cavernoma.

The paper summarizes the clinical experience of professor ZHANG Ren in the staging treatment with characteristic acupuncture techniques for oculomotor paralysis. According to the symptoms of oculomotor paralysis, the staging treatment is given, in which acupuncture is dominant and the needling techniques are optioned in compliance with the symptoms. In the early, middle and late stages of illness, three different acupuncture therapies are delivered accordingly, i.e. the combination of the point-toward-point needling at the four acupoints located on the forehead and the electroacupuncture with disperse-dense wave, the surrounding needling and the triple needling at the acupoints around the eyeball, as well as the perpendicular needle insertion at the three acupoints within the orbit. Professor ZHANG Ren lays the stress on identifying the etiology and differentiating the symptoms, as well as the early intervention for the disease. For the intractable cases, the comprehensive regimen such as acupoint injection, dermal needling and auricular point sticking is supplemented. During treatment, the spirit harmonization is greatly considered to ensure the effectiveness. On the basis of the staging acupuncture therapy, the acupuncture technique for harmonizing the spirit and regulating qi is combined to obtain the favorable clinical effect on oculomotor paralysis.
总结张仁教授运用特色针法分期治疗动眼神经麻痹的临证经验。张仁教授结合动眼神经麻痹症状分期论治，法随症变，针对早期、中期、晚期主症不同而分别运用额四针透刺法联合疏密波电针法、目六针眼球围刺法及齐刺法和眼三针眶内直刺法治疗；强调审因辨治及早介入治疗，侧重用针，针对难治病例辅以穴位注射、皮肤针、耳穴贴压等综合施术；在治疗过程中重视治神，善用“调神理气”针法，同时强调治疗贵在坚持，临床疗效较好。.

Objective: To evaluate the effects of re-tucking the superior oblique muscle on recurrent or residual compensatory head position. Methods: A retrospective case series study was conducted. 12 recurrent or residual compensatory head position patients (12 eyes) with congenital superior oblique palsy who underwent superior oblique re-tucking in Tianjin Eye Hospital from March 2015 to February 2021 were included. All patients had a history of superior oblique tucking procedure and showed signs of superior oblique muscle palsy without inferior oblique muscle overaction. During surgery, the Guyton forced duction test is used to evaluate the relaxation of the superior oblique muscle tendon, which affects the re-tucking length of the muscle.Their head position, vertical deviation, eye movement, fovea-disa angle, and Bielschowsky head tilt test were assessed pre-and post-surgery. Statistical analysis was performed using ttest and paired samples Wilcoxon signed rank test. Results: Out of the 12 patients, 8 were male and 4 were female, aged between 2 and 9 years. The initial surgery was done at age 6, with a superior oblique recession length of (7.17±1.03) mm. Recurrent head tilt occurred in 11 patients after (3.82±0.98) months postoperatively, and 1 patient had residual head tilt, with a followup period of six months or more. Ocular motility examination revealed underaction of the superior oblique muscle, positive Bielschowsky\'s head tilt test, and Guyton forced duction tese indicating relaxation of the paralyzed superior oblique muscle tendon. Scar adhesion was observed at the stop of the superior oblique muscle, as well as the previous sutures. The scar and the sutures around the stop of the superior oblique muscle were released, the mean re-tucking amount was(7.83±1.59)mm. Follow-up at 12 to 18 months postoperatively showed disappearance of compensatory head position, significant improvement in superior oblique muscle lag, normal ocular motility, and no occurrence of Brown syndrome. The results of Bielschowsky head tilt were negative in 9 cases and still positive in 3 cases after superior oblique re-tucking. The primary vertical deviation was 2.5 (2.0, 5.3) prism diopter pre-operatively and 1 (0, 1) prism diopter post-operatively, respectively. The difference was statistically significant (U=6.00, P<0.001). The total amount of FDA in both eyes was (-22.04±5.47)° and (-15.27±6.08)° pre-and post-operatively, respectively. The difference was statistically significant (t=2.87, P=0.009). All 12 patients have normal eye movement after superior oblique re-tucking procedure. All patients had no compensatory head position at last follow-up. Conclusions: Superior oblique re-tucking is suitable for patients with relaxation of the superior oblique muscle tendon and extrocular rotation as the main sign. It can effectively and safely correct the recurrent or residual compensatory head position after re-tucking the superior oblique muscle.
目的： 观察上斜肌再折叠术矫正先天性上斜肌麻痹患者首次手术后复发或残留代偿头位的临床疗效。 方法： 回顾性系列病例研究。收集2015年3月至2021年7月行上斜肌再折叠术治疗复发或残留代偿头位的12例（12只眼）先天性上斜肌麻痹患者的临床资料，患者均有上斜肌折叠术史，术后残留或复发代偿头位，第一眼位垂直斜视度数较小，眼球运动检查见受累眼上斜肌运动落后，不伴同侧下斜肌亢进。术中全身麻醉下行Guyton被动牵拉试验评估上斜肌肌腱松弛程度，根据上斜肌肌腱松弛程度来决定上斜肌再折叠长度。随访并观察患者手术前后代偿头位、第一眼位垂直斜视度数、眼球运动、彩色眼底相、Bielschowsky征的变化。采用t检验和配对样本秩和检验进行统计学分析。 结果： 12例患者中，男性8例，女性4例；年龄范围为2~9岁，首次手术年龄为6（5，7）岁，首次上斜肌折叠术的上斜肌折叠长度为（7.17±1.03）mm，11例患者术后（3.82±0.98）个月出现复发歪头，1例患者为术后残留歪头，复发或残留头位随访半年及以上。所有患者眼球运动检查提示上斜肌落后，Bielschowsky征阳性，术中Guyton被动牵拉试验提示麻痹眼上斜肌肌腱松弛，探查上斜肌后松解上斜肌止端周围瘢痕，根据牵拉试验的上斜肌肌腱松弛程度行上斜肌再折叠术，再次折叠上斜肌的长度为（7.83±1.59）mm。术后随访12~18个月，患者术后代偿头位均消失，上斜肌落后明显改善，眼球运动正常，无Brown综合征发生。9例患者Bielschowsky征转为阴性，3例患者仍为阳性。术前第一眼位斜视度数为2.5（2.0，5.3）三棱镜度，术后为1（0，1）三棱镜度，两者差异有统计学意义（U=6.00，P<0.001）。黄斑中心凹-视盘中心夹角度数（FDA）术前为（-22.04±5.47）°，术后为（-15.27±6.08）°，差异有统计学意义（t=2.87，P=0.009）。所有患者歪头症状均得到满意改善，随访效果稳定，未发生回退。 结论： 上斜肌再折叠术适用于上斜肌肌腱松弛和以眼球外旋转为主要体征的上斜肌麻痹患者，能有效且安全地矫正上斜肌折叠术后复发或残留的代偿头位。.

暂无摘要。

BACKGROUND: Guillain-Barré syndrome (GBS), as the most common cause of acute flaccid paralysis worldwide, is considered a part of a clinical spectrum in which discrete, complete, or incomplete forms of GBS and overlapping syndromes lie on the basis of their clinical features. The term overlapping Miller Fisher syndrome (MFS)/GBS is used when patients with MFS also suffer from progressive motor weakness of the limbs. Anti-ganglioside GQ1b has been specifically associated with MFS and ophthalmoplegia.
METHODS: Here, we report a Chinese girl who was diagnosed with overlapping MFS/GBS showing acute flaccid paralysis of all four limbs, sensory symptoms, cranial nerve dysfunction, autonomic involvement, ophthalmoplegia, and ataxia. She had high serum and cerebrospinal fluid titres of monospecific anti-GM4 IgG antibody instead of anti-GQ1b antibody in the acute phase.
CONCLUSIONS: Anti-GM4 antibodies usually coexist with other antiganglioside antibodies, leading to missed diagnoses. The findings of the present study show that antibodies to ganglioside GM4 may in overlapping MFS/GBS as the lone immunological factors.

OBJECTIVE: To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy.
METHODS: A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients.
RESULTS: After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period.
CONCLUSIONS: Repeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed.
BACKGROUND: This study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285.

The differential diagnosis of isolated ophthalmoplegia includes a range of pathologies. In this case, a 26-year-old man of Han nationality presented with ophthalmoplegia. Neuroimaging revealed an atypical focal lesion in the interpeduncular fossa. Initial systemic workup indicated intracranial Mycobacterium tuberculosis infection, but there was no evidence to support a diagnosis of other autoimmune diseases (e.g., myasthenia gravis or multiple sclerosis). Neuroimaging follow-up over the next 3 years revealed progression from atypical solitary lesions to multifocal lesions in the white matter of the brain. Key immunological markers were observed in cerebrospinal fluid during follow-up, suggesting the evolution of multiple sclerosis. Ophthalmoplegia with a focal lesion in the interpeduncular fossa was an unusual set of symptoms indicating multiple sclerosis onset. The findings in this case suggest that M. tuberculosis infection is an important but overlooked factor involved in the pathogenesis of multiple sclerosis. Upon initial detection, atypical lesions should receive sufficient attention and patients should undergo systematic screening to identify M. tuberculosis infection and its associated immunological abnormalities.

UNASSIGNED: The aim of the study was to investigate the clinical characteristics of isolated oculomotor paralysis (OP) cases caused by pure midbrain infarction (MI) with pupil sparing.
UNASSIGNED: Patients with pure MI and pontine infarction (PI) at our hospital were included in this study. We compared the blood pressure and lipid levels between the two groups. And the clinical data and imaging features were summarized.
UNASSIGNED: In total, 33 and 35 patients were included in the MI and PI groups, respectively. There was no significant difference in the distribution of age (64.9 ±10.0 vs. 65.1 ±10.8 years, p = 0.927) and males (84.8% vs. 74.3%, p = 0.282) between the MI and PI groups, respectively. The pure MI group had a comparable level of serum lipoprotein and cardiovascular risk factors compared with the PI group except for a lower proportion of hypertension (57.6% vs. 85.7%, p = 0.010). The majority (72.7%) of culprit lesions in the pure MI group was located in the paramedian area of the midbrain, and the ocular muscle palsies mostly involved the medial rectus (75.8%).
UNASSIGNED: The Chinese patients with OP caused by pure MI were mainly characterized with rapidly progressive symptoms, multiple cerebrovascular risk factors, and typical MRI signs. Further efforts should be made in the differential diagnosis of this atypical midbrain syndrome.

BACKGROUND: Progressive external ophthalmoplegia (PEO) is a common subtype of mitochondrial encephalomyopathy.
OBJECTIVE: The study aimed to investigate the relationship between mitochondrial DNA (mtDNA) abnormalities, muscle pathology, and clinical manifestations in Chinese patients with single large-scale mtDNA deletion presenting with PEO.
METHODS: This is a retrospective single-center study. Patients with PEO who had a single large deletion in mitochondrial DNA were included in this study. The associations were analyzed between mtDNA deletion patterns, myopathological changes, and clinical characteristics.
RESULTS: In total, 155 patients with mitochondrial PEO carrying single large-scale mtDNA mutations were enrolled, including 137 chronic progressive external ophthalmoplegia (CPEO) and 18 Kearns-Sayre syndrome (KSS) patients. The onset ages were 9.61 ± 4.12 in KSS and 20.15 ± 9.06 in CPEO. The mtDNA deletions ranged from 2225 bp to 9131 bp, with m.8470_13446del being the most common. The KSS group showed longer deletions than the CPEO group (p = 0.004). Additionally, a higher number of deleted genes encoding respiratory chain complex subunits (p = 0.001) and tRNA genes (p = 0.009) were also observed in the KSS group. A weak negative correlation between the mtDNA deletion size and ages of onset (p < 0.001, r = -0.369) was observed. The proportion of ragged red fibers, ragged blue fibers, and cytochrome c negative fibers did not correlate significantly with onset ages (p > 0.05). However, a higher percentage of abnormal muscle fibers corresponds to an increased prevalence of exercise intolerance, limb muscle weakness, dysphagia, and cerebellar ataxia.
CONCLUSIONS: We reported a large Chinese cohort consisting of mitochondrial PEO patients with single large-scale mtDNA deletions. Our results demonstrated that the length and locations of mtDNA deletions may influence onset ages and clinical phenotypes. The severity of muscle pathology could not only indicate diagnosis but also may be associated with clinical manifestations beyond the extraocular muscles.