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Lafora Disease Presenting with Ataxia and DM1: A Case Study. 以共济失调和DM1为表现的拉福拉病个案研究
Pub Date : 2024-12-30
Ramin Khanalizadeh, Kosar Karimi

Here we presented a rare case of Lafora disease with neuropathy, ataxia and progression of symptoms into type one DM, GTCS and myoclonus during years. We believe that it is important to keep the diagnosis of Lafora disease in mind in every child presenting with myoclonus especially when mental and cerebellar deficits develop as well. Keywords: Drug-resistant seizure, Ataxia, Myoclonic jerky movements, Lafora.

在此,我们报告一例罕见的拉福拉病伴神经病变,共济失调,多年来症状进展为1型糖尿病,GTCS和肌阵挛。我们认为,重要的是要保持拉福拉病的诊断在每一个儿童呈现肌阵挛,特别是当精神和小脑缺陷发展以及。关键词:耐药癫痫,共济失调,肌阵挛性抽搐,拉福拉
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引用次数: 0
Cure the Incurable: Update of Treatment in Inherited Neuromuscular Disorders. 治愈不治之症:遗传性神经肌肉疾病治疗的最新进展。
Pub Date : 2024-12-30
Cheng-Hao Yu, Kuan-Lin Lai

Originally thought to be incurable, huge therapeutic progress has been made in recent years in the field of inherited neuromuscular disorders. Approaches aiming to rescue the underlying pathophysiology, i.e. loss-of-function or gain-of-function mutations, have been developed via end-product replacement or gene delivery/modulation, with promising results. In the review, advanced treatment in some of the inherited neuromuscular disorders will be discussed. On the other hand, it has been found more than 1000 genes are responsible for the clinical diversities in this group of diseases, and finding a way which owns the therapeutic potential to various diseases is the optimal goal. The discovery of CRISPR-Cas9 system in the last decade offers such an opportunity and is under rigorous investigation. This important issue will also be discussed. Keywords: CRISPR-Cas9, gene therapy, gene delivery/modulation, inherited neuromuscular disorders, therapeutic advances.

最初被认为是无法治愈的,近年来在遗传性神经肌肉疾病领域取得了巨大的治疗进展。旨在挽救潜在病理生理的方法,即功能丧失或功能获得突变,已经通过最终产物替代或基因传递/调节开发出来,并取得了有希望的结果。在这篇综述中,将讨论一些遗传性神经肌肉疾病的先进治疗方法。另一方面,已经发现超过1000个基因负责这类疾病的临床多样性,找到一种对各种疾病具有治疗潜力的方法是最理想的目标。近十年来CRISPR-Cas9系统的发现提供了这样一个机会,并正在进行严格的研究。这个重要的问题也将被讨论。关键词:CRISPR-Cas9,基因治疗,基因传递/调控,遗传性神经肌肉疾病,治疗进展
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引用次数: 0
Recent Advance in Disease Modifying Therapies for Spinal Muscular Atrophy. 脊髓肌肉萎缩症疾病修饰疗法的最新进展。
Pub Date : 2024-09-30
Li-Kai Tsai, Chen-Hung Ting, Yo-Tsen Liu, Cheng-Tsung Hsiao, Wen-Chin Weng

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease characterized by progressive weakness and atrophy of skeletal muscles. With homozygous survival motor neuron 1 (SMN1) gene mutation, all SMA patients have at least one copy of the SMN2 gene, which provides an opportunity for drug targeting to enhance SMN expression. Current three disease modifying drugs, including nusinersen, onasemnogene abeparvovec, and risdiplam, have demonstrated impressive effectiveness in SMA treatment. Nusinersen is an antisense oligonucleotide targeting SMN2 pre-messenger RNA (mRNA) to modify alternative splicing and is effective in SMA children and adults, administrating via intermittent intrathecal injection. Onasemnogene abeparvovec is an adeno-associated viral vector carrying human SMN1 gene, featuring intravenous injection once in a lifetime for SMA patients less than 2 years of the age. Risdiplam is a small molecule also targeting SMN2 pre-mRNA and is effective in SMA children and adults with administration via oral intake once per day. Patients with SMA should receive these disease modifying therapies as soon as possible to not only stabilize disease progression, but potentially obtain neurological improvement. The development in these therapies has benefited patients with SMA and will potentially provide insight in future drug discovery for other neurodegenerative diseases. Keywords: Adeno-associated viral vector, antisense oligonucleotide, disease modifying therapy, gene therapy, motor neuron disease, spinal muscular atrophy.

脊髓性肌萎缩症(SMA)是一种常染色体隐性遗传的运动神经元疾病,以骨骼肌进行性无力和萎缩为特征。由于同卵生存运动神经元 1(SMN1)基因突变,所有 SMA 患者都至少有一个 SMN2 基因拷贝,这为靶向药物增强 SMN 表达提供了机会。目前,包括纽西奈森(nusinersen)、onasemnogene abeparvovec 和利迪普兰(risdiplam)在内的三种疾病调节药物已在 SMA 治疗中显示出令人瞩目的疗效。Nusinersen是一种反义寡核苷酸,靶向SMN2前信使RNA(mRNA)以改变替代剪接,通过间歇性鞘内注射对SMA儿童和成人有效。Onasemnogene abeparvovec 是一种携带人类 SMN1 基因的腺相关病毒载体,对 2 岁以下的 SMA 患者终身静脉注射一次。Risdiplam 也是一种靶向 SMN2 前核糖核酸的小分子药物,每天口服一次,对 SMA 儿童和成人有效。SMA患者应尽快接受这些疾病调节疗法,不仅能稳定疾病进展,还有可能改善神经功能。这些疗法的开发使 SMA 患者受益匪浅,并有可能为未来其他神经退行性疾病的药物研发提供启示。关键词腺相关病毒载体 反义寡核苷酸 疾病调节疗法 基因疗法 运动神经元疾病 脊髓性肌萎缩症
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引用次数: 0
Application of Perfusion Imaging in the Telehealth Setting for Acute Ischemic Stroke. 在远程医疗环境中应用灌注成像治疗急性缺血性中风。
Pub Date : 2024-06-30
Michael Valente, Thanh Phan, Mark Parsons, Henry Ma

In the remote telehealth setting, computed tomography perfusion (CTP) provides important information in assessing the suitability of reperfusion therapy for patients with stroke syndromes. This review will discuss key concepts surrounding the use of CTP, including basic science, clinical applications, pitfalls, recent trials, and technical considerations. CTP can enhance decision‑making for patients who are in the extended window from stroke onset, and this review will address key concepts relevant to its use.

在远程远程医疗环境中,计算机断层扫描灌注(CTP)为评估卒中综合征患者再灌注治疗的适宜性提供了重要信息。本综述将讨论有关使用 CTP 的关键概念,包括基础科学、临床应用、误区、最新试验和技术注意事项。CTP 可为处于卒中发病后延长窗口期的患者加强决策,本综述将讨论与使用 CTP 相关的关键概念。
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引用次数: 0
Bilateral Medial Medullary Infarct with Unique Radiological Presentation. 双侧髓质内侧梗死,有独特的放射学表现。
Pub Date : 2024-03-30 DOI: 10.4103/ANT.33-1_111_0017
Güngör Çakmakci, Mustafa Çetiner, Niyazi Uysal, Fatma Akkoyun Arikan, Sibel Canbaz Kabay

Bilateral medial medullary infarction is a rare subtype of stroke.The typical heart-shaped appearance on magnetic resonance imaging is pathognomonic for bilateral medial medullary syndrome. Vertebrobasilar dolichoectasia is a condition characterized by tortuous dilatation and marked enlargement of the basilar and vertebral arteries, and it may cause posterior circulation infarction. We present the case of a 55-year-old female patient with complaints of speech disorder, regression in consciousness, and difficulty breathing. Diffusion-weighted imaging examination was normal on arrival. In the cranial imaging after 24 hours, acute infarction was observed in the bilateral medial medullary area. Time-of-flight magnetic resonance angiography revealed vertebrobasilar dolichoectasia. In this report, a case of bilateral medial medullary infarction with a unique radiological appearance accompanied by vertebrobasilar dolichoectasia, which is rarely reported in the literature, is presented. Keywords: Stroke, infarct, bilateral medial medullary infarction, heart appearance.

双侧内侧髓质梗死是一种罕见的脑卒中亚型。磁共振成像上典型的心形表现是双侧髓内侧综合征的病理特征。椎-基底动脉窦扩张是一种以基底动脉和椎动脉弯曲扩张和明显增大为特征的疾病,可能导致后循环梗死。我们报告一例55岁女性患者,主诉言语障碍、意识减退和呼吸困难。抵达时扩散加权成像检查正常。在24小时后的颅骨成像中,在双侧髓内侧区域观察到急性梗死。飞行时间磁共振血管造影术显示椎基底动脉硬化。在本报告中,报告了一例双侧内侧髓质梗死,具有独特的放射学表现,并伴有椎基底动脉硬化,这在文献中很少报道。关键词:脑卒中,梗死,双侧髓质内侧梗死,心脏外观。
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引用次数: 0
Myalgia! Where does it come from? 肌痛!它从何而来?
Pub Date : 2023-12-30
Hsun-Hua Lee, Chih-Cheng Chen

Myalgia (also called muscle pain or muscle ache) is a symptom associated with many diseases, including fibromyalgia, neurodegenerative diseases, degenerative spine diseases, etc. Myalgia is a major medical problem affecting 60~85% of the population (lifetime prevalence). However, our understanding of chronic myalgia is still limited and effective treatment for intractable myalgia like fibromyalgia is still lacking. Although multifactorial, one known source of muscle pain is tissue acidosis. Experimental muscle pain can be induced by the intramuscular infusion of a buffered acidic solution in humans. As well, animal studies have revealed that acidic infusion activates chemosensitive nociceptors via the proton-sensing ion channels and receptors. Intriguingly, acid signaling in muscle afferents is promiscuous and could be either pro-nociceptive or antinociceptive, so we have coined the term sngception to describe the somatosensory function of acid sensation. Recent single-cell RNAseq studies have shown proton-sensing ion channels and receptors are expressed in all subpopulations of the somatosensory neurons, including nociceptors and non-nociceptive mechanoreceptors. Here, we address how the acid signaling is integrated in muscle afferents and why muscle pain can be chronic and intractable in mouse models of fibromyalgia. Besides acidosis, we have recently found oxidative stress can be another factor to activate proton-sensing ion channels and thus trigger fibromyalgia-like pain in mice. Together, understanding how the acid signaling works in muscle afferents will provide novel therapeutic strategies for myalgia.

肌痛(也叫肌肉痛或肌肉酸痛)是一种与许多疾病相关的症状,包括纤维肌痛、神经退行性疾病、退行性脊柱疾病等。肌痛是影响60~85%人口的主要医学问题(终生患病率)。然而,我们对慢性肌痛的了解仍然有限,对顽固性肌痛如纤维肌痛的有效治疗仍然缺乏。虽然是多因素的,但肌肉疼痛的一个已知来源是组织酸中毒。实验性肌肉疼痛可通过在人体肌肉内灌注一种缓冲酸性溶液而引起。此外,动物研究表明,酸性输注通过质子感应离子通道和受体激活化学敏感伤害感受器。有趣的是,肌肉传入事件中的酸信号是混杂的,可能是促痛觉的,也可能是抗痛觉的,所以我们创造了“痛觉”这个术语来描述酸感觉的体感功能。最近的单细胞RNAseq研究表明,质子感应离子通道和受体在所有体感觉神经元亚群中都有表达,包括伤害感受器和非伤害感受器。在这里,我们讨论酸信号是如何在肌肉传入事件中整合的,以及为什么在纤维肌痛小鼠模型中肌肉疼痛是慢性和难治性的。除了酸中毒,我们最近发现氧化应激可能是激活质子感应离子通道的另一个因素,从而引发小鼠纤维肌痛样疼痛。总之,了解酸信号如何在肌肉传入事件中起作用将为肌痛提供新的治疗策略。
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引用次数: 0
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Acta neurologica Taiwanica
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