Acta neurologica Taiwanica最新文献

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.

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.

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.

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.

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.

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.