Analysis of splicing abnormalities in the white matter of myotonic dystrophy type 1 brain using RNA sequencing.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by the genomic expansion of CTG repeats, in which RNA-binding proteins, such as muscleblind-like protein, are sequestered in the nucleus, and abnormal splicing is observed in various genes. Although abnormal splicing occurs in the brains of patients with DM1, its relation to central nervous system symptoms is unknown. Several imaging studies have indicated substantial white matter defects in patients with DM1. Here, we performed RNA sequencing and analysis of CTG repeat lengths in the frontal lobe of patients with DM1, separating the gray matter and white matter, to investigate splicing abnormalities in the DM1 brain, especially in the white matter. Several genes showed similar levels of splicing abnormalities in both gray and white matter, with an observable trend toward an increased number of repeats in the gray matter. These findings suggest that white matter defects in DM1 stem from aberrant RNA splicing in both gray and white matter. Notably, several of the genes displaying abnormal splicing are recognized as being dominantly expressed in astrocytes and oligodendrocytes, leading us to hypothesize that splicing defects in the white matter may be attributed to abnormal RNA splicing in glial cells.

Additional Steroid Therapy for Delayed Facial Palsy in Miller Fisher Syndrome.

Miller Fisher syndrome (MFS) is a variant of Guillain-Barré syndrome. Delayed facial palsy (DFP) is a symptom that occurs after other neurological symptoms begin to recover within four weeks from the onset of MFS. As there have been few detailed reports about DFP in MFS cases treated with additional immunotherapy, we investigated three cases of DFP in MFS treated with additional steroid therapies. The duration of facial palsy in our cases was 12-24 days. No severe adverse effects were observed. Although adverse side effects should be carefully monitored, additional steroid therapy might be a treatment option for MFS-DFP.

[Eclizumab in the treatment of myasthenia gravis crisis complicating invasive thymoma: a case study of efficacy].

A 40-year-old male patient was diagnosed with invasive thymoma and myasthenia gravis in 2015. In 2016 and 2017, he experienced myasthenic crises, with an increase in size of invasive thymoma. In 2018, he received chemotherapy for the invasive thymoma. After 2 months, his symptoms rapidly progressed to myasthenic crisis with severe bulbar and respiratory symptoms, despite the significant effect of chemotherapy for the thymoma. High-dose corticosteroid, multiple plasma exchanges, and intravenous immunoglobulin did not improve the symptoms. Thus, eculizumab was administered, resulting in an improvement in his conditions. To our knowledge, this is the first report showing that eculizumab may improve myasthenic crisis with invasive thymoma.

Proportion of Japanese outpatients filling prescriptions for long-term medication regimens.

Aim: Our study aimed to clarify how long outpatients with chronic diseases such as hypertension continuously fill prescriptions for the same medications as those prescribed initially and how many medications they take over the long term. Methods: Medication records from April 1, 2016 to March 31, 2017 with total days between initial and final dispensation date ≥330 days and total days of medication supplies ≥180 days were extracted from an electronic database in a Japanese community pharmacy chain. The continuity of refilling medications over 1 year (ie, medication fill adherence) was measured using the medication possession ratio (MPR). Results: A total of 34,549 outpatients received long-term medications under the above conditions (4.4% of all patients in the database). Mean age was 66.0±17.4 years; 63.1% were ≥65 years. The mean number of medications prescribed per patient was 3.2±2.3. More than one-fifth of patients (22.6%) were taking ≥5 medications. The mean MPR for patients overall was 93.6±11.2%; 87.2% of patients had an MPR ≥80% but <110%. Amlodipine besylate, an antihypertensive, was the most commonly prescribed drug (n=5,537 patients). Conclusion: Outpatients that received long-term medications with no change in prescription had an MPR >90% for around 3 medications. It can be reasonably assumed that these patients could receive a longer-term medication supply with the partial fills based on a physician's instruction ("Bunkatu Chozai" in Japanese). This longer-term supply would be similar to a basic prescription refill, but would require a physician's signature allowing for partial refills rather than a new prescription for each refill.