Macroglossia in rapidly progressive inclusion body myositis.

Inclusion body myositis (IBM) is a refractory muscle disease characterized by inflammatory and degenerative features in myofibers. Macroglossia is common in systemic amyloid light chain amyloidosis; however, no reports have been published on patients with IBM. We encountered a female patient with clinicopathologically defined IBM who exhibited relatively rapid progression of dysphagia, gait disturbance, and macroglossia. Muscle biopsy demonstrated endomysial mononuclear inflammatory infiltrates, fiber necrosis and regeneration with rimmed vacuoles, and sarcoplasmic inclusions of p62. Tongue biopsy demonstrated fiber degeneration with fatty replacement and fibrosis, nonnecrotic fibers surrounded and invaded by mononuclear cells, and sarcoplasmic dotlike inclusions of p62. Based on the parotid gland, lip, and muscle biopsy, she was diagnosed as having IBM with Sjögren's syndrome. She was treated with steroid pulse and intravenous immunoglobulin therapy followed by oral administration of prednisolone, which resulted in temporary clinical improvement. Macroglossia might be an indicator of immunotherapy effectiveness.

Impact of non-motor fluctuations on QOL in patients with Parkinson's disease.

Introduction: Long-term levodopa treatment in patients with Parkinson's disease (PwPD) often causes motor fluctuations, which are known to affect their quality of life (QOL). These motor fluctuations may be accompanied by fluctuations in non-motor symptoms. There is no consensus on how non-motor fluctuations affect QOL. Methods: This was a single-center, retrospective study and included 375 patients with Parkinson's disease (PwPD) who visited the neurology outpatient department of Fukuoka University Hospital between July 2015 and June 2018. All patients were evaluated for age, sex, disease duration, body weight, and motor symptoms by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, depression scale by the Zung self-rating depression scale, apathy scale, and cognitive function by the Japanese version of The Montreal Cognitive Assessment. A nine-item wearing-off questionnaire (WOQ-9) was used to assess the motor and non-motor fluctuations. QOL in PwPD was investigated using the eight-item Parkinson's Disease Questionnaire (PDQ-8). Results: In total, 375 PwPD were enrolled and classified into three groups according to the presence or absence of motor and non-motor fluctuations. The first group included 98 (26.1%) patients with non-motor fluctuations (NFL group), the second group included 128 (34.1%) patients who presented with only motor fluctuations (MFL group), and the third group included 149 (39.7%) patients without fluctuations in motor or non-motor symptoms (NoFL group). Among them, the PDQ-8 SUM and SI were significantly higher in the NFL group than in the other groups (p < 0.005), implying that the NFL group had the poorest QOL among groups. Next, multivariable analysis showed that even one non-motor fluctuation was an independent factor that worsened QOL (p < 0.001). Conclusion: This study showed that PwPD with non-motor fluctuation had a lower QOL than those with no or only motor fluctuation. Moreover, the data showed that PDQ-8 scores were significantly reduced even with only one non-motor fluctuation.

Role of cytochrome P450 for vitamin D metabolisms in patients with neurodegenerative disorders.

Introduction: We previously reported lower serum 25-hydroxyvitamin D concentrations in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and Multiple system atrophy (MSA) compared to healthy controls (HC), whereas 1,25-di-hydroxyvitamin D levels were solely lower in MSA patients. We investigate serum concentrations of P450 involved in Vitamin D(VD) hydroxylation to clarify the responsible hydroxylase for the low serum concentrations of VD metabolites. Methods: A total of 79 individuals were enrolled including 20 HC, 20 AD, 19 PD and 20 MSA patients. The serum concentrations of P450 involved in VD hydroxylation were assayed by ELISA. The data were analyzed by the nonparametric Kruskal-Wallis test between groups. Results: Though CYP2R1 and CYP27A1 mediate 25-hydroxylation for VD, CYP2R1 is the main hydroxylase, and CYP27A1 is also involved in VD synthesis. CYP2R1 concentrations showed no differences among groups, while lower CYP27A1 concentrations were found in PD (p < 0.05) and MSA (p < 0.005) compared to HC and differences between AD and MSA (p < 0.05), however no differences between PD and MSA. CYP27B1 is the main 1α-hydroxylase for 25-hydroxyvitamin D and showed differences between HC and PD (p < 0.05), between HC and MSA (p < 0.005) and between PD and MSA (p = 0.055). CYP24A1, which inactivate 1,25-di-hydroxyvitamin D, showed no differences among groups. Conclusions: CYP27A1 might affect VD synthesis and cause low 25-hydroxyvitamin D levels in AD, PD and MSA patients. Low 1,25-di-hydroxyvitamin D levels in MSA patients might be caused by impaired feedback mediated by CYP27B1.

Renal function in amyotrophic lateral sclerosis patients on long-term treatment with edaravone.

ABSTRACT: Edaravone, a free radical-scavenger, was approved in Japan for the treatment of amyotrophic lateral sclerosis (ALS). However, the effect of the drug on renal function in ALS patients remains unclear. This study aimed to investigate renal function in ALS patients on long-term treatment with edaravone by measuring the serum estimated glomerular filtration rate based on cystatin C (eGFR-CysC).In a retrospective study, the data of ALS patients who were treated with over 10 cycles of intravenous edaravone treatment and were evaluated by eGFR-CysC before and after 10 cycles of treatment between July 2015 and June 2018 were analyzed. Then, the results were compared with those of a control ALS group that had never been treated with edaravone.There were 11 patients with ALS who received over 10 cycles of intravenous edaravone treatment. The mean interval between the first and final eGFR-CysC measurements was 18.7 ±â€Š7.9 months. Three patients (27.3%) had >20 mL/min/1.73 m2 decrease in serum eGFR-CysC. However, no patients discontinued edaravone treatment because of renal dysfunction. The average variation rate of eGFR-CysC was not different between the long-term edaravone group (0.29 ±â€Š1.07) and the control group (-0.34 ±â€Š0.40).This retrospective, single-center analysis showed no clinical exacerbation of renal function in ALS patients who received long-term treatment with edaravone.

The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker.

BACKGROUND: MicroRNA-221 (miR-221) is known to be abnormally expressed in malignant melanoma (MM) cells, and it favors the induction of the malignant phenotype through down-modulation of p27Kip1/CDKN1B and the c-KIT receptor. This suggests that the serum level of miR-221 might increase in patients with MM and thus could be used as a new tumor marker. OBJECTIVE: To evaluate the possibility that the serum miR-221 level can be a marker of MM. METHODS: Serum samples were obtained from 94 MM patients and 20 healthy controls. MicroRNAs were purified from serum, and miR-221 levels were measured by quantitative real-time polymerase chain reaction. RESULTS: Circulating miR-221 was detectable and could be quantified in serum samples. MM patients had significantly higher miR-221 levels than healthy controls. Among the MM patients, the miR-221 levels were significantly increased in patients with stage I-IV MM compared to those with MM in situ, and the levels were correlated with tumor thickness. Moreover, a longitudinal study revealed a tendency for the miR-221 levels to decrease after surgical removal of the primary tumor, and to increase again at recurrence. CONCLUSIONS: Serum levels of miR-221 were significantly increased in MM patients and may be useful not only for the diagnosis of MM, but also for the differentiating MM in situ from stage I-IV MM, and for evaluating tumor progression and monitoring patients during the follow-up period. In addition, considering that the serum levels of miR-221 were correlated with tumor thickness, miR-221 might also be useful as a prognostic marker for patients with MM.