The diversity of hereditary neuromuscular diseases: Experiences from molecular diagnosis.

BACKGROUND: Hereditary neuromuscular diseases (NMDs) are a group of rare disorders, and the diagnosis of these diseases is a substantial burden for referral centers. Although next-generation sequencing (NGS) has identified a large number of genes associated with hereditary NMDs, the diagnostic rates still vary across centers. METHODS: Patients with a suspected hereditary NMD were referred to neuromuscular specialists at the National Taiwan University Hospital. Molecular diagnoses were performed by employing a capture panel containing 194 genes associated with NMDs. RESULTS: Among the 50 patients referred, 43 had a suspicion of myopathy, and seven had polyneuropathy. The overall diagnostic rate was 58%. Pathogenic variants in 19 genes were observed; the most frequent pathogenic variant found in this cohort (DYSF) was observed in only four patients, and 10 pathogenic variants were observed in one patient each. One case of motor neuron disease was clinically mistaken for myopathy. A positive family history increased the diagnostic rate (positive: 72.7% vs. negative: 56.3%). Fourteen patients with elevated plasma creatine kinase levels remained without a diagnosis. CONCLUSION: The application of NGS in this single-center study proves the great diversity of hereditary NMDs. A capture panel is essential, but high-quality clinical and laboratory evaluations of patients are also indispensable.

Effect of mannitol on cerebrovascular pressure reactivity in patients with intracranial hypertension.

BACKGROUND/PURPOSE: Mannitol is commonly used in patients with increased intracranial pressure (ICP), but its effect on cerebrovascular pressure reactivity (CVPR) is uncertain. We analyzed the changes of pressure reactivity index (PRx) during the course of mannitol treatment. METHODS: Twenty-one patients who received mannitol treatment for increased ICP were recruited prospectively. Continuous waveforms of arterial blood pressure (ABP) and ICP were collected simultaneously for 60 minutes (10 minutes at baseline and 50 minutes since mannitol administration) during 37 events of mannitol treatment. The correlation coefficients between the mean ABP and ICP were averaged every 10 minutes and labeled as the PRx. The linear correlation of six time points of PRx in each event was calculated to represent the trend of CVPR changes. The negative slope of correlation was defined as improvement in CVPR under mannitol treatment and vice versa. RESULTS: At baseline, the average of ICP was 26.0 ± 9.1 mmHg and the values of PRx were significantly correlated with ICP (p = 0.0044, r = 0.46). After mannitol administration, the average of ICP decreased significantly to 21.2 ± 11.1 mmHg (p = 0.036), and CVPR improved in 59.4 % of all events. Further analysis showed that low baseline cerebral perfusion pressure was the only hemodynamic parameter significant association with the improvement of CVPR after mannitol treatment (p = 0.039). CONCLUSION: Despite lowering ICP, mannitol may have diverse effects on CVPR in patients with intracranial hypertension. Our study suggests that mannitol infusion may have a beneficial effect on CVPR, particularly in those with a low cerebral perfusion pressure at baseline.

Unravelling the mechanisms of underweight in Parkinson's disease by investigating into the role of gut microbiome.

Approximately half of patients with Parkinson's disease (PD) suffer from unintentional weight loss and are underweight, complicating the clinical course of PD patients. Gut microbiota alteration has been proven to be associated with PD, and recent studies have shown that gut microbiota could lead to muscle wasting, implying a possible role of gut microbiota in underweight PD. In this study, we aimed to (1) investigate the mechanism underlying underweight in PD patients with respect to gut microbiota and (2) estimate the extent to which gut microbiota may mediate PD-related underweight through mediation analysis. The data were adapted from Hill-Burns et al., in which 330 participants (199 PD, 131 controls) were enrolled in the study. Fecal samples were collected from participants for microbiome analysis. 16S rRNA gene sequence data were processed using DADA2. Mediation analysis was performed to quantify the effect of intestinal microbial alteration on the causal effect of PD on underweight and to identify the key bacteria that significantly mediated PD-related underweight. The results showed that the PD group had significantly more underweight patients (body mass index (BMI) < 18.5) after controlling for age and sex. Ten genera and four species were significantly different in relative abundance between the underweight and non-underweight individuals in the PD group. Mediation analysis showed that 42.29% and 37.91% of the effect of PD on underweight was mediated through intestinal microbial alterations at the genus and species levels, respectively. Five genera (Agathobacter, Eisenbergiella, Fusicatenibacter, Roseburia, Ruminococcaceae_UCG_013) showed significant mediation effects. In conclusion, we found that up to 42.29% of underweight PD cases are mediated by gut microbiota, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria, which indicates that the pro-inflammatory state, disturbance of metabolism, and interference of appetite regulation may be involved in the mechanism of underweight PD.

Subacute combined degeneration caused by nitrous oxide intoxication: case reports.

PURPOSE: Case reports with a comprehensive review of the current literature concerning subacute combined degeneration induced by nitrous oxide inhalation. A differential diagnosis should be considered when young patients present with progressive myelopathy because that the misuse of nitrous oxide has potentially serious outcomes. CASES REPORT: Three young patients aged from 18 to 24, one male and two females, were diagnosed with progressive ascending numbness in four limbs or both legs and ataxia. They all had been inhaling nitrous oxide from whipped-cream containers for several months. A cervicothoracic magnetic resonance imaging scan revealed long segmental hyperintensity changes at the posterior column of the spinal cord. Serological examination showed a low level of vitamin B12. Subacute combined degeneration of the spinal cord was diagnosed and the etiology was considered related to nitrous oxide misuse. Their neurological status, neuroimage, and neurophysiologic condition improved after vitamin B12 supplementation and cessation of nitrous oxide inhalation. CONCLUSION: Iatrogenic usage of nitrous oxide apparently resulted in subacute combined degeneration in our three patients. Recently, nitrous oxide misuse has increased among young people. Subacute combined degeneration of the spinal cord should be considered as a possible outcome of such abuse.

The impact of nonmotor symptoms on quality of life in patients with Parkinson's disease in Taiwan.

PURPOSE: The nonmotor symptoms (NMS) of Parkinson's disease (PD) are important factors for quality of life (QoL). Few studies on NMS have been conducted in Asian PD patients. Additionally, effects of anti-PD drugs on risk of NMS are still controversial. We therefore conducted this hospital-based cross-sectional study to examine the clinical factors, including concomitant anti-PD medication use, on the occurrence of NMS and QoL in Taiwanese PD patients. PATIENTS AND METHODS: PD patients who received long-term follow-up in the movement disorders clinics were enrolled and received NMS questionnaire (NMSQuest) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). Spearman's rank correlation coefficient was checked for the correlation between clinical factors and NMSQT/PDQSI. Multiple linear regressions were applied to assess the influence of clinical factors on NMSQT/PDQSI. RESULTS: A total of 210 PD patients (mean age 66.1±9.86 years, Hoehn and Yahr stage 2.2±0.9) were included in this study. Up to 98% of patients reported at least one symptom of NMS. The most prevalent symptom was urinary complaints (56%), followed by memory/apathy (30%) and depression/anxiety (28%). The correlation between NMSQT and PDQSI was strong (r s=0.667), especially the item of depression/anxiety (r s=0.607). The regression model for NMSQT indicated that disease duration and severity, but not pharmacological therapy, were major predictors of NMS. CONCLUSION: Our data indicated a high prevalence rate of NMS in PD patients. Among symptoms of NMS, depression and anxiety had the greatest impact on QoL. Concomitant anti-PD medication use did not affect the occurrence of NMS and QoL.