PCDHA9 as a candidate gene for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.

Venous blood parameters in determination of respiratory impairment in amyotrophic lateral sclerosis.

This study aimed to investigate the relationship between venous blood parameters and respiratory functions in patients with amyotrophic lateral sclerosis (ALS) and develop a model to predict respiratory impairment for individual patients with ALS. A total of 416 ALS patients were included in the study, and various hematologic and biochemical laboratory parameters as well as demographic and clinical factors were collected and compared. A multivariable logistic regression model was constructed to assess the association between FVC and venous blood biomarkers and clinical factors. The results showed that along with onset age, bulbar-onset, disease duration, BMI, eosinophil count (EO#), basophil count (BASO#), creatinine (CREA), uric acid (URCI) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL/HDL) ratio were associated with reduced FVC. The area under the ROC curve is 0.735 for the test set and 0.721 for the validation set. The study also developed a relatively acceptable model for predicting respiratory impairment in ALS patients. These findings suggest that EO#, BASO#, CREA, URIC and LDL/HDL ratio can be useful in assessing FVC in ALS and can be easily accessible, accurate, and low-cost parameters.

Prevalence and associated factors of frailty and sarcopenia in multiple system atrophy and progressive supranuclear palsy: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of, and clinicodemographic factors associated with, frailty and sarcopenia in patients with multiple system atrophy or progressive supranuclear palsy. METHODS: A total of 264 participants were recruited in this study. Demographic and clinical data were collected through structured interviews. Frailty was assessed with the clinical frailty scale (CFS), and sarcopenia was assessed with the simple five-item scoring questionnaire (SARC-F). RESULTS: The prevalence of frailty and sarcopenia was 48.57% and 35.71% in multiple system atrophy, and 51.09% and 39.13% in progressive supranuclear palsy. Multiple system atrophy patients with frailty or sarcopenia were more likely to be female and have longer disease duration, greater motor impairment, greater non-motor burden, and lower life quality. In multiple system atrophy, frailty was associated with reduced motor function and sarcopenia was associated with female sex, reduced motor function, and orthostatic hypotension. Progressive supranuclear palsy patients with frailty or sarcopenia had more severe motor impairment and non-motor burden, longer disease duration, and lower life quality. In progressive supranuclear palsy, frailty was associated with mentation and gait/midline symptoms, while sarcopenia was associated with reduced daily activity and severe gait/midline symptoms. CONCLUSION: Frailty and sarcopenia may be more common among patients with multiple system atrophy or progressive supranuclear palsy than among the general population, and they are associated with more severe forms of the two diseases. Prospective studies are necessary to clarify causal relationships between frailty/sarcopenia and clinical manifestations of multiple system atrophy and progressive supranuclear palsy.

A Prediction Model for Peak Expiratory Flow Derived From Venous Blood Biomarkers and Clinical Factors in Amyotrophic Lateral Sclerosis.

Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

Cerebrospinal Fluid Biomarkers in Multiple System Atrophy Relative to Parkinson's Disease: A Meta-Analysis.

OBJECTIVE: To investigate the differences of candidate cerebrospinal fluid (CSF) biomarkers associated with multiple system atrophy (MSA) and Parkinson's disease (PD). METHOD: Here, a systematic review and meta-analysis were conducted on studies related to CSF biomarkers associated with MSA and PD obtained from PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I 2 statistic while Egger's test was used to test for existing publication bias. RESULTS: MSA patients had higher CSF t-tau (SMD = 0.41, 95% CI: 0.10 to 0.72) and YKL-40 (SMD = 0.63, 95% CI 0.12 to1.15) as well as DJ-1 (SMD = 1.05, 95% CI 0.67 to 1.42) levels than PD patients, while CSF p-tau (SMD = -0.17, 95% CI, -0.31 to -0.02) and Aß-42 (SMD = -0.33, 95% CI, -0.55 to -0.12) levels in MSA patients were lower than those in PD patients. There were no differences in CSF's GFAP and Flt3 ligand levels in both MSA and PD patients. CONCLUSION: The study revealed the differences in CSF biomarker levels between MSA and PD cohorts that can be further explored to clinically distinguish MSA from PD.

Fatigue prevalence and associated factors in patients with multiple system atrophy.

OBJECTIVE: Fatigue was reported a determinant of poor quality of life in multiple system atrophy (MSA) patients. This study aimed to determine fatigue prevalence and associated demographic, motor, and non-motor symptoms in MSA patients. MATERIALS AND METHODS: A total of 174 MSA patients met "Probable" diagnostic criteria were included in this cross-sectional study. Fatigue Severity Scale (FSS) was used to measure fatigue prevalence. Unified MSA Rating Scale (UMSARS), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale-17 (HDRS-17), Hamilton Anxiety Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), and Mini-Mental State Exam (MMSE) were used for comprehensive clinical assessments. Nonparametric Mann-Whitney or Pearson's chi-square test was used to compare the patient score with or without fatigue (defined as a mean FSS score≥4). Binary logistic regression analysis was performed to determine features independently associated with the presence of fatigue. RESULTS: Fifty (28.7%) patients enrolled reported fatigue. Results of multivariate analysis revealed that anxiety (OR = 3.01, 95% CI = 1.43-6.31), excessive daytime sleepiness (OR = 2.70, 95% CI = 1.23-5.90), and use of sleep medicine (OR = 3.58, 95% CI = 1.39-9.24) were significantly associated with fatigue in MSA patients. CONCLUSIONS: Fatigue is common in our MSA patients. Anxiety, excessive daytime sleepiness, and current sleep medicine use may be associated with an increased risk of fatigue. However, the severity of motor symptoms may not be associated with fatigue. Our findings highlight the need to identify, investigate, and treat fatigue in MSA.

Lymphocyte-based ratios for predicting respiratory failure in Guillain-Barré syndrome.

PURPOSE: Up to 20-30% of patients with Guillain-Barré syndrome (GBS) suffer serious clinical manifestations such as respiratory failure. We aim to determine whether two new prognostic biomarkers, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), could reliably predict respiratory failure in GBS.we MATERIALS AND METHODS: Data from 426 patients diagnosed at our center with GBS between January 2015 and July 2019 were retrospectively analyzed. Data were collected from the hospital database. Logistic regression and receiver operating characteristic curves were used to examine whether NLR alone, PLR alone or the combination, as measured at admission, could predict respiratory failure during hospitalization. Nomograms for predicting respiratory failure in GBS individuals were established, and predictive accuracy was evaluated using Harrell's concordance index (C-index). RESULTS: A total of 74 (17%) patients developed respiratory failure during hospitalization, and this was predicted independently by neutrophil count, NLR, PLR, and a combined "NLR-PLR" index, with the combined index performing best. The C-index of nomograms was 0.952 (95%CI 0.930-0.974) when NLR-PLR was included, or 0.933 (95%CI 0.911-0.955) when it was excluded. CONCLUSIONS: The prognostic biomarkers NLR and PLR may be independent predictors of respiratory failure in GBS. Combining the two indices may be more effective than either one on its own.

LRP10 Mutations May Correlate with Sporadic Parkinson's Disease in China.

LDL receptor-related protein (LRP) 10 was recently identified as a Parkinson's disease gene through genome-wide linkage and sequencing analysis, but its role in Parkinson's disease in various populations is still unclear. The aim of this study was to determine the frequency and spectrum of LRP10 mutations in a cohort of Parkinson's disease patients from mainland China. All LRP10 exons and their flanking intron regions were screened by direct sequencing in 567 unrelated Parkinson's disease patients and 600 unrelated controls. We detected 29 exonic or splicing variants in 79 patients with Parkinson's disease. Five variants (c.A181C:p.I61L, c.C652T:p.Q218X, c.C833T:p.T278I, c.T1592G:p.I531S, c.T1697C:p.L566P) were predicted to be disease-causing or damaging by multiple in silico tools. Our study provides genetic evidence that LRP10 defects may correlate with sporadic Parkinson's disease.

Clinical value of C-reactive protein/albumin ratio in Guillain-Barré syndrome.

BACKGROUND: Respiratory failure in patients with Guillain-Barré syndrome (GBS) can lead to serious complications and dysfunctions, emphasizing the importance of early detection. The C-reactive protein-to-albumin ratio (CAR) is emerging as a novel inflammatory marker for predicting neurological outcome. We aimed to identify the association of CAR with respiratory failure and short-term outcome in GBS patients. METHODS: A total of 200 patients diagnosed with GBS were retrospectively analyzed. Data were collected from an electronic database. The associations of C-reactive protein (CRP), albumin, and CAR at admission with outcomes were evaluated by logistic regression analysis. Using receiver operating characteristic curves, we calculated the cutoff value for the CAR and compared its discriminatory power with that of C-reactive protein alone. RESULTS: Fifty-two (26%) patients showed poor short-term outcome, and 50 (25%) developed respiratory failure. CAR > 0.21 was an independent predictor of respiratory failure, and CAR > 0.19 was an independent predictor of poor short-term outcome. CAR showed a better predictive value than CRP alone. In addition, the c-index of the predictive nomogram for respiratory failure was higher when it included CAR (0.962) than when it did not (0.958). A similar result was observed for the predictive nomogram for poor short-term outcome (0.953 vs 0.947). CONCLUSION: CAR > 0.21, a novel inflammatory biomarker, is independently associated with the occurrence of respiratory failure in GBS patients, while CAR > 0.19 is independently associated with poor short-term outcome. CAR may help identify GBS patients at high risk of poor prognosis.

Non-motor symptoms are associated with midline tremor in essential tremor.

OBJECTIVES: Essential tremor (ET) patients presenting tremor in the midline structures may be a distinct subtype of the syndrome. Therefore, we sought to explore the clinical manifestations, especially non-motor symptoms (NMS) of Chinese ET patients with midline tremor (MT). METHODS: In the cross-sectional study, we grouped 290 definite or probable ET patients based on their MT conditions. The NMS in ET patients were evaluated using the NMS scale (NMSS). NMS and other clinical correlates were then compared among subgroups with, and without MT. RESULTS: We revealed that 39.0%, 27.6%, and 6.9% of the patients respectively had neck, voice, and facial tremors. With the accumulation of tremor in midline structures, NMS became more severe and prevalent. Logistic regression analyses revealed that factors such as: female gender (OR = 2.164, 95% CI: 1.307-3.583), having least or highest action arm tremor (OR = 2.512, 95% CI: 1.520-4.151), having higher score of sleep/fatigue domain (OR = 1.692, 95% CI: 1.004-2.850) and mood/apathy (OR = 1.926, 95% CI: 1.143-3.246) domain, to be independently associated with MT manifestation. CONCLUSIONS: Our study demonstrates the heterogeneity of symptoms in ET patients with MT, especially in prominent NMS. In addition, the discrepancy of NMS between patients with, and without MT provides novel insight into the underlying pathophysiology and therapeutic of ET.

A nomogram to predict mechanical ventilation in Guillain-Barré syndrome patients.

INTRODUCTION: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis, with up to 20%-30% of patients requiring mechanical ventilation. The aim of our study was to develop and validate a mechanical ventilation risk nomogram in a Chinese population of patients with GBS. METHODS: A total of 312 GBS patients were recruited from January 1, 2015, to June 31, 2018, of whom 17% received mechanical ventilation. The least absolute shrinkage and selection operator (LASSO) regression model was used to select clinicodemographic characteristics and blood markers that were then incorporated, using multivariate logistic regression, into a risk model to predict the need for mechanical ventilation. The model was characterized and assessed using the C-index, calibration plot, and decision curve analysis. The model was validated using bootstrap resampling in a prospective study of 114 patients recruited from July 1, 2018, to July 10, 2019. RESULTS: The predictive model included hospital stay, glossopharyngeal and vagal nerve deficits, Hughes functional grading scale scores at admission, and neutrophil/lymphocyte ratio (NLR). The model showed good discrimination with a C-index value of 0.938 and good calibration. A high C-index value of 0.856 was reached in the validation group. Decision curve analysis demonstrated the clinical utility of the mechanical ventilation nomogram. CONCLUSIONS: A nomogram incorporating hospital stay, glossopharyngeal and vagal nerve deficits, Hughes functional grading scale scores at admission, and NLR may reliably predict the probability of requiring mechanical ventilation in GBS patients.

Acute Flaccid Paralysis as the Initial Manifestation of Japanese Encephalitis: a Case Report.

Japanese encephalitis (JE) is a clinical disease caused by inflammation of the central nervous system. The symptoms of this disease range broadly in severity from mild febrile illness to acute meningomyeloencephalitis. JE has been associated with a variety of neurological abnormalities, such as altered sensorium, seizures, focal neurological deficit, and acute flaccid paralysis (AFP). However, to date, AFP has never been reported as an initial manifestation of JE. Here, we present a case of AFP manifesting as the initial symptom of JE in a Chinese patient. A 30-year-old Chinese man was admitted to the West China Hospital of Sichuan University after experiencing AFP in the right upper limb, followed by hyperpyrexia and unconsciousness. Assay of cerebrospinal fluid from a lumbar puncture revealed high levels of proteins and anti- JE virus IgM antibodies. Intravenous acyclovir was administered; however, the weakness persisted and more extensive muscle wasting from the proximal to distal right upper limb occurred over 7 months. This case report highlights that JE needs to be added to the differential diagnosis of AFP in adults, especially in JE endemic seasons and areas.

Lack of association between appendectomy and Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Accumulation of aggregated α-synuclein from the enteric nervous system is believed to be involved in the pathogenesis of Parkinson's disease (PD). The appendix contains abundant α-synuclein and lacks a blood-tissue barrier, suggesting that appendectomy might reduce α-synuclein aggregation, and therefore the risk of PD. Studies on this intriguing possibility have not come to consistent conclusions. METHODS: PubMed, Embase (via Ovid), and the Cochrane Controlled Register of Trials were searched for studies published through February 20, 2019 on the potential relationship between appendectomy and PD. Two reviewers independently screened literature, extracted data and evaluated the quality of included studies. Data were summarized as pooled effect sizes (RRs or SMDs) with 95% confidence intervals (CIs), which were calculated using the inverse variance method and a random-effects model. Heterogeneity was assessed using the I2 statistic and explored in subgroup analyses. RESULTS: Of the 408 references screened, six studies involving 3,554,540 people were included eventually. Appendectomy did not significantly affect PD risk (RR 1.02, 95% CI 0.87-1.20, I2 = 83.1%, P = 0.789) or delay its onset (SMD 0.21, 95% CI - 0.03 to 0.44, I2 = 43.4%, P = 0.083). CONCLUSION: The available evidence suggests no protective effect of appendectomy against PD. Future studies should seek to clarify the role of inflammation, α-synuclein pathology and the gut-brain axis in PD pathogenesis.

Association between REM sleep behavior disorder and impulsive-compulsive behaviors in Parkinson's disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Both REM sleep behavior disorder (RBD) and impulsive-compulsive behaviors (ICBs) are well-recognized non-motor features in patients with Parkinson's disease (PD). Studies have given contradictory results about the potential association between RBD and ICBs. METHODS: PubMed, Embase (via Ovid), and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases were systematically searched till August 20, 2019 to identify studies that explored the possible correlation between RBD and ICBs in patients with PD. Two authors independently screened records, extracted data and evaluated quality of included studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by employing a random or fixed-effects model. We performed subgroup and sensitivity analyses, and we assessed potential publication bias. RESULTS: A total of 134 references were screened and 10 studies involving 2781 PD patients were included. Overall, RBD was associated with a more than twofold higher risk of developing ICBs (OR 2.12, 95% CI 1.43-3.14, I2 = 56.7%, P < 0.01). Similar results were obtained in sensitivity analyses and in meta-analyses of subgroups stratified based on multivariable adjustment and methods for diagnosing RBD and ICBs. No significant risk of publication bias was found. CONCLUSION: RBD in PD is confirmed to be a risk factor for ICBs. Clinicians should be aware of this association to help them improve patient management.

Clinical features of multiple system atrophy with or without rapid eye movement behavior disorder: a cross-sectional study in southwest China.

OBJECTIVE: The aim of this study was to investigate the prevalence of rapid eye movement behavior disorder (RBD) in Chinese patients with multiple system atrophy (MSA) and to compare motor and non-motor symptoms and sleep disturbance of MSA patients with and without RBD. METHODS: A total of 55 patients who were consecutively admitted to West China Hospital of Sichuan University from 2016 to 2019 and subsequently diagnosed with probable MSA were enrolled in this cross-sectional study. The diagnosis of RBD was based on the results of video polysomnography (PSG) and a history of abnormal sleep-related behaviors. The patients were divided into two groups: those with RBD and those without. These two groups were then compared in terms of severity of motor symptoms (Unified Multiple System Arophy Rating Scale) and non-motor symptoms (Non-Motor Symptoms Scale, Mini-Mental State Examination score, Epworth Sleepiness Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale) and sleep parameters as recorded on PSG. RESULTS: Of the 55 patients (35 males), 18 (33%, 13 males) were diagnosed with RBD. Patients with or without RBD did not differ in demographic characteristics, clinical features, or sleep parameters based on PSG. CONCLUSION: There was no difference in motor and non-motor symptoms between MSA patients with or without RBD, indicating that the presence of RBD may not be significantly associated with the severity of motor or non-motor dysfunction in MSA.

Clinical characteristics of patients with essential tremor or essential tremor plus.

BACKGROUND: The International Parkinson and Movement Disorder Society introduced the category of essential tremor (ET)-plus in its new ET classification scheme, but how the clinical correlates of ET-plus differ from those of "pure" ET is unclear. By comparing the clinical characteristics of ET and ET-plus patients, we expect to better understand the impact and invoked questions of the new classification on clinical practice. METHODS: We reviewed the medical records of 280 ET syndrome patients in an ongoing cross-sectional study in a Chinese population and reclassified them according to the new criteria. Clinico-demographic characteristics were compared between ET and ET-plus patients. Risk factors of diagnosis of ET-plus were explored using logistic regression. RESULTS: A total of 121 patients (50.8%) were reclassified as having ET and 117 as having ET-plus. ET-plus group was significantly older at tremor onset, less educated, and more likely to have cranial tremor, depression symptom, anxiety symptom, and probable REM sleep behavior disorder. ET-plus group also showed more severe upper limb tremor and cognition impairment. Regression analysis identified four independent risk factors associated with ET-plus: late tremor onset (OR 3.04, 95%CI 1.60-5.79), less educated (OR 0.91, 95%CI 0.85-0.97), severe upper limb tremor (OR 2.46, 95%CI 1.30-4.62), and presence of cranial tremor (OR 2.30, 95%CI 1.20-4.41). CONCLUSIONS: The new classification scheme emphasized that ET syndrome is heterogeneous. ET-plus cannot be seen as a subtype or a diagnosis of ET syndrome, but rather as a placeholder, representing an area of current scientific uncertainty.

Prevalence and Risk Factors of Depression and Anxiety in Essential Tremor Patients: A Cross-Sectional Study in Southwest China.

Background: Essential tremor (ET) is one of the most common movement disorders, and it has been associated with anxiety and depression, but risk factors for these mental symptoms are unclear. This study aimed to evaluate the prevalence and potential risk factors of depression and anxiety in ET patients in China. Methods: This cross-sectional study involved 245 Han Chinese patients with ET. Depression was assessed using the Hamilton Depression Rating Scale-24 Items, and anxiety was assessed using the Hamilton Anxiety Rating Scale. Clinico-demographic characteristics were compared between patients with or without depression or anxiety. Results: We revealed that 63.3% of patients had at least mild anxiety and 54.3% had at least mild depression. Severity of anxiety or depression was correlated with lower Mini-Mental State Exam score (P = 0.028 and P = 0.002, respectively), higher self-report functional disability score (P = 0.027 and P = 0.003, respectively), as well as the presence of tremor in the neck (both P < 0.001), face (P = 0.025 and P < 0.001, respectively), or voice (both P < 0.001). Binary logistic regression identified female sex, presence with cranial tremor, and greater functional disability score as risk factors of anxiety; the last two factors were also the determinants of depression. Neither anxiety nor depression correlated with physician-assessed severity of arm or leg tremor. Conclusion: Chinese ET patients show high prevalence of depression and anxiety. ET patients should be screened for these mental symptoms, especially women and those with cranial tremor and self-reported functional disability.

Association between suicide and multiple sclerosis: An updated meta-analysis.

BACKGROUND: Whether multiple sclerosis is associated with a higher rate of suicide remains controversial. Therefore, we aimed to evaluate the risk of suicide in multiple sclerosis patients based on meta-analysis of previously published data. METHODS: We searched for studies that measured the suicide risk in multiple sclerosis patients compared with general population that were published up to 1 December 2018 in PubMed, EMBASE, and Web of Science databases. Sixteen studies fulfilled the eligibility criteria. We performed random-effects meta-analyses to calculate suicide rate ratio (SRR) and 95% confidence intervals (CIs) for patients with multiple sclerosis. RESULTS: The association between suicide and multiple sclerosis was statistically significant with a pooled SRR 1.72 (95%CI 1.48-1.99, I-squared = 55.0%). Risk of suicide at diagnosis of multiple sclerosis (SRR 2.12, 95% CI 1.84-2.46; I-squared = 4.4%) was higher than the risk of suicide at symptom onset (SRR 1.69; 95% CI 1.43-2.00; I-squared = 0.0%). Gender may exert an influence on the impact of sex on the association between MS multiple sclerosis and suicide, but this requires is controversial and need more further studies to demonstrate. CONCLUSION: Our meta-analysis shows a significant association between suicide and multiple sclerosis, although ethnic and geographical differences were not considered. These findings should be confirmed and extended in future large studies.

Frequency and factors related to drooling in Chinese patients with multiple system atrophy: a cross-sectional study.

PURPOSE: Drooling is a common symptom of neurodegenerative diseases. We aimed to explore the frequency of drooling and its relationship to clinical features in a relatively large cohort of Chinese patients with multiple system atrophy (MSA). METHODS: We conducted a cross-sectional survey of 143 patients with MSA. Patients with drooling were identified as those with a score ≥ 1 on item 6 of the Unified Parkinson's Disease Rating Scale. Additional scales were used to rate daily functionality, neurologic and cognitive capabilities, levels of anxiety and depression, and sleep quality. These results were compared between patients with and without drooling. RESULTS: The frequency of drooling in this cohort was 59.4% (85/143). Drooling was associated with significantly poorer scores on the Unified MSA Rating Scale (subscore I, subscore II, subscore IV, total score), Pittsburgh Sleep Quality Index, Hamilton Depression Scale, Hamilton Anxiety Scale, and Mini-Mental State Examination. After adjusting for confounders, regression analysis identified two independent risk factors for drooling: parkinsonism-associated MSA (OR 2.54, 95% CI 1.15-5.65) and hypomimia (OR 3.18, 95% CI 1.32-7.68). CONCLUSIONS: Drooling is relatively common among Chinese MSA patients, and parkinsonism-associated MSA and hypomimia appear to be independent risk factors for drooling. The severity of this symptom correlates with the presence of severe motor symptoms, anxiety, depression, and sleep disorders.

Systematic review and meta-analysis of observational studies to understand the prevalence of restless legs syndrome in multiple sclerosis: an update.

OBJECTIVE: Multiple sclerosis (MS) is related to the demyelination of intracranial nerves at multiple sites, while restless legs syndrome (RLS) appears to be caused by dysfunction of the dopaminergic system. Since RLS prevalence is higher among MS patients than in the general population, we carried out an updated meta-analysis to understand whether the two diseases might be associated. METHOD: Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were searched for observational and case-controlled studies of RLS prevalence in MS. Eligible studies were meta-analyzed using Stata 12.0. RESULTS: Pooled RLS prevalence among MS patients of various ethnicities was 26%, and prevalence was lower in Asia (20%) than outside Asia (27%). Prevalence was higher among cross-sectional studies (30%) than among case-control studies (23%). RLS prevalence was higher among female than male MS patients (26% vs. 17%), and it was higher among MS patients than among healthy controls (OR 3.96, 95%CI 3.29-4.77, p < 0.001). CONCLUSION: Our meta-analysis updates the most recent meta-analysis in 2013 and provides perhaps the first reliable pooled estimate of RLS prevalence in MS. The available evidence strongly suggests that RLS risk is higher among MS patients than healthy controls.