Cognitive impairment in Chinese adult patients with type III spinal muscular atrophy without disease-modifying treatment.

Objective: Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by the degeneration of motor neurons in the spinal cord. It remains uncertain whether the cognitive performance of adult patients with SMA is impaired. The objective of this study was to assess the cognitive profile of adult Chinese patients with SMA and the association between clinical features and cognitive ability, particularly executive function. Methods: This cross-sectional study included 22 untreated adult patients with type III SMA and 20 healthy subjects. The following variables were assessed: general intelligence, memory, attention, language, executive function, depression, anxiety, and other demographic and clinical parameters. In addition, physical function was evaluated using the Hammersmith Functional Motor Scale Expanded (HFMSE), the Revised Upper Limb Module (RULM), and the 6-Minute Walk Test (6MWT). Results: SMA patients had lower scores than healthy subjects in the Verbal Fluency Test, Stroop effect, Total Errors, Perseverative Responses, Perseverative Errors, and Non-perseverative Errors in the Wisconsin Card Sorting Test, showing impaired abilities of SMA patients in executive function. In the Attention Network Test (ANT), the results indicated that the SMA patients also had selective deficits in their executive control networks. Ambulant patients had better executive function test performance than non-ambulant ones. Compromised executive abilities in patients with SMA were correlated with a younger age at onset, poorer motor function, and higher levels of anxiety and depression. Conclusion: Our study presented the distribution of cognitive impairment in a Chinese cohort with SMA. Patients with type III SMA showed selective deficits in executive function, which may be associated with disease severity, physical impairment, depression and anxiety. Future cognitive studies, accounting for motor and emotional impairment, are needed to evaluate if executive impairment is driven by specific brain changes or by those confounding factors.

High-Definition Transcranial Direct Current Stimulation Improves Decision-Making Ability: A Study Based on EEG.

High-definition transcranial direct current stimulation (HD-tDCS) has been shown to modulate decision-making; however, the neurophysiological mechanisms underlying this effect remain unclear. To further explore the neurophysiological processes of decision-making modulated by HD-tDCS, health participants underwent ten anodal (n = 16)/sham (n = 17) HD-tDCS sessions targeting the left DLPFC. Iowa gambling task was performed simultaneously with electroencephalography (EEG) before and after HD-tDCS. Iowa gambling task performance, the P300 amplitude, and the power of theta oscillation as an index of decision-making were compared. Behavioral changes were found that showed anodal HD-tDCS could improve the decision-making function, in which participants could make more advantageous choices. The electrophysiological results showed that the P300 amplitude significantly increased in CZ, CPZ electrode placement site and theta oscillation power significantly activated in FCZ, CZ electrode placement site after anodal HD-tDCS. Significant positive correlations were observed between the changes in the percent use of negative feedback and the changes in theta oscillation power before and after anodal HD-tDCS. This study showed that HD-tDCS is a promising technology in improving decision-making and theta oscillation induced by may be a predictor of improved decision-making.

Case report: Anti-GAD65 antibody-associated autoimmune encephalitis following HPV vaccination.

Human papillomavirus (HPV) infection is a sexually transmitted disease that may lead to cervical cancer. HPV vaccines have been implemented widely to prevent this. While generally few complications of vaccination are reported, there have been occasional reports of adverse reactions post-vaccination. The safety profile of the HPV vaccine is reassuring. However, since its introduction, several serious post-vaccination central nervous system complications have been reported; however, causality has not been established. Herein, we describe a 39-year-old woman who developed seizures and experienced a rapid decline in memory shortly after her first dose of the HPV vaccine. Cranial magnetic resonance imaging and cerebrospinal fluid analysis were performed, and the patient was diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-associated autoimmune encephalitis. She responded well to high-dose glucocorticoids. Four-month follow-up revealed full recovery and absence of recurrence. Since the HPV vaccine is administered worldwide, this case should raise clinicians' awareness regarding the possible CNS complications related to vaccinations, such as anti-GAD65 antibody-associated AE.

Case Report: Migraine-Like Headache With Visual Aura Initiated by Endovascular Coiling Treatment for a Posterior Cerebral Artery Aneurysm.

Cervical, anterior, and middle cerebral artery aneurysm is a causative factor for migraine, and endovascular treatment usually improves migraine headache. Posterior cerebral artery (PCA) aneurysm is a rare condition, and its association with migraine is very rarely reported. In addition, endovascular coiling treatment causing migraine-like headache has never been reported. Here, we describe a newly developed migraine-like headache with visual aura after endovascular coiling treatment for PCA aneurysm in a 31-year-old female patient. One month after the endovascular therapy, the patient stopped using the antiplatelet agents clopidogrel and aspirin and presented with an episodic headache attack twice a month with typical migraine features, including visual aura, right-sided temporal throbbing pain accompanied with nausea, vomiting, and photophobia. The recurrence of migraine-like headache with visual aura was terminated by clopidogrel administration. The generation of the migraine-like headache with visual aura is probably associated with microemboli due to endovascular coiling. This case supports the hypothesis that migraine with aura can be associated with microemboli of variant origins.

Risk stratification for REM sleep behavior disorder in patients with Parkinson's disease: A PRISMA-compliant meta-analysis and systematic review.

This study aimed to compare whether the characteristics of Parkinson's disease (PD) patients between probably rapid eye movement sleep behavior disorder (RBD) and confirmed RBD versus non-RBD are differing using a meta-analytic approach. We systematically searched PubMed, EmBase, and the Cochrane library for eligible studies throughout October 2018 in this meta-analysis. The clinical characteristics of PD patients presented with probably RBD, confirmed RBD, or non-RBD were analyzed. The pooled odds ratios and weighted mean differences with corresponding 95 % confidence intervals were calculated for categories and continuous data, respectively. All the pooled analyses were conducted using random-effects model. Forty-seven studies recruited a total of 8019 PD patients were included in the final meta-analysis. The summary results indicated significant differences between probable RBD and non-RBD for PD duration, levodopa dosage daily, Hoehn-Yahr stage, UPDRS-III, UPDRS-motor score, UPDRS activity of daily living, Epworth Sleepiness scale, male percentage, dyskinesia, orthostatic hypotension, constipation, and fluctuations present. Moreover, confirmed RBD versus non-RBD showed significant differences for age, PD duration, levodopa dosage daily, Mini-Mental State Examination, Hoehn-Yahr stage, UPDRS-motor score, Epworth Sleepiness scale, male percentage, dyskinesia, hallucination, insomnia, dementia, orthostatic hypotension, falls, and fluctuations present. Furthermore, the difference of confirmed RBD versus non-RBD was significantly elderly than probable RBD versus non-RBD. Moreover, PD patients with confirmed RBD with lower Mini-Mental State Examination as compared with probable RBD corresponding PD patients without RBD. In addition, PD patients with confirmed RBD versus probable RBD was associated with high Hoehn-Yahr stage as compared with non-RBD. Finally, patients with confirmed RBD with high incidence of insomnia as compared with probable RBD corresponding PD patients without RBD. The results provide the comprehensive differences in the patients' characteristics among probable RBD, confirmed RBD, and non-RBD in PD patients.

Improved Cognitive Promotion through Accelerated Magnetic Stimulation.

Noninvasive brain stimulation to enhance cognition is an area of increasing research interest. Theta burst stimulation (TBS) is a novel accelerated form of stimulation, which more closely mimics the brain's natural firing patterns and may have greater effects on cognitive performance. We report here the comparative assessment of the effect of conventional high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) protocols and TBS protocols on cognition enhancement in healthy controls. Sixty healthy adults (34 males and 26 females) were randomized and counterbalanced and assigned to HF-rTMS (n = 20), TBS (n = 20), or sham (n = 20) groups. The promotion effects of different parameters of prefrontal stimulation on working memory and executive function were compared, as assessed by performance in N-back tasks and the Wisconsin Card Sorting Test (WCST). Both HF-rTMS and intermittent TBS (iTBS) groups displayed a significant improvement in N-back tasks, with an effect size of 0.79 and 1.50, respectively. Furthermore, the iTBS group displayed a significant improvement in the WCST, with an effect size of 0.84. The iTBS group demonstrated higher effect sizes than the HF-rTMS group (t = 2.68, p = 0.011), with an effect size of 0.85. However, no improvement in other tasks was observed (p > 0.05). Intermittent TBS has a stronger cognitive promoting effect than conventional rTMS. In summary, our findings provide direct evidence that iTBS may be a superior protocol for cognitive promotion.

Serial Dopamine Transporter Imaging of Nigrostriatal Function in Parkinson's Disease With Probable REM Sleep Behavior Disorder.

The current study aimed to confirm whether probable rapid eye movement sleep behavior disorder (pRBD) is associated with a specific pattern of striatal dopamine depletion in an international, multicenter, prospective cohort of patients with Parkinson's disease (PD). Two hundred and seventy de novo, drug-naïve patients with PD underwent dopamine transporter (DAT) single photon emission computed tomography with 123I-FP-CIT at baseline and 1, 2, and 4 years after the initial scan. The diagnosis of pRBD was based on the 10-item RBD Screening Questionnaire. Striatal DAT binding levels and their rates of decline were compared between patients with pRBD and those without. At baseline, patients in the PD-pRBD+ group showed lower striatal DAT binding in the caudate (which was more pronounced in the less-affected hemisphere) and in the putamen. During the 4-year follow-up, patients in the PD-pRBD+ group consistently exhibited greater DAT loss than patients in the PD-pRBD- group with comparable disease duration in all four striatal subregions. These patients also exhibited a more rapid decrease in DAT binding in the caudate and a less prominent interhemispheric asymmetry in the putamen. The distinct pattern of striatal DAT depletion may contribute to a more malignant phenotype of PD associated with RBD, specifically faster progression of motor symptoms.

Efficacy and Safety of Thrombolytic Therapy for Stroke with Unknown Time of Onset: A Meta-Analysis of Observational Studies.

BACKGROUND: Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies available for patients with known-onset stroke (KOS). Whether rt-PA treatment would improve functional outcomes in patients with stroke with unknown time of onset (UTOS) is undetermined, we aimed to systematically assess the efficacy and safety of thrombolysis for UTOS patients in this meta-analysis. METHODS: A systematic literature search of Medline, Embase, and Cochrane Library was conducted. We considered the relevant data comparing thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients or thrombolyzed UTOS patients versus thrombolyzed KOS patients. Treatment efficacy and safety were measured according to modified Rankin Scale scores of 0-2 (mRS 0-2), and the presence of spontaneous intracerebral hemorrhage (SICH) or mortality at 90 days respectively. RESULTS: A total of 11 studies with 2581 patients meeting the inclusion criteria were included in the meta-analysis. All the patients had an ischemic lesion that was assessed by imaging including computed tomography or magnetic resonance imaging. Among these studies, 6 compared the thrombolytic efficacy in thrombolyzed UTOS patients with that in nonthrombolyzed UTOS patients (mRS 0-2: odds ratio [OR] =1.76, 95% confidence interval [CI] 1.11-2.81, P = .02), and 8 studies compared thrombolyzed UTOS patients with thrombolyzed KOS patients (mRS 0-2: OR = 0.87, 95% CI 0.66-1.15, P = .33). The incidence of SICH and mortality at 90 days had no difference between thrombolyzed UTOS patients versus nonthrombolyzed UTOS patients and thrombolyzed UTOS patients versus thrombolyzed KOS patients (all P > .05). CONCLUSIONS: Data from observational studies suggest that thrombolysis for UTOS patients had significantly favorable outcomes at 90 days compared with nonthrombolyzed patients.

Effect of Intensive and Standard Lipid-Lowering Therapy on the Progression of Stroke in Patients With Coronary Artery Syndromes: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis demonstrated the effect of intensive versus standard statins on the risk of stroke in patients with coronary artery syndromes (CAS). PubMed, Embase, the Cochrane library, and clinicaltrials.gov were searched, and the retrieved studies were undertaken for randomized controlled trials (RCTs) throughout September 2018. Studies that were designed as RCTs and recruited at least 1000 CAS patients followed up greater than 1 year were eligible for this study. The summary relative risk with the 95% confidence interval was used as an effect estimate and calculated using the random-effects model. Five RCTs comprising a total of 39,612 coronary syndrome patients with reported 1236 stroke events were included in this meta-analysis. The summary result indicated a 14% reduction in the risk of stroke in CAS patients receiving intensive statin therapy as compared to standard statin therapy. The significant differences mainly occurred in mean age ≥60 years (P = 0.007), percentage of males ≥80% (P = 0.011), percentage diabetes mellitus ≥ 15% (P = 0.018), percentage hypertension ≥50% (P = 0.030), percentage of current smokers <30% (P = 0.011), percentage of prior myocardial infarction ≥50% (P = 0.011), percentage of peripheral arterial disease ≥10% (P = 0.030), patients with stable CAS (P = 0.011), patients using atorvastatin (P = 0.015), follow-up duration ≥3 years (P = 0.011), and study with moderate quality (P = 0.013). Intensive statin therapy should be considered for CAS patients at high risk of stroke events. Further large-scale RCT should be conducted to verify the results of stratified analysis in this study.

A transcranial sonography study of brainstem and its association with depression in idiopathic generalized epilepsy with tonic-clonic seizures.

Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with depression. But, up to date, the association of BR alterations in TCS with depression in patients with epilepsy has never been reported. This study was to investigate the possible role of BR examination via TCS in patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-TCS) and depression. Forty-six patients with IGE-TCS and 45 healthy controls were recruited. Echogenicity of the caudate nuclei (CN), lentiform nuclei (LN), substantia nigra (SN), and BR and widths of the lateral ventricle (LV) frontal horns and the third ventricle (TV) were assessed via TCS. The determination of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), and depression severity measured by Chinese version Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E) and Beck Depression Inventory-II (BDI-II). The width of TV in patients with epilepsy was found significantly larger than that in healthy controls (p = 0.001), but there was no significant difference in TV width between patients with IGE-TCS with and without depression. There were no significant differences between patients with IGE-TCS and healthy controls in LV frontal horn width, as well as in SN, CN, LN, and BR echogenicity. Here, it seems that patients with IGE-TCS were detected with smaller SN echogenic area compared with controls though they had no statistical significance. Patients with IGE-TCS with hypoechogenic BR had significantly higher C-NDDI-E and BDI-II scores than those with normal BR signal, and most patients with IGE-TCS with depression exhibited hypoechogenic BR, but few patients with IGE-TCS without depression exhibited hypoechogenic BR. In conclusion, BR echogenic signal alterations in TCS can be a biomarker for depression in epilepsy, but it might not be associated with epilepsy itself. The alterations of SN echogenic area and TV width in TCS may reflect a potential role of SN and diencephalon structure in the pathogenesis of epilepsy, which needs to be further elucidated.

Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis.

OBJECTIVE: A 2-stage genome-wide association was conducted to explore the genetic etiology of amyotrophic lateral sclerosis (ALS) in the Chinese Han population. METHODS: Totally, 700 cases and 4,027 controls were genotyped in the discovery stage using Illumina Human660W-Quad BeadChips. Top associated single nucleotide polymorphisms from the discovery stage were then genotyped in an independent cohort with 884 cases and 5,329 controls. Combined analysis was conducted by combining all samples from the 2 stages. RESULTS: Two novel loci, 1p31 and 12p11, showed strong associations with ALS. These novel loci explained 2.2% of overall variance in disease risk. Expression quantitative trait loci searches identified TYW/CRYZ and FGD4 as risk genes at 1p13 and 12p11, respectively. CONCLUSIONS: This study identifies novel susceptibility genes for ALS. Identification of TYW3/CRYZ in the current study supports the notion that insulin resistance may be involved in ALS pathogenesis, whereas FGD4 suggests an association with Charcot-Marie-Tooth disease.

Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis.

OBJECTIVE: This study aimed to conduct a meta-analysis to explore and summarise the evidence regarding the association between obstructive sleep apnoea (OSA) and the subsequent risk of vascular outcomes and all-cause mortality. METHODS: Electronic databases PubMed, Embase and the Cochrane Library were searched to identify studies conducted through May 2016. Prospective cohort studies that reported effect estimates with 95% CIs of major adverse cardiac events (MACEs), coronary heart disease (CHD), stroke, cardiac death, all-cause mortality and heart failure for different levels versus the lowest level of OSA were included. RESULTS: A total of 16 cohort studies reporting data on 24 308 individuals were included. Of these, 11 studies reported healthy participants, and the remaining five studies reported participants with different diseases. Severe OSA was associated with an increased risk of MACEs (relative risk (RR): 2.04; 95% CI 1.56 to 2.66; P<0.001), CHD (RR: 1.63; 95% CI 1.18 to 2.26; P=0.003), stroke (RR: 2.15; 95% CI 1.42 to 3.24; P<0.001), cardiac death (RR: 2.96; 95% CI 1.45 to 6.01; P=0.003) and all-cause mortality (RR: 1.54; 95% CI 1.21 to 1.97; P<0.001). Moderate OSA was also significantly associated with increased risk of MACEs (RR: 1.16; 95% CI 1.01 to 1.33; P=0.034) and CHD (RR: 1.38; 95% CI 1.04 to 1.83; P=0.026). No significant association was found between mild OSA and the risk of vascular outcomes or all-cause mortality (P>0.05). Finally, no evidence of a factor-specific difference in the risk ratio for MACEs among participants with different levels of OSA compared with those with the lowest level of OSA was found. CONCLUSIONS: Severe and moderate OSAs were associated with an increased risk of vascular outcomes and all-cause mortality. This relationship might differ between genders. Therefore, further large-scale prospective studies are needed to verify this difference.

Clinical variations in Parkinson's disease patients with or without REM sleep behaviour disorder: a meta-analysis.

This study aimed to evaluate the clinical variations in patients with Parkinson's disease (PD) with (PDRBD) or without REM sleep behaviour disorder (RBD) (Non-RBD), and PDRBD patients were classified into Confirmed-RBD (definite diagnosis with polysomnography, PSG) and Probable-RBD (without PSG re-confirmation). The clinical difference between the groups of patients was measured as an odds ratio (OR) or standardized mean difference (SMD, Cohen d). A total of 31 articles with data from 5,785 participants were obtained for our analysis. Overall, the occurrence of Confirmed-RBD was more frequent in male patients (OR = 1.25; p = 0.038), elderly patients (SMD = 0.25; p = 0.000), and patients with longer disease duration (SMD = 0.30; p = 0.000), increased Hoehn-Yahr scale (SMD = 0.30; p = 0.000), and higher UPDRS-III score (SMD = 0.38; p = 0.002). On the other hand, the frequency of Probable-RBD was increased with disease duration (SMD = 0.29; p = 0.000), Hoehn-Yahr scale (SMD = 0.30; p = 0.000), and UPDRS-III score (SMD = 0.26; p = 0.001). Our study indicate that PDRBD patients may have different clinical features compared to patients with Non-RBD.

Ophthalmoplegia starting with a headache circumscribed in a line-shaped area: a subtype of ophthalmoplegic migraine?

Recurrent painful ophthalmoplegic neuropathy (RPON), formerly named ophthalmoplegic migraine (OM), is a rare condition characterized by the association of unilateral headaches and the ipsilateral oculomotor nerve palsy. The third cranial nerve is most commonly involved in the recurrent attacks. But it is still debated whether a migraine or an oculomotor neuropathy may be the primary cause of this disorder. Here, we report an elder patient who had a recurrent ophthalmoplegia starting with an unilateral headache circumscribed in an area shaped in a line linking the posterior-parietal region and the ipsilateral eye. And the headache had couple of features similar to that of migraine, such as past history of recurrent migraine attacks, accompaniments of nausea, vomiting, and phonophobia, response to flunarizine and sodium valproate. We may herein report a subtype of OM but not a RPON. This case report indicates that OM may exist as an entity and some OM may be wrongly grouped under the category of RPON in the current international headache classification.