Acquired tonsillar herniation related to spontaneous intracranial hypotension: case reports.

Background: Acquired prolapse of the cerebellar tonsils in spontaneous intracranial hypotension (SIH) patients is rare. This study aims to evaluate neuroimaging changes of acquired prolapse of the cerebellar tonsils below the foramen magnum in SIH patients due to spontaneous spinal cerebrospinal fluid leakage, which was treated by targeted epidural blood patches (EBP). Methods: We retrospectively reviewed clinical and neuroimaging characteristics of 5 cases of SIH with acquired prolapse of the cerebellar tonsils that received targeted EBP in our institution from January 2013 to December 2016. Results: Of these SIH patients, all of them suffered from an orthostatic headache. Initial cranial MRI demonstrated descent of the cerebellar tonsils ≥5 mm. Intrathecal gadolinium-enhanced spinal MR myelography and/or spinal MR hydrography were performed to evaluate the level of spinal cerebrospinal fluid leakage. Symptoms were alleviated in all 5 patients after two (n = 4), or three (n = 1) targeted EBP during hospitalization. Follow-up cranial MRI revealed that the descent of cerebellar tonsils was reversed after EBP treatment. Conclusion: Acquired tonsillar herniation can occur in patients with SIH and spinal cerebrospinal fluid leakage. Symptoms of these patients may be resolved and radiologic findings may be reversed after EBP treatment.

Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery.

Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.

Clinical value of dual-energy CT for predicting occult metastasis in central neck lymph nodes of papillary thyroid carcinoma.

OBJECTIVES: To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). METHODS: Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. RESULTS: A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology. (1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40 keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. CONCLUSIONS: DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. CLINICAL RELEVANCE STATEMENT: Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. KEY POINTS: • Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. • Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. • Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.

Bed Rest as a Protective Factor for Subdural Hematoma in Spontaneous Intracranial Hypotension: A Retrospective Study.

BACKGROUND: Subdural hematoma (SDH) is a potentially life-threatening complication in patients with spontaneous intracranial hypotension (SIH). Though bed rest is the basis of conservative treatment, no clear evidence exists regarding the association between bed rest and the later complication of SDH in these patients. OBJECTIVES: This study aimed to evaluate the association between bed rest and SDH development in patients with SIH. STUDY DESIGN: A retrospective study was conducted from March 2013 through December 2019. Four hundred twenty adult patients diagnosed with SIH were enrolled. Clinical presentations and radiographic findings were recorded. The cumulative duration of bed rest in hours was used to measure the bed rest length. The clinical outcomes during follow-up were assessed. METHODS: Categorical data were compared using chi-square tests; continuous data were compared using the Mann-Whitney U test or Kruskal-Wallis test. A backwards stepwise Cox proportional hazard regression model adjusted with confounders which differed between SDH and non-SDH in univariate analysis was used to estimate the risk of cumulative duration of bed rest for SDH. A stratified Cox regression was performed to exclude the effect of the treatment algorithm. RESULTS: Of the 420 patients with SIH, 88 (21%) were in the SDH Group and 332 (79%) were in the non-SDH (NSDH) Group. The cumulative duration of bed rest in hours was a protective factor for SDH in SIH (Hazard Ratio [HR] = 0.997; P < 0.001). A stratified Cox regression analysis showed that the cumulative duration of bed rest remained a protective factor for SDH both in patients who received conservative treatment before admission (HR = 0.997; P < 0.001) and in those who did not (HR = 0.996; P = 0.061). Age (HR = 1.029, 95% CI, 1.009-1.050; P = 0.004) and orthostatic headache (HR = 4.770, 95% 95% CI, 2.177-10.450; P < 0.001) were risk factors for SDH in SIH. The clinical outcomes, including length of hospital stay, epidural blood patch (EBP) therapy, and repeated EBP therapy, were higher in the SDH Group. The revisit rate was similar between the 2 groups. LIMITATIONS: Retrospective studies are susceptible to different radiological procedures and therapeutic strategies. A bed rest score based on a patient's memory is susceptible to recognition and reporting bias. This is a single-center study and the sample size is not large. The validity of the bed rest scale has not been previously evaluated in any other study. CONCLUSIONS: Bed rest was a protective factor for SDH in patients with SIH. With more time and proper treatment, patients with SIH who have an SDH can achieve good prognosis in the long term.

Safety and Effectiveness of Rasagiline in Chinese Patients with Parkinson's Disease: A Prospective, Multicenter, Non-interventional Post-marketing Study.

INTRODUCTION: Rasagiline is indicated for treating idiopathic Parkinson's disease (PD) as monotherapy and adjunct therapy to levodopa in patients. OBJECTIVES: To assess the post-marketing safety and tolerability of rasagiline in Chinese PD patients, as well as its effectiveness in improving motor symptoms. METHODS: This prospective, non-interventional, multicenter, cohort study included PD patients administered rasagiline monotherapy or adjunct therapy to levodopa. The primary outcome was the incidence of adverse drug reactions (ADRs) according to MedDRA® (version 22.0), and the secondary outcomes were the Parkinson's Disease Unified Rating Scale (UPDRS) part III, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Global-Improvement (CGI-I), assessed at Weeks 4, 12, and 24. RESULTS: In total, 734 patients, 95 in the monotherapy subgroup and 639 in the adjunct therapy subgroup, were included in the safety population. The incidence rates of all ADRs were comparable between the monotherapy (15.8%) and adjunct therapy (13.6%) subgroups. The most common ADRs by system organ class were nervous system disorders (5.6%), gastrointestinal disorders (3.3%), psychiatric disorders (1.8%), vascular disorders (1.2%), and general disorders and administration site conditions (1.1%). Five (0.7%) participants experienced 5 serious ADRs. Improvements in UPDRS part III, CGI-S and CGI-I at Weeks 4, 12 and 24 from baseline were observed. CONCLUSIONS: Safety data in this study indicated no extra safety concerns. Rasagiline is generally safe and well tolerated in Chinese PD patients. The safety profile and tolerability were in line with the established safety profile. Moreover, rasagiline reduced the severity of PD motor symptoms, confirming findings by previous clinical trials.

Neurocircuitry underlying the antidepressant effect of retrograde facial botulinum toxin in mice.

BACKGROUNDS: Botulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized. RESULTS: Here, we modeled MDD using mice subjected to chronic restraint stress (CRS). By pre-injecting BoNT/A into the unilateral whisker intrinsic musculature (WIM), and performing behavioral testing, we showed that pre-injection of BoNT/A attenuated despair- and anhedonia-like phenotypes in CRS mice. By applying immunostaining of BoNT/A-cleaved SNAP25 (cl.SNAP25197), subcellular spatial localization of SNAP25 with markers of cholinergic neurons (ChAT) and post-synaptic membrane (PSD95), and injection of monosynaptic retrograde tracer CTB-488-mixed BoNT/A to label the primary nucleus of the WIM, we demonstrated that BoNT/A axonal retrograde transported to the soma of whisker-innervating facial motoneurons (wFMNs) and subsequent transcytosis to synaptic terminals of second-order neurons induced central effects. Furthermore, using transsynaptic retrograde and monosynaptic antegrade viral neural circuit tracing with c-Fos brain mapping and co-staining of neural markers, we observed that the CRS-induced expression of c-Fos and CaMKII double-positive neurons in the ventrolateral periaqueductal grey (vlPAG), which sent afferents to wFMNs, was down-regulated 3 weeks after BoNT/A facial pre-administration. Strikingly, the repeated and targeted silencing of the wFMNs-projecting CaMKII-positive neurons in vlPAG with a chemogenetic approach via stereotactic injection of recombinant adeno-associated virus into specific brain regions of CRS mice mimicked the antidepressant-like action of BoNT/A pre-treatment. Conversely, repeated chemogenetic activation of this potential subpopulation counteracted the BoNT/A-improved significant antidepressant behavior. CONCLUSION: We reported for the first time that BoNT/A inhibited the wFMNs-projecting vlPAG excitatory neurons through axonal retrograde transport and cell-to-cell transcytosis from the injected location of the WIM to regulate depressive-like phenotypes of CRS mice. For the limited and the reversibility of side effects, BoNT/A has substantial advantages and potential application in MDD.

Diffusion along perivascular spaces as marker for impairment of glymphatic system in Parkinson's disease.

The brain glymphatic system is involved in the clearance of misfolding α-synuclein, the impaired glymphatic system may contribute to the progression of Parkinson's disease (PD). We aimed to analyze the diffusion tensor image along the perivascular space (DTI-ALPS) and perivascular space (PVS) burden to reveal the relationship between the glymphatic system and PD. A cross-sectional study using a 7 T MRI of 76 PD patients and 48 controls was performed to evaluate the brain's glymphatic system. The DTI-ALPS and PVS burden in basal ganglia were calculated. Correlation analyses were conducted between DTI-ALPS, PVS burden and clinical features. We detected lower DTI-ALPS in the PD subgroup relative to controls, and the differences were more pronounced in patients with Hoehn & Yahr stage greater than two. The decreased DTI-ALPS was only evident in the left hemisphere in patients in the early stage but involved both hemispheres in more advanced PD patients. Decreased DTI-ALPS were also correlated with longer disease duration, higher Unified Parkinson's Disease Rating Scale motor score (UPDRS III) and UPDRS total scores, as well as higher levodopa equivalent daily dose. Moreover, the decreased DTI-ALPS correlated with increased PVS burden, and both indexes correlated with PD disease severity. This study demonstrated decreased DTI-ALPS in PD, which might initiate from the left hemisphere and progressively involve right hemisphere with the disease progression. Decreased DTI-ALPS index correlated with increased PVS burden, indicating that both metrics could provide supporting evidence of an impaired glymphatic system. MRI evaluation of the PVS burden and diffusion along PVS are potential imaging biomarkers for PD for disease progression.

(+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate.

Background and purpose: Neutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis. Methods: Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis in vitro. Neutrophils treated with (+)-borneol at three different time points (-30 min, 0, and 30 min) associated with PMA stimulation were used to examine the effect of (+)-borneol on the formation of NETs. The ROS generation of neutrophils was also measured to explore the potential mechanism of the inhibitory effect of (+)-borneol on NETosis. Results: (+)-Borneol pretreatment inhibited NETosis induced by PMA. Immunofluorescence staining visualized and confirmed the inhibitory effect. (+)-Borneol inhibited the burst of ROS in neutrophils caused by PMA. Suppressing NADPH oxidase or protein kinase C (PKC) eliminated the effect of (+)-borneol on NETosis. Moreover, inhibiting Toll-like receptor 2 (TLR2) led to increased NETosis which can be inhibited by (+)-borneol. Conclusion: (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation in vitro. (+)-Borneol therapy may be effective in some NET-dependent conditions.

A Case Report of Neuronal Intranuclear Inclusion Disease Presenting With Recurrent Migraine-Like Attacks and Cerebral Edema: A Mimicker of MELAS.

Background: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease associated with the GGC repeats in the 5'-untranslated region (5'UTR) of NOTCH2NLC. NIID exhibits a wide range of clinical manifestations. However, patients presenting with recurrent migraine-like attacks and cerebral edema have only rarely been reported. Case Presentation: A Chinese female suffered probable migraines with aura for 10 years. At age of 51, aggravating migraine-like attacks co-occurred with a sudden encephalopathy-like episode. Brain MRI showed right cerebral edema and cortical enhancement. Serum lactic acid level was elevated at rest and significantly increased after a simplified serum lactic acid exercise test. The initial diagnosis was MELAS, while NIID was suspected after faint DWI high-intensity signals in the corticomedullary junction was retrospectively recognized. Mitochondrial genome sequencing and gene panel analysis of nuclear genes related to mitochondrial diseases failed to find any causative variants. Repeat-primed PCR and fluorescence amplicon length PCR of NOTCH2NLC gene identified an abnormal expansion of 118 GGC repeats in the 5'UTR of NOTCH2NLC gene. Conclusion: NIID should be taken into account for differential diagnosis of migraines and MELAS-like episodes. Besides the corticomedullary hyperintensity on DWI, cortical enhancement in contrast-enhanced brain MRI may also be a brain image marker for the differential diagnosis between MELAS and NIID with MELAS-like episodes.

Intracranial hypotension as a contributor to isolated cortical vein thrombosis.

BACKGROUND: Isolated cortical vein thrombosis (ICVT), a rare type of cerebral venous thrombosis (CVT), is diagnostically challenging in some cases, and intracranial hypotension (IH) is known to cause CVT. METHODS: In this study, we reviewed the clinical and imaging characteristics of ICVT in patients with IH caused by spinal cerebrospinal fluid leakage, based on a literature review and investigation of cases from our hospital. RESULTS: Between January 1, 2007, and November 1, 2019, 735 patients were diagnosed with IH at our hospital; three patients developed ICVT (incidence ~ 0.4%, 3/735), and the literature review yielded an additional 23 cases. Therefore, 26 patients (mean age 35.9 ± 11.4 years old) were included in this study. The most common symptoms were headache (100.0%, 26/26), focal neurological deficits (53.8%, 14/26), and seizure (34.6%, 9/26). The initial headache was orthostatic in 96.2% (25/26) of patients, and 38.5% (10/26) of patients reported a change in the headache pattern following diagnosis of ICVT. Neuroimaging findings associated with ICVT included the cord sign (61.5%, 16/26) and parenchymal brain lesions (46.2%, 12/26), such as intracerebral hemorrhage (30.8%, 8/26), hemorrhagic infarcts (11.5%, 3/26), and localized edema (11.5%, 3/26). The percentage of patients who received anticoagulation and epidural blood patch therapy was similar (69.2% [18/26] vs. 65.4% [17/26]), and most patients recovered completely (92.3%, 24/26). CONCLUSION: IH should be considered in the differential diagnosis in patients with ICVT. Knowledge of the relevant clinical and neuroimaging features is important to facilitate early diagnosis for favorable prognosis.

Inferring the Individual Psychopathologic Deficits With Structural Connectivity in a Longitudinal Cohort of Schizophrenia.

The prediction of schizophrenia-related psychopathologic deficits is exceedingly important in the fields of psychiatry and clinical practice. However, objective association of the brain structure alterations to the illness clinical symptoms is challenging. Although, schizophrenia has been characterized as a brain dysconnectivity syndrome, evidence accounting for neuroanatomical network alterations remain scarce. Moreover, the absence of generalized connectome biomarkers for the assessment of illness progression further perplexes the prediction of long-term symptom severity. In this paper, a combination of individualized prediction models with quantitative graph theoretical analysis was adopted, providing a comprehensive appreciation of the extent to which the brain network properties are affected over time in schizophrenia. Specifically, Connectome-based Prediction Models were employed on Structural Connectivity (SC) features, efficiently capturing individual network-related differences, while identifying the anatomical connectivity disturbances contributing to the prediction of psychopathological deficits. Our results demonstrated distinctions among widespread cortical circuits responsible for different domains of symptoms, indicating the complex neural mechanisms underlying schizophrenia. Furthermore, the generated models were able to significantly predict changes of symptoms using SC features at follow-up, while the preserved SC features suggested an association with improved positive and overall symptoms. Moreover, cross-sectional significant deficits were observed in network efficiency and a progressive aberration of global integration in patients compared to healthy controls, representing a group-consensus pathological map, while supporting the dysconnectivity hypothesis.

Choice of intravenous thrombolysis therapy in patients with mild stroke complaining of acute dizziness.

BACKGROUND: Quick identification of patients with mild ischemic stroke complaining of dizziness from other patients with benign peripheral vestibular disorders who also experience dizziness in the emergency department (ED) may be difficult. Decision-making on intravenous thrombolysis therapy (IVT) in patients whose chief symptoms include acute dizziness or vertigo remains a severe challenge for ED physicians. This study evaluated the diagnosis, treatment processes and the short-term outcomes in patients with mild vestibular stroke in the ED. METHODS: A total of 89 consecutive patients with mild ischemic stroke primarily presenting with vestibular symptoms, who arrived at ED within 4.5 after onset, and were admitted at the stroke center of Zhejiang Provincial People's Hospital between January 2015 and March 2021 were retrospectively enrolled. Patients treated with IVT (n = 47) were compared to patients without IVT (n = 42) in terms of demographics, onset-to-door time (ODT), baseline clinical characteristics, risk factors of stroke, imaging findings, and short-term outcomes. The correlation between these parameters and IVT decision-making was analyzed. RESULTS: Patients in IVT group more frequently presented with shorter ODT, focal neurological deficits (dysarthria, facial palsy, hemiglossoplegia, hemiparesis, hemisensory loss), disabling deficits, higher baseline National Institute of Health Stroke Scale (NIHSS) scores, and underwent multi-mode imaging before a decision. A higher proportion of isolated vestibular symptoms, acute transient vestibular syndrome, and vestibulo-vagal symptoms were found in the no-IVT group. There were no differences in demographics between the two groups. ODT was negatively correlated with the decision-making on IVT, and baseline NIHSS scores were positively correlated with the decision-making on IVT. CONCLUSION: ODT and baseline NIHSS scores were correlated with the IVT decision in mild stroke patients primarily presenting with vestibular symptoms. Severe vestibular symptoms and disabling deficits were weakly associated with IVT decision, while the vestibulo-oculomotor signs and multi-mode imaging did not result as the influencing factors promoting the IVT decision-making for mild vestibular stroke.

Neurological and psychiatric presentations associated with COVID-19.

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.

Pathological Gait Signatures of Post-stroke Dementia With Toe-Off and Heel-to-Ground Angles Discriminate From Alzheimer's Disease.

Given the limited power of neuropsychological tests, there is a need for a simple, reliable means, such as gait, to identify mild dementia and its subtypes. However, gait characteristics of patients with post-stroke dementia (PSD) and Alzheimer's disease (AD) are unclear. We sought to describe their gait signatures and to explore gait parameters distinguishing PSD from post-stroke non-dementia (PSND) and patients with AD. We divided 3-month post-stroke patients into PSND and PSD groups based on the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the activity of daily living (ADL). Thirty-one patients with AD and thirty-two healthy controls (HCs) were also recruited. Ten gait parameters in one single and two dual-task gait tests (counting-backward or naming-animals while walking) were compared among the groups, with adjustment for baseline demographic covariates and the MMSE score. The area under the receiver operating characteristic curve (AUC) was used to identify parameters discriminating PSD from individuals with PSND and AD. Patients with PSD and patients with AD showed impaired stride length, velocity, stride time, and cadence while patients with PSD had altered stance and swing phase proportions (all p ≤ 0.01, post hoc). Patients with AD had smaller toe-off (ToA) and heel-to-ground angles (HtA) (p ≤ 0.01) than HCs in dual-task gait tests. Individuals with PSD had a shorter stride length, slower velocity, and altered stance and swing phase percentages in all tests (p ≤ 0.01), but a higher coefficient of variation of stride length (CoVSL) and time (CoVST) only in the naming animals-task gait test (p ≤ 0.001) than individuals with PSND. ToA and HtA in the naming animals-task gait test were smaller in individuals with AD than those with PSD (p ≤ 0.01). Statistical significance persisted after adjusting for demographic covariates, but not for MMSE. The pace and the percentage of stance or swing phase in all tests, CoVST in the dual-task paradigm, and CoVSL only in the naming animals-task gait test (moderate accuracy, AUC > 0.700, p ≤ 0.01) could distinguish PSD from PSND. Furthermore, the ToA and HtA in the naming animals-task gait paradigm discriminated AD from PSD (moderate accuracy, AUC > 0.700, p ≤ 0.01). Thus, specific gait characteristics could allow early identification of PSD and may allow non-invasive discrimination between PSD and AD, or even other subtypes of dementia.

Structural and Functional Deficits in Patients with Poststroke Dementia: A Multimodal MRI Study.

Although many neuroimaging studies have reported structural and functional abnormalities in the brains of patients with cognitive impairments following stroke, little is known about the pattern of such brain reorganization in poststroke dementia (PSD). The present study was aimed at investigating alterations in spontaneous brain activity and gray matter volume (GMV) in PSD patients. We collected T1-weighted and resting-state functional magnetic resonance imaging data from 20 PSD patients, 24 poststroke nondementia (PSND) patients, and 21 well-matched normal controls (NCs). We compared the differences among the groups in GMV and the fractional amplitude of low-frequency fluctuations (fALFF). Then, we evaluated the relationship between these brain measures and cognitive assessments and explored the possible distinguisher for PSD by receiver operating characteristic (ROC) curve analysis. PSD patients showed smaller GMV in the right superior temporal gyrus and lower fALFF values in the right inferior frontal gyrus than both PSND patients and NCs, but such differences were not observed between PSND patients and NCs. Moreover, GMV in the left medial prefrontal cortex showed a significant positive correlation with the Mini-Cog assessment in PSD patients, and GMV in the left CPL displayed the highest area under the ROC curve among all the features for classifying PSD versus PSND patients. Our findings suggest that PSD patients show dementia-specific structural and functional alteration patterns, which may help elucidate the pathophysiological mechanisms underlying PSD.

Inhibition of endoplasmic reticulum stress reverses synaptic plasticity deficits in striatum of DYT1 dystonia mice.

BACKGROUND AND OBJECTIVE: Striatal plasticity alterations caused by endoplasmic reticulum (ER) stress is supposed to be critically involved in the mechanism of DYT1 dystonia. In the current study, we expanded this research field by investigating the critical role of ER stress underlying synaptic plasticity impairment imposed by mutant heterozygous Tor1a+/- in a DYT1 dystonia mouse model. METHODS: Heterozygous Tor1a+/- mouse model for DYT1 dystonia was established. Wild-type (Tor1a+/+, N=10) and mutant (Tor1a+/-, N=10) mice from post-natal day P25 to P35 were randomly distributed to experimental and control groups. Patch-clamp and current-clamp recordings of SPNs were conducted with intracellular electrodes for electrophysiological analyses. Striatal changes of the direct and indirect pathways were investigated via immunofluorescence. Golgi-Cox staining was conducted to observe spine morphology of SPNs. To quantify postsynaptic signaling proteins in striatum, RNA-Seq, qRT-PCR and WB were performed in striatal tissues. RESULTS: Long-term depression (LTD) was failed to be induced, while long-term potentiation (LTP) was further strengthened in striatal spiny projection neurons (SPNs) from the Tor1a+/- DYT1 dystonia mice. Spine morphology analyses revealed a significant increase of both number of mushroom type spines and spine width in Tor1a+/- SPNs. In addition, increased AMPA receptor function and the reduction of NMDA/AMPA ratio in the postsynaptic of Tor1a+/- SPNs was observed, along with increased ER stress protein levels in striatum of Tor1a+/- DYT1 dystonia mice. Notably, ER stress inhibitors, tauroursodeoxycholic acid (TUDCA), could rescue LTD as well as AMPA currents. CONCLUSION: The current study illustrated the role of ER stress in mediating structural and functional plasticity alterations in Tor1a+/- SPNs. Inhibition of the ER stress by TUDCA is beneficial in reversing the deficits at the cellular and molecular levels. Remedy of dystonia associated neurological and motor functional impairment by ER stress inhibitors could be a recommendable therapeutic agent in clinical practice.

Enzymatic/Magnetic Hybrid Micromotors for Synergistic Anticancer Therapy.

Micro/nanomotors (MNMs), which propel by transforming various forms of energy into kinetic energy, have emerged as promising therapeutic nanosystems in biomedical applications. However, most MNMs used for anticancer treatment are only powered by one engine or provide a single therapeutic strategy. Although double-engined micromotors for synergistic anticancer therapy can achieve more flexible movement and efficient treatment efficacy, their design remains challenging. In this study, we used a facile preparation method to develop enzymatic/magnetic micromotors for synergetic cancer treatment via chemotherapy and starvation therapy (ST), and the size of micromotors can be easily regulated during the synthetic process. The enzymatic reaction of glucose oxidase, which served as the chemical engine, led to self-propulsion using glucose as a fuel and ST via a reduction in the energy available to cancer cells. Moreover, the incorporation of Fe3O4 nanoparticles as a magnetic engine enhanced the kinetic power and provided control over the direction of movement. Inherent pH-responsive drug release behavior was observed owing to the acidic decomposition of drug carriers in the intracellular microenvironment of cancer cells. This system displayed enhanced anticancer efficacy owing to the synergetic therapeutic strategies and increased cellular uptake in a targeted area because of the improved motion behavior provided by the double engines. Therefore, the demonstrated micromotors are promising candidates for anticancer biomedical microsystems.

Normal-sized basal ganglia perivascular space related to motor phenotype in Parkinson freezers.

Changes in basal ganglia (BG) perivascular spaces (PVSs) are related to motor and cognitive behaviors in Parkinson's disease (PD). However, the correlation between the initial motor phenotype and PVSs distribution/burden in PD freezing of gait (FOG) remains unclear. In addition, the normal-sized PVSs (nPVSs) have not been well-studied. With high-resolution 7T-MRI, we studied nPVSs burden in BG, thalamus, midbrain and centrum semiovale. The numbers and volume of nPVSs were assessed in 10 healthy controls, 10 PD patients without FOG, 20 with FOG [10 tremor dominant (TD), 10 non-TD subtype]. Correlation analyses were further performed in relation to clinical parameters. In this proof of concept study, we found that the nPVS burden of bilateral and right BG were significantly higher in freezers. A negative correlation existed between the tremor score and BG-nPVSs count. A positive correlation existed between the levodopa equivalent daily dose and BG-nPVSs count. The nPVS burden correlated with the progression to FOG in PD, but the distribution and burden of nPVS differ in TD vs. non-TD subtypes. High resolution 7T-MRI is a sensitive and reliable tool to evaluate BG-nPVS, and may be a useful imaging marker for predicting gait impairment that may evolve into FOG in PD.

MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1.

Cerebral ischemia-reperfusion (CI/R) injury is a serious complication when treating patients experiencing ischemic stroke. Although the microRNA miR-27a-3p reportedly participates in ischemia/reperfusion (I/R) injury, its actions in CI/R remain unclear. To mimic CI/R in vitro, HT22 cells were subjected to oxygen glucose deprivation/reoxygenation (OGD/R). The results indicate that OGD inhibited growth and induced apoptosis among HT22 cells. The apoptosis was accompanied by increases in activated caspases 3 and 9 and decreases in Bcl-2. Oxidative stress was also increased, as indicated by increases in ROS and malondialdehyde and decreases in glutathione and superoxide dismutase. In addition, OGD induced G1 arrest in HT22 cells with corresponding upregulation of FOXO1 and p27 Kip1, suggesting the cell cycle arrest was mediated by FOXO1/p27 Kip1 signaling. Notably, FOXO1 was found to be the direct target of miR-27a-3p in HT22 cells. MiR-27a-3p was downregulated in OGD/R-treated HT22 cells, and miR-27a-3p mimics partially or entirely reversed all of the in vitro effects of OGD. Moreover, miR-27a-3p agomir significantly alleviated the symptoms of CI/R in vivo in a rat model of CI/R. Thus, MiR-27a-3p appears to suppress CI/R injury by targeting FOXO1.

Exosomes derived from human induced pluripotent stem cell-derived neural progenitor cells protect neuronal function under ischemic conditions.

Compared with other stem cells, human induced pluripotent stem cells-derived neural progenitor cells (iPSC-NPCs) are more similar to cortical neurons in morphology and immunohistochemistry. Thus, they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes. Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury. However, there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons. In this study, we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95% N2 and 5% CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes. Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen- and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium. Additionally, it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons. Further, it increased the length of the longest neurite in the oxygen- and glucose-deprived neurons. These findings validate the hypothesis that exosomes from iPSC-NPCs exhibit a neuroprotective effect on oxygen- and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth. This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (approval No. SRRSH20191010) on October 10, 2019.