Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Gait impairment-related axonal degeneration in Parkinson's disease by neurite orientation dispersion and density imaging.

Microstructural alterations in the brain networks of Parkinson's disease (PD) patients are correlated with gait impairments. Evaluate microstructural alterations in the white matter (WM) fiber bundle tracts using neurite orientation dispersion and density imaging (NODDI) technique in PD versus healthy controls (HC). In this study, 24 PD patients and 29 HC were recruited. NODDI and high-resolution 3D structural images were acquired for each participant. The NODDI indicators, including the intracellular neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), were compared between the two groups. Diffusion-weighted (DW) images were preprocessed using MRtrix 3.0 software and the orientation distribution function to trace the main nerve fiber tracts in PD patients. Quantitative gait and clinical assessment scales were used to compare the medication "ON" and "OFF" states of PD patients. The NDI, ODI, and ISO values of the WM fiber bundles were significantly higher in PD patients compared to HC. Fiber bundles, including the anterior thalamic radiation, corticospinal tract, superior longitudinal fasciculus, forceps major, cingulum, and inferior longitudinal fasciculus, were found to be significantly affected in PD. The NDI changes of PD patients were well correlated with stride lengths in the "ON" state; ODI changes were correlated with the stride time in the "ON" and "OFF" states and ISO changes were correlated with the stride time and cadence in the "ON" state. In conclusion, combination of NODDI technique and gait parameters can help detect gait impairment in PD patients early and accurately.

Mesenchymal stromal cell biotherapy for Parkinson's disease premotor symptoms.

Parkinson's disease (PD) is a neurodegenerative disorder with motor deficits due to nigrostriatal dopamine depletion and with the non-motor/premotor symptoms (NMS) such as anxiety, cognitive dysfunction, depression, hyposmia, and sleep disorders. NMS is presented in at least one-fifth of the patients with PD. With the histological information being investigated, stem cells are shown to provide neurotrophic supports and cellular replacement in the damaging brain areas under PD conditions. Pathological change of progressive PD includes degeneration and loss of dopaminergic neurons in the substantia nigra of the midbrain. The current stem cell beneficial effect addresses dopamine boost for the striatal neurons and gliovascular mechanisms as competing for validated PD drug targets. In addition, there are clinical interventions for improving the patient's NMS and targeting their autonomic dysfunction, dementia, mood disorders, or sleep problems. In our and many others' research using brain injury models, multipotent mesenchymal stromal cells demonstrate an additional and unique ability to alleviate depressive-like behaviors, independent of an accelerated motor recovery. Intranasal delivery of the stem cells is discussed for it is extensively tested in rodent animal models of neurological and psychiatric disorders. In this review, we attempt to discuss the repairing potentials of transplanted cells into parkinsonism pathological regions of motor deficits and focus on preventive and treatment effects. From new approaches in the PD biological therapy, it is believed that it can as well benefit patients against PD-NMS.

Probiotics for constipation and gut microbiota in Parkinson's disease.

INTRODUCTION: Constipation is one of the common non-motor symptoms in Parkinson's disease that significantly impacts patient quality of life. Probiotics supplementation may improve constipation symptoms, but its effect on the gut microbiota population is unclear. METHODS: In this randomized controlled study, 46 PD patients with constipation according to Rome Ⅲ criteria were recruited. The number of complete bowel movements per week, degree of defecation effort, Bristol stool Scale (BSS), Patient Assessment of Constipation symptom (PAC-SYM) and Patient assessment of constipation quality of life questionnaire (PAC-QOL) were collected pre- and post-intervention to evaluate the constipation symptoms. In addition, fresh feces of subjects before and after intervention and healthy controls were collected for 16s rRNA gene V3-V4 region sequencing to compare bacterial flora differences. RESULTS: Compared with the control group, the treatment group increased the average number of complete bowel movements per week (1.09 ± 1.24 vs. 0.04 ± 0.64, P < 0.001). Probiotics supplementation reduced the BSS score (0.65 ± 0.93 vs. -0.17 ± 0.94, P = 0.004), PAC-SYM score (4.09 ± 6.31 vs. -1.83 ± 4.14, P < 0.001), PAC-QOL score (10.65 ± 16.53 vs. 0.57 ± 12.82, P = 0.042), and degree of defecation effort score (1.00 ± 0.80 vs. 0.00 ± 0.30, P < 0.001). The improvement rate of constipation in the probiotics group was significantly higher than that in the control group (52.2% vs. 8.7%, P = 0.001). PD patients showed intestinal flora disorders compared to healthy controls. After 12 weeks of probiotics treatment, g_Christensenella_sp._Marseille-P2437 significantly increased, while g_Eubacterium_oxidoreducens_group, g_Eubacterium_hallii_group and s_Odoribacter_sp._N54.MGS-14 decreased (p < 0 0.05). CONCLUSIONS: Probiotics treatment can effectively improve the constipation symptoms of PD patients and positively affected the gut microbiota.

Brain Surface Area Alterations Correlate With Gait Impairments in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease with progressive gait, cognition, and overall functional decline. Surface area changes are frequently seen with aging. In neurodegenerative diseases, the changes can be evident with disease progression. The current study aimed to study the regional microstructural alterations using surface-based morphometry to correlate with gait measures of the pace and rhythm domains in PD patients. We hypothesize that specific regional surface changes can be associated with PD gait impairments. Surface analysis might provide a useful tool for assessing PD for functional status and specific motor domains, such as gait in PD, and potentially could serve as an imaging marker in conjunction with other imaging markers. Twenty-seven PD patients and 37 healthy controls were included. The clinical assessment included Mini-Mental State Exanimation, PD motor assessment, clinical gait testing, and objective/quantitative gait assessment. For patients with PD, all motor and gait testing were performed during both OFF and ON medication states. Three Tesla MRI and high-resolution 3D structural images were acquired with an MP-RAGE pulse sequence. Structural image data preprocessing was performed using the DPABISurf toolbox. Clinical characteristics between PD and control group were compared, and correlation between the surface area and behavioral data were analyzed. At the left lateral temporal cortex (LTC) and right inferior parietal cortex (IPC), PD patients have significantly larger surface areas when compared to controls (P < 0.05) using surface-based morphometry. The surface area changes of the left LTC and right IPC were associated with the worse performance of gait assessed by Berg Balance Scale and Timed Up and Go during OFF (P < 0.01). The left LTC area changes significantly correlated with the number of steps, velocity, and the stride length of the pace domain in the ON state. Our findings suggest that PD is associated with a characteristic regional pattern of larger surface area in the left LTC and right IPC. These regional changes were associated with the pace domain of the gait in the ON state. Overall, surface-based analyses might provide a useful tool for assessing PD for functional status and specific motor domains, such as gait in PD, and potentially could serve as an imaging marker.

Corrigendum: A Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhood.

[This corrects the article DOI: 10.3389/fneur.2021.675616.].

A Novel Variation in the Mitochondrial Complex I Assembly Factor NDUFAF5 Causes Isolated Bilateral Striatal Necrosis in Childhood.

Background: Bilateral striatal necrosis (BSN) is characterized by symmetrical degeneration, predominantly of the caudate and putamen nucleus, in the basal ganglia. It is associated with numerous acquired and hereditary neuro-developmental and motor dysfunction-related pathological conditions. BSN results in high morbidity and mortality among infants and children, and its diagnosis is clinically challenging due to several overlapping disease phenotypes. Therefore, a precise genetic diagnosis is urgently needed for accurate genetic counseling and improved prognostic outcomes as well. Objective: To identify novel missense mutations in the NDUFAF5 gene as a cause of childhood BSN in members of a Chinese family and summarize the clinical characteristics of patients with the NDUFAF5 gene mutations. Methods: This study included a large family living in a remote northwestern area of China. Three siblings developed a neurological disorder characterized by generalized dystonia within the first decade of their lives. Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) showed bilateral lesions of the putamen. Biochemical and genetic approaches were used to identify the cause of BSN. Results: Sequence analysis showed no pathogenic variation in PANK2, SLC25A19, SLC19A3, and NUP62 genes and in the entire mitochondrial genome as well. Whole-exome sequencing revealed compound heterozygous mutations consisting of NDUFAF5:c.425A > C(p.E142A) and c.836T > G (p.M279R). The father, a healthy sister, and a healthy brother of the affected siblings carried the c.836T > G mutation, and the mother carried the c.425A > C mutation. These variants were absent in 100 ethnically matched non-BSN controls. In silico analysis demonstrated that the E142A and M279R mutations in NDUFAF5 protein significantly perturbed the normal conformation of the protein due to alterations in the hydrogen bonding patterns around the evolutionarily conserved catalytic domains, leading to its loss of function in the early stage of mitochondrial complex I assembly. Conclusions: We identified a novel compound heterozygous mutation (c.425A > C and c.836T > G) in the NDUFAF5 gene as the potential cause of autosomal recessive childhood BSN, which extended the pathogenic variation spectrum of the NDUFAF5 gene. This study provides substantial evidence for further improvement of genetic counseling and better clinical management of BSN affected individuals.

Next-generation sequencing combined with serological tests based pathogen analysis for a neurocysticercosis patient with a 20-year history:a case report.

BACKGROUND: Neurocysticercosis (NCC) is the most common helminthic infection of the central nervous system (CNS) caused by the larval stage of Taenia solium. Accurate and early diagnosis of NCC remains challenging due to its heterogeneous clinical manifestations, neuroimaging deficits, variable sensitivity, and specificity of serological tests. Next-generation sequencing (NGS)-based pathogen analysis in patient's cerebrospinal fluid (CSF) with NCC infection has recently been reported indicating its diagnostic efficacy. In this case study, we report the diagnosis of a NCC patient with a symptomatic history of over 20 years using NGS analysis and further confirmation of the pathology by immunological tests. CASE PRESENTATION: This study reports the clinical imaging and immunological features of a patient with a recurrent headache for more than 20 years, which worsened gradually with the symptom of fever for more than 7 years and paroxysmal amaurosis for more than 1 year. By utilizing NGS technique, the pathogen was detected in patient's CSF, and the presence of Taenia solium-DNA was confirmed by a positive immunological reaction to cysticercus IgG antibody in CSF and serum samples. The symptoms of the patient were alleviated, and the CSF condition was improved substantially after the anti-helminthic treatment. CONCLUSIONS: This study suggests that combining CSF NGS with cysticercus IgG testing may be a highly promising approach for diagnosing the challenging cases of NCC. Further studies are needed to evaluate the parasitic DNA load in patients' CSF for the diagnosis of disease severity, stage, and monitoring of therapeutic responses.

Prevalence and profile of nocturnal disturbances in Chinese patients with advanced-stage Parkinson's disease: a cross-sectional epidemiology study.

BACKGROUND: The impact of nocturnal disturbance (ND) in Parkinson's disease on quality of life of patients in Western Countries is increasingly understood. Our study aimed to investigate ND prevalence and its quality of life impact in patients with advanced Parkinson's disease in China. METHODS: In a multicenter, tertiary-care hospital, outpatient-based, cross-sectional study, patients with advanced Parkinson's disease (Modified Hoehn & Yahr [H&Y] Stage II-IV with ≥3 h awake "off" time/day) from 10 tertiary hospitals throughout China completed the Parkinson's Disease Sleep Scale-2 (PDSS-2) and Parkinson's Disease Questionnaire-39 (PDQ-39). The primary endpoint was the percentage of patients with significant ND (PDSS-2 total score ≥ 15). Additional endpoints were demographic and clinical characteristics, PDSS-2 and PDQ-39 total and subscale scores, correlation between PDSS-2 and PDQ-39, and risk factors for ND and higher PDSS-2 or PDQ-39 scores. RESULTS: Of 448 patients analyzed (mean age 63.5 years, 47.3% female), 70.92% (95% confidence interval: 66.71, 75.13) had significant ND. Presence of ND and higher PDSS-2 scores were associated with longer disease duration and higher H&Y stage. Presence of ND was also associated with more awake "off" time/day and female sex. PDQ-39 scores were significantly worse for patients with ND versus those without ND; worse scores were associated with more awake "off" time/day, female sex, and higher H&Y stage. PDSS-2 and PDQ-39 total scores were associated: Pearson correlation coefficient 0.62 (p < 0.001). CONCLUSIONS: In China, ND was highly prevalent in patients with advanced Parkinson's disease and adversely impacted quality of life. This study highlights the importance of early diagnosis and optimized management of ND in patients with Parkinson's disease in China.

Rhombencephalitis due to Listeria monocytogenes infection with GQ1b antibody positivity and multiple intracranial hemorrhage: a case report and literature review.

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium that causes central nervous system infection. We report a case of rhombencephalitis caused by L. monocytogenes infection, which mimicked Bickerstaff's brainstem encephalitis, and GQ1b antibody positivity and multiple intracranial foci were observed. A 68-year-old male patient presented with a nonspecific prodrome of faintness, forehead tightness, and walking instability. This was followed by progressive cranial nerve palsies, limb weakness, cerebellar signs, hyperpyrexia, and impaired consciousness. Brain imaging showed multiple abnormal brainstem and cerebellar signals that were accompanied by blood infiltration without any lesion enhancement. Serum GQ1b antibody positivity led to an initial diagnosis of Bickerstaff's brainstem encephalitis, which was treated with immunosuppressive therapy with limited efficacy. A pathogen examination helped confirm L. monocytogenes infection. A combination of meropenem and trimethoprim-sulfamethoxazole therapy was applied and the patient recovered without sequelae. The symptoms and imaging of Listeria rhombencephalitis are nonspecific. Accurate diagnosis and prompt treatment of this condition are essential. Whether Listeria infection triggers an autoimmune response remains unclear.

The Effects of Dietary Nutrition on Sleep and Sleep Disorders.

Sleep disorder significantly affects the life quality of a large number of people but is still an underrecognized disease. Dietary nutrition is believed to play a significant impact on sleeping wellness. Many nutritional supplements have been used trying to benefit sleep wellness. However, the relationship between nutritional components and sleep is complicated. Nutritional factors vary dramatically with different diet patterns and depend significantly on the digestive and metabiotic functions of each individual. Moreover, nutrition can profoundly affect the hormones and inflammation status which directly or indirectly contribute to insomnia. In this review, we summarized the role of major nutritional factors, carbohydrates, lipids, amino acids, and vitamins on sleep and sleep disorders and discussed the potential mechanisms.

The Roles of Monocyte and Monocyte-Derived Macrophages in Common Brain Disorders.

The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.

Neurological symptoms of familial hemophagocytic lymphohistiocytosis type 2.

Hemophagocytic lymphohistiocytosis with central nervous system involvement is caused by inflammatory factor storms. The inflammatory factors invade the blood-brain barrier and further infiltrate brain tissue resulting in associated neurological and/or psychiatric symptoms in hemophagocytic lymphohistiocytosis with central nervous system involvement patients. This case report is based on a 14-year-old male patient who experienced intermittent dizziness and blurred vision about five years before admission as well as lower limb weakness and unstable walking approximately three years before admission. His brain MRI showed abnormal signals in the bilateral cerebellar hemisphere and vermis, right occipital lobe, and bilateral basal ganglia. The cerebrospinal fluid examination revealed an increase in nucleated cells, mainly monocytes, and elevated protein. He had no typical manifestation of hemophagocytic lymphohistiocytosis in the early stage, such as fever, cytopenia, or hepatosplenomegaly. He was misdiagnosed with meningoencephalitis or tuberculous meningitis. Perforin gene detection revealed a mutation in the PRF1 gene. The final diagnosis of type 2 familial hemophagocytic lymphohistiocytosis was made based on the neurological symptoms and genetic test. The possibility of hemophagocytic lymphohistiocytosis needs to be considered in patients with unexplained central nervous system symptoms, even if the patient does not have typical hemophagocytic lymphohistiocytosis symptoms, such as fever, cytopenia, or hepatosplenomegaly. We present the neurological symptoms of familial hemophagocytic lymphohistiocytosis type 2.

Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients.

OBJECTIVE: The current study aimed to investigate the prevalence and risk factors of restless legs syndrome (RLS) in patients undergoing hemodialysis, as well as the mortality and risks of cardiovascular and cerebrovascular events. METHODS: A total of 354 hemodialysis patients from four hospitals were enrolled. RLS was diagnosed using the International RLS Study Group (IRLSSG) criteria. The patients were evaluated face-to-face using the IRLSSG rating scale, Epworth Sleepiness Scale (ESS), Hamilton Anxiety Scale, Hamilton Depression Scale, and Pittsburgh Sleep Quality Index (PSQI). The patients were followed up for 9 months. Death was considered an endpoint event. The cardiovascular and cerebrovascular events were investigated. RESULTS: The prevalence of RLS in hemodialysis patients was 40.7% and was associated with factors such as duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. The scores of the PSQI, ESS, and Hamilton Depression Scale in the RLS group were significantly higher than those in the non-RLS group (p < 0.05). During follow-ups, the incidence rate of cardiovascular diseases was 18.8% in the RLS group and 8.6% in the non-RLS group (p < 0.005). The IRLSSG rating scores were significantly higher in RLS patients with kidney transplantation failure compared with those without transplantation (p < 0.05). CONCLUSION: The prevalence of RLS was high in hemodialysis patients. The risk factors of RLS included duration of hemodialysis, hypersensitive C-reactive protein, hyperparathyroidism, glycosylated serum protein, and erythropoietin treatment. RLS affected sleep quality and emotion and increased the risk of cardiovascular diseases in hemodialysis patients. RLS was more severe in patients with kidney transplantation failure compared with those without transplantation.

A case report: 1-year follow-up of cerebral sparganosis mansoni with a stroke-like onset.

BACKGROUND: Sparganosis mansoni is a parasitic disease caused by infection with the larvae of Spirometra spp. tapeworms. Its clinical manifestations and severity depend on the migration and the location of the parasites. The proportion of cerebral sparganosis in all Spirometra mansoni infections is 13.5% in Thailand and 12.4% in China. In the clinical setting, cerebral sparganosis is often misdiagnosed due to atypical characteristics, irregular intracranial location, and atypical epidemiology. CASE PRESENTATION: The patient in the case study suffered from an acute paroxysmal attack of lateral numbness, accompanied with focal epilepsy. He was admitted to the neurology department as a stroke patient but was later diagnosed with cerebral sparganosis mansoni following lab and radiology investigations. He was fully recovered and free of Spirometra mansoni one year after initial consultation following several courses of oral praziquantel. The current report focuses on the diagnosis, treatment and follow up of this patient. CONCLUSIONS: A case of cerebral sparganosis mansoni with a stroke-like onsetsuggests that in the clinical diagnosis, neurologists should pay attention to brain lesions and look out for the possibility of neuroparasitic infections when dealing with patients with stroke-like onset accompanied by epilepsy. Detections of relevant antibodies in blood and cerebrospinal fluid may be necessary. The combination of the epidemiological history, clinical manifestations, detection of parasite antibody, head radiology, pathological biopsy, and identification of parasites will help us in diagnosis and differential diagnosis.

Clinical and radiological characteristics of restless legs syndrome following acute lacunar infarction.

BACKGROUND: Recent studies have suggested that cerebral ischemic infarction may contribute to the development of restless legs syndrome (RLS). This study analyzed the clinical and radiological profiles of RLS with onset after acute lacunar infarction. METHODS: In this retrospective study we enrolled 244 consecutive patients with acute lacunar infarction between January 2012 and June 2014. RLS was identified and evaluated based on the International RLS Rating Scale (IRLS-RS). Individual sleep quality was assessed using the Epworth Sleepiness Scale (ESS). Psychological state was also assessed using the Hamilton Depression Scale (HDS) and the Hamilton Anxiety Scale (HAS). RESULTS: The incidence of RLS in patients with lacunar infarction was 5.33%. Our participant group consisted of nine males and four females. Three patients had symptoms in bilateral limbs, and 10 patients had symptoms only contralateral to the cerebral infarction. The infarctions were localized to the pons, centrum semiovale, thalamus, putamen, medulla, and occipital lobe. Contralateral paralysis was found in 13 patients, and contralateral sensory deficit in seven patients. The average IRLS-RS, ESS, HDS, HAS scores were 19.07 ± 8.70, 4.69 ± 5.82, 4.38 ± 4.68, and 3.85 ± 4.76, respectively. Nine patients had diabetes mellitus. After administration of dopaminergic drugs, patients' RLS significantly improved. CONCLUSIONS: The incidence of RLS after acute lacunar infarction was 5.33%. Pons, centrum semiovale, and basal ganglia were the common locations of responsible lesions. Compared to idiopathic RLS, symptoms of RLS after acute lacunar infarction appeared more unilateral and more likely involved the arm. Moreover, diabetes mellitus may be a risk factor for RLS in stroke patients.

Restless legs syndrome secondary to pontine infarction: Clinical analysis of five cases.

OBJECTIVE: Pontine infarction is a common type of stroke in the cerebral deep structures, resulting from occlusion of small penetrating arteries, may manifest as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction, but patients presenting with restless legs syndrome (RLS) are extremely rare. Herein, we reported five cases with RLS as a major manifestation of pontine infarction. METHODS: Five cases of pontine infarction related RLS were collected from July 2013 to February 2016. The diagnosis of RLS was made according to criteria established by the International RLS Study Group (IRLSSG) in 2003. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Severity of RLS was based on the International RLS Rating Scale (IRLS-RS). Sleep quality was assessed by Epworth Rating Scale (ERS), and individual emotional and psychological states were assessed by Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). RESULTS: The laboratory data at the onset including hemoglobin, serum concentration of homocysteine, blood urea nitrogen (BUN), creatinine, electrolytes, and thyroid hormones were normal. The electroencephalogram (EEG), lower-extremity somatosensory evoked potential (SEP), and nerve conduction velocity (NCV) in four limbs were normal. The average period of follow-up was 34.60 ± 12.76 months. The MRI examination showed acute or subacute pontine infarction lesions, 3 cases in the rostral inner side, 1 case in the rostral lateral and inner side, and 1 case in rostral lateral side. The neurological deficits included weakness in 4 cases, contralateral sensory deficit in 1 case, and ataxia in 2 cases. All 5 patients presented with symptom of RLS at or soon after the onset of infarction and 4 patients experienced uncomfortable sensations in the paralyzed limbs contralateral to the ischemic lesion. Their neurological deficits improved significantly 2 weeks later, but the symptoms of RLS did not resolve. Among them, 3/5 patients were treated with dopaminergic drugs. At the end of the follow-up, RLS symptom eventually resolved in 3 patients but persisted in two. The IRLS-RS, NIHSS and mRS scores were significantly lower at the onset than those at the last follow-up (P = 0.035, 0.024 and 0.049, respectively). However, there was no significant difference in the ERS, HDS and HAS scores (P = 0.477, 0.226 and 0.778, respectively). CONCLUSION: RLS can be an onset manifestation of pontine infarction, clinicians should be aware of this potential symptom. RLS usually occurs in the paralyzed limbs contralateral to the infarction lesion. The pathogenesis still needs further investigation.

miR-138 promotes migration and tube formation of human cytomegalovirus-infected endothelial cells through the SIRT1/p-STAT3 pathway.

Human cytomegalovirus (HCMV) has been reported to be linked to vascular disease through the induction of neovessel formation. We have previously reported that microRNA (miR)-217 and miR-199a-5p enhance endothelial angiogenesis via inhibition of sirtuin 1 (SIRT1) in HCMV-infected human umbilical vein endothelial cells (HUVECs). Here, we found that miR-138 also suppressed the expression of the SIRT1 protein and stimulated phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). Moreover, the regulation of p-STAT3 expression mediated by SIRT1 was found to promote HCMV-induced angiogenesis. These findings revealed that miR-138 might promote angiogenesis of HCMV-infected HUVECs by activating the SIRT1-mediated p-STAT3 pathway, and this could provide novel insights into HCMV-induced angiogenesis.