Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

Stroke-like onset of calcified brain metastases with Wallerian degeneration: a case report and review of the literature.

INTRODUCTION: Metastatic brain tumors are a common complication of systemic cancer. They tend to have a chronic onset and are located at the gray-white junction of the cerebral hemispheres, those larger than 9.4 mm in diameter are often accompanied by substantial vasogenic edema. Herein, we report a rare case of calcified metastatic adenocarcinoma with Wallerian degeneration. In addition, we discuss the atypical manifestations of brain metastases. CASE REPORT: A 71-year-old man who went through stroke-like onset twice during 8 months with a history of resection of the left pulmonary adenocarcinoma 5 years prior was examined. Diffusion weighted magnetic resonance imaging of the brain showed an enlarged open-ring-shaped hyperintensity on the left periventricular white matter and basal ganglia, with Wallerian degeneration on the left cerebral peduncle. Brain computed tomography revealed nodular calcification of the lesion. The pathology of stereotactic biopsy indicated metastatic adenocarcinoma. CONCLUSION: When patients present with acute nervous system symptoms and a previous history of cancer, the possibility of metastases should be considered, even if neuroimaging is atypical.

Myelin oligodendrocyte glycoprotein antibody-associated disease preceding primary central nervous system lymphoma: causality or coincidence?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphomatous malignancy that affects the brain, spinal cord, leptomeninges, or eyes, in the absence of systemic diffusion. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly identified benign immune-mediated CNS inflammatory disorder with specific anti-MOG antibody seropositivity. These two seemingly unrelated nosological entities both have abundant clinical and radiological manifestations, and whether there is a potential link between them is unclear. CASE REPORT: We describe a 49-year-old man who presented progressive headache, dizziness, and unsteady gait with multifocal scattered T2 hyperintensities with contrast enhancement. The serum anti-MOG antibody test was positive, and a brain biopsy showed inflammatory infiltration. Initially, he was diagnosed with MOGAD and his condition improved after corticosteroid therapy. The patient relapsed with exacerbation of symptoms and neuroimaging showed new mass-forming lesions four months later. A second brain biopsy confirmed PCNSL. DISCUSSION: This is the first report of histologically confirmed successive MOGAD and PCNSL. Our case broadens the phenotypic spectrum of sentinel lesions in PCNSL. Though rare, PCNSL should be considered in patients diagnosed with benign CNS inflammatory disorder and responding well to steroid treatment when their clinical symptoms worsen and the imaging deteriorates. A timely biopsy is critical for accurate diagnosis and appropriate therapy.

Phenotyping the late- and younger-onset neuronal surface antibody-mediated autoimmune encephalitis: a multicenter study.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (<45) groups. The results showed that 56 (41.8%) patients were classified as late-onset NSAE, and 78 (58.2%) as younger-onset NSAE. There were more males, especially in the late-onset group (P = 0.036). Prodromal symptoms were more common in the younger-onset group (P = 0.004). Among the onset symptoms, more late-onset patients presented as seizures, while more younger-onset patients presented as psychiatric symptoms. Throughout the disease course, the late-onset patients were more likely to have memory dysfunction (P < 0.001), but less likely to have central hypoventilation (P = 0.045). The late-onset patients also had a significantly lower modified Rankin Scale score on admission (P = 0.042), required intensive care unit (ICU) admission less frequently during hospitalization (P = 0.042) and had a shorter hospital stay (P = 0.014). Our study revealed that the late- and younger-onset NSAE had a distinct spectrum of demographic features, presentations, and prognoses. More attention is needed for the younger-onset patients, given a higher disease severity on admission, more frequent requirement for ICU admission and longer length of stay.

Evaluation of CSF albumin quotient in neuronal surface antibody-associated autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Disruption of brain barriers is considered to be involved in the pathogenesis of neuronal surface antibody-associated autoimmune encephalitis (NSAE), but few studies have focused on their relationship. We aimed to explore the association between the integrity of brain barriers and clinical and paraclinical characteristics in patients with NSAE. METHODS: This retrospective study consecutively recruited patients with NSAE. The cerebrospinal fluid (CSF) / serum albumin quotient (Qalb) was used to evaluate the function of brain barriers. The data on demographic information, clinical manifestations, magnetic resonance imaging (MRI), CSF findings and prognosis were collected and analyzed. RESULTS: Of the 93 patients included, 33 (35.5%) patients were assigned to the elevated Qalb group and 60 (64.5%) patients to the normal Qalb group. Males and prodromal symptoms were more common in elevated Qalb group (both P < 0.05). The CSF white blood cell, protein, immunoglobulin G and albumin were significantly higher in elevated Qalb group (all P < 0.05). Patients with elevated Qalb were more likely to have brain lesions on MRI (60.6% versus 33.3%, P = 0.011). The modified Rankin Scale (mRS) scores at discharge and at last follow-up were significantly higher in patients with elevated Qalb than those with normal Qalb (both P < 0.05). After univariate and multivariate analyses, Qalb elevation (adjusted odds ratio = 3.96, 95% confidence interval = 1.15-13.59, P = 0.029) was demonstrated as the only independent risk factor for a poor prognosis. DISCUSSION: Males, prodromal symptoms, brain lesions on MRI, CSF pleocytosis, and elevated CSF protein were more common in NSAE patients with increased Qalb. Qalb elevation was an independent prognostic indicator for a poor prognosis in NSAE.

Detecting vulnerable carotid plaque and its component characteristics: Progress in related imaging techniques.

Carotid atherosclerotic plaque rupture and thrombosis are independent risk factors for acute ischemic cerebrovascular disease. Timely identification of vulnerable plaque can help prevent stroke and provide evidence for clinical treatment. Advanced invasive and non-invasive imaging modalities such as computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy can be employed to image and classify carotid atherosclerotic plaques to provide clinically relevant predictors used for patient risk stratification. This study compares existing clinical imaging methods, and the advantages and limitations of different imaging techniques for identifying vulnerable carotid plaque are reviewed to effectively prevent and treat cerebrovascular diseases.

Lymphomatosis cerebri: a rare diffuse leukoencephalopathy you should never miss.

INTRODUCTION: Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma that diffusely involves throughout the brain. In recent years, increasingly reported cases have notably broadened the spectrum of clinical and radiological features; however, it remains a great diagnostic challenge. CASE REPORT: We reported an atypical case of LC presented with subacute onset of focal neurological deficits and diffuse T2 hyperintensities without contrast enhancement on magnetic resonance imaging. He was initially considered as inflammatory leukoencephalopathy and received empirical corticosteroids, showing a dramatically clinical response. Three months later, the patient relapsed with deteriorating symptoms and enlarged brain lesions with mass-like enhancement. A diagnosis of LC was finally established according to the radiological and pathological findings. DISCUSSION: Though rare, LC should always be kept as a differential diagnosis of diffuse leukoencephalopathy. Neurologists should be aware of every detailed information about LC to avoid a delay of diagnostic biopsy in clinical practice.

Occurrence of Intracranial Hemorrhage and Associated Risk Factors in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is thought to be a rare but probably underestimated presentation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We conducted a systematic review and meta-analysis with the aim of comprehensively revealing the occurrence of ICH in patients with CADASIL. METHODS: English-language studies published up to September 30, 2021 were searched for in the MEDLINE (PubMed), Web of Science, and Cochrane Library databases. The design, patient characteristics, occurrence rate of ICH, and associated risk factors were retrieved for each identified relevant study. RESULTS: We enrolled 13 studies in the final meta-analysis, which included 1,310 patients with CADASIL. The probability of ICH occurrence in patients with CADASIL was 10.1% (95% confidence interval [CI]=5.6%-18.0%, I²=85.1%). When stratified by geographic region, the occurrence rate of ICH was much higher in Asians (17.7%; 95% CI=11.0%-28.5%, I²=76.3%) than in Europeans (2.0%; 95% CI=0.4%-10.8%, I²=82.8%). A higher burden of cerebral microbleeds (CMBs) and a history of hypertension were the most commonly recorded risk factors for ICH, which were available for three and two of the included studies, respectively. CONCLUSIONS: Our study suggests that ICH is an important clinical manifestation of CADASIL, especially in Asians. A higher burden of CMBs and the existence of hypertension were found to be associated with a higher probability of ICH occurrence in patients with CADASIL.

First-line immunotherapy of neuronal surface antibody-mediated autoimmune encephalitis: Assessment of therapeutic effectiveness and cost-efficiency.

OBJECTIVE: To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China. METHODS: Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency. RESULTS: Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP. CONCLUSION: The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

The Role of Exosomes as Mediators of Neuroinflammation in the Pathogenesis and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive dementia. Accumulation of ß-amyloid peptide 1-42 and phosphorylation of tau protein in the brain are the two main pathological features of AD. However, comprehensive studies have shown that neuroinflammation also plays a crucial role in the pathogenesis of AD. Neuroinflammation is associated with neuronal death and abnormal protein aggregation and promotes the pathological process of ß-amyloid peptide 1-42 and tau protein. The inflammatory components associated with AD include glial cells, complement system, cytokines and chemokines. In recent years, some researchers have focused on exosomes, a type of membrane nano vesicles. Exosomes can transport proteins, lipids, microRNAs and other signaling molecules to participate in a variety of signaling pathways for signal transmission or immune response, affecting the activity of target cells and participating in important pathophysiological processes. Therefore, exosomes play an essential role in intercellular communication and may mediate neuroinflammation to promote the development of AD. This paper reviews the occurrence and development of neuroinflammation and exosomes in AD, providing a deeper understanding of the pathogenesis of AD. Furthermore, the role of exosomes in the pathogenesis and treatment of AD is further described, demonstrating their potential as therapeutic targets for neuroinflammation and AD in the future.

Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome: A state-of-the-art review.

The Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome (KLHL 11-PNS) was first identified in 2019. This novel antibody, targeting the intracellular KLHL 11 antigen, can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. It is thought to be a biomarker for a T-cell autoimmunity response. The most likely immunopathogenesis of KLHL 11-PNS appears to be linked to cytotoxic T-cell-mediated neuronal injury and loss. Patients have adult-male predilection, rhombencephalitis (brainstem and / or cerebellar involvement), and a robust oncological correlation with testicular germ cell tumors (predominately seminoma). Brain magnetic resonance imaging demonstrated T2 / fluid-attenuated inversion recovery hyperintensities and atrophy of the temporal lobe, cerebellum, and brainstem. Most patients responded poorly to immunotherapy and oncotherapy and thus had a poor long-term prognosis. We review the literature and provide an update of current knowledge regarding KLHL 11-PNS, including epidemiology, underlying mechanism, clinical presentations, paraclinical and oncological findings, diagnostic workup, and treatment approaches.

Seizures and epilepsy in multiple sclerosis, aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease.

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

New cerebral microbleeds in AF patients on non-vitamin K oral anticoagulants or warfarin: One-year follow-up.

ABSTRACT: Anticoagulant treatment increases the risk of intracerebral hemorrhage (ICH), but whether the treatment, more specifically non-vitamin K oral anticoagulants (NOACs), increases the risk of cerebral microbleeds (CMBs) remains uncertain. We performed this study to investigate the development of new CMBs due to NOACs or warfarin treatment in patients with atrial fibrillation (AF).We prospectively recruited AF patients before anticoagulation from June 2016 to June 2018. We performed susceptibility-weighted imaging (SWI) examinations on all enrolled AF patients and re-examined SWI 1 year later. We compared demographic features and new CMBs between the NOACs group and the warfarin group. Univariate analysis of clinical factors was performed according to the development of new CMBs; and age, a HAS-B(L)ED score, warfarin use, and the presence of baseline CMBs were then selected for inclusion in the multivariate logistic regression model.A total of 72 AF patients were recruited, 29 of whom were assigned to the NOACs group and 43 to the warfarin group. Finally, 1 patient in the NOACs group (3.4%) and 9 patients (20.9%) in the warfarin group developed new CMBs after 1 year follow-up (P = .08). Univariate analysis showed that age, a HAS-B(L)ED score ≥4, the presence of baseline CMBs were associated with the development of new CMBs (P < .05). And multivariate regression analysis showed baseline CMBs (P = .03, odds ratio = 6.37, 95% confidence interval 1.15-35.36) was independently related to the increase in new CMBs.AF patients treated with NOACs may have a decreased trend in the development of new CMBs compared with those treated with warfarin. Baseline CMBs increased the frequency of new CMBs during anticoagulant treatment. The development of new CMBs in AF patients with anticoagulation requires further longitudinal studies with longer follow-up in larger samples.

Evaluation of the Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes in China.

Background: Recently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China. Methods: An eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored. Results: The cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria. Conclusion: The updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

Association between plasminogen activator inhibitor-1 gene polymorphisms and susceptibility to Parkinson's disease in Chinese patients.

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disease that usually leads to memory impairment, cognitive decline and dementia. Previous studies have reported that plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms play important roles in cardiovascular diseases, obesity, inflammation and other diseases. However, the role of PAI-1 in the diagnosis of Parkinson's disease has not been reported so far. METHODS: This study was a case-control study. This study included 131 PD patients and 97 healthy volunteers. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphic loci of five different regions in PAI-1 gene (rs2227631, rs1799889, rs6092, rs2227694 and rs7242). 60 PD patients and 60 healthy volunteers were selected to detect the plasma PAI-1 concentration. The allele and genotype frequencies of SNPs were assessed using the SHEsis program. RESULTS: We found that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in the PD patients. Statistically significant difference for rs1799889 could be observed in overdominant model. In subgroup analysis, a significant difference in genotype frequency distribution and allele frequency was found for rs2227631 and rs1799889 between early-onset PD group and the control group. For cognitive dysfunction, the subcomponent showed that GG genotype frequency and G allele frequency of rs2227631 was significantly higher in normal cognition group. The codominant model of rs1799889 was significantly different between the cognitive impairment group and the control group. In addition, the expression of PAI-1 in plasma of PD patients was significantly higher than that of controls, and further analysis showed that the expression of PAI-1 in patients with cognitive impairment was significantly higher than that in patients with cognitive normal. CONCLUSION: Our results indicate that the PAI-1 gene rs2227631 and rs1799889 polymorphisms were significantly associated with PD susceptibility in the Chinese Han population. PAI-1 has the potential to become a new therapeutic target and diagnostic marker.

Anti-Ma2 Antibody-Associated Paraneoplastic Neurological Syndromes: A Pilot Study.

Paraneoplastic neurologic syndromes (PNSs) are a heterogeneous group of disorders caused by the remote effects of cancer with immune-mediated pathogenesis. Anti-Ma2 antibody was defined as one of the well-characterized onconeural antibodies that could help establish a definite PNS diagnosis. We aimed to report and explore patients with anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) who frequently exhibit sensorimotor neuropathy (SMN) using a new method of factor analysis of mixed data (FAMD). Clinical data from a case series of eight patients with definite diagnoses were retrospectively reviewed. FAMD conducted further analyses with a comprehensive visualization in R software. Our cohort, with a predominance of females (5/8), presented more frequently with SMN (4/8), followed by limbic encephalitis (LE) (3/8). Two patients with LE were found to have a testicular germ-cell tumor and a thymoma, respectively. In addition, a patient who developed chronic SMN was diagnosed with multiple myeloma (MM) involving multiple organs. FAMD exhibited the overall features into a two-dimensional coordinate and located each individual into their corresponding position with high relevance. It provided a clue for determining their potential relationships and predictors. Our findings indicated that Ma2-PNS could frequently involve the peripheral nervous system, MM might be one of its associated cancers with a presentation of chronic SMN, and FAMD might be a clinically valuable tool.

Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States.

OBJECTIVE: This research attempted to explore the neuroprotective effect of choline and establish evidence for future dietary recommendations and nutritional interventions to maintain a proper cognitive function among elders aged >60 years in the US. METHOD: This cross-sectional study retrieved data of 2,393 eligible elderly participants from the 2011-2014 National Health and Nutrition Examination Survey. Combining dietary and supplement choline intake, total choline intake was evaluated using the 24-hour dietary recall method and the dietary supplement questionnaire. Total choline intake was categorized into tertiles, which ranged at <187.60 mg/day (T1), 187.60-399.50 mg/day (T2), and >399.50 mg/day (T3). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, Animal Fluency (AF) test, and Digit Symbol Substitution test (DSST) was used to measure cognitive function. Participants who scored the lowest 25th percentile in each cognitive test were classified in the low cognitive function (LC) group. Logistic regression models were implemented to examine the association between total choline intake and the incidence of LC. RESULTS: In the CERAD test, the risk of LC was significantly lower in T2 than T1 (OR: 0.668, 95% CI: 0.493-0.904, and P = 0.006) when adjusted for age, gender, BMI, alcohol consumption, and hypertension. Similarly, T2 was associated with a significantly lower risk of LC when assessed by the AF test (OR: 0.606, 95% CI: 0.580-0.724, and P < 0.001) and DSST (0.584, 95% CI: 0.515-0.661, and P < 0.001). In all three cognitive measures, the T3 of the total choline intake was not associated with cognitive function compared to T1. CONCLUSION: Total choline intake at 187.06-399.50 mg/day reduces the risk of LC by approximately 50% compared to intake at <187.6 mg/day. The findings of this research may be used to establish dietary recommendations and nutritional interventions to optimize the cognitive function among elders.