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.

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.

Predictors and prevalence of COVID-19 vaccination in patients with focal epilepsy following resection surgery.

BACKGROUND AND PURPOSE: In light of the ongoing COVID-19 pandemic, vaccination has emerged as the primary and most effective solution. The aim of this study was to examine compliance rates of vaccination and explore the factors that predict vaccine uptake among patients with epilepsy (PWE) who have undergone resection surgery. METHOD: To examine the variations in vaccination coverage, safety concerns, and factors influencing vaccination hesitancy among PWE who have undergone resection surgery, this study recruited patients with at least one-year follow-up. We utilized questionnaires to gather clinical characteristics and obtain information regarding COVID-19 vaccines. RESULTS: Among the 303 patients included in the study, a majority of 229 (75.58%) achieved a seizure-free outcome (Engel Ia). Of these patients, 178 (58.75%) received at least one dose of COVID-19 vaccine, and the vaccination rate has remained relatively consistent over the past six months. Nearly 94.95% of those who received the vaccine completed the full vaccination regimen, with the majority (n = 174, 97.75%) opting for an inactivated vaccine. Only three patients reported side effects unrelated to epilepsy, and one patient experienced a worsening of typical aura seizures within one month after vaccination. Notably, significant positive associations were observed between COVID-19 vaccine acceptance and adulthood (age 18 years or older) (OR = 1.820, 95% CI = 1.018-3.252, p = 0.043) as well as achieving a seizure-free outcome (OR = 2.823, 95% CI = 1.619-4.921, p < 0.001). Regarding the unvaccinated patients, approximately one-fifth expressed willingness to receive a future COVID-19 vaccine, while the remainder were hesitant (41.60%) or unsure (39.20%) about vaccination. These reservations mainly stemmed from concerns about the potential worsening of seizures and vaccine safety. CONCLUSIONS: Inactivated vaccines can be considered safe for individuals with epilepsy who have undergone resection surgery. The likelihood of being vaccinated was found to be comparatively higher among the cohort with seizure-free status or adults. To promote COVID-19 vaccination among children, it is crucial to implement comprehensive education and public awareness campaigns that emphasize the safety of vaccines. These efforts will help encourage widespread acceptance of vaccination and ensure the well-being of individuals with epilepsy.

COVID-19 vaccination hesitancy and safety among adult people with epilepsy in eastern China.

OBJECTIVE: This study assesses the hesitancy and safety of vaccination administration for the novel 2019 Coronavirus Disease (COVID-19) among adult people with epilepsy (PWE). METHODS: We recruited adult PWE who visited the outpatient epilepsy clinic from August 2021 to February 2022. We administered a structured questionnaire and a face-to-face interview regarding demographic factors, epilepsy characteristics, and relevant vaccine issues to all patients. Factors related to receiving a vaccine and epilepsy-related events after vaccination were then analyzed. RESULTS: A total of 501 PWE were surveyed; 288 were unvaccinated and 213 were vaccinated. Patients without jobs (OR: 0.59; 95% CI: 0.37-0.95, p = 0.03) were less likely to receive the vaccine compared to students or those with jobs. Other factors associated with vaccination were a higher number of anti-seizure medications (OR: 0.72; 95% CI: 0.55-0.95, p = 0.02) and a lower pre-vaccine seizure frequency (OR: 2.21; 95% CI: 1.06-4.59, p = 0.03). Of the 213 vaccinated patients, 10 (4.70%) reported at least one local and/or systemic side effect. Most patients (92.50%) did not report worse seizures within one month of vaccination. Poor ASM adherence (OR: 15.06; 95% CI: 1.75-129.87, p = 0.01) and fatigue/stimulant drinks such as caffeine (OR: 50.59; 95% CI: 7.57-337.94, p < 0.01) were significantly associated with seizure worsening within one month of receiving the COVID-19 vaccination. CONCLUSION: Almost two-fifths of patients with adult PWE have received a COVID-19 vaccine. Attention should be paid to educating epilepsy patients without jobs on the significance and safety of the vaccine. There was a low risk of seizure worsening in the short term after vaccination in PWE.

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.

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.

Managing depression and anxiety in patients with epilepsy in eastern China: A survey of epilepsy health professionals in Zhejiang Province.

OBJECTIVE: We aimed to evaluate the assessment and management of epilepsy with anxiety and depression, and their clinical practice based on a survey. METHODS: A cross-sectional survey of epilepsy health professionals was undertaken in Zhejiang Province using the modified International League Against Epilepsy (ILAE) Psychology Task Force questionnaire. We recorded the characteristics of participants and the practice of screening, referral, and treatment for depression and anxiety disorders. A total of 146 participants joined in the survey, of which 76.0% were neurologists, and 69 participants were the member of the Zhejiang Association Against Epilepsy (ZAAE). RESULTS: This survey revealed that almost all participants (87.7%) agreed that screening for depression and anxiety in patients with epilepsy (PWEs) was very important; however, the frequency of screening was very low (41.1% of participants screened less than 10% of patients, and 34.2% participants screened between 10% and 30% of patients). A higher frequency of screening was reported in the member group and compared with that in the non-member group (P = 0.025). The main barrier to screening was the lack of time during clinic visits: 81.5% participants included screening questions as part of their clinical review. When anxiety/depression was diagnosed, the next step should be to refer patients to a psychiatrist (78.1%). No standardized procedures and lack of mental health specialists trained to assess and/or manage PWEs, were the main barriers to follow-up assessment and management. Lack of appropriately trained mental health specialists was also the main barrier to psychological treatment for depression and anxiety. CONCLUSION: This survey highlighted that epilepsy healthcare professionals in Zhejiang province agreed on the importance of screening for psychiatric comorbidities in PWEs; however, the screening and management were actually insufficient. Certain barriers to screening, referral, and treatment were presented and improvements were recommended.

Evaluation of brain and spinal cord lesion distribution criteria at disease onset in distinguishing NMOSD from MS and MOG antibody-associated disorder.

OBJECTIVE: To validate the recently proposed imaging criteria in distinguishing aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD) at disease onset in a Chinese population. METHODS: We enrolled 241 patients in this retrospective study, including 143 AQP4-ab-seropositive NMOSD, 73 MS, and 25 MOG-AD. Cacciaguerra's criteria were described as fulfillment of at least 2/5 conditions including the absence of the combined juxtacortical/cortical lesions, the presence of longitudinal extensive transverse myelitis (LETM) lesions, the presence of periependymal-lateral ventricles lesions, the absence of Dawson's fingers lesions, and the absence of periventricular lesions. RESULTS: Fulfillment of at least 3/5 conditions was able to differentiate NMOSD from MS with a good diagnostic performance (accuracy = 0.92, sensitivity = 0.91, specificity = 0.93), yet failed to differentiate NMOSD from MOG-AD. LETM lesions showed the highest accuracy (0.78), sensitivity (0.70), and specificity (0.97) for NMSOD. CONCLUSION: Our research suggested the utility of Cacciaguerra's criteria in a Chinese population at disease onset. A better diagnostic performance in NMOSD could be attained with at least 3/5 conditions fulfilled. Yet their utility in distinguishing NMOSD from MOG-AD was limited.

Prediction of antiepileptic drug treatment outcomes of patients with newly diagnosed epilepsy by machine learning.

OBJECTIVE: The objective of this study was to build a supervised machine learning-based classifier, which can accurately predict the outcomes of antiepileptic drug (AED) treatment of patients with newly diagnosed epilepsy. METHODS: We collected information from 287 patients with newly diagnosed epilepsy between 2009 and 2017 at the Second Affiliated Hospital of Zhejiang University. Patients were prospectively followed up for at least 3 years. A number of features, including demographic features, medical history, and auxiliary examinations (electroencephalogram [EEG] and magnetic resonance imaging [MRI]) are selected to distinguish patients with different remission outcomes. Seizure outcomes classified as remission and never remission. In addition, remission is further divided into early remission and late remission. Five classical machine learning algorithms, i.e., Decision Tree, Random Forest, Support Vector Machine, XGBoost, and Logistic Regression, are selected and trained by our dataset to get classification models. RESULTS: Our study shows that 1) compared with the other four algorithms, the XGBoost algorithm based machine learning model achieves the best prediction performance of the AED treatment outcomes between remission and never remission patients with an F1 score of 0.947 and an area under the curve (AUC) value of 0.979; 2) The best discriminative factor for remission and never remission patients is higher number of seizures before treatment (>3); 3) XGBoost-based machine learning model also offers the best prediction between early remission and later remission patients, with an F1 score of 0.836 and an AUC value of 0.918; 4) multiple seizure type has the highest dependence to the categories of early and late remission patients. SIGNIFICANCES: Our XGBoost-based machine learning classifier accurately predicts the most probable AED treatment outcome of a patient after he/she finishes all the standard examinations for the epilepsy disease. The classifier's prediction result could help disease guide counseling and eventually improve treatment strategies.

Active epilepsy prevalence, the treatment gap, and treatment gap risk profile in eastern China: A population-based study.

We measured the prevalence of active epilepsy and investigated the treatment gap and treatment gap risk profile in eastern China. This was a cross-sectional population-based survey conducted in Zhejiang, China, from October 2013 to March 2014. A total 54,976 people were selected using multi-stage cluster sampling. A two-stage questionnaire-based process was used to identify patients with active epilepsy and to record their demographic, socioeconomic, and epilepsy-related features. Logistic regression analysis was used to analyze risk factors of the treatment gap in eastern China, as adjusted for age and sex. We interviewed 50,035 people; 118 had active epilepsy (2.4‰), among which the treatment gap was 58.5%. In multivariate analysis, failure to receive appropriate antiepileptic treatment was associated with higher seizure frequency of 12-23 times per year (adjusted odds ratio=6.874; 95% confidence interval [CI]=2.372-19.918), >24 times per year (adjusted odds ratio=19.623; 95% CI=4.999-77.024), and a lack of health insurance (adjusted odds ratio=7.284; 95% CI=1.321-40.154). Eastern China has relatively lower prevalence of active epilepsy and smaller treatment gap. Interventions aimed at reducing seizure frequency, improving the health insurance system should be investigated as potential targets to further bridge the treatment gap.

Prevalence and predictors of subclinical seizures during scalp video-EEG monitoring in patients with epilepsy.

OBJECTIVE: This study first aimed to establish the prevalence and predictors of subclinical seizures in patients with epilepsy undergoing video electroencephalographic monitoring, then to evaluate the relationship of sleep/wake and circadian pattern with subclinical seizures. METHODS: We retrospectively reviewed the charts of 742 consecutive patients admitted to our epilepsy center between July 2012 and October 2014. Demographic, electro-clinical data and neuroimage were collected. RESULTS: A total of 148 subclinical seizures were detected in 39 patients (5.3%) during video electroencephalographic monitoring. The mean duration of subclinical seizures was 47.18 s (range, 5-311). Pharmacoresistant epilepsy, abnormal MRI and the presence of interictal epileptiform discharges were independently associated with subclinical seizures in multivariate logistic regression analysis. Subclinical seizures helped localizing the presumed epileptogenic zone in 24 (61.5%) patients, and suggested multifocal epilepsy in five (12.8%). In addition, subclinical seizures occurred more frequently in sleep and night than wakefulness and daytime, respectively, and they were more likely seen between 21:00-03:00 h, and less likely seen between 09:00-12:00 h. Thirty patients (76.9%) had their first subclinical seizures within the first 24 h of monitoring while only 7.7% of patients had their first subclinical seizures detected within 20 min. CONCLUSION: Subclinical seizures are not uncommon in patients with epilepsy, particularly in those with pharmacoresistant epilepsy, abnormal MRI or interictal epileptiform discharges. Subclinical seizures occur in specific circadian patterns and in specific sleep/wake distributions. A 20-min VEEG monitoring might not be long enough to allow for their detection.

Depression and anxiety are associated with reduced antiepileptic drug adherence in Chinese patients.

OBJECTIVE: The aim of this study was to investigate the association of depression and anxiety with adherence to antiepileptic drugs (AEDs) in Chinese patients with epilepsy. METHODS: A total of 184 Chinese patients with epilepsy, and without cognitive impairment, underwent psychometric tests: the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Adherence to antiepileptic drugs was measured by the eight-item Morisky Medication Adherence Scale (MMAS-8). Data on patients' demographic characteristics, disease characteristics, and treatment characteristics were also collected. RESULTS: The MMAS-8 indicated that 39.7% of the patients had low adherence, 34.2% had moderate adherence, and 26.1% had high adherence. Demographic, disease, and treatment characteristics were not significantly different between the low adherence group and the moderate-to-high adherence group. Thirty-six (19.6%) patients had moderate-to-severe depression according to the BDI, and 47 (25.5%) patients were considered anxious according to the BAI. A significant difference in depression scores was found between the low adherence group and the moderate-to-high adherence group (χ(2)=13.625, P<0.001). We also found a significant difference in anxiety scores between the two groups (χ(2)=8.331, P=0.004). Pearson's correlations indicated that depression scores (r=-0.281, P<0.001) and anxiety scores (r=-0.255, P<0.001) were negatively correlated with adherence. Negative correlations were found between BDI scores and items 2, 7, and 8 of the MMAS-8 (P<0.05); negative correlations were also found between BAI scores and items 3 and 6-8 (P<0.05). CONCLUSION: Depression and anxiety were associated with reduced antiepileptic drug adherence in Chinese patients. Addressing depression and anxiety among patients with epilepsy may help improve adherence to AEDs.

Reliability and validity of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E).

OBJECTIVE: The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E). METHODS: A total of 248 Chinese patients with epilepsy underwent psychometric tests, including the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI), the Chinese version of the Beck Depression Inventory - II (C-BDI-II), and the C-NDDI-E. RESULTS: None of the patients had difficulties understanding or completing the C-NDDI-E. Cronbach's α coefficient was 0.824. At a cutoff score of ≥14, the C-NDDI-E had a sensitivity of 0.854, a specificity of 0.899, a positive predictive value of 0.625, and a negative predictive value of 0.969. The scores for the C-NDDI-E were positively correlated with those for the C-BDI-II (P<0.001). CONCLUSION: The C-NDDI-E is a reliable and valid screening tool for the detection of major depression in Chinese patients with epilepsy.

Analyzing reliability of seizure diagnosis based on semiology.

This study aimed to determine the accuracy of seizure diagnosis by semiological analysis and to assess the factors that affect diagnostic reliability. A total of 150 video clips of seizures from 50 patients (each with three seizures of the same type) were observed by eight epileptologists, 12 neurologists, and 20 physicians (internists). The videos included 37 series of epileptic seizures, eight series of physiologic nonepileptic events (PNEEs), and five series of psychogenic nonepileptic seizures (PNESs). After observing each video, the doctors chose the diagnosis of epileptic seizures or nonepileptic events for the patient; if the latter was chosen, they further chose the diagnosis of PNESs or PNEEs. The overall diagnostic accuracy rate for epileptic seizures and nonepileptic events increased from 0.614 to 0.660 after observations of all three seizures (p < 0.001). The diagnostic sensitivity and specificity of epileptic seizures were 0.770 and 0.808, respectively, for the epileptologists. These values were significantly higher than those for the neurologists (0.660 and 0.699) and physicians (0.588 and 0.658). A wide range of diagnostic accuracy was found across the various seizures types. An accuracy rate of 0.895 for generalized tonic-clonic seizures was the highest, followed by 0.800 for dialeptic seizures and then 0.760 for automotor seizures. The accuracy rates for myoclonic seizures (0.530), hypermotor seizures (0.481), gelastic/dacrystic seizures (0.438), and PNESs (0.430) were poor. The reliability of semiological diagnosis of seizures is greatly affected by the seizure type as well as the doctor's experience. Although the overall reliability is limited, it can be improved by observing more seizures.

Diagnostic yield of inpatient video-electroencephalographic monitoring: experience from a Chinese comprehensive epilepsy center.

Video-electroencephalographic monitoring (VEEG) is useful in the diagnosis of seizure disorders; however, its diagnostic yield in developing countries is not well known. The current study retrospectively reviewed the charts of 484 consecutive patients who were admitted to our center between July 2012 and September 2013. Of these patients, 298 (61.6%) were admitted for diagnostic clarification and underwent VEEG for a mean duration of 1.3days (range=1-9days). The patients were divided into two groups: those whose diagnosis was changed and those whose diagnosis was not changed as a result of VEEG. A patient with a preadmission diagnosis of epilepsy who was discharged with a diagnosis of nonepileptic events (NEEs) or who was further classified as focal/generalized epilepsy on discharge was included in the "change in diagnosis" group. A patient admitted with an uncertain diagnosis and discharged with a diagnosis of NEEs or epilepsy (including focal epilepsy and generalized epilepsy) was also included in the "change in diagnosis" group. Video-electroencephalographic monitoring recorded typical ictal events (epileptic events or nonepileptic events) in 147 (49.3%) of the patients admitted for diagnostic clarification. In total, 181 (60.7%) patients had a change in diagnosis after VEEG. Among them, 103 (56.9%) patients had a preadmission diagnosis of epilepsy, which was further classified as focal epilepsy (88 patients) or generalized epilepsy (15 patients); the diagnosis of NEEs and epilepsy was clarified in 78 (43.1%) patients. The number of patients diagnosed with NEEs increased from 31 (10.4%) on admission to 88 (29.5%) on discharge. Among all the patients admitted for diagnostic clarification, therapeutic plans were changed for 104 (57.5%) patients. In 117 (39.3%) patients with no diagnostic change, VEEG evaluation provided confirmative diagnostic information in 47 (15.8%) patients and no additional diagnostic information in 70 (23.5%) patients. The study indicates that VEEG is useful in terms of clarifying seizure diagnoses and evaluating seizure frequency. In our cohort study, VEEG of a relatively short mean duration produced a comparable diagnostic yield as that reported in other studies.

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.

Seizures and electrophysiological features in familial cortical myoclonic tremor with epilepsy 1.

OBJECTIVES: To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a large Chinese cohort. METHODS: We systematically evaluated 125 FCMTEtype 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene in China. RESULTS: Among the 28 probands, epileptic seizures (96.4%, 27/28) were the most common reason for an initial clinic visit. Ninety-seven (77.6%, 97/125) patients had experienced seizures. The seizures onset age was 36.5 ± 9.0 years, which was 6.9 years later than cortical tremors. The seizures were largely rare (<1/year, 58.8%) and occasional (1-6/year, 37.1%). Prolonged prodromes were reported in 57.7% (56/97). Thirty-one patients (24.8%, 31/125) reported photosensitivity history, and 79.5% (31/39) had a photoparoxysmal response. Interictal epileptiform discharges (IEDs) were recorded in 69.1% (56/81) of patients. Thirty-three patients showed generalized IEDs and 72.7% (24/33) were occipitally dominant, while 23 patients presented with focal IEDs with 65.2% (15/23) taking place over the occipital lobe. Overnight EEG of FCMTE patients displayed paradoxical sleep-wake fluctuation, with a higher average IED index of 0.82 ± 0.88/min during wakefulness and a lower IED index of 0.04 ± 0.06/min during non-rapid eye movement sleep stages I-II. INTERPRETATION: FCMTE type 1 has a benign course of epilepsy and distinct clinical and electrophysiological features. In addition to a positive family history and cortical myoclonus tremor, the seizure prodromes, specific seizure triggers, photosensitivity, distribution of IEDs, and unique fluctuations during sleep-wake cycle are cues for proper genetic testing and an early diagnosis of FCMTE.

Serum urate and the risk of Parkinson's disease: results from a meta-analysis.

OBJECTIVE: Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD. METHODS: We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender. RESULTS: Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72). CONCLUSIONS: In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

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.