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Although some patients have persistent symptoms or develop new symptoms following coronavirus disease 2019 (COVID-19) infection, neuropsychiatric aspects of long COVID are not well known. This review summarizes and provides an update on the neuropsychiatric dimensions of long COVID. Its neuropsychiatric manifestations commonly include fatigue, cognitive impairment, sleep disorders, depression, anxiety, and post-traumatic stress disorder. There are no specific tests for long COVID, but some characteristic findings such as hypometabolism on positron emission tomography have been reported. The possible mechanisms of long COVID include inflammation, ischemic effects, direct viral invasion, and social and environmental changes. Some patient characteristics and the severity and complications of acute COVID-19 infection may be associated with an increased risk of neuropsychiatric symptoms. Long COVID may resolve spontaneously or persist, depending on the type of neuropsychiatric symptoms. Although established treatments are lacking, various psychological and pharmacological treatments have been attempted. Vaccination against COVID-19 infection plays a key role in the prevention of long coronavirus disease. With differences among the SARS-CoV-2 variants, including the omicron variant, the aspects of long COVID are likely to change in the future. Further studies clarifying the aspects of long COVID to develop effective treatments are warranted. This article is protected by copyright. All rights reserved.

Versive seizures, consisting of forced, involuntary, sustained and unnatural turning of eyes and head toward one side, lateralize to the hemisphere contralateral to the direction of the eye and head turn. The characteristics of eye and head movements in version have been rarely and incompletely studied in spontaneous epileptic seizures as opposed to direct cortical stimulation studies.We performed a single center retrospective analysis of a cohort of 28 patients with 43 seizures, who had been admitted to the adult epilepsy monitoring unit at University Hospitals Cleveland Medical Center between January 2009 and August 2020. We only included patients with clear, high-resolution seizure videos and interpretable EEG.The eye movements were conjugate and contralateral to the hemisphere of seizure onset in 100% of the focal-onset seizures. The eye movements were saccadic in 89.3% with a predominant vector in oblique upward direction in 86.8% of the seizures. Head deviation was present in 100% of the seizures and the eyes and head deviated in the same direction in 97.6% of the seizures. In addition to deviation along the horizontal meridian, there was a vertical component to the head deviation as well, as evidenced by movement of the chin upward along the vertical axis in 93% of the seizures, thus indicating strong activation of the sternocleidomastoid muscle ipsilateral to the hemisphere of seizure onset. Concomitant facial motor activity ipsilateral to the direction of version was seen in 93% of the seizures. The most common pattern was a clonic superimposed on tonic facial contraction.Version remains a reliable and highly lateralizing sign. The majority of the eye movements during version occur in a saccadic fashion rather than one smooth movement, mostly in an oblique upward direction. Head deviation is very closely associated with eye deviation, thus indicating a common symptomatogenic zone for both, which is most likely the frontal eye field. A high concurrence of ipsilateral facial motor activity with version is likely because of close proximity of the frontal eye field to the face area in the primary motor cortex.

Localized Listeria infection predominantly occurs in the prosthetic and hip joints. We herein report a case of Listeria monocytogenes ankle osteomyelitis in a 73-year-old man receiving adalimumab who was transferred to our hospital because of suspected rheumatoid arthritis (RA) flare. He reported a four-month history of left ankle swelling. A surgical biopsy revealed L. monocytogenes osteomyelitis in the left tibia and talus bones. The patient was successfully treated with antibiotics and surgical debridement. Thus, infection due to L. monocytogenes can present as ankle osteomyelitis in immunocompromised patients and may mimic an RA flare.

Objective We clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. Methods We studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70–110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. Results The dynamic atlas demonstrated transient high-gamma suppression in the striatal cortex before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. Conclusions We successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. Significance Measuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.

Objective To investigate seizure control in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic. Method A systematic review and meta-analysis was conducted, and the MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies that reported seizure control in patients with epilepsy during the COVID-19 pandemic were included. Pooled proportions with 95% confidence intervals (CIs) of patients with epilepsy who experienced seizure worsening during the COVID-19 pandemic were assessed using a random-effects model. The quality of the assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Subgroup analyses were performed, excluding studies with reports of seizures worsening from caregivers. Results A total of 24 studies with 6,492 patients/caregivers were included in the meta-analysis. The pooled proportion of seizure worsening was 18.5% (95% CI: 13.9-23.6; I

Cranial nerve palsy associated with coronavirus disease 2019 (COVID-19) is rare. We herein report the first Asian case of the immediate onset of isolated and unilateral abducens nerve palsy (ANP) accompanied with COVID-19 infection. A 25-year-old man developed diplopia one day after the COVID-19 symptom onset. Neurological examination revealed limitation of left eye abduction without ataxia and hyporeflexia. Negative anti-ganglioside antibody results and mild albuminocytological dissociation were noted. The patient was diagnosed with left ANP accompanied by COVID-19 infection. The ANP spontaneously recovered without treatment. ANP can develop during the early phase of COVID-19 infection and adversely affect patients' quality of life.

Viola W Zhu, 1,* Misako Nagasaka, 2, 3,* Takafumi Kubota, 4 Kunil Raval, 5 Natasha Robinette, 6 Octavio Armas, 7 Wajd Al-Holou, 8 Sai-Hong Ignatius Ou 1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; 2Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA; 3Department of Advanced Medical Innovations, St. Marianna University Graduate School of Medicine, Kawasaki, Japan; 4Department of Neurology, Sapporo Nishimaruyama Hospital, Sapporo, Japan; 5Department of Pathology, Wayne State University, Detroit, MI, USA; 6Department of Oncology, Imaging Division, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; 7Department of Pathology, Sharp Grossmont Hospital, La Mesa, CA, USA; 8Department of Neurosurgery, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA*These authors contributed equally to this workCorrespondence: Sai-Hong Ignatius OuChao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology/Oncology, University of California Irvine, 200 Manchester Dr, Suite 410, Orange, CA 92868, USATel +1714-456-8104Fax +1714-456-2242Email siou@uci.eduAbstract: Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs.Keywords: CNS, radiation necrosis, lorlatinib, ALK-rearranged NSCLC, alectinib &nbsp

This paper aims to discover the extent to which university members in Japan support the National University Corporation (NUC) system, a higher educational reform introduced in 2004. In particular, ...

With the prevalence of endoscopic submucosal dissection and endoscopic full thickness resection, which enable complete resection of T1 colorectal cancer with a negative margin, the treatment strategy following endoscopic resection has become more important. The necessity of secondary surgical resection is determined on the basis of the risk of lymph node metastasis according to the histopathological findings of resected specimens because ~10% of T1 colorectal cancer cases have lymph node metastasis. The current Japanese treatment guidelines state four risk factors for lymph node metastasis: lymphovascular invasion, histological differentiation, depth of submucosal invasion, and tumor budding. These guidelines have succeeded in stratifying the low-risk group for lymph node metastasis, in which endoscopic resection alone is acceptable for cure. On the other hand, there are some problems: there is variation in diagnosis methods and low interobserver agreement for each pathological factor and 90% of surgical resections are unnecessary, with lymph node metastasis negativity. To ensure patients with T1 colorectal cancer receive more appropriate treatment, these problems should be addressed. In this systematic review, we gave some suggestions to these practical issues of four pathological factors as predictors.

This study aimed to evaluate the relationship between status epilepticus (SE) and cardiorespiratory comorbidity in patients with epilepsy.We conducted a population-based study using cloud-based aggregated electronic medical records from53 million patients in the US (Explorys, IBM Watson; January 1999 to November 2020). During the study period, we identified patients with epilepsy with SE. Patients with a history of cardiac arrest, anoxic encephalopathy, and/or cerebrovascular disease were excluded. We reported the prevalences and prevalence ratios of cardiorespiratory and medical comorbidities using age- and sex-adjusted standardization.We identified 494,790 patients with epilepsy and 19,190 had SE. Cardiovascular and respiratory diseases were statistically significantly more prevalent in patients with epilepsy with SE than in those without SE (adjusted prevalence ratio (APR) 1.13, prevalence 68.7% [95% confidence interval (CI): 67.6-69.9] vs 60.9% [95% CI: 60.7-61.1]) and (APR 1.25, 73.1% [95% CI: 71.8-74.3] vs 58.4% [95% CI: 58.1-58.6]), respectively. Aspiration pneumonia (APR 3.12, 0.47% [95% CI: 0.37-0.57] vs 0.15% [95% CI: 0.14-0.16]) and acute respiratory distress syndrome (APR 2.40, 0.47% [95% CI: 0.37-0.57] vs 0.20% [95% CI: 0.18-0.21]) were more prevalent in patients with epilepsy with SE. Common cardiovascular risk factors such as diabetes mellitus (APR 1.13, 17.1% [95% CI: 16.5-17.6] vs 15.1% [95% CI: 1.50-15.2]) and hypertension (APR 1.28, 10.6% [95% CI: 10.2-11.0] vs 8.31% [95% CI: 8.23-8.39]) were also more common in patients with epilepsy with SE.In this population-based study, patients with epilepsy with SE had a statistically significantly higher prevalence of cardiorespiratory comorbidities than in those without SE.

This study aimed to investigate the factors affecting the unwillingness of physicians involved in epilepsy care to continue telemedicine during the coronavirus disease 2019 (COVID-19) pandemic in Japan.This was a national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan) which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES). We asked physicians who conducted telemedicine in patients with epilepsy (PWE) during the COVID-19 pandemic at four clinics and 21 hospitals specializing in epilepsy care in Japan from March 1 to April 30, 2021. The following data were collected: (1) participant profile, (2) characteristics of PWE treated by telemedicine, and (3) contents and environmental factors of telemedicine. Statistically significant variables (p 0.05) in the univariate analysis were analyzed in a multivariate binary logistic regression model to detect the independently associated factors with the unwillingness to continue telemedicine.Among the 115 respondents (response rate: 64%), 89 were included in the final analysis. Of them, 60 (67.4%) were willing to continue telemedicine, and 29 (32.6%) were unwilling. In the univariate binary logistic regression analysis, age (Odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.10-3.09, p = 0.02), psychiatrist (OR = 5.88, 95% CI 2.15-16.08, p = 0.001), hospital (OR = 0.10, 95% CI 0.01-0.94, p = 0.04), the number of COVID-19 risk factors in the participant (OR = 2.88, 95% CI 1.46-5.69, p = 0.002), the number of COVID-19 risk factors in the cohabitants (OR = 2.52, 95% CI 1.05-6.01, p = 0.04), COVID-19 epidemic area (OR = 4.37, 95% CI 1.18-16.20, p = 0.03), consultation time during telemedicine (OR = 2.51, 95% CI 1.32-4.76, p = 0.005), workload due to telemedicine (OR = 4.17, 95% CI 2.11-8.24, p 0.001) were statistically significant. In the multivariate binary logistic regression analysis, workload due to telemedicine (OR = 4.93, 95% CI 1.96-12.35) was independently associated with the unwillingness to continue telemedicine.This national-level cross-sectional survey found that workload due to telemedicine among physicians involved in epilepsy care was independently associated with the unwillingness to continue telemedicine.

OBJECTIVE To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. METHOD In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants' profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. RESULTS Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. CONCLUSION We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

ObjectiveWe clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state.MethodsWe studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation.ResultsThe whole-brain level dynamic atlas demonstrated transient high-gamma suppression in the striatal region before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%.ConclusionsWe successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades.SignificanceMeasuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.Highlights-The whole-brain level dynamic atlas animated spontaneous high gamma modulations associated with saccadic eye movements.-Preceding high gamma activity in the striatal cortex predicted the direction and duration of the upcoming saccades.-Saccade-related high-gamma modulations localized the stimulation-defined visual cortex with an accuracy of 95%.

To the Editor,Harandian et al. [1] reviewed the prevalence of immediate adverse reactions to penicillin antibiotics in patients with reported penicillin allergy in 2016. They assessed the effect of...

The review question: What is the clinical effectiveness of proton pump inhibitor (PPI) therapy on sleep disturbances in patients with gastroesophageal reflux disease (GERD)? The following databases should be use: CENTRAL; MEDLINE; EMBASE; WHO-ICTRP; ClinicalTrials.gov. Types of study to be included: Prospective, randomized controlled trials describing PPI therapy for patients with GERD and sleep disturbances will be assessed for eligibility. Crossover studies, cluster randomized studies, will be excluded. Studies conducted by quasi-experimental methods will be excluded. Retrospective studies will be excluded. No exclusion will be made for observation periods. Main outcome(s): Change in sleep time and quality. Additional outcome(s): Change in pH impedance parameters (acid exposure, number of refluxes episodes); Change in reflux symptoms; All adverse events: Proportion of people who developed an adverse event according to the original author's definition. We will perform meta-analysis of the above outcomes using random effect models.Besides, we will assess heterogeniety and publication bias.

Struct member-related memory leak can become a serious problem. Linux kernel is not an exception. According to our study of Linux Kernel patches, 54.6% of all memory leak-related patches within the last two years were related to the leak of struct members. This occurs when a struct is freed before freeing its dynamically allocated struct members. Detecting these bugs in large-scale software requires to reduce analysis cost for scalability and effectively collect the state of a struct and its members.In this paper, we present a simple static-analysis approach to detect struct member-related memory leak in the Linux Kernel. Our analysis first collects alloc/free information by conducting a path-insensitive analysis. To efficiently conduct inter-procedural analysis, we introduce error-code analysis, which is an optimization to efficiently pass back the alloc/free information by focusing on the return value of callee and its use in the caller. When detecting a struct free, we scan through the collected information to detect any member that remains unfreed, and generate warnings to them. We evaluated our method by analyzing the Linux Kernel 5.3-rc4, and found two new bugs. Both of the bugs were reviewed and confirmed by Linux Kernel developers.

Highlights • COVID-19 effects were studied in patients with comorbid neurological disorder. • This review included 26 reports of comorbid neurological disorder and COVID-19. • Papers were identified from the MEDLINE (PubMed) and medRxiv databases. • Overall, 22.0 % of patients had severe COVID-19 course. • Notably, 31.9 % of patients experienced an exacerbation of preexisting neurological symptoms., Background Patients with chronic diseases usually develop severe 2019 coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on patients with neurological disorders. We conducted a systematic review to evaluate the severity of COVID-19 and its effect on preexisting neurological symptoms in patients with comorbid neurological disorder and COVID-19. Methods We searched the MEDLINE (PubMed) and medRxiv databases for reports of patients with both neurological disorders and COVID-19. Studies reporting data on changes in the symptoms of preexisting neurological disorders and/or the severity of COVID-19 were included. Results Twenty-six articles with 2278 patients with comorbid neurological disorder and COVID-19 were identified. Of 232 patients, 74 (31.9 %) showed exacerbation of preexisting neurological symptoms of dementia (55/92; 59.5 %), Parkinson’s disease (10/17; 58.8 %), epilepsy (1/1; 100 %), and unspecified neurological disorders (8/106; 7.5 %). Of 2168 patients, 478 (22.0 %) showed severe COVID-19 course. These included patients with cerebrovascular disease (86/445; 19.3 %), dementia (70/316; 22.2 %), Parkinson’s disease (25/214; 11.7 %), multiple sclerosis (28/71; 39.4 %), spinal cord injury (5/7; 71.4 %), and unspecified neurological disorders (254/1011; 25 %). Conclusions Patients with comorbid neurological disorders and COVID-19 may develop more severe preexisting neurological symptoms and COVID-19. Clinicians should be aware of the risk of symptom exacerbation and severe COVID-19 in patients with neurological disease and should focus on the prevention and early care of COVID-19.

Tuberoinfundibular dopaminergic (TIDA) neurons in the arcuate nucleus (ARC) of the hypothalamus play a role in inhibiting prolactin (PRL) secretion from the anterior pituitary. PRL is involved in a variety of behaviors, including feeding. Consequently, we hypothesized that fasting might reduce the activity of TIDA neurons, which might alter PRL secretion. However, direct examinations of TIDA neuron activity are difficult. Recently, transgenic mice were generated that expressed green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase gene. We first determined that GFP in the dorsomedial ARC was a reliable marker of TIDA neurons. Then, we performed electrophysiology and immunocytochemistry in GFP-labeled TIDA neurons to examine whether different feeding conditions could change their activity. Eight-week-old male mice were fed or fasted for 24 h. After sacrifice, we prepared acutely isolated brain slices for conducting whole-cell voltage-clamp recordings. TIDA neurons were identified with fluorescence microscopy. The mean amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced in fasting mice compared to fed mice, but different feeding conditions did not affect the mean mEPSC intervals. This result suggested that fasting reduced the number of excitatory synaptic inputs to TIDA neurons. To determine whether a reduction in excitatory synaptic inputs would cause a reduction in TIDA neuron activity, we examined the effect of 24-h fasting on c-Fos expression in the ARC. We found that fasting significantly reduced the number of Fos-positive TIDA neurons. In addition, serum PRL levels were significantly increased. Taken together, the present findings suggested that short-term fasting attenuated TIDA neuron activity.

Objective To investigate psychological comorbidities in patients with epilepsy during the coronavirus disease 2019 (COVID-19) pandemic. Method A systematic review and meta-analysis approach was used to comprehensively search MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov databases for relevant studies. Studies that reported psychological stress in patients with epilepsy during the COVID-19 pandemic were included. Psychological comorbidities were defined as anxiety, depression, and sleep disturbance. Pooled proportions of psychological comorbidities with 95% confidence intervals (CIs) were assessed using a random-effects model. The quality of assessment for each study, heterogeneity between the studies, and publication bias were also evaluated. Results A total of 28 studies with 7959 patients/caregivers were included in the meta-analysis. The pooled proportions of anxiety/worry, depression/bad mood, and sleep disturbance were 38.9% (95% CI: 31.3–46.7); I2 = 97%; p Conclusion Although the heterogeneity was high, our results showed a relatively high incidence of psychological comorbidities. Therefore, clinicians need to intervene early in the stress of patients with epilepsy to prevent worsening of stress, which can result in seizure worsening.

OBJECTIVE: We aimed to investigate the association between telemedicine and the incidence of status epilepticus (SE) in patients with epilepsy (PWE) during the coronavirus disease 2019 (COVID-19) pandemic using a large population database in the United States. METHODS: We performed a retrospective analysis of a private, cloud-based healthcare platform (Explorys Inc., Cleveland, Ohio, USA). We compared each of the previously reported risk factors for SE, such as child, male, and refractory epilepsy, using the chi-square test or Fisher's exact test in two groups: PWE with SE or without SE. We determined whether telemedicine could be a risk factor for the incidence of SE using multivariate binary logistic regression analysis incorporating statistically significant variables in the chi-square test or Fisher's exact test (p