A case of coagulation factor V inhibitor induced by immune checkpoint inhibitor therapy.

A 73-year-old woman with lung adenocarcinoma (cT4N3M1a: Stage IVA) was treated with atezolizumab as the eighth line of therapy. Four weeks after the fourth dose of atezolizumab, the prothrombin time (PT) and activated thromboplastin time (APTT) were prolonged. Coagulation factor V (FV) activity was decreased, and FV inhibitors were observed. There was no history of PT or APTT prolongation or bleeding before the use of atezolizumab. Atezolizumab-induced coagulation FV inhibitor was diagnosed. After 2 weeks, the PT and APTT spontaneously normalized. FV activity improved and the FV inhibitors disappeared after 6 and 9 weeks, respectively.

Effect of vagus nerve stimulation against generalized seizure and status epilepticus recurrence.

Objective: Vagus nerve stimulation (VNS) is a palliative surgery for drug-resistant epilepsy. The two objectives of this study were to (1) determine the seizure type most responsive to VNS and (2) investigate the preventive effect on status epilepticus (SE) recurrence. Methods: We retrospectively reviewed 136 patients with drug-resistant epilepsy who underwent VNS implantation. We examined seizure outcomes at 6, 12, and 24 months following implantation of VNS as well as at the last visit to the Juntendo Epilepsy Center. Univariate analysis and multivariate logistic regression models were used to estimate the prognostic factors. Results: 125 patients were followed up for at least 1 year after VNS implantation. The percentage of patients with at least a 50% reduction in seizure frequency compared with prior to VNS implantation increased over time at 6, 12, and 24 months after VNS implantation: 28, 41, and 52%, respectively. Regarding overall seizure outcomes, 70 (56%) patients responded to VNS. Of the 40 patients with a history of SE prior to VNS implantation, 27 (67%) showed no recurrence of SE. The duration of epilepsy, history of SE prior to VNS implantation and seizure type were correlated with seizure outcomes after VNS implantation in univariate analysis (p = 0.05, p < 0.01, and p = 0.03, respectively). In multivariate logistic regression analysis, generalized seizure was associated with VNS response [odds ratio (OR): 4.18, 95% CI: 1.13-15.5, p = 0.03]. A history of SE prior to VNS implantation was associated with VNS non-responders [(OR): 0.221, 95% CI: 0.097-0.503, p < 0.01]. The duration of epilepsy, focal to bilateral tonic-clonic seizure and epileptic spasms were not significantly associated with VNS responders (p = 0.07, p = 0.71, and p = 0.11, respectively). Conclusion: Following 125 patients with drug-resistant epilepsy for an average of 69 months, 56% showed at least 50% reduction in seizure frequency after VNS implantation. This study suggests that generalized seizure is the most responsive to VNS, and that VNS may reduce the risk of recurrence of SE. VNS was shown to be effective against generalized seizure and also may potentially influence the risk of further events of SE, two marker of disease treatment that can lead to improved quality of life.

The association of circulating endocannabinoids with cancer cachexia: A cross-sectional study.

BACKGROUND & AIMS: Endocannabinoids (eCBs) are involved in various physiological functions such as appetite, metabolism, and inflammation. Although deterioration of these functions is often observed in patients with refractory cancer cachexia (RCC), the relationship between circulating eCBs and cancer cachexia remains unknown. This study aimed to evaluate the relationship between circulating levels of eCBs and clinical findings in patients with RCC. METHODS: Circulating N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG) levels were measured in 39 patients with RCC (36% females, median age and IQR: 79 and 69-85), and 18 age- and sex-matched controls who received medical therapy for non-communicable diseases, using liquid chromatography with tandem mass spectrometry. In the RCC group, relationships between eCB levels and clinical findings-such as anorexia, awareness of pain, performance status, and survival period-were also examined. As anti-inflammatory drugs can influence the action and metabolism of eCBs, the following two analyses were conducted. In analysis 1, all participants were included, and in analysis 2, participants receiving any anti-inflammatory drugs were excluded. RESULTS: Serum AEA and 2-AG levels were more than twice as high in the RCC group than in those in the control group in both analyses. In analysis 1, only 8% of patients reported normal appetite assessed using the numerical rating scale (NRS), and serum AEA levels were negatively correlated with the NRS scores (R = -0.498, p = 0.001). Serum 2-AG levels were positively correlated with serum triglyceride levels (R = 0.419, p = 0.008). Both AEA and 2-AG levels were positively correlated with serum C-reactive protein (CRP) levels (AEA: R = 0.516, p < 0.001; 2-AG: R = 0.483, p = 0.002). Multiple linear regression analysis in the form of a stepwise procedure was performed; NRS scores and CRP levels showed a significant association with AEA levels (NRS: p = 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.426. Similarly, triglyceride and CRP levels showed a significant association with the log of 2-AG levels (triglycerides: p < 0.001; CRP: p < 0.001), with an adjusted R2 value of 0.442. In analysis 2, serum AEA levels were negatively correlated with the NRS scores (R = -0.757, p < 0.001), whereas serum triglyceride levels were positively correlated with 2-AG levels (R = 0.623, p = 0.010). CONCLUSIONS: Circulating eCB levels were significantly higher in patients with RCC than those in controls. In patients with RCC, circulating AEA may play a role in anorexia, whereas 2-AG may play a role in serum triglyceride levels.

Proper Therapy Selection Improves Epilepsy Outcomes in Patients With Multilobar Sturge-Weber Syndrome.

BACKGROUND: Hemispherectomy is an optimal treatment for patients with Sturge-Weber syndrome (SWS) affecting the whole hemisphere; however, a consensus has not been reached regarding therapeutic choices for those with involvement of two to three lobes. In this study, we compared seizure and cognitive outcomes between medical and surgical treatment groups in patients with multilobar involvement. METHODS: We evaluated 50 patients with multilobar involvement. Surgical indications included (1) antiepileptic drug (AED)-resistant seizures; (2) developmental delay; and (3) cortical atrophy. Twenty-nine patients were classified in the medical treatment group (MTG), and 21 patients were in the surgical treatment group (STG). Seizure type and frequency, SWS electroencephalography score (SWS-EEGS), and pretherapeutic and posttherapeutic SWS neurological scores (SWS-NS) were compared between groups. Median ages at the initial evaluation of the MTG and STG were 4 and 2 years, and at the final evaluation were 13 and 17 years, respectively. RESULTS: The STG had a higher incidence (76.2%) of focal to bilateral tonic-clonic seizures and status epilepticus, although no difference in SWS-EEGS. Seizure and cognitive subcategories of SWS-NS at initial evaluation were worse in the STG (P = 0.025 and P = 0.007). The seizure subcategory in MTG and STG improved after therapy (P = 0.002 and P = 0.001). Cognition was maintained in MTG and improved in STG (P = 0.002). The seizure-free rates in MTG and STG were 58.6% and 85.7%, respectively. CONCLUSIONS: Appropriate therapeutic choices improved seizure outcomes. Although patients who required surgery had more severe epilepsy and cognitive impairment, surgery improved both.

Plasma ApoE4 Levels Are Lower than ApoE2 and ApoE3 Levels, and Not Associated with Plasma Aß40/42 Ratio as a Biomarker of Amyloid-ß Amyloidosis in Alzheimer's Disease.

BACKGROUND: APOE4 is the strongest risk factor for Alzheimer's disease (AD). However, limited information is currently available on APOE4 and the pathological role of plasma apolipoprotein E (ApoE) 4 remains unclear. OBJECTIVE: The aims of the present study were to measure plasma levels of total ApoE (tE), ApoE2, ApoE3, and ApoE4 using mass spectrometry and elucidate the relationships between plasma ApoE and blood test items. METHODS: We herein examined plasma levels of tE, ApoE2, ApoE3, and ApoE4 in 498 subjects using liquid chromatograph-mass spectrometry (LC-MS/MS). RESULTS: Among 498 subjects, mean age was 60 years and 309 were female. tE levels were distributed as ApoE2/E3 = ApoE2/E4 >ApoE3/E3 = ApoE3/E4 >ApoE4/E4. In the heterozygous group, ApoE isoform levels were distributed as ApoE2 >ApoE3 >ApoE4. ApoE levels were not associated with aging, the plasma amyloid-ß (Aß) 40/42 ratio, or the clinical diagnosis of AD. Total cholesterol levels correlated with the level of each ApoE isoform. ApoE2 levels were associated with renal function, ApoE3 levels with low-density lipoprotein cholesterol and liver function, and ApoE4 levels with triglycerides, high-density lipoprotein cholesterol, body weight, erythropoiesis, and insulin metabolism. CONCLUSION: The present results suggest the potential of LC-MS/MS for the phenotyping and quantitation of plasma ApoE. Plasma ApoE levels are regulated in the order of ApoE2 >ApoE3 >ApoE4 and are associated with lipids and multiple metabolic pathways, but not directly with aging or AD biomarkers. The present results provide insights into the multiple pathways by which peripheral ApoE4 influences the progression of AD and atherosclerosis.

Machine learning predicts blood lactate levels in children after cardiac surgery in paediatric ICU.

BACKGROUND: Although serum lactate levels are widely accepted markers of haemodynamic instability, an alternative method to evaluate haemodynamic stability/instability continuously and non-invasively may assist in improving the standard of patient care. We hypothesise that blood lactate in paediatric ICU patients can be predicted using machine learning applied to arterial waveforms and perioperative characteristics. METHODS: Forty-eight post-operative children, median age 4 months (2.9-11.8 interquartile range), mean baseline heart rate of 131 beats per minute (range 33-197), mean lactate level at admission of 22.3 mg/dL (range 6.3-71.1), were included. Morphological arterial waveform characteristics were acquired and analysed. Predicting lactate levels was accomplished using regression-based supervised learning algorithms, evaluated with hold-out cross-validation, including, basing prediction on the currently acquired physiological measurements along with those acquired at admission, as well as adding the most recent lactate measurement and the time since that measurement as prediction parameters. Algorithms were assessed with mean absolute error, the average of the absolute differences between actual and predicted lactate concentrations. Low values represent superior model performance. RESULTS: The best performing algorithm was the tuned random forest, which yielded a mean absolute error of 3.38 mg/dL when predicting blood lactate with updated ground truth from the most recent blood draw. CONCLUSIONS: The random forest is capable of predicting serum lactate levels by analysing perioperative variables, including the arterial pressure waveform. Thus, machine learning can predict patient blood lactate levels, a proxy for haemodynamic instability, non-invasively, continuously and with accuracy that may demonstrate clinical utility.

Impact of accumulative smoking exposure and chronic obstructive pulmonary disease on COVID-19 outcomes: report based on findings from the Japan COVID-19 task force.

OBJECTIVES: Smoking and chronic obstructive pulmonary disease (COPD) are risk factors for severe COVID-19. However, limited literature exists on the effect of COPD and smoking on COVID-19 outcomes. This study examined the impact of smoking exposure in pack-years (PY) and COPD on COVID-19 outcomes among smokers in Japan. METHODS: The study included 1266 smokers enrolled by the Japan COVID-19 task force between February 2020 and December 2021. PY and COPD status was self-reported by patients. Patients were classified into the non-COPD (n = 1151) and COPD (n = 115) groups; the non-COPD group was further classified into <10 PY (n = 293), 10-30 PY (n = 497), and >30 PY (n = 361). The study outcome was the need for invasive mechanical ventilation (IMV). RESULTS: The incidence of IMV increased with increasing PY and was highest in the COPD group (<10 PY = 7.8%, 10-30 PY = 12.3%, >30 PY = 15.2%, COPD = 26.1%; P <0.001). A significant association was found for IMV requirement in the >30 PY and COPD groups through univariate (odds ratio [OR]: >30 PY = 2.11, COPD = 4.14) and multivariate (OR: >30 PY = 2.38; COPD = 7.94) analyses. Increasing PY number was also associated with increased IMV requirement in patients aged <65 years. CONCLUSION: Cumulative smoking exposure was positively associated with COVID-19 outcomes in smokers.

Epilepsy surgery without lipoma removal for temporal lobe epilepsy associated with lipoma in the Sylvian fissure.

Epileptic seizure is the common symptom associated with lipomas in the Sylvian fissure (Sylvian lipomas). Removal of these lipomas carries risks of hemorrhage and brain damage. We report a surgical strategy of not removing the lipoma in a case of intractable temporal lobe epilepsy associated with Sylvian lipoma. We performed anterior temporal lobectomy with preservation of the pia mater of the Sylvian fissure and achieved seizure freedom. Focal cortical dysplasia type 1 of the epileptic neocortex adjacent to the Sylvian lipoma was pathologically diagnosed. We recommend our surgical procedure in similar cases to avoid complications and achieve adequate seizure control.

Clinical clustering with prognostic implications in Japanese COVID-19 patients: report from Japan COVID-19 Task Force, a nation-wide consortium to investigate COVID-19 host genetics.

BACKGROUND: The clinical course of coronavirus disease (COVID-19) is diverse, and the usefulness of phenotyping in predicting the severity or prognosis of the disease has been demonstrated overseas. This study aimed to investigate clinically meaningful phenotypes in Japanese COVID-19 patients using cluster analysis. METHODS: From April 2020 to May 2021, data from inpatients aged ≥ 18 years diagnosed with COVID-19 and who agreed to participate in the study were collected. A total of 1322 Japanese patients were included. Hierarchical cluster analysis was performed using variables reported to be associated with COVID-19 severity or prognosis, namely, age, sex, obesity, smoking history, hypertension, diabetes mellitus, malignancy, chronic obstructive pulmonary disease, hyperuricemia, cardiovascular disease, chronic liver disease, and chronic kidney disease. RESULTS: Participants were divided into four clusters: Cluster 1, young healthy (n = 266, 20.1%); Cluster 2, middle-aged (n = 245, 18.5%); Cluster 3, middle-aged obese (n = 435, 32.9%); and Cluster 4, elderly (n = 376, 28.4%). In Clusters 3 and 4, sore throat, dysosmia, and dysgeusia tended to be less frequent, while shortness of breath was more frequent. Serum lactate dehydrogenase, ferritin, KL-6, D-dimer, and C-reactive protein levels tended to be higher in Clusters 3 and 4. Although Cluster 3 had a similar age as Cluster 2, it tended to have poorer outcomes. Both Clusters 3 and 4 tended to exhibit higher rates of oxygen supplementation, intensive care unit admission, and mechanical ventilation, but the mortality rate tended to be lower in Cluster 3. CONCLUSIONS: We have successfully performed the first phenotyping of COVID-19 patients in Japan, which is clinically useful in predicting important outcomes, despite the simplicity of the cluster analysis method that does not use complex variables.

A case of microcystic meningioma associated with acute subdural hematoma in the posterior cranial fossa.

A 53-year-old woman was brought to the emergency room with headache and progressive deterioration of consciousness. Radiological examinations revealed acute subdural hematoma extending along the cerebellar tentorium to the falx cerebri, and a mass lesion with hemorrhage in the left cerebellum, with acute hydrocephalus. Emergency tumor and hematoma removal with decompressive craniectomy of the occiput was performed. Histopathological diagnosis was microcystic meningioma. Postoperatively, the patient recovered to clear consciousness with sequelae of left cerebellar ataxia, cerebellar dysarthria, and vertigo. This case of tentorial microcystic meningioma associated with acute subdural hematoma in the posterior cranial fossa is extremely rare, with only reported 4 similar cases.

Surgery for intractable epilepsy after severe encephalopathy with reversible splenial lesion and new onset hippocampal lesion associated with parechovirus.

We describe a case of severe encephalopathy with reversible splenial lesion associated with parechovirus, followed by intractable temporal lobe epilepsy (TLE), which was improved by epilepsy surgery. A 3-year-old girl was admitted because of fever, consciousness disturbance and generalized tonic clonic seizure. Her seizure lasted for four hours. Fluid-attenuated inversion recovery (FLAIR) showed a hyperintensity in the splenium of the corpus callosum. Electroencephalogram (EEG) demonstarated continuous diffuse epileptic activity represented by synchronous and rhythmic high-amplitude spikes and waves, which led to the diagnosis of status epilepticus. Her consciousness was improved with fosphenytoin, midazolam and methylprednisolone pulse after 3 days. Seven days later, FLAIR hyperintensity in the splenium of the corpus callosum was disappeared; however, a hyperintensity in the right hippocampus was detected. Since the stool examination was positive for parechovirus, her final diagnosis was reversible splenial lesion syndrome (RESLES) associated with parechovirus. At age 8, she experienced epigastric sensation and consciousness disturbance once a week. Based on the scalp EEG and radiological findings, she was diagnosed with intractable right TLE. We performed a right selective amygdalohippocampectomy and anterior temporal disconnection at 10 years of age. One year and 3 months after surgery, she was seizure free. To our knowledge, this is the first report of severe febrile epilepticus status. with RESLES associated with parechovirus, followed by intractable TLE, which was resolved by epilepsy surgery.

Impact of Atrial Fibrillation on Fontan Circulation: Fontan Computational Model.

BACKGROUND: Patients with Fontan circulation may have heart failure resulting in atrial fibrillation during the late phase. Inotropic effects to ameliorate hemodynamics on the Fontan circulation are not well understood, especially when in atrial fibrillation. This study was performed to determine whether dobutamine therapy in patients with Fontan circulation has limited effects on improving hemodynamics. METHODS: Lumped computational models (sinus and atrial fibrillation) were used, including biventricular, atriopulmonary connection, and extracardiac total cavopulmonary connection Fontan models. The condition of atrial fibrillation including lack of atrial beat, irregular ventricular contraction, and time-varying elastance for the ventricle was introduced. A different dose of dobutamine was given by varying the elastance of the ventricle, heart rate, and peripheral resistance. RESULTS: In all models, the cardiac output decreased by 22.5% to 25.8% in atrial fibrillation. At 10 µg · kg-1 · min-1 dobutamine in sinus rhythm, the cardiac output increased by 32.3% in the biventricular model but by only 9.2% (P < .001) and 9.1% (P < .001) in the atriopulmonary connection and total cavopulmonary connection Fontan models, respectively. At 10 µg · kg-1 · min-1 dobutamine in atrial fibrillation, the percent increase in the cardiac output in the Fontan circulation (11.8% increase in atriopulmonary connection, P < .001; and 11.9% increase in total cavopulmonary connection, P < .001) was significantly less than that in the biventricular circulation (32.3% increase). CONCLUSIONS: In the Fontan circulation, atrial fibrillation itself reduced the cardiac output by approximately 25%, and dobutamine had a limited effect on increasing the cardiac output, especially when in atrial fibrillation. Maintaining sinus rhythm in patients with Fontan circulation is very important.

Delineation of the epileptogenic zone by Phase-amplitude coupling in patients with Bottom of Sulcus Dysplasia.

PURPOSE: The removal of the bottom of sulcus dysplasia (BOSD) often includes the gyral crown; however, this method has been controversial. We hypothesized that the epileptogenic zone of the BOSD does not include the gyral crown. To reveal the depth and extent of the epileptogenic zone of the BOSD, we applied the two electrophysiological modalities: (1) the occurrence rate (OR) of high-frequency oscillations (HFOs) and (2) modulation index (MI), reflecting the strength of phase-amplitude coupling between HFOs and slow oscillations. METHODS: We investigated the ripples [80-200 Hz] and fast ripples [200-300 Hz]) in HFOs and MI (HFOs [80-300 Hz] and slow oscillations [3-4 Hz]). We opened the sulcus at the BOSD and implanted the subdural electrodes directly over the MRI visible lesion. All patients (n = 3) underwent lesionectomy and the gyral crown was preserved. RESULTS: Pathological findings demonstrated focal cortical dysplasia type IIb and seizure freedom was achieved. The OR of the HFOs was not significantly different between the BOSD and the gyral crown. In contrast, the MI between HFOs and slow oscillations in the BOSD was significantly higher than that in the gyral crown. CONCLUSION: High MI values distinguished the epileptogenic BOSD from the non-epileptogenic gyral crowns. MI could be a more informative biomarker of epileptogenicity than the OR of HFOs in a subset of patients with the BOSD.

Can intraoperative electrocorticography be used to minimize the extent of resection in patients with temporal lobe epilepsy associated with hippocampal sclerosis?

OBJECTIVE: Tailored surgery to extensively resect epileptogenic lesions using intraoperative electrocorticography (ioECoG) may improve seizure outcomes. However, resection of large areas is associated with decreased memory function postoperatively. The authors assessed whether ioECoG could provide useful information on how to minimize the focus resection and obtain better seizure outcomes without memory deterioration. They examined the postoperative seizure-free period and memory alteration in a retrospective cohort of patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) in whom the extent of removal was determined using ioECoG findings. METHODS: The authors enrolled 82 patients with TLE associated with HS who were treated surgically. Transsylvian amygdalohippocampectomy was indicated as the first step. When visual inspection identified interictal epileptic discharges from the lateral temporal lobe on ioECoG, anterior temporal lobectomy (ATL) was eventually performed. The patients were divided into the selective amygdalohippocampectomy (SA, n = 40) and ATL (n = 42) groups. Postoperative seizure outcomes were assessed at 1, 2, 3, 5, and 7 years postoperatively using the International League Against Epilepsy classification. The Kaplan-Meier survival analysis was applied to evaluate the period of seizure recurrence between the SA and ATL groups. Factors attributed to seizure recurrence were analyzed using the Cox proportional hazards model, and they were as follows: epileptic focal laterality; age at seizure onset (< 10 or ≥ 10 years old); seizure frequency (more than weekly or less than weekly seizures); history of focal to bilateral tonic-clonic seizure; infectious etiology; and surgical procedure. The Wechsler Memory Scale-Revised was used to evaluate memory function pre- and postoperatively. RESULTS: Seizure outcomes were significantly worse in the SA group than in the ATL group at 2 years postoperatively (p = 0.045). The International League Against Epilepsy class 1 outcomes at 7 years postoperatively in the SA and ATL groups were 63% and 81%, respectively. Kaplan-Meier analysis showed that seizure recurred significantly earlier in the SA group than in the ATL group (p = 0.031). The 2-way ANOVA analysis was used to compare the SA and ATL groups in each memory category, and revealed that there was no significant difference regardless of the side of surgery. CONCLUSIONS: Visual assessment of ioECoG cannot be used as an indicator to minimize epileptic focus resection in patients with TLE associated with HS. ATL is more effective in obtaining seizure-free outcomes; however, both ATL and SA can preserve memory function.

Case Report: Subtotal Hemispherotomy Modulates the Epileptic Spasms in Aicardi Syndrome.

The mechanism of epileptic spasms (ES) in Aicardi syndrome (AS) remains obscure. We compared intraoperative high-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) before and after subtotal hemispherotomy in a 3-month-old girl with drug-resistant ES secondary to AS. Fetal ultrasonography showing corpus callosum agenesis, bilateral ventricular dilatation, and a large choroid plexus cyst confirmed AS diagnosis. Her ES started when she was 1 month old and had ten series of clustered ES per day despite phenobarbital and vitamin B6 treatment. After subtotal hemispherotomy, her ES dramatically improved. We analyzed two intraoperative electrocorticography modalities: (1), occurrence rate (OR) of HFOs; (2), PAC of HFOs and slow wave bands in the frontal, central, and parietal areas. We hypothesized that HFOs and PAC could be the biomarkers for efficacy of subtotal hemispherotomy in AS with ES. PAC in all three areas and OR of HFOs in the frontal and parietal areas significantly decreased, while OR of HFOs in the central area remained unchanged after subtotal hemispherotomy. We have demonstrated the usefulness of evaluating intraoperative HFOs and PAC to assess subtotal hemispherotomy effectiveness in AS patients with ES. Disconnecting the thalamocortical and subcortical pathways in the epileptic network plays a role in controlling ES generation.

Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome.

BACKGROUND: Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. METHODS: We enrolled 112 patients and classified them according to LCM distribution: (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). RESULTS: The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups' EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. CONCLUSION: Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.

Relapse of Herpes Simplex Encephalitis by Epilepsy Surgery 35 Years after the First Infection: A Case Report and Literature Review.

Late relapse of herpes simplex encephalitis (HSE) is defined as the recurrence of HSE more than 3 months after the initial exposure. The postoperative diagnosis of HSE following neurosurgery is complicated because the clinical presentation can mimic other common complications of neurosurgery. Cerebrospinal fluid polymerase chain reactions (CSF-PCR) is the gold standard for the diagnosis of HSE. We describe a case of late HSE relapse after epilepsy surgery in a patient who required a brain biopsy due to repeated negative CSF-PCR results. A 38-year-old woman had a history of HSE from the age of 3 years. She had intractable epilepsy from the age of 20 years and underwent right posterior quadrant disconnection (PQD) at the age of 38 years. Postoperatively, she had a right hemispheric intracerebral hemorrhage (ICH) and her consciousness was gradually worsening. Her consciousness improved after removal of the ICH. However, her consciousness gradually deteriorated again. Fluid-attenuated inversion recovery (FLAIR) revealed bilateral hyperintensity in the frontal lobes, including the white matter. CSF-PCR for herpes simplex virus (HSV) was performed twice, but yielded negative results. We performed a brain biopsy to target FLAIR hyperintensity in the right frontal lobe. PCR of the brain specimen was positive for HSV. Her consciousness improved with acyclovir, methylprednisolone, and cyclophosphamide. To our knowledge, this is a case of HSE induced by epilepsy surgery which had the longest duration until relapse after the initial HSE episode. A brain biopsy can be used to confirm the diagnosis of suspected HSE when CSF-PCR results are negative.

The utility of serial procalcitonin measurements in addition to pneumonia severity scores in hospitalised community-acquired pneumonia: A multicentre, prospective study.

OBJECTIVES: The usefulness of serial procalcitonin (PCT) measurements for predicting the prognosis and treatment efficacy for hospitalised community-acquired pneumonia (CAP) patients was investigated. METHODS: This prospective, multicentre, cohort study enrolled consecutive CAP patients who were hospitalised at 10 hospitals in western Japan from September 2013 to September 2016. PCT and C-reactive protein (CRP) were measured on admission (PCT D1 and CRP D1), within 48-72 h after admission (PCT D3 and CRP D3), and within 144-192 h after admission. CURB-65 and the Pneumonia Severity Index (PSI) were assessed on admission. The primary outcome was 30-day mortality; secondary outcomes were early and late treatment failure rates. RESULTS: A total of 710 patients were included. The 30-day mortality rate was 3.1%. On multivariate analysis, only PCT D3/D1 ratio >1 [odds ratio (95% confidence interval): 4.33 (1.46-12.82),P = 0.008] and PSI [odds ratio (95% confidence interval): 2.32 (1.07-5.03), P = 0.03] were significant prognostic factors. Regarding treatment efficacy, PCT D3/D1 >1 was a significant predictor of early treatment failure on multivariate analysis. PCT D3/D1 with the PSI significantly improved the prognostic accuracy over that of the PSI alone. CONCLUSIONS: PCT should be measured consecutively, not only on admission, to predict the prognosis and treatment efficacy in CAP.

Oral Immunization with Soybean Storage Protein Containing Amyloid-ß 4-10 Prevents Spatial Learning Decline.

Amyloid-ß (Aß) plays a central role in the pathogenesis of Alzheimer's disease (AD). Because AD pathologies begin two decades before the onset of dementia, prevention of Aß amyloidosis has been proposed as a mean to block the pathological cascade. Here, we generate a transgenic plant-based vaccine, a soybean storage protein containing Aß4-10, named Aß+, for oral Aß immunization. One mg of Aß+ or control protein (Aß-) was administered to TgCRND8 mice once a week from 9 weeks up to 58 weeks. Aß+ immunization raised both anti-Aß antibodies and cellular immune responses. Spatial learning decline was prevented in the Aß+ immunized group in an extended reference memory version of Morris water maze test from 21 to 57 weeks. In Tris-buffered saline (TBS), sodium dodecyl sulfate (SDS), and formic acid (FA) serial extractions, all sets of Aß species from Aß monomer, low to high molecular weight Aß oligomers, and Aß smears had different solubility in TgCRND8 brains. Aß oligomers decreased in TBS fractions, corresponding to an increase in high molecular weight Aß oligomers in SDS extracts and Aß smears in FA fraction of the Aß+ treated group. There was significant inhibition of histological Aß burden, especially in diffuse plaques, and suppression of microglial inflammation. Processing of amyloid-ß protein precursor was not different between Aß+ and Aß- groups. No evidence of amyloid-related inflammatory angiopathy was observed. Thus, Aß+ oral immunization could be a promising, cheap, and long-term safe disease-modifying therapy to prevent the pathological process in AD.