Effects and safety of high-frequency rTMS in subacute ischemic stroke patients.

OBJECTIVE: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown benefits in chronic stroke, its application in subacute ischemic stroke remains underexplored. This study aims to investigate the effects and safety of lesion-side HF-rTMS in subacute ischemic stroke. METHODS: Prospective lesion-side HF-rTMS was conducted on consecutive ischemic stroke patients within 3 days of onset from February 2019 to June 2022. Inclusion criteria required persistent paralysis (NIHSS score ≥ 1 for at least 7 days). Exclusion criteria comprised cortical infarction, disturbance of consciousness, and age over 80 years. A conventional rehabilitation group meeting the same criteria from June 2015 to January 2019 served as a comparison. We compared the two groups regarding clinical background and outcome. We also evaluated incidence of epilepsy and exacerbation of the NIHSS score in the rTMS group. RESULTS: Seventy-eight patients participated, with 50% in the HF-rTMS group. Median time from onset to HF-rTMS initiation was 9 (IQR 7-12) days. A favorable outcome (modified Rankin Scale score 0-2) at 3 months was more frequent in the rTMS group (80% vs. 44%, p = 0.002). HF-rTMS was independently associated with a favorable outcome at 3 months (OR = 5.60, 95% CI = 1.53-20.50, p = 0.009). No cases of epilepsy or exacerbation of NIHSS score were observed. CONCLUSIONS: HF-rTMS demonstrates potential effectiveness and safety in subacute ischemic stroke patients.

Bathing-Related Ischemic Stroke: Association between Stroke Subtype and Cerebral Small Vessel Disease.

AIMS: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS. METHODS: Consecutive patients with ischemic stroke between October 2012 and February 2022 were retrospectively screened. The inclusion criteria were: 1) onset-to-door time within 7 days; and 2) availability of the results of MRI evaluation of CSVD markers during hospitalization. BIS was defined as an ischemic stroke that occurred while or shortly after bathing. We investigated the incidence of the stroke subtype and the correlation between CSVD markers and BIS. RESULTS: 1,753 ischemic stroke patients (1,241 [71%] male, median age 69 years) were included. 57 patients (3%) were included in the BIS group. A higher frequency of large artery atherosclerosis (LAA) (prevalence ratio [PR] 2.069, 95% confidence interval [CI] 1.089 to 3.931, p=0.026) and lower frequency of cardio-embolism (CES) (PR 0.362, 95% CI 0.132 to 0.991, p=0.048) in BIS cases were identified. Moreover, lower periventricular hyperintensity (PVH) Fazekas grade (PR 0.671, 95% CI 0.472 to 0.956, p=0.027) and fewer cerebral microbleeds (CMBs) in deep brain region (PR 0.810, 95%CI 0.657 to 0.999, p=0.049) were associated with BIS cases. CONCLUSIONS: The BIS group was more likely to develop LAA and less likely to develop CES. Lower PVH grade and fewer CMBs in deep brain region were associated with the development of BIS.

Magnetic Resonance Imaging/cerebrospinal Fluid-negative Myelitis Following COVID-19 with a Dramatic Response to Early Aggressive Immunosuppressive Therapy.

A 57-year-old man presented with subacute-onset paraparesis, bilateral dysesthesia in his lower extremities, and bladder/bowel disturbance six weeks after being infected with SARS-CoV-2 infection (COVID-19). A neurological examination suggested transverse myelitis at the level of the lower thoracic spinal cord. However, repeated spinal magnetic resonance imaging (MRI) showed no abnormalities in the spinal cord. Laboratory and cerebrospinal fluid (CSF) tests ruled out other etiologies of myelitis, eventually suggesting COVID-19-associated myelitis. Aggressive immunosuppressive therapy, started soon after hospitalization, dramatically improved his symptoms. Early aggressive immunosuppressive therapy should therefore be considered in cases of MRI/CSF-negative myelitis associated with COVID-19.

Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

Peripheral immune profile in drug-naïve dementia with Lewy bodies.

BACKGROUND: Accumulating evidence suggests that peripheral inflammation is associated with the pathogenesis of Parkinson's disease (PD). We examined peripheral immune profiles and their association with clinical characteristics in patients with DLB and compared these with values in patients with PD. METHODS: We analyzed peripheral blood from 93 participants (drug-naïve DLB, 31; drug-naïve PD, 31; controls, 31). Absolute leukocyte counts, absolute counts of leukocyte subpopulations, and peripheral blood inflammatory indices such as neutrophil-to-lymphocyte ratio were examined. Associations with clinical characteristics, cardiac sympathetic denervation, and striatal 123I-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) binding were also examined. RESULTS: Patients with DLB had lower absolute lymphocyte and basophil counts than did age-matched controls (both; p < 0.005). Higher basophil counts were marginally associated with higher global cognition (p = 0.054) and were significantly associated with milder motor severity (p = 0.020) and higher striatal 123I-FP-CIT binding (p = 0.038). By contrast, higher basophil counts were associated with more advanced PD characterized by decreased global cognition and severe cardiac sympathetic denervation. Although lower lymphocyte counts had relevance to more advanced PD, they had little relevance to clinical characteristics in patients with DLB. Higher peripheral blood inflammatory indices were associated with lower body mass index in both DLB and PD. CONCLUSIONS: As in patients with PD, the peripheral immune profile is altered in patients with DLB. Some peripheral immune cell counts and inflammatory indices reflect the degree of disease progression. These findings may deepen our knowledge on the role of peripheral inflammation in the pathogenesis of DLB.

Necrotising fasciitis with extensive necrosis caused by Lactobacillus: a case report.

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.

Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

Retropharyngeal abscess due to Fusobacterium necrophorum complicated by progressive internal carotid artery stenosis and multiple cranial nerve palsies.

BACKGROUND: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. METHODS: A 36-year-old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. RESULTS: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. CONCLUSIONS: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation.

Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer.

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .

Relation between severity of cerebral small vessel disease and pulsatility index of internal carotid artery in small vessel occlusion.

BACKGROUND AND PURPOSE: The total small vessel disease (SVD) score, calculated using magnetic resonance imaging (MRI), is used to assess the risk of cerebral infarction. Stroke patients with total SVD scores of three or higher are reported to have a significantly increased risk of recurrent stroke. Similar to the total SVD score, carotid ultrasonography findings have been reported to be indicators of atherosclerosis. Although the total SVD score effectively reflects SVD progression, its correlation with carotid ultrasonography findings remains unknown. We aimed to investigate whether there is a relationship between these two factors. METHODS: Patients with small-vessel occlusion within 24 h of onset were retrospectively selected. Atherosclerotic factors were evaluated using the left-right average Gosling pulsatility index (PI) in the internal carotid artery (ICA-PI) and cardio-ankle vascular index (CAVI). Differences in clinical backgrounds, including atherosclerotic factors, were evaluated by dividing patients into two groups: those with a total SVD score of two or less (low-score group) and those with scores of three or more (high-score group). RESULTS: A total of 122 patients were included in this study. ICA-PI was significantly higher in the high-score group than in the low-score group. A high score was independently correlated with ICA-PI after adjusting for age, CAVI, smoking, and history of secondary atherosclerosis. CONCLUSIONS: Increased ICA-PI was associated with a high total SVD score in acute small-vessel occlusion and may be an alternative method for predicting the total SVD score, enabling the administration of interventions to prevent stroke relapse without the need for MRI.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Thin aortic arch plaque is associated with the development of atrial fibrillation for embolic stroke of undetermined source in patients with an insertable cardiac monitor.

BACKGROUND AND OBJECTIVE: This study's objective is to investigate whether mild aortic arch plaque is associated with the development of atrial fibrillation (AF) in stroke patients with embolic stroke of undetermined source (ESUS) during the first year following the implantation of an insertable cardiac monitor (ICM). METHODS: The participants in this cross-sectional observational study were consecutive patients with ESUS, even after transesophageal echocardiography. We assessed the relationship between the thickness of the participants' aortic arch plaque and AF detected after ICM implantation. RESULTS: Of the 50 consecutive patients with ESUS enrolled in this study, 12 (24%) developed AF. We observed that thicker aortic arch plaque was associated with undetected AF (2.3 mm vs. 1.2 mm, p < 0.001). Aortic arch plaque thickness was independent associated with undetected AF (OR 54.00, 95% CI 2.706-1077.544, p = 0.009). When the cut-off value for aortic arch plaque thickness was 1.8 mm, the sensitivity and specificity were 71.1% and 91.7%, respectively (95% CI = 0.75-0.98, p < 0.001). Also, patients having both aortic arch plaque with a thickness < 1.8 mm and a CHADS2 score ≥ 4 were more likely to have detectable AF than no AF (88% vs. 12%, p < 0.001). CONCLUSION: A thinner aortic arch plaque was associated with the development of AF. Patients with mild aortic plaques below 4 mm but ≥1.8 mm in thickness and without other high-risk features are less likely to have paroxysmal AF on ICM, and these plaques may be a possible source of embolism for their strokes.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

AIMS: Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS). METHODS: Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h). The exclusion criteria were (1) on-admission NIHSS scores ＞10, (2) a modified Rankin Scale (mRS) score ≥ 2 prior to stroke onset, (3) incomplete data (no urinalysis ≤ 3 days after admission or no mRS score at 90 days from stroke onset), and (4) an active malignancy. Patients at 90 days post-discharge were divided into those with favorable mRS scores of 0-1 and those with unfavorable mRS scores of 2-6. Clinical backgrounds were compared for (1) patients with positive and negative urinary IgG results, and (2) patients with favorable and unfavorable outcomes. RESULTS: Of our study's 210 patients (164=male, median age=68, median eGFR=53.2 ml/min/1.73 m2), 30 (14%) presented with positive urinary IgG, which was associated with cardiovascular risk factors. Higher BNP, higher D-dimer, lower eGFR, and higher CAVI were associated with higher positive urinary IgG. The favorable group, comprising 155 (74%) patients, had higher negative urinary IgG than the unfavorable group (89% vs 76%, P=0.026). No statistical difference emerged regarding microalbuminuria (29% vs 29%, P=1.000). CONCLUSION: In MAIS, urinary IgG was associated with both the presence of atherosclerosis and an unfavorable outcome at 90 days after stroke onset.

Deep and infratentorial cerebral microbleeds are related to wake-up stroke by large-artery atherosclerosis and cardioembolism.

BACKGROUND AND AIMS: Circadian variability of blood pressure (BP) and hypercoagulation in the morning have been proposed as underlying mechanisms of wake-up stroke (WUS). The aim was to determine the impact of cerebral microbleeds (CMBs), showing BP fluctuation and background hypercoagulability, on WUS. METHODS: Consecutive patients with acute ischemic stroke onset-to-door time within one week were screened. WUS was defined as an ischemic stroke that occurred during sleep at night. CMBs were categorized into three: "strictly Lobar", "strictly Deep (D) and/or Infratentorial (I)", and "Mixed". Moderate to severe CMBs were defined as having more than three in total. First, whether CMBs are associated with WUS was examined. Second, the same analysis was performed according to the stroke subtype classified as large-artery atherosclerosis (LAA), cardioembolism (CE), and small-vessel occlusion (SVO). RESULTS: A total of 1477 patients (1059 [72%] male, median age 69 years) were included, and WUS was observed in 363 (25%) patients. On Poisson regression analysis with a robust variance estimator in the total cohort, moderate to severe strictly D and/or I CMBs (PR 1.505, 95% CI 1.154-1.962, p = 0.003) were associated with WUS. From the perspective of stroke subtype, the same result was confirmed in LAA (PR 2.223, 95% CI 1.036-4.768, p = 0.040) and CE (PR 1.668, 95% CI 1.027-2.709, p = 0.039), not SVO. CONCLUSIONS: The presence of moderate to severe strictly D and/or I CMBs might be associated with the development of WUS. By stroke subtype, the same result was confirmed in LAA and CE.

Arachidonic acid level is related to early motor recovery following intracerebral hemorrhage with severe motor paralysis.

BACKGROUND: Low arachidonic acid (AA) levels are reportedly associated with unfavorable outcomes in intracerebral hemorrhage (ICH). OBJECTIVE: We aimed to clarify whether serum AA levels might be associated with a good recovery from severe motor paralysis in the early stage of hospitalization. METHODS: From among consecutive ICH patients between October 2012 and December 2021, patients with a sum of upper and lower extremity National Institutes of Health stroke scale (NIHSS) scores of 4-8 at admission (severe motor paralysis) were included. We defined good early recovery from severe motor paralysis as a sum of upper and lower extremity NIHSS scores of 0-3 on day 7 after admission, and that of individual upper and lower extremities as NIHSS scores of 0-1 on day 7 after admission. We aimed to assess whether serum AA levels might be associated with good early recovery from severe motor paralysis. RESULTS: We screened 377 consecutive ICH patients, including 140 with severe motor paralysis (88 (63%) males, median age 64 years). Recovery from severe motor paralysis was seen in 48 (34%). Higher AA levels (PR 1.243, 95% CI 1.042 to 1.483, p = 0.016) were independently associated with good overall recovery, and good recovery of upper and lower extremities separately (upper extremity: PR 1.319, 95% CI 1.101 to 1.580, p = 0.003; lower extremity: PR 1.293, 95% CI 1.115 to 1.499, p = 0.001). CONCLUSIONS: Higher AA levels may contribute to a good early motor recovery in patients with severe motor paralysis due to ICH.

[A case of cryptogenic new-onset refractory status epilepticus (NORSE) in which cerebrospinal fluid IL-6 was elevated with increased seizure frequency early in the disease: a case report].

A 25-year-old male presented with clonic seizures three days following a fever. The patient developed status epilepticus and required mechanical ventilation and intravenous anesthesia. The patient's epileptic seizures persisted despite administering intravenous anesthesia and multiple anti-epileptic drugs. The clinical presentation in this case, without pre-existing relevant neurological disorder and an active structural, toxic, or metabolic cause in the acute phase, was compatible with new-onset refractory status epilepticus (NORSE). After immunotherapy, including intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulin therapy, the epileptic discharge on electroencephalogram (EEG) decreased gradually, and mechanical ventilation was discontinued. Neversless the final outcome was poor. The patient's condition was finally diagnosed as cryptogenic NORSE. The IL-6 levels in the cerebrospinal fluid showed a significant increase between day 6 and 11 after onset, during which time there was a rapid escalation in seizure frequency on EEG. Considering this, IL-6 may be involved in the process of seizure exacerbation.

Follow-Up Diffusion-Weighted Image Reveals Delayed Appearance of Ischemic Lesions in Suspected Transient Ischemic Attack.

INTRODUCTION: In patients suspected of transient ischemic attack (TIA), it is not uncommon to find no lesion on the diffusion-weighted image (DWI) on admission but a delayed appearance on the follow-up DWI. METHODS: Enrolled patients met the following criteria: (1) MRI performed within 24 hours of onset and seven days after admission; (2) National Institutes of Health Stroke Scale (NIHSS) score ≦4 on admission; (3) pre-stroke modified Rankin scale (mRS) score of 0-1. Patients were divided as follows: no lesion on the first DWI and a new lesion on the second DWI (delayed-specified ischemic stroke; DSIS); and no lesion on either the first or second DWI (well-screened TIA; WSTIA). We compared both groups regarding the clinical background and the outcome at three months. RESULTS: We identified 144 cases (male 70%; median age 64 years; DSIS, n=34) between October 2012 and March 2019. DSIS was older (71 vs. 60 years, p=0.006) and had a higher NIHSS score on admission (1 vs. 0, p=0.041), a higher rate of large vessel occlusion (LVO) (17% vs. 2%, p=0.008), and symptom duration over one hour (82% vs. 64%, p=0.041). A favorable outcome mRS score of 0-1 at three months was less frequent in DSIS (85% vs. 96%, p=0.004). Age/10 (OR 1.62, 95%CI 1.17-2.24; p=0.004) and LVO (OR 10.84, 95%CI 1.87-63.06; p=0.008) were independent factors for DSIS. CONCLUSIONS: In suspected TIA with age or LVO but no lesion in the initial DWI, the second DWI should be considered to identify the delayed appearance of an ischemic stroke.

Interactive effect of orthostatic hypotension on gray matter atrophy associated with hyposmia and RBD in de novo Parkinson's disease.

BACKGROUND: Orthostatic hypotension (OH) is a potential modifiable risk factor for cognitive impairment in patients with Parkinson's disease (PD). Although other risk factors for dementia, hyposmia and REM sleep behavior disorder (RBD), are closely associated with autonomic dysfunction in PD, little is known about how these risk factors influence cognitive function and cerebral pathology. OBJECTIVE: We investigated how these three factors contribute to gray matter atrophy by considering the interaction of OH with hyposmia and RBD. METHODS: We analyzed cortical thickness, subcortical gray matter volume, and cognitive measures from 78 patients with de novo PD who underwent the head-up tilt test for the diagnosis of OH. RESULTS: Whole-brain analyses with Monte Carlo corrections revealed that hyposmia was associated with decreased cortical thickness in a marginal branch of the cingulate sulcus among patients with OH, and cortical thickness in this area correlated with cognitive functioning only in patients with OH. Subcortical gray matter volume analysis indicated that severe RBD was associated with decreased volume in the left hippocampus and bilateral amygdala among patients with OH. CONCLUSION: Even in early PD, OH exerts effects on gray matter atrophy and cognitive dysfunction by interacting with RBD and hyposmia. OH might exacerbate cerebral pathology induced by hyposmia or RBD.

Plasmodesmata mediate cell-to-cell transport of brassinosteroid hormones.

Brassinosteroids (BRs) are steroidal phytohormones that are essential for plant growth, development and adaptation to environmental stresses. BRs act in a dose-dependent manner and do not travel over long distances; hence, BR homeostasis maintenance is critical for their function. Biosynthesis of bioactive BRs relies on the cell-to-cell movement of hormone precursors. However, the mechanism of the short-distance BR transport is unknown, and its contribution to the control of endogenous BR levels remains unexplored. Here we demonstrate that plasmodesmata (PD) mediate the passage of BRs between neighboring cells. Intracellular BR content, in turn, is capable of modulating PD permeability to optimize its own mobility, thereby manipulating BR biosynthesis and signaling. Our work uncovers a thus far unknown mode of steroid transport in eukaryotes and exposes an additional layer of BR homeostasis regulation in plants.

Stroke in Patients With Common Noncancerous Gynecologic Diseases: A Multicenter Study in Japan.

Background and Objectives: Gynecologic diseases such as uterine fibroids, endometriosis, and adenomyosis are common in women of reproductive age. Case reports and small case series have reported ischemic stroke in women with such common noncancerous gynecologic diseases, and their cause of stroke is frequently attributed to cryptogenic stroke or unconventional mechanisms related to hypercoagulability. However, stroke etiology and prognosis are not well known. We assessed the prevalence of and stroke mechanisms related to common noncancerous gynecologic diseases using hospital-based clinical data. Methods: We retrospectively identified consecutive female patients with common noncancerous gynecologic diseases (uterine fibroids, endometriosis, and adenomyosis) diagnosed with ischemic stroke/transient ischemic attack (TIA) between the ages of 20 and 59 years admitted to 10 stroke centers in Japan by reviewing prospectively collected data between 2017 and 2019. The clinical, laboratory, and neuroimaging features were evaluated and compared between patients with conventional stroke mechanisms (CSMs) (large artery atherosclerosis, small vessel occlusion, cardioembolism, and other determined etiology) and non-CSMs (cryptogenic stroke and causes related to hypercoagulability such as nonbacterial thrombotic endocarditis and paradoxical embolism) according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Results: Of the 470 female patients with ischemic stroke/TIA, 39 (8%) (37 ischemic stroke and 2 TIA) had common noncancerous gynecologic diseases. The most common gynecologic diseases were uterine fibroids in 24 (62%) patients, followed by endometriosis in 9 (23%) and adenomyosis in 6 (15%). Twenty patients (51%) were assigned to the non-CSMs group, and 19 patients (49%) were assigned to the CSMs group. Adenomyosis and endometriosis were more frequent in the non-CSMs group than in the CSMs group. CA125 and D-dimer levels were higher in the non-CSMs group than in the CSMs group. Multiple vascular territory infarcts were frequent in patients with adenomyosis (60%) and endometriosis (43%) in the non-CSMs group. No stroke recurrence or death was observed within 3 months after discharge in both the CSMs and non-CSMs groups. Outcomes at 3 months after discharge were similar in both groups. Discussion: In patients with common noncancerous gynecologic diseases, hypercoagulopathy may play a role in the pathogenesis of ischemic stroke/TIA without CSMs.