Subarachnoid iodine leakage on dual-energy computed tomography after mechanical thrombectomy is associated with malignant brain edema.

BACKGROUND: Dual-energy computed tomography (DE-CT) can differentiate between hemorrhage and iodine contrast medium leakage following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We determined whether subarachnoid hemorrhage (SAH) and subarachnoid iodine leakage (SAIL) on DE-CT following MT were associated with malignant brain edema (MBE). METHODS: We analyzed the medical records of 81 consecutive anterior circulation AIS patients who underwent MT. SAH or SAIL was diagnosed via DE-CT performed immediately after MT. We compared the procedural data, infarct volumes, MBE, and modified Rankin scale 0-2 at 90 days between patients with and without SAH and between patients with and without SAIL. Furthermore, we evaluated the association between patient characteristics and MBE. RESULTS: A total of 20 (25%) patients had SAH and 51 (63%) had SAIL. No difference in diffusion-weighted imaging (DWI)-infarct volume before MT was observed between patients with and without SAH or patients with and without SAIL. However, patients with SAIL had larger DWI-infarct volumes 1 day following MT than patients without SAIL (95 mL vs 29 mL; p=0.003). MBE occurred in 12 of 81 patients (15%); more patients with SAIL had MBE than patients without SAIL (22% vs 3%; p=0.027). Severe SAIL was significantly associated with MBE (OR, 12.5; 95% CI, 1.20-131; p=0.006), whereas SAH was not associated with MBE. CONCLUSION: This study demonstrated that SAIL on DE-CT immediately after MT was associated with infarct volume expansion and MBE.

Associations for progression of cerebral small vessel disease burden in healthy adults: the Kashima scan study.

To investigate the association between vascular risk factors and progression of cerebral small vessel disease (SVD), we conducted a longitudinal study with neurologically healthy cohort composed mostly of middle-aged adults (n = 665, mean age, 57.7 years). Subjects, who had both baseline data of brain health examinations including MRI and follow-up MRI at least 1 year after the baseline MRI, were included this study. The presence of features of SVD, including lacunes, cerebral microbleeds, white matter hyperintensity, and basal ganglia perivascular spaces were summed to obtain "total SVD score" (range, 0-4). Progression of SVD was evaluated among subjects with a total SVD score of ≤ 3 and was defined as a ≥ 1 point increase in that score at follow-up relative to baseline. As the primary analysis, multivariate logistic regression analyses were performed to determine the associations of progression of SVD at baseline. The median follow-up period was 7.3 years and progression of SVD was observed in 154 subjects (23.2%). Even after adjustment with confounders multivariate logistic regression analyses showed that progression of SVD was associated with age (per 10-year increase, odds ratio [OR]: 2.08, 95% confidence interval [CI] 1.62-2.67), hypertension (OR 1.55, 95%CI 1.05-2.29), systolic blood pressure (BP) (per standard deviation [SD] increase, OR 1.27, 95%CI 1.04-1.54), diastolic BP (per SD increase, OR 1.23, 95%CI 1.01-1.50), and mean arterial pressure (per SD increase, OR 1.27, 95%CI 1.04-1.55). Age and high blood pressure appear to play key roles in the progression of cerebral small vessel burden after mid-life.

Customization of a passive surgical support robot to specifications for ophthalmic surgery and preliminary evaluation.

PURPOSE: To customize a passive surgery support robot for ophthalmic surgery and preliminarily evaluate its performance. STUDY DESIGN: Prospective observational study. METHODS: The range of motion of the arm was analyzed during ophthalmic surgery and, based on this analysis, a commercially available passive robot was customized for surgical support for ophthalmic surgery; following which a prototype robot was constructed. To examine the effects on the brachial muscle during surgical operations with and without the prototype robot, surface electromyograms of the biceps and triceps were analyzed after performing continuous curvilinear capsulorrhexis (CCC) and suturing the sclerocorneal wound in a cataract surgery simulation. Six surgeons performed cataract surgery, and the degree of arm stability and muscle fatigue during surgery were evaluated using a visual analog scale. RESULTS: During surgery, the prototype robot enabled fixation of the elbow and wrist at any position within the surgeon's range of motion, expanding the range of motion of the hand and fingers and stabilizing operability. Surface electromyography showed a significant decrease in the mean amplitude value of the biceps brachii during both CCC and suturing (p < 0.0001). No significant difference was observed in the triceps brachii. The arm stability and muscle fatigue were improved by 83.3% on the visual analog scale with the prototype robot compared with that without protpotype robot. CONCLUSION: The use of a passive prototype robot may improve arm stability and reduce muscle fatigue during ophthalmic surgery.

Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Introduction: Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. Methods and design: This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Results: Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). Conclusion: The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Dysautonomia associated with immune checkpoint inhibitors.

OBJECTIVE: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). METHODS: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. RESULTS: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. CONCLUSION: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2.

Background The aim of this study was to determine the associations of cerebral small vessel disease (SVD) burden with renal dysfunction and albuminuria in patients taking oral antithrombotic agents. Methods and Results Patients who newly started or continued taking oral antiplatelets or anticoagulants were enrolled in a prospective, multicenter, observational study. Obligatorily acquired multimodal magnetic resonance imaging at registration with prespecified imaging conditions was assessed for cerebral microbleeds, white matter hyperintensities, enlarged basal ganglia perivascular spaces, or lacunes, and an ordinal SVD score was calculated (range, 0-4). Multivariable adjusting covariates were age, sex, hypertension, diabetes, dyslipidemia, current smoking, drinking, and estimated glomerular filtration rate (eGFR). Of 5324 patients (1762 women; median age, 73 years), 4797 (90.1%) patients were taking oral antithrombotic agents for secondary stroke prevention. Cerebral microbleeds were present in 32.7%, confluent white matter hyperintensities in 51.8%, extensive basal ganglia perivascular spaces in 38.9%, and lacunes in 59.4%. Median SVD score was 2. Compared with eGFR category G1 (eGFR ≥90 mL/min per 1.73 m2), adjusted odds ratios for SVD score increment were 1.63 (95% CI, 1.11-2.39) at category G4 (eGFR 15-<30 mL/min per 1.73 m2) and 2.05 (95% CI, 1.33-3.16) at G5 (eGFR <15 mL/min per 1.73 m2). Corresponding odds ratios relative to urinary albumin-to-creatinine ratio (ACR) category A1 (ACR <30 mg/g) were 1.29 (95% CI, 1.12-1.49) for category A2 (ACR 30-<300 mg/g) and 1.37 (95% CI, 1.05-1.77) for A3 (ACR ≥300 mg/g). When combined eGFR and ACR categories were assessed, risks for SVD score increment generally increased as eGFR decreased and ACR increased. Conclusions Both reduced eGFR and albuminuria were independently associated with increased cerebral SVD burden in patients requiring oral antithrombotic medication mainly for secondary stroke prevention. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01581502; URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

[Central nervous system involvement of graft versus host disease after allogeneic hematopoietic stem cell transplantation for adult T cell leukemia].

A 54-year-old woman was diagnosed with acute adult T-cell leukemia (ATL) in November 2015 and underwent allogeneic hematopoietic stem cell transplantation in March 2016. Cognitive impairment appeared suddenly around May 2019, and MRI of the brain showed cerebral white matter lesions. Cerebrospinal fluid examination showed no significant findings other than elevated protein. Brain biopsy showed inflammatory cells, (mainly CD8-positive T lymphocytes), infiltrating the white matter. Based on the pathological findings and the history of chronic graft versus host disease (GVHD) in the lungs and intestines, we diagnosed central nervous system involvement of GVHD (CNS-GVHD). Immunotherapy with steroids and mycophenolate mofetil resulted in improvement of the cognitive dysfunction and inflammatory findings in the spinal fluid. This case is the first report of CNS-GVHD in ATL, suggesting the importance of diagnosis by brain biopsy and the efficacy of immunotherapy.

[Multiple cerebral infarctions in the deep perforator regions in a case of idiopathic hypereosinophilic syndrome].

A 61-year-old man was admitted to our hospital due to cerebral infarction in the pons and the right putamen. On admission (day 3 from symptom onset), laboratory testing showed a white blood cell count of 13,100/µl with hypereosinophilia of 3,734/µl. As deep vein thrombosis was detected on contrast-enhanced CT, we started anticoagulation therapy. There were no cardio-embolic sources, including right-to-left shunt, but eosinophil infiltration was found in biopsy specimens of the gastric mucosa. These findings allowed us to diagnose multiple perforator infarction due to idiopathic hypereosinophilic syndrome (idiopathic HES). After the administration of oral prednisolone was started on day 10, his hypereosinophilia rapidly improved, and no recurrence of deep perforator infarction occurred other than a symptomatic infarction in the left putamen at day 19. There are a few reports of idiopathic HES with multiple infarctions developing in deep perforator regions. The current case suggests that idiopathic HES could cause multiple cerebral infarction restricted to deep perforator areas.

Clinical and Radiological Characteristics of Intracranial Artery Dissection Using Recently Proposed Diagnostic Criteria.

BACKGROUND: Data on the clinical and radiological characteristics of intracranial artery dissection (IAD) have remained limited. Our purpose was to reveal the clinical and radiological characteristics of IAD according to diagnostic criteria for IAD as recently reported by a group of international experts. METHODS: Patients were retrospectively enrolled using a prospective single-center stroke registry between 2011 and 2016. Baseline characteristics and radiological findings including conventional magnetic resonance imaging (MRI) sequences, magnetic resonance angiography (MRA), high-resolution 3-dimensional T1-weighted imaging (HR-3D-T1WI), and digital subtraction angiography were reviewed. We performed statistical comparisons to determine which findings from which modalities are useful. RESULTS: We identified 118 patients with suspected artery dissection, with 64 patients (median age, 51 [interquartile range, 45-56) years; 16 women) finally meeting the criteria for definite (n = 47), probable (n = 15), or possible (n = 2) idiopathic IAD. Ischemic stroke alone was found in 31 patients (48%) on admission. There were 36 patients (56%) suffering from hypertension and 39 (61%) with smoking history. The vertebral artery alone was the most affected in 42 patients (66%). Intramural hematoma (IMH) was more frequently detected on HR-3D-T1WI than on conventional MRI/MRA (odds ratio, 4.72; 95% confidence interval, 1.71-13.00). In 54 patients (84%), the modified Rankin Scale score after 3 months was 0-1. CONCLUSIONS: Male dominance and age at IAD onset were similar to previous studies, and more than half had hypertension and smoking history. We confirmed that HR-3D-T1WI is useful for detecting IMH in the diagnostic criteria.