Detection of episodic nocturnal hypercapnia in patients with neurodegenerative disorders.

PURPOSE: Episodic nocturnal hypercapnia (eNH) in transcutaneous carbon dioxide pressure (PtcCO2) corresponding to rapid eye movement sleep hypoventilation is a useful biomarker for detecting nocturnal hypoventilation. However, the relationship between eNH and neurodegenerative diseases with sleep-related breathing disorders (SRBDs) is unknown. The aim of this study was to evaluate the relationship between eNH and nocturnal hypoventilation in neurodegenerative diseases. METHODS: Patients with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, and idiopathic normal pressure hydrocephalus, were enrolled and received overnight PtcCO2 monitoring. The patients were divided into groups for eNH and sleep-associated hypoventilation (SH) prevalence analysis: A (ALS), B (MSA), and C (others). RESULTS: Among 110 patients, twenty-three (21%) and 10 (9%) of the patients met eNH and SH criteria, respectively. eNH and SH were significantly more frequent in groups A and B than in C. The prevalence of SH in the patients with eNH was 39% whereas most of patients with SH (90%) presented with eNH. Among patients with daytime carbon dioxide pressure in arterial blood ≤ 45 mmHg, eNH frequency was 13%, whereas none of the patients met SH criteria. The frequency of noninvasive positive pressure ventilation after PtcCO2 monitoring was significantly higher in those with than without eNH. CONCLUSIONS: eNH is common in patients with MSA and ALS who present with SRBD. eNH with overnight PtcCO2 monitoring is a useful biomarker to detect hypoventilation among neurodegenerative diseases with different SRBD mechanisms.

A case of ischemic stroke associated with protein-losing gastroenteropathy and protein S deficiency.

Protein-losing gastroenteropathies are characterized by an excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoalbuminemia. Some rare cases are complicated with ischemic stroke. We report a 24-year-old woman who developed acute dysarthria and right hemiplegia 4 months after delivering her first baby by cesarean section. Diffusion-weighted magnetic resonance imaging showed a high-intensity signal in the left anterior cerebral artery territory and middle cerebral artery territory. She had marked hypoalbuminemia and decreased protein S activity. We identified protein-losing gastroenteropathy as the cause of the hypoalbuminemia, and she had a missense mutation of the PROS 1 gene, which was associated with decreased protein S activity. We speculated that the development of protein-losing gastroenteropathy accelerated the decline in protein S activity and caused cerebral infarction.

Clinical features and efficacy of reperfusion therapy in minor ischemic stroke patients with atrial fibrillation.

The efficacy of reperfusion therapy (RT) using intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy for minor ischemic stroke (MIS) has not yet been established. The present study aimed to elucidate the clinical features of MIS patients with atrial fibrillation (AF) and examine whether they could be potential candidates for RT. Data of MIS patients, defined as those with a score ≤ 5 on the National Institute of Health Stroke Scale, were extracted from patients admitted to our hospital between 2006 and 2018, and clinical characteristics were compared between the AF and non-AF groups. Thereafter, the impact of RT on outcomes in the AF- group was evaluated using the modified Rankin scale (mRS) score 3 months after onset and compared to that of standard medical therapy (SMT) using propensity score matching (PSM). Of 10,483 stroke patients, 3003 were shortlisted, and 457 AF patients and 2546 non-AF patients were finally selected. Patients in the AF group had more RT (13.3% vs. 5.7%, p < 0.001) than those in the non-AF group. Using PSM, 53 patients each were extracted from the AF-RT and AF-SMT groups. The frequencies of mRS = 0 or 1 for the AF-RT and AF-SMT groups were 69.8% and 64.2% (p = 0.536), respectively, with a significant difference in mRS = 0 (56.5% vs. 34.0%, p = 0.019). The present study found that MIS patients with AF underwent more RT than those without AF and that RT compared favorably with SMT for them; further study is warranted to examine whether these patients could be good candidates for RT.

Blood Pressure Variability in Acute Ischemic Stroke: Influence of Infarct Location in the Insular Cortex.

BACKGROUND: The aim of this study was to elucidate the influence of insular infarction on blood pressure (BP) variability and outcomes according to the region of the insular cortex affected. METHODS: A total of 90 patients diagnosed with acute unilateral ischemic stroke were registered. The BP variability was calculated over 24 h after admission (hyperacute) and for 2-3 days after admission (acute). Patients were classified into groups of right and left, and then right anterior, right posterior, left anterior, and left posterior insular infarction. RESULTS: Patients with insular infarction showed a significantly larger infarct volume, higher modified Rankin scale scores, and lower SD and coefficient of variation (CV) of -systolic BP in the hyperacute phase than shown by patients without insular infarction (p < 0.01, p < 0.01, p = 0.02, and p = 0.03, respectively). The SD and CV of systolic BP in the hyperacute phase showed significant differences among the 3 groups with right insular infarction, with left insular infarction, and without insular infarction (p < 0.05 and p < 0.05, respectively). There was a tendency for the systolic BP variability to be lower in patients with right anterior insular infarction than in patients with infarcts in other areas. CONCLUSION: The right insular cortex, especially the anterior part, might be a hub for autonomic nervous regulation.

Assessment Model to Identify Patients With Stroke With a High Possibility of Discharge to Home: A Retrospective Cohort Study.

BACKGROUND AND PURPOSE: Discharge planning for inpatients with acute stroke can enhance reasonable use of healthcare resources, as well as improve clinical outcomes and decrease financial burden of patients. Especially, prediction for discharge destination is crucial for discharge planning. This study aimed to develop an assessment model to identify patients with a high possibility of discharge to home after an acute stroke. METHODS: We reviewed the electronic medical records of 3200 patients with acute stroke who were admitted to a stroke center in Japan between January 1, 2011, and December 31, 2015. The outcome variable was the discharge destination of postacute stroke patients. The predictive variables were identified through logistic regression analysis. Data were divided into 2 data sets: the learning data set (n=2240) for developing the instrument and the test data set (n=960) for evaluating the predictive capability of the model. RESULTS: In all, 1548 (48%) patients were discharged to their homes. Multiple logistic regression analysis identified 5 predictive variables for discharge to home: living situation, type of stroke, functional independence measure motor score on admission, functional independence measure cognitive score on admission, and paresis. The assessment model showed a sensitivity of 85.0% and a specificity of 75.3% with an area under the curve equal to 0.88 (95% confidence interval, 0.86-0.89) when the cutoff point was 10. On evaluating the predictive capabilities, the model showed a sensitivity of 88.0% and a specificity of 68.7% with an area under the curve equal to 0.87 (95% confidence interval, 0.85-0.89). CONCLUSIONS: We have developed an assessment model for identifying patients with a high possibility of being discharged to their homes after an acute stroke. This model would be useful for health professionals to adequately plan patients' discharge soon after their admission.

Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic Arch Dissection.

Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media.

Early administration of non-vitamin K antagonist oral anticoagulants for acute ischemic stroke patients with atrial fibrillation in comparison with warfarin mostly combined with heparin.

BACKGROUND: This study evaluated the rates of new lesions on diffusion-weighted images (DWIs) of magnetic resonance imaging (MRI) and hemorrhagic transformation (HT) during 2 weeks after acute ischemic stroke (AIS) in patients with atrial fibrillation (Af) who were given one of the non-vitamin K antagonist oral anticoagulants (NOACs); this was then compared with those who were given warfarin. METHODS AND RESULTS: Consecutive AIS patients with Af were enrolled between January 2008 and June 2013, and those selected were patients who had a MRI that included DWIs both on admission and after 2 weeks, and those given only wafrarin (warfarin group) or only one of the NOACs (NOAC group) within 2 weeks of admission. Of all 257 enrolled patients, 50 patients were selected for the NOAC group (median age of 80.0 years) and 125 patients for the warfarin group (median age of 80.0 years). Both NOAC and warfarin were started at a median of the second day after admission. There was no significant difference in the rates of new lesions on DWIs (26.0% vs. 28.0%, P=0.7888) and HT (30.0% vs. 39.2%, P=0.2536) between the NOAC and warfarin groups. The NOAC group had a lower rate of concomitant use of heparin (44.0% vs. 92.8%, P<0.0001) than the warfarin group. CONCLUSIONS: This study suggests that NOACs are suitable for AIS patients with Af, perhaps even better than warfarin, given their simplicity.

Effects of Meteorological Conditions on the Risk of Ischemic Stroke Events in Patients Treated with Alteplase--HEWS-tPA.

BACKGROUND: Predicting a day that presents a high risk for the occurrence of ischemic stroke events may enable health professionals to prepare for emergency stroke therapy more properly. We evaluated the association between meteorological conditions and the frequency of ischemic stroke events in Japanese patients. METHODS: Ischemic stroke patients (n = 299) who were treated with alteplase at 9 stroke hospitals in 3 restricted areas were examined. The daily rates of ischemic stroke events were compared with the daily mean thermo-hydrological index (THI), the atmospheric pressure, and the daily changes of these variables for the 6 days preceding an ischemic stroke event using Poisson regression analysis. RESULTS: We trisected onset days based on the THI (low-temperature, intermediate-temperature, and high-temperature), atmospheric pressure (low-pressure, intermediate-pressure, and high-pressure), changes in THI for preceding 6 days from the previous day (cooler, unchanged-temperature, and warmer), and changes in atmospheric pressure (decreased-pressure, unchanged-pressure, and increased-pressure). The frequency of ischemic stroke was significantly higher on low-temperature or high-pressure days (risk ratio, 1.398, P = .022; risk ratio, 1.374, P = .039), on warmer-temperature days, and when atmospheric pressure varied from the day before (P < .05). There were significantly lower risks for ischemic stroke events on cooler-temperature days, and higher risks were associated with a variation in atmospheric pressure 3 days before the onset from 4 days before (P < .05). CONCLUSIONS: There were higher risks for ischemic stroke events associated with low ambient temperature, high atmospheric pressure, increased temperature, and varied atmospheric pressure. Also, atmospheric pressure variation 3 days before may be associated.

Multicenter Study of Intravenous Recombinant Tissue Plasminogen Activator Infusion around Hiroshima, Japan: The Hiroshima Acute Stroke Retrospective and Prospective Registry Study.

OBJECTIVE: Approximately 10 years have passed since intravenous (IV) recombinant tissue plasminogen activator therapy was approved in Japan. The aim of this retrospective study was to identify the effectiveness and safety of IV alteplase therapy with the Japanese original dose around Hiroshima via consideration of the patients' backgrounds, examination findings, and outcomes. METHODS: All consecutive patients with ischemic stroke who received IV alteplase therapy between October 2005 and October 2010 were registered. RESULTS: Four hundred twenty-nine patients with ischemic stroke (172 female [40.1%], mean age 73.7 ± 11.8 years) were registered. The proportion of patients over 75 years old was 51.5% (221 patients). The median National Institutes of Health Stroke Scale (NIHSS) scores at admission were 13 (interquartile range, 9-19), and the NIHSS scores 24 hours after alteplase infusion were 8 (interquartile range, 3-15). The proportion of intracerebral hemorrhage within the initial 36 hours was 20.2% (86 patients). After the multivariate regression analysis, a history of hypertension (odds ratio = 4.14; 95% confidence interval, 1.32-14.79; P = .01) and no recanalization (odds ratio = 10.10; 95% confidence interval, 3.03-39.33; P < .0001) were independently associated with a modified Rankin Scale (mRS) score of 2 or higher at 3 months. Patients over 75 years old were not significantly associated with an intracerebral hemorrhage within the initial 36 hours and an mRS score of 2 or higher at 3 months. CONCLUSIONS: The results of our study demonstrated that IV alteplase therapy with the Japanese original dose was effective and exhibited a safety profile similar to other studies. Moreover, we should not hesitate to IV alteplase therapy simply because of advanced age.

Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal.

BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

Can early effective anticoagulation prevent new lesions on magnetic resonance imaging in acute cardioembolic stroke?

BACKGROUND: The timing of warfarin administration for acute ischemic stroke (AIS) patients with atrial fibrillation (Af) has not been established. We hypothesized that achieving targeted prothrombin time and international normalized ratio (PT-INR) at 2 weeks could prevent AIS patients with Af from developing a new lesion on diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: Of consecutively enrolled AIS patients with Af between 2008 and 2011, we selected the patients who were given warfarin within 2 weeks of admission and had DW-MRI and blood test for PT-INR both on admission and at 2 weeks. Warfarin was started as early as possible and heparin was administered until the targeted PT-INR (2.0-3.0 for patients aged <70 years or 1.6-2.6 for those aged ≥70 years) was achieved. RESULTS: One hundred and twenty-three patients were selected, consisting of 88 patients without a new lesion and 35 patients with a new lesion. Patients with a new lesion had a significantly higher median score on National Institutes of Health Stroke Scale (11.0 vs. 5.5, P = .0053), a lower rate of achieving targeted PT-INR at 2 weeks (25.7% vs. 48.9%, P = .0190), and a lower median dosage of warfarin at 2 weeks (2.0 mg vs. 2.5 mg, P = .0209) than patients without a new lesion. Multivariate logistic regression analysis showed that failure to achieve targeted PT-INR (P = .0298) was significantly associated with the occurrence of a new lesion. CONCLUSIONS: Our findings suggest that achieving targeted PT-INR at 2 weeks by using warfarin prevents new lesions in AIS patients with Af.

Safety evaluation of substituting clopidogrel for ticlopidine in Japanese patients with ischemic stroke--Hiroshima ticlopidine, clopidogrel safe exchange trial.

BACKGROUND: Clopidogrel is sometimes substituted for ticlopidine when cerebrovascular or cardiovascular patients develop hematologic abnormalities after ticlopidine treatment. However, the adverse event rate after the substitution to clopidogrel remains undetermined. Therefore, in this study, we aimed to define the risk of adverse events after substituting clopidogrel for ticlopidine without a washout period. METHODS: We prospectively enrolled patients older than 20 years who had a history of noncardioembolic strokes, including transient ischemic attacks, were treated with ticlopidine for at least 6 months. This study was conducted from August 26, 2008, when the first patient was enrolled, to January 16, 2012, the date of the last patient examination, at 8 active stroke centers in Hiroshima, Japan. We excluded patients who had severe disabilities, evidence of cardioembolic stroke, or history of a bleeding event. Each patient received clopidogrel (either 50 mg or 75 mg) once a day in place of ticlopidine without a washout period. Follow-up exams were scheduled within 12 months after the medication substitution. The primary end point of this study was adverse events of interest, including clinically significant reduced blood cell counts, hepatic dysfunction, bleeding, and other serious side effects. RESULTS: In this study, 110 patients were enrolled and analyzed in an intent-to-treat manner (modified intent to treat). Within the scheduled follow-up periods, 9 primary end point events were observed in separate patients. The primary end point events were observed at a rate of 8.4% per year (Kaplan-Meier method). At the time of enrolment, 16 patients met the exclusion criteria, of which 8 recovered from their abnormal hematologic results to the institutional normal limit after the substitution of ticlopidine for clopidogrel (57.4% per year). CONCLUSIONS: The adverse event rates after the substitution of ticlopidine for clopidogrel is similar to the adverse event rates of patients who were initially treated with clopidogrel. The substitution of clopidogrel for ticlopidine should be considered for patients who develop hematologic abnormalities from ticlopidine treatment.

The association between hyperintense vessel sign and final ischemic lesion differ in its location.

BACKGROUND: The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit. METHODS: A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score. RESULTS: An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06). CONCLUSIONS: Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis.

Interleukin 1 beta promoter polymorphism is associated with keratoconus in a Japanese population.

PURPOSE: Polymorphisms in the interleukin 1 alpha (IL1A) and IL1B gene regions were previously associated with keratoconus in a Korean population. In the present study, we investigated whether the IL1A and IL1B polymorphisms are associated with keratoconus in a Japanese population. METHODS: A total of 169 Japanese patients with keratoconus and 390 Japanese healthy controls were recruited. We genotyped one IL1A single nucleotide polymorphism (SNP; rs2071376) and two IL1B SNPs (rs1143627 and rs16944) to compare the frequencies of alleles, genotypes, and haplotypes between cases and controls. RESULTS: Statistically significant association was observed for rs1143627 (-31 T>C) in the IL1B promoter region; the T allele of rs1143627 was associated with an increased risk of keratoconus (p=0.014, corrected p value [pc]=0.043, odds ratio=1.38). The C allele of rs16944 (-511 C>T) in the IL1B promoter region had a 1.33-fold increased risk of keratoconus, although this increase did not reach statistical significance (p=0.033, pc=0.098). The TT genotype of rs1143627 was weakly associated with an increased risk of keratoconus (p=0.033, pc=0.099, odds ratio=1.52). However, no significant differences were found in the allele and genotype frequencies between the cases and controls for rs2071376 in IL1A. Regarding haplotypic diversity, the haplotype created by the T allele of rs1143627 and C allele of rs16944 was associated with a 1.72-fold increased risk of keratoconus (p=4.0×10(-5), pc=1.6×10(-4)). CONCLUSIONS: Our results replicate associations reported recently in a Korean population. Thus, IL1B may play an important role in the development of keratoconus through genetic polymorphisms.

Antiplatelet therapy as a risk factor for microbleeds in intracerebral hemorrhage patients: analysis using specific antiplatelet agents.

BACKGROUND: Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds. METHODS: We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine). RESULTS: Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501). CONCLUSIONS: Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results.

[Recanalization of an occluded artery of Percheron causing acute bilateral thalamic infarction].

An 87-year-old woman was admitted with acute onset of disturbed consciousness. On neurological examination, both pupils were dilated and non-reactive to light. Decerebrate rigidity was present. Babinski testing was positive. CTA suggested an isolated left P1 segment occlusion. The P2 segment was supplied from the left internal carotid artery via the posterior communicating artery. MRI showed bilateral paramedian thalamic infarctions. Because occlusion of the artery of Percheron was suspected, intravenous thrombolysis was performed. Digital subtraction angiography (DSA) revealed occlusion of the left P1 segment and spontaneous recanalization before endovascular treatment. Her consciousness improved immediately. When acute bilateral thalamic infarction suggests top of the basilar artery syndrome but no basilar artery occlusion is found, occlusion of the artery of Percheron should be considered. Thrombectomy of the affected P1 segment may be needed.

Circadian Fluctuation Changes in Intraocular Pressure Measured Using a Contact Lens Sensor in Patients with Glaucoma after the Adjunctive Administration of Ripasudil: A Prospective Study.

Nocturnal and circadian intraocular pressure (IOP) fluctuations are important issues in glaucoma treatment. Ripasudil 0.4% eye drops, a new glaucoma medication, lowers IOP by increasing aqueous humor outflow through the trabecular meshwork. We aimed to compare differences between circadian IOP fluctuations measured using a contact lens sensor (CLS) before and after administering 0.4% ripasudil eye drops adjunctively to patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Patients with POAG (n = 1) and NTG (n = 5) underwent 24 h IOP monitoring with a CLS before and after administering ripasudil eye drops every 12 h (8 a.m., 8 p.m.) for 2 weeks without discontinuing currently used glaucoma medications. No vision-threatening adverse event occurred. The reduction in IOP fluctuation and the reduction in the SD of IOP in 24 h, awake time and sleep time did not reach statistical significance. The baseline office-hour IOP, which was measured using Goldmann applanation tonometry (GAT), ranged in the low teens, and the reduction in office-hour IOP also did not show a significant difference. Further study is necessary to evaluate whether the low baseline IOP with less IOP reduction relates to attenuated IOP fluctuation reduction.

'Raisin bread sign' feature of pontine autosomal dominant microangiopathy and leukoencephalopathy.

Pontine autosomal dominant microangiopathy and leukoencephalopathy is one of hereditary cerebral small vessel diseases caused by pathogenic variants in COL4A1 3'UTR and characterized by multiple small infarctions in the pons. We attempted to establish radiological features of this disease. We performed whole exome sequencing and Sanger sequencing in one family with undetermined familial small vessel disease, followed by clinicoradiological assessment and a postmortem examination. We subsequently investigated clinicoradiological features of patients in a juvenile cerebral vessel disease cohort and searched for radiological features similar to those found in the aforementioned family. Sanger sequencing was performed in selected cohort patients in order to detect variants in the same gene. An identical variant in the COL4A1 3'UTR was observed in two patients with familial small vessel disease and the two selected patients, thereby confirming the pontine autosomal dominant microangiopathy and leukoencephalopathy diagnosis. Furthermore, postmortem examination showed that the distribution of thickened media tunica and hyalinized vessels was different from that in lacunar infarctions. The appearance of characteristic multiple oval small infarctions in the pons, which resemble raisin bread, enable us to make a diagnosis of pontine autosomal dominant microangiopathy and leukoencephalopathy. This feature, for which we coined the name 'raisin bread sign', was also correlated to the pathological changes.

A case of giant cell arteritis lacking typical symptoms presenting with recurrent cerebellar infarctions: A case report and case-based review.

Giant cell arteritis (GCA) occasionally presents with ischaemic stroke. Generally, symptoms related to GCA or elevated levels of inflammation markers would be a clue for the diagnosis of GCA. However, we encountered a rare case of GCA that presented with recurrent cerebellar infarctions without symptoms related to GCA (headache, fever, or jaw claudication). Furthermore, C-reactive protein levels, measured at the time of two of the stroke attacks, were within the normal range. On physical examination, the temporal arteries were prominent and weakly pulsatile. Temporal artery ultrasonography showed halo signs, and temporal artery biopsy revealed GCA. To our knowledge, this is the first case of GCA presenting with recurrent ischaemic stroke lacking GCA features but diagnosed before death. Considering this case-based review, we suggest that GCA may have been missed in elderly patients with ischaemic stroke, especially in those with posterior circulation infarction. Therefore, physical examination of the temporal arteries, temporal artery ultrasonography, and vessel wall magnetic resonance imaging may be useful in those patients.

Prophylactic antibiotics for postcataract surgery endophthalmitis: a systematic review and network meta-analysis of 6.8 million eyes.

To reveal optimal antibiotic prophylactic regimen for postoperative endophthalmitis (POE), we conducted systematic review and network meta-analysis. A total of 51 eligible original articles, including two randomized controlled trials, were identified. In total, 4502 POE cases occurred in 6,809,732 eyes (0.066%). Intracameral injection of vancomycin had the best preventive effect (odds ratio [OR] 0.03, 99.6% confidence interval [CI] 0.00-0.53, corrected P-value = 0.006, P-score = 0.945) followed by intracameral injection of cefazoline (OR 0.09, 99.6% CI 0.02-0.42, corrected P-value < 0.001, P-score = 0.821), cefuroxime (OR 0.18, 99.6% CI 0.09-0.35, corrected P-value < 0.001, P-score = 0.660), and moxifloxacin (OR 0.36, 99.6% CI 0.16-0.79, corrected P-value = 0.003, P-score = 0.455). While one randomized controlled trial supported each of intracameral cefuroxime and moxifloxacin, no randomized controlled trial evaluated vancomycin and cefazoline. Sensitivity analysis focusing on the administration route revealed that only intracameral injection (OR 0.19, 99.4% CI 0.12-0.30, corrected P-value < 0.001, P-score = 0.726) significantly decreased the risk of postoperative endophthalmitis. In conclusion, intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin prevented POE.