Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Post-stroke upper limb recovery is correlated with dynamic resting-state network connectivity.

Motor recovery is still limited for people with stroke especially those with greater functional impairments. In order to improve outcome, we need to understand more about the mechanisms underpinning recovery. Task-unbiased, blood flow-independent post-stroke neural activity can be acquired from resting brain electrophysiological recordings and offers substantial promise to investigate physiological mechanisms, but behaviourally relevant features of resting-state sensorimotor network dynamics have not yet been identified. Thirty-seven people with subcortical ischaemic stroke and unilateral hand paresis of any degree were longitudinally evaluated at 3 weeks (early subacute) and 12 weeks (late subacute) after stroke. Resting-state magnetoencephalography and clinical scores of motor function were recorded and compared with matched controls. Magnetoencephalography data were decomposed using a data-driven hidden Markov model into 10 time-varying resting-state networks. People with stroke showed statistically significantly improved Action Research Arm Test and Fugl-Meyer upper extremity scores between 3 weeks and 12 weeks after stroke (both P < 0.001). Hidden Markov model analysis revealed a primarily alpha-band ipsilesional resting-state sensorimotor network which had a significantly increased life-time (the average time elapsed between entering and exiting the network) and fractional occupancy (the occupied percentage among all networks) at 3 weeks after stroke when compared with controls. The life-time of the ipsilesional resting-state sensorimotor network positively correlated with concurrent motor scores in people with stroke who had not fully recovered. Specifically, this relationship was observed only in ipsilesional rather in contralesional sensorimotor network, default mode network or visual network. The ipsilesional sensorimotor network metrics were not significantly different from controls at 12 weeks after stroke. The increased recruitment of alpha-band ipsilesional resting-state sensorimotor network at subacute stroke served as functionally correlated biomarkers exclusively in people with stroke with not fully recovered hand paresis, plausibly reflecting functional motor recovery processes.

Persistence and dynamic structures of diverse cephalosporinase genes in nontyphoidal Salmonella in cross-sectional surveillance in Taiwan.

OBJECTIVES: Nontyphoidal Salmonella (NTS) is a major foodborne pathogen causing from acute gastroenteritis to bacteraemia, particularly in paediatric and elderly patients. Antimicrobial resistance of NTS, especially resistance to extended-spectrum cephalosporins, has emerged over the past decades. METHODS: Thirteen NTS isolates resistant to ceftriaxone or cefotaxime were collected from a teaching hospital in Taipei, and another three from a tertiary hospital, in New Taipei City, Taiwan, from September 2018 to December 2019. Ten other archived isolates from 2000 to 2017 were also obtained. Complete genomes of the 26 isolates were obtained. Serovars, sequence types, resistomes, genetic relatedness, and sequence comparison of plasmids were analyzed. RESULTS: Serogroups B, C2 and E were significantly associated with ampicillin resistance. Over 90% of these 26 isolates are susceptible to carbapenems and colistin. Genomic epidemiology of these isolates shows that blaCMY-2-harbouring isolates in different serovars were prevalent over two decades, presumably resulting from highly mobile IncI1 plasmid harbouring blaCMY-2. One type of the IncI1 plasmids contained a mobile element, IS26, which might be involved in the acquisition of antimicrobial resistance genes. Two emerging serovars, S. Goldcoast ST358 harbouring blaCTX-M-55 on IncHI2 plasmids and S. Anatum ST64 harbouring blaDHA-1 on IncA/C2 plasmids persisted in Taiwan, possibly through the clonal spread. Integration of complete or partial plasmid sequences into host chromosomes or multiplications of the antimicrobial resistance genes also appears to be mediated by IS26, in the two emerging clones. CONCLUSION: The dynamic movement of cephalosporinase genes mediated by IS26 in NTS is of great concern.

Perception of transitional care quality associated with functional outcomes among patients with fractures and stroke in Taiwan.

This study aimed to examine the relationship between self-perceived quality of transitional care and functional outcome among patients with stroke and fractures. The Care Transition Measure (CTM-15) was used to survey patient's self-perceived transitional care quality before discharge. General estimating equations were used to investigate the influences of transitional care quality on patient's functional outcomes at before, 1 week after, and 1 or 3 months after discharge. Among stroke patients, higher CTM-15 scores were positively associated with greater outcome in Instrumental Activities of Daily Living (IADL) following discharge. Higher scores for "reader-friendly written care plan," "consideration of patient's preferences," and "understanding of health management" had significantly positive effects on functional recovery in IADL among both patient groups following discharge. These findings suggest that heterogeneity in transitional care needs between medical and surgical patients shall not be overlooked. A one-size-fits-all strategy may be insufficient for ensuring patient care continuity following discharge.

Perception of the Use of the Direct Observation of Procedural Skills in Occupational Therapy Postgraduate Year Training in Taiwan: Survey of the Perspectives of Trainees and Supervisors.

Introduction: Assessment of clinical competence is a significant part of the training for young occupational therapists (OTs). Objective and systematic assessment allows both supervisors and trainees to be aware of the training objectives and monitor the progress. The direct observation of procedural skills (DOPS) is a work-based assessment to evaluate professional knowledge, skills, and attitude in clinical training. This study investigated the perspectives of OT educators and trainees on using DOPS and their discrepancy for OT postgraduate year (PGY) training. Methods: This study used a quantitative online survey. Eighty-six supervisors and 41 trainees of OT PGY training programs from 95 hospitals returned the questionnaire (a 90.5% return rate), and 64 supervisors and 30 trainees who used DOPS were analyzed. Outcomes included the practicality in using the DOPS in clinical settings, the ease of rating the DOPS, and advantages and the disadvantages of the DOPS. Results: Most respondents reported that completing one DOPS required at least 11 minutes for direct observation (11-40 minutes: teacher 92.2%; trainee 80.6%). Most respondents (teacher 96.9%, trainee 96.8%) had feedback after direct observation of DOPS, and about half of the feedback assessments took 5 to 10 minutes (teacher 53.1%, trainee 48.4%). Most OT educators and trainees agreed that clinical resources were sufficient and that DOPS matched with OT training goals, benefited OT competence training, and had a fair, objective, and consistent scoring system. Significantly higher percentages of OT trainees felt stressed in and satisfied with the DOPS assessment than trainers. Differences between teachers and trainees regarding easiness of rating DOPS items were not significant. Conclusion: Most OT educators and trainees agreed that DOPS was a practical and appropriate assessment for OT PGY training.

The 2023 Taiwan Stroke Society Guidelines for the management of patients with intracranial atherosclerotic disease.

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline consensus group developed recommendations for management of patients with ICAD via consensus meetings based on updated evidences. Each proposed class of recommendation and level of evidence was approved by all members of the group. The guidelines cover six topics, including (1) epidemiology and diagnostic evaluation of ICAD, (2) nonpharmacological management of ICAD, (3) medical therapy for symptomatic ICAD, (4) endovascular thrombectomy and rescue therapy for acute ischemic stroke with underlying ICAD, (5) endovascular interventional therapy for postacute symptomatic intracranial arterial stenosis, and (6) surgical treatment of chronic symptomatic intracranial arterial stenosis. Intensive medical treatment including antiplatelet therapy, risk factor control, and life style modification are essential for patients with ICAD.

Effects of comorbid alcohol use disorder on bipolar disorder: Focusing on neurocognitive function and inflammatory markers.

BACKGROUND: Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers. METHOD: We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-ß1 (TGF-ß1), and brain-derived neurotrophic factor (BDNF)] were assessed. RESULTS: BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05). CONCLUSION: Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Effects of bihemispheric transcranial direct current stimulation on motor recovery in subacute stroke patients: a double-blind, randomized sham-controlled trial.

BACKGROUND: Bihemispheric transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can simultaneously modulate bilateral corticospinal excitability and interhemispheric interaction. However, how tDCS affects subacute stroke recovery remains unclear. We investigated the effects of bihemispheric tDCS on motor recovery in subacute stroke patients. METHODS: We enrolled subacute inpatients who had first-ever ischemic stroke at subcortical regions and moderate-to-severe baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score 2-56. Participants between 14 and 28 days after stroke were double-blind, randomly assigned (1:1) to receive real (n = 13) or sham (n = 14) bihemispheric tDCS (with ipsilesional M1 anode and contralesional M1 cathode, 20 min, 2 mA) during task practice twice daily for 20 sessions in two weeks. Residual integrity of the ipsilesional corticospinal tract was stratified between groups. The primary efficacy outcome was the change in FMA-UE score from baseline (responder as an increase ≥ 10). The secondary measures included changes in the Action Research Arm Test (ARAT), FMA-Lower Extremity (FMA-LE) and explorative resting-state MRI functional connectivity (FC) of target regions after intervention and three months post-stroke. RESULTS: Twenty-seven participants completed the study without significant adverse effects. Nineteen patients (70%) had no recordable baseline motor-evoked potentials (MEP-negative) from the paretic forearm. Compared with the sham group, the real tDCS group showed enhanced improvement of FMA-UE after intervention (p < 0.01, effect size η2 = 0.211; responder rate: 77% vs. 36%, p = 0.031), which sustained three months post-stroke (p < 0.01), but not ARAT. Interestingly, in the MEP-negative subgroup analysis, the FMA-UE improvement remained but delayed. Additionally, the FMA-LE improvement after real tDCS was not significantly greater until three months post-stroke (p < 0.01). We found that the individual FMA-UE improvements after real tDCS were associated with bilateral intrahemispheric, rather than interhemispheric, FC strengths in the targeted cortices, while the improvements after sham tDCS were associated with predominantly ipsilesional FC changes after adjustment for age and sex (p < 0.01). CONCLUSIONS: Bihemispheric tDCS during task-oriented training may facilitate motor recovery in subacute stroke patients, even with compromised corticospinal tract integrity. Further studies are warranted for tDCS efficacy and network-specific neuromodulation. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov: (ID: NCT02731508).

Monogenic Causes in Familial Stroke Across Intracerebral Hemorrhage and Ischemic Stroke Subtypes Identified by Whole-Exome Sequencing.

Whole exome sequencing (WES) has been used to detect rare causative variants in neurological diseases. However, the efficacy of WES in genetic diagnosis of clinically heterogeneous familial stroke remains inconclusive. We prospectively searched for disease-causing variants in unrelated probands with defined familial stroke by candidate gene/hotspot screening and/or WES, depending on stroke subtypes and neuroimaging features at a referral center. The clinical significance of each variant was determined according to the American College of Medical Genetics guidelines. Among 161 probands (mean age at onset 53.2 ± 13.7 years; male 63.4%), 33 participants (20.5%) had been identified with 19 pathogenic/likely pathogenic variants (PVs; WES applied 152/161 = 94.4%). Across subtypes, the highest hit rate (HR) was intracerebral hemorrhage (ICH, 7/18 = 38.9%), particularly with the etiological subtype of structural vasculopathy (4/4 = 100%, PVs in ENG, KRIT1, PKD1, RNF213); followed by ischemic small vessel disease (SVD, 15/48 = 31.3%; PVs in NOTCH3, HTRA1, HBB). In contrast, large artery atherosclerosis (LAA, 4/44 = 9.1%) and cardioembolism (0/11 = 0%) had the lowest HR. NOTCH3 was the most common causative gene (16/161 = 9.9%), presenting with multiple subtypes of SVD (n = 13), ICH (n = 2), or LAA (n = 1). Importantly, we disclosed two previously unreported PVs, KRIT1 p.E379* in a familial cerebral cavernous malformation, and F2 p.F382L in a familial cerebral venous sinus thrombosis. The contribution of monogenic etiologies was particularly high in familial ICH and SVD subtypes in our Taiwanese cohort. Utilizing subtype-guided hotspot screening and/or subsequent WES, we unraveled monogenic causes in 20.5% familial stroke probands, including 1.2% novel PVs. Genetic diagnosis may enable early diagnosis, management and lifestyle modification. Among 161 familial stroke probands, 33 (20.5%) had been identified pathogenic or likely pathogenic monogenic variants related to stroke. The positive hit rate among all subtypes was high in intracerebral hemorrhage (ICH) and ischemic small vessel disease (SVD). Notably, two previously unreported variants, KRIT1 p.E379* in a familial cerebral cavernous malformation and F2 p.F382L in familial cerebral venous sinus thrombosis, were disclosed. CVT cerebral venous thrombosis; HTN Hypertensive subtype; LAA large artery atherosclerosis; SV structural vasculopathy; U Undetermined.

The 2020 Taiwan Stroke Society guidelines for blood pressure control at the acute stage of ischemic stroke.

The 2020 Taiwan Stroke Society (TSS) guidelines for blood pressure (BP) control related to ischemic stroke update the 2015 TSS BP guidelines. The early management of acute ischemic stroke has evolved rapidly in the previous two decades. Since the publication of the previous version of the TSS BP guidelines, many studies have addressed BP management in ischemic stroke. Particularly, several successful endovascular thrombectomy (EVT) trials published in 2015 led to a new era of acute treatment for ischemic stroke. With the ever-increasing use of EVT, evidence-based guidelines for ideal BP management during and after EVT are urgently needed. Consequently, the 2020 guidelines are updating and providing recommendations on BP control for the treatment and prevention of ischemic stroke based on new evidence. The present study encompasses the most important chapter of the 2020 Taiwan BP guidelines: BP control at the acute stage of ischemic stroke. We incorporated the most updated evidence regarding BP control at the acute stage of ischemic stroke in patients receiving or not receiving acute reperfusion therapy and provided specific recommendations for different treatment subgroups accordingly.

Strategic infarct location for post-stroke seizure.

Post-stroke seizure (PSS) can have a strong negative impact on functional recovery after stroke. Researchers have identified numerous risk factors of PSS; however, the relationship between infarction location and PSS remains unclear. We recruited patients who presented with an acute cerebral infarction between 2012 and 2017 and suffered from seizures within 1 year after stroke (PSS group). PSS group was subgrouped into early-PSS and late-PSS groups based on the interval between seizure and stroke. We also recruited an equal number of acute cerebral infarction patients without post-stroke seizures during the follow-up period (Non-PSS group). All brain MRIs from the two groups were processed, whereupon normalized infarct maps from the PSS and Non-PSS groups were compared via voxel- and volumetric-based analyses. A total of 132 subjects were enrolled in the study, including PSS (n = 66, consisting of 31 early-PSS and 35 late-PSS) and Non-PSS (n = 66) patients. No significant differences were observed between the two groups in terms of stroke lateralization or severity. Image analysis revealed that the volume of infarction was larger in the PSS group than in the Non-PSS group; however, the difference did not reach the level of significance. Unlike the Non-PSS group, the PSS group presented hot spots over the left central region, left superior parietal lobule, and right frontal operculum. We observed differences between the distribution of hot spots among patients with early-PSS and those with late-PSS. We found that some brain regions were significantly associated with the development of PSS after ischemic stroke, and these regions differed between cases of early and late PSS. It appears that the location of infarction could help clinicians assess the risk of PSS in specific post-stroke stages.

2021 Taiwan Stroke Society Guidelines of blood pressure control for ischemic stroke prevention.

BACKGROUND: Since the publication of the 2015 Taiwan Stroke Society Blood Pressure for Treatment and Prevention of Stroke Guideline (2015 TSS BP Guideline), several new clinical studies have addressed whether a stricter blood pressure (BP) target would be effective for stroke prevention. METHODS: TSS guideline consensus group provides recommendations on BP targets for stroke prevention based on updated evidences. RESULTS: The present guideline covers five topics: (1) diagnosis of hypertension; (2) BP control and primary prevention of ischemic stroke; (3) BP control and secondary prevention of ischemic stroke; (4) BP control and secondary prevention of large artery atherosclerosis ischemic stroke; and (5) BP control and secondary prevention of small vessel occlusion ischemic stroke. CONCLUSION: The BP target for most stroke patients with hypertension is <130/80 mm Hg.

Serotonin Modulates the Correlations between Obsessive-compulsive Trait and Heart Rate Variability in Normal Healthy Subjects: A SPECT Study with [123I]ADAM and Heart Rate Variability Measurement.

Objective: The impact of serotonergic system on obsessive-compulsive disorder (OCD) is well studied. However, the correlation between OC presentations and autonomic nervous system (ANS) is still unclear. Furthermore, whether the correlation might be modulated by serotonin is also uncertain. Methods: We recruited eighty-nine healthy subjects. Serotonin transporter (SERT) availability by [123I]ADAM and heart rate variability (HRV) tests were measured. Symptoms checklist-90 was measured for the OC presentations. The interaction between HRV and SERT availability were calculated and the correlation between HRV and OC symptoms were analyzed after stratified SERT level into two groups, split at medium. Results: The interactions were significant in the factors of low frequency (LF), high frequency (HF), and root mean square of successive differences (RMSSD). Furthermore, the significantly negative correlations between OC symptoms and the above HRV indexes existed only in subjects with higher SERT availability. Conclusion: OC symptoms might be correlated with ANS regulations in subjects with higher SERT availability.

Neutrophil-to-lymphocyte ratio in predicting neurologic outcome of patients with acute ischemic stroke treated with intravenous thrombolytics.

BACKGROUND: Recombinant tissue plasminogen activator (rtPA) is currently the most standard treatment for patients with acute ischemic stroke (AIS). However, rtPA treatment may further enhance the immune response poststroke. This study is to investigate the clinical utility of white blood-based inflammatory biomarkers in predicting neurologic outcomes among AIS patients receiving rtPA. METHODS: A retrospective observational cohort study of 100 patients with AIS treated with intravenous rtPA was conducted in an urban tertiary hospital in Taiwan. Favorable neurological outcome defined as modified Rankin Scale (mRS) score 0 to 2 in poststroke follow-up was the primary outcome measure. Baseline and post-rtPA neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were investigated for potential predictors. RESULTS: These patients had a mean age of 71.3 ± 13.7 years and the average of initial National Institute of Health Stroke Scale was 12.7 ± 6.5. Using multiple regression analysis, PLR was not an independent factor; however, both baseline and post-rtPA NLR were independent factors predicting favorable neurological outcome at 3, 6, 12 months after a stroke. The area under the receiver operating characteristic curve for baseline and post-rtPA NLR were 0.645 (95% confidence interval [CI], 0.537-0.753) and 0.769 (95% CI, 0.676-0.862) (Z score = 2.086) in 3-month, 0.645 (95% CI, 0.537-0.752) and 0.791 (95% CI, 0.701-0.880) (Z score = 2.471) in 6-month, and 0.646 (95% CI, 0.538-0.754) and 0.813 (95% CI, 0.728-0.898) (Z score = 2.857) in 12-month poststroke follow-up. CONCLUSION: For AIS patients treated with rtPA, both lower baseline and post-rtPA NLR levels were independently associated with a favorable neurologic outcome in serial mid- and long-term follow-up. Post-rtPA NLR was superior to baseline NLR in discriminative performance for neurologic prognosis.

Long-term cognitive and multimodal imaging outcomes after carotid artery stenting vs intensive medication alone for severe asymptomatic carotid stenosis.

BACKGROUND: Severe carotid stenosis is associated with cognitive impairment, which may be attributed to asymptomatic microembolism and/or chronic hypoperfusion. We aim to evaluate the long-term cognitive and brain connectivity outcomes of carotid artery stenting (CAS) for asymptomatic ≥70% stenosis of the extracranial internal carotid artery (ICA). METHODS: We conducted a non-randomized controlled study to compare intensive medical therapy alone (Med) or in combination with carotid artery stenting for the composite vascular events, neuropsychological, and multimodal magnetic resonance perfusion imaging and diffusion tensor imaging outcomes. RESULTS: Sixty-nine patients were followed for a mean of 2.3 years (31 Med, 38 CAS) and 11 patients had composite vascular events of all-cause death, ischemic stroke, or myocardial infarction (6 Med vs 5 CAS). Forty-six asymptomatic subjects completed neuropsychological and multimodality imaging follow-ups (23 Med, 23 CAS). Compared to the Med group, the CAS group had a modest improvement of 12-item delayed verbal memory (8.9 ± 2.4 to 9.8 ± 2.7 vs 9.0 ± 2.1 to 8.9 ± 2.3, p = 0.04), but not in global cognition, attention or executive function, which was associated with increased structural connectivity of fractional anisotropy at the ipsilateral deep white matter. Importantly, the memory improvement was correlated with the perfusion increment at the ipsilateral middle cerebral artery territory. CONCLUSION: For asymptomatic extracranial carotid steno-occlusion, successful carotid revascularization in addition to intensive medical treatment may potentially benefit cognitive reserve and connectivity strength which are partly attributed to restoration of non-critical hypoperfusion.

Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study.

BACKGROUND: The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. METHODS: We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. RESULT: The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. CONCLUSIONS: Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.

Application of Flat-Panel Volume Computed Tomography to Evaluate Cerebral Hemorrhage After Mechanical Thrombectomy of Acute Embolic Stroke of the Anterior Circulation.

OBJECTIVE: The aim of the study was to evaluate cerebral hemorrhage (CH) and contrast media leakage (CML or commonly synonymous with "contrast staining") differentiation on flat-panel volume computed tomography (FPVCT) after intra-arterial mechanical thrombectomy. METHODS: We evaluated patients with hyperattenuation on FPVCT after intra-arterial mechanical thrombectomy between 2018 and 2021 by multiple parameters on CT angiography, FPVCT, CT, and/or magnetic resonance imaging. RESULTS: The CH (n = 43) versus CML (n = 24) groups revealed: (1) regional anatomical characteristics (preserved and distorted): 7 of 43 (9.6%) and 36 of 43 (83.7%) versus 22 of 24 (91.7%) and 2 of 24 (8.3%, P < 0.001); (2) thrombus in proximal two-thirds versus distal one-thirds M1 segment of middle cerebral artery (preserved and distorted): 17 of 21 (81.0%) and 4 of 21 (19.0%) versus 5 of 11 (45.5%) and 6 of 11 (54.5%, P = 0.040); and (3) average density ratio: 1.83 ± 0.65 versus 1.35 ± 0.13 (P = 0.004). CONCLUSIONS: Contrast media leakage can be differentiated from CH by preserved regional anatomical characteristics and relatively low average density ratio on FPVCT. Patients with CML who have embolism in proximal two thirds of M1 segment are more likely to develop hyperattenuation with preserved regional anatomy.

Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults.

BACKGROUND: Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. METHODS: We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16-30 and 31-45 years. RESULTS: Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. CONCLUSION: An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16-30.

Antimicrobial Resistance Mechanisms and Virulence of Colistin- and Carbapenem-Resistant Acinetobacter baumannii Isolated from a Teaching Hospital in Taiwan.

Acinetobacter baumannii, a Gram-negative bacterium, is an important nosocomial pathogen. Colistin-resistant A. baumannii is becoming a new concern, since colistin is one of the last-line antibiotics for infections by carbapenem-resistant A. baumannii. From 452 carbapenem-resistant isolates collected in a teaching hospital in Taipei, Taiwan, we identified seven that were resistant to colistin. Carbapenem resistance in these isolates is attributed to the presence of carbapenemase gene blaOXA-23 in their genomes. Colistin resistance is presumably conferred by mutations in the sensor kinase domain of PmrB found in these isolates, which are known to result in modification of colistin target lipid A via the PmrB-PmrA-PmrC signal transduction pathway. Overexpression of pmrC, eptA, and naxD was observed in all seven isolates. Colistin resistance mediated by pmrB mutations has never been reported in Taiwan. One of the seven isolates contained three mutations in lpxD and exhibited an altered lipopolysaccharide profile, which may contribute to its colistin resistance. No significant difference in growth rates was observed between the isolates and the reference strain, suggesting no fitness cost of colistin resistance. Biofilm formation abilities of the isolates were lower than that of the reference. Interestingly, one of the isolates was heteroresistant to colistin. Four of the isolates were significantly more virulent to wax moth larvae than the reference.