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Although findings from published studies suggest post-stroke aphasia is associated with an increased risk of dementia, few studies have evaluated its association in a nationally representative cohort with long-term follow-up. No studies have reported data by type of stroke. Therefore, we examined the association between post-stroke aphasia and the risk of developing dementia.Using claims data from Taiwan's universal health insurance program, a cohort of patients ≥18 years old with an initial hospitalization for stroke in 2002-2005 were identified and followed up until December 31, 2016. Patients with newly diagnosed aphasia during stroke hospitalization or within 6 months of discharge were defined as the aphasia group. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing overall, vascular, and non-vascular dementia in patients with and without post-stroke aphasia.During a median follow-up period of 7.9 and 8.6 years for the aphasia (n=17063) and non-aphasia groups (n=105940), respectively, overall dementia incidence was similar, whereas vascular dementia incidence was higher in the aphasia group (7.52 vs. 5.52 per 1000 person-years). The adjusted HRs (95% confidence intervals) were 1.11 (1.06-1.17), 1.42 (1.31-1.53), and 0.94 (0.88-1.01) for overall, vascular, and non-vascular dementia, respectively. The association between aphasia and the risk of vascular dementia did not differ by stroke type (P for interaction=0.43). The analysis of 16856 propensity score-matched pairs revealed similar results.Patients with post-stroke aphasia have an increased risk of developing vascular dementia irrespective of the type of stroke.

Chinese have a higher stroke incidence and a different distribution of ischemic stroke (IS) subtypes as compared with Caucasians. Herein we aimed to investigate the prevalence and associations of major risk factors in IS and its subtypes in Chinese patients. From 2006 to 2011, we included 4953 acute IS patients consecutively recruited in National Taiwan University Hospital Stroke Registry (mean age 68 years; male 59%). For each risk factor, we accessed the proportion in all IS patients, and calculated odds ratios for each main IS subtype versus other subtypes. Multiple logistic regression models were used to adjust for confounders, and to examine the associations of risk factors with IS subtypes. Compared with other ischemic subtypes, large artery atherosclerotic and lacunar strokes were associated with hypertension, diabetes, and hyperlipidaemia, while cardioembolic strokes were associated with ischemic heart disease. Furthermore, the associations with hypertension and diabetes became stronger in lacunar strokes after adjusting for confounders, but not in other ischemic subtypes. Here we report the variable effects of risk factors on different IS subtypes in Chinese patients in Taiwan. Our findings could help shed light on different mechanisms of IS subtypes and provide targets to make more effective strategies for IS prevention.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Background Chinese populations are reported to have a different distribution of ischemic stroke subtypes compared with Caucasians. Aims To understand this better, we aimed to evaluate the differences in prevalence of risk factors in ischemic stroke and their distributions among ischemic stroke subtypes in Chinese vs. Caucasians. Summary or review We systematically sought studies conducted since 1990 with data on frequency of risk factors among ischemic stroke subtypes in Chinese or Caucasians. For each risk factor, we calculated study-specific and random effects pooled estimates in Chinese and Caucasians separately for: prevalence among ischemic stroke; odds ratios, comparing prevalence for each ischemic stroke subtype vs. all others. We included seven studies among 16 199 Chinese, and eleven among 16 189 Caucasian ischemic stroke patients. Risk factors studied were hypertension, diabetes, atrial fibrillation, ischemic heart disease, hypercholesterolemia, smoking and alcohol. Chinese ischemic stroke patients had younger onset of stroke than Caucasians, similar prevalence of hypertension, diabetes, smoking and alcohol, and significantly lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia. Risk factor associations with ischemic stroke subtypes were mostly similar among Chinese and Caucasian ischemic stroke patients. Compared with all other ischemic subtypes, diabetes was more common in large artery stroke, atrial fibrillation and ischemic heart disease in cardioembolic stroke, and hypertension and diabetes in lacunar stroke. Conclusion Our study showed a lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia in Chinese, and mostly similar risk factor associations in Chinese and Caucasian ischemic stroke patients. Further analyses of individual patient data to allow adjustment for confounders are needed to confirm and extend these findings.

Aims Impaired social function has been described in patients following stroke. The present study was designed to explore the degree of impairment in the ability to infer mental states in others, or cognitive and affective theory of mind, and empathy, in patients with stroke. Method A total of 34 patients with stroke were compared to 40 control subjects on tasks testing verbal and non-verbal theory of mind and empathy. Results Results indicated that patients with stroke were significantly impaired in both cognitive and affective theory of mind, even controlling for basic cognitive function and emotional processing. The patients with right stroke had poorer performance than those with left stroke on the cognitive component of non-verbal theory of mind. On the subscale of cognitive empathy, the right stroke group had poorer performance on perspective-taking than the control group. Conclusion The right hemisphere may play an important role in decoding non-verbal cues to infer others' minds as well as the processing of empathy, especially the ability of perspective-taking.

Objective Acute carbon monoxide (CO) poisoning poses a significant threat to the central nervous system. It can cause brain injury and diverse neurological deficits including persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). The study aimed to investigate the long-term impacts of acute CO poisoning on brain perfusion and neurological function, and to explore potential differences between PNS and DNS patients. Methods We evaluated brain perfusion using 99m Tc ethyl cysteinate (ECD) brain single photon emission computed tomography (SPECT) and assessed clinical neurological symptoms and signs one month following acute poisoning. For DNS patients, ECD SPECT and clinical evaluation were performed when their delayed symptoms appeared. All patients had follow-up SPECT imaging, along with clinical assessments six months following poisoning. Results 12 PNS and 12 DNS patients were recruited between 2007 and 2010. Clinically, the main characteristic presentations were cognitive decline, emotional instability, and gait disturbance. SPECT imaging demonstrated consistent frontal hypoperfusion of varying severities in all patients, which decreased in severity at follow-up imaging. DNS patients usually had more severe symptoms and perfusion defects, along with worse clinical outcomes than the PNS group. Conclusion These results suggest that acute CO poisoning might lead to long term brain injuries and neurological sequelae, particularly in DNS patients.

Background Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems. Methods We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies’ characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype. Summary of review We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78–0.97 [six studies, 518 cases], mechanistic 0.89–0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80–1 [three studies, 137 cases], mechanistic 0.92–0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative. Conclusions Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines.

Ethnopharmacological relevance Gastrodia elata (GE) Blume (family Orchidaceae) is a traditional Chinese herbal medicine for treating headaches, dizziness, tetanus, and epilepsy, indicating neuronal protective functions. Aim of the study To evaluate the neuroprotection of GE and its molecular mechanism in preventing serum deprivation-induced PC12 cell apoptosis. Materials and methods An MTT assay and Hoechst staining were used to respectively validate serum deprivation-induced cell death and apoptosis. Cyclic (c)AMP formation and protein kinase (PK)A activity were also measured after GE treatment. Western blotting was used to detect the phosphorylation of the cAMP response element-binding (CREB) protein. Transient transfection of a dominant negative CREB was used to validate the importance of CREB. Results GE targeted the adenosine A2A receptor (A2A-R). GE increased cAMP formation, PKA activity, and phosphorylation of the CREB protein. GE-induced CREB protein phosphorylation and protection was blocked by a PKA inhibitor and overexpression of the dominant negative CREB, respectively. Conclusions These results support the neuroprotective effects of GE. The protective mechanism might be mediated through an A2A-R/cAMP/PKA/CREB-dependent pathway.

Sarcoidosis is a chronic inflammatory disease that involves multiple systems. Complications in the nervous system are rare, especially in Asia. This report describes an unusual case of neurosarcoidosis affecting the spinal cord and other systems in a 53-year-old Taiwanese women patient. The patient presented with subacute onset of right arm radicular pain followed by quadriparesis. Magnetic resonance imaging revealed a hyperintense lesion on T2WI in the cervical spinal cord. The patient also had a history of facial neuropathy, bilateral parotid enlargement, intrathoracic lymphadenopathy, hypercalcemia, nephrocalcinosis, and renal function impairment. Parotid gland biopsy showed granulomatous lesion with multinucleated giant cells. Sarcoidosis was diagnosed after other possibilities were excluded. Oral steroid treatment resulted in initial significant clinical improvement. Awareness of the systemic and neurological presentations of sarcoidosis can prompt the correct diagnosis and treatment.

There are few previous studies on the relationship between cerebral infarction and acute anemia. This study presents patients with cerebral infarction in acute anemia due to marked blood loss and aims to clarify the stroke nature and possible mechanism. Patients with acute cerebral infarction and anemia following marked blood loss without systemic hypotension were recruited from 2001 to 2009. Clinical characteristics, particularly hemoglobin level, and neuroimaging findings were reviewed in detail to analyze the stroke nature and verify the possible pathogenesis. Twelve patients (males 8; mean age 74.9 years) were included. Eleven patients had cerebral infarction after acute massive gastrointestinal bleeding, and one had cerebral infarction following postoperative extensive hematoma during hospitalization. In all patients, borderzone infarction was the most characteristic finding: six had unilateral and six had bilateral borderzone infarction. Mean hemoglobin at infarction after acute blood loss was 5.8 g/dl, with 46% reduction from baseline. Of nine patients receiving detailed extracranial and intracranial vascular studies, none had severe carotid stenosis and six had intracranial stenosis. The arterial borderzones are the most vulnerable regions to a fall in cerebral perfusion. Acute anemia may produce cerebral blood flow insufficiency, reduce oxygen-carrying capacity, and result in distal-field tissue ischemic injury when hemoglobin level decreases below a critical level, especially in patients with intracranial stenosis.

Migraine is a common disorder in young women, but it is rarely associated with ischemic stroke. According to previous stroke registries, migrainous infarcts account for 0.5% to 1.5% of all ischemic strokes and about 10% to 14% of young ischemic strokes. 1,2 The pathophysiologic mechanism of migrainous infarction is still unclear. Here we report a patient with a migraine history in whom acute cerebral infarction developed during a migraine attack due to an arterial vasospasm, which was illustrated by serial transcranial Doppler sonography (TCD).

Detection of regional cerebral blood flow (rCBF) and/or brain magnetic resonance imaging (MRI) has been used to investigate functional defect of brain caused by carbon monoxide (CO) poisoning. In this report, we attempted to demonstrate the correlation of changes in brain singlephoton emission computed tomography (SPECT) and diffusion-tensor MR image (DTI) with functional improvement of severe delayed neuropsychiatric sequelae (DNS) after CO intoxication during the treatment of hyperbaric oxygen therapy (HBOT).The patient had normal activities of daily life after he recovered from acute CO poisoning. One month later, he presented symptoms of declined cognitive functioning, aphasia, apraxia, dysphagia, muscle rigidity, urine and fecal incontinence. After one course of HBOT, these symptoms improved significantly and the patient could regain most of his previous functioning. The patient's improvement was evidenced by increased rCBF in Brodmann areas 7, 8, 11 and 40, as well as higher mean fractional anisotropy (FA) value of DTI.Although the efficacy of HBOT in DNS patients is still needed to be evaluated in large clinical study, these data suggest that HBOT may be the choice to improve DNS efficiently and shorten the duration of suffering with favorable outcome.

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Diabetic mellitus (DM) has many well-known complications. However, there is one rare complication, diabetic muscle infarction (DMI), which is usually under diagnosed. Hereby, we present a 53-year-old Chinese man with a history of DM, hypertension and atrial fibrillation. He had acute onset of severe left lower leg pain and swelling with difficulty in walking 4 days before admission. Physical examination revealed non-pitting and non-erythematous swelling with cold sensation of the left medial calf muscles. Magnetic resonance image (MRI) showed homogenous high signal changes in the calf muscles on T2 images, which indicated DMI. After anticoagulation treatment, the patient had a fair recovery within 4 weeks and he could walk by himself thereafter. DMI is a rare complication of poorly controlled DM. It does have a characteristic clinical presentation and MRI findings. Increased clinical awareness is important for early recognition and correct treatment.

Objective: We aimed to systematically assess the evidence for differences in the incidence of stroke and distribution of its subtypes in Chinese compared with white populations. Methods: We comprehensively sought studies conducted since 1990 in Chinese populations of 1) first-ever stroke incidence (community-based studies only), and 2) pathologic types/subtypes of stroke (hospital- or community-based studies of first-ever or recurrent strokes). We identified community-based studies in white populations from a recent systematic review. For each study, we calculated age-standardized stroke incidence and the proportions of each pathologic type and ischemic subtype, using random-effects meta-analysis to pool proportions of stroke types/subtypes in Chinese and in white populations. Results: Age-standardized annual first-ever stroke incidence in community-based studies was higher among Chinese than white populations (for ages 45–74 years, range 205–584 vs 170–335 per 100,000, respectively). Intracerebral hemorrhage accounted for a larger, more variable proportion of strokes in China than Taiwan (range 27%–51% vs 17%–28%), in Chinese community-based than hospital-based studies (27%–51% vs 17%–30%), and in community-based Chinese than white studies (pooled proportion 33% vs 12%). Although the overall proportion of lacunar ischemic stroke appeared higher in Chinese than white populations, variable study methodologies precluded reliable comparisons. Conclusions: There is good evidence for a slightly higher overall stroke incidence and higher proportion of intracerebral hemorrhage in Chinese vs white populations, but no clear evidence for different distributions of ischemic stroke subtypes. Studies using comparable, population-based case ascertainment and similar classification methods are needed to address this.

Impaired social function has been described in patients following stroke. The present study was designed to explore the degree of impairment in the ability to infer mental states in others, or cognitive and affective theory of mind, and empathy, in patients with stroke.A total of 34 patients with stroke were compared to 40 control subjects on tasks testing verbal and non-verbal theory of mind and empathy.Results indicated that patients with stroke were significantly impaired in both cognitive and affective theory of mind, even controlling for basic cognitive function and emotional processing. The patients with right stroke had poorer performance than those with left stroke on the cognitive component of non-verbal theory of mind. On the subscale of cognitive empathy, the right stroke group had poorer performance on perspective-taking than the control group.The right hemisphere may play an important role in decoding non-verbal cues to infer others' minds as well as the processing of empathy, especially the ability of perspective-taking.

Transcranial Doppler imaging (TCDI) has been used as a noninvasive diagnostic tool to differentiate Parkinson's disease (PD) from atypical parkinsonism by detecting hypere- chogenicity in the substantia nigra (SN). To our knowledge, no TCDI data are available for Asian populations, and TCDI sensitivity is uncertain across populations. Early-onset PD (EOPD) represents a specific PD subtype based on clinical features and pathogenic mechanisms. It is not known if EOPD patients have abnormal echogenicity in SN comparable to late-onset PD (LOPD) patients. We assessed the area of SN hyperechogenicity (hyper-SN) and a ratio of hyper-SN over ipsilateral midbrain (S/M ratio) with TCDI in 164 healthy Taiwanese, 40 EOPD patients, and 40 LOPD patients. The upper 95th percentile values for hyper-SN and S/M ratio were 0.20 cm 2 and 0.07. Our results indicate that S/M ratio is a more sensitive measure than hyper-SN in diagnosing PD. Approxi- mately 92.5% of the LOPD patients and 57.5% of the EOPD patients had S/M ratios 0.07. Enlarged hyperechogenicity of SN is a common finding in LOPD, but not in EOPD. Iron- independent mechanisms of SN cell degeneration in EOPD distinct from that in LOPD might contribute to the sonographic findings. © 2007 Movement Disorder Society

Recently, transcranial color-coded sonography (TCCS) has been found to have a diagnostic value in patients with idiopathic Parkinson's disease (IPD), which displays increased hyperechogenicity at the substantia nigra (SN). To use TCCS, to assess the difference in SN hyperechogenicity and intracranial hemodynamics among subjects with IPD, vascular parkinsonism (VP) and controls. Eighty IPD and 30 VP patients, and 60 controls were recruited into this study. The hyperechogenicity area at the SN and midbrain were calculated by encircling the outer circumference from the ipsilateral temporal window, using TCCS in each subject. The hemodynamics of intracranial large arteries, including flow velocity and pulsatility index (PI), were also measured. The presence of SN hyperechogenicity was significantly higher in the IPD patients than in the VP patients and controls (84% vs. 20% & 5%, respectively, p < 0.001). In IPD patients, the SN hyperechogenicity was correlated with the neurological severity and disease duration. Twenty-five (66.7%) VP patients had obvious vascular abnormality, as seen in TCCS study. The mean PI was significantly more elevated in the VP patients than those in the IPD patients and controls (all p < 0.05), but there was no significant difference of flow velocities among the VP, IPD patients and controls. TCCS, combining B-mode imaging for SN echogenicity and trancranial Doppler for intracranial hemodynamics, is a useful diagnostic tool in the differentiation between IPD and VP. These findings also suggest that multiple subcortical vascular lesions may damage the basal ganglia and thalamocortical circuit and result in parkinsonism features in VP patients.

Background and Purpose. Atherosclerosis is the main cause of common carotid artery occlusion in most reports. This study aimed to identify the major causes of common carotid artery occlusion and compare the clinical features and carotid duplex ultrasonography findings of patients with common carotid artery occlusion attributable to each cause. Methods. Patients with common carotid artery occlusion documented by carotid duplex ultrasonography at the Neurovascular Laboratory (National Taiwan University Hospital) from 1988 to 2003 were included. Medical records and ultrasonographic findings were reviewed in detail to clarify the possible etiology of common carotid artery occlusion. Results. A total of 44 patients (male, 27 [61%]; female, 17 [39%]; mean age, 58 years) had common carotid artery occlusion attributable to a carotid duplex ultrasonography–identifiable cause. The causes of common carotid artery occlusion included atherosclerosis (17 [39%]), Takayasu's arteritis (11 [25%]), postirradiation arteriopathy (7 [16%]), cardiac embolism (6 [14%]), syphilis (1), blunt trauma (1), and homocystinuria (1). Among the patients with common carotid artery occlusion due to the 4 major causes, 27 (66%) had ischemic stroke and 14 (34%) had no symptoms or nonlocalizing symptoms. The frequency of symptomatic com mon carotid artery occlusion was 83% in those with cardioembolism, 76% in those with atherosclerosis, 71% in those with postirradiation arteriopathy, and 36% in those with Takayasu's arteritis. Common carotid artery occlusion usually involved the carotid bulb and distal common carotid artery in atherosclerosis (88%) and postirradiation arteriopathy (100%), but not in Takayasu's arteritis (27%). Echogenicity of occluded material was heterogeneous in atherosclerosis and post-irradiation arteriopathy patients but homogeneous in all Takayasu's arteritis patients. The authors postulate that the thrombotic mechanism might differ according to etiology. Con clusions. The causes of common carotid artery occlusion are diverse. Atherosclerosis, Takayasu's arteritis, and post-irradiation arteriopathy are the most common causes of com mon carotid artery occlusion in Taiwan. The clinical features, pathophysiology, and carotid duplex ultrasonography findings vary according to the cause of common carotid artery occlusion.