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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.

Aims/Introduction To elucidate whether axonal changes arise in the prediabetic state and to find a biomarker for early detection of neurophysiological changes. Materials and Methods We enrolled asymptomatic diabetes patients, as well as prediabetic and normoglycemic individuals to test sensory nerve excitability, and we analyzed those findings and their correlation with clinical profiles. Results In nerve excitability tests, superexcitability in the recovery cycle showed increasing changes in the normoglycemic, prediabetes and diabetes cohorts (−19.09 ± 4.56% in normoglycemia, −22.39 ± 3.16% in prediabetes and −23.71 ± 5.15% in diabetes, P = 0.002). Relatively prolonged distal sensory latency was observed in the median nerve (3.12 ± 0.29 ms in normoglycemia, 3.23 ± 0.38 ms in prediabetes and 3.45 ± 0.43 ms in diabetes, P = 0.019). Superexcitability was positively correlated with fasting plasma glucose (r = 0.291, P = 0.009) and glycated hemoglobin (r = 0.331, P = 0.003) in all participants. Conclusions Sensory superexcitability and latencies are the most sensitive parameters for detecting preclinical physiological dysfunction in prediabetes. In addition, changes in favor of superexcitability were positively correlated with glycated hemoglobin for all participants. These results suggest that early axonal changes start in the prediabetic stage, and that the monitoring strategy for polyneuropathy should start as early as prediabetes., We explored early changes of axonal function in prediabetes using axonal excitability test. The changes progressed from normoglycemia, prediabetes and early diabetes. Superexcitability is the most sensitive parameter for sensory axonal dysfunction. Fasting sugar and glycated hemoglobin were correlated with superexcitability in all participants.

The influence of aneurysmal subarachnoid hemorrhage (SAH) on brain microcirculation has not yet been systematically investigated. We established an animal model to examine (1) the brain surface microcirculation (2) the influences of cerebrospinal fluid (CSF) from aneurysmal SAH on the brain surface microcirculation. A rat SAH model was induced by injection of autologous arterial blood into the cisterna magnum, and the brain surface microcirculation was evaluated by a capillary videoscope with craniotomy at the fronto-parietal region. CSF from SAH rats and SAH patients was applied on the brain surface of naïve rats to assess the resulting microcirculatory changes. In the SAH rats, diffuse constriction of cortical arterioles within 24 hours of SAH was observed. Similar patterns of microcirculation impairment were induced on normal rat brain surfaces via application of CSF from SAH rats and SAH patients. Furthermore, the proportion of subjects with arteriolar vasoconstriction was significantly higher in the group of SAH patients with delayed ischemic neurological deficits (DIND) than in those without DIND (p

Evidence shows possible benefits from continuous drainage by lumbar drain after aneurysmal subarachnoid hemorrhage (SAH). Under the hypothesis that compartmentalization occurs between the ventricle and subarachnoid space after massive SAH, this study aimed to evaluate the biochemical differences between ventricular and intrathecal cerebrospinal fluid (CSF) and assess the role of CSF lactate in shunt-dependent hydrocephalus (SDHC) after aneurysmal SAH.Patients with modified Fisher grade III/IV aneurysmal SAH who underwent early obliteration were evaluated. Intrathecal and intraventricular CSF were obtained on day 7 post-SAH to measure their biochemical composition in terms of total protein, glucose, ferritin, and lactate. The associations of SDHC with the clinical parameters and CSF data were analyzed.There were 28 patients (mean age, 55.4 y; males, 46.6%), including 18 (64.3%) with SDHC. Intrathecal CSF had significantly higher levels of total protein, ferritin, hemoglobin, and lactate but lower glucose level than intraventricular CSF (all P0.0001). By multivariate analysis of clinical and CSF parameters, elevated intrathecal CSF lactate (P = 0.036) and the presence of intraventricular hemorrhage (P = 0.05) were independent factors associated with SDHC. Moreover, intrathecal lactate5.5 μM effectively predicted the occurrence of SDHC (odds ratio: 32, 95% confidence interval: 3.8-270.8; P = 0.0015).By compartmentalization of the subarachnoid space after SAH, intrathecal lactate level is a useful predictive parameter for long-term SDHC in patients with aneurysmal SAH patients.

OBJECTIVEDirect brain compression and secondary injury due to increased intracranial pressure are believed to be the pathognomic causes of a grave outcome in acute subdural hemorrhage (aSDH). However, ischemic damage from aSDH has received limited attention. The authors hypothesized that cerebral microcirculation is altered after aSDH. Direct visualization of microcirculation was conducted in a novel rat model.METHODSA craniectomy was performed on each of the 18 experimental adult Wistar rats, followed by superfusion of autologous arterial blood onto the cortical surface. Changes in microcirculation were recorded by capillary videoscopy. Blood flow and the partial pressure of oxygen in the brain tissue (PbtO2) were measured at various depths from the cortex. The brain was then sectioned for pathological examination. The effects of aspirin pretreatment were also examined.RESULTSInstantaneous vasospasm of small cortical arteries after aSDH was observed; thrombosis also developed 120 minutes after aSDH. Reductions in blood flow and PbtO2 were found at depths of 2–4 mm. Blood-brain barrier disruption and thrombi formation were confirmed using immunohistochemical staining, while aspirin pretreatment reduced thrombosis and the impairment of microcirculation.CONCLUSIONSMicrocirculation impairment was demonstrated in this aSDH model. Aspirin pretreatment prevented the diffuse thrombosis of cortical and subcortical vessels after aSDH.

Objective To determine whether perfusion computed tomography (CT) is useful for identifying patients with poor-grade subarachnoid hemorrhage (SAH) with reversible etiologies and whether early obliteration in patients with poor-grade aneurysmal SAH leads to favorable outcomes. Methods Patients with new-onset aneurysmal SAH in World Federation of Neurological Surgeons (WFNS) grade IV or V neurologic condition who had perfusion CT performed at admission were eligible for the study. The study retrospectively enrolled 38 patients seen between January 2007 and July 2009. The decision to perform an early obliteration was made by the family after a discussion with the neurosurgeons, neurointensivists, and interventional radiologists. The functional outcomes were correlated with the Glasgow Outcome Scale (GOS) at 6 months, and quantitative perfusion CT data were collected. Results This study included 10 (26%) grade IV and 28 (74%) grade V patients. Favorable outcomes occurred in 19 (50%) patients, and 11 (29%) patients died. After a multivariate logistic regression analysis of the parameters, older age (odds ratio 1.104, P = 0.0317), bilateral prolonged mean transient time (MTT) at the thalami (odds ratio 4.155, P = 0.0362), and early obliteration (odds ratio 0.098, P = 0.003) were predictive of poor outcome. Conclusions Early bilateral prolonged MTT at the thalami and old age are associated with a poor outcome. Early obliteration benefits a significant portion of SAH patients.

Ischemia is an important etiology of painful neuropathies. We generated a mouse system of ischemic neuropathy by ligation-reperfusion of the femoral artery to mimic neuropathic pain and nerve injury patterns observed clinically. Mice exhibited spontaneous neuropathic pain behaviors, which were most obvious after ischemia for 5 h. Mechanical and cold allodynia developed by post-operative day (POD) 7 and persisted through the experimental period up to POD 56. Neuropathic pain behaviors were alleviated with intraperitoneal gabapentin (50 and 100 mg/kg) in a dose-dependent manner. Large-fiber deficit assessed with nerve conduction studies was demonstrated by reduced amplitudes of the compound muscle action potential (CMAP) on POD 7 (48.4% of the control side, p < 0.001). Small-fiber impairment was demonstrated by decreased epidermal nerve density (END) on POD 7 (29.1% of the control side, p < 0.001). Reductions in CMAP amplitudes and ENDs persisted through POD 56. Our system replicated the clinical manifestations of ischemic neuropathy: (1) neuropathic pain with cold and mechanical allodynia and (2) nerve injury to both large and small fibers with pathologic and physiologic evidence. This system produced by a simple procedure provides an opportunity to investigate mechanisms and further treatments of ischemic neuropathy on genetically engineered mice.

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005–1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

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.

Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients.Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed.The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 μM, with higher values predicting unfavorable outcome (82.4% accuracy).The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.

The object of this study was to identify the clinical features and outcomes of a subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH) who had active contrast extravasation from a ruptured aneurysm during initial cerebral CT angiography (CTA).The authors performed a retrospective study of spontaneous SAH cases involving patients treated at their institute. They identified 9 cases in which active contrast extravasation was evident on the initial CT angiogram. Another 12 similar cases were also identified in a literature review and data was gathered from these cases to evaluate the outcomes.Analysis of all 21 cases revealed that the overall outcomes in cases characterized by active aneurysmal bleeding during CTA were poor. Seventy-six percent of patients had unfavorable results. Patients who showed poor neurological status at presentation died no matter what kind of treatment they received. In contrast, patients who presented with good neurological status initially had a chance of favorable outcome. Among the patients with good initial neurological status, most demonstrated rapid deterioration of their condition during the CTA examination; only those who received immediate and effective decompressive surgery and aneurysm obliteration had good results.Active aneurysmal rebleeding during CTA is an uncommon but devastating event. Though the mortality of this distinct group of patients remains high, a clinical subgroup may benefit from immediate surgery. Patients with good initial neurological status who show rapid neurological deterioration may still have a favorable outcome if they undergo timely and successful decompressive surgery and proper aneurysm obliteration. Patients who present with poor neurological status do badly, and there is no effective treatment for such patients.

Traumatic subdural effusion (TSE) is a common sequela of traumatic brain injury. Surgical intervention is suggested only when TSE exerts mass effect. The authors have found that many patients with TSE exerting mass effect have concomitant hydrocephalus. Patient experiencing this occurrence were studied, and the pathogenesis of this phenomenon was discussed in the context of recent advances in the understanding of CSF circulation.During a 2-year period, the authors' institution treated 14 patients with TSE who developed hydrocephalus, after 1 of the patients suffered subdural drainage and other 13 received subdural peritoneal shunt (SPSs). Thirteen of those who had SPSs received programmable ventriculoperitoneal shunts (VPSs) for the hydrocephalus. The clinical characteristics as well as the imaging and operative findings of these patients were reviewed.All patients with symptomatic TSE exerting mass effect received SPSs. All of these patients had a modified Frontal Horn Index of more than 0.33 at presentation, and high opening pressure on durotomy. Following a brief period (4-7 days) of clinical improvement, the condition of all patients deteriorated due to hydrocephalus. Programmable VPSs were inserted with the initial pressure set at approximately 8-10 cm H(2)O according to opening pressure at ventriculostomy. Shunt valve pressure was gradually decreased to 5-7 cm H(2)O, according to clinical and radiological follow-up.Elevated modified Frontal Horn Index in patients with TSE is suggestive of concomitant hydrocephalus. The authors propose that tearing of the dura-arachnoid plane following trauma contributes to TSE and may also impede CSF circulation, causing hydrocephalus. Shunt pressure was adjusted to relative low pressure, indicating the old age of the patients and poor reexpansion of brain parenchyma after the mass effect. Subdural peritoneal shunts and VPSs are indicated in those patients with TSE exerting mass effect with concomitant hydrocephalus.

Background Intraventricular hemorrhage, a frequent complication of intracerebral supratentorial hemorrhage, is associated with high rates of morbidity and mortality. Several methods have recently been developed for accelerating the clearance of intraventricular blood clots, especially during massive IVH. The present study was conducted to evaluate the interhemispheric, transcorpus callosal approach with septostomy for the management of supratentorial hemorrhage with intraventricular extension. Methods Eighteen patients with primary IVH or thalamic/caudate hemorrhage complicated by IVH received an operation for removal of intraventricular blood clots by the interhemispheric, transcorpus callosal approach with septostomy. All patients received a brain CT examination before and after surgery. Clinical outcomes were assessed 6 months after surgery by the GOS. Results Good clinical outcomes (GOS scores ≥4) were achieved in 45.6% of patients. In the patients with poor clinical outcome, the mean age was older ( P = .001) and diabetes mellitus was more common ( P = .04). Patients with thalamic hemorrhage with rupture into the third ventricle had worse clinical outcomes ( P = .04). The overall mortality rate at 6 months postsurgery was 5.6%. Conclusion The interhemispheric, transcorpus callosal approach with septostomy is safe and effective for direct removal of intraventricular blood clots during treatment of supratentorial hemorrhage with intraventricular extension. Further investigations involving more cases are needed to assess more fully the extent of improvement in clinical outcome attributable to this approach.

Background Skin denervation in vasculitic neuropathy has rarely been documented despite frequent manifestations of small-fiber neuropathy including reduced sensitivity and neuropathic pain. Recently, skin biopsy has been established as a new approach to diagnose small-fiber sensory neuropathy. Objectives To investigate the pathologic features of cutaneous nerves and to evaluate inflammatory vasculopathy in the skin of patients with vasculitis. Design Case series. Setting National Taiwan University Hospital, Taipei. Patients Six patients with vasculitic neuropathy. Interventions Patients had 3-mm punch biopsy specimens taken from the distal part of the leg (without active vasculitic lesions) and a sural nerve biopsy specimen was taken in addition to detailed neurologic examinations, laboratory investigations, and nerve conduction studies. Main Outcome Measures Results of nerve conduction studies, epidermal nerve fiber density studies, and immunohistochemistry. Results All 6 patients had combined large- and small-nerve-fiber involvement on the neurologic examinations. Nerve conduction studies showed a pattern of axonal neuropathy or mononeuropathy multiplex. Epidermal nerve fiber densities were significantly reduced in the skin of all patients, consistent with concomitant small-fiber neuropathies. Perivascular infiltration by T cells and macrophages was demonstrated by immunohistochemistry. All patients experienced neurologic improvement in muscle strength and alleviation of sensory symptoms after immunotherapy with corticosteroids, plasma exchange, or cyclophosphamide. Conclusions Small-diameter sensory nerves are affected in vasculitis in addition to the well-known effect of vasculitis on large-diameter nerves. Significant inflammatory vasculopathy is present in the skin despite the absence of clinically active vasculitic lesions.