Smoking Paradox in Stroke Survivors?: Uncovering the Truth by Interpreting 2 Sets of Data.

Background and Purpose- The observation that smokers with stroke could have better outcome than nonsmokers led to the term "smoking paradox." The controversy of such a complex claim has not been fully settled, even though different case mix was noted. Analyses were conducted on 2 independent data sets to evaluate and determine whether such a paradox truly exists. Methods- Taiwan Stroke Registry with 88 925 stroke cases, and MJ cohort with 541 047 adults participating in a medical screening program with 1630 stroke deaths developed during 15 years of follow-up (1994-2008). Primary outcome for stroke registry was functional independence at 3 months by modified Rankin Scale score ≤2, for individuals classified by National Institutes of Health Stroke Scale score at admission. For MJ cohort, mortality risk by smoking status or by stroke history was assessed by hazard ratio. Results- A >11-year age difference in stroke incidence was found between smokers and nonsmokers, with a median age of 60.2 years for current smokers and 71.6 years for nonsmokers. For smokers, favorable outcome in mortality and in functional assessment in 3 months with modified Rankin Scale score ≤2 stratified by the National Institutes of Health Stroke Scale score was present but disappeared when age and sex were matched. Smokers without stroke history had a ≈2-fold increase in stroke deaths (2.05 for ischemic stroke and 1.53 for hemorrhagic stroke) but smokers with stroke history, 7.83-fold increase, overshadowing smoking risk. Quitting smoking at earlier age reversed or improved outcome. Conclusions- "The more you smoke, the earlier you stroke, and the longer sufferings you have to cope." Smokers had 2-fold mortality from stroke but endured stroke disability 11 years longer. Quitting early reduced or reversed the harms.

Early white matter injuries associated with dopamine transporter dysfunction in patients with acute CO intoxication: A diffusion kurtosis imaging and Tc-99m TRODAT-1 SPECT study.

PURPOSE: Patients with CO intoxication were demonstrated to exhibit white matter (WM) injuries, changes in substantia nigra, dopamine transporter dysfunctions of striatum and Parkinsonism symptoms. We aimed to investigate the relationship between WM injuries of dopaminergic pathways and dopamine transporter dysfunctions of the striatum in patients with acute CO intoxication using both diffusion kurtosis imaging (DKI) and single photon-emission computed tomography (SPECT). MATERIALS AND METHODS: Seventeen patients with acute CO intoxication and 19 age- and gender-matched healthy subjects were enrolled. DKI data were acquired from all participants and Tc-99m-TRODAT-1 SPECT scan was performed on each patient. DKI datasets were fitted to obtain axial, radial and mean diffusivity, fractional anisotropy, axial, radial and mean kurtosis for voxel-based comparison. In addition, the TRODAT-1 binding ratio of the striatum was calculated using the occipital cortices as a reference. In significant regions, correlational analysis was performed to understand the relationship between DKI indices and TRODAT-1 binding ratio. RESULTS: The results showed that DKI indices were significantly altered in multiple WM regions broadly involving the basal ganglia-thalamocortical circuit and nigrostriatal pathway. The correlation analysis further revealed significant correlations between DKI indices and the TRODAT-1 binding ratio in the nigrostriatal pathway (absolute correlation coefficients ranged from 0.5992 to 0.6950, p<0.05), suggesting that CO-induced early WM injuries were associated with dopamine transporter dysfunctions of striatum. CONCLUSION: We concluded that DKI and Tc-99m-TRODAT-1 SPECT scans were helpful in early detection of global WM injuries associated with dysfunctions of dopamine transporter in patients with acute CO intoxication. KEY POINTS: • Voxel-based diffusion kurtosis imaging analysis was helpful in globally detecting early white matter injuries in patients with acute CO intoxication. • CO-induced early white matter injuries were broadly located in basal ganglia-thalamocortical circuit and nigrostriatal pathway. • Early white matter injuries in dopaminergic pathways were significantly correlated with dopamine transporter dysfunctions of the striatum.

One-Year Risk of Recurrent Stroke and Death Associated with Vertebrobasilar Artery Stenosis and Occlusion in a Cohort of 10,515 Patients.

BACKGROUND: The natural history of vertebrobasilar artery (VBA) stenosis or occlusion remains understudied. METHODS: Patients with diagnosis of ischemic stroke or transient ischemic attack (TIA) who were noted to have VBA stenosis based on computed tomography or magnetic resonance imaging or catheter-based angiogram were selected from Taiwan Stroke Registry. Cox proportional hazards model was used to determine the hazards ratio (HR) of recurrent stroke and death within 1 year of index event in various groups based on severity of VBA stenosis (none to mild: 0-49%; moderate to severe: 50-99%: occlusion: 100%) after adjusting for differences in demographic and clinical characteristics between groups at baseline evaluation. RESULTS: None to mild or moderate to severe VBA stenosis was diagnosed in 6972 (66%) and 3,137 (29.8%) among 10,515 patients, respectively, and occlusion was identified in 406 (3.8%) patients. Comparing with patients who showed none to mild stenosis of VBA, there was a significantly higher risk of recurrent stroke (HR 1.21, 95% CI 1.01-1.45) among patients with moderate to severe VBA stenosis. There was a nonsignificantly higher risk of recurrent stroke (HR 1.49, 95% CI 0.99-2.22) and significantly higher risk of death (HR 2.21, 95% CI 1.72-2.83), among patients with VBA occlusion after adjustment of potential confounders. CONCLUSIONS: VBA stenosis or occlusion was relatively prevalent among patients with TIA or ischemic stroke and associated with higher risk of recurrent stroke and death in patients with ischemic stroke or TIA who had large artery atherosclerosis.

Treatment and prognosis of subdural hematoma in patients with spontaneous intracranial hypotension.

OBJECTIVE: The objective of this article is to elucidate the outcome, prognostic predictors and timing of surgical intervention for subdural hematoma (SDH) in patients with spontaneous intracranial hypotension (SIH). METHODS: Patients with SDH were identified retrospectively from 227 consecutive SIH patients. Data were collected on demographics, clinical courses, neuroimaging findings, and treatment of SDH, which was later divided into conservative treatment, epidural blood patches (EBP), and surgical intervention. Poor outcome was defined as severe neurological sequelae or death. RESULTS: Forty-five patients (20%) with SDH (mean maximal thickness 11.9 ± 6.2 mm) were recruited. All 15 patients with SDH <10 mm achieved good outcomes by either conservative treatment or EBP. Of 30 patients with SDH ≥10 mm, patients with uncal herniation (n = 3) had poor outcomes, even after emergent surgical evacuation (n = 2), compared to those without (n = 27) (100% vs. 0%, p < 0.001). Fourteen patients underwent surgical evacuation, resulting in good outcomes in all 12 who received early intervention and poor outcomes in the remaining two who received delayed intervention after Glasgow Coma Scale (GCS) score ≤8 (100% vs. 0%, p = 0.01). CONCLUSIONS: Uncal herniation results in poor outcomes in patients with SIH complicated with SDH. In individuals with SDH ≥10 mm and decreased GCS scores, early surgical evacuation might prevent uncal herniation.

Increased intracortical inhibition in hyperglycemic hemichorea-hemiballism.

Hemichorea-hemiballism (HC-HB) in uncontrolled diabetes mellitus is an uncommon manifestation of hyperglycemia. The pathophysiology of hyperglycemic HC-HB is not well understood. A previous report showed increased intracortical inhibition in the motor cortex in a patient with diabetes with HC-HB. The objective of this study is to investigate motor cortex excitability in patients with hyperglycemic HC-HB. We hypothesized that intracortical inhibition measured with transcranial magnetic stimulation, which likely reflects the excitability of cortical γ-aminobutyric acid (GABA)ergic circuits, would be impaired in patients with hyperglycemic HC-HB. We studied 15 patients with mean age 71.5 years (range, 48-94 y) and 12 age-matched healthy subjects. The motor cortex contralateral to the hemichorea was tested. Transcranial magnetic stimulation measures included motor evoked potential, recruitment curve, GABAA mediated short interval intracortical inhibition, intracortical facilitation, and GABAB mediated silent period duration and long interval intracortical inhibition. No significant difference was found in motor threshold, recruitment curve response, short interval intracortical inhibition, or intracortical facilitation in both rest and active conditions between patients with hyperglycemic HC-HB and normal subjects. However, long interval intracortical inhibition was significantly increased during muscle activation but not at rest in patients with hyperglycemic HC-HB. The silent period duration is also increased in patients with hyperglycemic HC-HB. We concluded that long interval intracortical inhibition and silent period are increased in the motor cortex contralateral to the hemichorea in hyperglycemic HC-HB, but only during muscle activation. Hemichorea-hemiballism may be associated with increased GABAB receptor-mediated inhibitory activity in the motor cortex.

Comparison of activities of daily living impairments in Parkinson's disease patients as defined by the Pill Questionnaire and assessments by neurologists.

OBJECTIVES: To compare the clinical judgment of experienced neurologists after interviewing Parkinson's disease (PD) patients and their caregivers with the use of the Pill Questionnaire to determine the presence of impairments on activities of daily living (ADL). BACKGROUND: ADL impairment is a criterion for the diagnosis of dementia associated with PD. The Pill Questionnaire has been recommended as a screening tool to assess ADL impairment in PD patients, but its usefulness and validity have not been fully investigated. METHODS: We recruited idiopathic PD patients from 12 hospitals in Taiwan, and the patients underwent clinical assessments, a neuropsychological test battery and the Unified Parkinson Disease Rating Scale evaluation. The Pill Questionnaire was administered by study assistants. Patient and caregiver interviews were performed by experienced neurologists who were blinded to the Pill Questionnaire results. RESULTS: In total, 284 PD patients (mean age 71.8±9 years, mean education 8.7±5.3 years, mean disease duration 5.4±5.3 years) were recruited. 63 patients showed ADL impairment by the Pill Questionnaire, and 108 patients showed ADL impairment by neurologists' clinical interviews. κ Statistics showed moderate agreement between the two methods (κ=0.521, p<0.001). Of the 108 patients who were diagnosed with ADL impairment by neurologists, only 56 patients (51.9%) showed impairment according to the Pill Questionnaire. Most of the missed patients had milder cognitive impairment and lower motor disability. CONCLUSIONS: A comprehensive interview is essential to determine the presence of ADL impairment in PD patients, especially in patients with early PD.

Mechanically treated Mn2O3 triggers peracetic acid activation for superior non-radical oxidation of micropollutants: Identification of reactive complexes.

This study used a simple mechanical ball milling strategy to significantly improve the ability of Mn2O3 to activate peracetic acid (PAA) for sustainable and efficient degradation of organic micropollutant (like bisphenol A, BPA). BPA was successfully removed and detoxified via PAA activation by the bm-Mn2O3 within 30 min under neutral environment, with the BPA degradation kinetic rate improved by 3.4 times. Satisfactory BPA removal efficiency can still be achieved over a wide pH range, in actual water and after reuse of bm-Mn2O3 for four cycles. The change in hydrophilicity of Mn2O3 after ball milling evidently elevated the affinity of Mn2O3 for binding to PAA, while the reduction in particle size exposed more active sites contributing partially to catalytic oxidation. Further analysis revealed that BPA oxidation in the ball mill-treated Mn2O3 (bm-Mn2O3)/PAA process mainly depends on the bm-Mn2O3-PAA complex (i.e., Mn(III)-OO(O)CCH3) mediated non-radical pathway rather than R-O• and Mn(IV). Especially, the existence of the Mn(III)-PAA complex was definitely verified by in situ Raman spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Simultaneously, density functional theory calculations determined that PAA adsorbs readily on manganese sites thereby favoring the formation of Mn(III)-OO(O)CCH3 complexes. This study advances an in-depth understanding of the underlying mechanisms involved in the manganese oxide-catalyzed activation of PAA for superior non-radical oxidation of micropollutants.

Transcallosal inhibition in patients with callosal infarction.

Recent studies in normal subjects suggested that callosal motor fibers pass through the posterior body of the corpus callosum (CC), but this has not been tested in patients with callosal infarction. The objective of this study is to define the pathways involved in transcallosal inhibition by examining patients with infarctions in different subregions of the CC. We hypothesized that patients with lesions in the posterior one-half of the CC would have greater reduction in transcallosal inhibition between the motor cortices. Twenty-six patients with callosal infarction and 14 healthy subjects were studied. The callosal lesions were localized on sagittal MRI and were attributed to one of five segments of the CC. Transcranial magnetic stimulation was used to assess ipsilateral silent period (iSP) and short- and long-latency interhemispheric inhibition (SIHI and LIHI, respectively) originating from both motor cortices. The results showed that the iSP areas and durations were markedly reduced bilaterally in patients with callosal infarction compared with normal subjects. Patients with callosal infarctions also had less IHI bidirectionally compared with normal subjects. iSP areas and durations were lower in patients with lesions than in patients without lesions in segment 3 (posterior midbody) of the CC. Lesion burden in the posterior one-half of the CC negatively correlated transcallosal inhibition measured with iSP and SIHI. Our study suggests that callosal infarction led to reduced transcallosal inhibition, as measured by iSP, SIHI, and LIHI. Fibers mediating transcallosal inhibition cross the CC mainly in the posterior one-half.

Longitudinal gray matter changes of the pain matrix in patients with carbon monoxide intoxication: A voxel-based morphometry study.

PURPOSE: Carbon monoxide (CO) intoxication causes gray matter (GM) changes and headache symptom in patients with CO intoxication, but the headache-associated GM changes are not well understood. The purpose of this study was to perform a voxel-based morphometry (VBM) analysis to investigate longitudinal GM changes of brain pain matrix in patients with CO intoxication. METHODS: This prospective study enrolled 24 patients with CO intoxication and 20 healthy controls. Whole brain high-resolution T1-weighted images were acquired in both groups and were repeated in patients at 1 week, and 1, 3, and 9 months after CO exposure. VBM was performed to detect global GM changes in patients with CO intoxication, and the automated anatomical labeling template was utilized to estimate the distribution of significant GM clusters in the brain. RESULTS: GM volumes were significantly decreased mainly in the frontal and occipital lobes, including several pain-matrix regions 1 week after CO intoxication. The regions with significant GM changes further involved the central GM structures and the periaqueductal gray (pain-modulating center) at 1 and 3 months after CO intoxication, but the alterations were partially normalized in the frontal lobe and cerebellum 9 months after CO intoxication. Significant negative correlations were revealed between GM volume and duration of coma in the pain matrix regions. Moreover, five patients exhibited delayed neuropsychiatric sequelae (DNS) and had greater GM volume changes than non-DNS patients. CONCLUSION: VBM analysis is helpful to understand the longitudinal GM changes of the pain matrix in patients with CO intoxication.

Right Hemihepatectomy via an Anterior Approach for Hepatocellular Carcinoma in a Situs Inversus Totalis Patient.

Situs inversus totalis (SIT) is a rare congenital condition in which the usual position of the organs is reversed from left to right as a mirror image of the normal situation. Due to the abnormal transposition, this represents a technical challenge for the surgeon. In the present study, right hemihepatectomy via the anterior approach was performed for a 68-year-old hepatocellular carcinoma (HCC) patient with SIT. SIT was diagnosed by chest X-ray and computed tomography. The tumors were located in segments VIII and VI of the liver, and there was no metastasis to the lymph nodes and distant organs. Hemihepatic vascular inflow occlusion was performed using the selective intra-Glissonian approach. The middle hepatic vein was preserved under the guidance with intraoperative ultrasonography. The present case suggests that right hemihepatectomy via the anterior approach may be a safe, feasible, and effective procedure for HCC patients with SIT.

Evaluating Mild Cognitive Dysfunction in Patients with Parkinson's Disease in Clinical Practice in Taiwan.

Our study aimed to examine the contribution of commonly used tools, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and develop a formula for conversion of these tests in the Chinese population. We also create a predictive model for the detection of Chinese patients' mild cognitive impairment (MCI). We recruited 168 patients with Parkinson's disease (PD) from 12 medical centres or teaching hospitals in Taiwan, and each participant received a comprehensive neuropsychological assessment. Logistic regression analysis was conducted to find predictors of MCI with the help of a generalized additive model. We found that patients with an MMSE > 25 or a MoCA > 21 were less likely to have MCI. The discrimination powers of the two tests used for detecting MCI were 0.902 and 0.868, respectively, as measured by the area under the receiver operating characteristic curve (ROC). The best predictive model suggested that patients with a higher MMSE score, delayed recall scores of the 12-item Word Recall Test ≥ 5.817, and no test decline in the visuospatial index were less likely to have MCI (ROC = 0.982). Our findings have clinical utility in MCI detection in Chinese PD and need a larger sample to confirm.

Proton magnetic resonance spectroscopy in Kennedy disease.

The purpose of this study was to investigate the metabolic abnormalities in Kennedy disease (KD) patients using proton magnetic resonance spectroscopy. Five patients with KD showing typical phenotype were compared with eight age-matched, healthy control subjects. Relative metabolite concentrations for N-acetyl-aspartate (NAA), choline (Cho) and phosphocreatine (Cr) and lactate (Lac) were measured in the motor cortex and the brainstem area. In the motor cortex, NAA/Cr ratio was significantly reduced in KD patients (P=0.04). In the brainstem area, metabolic ratios including NAA/Cho, NAA/Cr and Cho/Cr failed to show significant difference between KD patients and normal controls. No pathologic Lac signal was noted in patients and controls. These findings corroborate a previous study indicating an involvement of the motor cortices in patients with KD.

Extra-Glissonian Approach for Laparoscopic Liver Right Anterior Sectionectomy.

BACKGROUND: Open right anterior sectionectomy, which involves resection of liver segments 5 and 8, has been reported to have similar postoperative mortality rates as right hepatectomy, but it has a decreased risk in developing posthepatectomy liver failure. Totally laparoscopic right anterior sectionectomy is technically demanding and has rarely been reported in hepatocellular carcinoma (HCC) patients with cirrhosis. METHODS: Our experience in carrying out totally laparoscopic right anterior sectionectomy on four consecutive HCC patients with cirrhosis from November 2016 to August 2017 using the extraglissonian approach formed the basis of this report. RESULTS: All four patients had hepatitis B-related HCC. The mean operation time was 502 ± 55 minutes. All patients underwent intermittent Pringle's Maneuver with cycles of clamp/unclamp times of 15/5 minutes for the left-sided liver transection plane, and intermittent right hemihepatic vascular inflow occlusion with cycles of clamp/unclamp times of 30/5 minutes for the right-sided liver transection plane. The mean Pringle's Maneuver time was 58.8 ± 11.4 minutes and the mean right hemihepatic vascular inflow occlusion time was 66.3 ± 11.1 minutes. The mean intraoperative blood loss was 512 ± 301 mL. No patients required any blood transfusion. There was no conversion to open surgery. Postoperative complications included intra-abdominal bleeding requiring reoperation for hemostasis (n = 1), intra-abdominal collection requiring percutaneous drainage (n = 1), and right pleural effusion requiring percutaneous drainage (n = 1). There was no 90-day postoperative mortality. The mean hospital stay was 10.7 ± 2.9 days. After a median follow-up of 10 (range, 6-16) months, one patient developed HCC recurrence in the liver remnant. CONCLUSION: Totally laparoscopic right anterior sectionectomy using the extraglissonian approach was technically feasible and safe in expert hands. More data are needed to assess the long-term oncological survival outcomes.

Electrophysiological features of myoclonus-dystonia.

Inherited myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonus and dystonia that often improves with alcohol. To examine the electrophysiologic characteristics of M-D, we studied 6 patients from 4 different families and 9 age-matched healthy subjects. Neurophysiological studies performed include electromyography (EMG)-electroencephalography (EEG) polygraphy, jerk-locked back-averaged EEG, somatosensory evoked potentials (SEP), long-latency reflex (LLR) to median and digital nerve stimulation, and transcranial magnetic stimulation studies with short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI). All 6 patients showed myoclonus and dystonia on clinical examination and EMG testing. The EMG burst durations ranged from 30.4 to 750.6 milliseconds (mean, 101.5 milliseconds). Jerk-locked back-averaged EEG failed to reveal any preceding cortical correlates. Median nerve SEP revealed no giant potential. No patients had exaggerated LLR to median or digital nerve stimulation. There was no significant difference in SICI, ICF, and LICI between M-D patients and normal subjects. Myoclonus in inherited M-D is likely of subcortical origin. Normal intracortical inhibition and facilitation suggest that the GABAergic circuits in the motor cortex are largely intact and that the mechanisms of myoclonus and dystonia are different from those for cortical myoclonus and other dystonic disorders.

Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases.

Polyglutamine (poly-Q) diseases are late-onset neurodegenerative disorders arising from the expansion of an unstable CAG repeat in the affected gene, which is translated to a tract of glutamine residues. This kind of mutant proteins may be aggregated and accumulated, and thereby enhance cellular oxidative stress. In one of our previous studies (Free Radic. Res. 2003;37:1307-17), we found that alteration in the leukocyte mtDNA content is very sensitive to the level of oxidative stress in blood. Thus, we proposed that leukocyte mtDNA content may be used as a biomarker to predict the severity of clinical manifestation of poly-Q diseases. We recruited 50 healthy subjects and 114 patients with poly-Q diseases, including spinal cerebellar atrophy 2/3, spinal bulbar muscular atrophy, and Huntington chorea. We found that mtDNA in leukocytes was depleted in patients with poly-Q diseases (P<0.05). Moreover, the results showed that patients with lower mtDNA content more frequently manifested multiple-symptom disorders and had high CAG repeat numbers in the mutant genes. In conclusion, we suggest that leukocyte mtDNA content correlates with the length of GAG repeat and may serve as an index of the severity of poly-Q diseases.

Laparoscopic Right Hepatectomy Via an Anterior Approach for Hepatocellular Carcinoma.

BACKGROUND AND OBJECTIVES: In the past, right hepatectomy via the anterior approach has been regarded as one of the many standard approaches for hepatectomy. However, total laparoscopic right hepatectomy from the anterior approach has been regarded as technically challenging. We report our experience in using the anterior approach in total laparoscopic right hepatectomy for hepatocellular carcinoma (HCC). METHODS: From June 2013 through December 2015, five consecutive patients underwent total laparoscopic right hepatectomy using the anterior approach, but without the hanging maneuver. RESULTS: The mean operative time was 360 (range, 300-480) minutes, and the mean blood loss was 340 (110-600) mL. No patient needed any blood transfusion. There was no conversion to open surgery. Ascites, pleural effusion, and bile leakage occurred in 2, 1, and 1 patients, respectively. No patients expired as a result of the surgery or liver failure. The mean hospital stay was 7 (4-15) days. All patients had R0 resection. After a mean follow-up of 22 (8-33) months, no patients experienced recurrence of disease. CONCLUSION: Total laparoscopic right hepatectomy using the anterior approach is feasible and safe.

Comparison Between Aspirin and Clopidogrel in Secondary Stroke Prevention Based on Real-World Data.

Background Clopidogrel was thought to be superior to aspirin for secondary prevention of vascular diseases in clinical trials. In this study we assessed the safety and efficacy of clopidogrel versus aspirin in real-world practice by using the Taiwan Stroke Registry. Methods and Results Patients with ischemic stroke (2006-2016) on aspirin or clopidogrel for secondary stroke prevention were identified in the Taiwan Stroke Registry. Stroke recurrence and mortality rates in patients receiving aspirin (N=34 679) were compared with those receiving clopidogrel (N=7611) during a 12-month follow-up period. Propensity score matching and conditional Cox proportional hazards regression model were applied to control confounding factors with 6443 patients in each group. After propensity score matching, stroke recurrence rates were comparable between groups, with 223 patients in the aspirin (3.46%) and 244 in the clopidogrel group (3.79%) (hazard ratio=1.13, 95% confidence interval=0.89-1.43, P=0.311). However, the mortality rate was significantly higher in the clopidogrel group (362 patients, 5.62%) than in the aspirin group (302 patients, 4.69%) (hazard ratio=1.30, 95% confidence interval=1.07-1.58, P=0.008). Results were consistent before and after propensity score matching. Conclusions Clopidogrel was as effective as aspirin for prevention of recurrent stroke in real-world practice. However, the mortality rate was significantly higher in the clopidogrel than in the aspirin group.

Renal function is associated with 1-month and 1-year mortality in patients with ischemic stroke.

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 <15 mL/min/1.73 m2 or on dialysis. Risks of 1-month mortality and 1-year mortality after ischemic stroke were investigated by the eGFR level. 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 <15 mL/min/1.73 m2 or dialysis than in patients with eGFR ≥90 mL/min/1.73 m2 (2.88 versus 0.56 per 1000 person-days). The adjusted hazard ratio (HR) of 1-month mortality increased from 1.31 (95% CI = 1.08-1.59) for patients with eGFR 60-89 mL/min/1.73 m2 to 2.33 (95% CI = 1.80-3.02) for patients with eGFR < 15 mL/min/1.73 m2 or on dialysis. 3226 patients died within one year. The adjusted HR of mortality increased from 1.38 (95% CI = 1.21-1.59) for patients with eGFR 60-89 mL/min/1.73 m2 to 2.60 (95% CI 2.18-3.10) for patients with eGFR < 15 mL/min/1.73 m2 or on dialysis, compared to patients with eGFR ≥ 90 mL/min/1.73 m2. CONCLUSIONS: After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

A follow-up study in a Taiwanese family with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome.

BACKGROUND/PURPOSE: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome is often associated with A3243G point mutation of mitochondrial DNA (mtDNA). We previously described a MELAS family characterized by harboring an additional approximately 260 bp tandem duplication in the D-loop and a novel C3093G point mutation in the 16S rRNA gene of mtDNA in the proband. We studied the clinical progression and fluctuation of mtDNA mutations in this Taiwanese MELAS family. METHODS: We followed up the clinical course in all members of this family (1 proband, her mother and 3 sons) for 12 years. Mutations of mtDNA in serial muscle biopsies of the proband and blood samples and hair follicles taken at different time points from the members of this family were analyzed. RESULTS: The proband developed repeated stroke-like episodes, chronic intestinal pseudo-obstruction, polyneuropathy, progressive renal failure and dilated cardiomyopathy with heart failure. During the follow-up period, the mother and one of the siblings of the proband developed stroke-like episodes at age 62 and 12, respectively. There was no significant difference in the proportions of mtDNA with A3243G mutation among five serial muscle biopsies of the proband. In one carrier (I-2), the proportion of A3243G mutated mtDNA in blood cells was slightly increased with disease progression. CONCLUSION: This study underlines the importance of early detection of extraneuromuscular symptoms in the members of a family with MELAS syndrome by adequate follow-up. The age of onset of stroke-like episode in MELAS syndrome may be as late as 62 years. We suggest that the manifestations of MELAS syndrome in this family might be associated with the additional approximately 260 bp tandem duplication in the D-loop region and the coexistence of C3093G mutation in the 16S rRNA gene with the A3243G mutation of mtDNA.