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1.
QJM ; 112(12): 891-899, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31350560

ABSTRACT

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.


Subject(s)
Brain Ischemia/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Stroke/drug therapy , Aged , Coronary Artery Disease/epidemiology , Coronary Artery Disease/etiology , Databases, Factual , Epidemiologic Studies , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/epidemiology , Male , Middle Aged , Patient Discharge/statistics & numerical data , Recurrence , Risk Factors , Stroke/mortality , Stroke/prevention & control , Taiwan/epidemiology , Time Factors , Treatment Outcome
2.
Genes Brain Behav ; 18(5): e12490, 2019 06.
Article in English | MEDLINE | ID: mdl-29883038

ABSTRACT

Metabolic connectivity as showed by [18F] fluorodeoxyglucose (FDG) positron emission tomography (FDG-PET) reflects neuronal connectivity. The aim of this study was to investigate the genetic impact on metabolic connectivity in default mode subnetworks and its clinical-pathological relationships in patients with Alzheimer's disease (AD). We separately investigated the modulation of 2 default mode subnetworks, as identified with independent component analysis, by comparing APOE-ε4 carriers to noncarriers with AD. We further analyzed the interaction effects of APOE (APOE-ε4 carriers vs noncarriers) with PICALM (rs3851179-GG vs rs3851179-A-allele carriers) on episodic memory (EM) deficits, reduction in cerebral metabolic rate for glucose (CMRgl) and decreased metabolic connectivity in default mode subnetworks. The metabolic connectivity in the ventral default mode network (vDMN) was positively correlated with EM scores (ß =0.441, P < .001). The APOE-ε4 carriers had significantly lower metabolic connectivity in the vDMN than the APOE-ε4 carriers (t(96) = -2.233, P = .028). There was an effect of the APOE-PICALM (rs3851179) interactions on reduced CMRgl in regions of vDMN (P < .001), and on memory deficits (F3,93 =5.568, P = .020). This study identified that PICALM may modulates memory deficits, reduced CMRgl and decreased metabolic connectivity in the vDMN in APOE-ε4 carriers. [18F] FDG-PET-based metabolic connectivity may serve a useful tool to elucidate the neural networks underlying clinical-pathological relationships in AD.


Subject(s)
Alzheimer Disease/genetics , Apolipoproteins E/genetics , Connectome , Memory , Monomeric Clathrin Assembly Proteins/genetics , Aged , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Polymorphism, Single Nucleotide , Positron-Emission Tomography
3.
QJM ; 110(9): 565-570, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28383687

ABSTRACT

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.


Subject(s)
Alzheimer Disease , Behavioral Symptoms , Caregivers/psychology , Cost of Illness , Nootropic Agents/therapeutic use , Quality of Life , Adaptation, Psychological , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Alzheimer Disease/therapy , Behavioral Symptoms/diagnosis , Behavioral Symptoms/etiology , Behavioral Symptoms/therapy , China , Cognition , Female , Humans , Male , Mental Competency/psychology , Middle Aged , Neuropsychological Tests , Prospective Studies , Psychiatric Status Rating Scales , Treatment Outcome
4.
Clin Genet ; 92(4): 397-404, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28170089

ABSTRACT

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.


Subject(s)
Epilepsies, Partial/genetics , Genetic Predisposition to Disease , Repressor Proteins/genetics , TOR Serine-Threonine Kinases/genetics , Adolescent , Child , Child, Preschool , Epilepsies, Partial/pathology , Female , GTPase-Activating Proteins , Humans , Male , Mechanistic Target of Rapamycin Complex 1/genetics , Mutation , Pedigree , RNA Splicing/genetics , Exome Sequencing
5.
Eur J Neurol ; 22(5): 845-52, e59-60, 2015 May.
Article in English | MEDLINE | ID: mdl-25690304

ABSTRACT

BACKGROUND AND PURPOSE: Although parkinsonism after carbon monoxide (CO) intoxication is well known, neurotransmitter deficient networks that are responsible for the severity of parkinsonism have rarely been systemically evaluated. METHODS: Eighteen patients with CO-related parkinsonism and nine age- and sex-matched controls were enrolled for detailed neurological examinations, three-dimensional T1-weighted images, diffusion tensor imaging and (18)F-9-fluoropropyl-(+)-dihydrotetrabenzazine ((18)F-FP-(+)-DTBZ) positron emission tomography (PET). The structural analysis included voxel-based morphometry to assess grey matter atrophy and tract-based spatial statistics related to white matter involvement. For presynaptic monoaminergic assessment, volume of interest analysis in six subcortical regions and non-parametric voxel-wise comparison were performed on PET images with estimation of registration parameters from magnetic resonance images. All the imaging modalities were compared between the patients and controls. For the patients, a regression model for correlation with cognitive behaviour and Unified Parkinson's Disease Rating Scale (UPDRS) score was used. RESULTS: In the patients, monoaminergic deficit networks were found in the caudate, anterior putamen, anterior insular, thalamus and anterior cingulate cortex. The UPDRS revealed significant correlations with the prefrontal white matter fractional anisotropy values and with the (18)F-FP-(+)-DTBZ uptake values in the caudate nucleus, insular, medial prefrontal and dorsomedial thalamus. The neuropsychiatric inventory score correlated with the (18)F-FP-(+)-DTBZ uptake values in the anterior cingulate cortex and dorsolateral prefrontal cortex. CONCLUSIONS: Our study demonstrated monoaminergic deficits and white matter damage networks in CO-related parkinsonism that determined the severity of parkinsonism or behaviour changes. As the substantia nigra was spared, the monoaminergic topography of involvement suggests a different pathophysiology in CO-related parkinsonism.


Subject(s)
Biogenic Monoamines/metabolism , Carbon Monoxide Poisoning/complications , Parkinson Disease, Secondary , Positron-Emission Tomography/methods , White Matter/pathology , Adult , Female , Fluorine Radioisotopes/metabolism , Humans , Male , Middle Aged , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/pathology , Parkinson Disease, Secondary/physiopathology , Severity of Illness Index , Tetrabenazine/analogs & derivatives , Tetrabenazine/metabolism
6.
Eur J Neurol ; 20(8): 1191-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23581395

ABSTRACT

BACKGROUND AND PURPOSE: Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation. METHODS: Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow-up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed. RESULTS: In cross-sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (ß = -0.35, P = 0.009). The CASI scores correlated with temporo-parietal PI (Pearson r range 0.3-0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74). CONCLUSIONS: Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/psychology , Cerebrovascular Circulation/physiology , Cognition Disorders/blood , Cognition Disorders/psychology , Homocysteine/blood , Aged , Aged, 80 and over , Alzheimer Disease/complications , Brain/diagnostic imaging , Cognition Disorders/etiology , Disease Progression , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Perfusion , Risk Factors , Tomography, Emission-Computed, Single-Photon
7.
Eur J Neurol ; 19(12): 1532-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22642922

ABSTRACT

BACKGROUND: Increased plasma nuclear and mitochondrial DNA levels may be connected to disease severity following spontaneous intra-cerebral haemorrhage (ICH). This study tested the hypothesis that plasma nuclear and mitochondrial DNA levels are substantially increased in acute ICH and can predict treatment outcomes. METHODS: Serial plasma nuclear and mitochondrial DNA levels were examined in 60 consecutive patients admitted within 24 h after onset of spontaneous ICH and in 60 volunteer control subjects. Additional samples were obtained on days 4, 7, 10, and 14 after onset of ICH regardless of clinical deterioration. RESULTS: Only plasma nuclear DNA, not plasma mitochondrial DNA, levels in patients with spontaneous ICH significantly correlated with Glasgow Coma Scale (GCS) (r = -0.467, P = 0.001) and ICH volume (r = 0.515, P ≤ 0.001) on presentation. Plasma nuclear DNA levels increased significantly from day 1 to day 7 in patients with poor outcome. Higher plasma nuclear DNA levels (cut-off value >18.7 ng/ml) on presentation were associated with poor outcomes in spontaneous ICH patients. CONCLUSION: Plasma nuclear DNA levels reflect the severity of cerebral damage such that higher levels are associated with poorer outcome. Plasma nuclear DNA level can be considered a neuropathologic marker of acute spontaneous ICH.


Subject(s)
Biomarkers/blood , Cell Nucleus/metabolism , Cerebral Hemorrhage/blood , DNA, Mitochondrial/blood , DNA/blood , Adult , Aged , Area Under Curve , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Prognosis , ROC Curve , Sensitivity and Specificity
8.
AJNR Am J Neuroradiol ; 32(7): 1333-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21596808

ABSTRACT

BACKGROUND AND PURPOSE: The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms. MATERIALS AND METHODS: Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed. RESULTS: Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up. CONCLUSIONS: The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.


Subject(s)
AIDS-Related Opportunistic Infections/pathology , Brain/pathology , Cognition Disorders/pathology , Diffusion Tensor Imaging , Meningitis, Cryptococcal/pathology , AIDS-Related Opportunistic Infections/complications , Adult , Aged , Chronic Disease , Cognition Disorders/etiology , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Meningitis, Cryptococcal/complications , Middle Aged , Neuropsychological Tests , Prospective Studies
9.
Clin Microbiol Infect ; 17(4): 615-20, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20491832

ABSTRACT

Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacterial Infections/drug therapy , Brain Abscess/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
10.
Curr Alzheimer Res ; 7(6): 527-33, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20455861

ABSTRACT

BACKGROUND: White matter hyper-intensities (WMHs) on magnetic resonance imaging (MRI) are commonly found in Alzheimer's disease (AD). Cerebro-vascular risk factors including plasma total homocysteine (tHcy) may result in WMHs. This study examined the association between tHcy and WMHs, and their effects on cognitive functions in AD patients over a two-year follow-up period. METHODS: One hundred and fifty-seven AD patients with a clinical dementia rating of 1 or 2 were enrolled and follow-up for two years. tHcy, biochemistry tests, and mini-mental state examination (MMSE) scores were collected. WMHs were visually rated on brain MRI and classified as deep white matter hyper-intensities (DWMHs) or peri-ventricular white matter hyper-intensities (PWMHs). MMSEs were performed every six months to survey cognitive decline. RESULTS: In the cross sectional study, tHcy was significantly associated with total WMHs especially in DWMHs even after adjusting for age and other cerebrovascular risk factors. Initial MMSE was inversely correlated with WMH severity but not with tHcy level. In the longitudinal analysis, no differences were found either in tHcy or WMHs score in the two AD groups defined by the cognitive decline rate. CONCLUSIONS: tHcy is an independent risk factor for developing moderate to severe DWMHs in AD but shows non-significant effect on cognitive performance. The close association between high WMH score and poor initial MMSE suggests an additive impact in AD. The long-term effect of elevated tHcy on cognitive decline was not conclusive in the two-year follow-up period.


Subject(s)
Alzheimer Disease/blood , Alzheimer Disease/pathology , Brain/pathology , Homocysteine/blood , Nerve Fibers, Myelinated/pathology , Aged , Aged, 80 and over , Alzheimer Disease/complications , Analysis of Variance , Blood Glucose/physiology , Cholesterol/blood , Cross-Sectional Studies , Fasting , Female , Humans , Logistic Models , Longitudinal Studies , Magnetic Resonance Imaging/methods , Male , Mental Status Schedule , Neuropsychological Tests
11.
QJM ; 103(3): 169-75, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20129945

ABSTRACT

BACKGROUND: Increased levels of plasma nuclear and mitochondrial DNA have been reported in critically ill patients. We tested the hypothesis that plasma nuclear and mitochondrial DNA are substantially increased in acute bacterial meningitis and decrease after antimicrobial therapy, and that plasma nuclear and mitochondrial DNA levels can predict treatment outcomes. METHODS: We examined serial plasma nuclear and mitochondrial DNA levels in 22 adult community-acquired bacterial meningitis (ACABM) patients. The plasma nuclear and mitochondrial DNA levels were also evaluated in 11 aseptic meningitis patients and 22 volunteer subjects during the study period. RESULTS: All of the both bacterial and aseptic meningitis groups had a higher plasma DNA levels on admission as compared with those of volunteer groups. Levels of plasma nuclear and mitochondrial DNA in ACABM cases were significantly increased initially and substantially decreased thereafter. Both plasma nuclear DNA and plasma mitochondrial DNA levels at presentation are significantly negative correlate with modified Barthel Index (average) (r = -0.639, P = 0.004 and r = -0.551, P = 0.018) at 3 months after discharge (average), respectively, in this study. Both higher plasma nuclear (cutoff value of >169 ng/ml) and mitochondrial DNA levels (cutoff value of >58.9 ng/ml) at presentation were associated with poor outcome in ACABM patients. CONCLUSION: Based on our results, the higher plasma DNA levels were associated with a poorer outcome. Therefore, we look forward to more prospective multicenter investigations specifically to confirm the predictive value of plasma DNA levels in outcome prediction.


Subject(s)
DNA, Mitochondrial/metabolism , DNA/metabolism , Meningitis, Bacterial/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Community-Acquired Infections/epidemiology , Community-Acquired Infections/metabolism , Epidemiologic Methods , Female , Humans , Male , Meningitis, Aseptic/blood , Meningitis, Bacterial/epidemiology , Middle Aged
12.
Eur J Neurol ; 16(10): 1144-50, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19486137

ABSTRACT

BACKGROUND AND PURPOSE: Dementia remains an exclusion criterion in diagnosing multiple system atrophy (MSA). This study aimed to determine the cognitive changes and brain atrophy patterns in the Parkinsonian (MSA-P) and cerebellar (MSA-C) variants of MSA. METHODS: Voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and neuro-psychological tests were applied to 10 MSA-C and 13 MSA-P patients, and compared to 37 age-matched controls. Correlation analyses were performed between cognitive test results and morphometric data extracted from the VBM data. RESULTS: In neuro-psychological testing, the 23 MSA patients scored lower in the Stroop interference test and took longer in the trail-making test as compared with the controls, whereas MSA-C performed worse than MSA-P in the memory scores, Stroop test, and time to complete the trail-making test. MSA, as a group, showed atrophy in the cerebellum, insular cortex, fusiform gyrus, inferior orbito-frontal gyrus, superior temporal gyrus, and caudate nucleus. Memory scores correlated well with pre-frontal lobe atrophy but not in the insular area. CONCLUSION: In conclusion, although dementia is not a typical presenting feature of MSA and is regarded as a sub-cortical movement disorder, frontal atrophy, cognitive changes, and dementia are identifiable as MSA progresses.


Subject(s)
Brain/pathology , Cognition Disorders/pathology , Movement Disorders/pathology , Multiple System Atrophy/diagnosis , Multiple System Atrophy/pathology , Atrophy/pathology , Brain Mapping , Cognition Disorders/complications , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Movement Disorders/complications , Multiple System Atrophy/complications , Neuropsychological Tests , Regression Analysis
13.
QJM ; 102(1): 57-62, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19015144

ABSTRACT

BACKGROUND: About 50% of status epilepticus (SE) patients have no previous history of epilepsy, but often have worse outcome. The aim of this study was to evaluate potential risk factors that are predictive of poor outcome in non-selected de novo status epilepticus patients. METHODS: Eighty-three adult status epilepticus patients without a pre-existing history of epilepsy that were admitted to hospital for treatment were enrolled in this 11-year retrospective study. The baseline prognostic variables were analyzed based on stepwise logistic regression analysis after a minimum of one-and-half years of follow-up. RESULTS: The overall fatality rate was 55.4% (46/83) during the study period. Poor outcome was associated with older age, presence of refractory status epilepticus, potential fatal etiologies, lower GCS score at presentation and level of consciousness on admission. The results of stepwise logistic regression demonstrated that age on presentation and potential fatal etiologies were independently associated with presence of poor outcome, and any increase in age by 1 year increases poor outcome by 7.5%. CONCLUSION: The outcome for those with de novo status epilepticus is poor and this poor outcome may be attributed to the older age at onset and the potential fatal underlying conditions such as infection and metabolic derangement.


Subject(s)
Outcome Assessment, Health Care , Status Epilepticus/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Female , Glasgow Outcome Scale , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Status Epilepticus/diagnosis , Young Adult
14.
Eur J Neurol ; 15(6): 559-64, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18410374

ABSTRACT

BACKGROUND AND PURPOSE: To study the clinical characteristics of hypokalemic thyrotoxic periodic paralysis (hoTPP) and identify the predictors of recurrent paralytic attacks before achieving the euthyroid status. METHODS: We retrospectively analyzed 45 hoTPP patients who were admitted during the 7-year study period. RESULTS: A tendency towards male predominance was observed among the 45 patients (91.1%, 41/45). The mean onset age was 32.9 +/- 10.0 years (range: 16-54 years). No significant differences were observed in the onset age between male and female patients. Precipitating factors included rest/sleep at night, hot weather, upper respiratory tract infections (URIs), and excessive physical activities. Atypical weakness was observed in nine (20%, 9/45) patients. One patient initially diagnosed with sporadic periodic paralysis eventually developed hoTPP. DISCUSSION: In provocative tests, hypokalemia was not a consistent finding during paralytic attacks. Before achieving the euthyroid status, the rate of recurrent attacks was as high as 62.2%, and peaked in the first 3 months after hoTPP was diagnosed. Patients with URIs exhibited a higher incidence of recurrent paralytic attacks than those without (odds ratio = 13.00; 95% confidence interval = 1.08-156.08; P = 0.04).


Subject(s)
Hypokalemic Periodic Paralysis/physiopathology , Thyroid Diseases/physiopathology , Age of Onset , Female , Humans , Hypokalemic Periodic Paralysis/epidemiology , Male , Retrospective Studies , Risk Factors , Sex Factors , Thyroid Diseases/epidemiology
15.
Eur J Neurol ; 15(5): 451-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18325027

ABSTRACT

BACKGROUND AND PURPOSE: Seizures are important neurologic complications of spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of the risk factors of seizures following aneurysmal SAH is needed to predict those who will require treatment. METHODS: A total of 137 adult patients were enrolled in this two-year retrospective study. Baseline prognostic variables were analyzed based on Cox's proportional hazards model after a minimum of one-year follow-up. RESULTS: Seizures occurred in 21 patients who had SAH, including acute symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137). None progressed to status epilepticus during hospitalization. After a minimum of one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients with seizures and 3.1 +/- 1.1 for those without. CONCLUSIONS: Higher mean World Federation of Neurological Societies grade on presentation was predictive of seizure, but seizure itself was not a significant prognostic predictor after a minimum of one-year follow-up. Regarding potential side effects of anti-epileptic drugs, anti-epileptic therapy should be carefully administered to patients with seizures after aneurysmal SAH.


Subject(s)
Risk Factors , Seizures/etiology , Subarachnoid Hemorrhage/complications , Adult , Aged , Aged, 80 and over , Cerebral Angiography , Female , Follow-Up Studies , Humans , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Subarachnoid Hemorrhage/pathology
16.
QJM ; 101(3): 225-30, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18234734

ABSTRACT

BACKGROUND: Increased levels of cerebrospinal fluid (CSF) 14-3-3 proteins have been reported in acute bacterial meningitis. We tested the hypothesis that CSF 14-3-3 protein levels are substantially increased in acute bacterial meningitis and decreased after anti-microbial therapy, and that CSF 14-3-3 protein levels can predict treatment outcomes. METHODS: We examined serial pan-CSF 14-3-3 (14-3-3-P) protein and five major isoform (beta, gamma, epsilon, eta, zeta) levels in 29 adult community-acquired bacterial meningitis (ACABM) patients. The CSF 14-3-3 protein levels were also evaluated in 12 aseptic meningitis patients during the study period. RESULTS: All of the meningitis patients had a positive result on admission. Levels of CSF 14-3-3 protein in ACABM cases were significantly increased initially, and substantially decreased thereafter. Most of those who survived (survivors = 25 and non-survivors = 4) had nearly cleared their 14-3-3 protein from the CSF before discharge. Conversely, patients who died never cleared their CSF 14-3-3 protein. The median value of CSF 14-3-3-P and 14-3-3 gamma, 14-3-3 eta and 14-3-3 epsilon isoforms on admission in the bacterial meningitis group were 173.7, 137.7, 42.2 and 9.1, respectively, which were statistically significant than those of the aseptic meningitis group (48.4, 39.6, 2.5 and 0, respectively). Stepwise logistic regression analysis showed only CSF 14-3-3 gamma isoform on admission was independently associated with outcome (P = 0.05, OR = 0.991). CONCLUSION: Serial 14-3-3 protein gamma isoform actually meets the major requirements for outcome prediction in the treatment of ACABM patients. Assay of the 14-3-3 protein gamma isoform should be added as a neuro-pathologic marker among the panel of conventional CSF parameters.


Subject(s)
14-3-3 Proteins/cerebrospinal fluid , Meningitis, Bacterial/cerebrospinal fluid , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/cerebrospinal fluid , Community-Acquired Infections/cerebrospinal fluid , Community-Acquired Infections/drug therapy , Community-Acquired Infections/mortality , Female , Humans , Leukocyte Count , Logistic Models , Male , Meningitis, Aseptic/cerebrospinal fluid , Meningitis, Aseptic/drug therapy , Meningitis, Aseptic/mortality , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/mortality , Middle Aged , Prognosis , Prospective Studies , Protein Isoforms/cerebrospinal fluid , ROC Curve , Survival Rate
17.
Eur J Neurol ; 15(4): 428-30, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18284425

ABSTRACT

The clinical data and cerebrospinal fluid (CSF) 14-3-3-gamma protein detection of eight adult HIV-negative cryptococcal meningitis (CM) cases were examined. The eight cases included six males and two females aged 35-70 years (mean = 49.8 years). The duration between the onset of CM symptoms and the first CSF study ranged from 1 to 60 days. Initial neuroimaging study was abnormal in 87.5% (7/8) of the cases. All the eight had positive initial and subsequent follow-up CSF 14-3-3-gamma protein detection. The densitometric values of CSF 14-3-3-gamma protein were not correlated with either the CSF white blood cell counts or the therapeutic results. The therapeutic results showed that three cases died and five survived. Significant neurologic deficits were shown in 60% (3/5) of the survivors. This study revealed that HIV-negative CM patients have elevated CSF 14-3-3-gamma protein levels, and that this level is not changed with a short-term treatment.


Subject(s)
14-3-3 Proteins/cerebrospinal fluid , HIV Seronegativity , Meningitis, Cryptococcal/cerebrospinal fluid , Adult , Aged , Female , Humans , Male , Middle Aged
18.
Infection ; 36(1): 15-22, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18193387

ABSTRACT

BACKGROUND: Many factors may influence the epidemiologic trend of adult bacterial meningitis (ABM). The objective of this study was to analyze recent epidemiologic trends of ABM in order to provide a better therapeutic strategy. MATERIALS AND METHODS: The clinical features, laboratory data, and therapeutic outcomes of 181 ABM cases collected in the last 6.5 years (July 1999-December 2005) were analyzed. The results were compared with those of our previous study (202 cases, January 1986-June 1999). RESULTS: The 181 cases consisted of 130 men (age range: 18-82 years) and 51 women (age range: 18-78 years). Monomicrobial infection and mixed infection were found in 165 cases and 16 cases, respectively. A preceding postneurosurgical state was noted in 56.9% (103/181) of cases. Despite a decrease in incidence, Klebsiella pneumoniae (25.5%, 42/165) was still the most common pathogen. A marked increase of Acinetobacter meningitis (11.5%, 19/165) was noted, which replaced Pseudomonas meningitis as the second most common Gram-negative pathogen in ABM. A marked increase in staphylococcal infection, accounting for 23% (38/165) of all cases, was also noted, of which 76% (29/38) were methicillin-resistant strains. The therapeutic result showed a mortality rate of 30.3% (55/181). Significant prognostic factors included septic shock and age at infection. CONCLUSIONS: This study revealed a change in the epidemiologic trend of ABM, with an increase in the number of patients with a postneurosurgical state and a rising incidence of Acinetobacter and staphylococcal infections. Clinicians should pay greater attention to these changes, which may affect their management of ABM.


Subject(s)
Community-Acquired Infections/epidemiology , Cross Infection/epidemiology , Gram-Negative Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/epidemiology , Meningitis, Bacterial/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Community-Acquired Infections/microbiology , Cross Infection/microbiology , Female , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/microbiology , Humans , Male , Meningitis, Bacterial/classification , Meningitis, Bacterial/etiology , Meningitis, Bacterial/microbiology , Middle Aged , Prognosis , Retrospective Studies , Taiwan/epidemiology
19.
Eur J Neurol ; 15(1): 61-5, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18042240

ABSTRACT

We examined clinical presentations, neuropsychological findings, and perfusion patterns of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) in patients with early stage dementia with Lewy bodies (DLB) (n = 17) and Parkinson's disease (PD) (n = 16), with age-matched healthy controls (n = 10). Seven paired regions of interest (ROIs) were drawn manually including inferior frontal, temporal, parietal, occipital, parieto-occipital junction, striatum and thalamus for semiquantitative measurement. Neuropsychological tests were applied for clinical correlation. The SPECT results showed significant hypoperfusion in DLB group in frontal, parietal, thalamus, temporal ROIs compared with controls (P < 0.01) whilst signals in temporal areas was significantly reduced compared with PD group (P < 0.05). Neuropsychological tests showed that DLB patients had deficits in mental manipulation, short-term memory, abstract thinking, drawing and semantic verbal fluencies (P < 0.05, compared with control). In addition, DLB group had lower scores than those with PD in mental manipulation, drawing and semantic verbal fluency (P < 0.05). Our study showed that even in early stages of DLB, neuropsychological and perfusion patterns were evident and may be different from PD group, despite they shared certain similarities both in neuropsychological and image findings compared with age-matched controls.


Subject(s)
Cysteine/analogs & derivatives , Lewy Body Disease/diagnostic imaging , Lewy Body Disease/psychology , Organotechnetium Compounds , Parkinson Disease/diagnostic imaging , Parkinson Disease/psychology , Tomography, Emission-Computed, Single-Photon/methods , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/pathology , Brain/physiopathology , Cerebrovascular Circulation , Cognition Disorders/diagnostic imaging , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Diagnosis, Differential , Disease Progression , Early Diagnosis , Female , Humans , Lewy Body Disease/physiopathology , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/physiopathology , Predictive Value of Tests , Sensitivity and Specificity
20.
Jpn J Infect Dis ; 60(6): 397-9, 2007 Nov.
Article in English | MEDLINE | ID: mdl-18032844

ABSTRACT

We analyzed the clinical and laboratory characteristics, therapeutic outcome and prognostic factors of 25 cases of cerebrospinal fluid (CSF) culture-proven Pseudomonas aeruginosa adult bacterial meningitis (ABM). Twelve P. aeruginosa strains, isolated from clinical CSF specimens, were tested for antibiotic susceptibility. The 25 cases included 17 men and 8 women, aged 17 to 86 years (median=51). Of the 25 cases of P. aeruginosa ABM, 18 were the result of postneurosurgical infection and the other 7 were spontaneous infections. The latter 7 cases had serious underlying medical conditions. The antibiotic susceptibility rates of the 12 strains were as follows: ceftriaxone 16.7% (2/12), ceftazidime 91.7% (11/12), cefepime 83.3% (10/12), imipenem 83.3% (10/12), meropenem 83.3% (10/12) and ciprofloxacin 66.7% (8/12). The therapeutic results showed an overall mortality rate of 40% (10/25). The emergence of third-generation cephalosporin-resistant P. aeruginosa strains cultured from clinical CSF specimens in recent years has resulted in a therapeutic challenge in the treatment of ABM.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Meningitis, Bacterial , Neurosurgical Procedures/adverse effects , Postoperative Complications , Pseudomonas Infections , Pseudomonas aeruginosa/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Female , Humans , Male , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/etiology , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/mortality , Middle Aged , Postoperative Complications/drug therapy , Postoperative Complications/etiology , Postoperative Complications/microbiology , Postoperative Complications/mortality , Pseudomonas Infections/drug therapy , Pseudomonas Infections/etiology , Pseudomonas Infections/microbiology , Pseudomonas Infections/mortality , Pseudomonas aeruginosa/drug effects
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