Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To d...Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location. Results: Overall, 72.9%of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10%increase [95%CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95%CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95%CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95%CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95%CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95%CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95%CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95%CI: 0.92, 0.98; p= 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes. Conclusions: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.展开更多
Objective. -The aim of the present research was to verify the levels of the soluble adhesion molecules sL-and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial sa...Objective. -The aim of the present research was to verify the levels of the soluble adhesion molecules sL-and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)-1 and very late activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor-α[TNF-α], interleukin-1β[IL-1β], IL-4, and IL6) were also determined and correlated with those of adhesion molecules. Patients and Methods. -Seven MWoA patients were admitted in the hospital during attacks and blood samples were taken immediately after catheter insertion, at 1, 2, and 4 hours after attack onset, and within 2 hours after its termination. The levels of adhesion molecules and cytokines were measured with ELISA method. The expression of LFA-1 and VLA-4 was assessed by flow cytometry. Results. -A parallel transient increase of sICAM-1, TNF-α, and IL-6 was observed in the first 2 hours after attack onset compared with the time of catheter insertion (P< .0001, < .001, and < .003, respectively). The proportion of CD4+and CD8+T-cells expressing high levels of LFA-1 showed instead a progressive down-regulation with significantly lower percentages at 2 and 4 hours after attack onset (P < .01 and < .022, respectively). No variation in the percentage of VLA-4 expressing cells was observed at any time of the study. Conclusions. -The transient increase in sICAM-1 and TNF-αfound in the internal jugular blood of MWoA patients assessed ictally can be induced by sensory neuropeptides released from activated trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and the down-regulation of LFA-1 expression by lymphocytes could antagonize their transvascular migration, supporting the hypothesis of sterile inflammation in the dura mater during migraine attacks.展开更多
The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Park...The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson’s disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82%of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson’s disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2%(1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2%(1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5%(3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson’s disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and pontocerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes.We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.展开更多
In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points i...In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points in Appel ALS (AALS) score or (b) tracheostomy free survival was investigated. The median survival of ALS patients with baseline FVC < 75%was 2.91 years, compared with 4.08 years for patients with baselineFVC >75%(p < 0.001). Patients with baseline FVC < 75%progressed more rapidly (taking 8.0 months to progress 20 AALS points) compared with patients with baseline FVC >75%(10.0 months, p < 0.001). Moreover, FVC at first examination was identified as a significant predictor of survival and disease progression in both univariate and multivariate Cox regression models, after adjustment for age, sex, site of onset, diagnostic delay, riluzole therapy, and use of bilateral positive airway pressure and percutaneous endoscopic gastrostomy (p < 0.001). We conclude that a single FVC value obtained at an initial visit may serve as a clinically meaningful predictor of survival and disease progression in ALS.展开更多
Objective: To characterize long-term mortality following intracerebral hemorrhage (ICH) in two large population-based cohorts assembled more than a decade apart. Methods: All patients age ≥18 hospitalized with nontra...Objective: To characterize long-term mortality following intracerebral hemorrhage (ICH) in two large population-based cohorts assembled more than a decade apart. Methods: All patients age ≥18 hospitalized with nontraumatic ICH in the Greater Cincinnati/Northern Kentucky area were identified during 1988 (Cohort 1) and from May 1998 to July 2001 and August 2002 to April 2003 (Cohort 2). Mortality was tabulated using actuarial methods and compared with a log-rank test. Results: There were 183 patients with ICH in Cohort 1 and 1,041 patients in Cohort 2. Patients in Cohort 1 were more likely to be white (p = 0.024) and undergo operation for their ICH (p = 0.002), whereas patients in Cohort 2 were more commonly on anticoagulants (p < 0.001). Among patients in Cohort 1, mortality at 7 days, 1 year, and 10 years was 31, 59, and 82%. Among patients in Cohort 2, mortality at 7 days and 1 year was 34 and 53%. Mortality rates did not differ between cohorts by logrank test (p = 0.259). Conclusions: Intracerebral hemorrhage (ICH) mortality did not improve significantly between study periods. Operation for ICH became less frequent, whereas anticoagulant-associated ICH became more common.展开更多
Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for...Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.展开更多
Background: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer’s disease, and may both have a negative impact on the progression of the illness. Objectives: To examine the ...Background: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer’s disease, and may both have a negative impact on the progression of the illness. Objectives: To examine the clinical correlates of apathy in Alzheimer’s disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. Methods: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. Results: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p < 0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). Conclusions: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.展开更多
Background: National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predi...Background: National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predictors, and the achievement of national guideline target lipid goals among ischemic stroke survivors. Methods: The authors abstracted data from the Vitamin Intervention for Stroke Prevention (VISP) study database from the United States and Canada to incorporate into algorithms for initiating statin therapy according to the National Cholesterol Education Program (NCEP) guidelines for high-risk individuals. The authors applied these algorithms to all study subjects. Univariate as well as multivariate associations for target lipid levels and statin implementation were then evaluated utilizing pertinent demographic, clinical, and laboratory data. Results: Of 2,894 subjects in the analysis dataset, 38%were women; 71%were recruited in the United States and 29%in Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL) level ≥130 mg/dL and 124 of these (47%) were not on statin. Among those high-risk persons on statin treatment, only 42%had an LDL ≤100 mg/dL. Subjects in the overall cohort were more likely to be on a statin if they were treated in the United States or had a history of hypertension or coronary artery disease. Conclusions: Approximately one out of three guideline-eligible high vascular risk ischemic stroke patients in this study had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals.展开更多
Objective. -To examine the associations between severe headaches (SH), psychological distress, and comorbid conditions among U.S. adults. Background. -The lifetime prevalence of headaches is over 90%and headaches, par...Objective. -To examine the associations between severe headaches (SH), psychological distress, and comorbid conditions among U.S. adults. Background. -The lifetime prevalence of headaches is over 90%and headaches, particularly migraines, have been associated with disability, increased healthcare costs, and mood disorders. Methods. -We analyzed data obtained from adults aged 18 years or older (n = 29,828) who participated in the 2002 National Health Interview Survey, an ongoing, computer-assisted personal interview of a representative sample of the U.S. population. Results. -Approximately 15.1%of adults aged 18 years or older reported SH in the previous 3 months. Those reporting such headaches were significantly more likely, than those who did not, to report insomnia, excessive sleepiness, recurrent pain, and depressive or anxiety symptoms during the preceding 12 months. Approximately 88%of those who reported having had SH within the previous 3 months also indicated that they had at least one comorbid medical condition, relative to 67%of those without SH. Conclusion. -Despite their episodic nature, our results suggest that SH are associated with impairments in both physical and mental health. As the presence of SH may serve as an indicator of significant psychological distress and medical comorbidities, eliciting information about their occurrence during a standard medical examination appears to be warranted.展开更多
Experimental models of Parkinson’s disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypoth...Experimental models of Parkinson’s disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson’s disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP)-like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson’s disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motorevoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8%of baseline at T30) but not in patients off medication (T30: +0.07%of baseline in the non-dyskinetic, +27%in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9%of baseline MEP)-but not in the dyskinetic group (T30: -9.2%of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson’s disease off medications and is restored by levodopa in nondyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.展开更多
Objective. -To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background. -Currently, no triptan is approved ...Objective. -To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background. -Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods. -This was a randomized (1:1:1), placebo-controlled, doubleblind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ≥6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results. -Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42%vs. 33%, respectively; P= .046) and 2 hours (68%vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61%vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions. -This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.展开更多
Objective. -The aim of the present study was to evaluate cardiac performance of patients with migraine attacks during the overload produced by phenylephrine infusion. Background. -It is known that circulatory changes ...Objective. -The aim of the present study was to evaluate cardiac performance of patients with migraine attacks during the overload produced by phenylephrine infusion. Background. -It is known that circulatory changes occur during migraine. However, the relationship between this finding and transient cardiac dysfunction is still unknown. Methods. -By means of two-dimensional direct M-mode echocardiography, we measured fractional shortening, ejection fraction, and mean velocity of circumferential fibers shortening in 18 patients with migraine and in 10 normal subjects as a control group. These measures were performed in two different periods: during attack-free intervals and during attacks. Pain intensity of typical migraine attack was evaluated on a 0 to 10 scale. Results. -Cardiac size and function were normal at rest in both groups. However, during migraine attacks, phenylephrine infusion provoked significant decrease in fractional shortening,EF, and mean velocity of circumferential fibers shortening, followed by concomitant increase of headache severity. On the other hand, during the attack-free interval and in the control group phenylephrine infusion did not show significant changes in cardiac function parameters. Conclusions. -Our data suggest that left ventricular dysfunction during the phenylephrine test could participate in the complex pathophysiological mechanism of migraine attacks.展开更多
Objective: To evaluate the effect of IV recombinant tissue plasminogen activator (rt-PA) in patients with hyperdense artery sign (HAS) on initial CT scan. Methods: The authors determined the differential effect of IV ...Objective: To evaluate the effect of IV recombinant tissue plasminogen activator (rt-PA) in patients with hyperdense artery sign (HAS) on initial CT scan. Methods: The authors determined the differential effect of IV rt-PA (0.9 mg/kg) in patients with HAS by testing the interaction of rt-PA and HAS in a logistic regression model after adjusting for age, sex, initial NIH Stroke Scale score (NIHSSS), time to randomization, systolic blood pressure, serum glucose, body temperature, and rt-PA in 616 patients treated within 3 hours of symptom onset. Outcomes evaluated included intracranial hemorrhage, modified Rankin scale (mRS) 0-1, Barthel Index (BI) of ≥95, Glasgow Outcome Scale (GOS) of 0-1, NIHSSS 0-1, and death at 90 days. Results: HAS was detected on the initial CT scan in 91 (15%) of the 616 patients by an independent neuroradiologist. Significantly lower rates of mRS 0-1, BI ≥95, GOS of 0-1, or NIHSSS 0-1 at 90 days were observed among patients with HAS. IV rt-PA significantly increased the rates of mRS 0-1, BI ≥95, GOS of 0-1, or NIHSSS 0-1 at 90 days after adjusting for potential confounders without any significant modifying effect (interaction) of HAS. Among the 91 patients with HAS, rt-PA use demonstrated a trend or significance for increased adjusted rates of favorable outcomes by mRS (p = 0.04), BI (p = 0.1), GOS (p = 0.03), and NIHSSS (p = 0.01). Conclusion: Although hyperdense artery sign is associated with poor outcome, IV recombinant tissue plasminogen activator may be beneficial in this subgroup of patients with ischemic stroke.展开更多
文摘Background: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome. Methods: To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location. Results: Overall, 72.9%of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10%increase [95%CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95%CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95%CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95%CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95%CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95%CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95%CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95%CI: 0.92, 0.98; p= 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes. Conclusions: Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.
文摘Objective. -The aim of the present research was to verify the levels of the soluble adhesion molecules sL-and sE-selectins, intercellular adhesion molecule (sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal jugular venous blood taken from migraine patients without aura (MWoA) during attacks. The expression of leukocyte function antigen (LFA)-1 and very late activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular venous blood. Levels of certain proinflammatory cytokines (tumor necrosis factor-α[TNF-α], interleukin-1β[IL-1β], IL-4, and IL6) were also determined and correlated with those of adhesion molecules. Patients and Methods. -Seven MWoA patients were admitted in the hospital during attacks and blood samples were taken immediately after catheter insertion, at 1, 2, and 4 hours after attack onset, and within 2 hours after its termination. The levels of adhesion molecules and cytokines were measured with ELISA method. The expression of LFA-1 and VLA-4 was assessed by flow cytometry. Results. -A parallel transient increase of sICAM-1, TNF-α, and IL-6 was observed in the first 2 hours after attack onset compared with the time of catheter insertion (P< .0001, < .001, and < .003, respectively). The proportion of CD4+and CD8+T-cells expressing high levels of LFA-1 showed instead a progressive down-regulation with significantly lower percentages at 2 and 4 hours after attack onset (P < .01 and < .022, respectively). No variation in the percentage of VLA-4 expressing cells was observed at any time of the study. Conclusions. -The transient increase in sICAM-1 and TNF-αfound in the internal jugular blood of MWoA patients assessed ictally can be induced by sensory neuropeptides released from activated trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and the down-regulation of LFA-1 expression by lymphocytes could antagonize their transvascular migration, supporting the hypothesis of sterile inflammation in the dura mater during migraine attacks.
文摘The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson’s disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82%of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson’s disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2%(1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2%(1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5%(3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson’s disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and pontocerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes.We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.
文摘In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points in Appel ALS (AALS) score or (b) tracheostomy free survival was investigated. The median survival of ALS patients with baseline FVC < 75%was 2.91 years, compared with 4.08 years for patients with baselineFVC >75%(p < 0.001). Patients with baseline FVC < 75%progressed more rapidly (taking 8.0 months to progress 20 AALS points) compared with patients with baseline FVC >75%(10.0 months, p < 0.001). Moreover, FVC at first examination was identified as a significant predictor of survival and disease progression in both univariate and multivariate Cox regression models, after adjustment for age, sex, site of onset, diagnostic delay, riluzole therapy, and use of bilateral positive airway pressure and percutaneous endoscopic gastrostomy (p < 0.001). We conclude that a single FVC value obtained at an initial visit may serve as a clinically meaningful predictor of survival and disease progression in ALS.
文摘Objective: To characterize long-term mortality following intracerebral hemorrhage (ICH) in two large population-based cohorts assembled more than a decade apart. Methods: All patients age ≥18 hospitalized with nontraumatic ICH in the Greater Cincinnati/Northern Kentucky area were identified during 1988 (Cohort 1) and from May 1998 to July 2001 and August 2002 to April 2003 (Cohort 2). Mortality was tabulated using actuarial methods and compared with a log-rank test. Results: There were 183 patients with ICH in Cohort 1 and 1,041 patients in Cohort 2. Patients in Cohort 1 were more likely to be white (p = 0.024) and undergo operation for their ICH (p = 0.002), whereas patients in Cohort 2 were more commonly on anticoagulants (p < 0.001). Among patients in Cohort 1, mortality at 7 days, 1 year, and 10 years was 31, 59, and 82%. Among patients in Cohort 2, mortality at 7 days and 1 year was 34 and 53%. Mortality rates did not differ between cohorts by logrank test (p = 0.259). Conclusions: Intracerebral hemorrhage (ICH) mortality did not improve significantly between study periods. Operation for ICH became less frequent, whereas anticoagulant-associated ICH became more common.
文摘Cerebrospinal fluid (CSF) pressure and composition are generally thought to be homogeneous within small limits throughout all CSF compartments. CSF sampled during lumbar puncture therefore should be representative for all CSF compartments. On the basis of clinical findings, histology and biochemical markers, we present for the first time strong evidence that the subarachnoid spaces (SAS) of the optic nerve (ON) can become separated from other CSF compartments in certain ON disorders, thus leading to an ON sheath compartment syndrome. This may result in an abnormal concentration gradient of CSF molecular markers determined in locally sampled CSF compared with CSF taken during lumbar puncture.
文摘Background: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer’s disease, and may both have a negative impact on the progression of the illness. Objectives: To examine the clinical correlates of apathy in Alzheimer’s disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. Methods: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. Results: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p < 0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). Conclusions: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.
文摘Background: National cholesterol guidelines have defined high vascular risk individuals as those who could potentially benefit most from statin therapy. The authors aimed to determine the rate of statin use, its predictors, and the achievement of national guideline target lipid goals among ischemic stroke survivors. Methods: The authors abstracted data from the Vitamin Intervention for Stroke Prevention (VISP) study database from the United States and Canada to incorporate into algorithms for initiating statin therapy according to the National Cholesterol Education Program (NCEP) guidelines for high-risk individuals. The authors applied these algorithms to all study subjects. Univariate as well as multivariate associations for target lipid levels and statin implementation were then evaluated utilizing pertinent demographic, clinical, and laboratory data. Results: Of 2,894 subjects in the analysis dataset, 38%were women; 71%were recruited in the United States and 29%in Canada. Of 769 high-risk subjects, 262 (34%) had a low-density lipoprotein (LDL) level ≥130 mg/dL and 124 of these (47%) were not on statin. Among those high-risk persons on statin treatment, only 42%had an LDL ≤100 mg/dL. Subjects in the overall cohort were more likely to be on a statin if they were treated in the United States or had a history of hypertension or coronary artery disease. Conclusions: Approximately one out of three guideline-eligible high vascular risk ischemic stroke patients in this study had low-density lipoprotein cholesterol concentrations above qualifying levels for pharmacologic therapy, but half of these patients were not taking a statin, and of those receiving statin treatment, less than half were within recommended lipid goals.
文摘Objective. -To examine the associations between severe headaches (SH), psychological distress, and comorbid conditions among U.S. adults. Background. -The lifetime prevalence of headaches is over 90%and headaches, particularly migraines, have been associated with disability, increased healthcare costs, and mood disorders. Methods. -We analyzed data obtained from adults aged 18 years or older (n = 29,828) who participated in the 2002 National Health Interview Survey, an ongoing, computer-assisted personal interview of a representative sample of the U.S. population. Results. -Approximately 15.1%of adults aged 18 years or older reported SH in the previous 3 months. Those reporting such headaches were significantly more likely, than those who did not, to report insomnia, excessive sleepiness, recurrent pain, and depressive or anxiety symptoms during the preceding 12 months. Approximately 88%of those who reported having had SH within the previous 3 months also indicated that they had at least one comorbid medical condition, relative to 67%of those without SH. Conclusion. -Despite their episodic nature, our results suggest that SH are associated with impairments in both physical and mental health. As the presence of SH may serve as an indicator of significant psychological distress and medical comorbidities, eliciting information about their occurrence during a standard medical examination appears to be warranted.
文摘Experimental models of Parkinson’s disease have demonstrated abnormal synaptic plasticity in the corticostriatal system, possibly related to the development of levodopa-induced dyskinesias (LID). We tested the hypothesis that LID in Parkinson’s disease is associated with aberrant plasticity in the human motor cortex (M1). We employed the paired associative stimulation (PAS) protocol, an experimental intervention involving transcranial magnetic stimulation (TMS) and median nerve stimulation capable of producing long-term potentiation (LTP)-like changes in the sensorimotor system in humans. We studied the more affected side of 16 moderately affected patients with Parkinson’s disease (9 dyskinetic, 7 non-dyskinetic) and the dominant side of 9 age-matched healthy controls. Motorevoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. PAS significantly increased MEP size in controls (+74.8%of baseline at T30) but not in patients off medication (T30: +0.07%of baseline in the non-dyskinetic, +27%in the dyskinetic group). Levodopa restored the potentiation of MEP amplitudes by PAS in the non-dyskinetic group (T30: +64.9%of baseline MEP)-but not in the dyskinetic group (T30: -9.2%of baseline). PAS prolonged CSP duration in controls. There was a trend towards prolongation of CSP in the non-dyskinetic group off medications but not in the dyskinetic group. Levodopa did not restore CSP prolongation by PAS in the dyskinetic group. Our findings suggest that LTP-like plasticity is deficient in Parkinson’s disease off medications and is restored by levodopa in nondyskinetic but not in dyskinetic patients. Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID.
文摘Objective. -To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background. -Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods. -This was a randomized (1:1:1), placebo-controlled, doubleblind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ≥6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results. -Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42%vs. 33%, respectively; P= .046) and 2 hours (68%vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61%vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions. -This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.
文摘Objective. -The aim of the present study was to evaluate cardiac performance of patients with migraine attacks during the overload produced by phenylephrine infusion. Background. -It is known that circulatory changes occur during migraine. However, the relationship between this finding and transient cardiac dysfunction is still unknown. Methods. -By means of two-dimensional direct M-mode echocardiography, we measured fractional shortening, ejection fraction, and mean velocity of circumferential fibers shortening in 18 patients with migraine and in 10 normal subjects as a control group. These measures were performed in two different periods: during attack-free intervals and during attacks. Pain intensity of typical migraine attack was evaluated on a 0 to 10 scale. Results. -Cardiac size and function were normal at rest in both groups. However, during migraine attacks, phenylephrine infusion provoked significant decrease in fractional shortening,EF, and mean velocity of circumferential fibers shortening, followed by concomitant increase of headache severity. On the other hand, during the attack-free interval and in the control group phenylephrine infusion did not show significant changes in cardiac function parameters. Conclusions. -Our data suggest that left ventricular dysfunction during the phenylephrine test could participate in the complex pathophysiological mechanism of migraine attacks.
文摘Objective: To evaluate the effect of IV recombinant tissue plasminogen activator (rt-PA) in patients with hyperdense artery sign (HAS) on initial CT scan. Methods: The authors determined the differential effect of IV rt-PA (0.9 mg/kg) in patients with HAS by testing the interaction of rt-PA and HAS in a logistic regression model after adjusting for age, sex, initial NIH Stroke Scale score (NIHSSS), time to randomization, systolic blood pressure, serum glucose, body temperature, and rt-PA in 616 patients treated within 3 hours of symptom onset. Outcomes evaluated included intracranial hemorrhage, modified Rankin scale (mRS) 0-1, Barthel Index (BI) of ≥95, Glasgow Outcome Scale (GOS) of 0-1, NIHSSS 0-1, and death at 90 days. Results: HAS was detected on the initial CT scan in 91 (15%) of the 616 patients by an independent neuroradiologist. Significantly lower rates of mRS 0-1, BI ≥95, GOS of 0-1, or NIHSSS 0-1 at 90 days were observed among patients with HAS. IV rt-PA significantly increased the rates of mRS 0-1, BI ≥95, GOS of 0-1, or NIHSSS 0-1 at 90 days after adjusting for potential confounders without any significant modifying effect (interaction) of HAS. Among the 91 patients with HAS, rt-PA use demonstrated a trend or significance for increased adjusted rates of favorable outcomes by mRS (p = 0.04), BI (p = 0.1), GOS (p = 0.03), and NIHSSS (p = 0.01). Conclusion: Although hyperdense artery sign is associated with poor outcome, IV recombinant tissue plasminogen activator may be beneficial in this subgroup of patients with ischemic stroke.
