Neuroplasticity is essential for recovery after stroke and is the target for new stroke therapies. During recovery from subcortical motor stroke, brain activations associated with movement may appear normal despite residual functional impairment. This raises an important question: how far does recovery of motor performance depend on the processes that precede movement execution involving the premotor and prefrontal cortex, rather than recovery of the corticospinal system alone?
We examined stroke patients with functional magnetic resonance imaging while they either imagined or executed a finger-thumb opposition sequence. In addition to classical analyses of regional activations, we studied neuroplasticity in terms of differential network connectivity using structural equation modeling. The study included 8 right-handed patients who had suffered a left-hemisphere subcortical ischemic stroke with paresis, and 13 age-matched healthy controls.
With good functional recovery, the regional activations had returned to normal in patients. However, connectivity within the extended motor network remained abnormal. These abnormalities were seen predominantly during motor imagery and correlated with motor performance.
Our results indicate that neuroplasticity can manifest itself as differences in connectivity among cortical areas remote from the infarct, rather than in the degree of regional activation. Connection strengths between nodes of the cortical motor network correlate with motor outcome. The altered organization of connectivity of the prefrontal areas may reflect the role of the prefrontal cortex in higher order planning of movement. Our results are relevant to the assessment and understanding of emerging physical and neurophysiological therapies for stroke rehabilitation.
A wide range of experimental studies have provided evidence that a night of sleep contributes to memory consolidation. Mental rotation (MR) skill is characterized by fundamental aspect of both cognitive and motor abilities which can be improved within practice sessions, but little is known about the effect of consolidation after MR practice. In the present study, we investigated the effect of MR training and the following corresponding day- and sleep-related time consolidations in taking into account the well-established gender difference in MR. Forty participants (20 women) practiced a computerized version of the Vandenberg and Kuse MR task. Performance was evaluated before MR training, as well as prior to, and after a night of sleep or a similar daytime interval. Data showed that while men outperformed women during the pre-training test, brief MR practice was sufficient for women to achieve equivalent performance. Only participants subjected to a night of sleep were found to enhance MR performance during the retest, independently of gender. These results provide first evidence that a night of sleep facilitates MR performance compared with spending a similar daytime interval, regardless gender of the participants. Since MR is known to involve motor processes, the present data might contribute to schedule relevant mental practice interventions for fruitful applications in rehabilitation and motor learning processes.
Introduction: Motor imagery (MI) is the mental rehearsal of a motor first person action-representation. There is interest in using MI to access the motor network after stroke. Conventional fMRI modeling has shown that MI and executed movement (EM) activate similar cortical areas but it remains unknown whether they share cortical networks. Proving this is central to using MI to access the motor network and as a form of motor training. Here we use multivariate analysis (tensor independent component analysis-TICA) to map the array of neural networks involved during MI and EM.
Methods: Fifteen right-handed healthy volunteers (mean-age 28.4 years) were recruited and screened for their ability to carry out MI (Chaotic MI Assessment). fMRI consisted of an auditory-paced (1 Hz) right hand finger-thumb opposition sequence (2,3,4,5; 2…) with two separate runs acquired (MI & rest and EM & rest: block design). No distinction was made between MI and EM until the final stage of processing. This allowed TICA to identify independent-components (IC) that are common or distinct to both tasks with no prior assumptions.
Results: TICA defined 52 ICs. Non-significant ICs and those representing artifact were excluded. Components in which the subject scores were significantly different to zero (for either EM or MI) were included. Seven IC remained. There were IC's shared between EM and MI involving the contralateral BA4, PMd, parietal areas and SMA. IC's exclusive to EM involved the contralateral BA4, S1 and ipsilateral cerebellum whereas the IC related exclusively to MI involved ipsilateral BA4 and PMd.
Conclusion: In addition to networks specific to each task indicating a degree of independence, we formally demonstrate here for the first time that MI and EM share cortical networks. This significantly strengthens the rationale for using MI to access the motor networks, but the results also highlight important differences.
motor imagery; functional imaging; fMRI; mental imagery; brain mapping
The 5-hydroxytryptamine type 2a (5-HT2A) selective radiotracer [18F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [18F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [18F]altanserin is suitable for quantification of 5-HT2A receptor availability in rats.
[18F]altanserin; animal; brain; 5-HT2A; modeling; PET
Age has a differential effect on cognition, with word retrieval being one of the cognitive domains most affected by aging. This study examined the functional and structural neural correlates of phonological word retrieval in younger and older adults using word and picture rhyme judgment tasks. Although the behavioral performance in the fMRI task was similar for the two age groups, the older adults had increased activation in the right pars triangularis across tasks and in the right pars orbitalis for the word task only. Increased activation together with preserved performance in the older participants would suggest that increased activation was related to compensatory processing. We validated this hypothesis by showing that right pars triangularis activation during correct rhyme judgments was highest in participants who made overall more errors, therefore being most error-prone. Our findings demonstrate that the effect of aging differ in adjacent but distinct right inferior frontal regions. The differential effect of age on word and picture tasks also provides new clues to the level of processing that is most affected by age in speech production tasks. Specifically, we suggest that right inferior frontal activation in older participants is needed to inhibit errors.
EEG/MEG source localization based on a “distributed solution” is severely underdetermined, because the number of sources is much larger than the number of measurements. In particular, this makes the solution strongly affected by sensor noise. A new way to constrain the problem is presented. By using the anatomical basis of spherical harmonics (or spherical splines) instead of single dipoles the dimensionality of the inverse solution is greatly reduced without sacrificing the quality of the data fit. The smoothness of the resulting solution reduces the surface bias and scatter of the sources (incoherency) compared to the popular minimum-norm algorithms where single-dipole basis is used (MNE, depth-weighted MNE, dSPM, sLORETA, LORETA, IBF) and allows to efficiently reduce the effect of sensor noise. This approach, termed Harmony, performed well when applied to experimental data (two exemplars of early evoked potentials) and showed better localization precision and solution coherence than the other tested algorithms when applied to realistically simulated data.
Leukoaraiosis and cerebral microbleeds (CMB), which represent cerebral microangiopathy, commonly coexist in patients with acute lacunar stroke. Since they may have different impacts on stroke prognosis and treatment, it is important to know the factors associated with leukoaraiosis-predominant vs. CMB-predominant microangiopathies.
We prospectively recruited 226 patients with acute lacunar infarction and divided them into four groups according to the Fazekas’ score and the presence of CMB: mild, red (predominant CMB), white (predominant leukoaraiosis) and severe microangiopathy groups. For comparison, we also evaluated 50 patients with intracerebral hemorrhage (ICH). We evaluated the clinical and laboratory findings of microangiopathy subtypes in patients with acute lacunar stroke and then compared them with those of primary ICH.
The risk factor profile was different among the groups. Patients with acute lacunar infarct but mild microangiopathy were younger, predominantly male, less hypertensive, and more frequently had smoking and heavy alcohol habits than other groups. The risk factor profile of red microangiopathy was similar to that of ICH but differed from that of white microangiopathy. The subjects in the white microangiopathy group were older and more frequently had diabetes than those in the red microangiopathy or ICH group. After adjustments for other factors, age [odds ratio (OR) 1.13; 95% confidence interval (CI) 1.08–1.18; p<0.001] and diabetes (OR 2.28; 95% CI 1.02–5.13; p = 0.045) were independently associated with white microangiopathy, and age (OR 1.05; 95% CI 1.01–1.08; p = 0.010) was independent predictor for red microangiopathy compared to mild microangiopathy.
Patients with acute lacunar infarction have a different risk factor profile depending on microangiopathic findings. Our results indicate that diabetes may be an one of determinants of white (leukoaraiosis-predominant) microangiopathy, whereas smoking and alcohol habits in relatively young people may be a determinants of mild microangiopahic changes in patients with lacunar infarction.
Depicting the salvageable tissue is increasingly used in the clinical setting following stroke. As absolute cerebral blood flow (CBF) is difficult to measure using perfusion magnetic resonance or computed tomography and has limitations as a penumbral marker, time-based variables, particularly the mean transit time (MTT), are routinely used as surrogates. However, a direct validation of MTT as a predictor of the penumbra threshold using gold-standard positron emission tomography (PET) is lacking. Using 15O-PET data sets obtained from two independent acute stroke samples (N=7 and N=30, respectively), we derived areas under the curve (AUCs), optimal thresholds (OTs), and 90%-specificity thresholds (90%-Ts) from receiver operating characteristic curves for absolute MTT, MTT delay, and MTT ratio to predict three penumbra thresholds (‘classic': CBF <20 mL/100 g per min; ‘normalized': CBF ratio <0.5; and ‘stringent': both CBF <20 mL/100 g per min and oxygen extraction fraction >0.55). In sample 1, AUCs ranged from 0.79 to 0.92, indicating good validity; OTs ranged from 7.8 to 8.3 seconds, 2.8 to 4.7 seconds, and 151% to 267% for absolute MTT, MTT delay, and MTT ratio, respectively, while as expected, 90%-Ts were longer. There was no significant difference between sample 1 and sample 2 for any of the above measurements, save for a single MTT parameter with a single penumbra threshold. These consistent findings from gold-standard PET obtained in two independent cohorts document that MTT is a very good surrogate to CBF for depicting the penumbra threshold.
acute stroke; brain ischemia; cerebral blood flow; neurophysiology; positron emission tomography
Hippocampal atrophy, posterior cingulate and frontal glucose hypometabolism, and white-matter tract disruption are well-described early macroscopic events in Alzheimer’s disease. The relationships between these three types of alterations have been documented in previous studies, but their chronology still remains to be established. The present study used multi-modal Fluorodeoxyglucose - Positron Emission Tomography and Magnetic Resonance Imaging longitudinal data to address this question in patients with amnestic Mild Cognitive Impairment. We found unidirectional, specific sequential relationships between: i) baseline hippocampal atrophy and both cingulum bundle (r=0.70; p=3.10−3) and uncinate fasciculus (r=0.75; p=7.10−4) rate of atrophy; ii) baseline cingulum bundle atrophy and rate of decline of posterior (r=0.72; p=2.10−3) and anterior (r=0.74; p=1.10−3) cingulate metabolism; and iii) baseline uncinate white matter atrophy and subgenual metabolism rate of change (r=0.65; p=6.10−3). Baseline local grey matter atrophy was not found to contribute to hypometabolism progression within the posterior and anterior cingulate as well as subgenual cortices. These findings suggest that hippocampal atrophy progressively leads to disruption of the cingulum bundle and uncinate fasciculus, which in turn leads to glucose hypometabolism of the cingulate and subgenual cortices, respectively. This study reinforces the relevance of remote mechanisms above local interactions to account for the patterns of brain alteration observed in amnestic Mild Cognitive Impairment, and provides new avenues to assess the sequence of events in complex diseases characterized by multiple manifestations.
Aged; Aged, 80 and over; Alzheimer Disease; metabolism; pathology; Atrophy; Brain; metabolism; pathology; Cerebral Cortex; metabolism; pathology; Female; Follow-Up Studies; Hippocampus; metabolism; pathology; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Fibers, Myelinated; metabolism; pathology; Time Factors; Alzheimers disease; MRI/fMRI; PET imaging; white matter; hippocampus
In this study, we show a basis function method (BAFPIC) for voxelwise calculation of kinetic parameters (K1, k2, k3, Ki) and blood volume using an irreversible two-tissue compartment model. BAFPIC was applied to rat ischaemic stroke micro-positron emission tomography data acquired with the hypoxia tracer [18F]fluoromisonidazole because irreversible two-tissue compartmental modelling provided good fits to data from both hypoxic and normoxic tissues. Simulated data show that BAFPIC produces kinetic parameters with significantly lower variability and bias than nonlinear least squares (NLLS) modelling in hypoxic tissue. The advantage of BAFPIC over NLLS is less pronounced in normoxic tissue. Ki determined from BAFPIC has lower variability than that from the Patlak–Gjedde graphical analysis (PGA) by up to 40% and lower bias, except for normoxic tissue at mid-high noise levels. Consistent with the simulation results, BAFPIC parametric maps of real data suffer less noise-induced variability than do NLLS and PGA. Delineation of hypoxia on BAFPIC k3 maps is aided by low variability in normoxic tissue, which matches that in Ki maps. BAFPIC produces Ki values that correlate well with those from PGA (r2=0.93 to 0.97; slope 0.99 to 1.05, absolute intercept <0.00002 mL/g per min). BAFPIC is a computationally efficient method of determining parametric maps with low bias and variance.
basis function; [18F]fluoromisonidazole; FMISO; kinetic modelling; parametric mapping; positron emission tomography
The neural correlates of inner speech have been investigated previously using functional imaging. However, methodological and other limitations have so far precluded a clear description of the neural anatomy of inner speech and its relation to overt speech. Specifically, studies that examine only inner speech often fail to control for subjects’ behaviour in the scanner and therefore cannot determine the relation between inner and overt speech. Functional imaging studies comparing inner and overt speech have not produced replicable results and some have similar methodological caveats as studies looking only at inner speech. Lesion analysis can avoid the methodological pitfalls associated with using inner and overt speech in functional imaging studies, while at the same time providing important data about the neural correlates essential for the specific function. Despite its advantages, a study of the neural correlates of inner speech using lesion analysis has not been carried out before. In this study, 17 patients with chronic post-stroke aphasia performed inner speech tasks (rhyme and homophone judgements), and overt speech tasks (reading aloud). The relationship between brain structure and language ability was studied using voxel-based lesion–symptom mapping. This showed that inner speech abilities were affected by lesions to the left pars opercularis in the inferior frontal gyrus and to the white matter adjacent to the left supramarginal gyrus, over and above overt speech production and working memory. These results suggest that inner speech cannot be assumed to be simply overt speech without a motor component. It also suggests that the use of overt speech to understand inner speech and vice versa might result in misleading conclusions, both in imaging studies and clinical practice.
stroke; aphasia; inner speech; voxel-based lesion–symptom mapping
2009;132(Pt 12):e133; author reply e134.
Alzheimer Disease; metabolism; physiopathology; radionuclide imaging; Atrophy; metabolism; physiopathology; radionuclide imaging; Biological Markers; analysis; metabolism; Early Diagnosis; Energy Metabolism; physiology; Fluorodeoxyglucose F18; diagnostic use; Gyrus Cinguli; metabolism; physiopathology; radionuclide imaging; Humans; Neural Pathways; metabolism; physiopathology; radionuclide imaging; Positron-Emission Tomography; methods; Predictive Value of Tests
A sensitive marker for monitoring progression of early Alzheimer’s Disease (AD) would help to develop and test new therapeutic strategies. The present study aimed at investigating brain metabolism changes over time, as potential monitoring marker, in patients with amnestic Mild Cognitive Impairment (aMCI), according to their clinical outcome (converters or non-converters), and in relation to their cognitive decline. Seventeen aMCI patients underwent MRI and 18FDG-PET scans both at inclusion and 18 months later. Baseline and follow-up PET data were corrected for partial volume effects and spatially normalized using MRI data, scaled to the vermis and compared using SPM2. ‘PET-PAC’ maps reflecting metabolic percent annual changes were created for correlation analyses with cognitive decline. In the whole sample, the greatest metabolic decrease concerned the posterior cingulate-precuneus area. Converters had significantly greater metabolic decrease than nonconverters in two ventro-medial prefrontal areas, the subgenual (BA25) and anterior cingulate (BA24/32). PET-PAC in BA25 and BA24/32 combined allowed complete between-group discrimination. BA25 PET-PAC significantly correlated with both cognitive decline and PET-PAC in the hippocampal region and temporal pole, while BA24/32 PET-PAC correlated with posterior cingulate PET-PAC. Finally, the metabolic change in BA8/9/10 was inversely related to that in BA25 and showed relative increase with cognitive decline, suggesting that compensatory processes may occur in this dorso-medial prefrontal region. The observed ventro-medial prefrontal disruption is likely to reflect disconnection from the hippocampus, both indirectly through the cingulum bundle and posterior cingulate cortex for BA24/32, and directly through the uncinate fasciculus for BA25. Altogether, our findings emphasize the potential of 18FDG-PET for monitoring early AD progression.
Aged; Aged, 80 and over; Alzheimer Disease; complications; metabolism; psychology; radionuclide imaging; Amnesia; etiology; metabolism; radionuclide imaging; Brain; metabolism; radionuclide imaging; Brain Mapping; methods; Cognition Disorders; etiology; metabolism; radionuclide imaging; Disease Progression; Female; Fluorodeoxyglucose F18; diagnostic use; Follow-Up Studies; Humans; Image Interpretation, Computer-Assisted; methods; Magnetic Resonance Imaging; methods; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; methods; amnestic Mild Cognitive Impairment; 18FDG-PET monitoring; ventro-medial prefrontal cortex; longitudinal study
In early Alzheimer’s disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural MRI and 18FDG-PET in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity and grey matter metabolism by means of a whole brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus and mammillary bodies (all part of Papez’ circuit), as well as the right temporo-parietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.
Aged; Aged, 80 and over; Alzheimer Disease; complications; pathology; radionuclide imaging; Atrophy; Brain Mapping; Case-Control Studies; Female; Fluorodeoxyglucose F18; metabolism; Hippocampus; pathology; radionuclide imaging; Humans; Image Processing, Computer-Assisted; methods; Magnetic Resonance Imaging; methods; Male; Middle Aged; Neuroglia; pathology; radionuclide imaging; Neurons; pathology; radionuclide imaging; Neuropsychological Tests; Positron-Emission Tomography; methods; Statistics as Topic; Alzheimer disease; Hippocampus; white matter; Deafferentation; Morphometry; Positron Emission Tomography
Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies.
Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients.
These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.
The recent “Advanced Neuroimaging for Acute Stroke Treatment” meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.
Imaging has become a cornerstone of stroke management, translating pathophysiological knowledge to everyday decision-making. Plain computed tomography is widely available and remains the standard for initial assessment: the technique rules out haemorrhage, visualizes the occluding thrombus and identifies early tissue hypodensity and swelling, which have different implications for thrombolysis. Based on evidence from positron emission tomography (PET), however, multimodal imaging is increasingly advocated. Computed tomography perfusion and angiography provide information on the occlusion site, on recanalization and on the extent of salvageable tissue. Magnetic resonance-based diffusion-weighted imaging (DWI) has exquisite sensitivity for acute ischaemia, however, and there is increasingly robust evidence that DWI combined with perfusion-weighted magnetic resonance imaging (PWI) and angiography improves functional outcome by selecting appropriate patients for thrombolysis (small DWI lesion but large PWI defect) and by ruling out those who would receive no benefit or might be harmed (very large DWI lesion, no PWI defect), especially beyond the 3-hour time window. Combined DWI–PWI also helps predict malignant oedema formation and therefore helps guide selection for early brain decompression. Finally, DWI–PWI is increasingly used for patient selection in therapeutic trials. Although further methodological developments are awaited, implementing the individual pathophysiologic diagnosis based on multimodal imaging is already refining indications for thrombolysis and offers new opportunities for management of acute stroke patients.
Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.
Robot-aided gait therapy offers a promising approach towards improving gait function in individuals with neurological disorders such as stroke or spinal cord injury. However, incorporation of appropriate control strategies is essential for actively engaging the patient in the therapeutic process. Although several control algorithms (such as assist-as-needed and error augmentation) have been proposed to improve active patient participation, we hypothesize that the therapeutic benefits of these control algorithms can be greatly enhanced if combined with a motor learning task to facilitate neural reorganization and motor recovery. Here, we describe an active robotic training approach (patient-cooperative robotic gait training combined with a motor learning task) using the Lokomat and pilot-tested whether this approach can enhance active patient participation during training. Six neurologically intact adults and three chronic stroke survivors participated in this pilot feasibility study. Participants walked in a Lokomat while simultaneously performing a foot target-tracking task that necessitated greater hip and knee flexion during the swing phase of the gait. We computed the changes in tracking error as a measure of motor performance and changes in muscle activation as a measure of active subject participation. Repeated practice of the motor-learning task resulted in significant reductions in target-tracking error in all subjects. Muscle activation was also significantly higher during active robotic training compared to simply walking in the robot. The data from stroke participants also showed a trend similar to neurologically intact participants. These findings provide a proof-of-concept demonstration that combining robotic gait training with a motor learning task enhances active participation.
Background and Purpose
Good reliability of methods to assess the extent of ischemia in acute stroke is important for implementation in clinical practice, especially between observers with varying experience. Our aim was to determine inter- and intra-observer reliability of the 1/3 middle cerebral artery (MCA) rule and the Alberta Stroke Program Early CT Score (ASPECTS) for different CT modalities in patients suspected of acute ischemic stroke.
We prospectively included 105 patients with acute neurological deficit due to suspected acute ischemic stroke within 9 hours after symptom onset. All patients underwent non-contrast CT, CT perfusion and CT angiography on admission. All images were evaluated twice for presence of ischemia, ischemia with >1/3 MCA involvement, and ASPECTS. Four observers evaluated twenty scans twice for intra-observer agreement. We used kappa statistics and intraclass correlation coefficient to calculate agreement.
Inter-observer agreement for the 1/3 MCA rule and ASPECTS was fair to good for non-contrast CT, poor to good for CT angiography source images, but excellent for all CT perfusion maps (cerebral blood volume, mean transit time, and predicted penumbra and infarct maps). Intra-observer agreement for the 1/3 MCA rule and ASPECTS was poor to good for non-contrast CT, fair to moderate for CT angiography source images, and good to excellent for all CT perfusion maps.
Between observers with a different level of experience, agreement on the radiological diagnosis of cerebral ischemia is much better for CT perfusion than for non-contrast CT and CT angiography source images, and therefore CT perfusion is a very reliable addition to standard stroke imaging.
Untreated acute mild stroke patients have substantial 90-day disability rates and worse outcomes than those who are treated with thrombolysis. There is little information regarding which patients with acute mild stroke will benefit from thrombolysis. We sought to investigate factors that are associated with early neurological deterioration (END) and poor prognosis in patients with acute mild stroke.
This was a retrospective study of consecutively registered patients with acute mild stroke (NIHSS ≤3) at our tertiary stroke center between October 2008 and December 2011. END was defined as an increase in NIHSS ≥2 points between hospital days 0 and 5. Modified Rankin Scale (mRS) scores of 0–1 at 90 days post-stroke were defined as favorable outcomes.
A total of 378 (mean age, 65.9±13.0 years) patients were included in this study. END occurred in 55 patients (14.6%). IV-thrombolysis was performed in only 9 patients. Symptomatic arterial occlusion on the initial MRA was independently associated with END (OR, 2.206; 95% CI, 1.219–3.994; p = 0.009) by multivariate logistic regression. Of the 119 patients with symptomatic arterial occlusion, ICA occlusion was independently associated with END (OR, 8.606; 95% CI, 2.312–32.043; p = 0.001).
This study demonstrates that symptomatic arterial occlusion may be an important predictor of END in patients with acute mild stroke. It may therefore be important to consider that acute ischemic stroke with symptomatic arterial occlusion and low NIHSS scores may not represent mild stroke in acute periods.
Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital complications, including seizures, remains unclear. One study associated onset TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no other studies have confirmed this relationship. This study aims to assess the impact of onset TCA on in-hospital complications, poor functional outcome, mortality, and epilepsy at 3 months.
Analysis of a prospective study cohort of 1479 SAH patients admitted to Columbia University Medical Center between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified based on accounts of emergency care providers or family witnesses.
TCA at onset was described in 170 patients (11%). Patients with onset TCA were younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%, P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral blood than those without onset TCA (all, P<0.001). After adjusting for known confounders, onset TCA was significantly associated with in-hospital seizures (OR 3.80, 95%-CI: 2.43–5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06–2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21–2.58, P = 0.003). At 3 months, however, onset TCA was not associated with poor functional outcome, mortality, and epilepsy after adjusting for age, admission clinical grade, and cisternal blood volume.
Onset TCA is not a rare event as it complicates 11% of cases of SAH. New and clinically relevant findings are the association of onset TCA with in-hospital seizures, pneumonia and delayed cerebral ischemia. Despite the increased risk of in-hospital complications, onset TCA is not associated with disability, mortality, and epilepsy at 3 months.
The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I–VIII). Within these lesion types, lesion types IV–V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones.
Eighty-three consecutive patients (45 male (54.2%); age 54–88 years (mean 73.2 years)) presenting with an asymptomatic carotid stenosis of 50–99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I–VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance.
Six out of 83 patients (7.2%) were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months.
During follow-up, n = 9 (11.7%) ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV–V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7%) vs. n = 0 (0%) during follow-up). Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII) than in patients with the high-risk lesion types (IV–V and VI) (log rank test P<0.0001).
MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. MRI could improve selection criteria for invasive therapy in the future.
Fast in-vivo high resolution diffusion tensor imaging (DTI) of the mouse brain has recently been shown to enable cohort studies by the combination of appropriate pulse sequences and cryogenically cooled resonators (CCR). The objective of this study was to apply this DTI approach at the group level to β-amyloid precursor protein (APP) transgenic mice.
Twelve mice (5 wild type, 7 APP transgenic tg2576) underwent DTI examination at 1562×250 µm3 spatial resolution with a CCR at ultrahigh field (11.7 T). Diffusion images were acquired along 30 gradient directions plus 5 references without diffusion encoding with a total acquisition time of 35 minutes. Fractional anisotropy (FA) maps were statistically compared by whole brain-based spatial statistics (WBSS) at the group level vs. wild type controls.
FA-map comparison showed characteristic regional patterns of differences between the groups with localizations associated with Alzheimer’s disease in humans, such as the hippocampus, the entorhinal cortex, and the caudoputamen.
In this proof-of-principle study, regions associated with amyloid-β deposition could be identified by WBSS of FA maps in APP transgenic mice vs. wild type mice. Thus, DTI in the mouse brain acquired at 11.7 T by use of a CCR was demonstrated to be feasible for cohort studies.