Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Intravenous thrombolysis of basilar artery occlusion: thrombus length versus recanalization success.

BACKGROUND AND PURPOSE: In middle cerebral artery occlusion, probability of recanalization after intravenous tissue-type plasminogen activator thrombolysis (IVT) was reported to drop <1% for thrombi exceeding 8 mm. We aimed to evaluate the effect of thrombus length and location on success of recanalization after IVT in basilar artery occlusion. METHODS: We evaluated 164 consecutive patients with angiography-proven basilar artery occlusion and available thrombus length. We excluded 24 patients who underwent endovascular treatment. All included patients (n=140) received IVT. Thrombolysis in myocardial infarction 2 to 3 was considered as successful recanalization. RESULTS: Of the 140 included patients, 37 (26.4%) lacked post-treatment angiography, mostly because of early death. Of the remaining 103 patients, those with recanalization had shorter thrombi (median, 5.5 mm and mean, 9.7 mm) when compared with those with nonrecanalized (median, 15.0 mm and mean, 16.6 mm; P<0.001). Thrombi shorter than 10 mm had 70% to 80% probability of recanalization, whereas 10 to 20 mm, 20 to 30 mm, and >30 mm long thrombi had probabilities of 50% to 70%, 30% to 50%, and 20% to 30%, respectively. Patients with thrombi <10 mm (n=52) and recanalization had more frequently top-of-the basilar (92.5%) and less frequently caudal or midbasilar (7.5%) clot location (P=0.01). In multivariable analysis, thrombus length was independently associated with recanalization (P=0.001). Their relationship remained linear across all lengths. CONCLUSIONS: Although recanalization of basilar artery occlusion with IVT depends on thrombus length, its probability even in patients with thrombi >30 mm (20%-30%) was substantially higher than minimal recanalization of middle cerebral artery thrombi exceeding 8 mm. There was no threshold length, beyond which basilar artery occlusion recanalization with IVT could ad hoc be deemed hopeless.

Predictors of early mortality in young adults after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Patient and radiological characteristics of intracerebral hemorrhage (ICH), surgical treatment, and outcome after ICH are interrelated. Our purpose was to define whether these characteristics or surgical treatment correlate with mortality among young adults. METHODS: We retrospectively reviewed clinical and imaging data of all first-ever nontraumatic patients with ICH between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 and linked these data with national causes of death registry. A logistic regression analysis of factors associated with 3-month mortality and a propensity score comparison between patients treated conservatively and operatively was performed. RESULTS: Among the 325 eligible patients (59.4% men), factors associated with 3-month mortality included higher National Institutes of Health Stroke Scale score, infratentorial location, hydrocephalus, herniation, and multiple hemorrhages. Adjusted for these factors, as well as demographics, ICH volume, and the underlying cause, surgical evacuation was associated with lower 3-month mortality (odds ratio, 0.06; 95% confidence interval, 0.02-0.21). In propensity score-matched analysis, 3-month case fatality rates were 3-fold in those treated conservatively (27.5% versus 7.8%; P<0.001). CONCLUSIONS: The predictors of short-term case fatality are alike in young and elderly patients with ICH. However, initial hematoma evacuation was associated with lower 3-month case fatality in our young patients with ICH.

Thrombolysis of basilar artery occlusion: impact of baseline ischemia and time.

OBJECTIVE: To evaluate the impact of extensive baseline ischemic changes on functional outcome after thrombolysis of basilar artery occlusion (BAO), and to study the effect of time to treatment in the absence of such findings. METHODS: We prospectively evaluated 184 consecutive patients with angiography-proven BAO. The majority of patients received intravenous alteplase and concomitant full-dose heparin. Extensive baseline ischemia was defined as posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) < 8. Onset-to-treatment time (OTT) was evaluated both as a continuous and as a categorical variable (0-6 hours, 6-12 hours, 12-24 hours, and 24-48 hours). Successful recanalization means thrombolysis in myocardial infarction (TIMI) = 2 to 3. Symptomatic intracranial hemorrhage (sICH) was evaluated with National Institute of Neurological Disorders and Stroke, European Cooperative Acute Stroke Study II, and Safe Implementation of Thrombolysis in Stroke criteria. Poor 3-month outcome was defined as modified Rankin Scale score of 3 to 6. RESULTS: The majority (96%) of patients with baseline pc-ASPECTS < 8 had poor 3-month outcome, and a similar number (94%) was observed in those of them with confirmed recanalization (51.5%). In contrast, half of the patients with pc-ASPECTS ≥ 8 and successful recanalization (73.2%) achieved good outcome. In these patients, OTT was associated with poor outcome neither as a continuous nor as a categorical variable. Factors independently associated with poor outcome were greater age and baseline National Institutes of Health Stroke Scale, lack of recanalization, history of atrial fibrillation, and sICH. In the model including the whole cohort (patients with any pc-ASPECTS), pc-ASPECTS < 8 was independently associated with poor outcome (odds ratio = 5.83, 95% confidence interval = 1.09-31.07). INTERPRETATION: In the absence of extensive baseline ischemia, recanalization of BAO up to 48 hours was seldom futile and produced good outcomes in 50% of patients, which was independent of time to treatment.

Responsiveness and functional connectivity of the scene-sensitive retrosplenial complex in 7-11-year-old children.

Brain imaging studies have identified two cortical areas, the parahippocampal place area (PPA) and the retrosplenial complex (RSC), that respond preferentially to the viewing of scenes. Contrary to the PPA, little is known about the functional maturation and cognitive control of the RSC. Here we used functional magnetic resonance imaging and tasks that required attention to scene (or face) images and suppression of face (or scene) images, respectively, to investigate task-dependent modulation of activity in the RSC and whole-brain functional connectivity (FC) of this area in 7-11-year-old children and young adults. We compared responsiveness of the RSC with that of the PPA. The RSC was selectively activated by scene images in both groups, albeit less than the PPA. Children modulated activity between the tasks similarly in the RSC and PPA, and to the same extent as adults in PPA, whereas adults modulated activity in the RSC less than in PPA. In children, the whole brain FC of the RSC was stronger in the Sf than Fs task between the left RSC and right fusiform gyrus. The between groups comparison suggested stronger FC in children than adults in the Sf task between the right RSC and the left inferior parietal lobule and intraparietal sulcus. Together the results suggest that the function of the RSC and the related networks undergo dynamic changes over the development from 7-11-year-old children to adulthood.

Task-dependent activations of human auditory cortex to prototypical and nonprototypical vowels.

Research in auditory neuroscience has largely neglected the possible effects of different listening tasks on activations of auditory cortex (AC). In the present study, we used high-resolution fMRI to compare human AC activations with sounds presented during three auditory and one visual task. In all tasks, subjects were presented with pairs of Finnish vowels, noise bursts with pitch and Gabor patches. In the vowel pairs, one vowel was always either a prototypical /i/ or /ae/ (separately defined for each subject) or a nonprototype. In different task blocks, subjects were either required to discriminate (same/different) vowel pairs, to rate vowel "goodness" (first/second sound was a better exemplar of the vowel class), to discriminate pitch changes in the noise bursts, or to discriminate Gabor orientation changes. We obtained distinctly different AC activation patterns to identical sounds presented during the four task conditions. In particular, direct comparisons between the vowel tasks revealed stronger activations during vowel discrimination in the anterior and posterior superior temporal gyrus (STG), while the vowel rating task was associated with increased activations in the inferior parietal lobule (IPL). We also found that AC areas in or near Heschl's gyrus (HG) were sensitive to the speech-specific difference between a vowel prototype and nonprototype during active listening tasks. These results show that AC activations to speech sounds are strongly dependent on the listening tasks.

Regulation of brain activity in the fusiform face and parahippocampal place areas in 7-11-year-old children.

Developmental studies have demonstrated that cognitive processes such as attention, suppression of interference and memory develop throughout childhood and adolescence. However, little is currently known about the development of top-down control mechanisms and their influence on cognitive performance. In the present study, we used functional magnetic resonance imaging to investigate modulation of activity in the ventral visual cortex in healthy 7-11-year-old children and young adults. The participants performed tasks that required attention to either face (Fs task) or scene (Sf task) images while trying to ignore distracting scene or face images, respectively. A face-selective area in the fusiform gyrus (fusiform face area, FFA) and an area responding preferentially to scene images in the parahippocampal gyrus (parahippocampal place area, PPA) were defined using functional localizers. Children responded slower and less accurately in the tasks than adults. In children, the right FFA was less selective to face images and regulation of activity between the Fs and Sf tasks was weaker compared to adults. In the PPA, selectivity to scenes and regulation of activity, there according to the task demands were comparable between children and adults. During the tasks, children activated prefrontal cortical areas including the middle (MFG) and superior (SFG) frontal gyrus more than adults. Functional connectivity between the right FFA and left MFG was stronger in adults than children in the Fs task. Children, on the other hand, had stronger functional connectivity than adults in the Sf task between the right FFA and right PPA and between right MFG and medial SFG. There were no group differences in the functional connectivity between the PPA and the prefrontal cortex (PFC). Together the results suggest that, in 7-11-year-old children, the FFA is still immature, whereas the selectivity to scenes and regulation of activity in the PPA is comparable to adults. The results also indicated functional immaturity of the PFC in children compared to adults and weaker connectivity between the PFC and the rFFA, explaining the weaker regulation of activity in the rFFA between the Fs and Sf tasks.

Task-dependent activations of human auditory cortex during spatial discrimination and spatial memory tasks.

In the present study, we applied high-resolution functional magnetic resonance imaging (fMRI) of the human auditory cortex (AC) and adjacent areas to compare activations during spatial discrimination and spatial n-back memory tasks that were varied parametrically in difficulty. We found that activations in the anterior superior temporal gyrus (STG) were stronger during spatial discrimination than during spatial memory, while spatial memory was associated with stronger activations in the inferior parietal lobule (IPL). We also found that wide AC areas were strongly deactivated during the spatial memory tasks. The present AC activation patterns associated with spatial discrimination and spatial memory tasks were highly similar to those obtained in our previous study comparing AC activations during pitch discrimination and pitch memory (Rinne et al., 2009). Together our previous and present results indicate that discrimination and memory tasks activate anterior and posterior AC areas differently and that this anterior-posterior division is present both when these tasks are performed on spatially invariant (pitch discrimination vs. memory) or spatially varying (spatial discrimination vs. memory) sounds. These results also further strengthen the view that activations of human AC cannot be explained only by stimulus-level parameters (e.g., spatial vs. nonspatial stimuli) but that the activations observed with fMRI are strongly dependent on the characteristics of the behavioral task. Thus, our results suggest that in order to understand the functional structure of AC a more systematic investigation of task-related factors affecting AC activations is needed.

Activation in parietal operculum parallels motor recovery in stroke.

Motor recovery after stroke requires continuous interaction of motor and somatosensory systems. Integration of somatosensory feedback with motor programs is needed for the automatic adjustment of the speed, range, and strength of the movement. We recorded somatosensory evoked fields (SEFs) to tactile finger stimulation with whole-scalp magnetoencephalography in 23 acute stroke patients at 1 week, 1 month, and 3 months after stroke to investigate how deficits in the somatosensory cortical network affect motor recovery. SEFs were generated in the contralateral primary somatosensory cortex (SI) and in the bilateral parietal opercula (PO) in controls and patients. In the patients, SI amplitude or latency did not correlate with any of the functional outcome measures used. In contrast, the contralateral PO (cPO) amplitude to the affected hand stimuli correlated significantly with hand function in the acute phase and during recovery; the weaker the PO activation, the clumsier the hand was. At 1 and 3 months, enhancement of the cPO activation paralleled the improvement of the hand function. Whole-scalp magnetoencephalography measurements revealed that dysfunction of somatosensory cortical areas distant from the ischemic lesion may affect the motor recovery. Activation strength of the PO paralleled motor recovery after stroke, suggesting that the PO area is an important hub in mediating modulatory afferent input to motor cortex.

Lower brain diffusivity in postpartum period compared to late pregnancy: results from a prospective imaging study of multiple sclerosis patients.

INTRODUCTION: A positive correlation has been observed between multiple sclerosis (MS) disease activity status and the apparent diffusion coefficient (ADC) of the brain. Moreover, the relapse frequency of MS has been reported to decrease during pregnancy and increase postpartum. The aim of this study was to evaluate whether ADC histograms correlate with MS activity during pregnancy and postpartum, with a leading hypothesis that the ADC would increase postpartum compared to pregnancy. METHODS: Magnetic resonance imaging, as well as diffusion-weighted imaging, was performed in 19 patients with relapsing-remitting MS once during the third trimester and once 4-12 weeks postpartum. Brain tissue was extracted from nonbrain tissue with an automated computer program, and whole-brain histograms were generated. New or growing T2 lesions in postpartum images were counted on T2-weighted images. RESULTS: In conventional brain magnetic resonance imaging, a significant increase in T2-lesion load was seen in postpartum images; 58% of patients showed signs of disease activity on their postpartum scan. Despite of this, and contrary to the original hypothesis, whole-brain ADC values were significantly lower in the postpartum period compared to the time of pregnancy. CONCLUSION: This is the first study to address the ADC of the brain during pregnancy and postpartum period. We hypothesize that the higher ADC values observed during pregnancy in this study reflect the physiological status of the cerebral vasculature during pregnancy (generalized vasodilatation of downstream resistance arterioles and an increase of endothelial permeability), which overwhelm the alterations in ADC values normally seen related to MS activity.

Probing modifications of cortical excitability during stroke recovery with navigated transcranial magnetic stimulation.

OBJECTIVE: To follow cortical excitability changes during recovery from stroke with navigated transcranial magnetic stimulation (nTMS), in particular, to characterize changes of short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), to correlate them with recovery of upper extremity function, and to detect possible shifts of cortical hand representations. METHODS: Single and paired pulse nTMS were delivered to the hemisphere with infarction and to the hemisphere without infarction in 14 first-ever stroke patients at 1 (T1) and 3 months (T2) after stroke. Electromyographic responses to nTMS stimulation were recorded from the first dorsal interosseus muscles. nTMS was used to ensure an accurate coil repositioning in repeated measurements. Hand function recovery was clinically evaluated using the Action Research Arm Test (ARAT) and 9-hole peg test (9-HPT). RESULTS: SICI and ICF were modulated in both hemispheres during recovery. Inhibition in the hemisphere without infarction correlated significantly with the affected hand performance at T2; stronger disinhibition (poor inhibition) was associated with worse hand performance. Location of hand muscle representations was shifted in 3 well-recovered patients out of 14 patients at T2. CONCLUSIONS: In line with earlier studies, disinhibition in the hemisphere without infarction may be related to poor recovery of the affected hand. Usage of the affected hand during stroke recovery seems to influence these cortical excitability changes. nTMS is a valuable tool for tracking muscle cortical representation changes during brain reorganization.

Intravenous thrombolysis of basilar artery occlusion: predictors of recanalization and outcome.

BACKGROUND AND PURPOSE: Basilar artery occlusion has a high mortality rate (85% to 95%) if untreated. We describe a large single-center cohort treated mostly with intravenous alteplase and heparin. METHODS: The cohort included 116 patients with angiography-verified basilar artery occlusion. We studied baseline characteristics, frequencies of recanalization and symptomatic intracranial hemorrhage, and 3-month outcome (modified Rankin Scale [mRS]). RESULTS: Thirty patients (25.9%) had mRS 0 to 2, 42 patients (36.2%) had moderate outcome (mRS, 0-3), 26 patients (22.4%) required daily help (mRS, 4-5), and 48 patients (41.4%) died. Eighteen patients (15.7%) developed symptomatic intracranial hemorrhage. In patients with post-treatment angiogram available (n=91), 59 patients (64.8%) had a complete or partial recanalization. Radiological location of basilar artery occlusion was known in 55 of 91 instances, and recanalization was associated directly with clot location at the top-of-basilar (odds ratio, 4.8 [1.1-22]; P=0.048). Independent outcome (mRS 0-2) was associated with lower age and National Institutes of Health Stroke Scale (NIHSS) score at baseline. Age, nil or minimal recanalization, and symptomatic intracranial hemorrhage were independently associated with fatal outcome. Sixteen of 71 patients (22.5%) who presented with coma eventually reached moderate outcome, and additional 8 patients (11.3%) progressed to mRS 4. CONCLUSIONS: Whereas recanalization after intravenous thrombolysis strongly predicts survival and moderate outcome, therapeutic techniques should concentrate on clot location. Although most adverse baseline variables, age, symptom severity, but also coma are beyond control, it should not preclude thrombolysis, which may permit independent survival.

Post-thrombolytic hyperglycemia and 3-month outcome in acute ischemic stroke.

BACKGROUND: Treating hyperglycemia in acute ischemic stroke may be beneficial, but knowledge on its prognostic value and optimal target glucose levels is scarce. We investigated the dynamics of glucose levels and the association of hyperglycemia with outcomes on admission and within 48 h after thrombolysis. METHODS: We included 851 consecutive patients with acute ischemic stroke treated with intravenous thrombolysis in the Helsinki University Central Hospital during 1998-2008. Outcome measures were unfavorable 3- month outcome (3-6 on the modified Rankin Scale), death, and symptomatic intracerebral hemorrhage (sICH) according to NINDS criteria. Hyperglycemia was defined as a blood glucose level of ≥8.0 mmol/l. Four groups were identified based on (a) admission and (b) peak glucose levels 48 h after thrombolysis: (1) persistent normoglycemia (baseline plus 48-hour normoglycemia), (2) baseline hyperglycemia (48-hour normoglycemia), (3) 48-hour hyperglycemia (baseline normoglycemia), and (4) persistent hyperglycemia (baseline plus 48-hour hyperglycemia). RESULTS: 480 (56.4%) of our patients (median age 70 years; onset-to-needle time 199 min; National Institutes of Health Stroke Scale score 9), had persistent normoglycemia, 59 (6.9%) had baseline hyperglycemia, 175 (20.6%) had 48-hour hyperglycemia, while persistent hyperglycemia appeared in 137 (16.1%) patients. Persistent and 48-hour hyperglycemia independently predicted unfavorable outcome [odds ratio (OR) = 2.33, 95% confidence interval (CI) = 1.41-3.86, and OR = 2.17, 95% CI = 1.30-3.38, respectively], death (OR = 6.63, 95% CI = 3.25-13.54, and OR = 3.13, 95% CI = 1.56-6.27, respectively), and sICH (OR = 3.02, 95% CI = 1.68-5.43, and OR = 1.89, 95% CI = 1.04-3.43, respectively), whereas baseline hyperglycemia did not. CONCLUSIONS: Hyperglycemia (≥8.0 mmol/l) during 48 h after intravenous thrombolysis of ischemic stroke is strongly associated with unfavorable outcome, sICH, and death.

[Diagnosis and treatment of cerebral sinus thrombosis]. / Aivojen sinustromboosin diagnostiikka ja hoito.

Cerebral sinus thrombosis is a rare disease appearing mostly in young women. Typical symptoms include headache, convulsions, visual deterioration and various symptoms of neurological deficits. Magnetic resonance imaging of the brain and venous sinuses is the diagnostic cornerstone, whereby an obstructed venous sinus, thrombus mass and potential intracerebral lesions such as venous infarction or hemorrhage are diagnosed. Anticoagulant therapy should be initiated immediately once the diagnosis is confirmed.

[Brain imaging of patients with memory disorders]. / Muistipotilaan aivojen kuvantaminen.

Indications for brain imaging include potentially treatable intracranial causes (e.g. normal-pressure hydrocephalus, tumors, subdural hematoma) and especially characteristic features of memory disorders and differential diagnostics of such conditions. Since the primary structural changes in the most common progressive memory disorder, Alzheimer's disease, are seen in the inner temporal lobe, appropriate imaging of these structures is essential in early diagnosis.

Comatose With Basilar Artery Occlusion: Still Odds of Favorable Outcome With Recanalization Therapy.

Background: Around 30-60% of patients with basilar artery occlusion (BAO) present with coma, which is often considered as a hallmark of poor prognosis. Aim: To examine factors that will help predict outcomes in patients with BAO comatose on admission. Methods: A total of 312 patients with angiography-proven BAO were analyzed. Comas were assessed as Glasgow Coma Scale (GCS) of ≤8 or impaired level of consciousness ascertained in the medical records. Outcomes were evaluated with the modified Rankin Scale (mRS) over a phone call at 3 months. In our study, 53 patients were excluded due to inadequate data on the level of consciousness. Results: In total, 103/259 (39.8%) of BAO patients were comatose on admission. Factors associated with acute coma were higher age, coronary artery disease, convulsions, extent of early ischemia by posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) < 8, absence of patent posterior collateral vasculature, and occlusion over multiple segments of BA. A total of 21/103 (20.4%) of comatose patients had a favorable outcome (mRS 0-3), and 12/103 (11.7%) had a good outcome (mRS 0-2). Factors associated with a favorable outcome in comatose BAO patients were younger age (p = 0.010), less extensive baseline ischemia (p = 0.027), recanalization (p = 0.013), and avoiding symptomatic intracranial hemorrhage (sICH) (p = 0.038). Factors associated with the poorest outcome or death (mRS 5-6) were older age (p = 0.001), diabetes (p = 0.022), atrial fibrillation (p = 0.016), lower median GCS [4 (IQR 3.6) vs. 6 (5-8); p = 0.006], pc-ASPECTS < 8 (p = 0.003), unsuccessful recanalization (p = 0.006), and sICH (p = 0.010). Futile recanalization (mRS 4-6) was significantly more common in comatose patients (49.4 vs. 18.5%, p < 0.001). Conclusions: One in five BAO patients with acute coma had a favorable outcome. Older patients with cardiovascular comorbidities and already existing ischemic lesions before reperfusion therapies tended to have a poor prognosis, especially if no recanalization is achieved and sICH occurred.

Task-dependent activations of human auditory cortex during pitch discrimination and pitch memory tasks.

The functional organization of auditory cortex (AC) is still poorly understood. Previous studies suggest segregation of auditory processing streams for spatial and nonspatial information located in the posterior and anterior AC, respectively (Rauschecker and Tian, 2000; Arnott et al., 2004; Lomber and Malhotra, 2008). Furthermore, previous studies have shown that active listening tasks strongly modulate AC activations (Petkov et al., 2004; Fritz et al., 2005; Polley et al., 2006). However, the task dependence of AC activations has not been systematically investigated. In the present study, we applied high-resolution functional magnetic resonance imaging of the AC and adjacent areas to compare activations during pitch discrimination and n-back pitch memory tasks that were varied parametrically in difficulty. We found that anterior AC activations were increased during discrimination but not during memory tasks, while activations in the inferior parietal lobule posterior to the AC were enhanced during memory tasks but not during discrimination. We also found that wide areas of the anterior AC and anterior insula were strongly deactivated during the pitch memory tasks. While these results are consistent with the proposition that the anterior and posterior AC belong to functionally separate auditory processing streams, our results show that this division is present also between tasks using spatially invariant sounds. Together, our results indicate that activations of human AC are strongly dependent on the characteristics of the behavioral task.

Cognitive and motor loops of the human cerebro-cerebellar system.

We applied fMRI and diffusion-weighted MRI to study the segregation of cognitive and motor functions in the human cerebro-cerebellar system. Our fMRI results show that a load increase in a nonverbal auditory working memory task is associated with enhanced brain activity in the parietal, dorsal premotor, and lateral prefrontal cortices and in lobules VII-VIII of the posterior cerebellum, whereas a sensory-motor control task activated the motor/somatosensory, medial prefrontal, and posterior cingulate cortices and lobules V/VI of the anterior cerebellum. The load-dependent activity in the crus I/II had a specific relationship with cognitive performance: This activity correlated negatively with load-dependent increase in RTs. This correlation between brain activity and RTs was not observed in the sensory-motor task in the activated cerebellar regions. Furthermore, probabilistic tractography analysis of the diffusion-weighted MRI data suggests that the tracts between the cerebral and the cerebellar areas exhibiting cognitive load-dependent and sensory-motor activity are mainly projected via separated pontine (feed-forward tracts) and thalamic (feedback tracts) nuclei. The tractography results also indicate that the crus I/II in the posterior cerebellum is linked with the lateral prefrontal areas activated by cognitive load increase, whereas the anterior cerebellar lobe is not. The current results support the view that cognitive and motor functions are segregated in the cerebellum. On the basis of these results and theories of the function of the cerebellum, we suggest that the posterior cerebellar activity during a demanding cognitive task is involved with optimization of the response speed.

Off-label thrombolysis is not associated with poor outcome in patients with stroke.

BACKGROUND AND PURPOSE: Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use. METHODS: All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables. RESULTS: One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage. CONCLUSIONS: Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.

Increasing top-down suppression from prefrontal cortex facilitates tactile working memory.

Navigated transcranial magnetic stimulation (TMS) combined with diffusion-weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM.