The History of Endovascular Stroke Treatment: From Local Intraarterial Fibrinolysis to Stent Retriever Thrombectomy.

BACKGROUND: Acute thromboembolic occlusions of large intracranial arteries are associated with high rates of permanent disability and mortality. Intravenous thrombolysis (IVT) in these patients resulted in an inadequate rate of recanalization and has had limited clinical success. Various endovascular procedures have been attempted to remove intracranial thrombi and reopen occluded vessels. These technical innovations led to the publication of initial case reports, but the methods ultimately did not endure. Endovascular treatment of acute cerebral ischemia was performed only rarely and in selected centers as part of individualized curative attempts. The Solitaire stent was originally developed to treat intracranial aneurysms through stent-assisted coil occlusion. The suggestion that this stent could also be used for intracranial thrombectomy was made as early as 2003 and was clinically confirmed in 2008. Releasing a Solitaire stent into an embolically occluded large cerebral artery, with an incubation time of approximately 3 minutes and slow retraction of the stent, has led to unprecedented success rates of thrombus removal and (sub)total recanalization in more than 90 % of patients. METHODS: This review article aimed to describe the steps in the development of endovascular stroke therapy, beginning with intra-arterial thrombolysis and early technical innovations leading to the eventual success of stent retriever thrombectomy. CONCLUSION: The potential for mechanical recanalization of acutely occluded large cerebral arteries could not be fully exploited until the advent of stent retriever thrombectomy. The entire concept of stroke treatment fundamentally changed after complete and rapid recanalization first became possible. Randomized controlled trials have shown superiority of stent retriever thrombectomy over IVT. An unparalleled boom in endovascular stroke therapy followed. KEY POINTS: · The history of endovascular stroke treatment was marked by setbacks in the first three decades.. · Stent retriever thrombectomy is the first procedure enabling recanalization of acute large intracranial artery occlusions in more than 90 % of patients.. · Stent retriever thrombectomy has transformed stroke care and neuroradiology in unprecedented ways.. · Further technical improvements will enable even faster, safer, complete recanalization in the near future.. · Further improvements in clinical outcomes will probably be determined by aspects beyond endovascular methods alone..

Non-Invasive Intracranial Pressure Monitoring.

(1) Background: Intracranial pressure (ICP) monitoring plays a key role in the treatment of patients in intensive care units, as well as during long-term surgeries and interventions. The gold standard is invasive measurement and monitoring via ventricular drainage or a parenchymal probe. In recent decades, numerous methods for non-invasive measurement have been evaluated but none have become established in routine clinical practice. The aim of this study was to reflect on the current state of research and shed light on relevant techniques for future clinical application. (2) Methods: We performed a PubMed search for "non-invasive AND ICP AND (measurement OR monitoring)" and identified 306 results. On the basis of these search results, we conducted an in-depth source analysis to identify additional methods. Studies were analyzed for design, patient type (e.g., infants, adults, and shunt patients), statistical evaluation (correlation, accuracy, and reliability), number of included measurements, and statistical assessment of accuracy and reliability. (3) Results: MRI-ICP and two-depth Doppler showed the most potential (and were the most complex methods). Tympanic membrane temperature, diffuse correlation spectroscopy, natural resonance frequency, and retinal vein approaches were also promising. (4) Conclusions: To date, no convincing evidence supports the use of a particular method for non-invasive intracranial pressure measurement. However, many new approaches are under development.

Results of the pToWin Study: Using the pCONUS Device for the Treatment of Wide-Neck Intracranial Aneurysms.

Coil embolization has become a well-established option for the treatment of intracranial aneurysms. Yet, wide-neck bifurcation aneurysms (WNBAs) remain a challenge. The pCONUS is the first generation of a stent-like implant for the bridging of WNBAs to enable coiling. The pToWin study was a prospective, single-arm, multicenter study conducted to analyze the safety and efficacy of the pCONUS in the treatment of WNBAs. The primary effectiveness endpoint was the rate of adequate occlusion of the aneurysm at 3-6 and 7-12 months. The primary safety endpoint was the occurrence of major ipsilateral stroke or neurological death during the follow-up. A total of 115 patients were included. Aneurysm locations were the middle cerebral artery in 52 (45.2%), the anterior communicating artery in 35 (30.4%), the basilar artery in 23 (20%), the internal carotid artery terminus in three (2.6%), and the pericallosal artery in two (1.7%) patients. Treatment was successfully performed in all but one patient. The morbi-mortality rate was 1.9% and 2.3% at 3-6 and 7-12 months, respectively. Of the aneurysms, 75.0% and 65.6% showed adequate occlusion at 3-6 and 7-12 months, respectively. pCONUS offers a safe and reasonably effective treatment of WNBAs, demonstrated by acceptable adequate aneurysm occlusion and low rates of adverse neurologic events.

Language Dominance in Patients With Malformations of Cortical Development and Epilepsy.

Background: Language function may be reorganized in patients with malformations of cortical development (MCD). This prospective cohort study aimed in assessing language dominance in a large group of patients with MCD and epilepsy using functional MRI (fMRI). Methods: Sixty-eight patients (40 women) aged 10-73 years (median, 28.0; interquartile range, 19) with MCD and epilepsy underwent 1.5 T MRI and fMRI (word generation task). Single-subject image analysis was performed with statistical parametric mapping (SPM12). Language lateralization indices (LIs) were defined for statistically significantly activated voxels in Broca's and Wernicke's areas using the formula: LI = (V L - V R)/(V L + V R) × 100, where V L and V R were sets of activated voxels on the left and on the right, respectively. Language laterality was considered typical if LI was between +20 and +100 or atypical if LI was between +19 and -100. Results: fMRI signal was elicited in 55 of 68 (81%) patients. In 18 of 55 (33%) patients, language dominance was typical, and in 37 of 55 (67%) patients, atypical (in 68%, right hemispheric; in 32%, bilateral). Language dominance was not influenced by handedness, electroclinical, and imaging features. Conclusions: In this prospective study on a large group of patients with MCD and epilepsy, about two-thirds had atypical language dominance. These results may contribute to assessing risks of postsurgical language deficits and could assist in planning of "cortical mapping" with intracranial electrodes in patients who undergo presurgical assessment.

Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Shank Muscle Strength Training Changes Foot Behaviour during a Sudden Ankle Supination.

BACKGROUND: The peroneal muscles are the most effective lateral stabilisers whose tension braces the ankle joint complex against excessive supination. The purpose of this study was to identify the morphological and biomechanical effects of two machine-based shank muscle training methods. METHODS: Twenty-two healthy male recreationally active sports students performed ten weeks of single-set high resistance strength training with 3 training sessions per week. The subjects conducted subtalar pronator/supinator muscle training (ST) with the right leg by using a custom-made apparatus; the left foot muscles were exercised with machine-based talocrural plantar and dorsiflexor training (TT). Muscle strength (MVIC), muscle volume and foot biomechanics (rearfoot motion, ground reaction forces, muscle reaction times) during a sudden ankle supination were recorded before and after the intervention. RESULTS: Compared to TT, ST resulted in significantly higher pronator (14% vs. 8%, P<0.01) and supinator MVIC (25% vs. 12%, P<0.01). During sudden foot inversions, both ST and TT resulted in reduced supination velocity (-12%; P<0.01). The muscle reaction onset time was faster after the training in peroneus longus (PL) (P<0.01). Muscle volume of PL (P<0.01) and TA (P<0.01) increased significantly after both ST and TT. CONCLUSION: After both ST and TT, the ankle joint complex is mechanically more stabilised against sudden supinations due to the muscle volume increase of PL and TA. As the reduced supination velocities indicate, the strength training effects are already present during free-fall. According to a sudden ankle supination in standing position, both machine-based dorsiflexor and pronator strength training is recommended for enhancing the mechanical stability of the ankle.

Midbrain-hindbrain malformations in patients with malformations of cortical development and epilepsy: a series of 220 patients.

Midbrain-hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features. Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20-44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain-hindbrain structures were visually assessed by three independent raters. MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I - to abnormal neuronal proliferation; category II - to abnormal neuronal migration; and category III - due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM. The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes.

Variability of clinical functional MR imaging results: a multicenter study.

PURPOSE: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

Caffeine and cognition in functional magnetic resonance imaging.

Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

Differentiation of SCA2 from MSA-C using proton magnetic resonance spectroscopic imaging.

PURPOSE: To assess and compare biochemical and volumetric features of the cerebellum in patients with spinocerebellar ataxia type 2 (SCA2) and patients with the cerebellar variant of multiple system atrophy (MSA-C). MATERIALS AND METHODS: Nine genetically assigned SCA2 patients and six MSA-C patients who met the clinical criteria of MSA-C underwent a clinical and neuroradiological workup with respect to cerebellar features. The MR protocol consisted of a sagittal T1-weighted three-dimensional fast low-angle shot (3D FLASH) sequence and a transversal T2- and spin-density-weighted turbo spin-echo sequence. The proton magnetic resonance spectroscopic imaging ((1)H-MRSI) protocol consisted of two chemical shift imaging (CSI) sequences (echo time (TE) = 20 and 135 msec). RESULTS: Both short- and long-TE MR spectroscopy (MRS) images showed significant decreases in values for N-acetylaspartate to creatine (NAA/Cr), and choline to creatine (Cho/Cr) ratios in MSA-C and SCA2 compared to normal controls, though there was no difference between the two patient groups. In contrast, distinct cerebellar lactate (Lac) peaks were detected in seven SCA2 patients, and small peaks were detected in two. However, we did not detect any definite Lac peak in MSA-C or control subjects. CONCLUSION: MRSI revealed Lac pathology in SCA2 but not in MSA-C. Whether this indicates distinct pathogenetic mechanisms of cerebellar degeneration remains to be established.

Neural substrates for episodic encoding and recognition of unfamiliar faces.

Functional MRI was used to investigate brain activation in healthy volunteers during encoding of unfamiliar faces as well as during correct recognition of newly learned faces (CR) compared to correct identification of distractor faces (CF), missed alarms (not recognizing previously presented faces, MA), and false alarms (incorrectly recognizing newly presented faces, FA). Encoding was associated with frontal, occipital/fusiform, thalamic, and cerebellar activation. CR produced activation in frontal and cerebellar regions, whereas CF activated frontal and occipitotemporal regions as well as the thalamus. In contrast, MA was associated with frontal and thalamic activation, and FA with frontal activation. The CR minus CF comparison showed left lateral prefrontal and parietal activation, while no suprathreshold positive signal changes were detected when subtracting the other conditions (CR minus MA, CR minus FA, and vice versa). These results support the view that the successful episodic retrieval of newly learned faces is based on a dorsal visual stream mechanism.

Sex differences in brain activation patterns during processing of positively and negatively valenced emotional words.

BACKGROUND: Previous studies have suggested that men and women process emotional stimuli differently. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences in regional cerebral activity during the perception of positive or negative emotions. METHOD: The experiment comprised two emotional conditions (positively/negatively valenced words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy volunteers (19 males, 19 females) were investigated. A direct comparison of brain activation between men and women revealed differential activation in the right putamen, the right superior temporal gyrus, and the left supramarginal gyrus during processing of positively valenced words versus non-words for women versus men. By contrast, during processing of negatively valenced words versus non-words, relatively greater activation was seen in the left perirhinal cortex and hippocampus for women versus men, and in the right supramarginal gyrus for men versus women. CONCLUSIONS: Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying the gender disparity of neuropsychiatric diseases such as mood disorders.

The neural regions sustaining episodic encoding and recognition of objects.

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects.

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.

Contact force- and amplitude-controllable vibrating probe for somatosensory mapping of plantar afferences with fMRI.

PURPOSE: To study cerebral responses evoked from mechanoreceptors in the human foot sole using a computer-controlled vibrotactile stimulation system. MATERIALS AND METHODS: The stimulation system consisted of two stationary moving magnet actuators with indentors to gently contact and vibrate the foot sole during functional MRI (fMRI) experiments. To allow independent settings of contact force (0-20 N) and intensity of vibration (frequency range=20-100 Hz) the actuators were controlled by a digital servo loop. For fMRI experiments with complex stimulus protocols, both vibrating probes were further operated under supervisory control. RESULTS: The MR compatibility of this electromagnetic system was tested in a 1.5T scanner with an actively shielded magnet (Siemens Magnetom Sonata). Blood oxygenation level-dependent (BOLD) responses were detected in the contralateral left pre- and postcentral gyrus, bilaterally within the secondary somatosensory cortex, bilaterally within the supplementary motor cortex, and bilaterally within the anterior cingular gyrus. CONCLUSION: This stimulation device provides a new tool for identifying cerebral structures that convey sensory information from the foot region, which is of promising diagnostic value, particularly for assessing sensorimotor deficits resulting from brain lesions.

Language lateralization in temporal lobe epilepsy: a comparison between fMRI and the Wada Test.

PURPOSE: Recent studies have claimed that language functional magnetic resonance imaging (fMRI) can identify language lateralization in patients with temporal lobe epilepsy (TLE) and that fMRI-based findings are highly concordant with the conventional assessment procedure of speech dominance, the intracarotid amobarbital test (IAT). METHODS: To establish the power of language fMRI to detect language lateralization during presurgical assessment, we compared the findings of a semantic decision paradigm with the results of a standard IAT in 68 patients with chronic intractable right and left temporal lobe epilepsy (rTLE, n=28; lTLE, n=40) who consecutively underwent a presurgical evaluation program. The patient group also included 14 (20.6%) subjects with atypical (bilateral or right hemisphere) speech. Four raters used a visual analysis procedure to determine the laterality of speech-related activation individually for each patient. RESULTS: Overall congruence between fMRI-based laterality and the laterality quotient of the IAT was 89.3% in rTLE and 72.5% in lTLE patients. Concordance was best in rTLE patients with left speech. In lTLE patients, language fMRI identified atypical, right hemisphere speech dominance in every case, but missed left hemisphere speech dominance in 17.2%. Frontal activations had higher concordance with the IAT than did activations in temporoparietal or combined regions of interest (ROIs). Because of methodologic problems, recognition of bilateral speech was difficult. CONCLUSIONS: These data provide evidence that language fMRI as used in the present study has limited correlation with the IAT, especially in patients with lTLE and with mixed speech dominance. Further refinements regarding the paradigms and analysis procedures will be needed to improve the contribution of language fMRI for presurgical assessment.

Gender differences in regional cerebral activity during the perception of emotion: a functional MRI study.

Whether men activate different brain regions during various emotions compared to women or whether gender differences exist in transient emotional states has been the subject of only few studies. We used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences during the perception of positive or negative emotions. The experiment comprised two emotional conditions (pleasant/unpleasant visual stimuli) during which fMRI data were acquired. Altogether, 38 healthy volunteers (19 males, 19 females) were investigated. When subtracting the activation values of men from those of women, suprathreshold positive signal changes were detected in the right posterior cingulate, the left putamen and the left cerebellum during positive mood induction, and in bilateral superior temporal gyri and cerebellar vermis during negative mood induction. The subtraction of activation values of women from those of men yielded no significant differences. Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying gender-related vulnerability of the prevalence and severity of neuropsychiatric disorders.

Human brain structures related to plantar vibrotactile stimulation: a functional magnetic resonance imaging study.

The purpose of this study was to investigate the sensorimotor cortex response to plantar vibrotactile stimulation using a newly developed MRI compatible vibration device. Ten healthy subjects (20-45 years) were investigated. Vibrotactile stimulation of the sole of the foot with a frequency of 50 Hz and a displacement of 1 mm was performed during fMRI (echo-planar imaging sequence at 1.5 T) using an MRI compatible moving magnet actuator that is able to produce vibration frequencies between 0 and 100 Hz and displacement amplitudes between 0 and 4 mm. The fMRI measurement during vibrotactile stimulation of the right foot revealed brain activation contralaterally within the primary sensorimotor cortex, bilaterally within the secondary somatosensory cortex, bilaterally within the superior temporal, inferior parietal, and posterior insular region, bilaterally within the anterior and posterior cingular gyrus, bilaterally within the thalamus and caudate nucleus, contralaterally within the lentiform nucleus, and bilaterally within the anterior and posterior cerebellar lobe. The advantages of the new MRI compatible vibration device include effective transmission of the stimulus and controlled vibration amplitudes, frequencies, and intensities. The results indicate that plantar vibration can be a suitable paradigm to observe activation within the sensorimotor network in fMRI. Furthermore, the method may be used to determine the optimal responsiveness of the individual sensorimotor network.