Utility of standard diffusion-weighted magnetic resonance imaging for the identification of ischemic optic neuropathy in giant cell arteritis.

This study assessed diffusion abnormalities of the optic nerve (ON) in giant cell arteritis (GCA) patients with acute onset of visual impairment (VI) using diffusion-weighted magnetic resonance imaging (DWI). DWI scans of GCA patients with acute VI were evaluated in a case-control study. Two blinded neuroradiologists assessed randomized DWI scans of GCA and controls for ON restricted diffusion. Statistical quality criteria and inter-rater reliability (IRR) were calculated. DWI findings were compared to ophthalmological assessments. 35 GCA patients (76.2 ± 6.4 years; 37 scans) and 35 controls (75.7 ± 7.6 years; 38 scans) were included. ON restricted diffusion was detected in 81.1% (Reader 1) of GCA scans. Localization of ON restricted diffusion was at the optic nerve head in 80.6%, intraorbital in 11.1% and affecting both segments in 8.3%. DWI discerned affected from unaffected ON with a sensitivity, specificity, positive and negative predictive value of 87%/99%/96%/96%. IRR for ON restricted diffusion was κinter = 0.72 (95% CI 0.59-0.86). DWI findings challenged ophthalmologic diagnoses in 4 cases (11.4%). DWI visualizes anterior and posterior ON ischemia in GCA patients with high sensitivity and specificity, as well as substantial IRR. DWI may complement the ophthalmological assessment in patients with acute VI.

Detectability of Retinal Diffusion Restriction in Central Retinal Artery Occlusion is Linked to Inner Retinal Layer Thickness.

PURPOSE: To investigate retinal microstructure differences in central retinal artery occlusion (CRAO) patients with and without visible retinal diffusion restriction (RDR) on diffusion-weighted magnetic resonance imaging (DWI). METHODS: Consecutive CRAO patients with available optical coherence tomography (OCT) and DWI, both performed within 7 days after symptom onset, were included in a retrospective cohort study. The OCT scans were reviewed to assess retinal layer thickness, optical intensity and structural integrity. The OCT findings were compared between patients with and without visible RDR on DWI using Mann-Whitney U or Pearson's Χ2 test. RESULTS: A total of 56 patients (mean age 70.8 ± 12.8 years) were included. RDR was observed in 38 subjects (67.9%) with visually correlating low ADC map in 26 of 38 cases (68.4%). Superior and inferior parafoveal macular thickness measurements (SMT, IMT) of RDR negative patients were significantly lower when compared to RDR+ patients (370.5 ± 43.8 µm vs. 418.2 ± 76.0 µm, p = 0.016; 374.4 ± 42.9 µm vs. 428.8 ± 63.2 µm, p = 0.004) due to differences in inner retinal layer thickness (IRLT, 188.8 ± 34.4 µm vs. 234.7 ± 49.0 µm, p = 0.002). IRLT values of RDR negative patients were higher in 1.5T compared to 3T the DWI (205.0 ± 26.0 µm vs. 168.6 ± 32.8 µm, p = 0.026). CONCLUSIONS: Detectability of RDR is likely contingent upon the degree of ischemic retinal swelling in CRAO. Technical adjustments to the DWI protocol, such as increased field strength, may improve visibility of RDR.

Retinal diffusion restrictions in acute branch retinal arteriolar occlusion.

This study sought to investigate the occurrence of retinal diffusion restrictions (RDR) in branch retinal arteriolar occlusion (BRAO) using standard brain diffusion-weighted imaging (DWI). Two radiologists assessed DWI MRI scans of BRAO patients for RDR in a retrospective cohort study. Inter- and intrarater reliability were calculated using Kappa statistics. Detection rates of RDR were compared among MRI scans with varying field strength, sequence type and onset-to-DWI time intervals. 85 BRAO patients (63.1 ± 16.5 years) and 89 DWI scans were evaluated. Overall sensitivity of RDR in BRAO was 46.1% with visually correlating low ADC signal in 56.1% of cases. Localization of RDR matched distribution of fundoscopic retinal edema in 85% of patients. Inter- and intra-rater agreement for RDR in BRAO was κinter = 0.64 (95% CI 0.48-0.80) and κintra = 0.87 (95% CI 0.76-0.96), respectively. RDR detection rate tended to be higher for 3T, when compared to 1.5T MRI scans (53.7% vs. 34.3%%; p = 0.07). RDR were identified within 24 h up to 2 weeks after onset of visual impairment. RDR in BRAO can be observed by means of standard stroke DWI in a substantial proportion of cases, although sensitivity and interrater reliability were lower than previously reported for complete central retinal artery occlusion.

Time Course and Clinical Correlates of Retinal Diffusion Restrictions in Acute Central Retinal Artery Occlusion.

BACKGROUND AND PURPOSE: Retinal diffusion restrictions were recently identified as a regular finding in acute central retinal artery occlusion. We sought to investigate the influence of technical MR imaging and clinical parameters on the detection rate of retinal diffusion restrictions on standard brain DWI. MATERIALS AND METHODS: In this retrospective cohort study, MR imaging scans of patients with central retinal artery occlusion were assessed by 2 readers for retinal diffusion restrictions on DWI performed within 2 weeks after vision loss. The influence of clinical and technical MR imaging parameters and the time interval between symptom onset and DWI on the presence of retinal diffusion restrictions were evaluated. RESULTS: One hundred twenty-seven patients (mean age, 69.6 [SD 13.9] years; 59 women) and 131 DWI scans were included. Overall, the MR imaging sensitivity of retinal diffusion restrictions in acute central retinal artery occlusion was 62.6%-67.2%. Interrater and intrarater agreement for retinal diffusion restrictions was "substantial" with κinter = 0.70 (95% CI, 0.57-0.83) and κintra = 0.75 (95% CI, 0.63-0.88). Detection of retinal diffusion restrictions did not differ with differences in field strengths (1.5 versus 3T, P = .35) or sequence type (P = .22). Retinal diffusion restrictions were consistently identified within the first week with a peak sensitivity of 79% in DWI performed within 24 hours after symptom onset. Sensitivity of retinal diffusion restrictions declined in the second week (10.0%, P < .001). Absence of retinal diffusion restrictions was more prevalent in patients without fundoscopic retinal edema (60% versus 27.1%, P = .004) and with restitution of visual acuity at discharge (75% versus 28.4%, P = .006). CONCLUSIONS: Retinal diffusion restrictions in acute central retinal artery occlusion can be reliably identified on DWI performed within 24 hours and 1 week after onset of visual impairment. Detectability of retinal diffusion restrictions is dependent on the clinical course of the disease.

Characteristics associated with outcome in patients with first-ever posterior fossa stroke.

BACKGROUND AND PURPOSE: Factors such as infarct volume, infarct location and symptom severity can considerably influence long-term outcome in posterior fossa strokes. The decision about therapy can sometimes be complicated by discrepancies between infarct volume and clinical severity. We aimed to evaluate imaging and clinical parameters possibly influencing long-term outcome in patients with first-ever posterior fossa stroke. METHODS: Imaging was performed on a 3-T magnetic resonance imaging scanner. Sixty-one of 1795 patients from the observational 1000Plus and LOBI studies (NCT00715533 and NCT02077582, clinicaltrials.org) were enrolled, meeting the inclusion criteria of first-ever posterior fossa stroke and magnetic resonance imaging examination within 24 h after symptom onset. Infarcts were classified as belonging to a proximal, middle or distal territory location in the posterior fossa. Good outcome was defined as a modified Rankin scale score of ≤1 at 3 months. RESULTS: The largest lesion volumes on diffusion-weighted imaging on day 0 and fluid attenuation inversion recovery (FLAIR) on day 6 were found in the middle territory location with a median volume of 0.4 mL on diffusion-weighted imaging and 1.0 mL on FLAIR on day 6 versus 0.1/0.3 mL in the proximal and 0.1/0.1 mL in the distal territory location of the posterior fossa, respectively. Parameters associated with poor outcome were older age (P = 0.005), higher National Institutes of Health Stroke Scale score on admission/discharge (P = 0.016; P = 0.001), larger lesion volumes on FLAIR on day 6 (P = 0.013) and dysphagia (P = 0.02). There was no significant association between infarct location and modified Rankin scale score on day 90. CONCLUSION: Infarct volume and clinical severity, but not infarct location, were the main contributors to poor long-term outcome in first-ever posterior fossa strokes.

Right insular infarction and mortality after ischaemic stroke.

BACKGROUND AND PURPOSE: Several studies have described an association between insular infarction and mortality. Large infarcts often include the insula and lesion size is associated with mortality. We hypothesized that there is an association between insular infarction and mortality independent of lesion volume. METHODS: We included consecutive stroke patients between 1 September 2008 and 11 November 2012 from the 1000Plus database with an acute ischaemic lesion on diffusion-weighted imaging on day 1 and a completed 90-day follow-up. Insular infarct location was determined using the in-house software Stroke Lesion Atlas. In multiple Cox regression analysis (dependent variable: mortality), we adjusted for insular infarcts, age, lesion volume, history of atrial fibrillation, National Institutes of Health Stroke Scale and previous stroke. RESULTS: We included 736 patients, of whom 168 had an insular infarction. Within a medium follow-up time of 107 days, cumulative survival was 90% in patients with insular infarction and 99% in patients without insular infarction (P < 0.001). Right insular infarction was independently associated with mortality (hazard ratio, 2.60; confidence interval, 1.3-5.4; P = 0.010). CONCLUSIONS: In our study, right insular involvement was a prognostic marker for mortality after ischaemic stroke. A selection bias towards patients able to give informed consent warrants further studies.

The Cortical Signature of Central Poststroke Pain: Gray Matter Decreases in Somatosensory, Insular, and Prefrontal Cortices.

It has been proposed that cortical structural plasticity plays a crucial role in the emergence and maintenance of chronic pain. Various distinct pain syndromes have accordingly been linked to specific patterns of decreases in regional gray matter volume (GMV). However, it is not known whether central poststroke pain (CPSP) is also associated with cortical structural plasticity. To determine this, we employed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcortical sensory stroke with (n = 23) and without CPSP (n = 22), and healthy matched controls (n = 31). CPSP patients showed decreases in GMV in comparison to healthy controls, involving secondary somatosensory cortex (S2), anterior as well as posterior insular cortex, ventrolateral prefrontal and orbitofrontal cortex, temporal cortex, and nucleus accumbens. Comparing CPSP patients to nonpain patients revealed a similar but more restricted pattern of atrophy comprising S2, ventrolateral prefrontal and temporal cortex. Additionally, GMV in the ventromedial prefrontal cortex negatively correlated to pain intensity ratings. This shows for the first time that CPSP is accompanied by a unique pattern of widespread structural plasticity, which involves the sensory-discriminative areas of insular/somatosensory cortex, but also expands into prefrontal cortex and ventral striatum, where emotional aspects of pain are processed.

[Mobile CT: technical aspects of prehospital stroke imaging before intravenous thrombolysis]. / CT im Notarztwagen: technische Aspekte der prähospitalen radiologischen Schlaganfalldiagnostik vor systemischer Thrombolyse.

PURPOSE: To reduce the time from symptom onset to treatment with tissue plasminogen activator (tPA) in ischemic stroke, an ambulance was equipped with a CT scanner. We analyzed process and image quality of CT scanning during the pilot study regarding image quality and safety issues. MATERIALS AND METHODS: The pilot study of a stroke emergency mobile unit (STEMO) ran over a period of 12 weeks on 5 weekdays from 7a.m. to 6:30 p.m. A teleradiological service for the justifying indication and reporting was established. The radiographer was responsible for the performance of the CT scan on the ambulance. 64 cranial CT scans and 1 intracranial CT angiography were performed. We compared times from ambulance alarm to treatment decision (time of last brain scan) with a cohort of 50 consecutive tPA treatments before implementation of STEMO. RESULTS: 62 (95%) of the 65 scans performed had sufficient quality for reading. Technical quality was not optimal in 45 cases (69%) mainly caused by suboptimal positioning of patient or eye lens protection. Motion artefacts were observed in 8 exams (12%). No safety issues occurred for team or patients. 23 patients were treated with thrombolysis. Time from alarm to last CT scan was 18 minutes shorter than in the tPA cohort before STEMO implementation. CONCLUSION: A teleradiological support for primary stroke imaging by CT on-site is feasible, quality-wise of diagnostic value and has not raised safety issues.

Remote activation of referred phantom sensation and cortical reorganization in human upper extremity amputees.

Phantom limb sensation, whether painful or not, frequently occurs after peripheral nerve lesions. It can be elicited by stimulating body parts adjacent to the amputation site (referred to as phantom sensation) and it is often similar in quality to the stimulation at the remote site. The present study induced referred phantom sensations in two upper limb amputees. Neuroelectric source imaging (ESI) as well as functional magnetic resonance imaging (fMRI) was used to assess reorganization in primary somatosensory cortex (SI). Whereas recent studies found mislocalization of sensation related to stimulation mainly in regions adjacent and ipsilateral to the amputation site, we report here the elicitation of phantom sensation in the arm by stimulation in the lower body part both ipsi- and contralateral to the amputation in two arm amputees. The fMRI evaluation of one patient showed no shift in the location of the foot whereas ESI revealed major reorganization of the mouth region in primary somatosensory cortex in both patients. These data suggest that cortical structures other than SI might be contributing to the phenomenon of referred sensation. Candidate structures are the thalamus, secondary somatosensory cortex, posterior parietal cortex and prefrontal cortex.

Somatotopic organization of human secondary somatosensory cortex.

This fMRI study investigated the human somatosensory system, especially the secondary somatosensory cortex (SII), with respect to its potential somatotopic organization. Eight subjects received electrical stimulation on their right second finger, fifth finger and hallux. Within SII, the typical finding for both fingers was a representation site within the contralateral parietal operculum roughly halfway between the lip of the lateral sulcus and its fundus, whereas the representation site of the hallux was found more medially to this position at the fundus of the lateral sulcus, near the posterior pole of the insula. Somatotopy in SII seems to be less fine-grained than in primary somatosensory cortex (SI), as, in contrast to SI, no separate representations of the two fingers in SII were observed. A similar somatotopic representation pattern between fingers and the hallux was also observed within ipsilateral SII, indicating somatotopy of contra- as well as ipsilateral SII using unilateral stimulation. Further areas exhibiting activation were found in the superior and inferior parietal lobule, in the supplementary and cingulate motor area, and in the insula.

Representational overlap of adjacent fingers in multiple areas of human primary somatosensory cortex depends on electrical stimulus intensity: an fMRI study.

Functional magnetic resonance imaging (fMRI) was used to examine the influence of non-painful electrical stimulus intensity on the BOLD response in human primary somatosensory cortex (SI). In ten healthy subjects, index and middle finger of the right hand were stimulated separately at two different stimulus intensities. The activated volume of single finger representations as well as the volume of representational overlap of the two activations increased following an increase in stimulus intensity. This effect was seen in two different subdivisions of SI, one in the depth of the central sulcus, presumably corresponding to Brodmann area (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both areas relative overlap increased significantly from low to high stimulus intensity. Relative overlap did not change when different correlation thresholds were employed arguing against an unspecific 'spillover effect'. Analysis of signal intensity time courses indicated that the response difference to high versus low stimulus strength was not present during the initial seconds of stimulation, during which both led to a similar signal intensity increase. Only during the following maintenance level of the response did the response to high stimulus intensity reach a significantly higher plateau level than the one due to low intensity stimulation, an effect which was present in both areas, BA 3b and BA 1/2, respectively.

The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees.

In this study 16 unilateral upper extremity amputees participated in a comprehensive psychophysiological examination that included the assessment of painful and non-painful phantom and stump sensations, thermal and electric perception as well as two-point discrimination thresholds, the detailed analysis of referred sensation and the measurement of reorganizational changes in primary somatosensory cortex using neuroelectric source imaging. Reorganization of the primary somatosensory cortex was associated with increased habitual phantom limb pain, telescoping, non-painful stump sensations and painful referred sensation induced by painful stimulation. It was unrelated to non-painful phantom sensations, non-painful referred sensation elicited by painful or non-painful stimulation, painful referred sensation elicited by non-painful stimulation, perception thresholds and stump pain. These data substantiate the hypothesis that painful and non-painful phantom phenomena are mediated by different neural substrates.

Multimodal EEG analysis in man suggests impairment-specific changes in movement-related electric brain activity after stroke.

Movement-related slow cortical potentials and event-related desynchronization of alpha (alpha-ERD) and beta (beta-ERD) activity after self-paced voluntary triangular finger movements were studied in 13 ischaemic supratentorial stroke patients and 10 age-matched control subjects during movement preparation and actual performance. The stroke patients suffered from central arm paresis (n = 8), somatosensory deficits (n = 3) or ideomotor apraxia (n = 2). The multimodal EEG analysis suggested impairment-specific changes in the movement-related electrical activity of the brain. The readiness potential of paretic subjects was centred more anteriorly and laterally; during movement, they showed increased beta-ERD at left lateral frontal recording sites. Patients with somatosensory deficits showed reduced alpha-ERD and beta-ERD during both movement preparation and actual performance. Patients with ideomotor apraxia showed more lateralized frontal movement-related slow cortical potentials during both movement preparation and performance, and reduced left parietal beta-ERD during movement preparation. We conclude that (i) disturbed motor efference is associated with an increased need for excitatory drive of pyramidal cells in motor and premotor areas or an attempt to drive movements through projections from these areas to brainstem motor systems during movement preparation; (ii) an undisturbed somatosensory afference might contribute to the release of relevant cortical areas from their 'idling' state when movements are prepared and performed; and (iii) apraxic patients have a relative lack of activity of the mesial frontal motor system and the left parietal cortex, which is believed to be part of a network subserving ideomotor praxis.

fMRI shows multiple somatotopic digit representations in human primary somatosensory cortex.

Using electrical finger nerve stimulation in normal human subjects, fMRI detected separate representations for all 5 fingers in the primary somatosensory cortex. Responses were located in the posterior wall of the deep central sulcus (most likely corresponding to Brodmann Area (BA) 3b), and the anterior (BA 1) or posterior crown of the postcentral gyrus (BA 2) with rare activations in BA 3a and 4. In BA 3b we found a regular somatotopic mediolateral digit arrangement for fingers 5 to 1 with a mean Euclidean distance of 16 mm between fingers 1 and 5. In contrast BA 1/2 showed a greater number of adjacent activation foci with significantly more overlap and partly even reversed ordering of neighbouring fingers.

Constraint-induced movement therapy for motor recovery in chronic stroke patients.

OBJECTIVE: Assessment of the effectiveness of constraint-induced (CI) movement therapy and quantitative evaluation of the effects of CI therapy. DESIGN: Intervention study; case series; pretreatment to posttreatment measures and follow-up 3 months after intervention. SETTING: An outpatient department. PATIENTS: Five chronic stroke patients with moderate motor deficit; convenience sample. INTERVENTIONS: CI therapy consisting of restraint of the unaffected upper extremity in a sling for 14 days combined with 6 hours of training per weekday of the affected upper extremity. MAIN OUTCOME MEASURES: Actual Amount of Use Test (AAUT), Motor Activity Log (MAL), Wolf Motor Function Test (WMFT), and Arm Motor Ability Test (AMAT) RESULTS: There was a substantial improvement in the performance times of the laboratory tests (AMAT, WMFT, p < or = .039) and in the quality of movement (AMAT, WMFT, p < or = .049; MAL, p = .049), particularly in the use of the extremity in "real world" environments (AAUT, p = .020), supported by results of quantitative evaluation. The effect sizes were large and comparable to those found in previous studies of CI therapy. CONCLUSIONS: CI therapy is an efficacious treatment for chronic stroke patients, especially in terms of real world outcome.

Plasticity in the motor system related to therapy-induced improvement of movement after stroke.

Neuroplasticity might play a beneficial role in the recovery of function after stroke but empirical evidence for this is lacking thus far. Constraint-induced (CI) therapy was used to increase the use of a paretic upper extremity in four hemiparetic stroke patients. Dipole modeling of steady-state movement-related cortical potentials was applied before and after training and 3 months later. The source locations associated with affected hand movement were unusual at follow-up because activation of the ipsilateral hemisphere was found in the absence of mirror movements of the unaffected hand. This long-term change may be considered as an initial demonstration of large-scale neuroplasticity associated with increased use of the paretic limb after application of CI therapy.

fMRI assessment of somatotopy in human Brodmann area 3b by electrical finger stimulation.

Functional magnetic resonance imaging (fMRI) is capable of detecting focal brain activation induced by electrical stimulation of single fingers in human subjects. In eight subjects somatotopic arrangement of the second and fifth finger was found in Brodmann area 3b of the primary somatosensory cortex. In four subjects the representation area of the second finger was located lateral and inferior to the fifth finger; in one subject the somatotopy was reversed. In three subjects representation areas of the two fingers in Brodmann area 3b were found overlapping. Additional activated areas were found on the crown of ipsilateral and contralateral postcentral gyrus (Brodmann areas 1 and 2) and posterior parietal cortex.

Cerebral haemoglobin oxygenation during sustained visual stimulation--a near-infrared spectroscopy study.

Using near-infrared spectroscopy, we investigated the time-course of the concentrations of oxygenated haemoglobin, [oxy-Hb], and deoxygenated haemoglobin [deoxy-Hb], in the occipital cortex of healthy human adults during standard sustained visual stimulation. Within a few seconds after stimulation (by coloured dodecahedron), we observed a decrease in [deoxy-Hb], peaking after 13 s ('initial undershoot'). In the subsequent 1-2 min, in seven out of ten subjects, [deoxy-Hb] gradually returned to a plateau closer to the baseline level. After cessation of stimulation, there was a 'post-stimulus overshoot' in [deoxy-Hb]. There was a statistically significant correlation between the size of the 'initial undershoot' and the post-stimulus overshoot'. The concentration of oxyhaemoglobin increased upon functional activation. However, in the mean across all subjects there was no 'initial overshoot'. After approximately 19 s it reached a plateau and remained constantly elevated throughout the activation period. After cessation of activation there was a 'post-stimulus undershoot' of oxyhaemoglobin. It is important to consider the time-course of haemoglobin oxygenation when interpreting functional activation data, especially those data obtained with oxygenation-sensitive methods, such as BOLD-contrast fMRI.