Striatal Infarction Elicits Secondary Extrafocal MRI Changes in Ipsilateral Substantia Nigra

Focal ischemia may induce pathological alterations in brain areas distant from the primary lesion. In animal models, exofocal neuron death in the ipsilateral midbrain has been described after occlusion of the middle cerebral artery (MCA). Using sequential magnetic resonance imaging (T2- and diffusion- weighted) at 3 Tesla, we investigated acute ischemic stroke patients on days 1, 2, 6, 8, and 10 after stroke onset. Sixteen consecutive patients who had suffered a stroke involving the caudate nucleus and/or putamen of either hemisphere were recruited into the study. Four additional patients with strokes sparing the caudate nucleus and putamen but encompassing at least one- third of the MCA territory served as controls. Ischemic lesions involving striatal structures resulted in hyperintense lesions in ipsilateral midbrain that emerged between days 6 and 10 after stroke and were not present on the initial scans. In contrast, none of the control stroke patients developed secondary midbrain lesions. Hyperintense lesions in the pyramidal tract or the brain stem caused by degeneration of the corticospinal tract could be clearly distinguished from these secondary midbrain gray matter lesions and were detectable from day 2 after ischemia. Co-registration of high-resolution images with a digitized anatomic atlas revealed localization of secondary lesions primarily in the substantia nigra pars compacta. Apparent diffusion coefficient (ADC) values in the secondary lesions showed a delayed sharp decline through day 10. Normalization of ADC values was observed at late measurements. Taken together, our study demonstrates that striatal infarction elicits delayed degenerative changes in ipsilateral substantia nigra pars compacta

Automated real-time text messaging as a means for rapidly identifying acute stroke patients for clinical trials

Background Recruiting stroke patients into acute treatment trials is challenging because of the urgency of clinical diagnosis, treatment, and trial inclusion. Automated alerts that identify emergency patients promptly may improve trial performance. The main purposes of this project were to develop an automated real-time text messaging system to immediately inform physicians of patients with suspected stroke and to test its feasibility in the emergency setting. Methods An electronic standardized stroke algorithm (SSA) was implemented in the clinical information system (CIS) and linked to a remote data capture system. Within 10 minutes following the documentation and storage of basic information to CIS, a text message was triggered for patients with suspected stroke and sent to a dedicated trial physician. Each text message provided anonymized information on the exact department and unit, date and time of admission, age, sex, and National Institute of Health Stroke Scale (NIHSS) of the patient. All necessary information needed to generate a text message was already available – routine processes in the emergency department were not affected by the automated real-time text messaging system. The system was tested for three 4-week periods. Feasibility was analyzed based on the number of patients correctly identified by the SSA and the door-to-message time. Results In total, 513 text messages were generated for patients with suspected stroke (median age 74 years (19–106); 50.3% female; median NIHSS 4 (0–41)), representing 96.6% of all cases. For 48.3% of these text messages, basic documentation was completed within less than 1 hour and a text message was sent within 60 minutes after patient admission. Conclusions The system proved to be stable in generating text messages using IT-based CIS to identify acute stroke trial patients. The system operated on information which is documented routinely and did not result in a higher workload. Delays between patient admission and the text message were caused by delayed completion of basic documentation. To use the automated real-time text messaging system to immediately identify emergency patients suitable for acute stroke trials, further development needs to focus on eliminating delays in documentation for the SSA in the emergency department

results of the prospective observational Berlin Beat of Running study

Objectives: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The ‘Berlin Beat of Running’ study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. Design: Prospective observational cohort study including healthy volunteers. Setting and participants: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2–3 days prior, directly after and 1–2 days after the race. Results: Overall, 108 athletes (median 48 years (IQR 45–53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. Conclusions: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. Trial registration: ClinicalTrials.gov NCT01428778; Results

a clinical study protocol

Introduction The approved analgesic and anti-inflammatory drugs ibuprofen and indometacin block the small GTPase RhoA, a key enzyme that impedes axonal sprouting after axonal damage. Inhibition of the Rho pathway in a central nervous system-effective manner requires higher dosages compared with orthodox cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury (SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho inhibition. This has been reassessed by a meta-analysis of the underlying experimental evidence, which indicates an overall effect size of 20.2% regarding motor outcome achieved after ibuprofen/indometacin treatment compared with vehicle controls. In addition, ibuprofen/indometacin may also limit sickness behaviour, non-neurogenic systemic inflammatory response syndrome (SIRS), neuropathic pain and heterotopic ossifications after SCI. Consequently, ‘small molecule’-mediated Rho inhibition after acute SCI warrants clinical investigation. Methods and analysis Protocol of an investigator-initiated clinical open-label pilot trial on high-dose ibuprofen treatment after acute traumatic, motor-complete SCI. A sample of n=12 patients will be enrolled in two cohorts treated with 2400 mg/day ibuprofen for 4 or 12 weeks, respectively. The primary safety end point is an occurrence of serious adverse events, primarily gastroduodenal bleedings. Secondary end points are pharmacokinetics, feasibility and preliminary effects on neurological recovery, neuropathic pain and heterotopic ossifications. The primary safety analysis is based on the incidence of severe gastrointestinal bleedings. Additional analyses will be mainly descriptive and casuistic. Ethics and dissemination The clinical trial protocol was approved by the responsible German state Ethics Board, and the Federal Institute for Drugs and Medical Devices. The study complies with the Declaration of Helsinki, the principles of Good Clinical Practice and all further applicable regulations. This safety and pharmacokinetics trial informs the planning of a subsequent randomised controlled trial. Regardless of the result of the primary and secondary outcome assessments, the clinical trial will be reported as a publication in a peer-reviewed journal. Trial registration number NCT02096913; Pre-results

Preserved Responsiveness of Secondary Somatosensory Cortex in Patients with Thalamic Stroke

Cortical representations may change when somatosensory input is altered. Here, we investigated the functional consequences of partial ‘‘central’ ’ deafferentation of the somatosensory cortex due to a lesion of the ventroposterior lateral nucleus (VPL) in patients at a chronic stage after solitary infarction of the thalamus. Event-related functional magnetic resonance imaging during electrical index finger stimulation of the affected and nonaffected side was performed in 6 patients exhibiting contralesional sensory deficits (mainly hypesthesia). Involvement of the VPL and additional nuclei was determined by high-resolution magnetic resonance imaging (MRI) and subsequent MRI-to-atlas coregistration. For the group, statistical parametric maps showed a reduced activation of contralateral primary somatosensory cortex (SI) in response to stimulation of the affected side. However, no significant difference in the activation of contralateral secondary somatosensory cortex (SII) compared with stimulation of the nonaffected side was detected. Correspondingly, the ratio of SII-to-SI activation for the ipsilesional hemisphere was markedly elevated as compared with the contralesional hemisphere. For preserved responsiveness of SII in thalamic stroke comparable with that of the contralesional hemisphere, possible explanations are a direct thalamocortical input to SII mediating parallel information processing, nonlinear response behavior of SII in serial processing, or reorganizational processes that evolved over time

TRIALS METHODOLOGY Open Access

Automated real-time text messaging as a means for rapidly identifying acute stroke patients for clinical trial

Subacute hyperintensity in ipsilateral midbrain at a delayed time point after striatal stroke.

<p>(A, B) MRI scans of two exemplary patients showing primary ischemic lesion confined to striatum (A) or involving striatum (B) in axial diffusion-weighted (DWI, left) and coronal T2-weighted (T2) imaging (white arrows; 2^nd from left). On the right side, coronal views through the midbrain display the development of an ipsilateral hyperintense lesion occuring between days 6 to 10 after stroke (red arrows). Note that corticospinal degeneration (blue arrows in B) associated with cortical involvement is detectable before the emergence of these secondary exofocal changes in midbrain. (C) Frequency of the anatomic distributions of the primary ischemic lesions (12 striatal stroke and 4 control stroke patients). Lesions are overlayed on the ICBM human brain template. Infarcts associated with secondary midbrain changes are coded in red, infarcts not associated with midbrain changes are coded in blue. Only frequencies of at least 25% are displayed. (D) Localization of secondary exofocal midbrain changes (n = 12 striatal stroke patients). For the purpose of this illustration, secondary lesions (day 10 or latest available scan before day 10) were adjusted to and superimposed on coronal and transverse T1-weighted images of a single patient.</p

Ischemic lesions of striatum elicit secondary changes in ipsilateral substantia nigra.

<p>(A) Color coding of the relative frequency of “ischemic” voxels in the primary ischemic lesion of striatal stroke patients (n = 12) who subsequently developed secondary midbrain changes. Cd: Caudate nucleus (n_max = 11); Pu: putamen (n_max = 10). (B) Color coding of the relative frequency of voxels showing secondary changes in midbrain in these patients. SNC: substantia nigra, pars compacta (n_max = 9). SNR: substantia nigra, pars reticulata. Numbers ranging from -12.5 to +21.2 denote Talairach y-coordinates.</p

Baseline characteristics of study participants.

<p>Baseline characteristics of study participants.</p

MRI findings in striatal stroke patients and control stroke patients.

<p>Clear evidence of a secondary lesion is denoted by “+”. “++” denotes especially large secondary lesions. Patients 1 through 12 showed clear evidence for delayed midbrain changes (DWI and T2) in ipsilateral substantia nigra occurring between days 6 and 10. Despite heavy motion artifacts, scans of patients 13 through 15 still showed some evidence for secondary midbrain changes (+). Several patients missed scans (n.d.). The primary reason for this was that patients had either been transferred to a rehabilitation center or discharged. Control stroke patients (patients 17 through 20) did not show evidence of secondary midbrain changes. Note that cortical involvement or the overall size of the infarct did not affect the development of secondary midbrain changes. Normalization of ADC was observed at late measurements in single patients (days 72, 90, and 144).</p><p>MRI findings in striatal stroke patients and control stroke patients.</p