Modeling the Optimal Transportation for Acute Stroke Treatment : Impact of Diurnal Variations in Traffic Rate.

PURPOSE: Prolonged transfer times between the primary stroke center (PSC) and the comprehensive stroke center (CSC) are one of the major causes of treatment delay for endovascular stroke treatment. We aimed to analyze the effect of the diurnal variations in traffic rates at weekdays and weekends on the catchment area size of three transportation paradigms, i.e. mothership, drip-and-ship (DS) and drip-and-drive (DD). METHODS: A conditional probability model that predicts the probability of good outcome for patients with suspected large vessel occlusion was used to analyze the prehospital stroke triage in northwest Germany and produce catchment area maps. Transportation times were calculated during each hour of a weekday and a Sunday using Google Maps. For comparison, real DD transportation times from our CSC in Hamburg-Eppendorf (blinded for review) to a PSC in Lüneburg were prospectively recorded. RESULT: On weekdays, the mothership catchment area was the largest (≥40,000 km2, 63%) except for a decrease during morning rush hours, when the DD catchment area was highest (30,879 km2, 48%). The DS catchment area was higher than the DD catchment area during the afternoon rush hours both during the week as well as on Sundays. CONCLUSION: Our study showed a considerable impact of the diurnal variations in traffic rate and direction of travel on optimal stroke transportation. Stroke systems of care should take real time traffic information into account.

'Drip-and-drive': shipping the neurointerventionalist to provide mechanical thrombectomy in primary stroke centers.

BACKGROUND: To satisfy the increasing demand of mechanical thrombectomy (MT) for acute ischemic stroke treatment, new organizational concepts for patient care are required. This study evaluates time intervals of acute stroke management in two stroke care models, including one based on transportation of the interventionalist from a comprehensive stroke center (CSC) to treat patients in two primary stroke centers (PSC). We hypothesized that time intervals were not inferior for the 'drip-and-drive' concept compared with the traditional 'drip-and-ship' concept. METHODS: Patients treated with MT at the PSC ('drip-and-drive', 'D+D group') were compared with patients transferred from PSC to CSC for MT ('drip-and-ship', 'D+S group') with regard to time delays. Time intervals assessed were: symptom onset to initial CT, to angiography, and to recanalization; time from initial CT to telephone call activation, to arrival, and to angiography; and time from telephone call activation to arrival and from arrival to angiography. RESULTS: 42 patients were treated at the PSC after transfer of the interventionalist, and 32 patients were transferred to the CSC for MT. The groups did not differ with regard to median Onset-CT and CT-Phone times. Significant differences between the groups were found for the primary outcome measure CT-Arrival time ('D+D group': median 121 (IQR 108-134) min vs 181 (157-219) min for the 'D+S group'; P<0.001). Time difference between the groups increased to more than 2 hours for median CT-Angio times (median 123 (IQR 93-147) min vs 252 (228-275) min; P<0.001). CONCLUSION: Time intervals for the 'D+D group' were not inferior to those of the 'D+S group'. Moreover, under certain conditions, the 'drip-and-drive' concept might even be superior.

Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease.

BACKGROUND: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q(10) (CoQ(10)) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons. OBJECTIVE: To determine whether nanoparticular CoQ(10) is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial. SETTING: Academic and nonacademic movement disorder clinics. PATIENTS: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention Random assignment to placebo or nanoparticular CoQ(10) (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment. MAIN OUTCOME MEASURE: The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of the sum score of the UPDRS parts II and III between the baseline and 3-month visits. RESULTS: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ(10) group (P = .82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ(10) group. The frequency and quality of adverse events were similar in both treatment groups. CONCLUSIONS: Nanoparticular CoQ(10) at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ(10) does not display symptomatic effects in midstage Parkinson disease.

Cortical processing of esophageal sensation is related to the representation of swallowing.

The esophagus plays a major role in the act of swallowing. The aim of the present investigation was to apply whole-head magnetoencephalography in order to study the cortical processing of esophageal sensation in healthy humans in whom the cortical representation of swallowing had been established previously. The proximal esophagus was stimulated in nine participants by intermittent 5 ml water infusion. Submental EMG recording was used to identify trials, which were contaminated by subsequent swallowing. Esophageal stimulation led to changes in rhythmic activity of the brain that were localized in the left lateral primary sensorimotor cortex. The pattern of cortical activation showed the same hemispheric lateralization as that of volitional swallowing, however, being localized more lateral. The close anatomical vicinity of these two functions points to an important physiological link between the cortical processing of esophageal sensation and the cortical control of swallowing.

Changing cortical excitability with low-frequency transcranial magnetic stimulation can induce sustained disruption of tactile perception.

Transcranial magnetic stimulation (TMS) is promising as a therapeutic tool, and TMS of the motor system has served as a model for regionally specific modulations of cortical excitability. It is unclear, however, to what extent response characteristics of the motor cortex are representative of other brain systems. We wanted to determine whether TMS could induce a sustained disruption of somatosensory processing beyond the stimulation duration, similar to observations in the motor system. We applied 1-Hz TMS at 110% of subjects' motor thresholds for a variable duration over the right and left somatosensory cortex before subjects performed a tactile frequency discrimination task with the left hand. Tactile discrimination was impaired only after TMS over the right somatosensory cortex (analysis of variance: p <.01). The duration of this impairment correlated with the duration of the preceding TMS; the effect lasted approximately 2 min after 5 min of TMS, 4 min after 10 min of TMS, and 8 min after 20 min of TMS. Two conclusions arise: 1) low-frequency TMS can interfere with tactile perception in a robust and sustained way, and 2) TMS dosing parameters effective in the motor system are also effective in the somatosensory system and may reflect a modality-independent response characteristic of the cerebral cortex.

Reproducibility of hemispheric blood flow increases during line bisectioning.

OBJECTIVES: To determine if attention-related changes of hemispheric perfusion increases, as assessed by blood-flow sensitive techniques, are as reliable as language-related hemispheric perfusion increases. METHODS: The reproducibility of hemispheric blood flow velocity increases during a line bisection task was assessed with functional transcranial Doppler sonography. RESULTS: Over repeated examinations, the index of lateralization of 20 healthy subjects showed a high test-retest reproducibility (r=0.9, P<0.01). No practice effects were detected over the course of 10 re-assessments of one subject. CONCLUSIONS: Hemispheric lateralization of visuospatial attention is a robust phenomenon and can be reliably determined using perfusion sensitive measurements. Future studies should focus on investigating lesion-related reorganization of attentional processing with blood-flow sensitive techniques.

Pattern of cortical reorganization in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study.

Depending on individual lesion location and extent, reorganization of the human motor system has been observed with a high interindividual variability. In addition, variability of forces exerted, of motor effort, and of movement strategies complicates the interpretation of functional imaging studies. We hypothesize that a general pattern of reorganization can be identified if a homogeneous patient population is chosen and experimental conditions are controlled. Patients with amyotrophic lateral sclerosis (ALS) and healthy volunteers were trained to perform a simple finger flexion task with 10% of each individual's maximum grip force with constant movement amplitude and frequency. The activation pattern in ALS patients was distinctly different to that in healthy controls: In ALS patients, motor cortex activation was located more anteriorly, encompassing the premotor gyrus. The cluster volume within the supplementary motor area (SMA) was higher and shifted toward the pre-SMA. Contralateral inferior area 6 and bilateral parietal area 40 revealed higher cluster volumes. Our results demonstrate a general pattern of functional changes after motor neuron degeneration. They support the concept of a structurally parallel and functionally specialized organization of voluntary motor control. Degeneration of the first and second motor neurons leads to enhanced recruitment of motor areas usually involved in initiation and planning of movement. Partial compensation between functionally related motor areas seems to be a strategy to optimize performance if the most efficient pathway is unavailable.

Phantom sensations following acute pain.

In human amputees with painful phantom sensations, mislocalizations of tactile stimuli to the phantom increase with the amount of cortical representational reorganization and the extent of phantom pain. A similar phenomenon was incidentally encountered in healthy subjects. For reasons unrelated to the question of mislocalization, we performed a study involving the application of experimental acute pain to the hand followed by non-noxious tactile stimulation of the ipsilateral lip. During lip stimulation, two out of six subjects spontaneously reported perceiving an additional phantom-like sensation in the hand synchronously to the non-noxious lip stimulation. Similar, although more diffuse, phantom sensations were observed in two out of seven additional subjects who were then tested specifically for this effect. The observation is compatible with a pain-induced hyperresponsiveness of the cortical hand area to somatotopically adjacent inputs from the lip. This suggests that, even in the absence of deafferentation, pain can lead to a representational reorganization.