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Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population.Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921.Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [Interpretation: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke.Funding: National Health and Medical Research Council of Australia.

Decompressive hemicraniectomy (DHC) can improve outcomes for patients with severe forms of acute ischemic stroke (AIS), but the evidence is mainly derived from non-thrombolyzed patients. We aimed to determine the characteristics and outcomes of early DHC in thrombolyzed AIS participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Post-hoc analyses of ENCHANTED, an international, partial-factorial, open, blinded outcome-assessed, controlled trial in 4557 thrombolysis-eligible AIS patients randomized to low- versus standard-dose intravenous alteplase (Arm A, n = 2350), intensive versus guideline-recommended blood pressure control (Arm B, n = 1280), or both (Arms A + B, n = 947). Logistic regression models were used to identify baseline variables associated with DHC, with inverse probability of treatment weights employed to eliminate baseline imbalances between those with and without DHC. Logistic regression was also used to determine associations of DHC and clinical outcomes of death/disability, major disability, and death (defined by scores 2–6, 3–5, and 6, respectively, on the modified Rankin scale) at 90 days post-randomization. There were 95 (2.1%) thrombolyzed AIS patients who underwent DHC, who were significantly younger, of non-Asian ethnicity, and more likely to have had prior lipid-lowering treatment and severe neurological impairment from large vessel occlusion than other patients. DHC patients were more likely to receive other management interventions and have poor functional outcomes than non-DHC patients, with no relation to different doses of intravenous alteplase. Compared to other thrombolyzed AIS patients, those who received DHC had a poor prognosis from more severe disease despite intensive in-hospital management.

Background We explored the influence of low-dose intravenous alteplase and intensive blood pressure lowering on outcomes of acute ischemic stroke according to status/location of vascular obstruction in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods ENCHANTED was a multicenter, quasi-factorial, randomized trial to determine efficacy and safety of low- versus standard-dose intravenous alteplase and intensive- versus guideline-recommended blood pressure lowering in acute ischemic stroke patients. In those who had baseline computed tomography or magnetic resonance imaging angiography, the degree of vascular occlusion was grouped according to being no (NVO), medium (MVO), or large (LVO). Logistic regression models were used to determine 90-day outcomes (modified Rankin scale [mRS] shift [primary], other mRS cut-scores, intracranial hemorrhage, early neurologic deterioration, and recanalization) by vascular obstruction status/site. Heterogeneity in associations for outcomes across subgroups was estimated by adding an interaction term to the models. Results There were 940 participants: 607 in alteplase arm only, 243 in blood pressure arm only, and 90 assigned to both arms. Compared to the NVO group, functional outcome was worse in LVO (mRS shift, adjusted OR [95% CI] 2.13 [1.56–2.90]) but comparable in MVO (1.34 [0.96–1.88]) groups. There were no differences in associations of alteplase dose or blood pressure lowering and outcomes across NVO/MVO/LVO groups (mRS shift: low versus standard alteplase dose 0.84 [0.54–1.30]/0.48 [0.25–0.91]/0.99 [0.75–2.09], Pinteraction = 0.28; intensive versus standard blood pressure lowering 1.32 [0.74–2.38]/0.78 [0.31–1.94]/1.24 [0.64–2.41], Pinteraction = 0.41), except for a borderline significant difference for intensive blood pressure lowering and increased early neurologic deterioration (0.63 [0.14–2.72]/0.17 [0.02–1.47]/2.69 [0.90–8.04], Pinteraction = 0.05). Conclusions Functional outcome by dose of alteplase or intensity of blood pressure lowering is not modified by vascular obstruction status/site according to analyses from ENCHANTED, although these results are compromised by low statistical power. Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01422616

Objective: To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P interaction ≥0.07). Conclusions: We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.

ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2–6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2–6, adjusted odds ratio [95% confidence interval] 0.60 [0.47–0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2–6, 1.04 [0.87–1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616.

Introduction: Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by a deficiency or absence of alpha-galactosidase A (α-GAL A) enzyme, where stroke can be a serious complication. The aim of this study is to determine the feasibility of centralized screening for FD, among young stroke adults registered in the national Australian Stroke Clinical Registry (AuSCR).Methods: The study was conducted in young (age 18 – 55 years) survivors of acute stroke of unknown etiology registered in AuSCR at hospitals in Queensland, Tasmania, New South Wales, and Victoria during 2014 – 2015; and who, at the 3-month outcome assessment, agreed to be re-contacted for future research. Descriptive analyses of case identification from responses and specific enzyme and DNA sequencing analyses were conducted for α-galactosidase A (α-GLA) from dried blood spot (DBS) testing.Results: Of 326 AuSCR-identified patients invited to participate, 58 (18%) provided consent but six were subsequently unable to provide a blood sample and two later withdrew consent to use their data. Among the remaining 50 participants (median age 53 years [48 – 56 years]; 47% female), 67% had experienced an acute ischemic stroke. All males (n = 27) had an initial screen for α-GLA enzyme activity of whom seven with low enzyme levels had normal secondary α-GLA gene analysis. All females (n = 23) had genetic analysis, with one shown to have a pathogenic c.352C>T p.(Arg118Cys) missense mutation of the α-GLA gene for FD.Conclusions: These findings provide logistical data for embedding a process of automated central stroke registry screening for an additional case-finding tool in FD.

BACKGROUND AND PURPOSE This was an investigation of the differential effects of early intensive versus guideline-recommended blood pressure (BP) lowering between lacunar and non-lacunar acute ischaemic stroke (AIS) in the BP arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS In 1,632 participants classified as having definite or probable lacunar (n = 454 [27.8%]) or non-lacunar AIS according to pre-specified definitions based upon clinical and adjudicated imaging findings, mean BP changes over days 0-7 were plotted, and systolic BP differences by treatment between subgroups were estimated in generalized linear models. Logistic regression models were used to estimate the BP treatment effects on 90-day outcomes (primary, an ordinal shift of modified Rankin scale scores) across lacunar and non-lacunar AIS after adjustment for baseline covariables. RESULTS Most baseline characteristics, acute BP and other management differed between lacunar and non-lacunar AIS, but mean systolic BP differences by treatment were comparable at each time point (all pinteraction > 0.12) and over 24 h post-randomization (-5.5, 95% CI -6.5, -4.4 mmHg in lacunar AIS vs. -5.6, 95% CI -6.3, -4.8 mmHg in non-lacunar AIS, pinteraction = 0.93). The neutral effect of intensive BP lowering on functional outcome and the beneficial effect on intracranial haemorrhage were similar for the two subgroups (all pinteraction > 0.19). CONCLUSIONS There were no differences in the treatment effect of early intensive versus guideline-recommended BP lowering across lacunar and non-lacunar AIS.

ObjectiveTo test the hypothesis that imaging signs of ‘brain frailty’ and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED).MethodsBlinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs.Results2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose.ConclusionsNon-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose.

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL.

Background and Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm. Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63–10.50]; with LVO 4.92 [0.87–27.86]; no LVO 6.16 [1.57–24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12–20.26]). Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Uncertainty exists over the prognostic significance of pyrexia in acute intracerebral haemorrhage (ICH). We aimed to determine the association of elevated body temperature with clinical and imaging outcomes among participants of the main Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2).Post-hoc analyses of INTERACT2, an international open, blinded outcome assessed, randomised trial of 2839 patients with spontaneous ICH (6 h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) randomly assigned to intensive (SBP target140 mmHg) or guideline-recommended (SBP target 180 mmHg) BP management. Multivariable logistic regression was used to determine associations of elevated baseline body temperature (37.5 vs. ≥37.5 °C) and 90-day clinical outcome defined on the modified Rankin scale (mRS). Analysis of covariance determined relations of body temperature and haematoma and perihaematomal oedema (PHE) volumes, at baseline and 24 h post-randomisation.Of 2792 participants with data available at admission, 39 (1.4%) patients had elevated body temperature ≥ 37.5 °C. Elevated body temperature was significantly associated with 90-day mortality (adjusted odds ratio 2.44; 95% confidence interval 1.02-5.82; P = .044) but not with major disability alone (mRS scores 3-5) and combination death or major disability (mRS scores 3-6). Elevated body temperature was also associated with larger PHE volume at baseline (10.89 vs. 3.14 cmEarly pyrexia in mild to moderate ICH is associated with greater mortality and larger PHE volume, suggesting an early inflammatory-mediated reaction.www.clinicaltrials.gov (NCT00716079).

ObjectiveWe performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).MethodsWe searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3–6 or 2–6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.ResultsWe included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).ConclusionsFLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.PROSPERO registration numberCRD42019131168.

Objective: To explore the duration of tPCS after effects given different durations of stimulation on power and interhemispheric coherence of the EEG frequency bands. Our hypothesis was that longer tPCS duration would induce a differential effect on the EEG analysis and a longer duration of after effects on the EEG frequency bands.Materials and Methods: We conducted a double blind, sham controlled study in which forty healthy subjects were randomized to receive a single session of either 10, 20, 30 min of active (2 mA, random frequency between 6 and 10 Hz, ear clip montage) or sham tPCS. EEG was recorded before and after the intervention to assess tPCS induced after effects.Results: We found that 10 and 20 min of active tPCS induced a significant increase in alpha (p = 0.004) and theta (p = 0.006) coherence in the frontal region as compared with the sham stimulation. No significant changes were found with 30 min of stimulation (p < 0.05). The Kaplan Meier analysis showed that 10 and 20 min of tPCS induced after effects that lasted 50 min.Conclusions: These results evidence the nonlinear relationship between the stimulation duration and the tPCS after effects, suggesting the presence of homeostatic mechanisms., This study was supported in part by a grant from BrainGear Inc. Dr. LMQ received funding support from an Institutional National Research Service Award from the National Center for Complementary and Integrative Health grant T32AT000051, the Ryoichi Sasakawa Fellowship Fund, and by the Program in Placebo Studies at Beth Israel Deaconess Medical Center.

8 p., We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (−53.38 ± 53.12% vs −22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30–60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. Perspective High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.

Objective: The impact of visuospatial attention on perception with supraliminal stimuli and stimuli at the threshold of conscious perception has been previously investigated. In this study, we assess the cross-modal effects of visuospatial attention on conscious perception for near-threshold somatosensory stimuli applied to the face. Methods: Fifteen healthy participants completed two sessions of a near-threshold cross-modality cue-target discrimination/conscious detection paradigm. Each trial began with an endogenous visuospatial cue that predicted the location of a weak near-threshold electrical pulse delivered to the right or left cheek with high probability (∼75%). Participants then completed two tasks: first, a forced-choice somatosensory discrimination task (felt once or twice?) and then, a somatosensory conscious detection task (did you feel the stimulus and, if yes, where (left/right)?). Somatosensory discrimination was evaluated with the response reaction times of correctly detected targets, whereas the somatosensory conscious detection was quantified using perceptual sensitivity (d′) and response bias (beta). A 2 × 2 repeated measures ANOVA was used for statistical analysis. Results: In the somatosensory discrimination task (1st task), participants were significantly faster in responding to correctly detected targets (p < 0.001). In the somatosensory conscious detection task (2nd task), a significant effect of visuospatial attention on response bias (p = 0.008) was observed, suggesting that participants had a less strict criterion for stimuli preceded by spatially valid than invalid visuospatial cues. Conclusions: We showed that spatial attention has the potential to modulate the discrimination and the conscious detection of near-threshold somatosensory stimuli as measured, respectively, by a reduction of reaction times and a shift in response bias toward less conservative responses when the cue predicted stimulus location. A shift in response bias indicates possible effects of spatial attention on internal decision processes. The lack of significant results in perceptual sensitivity (d′) could be due to weaker effects of endogenous attention on perception.

7 p., Introduction: Phantom limb pain may be present in up to 80% of patients subjected to amputation because oftrauma or peripheral vascular disease. Severalfactors have been associated with its occurrence, including pre-amputation pain, the etiology, and the amputation level. Objective: To review the current status of the pathophysiological mechanisms, treatment options and their efficacy for the management of phantom limb pain. Method: Non-systematic review ofthe literature in PubMed and Cochrane, of articles describing the pathophysiology and treatment of phantom limb pain. Results and conclusions: The proposed pathophysiological mechanisms are still in research and include peripheral, central and psychologicalfactors. Treatment options are still limited, and less than 10% of patients report long-term improvement., Introducción: El dolor de miembro fantasma puede ocurrir hasta en el 80% de los sujetos con amputación por trauma o enfermedad vascular periférica. Varios factores se han asociado a su generación, como el dolor preamputación, la etiología y el nivel de la amputación. Objetivo: Revisar el estado actual de los mecanismos fisiopatológicos, las opciones de tratamiento y su eficacia en el dolor de miembro fantasma. Métodos: Se realizó una revisión de la literatura no sistemática en las bases de datos PubMedy Cochrane sobre artículos que describieran la fisiopatología y el tratamiento del dolor de miembro fantasma. Resultados y conclusiones: Los mecanismos fisiopatológicos propuestos aún se encuentran en investigación e incluyen factores periféricos, centrales y psicológicos. Las opciones de tratamiento continúan siendo limitadas, y menos del 10% reportan mejoría a largo plazo.

Introducción:El dolor de miembro fantasma puede ocurrir hasta en el 80% de los sujetos con amputación por trauma o enfermedad vascular periférica. Varios factores se han asociado a su generación, como el dolor preamputación, la etiología y el nivel de la amputación. Objetivo:Revisar el estado actual de los mecanismos fisiopatológicos, las opciones de tratamiento y su eficacia en el dolor de miembro fantasma. Métodos:Se realizó una revisión de la literatura no sistemática en las bases de datos PubMed y Cochrane sobre artículos que describieran la fisiopatología y el tratamiento del dolor de miembro fantasma. Resultados y conclusiones: Los mecanismos fisiopatológicos propuestos aún se encuentran en investigación e incluyen factores periféricos, centrales y psicológicos. Las opciones de tratamiento continúan siendo limitadas, y menos del 10% reportan mejoría a largo plazo. Introduction:Phantom limb pain may be present in up to 80% of patients subjected to amputation because of trauma or peripheral vascular disease. Several factors have been associated with its occurrence, including pre-amputation pain, the etiology, and the amputation level. Objective: To review the current status of the pathophysiological mechanisms, treatment Opioid options and their efficacy for the management of phantom limb pain. Method:Non-systematic review of the literature in PubMed and Cochrane, of articles describing the pathophysiology and treatment of phantom limb pain. Results and conclusions: The proposed pathophysiological mechanisms are still in research and include peripheral, central and psychological factors. Treatment options are still limited, and less than 10% of patients report long-term improvement.

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has been extensively studied. While there have been initial positive results in some clinical trials, there is still variability in tDCS results. The aim of this article is to review and discuss patents assessing novel methods to optimize the use of tDCS. A systematic review was performed using Google patents database with tDCS as the main technique, with patents filling date between 2010 and 2015. Twenty-two patents met our inclusion criteria. These patents attempt to address current tDCS limitations. Only a few of them have been investigated in clinical trials (i.e., high-definition tDCS), and indeed most of them have not been tested before in human trials. Further clinical testing is required to assess which patents are more likely to optimize the effects of tDCS. We discuss the potential optimization of tDCS based on these patents and the current experience with standard tDCS.

WCN 2013 No: 2844 Topic: 9 — Pain Effects of transcranial magnetic stimulation in the treatment of phantom limb pain in landmine victims: A randomized clinical trial M. Malavera, F. Silva, R. Garcia, J. Quiros, M. Dallos, A. Pinzon. Fundacion Cardiovascular de Colombia, Floridablanca, Colombia, Neuroscience, Fundacion Cardiovascular de Colombia, Floridablanca, Colombia, Harvard Medical School, Boston, MA, USA, Santander, Fundacion Cardiovascular de Colombia, Floridablanca, Universidad Industrial de Santander, Bucaramanga, Colombia The rTMS on motor cortex (M1) has efficacy of 52–88% in some refractory neurogenic pain by descending modulation of corticothalamic tract. The aim is to evaluate the efficacy of rTMS in the treatment of PLP in victims of anti-personnel landmines. We performed a randomized, double-blind placebo-controlled trial in 49 patients with unilateral amputation, 26 patients received real rTMS over the hand area of M1 contralateral to amputated leg and 23 patients received sham. A Visual Analogue Scale (VAS) was administered at baseline, after 15 and 30 days of last session. There were no significant differences when the percentage change of VAS at 15 days (−53.2 ± 54.2 vs −28.2 ± 58.4, p = 0.11) or at 30 days (−43.6 ± 48.6 vs −21.5 ± 53.4, p = 0.14) was analyzed comparing both groups, however, a significant difference in the proportion of subjects who presented a decrease greater than 30% in VAS at 15 days in the active group vs placebo (69.2% vs 39.1%, p = 0.03) and a tendency at 30 days (58.3% vs 33.3%, p = 0.09) was observed. The analysis of a subgroup of subjects with less than 10 years since amputation (n = 38) showed differences between the percentage change at 15 days (−51.2 ± 59.5 vs 55.7, p = 0.05), and at 30 days (−49.4 ± 48.9 vs −9.9 ± 46.7, p = 0.02). There were clear differences in the proportion of subjects with a decrease in more than 30% of pain at 15 days (68.4 vs 31.6%, p = 0.02) and at 30 days (61.1 vs 23.5, p = 0.02). doi:10.1016/j.jns.2013.07.1880 Abstract — WCN 2013 No: 3061 Topic: 9 — Pain Effect of manipulative therapy in combination with kinesio taping on cervicothoracic pain in highly qualified athletes WCN 2013 No: 3061 Topic: 9 — Pain Effect of manipulative therapy in combination with kinesio taping on cervicothoracic pain in highly qualified athletes V. Zabarovski, L. Vasilevskaya, L. Anatskaia. Neurology, Republican Research and Practical Center of eurology and Neurosurgery