Effects of photobiomodulation on pain, lactate and muscle performance (ROM, torque, and EMG parameters) of paretic upper limb in patients with post-stroke spastic hemiparesis-a randomized controlled clinical trial.

The objective of the study was to investigate the impact of photobiomodulation (PBM) on the paretic upper limb in post-stroke patients with spastic hemiparesis and to understand the potential of PBM as a long-term non-invasive therapy for reducing the side effects caused by spasticity in the hemiparetic upper limb after a stroke. This is a double-blind randomized clinical trial constituted of 27 participants, being Control group (CG = 12 healthy individuals) and PBM group (PBMG = 15 post-stroke individuals). In the CG, the baseline blood lactate (BL) was evaluated, followed by the evaluation of the IC torque of the biceps and triceps muscles, with the isokinetic dynamometer associated with surface electromyography (EMG) and, subsequently, a new measurement of BL. The PBMG received 10 sessions of treatment with PBM (780 nm, Power: 100 mV, Power Density: 3.18 W/cm2, Energy: 4 J, Fluency: 127.4 J/cm2, Time: 40 s per point and 1.280 s total, Spot: 0.0314 cm2, 32 Points: 16 points (brachial biceps) and 16 points (brachial triceps) applied with contact at 90°, Total Energy: 64 J), which in the pre-treatment evaluation measured BL, the visual analogue scale (VAS) of pain; torque and EMG of the same muscles in the IC, subsequently, a new measurement of VAS and BL, and measurement of range of motion (ROM) during the reaching movement. At the conclusion of the ten sessions, all participants underwent a reassessment, wherein all tests originally administered during the initial evaluation were repeated. Subsequently, the data were analyzed using the Shapiro-Wilk normality test. For related data, the paired t-test was used for normal distributions and the Wilcoxon test for non-normal data. For unrelated data, the t test was used for normal distributions and the Mann-Whitney test for non-normal data. Muscle torque was higher for the CG, with a significant difference (CGxPBMG = p < 0.0001). There was no significant difference between the EMG values of the CG in relation to the Pre-PBM phase and with the Post-PBM phase of the PBMG (p > 0.05). On the other hand, there was a 38% reduction in pain reported by hemiparetic patients (p = 0.0127) and a decrease in BL in the PBMG. Post-PBM ROM increased by 46.1% in the elbow extension of the paretic limb. In conclusion, Photobiomodulation (PBM) demonstrated significant improvements in muscle performance, reducing fatigue and pain levels, and enhancing range of motion in post-stroke patients with spastic hemiparesis. These findings support the potential integration of PBM into rehabilitation protocols, but further research and clinical trials are needed to validate and expand upon these promising outcomes.

Study of transcranial therapy 904 nm in experimental model of stroke.

Cerebrovascular accidents (CVAs), commonly known as strokes, can damage the brain through vascular injuries caused by either blood vessel blockages (ischemic stroke) or ruptures (hemorrhagic stroke) which disrupt regular brain blood supply and can cause severe damage to the individual. The objective of the present study was to evaluate the effects of photobiomodulation with a light-emitting diode (LED) device (904 nm, 110 mW, 7 J/cm2) on neurogenesis, muscle resistance, and motor behavior in animals submitted to an experimental model of hemiplegia. The sample consisted of 30 Wistar rats, divided into two groups: control group (GC) and 904-nm LED-treated group (TG). All animals underwent stereotactic surgery for electrode implant and subsequent electrolytic injury to induce an ischemic stroke. TG was subjected to daily LED irradiation (904 nm, 110 mW, 7 J/cm2) for 63 s. Suspension test results indicate an improvement of TG muscle resistance when compared with baseline evaluation (BLT); a reduction in open-field freezing time and the number of fecal bolus pellets suggest diminished anxiety induced by 904-nm LED treatment on treatment days 7 and 21 (TG7 and TG21) compared with the baseline results; and lastly, histological analysis showed important signs of neurogenesis in TG in comparison to CG, especially on treatment days 7 and 21 (TG7 and TG21). In conclusion, the present study suggests that 904-nm LED irradiation may beneficially affect neurogenesis, muscle resistance, and animal motor behavior following ischemic CVA.

MR-based treatment planning in radiation therapy using a deep learning approach.

PURPOSE: To develop and evaluate the feasibility of deep learning approaches for MR-based treatment planning (deepMTP) in brain tumor radiation therapy. METHODS AND MATERIALS: A treatment planning pipeline was constructed using a deep learning approach to generate continuously valued pseudo CT images from MR images. A deep convolutional neural network was designed to identify tissue features in volumetric head MR images training with co-registered kVCT images. A set of 40 retrospective 3D T1-weighted head images was utilized to train the model, and evaluated in 10 clinical cases with brain metastases by comparing treatment plans using deep learning generated pseudo CT and using an acquired planning kVCT. Paired-sample Wilcoxon signed rank sum tests were used for statistical analysis to compare dosimetric parameters of plans made with pseudo CT images generated from deepMTP to those made with kVCT-based clinical treatment plan (CTTP). RESULTS: deepMTP provides an accurate pseudo CT with Dice coefficients for air: 0.95 ± 0.01, soft tissue: 0.94 ± 0.02, and bone: 0.85 ± 0.02 and a mean absolute error of 75 ± 23 HU compared with acquired kVCTs. The absolute percentage differences of dosimetric parameters between deepMTP and CTTP was 0.24% ± 0.46% for planning target volume (PTV) volume, 1.39% ± 1.31% for maximum dose and 0.27% ± 0.79% for the PTV receiving 95% of the prescribed dose (V95). Furthermore, no significant difference was found for PTV volume (P = 0.50), the maximum dose (P = 0.83) and V95 (P = 0.19) between deepMTP and CTTP. CONCLUSIONS: We have developed an automated approach (deepMTP) that allows generation of a continuously valued pseudo CT from a single high-resolution 3D MR image and evaluated it in partial brain tumor treatment planning. The deepMTP provided dose distribution with no significant difference relative to a kVCT-based standard volumetric modulated arc therapy plans.

Photobiomodulation for traumatic brain injury and stroke.

There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).

Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.

Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.

Effects of low-level laser therapy (LLLT 808 nm) on lower limb spastic muscle activity in chronic stroke patients.

A cerebrovascular accident (CVA) may affect basic motor functions, including spasticity that may be present in the upper extremity and/or the lower extremity, post-stroke. Spasticity causes pain, muscle force reduction, and decreases the time to onset of muscle fatigue. Several therapeutic resources have been employed to treat CVA to promote functional recovery. The clinical use of low-level laser therapy (LLLT) for rehabilitation of muscular disorders has provided better muscle responses. Thus, the aim of this study was to evaluate the effect of the application of LLLT in spastic muscles in patients with spasticity post-CVA. A double-blind clinical trial was conducted with 15 volunteer stroke patients who presented with post-stroke spasticity. Both males and females were treated; the average age was 51.5 ± 11.8 years old; the participants entered the study ranging from 11 to 48 months post-stroke onset. The patients participated in three consecutive phases (control, placebo, and real LLLT), in which all tests of isometric endurance of their hemiparetic lower limb were performed. LLLT (diode laser, 100 mW 808 nm, beam spot area 0.0314 cm(2), 127.39 J/cm(2)/point, 40 s) was applied before isometric endurance. After the real LLLT intervention, we observed significant reduction in the visual analogue scale for pain intensity (p = 0.0038), increased time to onset of muscle fatigue (p = 0.0063), and increased torque peak (p = 0.0076), but no significant change in the root mean square (RMS) value (electric signal in the motor unit during contraction, as obtained with surface electromyography). Our results suggest that the application of LLLT may contribute to increased recruitment of muscle fibers and, hence, to increase the onset time of the spastic muscle fatigue, reducing pain intensity in stroke patients with spasticity, as has been observed in healthy subjects and athletes.

Massive macroglossia secondary to angioedema: a review and presentation of a case.

Macroglossia is a rare condition, but can severely affect the oral and maxillofacial region. Angioedema is a condition resulting from multiple mechanisms, all of which can result in macroglossia. This report describes an unusual case of acquired macroglossia in an adult resulting from chronic edema secondary to angioedema in the setting of stroke. The patient had a morbidly enlarged tongue and presented with clinical signs and symptoms consistent with massive macroglossia. She required surgical intervention for acute management of her symptoms and definitive treatment of her macroglossia.

Incremental treatments with laser therapy augments good behavioral outcome in the rabbit small clot embolic stroke model.

Transcranial near-infrared laser therapy (TLT) improves behavioral outcome in animal stroke models when applied as single treatment within the 24 h of the stroke onset. It is unknown if the multiple TLT treatments have an added beneficial effect. We aim to determine whether multiple irradiations with TLT would have further improvement in behavioral outcomes in the rabbit small clot embolic stroke model (RSCEM). Using the RSCEM, two and three TLT treatments (7.5-20 mW/cm(2)) were compared against single laser treatment alone (7.5-10.8 mW/cm(2)). Two sham irradiation groups were added for the control curves. The double treatment group received TLT at 3 and 5 h and the triple treatment group at 2, 3, and 4 h after embolization. Behavioral analysis was conducted 24 h after embolization using a dichotomized behavioral score. The determination of the effective clot amount (milligrams) that produces neurological deficits in 50 % of the rabbits (P 50) was used to compare TLT treatments with the sham. The P 50 for double treatment was 5.47 ± 0.90, with n = 39; the corresponding P 50 value for a single treatment was 3.87 ± 0.73, with n = 38; and the corresponding control curve was 3.25 ± 0.4, n = 32. The P 50 for triple treatment was 5.91 ± 0.49, with n = 23; the corresponding P 50 value for a single treatment was 3.09 ± 0.59, with n = 15, and the corresponding control curve was 1.71 ± 0.26, with n = 17. The triple treatment had 91 % improvement when compared with the single treatment and 245 % improvement when compared with the sham. The present study suggests that the additional TLT treatments provide further behavioral improvement when given during the acute ischemic stroke phase.

The effects of transcranial laser photobiomodulation and neuromuscular electrical stimulation in the treatment of post-stroke dysfunctions.

Post-stroke sequelae includes loss functions, such as cognitive and sensory-motor which lead to emotional and social problems, reducing quality of life and well-being. The main aim of our study was to investigate the effects of transcranial laser photobiomodulation together with neuromuscular electrical stimulation (NMES) in post-stroke patients. We performed a clinical trial and an ex vivo study. For the clinical trial, hemiplegic patients were separated into two groups: Treated Group (TG): Hemiplegics treated with transcranial laser (on) associated with NMES (on) and; Placebo Group (PG): Hemiplegics treated with placebo transcranial laser (off) associated with NMES (on). The cluster prototype includes 12 diode laser beams (4 × 660 nm, 4 × 808 nm and 4 × 980 nm) with average power of 720 mW per cluster applied during one minute, leading to 43.2 J energy per cluster. Fifteen regions for all head were irradiated by cluster, leading to 648 J energy per session. The parameters of NMES of the paretic limbs to generate extension wrist and ankle dorsiflexion were symmetrical biphasic rectangular waveforms, 50 Hz frequency, 250 µs pulse duration, and adjustable intensity to maintain the maximum range of motion (amplitude between 0 and 150 mA). Our clinical trial showed improvement of cognitive function, pain relief, greater manual dexterity, enhancement of physical and social-emotional health which lead to better quality of life and well-being. There was also increased temperature in the treated regions with laser and NMES. For the ex vivo study, the distribution of infrared and red radiation after penetration through the cranium and hemihead of cadavers were showed. Therefore, transcranial laser photobiomodulation associated with NMES can be an important therapeutic resource for rehabilitation after stroke.

Increased Improvement in Speech-Language Skills After Transcranial Photobiomodulation Plus Speech-Language Therapy, Compared to Speech-Language Therapy Alone: Case Report with Aphasia.

Objective: This is a case report showing that transcranial photobiomodulation (tPBM) combined with traditional, speech-language therapy improved and accelerated the results from speech-language therapy, in a stroke person with aphasia (PWA). Background: tPBM is a safe, noninvasive technique using red and near-infrared light to improve the metabolism of cells. tPBM helps by promoting neuromodulation, while decreasing neuroinflammation and promoting vasodilation. Several studies have shown that tPBM can help individuals with stroke or traumatic brain injury achieve significant cognitive improvements. Methods: A 38-year-old female, who sustained an ischemic stroke on the left side of the brain, received two, 5-month series of treatments. The first series of treatments included traditional speech-language therapy, for the first 5 months poststroke. The second series of treatments included tPBM in combination with speech-language therapy, for the next 5 months. The tPBM treatments included application of red (630 and 660 nm) and near-infrared (850 nm) wavelengths of photons applied to left hemisphere scalp areas. The major cortical language areas were subjacent to the scalp placements along the line of the Sylvian fissure. At each session, first a light-emitting diode (LED) cluster head with red (630 and 660 nm) and near-infrared (850 nm) wavelengths, with an irradiance (power density) of 200 mW/cm2, a beam size of 4.9 cm2, and a fluence (energy density) of 12 J/cm2 per minute, was applied to the left side of the scalp/brain, along the Sylvian fissure for 60 sec at each at the following eight, language network target areas: frontal pole, prefrontal cortex, and inferior frontal gyrus (Broca's area); supramarginal gyrus and angular gyrus in the parietal lobe; inferior motor/sensory cortex (mouth area); and posterior superior temporal gyrus (Wernicke's area) and superior temporal sulcus in the temporal lobe, for a total of 8 min. Second, for the next 20 min (1200 sec), simultaneous with speech-language therapy, an LED PBM helmet was applied to the scalp/head. This helmet contained 256 separate LED lights, near-infrared (810 nm) wavelength, 60 mW power per LED light, total power, 15 W; energy, 72 Joules; fluence, 28.8 J/cm2; and irradiance, 24 mW/cm2. Results and conclusions: During the initial, 5-month treatment series with traditional speech-language therapy only, there was little to no improvement in dysarthria and expressive language. During the second, 5-month treatment series, however, with tPBM applied first, to the left hemisphere only, and second, to both hemispheres during each session plus simultaneous speech-language therapy, there was marked improvement in the dysarthria and expressive language. After the first 5-month series, this PWA had utilized a slow rate of speech with a production of ∼25 to 30 words-per-minute during conversations and spontaneous speech. Utterance length was only 4-6 words with simple, grammatical structure. After the second, 5-month series of treatment combining tPBM plus speech-language therapy, the rate of speech increased to 80+ words-per-minute and utterance length was increased to 9-10 words, with more complex grammatical structure.

Photobiomodulation treatment inhibits neurotoxic astrocytic polarization and protects neurons in in vitro and in vivo stroke models.

The beneficial effects of photobiomodulation (PBM) on function recovery after stroke have been well-established, while its molecular and cellular mechanisms remain to be elucidated. The current study was designed to investigate the effect of PBM on synaptic proteins and astrocyte polarization of photothrombotic (PT)-stroke induced rats in vivo, and explore the possible effect of PBM treatment on oxygen-glucose deprivation (OGD)-induced neurotoxic astrocytic polarization in vitro. We reported that 2-min PBM treatment (808 nm) for 7 days significantly increased synaptic proteins and neuroprotective astrocytic marker S100 Calcium Binding Protein A10 (S100A10) and inhibited neurotoxic astrocytic marker C3d in the peri-infarct region after ischemic stroke. Cell culture studies of primary cortical neurons and N2a cells showed that single-dose PBM treatment could increase cellular viability, regulate the apoptotic proteins (Caspase 9, Bcl-xL and BAX) and preserve synaptic proteins following OGD exposure. Additionly, PBM decreased the levels of C3d, inducible nitric oxide synthase (iNOS) and interleukin 1ß (IL-1ß) on astrocytes exposed to OGD. In summary, we demonstrated that PBM could inhibit neurotoxic astrocytic polarization, preserve synaptic integrity and protect neurons against stroke injury both in vitro and in vivo.

Late Radiation-Induced Carotid Artery Stenosis and Stroke in Pediatric Patient Treated With Proton Radiation Therapy for Skull-Base Chordoma.

Radiation vasculopathy is a well-recognized late complication of radiation therapy. We present a case of a stroke 29 years after high-dose proton radiation therapy for skull-base chordoma due to occlusion of bilateral internal carotid arteries.

Intravascular Laser Irradiation of Blood Improves Functional Independence in Subacute Post-Stroke Patients: A Retrospective Observational Study from a Post-Stroke Acute Care Center in Taiwan.

Objective: To investigate the effect of intravascular laser irradiation of blood (ILIB) in patients with post-stroke disability. Background: Helium-neon intravascular laser at a wavelength of 632.8 nm has been applied in post-stroke rehabilitation for many years in Taiwan. Data were collected from our practice to validate its effectiveness. Materials and methods: This was a single-center, retrospective, observational study. Data from 34 patients with first-episode ischemic stroke who participated in the post-acute care program and had an initial modified Rankin Scale (mRS) score of 4 between July 2018 and June 2021 were retrospectively reviewed. Twelve patients who received conventional rehabilitation plus ILIB were in the ILIB group. Twenty-two patients who received conventional rehabilitation only were in the control group. Assessments, including the mRS, Barthel Index (BI), Berg Balance Scale (BBS), 6-min walk test (6MWT), and Fugl-Meyer Assessment of the upper extremity (FMA-UE), were performed to evaluate any post-treatment improvement. Results: Patients who received ILIB had significantly superior mRS scores than those who received only conventional rehabilitation (p = 0.028). Patients in the ILIB group experienced more improvements in the BI, 6MWT, and FMA-UE; however, these were nonsignificant. In addition, the control group experienced a greater improvement in the BBS than the ILIB group. Further studies are required to elucidate the mechanism of action of ILIB therapy fully. There was no major adverse event reported in patients receiving ILIB therapy. Conclusions: ILIB improved independence in post-stroke patients, suggesting that ILIB is a promising treatment for facilitating post-stroke recovery.

Virtual reality training enhances gait poststroke: a systematic review and meta-analysis.

Virtual reality (VR)-based interventions are gaining widespread attention for managing neurological disorders such as stroke. A metastatistical consensus regarding the intervention is strongly warranted. In this study, we attempt to address this gap in the literature and provide the current state of evidence for the effects of VR on gait performance. We conducted both between- and within-group meta-analyses to provide a state of evidence for VR. Moreover, we conducted a search adhering to PRISMA guidelines on nine databases. Out of 1866 records, 32 studies involving a total of 809 individuals were included in this review. Considering all included studies, significant enhancements in gait parameters were observed with VR-based interventions compared with conventional therapy. A between-group meta-analysis reported beneficial significant medium effects of VR training on cadence (Hedge's g = 0.55), stride length ((STrL; Hedge's g = 0.46), and gait speed (Hedge's g = 0.30). Similarly, a within-group meta-analysis further revealed positive medium effects of VR on cadence (Hedge's g = 0.76), STrL (Hedge's g = 0.61), and gait speed (Hedge's g = 0.69). Additional subgroup analyses revealed beneficial effects of joint application of VR and robot-assisted gait training on gait speed (Hedge's g = 0.50). Collectively, findings from this review provide evidence for the effectiveness of VR-based gait training for stroke survivors.

Increased Functional Connectivity Within Intrinsic Neural Networks in Chronic Stroke Following Treatment with Red/Near-Infrared Transcranial Photobiomodulation: Case Series with Improved Naming in Aphasia.

Objective: To examine effects of four different transcranial, red/near-infrared (NIR), light-emitting diode (tLED) protocols on naming ability in persons with aphasia (PWA) due to left hemisphere (LH) stroke. This is the first study to report beneficial effects from tLED therapy in chronic stroke, and parallel changes on functional magnetic resonance imaging (fMRI). Materials and methods: Six PWA, 2-18 years poststroke, in whom 18 tLED treatments were applied (3 × /week, 6 weeks) using LED cluster heads: 500 mW, red (633 nm) and NIR (870 nm), 22.48 cm2, 22.2 mW/cm2. Results: After Protocol A with bilateral LED placements, including midline, at scalp vertex over left and right supplementary motor areas (L and R SMAs), picture naming was not improved. P1 underwent pre-/postovert, picture-naming task-fMRI scans; P2 could not. After Protocol A, P1 showed increased activation in LH and right hemisphere, including L and R SMAs. After Protocol B with LEDs only on ipsilesional, LH side, naming ability significantly improved for P1 and P2; the fMRI scans for P1 then showed activation only on the ipsilesional LH side. After Protocol C with LED placements on ipsilesional LH side, plus one midline placement over mesial prefrontal cortex (mPFC) at front hairline, a cortical node of the default mode network (DMN), P3 and P4 had only moderate/poor response, and no increase in functional connectivity on resting-state functional-connectivity MRI. After Protocol D, however, with LED placements on ipsilesional LH side, plus over two midline nodes of DMN, mPFC, and precuneus (high parietal) simultaneously, P5 and P6 each had good response with significant increase in functional connectivity within DMN, p < 0.0005; salience network, p < 0.0005; and central executive network, p < 0.05. Conclusions: NIR photons can affect surface brain cortex areas subjacent to where LEDs are applied on the scalp. Improved naming ability was present with optimal Protocol D. Transcranial photobiomodulation may be an additional noninvasive therapy for stroke.

Effectiveness and safety of transcranial laser therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial-2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke. METHODS: This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score. RESULTS: We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P=0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of <16 showed a favorable outcome at 90 days on the primary end point (P<0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively. CONCLUSIONS: TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned.

High prevalence of unrecognized cerebral infarcts in first-ever stroke patients with cardioembolic sources.

BACKGROUND: With magnetic resonance imaging (MRI) analysis, we investigated the prevalence, clinical significance, and factors related to the presence of unrecognized cerebral infarcts in patients with first-ever ischaemic stroke. METHODS: We consecutively included patients who were admitted with first-ever stroke. Unrecognized cerebral infarct was defined as an ischaemic infarction or primary intracerebral hemorrhage on MRI irrelevant to the index stroke, without acute lesions on diffusion-weighted image. RESULTS: Of the total 203 patients, 78 (39.4%) patients were observed as having unrecognized cerebral infarct. Patients with high-risk cardioembolic sources (e.g., atrial fibrillation) more frequently had unrecognized stroke than those without (P = 0.008, 21/36 [58.3%] vs. 57/167 [34.1%]). On univariate analysis, male sex (P = 0.027) and cardioembolic source (P = 0.008) were associated with the presence of unrecognized cerebral infarcts. After adjustment for gender, age and risk factors, the presence of cardioembolic sources independently increased the risk of unrecognized cerebral infarct (P = 0.002, odds ratio 3.56, 95% confidence interval 1.58-8.02). Regarding clinical outcome at 3 months, the presence of unrecognized cerebral infarct was not associated with the poor clinical outcome. CONCLUSION: In our study, the presence of cardioembolic sources was an independent risk factor for the unrecognized cerebral infarct in patients with first-ever stroke.

Intravenous thrombolysis for acute ischemic stroke: the Malabar experience 2003 to 2008.

We report the 5-year experience with thrombolysis in acute ischemic stroke from a tertiary care hospital in the Malabar region of South India. All stroke patients thrombolyzed with intravenous recombinant tissue plasminogen activator (rt-PA) from May 2003 to May 2008 were studied in an open, non-randomized, prospective study. Of 2,308 ischemic stroke patients admitted, 57 patients (2.5%) were thrombolyzed with rt-PA (age range, 35-78 years: 40 males, 17 females). The time from presentation at the hospital to initiation of thrombolysis ranged from 15 to 120 minutes (median 50 minutes). The dose of rt-PA used was from 0.6 mg/kg to 0.9 mg/kg. At 3 months 29 patients (51%) were functionally independent, with a modified Rankin scale score of 2 or less. Seven patients (12%) died within 3 months; one had an intracerebral hemorrhage (1.7%). The benefit of treatment was seen in all stroke subtypes. We have been able to show that intravenous thrombolysis in acute ischemic stroke is safe, effective and feasible in our part of the world.

Radiotherapy systems using proton and carbon beams.

Radiotherapy using proton beams (proton therapy) is rapidly taking an important role among the techniques used in cancer therapy. At the end of 2007, 65.000 patients had been treated for cancer by proton beams in one of the 34 proton therapy facilities operating in the world. When compared to the now classical IMRT, and for a similar dose to the tumor, proton therapy provides a lower integral dose to the healthy organs surrounding the tumor. It is generally accepted that any reduction of the dose to healthy organs reduces the probability of radiation induced complications and of secondary malignancies. Proton therapy equipment can be obtained today from well established medical equipment companies such as Varian, Hitachi or Mitsubishi. But it is a Belgian company, Ion Beam Applications of Louvain-la-Neuve that is the undisputed leader in this market, with more than 55% of the world installed base. In addition to the now classical proton therapy equipments, using synchrotrons or cyclotrons as accelerators, new solutions have been proposed, claiming to be more compact and less expensive. A small startup company from Boston (Still Rivers) is proposing a very high magnetic field, gantry mounted superconducting synchrocyclotron. The us Company Tomotherapy is working to develop a new accelerator concept invented at Lawrence Livermore National Laboratory: the Dielectric Wall Accelerator. Besides proton beam therapy, which is progressively becoming an accepted part of radiation therapy, interest is growing for another form of radiotherapy using ions heavier than protons. Carbon ions have, even to a higher degree, the ballistic selectivity of protons. In addition, carbon ions stopping in the body exhibit a very high Linear Energy Transfer (LET). From this high LET results a very high Relative Biological Efficiency (RBE). This high RBE allows carbon ions to treat efficiently tumors who are radio-resistant and which are difficult to treat with photons or protons. The largest experience in carbon beam therapy comes from Japan, from the National Institute for Radiation Science (NIRS) in Chiba, where more than 4000 patients have been treated with carbon beams. In Europe, carbon beam therapy has been tested on a limited number of patients in GSI, a national laboratory for heavy ion research in Darmstadt. A clinical carbon therapy center has been developed by GSI and the prototype is located at the German National Cancer Research Center (DKFZ) in Heidelberg. This center (HICAT) is close to being completed, and should treat patients in 2009. Another national carbon therapy facility is under construction in Pavia (Italy), and is build by a group of Italian physics laboratories. Siemens has obtained the intellectual rights of the GSI design in Heidelberg, and has sold two other carbon therapy systems in Germany, one in Marburg and one in Kiel. All existing systems for carbon therapy use cyclotrons as accelerators. IBA has introduced the innovative concept of using a superconducting cyclotron for the acceleration of carbon ions for radiotherapy. The superconducting cyclotron technology should allow a reduction of the size and cost of carbon therapy facilities.

Infrared laser therapy for ischemic stroke: a new treatment strategy: results of the NeuroThera Effectiveness and Safety Trial-1 (NEST-1).

BACKGROUND AND PURPOSE: The NeuroThera Effectiveness and Safety Trial-1 (NEST-1) study evaluated the safety and preliminary effectiveness of the NeuroThera Laser System in the ability to improve 90-day outcomes in ischemic stroke patients treated within 24 hours from stroke onset. The NeuroThera Laser System therapeutic approach involves use of infrared laser technology and has shown significant and sustained beneficial effects in animal models of ischemic stroke. METHODS: This was a prospective, intention-to-treat, multicenter, international, double-blind, trial involving 120 ischemic stroke patients treated, randomized 2:1 ratio, with 79 patients in the active treatment group and 41 in the sham (placebo) control group. Only patients with baseline stroke severity measured by National Institutes of Health Stroke Scale (NIHSS) scores of 7 to 22 were included. Patients who received tissue plasminogen activator were excluded. Outcome measures were the patients' scores on the NIHSS, modified Rankin Scale (mRS), Barthel Index, and Glasgow Outcome Scale at 90 days after treatment. The primary outcome measure, prospectively identified, was successful treatment, documented by NIHSS. This was defined as a complete recovery at day 90 (NIHSS 0 to 1), or a decrease in NIHSS score of at least 9 points (day 90 versus baseline), and was tested as a binary measure (bNIH). Secondary outcome measures included mRS, Barthel Index, and Glasgow Outcome Scale. Primary statistical analyses were performed with the Cochran-Mantel-Haenszel rank test, stratified by baseline NIHSS score or by time to treatment for the bNIH and mRS. Logistic regression analyses were conducted to confirm the results. RESULTS: Mean time to treatment was >16 hours (median time to treatment 18 hours for active and 17 hours for control). Time to treatment ranged from 2 to 24 hours. More patients (70%) in the active treatment group had successful outcomes than did controls (51%), as measured prospectively on the bNIH (P=0.035 stratified by severity and time to treatment; P=0.048 stratified only by severity). Similarly, more patients (59%) had successful outcomes than did controls (44%) as measured at 90 days as a binary mRS score of 0 to 2 (P=0.034 stratified by severity and time to treatment; P=0.043 stratified only by severity). Also, more patients in the active treatment group had successful outcomes than controls as measured by the change in mean NIHSS score from baseline to 90 days (P=0.021 stratified by time to treatment) and the full mRS ("shift in Rankin") score (P=0.020 stratified by severity and time to treatment; P=0.026 stratified only by severity). The prevalence odds ratio for bNIH was 1.40 (95% CI, 1.01 to 1.93) and for binary mRS was 1.38 (95% CI, 1.03 to 1.83), controlling for baseline severity. Similar results held for the Barthel Index and Glasgow Outcome Scale. Mortality rates and serious adverse events (SAEs) did not differ significantly (8.9% and 25.3% for active 9.8% and 36.6% for control, respectively, for mortality and SAEs). CONCLUSIONS: The NEST-1 study indicates that infrared laser therapy has shown initial safety and effectiveness for the treatment of ischemic stroke in humans when initiated within 24 hours of stroke onset. A larger confirmatory trial to demonstrate safety and effectiveness is warranted.