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After stroke rehabilitation, many survivors of stroke exhibit persistent gait deficits. In previous work, we demonstrated significant gains in gait kinematics for survivors of chronic stroke using multichannel functional electrical stimulation with intramuscular electrodes (FES-IM). For this study, we tested the feasibility of combining FES-IM and gait robot technologies for treating persistent gait deficits after stroke. Six subjects, >/= 6 months after stroke, received 30-minute intervention sessions of combined FES-IM and gait robotics 4 days a week for 12 weeks. Feasibility was assessed according to three factors: (1) performance of the interface of the two technologies during intervention sessions, (2) clinicians' success in using two technologies simultaneously, and (3) subject satisfaction. FES-IM system hardware and software design features combined with the gait robot technology proved feasible to use. Each technology alone provided unique advantages and disadvantages of gait practice characteristics. Because of the unique advantages and disadvantages of each technology, gait deficits need to be accurately identified and a judicious treatment plan properly targeted before FES-IM, a gait robot, or both combined are selected. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the effect of integrating custom-designed hand therapy video games (HTVG) with contralaterally controlled functional electrical stimulation (CCFES) therapy., Methods: Fifty-two stroke survivors with chronic (>6 months) upper limb hemiplegia were randomized to 12 weeks of CCFES or CCFES + HTVG. Treatment involved self-administration of technology-mediated therapy at home plus therapist-administered CCFES-assisted task practice in the lab. Pre- and post-treatment assessments were made of hand dexterity, upper limb impairment and activity limitation, and cognitive function., Results: No significant between-group differences were found on any outcome measure, and the average magnitudes of improvement within both groups were small. The incidence of technical problems with study devices at home was greater for the CCFES + HTVG group. This negatively affected adherence and may partially explain the absence of effect of HTVG. At end-of-treatment, large majorities of both treatment groups had positive perceptions of treatment efficacy and expressed enthusiasm for the treatments., Conclusion: This study makes an important contribution to the research literature on the importance of environmental factors, concomitant impairments, and technology simplification when designing technology-based therapies intended to be self-administered at home. This study failed to show any added benefit of HTVG to CCFES therapy.Clinicaltrials.gov (NCT03058796).

Objective: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI., Methods: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). CSP characteristics were assessed across biceps (muscle power = 3-5) and triceps (muscle power = 1-3) representing stronger and weaker muscles, respectively. We assessed functional abilities using the Capabilities of the Upper Extremity Test (CUE-T)., Results: Participants with chronic SCI had prolonged CSPs for biceps but delayed and diminished CSPs for triceps compared to able-bodied participants. Early-onset CSPs for biceps and longer, deeper CSPs for triceps correlated with better CUE-T scores., Conclusions: Corticospinal inhibition is pronounced for stronger biceps but diminished for weaker triceps muscle in SCI indicating innervation relative to the level of injury matters in the study of CSP., Significance: Nevertheless, corticospinal inhibition or CSP holds relevance for upper extremity function following SCI., Competing Interests: Conflicts of Interest The authors report no potential conflict of interests., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Study Design: A multisite, randomized, controlled, double-blinded phase I/II clinical trial., Objective: The purpose of this clinical trial is to evaluate the safety, feasibility and efficacy of pairing noninvasive transcranial direct current stimulation (tDCS) with rehabilitation to promote paretic upper extremity recovery and functional independence in persons living with chronic cervical spinal cord injury (SCI)., Setting: Four-site trial conducted across Cleveland Clinic, Louis Stokes Veterans Affairs Medical Center of Cleveland and MetroHealth Rehabilitation Rehabilitation Institute of Ohio, and Kessler Foundation of New Jersey., Methods: Forty-four adults (age ≥18 years) with tetraplegia following cervical SCI that occurred ≥1-year ago will participate. Participants will be randomly assigned to receive anodal tDCS or sham tDCS given in combination with upper extremity rehabilitation for 15 sessions each over 3-5 weeks. Assessments will be made twice at baseline separated by at least a 3-week interval, once at end-of-intervention, and once at 3-month follow-up., Primary Outcome Measure(s): Primary outcome measure is upper extremity motor impairment assessed using the Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) scale. Functional abilities will be assessed using Capabilities of Upper Extremity-Test (CUE-T), while functional independence and participation restrictions will be evaluated using the self-care domain of Spinal Cord Independent Measure (SCIM), and Canadian Occupational Performance Measure (COPM)., Secondary Outcome Measures: Treatment-associated change in corticospinal excitability and output will also be studied using transcranial magnetic stimulation (TMS) and safety (reports of adverse events) and feasibility (attrition, adherence etc.) will also be evaluated., Trial Registration: ClincalTrials.gov identifier NCT03892746. This clinical trial is being performed at four sites within the United States: Cleveland Clinic (lead site), Louis Stokes Cleveland Veterans Affairs Medical Center (VAMC) and MetroHealth Rehabilitation Institute in Ohio, and Kessler Foundation in New Jersey. The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office., (© 2022. The Author(s), under exclusive licence to International Spinal Cord Society.)

The central nervous system (CNS) control of human gait is complex, including descending cortical control, affective ascending neural pathways, interhemispheric communication, whole brain networks of functional connectivity, and neural interactions between the brain and spinal cord. Many important studies were conducted in the past, which administered gait training using externally targeted methods such as treadmill, weight support, over-ground gait coordination training, functional electrical stimulation, bracing, and walking aids. Though the phenomenon of CNS activity-dependent plasticity has served as a basis for more recently developed gait training methods, neurorehabilitation gait training has yet to be precisely focused and quantified according to the CNS source of gait control. Therefore, we offer the following hypotheses to the field: Hypothesis 1. Gait neurorehabilitation after stroke will move forward in important ways if research studies include brain structural and functional characteristics as measures of response to treatment. Hypothesis 2. Individuals with persistent gait dyscoordination after stroke will achieve greater recovery in response to interventions that incorporate the current and emerging knowledge of CNS function by directly engaging CNS plasticity and pairing it with peripherally directed, plasticity-based motor learning interventions. These hypotheses are justified by the increase in the study of neural control of motor function, with emerging research beginning to elucidate neural factors that drive recovery. Some are developing new measures of brain function. A number of groups have developed and are sharing sophisticated, curated databases containing brain images and brain signal data, as well as other types of measures and signal processing methods for data analysis. It will be to the great advantage of stroke survivors if the results of the current state-of-the-art and emerging neural function research can be applied to the development of new gait training interventions., Competing Interests: The authors declare no conflicts of interest.

Gait deficits are often persistent after stroke, and current rehabilitation methods do not restore normal gait for everyone. Targeted methods of focused gait therapy that meet the individual needs of each stroke survivor are needed. Our objective was to develop and test a combination protocol of simultaneous brain stimulation and focused stance phase training for people with chronic stroke (>6 months). We combined Transcranial Direct Current Stimulation (tDCS) with targeted stance phase therapy using Virtual Reality (VR)-assisted treadmill training and overground practice. The training was guided by motor learning principles. Five users (>6 months post-stroke with stance phase gait deficits) completed 10 treatment sessions. Each session began with 30 min of VR-assisted treadmill training designed to apply motor learning (ML)-based stance phase targeted practice. During the first 15 min of the treadmill training, bihemispheric tDCS was simultaneously delivered. Immediately after, users completed 30 min of overground (ML)-based gait training. The outcomes included the feasibility of protocol administration, gait speed, Timed Up and Go (TUG), Functional Gait Assessment (FGA), paretic limb stance phase control capability, and the Fugl−Meyer for lower extremity coordination (FMLE). The changes in the outcome measures (except the assessments of stance phase control capability) were calculated as the difference from baseline. Statistically and clinically significant improvements were observed after 10 treatment sessions in gait speed (0.25 ± 0.11 m/s) and FGA (4.55 ± 3.08 points). Statistically significant improvements were observed in TUG (2.36 ± 3.81 s) and FMLE (4.08 ± 1.82 points). A 10-session intervention combining tDCS and ML-based task-specific gait rehabilitation was feasible and produced clinically meaningful improvements in lower limb function in people with chronic gait deficits after stroke. Because only five users tested the new protocol, the results cannot be generalized to the whole population. As a contribution to the field, we developed and tested a protocol combining brain stimulation and ML-based stance phase training for individuals with chronic stance phase deficits after stroke. The protocol was feasible to administer; statistically and/or clinically significant improvements in gait function across an array of gait performance measures were observed with this relatively short treatment protocol.

Background: Technologies that enhance motor learning-based therapy and are clinically deployable may improve outcome for those with neurological deficits. The MyoPro™ is a customized myoelectric upper extremity orthosis that utilizes volitionally generated weak electromyographic signals from paretic muscles to assist movement of an impaired arm. Our purpose was to evaluate MyoPro as a tool for motor learning-based therapy for individuals with chronic upper limb weakness., Methods: This was a pilot study of thirteen individuals with chronic moderate/severe arm weakness due to either stroke ( n = 7) or TBI ( n = 6) who participated in a single group interventional study consisting of 2 phases. The in-clinic phase included 18 sessions (2x per week, 27hrs of face-to-face therapy) plus a home exercise program. The home phase included practice of the home exercise program. The study did not include a control group. Outcomes were collected at baseline and at weeks 3, 5, 7, 9, 12, 15, and 18. Statistics included mixed model regression analysis., Results: Statistically significant and clinically meaningful improvements were observed on Fugl-Meyer (+7.5 points). Gains were seen at week 3, increased further through the in-clinic phase and were maintained during the home phase. Statistically significant changes in Modified Ashworth Scale, Range of Motion, and Chedoke Arm and Hand Activity Inventory were seen early during the in-clinic phase. Orthotic and Prosthetic User's Survey demonstrated satisfaction with the device throughout study participation. Both stroke and TBI participants responded to the intervention., Conclusions: Use of MyoPro in motor learning-based therapy resulted in clinically significant gains with a relatively short duration of in-person treatment. Further studies are warranted., Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03215771., Competing Interests: The authors disclose the following potential conflict of interest with respect to the research, authorship and or publication of this article: JN is paid consultant with Myomo, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pundik, McCabe, Skelly, Salameh, Naft, Chen, Tatsuoka and Fatone.)

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography-mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT ( p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.

Background: Somatosensory deficits are prevalent after stroke, but effective interventions are limited. Brain stimulation of the contralesional primary somatosensory cortex (S1) is a promising adjunct to peripherally administered rehabilitation therapies., Objective: To assess short-term effects of repetitive transcranial magnetic stimulation (rTMS) targeting contralesional (S1) of the upper extremity., Methods: Using a single-session randomized crossover design, stroke survivors with upper extremity somatosensory loss participated in 3 rTMS treatments targeting contralesional S1: Sham, 5 Hz, and 1 Hz. rTMS was delivered concurrently with peripheral of sensory electrical stimulation and vibration of the affected hand. Outcomes included 2-point discrimination (2PD), proprioception, vibration perception threshold, monofilament threshold (size), and somatosensory evoked potential (SEP). Measures were collected before, immediately after treatment, and 1 hour after treatment. Mixed models were fit to analyze the effects of the 3 interventions., Results: Subjects were 59.8 ± 8.1 years old and 45 ± 39 months poststroke. There was improvement in 2PD after 5-Hz rTMS for the stroke-affected ( F (2, 76.163) = 3.5, P = .035) and unaffected arm ( F (2, 192.786) = 10.6, P < .0001). Peak-to-peak SEP amplitudes were greater after 5-Hz rTMS for N33-P45 ( F (2, 133.027) = 3.518, P = .032) and N45-P60 ( F (2, 67.353) = 3.212, P = .047). Latencies shortened after 5-Hz rTMS for N20 ( F (2, 69.64) = 3.37, P = .04), N60 ( F (2, 47.343) = 4.375, P = .018), and P100 ( F (2, 37.608) = 3.537, P = .039) peaks. There were no differences between changes immediately after the intervention and an hour later., Conclusions: Short-term application of facilitatory high-frequency rTMS (5Hz) to contralesional S1 combined with peripheral somatosensory stimulation may promote somatosensory function. This intervention may serve as a useful adjunct in somatosensory rehabilitation after stroke.

Background: Upper limb motor deficits following traumatic brain injury are prevalent and effective therapies are needed. The purpose of this case report was to illustrate response to a novel therapy using a myoelectric orthosis in a person with TBI. Case description: A 42-year-old female, 29.5 years post-traumatic brain injury with diminished motor control/coordination, and learned nonuse of the right arm. She also had cognitive deficits and did not spontaneously use her right arm functionally., Intervention: Study included three phases: baseline data collection/device fabrication (five weeks); in-clinic training (2×/week for nine weeks); and home-use phase (nine weeks). The orthosis was incorporated into motor learning-based therapy. Outcomes: During in-clinic training, active range of motion, tone, muscle power, Fugl-Meyer, box and blocks test, and Chedoke assessment score improved. During the home-use phase, decrease in tone was maintained and all other outcomes declined but were still better upon study completion than baseline. The participant trained with the orthosis 70.12 h, logging over 13,000 repetitions of elbow flexion/extension and hand open/close., Discussion: Despite long-standing traumatic brain injury, meaningful improvements in motor function were observed and were likely the results of high repetition practice of functional movement delivered over a long duration. Further assessment in a larger cohort is warranted., (© The Author(s) 2020.)

Background: The prevalence of increased muscle tone after stroke is frequently reported as 30% to 40%, and the condition is often concurrent with motor control deficits, manifesting as an inability to isolate paretic-limb joint movements., Objective: The objectives of this retrospective analysis were to 1) report the prevalence of increased muscle tone in a convenience sample of 128 chronic stroke survivors with moderate/severe motor deficits and 2) quantify the relation between tone and motor impairment in chronic stroke survivors., Methods: Analyses included descriptive statistics and multiple regression modeling, with the modified Ashworth Scale score (MAS; tone) as a predictor of isolated joint movement control (Fugl-Meyer score [FM]; motor impairment)., Results: Increased muscle tone was present in 97% of subjects. Increased muscle tone was associated with impaired motor control (FM; upper extremity, P=0.008; lower extremity, P=0.03) after adjusting for age, time since stroke and sex. We found a significant difference between flexor and extensor strength for finger, elbow, hip and knee joints (P<0.002). Participants were classified in high and low MAS score groups. With high MAS score and for muscles of finger flexion and forearm pronation, we found a trend toward impaired strength of antagonist muscles (finger extensors and forearm supinators, respectively) as compared with low MAS score for these same muscle pairings., Conclusions: The prevalence of increased tone was higher in this study than in previous reports. Increased muscle tone in chronic stroke survivors with persistent motor dysfunction could be associated with impaired motor control and differential muscle strength of antagonistic muscles., (Published by Elsevier Masson SAS.)

Background . Effective treatment methods are needed for moderate/severely impairment chronic stroke. Objective . The questions were the following: (1) Is there need for long-dose therapy or is there a mid-treatment plateau? (2) Are the observed gains from the prior-studied protocol retained after treatment? Methods . Single-blind, stratified/randomized design, with 3 applied technology treatment groups, combined with motor learning, for long-duration treatment (300 hours of treatment). Measures were Arm Motor Ability Test time and coordination-function (AMAT-T, AMAT-F, respectively), acquired pre-/posttreatment and 3-month follow-up (3moF/U); Fugl-Meyer (FM), acquired similarly with addition of mid-treatment. Findings . There was no group difference in treatment response ( P ≥ .16), therefore data were combined for remaining analyses (n = 31; except for FM pre/mid/post, n = 36). Pre-to-Mid-treatment and Mid-to-Posttreatment gains of FM were statistically and clinically significant ( P < .0001; 4.7 points and P < .001; 5.1 points, respectively), indicating no plateau at 150 hours and benefit of second half of treatment. From baseline to 3moF/U: (1) FM gains were twice the clinically significant benchmark, (2) AMAT-F gains were greater than clinically significant benchmark, and (3) there was statistically significant improvement in FM ( P < .0001); AMAT-F ( P < .0001); AMAT-T ( P < .0001). These gains indicate retained clinically and statistically significant gains at 3moFU. From posttreatment to 3moF/U, gains on FM were maintained. There were statistically significant gains in AMAT-F ( P = .0379) and AMAT-T P = .003.

Individuals with stroke are often left with persistent upper limb dysfunction, even after treatment with traditional rehabilitation methods. The purpose of this retrospective study is to demonstrate feasibility of the implementation of an upper limb myoelectric orthosis for the treatment of persistent moderate upper limb impairment following stroke (>6 months)., Methods: Nine patients (>6 months post stroke) participated in treatment at an outpatient Occupational Therapy department utilizing the MyoPro myoelectric orthotic device. Group therapy was provided at a frequency of 1-2 sessions per week (60-90 minutes per session). Patients were instructed to perform training with the device at home on non-therapy days and to continue with use of the device after completion of the group training period. Outcome measures included Fugl-Meyer Upper Limb Assessment (FM) and modified Ashworth Scale (MAS)., Results: Patients demonstrated clinically important and statistically significant improvement of 9.0±4.8 points (p = 0.0005) on a measure of motor control impairment (FM) during participation in group training. It was feasible to administer the training in a group setting with the MyoPro, using a 1:4 ratio (therapist to patients). Muscle tone improved for muscles with MAS >1.5 at baseline., Discussion: Myoelectric orthosis use is feasible in a group clinic setting and in home-use structure for chronic stroke survivors. Clinically important motor control gains were observed on FM in 7 of 9 patients who participated in training., Competing Interests: Myomo provided an unrestricted grant to support a statistician. There are no other known competing interests on behalf of the authors. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Somatosensory function is critical to normal motor control. After stroke, dysfunction of the sensory systems prevents normal motor function and degrades quality of life. Structural neuroplasticity underpinnings of sensory recovery after stroke are not fully understood. The objective of this study was to identify changes in bilateral cortical thickness (CT) that may drive recovery of sensory acuity., Methods: Chronic stroke survivors (n = 20) were treated with 12 weeks of rehabilitation. Measures were sensory acuity (monofilament), Fugl-Meyer upper limb and CT change. Permutation-based general linear regression modeling identified cortical regions in which change in CT was associated with change in sensory acuity., Results: For the ipsilesional hemisphere in response to treatment, CT increase was significantly associated with sensory improvement in the area encompassing the occipital pole, lateral occipital cortex (inferior and superior divisions), intracalcarine cortex, cuneal cortex, precuneus cortex, inferior temporal gyrus, occipital fusiform gyrus, supracalcarine cortex, and temporal occipital fusiform cortex. For the contralesional hemisphere, increased CT was associated with improved sensory acuity within the posterior parietal cortex that included supramarginal and angular gyri. Following upper limb therapy, monofilament test score changed from 45.0 ± 13.3 to 42.6 ± 12.9 mm ( P = .063) and Fugl-Meyer score changed from 22.1 ± 7.8 to 32.3 ± 10.1 ( P < .001)., Conclusions: Rehabilitation in the chronic stage after stroke produced structural brain changes that were strongly associated with enhanced sensory acuity. Improved sensory perception was associated with increased CT in bilateral high-order association sensory cortices reflecting the complex nature of sensory function and recovery in response to rehabilitation.

Purpose: This study compared a novel self-management (TargetEd MAnageMent Intervention [TEAM]) versus treatment as usual (TAU) to reduce stroke risk in African American (AA) men., Design: Six-month prospective randomized controlled trial with outcomes evaluated at baseline, 3 months, and 6 months., Setting: Academic health center., Participants: Thirty-eight (age < 65) AA men who had a stroke or transient ischemic attack and a Barthel index score of >60 were randomly assigned to TEAM (n = 19) or TAU (n = 19)., Intervention: Self-management training, delivered in 1 individual and 4 group sessions (over 3 months)., Measures: Blood pressure, glycosylated hemoglobin (HbA 1c ), lipids, medication adherence, weight, and standardized measures of health behaviors (diet, exercise, smoking, substances), depression, and quality of life. Qualitative assessments evaluated the perspectives of TEAM participants., Analysis: T tests for paired differences and nonparametric tests. Thematic content qualitative analysis., Results: Mean age was 52.1 (standard deviation [SD] = 7.4) and mean body mass index was 31.4 (SD = 7.4). Compared to TAU, TEAM participants had significantly lower mean systolic blood pressure by 24 weeks, and there was also improvement in HbA 1c and high-density lipoprotein cholesterol ( P = .03). Other biomarker and health behaviors were similar between groups. Qualitative results suggested improved awareness of risk factors as well as positive effects of group support.

Background: Previous research on Uganda's poststroke population revealed that their level of dietary salt knowledge did not lead to healthier consumption choices., Purpose: Identify barriers and motivators for healthy dietary behaviors and evaluate the understanding of widely accepted salt regulation mechanisms among poststroke patients in Uganda., Methods: Convergent parallel mixed methods triangulation design comprised a cross-sectional survey (n = 81) and 8 focus group discussions with 7-10 poststroke participants in each group. We assessed participant characteristics and obtained insights into their salt consumption attitudes, perceptions, and knowledge. Qualitative responses were analyzed using an inductive approach with thematic analytic procedures. Relationships between healthy dietary salt compliance, dietary salt knowledge, and participant characteristics were assessed using logistic regression analyses., Results: Healthy dietary salt consumption behaviors were associated with basic salt knowledge (P < .0001), but no association was found between compliance and salt disease-related knowledge (P = .314). Only 20% and 7% obtained health-related salt knowledge from their health facility and educational sources, respectively, whereas 44% obtained this information from media personalities; 92% of participants had no understanding of nutrition labels, and only 25% of the study population consumed potash-an inexpensive salt substitute that is both rich in potassium and low in sodium., Conclusion: One barrier to healthy dietary consumption choices among Uganda's stroke survivors is a lack of credible disease-related information. Improving health-care provider stroke-related dietary knowledge in Uganda and encouraging the use of potash as a salt substitute would help reduce hypertension and thereby lower the risk of stroke., (Copyright © 2017 National Stroke Association. All rights reserved.)

Objective: We assessed 24-hour urine sodium levels as an index of dietary salt consumption and its association with dietary salt knowledge and hypertension among poststroke patients with and without a history of hypertension in Uganda., Methods: A case-control study in which poststroke patients with a history of hypertension (cases, n = 123) were compared to poststroke patients without known hypertension (controls, n = 112). Dietary salt intake was assessed by 24-hour urine sodium, a valid measure of dietary salt consumption. Dietary salt knowledge was determined by questionnaire. The independent relationships among salt knowledge, 24-hour urine sodium, and blood pressure control were assessed using multiple regression analysis., Results: High 24-hour urine sodium (≥8.5 g/d) was 2 times more prevalent among hypertensive poststroke patients than controls (p = 0.002). Patients with minimal poststroke disability who had a choice in determining their diets had higher urine sodium than their more disabled counterparts. Only 43% of the study population had basic dietary salt knowledge, 39% had adequate diet-disease-related knowledge, and 37% had procedural knowledge (report of specific steps being taken to reduce salt consumption). Dietary salt knowledge was similarly poor among cases and controls (p = 0.488) and was not related to education level (p = 0.205)., Conclusions: High urine sodium and high salt-diet preferences were more frequent among poststroke hypertensive patients in Uganda than in their nonhypertensive counterparts. There was, however, no difference in dietary salt knowledge between these groups. The development of educational strategies that include salt-diet preferences may lead to better blood pressure control in this high-risk population., (© 2016 American Academy of Neurology.)

Objective: Noninvasive brain stimulation (NIBS) can augment functional recovery following stroke; however, the technique lacks regulatory approval. Low enrollment in NIBS clinical trials is a key roadblock. Here, we pursued evidence to support the prevailing opinion that enrollment in trials of NIBS is even lower than enrollment in trials of invasive, deep brain stimulation (DBS)., Methods: We compared 2 clinical trials in stroke conducted within a single urban hospital system, one employing NIBS and the other using DBS, (1) to identify specific criteria that generate low enrollment rates for NIBS and (2) to devise strategies to increase recruitment with guidance from DBS., Results: Notably, we found that enrollment in the NIBS case study was 5 times lower (2.8%) than the DBS trial (14.5%) (χ(2) = 20.815, P < .0001). Although the number of candidates who met the inclusion criteria was not different (χ(2) = .04, P < .841), exclusion rates differed significantly between the 2 studies (χ(2) = 21.354, P < .0001). Beyond lack of interest, higher exclusion rates in the NIBS study were largely due to exclusion criteria that were not present in the DBS study, including restrictions for recurrent strokes, seizures, and medications., Conclusions: Based on our findings, we conclude and suggest that by (1) establishing criteria specific to each NIBS modality, (2) adjusting exclusion criteria based on guidance from DBS, and (3) including patients with common contraindications based on a probability of risk, we may increase enrollment and hence significantly impact the feasibility and generalizability of NIBS paradigms, particularly in stroke., (Copyright © 2016 National Stroke Association. All rights reserved.)

Background: Information regarding the increasing burden of non-communicable diseases such as stroke is largely unknown among the vulnerable communities. This analysis, which is part of a larger U.S. National Institute of Heath-funded Medical Education Partnership Initiative neurological disorder survey, assessed community knowledge and attitudes on stroke and stroke risk factors., Methods: A population cross-sectional survey was conducted in urban and rural Mukono, district, central Uganda. Through the systematic sampling method, data were gathered from 377 adult participants who were interviewed about selected aspects of stroke knowledge, attitudes and perception using a pretested structured questionnaire., Results: A total of 377 participants were enrolled (47% urban). The leading risk factors identified by the participants were stress (36.6%) and hypertension (28.9%) respectively. None of the study participants identified cigarette smoking as a stroke risk factor. Seventy six percent of the participants did not recognize stroke as a disease of the brain., Conclusion: Stroke knowledge is poor in both rural and urban Uganda. Tailored public health approaches that improve stroke awareness, knowledge and self management approaches are urgently needed to develop effective preventive measures and community response to stroke.

Objectives: Neuroplastic changes that drive recovery of shoulder/elbow function after stroke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors., Methods: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI) for the shoulder/elbow components of reach and a skilled motor function test (Arm Motor Abilities Test, AMAT), collected before and after treatment., Results: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was a linear relationship between greater functional gain (AMAT) and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke., Conclusions: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e., increase or decrease in task-related brain recruitment) for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases of recovery or different patterns of neuroplasticity that drive functional recovery.

Objective: To assess perceived facilitators and recommendations for stroke recovery and prevention among younger African-American (AA) men (age < 65 years) in order to inform the development and pilot testing of an intervention for this high-risk group., Methods: Focus group methodology was used to collect data from 10 community-dwelling AA stroke survivors and seven of their care partners (CPs) (N = 17). Thematic analysis of session transcripts and the constant comparative method were used to generate themes., Results: Participants cited facilitators to post-stroke care and recovery as Family Support, Stress Reduction, and Dietary Changes. Specific person-level recommendations for AA men included following established stroke guidelines, use of complementary and alternative medicine, and never give up recovery efforts. Community-level recommendations included making a list of community resources available, providing support and education to care partners, using videos that feature AA men to deliver information and use AA men stroke survivors to help disseminate the information. Provider and health system recommendations included consolidation of medical bills, improving provider communication skills, and making providers aware of needs specific to AA men and their families., Conclusions: While AA men and their CPs acknowledged and welcomed learning more about the American Health Association Stroke Prevention Guidelines, it is clear that they desired approaches that addressed their specific needs and preferences as young AA men who sometimes felt de-valued by their community and care providers. Specific person, community and care-system level approaches that are of perceived value to AA men offer potential to improve health outcomes and reduce health disparities.

Objective: To compare response to upper-limb treatment using robotics plus motor learning (ML) versus functional electrical stimulation (FES) plus ML versus ML alone, according to a measure of complex functional everyday tasks for chronic, severely impaired stroke survivors., Design: Single-blind, randomized trial., Setting: Medical center., Participants: Enrolled subjects (N=39) were >1 year postsingle stroke (attrition rate=10%; 35 completed the study)., Interventions: All groups received treatment 5d/wk for 5h/d (60 sessions), with unique treatment as follows: ML alone (n=11) (5h/d partial- and whole-task practice of complex functional tasks), robotics plus ML (n=12) (3.5h/d of ML and 1.5h/d of shoulder/elbow robotics), and FES plus ML (n=12) (3.5h/d of ML and 1.5h/d of FES wrist/hand coordination training)., Main Outcome Measures: Primary measure: Arm Motor Ability Test (AMAT), with 13 complex functional tasks; secondary measure: upper-limb Fugl-Meyer coordination scale (FM)., Results: There was no significant difference found in treatment response across groups (AMAT: P≥.584; FM coordination: P≥.590). All 3 treatment groups demonstrated clinically and statistically significant improvement in response to treatment (AMAT and FM coordination: P≤.009). A group treatment paradigm of 1:3 (therapist/patient) ratio proved feasible for provision of the intensive treatment. No adverse effects., Conclusions: Severely impaired stroke survivors with persistent (>1y) upper-extremity dysfunction can make clinically and statistically significant gains in coordination and functional task performance in response to robotics plus ML, FES plus ML, and ML alone in an intensive and long-duration intervention; no group differences were found. Additional studies are warranted to determine the effectiveness of these methods in the clinical setting., (Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Enhanced activation in the non-lesion hemisphere in stroke patients was widely observed during movement of the affected upper limb, but its functional role related to motor planning and execution is still unknown.This study was to characterize the activation in the non-lesion hemisphere during movement planning and execution by localizing sources of high-density electroencephalography (EEG) signal and estimating the source strength (current density [A/m]).Ten individuals with chronic stroke and shoulder/elbow coordination deficits and 5 healthy controls participated in the study.EEG (64 channels) was recorded from scalp electrodes while the subjects performed a reach task involving shoulder flexion and elbow extension of the affected (patients) or dominant (controls) upper extremity. Sources of the EEG were obtained and analyzed at 17 time points across movement preparation and execution phases. A 3-layer boundary element model was overlaid and used to identify the brain activation sources. A distributed current density model, low-resolution electromagnetic tomography (LORETA) L1 norm method, was applied to the data pre-processed by independent component analysis.Subjects with stroke had stronger source strength in the sensorimotor cortices during the movement compared with the controls. Their contralesional/lesional activation ratio (CTLR) for the primary motor cortices was significantly higher than that of the controls during the movement-planning phase, but not during the execution phase. The CTLR was higher in planning than in the execution phase in the stroke group.Excessive contralesional motor cortical activation appears to be more related to movement preparation rather than execution in chronic stroke.

Background: Neurological disorders are a common cause of morbidity and mortality in sub-Saharan African, but resources for their management are scarce. Collaborations between training institutions in developed and resource-limited countries can be a successful model for supporting specialty medical education and increasing clinical and research capacity., Case Report: This report describes a US National Institutes of Health (NIH) funded Medical Education Partnership Initiative (MEPI) to enhance expertise in neurology, developed between Makerere University College of Health Sciences in Kampala, Uganda, and Case Western Reserve University School of Medicine in Cleveland, OH, USA. This collaborative model is based on a successful medical education and research model that has been developed over the past two decades. The Ugandan and US teams have accumulated knowledge and 'lessons learned' that facilitate specialty expertise in neurological conditions, which are widespread and associated with substantial disability in resource-limited countries. Strengths of the model include a focus on community health care settings and a strong research component. Key elements include strong local leadership; use of remote technology, templates to standardize performance; shared exchanges; mechanisms to optimize sustainability and of dissemination activities that expand impact of the original initiative. Efficient collaborations are further enhanced by external and institutional support, and can be sequentially refined., Conclusion: Models such as the Makerere University College of Health Sciences - Case Western Reserve University partnership may help other groups initiate collaborative education programmes and establish successful partnerships that may provide the opportunity to expand to other chronic diseases. A benefit of collaboration is that learning is two-directional, and interaction with other international medical education collaborators is likely to be of benefit to the larger global health community.

Background: African Americans (AAs) who experience a first time stroke are younger and have double the stroke rate and more poststroke complications than other Americans., Objective: To assess perceived poststroke care barriers among younger AA men and their care partners (CPs) in order to inform the development of acceptable and effective improvements in poststroke care for this high-risk group., Methods: Ten community-dwelling AA stroke survivors and 7 of their CPs participated in focus groups and advisory board meetings. Survivors had stroke or transient ischemic attack within 1 year and a Barthel Index score ≯60. In focus groups, using a semi-structured interview guide, survivors and CPs identified self-perceived barriers and facilitators to poststroke care. Thematic analysis of session transcripts and the constant comparative method were used to generate themes., Results: Survivor age ranged from 34 to 64 years. Mean Barthel score was 95.5. CPs, all AA women, ranged in age from 49 to 61 years. Five CPs were wives, 1 was a fiancée, and 1 was a niece. Participants cited multiple personal, social, and societal stroke recovery challenges. Although hypertension and smoking risks were acknowledged, stress, depression, posttraumatic stress disorder, anger/frustration, personal identity change, and difficulty communicating unique needs as AA men were more frequently noted. Facilitators included family support, stress reduction, and dietary changes., Conclusions: Younger AA men and their CPs perceive multiple poststroke care barriers. Biological risk reduction education may not capture all salient aspects of health management for AA stroke survivors. Leveraging family and community strengths, addressing psychological health, and directly engaging patients with health care teams may improve care management.

Background. Arm spasticity is a challenge in the care of chronic stroke survivors with motor deficits. In order to advance spasticity treatments, a better understanding of the mechanism of spasticity-related neuroplasticity is needed. Objective. To investigate brain function correlates of spasticity in chronic stroke and to identify specific regional functional brain changes related to rehabilitation-induced mitigation of spasticity. Methods. 23 stroke survivors (>6 months) were treated with an arm motor learning and spasticity therapy (5 d/wk for 12 weeks). Outcome measures included Modified Ashworth scale, sensory tests, and functional magnetic resonance imaging (fMRI) for wrist and hand movement. Results. First, at baseline, greater spasticity correlated with poorer motor function (P = 0.001) and greater sensory deficits (P = 0.003). Second, rehabilitation produced improvement in upper limb spasticity and motor function (P < 0.0001). Third, at baseline, greater spasticity correlated with higher fMRI activation in the ipsilesional thalamus (rho = 0.49, P = 0.03). Fourth, following rehabilitation, greater mitigation of spasticity correlated with enhanced fMRI activation in the contralesional primary motor (r = -0.755, P = 0.003), premotor (r = -0.565, P = 0.04), primary sensory (r = -0.614, P = 0.03), and associative sensory (r = -0.597, P = 0.03) regions while controlling for changes in motor function. Conclusions. Contralesional motor regions may contribute to restoring control of muscle tone in chronic stroke.

Purpose: Recovery of the most basic shoulder-flexion/elbow-extension components of functional reach is critical for effective arm function following stroke. In order to understand the mechanisms of motor recovery, it is important to characterize the pattern of brain activation during the reach task., Methods: We evaluated 11 controls and 23 moderately to severely impaired chronic stroke survivors (>6 months), with impaired shoulder flexion and elbow extension. Measures were acquired for Arm Motor Ability Test (AMAT) and functional Magnetic Resonance Imaging (fMRI) during the basic shoulder/elbow reach., Results: First, in controls, lateralization of fMRI signal during the reach task was less pronounced in comparison to other tasks, and even further diminished after stroke (p < 0.05). Second, for the stroke group, centroid locations, for specific ipsilesional (contralateral to working limb) motor-sensory regions and for contralesional (ipsilateral to working arm) somatosensory and SMA regions, were significantly more distant from the centroid location of average healthy controls (p < 0.05). Third, both greater activation volume and greater degree of signal intensity were correlated with better motor function in stroke survivors., Conclusions: These findings can be useful in guiding the development of more targeted brain training methods for recovery of impaired reach coordination.

Purpose: Intensive gait training can produce improvements in gait and function (> 6 months after stroke); findings are mixed for enhanced life role participation. Therefore, it is unclear if improved gait and function translate into life role participation gain. Our objective was to evaluate whether intensive gait therapy can produce significant improvements in life role participation for chronic stroke survivors., Methods: In conjunction with a clinical gait training trial, we conducted a secondary analysis for a 44-member cohort with stroke (>6 months). Gait training interventions included exercise, body weight supported treadmill training (BWSTT), over-ground gait training, and functional electrical stimulation (FES) for 1.5 h/day, 4 days/wk for 12 weeks. Study measures included Tinetti Gait (TG) (gait impairment), Functional Independence Measure (FIM, function), Stroke Impact Scale Subscale of Life Role Participation (SISpart), and Craig Handicap Assessment & Reporting Technique (CHART, life-role participation). Analyses included Wilcoxon Signed Rank Test and PLUM Regression Model., Results: Gait interventions produced significant improvement in CHART (p = 0.020), SISpart (p = 0.011), FIM (p < 0.0001), and Tinetti Gait (p < 0.0001). Age, gender and time since stroke did not predict response to treatment., Conclusions: Intensive, multi-modal, long-duration gait therapy resulted in significant gain in life-role participation, according to a relatively comprehensive, homogeneous measure.

Objective: To investigate the functional connection between motor cortex and muscles, we measured electroencephalogram-electromyogram (EEG-EMG) coherence of stroke patients and controls., Methods: Eight healthy controls and 21 patients with shoulder and elbow coordination deficits were enrolled. All subjects performed a reaching task involving shoulder flexion and elbow extension. EMG of the anterior deltoid (AD) and brachii muscles (BB, TB) and 64-channel scalp EEG were recorded during the task. Time-frequency coherence was calculated using the bivariate autoregressive model., Results: Stroke patients had significantly lower corticomuscular coherence compared with healthy controls for the AD and BB muscles at both the beta (20-30 Hz) and lower gamma (30-40 Hz) bands during the movement. BH procedure (FDR) identified a reduced corticomuscular coherence for stroke patients in 11 of 15 scalp area-muscle combinations. There was no statistically significant difference between stroke patients and control subjects according to coherence in other frequency bands., Conclusion: Poorly recovered stroke survivors with persistent upper-limb motor deficits exhibited significantly lower gamma-band corticomuscular coherence in performing a reaching task., Significance: The study suggests poor brain-muscle communication or poor integration of the EEG and EMG signals in higher frequency band during reaching task may reflect an underlying mechanism producing movement deficits post-stroke.

Neuroprotective properties of ketosis may be related to the upregulation of hypoxia inducible factor (HIF)-1alpha, a primary constituent associated with hypoxic angiogenesis and a regulator of neuroprotective responses. The rationale that the utilization of ketones by the brain results in elevation of intracellular succinate, a known inhibitor of prolyl hydroxylase (the enzyme responsible for the degradation of HIF-1alpha) was deemed as a potential mechanism of ketosis on the upregulation of HIF-1alpha. The neuroprotective effect of diet-induced ketosis (3 weeks of feeding a ketogenic diet), as pretreatment, on infarct volume, after reversible middle cerebral artery occlusion (MCAO), and the upregulation of HIF-1alpha were investigated. The effect of beta-hydroxybutyrate (BHB), as a pretreatment, via intraventricular infusion (4 days of infusion before stroke) was also investigated following MCAO. Levels of HIF-1alpha and Bcl-2 (anti-apoptotic protein) proteins and succinate content were measured. A 55% or 70% reduction in infarct volume was observed with BHB infusion or diet-induced ketosis, respectively. The levels of HIF-1alpha and Bcl-2 proteins increased threefold with diet-induced ketosis; BHB infusions also resulted in increases in these proteins. As hypothesized, succinate content increased by 55% with diet-induced ketosis and fourfold with BHB infusion. In conclusion, the biochemical link between ketosis and the stabilization of HIF-1alpha is through the elevation of succinate, and both HIF-1alpha stabilization and Bcl-2 upregulation play a role in ketone-induced neuroprotection in the brain.

fMRI has been used to characterize the abnormal brain activity after stroke during attempted motor tasks, the change in brain activity accompanying spontaneous motor recovery, and response to interventions. However, many patients after stroke exhibit abnormally high effort during attempted movements, including undesired movements of the supposed quiescent, uninvolved limb, which could confound fMRI measures. We developed a method of identifying the potentially confounded scans, using EMG measures of muscle activity in the supposed quiescent limb. We found that there was no interference in the MRI signal from the EMG data acquisition system, during simultaneous use of both MRI and EMG. For EMG signal acquisition, as expected, we were able to identify EMG signal free of MRI noise contamination during the inter-scan interval between any given scan and its subsequent scan. We tested movement of the involved limb. We determined that when undesired muscle activation was present in the uninvolved, supposed quiescent limb, there was an over-estimation of the number of active voxels ranging from 10 to 11, depending upon the ROI.

Background: The elderly have significantly higher incidence of ischemic stroke and have higher mortality and morbidity compared with younger patients. Intracranial hemorrhage (ICH) after thrombolysis is one of the causes of unfavorable outcome. However, it is unclear whether age over 80 years is a predictor for hemorrhagic transformation after intravenous, intra-arterial, or a combination of both thrombolytic therapies., Methods: A database of 488 consecutive patients with ischemic stroke who received thrombolytic therapy was analyzed using logistic regression model to determine whether factors such as age over 80 years, demographic characteristics, onset to treatment time, severity of neurologic deficits, route of administration, blood glucose, or mean arterial pressure were associated with symptomatic ICH., Results: The rates of symptomatic hemorrhage were 12.82% and 10.4% in older and younger groups, respectively. The odds of symptomatic hemorrhage after thrombolytic therapy for patients over 80 years of age after adjusting for route of administration, National Institutes of Health Stroke Scale score, mean arterial pressure, and glucose was not significantly different from that of the younger age group (odds ratio [OR] = 1.64; 95% confidence interval [CI]: 0.729-3.66). Hyperglycemia (>150 mg/dL) was associated with increased odds of symptomatic ICH (OR = 2.32; 95% CI: 1.09-4.93). Patients older than 80 years had similar rates of recanalization (OR = 0.8; 95% CI: 0.4-1.8) and rates of asymptomatic ICH (OR = 2.40; 95% CI: 0.89-6.5)., Conclusions: Risks of ICH after thrombolysis for acute ischemic stroke are similar in patients over and under 80 years of age. Our data suggest that the decision to provide thrombolytic therapy should not be solely based on patient's age.

Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine several end-points to determine if the metabolic stress affects the developing brain. The uterine artery and uterine branch of the ovarian artery were occluded with aneurysm clamps for a period of 45 min, the clips removed and the metabolites in five regions of the perinatal brain were measured at 0, 2 and 6 h of reflow. Regional P-creatine, ATP and glucose levels were significantly depleted at the end of the 45 min occlusion. The levels of glycogen and glutamate at the end of the occlusion indicated a decreasing trend which was not significant. The concentration of citrate remained essentially unchanged at the end of the occlusion. To ensure that the insult was not lethal to the tissue, the recovery of the metabolites was examined at 2 and 6 h of reflow and generally the concentrations of the high-energy phosphates and glucose were normal or near-normal by 6 h of reperfusion in the five regions of the brain examined. The changes in the metabolites indicate that 45 min of hypoxia/ischemia is an appropriate model for studying neonatal development after fetal metabolic stress.

Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra. SD was elicited in one group of rats by injecting KCl directly into a frontal craniectomy and the wave of depolarization was recorded in two craniectomies 3 and 6 mm posterior to the first one. In a second group, the middle cerebral artery was occluded using the monofilament technique and a recording electrode was placed 5 mm lateral to the midline and 0.2 mm posterior to bregma. To determine the metabolic response in the penumbral region of the cortex ipsilateral to the occlusion, brains from both groups were frozen in situ when the deflection of the SD was maximal. The spatial metabolic response of SD in the ischemic cortex was compared to that in the non-ischemic cortex. Coronal sections of the brains were lyophilized, pieces of the dorsolateral cortex were dissected and weighed, and analyzed for ATP, P-creatine, inorganic phosphate (Pi), glucose, glycogen and lactate at varying distances anterior and posterior to the recording electrode. ATP and P-creatine levels were significantly decreased at the wavefront in both groups and the levels recovered after passage of the wavefront in the normal brain, but not in the ischemic brain. Glucose and glycogen levels were significantly decreased and lactate levels significantly increased in the tissue after the passage of the wavefront. While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex. SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised. Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra.

The regional energy status and the availability of metabolic substrates during brain development are important, since a variety of fetal metabolic insults have been increasingly implicated in the evolution of neonatal brain disorders. The response of the brain to a metabolic insult is determined, in large part, by the ability to utilize the various substrates for intermediary metabolism in order to maintain energy stores within the tissue. To ascertain if metabolic conditions of the fetal brain make it more or less vulnerable to a stress, the high-energy phosphates and glucose-related compounds were examined in five regions of the embryonic day 18 (E-18) fetal brain. Glucose and glycogen levels in the E-18 fetal brain were generally higher in the cerebellum and its neuroepithelium than in the hippocampus, cerebral cortex, and its neuroepithelium. Regional lactate and high-energy phosphate concentrations were essentially the same in the five regions. Subsequently, the metabolic profile was examined in the cerebral cortex and striatum from E-18, postpartum day 7 (P-7) and adult rats. At the various stages of development, there were only minimal differences in the high-energy phosphate levels in the striatum and cortex. Glucose levels, the primary substrate in the adult brain, were essentially unchanged throughout development. In contrast, lactate was significantly elevated by 6- and 2-fold over those in the adult brain in the E-18 and P-7 striatum and cortex, respectively. Another alternative substrate, beta-hydroxybutyrate, was also significantly elevated at E-18 and increased more than 2-fold at P-7, but was barely detectable in the adult cortex and striatum. Finally, glucose and lactate levels were examined in cerebrospinal fluid, blood, and brain from the E-18 brain to determine if a gradient among the compartments exists. The levels of both lactate and glucose exhibited a concentration gradient in the E-18 fetus: blood > cerebrospinal fluid > brain parenchyma. The results indicate that energy state in the fetal brain is comparable to that in the neonates and the adults, but that the availability of alternative substrates for intermediary metabolism change markedly with development. The age-dependent substrate specificity for intermediary metabolism could affect the response of the fetal brain to a metabolic insult.

Reperfusion injury is believed to contribute to the pathophysiology of ischemic cell death, but the precipitating factors have yet to be completely elucidated. The goal of this study was to examine if reflow-induced secondary energy failure is a component in the events that lead to cell death following increasing periods of middle cerebral artery (MCA) occlusion in Wistar rats. Discrete sections within the MCA distribution were dissected and analyzed for high-energy phosphates and glucose. Regional cerebral blood flow was determined by [14C]-iodoantipyrine technique in representative groups. The levels of ATP + P-creatine were initially depressed at the end of the focal ischemia and the concentrations in the penumbra were unchanged for up to 8 h after 2 h of ischemia which contrasts with response in the ischemic core, striatum, and penumbra where the HEP generally recovered to values near those of control only to decrease with increasing periods of reflow. The possibility of a rebound ischemia in secondary energy failure (SEF) was precluded by regional CBF values and concentrations of glucose that were significantly higher than the threshold for an ischemic effect. The depletion of cellular energy stores following SEF strongly indicates that the evolution of infarct during reflow results from loss of ATP and its synthesis.

We studied the intracellular pH in rat cerebral cortex of rats subjected to reversible total cerebral ischemia by cardiac arrest and resuscitation. Brain acidoses was more pronounced during ischemia in hyperglycemic rats (6.21 +/- 0.14) than in normoglycemic rats (6.56 +/- 0.07). Brain tissue lactate accumulated proportionally. Nevertheless, within 5 min of reperfusion, pHi in both normoglycemic and hyperglycemic groups had recovered to baseline levels, i.e. near 7.1-7.2, despite the fact that lactate concentrations were still elevated. These results demonstrate a rapid reversal of ischemic acidosis during recovery from 10 min of cardiac arrest, and suggest that acidosis, per se, may not be responsible for neuronal damage following cardiac arrest and resuscitation, even in hyperglycemic conditions.

Tissue acidosis is believed to be a key element in ischemic injury of neural tissue. The goal of this study was to determine whether persisting postischemic acidosis or the extent of acidosis would affect metabolic recovery following an ischemic event. Intracellular pH (pHi), adenosine triphosphate, phosphocreatine, and lactate levels were measured in the cerebral cortex during the early stages of reperfusion, following either 5 or 10 minutes of global ischemia in both normo- and hyperglycemic gerbils. A total of 130 gerbils were injected with a solution containing 1.5 ml Neutral Red (1%) (+/- 2.5 gm/kg glucose); 30 minutes later, the gerbils were placed under halothane anesthesia, and the carotid arteries were occluded for either 5 or 10 minutes. The brains were frozen in liquid nitrogen at 0, 15, 30, 60, and 120 seconds after reperfusion; they were sectioned and the block face was photographed to determine the pHi by using Neutral Red histophotometry. At the conclusion of the ischemia, the pHi in all groups had decreased significantly from a control value of 7.05 +/- 0.03) (mean +/- standard error of the mean). In normoglycemic brains, the pHi values fell to 6.71 +/- 0.04 and 6.68 +/- 0.11 after 5 and 10 minutes of ischemia, respectively. Hyperglycemic brains were more acidotic; values fell to 6.57 +/- 0.10 and 6.52 +/- 0.24 after 5 and 10 minutes of ischemia, respectively. Lactate levels were approximately fivefold greater than those of control tissue in normoglycemic brains, while lactate levels in hyperglycemic brains were increased eightfold. The adenosine triphosphate and phosphocreatine levels were depleted at the end of ischemia in all groups. After 2 minutes of reflow activity, the pHi levels in both normo- and hyperglycemic brains were restored to those of control values in the '5-minute ischemic group, while the pHi levels remained significantly depressed in the 10-minute ischemic group. Restoration of high-energy phosphates was similar in normoglycemic brains regardless of ischemic duration, recovering to only 20% of the restoration obtained in control tissue at 2 minutes. In hyperglycemic brains, however, there was complete recovery of high-energy phosphates by 2 minutes of reflow activity following 5 minutes of ischemia. Extending the ischemic period to 10 minutes in hyperglycemic brains slowed the rate of metabolic recovery to that observed in normoglycemic brains. The results indicate that the reflow period permits the rapid restoration of pHi levels substantially before the normalization of primary energetic compounds.(ABSTRACT TRUNCATED AT 400 WORDS)