[Electroacupuncture promotes gastrointestinal motility by activating autophagy of Cajal interstitial cells via downregulating PI3K/Akt/mTOR signaling pathway in stomach of diabetic gastro-paresis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36), "Sanyinjiao" (SP6) and "Liangmen" (ST21) on gastrointestinal motility, blood glucose content and expression of autophagy-related proteins 1 light chain 3 (LC3), p62, phosphatidyli-nositol-3 kinase (PI3K), protein kinase B (Akt), p-Akt and mammalian target protein of rapamycin (mTOR) of interstitial cells of Cajal (ICCs) in the cultured gastric antrum cells in diabetic gastroparesis (DGP) rats, so as to reveal its mechanisms underlying improvement of DGP. METHODS: A total of 45 Sprague Dawley (SD) rats were randomly divided into blank control, model, EA, medication (3-methyladenine, 3-MA) and EA+3-MA groups, with 9 rats in each group. The DGP model was established by intraperitoneal injection of 2% streptozotocin (STZ) combined with high-fat and high sugar diet for 8 weeks. The gastric emptying rate was measured by using gavage of phenol red (to measure the propelling length of the phenol red/total length of small intestine ×100%). The symptom score (mental state, coat color and luster, behavior and activity, stool traits) of rats was observed every week and the blood glucose content was measured by using a glucometer. EA (20 Hz/100 Hz, 2 mA) was applied to unilateral ST36, SP6 and ST21 alternatively for 15 min, once daily, 5 days a week for 3 weeks. Rats of the 3-MA and 3-MA+EA groups received intraperitoneal injection of 3-MA (30 mg·kg-1·d-1, 10 mg/mL), once daily, 5 days a week for 3 weeks. After 15 days' intervention, the rats were operated for gastric emptying rate test, specimen collection, isolation, and culture of primary ICCs. The expression levels of microtubule associated protein LC3, p62, PI3K, Akt, p-Akt and mTOR of ICCs of cultured gastric antrum cells were detected using Western blot, and the number of autophagosomes in ICC of gastric antrum was observed under transmission electron microscope. RESULTS: Compared with the blank control group, the symptom score, blood glucose, and the expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins were increased significantly (P<0.01), while the gastric emptying rate and ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein were significantly decreased (P<0.05, P<0.01) in the model group. In comparison with the model group, the increase of symptom score, blood glucose, and expression levels of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins and the decrease of gastric empty rate and LC3Ⅱ/LC3Ⅰ ratio and the expression level of class Ⅲ PI3K protein were all reversed in both EA and EA+3-MA groups (P<0.05, P<0.01), rather than in the 3-MA group. In addition, 3-MA also reversed modeling-induced increase of class Ⅰ PI3K, Akt, p-Akt and mTOR proteins expression (P<0.01). No significant differences were found between the EA and EA+3-MA in downregulating the levels of symptom score and blood glucose content, and in upregulating gastric empty rate(P>0.05). The effect of EA was notably superior to that of EA+3-MA in upregulating the ratio of LC3Ⅱ/LC3Ⅰ and the expression level of class Ⅲ PI3K protein, and in downregulating the expression of p62, class Ⅰ PI3K, Akt, p-Akt and mTOR proteins (P<0.05, P<0.01). The findings of transmission electron microscopy showed obvious swelling, breakage of some mitochondrial cristae in the ICC cells of antrum and no autophagosomes in the model group and 3-MA group, which was milder in the damage of mitochondrial cristae and marked increase in the autophagosomes in both EA and EA+3-MA groups. CONCLUSION: EA can improve the gastrointestinal motility and symptoms in DGP rats, which may be related to its functions in downregulating PI3K/Akt/mTOR signaling to promote autophagy level of ICC.

Clinical and molecular findings in a Turkish family with an ultra-rare condition, ELP2-related neurodevelopmental disorder.

Elongator is a multi-subunit protein complex bearing six different protein subunits, Elp1 to -6, that are highly conserved among eukaryotes. Elp2 is the second major subunit of Elongator and, together with Elp1 and Elp3, form the catalytic core of this essential complex. Pathogenic variants that affect the structure and function of the Elongator complex may cause neurodevelopmental disorders. Here, we report on a new family with three children affected with a severe form of intellectual disability along with spastic tetraparesis, choreoathetosis, and self injury. Molecular genetic analyses reveal a homozygous missense variant in the ELP2 gene (NM_018255.4 (ELP2): c.1385G > A (p.Arg462Gln)), while in silico studies suggest a loss of electrostatic interactions that may contribute to the overall stability of the encoded protein. We also include a comparison of the patients with ELP2-related neurodevelopmental disorder to those previously reported in the literature. Apart from being affected with intellectual disability, we have extremely limited clinical knowledge about patients harboring ELP2 variants. Besides providing support to the causal role of p.Arg462Gln in ELP2-related neurodevelopmental disorder, we add self-injurious behavior to the clinical phenotypic repertoire of the disease.

Oxygen Cost During Walking in Individuals With Stroke: Hemiparesis Versus Cerebellar Ataxia.

Background. Understanding the factors that limit mobility in stroke patients is fundamental for proposing appropriate rehabilitation strategies. A high oxygen cost during walking (Cw) has a strong impact on the community ambulation of hemiparetic patients. The Cw in poststroke cerebellar ataxia is poorly evaluated, unlike hemiparetic gait. Objective. To compare the oxygen cost/self-selected walking speed (S) relationship in stroke individuals with cerebellar ataxia or hemiparetic gait. Methods. Thirty-three subjects were included (14 cerebellar stroke, 19 hemispheric stroke), with stroke confirmed by brain imaging and able to walk without human assistance. We measured Cw using the Metamax3B. The relationship between Cw and self-selected walking speed was modelled by logistic regression and then compared between the cerebellar and hemispheric groups. Results. No significant difference was found between the 2 groups for all characteristics of the population, except motor impairments, spasticity, and ataxia (P < .01). We identified 2 separate Cw/S relationships with different logistic regression equations for the 2 groups. Faster than 0.4 m s-1, Cw was 30.6% to 39.9% higher in patients with cerebellar stroke in comparison with hemispheric stroke individuals. The Cw was correlated with ataxia (r = 0.88; P < .001) in the cerebellar group, whereas there was a correlation with motor impairments (r = -0.61; P < .01), spasticity (r = 0.59; P < .01), and ataxia (r = 0.81; P < .01) in hemispheric stroke individuals. Conclusion. The Cw in poststroke cerebellar ataxia is significantly higher compared with hemiparetic patients at an equivalent walking speed. The impact on community walking needs to be explored in stroke survivors with cerebellar stroke.

Limb linkage rehabilitation training-related changes in cortical activation and effective connectivity after stroke: A functional near-infrared spectroscopy study.

Stroke remains the leading cause of long-term disability worldwide. Rehabilitation training is essential for motor function recovery following stroke. Specifically, limb linkage rehabilitation training can stimulate motor function in the upper and lower limbs simultaneously. This study aimed to investigate limb linkage rehabilitation task-related changes in cortical activation and effective connectivity (EC) within a functional brain network after stroke by using functional near-infrared spectroscopy (fNIRS) imaging. Thirteen stroke patients with either left hemiparesis (L-H group, n = 6) and or right hemiparesis (R-H group, n = 7) and 16 healthy individuals (control group) participated in this study. A multichannel fNIRS system was used to measure changes in cerebral oxygenated hemoglobin (delta HbO2) and deoxygenated hemoglobin (delta HHb) in the bilateral prefrontal cortices (PFCs), motor cortices (MCs), and occipital lobes (OLs) during (1) the resting state and (2) a motor rehabilitation task with upper and lower limb linkage (first 10 min [task_S1], last 10 min [task_S2]). The frequency-specific EC among the brain regions was calculated based on coupling functions and dynamic Bayesian inference in frequency intervals: high-frequency I (0.6-2 Hz) and II (0.145-0.6 Hz), low-frequency III (0.052-0.145 Hz), and very-low-frequency IV (0.021-0.052 Hz). The results showed that the stroke patients exhibited an asymmetric (greater activation in the contralesional versus ipsilesional motor region) cortical activation pattern versus healthy controls. Compared with the healthy controls, the stroke patients showed significantly lower EC (p < 0.025) in intervals I and II in the resting and task states. The EC from the MC and OL to the right PFC in interval IV was significantly higher in the R-H group than in the control group during the resting and task states (p < 0.025). Furthermore, the L-H group showed significantly higher EC from the MC and OL to the left PFC in intervals III and IV during the task states compared with the control group (p < 0.025). The significantly increased influence of the MC and OL on the contralesional PFC in low- and very-low-frequency bands suggested that plastic reorganization of cognitive resources severed to compensate for impairment in stroke patients during the motor rehabilitation task. This study can serve as a basis for understanding task-related reorganization of functional brain networks and developing novel assessment techniques for stroke rehabilitation.

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis.

OBJECTIVES: Interleukin-21 (IL-21) is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis (AP) in two distinct clinical phases. Initially, a systemic inflammatory response syndrome may be followed by systemic sepsis from infected pancreatic necrosis, known as the "second hit." The expression and possible role of IL-21 in AP has not been established. METHODS: Thirty-six patients with mild, moderate, and severe AP (SAP) were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21. RESULTS: Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared with both the mild and control patient groups. At the protein level, IL-21 was elevated in SAP patients compared with those with mild pancreatitis, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic SAP patients and patients with pancreatic necrosis. CONCLUSIONS: Interleukin-21 is transiently elevated in SAP compared with the mild/moderate group, and hence IL-21 may contribute to the immune imbalance that occurs in AP.

Reorganization of Destabilized Nodes of Ranvier in ßIV Spectrin Mutants Uncovers Critical Timelines for Nodal Restoration and Prevention of Motor Paresis.

Disorganization of nodes of Ranvier is associated with motor and sensory dysfunctions. Mechanisms that allow nodal recovery during pathological processes remain poorly understood. A highly enriched nodal cytoskeletal protein ßIV spectrin anchors and stabilizes the nodal complex to actin cytoskeleton. Loss of murine ßIV spectrin allows the initial nodal organization, but causes gradual nodal destabilization. Mutations in human ßIV spectrin cause auditory neuropathy and impairment in motor coordination. Similar phenotypes are caused by nodal disruption due to demyelination. Here we report on the precise timelines of nodal disorganization and reorganization by following disassembly and reassembly of key nodal proteins in ßIV spectrin mice of both sexes before and after ßIV spectrin re-expression at specifically chosen developmental time points. We show that the timeline of nodal restoration has different outcomes in the PNS and CNS with respect to nodal reassembly and functional restoration. In the PNS, restoration of nodes occurs within 1 month regardless of the time of ßIV spectrin re-expression. In contrast, the CNS nodal reorganization and functional restoration occurs within a critical time window; after that, nodal reorganization diminishes, leading to less efficient motor recovery. We demonstrate that timely restoration of nodes can improve both the functional properties and the ultrastructure of myelinated fibers affected by long-term nodal disorganization. Our studies, which indicate a critical timeline for nodal restoration together with overall motor performance and prolonged life span, further support the idea that nodal restoration is more beneficial if initiated before any axonal damage, which is critically relevant to demyelinating disorders.SIGNIFICANCE STATEMENT Nodes of Ranvier are integral to efficient and rapid signal transmission along myelinated fibers. Various demyelinating disorders are characterized by destabilization of the nodal molecular complex, accompanied by severe reduction in nerve conduction and the onset of motor and sensory dysfunctions. This study is the first to report in vivo reassembly of destabilized nodes with sequential improvement in overall motor performance. Our study reveals that nodal restoration is achievable before any axonal damage, and that long-term nodal destabilization causes irreversible axonal structural changes that prevent functional restoration. Our studies provide significant insights into timely restoration of nodal domains as a potential therapeutic approach in treatment of demyelinating disorders.

Changes in spectroscopic biomarkers after transcranial direct current stimulation in children with perinatal stroke.

BACKGROUND: Perinatal stroke causes lifelong motor disability, affecting independence and quality of life. Non-invasive neuromodulation interventions such as transcranial direct current stimulation (tDCS) combined with intensive therapy may improve motor function in adult stroke hemiparesis but is under-explored in children. Measuring cortical metabolites with proton magnetic resonance spectroscopy (MRS) can inform cortical neurobiology in perinatal stroke but how these change with neuromodulation is yet to be explored. METHODS: A double-blind, sham-controlled, randomized clinical trial tested whether tDCS could enhance intensive motor learning therapy in hemiparetic children. Ten days of customized, goal-directed therapy was paired with cathodal tDCS over contralesional primary motor cortex (M1, 20 min, 1.0 mA, 0.04 mA/cm2) or sham. Motor outcomes were assessed using validated measures. Neuronal metabolites in both M1s were measured before and after intervention using fMRI-guided short-echo 3T MRS. RESULTS: Fifteen children [age(range) = 12.1(6.6-18.3) years] were studied. Motor performance improved in both groups and tDCS was associated with greater goal achievement. After cathodal tDCS, the non-lesioned M1 showed decreases in glutamate/glutamine and creatine while no metabolite changes occurred with sham tDCS. Lesioned M1 metabolite concentrations did not change post-intervention. Baseline function was highly correlated with lesioned M1 metabolite concentrations (N-acetyl-aspartate, choline, creatine, glutamate/glutamine). These correlations consistently increased in strength following intervention. Metabolite changes were not correlated with motor function change. Baseline lesioned M1 creatine and choline levels were associated with clinical response. CONCLUSIONS: MRS metabolite levels and changes may reflect mechanisms of tDCS-related M1 plasticity and response biomarkers in hemiparetic children with perinatal stroke undergoing intensive neurorehabilitation.

D-dimer levels and cerebral infarction in critically ill cancer patients.

BACKGROUND: D-dimer levels have been used in the diagnosis of a variety of thrombosis-related diseases. In this study, we evaluated whether measuring D-dimer levels can help to diagnose cerebral infarction (CI) in critically ill cancer patients. METHODS: We retrospectively evaluated all cancer patients who underwent brain magnetic resonance imaging (MRI) between March 2010 and February 2014 at the medical oncology intensive care unit (ICU) of Samsung Medical Center. Brain MRI scanning was performed when CI was suspected due to acute neurological deficits. We compared D-dimer levels between patients ultimately diagnosed as having or not having CI and analyzed diffusion-weighted imaging (DWI) lesion patterns. RESULTS: A total of 88 patients underwent brain MRI scanning due to clinical suspicion of CI; altered mental status and unilateral hemiparesis were the most common neurological deficits. CI was ultimately diagnosed in 43 (49%) patients. According to the DWI patterns, multiple arterial infarctions (40%) were more common than single arterial infarctions (9%). Cryptogenic stroke etiologies were more common (63%) than determined etiologies. There was no significant difference in D-dimer levels between patients with and without CI (P = 0.319). Although D-dimer levels were not helpful in diagnosing CI, D-dimer levels were associated with cryptogenic etiologies in critically ill cancer patients; D-dimer levels were higher in the cryptogenic etiology group than in the determined etiology group or the non-infarction group (P = 0.001). In multivariate analysis, elevated D-dimer levels (> 8.89 µg/mL) were only associated with cryptogenic stroke (adjusted OR 5.46; 95% confidence interval, 1.876-15.857). CONCLUSIONS: Abnormal D-dimer levels may support the diagnosis of cryptogenic stroke in critically ill cancer patients.

Neuromuscular Electrical Stimulation and Anabolic Signaling in Patients with Stroke.

INTRODUCTION: Stroke results in limited ability to produce voluntary muscle contraction and movement on one side of the body, leading to further muscle wasting and weakness. Neuromuscular electrical stimulation is often used to facilitate involuntary muscle contraction; however, the effect of neuromuscular electrical stimulation on muscle growth and strengthening processes in hemiparetic muscle is not clear. This study examined the skeletal muscle anabolic response of an acute bout of neuromuscular electrical stimulation in individuals with chronic stroke and healthy older adults. METHODS: Eleven individuals (59.8 ± 2.7 years old) were divided into a chronic stroke group (n = 5) and a healthy older adult control group (n = 6). Muscle biopsies were obtained before and after stimulation from the vastus lateralis of the hemiparetic leg for the stroke group and the right leg for the control group. The neuromuscular electrical stimulation protocol consisted of a 60-minute, intermittent stimulation train at 60 Hz. Phosphorylation of mammalian target of rapamycin and ribosomal protein S6 kinase beta-1 were analyzed by Western blot. FINDINGS: An acute bout of neuromuscular electrical stimulation increased phosphorylation of mammalian target of rapamycin (stroke: 56.0%; control: 51.4%; P = .002) and ribosomal protein S6 kinase beta-1 (stroke: 131.2%; control: 156.3%; P = .002) from resting levels to post-neuromuscular electrical stimulation treatment, respectively. Phosphorylated protein content was similar between stroke and control groups at both time points. CONCLUSION: Findings suggest that paretic muscles of patients with chronic stroke may maintain ability to stimulate protein synthesis machinery in response to neuromuscular electrical stimulation.

Postnatal Development of Spasticity Following Transgene Insertion in the Mouse ßIV Spectrin Gene (SPTBN4).

BACKGROUND: The L25 mouse line was generated by random genomic insertion of a lens-specific transgene. Inbreeding of L25 hemizygotes revealed an unanticipated spastic phenotype in the hind limbs. OBJECTIVE: The goals were to characterize the motor phenotype in the L25 mice and to map the transgene insert site within the mouse genome. METHODS: Six pairs of L25+/- mice were repeatedly mated. Beginning at weaning, all progeny were inspected for body weight and motor signs twice weekly until they displayed predefined ethical criteria for termination. The transgene insert site was determined by whole genome sequencing. Western blotting was used to compare the expression levels of beta-IV spectrin protein in the brain. RESULTS: Matings of hemizygous L25+/- × L25+/- mice yielded 20% (29/148) affected weanlings, identified by an abnormal retraction of the hind limbs when lifted by the tail, and a fine tremor. Affected mice were less mobile and grew more slowly than wild-type littermates. All affected mice required termination due to >15% loss of body weight (50% survival age 92 days). At the endpoint, mice showed varying degrees of spastic paresis or spastic paralysis localised to the hind limbs. Motor endplates remained fully innervated. Genome sequencing confirmed that the transgene was inserted in the locus of ßIV spectrin of L25 mice. Western blotting indicated that this random insertion had greatly reduced the expression of ßIV spectrin protein in the affected L25 mice. CONCLUSIONS: The results confirm the importance of ßIV spectrin for maintaining central motor pathway control of the hind limbs, and provide a developmental time course for the phenotype.

Longer-term impact of hemiparetic stroke on skeletal muscle metabolism-A pilot study.

BACKGROUND: Hemiparetic stroke leads to structural and metabolic alterations of skeletal muscle tissue, thereby contributing to functional impairment associated with stroke. In situ metabolic processes at tissue level in skeletal muscle have not been investigated. We hypothesize that muscular metabolic capacity is limited after hemiparetic stroke, and that changes affect rather the paretic than non-paretic limb. METHODS: Nine male hemiparetic stroke survivors (age, 62±8years; BMI, 28±4kg/m2; median stroke latency, 23months ranging from 7 to 34months poststroke) underwent dynamic in situ measurements of carbohydrate and lipid metabolism at fasting condition and during oral glucose tolerance testing, using bilateral microdialysis. Results were compared to 8 healthy male subjects of similar age and BMI. RESULTS: Tissue perfusion, fasting and postprandial profiles of interstitial metabolites glucose, pyruvate, lactate and glycerol did not differ between paretic and non-paretic muscle. Patients displayed higher fasting and postprandial dialysate glycerol levels compared to controls (P<0.001) with elevated plasma FFA (fasting FFA; 0.63±0.23 vs. 0.29±0.17mmol/L; P=0.004). Glycolytic activity was higher in patients vs. controls, with increased lactate production upon glucose load (P<0.001). CONCLUSIONS: An elevated lipolytic and glycolytic activity on tissue level suggests an impaired substrate metabolism with blunted oxidative metabolism in bilateral skeletal muscle in patients after hemiparetic stroke. Muscular metabolic properties did not differ between paretic and non-paretic leg. Further work is needed to investigate the clinical impact of this impaired muscular metabolic capacity in post-stroke patients.

A natural product inhibits the initiation of α-synuclein aggregation and suppresses its toxicity.

The self-assembly of α-synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson's disease and related conditions.

Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder of upper and lower motor neurons. Mutations in the gene encoding the nuclear matrix protein Matrin 3 have been found in familial cases of ALS, as well as autosomal dominant distal myopathy with vocal cord and pharyngeal weakness. We previously found that spinal cord and muscle, organs involved in either ALS or distal myopathy, have relatively lower levels of Matrin 3 compared to the brain and other peripheral organs in the murine system. This suggests that these organs may be vulnerable to any changes in Matrin 3. In order to determine the role of Matrin 3 in these diseases, we created a transgenic mouse model for human wild-type Matrin 3 using the mouse prion promoter (MoPrP) on a FVB background.We identified three founder transgenic lines that produced offspring in which mice developed either hindlimb paresis or paralysis with hindlimb and forelimb muscle atrophy. Muscles of affected mice showed a striking increase in nuclear Matrin 3, as well as the presence of rounded fibers, vacuoles, nuclear chains, and subsarcolemmal nuclei. Immunoblot analysis of the gastrocnemius muscle from phenotypic mice showed increased levels of Matrin 3 products migrating at approximately 120 (doublet), 90, 70, and 55 kDa. While there was no significant change in the levels of Matrin 3 in the spinal cord in the phenotypic mice, the ventral horn contained individual cells with cytoplasmic redistribution of Matrin 3, as well as gliosis. The phenotypes of these mice indicate that dysregulation of Matrin 3 levels is deleterious to neuromuscular function.

Práctica mental en la rehabilitación de pacientes con ictus. Una revisión sistemática / Mental practice in the rehabilitation of stroke patients. A systematic review

Objetivo. Realizar una revisión sistemática de la literatura para conocer la efectividad de la imaginería motora o práctica mental como tratamiento de pacientes con ictus en la recuperación motora del miembro superior e inferior. Estrategia de búsqueda. Se realizó una búsqueda sistemática de artículos científicos publicados, tanto en inglés como en castellano, desde octubre del 2012 hasta diciembre del 2014. Se evaluó la calidad metodológica mediante la escala de Jadad. Selección de los estudios. Se incluyeron un total de 12 artículos. La calidad metodológica de los estudios fue muy pobre en general. Solo cuatro artículos superaron la puntuación 3/5 en la escala Jadad. Síntesis de resultados. Se observó una gran heterogeneidad en la duración y en el número de participantes. El tiempo de tratamiento osciló entre los 5 y las 54 semanas. El tamaño muestral de los estudios estuvo comprendido de media entre 9 y 42 individuos. Los individuos incluidos en los trabajos presentaban hemiparesia, pudiendo afectar esta tanto a miembro superior como inferior, en una fase subaguda o crónica de la enfermedad. Conclusiones. La mayoría de los trabajos incluidos apenas detallaron los parámetros de las intervenciones. En aquellas publicaciones en las que se especificaron, el tiempo de duración por sesión osciló entre 15-20 minutos; con una frecuencia de tratamiento de tres días a la semana durante una media de cuatro semanas; en relación con el tipo de instrucciones, estas fueron principalmente auditivas y visuales; finalmente, el orden de aplicación de la terapia fue variable en relación con la terapia física convencional. Existieron elementos que no se especificaron como el número de ensayos por sesión, el tipo de imaginería empleada, el contexto o la localización de las sesiones (AU)

Objective. To conduct a systematic review of the literature to determine the effectiveness of motor imagery and mental practice as a treatment of patients with stroke for motor recovery of the upper and lower limb. Search strategy. We conducted a systematic search of scientific articles published in both English and Spanish from October 2012 to December 2014. Methodological quality was evaluated using the Jadad scale. Study selection. A total of 12 items were included. The methodological quality of the studies was generally poor. Only four articles exceeded a score of 3/5 on the Jadad scale. Synthesis of the results. There was wide heterogeneity in treatment duration and the number of participants. The treatment time ranged from 5 to 54 weeks. The average sample size of the studies included was between 9 and 42 individuals. Included individuals had hemiparesis, which could affect both the upper and lower limbs in the subacute and chronic phases. Conclusions. Most of the included studies did not describe the parameters of the interventions. In those that did specify them, the duration of each session was between 15 and 20 minutes, with a treatment frequency of three days per week for an average of four weeks. Instructions were auditory and visual. The order of application of the therapy varied in relation to conventional physical therapy. Numerous elements were not specified, such as the number of trials per session, the kind of imagery, and the context or location of the sessions (AU)

Glucose Uptake Is Decreased in Affected Lower Leg Muscles of Hemiparetic Persons during Level Walking.

Stroke patients suffer from gait disturbance due to altered leg muscle actions. Many kinesiological studies have investigated muscle actions, but the metabolic activity of muscles in stroke patients remains to be investigated. We therefore evaluated energy consumption in lower extremity muscles during level walking in hemiparetic individuals. Glucose uptake was measured by positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) in eight hemiparetic (mean age: 56 years) and 11 healthy (mean age: 26 years) participants. Standardized uptake ratio (SUR) was computed in each muscle to express the (18)F-FDG-uptake level. SUR was compared across gluteal, thigh, and lower leg muscles and across individual muscles within each muscle group. For each muscle, SUR was compared among the paretic limb of hemiparetic participants, the non-paretic limb of hemiparetic participants, and the right limb of healthy participants. In paretic limbs, mean SUR did not differ between the three muscle groups, or between individual muscles within each muscle group. SURs of paretic lower leg muscles and gluteus minimus muscle were significantly smaller than those of non-paretic limb and healthy participants (p < 0.05). In the non-paretic limb of hemiparetic participants, SUR of the lower leg muscles was larger than that of the thigh muscles (p < 0.05). Unexpectedly, SURs of medial hamstring and posterior tibial muscles were larger in the non-paretic limb of hemiparetic participants, compared to the right limb of healthy participants (p < 0.05). (18)F-FDG PET is useful to evaluate energy consumption levels of lower extremity muscles during level walking in hemiparetic individuals.

Tractografía en fenómeno de Kernohan: presentación de un caso de hematoma subdural agudo / Tractography in Kernohan’s phenomenon: report of a case of acute subdural haematoma

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Resting Energy Expenditure in Patients with Stroke during the Subacute Phases - Relationships with Stroke Types, Location, Severity of Paresis, and Activities of Daily Living.

BACKGROUND: The energy demands in patients with stroke during the subacute phases are unclear. However, this information is essential for appropriate clinical and nutritional management. The aims of this study were to determine the resting energy expenditure (REE) during the subacute phases, examine its relationships with stroke types, location, severity of hemiparesis, and activities of daily living (ADL), and evaluate whether estimation of REE from the Harris-Benedict equation (HB) requires the addition of a 'stress factor' to capture possible additional REE imposed by stroke. METHODS: We measured REE in 95 patients with subacute stroke (53.5 ± 16.6 days post-stroke) with indirect calorimetry, and compared it with predicted values of energy expenditure estimated from the HB (expressed as percentage). Patients were admitted for rehabilitation of their first ischemic or nonsurgical hemorrhagic stroke. The severity of hemiparesis was assessed with the motor items of the Stroke Impairment Assessment Set (SIAS). The ADL was assessed with the Functional Independence Measure (FIM). We compared REE and %HB of the two groups divided by hemiparesis severity and ADL limitation using the Student's t-test, and those of the five groups divided by stroke location. The correlations between REE and the motor items of the SIAS and the FIM score were assessed with the Spearman rank correlation test. A multiple regression analysis for REE was conducted. RESULTS: The average body weight (BW) was 57.1 ± 11.3 kg. The average body mass index (BMI) was 22.5 ± 4.0. The mean REE (%HB) was 1,271 ± 284 kcal/day (106.0 ± 17.3%). REE and %HB of the low ADL group was less than that of the high ADL group (p < 0.05). The REE had a positive correlation with the FIM score (rs = 0.51, p < 0.01). The motor items of the SIAS were not significantly correlated with REE. BW, FIM, and stroke location were independent predictors of REE. CONCLUSIONS: Analysis of energy expenditure suggests that stroke patients are not hypermetabolic during the subacute phase. The 'stress factor' in stroke patients during the subacute phase was 1.0-1.1. This finding provides important information for improving nutritional management during the subacute phase in patients with stroke.

Use of an ankle-foot orthosis improves aerobic capacity in subacute hemiparetic stroke patients.

OBJECTIVE: To investigate aerobic capacity with and without an ankle-foot orthosis (AFO) in subacute hemiparetic stroke patients. DESIGN: Prospective crossover intervention study. SETTING: Rehabilitation clinic in secondary care. PATIENTS: Patients diagnosed with first-ever cerebral stroke involving the cortical or subcortical area resulting in hemiparesis (n = 15, 8 men and 7 women; average age, 62.1 years). METHODS: All subjects participated in 2 continuous, symptom-limited, low-velocity graded treadmill exercise stress tests under 2 different conditions, namely, with and without an AFO. The rest interval between tests was at least 48 hours. The order of exercise stress tests was randomized. MAIN OUTCOME MEASUREMENTS: To assess cardiorespiratory responses, oxygen consumption, heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and respiratory exchange ratio were measured continuously throughout the test, and peak values were obtained. The rating of perceived exertion was recorded immediately after each test. The percentage of the age-predicted maximal heart rate and total exercise duration were also measured. Gait function was assessed by the Six-Minute Walk Test. RESULTS: Using an AFO significantly increased peak oxygen consumption and Six-Minute Walk Test results. Peak values of each of heart rate, systolic blood pressure, diastolic blood pressure, rate-pressure product, and respiratory exchange ratio, rating of perceived exertion, percentage of age-predicted maximal heart rate, and total exercise duration were similar regardless of AFO use. CONCLUSIONS: Use of an AFO may improve aerobic capacity in subacute hemiparetic stroke patients, and may improve energy efficiency and gait endurance.

Widespread sequence variations in VAMP1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins.

Botulinum neurotoxins (BoNT/A-G), the most potent toxins known, act by cleaving three SNARE proteins required for synaptic vesicle exocytosis. Previous studies on BoNTs have generally utilized the major SNARE homologues expressed in brain (VAMP2, syntaxin 1, and SNAP-25). However, BoNTs target peripheral motor neurons and cause death by paralyzing respiratory muscles such as the diaphragm. Here we report that VAMP1, but not VAMP2, is the SNARE homologue predominantly expressed in adult rodent diaphragm motor nerve terminals and in differentiated human motor neurons. In contrast to the highly conserved VAMP2, BoNT-resistant variations in VAMP1 are widespread across vertebrates. In particular, we identified a polymorphism at position 48 of VAMP1 in rats, which renders VAMP1 either resistant (I48) or sensitive (M48) to BoNT/D. Taking advantage of this finding, we showed that rat diaphragms with I48 in VAMP1 are insensitive to BoNT/D compared to rat diaphragms with M48 in VAMP1. This unique intra-species comparison establishes VAMP1 as a physiological toxin target in diaphragm motor nerve terminals, and demonstrates that the resistance of VAMP1 to BoNTs can underlie the insensitivity of a species to members of BoNTs. Consistently, human VAMP1 contains I48, which may explain why humans are insensitive to BoNT/D. Finally, we report that residue 48 of VAMP1 varies frequently between M and I across seventeen closely related primate species, suggesting a potential selective pressure from members of BoNTs for resistance in vertebrates.

Functional Recovery After Ischemic Stroke Is Associated With Reduced GABAergic Inhibition in the Cerebral Cortex: A GABA PET Study.

BACKGROUND: γ-Aminobutyric acid (GABA) plasticity plays an important role in stroke motor recovery in a mouse model. However, little is known about changes over time in neuronal excitability mediated by GABA receptors in human stroke patients. OBJECTIVES: To establish the mechanism of neuroplasticity during the recovery phase following ischemic stroke by assessing the changes in cerebral GABA activity using [(18)F]flumazenil ([(18)F]FMZ) positron emission tomography (PET). METHODS: A total of 10 patients with unilateral ischemic stroke were studied at 1 month (T0) and 3 months (T1) postonset using [(18)F]FMZ PET. Changes in regional GABAergic activity were assessed longitudinally, and values were also compared with those in 15 age-matched controls. Upper-extremity motor function was evaluated using the Fugl-Meyer score (FMS). RESULTS: During the follow-up period, statistical parametric mapping analysis demonstrated a decrease in GABAA receptor availability throughout the cerebral cortex and cerebellum, especially the contralateral hemisphere. GABAA availability in the bilateral primary motor cortex, contralateral supplemental motor cortex, and globus pallidus at T0 was positively correlated with the FMS score at T1 CONCLUSIONS: This is the first prospective, controlled longitudinal study showing that the change in GABA receptor availability over time is significantly related to motor recovery after stroke in humans. This work supports the rationale for a novel strategy to promote motor recovery after stroke.