Clinical Paralysis Research Articles

Consecutive Transcutaneous and Epidural Spinal Cord Neuromodulation to Modify Clinical Complete Paralysis—the Proof of Concept

ObjectiveTo evaluate the effect of transcutaneous (tSCS) and epidural electrical spinal cord stimulation (EES) in facilitating volitional movements, balance, and nonmotor functions, in this observational study, tSCS and EES were consecutively tested in 2 participants with motor complete spinal cord injury (SCI). Participants and MethodsTwo participants (a 48-year-old woman and a 28-year-old man), both classified as motor complete spinal injury, were enrolled in the study. Both participants went through a unified protocol, such as an initial electrophysiological assessment of neural connectivity, consecutive tSCS and EES combined with 8 wks of motor training with electromyography (EMG) and kinematic evaluation. The study was conducted from May 1, 2019, to December 31, 2021. ResultsIn both participants, tSCS reported a minimal improvement in voluntary movements still essential to start tSCS-enabled rehabilitation. Compared with tSCS, following EES showed immediate improvement in voluntary movements, whereas tSCS was more effective in improving balance and posture. Continuous improvement in nonmotor functions was found during tSCS-enabled and then during EES-enabled motor training. ConclusionResults report a significant difference in the effect of tSCS and EES on the recovery of neurologic functions and support consecutive tSCS and EES applications as a potential therapy for SCI. The proposed approach may help in selecting patients with SCI responsive to neuromodulation. It would also help initiate neuromodulation and rehabilitation therapy early, particularly for motor complete SCI with minimal effect from conventional rehabilitation.

An Analysis of Respiratory Muscle Paralysis of Adult Patients in Guillain-Barré Syndrome: A Retrospective Analysis.

Respiratory muscle paralysis is known as a very common complication of Guillain-Barré syndrome (GBS). However, most research has focused on its later stages rather than its earlier stages, including the prognosis of patients with this condition, or factors that act as early predictors of risk. Therefore, our study aimed to identify early predictors of respiratory muscle paralysis in patients with GBS and determine the short-term prognosis of such patients. We recruited 455 GBS patients (age ≥ 18) who had been hospitalized in the First Affiliated Hospital of Harbin Medical University between 2016 and 2021, retrospectively. We recorded clinical and laboratory data and used linear and logistic regression analysis to investigate the relationship between early clinical, examination results, and subsequent respiratory muscle paralysis. Among the 455 patients, 129 were assigned to a respiratory muscle paralysis group and 326 were assigned to a non-respiratory muscle paralysis group. Compared with the non-affected group, the time from onset to admission was shorter (p = 0.0003), and the Medical Research Council (MRC) score at admission and discharge was smaller in the affected group (p < 0.0001). Compared with the non-affected group, the affected group had higher Hughes and Erasmus GBS Respiratory Insufficiency Score (EGRIS) scores at admission and longer hospital stays (p < 0.0001). Patients in the affected group were more likely to have bulbar palsy and lung infections (p < 0.0001). To conclude, bulbar palsy, a higher EGRIS score and Hughes score at admission, a lower MRC score, and a shorter time between onset and admission, are all predictive risk factors for respiratory muscle paralysis in patients with GBS. An increase in any of these factors increases the risk of muscle paralysis. Patients with respiratory muscle paralysis have a poorer short-term prognosis than those without respiratory muscle paralysis. Therefore, we should attempt to identify patients with one or more of these characteristics in the early stages of admission, provide ventilation management, and administer IMV treatment if necessary.

The Effect of Climate on the Dose Requirements of Botulinum Toxin A in Cosmetic Interventions.

Botulinum toxin A to the glabella is a popular cosmetic intervention. Functional musculature differences may arise from chronic behavioral adjustment to high sun exposure levels, requiring greater doses. This could affect clinical practice globally. This study investigated the effect of climate on real-world doses. The authors conducted a comparative cohort study using data from a registry from a single provider practicing across two centers: the United Kingdom and Malta. They classified one center as low sun exposure (United Kingdom winter month treatment) and the other as high sun exposure (Malta summer months). Patients were followed up once every 3 weeks and received top-up doses until full clinical paralysis was achieved. To standardize the comparison, the study included only women aged 35 to 60 years undergoing glabellar botulinum toxin treatment by experienced clinicians following standard procedures from 2012 to 2019. Smokers, those not seeking maximal paralysis, those documented as not compliant with posttreatment advice, those with colds or fevers, and those with broken cold supply chains were excluded. Univariable and multivariable analyses were undertaken. A total of 523 patients were included: 292 "high-sun" patients and 231 "low-sun" patients. Mean total doses were significantly higher in the high-sun group (29.2 units versus 27.3 units; P = 0.0031). When correcting for age in multivariable analysis, the low-sun group still had lower total dose requirements ( P = 0.00574). Patients injected with glabellar botulinum toxin in high-sun climates may have significantly increased dose requirements to achieve maximal paralysis. Therapeutic, III.

Nutrition during extracorporeal life support: A review of pathophysiological bases and application of guidelines.

Patients on extracorporeal life support (ECLS), either for respiratory or cardiac support, are at high risk of malnutrition; guidelines on nutrition in critical care have not incorporated solid evidence regarding these settings. The aim of this narrative review is to gather the available evidence in the existing literature and transpose general principles to the ECLS population. A literature review of observational and interventional studies on nutrition during ECLS, and evaluation of nutrition guidelines in this perspective. Nutrition is paramount for improving outcomes in ECLS, as well as in critically ill patients. The caloric needs during ECLS can vary according to the severity of the clinical state, sedation, paralysis, and temperature stability. Precise evaluation of energy expenditure by indirect calorimetry is difficult because ECLS is a system dedicated to removing carbon dioxide; however, modified equations composed of carbon dioxide values taken from the membrane lung are available. Guidelines suggest starting early enteral nutrition (EN) with a hypocaloric (70%-80% of the needs) strategy, also in acute states such as septic or cardiogenic shock. Moreover, EN, despite previous concerns, is feasible in prone position, an increasingly adopted strategy during mechanical ventilation. The catabolic state is maximal in these patients, causing a protein and muscular reduction. Therefore, adequate protein delivery should be guaranteed by administering a high protein intake of up to 2g/kg/day. Studies on nutrition tailored to ECLS patients are warranted. Early hypocaloric EN with high protein intake, tailored on indirect calorimetry, may be the most appropriate option.

Detailed features and prognostic factors of twenty-three patients with drop finger caused by cervical radiculopathy: a retrospective multicentre study.

It has been reported that C7 and C8 nerve root impairment can cause drop finger; however, the clinical characteristics of each injured nerve root and post-operative outcomes remain unclear. This study aimed to investigate the detailed features and surgery-related prognostic factors of drop finger caused by cervical radiculopathy. We retrospectively investigated the clinical characteristics, paralysis patterns and surgery-related prognostic factors of 23 patients with drop finger caused by cervical radiculopathy who underwent posterior cervical foraminotomy. We classified paralysis into three patterns based on the fingers predominantly exhibiting extensor digitorum communis (EDC) muscle weakness: index finger side-dominant, middle and ring fingers-dominant and little finger side-dominant. The aetiologies were cervical disc hernia (CDH) in ten patients, cervical spondylotic radiculopathy (CSR) in eight and both CDH and CSR in five. The levels of the decompressed root were C7 in one patient, C8 in 11 and both C7 and C8 in 11. Scapular pain was frequently observed as the initial symptom (78%), especially in patients with only C8 nerve root disorder (91%). Drop finger recovered to a score of ≥ 3 on manual muscle testing in 17 patients; patients with the little finger side-dominant pattern tended to have poor recoveries. Patients with CDH improved significantly than those with CSR or both CDH and CSR (p < 0.05). Good surgical recovery of drop finger can be expected in patients with CDH and in those with index fingers-dominant and middle and ring fingers-dominant patterns.

Improved Assessment of Overall Health in Variably Aged Murine Models of Multiple Sclerosis With a Novel Frailty Index Tool.

The experimental autoimmune encephalomyelitis (EAE) model is the most commonly used animal model of multiple sclerosis (MS). However, phenotypic characterization of mice based on the traditional 5-point clinical paralysis scale does not fully capture disease progression. The frailty index (FI) conceptualizes frailty as the accumulation of health deficits and it is widely used to assess overall health in aging humans and preclinical models. Here, we adapted an established mouse FI tool for use in EAE mice and determined whether this could evaluate general signs of health in variably aged female EAE mice. The EAE-Clinical FI included 34 items related to clinical signs and deficits characteristic of aging and MS. This tool clearly showed more detailed EAE progression and severity at all ages, highlighting changes in systems other than motor paralysis measured with the traditional 5-point paralysis scale. When we induced disease at 3 and 6 months of age, mice showed typical EAE clinical manifestations with peak disease severity between 17 and 19 days post-induction and mean frailty scores of 0.36 ± 0.04 (3-month-old) and 0.43 ± 0.05 (6-month-old). By contrast, disease severity peaked after 14 days in 12-month-old mice. They showed atypical signs including wobbling, early belly drag, and splayed hindlegs that were better captured with the EAE-Clinical FI. Peak frailty scores also were higher than those of younger animals (0.54 ± 0.04). As MS most often develops in young to middle-aged people, this new tool may have significant value for use in EAE animal studies as a first step toward translation to people with MS.

Reactivation Viremia in Pediatric Sepsis.

Reactivation viremia is associated with adverse clinical outcomes and immune dysfunction in adults with sepsis. We determined the incidence of viremia and its association with clinical outcomes and immune paralysis phenotype in children with severe sepsis. Prospective cohort study. Single academic PICU from September 2016 to March 2018. Fifty-nine patients 2-17 years old treated for severe sepsis. None. We performed real-time polymerase chain reaction assays on whole blood specimens to determine the incidence of cytomegalovirus. Cytomegalovirus was detected in three patients (5%). All patients with cytomegalovirus viremia were seropositive, with an incidence of 13% in this subset. We additionally performed Epstein-Barr virus and human herpesvirus-6 polymerase chain reaction assays on last available specimens and detected Epstein-Barr virus in 4% and human herpesvirus-6 in 30% of the study population. Overall, viremia was not associated with clinical outcomes or immune function in univariable analyses. However, viremia was associated with lower odds of complicated course (defined as death within 28 d or ≥ 2 organ dysfunctions at 7 d) after controlling for age, Pediatric Risk of Mortality III score, and blood transfusion (adjusted odds ratio, 0.08; 95% CI, 0.01-0.84; p = 0.04). Children with severe sepsis had low rates of detectable viremia, which limited analyses of its association with clinical outcomes or immune paralysis phenotype. Given the rare occurrence of cytomegalovirus viremia, in particular, our study does not support a role for viremia as a biomarker of illness severity or as a modifiable risk factor of clinical outcomes for most patients. Future studies on the role of viremia in pediatric sepsis will need to consider the challenges posed by low rates of viremia in this population.

Side-to-End Hypoglossal-Facial Neurorrhaphy for Treatment of Complete and Irreversible Facial Paralysis after Vestibular Schwannoma Removal by Means of a Retrosigmoid Approach: A Clinical and Anatomic Study

Facial paralysis secondary to a complete and irreversible anatomic or functional lesion of the facial nerve (FN) causes severe functional and psychological disorders for the patient. A large number of surgical techniques have therefore been developed for FN repair. Our objective was to propose a surgical FN reanimation protocol for patients with irreversible anatomic or functional postsurgical injury of the FN in the cerebellopontine angle after vestibular schwannoma resection. The clinical study included a total of 16 patients undergoing side-to-end hypoglossal-facial neurorrhaphy (SEHFN) since 2010, in which the FN injury was always secondary to vestibular schwannoma surgery in the cerebellopontine angle using a retrosigmoid approach. All patients had complete clinical facial paralysis at the time of the SEHFN. The anatomic study was conducted using 3 heads and necks (6 SEHFN). Twelve months after surgery, FN function assessment with the House and Brackmann scale showed 2 patients with grade II, 13 patients with grade III, and only 1 patient with grade IV, and after 2 years, 4 patients had grade II, 11 patients had grade III, and 1 patient had grade IV. The average length of the anastomotic translocation portion of the FN in the anatomic study was 34.76 mm. Side-to-end epineural suture of the FN, mobilizing its mastoid segment on the hypoglossal nerve with partial section of the dorsal aspect of the hypoglossal nerve, is a safe anatomic surgical technique for FN reanimation with outstanding clinical results.

Post Temporal Bone Fracture Facial Paralysis: Strategies in Decision Making and Analysis of Efficacy of Surgical Treatment

Management of traumatic facial nerve injuries after temporal bone fractures is both challenging and controversial. The dilemma is whether to operate or not and if operating, when to operate and how much of the nerve to decompress. The aim of this study is to review our criteria for decision making in management of patients with temporal bone fracture induced facial nerve palsy, and analyze outcome of patients selected for surgical management. Review of 28 cases of temporal bone fracture between 2012 and 2016 was carried out. Patient assessment included clinical, audiological, computer tomography scans and electromyography (EMG) examinations. All 28 cases were initially started on conservative medical treatment. Based on criteria of complete clinical paralysis at onset, no improvement with conservative treatment and fibrillation potential in EMG, 10 cases underwent surgical decompression through the transmastoid approach. Among the 10 surgically-treated patients, lesions were predominantly found in geniculate ganglion area. Analysis of results after 12months revealed 70% of cases who underwent surgery had House Brackmann (HB) Grade I-II recovery. Good recovery was achieved in all 18 medically treated patients (HB Grade I-II). Candidate selection based on accurate clinical judgment and judicious use of electrodiagnostic tests plays a vital role in outcomes in the treatment of post traumatic facial injury. Early surgical intervention gave better results in our study.

Detection of Newcastle Disease Virus by Immunohistochemistry on the Brains of Laying Birds with Clinical Signs Torticollis and Curled Toe Paralysis

Poultry is one of animal protein sources that have been consumed much in Indonesia. Various of health disorders are caused by environmental changes, woof and infectious agents have caused decline in production and economic loss. One of diseases that have a big impact on poultry husbandry is Newcastle disease (ND). Newcastle disease virus (NDV) is an important disease in Indonesia, because this has spread around Indonesia and caused a big loss for poultry industry moreover, this has high morbidity and mortality and very rapid spread of the virus. The purpose of the research is to find out and determine a fast, exact and accurate, and efficient and effective application immunohistochemistry streptavidin biotin (IHK SB) test on NDV diagnosis affirmation and for NDV fast detection as a cause of disease on commercial laying hens with clinical torticollis and curled toe paralysis symptoms. The samples used in the form of tissues from 20 commercial laying hens with an indication of clinical torticollis and curled toe paralysis symptoms. Brains would be tested using streptavidin biotin. Inspection result data obtained by immunohistochemistry streptavidin biotin (IHK SB) method is analyzed in a descriptive and qualitative way. The result of the research proves that IHK SB coloration, NDV antigen could be detected on brains. Based on the result of the research, it could be concluded that IHK SB could be applied for NDV diagnosis affirmation and it proves that commercial laying hens with clinical torticollis and curled toe paralysis symptoms. Keywords: Newcastle disease virus, immunohistochemistry streptavidin biotin, torticollis, curled toe paralysis

Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine

In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE.

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene.

Objective:To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation.Methods:Twenty-nine Finnish patients identified with the c.3466G>A p.A1156T mutation in the SCN4A gene were extensively examined. In a subsequent study, 63 patients with similar myalgic phenotype and with negative results in myotonic dystrophy type 2 genetic screening (DM2-neg group) and 93 patients diagnosed with fibromyalgia were screened for the mutation. Functional consequences of the p.A1156T mutation were studied in HEK293 cells with whole-cell patch clamp.Results:The main clinical manifestation in p.A1156T patients was not myotonia or periodic paralysis but exercise- and cold-induced muscle cramps, muscle stiffness, and myalgia. EMG myotonic discharges were detected in most but not all. Electrophysiologic compound muscle action potentials exercise test showed variable results. The p.A1156T mutation was identified in one patient in the DM2-neg group but not in the fibromyalgia group, making a total of 30 patients so far identified. Functional studies of the p.A1156T mutation showed mild attenuation of channel fast inactivation.Conclusions:The unspecific symptoms of myalgia stiffness and exercise intolerance without clinical myotonia or periodic paralysis in p.A1156T patients make the diagnosis challenging. The symptoms of milder SCN4A mutations may be confused with other similar myalgic syndromes, including fibromyalgia and myotonic dystrophy type 2.

Evaluation of the dynactin 1 gene in Leonbergers and Labrador Retrievers with laryngeal paralysis

OBJECTIVE To sequence exons and splice consensus sites of the dynactin subunit 1 (DCTN1) gene in Leonbergers and Labrador Retrievers with clinical laryngeal paralysis. ANIMALS 5 unrelated Leonbergers with laryngeal paralysis, 2 clinically normal Leonbergers, 7 unrelated Labrador Retrievers with laryngeal paralysis, and 2 clinically normal Labrador Retrievers. PROCEDURES Primers were designed for the entire coding regions of the DCTN1 gene, a noncoding exon at the 5´ end of the gene, and a 900-bp single-nucleotide polymorphism (SNP)-rich region located 17 kb upstream of the DCTN1 gene by use of the CanFam3 assembly of the canine genome sequence. Sequences were generated and compared between clinically normal and affected dogs. The SNPs flanking the DCTN1 gene as well as a previously identified nonsynonymous SNP in exon 32 were genotyped in affected and clinically normal Leonbergers and Labrador Retrievers. RESULTS None of the affected dogs were homozygous for any mutation affecting coding regions or splicing consensus sequences. Of the 16 dogs tested for the missense SNP in exon 32, all were homozygous for the reference allele, except for 2 affected and 1 clinically normal Labrador Retriever and 1 clinically normal Leonberger. The DCTN1 gene sequences (5 dogs) and haplotypes of polymorphic markers surrounding the DCTN1 gene (all dogs) were not consistent with the hypothesis that laryngeal paralysis was associated with inheritance of the same DCTN1 disease-causing allele within all Labrador Retrievers or Leonbergers evaluated. CONCLUSIONS AND CLINICAL RELEVANCE Mutations in the DCTN1 gene did not appear to cause laryngeal paralysis in Leonbergers or Labrador Retrievers.

Acute compartment syndrome after intramedullary nailing of tibial shaft fracture. Three case reports

Acute compartment syndrome(ACS) is an urgent state in orthopedic surgery, which most often occurs secondarily to tibial shaft fracture. Delayed diagnosis of ACS can lead to very serious complications, including limb inefficiency or amputation. The diagnosis of ACS is based on characteristic clinical signs, like pain, paresthesia, pallor, paralysis, pulsessness, and poikilothermia. In patients with disorted logic contact diagnosis may be difficult and introduction of intercompartmental pressure measurement into diagnostic process may be useful. In this article three clinical cases of acute compartment syndrome after tibial diaphyseal fracture treated with intramedullary reamed locking nail from Departement of Trauma and Orthopedic Surgery will be presented. Profile of those patients fully corresponds to characteristic of patients that are most at risk for this type of complication. All patients were treated with urgent fasciotomy. Additionally, in treatment of wounds after fasciotomy also negative pressure wound therapy system and hyperbaric oxygen therapy were used. The final outcome of patients’ treatment correlates with time elapsed since the onset of symptoms.

Bone metastasis and RANKL

The mice with a disruption of Rank or Rankl exhibit normal mammary development during puberty, but their mammary epithelium fails to proliferate and form lobuloalveolar structures during pregnancy, resulting in the death of newborns. Hormone replacement therapy is associated with an increased risk of breast cancer. Importantly, specific deletion of RANK in mammary epithelium cells prevents both the onset and progression of medroxyprogesterone acetate (MPA) -driven mammary cancer and impairs self-renewal of breast cancer stem cells. Furthermore, RANK is highly expressed in several cancer cells. Functionally, it has been shown that RANKL can stimulate the directed migration of mammary epithelial cells as well as prostate cancer and melanoma cells toward a source of RANKL. In an in vivo metastasis model, OPG reduced the tumor burden in bones and ameliorated clinical paralysis, but did not affect the frequency of the spread of metastases into other tissues. These findings show that the RANK/RANKL system is crucial for mammary development, breast tumorigenesis and bone metastasis.

Does laminoplasty really improve neurological status in patients with cervical spinal cord injury without bone and disc injury? A prospective study about neurological recovery and early complications

Cervical spinal cord injury without bone and disc injury in patients with spinal cord compression is a fairly common problem in Japan. Because elderly Japanese population tend to have cervical spinal canal stenosis. However, there has been no consensus in the treatment of these patients. We conducted a prospective study to evaluate treatment outcomes and complications of these patients. Twenty-five patients had been enrolled in this study. Patients who had paralysis of ASIA impairment scale (AIS) A, B or C were included. With each new patient, we alternated whether he/she received surgical treatment (group S) or conservative treatment (group C). Eleven patients were assigned to each group. We compared the two groups' courses of treatment and complications by evaluating their neurological symptoms using the AIS and ASIA motor score (MS) documenting them at the time of injury and 3months later. The majority of clinical paralysis was found at the C3/4 level for both the groups. According to complications, there were seven urinary tract infections and four pneumonias in group S and one urinary tract infection and three pneumonias in group C. Both groups had an average MS of 42 at the time of injury. Three months later, the average MSs were 59 points in group S and 65 points in group C. In the present study, we found no significant difference in paralysis improvement between surgical and conservative treatment, although we observed a higher frequency of complications with surgery.

Needle electromyography at 1 month predicts paralysis of elbow flexion at 3 months in obstetric brachial plexus lesions

Treatment decisions in obstetric brachial plexus lesions are often based on clinical paralysis of elbow flexion at 3 months of age, when electromyography (EMG) is misleading because motor unit potentials (MUPs) occur in clinically paralytic muscles. We investigated whether EMG at 1 week or 1 month identifies infants with flexion paralysis at 3 months, allowing early referral. Forty-eight infants (27 females, 21 males) were prospectively studied. The presence or absence of flexion paralysis at around 1 week (median 9 d; range 5-17d), 1 month (median 31 d; range 24-53 d), and 3 months of age (median 87 d; range 77-106 d) was noted for clinical (shoulder external rotation, elbow flexion, extension, and supination) and EMG parameters (denervation activity, MUPs and polyphasic MUPs in the deltoid, biceps, and triceps muscles). At 1 month, the absence of biceps MUPs had a sensitivity of 95% for later flexion paralysis, and absence of deltoid MUPs had a sensitivity of 100% for flexion paralysis; the false-positive rates for the same findings were 21% and 33% respectively. EMG at 3 months was highly misleading as MUPs were seen in 19 of 20 clinically paralytic biceps muscles. EMG at 1 month can identify severe cases of flexion paralysis for early referral EMG of the biceps at 3 months is highly misleading; the discrepancy between the EMG and clinical testing may be due to abnormal axonal branching and aberrant central motor control.

IL-5 promotes induction of antigen-specific CD4+CD25+ T regulatory cells that suppress autoimmunity

AbstractImmune responses to foreign and self-Ags can be controlled by regulatory T cells (Tregs) expressing CD4 and IL-2Rα chain (CD25). Defects in Tregs lead to autoimmunity, whereas induction of Ag-specific CD4+CD25+ Tregs restores tolerance. Ag-specific CD4+CD25+ FOXP3+Tregs activated by the T helper type 2 (Th2) cytokine, IL-4, and specific alloantigen promote allograft tolerance. These Tregs expressed the specific IL-5Rα and in the presence of IL-5 proliferate to specific but not third-party Ag. These findings suggest that recombinant IL-5 (rIL-5) therapy may promote Ag-specific Tregs to mediate tolerance. This study showed normal CD4+CD25+ Tregs cultured with IL-4 and an autoantigen expressed Il-5rα. Treatment of experimental autoimmune neuritis with rIL-5 markedly reduced clinical paralysis, weight loss, demyelination, and infiltration of CD4+ (Th1 and Th17) CD8+ T cells and macrophages in nerves. Clinical improvement was associated with expansion of CD4+CD25+FOXP3+ Tregs that expressed Il-5rα and proliferated only to specific autoantigen that was enhanced by rIL-5. Depletion of CD25+ Tregs or blocking of IL-4 abolished the benefits of rIL-5. Thus, rIL-5 promoted Ag-specific Tregs, activated by autoantigen and IL-4, to control autoimmunity. These findings may explain how Th2 responses, especially to parasitic infestation, induce immune tolerance. rIL-5 therapy may be able to induce Ag-specific tolerance in autoimmunity.

Genetic inactivation of the p66 isoform of ShcA is neuroprotective in a murine model of multiple sclerosis

Although multiple sclerosis (MS) has traditionally been considered to be an inflammatory disease, recent evidence has brought neurodegeneration into the spotlight, suggesting that accumulated damage and loss of axons is critical to disease progression and the associated irreversible disability. Proposed mechanisms of axonal degeneration in MS posit cytosolic and subsequent mitochondrial Ca(2+) overload, accumulation of pathologic reactive oxygen species (ROS), and mitochondrial dysfunction leading to cell death. In this context, the role of the p66 isoform of ShcA protein (p66) may be significant. The ShcA isoform is uniquely targeted to the mitochondrial intermembrane space in response to elevated oxidative stress, and serves as a redox enzyme amplifying ROS generation in a positive feedforward loop that eventually mediates cell death by activation of the mitochondrial permeability transition pore. Consequently, we tested the hypothesis that genetic inactivation of p66 would reduce axonal injury in a murine model of MS, experimental autoimmune encephalomyelitis (EAE). As predicted, the p66-knockout (p66-KO) mice developed typical signs of EAE, but had less severe clinical impairment and paralysis than wild-type (WT) mice. Histologic examination of spinal cords and optic nerves showed significant axonal protection in the p66-KO tissue, despite similar levels of inflammation. Furthermore, cultured p66-KO neurons treated with agents implicated in MS neurodegenerative pathways showed greater viability than WT neurons. These results confirm the critical role of ROS-mediated mitochondrial dysfunction in the axonal loss that accompanies EAE, and identify p66 as a new pharmacologic target for MS neuroprotective therapeutics.

Rocuronium for nonemergent intubation of term and preterm infants

The aim of this study was to analyze clinical characteristics of rocuronium as premedication for nonemergent intubation in infants. Preterm infants requiring nonemergent intubation were randomized to receive atropine and fentanyl with or without rocuronium. Outcomes, patient characteristics and intubator's experience were noted. Onset, duration and degree of clinical paralysis were recorded for rocuronium group and for older infants receiving rocuronium per unit protocol. Forty-four intubations were randomized (20 rocuronium, 24 control). Groups were similar in chronological and corrected gestational age, weight and intubator's experience. Successful intubation on first attempt was achieved in 35% of intubations under rocuronium vs 8% of controls; rocuronium was the only significant variable by logistic regression (odds ratio=0.052, P=0.029). Complete paralysis was reported in 80% of 57 rocuronium intubations; onset ranged from 14 to 178 s (65.9±43.4), and duration from 1 to 60 min (16.3±13.5). Rocuronium facilitated successful intubation and provided clinical paralysis quickly in most infants.