Distinguishing reflex from non-reflex responses elicited by transcutaneous spinal stimulation targeting the lumbosacral cord in healthy individuals.

Transcutaneous spinal stimulation (TSS) studies rely on the depolarization of afferent fibers to provide input to the spinal cord; however, this has not been routinely ascertained. Thus, we aimed to characterize the types of responses evoked by TSS and establish paired-pulse ratio cutoffs that distinguish posterior root reflexes, evoked by stimulation of afferent nerve fibers, from motor responses, evoked by stimulation of efferent nerve fibers. Twelve neurologically intact participants (six women) underwent unipolar TSS (cathode over T11-12 spinal processes, anode paraumbilically) while resting supine. In six participants, unipolar TSS was repeated 2-3 months later and also compared to a bipolar TSS configuration (cathode 2.5 cm below T11-12, anode 5 cm above cathode). EMG signals were recorded from 16 leg muscles. A paired-pulse paradigm was applied at interstimulus intervals (ISIs) of 25, 50, 100, 200, and 400 ms. Responses were categorized by three assessors into reflexes, motor responses, or their combination (mixed responses) based on the visual presence/absence of paired-pulse suppression across ISIs. The paired-pulse ratio that best discriminated between response types was derived for each ISI. These cutoffs were validated by repeating unipolar TSS 2-3 months later and with bipolar TSS. Unipolar TSS evoked only reflexes (90%) and mixed responses (10%), which were mainly recorded in the quadriceps muscles (25-42%). Paired-pulse ratios of 0.51 (25-ms ISI) and 0.47 (50-ms ISI) best distinguished reflexes from mixed responses (100% sensitivity, > 99.2% specificity). These cutoffs performed well in the repeated unipolar TSS session (100% sensitivity, > 89% specificity). Bipolar TSS exclusively elicited reflexes which were all correctly classified. These results can be utilized in future studies to ensure that the input to the spinal cord originates from the depolarization of large afferents. This knowledge can be applied to improve the design of future neurophysiological studies and increase the fidelity of neuromodulation interventions.

Neuromodulation with transcutaneous spinal stimulation reveals different groups of motor profiles during robot-guided stepping in humans with incomplete spinal cord injury.

Neuromodulation via spinal stimulation has been investigated for improving motor function and reducing spasticity after spinal cord injury (SCI) in humans. Despite the reported heterogeneity of outcomes, few investigations have attempted to discern commonalities among individual responses to neuromodulation, especially the impact of stimulation frequencies. Here, we examined how exposure to continuous lumbosacral transcutaneous spinal stimulation (TSS) across a range of frequencies affects robotic torques and EMG patterns during stepping in a robotic gait orthosis on a motorized treadmill. We studied nine chronic motor-incomplete SCI individuals (8/1 AIS-C/D, 8 men) during robot-guided stepping with body-weight support without and with TSS applied at random frequencies between 1 and up to 100 Hz at a constant, individually selected stimulation intensity below the common motor threshold for posterior root reflexes. The hip and knee robotic torques needed to maintain the predefined stepping trajectory and EMG in eight bilateral leg muscles were recorded. We calculated the standardized mean difference between the stimulation conditions grouped into frequency bins and the no stimulation condition to determine changes in the normalized torques and the average EMG envelopes. We found heterogeneous changes in robotic torques across individuals. Agglomerative clustering of robotic torques identified four groups wherein the patterns of changes differed in magnitude and direction depending mainly on the stimulation frequency and stance/swing phase. On one end of the spectrum, the changes in robotic torques were greater with increasing stimulation frequencies (four participants), which coincided with a decrease in EMG, mainly due to the reduction of clonogenic motor output in the lower leg muscles. On the other end, we found an inverted u-shape change in torque over the mid-frequency range along with an increase in EMG, reflecting the augmentation of gait-related physiological (two participants) or pathophysiological (one participant) output. We conclude that TSS during robot-guided stepping reveals different frequency-dependent motor profiles among individuals with chronic motor incomplete SCI. This suggests the need for a better understanding and characterization of motor control profiles in SCI when applying TSS as a therapeutic intervention for improving gait.

Characteristics of rectus femoris activation and rectus femoris-hamstrings coactivation during force-matching isometric knee extension in subacute stroke.

The spectral properties of surface electromyographic (EMG) signal in the rectus femoris (RF) and the coactivation in the medial hamstrings (MH) were investigated in 45 stroke subjects (22 ± 12 days post-onset) and 30 age-matched healthy controls who performed unilateral knee extensions at maximum effort (100% MVC) and during 5-s force-matching tasks (10, 30, 50% MVC). The spectral properties were obtained through a power spectrum analysis based on Fast Fourier Transform. The coactivation was measured as the MH amplitude (%max) and MH/RF amplitude ratio. Force variability was expressed as the coefficient of variation. Both knee extensors and flexors were weaker in the paretic leg than the non-paretic and control legs (p < 0.001). A significantly higher relative power in the 5-13 and 13-30 Hz bands was found in the paretic than the non-paretic leg across all force levels (p ≤ 0.001) without changes in the 30-60 and 60-100 Hz bands or the mean and median frequencies. Regarding the antagonist coactivation, MH amplitude in the paretic leg was higher than in the non-paretic leg (submaximal levels, p < 0.0001) and the control leg (all force levels, p = 0.0005) with no differences between legs in the MH/RF ratio. The steadiness of the knee extension force was not related to the spectral properties of the agonist EMG or antagonistic coactivation. Greater coactivation was associated with weaker paretic knee flexors (p ≤ 0.0002). The overall results suggest variably altered agonist activation and antagonistic coactivation over the range of isometric knee extension contractions in subacute stroke.

Bipolar transcutaneous spinal stimulation evokes short-latency reflex responses in human lower limbs alike standard unipolar electrode configuration.

Noninvasive electrical stimulation targeting the posterior lumbosacral roots has been applied recently in reflexes studies and as a neuromodulation intervention for modifying spinal cord circuitry after an injury. Here, we characterized short-latency responses evoked by four bipolar electrode configurations placed longitudinally over the spinal column at different vertebral levels from L1 to T9. They were compared with the responses evoked by the standard unipolar (aka monopolar) electrode configuration (cathode at T11/12, anode over the abdominal wall). Short-latency responses were recorded in the rectus femoris, medial hamstrings, tibialis anterior, and soleus muscles, bilaterally, in 11 neurologically intact participants. The response recruitment characteristics (maximal amplitude, motor threshold) and amplitude-matched onset latencies and paired-pulse suppression (35-ms interstimulus interval) were assessed with 1-ms current-controlled pulses at intensities up to 100 mA. The results showed that short-latency responses can be elicited with all bipolar electrode configurations. However, only with the cathode at T11/12 and the anode 10 cm cranially (∼T9), the maximum response amplitudes were statistical equivalent (P < 0.05) in the medial hamstrings, tibialis anterior, and soleus but not the rectus femoris, whereas motor thresholds were not significantly different across all muscles. The onset latency and paired-pulse suppression were also not significantly different across the tested electrode configurations, thereby confirming the reflex nature of the bipolar short-latency responses. We conclude that the bipolar configuration (cathode T11/12, anode ∼T9) produces reflex responses that are ostensibly similar to those evoked by the standard unipolar configuration. This provides an alternative approach for neuromodulation intervention.NEW & NOTEWORTHY Transcutaneous spinal stimulation with the identified bipolar electrode configuration may offer several advantages for neuromodulation interventions over commonly used unipolar configurations: there are no associated abdominal contractions, which improves the participant's comfort; additional dermatomes are not stimulated as when the anode is over the abdominal wall or iliac crest, which may have unwanted effects; and, due to a more localized electrical field, the bipolar configuration offers the possibility of targeting cord segments more selectively.

Relations between knee and ankle muscle coactivation and temporospatial gait measures in patients without hypertonia early after stroke.

It is unclear whether muscle coactivation during gait is altered early after stroke and among which muscles. We sought to characterize muscle coactivation during gait in subacute stroke subjects without hypertonia and explore the relationship with temporospatial parameters. In 70 stroke (23 ± 12 days post-onset) and 29 age-matched healthy subjects, surface electromyography signals were used to calculate coactivation magnitude and duration between rectus femoris and medial hamstring (knee antagonistic coactivation), tibialis anterior and medial gastrocnemius (ankle antagonistic coactivation), and rectus femoris and medial gastrocnemius (extensor synergistic coactivation) during early double-support (DS1), early single-support (SS1), late single-support (SS2), late double-support (DS2), and swing (SW). Compared to both free and very-slow speeds of controls, stroke subjects had bilaterally decreased ankle coactivation magnitude in SS2 and duration in SS1 and SS2 as well as increased extensor coactivation magnitude in DS2 and SW. Both non-paretic knee and ankle coactivation magnitudes in SS2 moderately correlated with most temporospatial parameters (|r| ≥ 0.40). Antagonistic and synergistic coactivation patterns of the knee and ankle muscles during gait are altered bilaterally in subacute stroke subjects without lower limb hypertonia suggesting impairments in motor control. Greater coactivation magnitudes in the non-paretic knee and both ankles during the terminal stance (SS2) are associated with the overall worse gait performance. Unlike previously reported excessive coactivation or no change in chronic stroke, bilaterally decreased and increased coactivation patterns are present in subacute stroke. These findings warrant longitudinal studies to examine the evolution of changes in muscle coactivation from subacute to chronic stroke.

Knee Muscle Stretch Reflex Responses After an Intrathecal Baclofen Bolus in Neurological Patients With Moderate-to-Severe Hypertonia.

OBJECTIVES: To examine the prevalence, onset threshold, and response magnitude of stretch reflex response (SRR) in the knee extensors and flexors before and after an intrathecal baclofen (ITB) bolus injection in patients with moderate-to-severe hypertonia. MATERIALS AND METHODS: SRRs were elicited by reciprocal passive knee extension/flexion movements at preset angular velocities of 5, 60, 120, 180, 240, and 300°/s using an isokinetic dynamometer and recorded with surface electromyographic (EMG) electrodes placed over the knee extensors and flexors in 53 neurologic patients before and at 2.5 and 5 hours after an ITB injection via lumbar puncture. Outcome measures included the number of patients with presence/absence of SRRs, the number of SRRs per session, SRR onset threshold angle and velocity, and response magnitudes (peak EMG and area under the EMG curve) for each muscle. Pre-post comparisons were completed using the Fisher's exact and Wilcoxon signed rank tests. RESULTS: For both knee extensors and flexors, the proportion of patients with present SRRs (p < 0.0001) and the number of SRRs per session (p ≤ 0.027) decreased from pre- to post-ITB. The threshold velocity significantly increased post-injection in both muscles (p ≤ 0.001) without significant changes in the threshold angle. The response magnitudes significantly decreased in the knee extensors (p ≤ 0.016) but not the knee flexors after the injection. CONCLUSIONS: The prevalence and threshold velocity of SRR emerged as the most robust and practical parameters for assessing hyperreflexia during ITB bolus trial that can complement clinical assessment of muscle hypertonia.

Gait Impairments in Patients Without Lower Limb Hypertonia Early Poststroke Are Related to Weakness of Paretic Knee Flexors.

OBJECTIVE: To describe gait characteristics of patients without clinical evidence of lower limb hypertonia within 2 months of stroke and explore the relationship between gait and residual motor function. DESIGN: Cohort study. SETTING: Motion analysis laboratory in a tertiary-care free-standing rehabilitation hospital. PARTICIPANTS: Consecutive sample of 73 eligible inpatients (first-known stroke <2 months postonset, walking independently, modified Ashworth score of 0 in the paretic lower limb) and 27 healthy controls (N=100). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gait speed, stride and step lengths and cadences, stance time, single-support and double-support times, and associated symmetry measures in patients at self-selected normal speed and controls at very slow speed (51.1±32.6 cm/s and 61.9±21.8 cm/s, respectively, P=.115); Fugl-Meyer lower extremity motor score (FM-LE) and isometric knee flexion and extension strength in patients. RESULTS: Except the stride/step cadence, all temporospatial parameters significantly differed between the stroke and control participants. Furthermore, significantly greater asymmetries were found in the patients for the overall stance time, initial double-support and single-support times, and step cadence, reflecting smaller values in the paretic than nonparetic limb. Most temporospatial parameters moderately to strongly correlated with the gait speed (|r|: .72-.94, P<.0001), FM-LE (|r|: .42-.62, P≤.0005), and paretic knee flexor strength (|r|: .47-.57, P≤.0004). CONCLUSIONS: Gait of patients without clinical evidence of lower limb hypertonia within 2 months of stroke is characterized by many temporospatial deviations and asymmetries. The self-selected normal gait speed, FM-LE, and paretic knee flexor strength can discriminate gait impairments in these patients shortly before inpatient discharge. It remains to be determined whether the observed relationships between paretic knee flexor strength and gait measures warrant the development of interventions for strengthening of the paretic knee flexors in order to improve gait early poststroke.

Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance.

CD8+ T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8+ T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a-/-) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8+ T cells isolated from Il17a-/- mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8+ T cell cytotoxicity, which may have broad implications in other microbial infections and cancers. IMPORTANCE: Interleukin-17A (IL-17A) and CD8+ T cells regulate diverse immune functions in microbial infections, malignancies, and autoimmune diseases. IL-17A is a proinflammatory cytokine produced by diverse cell types, while CD8+ T cells (known as cytotoxic T cells) are major cells that provide immunity against intracellular pathogens. Previous studies have demonstrated a crucial role of CD8+ T cells in recovery from West Nile virus (WNV) infection. However, the role of IL-17A during WNV infection remains unclear. Here, we demonstrate that IL-17A protects mice from lethal WNV infection by promoting CD8+ T cell-mediated clearance of WNV. In addition, treatment of WNV-infected mice with recombinant IL-17A reduces the viral burden and increases survival of mice, suggesting a potential therapeutic. This novel IL-17A-CD8+ T cell axis may also have broad implications for immunity to other microbial infections and cancers, where CD8+ T cell functions are crucial.

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice.

West Nile virus (WNV) is a neurotropic ssRNA flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human TLR7 and TLR8 and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. In this article, we report that TLR8-deficient (Tlr8-/-) mice were resistant to WNV infection compared with wild-type controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8-/- mice were attributed to overexpression of Tlr7 and IFN-stimulated gene-56 expression, whereas reduced expression of the proapoptotic gene coding Bcl2-associated X protein was observed. Interestingly, suppressor of cytokine signaling (SOCS)-1 directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, whereas selective small interfering RNA knockdown of Socs-1 resulted in induced IFN-stimulated gene-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.

Increased alertness, better than posture prioritization, explains dual-task performance in prosthesis users and controls under increasing postural and cognitive challenge.

Sensorimotor impairments after limb amputation impose a threat to stability. Commonly described strategies for maintaining stability are the posture first strategy (prioritization of balance) and posture second strategy (prioritization of concurrent tasks). The existence of these strategies was examined in 13 below-knee prosthesis users and 15 controls during dual-task standing under increasing postural and cognitive challenge by evaluating path length, 95% sway area, and anterior-posterior and medial-lateral amplitudes of the center of pressure. The subjects stood on two force platforms under usual (hard surface/eyes open) and difficult (soft surface/eyes closed) conditions, first alone and while performing a cognitive task without and then with instruction on cognitive prioritization. During standing alone, sway was not significantly different between groups. After adding the cognitive task without prioritization instruction, prosthesis users increased sway more under the dual-task than single-task standing (p ≤ 0.028) during both usual and difficult conditions, favoring the posture second strategy. Controls, however, reduced dual-task sway under a greater postural challenge (p ≤ 0.017), suggesting the posture first strategy. With prioritization of the cognitive task, sway was unchanged or reduced in prosthesis users, suggesting departure from the posture second strategy, whereas controls maintained the posture first strategy. Individual analysis of dual tasking revealed that greater postural demand in controls and greater cognitive challenge in prosthesis users led to both reduced sway and improved cognitive performance, suggesting cognitive-motor facilitation. Thus, activation of additional resources through increased alertness, rather than posture prioritization, may explain dual-task performance in both prosthesis users and controls under increasing postural and cognitive challenge.

Weight compensation characteristics of Armeo®Spring exoskeleton: implications for clinical practice and research.

BACKGROUND: Armeo®Spring exoskeleton is widely used for upper extremity rehabilitation; however, weight compensation provided by the device appears insufficiently characterized to fully utilize it in clinical and research settings. METHODS: Weight compensation was quantified by measuring static force in the sagittal plane with a load cell attached to the elbow joint of Armeo®Spring. All upper spring settings were examined in 5° increments at the minimum, maximum, and two intermediate upper and lower module length settings, while keeping the lower spring at minimum. The same measurements were made for minimum upper spring setting and maximum lower spring setting at minimum and maximum module lengths. Weight compensation was plotted against upper module angles, and slope was analyzed for each condition. RESULTS: The Armeo®Spring design prompted defining the slack angle and exoskeleton balance angle, which, depending on spring and length settings, divide the operating range into different unloading and loading regions. Higher spring tensions and shorter module lengths provided greater unloading (≤6.32 kg of support). Weight compensation slope decreased faster with shorter length settings (minimum length = -0.082 ± 0.002 kg/°; maximum length = -0.046 ± 0.001 kg/°) independent of spring settings. CONCLUSIONS: Understanding the impact of different settings on the Armeo®Spring weight compensation should help define best clinical practice and improve fidelity of research.

Variability, frequency composition, and temporal regularity of submaximal isometric elbow flexion force in subacute stroke.

We compared variability, frequency composition, and temporal regularity of submaximal isometric elbow flexion force at 10, 20, 35, and 50 % of peak torque between 34 stroke subjects (5-48 days post-onset, both arms) and 24 age-matched controls (dominant arm), and related the findings in the paretic arm to motor impairment. Force variability was quantified by the coefficient of variation (CV), frequency composition by the median frequency and relative power in 0-3-, 4-6-, and 8-12-Hz bands, and regularity by the sample entropy (SampEn). The paretic elbow flexors showed significantly increased CV and relative power in 0-3-Hz band, decreased power in 4-6- and 8-12-Hz bands, and decreased SampEn compared to both the non-paretic and control elbow flexors (P ≤ 0.0002), with no differences between the latter two (P ≥ 0.012). With increasing contraction intensity, the relative power in different frequency bands was insufficiently modulated and SampEn excessively decreased in the paretic elbow flexors. Also, CV in the paretic elbow flexors was non-linearly related to the relative power in different frequency bands and SampEn across contraction intensities (rectangular hyperbolic fit, 0.21 ≤ R 2 ≤ 0.55, P ≤ 0.006), whereas no force parameter correlated with arm motor impairment. These results largely extend our previous findings in the paretic knee extensors to the elbow flexors in subacute stroke, except that here force variability was increased only in the paretic elbow flexors and modulation of force regularity with increasing contraction intensity showed the opposite, decreasing pattern, which was considerably exaggerated in the paretic muscles.

Intersegmental coordination scales with gait speed similarly in men and women.

We applied principal component analysis (PCA) to thigh, shank, and foot elevation angles to examine the impact of speed on intra-limb coordination during gait. The specific aims were to (1) determine speed-related changes in segment loadings on three principal components (PCs) and (2) examine differences between men and women. The subjects (26 women, 21 men) walked overground at five self-selected paces (very slow, slow, normal, fast, very fast). PCA yielded percent variation (PV) explained by each PC and thigh, shank, and foot loadings on PC1-PC3. These parameters were regressed against the speed normalized to body height (BH/s) to derive individual and aggregate slopes and P values, separately for men and women. PV1 increased with speed, whereas PV2 and PV3 decreased (all P < 0.001). The loadings of thigh and foot segments on PC1 increased with speed (0.14 and 0.04 per BH/s, P < 0.001, respectively), and the loading of shank decreased (-0.10, P < 0.001). Compared to PC1, the changes in segment loadings on PC3 were the opposite (thigh -0.18, shank 0.09, foot -0.04 per BH/s, P < 0.001). The changes in segment loadings on PC2 were inconsistent and generally small. The only significance (P = 0.006), albeit a minor difference between men and women, was in the slope of thigh loading on PC2 (-0.005 ± 0.019 and 0.015 ± 0.026 per BH/s, respectively). We conclude that intersegmental coordination during gait scales with speed, with the greatest impact on the thigh segment, but no differently between men and women.

Intersegmental coordination of gait after hemorrhagic stroke.

We compared gait using the planar law of intersegmental coordination between 14 hemorrhagic stroke subjects walking at a self-selected normal speed (56 ± 21 cm/s) and 15 age-matched healthy controls walking at a very slow speed (56 ± 19 cm/s). Sagittal plane elevation angles of the thigh, shank, and foot segments were submitted to principal component analysis. Additional outcome measures included the range of elevation angle and timing of peak elevation angle of the thigh, shank, and foot segments. The range of elevation angles at the shank and foot was significantly smaller in the paretic leg than non-paretic and control legs. Also, the peak elevation angle at the thigh occurred significantly later in the gait cycle in the paretic than control leg. Gait of both stroke and control subjects followed the planar law with the first two principal components explaining approximately 99% of the variance. However, the three-dimensional trajectory of elevation angles (gait loop) in stroke subjects deviated from the typical teardrop shape bilaterally, which was more exaggerated in the paretic leg. Compared to the non-paretic and control legs, the paretic leg showed significantly increased absolute loading of the thigh elevation angle and decreased absolute loadings of the shank and foot elevation angles on the first principal component, whereas the opposite was observed for the second principal component. Despite following the planar law, the gait of chronic stroke subjects is characterized by atypical timing of the thigh motion and disrupted intersegmental coordination of both legs.

West nile virus infection and myasthenia gravis.

INTRODUCTION: Viruses are commonly cited as triggers for autoimmune disease. It is unclear if West Nile virus (WNV) initiates autoimmunity. METHODS: We describe 6 cases of myasthenia gravis (MG) that developed several months after WNV infection. All patients had serologically confirmed WNV neuroinvasive disease. None had evidence of MG before WNV. RESULTS: All patients had stable neurological deficits when they developed new symptoms of MG 3 to 7 months after WNV infection. However, residual deficits from WNV confounded or delayed MG diagnosis. All patients had elevated acetylcholine receptor (AChR) antibodies, and 1 had thymoma. Treatment varied, but 4 patients required acetylcholinesterase inhibitors, multiple immunosuppressive drugs, and intravenous immune globulin or plasmapheresis for recurrent MG crises. CONCLUSIONS: The pathogenic mechanism of MG following WNV remains uncertain. We hypothesize that WNV-triggered autoimmunity breaks immunological self-tolerance to initiate MG, possibly through molecular mimicry between virus antigens and AChR subunits or other autoimmune mechanisms.

The contribution of walking speed versus recent stroke to temporospatial gait variability.

BACKGROUND: Inconsistent results have been reported for temporospatial gait variability after stroke. Given the large differences in gait speed across stroke subjects and relative to healthy controls, it is not clear which changes in temporospatial gait variability can be ascribed to the walking speed during gait evaluation versus the consequences of stroke. RESEARCH QUESTIONS: Does temporospatial gait variability differ between (1) stroke subjects grouped in clinically-relevant functional ambulation classes, (2) the paretic and non-paretic legs within each class, and (3) stroke and healthy subjects after controlling for gait speed? METHODS: Stroke subjects were evaluated at their comfortable speed < 2 months post-onset and classified into the household (<40 cm/s, n = 38), limited-community (40-80 cm/s, n = 35), and full-community (>80 cm/s, n = 14) walkers. Coefficients of variation (CVs) for paretic and non-paretic stance, initial double-support, and single-support times, step length, step cadence, and step width were compared across the stroke ambulation classes and between the two legs. For the parameters with significantly different CVs between stroke subjects and 33 age-matched controls walking at very-slow and free speeds, a 1-way ANCOVA was used with the gait speed as a covariate. RESULTS: For most step parameters, CVs were greater in slower stroke ambulation classes except for the smaller step width CV. The differences between the paretic and non-paretic legs emerged in slower walkers only. After controlling for the gait speed, CVs of stroke subjects no longer significantly differed from controls walking at very-slow speed. With controls walking at free speed, however, CVs for the paretic and non-paretic single-support times and the non-paretic step time remained significantly different. SIGNIFICANCE: Gait is more variable at slower speeds both in stroke subjects and healthy controls. After accounting for the free gait speed, the increased variability of only a few temporal parameters may be attributed to a recent stroke.

Pendulum test parameters are useful for detecting knee muscle hypertonia and quantifying response to an intrathecal baclofen bolus injection.

Our objective was to determine which pendulum test parameters are useful for detecting hypertonia in the knee muscles and assessing the group and individual responses to intrathecal baclofen (ITB) bolus injection among prospective pump recipients. We included 15 neurological patients with lower limb hypertonia (mainly spinal cord injury, n  = 7) and collected data the day before (baseline), and 2.5 and 5.0 h after the 50-µg ITB bolus injection. For comparison, data were collected in 15 healthy controls. The average over six test repetitions was obtained for the number of oscillations, swing time (SwingT), amplitudes of the first flexion and extension, maximum angular velocities of the first flexion (F1V) and extension (E1V), relaxation index, and damping coefficient (DampC). Across the patient group, all pendulum parameters indicated a significant decrease in hypertonia from baseline to postinjection (analysis of variance P  ≤ 0.004), except DampC. On the basis of the cutoffs from the receiver operating characteristic curve, all parameters were good or excellent discriminators of hypertonia in patients from normotonia in controls (area under the curve ≥0.85), with the highest sensitivity for SwingT and E1V (≥93%). Furthermore, all parameters except F1V revealed a significant shift from preinjection hypertonia to postinjection normotonia among patients (McNamar test P  ≤ 0.002, DampC excluded due to missing data), with the greatest responsiveness for E1V and relaxation index (≥73%). The results confirm the overall usefulness of pendulum test parameters in this patient population and indicate that some parameters are better at detecting hypertonia (SwingT, E1V) whereas others (E1V, relaxation index) are more responsive to the ITB injection.

Glial S100B is elevated in serum across the spectrum of West Nile virus infection.

INTRODUCTION: We previously reported that protein biomarkers of neuronal death and glial pathology were elevated in the cerebrospinal fluid of patients with West Nile virus (WNV) infection, including WNV fever. Therefore, we hypothesized that the glial biomarker S100B would also be elevated in serum across the spectrum of WNV disease. METHODS: Serum levels of S100B were measured by enzyme-linked immunoassay (ELISA) in 90 WNV patients (35 with neuroinvasive disease and 55 with WNV fever) and compared with 34 healthy controls. RESULTS: Serum S100B was significantly higher in patients (median 0.17 ng/ml) than in controls (0.09 ng/ml, P < 0.0001). Serum S100B was elevated in 16 cases (46%) with neuroinvasive disease and in 19 cases (35%) with WNV fever. CONCLUSIONS: The increase in serum S100B reaffirms pathological changes across the spectrum of WNV disease. The elevated S100B in over one third of WNV fever cases implies that neuroinvasion occurs in a much greater proportion of patients than anticipated by clinical and epidemiological data.

Electromyogram-lengthening velocity relation in plantar flexors during stance phase of gait in patients with hypertonia after acquired brain injury.

OBJECTIVE: To examine the velocity-dependent change in medial gastrocnemius (MG) activity during the stance phase of gait in patients with moderate to severe resting hypertonia after stroke or traumatic brain injury (TBI). DESIGN: Cohort study. SETTING: Motion analysis laboratory in a tertiary-care rehabilitation hospital. PARTICIPANTS: Convenience sample of patients with chronic TBI and stroke (n=11 each), and age- and sex-matched healthy controls (n=22). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Frequency and gain (steepness) of positive (>0) and significant positive (>0 and goodness of fit P≤.05) electromyogram-lengthening velocity (EMG-LV) linear regression slope in MG during the stance phase of gait. RESULTS: Positive and significant positive slopes were found significantly more often on the more affected (MA) than less affected (LA) side in patients with TBI but not stroke. Both the frequencies of positive and significant positive slopes on the MA side in patients with TBI were also significantly higher than in controls. However, neither the gain of positive nor significant positive EMG-LV slope was different between the MA and LA sides or in comparison with controls. Positive slope parameters were not related to Ashworth score on the MA side. CONCLUSIONS: The frequency and gain of positive EMG-lengthening slope did not effectively differentiate patients from controls, nor were they related to the resting muscle hypertonia. Motor output during MG lengthening in the stance phase of gait is apparently not exaggerated or related to resting hypertonia in patients with chronic TBI and stroke. Thus, changes in gait during stance cannot be ascribed to increased stretch reflex activity in MG muscle after acquired brain injury.