The strength of the patellar and Achilles tendon reflexes is not affected in uncomplicated pregnancy.

INTRODUCTION: Research on healthy pregnant women's reflexes is almost unheard of, even if an estimation of reflexes is a conventional part of the physical examination of preeclamptic patients, and hyperreflexia is generally considered to be a warning sign of eclampsia. The aim of the present study was to investigate the possible impact of gestation on tendon reflexes and the Babinski response, as examined in a clinical bed-side manner. MATERIAL AND METHODS: A prospective, single-blind, cross-sectional study. Three study groups comprised non-pregnant (n = 20), 14-18 weeks (n = 16), and 34-38 weeks (n = 15) healthy pregnant women respectively. Two experienced neurologists examined separately each participant's patellar reflexes, Achilles reflexes, and Babinski response and rated them on two different scales, National Institute of Neurological Disorders and Stroke (NINDS) scale and Mayo Clinic Scale for Tendon Reflex Assessment. Inter-observer estimations between the patient groups and the neurologists were made by mixed effect model methodology. RESULTS: The patellar and Achilles reflexes´ strengths were rated similarly in all three groups (p > 0.05). The inter-observer difference was non-significant between the neurologists´ estimations (p > 0.05). The neurologists estimated the Babinski response in a few cases as neutral (0), otherwise down (normal). CONCLUSIONS: The patellar and Achilles reflex strengths are not affected in uncomplicated pregnancy. There is good concordance between neurologists´ estimations of tendon reflex strengths rated on the NINDS and Mayo scales.

Altered cutaneous reflexes to non-noxious stimuli in the triceps surae of people with chronic incomplete spinal cord injury.

Following spinal cord injury (SCI) task-dependent modulation of spinal reflexes are often impaired. To gain insight into the state of the spinal interneuronal pathways following injury, we studied the amplitude modulation of triceps surae cutaneous reflexes to non-noxious stimuli during standing and early-to-mid stance phase of walking in participants with and without chronic incomplete SCI. Reflex eliciting nerve stimulation was delivered to the superficial peroneal, sural, and distal tibial nerves about the ankle. Reflexes were analyzed in the short (SLR, 50-80 ms post stimulation onset) and the medium (MLR, 80-120 ms) latency response windows. Further, the relation between cutaneous and H-reflexes was also examined during standing. In participants without injuries the soleus SLR was modulated task-dependently with nerve specificity, and the soleus and medial gastrocnemius MLRs were modulated task-dependently. In contrast, participants with SCI, no task-dependent or nerve-specific modulation of triceps cutaneous reflexes was observed. The triceps surae cutaneous and H-reflexes were not correlated in either group (r = 0.01-0.37). The presence of cutaneous reflexes but the absence of significant amplitude modulation may suggest impaired function of spinal interneuronal pathways in this population. The lack of correlation between the cutaneous and H-reflexes may suggest that interneurons that are involved in H-reflex modulation and cutaneous reflex modulation do not receive common input, or the impact of the common input is outweighed by other input. Present findings highlight the importance of examining multiple spinal reflexes to better understanding spinal interneuronal pathways that affect motor control in people after SCI.

Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia.

BACKGROUND: In Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes - depicted by digital gait recording - are related to disease severity in prodromal and early-to-moderate manifest SPG4 participants. METHODS: We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 participants. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force. RESULTS: By increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants. CONCLUSIONS: Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.

Characterizing the Experience of Spasticity after Spinal Cord Injury: A National Survey Project of the Spinal Cord Injury Model Systems Centers.

OBJECTIVE: To characterize the qualities that individuals with spinal cord injury (SCI) associate with their experience of spasticity and to describe the relationship between spasticity and perceived quality of life and the perceived value of spasticity management approaches. DESIGN: Online cross-sectional survey. SETTING: Multicenter collaboration among 6 Spinal Cord Injury Model Systems hospitals in the United States. PARTICIPANTS: Individuals with SCI (N=1076). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualities of Spasticity Questionnaire, modified Spinal Cord Injury-Spasticity Evaluation Tool (mSCI-SET), and the modified Patient-Reported Impact of Spasticity Measure (mPRISM). RESULTS: Respondents indicated that spasms most often occurred in response to movement-related triggering events. However, spontaneous spasms (ie, no triggering event) were also reported to be among the most common types. Frequency of spasms appears to decline with age. The highest frequency of spasms was reported by 56% of respondents aged <25 years and by only 28% of those >55 years. Stiffness associated with spasticity was reported to be more common than spasms (legs, 65% vs 54%; trunk, 33% vs 18%; arms, 26% vs 15%). Respondents reported negative effects of spasticity more commonly than positive effects. Based on their association with negative scores on the mSCI-SET and the mPRISM, the 5 most problematic experiences reported were stiffness all day, interference with sleep, painful spasms, perceived link between spasticity and pain, and intensification of pain before a spasm. Respondents indicated spasticity was improved more by stretching (48%) and exercise (45%) than by antispasmodics (38%). CONCLUSIONS: The experience of spasticity after SCI is complex and multidimensional, with consequences that affect mobility, sleep, comfort, and quality of life. Stiffness, rather than spasms, appears to be the most problematic characteristic of spasticity. Physical therapeutic interventions to treat spasticity warrant in-depth investigation.

Attenuating Neurogenic Sympathetic Hyperreflexia Robustly Improves Antibacterial Immunity After Chronic Spinal Cord Injury.

Spinal cord injury (SCI) disrupts critical physiological systems, including the cardiovascular and immune system. Plasticity of spinal circuits below the injury results in abnormal, heightened sympathetic responses, such as extreme, sudden hypertension that hallmarks life-threatening autonomic dysreflexia. Moreover, such sympathetic hyperreflexia detrimentally impacts other effector organs, including the spleen, resulting in spinal cord injury-induced immunodeficiency. Consequently, infection is a leading cause of mortality after SCI. Unfortunately, there are no current treatments that prophylactically limit sympathetic hyperreflexia to prevent subsequent effector organ dysfunction. The cytokine soluble tumor necrosis factor α (sTNFα) is upregulated in the CNS within minutes after SCI and remains elevated. Here, we report that commencing intrathecal administration of XPro1595, an inhibitor of sTNFα, at a clinically feasible, postinjury time point (i.e., 3 d after complete SCI) sufficiently diminishes maladaptive plasticity within the spinal sympathetic reflex circuit. This results in less severe autonomic dysreflexia, a real-time gauge of sympathetic hyperreflexia, for months postinjury. Remarkably, delayed delivery of the sTNFα inhibitor prevents sympathetic hyperreflexia-associated splenic atrophy and loss of leukocytes to dramatically improve the endogenous ability of chronic SCI rats to fight off pneumonia, a common cause of hospitalization after injury. The improved immune function with XPro1595 correlates with less noradrenergic fiber sprouting and normalized norepinephrine levels in the spleen, indicating that heightened, central sTNFα signaling drives peripheral, norepinephrine-mediated organ dysfunction, a novel mechanism of action. Thus, our preclinical study supports intrathecally targeting sTNFα as a viable strategy to broadly attenuate sympathetic dysregulation, thereby improving cardiovascular regulation and immunity long after SCI.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) significantly disrupts immunity, thus increasing susceptibility to infection, a leading cause of morbidity in those living with SCI. Here, we report that commencing intrathecal administration of an inhibitor of the proinflammatory cytokine soluble tumor necrosis factor α days after an injury sufficiently diminishes autonomic dysreflexia, a real time gauge of sympathetic hyperreflexia, to prevent associated splenic atrophy. This dramatically improves the endogenous ability of chronically injured rats to fight off pneumonia, a common cause of hospitalization. This preclinical study could have a significant impact for broadly improving quality of life of SCI individuals.

Hyperreflexia and enhanced ripple oscillations in the taurine-deficient mice.

In this study, we examined neuronal excitability and skeletal muscle physiology and histology in homozygous knockout mice lacking cysteine sulfonic acid decarboxylase (CSAD-KO). Neuronal excitability was measured by intracerebral recording from the prefrontal cortex. Skeletal muscle response was measured through stretch reflex in the ankle muscles. Specifically, we measured the muscle tension, amplitude of electromyogram and velocity of muscle response. Stretch reflex responses were evoked using a specialized stretching device designed for mice. The triceps surae muscle was stretched at various speeds ranging from 18 to 18,000° s-1. A transducer recorded the muscle resistance at each velocity and the corresponding EMG. We also measured the same parameter in anesthetized mice. We found that at each velocity, the CSAD-KO mice generated more tension and exhibited higher EMG responses. To evaluate if the enhanced response was due to neuronal excitability or changes in the passive properties of muscles, we anesthetize mice to eliminate the central component of the reflex. Under these conditions, CSAD-KO mice still exhibited an enhanced stretch reflex response, indicating ultrastructural alterations in muscle histology. Consistent with this, we found that sarcomeres from CSAD-KO muscles were shorter and thinner when compared to control sarcomeres. Neuronal excitability was further investigated using intracerebral recordings of brain waves from the prefrontal cortex. We found that extracellular field potentials in CSAD-KO mice were characterized by reduced amplitude of low-frequency brain waves (delta, theta, alpha, beta and gamma) and increased in the high low-frequency brain waves (slow and fast ripples). Increased slow and fast ripple rates serve as a biomarker of epileptogenic brain. We have previously shown that taurine interacts with GABAA receptors and induces biochemical changes in the GABAergic system. We suggest that taurine deficiency leads to alterations in the GABAergic system that contribute to the enhanced stretch reflex in CSAD-KO mice through biochemical mechanisms that involve alterations not only at the spinal level but also at the cortical level.

Functional assessment of stretch hyperreflexia in children with cerebral palsy using treadmill perturbations.

BACKGROUND: As hyperactive muscle stretch reflexes hinder movement in patients with central nervous system disorders, they are a common target of treatment. To improve treatment evaluation, hyperactive reflexes should be assessed during activities as walking rather than passively. This study systematically explores the feasibility, reliability and validity of sudden treadmill perturbations to evoke and quantify calf muscle stretch reflexes during walking in children with neurological disorders. METHODS: We performed an observational cross-sectional study including 24 children with cerebral palsy (CP; 6-16 years) and 14 typically developing children (TD; 6-15 years). Short belt accelerations were applied at three different intensities while children walked at comfortable speed. Lower leg kinematics, musculo-tendon lengthening and velocity, muscle activity and spatiotemporal parameters were measured to analyze perturbation responses. RESULTS: We first demonstrated protocol feasibility: the protocol was completed by all but three children who ceased participation due to fatigue. All remaining children were able to maintain their gait pattern during perturbation trials without anticipatory adaptations in ankle kinematics, spatiotemporal parameters and muscle activity. Second, we showed the protocol's reliability: there was no systematic change in muscle response over time (P = 0.21-0.54) and a bootstrapping procedure indicated sufficient number of perturbations, as the last perturbation repetition only reduced variability by ~ 2%. Third, we evaluated construct validity by showing that responses comply with neurophysiological criteria for stretch reflexes: perturbations superimposed calf muscle lengthening (P < 0.001 for both CP and TD) in all but one participant. This elicited increased calf muscle activity (359 ± 190% for CP and 231 ± 68% for TD, both P < 0.001) in the gastrocnemius medialis muscle, which increased with perturbation intensity (P < 0.001), according to the velocity-dependent nature of stretch reflexes. Finally, construct validity was shown from a clinical perspective: stretch reflexes were 1.7 times higher for CP than TD for the gastrocnemius medialis muscle (P = 0.017). CONCLUSIONS: The feasibility and reliability of the protocol, as well as the construct validity-shown by the exaggerated velocity-dependent nature of the measured responses-strongly support the use of treadmill perturbations to quantify stretch hyperreflexia during gait. We therefore provided a framework which can be used to inform clinical decision making and treatment evaluation.

Hyper-reflexia in Guillain-Barré syndrome: systematic review.

Areflexia or hyporeflexia is a mandatory clinical criterion for the diagnosis of Guillain-Barré syndrome (GBS). A systematic review of the literature from 1 January 1993 to 30 August 2019 revealed 44 sufficiently detailed patients with GBS and hyper-reflexia, along with one we describe. 73.3% of patients were from Japan, 6.7% from the USA, 6.7% from India, 4.4% from Italy, 4.4% from Turkey, 2.2% from Switzerland and 2.2% from Slovenia, suggesting a considerable geographical variation. Hyper-reflexia was more frequently associated with antecedent diarrhoea (56%) than upper respiratory tract infection (22.2%) and the electrodiagnosis of acute motor axonal neuropathy (56%) than acute inflammatory demyelinating polyneuropathy (4.4%). Antiganglioside antibodies were positive in 89.7% of patients. Hyper-reflexia was generalised in 90.7% of patients and associated with reflex spread in half; it was present from the early progressive phase in 86.7% and disappeared in a few weeks or persisted until 18 months. Ankle clonus or Babinski signs were rarely reported (6.7%); spasticity never developed. 53.3% of patients could walk unaided at nadir, none needed mechanical ventilation or died. 92.9% of patients with limb weakness were able to walk unaided within 6 months. Electrophysiological studies showed high soleus maximal H-reflex amplitude to maximal compound muscle action potential amplitude ratio, suggestive of spinal motoneuron hyperexcitability, and increased central conduction time, suggestive of corticospinal tract involvement, although a structural damage was never demonstrated by MRI. Hyper-reflexia is not inconsistent with the GBS diagnosis and should not delay treatment. All GBS variants and subtypes can present with hyper-reflexia, and this eventuality should be mentioned in future diagnostic criteria for GBS.

Rectus femoris hyperreflexia contributes to Stiff-Knee gait after stroke.

BACKGROUND: Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation. However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG. METHODS: The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle hyperreflexia and activation, healthy individuals voluntarily increased quadriceps activity using electromyographic (EMG) feedback during standing and pre-swing upon RF H-reflex elicitation. RESULTS: We observed a negative correlation (R = - 0.92, p = 0.001) between knee flexion angle and RF H-reflex amplitude in post-stroke SKG. In contrast, H-reflex amplitude in healthy individuals in presence (R = 0.47, p = 0.23) or absence (R = - 0.17, p = 0.46) of increased RF muscle activity was not correlated with knee flexion angle. We observed a body position-dependent RF H-reflex modulation between standing and walking in healthy individuals with voluntarily increased RF activity (d = 2.86, p = 0.007), but such modulation was absent post-stroke (d = 0.73, p = 0.296). CONCLUSIONS: RF reflex modulation is impaired in post-stroke SKG. The strong correlation between RF hyperreflexia and knee flexion angle indicates a possible regulatory role of spinal reflex excitability in post-stroke SKG. Interventions targeting quadriceps hyperreflexia could help elucidate the causal role of hyperreflexia on knee joint function in post-stroke SKG.

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.

[Autonomic hyperreflexia after spinal cord injury : perioperative management]. / L'hyperréflexie autonome après lésion médullaire : prise en charge en période périopératoire.

Spinal cord injury can have widespread consequences beyond the disruption of sensory and motor functions. Injury at or above the sixth thoracic spinal cord segment frequently leads to dysregulation of the autonomic nervous system, which results in a syndrome called autonomic hyperreflexia or dysreflexia. It is a hypertensive crisis triggered by visceral or somatic stimuli below the level of the injury and caused by sympathetic spinal reflexes not modulated by regulatory centers in the brain. Patients with spinal cord injuries frequently undergo surgery for multiple reasons. Because of the potentially lethal complications of autonomic hyperreflexia, physicians, and in particular anaesthesiologists, must be aware of the underlying pathophysiological mechanisms and adequate perioperative management.

Les lésions de la moelle épinière peuvent avoir de nombreuses conséquences autres que la perturbation des fonctions sensitives et motrices. Une lésion d'un niveau médullaire supérieur ou égal au sixième segment thoracique (T6) entraîne, fréquemment, une dysrégulation du système nerveux autonome et le développement d'un syndrome appelé hyperréflexie ou dysréflexie autonome. Il s'agit d'une crise hypertensive déclenchée par des stimuli viscéraux ou somatiques sous le niveau de la lésion et causée par des réflexes sympathiques médullaires non modulés par les centres régulateurs encéphaliques. Les patients porteurs de lésions médullaires bénéficient, régulièrement, d'interventions chirurgicales pour des raisons multiples. Les complications potentiellement létales de l'hyperréflexie autonome exigent des médecins et, en particulier, des anesthésistes-réanimateurs une connaissance des mécanismes physiopathologiques sous-jacents et une prise en charge péri-interventionnelle adéquate.

Modulation of soleus stretch reflexes during walking in people with chronic incomplete spinal cord injury.

In people with spasticity due to chronic incomplete spinal cord injury (SCI), it has been presumed that the abnormal stretch reflex activity impairs gait. However, locomotor stretch reflexes across all phases of walking have not been investigated in people with SCI. Thus, to understand modulation of stretch reflex excitability during spastic gait, we investigated soleus stretch reflexes across the entire gait cycle in nine neurologically normal participants and nine participants with spasticity due to chronic incomplete SCI (2.5-11 year post-injury). While the participant walked on the treadmill at his/her preferred speed, unexpected ankle dorsiflexion perturbations (6° at 250°/s) were imposed every 4-6 steps. The soleus H-reflex was also examined. In participants without SCI, spinal short-latency "M1", spinal medium latency "M2", and long-latency "M3" were clearly modulated throughout the step cycle; the responses were largest in the mid-stance and almost completely suppressed during the stance-swing transition and swing phases. In participants with SCI, M1 and M2 were abnormally large in the mid-late-swing phase, while M3 modulation was similar to that in participants without SCI. The H-reflex was also large in the mid-late-swing phase. Elicitation of H-reflex and stretch reflexes in the late swing often triggered clonus and affected the soleus activity in the following stance. In individuals without SCI, moderate positive correlation was found between H-reflex and stretch reflex sizes across the step cycle, whereas in participants with SCI, such correlation was weak to non-existing, suggesting that H-reflex investigation would not substitute for stretch reflex investigation in individuals after SCI.

Mitigation of sensory and motor deficits by acrolein scavenger phenelzine in a rat model of spinal cord contusive injury.

Currently there are no effective therapies available for the excruciating neuropathic pain that develops after spinal cord injuries (SCI). As such, a great deal of effort is being put into the investigation of novel therapeutic targets that can alleviate this pain. One such target is acrolein, a highly reactive aldehyde produced as a byproduct of oxidative stress and inflammation that is capable of activating the transient receptor potential ankyrin 1 (TRPA1) cation channel, known to be involved in the transmission and propagation of chronic neuropathic pain. One anti-acrolein agent, hydralazine, has already been shown to reduce neuropathic pain behaviors and offer neuroprotection after SCI. This study investigates another acrolein scavenger, phenelzine, for its possible role of alleviating sensory hypersensitivity through acrolein suppression. The results show that phenelzine is indeed capable of attenuating neuropathic pain behaviors in acute, delayed, and chronic administration schedules after injury in a rat model of SCI. In addition, upon the comparison of hydralazine to phenelzine, both acrolein scavengers displayed a dose-dependent response in the reduction of acrolein in vivo. Finally, phenelzine proved capable of providing locomotor function recovery and neuroprotection of spinal cord tissue when administered immediately after injury for 2 weeks. These results indicate that phenelzine may be an effective treatment for neuropathic pain after SCI and likely a viable alternative to hydralazine. We have shown that phenelzine can attenuate neuropathic pain behavior in acute, delayed, and chronic administration in post-SCI rats. This was accompanied by a dose-dependent reduction in an acrolein metabolite in urine and an acrolein adduct in spinal cord tissue, and the suppression of TRPA1 over-expression in central and peripheral locations post-trauma. Acrolein scavenging might be a novel therapeutic strategy to reduce post-SCI neuropathic pain.

[Pharmacotherapy of urinary incontinence in the elderly]. / Pharmakotherapie der Harninkontinenz im Alter.

The prevalence and the incidence of Urinary Incontinence is growing. Women suffer predominantly from stress and mixed urinary incontinence and men from urge incontinence. In elderly people, the pathophysiological and the physiological change in the lower urinary tract system must be considered as well as an underlying multimorbidity. Stress urinary incontinence is among others caused by an insufficient urethral closure mechanism and urge incontinence is followed by unhibited detrusor contractions. Medical treatment is beside other important conservative options only one part of the treatment strategy in incontinence. Duloxetine, a serotonine-norepinephrine reuptake inhibitore can increase activity of the external urethral sphincter and is able to reduce incontinence episodes in up to 64 %. Antagonists of muscarinic receptors can reduce urgency, frequency and urge incontinence as well as increase bladder capacity significantly. In Germany, darifenacin, fesoterodin, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride are available to treat urge incontinence. The efficacy of these agents are almost comparable in the elderly with the exception of oxybutynin IR. However, tolerability is different and not well studied in the elderly population with the exception of fesoterodin. Side effects, especially dry mouth, dizziness and constipation often limit their use. None of the agents show ideal efficacy or tolerability in all patients. Last summer therefore a ß3-agonist mirabegron was also introduced in Germany but was withdrawn.

Dendritic spine dysgenesis contributes to hyperreflexia after spinal cord injury.

Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI.

Acrolein contributes to TRPA1 up-regulation in peripheral and central sensory hypersensitivity following spinal cord injury.

Acrolein, an endogenous aldehyde, has been shown to be involved in sensory hypersensitivity after rat spinal cord injury (SCI), for which the pathogenesis is unclear. Acrolein can directly activate a pro-algesic transient receptor protein ankyrin 1 (TRPA1) channel that exists in sensory neurons. Both acrolein and TRPA1 mRNA are elevated post SCI, which contributes to the activation of TRPA1 by acrolein and consequently, neuropathic pain. In the current study, we further showed that, post-SCI elevation of TRPA1 mRNA exists not only in dorsal root ganglias but also in both peripheral (paw skin) and central endings of primary afferent nerves (dorsal horn of spinal cord). This is the first indication that pain signaling can be over-amplified in the peripheral skin by elevated expressions of TRPA1 following SCI, in addition over-amplification previously seen in the spinal cord and dorsal root ganglia. Furthermore, we show that acrolein alone, in the absence of physical trauma, could lead to the elevation of TRPA1 mRNA at various locations when injected to the spinal cord. In addition, post-SCI elevation of TRPA1 mRNA could be mitigated using acrolein scavengers. Both of these attributes support the critical role of acrolein in elevating TRPA1 expression through gene regulation. Taken together, these data indicate that acrolein is likely a critical causal factor in heightening pain sensation post-SCI, through both the direct binding of TRPA1 receptor, and also by boosting the expression of TRPA1. Finally, our data also further support the notion that acrolein scavenging may be an effective therapeutic approach to alleviate neuropathic pain after SCI. We propose that the trauma-mediated elevation of acrolein causes neuropathic pain through at least two mechanisms: acrolein stimulates the production of transient receptor protein ankyrin 1 (TRPA1) in both central and peripheral locations, and it activates TRPA1 channels directly. Therefore, acrolein appears to be a critical factor in the pathogenesis of post-SCI sensory hypersensitivity, becoming a novel therapeutic target to relieve both acute and chronic post-SCI neuropathic pain.

[Facial diplegia with atypical paresthesia. A variant of Guillain-Barré syndrome]. / Diplejía facial con parestesias. Una variante atípica del síndrome de Guillain-Barré.

Guillain-Barré syndrome is an acute demyelinating disease which presents in a classic form with muscular weakness and the lack of reflexes. There are multiple variations and atypical forms of the disease, being facial diplegia with paresthesia one of them. Also, the absence of reflexes in this syndrome is typical but not constant, since 10% of patients present reflexes. We describe a case of atypical presentation with bilateral facial palsy, paresthesia, brisk reflexes and weakness in the lower limbs in a 33 year old woman.

Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat.

Growing evidence suggests that oxidative stress, as associated with spinal cord injury (SCI), may play a critical role in both neuroinflammation and neuropathic pain conditions. The production of the endogenous aldehyde acrolein, following lipid peroxidation during the inflammatory response, may contribute to peripheral sensitization and hyperreflexia following SCI via the TRPA1-dependent mechanism. Here, we report that there are enhanced levels of acrolein and increased neuronal sensitivity to the aldehyde for at least 14 days after SCI. Concurrent with injury-induced increases in acrolein concentration is an increased expression of TRPA1 in the lumbar (L3-L6) sensory ganglia. As proof of the potential pronociceptive role for acrolein, intrathecal injections of acrolein revealed enhanced sensitivity to both tactile and thermal stimuli for up to 10 days, supporting the compound's pro-nociceptive functionality. Treatment of SCI animals with the acrolein scavenger hydralazine produced moderate improvement in tactile responses as well as robust changes in thermal sensitivity for up to 49 days. Taken together, these data suggest that acrolein directly modulates SCI-associated pain behavior, making it a novel therapeutic target for preclinical and clinical SCI as an analgesic. Following spinal cord injury (SCI), acrolein involvement in neuropathic pain is likely through direct activation and elevated levels of pro-nociceptive channel TRPA1. While acrolein elevation correlates with neuropathic pain, suppression of this aldehyde by hydralazine leads to an analgesic effect. Acrolein may serve as a novel therapeutic target for preclinical and clinical SCI to relieve both acute and chronic post-SCI neuropathic pain.

Relation between stretch and activation of the medial gastrocnemius muscle during gait in children with cerebral palsy compared to typically developing children.

Stretch hyperreflexia is often a target for treatment to improve gait in children with spastic cerebral palsy (CP). However, the presence of stretch hyperreflexia during gait remains debated. Therefore, we assessed the relation between gastrocnemius medialis muscle-tendon stretch and muscle activation during gait in children with CP compared to typically developing (TD) children. 3D gait analysis including electromyography (EMG) and dynamic ultrasound was carried out to assess, respectively gastrocnemius medialis activation and fascicle, belly, and tendon stretch during treadmill walking. Musculotendon-unit stretch was also estimated using OpenSim. Ratios of EMG/peak lengthening velocities and accelerations were compared between CP and TD. Velocity and acceleration peaks prior to EMG peaks were qualitatively assessed. EMG/velocity and EMG/acceleration ratios were up to 500% higher for CP (n = 14) than TD (n = 15) for most structures. Increased late swing muscle activation in CP was often preceded by fascicle and musculotendon-unit peak lengthening velocity, and early stance muscle activation by peaks in multiple structures. Increased muscle activation in CP is associated with muscle-tendon stretch during gait. Concluding, late swing muscle activation in CP appears velocity-dependent, whereas early stance activation can be velocity- and acceleration-dependent. These insights into stretch reflex mechanisms during gait can assist development of targeted interventions.

[Hereditary sensory and autonomic neuropathy 1E showing hyperreflexia: a case report].

A 52-year-old man had developed hearing loss since childhood, as well as recurrent foot ulcers and osteomyelitis since his forties. He presented with gait disturbance and dysarthria that had worsened over four years and a month, respectively. Neurological exams revealed cognitive impairment, proximal weakness of the lower extremities, generalized hyperrflexia, ataxia, sensory disturbances predominant in deep sensation, urinary retention, and gait instability. On nerve conduction study, no sensory nerve action potentials were evoked in the upper and lower limbs. Since his grandmother suffered from similar symptoms, we investigated genetic analysis, which revealed a missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene. He was subsequently diagnosed with hereditary sensory and autonomic neuropathy 1E (HSAN1E). It is important to recognize that increased deep tendon reflex can be observed in HSAN1E.