Refined sensory measures of neural repair in human spinal cord injury: bridging preclinical findings to clinical value

Sensory input from the periphery to the brain can be severely compromised or completely abolished after an injury to the spinal cord. Evidence from animal models suggests that endogenous repair processes in the spinal cord mediate extensive sprouting and that this might be further attenuated by targeted therapeutic interventions. However, the extent to which sprouting can contribute to spontaneous recovery after human spinal cord injury (SCI) remains largely unknown, in part because few measurement tools are available in order to non-invasively detect subtle changes in neurophysiology. The proposed application of segmental sensory evoked potentials (e.g., dermatomal contact heat evoked potentials and somatosensory evoked potentials) to assess conduction in ascending pathways (i.e., spinothalamic and dorsal column, respectively) differs from conventional approaches in that individual spinal segments adjacent to the level of lesion are examined. The adoption of these approaches into clinical research might provide improved resolution for measuring changes in sensory impairments and might determine the extent by which spontaneous recovery after SCI is mediated by similar endogenous repair mechanisms in humans as in animal model

Ankle dexterity remains intact in patients with incomplete spinal cord injury in contrast to stroke patients

Patients with either incomplete spinal cord injury (iSCI) or stroke suffer from muscle weakness in the lower limb and impaired ambulation. The assessment of motor function in iSCI has so far focused on measures of muscle strength, while in stroke extensive research has been directed towards upper limb motor control. Slowness of movements was reported to be a common motor impairment of patients with lesions of the central nervous system (CNS). It may result from muscle weakness and deficits in dexterity, which is two aspects of motor control that are dependent on cortico-spinal tract (CST) integrity and are crucial to ambulation. Thus, this study investigated the impact of CST damage either at spinal (iSCI) or cortical level (stroke) on ankle dexterity and maximal movement velocity (MMV). Twelve iSCI, stroke and control subjects were tested. The patients were matched for gender, age and maximal voluntary contraction (MVC) in ankle dorsi- and plantar-flexion muscles. Dexterity and MMV were tested in the supine position. CST function was assessed by motor evoked potentials (MEPs). In both groups of patients, MMV and MEP latencies were comparably deteriorated. However, dexterity was preserved in iSCI, but impaired in the hemiparetic stroke leg. Therefore, iSCI patients showed a high dexterity within the preserved muscle strength, but suffered primarily from reduced MMV. In stroke patients, both dexterity and MMV were reduced. These differences might be considered in rehabilitation programs and regeneration therapie

Design and evaluation of a low-cost instrumented glove for hand function assessment

BACKGROUND: The evaluation of hand function impairment following a neurological disorder (stroke and cervical spinal cord injury) requires sensitive, reliable and clinically meaningful assessment tools. Clinical performance measures of hand function mainly focus on the accomplishment of activities of daily living (ADL), typically rather complex tasks assessed by a gross ordinal rating; while the motor performance (i.e. kinematics) is less detailed. The goal of this study was to develop a low-cost instrumented glove to capture details in grasping, feasible for the assessment of hand function in clinical practice and rehabilitation settings. METHODS: Different sensor types were tested for output signal stability over time by measuring the signal drift of their step responses. A system that converted sensor output voltages into angles based on pre-measured curves was implemented. Furthermore, the voltage supply of each sensor signal conditioning circuit was increased to enhance the sensor resolution. The repeatability of finger bending trajectories, recorded during the performance of three ADL-based tasks, was established using the intraclass correlation coefficient (ICC). Moreover, the accuracy of the glove was evaluated by determining the agreement between angles measured with the embedded sensors and angles measured by traditional goniometry. In addition, the feasibility of the glove was tested in four patients with a pathological hand function caused by a cervical spinal cord injury (cSCI). RESULTS: A sensor type that displayed a stable output signal over time was identified, and a high sensor resolution of 0.5° was obtained. The evaluation of the glove's reliability yielded high ICC values (0.84 to 0.92) with an accuracy error of about ± 5°. Feasibility testing revealed that the glove was sensitive to distinguish different levels of hand function impairment in cSCI patients. CONCLUSIONS: The device satisfied the desired system requirements in terms of low cost, stable sensor signal over time, full finger-flexion range of motion tracking and capability to monitor all three joints of one finger. The developed rapid calibration system for easy use (high feasibility) and excellent psychometric properties (i.e. reliability and validity) qualify the device for the assessment of hand function in clinical practice and rehabilitation settings

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury

BACKGROUND Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). METHODS Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. RESULTS Enhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023). CONCLUSIONS These results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. SIGNIFICANCE We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment

Development of a human neuro-musculo-skeletal model for investigation of spinal cord injury

This paper describes a neuro-musculo-skeletal model of the human lower body which has been developed with the aim of studying the effects of spinal cord injury on locomotor abilities. The model represents spinal neural control modules corresponding to central pattern generators, muscle spindle based reflex pathways, golgi tendon organ based pathways and cutaneous reflex pathways, which are coupled to the lower body musculo-skeletal dynamics. As compared to other neuro-musculo-skeletal models which aim to provide a description of the possible mechanisms involved in the production of locomotion, the goal of the model here is to understand the role of the known spinal pathways in locomotion. Thus, while other models focus primarily on functionality at the overall system level, the model here emphasizes functional and topological correspondance with the biological system at the level of the subcomponents representing spinal pathways. Such a model is more suitable for the detailed investigation of clinical questions related to spinal control of locomotion. The model is used here to perform preliminary experiments addressing the following issues: (1) the significance of spinal reflex modalities for walking and (2) the relative criticality of the various reflex modalities. The results of these experiments shed new light on the possible role of the reflex modalities in the regulation of stance and walking speed. The results also demonstrate the use of the model for the generation of hypothesis which could guide clinical experimentation. In the future, such a model may have applications in clinical diagnosis, as it can be used to identify the internal state of the system which provides the closest behavioral fit to a patient's pathological conditio

Acute necrotizing encephalopathy (ANE1): rare autosomal-dominant disorder presenting as acute transverse myelitis

The term "acute transverse myelitis (ATM)” comprises various non-traumatic disorders that eventually can be associated with a focal myelopathy. Patients characteristically present with an acutely occurring paraparesis/plegia and require a comprehensive and timely diagnostic work up for the initiation of an appropriate treatment. We present a case of a 36-year-old female patient with a rare genetic disorder (ANE1: Acute Necrotizing Encephalopathy due to a RANBP2 mutation) who presented with an acute quadriplegia. Following an acute pulmonal infection, she rapidly (< 24h) developed a severe quadriplegia (total motor score 38) with some facial sensory symptoms (perioral hypoesthesia). Magnetic resonance imaging (MRI) revealed a combination of longitudinal extensive transverse myelitis and symmetrical thalamic lesions. A work-up for infectious and systemic diseases was negative; specifically, no findings related to multiple sclerosis, neuromyelitis optica or vascular disorders. After empirical high dose steroid treatment and rehabilitation therapy, the patient gained almost normal gait and upper limb function. She was found to carry an autosomal-dominant missense mutation in the RANBP2 gene predisposing for ANE. Gene segregation was confirmed in other family members that had been affected by other episodes of acute steroid-responsive encephalopathies. We propose that a redefined diagnostic workup of ATM might include ANE1, as the frequency of this rare disorder might be underestimate

Low depressive symptoms in acute spinal cord injury compared to other neurological disorders

The aim of the study was to reveal the incidence and time course of depressive symptoms following acute spinal cord injury (SCI) in relation to clinical outcomes for comparison to other neurological disorders with severe impairment. In patients with acute traumatic SCI (n=130), combined follow up assessments of neurological and functional outcomes, pain and patient-rated affective factors (e.g. mood, anxiety) were prospectively (1, 3, 6, 12months after injury) collected during rehabilitation and follow up in out-patient clinics. We related these to the severity of depressive symptoms (no, mild, moderate and severe) based on the Beck Depression Inventory (BDI) scores. The mean 65% of patients showed no depressive symptoms and 30% mild depressive symptoms, while less than 5% presented moderate to severe depressive symptoms. The group findings and symptoms in individual patients remained stable over 1year though patients revealed significant clinical recovery. Although two-thirds of the patients experienced pain, BDI scores were not related to pain intensity. BDI mean scores were only slightly higher than in control populations, but rather low compared to patients with other neurological disorders (e.g. stroke and multiple sclerosis) that are also associated with severe functional impairment. The prevalence of depressive symptoms following acute SCI is rather low and remains stable within the first year after injury despite the severe neurological impairment and loss of independency. In comparison to other neurological disorders that also involve brain function SCI patients seem to be less challenged by depressive symptoms that constitute additional burdens to respond to the severe functional impairment

The amplitude of lower leg motor evoked potentials is a reliable measure when controlled for torque and motor task

Abstract : Objectives : Motor evoked potential (MEP) amplitudes have the disadvantage of a high variability when repeatedly assessed. This affects the reliability of MEP amplitude measurements taken during the course of motor incomplete spinal cord injury (iSCI). The study investigated the reliability of anterior tibial (TA) MEP measures controlled for dorsal flexion torque and motor task. Methods : TA MEPs were recorded at 10, 20, 40 and 60% of maximal voluntary contraction (MVC) during a static and dynamic (isometric increase of dorsal flexion torque) motor task. To determine reliability, 20 healthy and five chronic iSCI subjects were tested twice (≥7 days) by the same investigator. Intraclass correlation coefficients (ICCs) were calculated. MEP amplitudes and latencies were compared between 20 healthy and 29 iSCI subjects. Results : The reliability of MEP amplitude was in general good (ICC ≥ 0.52) and was highest during the static task at 40% MVC (ICC = 0.77). The increased facilitation by the dynamic motor task showed the best reliability at 20% MVC (ICC = 0.48). The reliability was good to excellent for MEP latency (0.46 ≥ ICC ≥ 0.81), MVC (ICC ≥ 0.90) and for the TMS threshold required to evoke a MEP response (ICC ≥ 0.77). The torque generated by the MEP response ()0.02 ≥ ICC ≥ 0.55) and the duration of the silent period (0.07 ≥ ICC ≥ 0.50) were not reliable. Both MEP amplitudes and latencies differed significantly between healthy and iSCI subjects. Conclusions : Controlling for torque generation and motor task establishes a reliability of TA MEP amplitudes that is sufficient for longitudinal assessments in motor incomplete SC

Preoperative radiological and electrophysiological evaluation in 100 adolescent idiopathic scoliosis patients

This is a prospective study of spinal magnetic resonance imaging (MRI), electrophysiological recordings, and neurological examinations of 100 patients admitted for surgery for adolescent idiopathic scoliosis (AIS), which was conducted to assess the prevalence of structural and functional abnormalities within the spinal cord in patients with clinically normal neurologic condition. In all patients the clinical diagnosis and intact neurological condition was ascertained by a spinal orthopedic surgeon. Full-length spinal axis MRI studies (T1/T2 sequences) and somato-sensory evoked potentials of the tibial nerves (tSSEPs) were preoperatively assessed by independent evaluators blinded to the patients' medical histories. Structural spinal cord abnormalities were found in three of 100 AIS patients on MR imaging. In one patient a Chiari malformation type 1 with an accompanying syringomyelia was diagnosed, which required a suboccipital decompression. In the other two patients small thoracic syringomyelias were diagnosed. Abnormalities of spinal cord function were detected in 68% of the 100 patients: tSSEP latencies corrected for body height were increased in 56% of the patients; pathological differences between tSSEPs on the left and right sides were present in 17% (12% in combination with a prolongation of the latency). The findings of this study indicate that MRI and electrophysiological examinations are essential to assess spinal cord abnormalities that are clinically not detectable in AIS patients. Even in patients with intact neurologic condition and clinically typical right-curved thoracic scoliosis, the possibility of intraspinal pathologies should be ruled out by MRI. It is especially important to detect structural pathologies like syringomyelia and Chiari malformation before proceeding with scoliosis surgery, as these conditions are associated with a higher neurological risk during scoliosis surgery. The electrophysiological recordings made in the present study, with the high number of pathological tSSEPs, are indicative of functional abnormalities with a subclinical involvement of the recorded neuronal pathways. The relevance of the latter findings is not yet clear, but pre-operative tSSEP examinations offer the possibility of assessing alterations in spinal cord function that are undetectable by clinical examinatio