Renate Meindl

Risk factors for heterotopic ossification in patients with spinal cord injury: a case-control study of 264 patients.

Study Design. Case-control study. Objective. We designed a case-control study to analyze the risk factors associated with the development of heterotopic ossification (HO) in patients with traumatic spinal cord injury. Summary of Background Data. Patients with spinal cord injury have a high risk of developing HO, although the exact etiopathogenesis is still unknown. Several factors are known to be potential risk factors. However, we are not aware of any large clinical studies evaluating the risk factors for HO. Methods. Patients who were treated for a traumatic spinal cord injury in our hospital, and who subsequently developed HO, were identified by querying the electronic database at our hospital from 2002 to 2010. One hundred thirty-two patients and 132 controls were included. Our primary outcome measures were the risk of developing HO according to whether the patient had experienced a complete spinal cord lesion according to American Spinal Injury Association Impairment Scale; tetraplegia or paraplegia; cervical, thoracic, or lumbar injury; severe chest trauma; and the time interval between injury and surgery. Secondary risk factors explored were patient age; sex; presence and number of comorbidities; length of hospital and intensive care unit stay; associated traumatic injuries; presence of spasticity, pressure ulcers, deep venous thrombosis, and urinary tract infection; and pulmonary complications, such as pneumonia and necessity of tracheostomy. Results. Patients with associated spasticity and thoracic trauma, complete lesion, pneumonia, presence of tracheostomy, and urinary tract infection had a higher risk of developing HO. Conclusion. Adequate management of potential risk factors could help reduce the overall incidence of HO and outcome in patients with traumatic spinal cord injury.

Prostate size and PSA serum levels in male patients with spinal cord injury

OBJECTIVES To evaluate prostate size and serum prostate-specific antigen (PSA) levels in male patients with spinal cord injury (SCI). As a result of improved medical care, the life expectancy in patients with SCI today equals the life expectancy of the general population. Therefore, male patients with SCI are likely to develop benign prostatic hyperplasia or prostate cancer. Although animal experiments indicate that neurogenic factors play an important role in prostate growth, the influence of these factors is not well examined in humans. METHODS The data of 100 male patients with SCI and 575 noninjured men were evaluated. The inclusion criteria were age older than 35 years and SCI for longer than 2 years. The exclusion criteria were previous prostate surgery, acute urinary tract infection, and bladder or prostate cancer. PSA was measured by an immunoenzymatic assay, and the prostatic volume was assessed by transrectal ultrasonography. For analysis, patients were grouped according to age. RESULTS With increasing age, the mean prostate volume increased in the patients with SCI and in the control group. The mean PSA level increased with age in the control group and to a far lesser extent in the patients with SCI. Neither for the entire cohort nor for the subgroups delineated by age were the differences in mean PSA level and mean prostate volume between patients with SCI and the control group statistically significant. CONCLUSION Prostate growth is detectable in patients with SCI. Although there is a tendency toward a lower prostate volume and lower serum PSA level in patients with SCI, the differences were not statistically significant. According to our results, the reference ranges for PSA levels are not vastly different from the general reference ranges.

Exoskeletal Neuro-Rehabilitation in Chronic Paraplegic Patients – Initial Results

Treadmill training after traumatic spinal cord injury is established as a therapy to improve walking capabilities in incomplete injured patients. In this study we investigate walking capabilities after a three month period of HAL® exoskeleton supported treadmill training in patients with chronic (>6 month) complete/incomplete (ASIA A – ASIA C) spinal cord injury. We monitored walking distance, walking speed and walking time with additional analysis of functional improvement by using the 10-m-walk test, the timed-up-and-go test and the WISCI II score in combination with the ASIA classification.

Against the odds: what to expect in rehabilitation of chronic spinal cord injury with a neurologically controlled Hybrid Assistive Limb exoskeleton. A subgroup analysis of 55 patients according to age and lesion level

Objective Age and lesion level are believed to represent outcome predictors in rehabilitation of patients with chronic spinal cord injury (SCI). The Hybrid Assistive Limb (HAL) exoskeleton enables patients to perform a voluntary controlled gait pattern via an electromyography-triggered neuromuscular feedback system, and has been introduced as a temporary gait training tool in patients with SCI. The aim of this prospective pre- and postintervention study was to examine functional outcomes as a function of age and lesion level in patients with chronic incomplete SCI (iSCI) or chronic complete SCI (cSCI) with zones of partial preservation (ZPP) by using the HAL as a temporary training tool. Methods Fifty-five participants with chronic iSCI or cSCI (mean time since injury 6.85 ± 5.12 years) were classified according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) and divided by age (< 50 or ≥ 50 years), independent of lesion level, and also into 4 homogeneous groups according to lesion level. The subgroups were as follows: Subgroup 1, tetraplegic iSCI (n = 13) (C2-8, AIS C [n = 8] and AIS D [n = 5]); Subgroup 2, paraplegic iSCI with spastic motor behavior (n = 15) (T2-12, AIS C [n = 8] and AIS D [n = 7]); Subgroup 3, paraplegic cSCI with complete motor paraplegia and absence of spastic motor behavior (n = 18) (T11-L4 [AIS A], and ZPP from L-3 to S-1); and Subgroup 4, paraplegic iSCI with absence of spastic motor behavior (n = 9) (T12-L3, AIS C [n = 8] and AIS D [n = 1]). The training paradigm consisted of 12 weeks of HAL-assisted treadmill training (5 times/week). Baseline status was documented prior to intervention by using the AIS grade, Walking Index for SCI II (WISCI II) score, the 10-meter walk test (10MWT), and the 6-minute walk test (6MinWT). Training effects were assessed after 6 and 12 weeks of therapy, without HAL assistance. Results Overall, a time reduction of 47% in the 10MWT, self-selected speed (10MWTsss) (< 50 years = 56% vs ≥ 50 years = 37%) and an increase of 50% in the 6MinWT were documented. The WISCI II scores showed a mean gain of 1.69 levels. At the end of the study, 24 of 55 patients (43.6%) were less dependent on walking aids. Age had a nonsignificant negative influence on the 10MWTsss. Despite a few nonsignificant subgroup differences, participants improved across all tests. Namely, patients with iSCI who had spastic motor behavior improved to a nonsignificant, lesser extent in the 6MinWT. Conclusions The HAL-assisted treadmill training leads to functional improvements in chronic iSCI or cSCI, both in and out of the exoskeleton. An improvement of approximately 50% in the 10MWTsss and in gait endurance (6MinWT) can be expected from such training. The influences of SCI lesion level and age on functional outcome were nonsignificant in the present study. Older age (≥ 50 years) may be associated with smaller improvements in the 10MWTsss. An iSCI in paraplegic patients with spastic motor behavior may be a nonsignificant negative predictor in gait endurance improvements. Clinical trial registration no.: DRKS00010250 ( https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_DE.do ).

Neurorehabilitation in Chronic Paraplegic Patients with the HAL ® Exoskeleton – Preliminary Electrophysiological and fMRI Data of a Pilot Study

Training leads to increased neuronal excitability, decreased inhibition and different types of neuronal plasticity. Most studies focus on cortical plastic changes after cerebral lesions or in healthy humans. In this study, we investigate cortical excitability and plastic changes after a three month period of HAL® exoskeleton supported treadmill training in patients with chronic incomplete spinal cord injury by means of electrophysiological measurements and functional magnetic resonance imaging. Here we report preliminary results of four patients.

Exoskeletons for rehabilitation of patients with spinal cord injuries. Options and limitations

BACKGROUND Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. OBJECTIVES AND METHODS This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. RESULTS The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. CONCLUSION Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.ZusammenfassungHintergrundIm Rahmen des Lokomotiontrainings bei der Behandlung querschnittgelähmter Patienten kommen zunehmend mobile Exoskelette in der Rehabilitation und Hilfsmittelversorgung zum Einsatz.Fragestellung und MethodikDie derzeit auf dem Markt verfügbaren exoskelettalen Systeme werden beschrieben, ihre Möglichkeiten in der klinischen Anwendung und die dafür zurzeit vorhandene Evidenz dargestellt. Daraus werden Empfehlungen zur klinischen Anwendung der verschiedenen Exoskelette in der Rehabilitation querschnittgelähmter Patienten abgeleitet.ErgebnisseDie Anwendbarkeit unterschiedlicher Exoskelette als Therapiegerät ist mit jeweils unterschiedlicher Zielsetzung möglich. Elektromechanisch kontrollierte Exoskelette zeigen ihre Einsetzbarkeit insbesondere in der Mobilisation bei neurogenen Gangstörungen durch direkte Gangunterstützung. Der Einsatz des neuronal gesteuerten HAL®-Exoskeletts verspricht zusätzlich funktionelle Verbesserungen auch in der chronischen Phase einer Querschnittlähmung bei Patienten mit motorischen Restfunktionen, wenn sie nach dem Training ohne Exoskelett gehen. Ergebnisse, die positive Einflüsse auf Knochendichte, Blasen-Mastdarm-Funktion und Durchblutung zeigen, sind denkbar, aber noch nicht hinreichend belegt. Effekte hinsichtlich Spastikreduktion und Linderung neuropathischer Schmerzen sind bisher lediglich in Fallserien oder im Rahmen kleiner Studien berichtet worden.SchlussfolgerungExoskelette werden zunehmend bei querschnittgelähmten Patienten als „High-tech-Hilfsmittel“ zum Einsatz kommen, sind aber zurzeit im routinemäßigen Einsatz nicht etabliert. Neurologisch-kontrollierte Exoskelette versprechen einen positiven Einfluss auf die Behandlung akuter und chronischer Querschnittlähmungen und können damit eine zukünftige Alternative zum etablierten Lokomotiontraining darstellen.AbstractBackgroundMobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries.Objectives and methodsThis article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries.ResultsThe different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials.ConclusionAlthough exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury:

Background. Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. Objective. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Methods. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). Results. ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. Conclusions. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

Exoskelette in der Rehabilitation Querschnittgelähmter

BACKGROUND Mobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries. OBJECTIVES AND METHODS This article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries. RESULTS The different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials. CONCLUSION Although exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.ZusammenfassungHintergrundIm Rahmen des Lokomotiontrainings bei der Behandlung querschnittgelähmter Patienten kommen zunehmend mobile Exoskelette in der Rehabilitation und Hilfsmittelversorgung zum Einsatz.Fragestellung und MethodikDie derzeit auf dem Markt verfügbaren exoskelettalen Systeme werden beschrieben, ihre Möglichkeiten in der klinischen Anwendung und die dafür zurzeit vorhandene Evidenz dargestellt. Daraus werden Empfehlungen zur klinischen Anwendung der verschiedenen Exoskelette in der Rehabilitation querschnittgelähmter Patienten abgeleitet.ErgebnisseDie Anwendbarkeit unterschiedlicher Exoskelette als Therapiegerät ist mit jeweils unterschiedlicher Zielsetzung möglich. Elektromechanisch kontrollierte Exoskelette zeigen ihre Einsetzbarkeit insbesondere in der Mobilisation bei neurogenen Gangstörungen durch direkte Gangunterstützung. Der Einsatz des neuronal gesteuerten HAL®-Exoskeletts verspricht zusätzlich funktionelle Verbesserungen auch in der chronischen Phase einer Querschnittlähmung bei Patienten mit motorischen Restfunktionen, wenn sie nach dem Training ohne Exoskelett gehen. Ergebnisse, die positive Einflüsse auf Knochendichte, Blasen-Mastdarm-Funktion und Durchblutung zeigen, sind denkbar, aber noch nicht hinreichend belegt. Effekte hinsichtlich Spastikreduktion und Linderung neuropathischer Schmerzen sind bisher lediglich in Fallserien oder im Rahmen kleiner Studien berichtet worden.SchlussfolgerungExoskelette werden zunehmend bei querschnittgelähmten Patienten als „High-tech-Hilfsmittel“ zum Einsatz kommen, sind aber zurzeit im routinemäßigen Einsatz nicht etabliert. Neurologisch-kontrollierte Exoskelette versprechen einen positiven Einfluss auf die Behandlung akuter und chronischer Querschnittlähmungen und können damit eine zukünftige Alternative zum etablierten Lokomotiontraining darstellen.AbstractBackgroundMobile exoskeletons are increasingly being applied in the course of rehabilitation and provision of medical aids to patients with spinal cord injuries.Objectives and methodsThis article gives a description of the currently available exoskeletal systems and the clinical application including scientific and medical evidence, to derive recommendations regarding clinical practice of the various exoskeletons in the rehabilitation of patients with spinal cord injuries.ResultsThe different systems represent a useful adjunct to the therapeutic regimen depending on the medical objectives. Posture-controlled exoskeletons in particular enable mobilization of patients with neurological gait disorders via direct motion support. In addition the neurologically controlled exoskeleton HAL® leads to functional improvements in patients with residual muscular functions in the chronic phase of spinal cord injury in terms of improved walking abilities subsequent to training. However, beneficial effects on bone density, bladder function and perfusion are conceivable but not yet adequately supported by evidence. Positive effects on spasticity and neuropathic pain are currently based only on case series or small clinical trials.ConclusionAlthough exoskeletons are not yet an established tool in the treatment of spinal cord injuries, the systems will play a more important role in rehabilitation of patients with spinal cord injuries in the future. Neurologically controlled exoskeletons show beneficial effects in the treatment of acute and chronic spinal cord injuries and might therefore evolve to be a useful alternative to conventional locomotion training.

Muscle localization of heterotopic ossification following spinal cord injury

BACKGROUND CONTEXT Heterotopic ossification (HO) is a known complication especially in people with traumatic spinal cord injury (SCI). Although some risk factors have already been described, the pathophysiology of HO is still unknown. The pelvis is the most common region for HO occurrence. However, the prevalence of HO by muscle groups about the hip is not well described. PURPOSE To analyze the prevalence of early HO in muscle groups about the hip in 267 patients with SCI. PATIENT SAMPLE 267 patients with traumatic SCI and pelvic HO. METHODS Between January 2001 and December 2014, 267 patients with SCI were treated in our university hospital and were included in the study. Patients were routinely screened for HO using ultrasound. The diagnosis of HO was validated using magnetic resonance imaging (MRI) or computed tomography (CT). The primary outcome measure was the prevalence of HO by muscle groups around the hip. The following muscle groups around the hip were defined: (1) gluteal group, (2) adductor group, (3) iliopsoas group, and (4) deep muscle group. Additionally, the prevalence of concomitant trochanteric bursitis was recorded in all cases. RESULTS The gluteal group showed the highest HO prevalence with 55.8%, followed by the deep muscle group with 31.1%. Concomitant trochanteric bursitis was found in 62 patients (23.2%). No association between pelvic trauma and HO development was observed (n=16, 11%). CONCLUSIONS The most common muscular location for the occurrence of HO about the hip was the gluteal muscle group. Considering that no laboratory parameters are currently available for screening for HO, highly sensitive ultrasound screening examinations should be routinely performed, with particular attention paid to the gluteal muscles. Additionally, routine range of motion examination for extension and external rotation of the hip joint is warranted.

Hybrid Assistive Limb Exoskeleton HAL in the Rehabilitation of Chronic Spinal Cord Injury: Proof of Concept; the Results in 21 Patients.

INTRODUCTION The use of mobile exoskeletons is becoming more and more common in the field of spinal cord injury (SCI) rehabilitation. The hybrid assistive limb (HAL) exoskeleton provides a tailored support depending on the patients voluntary drive. MATERIALS AND METHODS After a pilot study in 2014 that included 8 patients with chronic SCI, this study of 21 patients with chronic SCI serves as a proof of concept. It was conducted to provide further evidence regarding the efficacy of exoskeletal-based rehabilitation. Functional assessment included walking speed, distance, and time on a treadmill, with additional analysis of functional mobility using the following tests: 10-meter walk test (10MWT), timed up and go (TUG) test, 6-minute walk test (6MWT), and the walking index for SCI II (WISCI-II) score. RESULTS After a training period of 90 days, all 21 patients significantly improved their functional and ambulatory mobility without the exoskeleton. Patients were assessed by the 6MWT, the TUG test, and the 10MWT, which also indicated an increase in the WISCI-II score along with significant improvements in HAL-associated walking speed, distance, and time. CONCLUSION Although, exoskeletons are not yet an established treatment in the rehabilitation of spinal cord injuries, the devices will play a more important role in the future. The HAL exoskeleton training enables effective, body weight-supported treadmill training and is capable of improving ambulatory mobility. Future controlled studies are required to enable a comparison of the new advances in the field of SCI rehabilitation with traditional over-ground training.