Provocative Stimulation of Growth Hormone: A Monozygotic Twin Study Discordant for Spinal Cord Injury

Abstract

Background/Objective: A blunted growth hormone (GH) response to provocative testing and/or low levels of plasma insulin-like growth factor-1 (IGF-I) have been reported in persons with spinal cord injury (SCI). A reduction in activity of the GH-IGF-I axis may have deleterious effects on body composition and function. Provocative testing for GH stimulation was performed to determine the response in monozygotic twins that were discordant for SCI.

Methods: GH stimulation testing was performed by the administration of intravenous arginine.

Results: Nine SCI twins with paraplegia, a mean age of 39 ± 9 years, and duration of injury of 14 ± 9 years were studied. The twins with SCI had a significantly lower body mass index than non-SCI twins (22.5 ± 4.0 vs 25.1 ± 4.2 kg/m²; P < 0.05); percent fat mass was greater in the twins with SCI (30 ± 11 % vs 22 ± 10%; P < 0.05). Baseline serum GH was correlated with percent fat only in the SCI twins. The response to GH provocative stimulation was less in the twins with SCI: peak GH response was 5.8 ± 6.6 vs 13.0 ± 7.3 ng/mL (P < 0.05), and sum GH response was 15.7 ± 15.6 vs 30.2 ± 17.3 ng/mL (P = 0.06). Although baseline serum GH was correlated with stimulated response in the SCI twins, this relationship was not found in the non-SCI twins. Adiposity was positively related to the provocative serum GH response in twins with SCI rather than negatively related, as noted in the non-SCI twins.

Conclusions: This study confirms and extends prior work that reported a reduction in stimulated GH release in persons with SCI, which was related to baseline values.     

Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury

Context/objective

To examine the effects of transcutaneous spinal cord stimulation (tSCS) on lower-limb spasticity.

Design

Interventional pilot study to produce preliminary data.

Setting

Department of Physical Medicine and Rehabilitation, Wilhelminenspital, Vienna, Austria.

Participants

Three subjects with chronic motor-incomplete spinal cord injury (SCI) who could walk ≥10 m.

Interventions

Two interconnected stimulating skin electrodes (Ø 5 cm) were placed paraspinally at the T11/T12 vertebral levels, and two rectangular electrodes (8 × 13 cm) on the abdomen for the reference. Biphasic 2 ms-width pulses were delivered at 50 Hz for 30 minutes at intensities producing paraesthesias but no motor responses in the lower limbs.

Outcome measures

The Wartenberg pendulum test and neurological recordings of surface-electromyography (EMG) were used to assess effects on exaggerated reflex excitability. Non-functional co-activation during volitional movement was evaluated. The timed 10-m walk test provided measures of clinical function.

Results

The index of spasticity derived from the pendulum test changed from 0.8 ± 0.4 pre- to 0.9 ± 0.3 post-stimulation, with an improvement in the subject with the lowest pre-stimulation index. Exaggerated reflex responsiveness was decreased after tSCS across all subjects, with the most profound effect on passive lower-limb movement (pre- to post-tSCS EMG ratio: 0.2 ± 0.1), as was non-functional co-activation during voluntary movement. Gait speed values increased in two subjects by 39%.

Conclusion

These preliminary results suggest that tSCS, similar to epidurally delivered stimulation, may be used for spasticity control, without negatively impacting residual motor control in incomplete SCI. Further study in a larger population is warranted.     

Gait impairments in a group of patients with incomplete spinal cord injury and their relevance regarding therapeutic approaches using functional electrical stimulation

The purpose of this study is to determine the most important impairments affecting the gait pattern of the incomplete spinal cord injury (SCI) patient and the potential impact of their treatment. The study consists of two parts. Firstly, a survey amongst 16 professionals was done to find out the impact of the impairments in incomplete-SCI patients. Secondly, gait data from 21 individuals were analyzed to determine the most common impairments. Frequently observed and relevant impairments were: inadequate hip extension (occurrence 76%), limited hip flexion (52%), limited knee flexion (71%), excess of plantar flexion (76%), and impaired foot contact (52%). In conclusion, for gait improvement in incomplete spinal cord injured patients not only ankle movements must be treated, which is done frequently, but also hip extension/flexion and knee flexion are important for gait restoration. The impact on the gait and potential solutions of these impairments are discussed.     

Breaking bad news in spinal cord injury; a qualitative study assessing the perspective of spinal cord injury survivors in Turkey

Prior abstract publication: 2^nd Medical Rehabilitation Congress; Nov 4–7, 2010; Ankara, Turkey

Objective: This study aims to investigate the process of breaking bad news from the perspective of spinal cord injury survivors.

Design: A cross sectional, qualitative study.

Setting: Community.

Participants: Fourteen spinal cord injury survivors.

Interventions: Subjects participated in a semi-structured interview about ‘when’, ‘where’ ‘by whom’ and ‘how’ they received and ‘would’ prefer to receive bad news.

Outcome measures: Answers to ‘how’ questions were coded according to SPIKES protocol (Setting, Perception, Invitation, Knowledge, Empathizing, Summary).

Results: Eight participants (57%) reported that they received bad news from a physician, mostly during rehabilitation. All would prefer to be informed by a physician and majority preferred to be gradually informed during rehabilitation. Half were not satisfied with the content of information. Only half felt that his/her physiatrist understood his/her emotional distress. Majority of participants who received bad news from physicians reported that the setting was private and their family members accompanied them.

Conclusion: Most spinal cord injury survivors were unsatisfied with knowledge and emotional support provided by rehabilitation physicians. Participants would prefer to receive bad news by a senior physiatrist in a planned meeting during rehabilitation.     

Inflammatory sacroiliitis in a man with spinal cord injury

BACKGROUND: Inflammatory sacroiliitis associated with spinal cord injury (SCI) as an unusual cause of elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level has not been reported previously to our knowledge. OBJECTIVE: To represent a case of SCI associated with bilateral sacroiliitis causing ESR and CRP level elevation. METHODS: Case report of a man with T9 paraplegia. FINDINGS: ESR and CRP levels were high. Pelvic radiography was nearly normal, except for mildly blurred sacroiliac joints with normal margins. A 3-phase bone scan revealed bilateral sacroiliitis and heterotopic ossification at medial side of the left knee. Past history was significant for a recent urinary tract infection. Indomethacin and etidronate were prescribed. Significant decreases in ESR and CRP level were seen 1 month later. CONCLUSIONS: Sacroiliitis might be an unusual cause of elevated ESR and CRP levels in patients with SCI. Sensory and motor deficits may obscure the typical clinical presentation; therefore, imaging studies are essential for the diagnosis.     

神经移植术治疗截瘫神经性膀胱的尿动力学观察

目的　评价神经转位移植术治疗陈旧性截瘫神经性膀胱病人的手术效果。　方法　回顾性分析40例胸腰段骨折致截瘫神经性膀胱病人肋间血管神经转位桥接骶神经根35例、尺神经转位吻合阴部神经5例手术前后尿动力学检测结果。　结果　骶根组35例术前最大尿流率(Qmax)均低于正常,术后20例恢复正常（57%）,10例明显改善(28.6%),术前后逼尿肌最大收缩力分别为（60±15cmH     

Regulation of cartilage growth by growth hormone and insulin-like growth factor I

A number of studies have shown that growth hormone (GH) and insulin-like growth factor-I (IGF-I) have important regulatory roles for skeletal growth. However, it has been a matter of controversy whether GH acts directly on cells in the growth plate or if the growth-promoting effects of GH are mediated by liver-derived (endocrine-acting) IGF-I. With the recognition that GH regulates the production of IGF-I in multiple extra-hepatic tissues, autocrine and paracrine functions of IGF-I have been suggested as important components of GH action. This review focuses on recent developments in our understanding of the cellular mechanisms by which GH promotes longitudinal bone growth and the inter-relationship between GH and IGF-I in the growth plate.     

Low-frequency fatigue in individuals with spinal cord injury

BACKGROUND/OBJECTIVE: This study examined magnitude and recovery of low-frequency fatigue (LFF) in the quadriceps after electrically stimulated contractions in spinal cord-injured (SCI) and able-bodied subjects. SUBJECTS: Nine SCI (ASIA A-C, levels C5-T9, injured 13.6 +/- 12.2 years) and 9 sedentary able-bodied subjects completed this study. METHODS: Fatigue was evoked in 1 thigh, and the nonfatigued leg served as a control. The fatigue test for able-bodied subjects lasted 15 minutes. For SCI, stimulation was adjusted so that the relative drop in force was matched to the able-bodied group. Force was assessed at 20 (P20) and 100 Hz (P100), and the ratio of P20/P100 was used to evaluate LFF in thighs immediately after, at 10, 20, and 60 minutes, and at 2, 4, 6, and 24 hours after a fatigue test. RESULTS: The magnitude of LFF (up to 1 hour after fatigue) was not different between able-bodied and patients with SCI. However, recovery of LFF over 24 hours was greater in able-bodied compared with patients with SCI in both the experimental (P < 0.001) and control legs (P < 0.001). The able-bodied group showed a gradual recovery of LFF over time in the experimental leg, whereas the SCI group did not. CONCLUSIONS: These results show that individuals with SCI are more susceptible to LFF than able-bodied subjects. In SCI, simply assessing LFF produced considerable LFF and accounted for a substantial portion of the response. We propose that muscle injury is causing the dramatic LFF in SCI, and future studies are needed to test whether "fatigue" in SCI is actually confounded by the effects of muscle injury.     

Epidemiology of traumatic spinal cord injury in Asia: a systematic review

Study design

A systematic review.

Background

The number of traumatic spinal cord injury (TSCI) reports grows annually, especially in China and Korea. The epidemiological characteristics of TSCI in Asia differ from those in other countries. Thus, we compiled epidemiological factors from Asia to compare with those from other countries.

Method

We searched articles published in any language between January 1980 to December 2011 using the terms “spinal cord injury”, “traumatic spinal cord injury”, “epidemiology”, and “Asia”. The articles were reviewed for information regarding TSCI incidence, total cases, case criteria, case source, causes of injury, male/female ratio, mean age, prospective or retrospective, neurological level of injury, extent of injury, and America Spinal Injury Association Impairment Scale (AIS)/grade.

Results

Epidemiological data were extracted from 39 reports in the published literature that met the inclusion criteria. Only two studies reported prevalence rates. Incidence rates ranged from 12.06 to 61.6 per million. The average age ranged from 26.8 to 56.6 years old. Men were at higher risk than women. Motor vehicle collisions (MVCs) and falls were the main causes of TSCI. However, several countries reported war wounds as the major cause. The neurological level and extent of injury were mixed, and most patients were categorized as AIS/Frankel grade A.

Conclusion

TSCI is an important public health problem and a major cause of paralysis. We must understand the epidemiology to implement appropriate preventative measures. Asian epidemiology is different from that in other regions, so intervention measures must be established according to population-specific characteristics.     

Outcomes of a home cycling program using functional electrical stimulation or passive motion for children with spinal cord injury: a case series

BACKGROUND/OBJECTIVE: Children with spinal cord injury (SCI) are at risk for musculoskeletal and cardiovascular complications. Stationary cycling using functional electrical stimulation (FES) or passive motion has been suggested to address these complications. The purpose of this case series is to report the outcomes of a 6-month at-home cycling program for 4 children with SCI. METHODS: Two children cycled with FES and 2 cycled passively at home for 1 hour, 3 times per week. OUTCOME MEASURES: Data collected included bone mineral density of the left femoral neck, distal femur, and proximal tibia; quadriceps and hamstring muscle volume; stimulated quadriceps and hamstring muscle strength; a fasting lipid profile; and heart rate and oxygen consumption during incremental upper extremity ergometry testing. RESULTS: The 2 children cycling with FES and 1 child cycling passively exhibited improved bone mineral density, muscle volume, stimulated quadriceps strength, and lower resting heart rate. For the second child cycling passively, few changes were realized. Overall, the lipid results were inconsistent, with some positive and some negative changes seen. CONCLUSIONS: This case series suggests that cycling with or without FES may have positive health benefits and was a practical home exercise option for these children with SCI.     

Functional electrical stimulation cycling in youth with spinal cord injury: A review of intervention studies

Context

Preliminary research suggests that functional electrical stimulation cycling (FESC) might be a promising intervention for youth with spinal cord injury (SCI).

Objective

To review the evidence on FESC intervention in youth with SCI.

Methods

Systematic literature searches were conducted during December 2012. Two reviewers independently selected titles, abstracts, and full-text articles. Of 40 titles retrieved, six intervention studies met inclusion criteria and were assessed using American Academy for Cerebral Palsy and Developmental Medicine Levels of Evidence and Conduct Questions for Group Design.

Results

The study results were tabulated based on levels of evidence, with outcomes categorized according to the International Classification of Functioning, Disability, and Health framework. Evidence from the six included studies suggests that FESC is safe for youth with SCI, with no increase in knee/hip injury or hip displacement. Results from one level II randomized controlled trial suggest that a thrice weekly, 6-month FESC program can positively influence VO₂ levels when compared with passive cycling, as well as quadriceps strength when compared with electrical stimulation and passive cycling.

Conclusions

FESC demonstrates limited yet encouraging results as a safe modality to mitigate effects of inactivity in youth with SCI. More rigorous research involving a greater number of participants is needed before clinicians can be confident of its effectiveness.     

继发性脊髓损伤的细胞凋亡研究现状

细胞凋亡，又称程序性细胞死亡，在继发性脊髓损伤过程中起着关键作用。本文对继发性脊髓损伤细胞凋亡的作用、诱导因素和防治途径作一综述。     

Long-term follow-up of spinal cord stimulation to restore cough in subjects with spinal cord injury

Abstract

Objective

To determine the long-term effects of the cough stimulation system.

Design

Nonrandomized clinical trial of subjects using the study device well beyond the period of close follow-up.

Setting

Use of the study device in the home setting.

Participants

Subjects (N = 10) implanted with the device for a minimum of 2 years (mean 4.6 ± 0.6 years).

Interventions

Application of daily stimulation.

Outcome measures

Airway pressure generation and other clinical assessments including ease in raising secretions, life quality, caregiver support, and incidence of respiratory tract infections were measured at 1 year and mean 4.6 years after implantation.

Results

Each subject continued to use the device on a regular basis. During SCS, mean maximum airway pressures were 103.1 ± 20.4 and 107.7 ± 23.0 cmH₂O at the 1-year and mean 4.6-year follow-up points, respectively (P < 0.05 compared with pre-implant and not significantly different (NS) compared with 1-year follow-up). Benchmarks related to ease in raising secretions and improvements in life quality related to respiratory care were maintained at the mean 4.6 year follow-up. The need for trained caregivers to provide other means of secretion management remained significantly below the pre-implant values (P < 0.05). The incidence of acute respiratory tract infections remained low at 0.2 ± 0.1 events/year, which is significantly below the pre-implant value of 1.4 ± 0.3 events/year (P < 0.05).

Conclusion

Subjects continued to use the system on a long-term basis beyond the period of close follow-up and to continued derive significant clinical benefits.     

The growth hormone/insulin-like growth factor-I system: implications for organ growth and development

Growth hormone (GH) and insulin-like growth factors (IGFs) are essential for normal growth and development during embryonic stages as well as postnatally. While GH has little effect on these processes prenatally, the IGFs are important during these stages. On the other hand the GH-IGF-I axis is important for pubertal growth. To determine whether postnatal growth and development are dependent on circulating or locally produced IGF-I, we deleted the IGF-I gene in the liver using the cre/LoxP system used for tissue-specific gene deletion. These animals demonstrated approximately 75%–80% reduction in circulating IGF-I and an approximate fourfold increase in circulating GH. Despite the marked reductions in circulating IGF-I, growth and development was apparently normal. Thus the original somatomedin hypothesis needs to be re-evaluated in the light of these new findings. Received: 5 September 1999 / Revised: 11 December 1999 / Accepted: 18 December 1999     

Simultaneously diagnosed pulmonary thromboembolism and hemopericardium in a man with thoracic spinal cord injury

Abstract

Background

Simultaneous pulmonary thromboembolism (PTE) and hemopericardium is a rare but life-threatening condition. As hemopericardium is a contraindication to anticoagulation treatment, it is challenging to handle both conditions together.

Objective

The objective of the study was to report a rare case of a man with thoracic spinal cord injury presenting with simultaneous PTE and hemopericardium.

Design

Case report.

Subject

A 43-year-old man with incomplete T9 paraplegia (American Spinal Injury Association Impairment Scale D) complained of fever one and a half months after spinal cord injury sustained in a fall.

Findings

During evaluation of fever origin, chest computed tomography and transthoracic echocardiogram revealed simultaneous PTE and hemopericardium. After serial echocardiograms over 2 days demonstrated stability, intravenous heparin, and oral warfarin were administered and his medical status was observed closely. Ultimately, both conditions improved without significant complications.

Conclusion

We report successful treatment of man with acute spinal cord injury who presented with simultaneously diagnosed PTE and hemopericardium, a rare complication involving two distinct and opposing pathological mechanisms and conflicting treatments.     

Stimulation of growth hormone secretion in children with X-linked hypophosphatemia

X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8±0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225±38 ng/ml and IGF binding protein-3 was 3.0±0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response tol-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.     

Age-related prevalence of low testosterone in men with spinal cord injury

Objective

To describe the relationship of advancing age in persons with chronic spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI compared to historical normative data from able-bodied men in the general population.

Design

Retrospective, cross-sectional study. Two hundred forty-three healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78 years were included in this retrospective analysis.

Results

Forty-six percent of men with SCI were identified as having low serum total testosterone concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in the Massachusetts Male Aging Study. Between the third and eighth decade of life, men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total testosterone, which is higher than values reported for each decade of life for able-bodied men in the Baltimore Longitudinal Study on Aging.

Conclusion

Compared with the general population, low serum total testosterone concentration occurs earlier in life in men with SCI, at a higher prevalence by decade of life, and their age-related decline in circulating total testosterone concentration is greater. Studies of T replacement therapy in men with SCI should assist in determining the possible functional and clinical benefits from reversing low serum total testosterone concentration.     

Simultaneously diagnosed pulmonary thromboembolism and hemopericardium in a man with thoracic spinal cord injury

Background

Simultaneous pulmonary thromboembolism (PTE) and hemopericardium is a rare but life-threatening condition. As hemopericardium is a contraindication to anticoagulation treatment, it is challenging to handle both conditions together.

Objective

The objective of the study was to report a rare case of a man with thoracic spinal cord injury presenting with simultaneous PTE and hemopericardium.

Design

Case report.

Subject

A 43-year-old man with incomplete T9 paraplegia (American Spinal Injury Association Impairment Scale D) complained of fever one and a half months after spinal cord injury sustained in a fall.

Findings

During evaluation of fever origin, chest computed tomography and transthoracic echocardiogram revealed simultaneous PTE and hemopericardium. After serial echocardiograms over 2 days demonstrated stability, intravenous heparin, and oral warfarin were administered and his medical status was observed closely. Ultimately, both conditions improved without significant complications.

Conclusion

We report successful treatment of man with acute spinal cord injury who presented with simultaneously diagnosed PTE and hemopericardium, a rare complication involving two distinct and opposing pathological mechanisms and conflicting treatments.     

经颅磁刺激运动诱发电位监测脊髓创伤的实验研究

目的：观察脊髓创伤与运动诱发电位的关系，了解运动诱发电位在脊髓中的传导通路。方法：对３９只猫采用脊髓Ａｌｅｎ损伤模型和部分切断伤模型进行经颅磁刺激运动诱发电位（ＴＭＳ－ＭＥＰ）监测。结果：脊髓轻度打击伤时，ＭＥＰ潜伏期即有明显延长，但恢复良好；中度打击伤时，ＭＥＰ潜伏期延长更明显，且不能完全恢复；重度打击伤时，大部分动物ＭＥＰ不能引出，至２４ｈ不能恢复。ＭＥＰ的改变与后肢功能变化及镜下脊髓病理改变一致。ＴＭＳ－ＭＥＰ对脊髓前索和外侧索的损伤敏感，并可间接反应脊髓柱后索损伤。结论：ＴＭＳ－ＭＥＰ经脊髓前索和外侧索传导，可敏感而准确地反映脊髓损伤后功能改变，是一种有效的监测脊髓功能的手段     

自血光量子疗法治疗不同时间脊髓损伤的实验研究

４０只家兔造成不完全性脊髓损伤，通过运动功能、脊髓诱发电位、光镜和电镜的对比，研究自血光量子疗法（ＡＬＱ）治疗不同时间脊髓损伤的效果。发现：ＡＬＱ６ｄ治疗组疗效最好；ＡＬＱ立即治疗组次之；对照组最差。说明ＡＬＱ有“双相”作用。一方面ＡＬＱ可以使血液稀释、血栓形成减少、组织灌注压提高和血流速度加快，伤后立即治疗则加重脊髓局部出血；另一方面又可以通过改善血液循环，促进出血、水肿吸收、消退，保护尚未受损的脊髓组织避免或减轻继发性损伤，促进功能恢复。实验结果提示：不完全性脊髓损伤应该根据损伤程度，伤后２～６ｄ开始ＡＬＱ治疗为宜。