Bone loss at the distal femur and proximal tibia in persons with spinal cord injury: imaging approaches, risk of fracture, and potential treatment options.

Persons with spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have severe bone loss below the level of lesion associated with increased risk of long-bone fractures. The pattern of bone loss in individuals with SCI differs from other forms of secondary osteoporosis because the skeleton above the level of lesion remains unaffected, while marked bone loss occurs in the regions of neurological impairment. Striking demineralization of the trabecular epiphyses of the distal femur (supracondylar) and proximal tibia occurs, with the knee region being highly vulnerable to fracture because many accidents occur while sitting in a wheelchair, making the knee region the first point of contact to any applied force. To quantify bone mineral density (BMD) at the knee, dual energy x-ray absorptiometry (DXA) and/or computed tomography (CT) bone densitometry are routinely employed in the clinical and research settings. A detailed review of imaging methods to acquire and quantify BMD at the distal femur and proximal tibia has not been performed to date but, if available, would serve as a reference for clinicians and researchers. This article will discuss the risk of fracture at the knee in persons with SCI, imaging methods to acquire and quantify BMD at the distal femur and proximal tibia, and treatment options available for prophylaxis against or reversal of osteoporosis in individuals with SCI.

Testicular responses to hCG stimulation at varying doses in men with spinal cord injury.

STUDY DESIGN: Prospective. OBJECTIVES: To test whether provocative stimulation of the testes identifies men with chronic spinal cord injury (SCI), a population in which serum testosterone concentrations are often depressed, possibly due to gonadal dysfunction. To accomplish this objective, conventional and lower than the conventional doses of human chorionic gonadotropin (hCG) were administered. METHODS: Thirty men with chronic SCI (duration of injury >1 year; 18 and 65 years old; 16 eugonadal (>12.1 nmol l-1) and 14 hypogonadal (⩽12.1 nmol l-1)) or able-bodied (AB) men (11 eugonadal and 27 hypogonadal) were recruited for the study. Stimulation tests were performed to quantify testicular responses to the intramuscular administration of hCG at three dose concentrations (ithat is, 400, 2000 and 4000 IU). The hCG was administered on two consecutive days, and blood was collected for serum testosterone in the early morning prior to each of the two injections; subjects returned on day 3 for a final blood sample collection. RESULTS: The average gonadal response in the SCI and AB groups to each dose of hCG was not significantly different in the hypogonadal or eugonadal subjects, with the mean serum testosterone concentrations in all groups demonstrating an adequate response. CONCLUSIONS: This work confirmed the absence of primary testicular dysfunction without additional benefit demonstrated of provocative stimulation of the testes with lower than conventional doses of hCG. Our findings support prior work that suggested a secondary testicular dysfunction that occurs in a majority of those with SCI and depressed serum testosterone concentrations.

Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

STUDY DESIGN: Prospective study. OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). METHODS: Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 µg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. RESULTS: The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (P<0.05). The SCI-responder group had a greater LH area under the curve to GnRH stimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. CONCLUSIONS: The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

International standards for neurological classification of spinal cord injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

STUDY DESIGN: Randomized controlled trial with single-blinded primary outcome assessment. OBJECTIVES: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). SETTING: Six SCI treatment centers in the United States and Israel. METHODS: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-B or better at ≥6 months. Safety was assessed by analysis of adverse events (AEs). RESULTS: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942). CONCLUSION: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury.

Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p < 0.0005), trunk (24.1 ± 4.1 vs. 25.8 ± 3.8 kg; p < 0.005), leg (14.5 ± 2.7 vs. 15.8 ±2.6 kg; p = 0.005), and arm (7.6 ± 2.3 vs. 8.0 ± 2.2 kg; p < 0.005) from baseline to month 12. After testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p < 0.01) and percent predicted basal energy expenditure (73 ± 9 vs. 79 ± 10%; p < 0.05) were significantly increased. In conclusion, testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

STUDY DESIGN: Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). OBJECTIVES: Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. SETTING: Subjects were recruited to one of six international study centers. METHODS: Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. RESULTS: Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. CONCLUSION: The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

Thyroid hormone changes in chronic spinal cord injury.

Spinal cord injury (SCI) impacts metabolic function and deranges various hormonal axes. Previous studies characterizing thyroid hormones in SCI reported depressed triiodothyronine (T3) and thyroxin (T4), primarily in acute tetraplegics. These studies cited an 11-13 percent incidence of low T3 syndrome (LT3S) in SCI patients, with an increased incidence in tetraplegics (20-36 percent). The purpose of this study was to evaluate thyroid function and determine the incidence and clinical relevance of LT3S in the chronic SCI population. Thyroid function tests were performed on 30 chronic SCI patients (14 tetraplegics and 16 paraplegics) and 30 age- and gender-matched controls. Mean T3 and T4 levels were significantly depressed in SCI patients relative to controls, while T3 resin uptake (T3RU) values were significantly elevated. LT3S only occurred in the SCI population with an incidence of 23.3 percent. SCI patients with LT3S did not differ significantly from those without in the level or completeness of injury, age or the interval since injury. They did, however, have co-existent pathology: decubiti, urinary tract infections, etc. When SCI patients with normal T3 were compared with controls, they still had depressed mean T3 levels. We conclude that LT3S occurs frequently in the chronic SCI population and suggest that depressed serum T3 levels may predispose SCI patients to sick euthyroidism in the face of minor pathologic insult.

Patient preference for in-exsufflation for secretion management with spinal cord injury.

An important aspect of respiratory management in patients with acute spinal cord injury (SCI) is the elimination of secretions. Methods utilized for secretion management in patients with SCI includes endotracheal suctioning and mechanical in-exsufflation (MI-E). Surveyed here is a group of patients with SCI who have had experience with both endotracheal suctioning and MI-E via tracheostomy, to determine patient opinions and experiences regarding the 2 techniques. The survey was administered to 18 patients with traumatic SCI, with an average age of 34. 72% were ASIA A, 22% percent were ASIA B, and 6% were ASIA C, with neurological level of injury ranging from C-1-T-3. Results indicate that patients found MI-E significantly less irritating (p < 0.001), less painful (p < 0.001), less tiring (p = 0.01), and less uncomfortable (p < 0.001) than endotracheal suctioning. In a direct comparison, 89% of patients preferred mechanical in-exsufflation to suctioning. In addition, 89% of patients found MI-E faster, 78% found MI-E more convenient, and 72% found MI-E more effective than suctioning. This study demonstrates that all measured aspects of patient experience are more positive for MI-E than for endotracheal suctioning.

Treatment of acute deep vein thrombosis in spinal cord injured patients with enoxaparin: a cost analysis.

Enoxaparin, a low molecular weight heparin, has been demonstrated to be effective in the prophylaxis and treatment of deep vein thrombosis (DVT) in the general population. This study presents an analysis of the costs of subcutaneous (SQ) enoxaparin compared with intravenous (IV) heparin. Data were gathered on six spinal cord injured (SCI) patients in an acute freestanding rehabilitation center who were initially treated with SQ enoxaparin (n=3) or IV heparin (n=3) for a proximal DVT. No patients in either group developed further clinical complications. Comparison of the total costs of each treatment was performed, including the direct cost of the drug, as well as some of the costs of administration. Although the cost of enoxaparin per unit dose is higher, the total costs of enoxaparin are slightly lower, because its labor and administration costs are less. Subcutaneous enoxaparin is a safe, cost-effective, and less labor-intensive treatment, and can be of substantial benefit in the treatment of DVT in SCI patients in the rehabilitation setting.

The ankle brachial index in chronic spinal cord injury: a pilot study.

BACKGROUND: Recent case reports implicate peripheral vascular disease (PVD) as an etiology for pressure ulcers (PU), failed myocutaneous flap surgeries, and amputation in spinal cord injury (SCI). Early detection of PVD is complicated by motor and sensory deficits in this population. The ankle-brachial index (ABI) is used to quantify PVD in the able-bodied population. We hypothesized that the ABI would be a useful screening tool for detecting PVD in patients with SCI. Differences in baseline blood pressure, as well as motor and sympathetic function, could potentially alter ABI, so values were studied in a sample of patients with SCI without risk factors or signs of PVD, and compared to those in able-bodied controls without PVD. METHODS: ABI values were measured in 15 healthy individuals with chronic complete SCI above the T6 level, who had no evidence for risk factors or physical findings of PVD, and compared with the values for a group of 10 able-bodied controls. RESULTS: No statistically significant difference in ABI was found between patients with SCI and the able-bodied comparison group. There was no statistically significant correlation between ABI and post-injury duration or incidence of PU. CONCLUSION: ABI may prove to be a useful screening device in individuals with SCI. Follow-up studies are needed to confirm these findings and to ascertain that the ABI correlates with presence and severity of PVD in patients with SCI who have risk factors and signs of PVD.

Anemia and serum protein deficiencies in patients with traumatic spinal cord injury.

This study was conducted to further investigate the natural history of the anemia, hypoproteinemia and hypoalbuminemia commonly observed in patients with traumatic spinal cord injury (SCI). Blood samples were taken from 46 traumatic SCI patients at the time of initial admission to an acute rehabilitation hospital and again approximately one year later during a routine follow-up appointment. At initial admission, 65 percent of patients were anemic (hemoglobin < 13.0 g/dl), 86.7 percent were hypoalbuminemic (albumin < 3.2 g/dl) and 48.9 percent were hypoproteinemic (total protein < 6.5 g/dl). Deficiencies were most commonly observed in tetraplegics and in patients with complete injuries. At the time of follow-up, 6.8 percent of patients were anemic, 2.2 percent demonstrated abnormally low serum protein concentrations and a significant (p = 0.01) decrease in the incidence of each deficiency was observed. Our findings suggest that anemia and decreased serum protein concentrations, while commonly observed in the acute SCI population, are much less frequently encountered in the more chronically injured. If noted in the chronic SCI patient, these deficiencies should alert clinicians to the likelihood of a concurrent process.

Does refrigeration of urine alter culture results in hospitalized patients with neurogenic bladders?

A prospective, blinded study of 40 hospitalized spinal cord injured (SCI) patients was conducted to evaluate the effects of refrigeration on urinalysis and culture results. Urine samples were divided, with one aliquot examined within 4 hours and the other after 24 hours of refrigeration. Comparisons using Wilcoxon Signed Rank analysis showed no significant difference between fresh and refrigerated samples in white blood cell (WBC) count (z = -0.353, p = 0.724), number of bacteria (z = -0.772, p = 0.440), leukocytes (z = -0.277, p = 0.782), or colony counts of E. fecalis, E. coli, Citrobacter, Pseudomonas, Streptococcus, Yeast, or Acinetobacter (z = -1.00, p = 0.317; z = 0.00, p = 1.0; z = 0.00, p = 1.0; z = 0.00, p = 1.0; z = -1.00, p = 0.317; z = 0.00, p = 1.0; z = 0.00, p = 1.0, respectively). A statistically significant difference between fresh and refrigerated samples was found with "mixed" organisms (z = -2.565, p = 0.010) and a difference approaching significance was found with Staph aureus (z = -1.841, p = 0.066), both with colony counts of less than 50 k. No changes in cultures or colony counts occurred following refrigeration that would have resulted in altered treatment regimens. This study indicates that refrigeration of urine samples for up to 24 hours in the hospital setting rarely causes changes in identified organism type and causes no clinically significant changes in urinalysis or urine culture results in SCI patients.

Levels of spinal cord injury and predictors of neurologic recovery.

A comprehensive physical examination of the patient with acute spinal cord injury is essential in determining the initial level of injury and is the most accurate method of prognosticating neurologic recovery. Understanding neurologic recovery helps predict ultimate functional capability and needs, and helps evaluate the effectiveness of pharmacologic and therapeutic interventions.

Heterotopic ossification after total hip replacement.

Heterotopic ossification (HO) is a common finding after total hip arthroplasty (THA), and may cause diminished hip range of motion and an antalgic gait. Although the etiology remains unclear, two theories currently prevail. In this article, the incidence, etiology, risk factors, and classifications of HO are discussed. Effective prophylactic treatments including radiation and anti-inflammatory medications are detailed. Once HO is present, the value of these treatments are doubtful and surgical excision may be required after bony maturity. With increasing THA projected as the population ages, the need for safe, effective, and inexpensive prophylaxis may be required.

Walker modification for ventilator-assisted individuals. Case report.

A case is presented of a 53-yr-old ambulatory ventilator-dependent individual who demonstrated that functional ambulation could be possible with a modified rolling walker. The patient used intermittent positive pressure ventilation delivered by noninvasive methods 24 h a day. For potentially ambulatory ventilator users, intensive rehabilitation and the use of a modified walker can improve medical, psychological and social status and permit the resumption of vocational activities. Mouth intermittent positive pressure ventilation is the method of choice for daytime ventilatory support during ambulation for individuals with severe chronic alveolar hypoventilation because of predominantly restrictive pulmonary syndromes.

Predicting neurologic recovery in traumatic cervical spinal cord injury.

OBJECTIVE: Traumatic spinal cord injury (SCI) affects 8,000 to 10,000 individuals per year in the United States. One of the most difficult tasks confronting the clinician is the discussion of neurologic recovery and prognosis with the patient and/or family. Our objective is to provide a guide for practitioners to accurately predict neurologic outcome in acute traumatic cervical SCI (tetraplegia). DATA SOURCE: Published reports obtained through MEDLINE search, texts, and studies presented at national conferences. STUDY SELECTION: Peer reviewed studies, in English language, that discussed prognosis after traumatic SCI. CONCLUSION: A comprehensive physical examination of the acute SCI patient is essential in determining the initial level and classification of the injury and is the most accurate method to predict neurologic recovery. Other diagnostic tests, including somatosensory evoked potentials, magnetic resonance imaging, and transcranial magnetic stimulation, may be helpful in further determining outcome when used in association with the clinical examination. The understanding of neurologic recovery should help predict ultimate functional capability and potential needs.

Mandatory clerkship in physical medicine and rehabilitation: effect on medical students' knowledge of physiatry.

OBJECTIVE: To study the effect of a 2-week clerkship on the perceptions and knowledge of physical medicine and rehabilitation (PM&R) among fourth-year medical students. DESIGN: Survey of fourth-year medical students before and after completion of a mandatory clerkship. RESULTS: Knowledge of PM&R by fourth-year medical students is marginal, but a clerkship increases the awareness of the practice of physiatry. CONCLUSIONS: Mandatory clerkships can help expose future physicians to the benefits of physiatric services and should be pursued by academic PM&R departments.

Factors influencing the specialty choice of the physical medicine and rehabilitation graduating class of 1994 and the entering class of 1995.

To understand better how career choices are made by physiatrists, a 16-item, 7-page questionnaire was sent to all 1994 graduating physical medicine and rehabilitation (PM&R) resident physicians in the United States. Of the 343 senior residents, 202 completed the questionnaire for a response rate of 59%. The questionnaire focused on the following areas: timing of the decision to enter PM&R; and how the medical school curriculum, certain groups of people, and certain specific factors influenced their choices. There were 130 factors modeled after the American Association of Medical Colleges (AAMC) annual medical student questionnaire that the recipients were asked to grade on a numerical scale: 1 = unimportant to 5 = very important. Of the graduating residents, 60.1% (119/198) made the decision to enter PM&R in their 3rd or 4th yr of medical school, 13.1% (26/198) in the first 2 yr, and 11.1% (22/198) after starting another residency. The five factors ranked most important in the decision were (mean rank score): sufficient time/flexibility for family obligations (4.60); opportunity to make a difference in peoples lives (4.57); interest in helping people (4.55); types of patient problems encountered (4.50); and consistency with personality (4.49). We also obtained the AAMC's 1993 annual data on medical students choosing PM&R. Their top five factors were the same as those listed by the graduating residents, but in a slightly different rank order. Profiles have also been derived on those graduating PM&R residents who chose an academic career (n = 68) v nonacademic (n = 133) and fellowship (n = 34) v nonfellowship (n = 163).