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.     

Basic and acidic fibroblast growth factors protect spinal motor neurones in vivo after experimental spinal cord injury

We studied the effect of a single focal injection of recombinant basic (FGF2) or acidic (FGF1) fibroblast growth factor on the survival of spinal motor neurones at 24 h after a standardized spinal cord contusion injury (SCI) in the rat. Both FGF2 and FGF1 (3 microg), microinjected into the injury site at 5 min post-injury (p.i.), protected at least two functionally important classes of spinal motor neurones, autonomic preganglionic neurones in the intermediolateral (IML) column and somatic motor neurones in the ventral horn (VH). Moreover, there was enhanced choline acetyltransferase (ChAT) immunoreactivity in surviving VH and IML neurones, suggesting an improved functional status. Thus, neurotrophic factors such as FGF2 and FGF1 may contribute to an overall strategy to treat acute SCI and improve recovery of function.     

Effect of naloxone on the bladder activity of rabbits with acute spinal injury

BACKGROUND: Naloxone enhances bladder activity in patients with chronic spinal cord injury. However, there are few reports on naloxone for bladder morbidity in acute spinal cord injury. METHODS: We performed a prospective, controlled study of the effects of naloxone on bladder function in rabbits with and without surgical transection of the spinal cord at the 10th thoracic vertebra. Acute and chronic stages of injury were defined according to bladder function. Naloxone was given intravenously at both stages, and intrathecally at the acute stage. Bladder activity was monitored by cystometry. Blood concentrations of methionine-enkephalin were measured by radioimmunoassay. RESULTS: Spinal cord injuries were acute 1 or 2 days after surgery, and chronic after 1 or 2 weeks. Bladder capacity significantly decreased after 0.01 mg of intravenous naloxone in uninjured control rabbits, and after 0.03 mg of intravenous naloxone in rabbits with chronic-phase injuries. During the acute-injury phase, 0.3 mg of intravenous naloxone, or 0.02 mg of intrathecal naloxone, was necessary to evoke the micturition reflex. No significant changes in blood enkephalin levels were seen before or after spinal cord injury. CONCLUSION: In rabbits with acute spinal cord injury, intrathecal naloxone evoked the micturition reflex at a much lower dose than did intravenous naloxone. Intrathecal naloxone promises to become a new therapy for the acute stage of spinal cord injury for active recovery of bladder function, and could replace current therapy.     

Assessment of lower urinary tract functional deficit in rats with contusive spinal cord injury

Traumatic spinal cord injury (SCI) produces lower urinary tract (LUT) dysfunction that has been studied in surgical transection models. Our aim was to assess LUT functional deficit in a clinically relevant model of incomplete SCI to investigate how partial preservation of supraspinal connections might affect LUT dysfunction. Standardized weight-drop contusion (10 g x 2.5 cm) or complete transection, was produced at T8 in female Sprague-Dawley rats. Behavioral tests were used to assess hind limb sensorimotor function at Day 1 after surgery and weekly thereafter. The urometric experiments were conducted on groups (n = 7) of uninjured rats and on injured rats during Weeks 1 and 2 after SCI (before and after spontaneous voiding was established) as well as Week 2 after a complete transection (n = 3). Under anesthesia, the bladder was continuously perfused with saline. Changes in bladder pressure and external urethral sphincter (EUS) electrical activity were monitored. The bladder was then dissected and weighed and both the bladder and spinal cord were fixed for pathoanatomical analyses. Our results indicate that several aspects of LUT dysfunction after contusive SCI were similar to transection, e.g., reduction of voiding efficiency (approximately 5% of normal value), decrease in inter-contraction interval (47%), increase in bladder capacity (8-fold), and weight (4.6-fold). One aspect appeared different from transection--partial recovery from acute bladder/sphincter dyssynergia. Because the coordination of bladder and EUS function is mediated by brainstem pathways, partial recovery of synergy after SCI was likely due to sparing of some relevant bulbospinal projections as was confirmed by retrograde transneuronal viral tracing.     

Defining assessment parameters in dual injuries: spinal cord injury and traumatic brain injury

Assessment parameters for muscle testing in the individual with a spinal cord injury (SCI) have been clearly defined by the American Spinal Injury Association (ASIA). However, the ASIA standard requires the individual's participation in reporting sensory information and he/she must be able to perform specific tasks to complete the examination. In an individual with a dual injury, a SCI and a traumatic brain injury (TBI), neurological assessment can be impeded by the individual's inability to participate in the exam. Assessment needs to incorporate both cognitive and physical parameters that will appropriately assess both injuries. This article reviews the assessment parameters for both spinal cord injury and traumatic brain injury and provides assessment guidelines for bedside evaluation of functional ability. In addition, a review of the biomechanics of injury will provide a model for understanding dual injury.     

Pulmonary complications in AIDS: CT appearances

We investigated 33 cervical spinal cord injury patients (25 males and eight females) without bony injury. Patients whose neurologic recovery had reached a plateau and who had evidence on imaging of persistent spinal cord compression were considered candidates for surgical decompression. When imaging did not show spinal cord compression or patients were maintaining a good neurologic recovery from the early days after injury, we pursued conservative treatment. Age at injury varied from 20 to 76 years (mean, 55.6). Average follow-up was 31 months. Twelve patients were treated conservatively (Group 1). Groups 2 and 3 had surgery. Group 2 (14 cases) had multi-level compression of spinal cord due to pre-existing cervical spine conditions such as ossification of posterior longitudinal ligament, cervical canal stenosis, and cervical spondylosis. Group 3 (7 cases) patients existed single-level compression of spinal cord by cervical disc herniations or spondylosis. We evaluated clinical results according to the Frankel classification, the American Spinal Injury Association (ASIA) scales and Japanese Orthopaedic Association (JOA) scores. Overall improvement of JOA and ASIA scores after treatment was 56.3 +/- 35.5% and 67.1 +/- 38.0%, respectively. Patients in Group 1 showed very good recovery after conservative treatment, with improvement of JOA and ASIA scores being 70.4 +/- 40.2% and 77.4 +/- 34.2%, respectively. The average interval between injury and operation was 4.3 +/- 4.4 months. The improvement of the surgically treated patients (Groups 2 and 3) in JOA and ASIA score was 48.2 +/- 30.7% and 61.2 +/- 39.6% respectively. We obtained good neurological recovery after operation, with significantly more improvement in Group 3 than in Group 2. No significant neurologic recovery had occurred preoperatively in these groups. In such patients operative intervention is essential for neurologic recovery.     

Role of group I metabotropic glutamate receptors in traumatic spinal cord white matter injury

Metabotropic glutamate receptors (mGluRs) participate in glutamate neural transmission, but their role in the pathophysiology of spinal cord injury (SCI) has not been explored. Accordingly, we examined the role of group I mGluRs, which are linked to phospholipase C, in mediating SCI using an in vitro model. A dorsal column segment was isolated from the spinal cord of adult rats, maintained in vitro, and injured by compression for 15 sec with a clip having a 2 g closing force. Under control conditions after SCI, the compound action potential (CAP) amplitude was reduced to 69.1 +/- 5.4% of baseline. Blockade of group I mGluR receptors with MCPG, 4CPG, or AIDA resulted in improved recovery of CAP amplitude (82.2 +/- 2.0%, 86.2 +/- 3.9%, and 86.0 +/- 2.5% of baseline, respectively). The group I/II agonist trans-ACPD and selective group I agonist DHPG exacerbated the posttraumatic reduction of CAP amplitude. The phospholipase C inhibitor U-73122 improved recovery of CAP amplitude after traumatic spinal cord axonal injury. Western blotting and immunocytochemistry demonstrated the presence of mGluR1alpha-immunopositive astrocytes and the absence of mGluR5 in spinal cord white matter. These studies are consistent with the hypothesis that activation of group I mGluR receptors after SCI exacerbates posttraumatic axonal injury through a phospholipase C dependent mechanism. The presence of mGluR1alpha labeling on astrocytes suggests a role for these cells in the pathophysiology of SCI. Additional studies in vivo, are required to further clarify the role of mGluRs in acute traumatic SCI.     

The central cholinergic stimulation in sinoaortic denervation. Effect of intracerebroventricular administration of cholinomimetic agents

Preclinical trials of intravenously administered 4-Aminopyridine (4-AP) have demonstrated transient improvements in neurological function in patients with longstanding spinal cord injury (SCI). The present report describes three patients with SCI who responded favourably in preclinical trials and who were subsequently administered oral (capsule) 4-AP (10 mg b.i.d. or t.i.d.) over a 4 month interval. The three patients (two male: 1 female) all had incomplete tetraplegia (ASIA levels C and D) with the neurological level of the lesion between C5-C7. Following the administration of 4-AP the patients demonstrated marked and sustained reductions in upper (n = 1) or lower extremity (n = 2) spasticity. Other clinical benefits of 4-AP were reduced pain (n = 1), restored muscle strength (n = 3), improved sensation (n = 2), voluntary control of bowel function (n = 1), and sustained penile tumescence (n = 2). The patients exhibited improved hand function (n = 1), enhanced mobility in transfers and gait (n = 2), with improved energy and endurance. Only trivial side effects (transient light-headedness) were observed. In one case, the enhanced neurological function allowed the patient to stand with support for the first time post injury (16 years). The time course of therapeutic response to the initial dose matched the pharmacokinetic elimination profile derived from serum and urine analysis. There was no evidence of renal or hepatic toxicity with prolonged use. These results indicate a therapeutic benefit of oral 4-Aminopyridine in the management of various neurological deficits in a select group of SCI patients.     

Spondyloarthropathies

OBJECTIVE: Prediction of outcome of ambulatory capacity and hand function in tetraplegic patients with spinal cord injury (SCI) using neurologic examination, according to the protocol of the American Spinal Injury Association (ASIA) and motor-evoked potentials (MEP). DESIGN: Correlation study on a prospective cohort. SETTING: SCI center, university hospital. PATIENTS: Thirty-six patients with acute and 34 with chronic SCI. OUTCOME MEASURES: (1) ASIA motor and sensory scores, (2) MEP recordings of upper and lower limb muscles, and (3) outcome of ambulatory capacity and hand function. RESULTS: In acute and chronic SCI, both the initial ASIA scores and the MEP recordings were significantly related (p < .0001) to the outcome of ambulatory capacity and hand function. In tetraplegic patients, the MEP of the abductor digiti minimi muscle (Spearman correlation coefficient, .75; p < .0001) and the ASIA motor score for the upper limbs (Spearman correlation coefficient, .83; p < .0001) were most related to the outcome of hand function. Ambulatory capacity could be predicted by the ASIA motor score of the lower limbs (Spearman correlation coefficient, .78; p < .0001) and by MEP recordings of the leg muscles (Spearman correlation coefficient, .77; p < .0001). In patients with acute SCI, for the period 6 months posttrauma, the ASIA motor score increased significantly (ANOVA, p < .05), whereas the ASIA sensory scores and MEP recordings were unchanged (ANOVA, p > 0.1). CONCLUSION: Both ASIA scores and MEP recordings are similarly related to the outcome of ambulatory capacity and hand function in patients with SCI. MEP recordings are of additional value to the clinical examination in uncooperative or incomprehensive patients. The combination of clinical examination and MEP recordings allows differentiation between the recovery of motor function (hand function, ambulatory capacity) and that of impulse transmission of descending motor tracts.     

The skeleton after spinal cord injury. Part 1. Theoretical aspects

Sublesional osteoporosis occurs after acute spinal cord injury (SCI), preferentially weakening the skeleton below the level of the neurological lesion. Although its pathogenesis is unclear, it resembles post-menopausal, high turnover osteoporosis. Physical and pharmacologic therapies are currently being tested for their ability to prevent early loss and restore lost bone. Although treatment strategies hold promise, preservation of skeletal strength after injury may ultimately rest on lifestyle decisions made early in life. If skeletal strength is to be maintained after SCI, ways must be found to optimize skeletal strength prior to injury, arrest early losses, and stabilize, if not restore, lost bone over time.     

Expression and structure of senescence marker protein-30 (SMP30) and its physiological function

STUDY DESIGN: The effect of epidural space perfusion with chilled saline solution (% 0.9 NaCl) on lipid peroxidation after experimental spinal cord injury in rats was evaluated. OBJECTIVES: The extent of lipid peroxidation is a useful parameter for evaluating the cellular disturbance caused by spinal cord trauma in experimental conditions. The protective effects of hypothermia against neurological injury resulting from trauma or ischemia both in experimental and clinical situations have been demonstrated. SETTING: Departments of Neurosurgery and Biochemistry, Cerrahpa?a Medical School, Istanbul, Turkey. METHODS: Twenty-five female Wistar Albino rats were used. There were five rats in group I (sham-operated), seven rats in group II (trauma), and eight rats in group III (epidural cooling). The remaining five rats were used for the pilot study to determine the spinal cord and body temperature. A clip compression method was used to produce acute spinal cord injury. In group III, 30 min after the trauma the injured spinal cord was cooled by perfusion of the epidural space with chilled saline solution (% 0.9 NaCl) with a flow rate of 5 ml/min for 30 min. At 2 h after trauma, all rats other than the ones used in the pilot study, were sacrificed and the spinal cords were excised. The extent of lipid peroxidation in the spinal cord was assessed by measuring the tissue content of malonil dialdehyde (MDA). RESULTS: The tissue MDA contents were 1.58 micromol MDA/gram wet weight (gww) in group I (sham-operated), 2.58 micromol MDA/gww in group 2 (trauma), and 1.77 micromol/gww in group 3 (epidural cooling), the differences being statistically significant. CONCLUSION: The results indicated that epidural cooling of traumatized spinal cord is effective in preventing secondary damage due to the peroxidation of lipid membranes.     

Differential signaling through the T cell receptor: from biochemistry to transplantation tolerance

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. Interpretation and conclusion: (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.     

Biochemical changes in denervated muscle identified by magnetic resonance spectroscopy

The significance of the ASIA (American Spinal Injury Association) scores and SSEP (somatosensory evoked potentials) recordings in predicting the recovery of bladder function was evaluated in 70 patients with acute, traumatic spinal cord injury (SCI). The patients were examined following admission to the rehabilitation centre (mean 10 days post-trauma) both clinically by the ASIA scores and electrophysiologically by tibial and pudendal SSEP recordings. The results of the initial examinations were related to the degree of recovery of bladder function of the patients assessed by urodynamic examination at the end of the rehabilitation programme (at least 6 months post-trauma). The recovery of somatic nerve function (external urethral sphincter function) involved in bladder function was correlated to both the initial ASIA scores and SSEP recordings (Spearman correlation, P < 0.001). The latter parameters, however, were not related to the outcome of autonomic nerve function (eg detrusor vesicae function) (Spearman correlation, P = 0.1). Therefore, the initial clinical and electrophysiological examinations are of value in assessment of the degree to which the patient will recover somatic nervous control of bladder function. However, these examinations are not indicative of urodynamic impairment. Therefore, urodynamic examination should be mandatory for the diagnostic assessment and therapeutical approach of bladder dysfunction in patients with acute SCI.     

Motor recovery following spinal cord injury associated with cervical spondylosis: a collaborative study

A prospective multicenter study was conducted within the National Model Spinal Cord Injury System program to examine neurological deficits and recovery patterns following spinal cord injury (SCI) in individuals with cervical spondylosis and without a spinal fracture. Nineteen patients were evaluated. Sixty-eight percent presented initially with motor incomplete lesions. Of those who presented with motor incomplete injuries at their initial examination, 69 percent had less deficit in the lower than in the upper extremities, indicative of a central cord syndrome. At follow-up, 12 subjects were unable to ambulate, four required assistance and three were able to ambulate independently. On the average, subjects doubled their initial Asia Motor Score (AMS) scores by one year following injury. Residual upper extremity weakness, however, limited the ability to ambulate. Recovery of motor strength in this group is comparable to that of individuals with incomplete tetraplegia in general but the proportion who regain ambulatory function is less.     

Cortical sensorimotor reorganization after spinal cord injury: an electroencephalographic study

The aim of this study was to determine if cortical motor representation and generators change after partial or complete paralysis after spinal cord injury (SCI). Previously reported evidence for a change in cortical motor function after SCI was derived from transcranial magnetic stimulation. These studies inferred a reorganization of the cortical motor system. We applied the new technique of high-resolution EEG to measure changes in cortical motor representation directly. We recorded and mapped the motor potential (MP) of the movement-related cortical potentials in 12 SCI patients and 11 control subjects. Results were analyzed using a distance metric to compare MP locations between patients and control subjects. EEG was coregistered with subject-specific MR images and a boundary element model created for dipole source analysis (DSA). When compared with normal control subjects, seven quadriparetics had posteriorly located MPs with finger movements. One paraparetic had a posterior MP with toe movements, but three who could not move the toes had normally located MPs on attempts to move. DSA confirmed the electrical field map distributions of the MPs. We are reporting a reorganization of cortical motor activity to a posterior location after SCI. These results suggest an important role of the somatosensory cortex (S1) in the recovery process after SCI.     

Distribution and latency of muscle responses to transcranial magnetic stimulation of motor cortex after spinal cord injury in humans

Noninvasive transcranial magnetic stimulation (TMS) of the motor cortex was used to evoke electromyographic (EMG) responses in persons with spinal cord injury (n = 97) and able-bodied subjects (n = 20, for comparative data). Our goal was to evaluate, for different levels and severity of spinal cord injury, potential differences in the distribution and latency of motor responses in a large sample of muscles affected by the injury. The spinal cord injury (SCI) population was divided into subgroups based upon injury location (cervical, thoracic, and thoracolumbar) and clinical status (motor-complete versus motor-incomplete). Cortical stimuli were delivered while subjects attempted to contract individual muscles, in order to both maximize the probability of a response to TMS and minimize the response latency. Subjects with motor-incomplete injuries to the cervical or thoracic spinal cord were more likely to demonstrate volitional and TMS-evoked contractions in muscles controlling their foot and ankle (i.e., distal lower limb muscles) compared to muscles of the thigh (i.e., proximal lower limb muscles). When TMS did evoke responses in muscles innervated at levels caudal to the spinal cord lesion, response latencies of muscles in the lower limbs were delayed equally for persons with injury to the cervical or thoracic spinal cord, suggesting normal central motor conduction velocity in motor axons caudal to the lesion. In fact, motor response distribution and latencies were essentially indistinguishable for injuries to the cervical or thoracic (at or rostral to T10) levels of the spine. In contrast, motor-incomplete SCI subjects with injuries at the thoracolumbar level showed a higher probability of preserved volitional movements and TMS-evoked contractions in proximal muscles of the lower limb, and absent responses in distal muscles. When responses to TMS were seen in this group, the latencies were not significantly longer than those of able-bodied (AB) subjects, strongly suggestive of "root sparing" as a basis for motor function in subjects with injury at or caudal to the T11 vertebral body. Both the distribution and latency of TMS-evoked responses are consistent with highly focal lesions to the spinal cord in the subjects examined. The pattern of preserved responsiveness predominating in the distal leg muscles is consistent with a greater role of corticospinal tract innervation of these muscles compared to more proximal muscles of the thigh and hip.     

Alteration of thromboxane A2/prostacyclin and their effect on spinal cord blood flow in experimental spinal cord injury in rats

In order to document the contribution of Thromboxane (TXA2) and Prostacyclin (PGI2) to the secondary damage following spinal cord injury (SCI) and their effects on spinal cord blood flow (SCBF), the alteration of SCBF, TXB2 and 6-keto-PGF1 alpha concentration in injury site (T13-L1) and adjacent cords (upper: T12, under: L2) were studied using a rat SCI model induced by Allen's weight drop method (50g-cm). The result showed that after SCI the SCBF in injury site significantly reduced during 1-2 hrs and reduced further during 4-8 hrs. The SCBF in adjacent cords also decreased during 4-8 hrs. TXB2 levels significantly increased at 1 hr and reached peak value at 4 hrs. The 6-keto-PGF1 alpha concentration also significantly increased at 1 hr and maintained that level for 24 hrs. The TXB2/6-keto-PGF1 alpha ratio was significantly elevated at 1 hr and reached its peak at 4 hrs after SCI, then gradually decreased to the preinjury level during 8-24 hrs. The negative correlation of SCBF with TXB2 concentration and TXB2/6-keto-PGF1 alpha ratio were appeared. The experimental results indicated that the imbalance of TXB2/6-keto-PGF1 alpha could be the main cause of microcirculatory disturbance and secondary damage in SCI.     

Neuroimaging and pathology of the spinal cord in compressive cervical myelopathy

Magnetic resonance imaging (MRI) has enabled us to see the spinal intramedullary pathology as differences in signal intensity. Intramedullary high intensity lesions were observed on T2-weighted MRI in patients with cervical spondylotic myelopathy (20.0%) and ossification of the posterior longitudinal ligament (OPLL) of the cervical spine (25.7%). The frequency of this findings was proportional to the clinical severity of myelopathy and degree of spinal cord compression. The pathophysiological basis of such signal abnormality was presumed to vary from acute edema to chronic myelomalacia. The intramedullary lesion on MRI is considered to be the main site of lesion responsible for the neurological symptom because of a good correlation between the neurological level and high intensity level. We found from nine autopsy cases of OPLL that there are distinct differences in severity and extent of pathological changes between the spinal cord with a boomerang-shaped cross-section and that with a triangular-shaped cross-section. In the boomerang-shaped cases, major pathological changes were restricted to the gray matter and the white matter was relatively well preserved. Secondary wallerian degeneration was restricted to the fasciclus cuneatus the fibers of which were derived from the affected segments. In the cases of a triangular shape, pathological changes were more severe, both white and gray matter were involved. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciclus gracilis, were observed. In conclusion, it is clinically very important to understand the pathological basis of the compressed spinal cord on neuroimages.