Central nervous system trauma : journal of the American Paralysis Association最新文献

This paper reviews a number of lines of evidence developed in our laboratories indicating that at least some components of neurologic disturbances following concussion may be attributable to increased functional activity of cholinergic systems located within specific brain regions. These lines of evidence include EEG studies indicating that disruption of the reticular activating system is not necessary for production of a reversible, flaccid, comatose state following low levels of concussion, systematic transection studies indicating that regions bounded by collicular and midpontine transections may contribute to at least motor components of the behavioral suppression associated with concussion, local rates of glucose utilization following fluid percussion injury increase in restricted areas bounded by collicular and midpontine transections; microinjection of carbachol (but not tetracaine) into these hypermetabolic regions produced behavioral suppression and electroencephalographic changes resembling those following concussion, systemic administration or microinjections of atropine, but not mecamylamine, antagonized the behavioral effects of carbachol, and data indicating that pharmacologic blockage of muscarinic cholinergic systems can attenuate neurologic deficits. Taken in conjunction with data from earlier clinical and laboratory studies, our research also indicates that anticholinergic therapy may potentially benefit head-injured patients.

The deleterious effects of Ca ionic entry into neurons has been speculated to be a final common pathway of cell death. However, a direct cause-effect relationship between Ca and neuronal death has been difficult to establish. Cells dying from any cause will accumulate Ca. The entry of Ca into neurons and the subsequent pathological changes associated with Ca entry consequently may be manifestations rather than causes of cell death. Recent work showing that extracellular Ca ionic activity becomes profoundly depressed in injured spinal cord and ischemic cerebral cortex prompted a new hypothesis on Ca mediated damage. We propose that the initial fall in extracellular Ca activity, resulting from the death of some cells in the tissue, increases the susceptibility of the surviving cells to Ca entry when extracellular Ca activity levels normalize and that this accounts for part of the secondary damage that has been observed in neural injury models. Such a phenomenon has been described in cardiac tissues. Dubbed Ca paradox, this phenomenon occurs when heart cells are perfused with Ca-free solutions for several minutes followed by the return to normal Ca-containing solutions. The cardiac cells die and undergo physiological, morphological, biochemical, and other changes. The evidence supporting a Ca paradox phenomenon in injured neural tissues is summarized. The therapeutic implications of Ca paradox in neural tissue injury are discussed.

Recent progress in the field of functional neuromuscular stimulation (FNS), that is, the restoration of purposeful movement to paralyzed limbs via stimulation, has enabled paraplegic individuals to stand up, walk, and even climb stairs (with assistance) and quadriplegics to hold and manipulate utensils and useful objects. A number of experimental and clinical FNS systems are considered, emphasizing the algorithms used to regulate movement under a variety of conditions (isometric, isotonic, dynamic load, reciprocal control) and the physiologic problems encountered. Further development of FNS systems is required to achieve patient acceptability in daily living. Three important factors will be use of implanted intramuscular or nerve stimulating electrodes, quantitative documentation of FNS-produced movements, and incorporation of force, position, and other modes of feedback to both the controller and the patient.

The main reason for using robotic technology to assist functionally limited individuals is that it could enable them to have increased control of their own lives. Evaluation of one prototype voice-controlled robotic aid has shown the feasibility of robotic-assisted tasks in four areas: activities of daily living, vocation, recreation, and physical therapy. Creation of a product, however, will require careful investigation of utility and potential marketability issues (such as safety and training) that will determine the acceptance of robotic technology in health and human service applications.

Using a scoring system designed to assess the severity of neurologic deficit in gerbils during and after temporary unilateral carotid occlusion, the effects of large doses of methylprednisolone sodium succinate (MPSS: Solu-Medrol sterile powder) on experimental stroke have been examined. By scoring gerbils hourly for torso curvature, circling, inability to walk, ptosis, barrel rolling, opisthotonus, generalized seizures, and loss of righting reflex, their level of neurologic deficit can be easily, quantitatively, and reproducibly evaluated. Approximately 37% of gerbils subjects to a 3-hour unilateral carotid occlusion attained average scores of 4.0-4.5 during the first hour. There was a slight, though not significant, worsening (increase) of scores over the 3-hour occlusion period that was not altered by pretreatment of gerbils with 60 mg/kg of MPSS 10 minutes before occlusion. Following removal of occlusion at 3 hours, gerbils recovered only minimally during the ensuing 4-hour period, with deficit scores remaining around 3.2 +/- 0.3. Pretreatment of gerbils with 60 mg/kg of MPSS, however, resulted in a striking improvement in their deficit scores to 1.6 +/- 0.2 (p less than 0.05) by 2 hours after occlusion removal. Treatment of gerbils with lower (30 mg/kg) or higher (100 mg/kg) doses of MPSS was not as effective in promoting improvement. The survival of 3-hour occluded gerbils was significantly enhanced by pretreatment with 60 mg/kg of MPSS. Vehicle-treated gerbils had survival rates of 41.7%, 16.7%, and 16.7% at 24 hours, 48 hours, and 7 days, respectively, compared with 90.9%, 72.7%, and 45.4%, respectively, for MPSS-treated gerbils.

In view of the evidence for the role of the central cholinergic pathways in memory and preliminary studies suggesting alteration of neurotransmitters after severe head injury, we completed a double-blind, placebo-controlled study of combined oral physostigmine and lecithin. Sixteen survivors of moderate to severe closed head injury who had unequivocal memory deficit were studied during the course of inpatient rehabilitation. Although the results generally indicated no difference in the effects of the physostigmine-lecithin combination as compared to lecithin alone, sustained attention on the continuous performance test was more efficient under physostigmine than placebo when the drug condition occurred first in the crossover design. Further investigation of neurotransmitter manipulation is warranted in patients with traumatic brain injury.

Previous experimental studies found that acute intoxication may alter the long-term outcome of standardized spinal cord injury resulting in increased spinal cord necrosis and impaired functional recovery. We examined the effects of acute intoxication (blood alcohol concentration of 100 mg/dl) on hemorrhage and axonal conduction three hours after moderate severity spinal cord contusion induced by a constrained stroke pneumatic impactor. The hemorrhagic spinal cord lesion resulting from standardized injury was significantly increased by acute intoxication. Both local hemorrhage at the injury site and rostro-caudal and total extent of hemorrhage were increased. Also, the ability of nerve axons to recover function during the first three hours post-contusion was impaired by intoxication. These findings confirm that increased post-contusion hemorrhage results when spinal cord contusion injury occurs in the presence of acute intoxication, and suggest that increased intramedullary hemorrhage may contribute to previously observed increases in anatomic damage and impaired functional recovery with alcohol intoxication.

The effectiveness of spinal cord stimulation for control of spasticity was studied in 59 spinal cord injury patients. SCS was markedly or moderately effective in reducing spasticity in 63% of the patients. We found that control of spasticity by SCS was not correlated with the severity of spasticity, the type of spasticity (flexor or extensor), or the ability to ambulate. However, stimulation was more effective in patients with incomplete cervical lesions than in complete cervical lesions. Stimulation below the lesion was more effective than above. We conclude that SCS was effective when electrodes were properly positioned below the lesion over the posterior aspect of the spinal cord in patients with some residual spinal cord function. We hypothesize that SCS controls spasticity by modification of activity of spinal-brainstem-spinal loops and by suppression of segmental excitation through antidromic activation of propriospinal pathways.