Generalists in SCI medicine: good, bad or indifferent?
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Biomedical subjects
Publications and source records attributed to R R Young.
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To estimate risk factors for pressure ulcers, we developed quantitative definitions for each of the nine general areas of risk outlined by the 1989 National Pressure Ulcer Advisory Panel (NPUAP) and evaluated each of these factors in a group of spinal cord injured patients by means of a retrospective chart review at a spinal cord injury referral center serving the New England area. All patients (n = 364) admitted to the spinal cord injury service between January 1, 1989 and December 31, 1990 were studied. We identified a pressure ulcer in 81 of 364 patients (22.3 percent). In the univariate analyses, pressure ulcers were associated with Frankel groups A to B with an odds ratio (OR) of 5.7 (95 percent confidence interval 2.8 to 11.9), low albumin with an OR of 4.9 (95 percent confidence interval 2.8 to 8.6), low hemoglobin with an OR of 2.5 (95 percent confidence interval 1.5 to 4.1), age > or = 60 years with an OR of 1.9 (95 percent confidence interval 1.2 to 3.2) and three independent measures of co-morbidity: Cumulative Illness Rating Scale (CIRS) with an OR of 3.7 (95 percent confidence interval 2.1 to 6.3), Charlson Index with an OR of 2.2 (95 percent confidence interval 1.3 to 3.8), and International Classification of Diseases, Ninth Revision, Clinical Modification count with an OR of 4.2 (95 percent confidence interval 2.4 to 7.2). In the logistic regression model, low albumin, CIRS and Frankel grade A to B and history of pressure ulcers were predictors.(ABSTRACT TRUNCATED AT 250 WORDS)
In order to quantify motor disabilities in Parkinson's disease (PD), we designed a compact, portable, neurophysiological system based upon a personal computer to measure tremor, bradykinesia, and muscle tone. Tremor was detected by solid state accelerometers and translated into a digital signal. The system displayed the root mean square displacements and frequency distribution of the tremor in the horizontal and vertical planes, along with a reconstructed graphic image of the displacement. Bradykinesia was measured using a panel that detects release and depression of switches in response to auditory and visual signals; the system calculated subjects' reaction times and movement times in milliseconds. Tone at the elbow was measured by strapping the upper extremity to a lightweight low-friction cradle and then passively moving the cradle with an instrumented handle. Signals representing torque and arm angle were processed by the computer and displayed in real time on the screen with stiffness as a mean slope in Nm/degree. In clinical tests, quantitative measures of tremor, movement time and rigidity were significantly abnormal in PD patients compared to control subjects. We conclude that this system is a convenient and accurate method to quantitate important aspects of the parkinsonian syndrome, and may be applied to quantitate other movement disorders.
Recurrent inhibition via Renshaw cells provides a mechanism by which spinal and supraspinal centers exert control over movement. The conditioned H-reflex technique of Pierrot-Deseilligny and Bussel permits noninvasive assessment of recurrent inhibitory pathways. We employed this technique to investigate changes in Renshaw cell activity due to nicotine (a potent CNS cholinergic agonist that excites Renshaw cells in animals) contained in inhaled tobacco smoke. In 10 normal subjects, cigarette smoking caused a large, rapid drop in the conditioned H-response amplitude, implying increased activation of Renshaw cells. The time course of the change in conditioned H-response amplitude closely approximated the known pharmacokinetics of inhaled nicotine. Nicotine administered via chewing gum had a much slower and less dramatic effect, probably due to the slower rise in blood levels with this mode of administration. Increased activity in Renshaw cells may contribute to spasticity in spinal cord-injured patients, raising the possibility that cigarette smoking could cause further increases in tone in such patients.
Advancements in the management of urologic complications such as the neurogenic bladder have been essential to improving the quality of life and longevity of patients with spinal cord injury. These advances are discussed in greater detail in the subsequent articles in this issue. Despite the many improvements that have been made in post-trauma care, spinal cord injury remains a devastating lesion of the nervous system. Current therapies have not proved to be particularly effective in preventing or reversing damage to the spinal cord. Still, every effort should be made to preserve remaining function and to prevent complications. The care of these patients has been significantly improved with the development of specialized multidisciplinary centers. The emphasis in current treatment focuses on rehabilitation and adaptation to the disability and on prevention of secondary disabilities. Research in basic and clinical neuroscience will result in better, more useful care and treatment for those with spinal cord injury. However, even then, a neurorehabilitation team will be essential to care for these patients. Continuing efforts must be made to ensure that people with spinal cord injury lead full and productive lives.
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Concentrated organic residues extracted from 5 blended aliquots of commercial beers were evaluated for their ability to induce sister chromatid exchange (SCE), chromosomal aberrations and forward mutation in Chinese hamster ovary (CHO) cells. Each extract was prepared by blending 4 commercial beers of similar ingredients and brewing method, passing the beer pool over XAD-2 resin, extracting the resin and concentrating the extract. Studies were performed both with and without metabolic activation using variable amounts of reconstituted residues from 225-fold concentrates of the blended samples. CHO cultures were treated with 0.75 microliters/ml through 10.0 microliters/ml of the concentrates in the SCE assays, 1.0 microliters/ml through 10.0 microliters/ml of the extracts in the aberration assays and 2.5 microliters/ml up to 20 microliters/ml for forward mutation assays. In preliminary screening for SCE as an indicator of potential DNA damage, a significant increase was observed for 3 of 5 concentrated samples; however, no increase in SCE was induced by any of the 5 samples when S9 was added as a source of exogenous metabolic activation. More definitive tests for induction of genetic events, i.e., chromosome aberrations and forward HGPRT mutations, were negative for all 5 extracts whether or not S9 mix was present. Since SCE were not induced in tests with metabolic activation and since there was no concordant aberration or point mutation induction, the preliminary indication of potential DNA damage shown by elevated SCE under conditions without metabolic activation appears to have little biological significance.
Perfluoro-n-decanoic acid (PFDA) is a perfluorinated fatty acid that produces hepatomegaly and increased peroxisomal beta-oxidation when administered to rodents. Chlorotrifluoroethylene (CTFE) trimer acid and CTFE tetramer acid are metabolites of the six- and eight-carbon oligomers of CTFE, respectively. They are structurally related to PFDA, and CTFE tetramer acid has caused toxic effects in rodents that are similar to those observed following PFDA administration. Because of the correlation between peroxisome proliferation and hepatocarcinogenesis, CTFE trimer acid, CTFE tetramer acid, and PFDA were evaluated in in vitro and in vivo/in vitro bioassays to assess their potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal mutagenicity assay, the hypoxanthineguanine phosphoribosyltransferase (HGPRT) locus Chinese hamster ovary gene mutation assay, the sister chromatid exchange (SCE) assay, chromosomal aberration assay, and an in vivo/in vitro unscheduled DNA synthesis (UDS) and S-phase DNA synthesis assay. All test articles were negative in the Ames assay, the HGPRT assay, and the SCE assay. In the chromosomal aberration assay CTFE trimer acid and CTFE tetramer acid were negative in cultures with and without S9 metabolic activation. PFDA was also negative in the absence of metabolic activation, but chromosomal aberrations were observed when PFDA was incubated in the presence of S9 fraction. All test articles were negative for inducing UDS but all induced S-phase replicative DNA synthesis 16 hr after administration of the test article to the test animals; only CTFE tetramer acid and PFDA induced S-phase synthesis 48 hr after dosing: the usual timepoint examined for this response.
We established the occurrence of headache in a group of 20 patients with traumatic transections of the cervical spinal cord. All but two patients had complete sensory lesions at levels varying from C2-3 to C7-8. Only three patients claimed to have no headaches at all although one of them had nuchal pains with fever. Twelve patients had "bladder" or "bowel headaches" or had had them in the past. These headaches were mostly generalized, throbbing or pounding in nature and severe in intensity. They were caused by obstruction of urinary flow and fecal impaction, respectively, and were associated with autonomic dysreflexia. Otherwise the headaches reported by the patients were mild although frequent in four, i.e once per week or more. These headaches were also mostly bilateral and lasted a relatively short time, i.e. less than one or two hours. The causes of these headaches were nonspecific for the group studied except for stimulation of the body which, however, probably depended on a mechanism similar to that of the bladder and bowel headaches. Migraine, either classic or common, was not reported by any of the patients.
Mechanisms underlying the development of spasticity after spinal cord injury are not understood. One spinal interneuron likely to be affected is the Renshaw cell, which acts to produce recurrent inhibition in motor neurons as well as inhibiting Ia interneurons. Descending pathways exert both excitatory and inhibitory control over Renshaw cell activity. We studied Renshaw cell activity in normal subjects and in patients with varying levels of spasticity after spinal cord injury using the conditioned H-reflex technique of Pierrot-Deseilligny and Bussel. A submaximal stimulus to the tibial nerve is presented prior to a supramaximal stimulus so that action potential collision permits an H reflex (H') to be elicited in response to the supramaximal stimulus. The amplitude of this H' reflex is affected by activity in recurrent inhibitory pathways. Patients with both complete and partial spinal cord lesions were studied; date of injury ranged from 1 month to 216 months prior to evaluation. In the 18 patients in whom H reflexes could be recorded, H' reflexes were absent in 13, in contrast to their uniform presence in normal subjects. We conclude that recurrent inhibition via Renshaw cell activity is increased in spinal cord injury, and that measures of recurrent inhibition may correlate well with some clinical measures of spasticity.
Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.
Fast isometric elbow flexor muscle contractions of specified amplitude in six normal subjects were compared with those of 11 patients with Parkinson's disease. Despite treatment, all patients exhibited deficits in this motor task. Three patients were able to produce rapid force pulses with normal contraction times, but the variability of their force responses was increased in comparison with the highly stereotyped responses produced by normal subjects. The other eight patients had prolonged contraction times and segmentation of the force profiles. The integrated area of the first agonist EMG burst and the rate of development of force (dF/dt) were less at any target level than what was needed to produce a fast response. The area of the EMG burst, however, did increase with target amplitude, and the relative increase of dF/dt, with target amplitude, was normal. It is concluded that the motor program subserving fast muscle contraction is preserved in Parkinson's disease, but its execution is characterised by improper scaling of motor output.
Disease of the spinal cord or cauda equina may cause pain, motor abnormalities, sensory disturbance, alteration of reflexes and muscle tone, and bladder dysfunction. These five neurologic abnormalities occur in various combinations, evolve rapidly or slowly, and result in one of eight possible spinal cord syndromes. When a particular syndrome is defined by neurologic history and examination, differential diagnosis is limited to only a few possible disorders. An appropriate neuroradiologic or electrophysiologic procedure done at this point will usually provide the correct diagnosis.
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Synchronization between pairs of single motor units simultaneously recorded from wrist extensor muscles was quantitated in 3 normal subjects during physiologic tremor (PT), beta-adrenergically enhanced physiologic tremor (EPT), and fast voluntary wrist flexion-extension movements mimicking tremor (VT). Cross-correlation histograms generated from the two spike trains of each motor unit pair demonstrated central or paracentral peaks in 13/19 recordings during PT, 22/36 during EPT, and 6/7 during VT. Relative peak area was used as a quantitative index of synchronization between the two motor units of each pair. It was lowest in PT, progressively increased in EPT as tremor amplitude increased, and highest in VT. In PT and lower amplitude EPT, the synchronization indexes were higher between motor units that discharged at the same or nearly the same frequency. In contrast, in higher amplitude EPT and VT, motor units with different firing frequencies were sometimes strongly synchronized as a consequence of double discharges in faster-firing motor units that had burst repetition rates in the range of slower-firing motor units discharging as singlets. Greater motor unit synchronization with increasing tremor amplitude in EPT may be secondary to a simultaneous increase in muscle spindle afferent activity from the tremulous muscle. Greatest synchronization in VT presumably reflects near maximal supraspinal and segmental common synaptic input onto motoneurons that generate VT. These results support a longstanding hypothesis that synchronization of motor units is the physiological basis for higher amplitude tremor.
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Motor axons supplying lumbrical muscles are less severely affected than axons supplying thenar muscles in the carpal tunnel syndrome; sometimes lumbrical motor fibers are less affected than digit 2 sensory fibers. This pattern is consistent with compression of both the anterior and posterior aspects of the median nerve in the carpal tunnel because nerve fibers responsible for thenar, lumbrical, and digit 2 functions lie in an anterior-posterior gradient within the distal median nerve. Recognition of lumbrical sparing supports the electrodiagnosis of carpal tunnel syndrome when the distal latency to thenar muscles or the palm-to-wrist mixed median nerve conduction velocity is normal.