Intraspinal drug infusion for chronic pain.
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Chronic Disease↗
Biomedical subjects
R D Penn
Publications and source records attributed to R D Penn.
Effect of repetitive lidocaine infusion on peripheral nerve.
Neurotoxicity in rat tibial nerve was assessed following injections of lidocaine through implanted catheters. Doses of 1 to 4% lidocaine in volumes sufficient to inhibit motor nerve function, were infused three times a day for 3 days. When 4% lidocaine was infused into a Silastic cuff surrounding the sciatic nerve, all function was lost and there was considerable nerve fiber degeneration. When 4% lidocaine was infused within the muscle pocket surrounding the nerve, but at some distance from the nerve, there was no measurable permanent loss of motor function, but occasional nerve fiber degeneration. In contrast, 1% lidocaine appeared to cause no neurotoxicity, even when infused within a surrounding cuff. In addition, 1% lidocaine injection did not cause damage to the underlying muscle. Therefore, intermittent nerve block with low concentrations of lidocaine appears to be nontoxic to nerve and muscle when administered during 3 days. However, long-term studies are needed before clinical usage can be considered, because there is the potential for nerve and muscle damage.
Animals↗
Movement deficits caused by hyperexcitable stretch reflexes in spastic humans.
Spastic patients were instructed to make accurate, rapid ankle dorsiflexion and plantarflexion movements over different distances to a target. Ankle position and surface electromyograms (EMGs) from tibialis anterior (TA) and soleus (SOL) muscles were recorded. In 3 of 8 spastic patients tested, dorsiflexion evoked velocity-dependent activation of the antagonist (SOL) muscle which impeded the movement to the extent that the limb unintentionally reversed movement direction. We propose that this activation is reflex in origin since it is tightly synchronized, has a large peak amplitude, occurs about 50 ms after the initiation of the movement, and is velocity dependent. One of the 3 patients who had reflex-induced antagonist activation in dorsiflexion also demonstrated sustained clonus during plantarflexion. This usually occurred only if the target had been overshot so that the return of the limb stretched the soleus muscle and triggered clonus. We conclude that in some patients, hyperactive stretch reflexes cause movement deficits.
Adult↗
Computerized tomographic scan assessment of alcoholic brain damage and its potential reversibility.
The assessment of alcoholic brain damage by computerized tomographic (CT) scanning is reviewed and discussed. Alcoholics showed greater cerebral atrophy than aged-matched neurological controls. Supratentorial atrophy measurements correlated significantly with some neurobehavioral assessment measures. The cerebral atrophy reversed in some subjects with maintained abstinence. Computerized assessment of cerebral spinal fluid volume (cerebral atrophy) and mean cerebral density showed decreased cerebral spinal fluid volume and increased cerebral density with maintained abstinence over 4 weeks in a group of 20 alcoholics. CT cerebellar measurements demonstrated atrophy in many subjects, but these measurements did not correlate with measures of ataxia, cognitive impairment, supratentorial atrophy measurements, or age. An example of a magnetic resonance imaging scan of an alcoholic is given. Its advantages in avoiding bony artifact for posterior fossa atrophy estimations and its potential for in vivo description and localization of central nervous system metabolic abnormalities in alcoholism are discussed.
Adult↗
Continuous intrathecal baclofen for severe spasticity.
Baclofen is the most effective drug for the treatment of rigidity and spasms caused by damage to the spinal cord, but frequently, relatively little relief is afforded and dose is limited by central side-effects. To improve the efficiency of drug delivery 6 patients received implantable programmable pumps with a catheter going into the lumbar subarachnoid space. Baclofen, at doses of 12 micrograms to 400 micrograms per day, was given for up to 7 months. With intraspinal treatment there was an immediate reduction of muscle tone to normal levels, and spontaneous spasms were eliminated. Patients experienced less discomfort, and daily activities were more easily accomplished.
Adult↗
Evaluation of cervical stimulation for chronic treatment of spasticity.
Electrical stimulation of the spinal cord (SCS) to reduce spasticity was evaluated in seven patients who, along with their physicians, perceived significant and prompt benefit from stimulation. In two 24-hour test periods, on or off stimulation, we used two independent methods of evaluation: quantitative measures of joint compliance and stretch reflexes, and a standardized neurologic examination. Neither method did better than chance in determining whether SCS was actually being received. Problems with the experimental protocol are discussed, but the results cannot be interpreted as supporting the efficacy of SCS as a treatment for spasticity.
Cerebral Palsy↗
Drug pumps for treatment of neurologic diseases and pain.
Implanted drug pumps provide a new way to infuse medication chronically to the nervous system in a selective fashion. They have been of value in treating pain of cancer and spasticity through spinal subarachnoid catheters. Treatment of Alzheimer's disease is currently being investigated using intraventricular bethanechol.
Alzheimer Disease↗
Intrathecal baclofen alleviates spinal cord spasticity.
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Adult↗
The ring technique for end-to-side microvascular anastomosis.
The ring technique for end-to-side microvascular anastomosis employs a resorbable polyglycolic acid ring to prevent stenosis and spasm at the anastomotic site. In 20 rats, the ring technique was compared with the conventional technique for constructing end-to-side anastomoses between the femoral (0.9-1.1 mm) and superficial epigastric (0.3-0.4 mm) arteries. The ring technique proved superior to the conventional end-to-side technique both in speed of execution and in patency at 3-4 weeks (100% vs 70%). Grossly and microscopically, the ring was completely resorbed at 3 wk.
Animals↗
Reduced spinal reflexes following intrathecal baclofen in the rabbit.
Intrathecal baclofen is effective in reducing polysynaptic spinal reflexes in awake rabbits. A single lumbar infusion of 2.5-5.0 ng drug caused a significant reduction in the crossed extensor response to electrical stimulation of the plantar surface of the hindlimb. This inhibition lasted 5 h or more. At doses of 3 micrograms or less, the forelimbs were unaffected.
Animals↗
The brain as a sponge: a computed tomographic look at Hakim's hypothesis.
Hakim's hypothesis, which explains the brain's adaptation to pressure in hydrocephalus and the enlargement of ventricular volume, was studied with computed tomographic (CT) scanning. The critical element in the theory is that brain water decreases when there is a pressure gradient within brain tissue. Extraaxial hematomas uniformly increase the CT density of adjacent brain tissue, and this is best explained by water shifts out of the tissue. In hydrocephalus cases studied early after shunting (10 days or less), a decrease in ventricular volume is accompanied by an overall decrease in the CT density of the brain. These CT changes support Hakim's view of the brain as a sponge that can change its hydration under pathological conditions.
Brain↗
Regulation of natural killer cell function by glass-adherent cells in patients with primary intracranial malignancies.
Natural killer (NK) cell function against the NK cell-sensitive myeloid leukemia cell line, K562, was measured in the peripheral blood mononuclear cells (PBMCs) of 17 patients with primary brain tumors (4 diagnosed as having low grade tumors and 13 diagnosed as having high grade (malignant) tumors). The ability of monocytes to control the levels of NK cell function in PBMCs from these patients was assessed in glass-adherent cell depletion studies. Most patient assessments were performed before surgical biopsy and diagnosis; most but not all patients were receiving dexamethasone at the time of immunity assessment. The results demonstrate that patients with primary malignant brain tumors have depressed levels of NK cell function in their PBMCs due to the suppressive actions of glass-adherent monocytes, whereas patients with low grade tumors have normal levels of function shown by this assay.
Adult↗
Lower extremity functional neuromuscular stimulation in cases of spinal cord injury.
Functional neuromuscular stimulation (FNS) provides a mechanism for the activation of muscles paralyzed by injury to the spinal cord. Although this technique was first used to treat patients with spinal cord injury over 20 years ago, only recent advances in electronics and biomechanics have made it a promising aid for the rehabilitation of these patients. Thus far, restoration of palmar prehension and lateral prehension in quadriplegics and of standing and biped gait in paraplegics has been achieved under carefully controlled laboratory conditions. This article reviews the current status of FNS and its potential as a practical tool to aid spinal cord-injured patients. Neurosurgeons who care for these patients might be expected to be involved in the future use of FNS if implantable systems are developed and tested.
Biofeedback, Psychology↗
Cancer pain relief using chronic morphine infusion. Early experience with a programmable implanted drug pump.
Fourteen patients were implanted with drug pumps to provide chronic epidural or intrathecal morphine to relieve pain due to cancer. A new programmable pump was used in seven of the patients and a constant infusion device was used in the other seven patients. Results, judged by subjective pain reports (on a 0 to 10 scale), decrease in oral narcotics, and change in activity level, were excellent in eight patients, good in five patients, and poor in one patient. The programmable device has the obvious advantage of being able to vary dose according to patient need and requires less frequent refilling. Four programmable pump failures occurred, two requiring replacement.
Adult↗
Chronic intratumoral chemotherapy of a rat tumor with cisplatin and fluorouracil.
In order to demonstrate the feasibility and efficacy of intratumoral chemotherapy, brain tumors in rats were treated by direct infusion of cisplatin or fluorouracil. Each animal was initially implanted in the midline cerebellum with a chronic stainless-steel cannula, and 2 weeks later 1 X 10(5) 9L cells were injected through the cannula. 8 days after tumor cell transplantation, a small implantable pump containing drug, or saline as a control, was connected up to the same cannula, and the solution was pumped into the tumor region for 7 days. The results showed that both drugs produced statistically significant increases in survival as compared to the controls.
Animals↗
Reciprocal excitation of antagonistic muscles as a differentiating feature in spasticity.
The electromyographic activity evoked by forced ankle rotation in spastic patients with cerebral palsy differs markedly from that found in normal subjects or in patients with adult-onset injuries to the central nervous system. Rapid dorsiflexion can produce a strong myotatic reflex electromyogram at 30 to 50 msec in the normal adult's stretched soleus muscle, while the antagonist tibialis anterior muscle quiet. The same is true of spastic patients whose injury has an adult onset. In patients with cerebral palsy this early response is found in both muscle groups. The pattern of "reciprocal excitation" is in marked contrast to the reciprocal inhibition normally seen. This reflex behavior suggests a fundamental developmental error in neuronal interconnections of the spinal cord in cerebral palsy.
Adolescent↗
Reciprocal excitation of muscle antagonists by the primary afferent pathway.
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Adult↗
Intracerebral chemotherapy: chronic microinfusion of cisplatin.
Cisplatin, a chemotherapeutic agent used to treat tumors in many parts of the body, does not reach brain tissue during systemic injection because of the blood-brain barrier and protein binding in the blood. To allow hydrophilic drugs, such as cisplatin, to reach brain neoplasms with minimal body toxicity, we tested chronic intracerebral microperfusion into the extracellular space of the brain in normal rats. Small stainless steel cannulas connected to osmotic minipumps were stereotactically placed in the midline cerebellum or frontal cortex, and cisplatin was pumped into the brain at the rate of 0.9 microgram/hour for periods of up to 7 days. Brain tissue was then analyzed for the total platinum content, at 1-mm intervals from the cannula tip, using atomic absorption spectroscopy. The results of the animal studies show that a platinum concentration of 2 ng/mg of tissue, wet weight, can be maintained over a 1-cm region of brain. If all of the extracellular platinum has remained in the active cisplatin form, then this would be equivalent to a drug concentration of 10 microM. Cisplatin at this constant level has been shown to have a therapeutic effect against various tumor lines in vitro. To extend these results to human brain neoplasms, we estimate that one cannula would be sufficient to treat a 1-cm tumor or a larger tumor that could be surgically reduced. For inoperable tumors of up to 2 cm in diameter, a multiple cannula system would be required to yield the 10 microM concentration throughout. For larger inoperable tumors, local infusion will not produce high enough drug levels. In conclusion, chronic intracerebral microinfusion can be used to produce adequate and sustained therapeutic drug levels over a considerable region of tissue without the problem of systemic toxicity.
Animals↗