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Biomedical subjects

Richard D Penn

Publications and source records attributed to Richard D Penn.

13 recordsLinked to original sources
PubMed2006

Intrathecal baclofen in the treatment of adult spasticity.

Medical management of adult spasticity, a condition of increased muscle tone and deep tendon reflexes, is often challenging and complex. Oral medications such as baclofen often have unacceptable supraspinal side effects at effective doses. Intrathecal baclofen delivered by an implanted catheter and pump system provides good relief of spasticity while overcoming these limitations. In this paper the authors survey the use of oral and intrathecal baclofen therapy, detail the surgical process, and explain the risks and benefits of the procedure.

Administration, Oral↗
PubMed2006

Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.

Adult↗
PubMed2006

Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic brains.

PURPOSE: To develop quantitative MRI techniques to measure, model, and visualize cerebrospinal fluid (CSF) hydrodynamics in normal subjects and hydrocephalic patients. MATERIALS AND METHODS: Velocity information was obtained using time-resolved (CINE) phase-contrast imaging of different brain regions. A technique was developed to measure the change of lateral ventricle (LV) size. The temporal relationships between the LV size change, CSF movement, and blood flow could then be established. The data were incorporated into a first-principle CSF hydrodynamic model. The model was then used to generate specific predictions about CSF pressure relationships. To better-visualize the CSF flow, a color-coding technique based on linear transformations was developed that represents the magnitude and direction of the velocity in a single cinematic view. RESULTS: The LV volume change of the eight normal subjects was 0.901+/-0.406%. Counterintuitively, the LV decreases as the choroid plexus expands, so that they act together to produce the CSF oscillatory flow. The amount of oscillatory flow volume is 21.7+/-10.6% of the volume change of the LV from its maximum to its minimum. CONCLUSION: The quantification and visualization techniques, together with the mathematical model, provide a unique approach to understanding CSF flow dynamics.

Adult↗
PubMed2005

Full-brain T1 mapping through inversion recovery fast spin echo imaging with time-efficient slice ordering.

Brain T1 mapping has important clinical applications in detecting brain disorders. Conventional T1 mapping techniques are usually based on inversion recovery spin echo (IRSE) imaging or its more time-efficient counterpart inversion recovery fast spin echo (IRFSE) imaging because they can deliver good image quality. Multiple inversion times are required to accurately estimate T1 over a wide range of values. Without acquisition optimization, both the IRSE and the IRFSE T1 mapping techniques require long scan times to image the whole brain. To reduce the scan time and maintain the quality of the T1 maps, we propose a new full-brain T1 mapping pulse sequence based on a multislice inversion recovery fast spin echo imaging using a time-efficient slice ordering technique.

Adult↗
PubMed2005

Pressure gradients in the brain in an experimental model of hydrocephalus.

OBJECT: The goal of this investigation was to establish whether pressure gradients exist between the ventricles, brain tissue, and subarachnoid space when acute or chronic hydrocephalus develops. Such gradients are hypothesized by many models of hydrocephalus, but considerable controversy continues about their existence. METHODS: A stereotactic frame was used for surgery in dogs to implant pressure sensors within the right lateral ventricle, the frontal lobe, and forward in the subarachnoid space. The dogs were allowed to recover for 10 to 14 days postoperatively. Then, 800 mg of sterile kaolin in water was injected into the cisterna magna region by using a percutaneous approach. Both real-time and long-term intracranial pressures were measured. Of the six dogs, one experienced an intracranial hemorrhage, one dog displayed status epilepticus after a second injection of kaolin and was killed, one experienced acute hydrocephalus, and three experienced mild chronic hydrocephalus. No consistent pressure differences were found in any dog between the ventricle, brain, and subarachnoid space before kaolin administration or afterward when hydrocephalus developed. In addition, no pulse pressure gradients occurred between the brain and the ventricle or subarachnoid space. CONCLUSIONS: Precise monitoring of pressure before and during the development of hydrocephalus did not detect pressure gradients between the ventricle, brain, and subarachnoid space. This was true for long-term measurements over weeks and for real-time measurements that allowed accurate assessment of pulse pressures. Theories predicting pressure gradients greater than the resolution of these sensors (0.5 mm Hg) across brain tissue have to be reevaluated in light of these findings.

Acute Disease↗
PubMed2003

Intrathecal medication delivery.

This brief review of intrathecal pain medication delivery has emphasized the unusual but useful pharmacology of CSF drug delivery, the new study definitely showing that the method is helpful in cancer pain, and the rare complication of mass formation at the catheter tip. As new medications are developed for intrathecal delivery, this field is likely to expand, especially if a wider range of dorsal horn receptor mechanisms underlying pain processing can be modified. The changes in spinal cord signaling that are induced by chronic pain states are being investigated, and new possibilities for intervention are likely. the availability of a reliable well-understood way of delivering such new therapies by implanted drug pumps will speed the process. Intrathecal morphine for chronic pain has an important role in helping many patients with a wide variety of pain conditions and, as with all pain treatment, is woefully underused.

Analgesics↗
PubMed2003

Continuous intrathecal clonidine and tizanidine in conscious dogs: analgesic and hemodynamic effects.

UNLABELLED: Alpha-2-adrenergic agonists, such as clonidine, produce antinociception in animal pain models after intrathecal administration. However, clinical usage is limited by cardiovascular side effects. To investigate alternative alpha(2)-adrenergic agonists as analgesics, we implanted six dogs with an intrathecal catheter and infusion pump. After baseline saline infusion, animals received clonidine or tizanidine (crossover study) each week at escalating doses of 125-750 microg/h. Analgesia, blood pressure, heart rate, respiratory rate, sedation, and coordination were evaluated. A 28-day safety study was performed with another nine dogs receiving intrathecal tizanidine (3 or 6 mg/d) or saline. Equal doses of clonidine and tizanidine produce the same antinociception in thermal withdrawal tests. Blood pressure was reduced with 125-500 microg/h of clonidine, but not with tizanidine at any dose. Clonidine 250 microg/h reduced heart rate by 45.8%, and five of six animals had bradyarrhythmias (marked bradycardia), whereas tizanidine decreased heart rate by 15.1% without arrhythmias, even at the largest dose. Respiratory rate decreased with 250 microg/h of clonidine and larger doses. Sedation or incoordination occurred only at the largest dose for either drug. The safety study indicated that 3 mg/d of tizanidine in dogs produced no side effects or histopathologic changes. Tizanidine may be a useful alternative in patients experiencing cardiovascular side effects with intrathecal infusion of clonidine. IMPLICATIONS: Clonidine is an effective spinal analgesic, but it is dose-limited by cardiovascular side effects. We compared the analgesic properties and side effects of clonidine with those of a similar drug, tizanidine. Continuous spinal infusion of tizanidine produced similar analgesia as clonidine, but with fewer adverse effects on blood pressure and heart rate.

Adrenergic alpha-Agonists↗
PubMed2002

Reaction time is not impaired by stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in patients with tremor.

We studied the effect of high-frequency electrical stimulation of the ventral-intermediate nucleus of the thalamus (Vim) in four patients implanted with chronic stimulators to determine whether this procedure adversely affects reaction time to a proprioceptive stimulus. Two patients had undergone this surgery for treatment of tremor resulting from Parkinson's disease insufficiently responsive to levodopa therapy and two patients for treatment of essential tremor. Reaction times to auditory, visual, cutaneous, and proprioceptive stimuli were tested in a simple motor task requiring flexion of the elbow joint to a visual target in response to each stimulus. Reaction times were tested postoperatively with and without the stimulator turned on. We found that reaction time for all stimulus modalities was not increased when the stimulator was turned on; in fact, reaction times were, on average, slightly shorter during stimulation, but this difference was not statistically significant. We conclude that transmission of somatosensory inputs, necessary for initiating voluntary movement, from the periphery to the cortex is not significantly impaired by stimulation of the ventral-intermediate nucleus of the thalamus in patients with pathological tremor.

Aged↗
PubMed1992

Octreotide: a potent new non-opiate analgesic for intrathecal infusion.

Somatostatin-14 has been reported to relieve severe cancer pain when given intraspinally. We have studied a stable analog, octreotide, which is suitable for long-term infusion by a drug pump. In preclinical trials in dogs, chronic intrathecal and intraventricular perfusion at 40 micrograms/h did not produce neurotoxicity. On the basis of these findings cancer patients with pain unrelieved by oral opiates were treated for periods of 13 to 91 days with intrathecal octreotide 5-20 micrograms/h. During octreotide infusion, pain scores were lower while oral opiate usage was reduced. No central or systemic side effects of intrathecal administration were seen. The pain relief occurred in patients who had previously not obtained satisfactory pain control with systemic or intrathecal opiates, which is consistent with a non-opiate spinal pathway. These preliminary findings, if confirmed, suggest that octreotide is a potent non-opiate analgesic appropriate for long-term intrathecal infusion.

Adult↗
PubMed1992

Effects of age and size on development of allodynia in a chronic pain model produced by sciatic nerve ligation in rats.

Sciatic nerve constriction injury in rats has been used by various investigators as a model of chronic pain exhibiting allodynia and hyperalgesia. Although rats ranging between 200 and 350 g (40-70 days old) at the time of operation have been used by various investigators, the effect of rat age and weight on the model has not been previously studied. We noted that a group of older rats failed to develop all the characteristics of the model and designed the present study to determine the effect of age and weight on the development of allodynia and hyperalgesia. Three groups of rats varying in age (54, 71, and 107 days) and weight (220-250 g, 270-350 g, and 370-470 g) with the experimental lesion were tested for hyperalgesia, cold allodynia, and tactile allodynia. We found that although the degree of hyperalgesia of all groups was the same, the oldest group had significantly longer response latencies to allodynia tests than the younger 2 groups. Responses to the cold test were no different than control in the oldest group. The results of the present study demonstrate that larger, older rats fail to develop allodynia after sciatic nerve ligation.

Aging↗
PubMed1990

Effect of intrathecal tizanidine on antinociception and blood pressure in the rat.

Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 micrograms producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 micrograms) and morphine (8 micrograms) in peak effect and duration. Doses as high as 250 micrograms produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 micrograms tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lightly anesthetized with halothane, was not affected by tizanidine injections up to 250 micrograms. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage.

Analgesics↗