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Richard D. Penn

✓ A total of 66 consecutive patients with severe spasticity of spinal cord origin were screened with intrathecal baclofen, and all but two responded with a two-point decrease in their Ashworth spasticity scale and/or spasm scale score. Of these, 62 elected to receive chronic intrathecal baclofen administration by means of an implanted delivery system. These patients have been followed for an average of 30 months (the first three for 81 months). Intrathecal baclofen has been well tolerated and all serious side effects were transient and have been managed by dose adjustments. The pump presently available has worked safely; the only problem has been stalling in 7% of these devices. The catheter system has had to be repaired in just over one-half of the patients and is the main cause of interruption of drug delivery. Of the 62 patients implanted, 52 (84%) continue to be treated adequately for spasticity; there are three poor long-term responders, four deaths due to underlying disease, and three whose participation has been voluntarily withdrawn. It is suggested that long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients.

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Gerhard Müller-Schwefe and Richard D. Penn

✓ The expanding use of intrathecal baclofen for spasticity has raised a concern about the treatment of overdose in these patients, since no specific baclofen antagonist is available. Since physostigmine has been reported to reverse the respiratory depression and somnolence due to opiates, the drug was tried for the treatment of baclofen overdose. In three cases, intravenous physostigmine (2 mg) completely reversed the respiratory depression and coma caused by boluses of 80 to 800 µg of lumbar intrathecal baclofen. Physostigmine, although not a specific antagonist, should provide increased safety for patients receiving intrathecal baclofen.

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Bruce Bartlow and Richard D. Penn

✓ The authors report a case in which trigeminal neuralgia and hearing loss developed 14 years after a severe head injury. Arteriography demonstrated a carotid-cavernous sinus fistula producing a large venous mass in the posterior fossa.

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Richard D. Penn and Jeffrey S. Kroin

✓ Seven patients with spasticity of spinal cord origin have been maintained for up to 2 years with continuous spinal intrathecal infusion of baclofen. Prior to treatment, all of the patients had severe rigidity in their lower limbs and most had frequent and extensive spontaneous spasms, all of which greatly interfered with their activities of daily living. Oral antispasmodic medications were ineffective or caused central side effects. The patients underwent implantation of a programmable drug pump connected to a lumbar subarachnoid catheter. Within days of beginning continuous intrathecal baclofen infusion, the muscle tone was reduced to normal levels and spasms were eliminated. Over the ensuing months, muscle tone remained normal, but short-duration spasms could be induced by some activities. The greatest benefits to the patients were improvement in activities of daily living and better sleep due to reduced spasms. The baclofen doses were increased over the first few months but then were stabilized or only increased slightly, with the maximum dose being 650 μg/day. The most serious complications were two drug overdoses which took several days to clear up and were due to malfunctions of an earlier pump model. Baclofen clearance from the cerebrospinal fluid occurs with a half-life of 5 hours. The most serious concern in maintaining patients indefinitely on intrathecal baclofen is whether drug tolerance will eventually occur.

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Richard D. Penn and Diane Kurtz

✓ The authors conducted quantitative analysis of computerized tomography (CT) scans to measure tumor size, cerebral edema, and regional blood volume in man. Mass lesions without edema caused a local reduction in blood volume. Cerebral edema also reduced blood volume in proportion to its severity. Consideration of the electrolyte changes and water shifts in white-matter edema suggested that the decrease in absorption coefficient seen in CT scans was due to the increase in water content. Thus, in cerebral edema separation of blood vessels as well as increased interstitial pressure decrease blood volume, and the regional differences in turn reflect pressure gradients within the brain.

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Richard D. Penn and Judith A. Paice

✓ Forty-three patients with intractable pain received intrathecal morphine delivered by implanted continuous-infusion (Infusaid) or programmable (Medtronic) devices. In 35 patients the pain was due to cancer, and eight patients had chronic nonmalignant pain. The origin of the nonmalignant pain included lumbar arachnoiditis, multiple sclerosis, severe osteoporosis resulting in a thoracic compression fracture, and intractable pain as a consequence of cancer therapy in individuals cured of their disease. Twenty-eight (80%) of the patients with cancer-related pain experienced excellent or good relief. Side effects were rare. Tolerance occurred infrequently and could be managed effectively. The results of this study support earlier studies on the application of chronic intrathecal morphine for intractable cancer pain. These findings also indicate that, in carefully selected patients, nonmalignant pain may be managed satisfactorily with this technique.

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Jeffrey S. Kroin, Gregory D. Bianchi and Richard D. Penn

✓ At present, it is not clear why drug tolerance develops in patients receiving intrathecal baclofen for the chronic treatment of spasticity of spinal origin. To investigate the mechanisms of tolerance to the gamma-aminobutyric acid (GABAB) agonist baclofen, rats were implanted with intrathecal catheters and continuously infused with either the drug or saline for 1, 3, or 7 days. The dose chosen, 1 µg/hr, initially caused profound hindlimb motor weakness, but by Day 7 the rats had adapted to the drug and exhibited only minimal motor impairment. The animals were sacrificed on Day 1, 3, or 7 and quantitative autoradiography was used to determine the binding density and affinity of the GABAB receptors in the substantia gelatinosa of the lumbar spinal cord. After I day of drug infusion there was no change in binding parameters, but after 3 and especially after 7 days there was a significant decrease in the GABAB binding density (74% and 66%, respectively) in baclofen-treated rats as compared to saline-treated control rats. This GABAB receptor down-regulation correlated with tolerance to the motor weakness in the baclofen-treated animals and suggests that similar mechanisms contribute to drug tolerance in patients.

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Cerebellar stimulation in man

Quantitative changes in spasticity

Richard D. Penn, Gerald L. Gottlieb and Gyan C. Agarwal

✓ The effects of chronic anterior lobe cerebellar stimulation on patients with cerebral palsy have been investigated using a new method of quantifying muscle rigidity and stretch reflexes. The ankle is oscillated sinusoidally, compliance is measured at several frequencies, and electromyographic activity of the extensor and flexor muscles is recorded. In some patients stimulation can reduce rigidity and coactivation of muscles immediately or slowly over days or months. In others no change is found.