In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplantation only and has not been revised since. Since then, pallidotomy and deep brain stimulation have emerged as additional treatment modalities but there exists no common tool for evaluation of, and between, the techniques. In 1996, within the framework of NECTAR (Network for European CNS Transplantation and Restoration), a dedicated program entitled "Neurosurgical Interventions in Parkinson's Disease" (NIPD) was funded by the European Union Biomed 2 program to develop a new Core Assessment Program for Surgical Interventional Therapies in PD (CAPSIT-PD) and to establish an European registry for patients with PD subjected to functional neurosurgery. This article presents the recommendations of this new program.

Core assessment program for surgical interventional therapies in Parkinson's disease (CAPSIT-PD).

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.

Intrathecal Baclofen for Severe Spinal Spasticity

Recent experimental studies and one clinical case have suggested that grafting tissue from the adrenal medulla into the brain may ameliorate the signs of Parkinson's disease. We describe t...

Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up

A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system.

✓ Autologous adrenal medullary tissue was transplanted to the striatum in two patients with severe parkinsonism. The aim was to provide the striatum with a new cellular source of catecholamines. Some rewarding effects were registered. This is the first time that such tissue has been transplanted in the human brain. The results merit further clinical trials.

Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials.

Plasma and cerebrospinal fluid levels of baclofen (Lioresal) at optimal therapeutic responses in spastic paresis.

We studied voluntary, velocity-controlled knee movements in 22 patients with spastic paraparesis (11 male, 11 female) and 22 healthy controls (11 male, 11 female). Torque and EMG activity of the quadriceps and the hamstring muscles were determined in maximal voluntary concentric (shortening) and eccentric (lengthening) actions of knee extensor and flexor muscles at constant movement velocities of 30, 60, 120 and 180 degrees/s, using an active, isokinetic dynamometer. In the spastic patients, the voluntary strength and the agonist EMG activity were reduced in all movements. The reduction was largest in concentric actions at high velocity. The antagonist EMG activity was reduced in the same proportion as the agonist EMG activity in eccentric actions. In concentric actions when stretch is imposed upon antagonists, the antagonist EMG activity increased with the velocity of stretch, indicating stretch reflex activation. In parallel with the stretch reflex activation of antagonists, there was reduced activation of the agonists compatible with Ia reciprocal inhibition of agonist motoneurons. When agonists were stretched in eccentric actions, stretch reflexes appeared to support the voluntary, agonist activation of knee flexor muscles but not knee extensors.

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Anders Mårtensson

Papers

Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials.

Plasma and cerebrospinal fluid levels of baclofen (Lioresal) at optimal therapeutic responses in spastic paresis.

Influences of muscle stretch reflexes on voluntary, velocity-controlled movements in spastic paraparesis.

Antiparetic and antispastic effects induced by tizanidine in patients with spastic paresis

Differences in effects in gamma and alpha spasticity induced by the GABA derivative baclofen (Lioresal).