Stimulation of plasmin activity by aspirin.

This study demonstrates an enhancing effect of aspirin on the amidolytic activity of plasmin. The stimulation of plasmin by aspirin was concentration-dependent and was attained at aspirin concentrations above 2 x 10(-4) M. Aspirin produced a small, reproducible and statistically significant stimulation of the chromogenic activity of plasmin upon H-D-Valyl-L-Leucyl-L-Lysine-p-nitroanilide (S-2251) or pyro-Glu-Gly-Arg-p-nitroanilide (S-2444). Kinetic analysis demonstrated a slight decrease in the affinity of plasmin for substrate S-2251 in the presence of aspirin, reflected by a change of the Km from 3.2 x 10(-4) M to 3.8 x 10(-4) M, and an increase of the Vm. The reciprocal Lineweaver-Burk curve indicated an uncompetitive type of stimulation. The stimulatory effect of aspirin was abolished by the lysine analogue 6-aminohexanoic acid (AHA) but not by the alpha-amino acid glutamic acid. The effect of AHA suggests a specific involvement of lysine binding sites (LBS) on plasmin in the interaction of the enzyme with aspirin. Transient acidification of plasmin abolished its response to aspirin, to AHA and to their combination. The addition of aspirin to diluted human control or pregnancy plasma in vitro stimulated the plasma-mediated cleavage of the chromogenic substrate S-2251. In contrast to its effect on plasmin, aspirin failed to change the activity of tissue-type or urokinase-type plasminogen activators. It is conceivable that in addition to the antithrombotic effect of aspirin ascribed to its interaction with the platelets, aspirin also directly stimulates plasmin activity.     

Stimulation of motor tracts in multiple sclerosis.

Percutaneous electrical stimulation of the motor cortex was used to evaluate corticospinal conduction to upper-limb motoneurons in 29 patients with multiple sclerosis. Central motor conduction abnormalities were correlated with clinical signs and somatosensory evoked potentials. Muscle responses to cortical stimulation were altered in 20 patients. The most common abnormality was increased central motor conduction time; in two cases the responses to cortical stimulation were absent. Abnormalities were also present in patients with no clinical evidence of corticomotoneuron deficit. Alterations of muscle responses and of somatosensory evoked potentials were usually correlated, but may appear independently. Both testing methods are useful in the study of patients with multiple sclerosis.     

Stimulation of cyclic AMP accumulation by pentylenetetrazol.

The convulsant agent, pentylenetetrazol (PTZ), increased the content of cyclic AMP (cAMP) in rat cortical slices incubated in vitro in physiologic media. This increase was partially reversed by theophylline. The addition of PTZ to maximally effective concentrations of either adenosine or 2-chloroadeosine resulted in a significantly greater than additive augmentation of cAMP accumulation, suggesting that PTZ may produce its effect by enhancing the action of endogenous adenosine. The PTZ response was not antagonized by either diphenylhydantoin, phenobarbital or ethosuximide.     

Stimulation of motor tracts in motor neuron disease.

The muscle responses evoked by cortical and cervical stimulation in 11 patients with motor neuron disease were studied. The muscle potential in the abductor pollicis brevis, evoked by median nerve stimulation and the somatosensory potential evoked by wrist stimulation were also studied. In eight of 11 patients there was absence or increased central delay of the responses evoked by cortical stimulation. In four patients muscle responses on cervical stimulation and muscle action potentials on median nerve stimulation were also altered, indicating peripheral abnormalities. Somatosensory responses evoked by wrist stimulation were normal. Electrophysiological techniques are helpful in estimating the site of motor involvement in motor neuron disease.     

Stimulation of the globus pallidus internus for childhood-onset dystonia.

We report the results of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 12 patients with childhood-onset generalized dystonia refractory to medication, including 3 patients with status dystonicus. There were 8 patients who had DYT1-negative primary dystonia, 1 had DYT1-positive dystonia, and 3 had symptomatic dystonia. Stimulation was effective in all but 1 patient. Dystonic postures and movements of the axis and limbs responded to DBS to a greater extent than oromandibular dystonia and fixed dystonic postures. These findings provide further evidence that pallidal stimulation is an effective treatment for intractable childhood-onset dystonia, including status dystonicus, and together with previous findings, suggest that it should be considered the treatment of choice for these conditions.     

Stimulation of peripheral nerves using a novel magnetic coil.

Magnetic nerve stimulation (MNS) using a novel figure-8 magnetic coil was compared with conventional electric nerve stimulation (ENS) in normal subjects and in patients with disorders of the peripheral nervous system. In contrast to previously tested coils, the virtual cathode of the novel coil was independent of the geometrical or electric conditions of the stimulated tissue. Maximal compound muscle action potentials (CMAPs) were elicited by MNS in all motor nerves tested. The slopes of the recruitment curves of ENS were steeper than those of MNS, indicating a comparatively lower maximal stimulation intensity and a higher intensity resolution of the magnetic stimulator. In four patients with entrapment syndromes at the ulnar groove, motor conduction velocities and amplitudes were similar for MNS and ENS across the affected nerve segment. However, in two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), CMAPs were slightly smaller following MNS. This new technique is a promising step toward the ultimate goal of replacing ENS with MNS.     

Stimulation of subthalamic fibre tracts reduces dyskinesias in STN-DBS.

Rarely, the postoperative management of patients with subthalamic deep brain stimulation (STN-DBS) is complicated by pharmacologically intractable dyskinesias. Here we report that in three of these patients additional stimulation of a proximal contact located within the subthalamic white matter may lead to a significant reduction of dyskinesias associated with STN-DBS. We propose that pallidofugal fiber tracts play a major role in the etiopathology of dyskinesias and their blockade through DBS may explain our observations.     

Effects of Posture on Stimulation Parameters in Spinal Cord Stimulation

Objective . To examine the importance of posture on the efficacy of spinal cord stimulation in a population of chronic pain patients previously implanted with a spinal cord stimulator. Materials and Methods . Electrode leads (Octrode 2098, ANS) were placed percutaneously into the epidural space under fluoroscopic control (BV29, Phillips, Inc.) at either the cervical or thoracic vertebral level. Stimulation parameters were measured at least 24 h after initial Implantation, and as long as 3 y. All patients were asked to look forward and remain still in one of three positions: lying, sitting, and standing. At each posture, electrical stimulation was applied to the spinal cord. The voltages and pulse widths necessary to produce threshold paresthesia, therapeutic stimulation, and uncomfortable sensations were recorded. A stimulus frequency of 100 Hz was used for all subjects. Results . As previously described by Barolat 1 , we found the thresholds for stimulation to be highest in the thoracic level. We also measured the largest usage range to be at this level. However, we found that this range varied greatly between patients and between postures. In 20 patients the threshold for paresthesia was lowest when lying, while in three patients it was lowest when sitting. The mean range and SD of stimulation required to achieve paresthesia at all three posture levels was found to be 0.113 ± 0.062 μC for leads in the cervical region (N = 11) and 0.494 ± 0.297 μC for leads in the thoracic region (N = 19). Conclusions . To provide adequate stimulation at all postures, multiple stimulation settings (programs) would be required.     

Vagus Nerve Stimulation

Summary: Left vagus nerve stimulation (VNS) is a promising new treatment for epilepsy. In 1997, VNS was approved in the United States as an adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. For some patients with partial-onset seizures, the adverse effects of antiepileptic drugs (AEDs) are intolerable; for others, no single AED or combination of anticonvulsant agents is effective. Cerebral resective surgery is an option to pharmacotherapy in some cases, but many patients with partial-onset seizures are not optimal candidates for intracranial surgery. VNS entails implantation of a programmable signal generator—the Neurocybernetic Prosthesis (NCP)—in the chest cavity. The stimulating electrodes of the NCP carry electrical signals from the generator to the left vagus nerve. Although the mechanism of action of VNS is not known, controlled studies have shown that it is safe and well-tolerated by patients with long-standing partial-onset epilepsy. Side effects, which are generally of mild to moderate severity, almost always disappear after the stimulation settings are adjusted. Encouraging results have also been reported in pediatric patients.