Epidural electric stimulation of posterior structures of the human lumbar spinal cord: 1. muscle twitches - a functional method to define the site of stimulation.

OBJECTIVES: To describe an electrophysiological method for determining the relation between lumbar cord dorsal roots and cathode of epidural electrode for spinal cord stimulation (SCS). MATERIALS AND METHODS: Data has been collected from 13 subjects who have been under evaluation of effectiveness of SCS for control of spasticity. Induced muscle twitches from both quadriceps (Q), adductors (A), hamstrings (H), tibial anterior muscles (TA) and triceps surae muscles (TS) were simultaneously recorded with surface-electrode polyelectromyography (pEMG) and analyzed for amplitudes, latency times and recruitment order. RESULTS: Stimulation of dorsal lumbar cord structures evoked characteristic EMG events during muscle twitch responses. Their amplitudes varied with stimulus strength. Latency times were rather invariable regardless of stimulus strength. Two distinct recruitment orders were demonstrated depending on whether the stimulating cathode was placed over the upper (=response from quadriceps and/or adductor muscles) or the lower (=response from tibialis anterior and triceps surae) lumbar cord segments. The chances to stimulate upper lumbar cord segments are best around the 12th thoracic vertebra. CONCLUSIONS: pEMG recording of muscle twitches enables us to accurately differentiate between upper and lower lumbar cord segments. Furthermore, our findings regarding amplitude, latency and recruitment order strongly suggest that we stimulate posterior roots not posterior columns of the lumbar spinal cord.

Does deep brain stimulation of the nucleus ventralis intermedius affect postural control and locomotion in Parkinson's disease?

The purpose of this study was to evaluate the effect of unilateral stimulation of the nucleus ventralis intermedius (VIM) on parkinsonian signs like postural stability and locomotion with respect to the severity of Parkinson's disease (PD). Seven patients with idiopathic PD were included in the study. Changes in visual cues on postural stability and step initiation were assessed on a fixed platform system with VIM stimulation switched either on (VIM ON) or off (VIM OFF), and compared with a control group of seven age-matched normal individuals. Sway scores (area and path) were significantly (p <0.05) higher in the parkinsonian patients with VIM OFF than with VIM ON as well as compared with the control subjects. No correlation was obtained between extent of sway scores and severity of contralateral tremor after cessation of VIM stimulation. Locomotion parameters, by contrast, were not influenced by VIM stimulation: latency until step initiation and walking-cycle time were the same among parkinsonian patients as among normal individuals, both in the presence and in the absence of VIM stimulation. In conclusion, our results indicate that tremor suppression by VIM stimulation improves postural stability.

Evaluation of micronuclei and chromosomal breakage in the 1cen-q12 region by the butadiene metabolites epoxybutene and diepoxybutane in cultured human lymphocytes.

1,3-Butadiene is a widely used industrial chemical and common environmental pollutant that has been associated with increased risks of leukemias and lymphomas. Butadiene and its metabolites, 1, 2-epoxybutene (EB) and diepoxybutane (DEB), have been shown to be genotoxic in a wide variety of test organisms. The objective of this research was to evaluate techniques for the rapid detection of chromosomal alterations occurring in humans exposed to butadiene. We have used a multicolored fluorescence in situ hybridization (FISH) method and the CREST-modified micronucleus assay to detect chromosomal breakage induced by EB (10-300 microM) and DEB (0.5-10 microM) in cultured human lymphocytes. A significant dose-related increase in the formation of micronuclei was seen in lymphocytes treated with DEB at concentrations as low as 2.5 microM, but not with EB over the dose range tested. Over 80% of the micronuclei induced by DEB were CREST-negative, indicating their origin from chromosomal breakage. Multicolor FISH using two adjacent chromosome-specific probes showed a significant increase in chromosomal breakage in the 1cen-q12 region induced by DEB at concentrations as low as 2.5 microM, but not by EB. Since DEB is likely to be one of the metabolites contributing to the genotoxic effects of butadiene, the sensitivity of the tandem FISH approach to detect breakage induced by diepoxybutane indicates that this technique may be useful for monitoring chromosomal alterations in butadiene-exposed workers.

Apomorphine test: a predictor for motor responsiveness to deep brain stimulation of the subthalamic nucleus.

The value of the apomorphine test as a predictor of the clinical outcome of deep brain stimulation of the subthalamic nucleus (STN) was evaluated in patients with advanced idiopathic Parkinson's disease (IPD) or multiple system atrophy (MSA). Thirteen IPD patients with severe diurnal fluctuations and one MSA patient not responding to dopaminergic drugs were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) and the timed finger tapping test (FTT), measured preoperatively on and off apomorphine and postoperatively on and off STN stimulation. UPDRS motor items 20-25 were assessed intraoperatively on and off STN stimulation when the clinically effective target was approached. The motor response to immediate intraoperative and long-term STN stimulation was correlated with results of the apomorphine test. The response to immediate intraoperative STN stimulation was accurately predicted by apomorphine challenge in all 13 IPD patients. Clinical outcome following long-term STN stimulation was correlated significantly with preoperative changes due to apomorphine measured with the UPDRS motor scores (r = 0.7125, P < 0.01) and FTT (r = 0.9276, P < 0.001). Moreover, comparison of long-term STN stimulation to preoperative drug treatment displayed a significant reduction in the duration of off-phases and a significant increase in the duration of on-phases. However, in the single patient with MSA no beneficial response was obtained either to apomorphine or to STN stimulation intraoperatively and during the postoperative externalized test period. Our results indicate that the apomorphine test can predict the outcome of immediate and long-term STN stimulation and may help in the selection of candidates for surgery.

Deep brain stimulation of the subthalamic nucleus for control of extrapyramidal features in advanced idiopathic parkinson's disease: one year follow-up.

UNLABELLED: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) with a quadripolar electrode was carried out in 9 patients with advanced idiopathic Parkinson's disease (PD) affected with severe diurnal motor fluctuations. The effect of bilateral STN stimulation was evaluated by clinical methods in all patients after 3 and 12 months. Assessment was based on the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests, the Schwab and England Activities of Daily Living and a diary chart to document motor fluctuations. Alterations in parkinsonian signs, motor performance and functional outcome were recorded postoperatively (1) under temporary complete withdrawal of both STN stimulation and medication; (2) in the presence of STN stimulation only; and (3) in the presence of both STN stimulation and medication. The results were compared with the preoperative data assessed in defined on-phase and defined off-phase. STN stimulation on (compared to STN stimulation off) results in a significant improvement in UPDRS motor scores: after 3 months from 50.5 +/- 14.3 to 27.8 +/- 5.8, and after 12 months from 49.4 +/- 14.1 to 27.1 +/- 7.1 (p < 0.01). There was a significant decrease in the average duration of off-periods from 8.82 +/- 2.47 hours to 1.00 +/- 1.06 hours (p < 0.001), a marked increase in on-periods without dyskinesia from 4.62 +/- 2.72 to 14.62 +/- 1.51 hours (p < 0.01), and a sharp drop in on-periods with dyskinesia from 2.87 (+/- 4.18) to 0.25 (+/- 0.97) hours (p < 0.05), which remained stable up to 12 months (off-periods: 1.25 +/- 1.58 hours, p < 0.001; on-periods without: 13.87 +/- 1.95 hours, p < 0.001; and on-periods wth dyskinesia: 0.37 +/- 1.06 hours, p < 0.05). However, our first PD patient with an implanted DBS electrode within the STN died from cardiac infarction two days after surgery. This sudden death was not linked either to surgery nor to stimulation - and happened by chance. Our findings confirm that STN stimulation is a suitable functional neurosurgical procedure for the modulation and control of PD signs associated with severe motor fluctuations, in that they demonstrate a beneficial effect which was fully sustained over a one year follow-up period. KEYWORDS: Subthalamic nucleus, deep brain stimulation, Parkinson's disease.

Persistence of chromosomal alterations affecting the 1cen-q12 region in a human lymphoblastoid cell line exposed to diepoxybutane and mitomycin C.

Multicolor fluorescence in situ hybridization (FISH) with tandem-labeling probes for the 1cen-q12 region is a potential biomarker for the detection of structural chromosomal aberrations (CAs) in human cells. To determine the suitability of this technique for biomonitoring humans exposed to 1,3-butadiene (BD) and to characterize the alterations induced as well as their stability over time, the human lymphoblastoid cell line AZH-1 was treated with 5 microM diepoxybutane (DEB) or the positive control mitomycin C (MMC; 0.1 microM) for 24 h. Following the removal of the test chemicals, cell cultures were grown for an additional 19 days in the absence of the test compound. Using the tandem FISH technique, aliquots from the main cultures were examined for the induction of CAs affecting the 1cen-q12 region at various intervals. A significant increase in chromosomal breakage/exchanges affecting the 1cen-q12 region was seen in both the DEB- and MMC-treated interphase and metaphase cells. The damage peaked at approximately 48 h following the addition of the test compound and declined with time. However, at day 20, the frequency of aberrant cells was still significantly higher than the control levels. For comparison, the frequency of micronuclei (MN) formed and their origin was determined using the cytochalasin B-modified MN assay and FISH with a pancentromeric probe. Showing a similar pattern, the frequency of centronere-negative MN peaked at 48 h, but however was not significantly elevated above control levels at 20 days. At early time points, aberrations detected using the FISH assay consisted of nearly equal proportions of unstable- and stable-type aberrations, while at the later time points, translocations were the predominant aberration type. In addition, the use of tandem-label FISH in combination with BrdU-immunfluorescence staining, showed that almost identical frequencies of structural aberrations could be seen in actively replicating and non-replicating cell populations. These studies indicate that a small but significant proportion of the alterations detected using this FISH technique persists over time and that this technique may be valuable for biomonitoring chromosomal alterations in BD-exposed populations.