Transcranial magnetic stimulation. Its role in the evaluation of patients with partial epilepsy.

Transcranial magnetic stimulation (TMS) is a relative new method in the evaluation of patients with various neurological diseases. With the introduction of repetitive (rapid rate) transcranial magnetic stimulators (RTMS), it has been possible to apply cortical stimuli with a stimulus rate up to 100 Hz. The preliminary results with TRMS suggest that it may be used in the study of speech lateralization. Seizures have been reported in patients with partial epilepsy during TMS. In these cases it remains uncertain whether the seizures were induced by the TMS or coincidentally with it. Minor changes in paroxysmal activity have been reported in some patients. These data suggest, that TMS is neither sensitive nor specific as an activation procedure of the epileptic focus in patients with partial epilepsy. Seizures have been provoked using RTMS, but its use as a seizure-inducing method is not yet evaluated.

EEG changes following repetitive transcranial magnetic stimulation in patients with temporal lobe epilepsy.

Transcranial magnetic stimulation (TMS) has been proposed as an epileptogenic activating procedure in the evaluation of patients with partial epilepsy. With the introduction of repetitive (rapid rate) transcranial magnetic stimulation (RTMS), it has been possible to apply cortical stimuli with a stimulus rate up to 50 Hz. This study was conducted in order to evaluate the epileptogenic effect of RTMS. Ten patients suffering from medically intractable temporal lobe epilepsy were included. As a part of the presurgical evaluation all patients were studied with ictal video-EEG scalp recordings during a period of discontinuation of the antiepileptic treatment. Eight RTMS trains were applied to left and right temporal and frontal areas, using a stimulus intensity of 1.2 x Tm (the motor threshold to a twitch in the right hand), a stimulus duration of 1 s and a stimulus frequency of 30 Hz. 50 Hz stimulations, with a stimulus duration of 1 s and a stimulus intensity of 1.2 x Tm, were applied on both anterior temporal regions, in total 10 TMS and 340 RTMS pulses to each patient. The numbers of sharp waves/spikes and low-frequency potentials were lower (P < 0.01) compared to prestimulus values and returned to prestimulation values within 10 min. In no cases paroxysmal activity was provoked and no seizures developed. The study indicates that RTMS as used in this study is not effective as an activation procedure for paroxysmal activity. As the risk of seizures may depend on the stimulus parameters, further studies are needed in order to evaluate the safety of the RTMS.

Organophosphate inhibition of human heart muscle cholinesterase isoenzymes.

The rate of acetylcholine hydrolysis of mammalian heart muscle influences cardiac responses to vagal innervation. We characterized cholinesterases of human left ventricular heart muscle with respect to both substrate specificity and irreversible inhibition kinetics with the organophosphorus inhibitor N,N'-di-isopropylphosphorodiamidic fluoride (mipafox). Specimens were obtained postmortem from three men and four women (61 +/- 5 years) with no history of cardiovascular disease. Myocardial choline ester hydrolyzing activity was determined with acetylthiocholine (ASCh; 1.25 mM), acetyl-beta-methylthiocholine (AbetaMSCh; 2.0 mM), and butyrylthiocholine (BSCh; 30 mM). After irreversible and covalent inhibition (60 min; 25 degrees C) with a wide range of mipafox concentrations (50 nM-5 mM), residual choline ester hydrolyzing activities were fitted to a sum of up to five exponentials using weighted least-squares non-linear curve fitting. In each ease, quality of curve fitting reached its optimum on the basis of a four component model. Final classification of heart muscle cholinesterases was achieved according to substrate hydrolysis patterns (nmol/min per g wet weight) and to second-order organophosphate inhibition rate constants k2 (1/mol per min); one choline ester hydrolyzing enzyme was identified as acetylcholinesterase (AChE; k2/mipafox = 6.1 (+/- 0.8) x 10(2)), and one as butyrylcholinesterase (BChE; k2/mipafox = 5.3 (+/- 1.1) x 10(3)). An enzyme exhibiting both ChE-like substrate specificity and relative resistance to mipafox inhibition (k2/mipafox = 5.2 (+/- 1.0) x 10(-1)) was classified as atypical cholinesterase.

Paired transcranial magnetic stimulations and motor evoked potentials.

We studied the effect of varying interstimulus intervals (ISI) on the motor evoked potentials (MEP) using paired transcranial magnetic stimulation (PTMS) during relaxation and voluntary contraction of the abductor pollicis brevis. At ISI > or = 10 ms two independent MEPs could be evoked. At ISIs between 12-30 ms the amplitudes of the MEPs evoked by the second (test) stimuli had larger amplitude and shorter latencies than the MEPs evoked by the first (conditioning) stimuli. At an ISI of 50 ms the second MEP were similar to the first, between 75 and 100 ms the second MEPs were inhibited and at ISI of 200 and 400 ms the second MEPs showed almost similar amplitudes and latencies compared to the first. During voluntary contraction, the amplitudes of the first MEPs was higher compared to relaxed responses. The amplitudes of the second MEPs showed a similar pattern as the relaxed responses, but with a relatively smaller increase between 12-30 ms (p < 0.01), and less inhibition at 75 and 100 ms (p < 0.01). The study shows that conditioning stimuli 12-30 ms before the test stimulus facilitates the second MEP, and an ISI between 75-100 ms inhibit the second MEP. Voluntary contraction exerts a facilatory effect and reduce inhibition in the corticospinal neurons. These findings may reflects the changes in excitability and inhibition in the cortico-spinal neurons.

Quantitative electromyographical changes in cervical dystonia after treatment with botulinum toxin.

Injection of botulinum toxin (BT) into affected neck muscles gives symptomatic relief to patients with cervical dystonia by causing a presynaptic block of acetylcholine release. In a retrospective study of 19 patients, we used the turns-amplitude analysis of the EMG interference pattern for the evaluation of electrophysiological changes as a function of time after BT treatment. EMG was performed immediately before and during injection, and muscles showing abnormally increased activity (> 100 turns/s at rest) were given botulinum toxin A (Oculinum (= Botox)) 40-120 units. A second EMG was done 6-30 weeks later. At attempted rest, the sternocleidomastoid muscle contralateral to the involuntary head rotation showed the most pronounced changes, possibly due to relatively large doses of BT, and the EMG changes were related to the time after BT treatment. Six weeks after treatment the muscle showed decreased turns/s, mean amplitude and ratio (turns/amplitude) at rest. At 30 weeks, turns and mean amplitude reached values as before treatment, while ratio was increased to 175% of the pre-treatment value. This pattern may reflect a reversible and random loss of muscles fibres, due to presynaptic denervation. At maximal voluntary contractions, no correlation was seen between time after BT treatment and quantitative EMG.

Quantitative EMG in cervical dystonia.

Within the latest years botulinum toxin A (BT) applied locally in affected muscles has gained a superior position in the treatment of cervical dystonia. EMG is often used as a guidance for the injections, which has caused a need for better knowledge about the electromyographic changes in the muscles involved. In the present study we used the turns-amplitude analysis for the quantitative evaluation of the EMG of the sternocleidomastoid muscles and posterior neck muscles in 44 patients with cervical dystonia, not previously treated with BT. Twelve healthy subjects were examined for comparison. At rest 13 patients showed abnormal activity (defined as > 100 turns/s) in the sternocleidomastoid muscle contralateral to the involuntary head rotation (CS) and the ipsi- and contralateral posterior neck muscles (IPN and CPN): 12 patients had abnormal activity in CS and IPN, and seven patients had abnormal activity in all muscles, including the ipsilateral sternocleidomastoid muscle (IS). Other combinations were seen less often. The distribution of muscles with abnormal activity was not always obvious from the clinical examination. CPN and IS, i.e., apparently unaffected muscles, showed reduced EMG activity during attempted maximal voluntary contraction, indicating difficulties in activating all motor units.

[Age related decrease of high density lipoproteins (HDL) in women after menopause. Quantification of HDL with genetically determined HDL arylesterase in women with healthy coronary vessels and in women with angiographically verified coronary heart disease]. / Zur altersabhängigen Verminderung von Lipoproteinen hoher Dichte (HDL) bei Frauen nach der Menopause. Quantifizierung von HDL über die genetisch determinierte HDL-Arylesterase bei koronargesunden Frauen und bei Frauen mit angiographisch gesicherter koronarer Herzkrankheit.

BACKGROUND: The decline in the concentration of high density lipoproteins (HDL) observed in postmenopausal women is thought to contribute to the increasing incidence of coronary artery disease (CAD) after menopause. Human serum arylesterase (EC 3.1.1.2) is exclusively associated with HDL. We therefore investigated possible differences in the decline of HDL-levels and of HDL-subfractions HDL2 and HDL3 between postmenopausal women without and with angiographically documented CAD. PATIENTS AND METHODS: HDL-, HDL2-and-HDL3- concentrations were studied in postmenopausal women with angiographically documented CAD (n = 24; 51 to 72 years mean: 62 years) and compared to HDL-parameters of women without CAD (n = 22; 51 to 81 years, mean: 58 years). Arylesterase activities of HDL2-and HDL3-subfractions and HDL2-cholesterol concentrations were determined after differential precipitation with polyethylene glycol (4.7 mM PEG). Phenotyping of HDL-arylesterase was achieved in CAD patients and in women without CAD after determining hydrolysis of arylesterase substrates paraoxon (PO) and phenylacetate (PA) by calculating paraoxonase/arylesterase activity ratios R (R = [PO]/[PA] x 1000): phenotype A (n = 26) with R < 2.5, phenotype AB (n = 16) with 5.0 < R < 10.7, and phenotype B (n = 4) with R > 13.5. RESULTS: In postmenopausal women with documented CAD, as compared to women without CAD, HDL-cholesterol (55 +/- 3 mg/dl vs. 69 +/- 3 mg/dl HDL2-arylesterase (25 +/- 1 kU/l vs. 33 +/- 2 kU/l), and HDL3-arylesterase (89 +/- 4 kU/l vs. 106 +/- 5 kU/I) were found to be significantly reduced. Analysis of the correlation of lipid parameters and age revealed in CAD patients, but not in postmenopausal women without CAD, a significant increase of total cholesterol (r = 0.42), and significant reductions of both HDL2-arylesterase (r = -0.47) and HDL3-arylesterase (r = 0.74) with increasing age. In contrast, HDL-cholesterol (r = -0.14) and HDL2-cholesterol (r = -0.06) of CAD patients showed only slight and non-significant reductions with age. Since HDL3-arylesterase was found to be age-dependently reduced in women without CAD (r = 0.17), HDL2-arylesterase of postmenopausal women, among all lipid parameters showed the most pronounced differences between women without CAD and CAD patients. The age-dependent decrease of HDL2-arylesterase in postmenopausal women with CAD does not result from an increased frequency of B-allele carriers in the subgroup of CAD patients with an age above the median (64 years). CONCLUSION: Genetically determined serum HDL-arylesterase is well suited to quantify HDL in postmenopausal women without and with CAD. HDL2-arylesterase of postmenopausal women should be evaluated as a screening parameter for both primary and secondary CAD prevention.

The Occurrence of Quartz in Coal Fly Ash Particles.

In spite of the presence of quartz, coal fly ash can be considered as a nuisance or inert dust. Respirable crystalline silica (e.g., quartz) is notorious for the induction of, for example, progressive massive fibrosis (PMF); besides, in 1997 the IARC stated that crystalline silica in the form of quartz or cristobalite from occupational sources is carcinogenic to humans. Quartz is present in both coal and residual ash. Ash originates from combustion of pulverised coal and, once removed from the flue gases by electrostatic precipitators (ESPs), it is called pulverized fuel ash (PFA). Thus, occupational exposure to PFA could also include exposure to silica. However, epidemiological studies did not show evidence of progressive massive fibrosis (PMF). In vitro tests demonstrated that PFA is less toxic than silica, and in vivo data of PFA did not support the importance of silica content for toxicity. Commissioned by the Dutch coal-fired power plants, KEMA has started a research project to determine the quartz content in coal and the corresponding PFA. It appears that on average 50% of the a-quartz in coal is found again in the total fraction of PFA (D50(ae) 31 µm, where Dsotae) is the aerodynamically mass median diameter), whereas 16% is found in an even finer fraction (D50(ae) 10 µm). The remaining part of the quartz is embedded in a glass phase. Scanning electron microscopy (SEM) with x-ray microanalyses (XMA) of cross-sections of 11,130 ash particles showed that quartz in PFA is present as unmelted sand particles. These quartz particles are angularly shaped. However, two types are to be distinguished: free coarse angular quartz particles (not respirable) and small angular quartz particles within the PFA particles. From the SEM/XMA results, it has to be concluded that the quartz in the respirable fraction is predominantly present within the original molten PFA particle. Since the effects of quartz are surface related, this elucidates the negative results of quartz-related effects of PFA in epidemiological, in vitro and in vivo studies. Besides, the amount of the total α-quartz in the respirable fraction of the ashes studied is less than 0.2%, so probably the Dutch occupational quartz standard of 0.075 mg m(-3) will not be exceeded.

Repetitive magnetic stimulation and motor evoked potentials.

The aim of the study was to evaluate the effect of varying stimulus rates of repetitive transcranial magnetic stimulation (RTMS) on the motor evoked potentials (MEPs) recorded from the right abductor pollicis brevis muscle (APB). Thirteen normals were included. Stimuli were applied to the cortex and to the median nerve at the wrist. The cortical stimuli were applied without and with facilitation. Stimulus intensity was 1.2 times the motor threshold (TmAPB) for cortical stimulation and supramaximal for peripheral stimulation. Stimulus rates were 1, 2, 3, 5, 10 and 20 Hz. Nine pulses were applied in each stimulus series. At stimulus rates between 1 and 3 Hz no amplitude changes were observed throughout the stimulation. At 5 Hz stimulation inhibition of some of the MEPs was observed followed by MEPs with increased amplitude. At 10 Hz stimulation some MEPs were totally inhibited, interrupted by an MEP with increased amplitude, resembling clonic contraction. At 20 Hz the inhibition of the MEPs decreased (P < 0.05) compared to 10 Hz stimulation. Facilitation decreased the inhibition at 5 and 10 Hz stimulation (P < 0.01). On peripheral stimulation a decrement was observed with stimulus rates of 10 and 20 Hz. The study shows that RTMS exerts a complex influence on the MEPs depending upon stimulus rates. The pronounced inhibition and excitation of the MEPs at 5 and 10 Hz stimulation possibly reflects inhibition and excitation in the cortico-spinal neurons.

Quantitative EMG in botulinum toxin treatment of cervical dystonia. A double-blind, placebo-controlled study.

We used turns-amplitude analysis of the EMG as a guidance for botulinum toxin (BT) treatment in 19 patients with cervical dystonia. At the first examination, muscles showing abnormal activity (> 100 turns/sec at rest) were given BT 75 units (10 patients) or placebo (9 patients). At subsequent examinations, about 6, 12 and 18 weeks after the start, BT 75 units were given to all hyperactive muscles. Six weeks after the first BT treatment the sternocleidomastoid muscle contralateral to the involuntary head rotation and the ipsilateral and contralateral posterior neck muscles (PNM) showed a reduction of involuntary activity, as indicated by reduced turns/sec and mean amplitude at rest. Similar changes were seen when comparing BT treatment with placebo. The reduction was greater in the contralateral sternocleidomastoid muscle than in PNM, suggesting that PNM need higher doses of BT. At maximal voluntary contraction, BT treated muscles showed unchanged turns/sec (5/6 tests), decreased mean amplitude and increased ratio (turns/amplitude). This may reflect a functional random loss of muscle fibres, combined with inability to activate all motor units. A high (89%) clinical success rate with BT therapy was obtained, and it is concluded that quantitative EMG is a useful tool for the precise identification of hyperactive muscles, for optimal placing of the injection cannula and for unbiased monitoring of the treatment effect.

Pregnancy and epilepsy: a retrospective study of 151 pregnancies.

OBJECTIVE: We studied the course of pregnancy in women with epilepsy to identify possible risk factors which might complicate the epilepsies and pregnancy outcomes. MATERIAL AND METHODS: Data were collected retrospectively from the records of 151 pregnancies in 124 women with epilepsy from 1978-1992. Epilepsy variables were compared with that of non-pregnant women with epilepsy matched for age. Obstetric and neonatal variables were compared with those of all deliveries in the same unit from 1979-1992 (n=38,983). RESULTS: Pregnancy among patients with epilepsy was more likely to occur in women with relatively mild epilepsy. In 12% of the pregnancies, the women were untreated while 71% were on monotherapy. Twenty-one percent had increased seizure frequency during the pregnancy. Perinatal deaths among newborns of epileptic mothers (1.3%) was more frequent but not significantly increased compared to the background population of 0.5% (95% CI 0.2-4.7). A total of 5.3% had congenital malformations compared to 1.5% in the controls (95% CI 2.3-10.3). No neural tube defects were observed. Maternal treatment with phenytoin was significantly related to the occurrence of congenital malformations, P=0.04. CONCLUSIONS: Most women with epilepsy have an uncomplicated pregnancy and normal healthy offsprings. Maternal treatment with phenytoin might be associated with congenital malformations. No other risk factors could be identified.