Role of the right dorsal premotor cortex in "physiological" mirror EMG activity.

A distributed cortical network enables the lateralization of intended unimanual movements, i.e., the transformation from a default mirror movement to a unimanual movement. Little is known about the exact functional organization of this "non-mirror transformation" network. Involvement of the right dorsal premotor cortex (dPMC) was suggested because its virtual lesion by high-frequency repetitive transcranial magnetic stimulation (rTMS) increased the excitability of the left primary motor cortex (M1) during unilateral isometric contraction of a left hand muscle (Cincotta et al., Neurosci Lett 367: 189-93, 2004). However, no behavioural effects were observed in that experimental protocol. Here we tested behaviourally twelve healthy volunteers to find out whether focal disruption of the right dPMC by "off-line" One Hz rTMS (900 pulses, 115% of resting motor threshold) enhances "physiological" mirroring. This was measured by an established protocol (Mayston et al., Ann Neurol 45: 583-94, 1999) that quantifies the mirror increase in the electromyographic (EMG) level in the isometrically contracting abductor pollicis brevis (APB) muscle of one hand during brief phasic contractions performed with the APB of the other hand. Mirroring in the right APB significantly increased after real rTMS of the right dPMC. In contrast, no change in mirroring was seen with sham rTMS of the right dPMC, real rTMS of the right M1, or real rTMS of the left dPMC. These findings strongly support the hypothesis that the right dPMC is part of the non-mirror transformation cortical network.

Modulatory effects of high-frequency repetitive transcranial magnetic stimulation on the ipsilateral silent period.

In healthy subjects, suprathreshold repetitive transcranial magnetic stimulation (rTMS) at frequencies >2 Hz prolongs the cortical silent period (CSP) over the course of the train. This progressive lengthening probably reflects temporal summation of the inhibitory interneurons in the stimulated primary motor cortex (M1). In this study, we tested whether high-frequency rTMS also modulates the ipsilateral silent period (ISP). In nine normal subjects, suprathreshold 10-pulse rTMS trains were delivered to the right M1 at frequencies of 3, 5, and 10 Hz during maximal isometric contraction of both first dorsal interosseous muscles. At 10 Hz, the second pulse of the train increased the area of the ISP; the other stimuli did not increase it further. During rTMS at 3 and 5 Hz, the ISP remained significantly unchanged. Control experiments showed that 10-Hz rTMS delivered at subthreshold intensity also increased the ISP. rTMS over the hand motor area did not facilitate ISPs in the biceps muscles. Finally, rTMS-induced ISP facilitation did not outlast the 10-Hz rTMS train. These findings suggest that rTMS at a frequency of 10 Hz potentiates the interhemispheric inhibitory mechanisms responsible for the ISP, partly through temporal summation. The distinct changes in the ISP and CSP suggest that rTMS facilitates intrahemispheric and interhemispheric inhibitory phenomena through separate neural mechanisms. The ISP facilitation induced by high-frequency rTMS is a novel, promising tool to investigate pathophysiological abnormal interhemispheric inhibitory transfer in various neurological diseases.

Physical interactions between induced electrical fields can have substantial effects on neuronal excitation during simultaneous TMS of two brain areas.

OBJECTIVE: To analyse the interactions between simultaneous or nearly simultaneous focal transcranial magnetic stimulation (TMS) of the motor cortex hand area (M1hand) of both hemispheres. METHODS: In 7 healthy subjects, motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration were elicited in the right hand by bihemispheric focal TMS of M1hand (8-shaped coils, monophasic current waveform, stimulus intensity 120% above motor threshold, TMS of right M1hand preceding TMS of left M1hand by 0-1000 micros), or by unilateral TMS of left M1hand alone. A dipole probe was used to measure the physical interactions between the two stimulating coils. RESULTS: Bihemispheric TMS markedly decreased MEP and CSP at intervals of 0 and 50 micros compared to unilateral TMS, whereas both measures increased at the interval of 150 micros. The dipole probe experiments showed that the physical interactions between the electrical fields of the two coils entirely explained the MEP and CSP findings, but only under the assumption that excitation of M1hand is not point-focal but extends over several centimetres. CONCLUSIONS: First, simultaneous focal TMS of distant brain sites may result in marked 'distortion' of brain excitation through physical interaction between the induced electrical fields. Second, these findings support the notion that excitation of human M1hand is relatively non-focal, even if a 'focal' stimulating coil and low stimulus intensity are used. SIGNIFICANCE: Potentially marked physical interaction between induced electrical fields must be taken into account when testing or disrupting distant brain sites with simultaneous focal TMS.

Adverse motor effects induced by antiepileptic drugs.

Cognitive effects of anti-epileptic drugs (AEDs) have been already extensively reported. In contrast, motor disturbances, frequently induced by these drugs, have not received similar attention. We review subjective and objective adverse motor effects of traditional and new AEDs. We discuss the methodological issues caused by the heterogeneous sources of information on drug adverse effects (controlled clinical studies, open studies, and case reports). We describe specific disturbances (vestibulocerebellar, dyskinesias, parkinsonism, tics, myoclonus, and tremor) as the effects of different AEDs on distinct motor circuitries. Finally, we summarize the role of sophisticated technical studies which provide a valuable insight into the specific or subtle effects of AEDs on the central nervous system.

Suprathreshold 0.3 Hz repetitive TMS prolongs the cortical silent period: potential implications for therapeutic trials in epilepsy.

OBJECTIVE: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by single-pulse TMS variables. METHODS: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus-response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed. RESULTS: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly. CONCLUSIONS: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9-1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.

Combined effect of sourdough lactic acid bacteria and additives on bread firmness and staling.

The effect of various sourdoughs and additives on bread firmness and staling was studied. Compared to the bread produced with Saccharomyces cerevisiae 141, the chemical acidification of dough fermented by S. cerevisiae 141 or the use of sourdoughs increased the volume of the breads. Only sourdough fermentation was effective in delaying starch retrogradation. The effect depended on the level of acidification and on the lactic acid bacteria strain. The effect of sourdough made of S. cerevisiae 141-Lactobacillus sanfranciscensis 57-Lactobacillus plantarum 13 was improved when fungal alpha-amylase or amylolytic strains such as L. amylovorus CNBL1008 or engineered L. sanfranciscensis CB1 Amy were added. When pentosans or pentosans, endoxylanase enzyme, and L. hilgardii S32 were added to the same sourdough, a greater delay of the bread firmness and staling was found. When pentosans were in part hydrolyzed by the endoxylanase enzyme, the bread also had the highest titratable acidity, due to the fermentation of pentoses by L. hilgardii S32. The addition of the bacterial protease to the sourdough increased the bread firmness and staling.

Conversion from thrice daily to twice daily administration of gabapentin (GBP) in partial epilepsy: analysis of clinical efficacy and plasma levels.

Gabapentin has been administered in placebo-controlled studies with a thrice daily (T.I.D.) schedule, because of its short half-life. However, clinical efficacy does not seem strictly related to plasma levels: a twice daily (B.I.D.) schedule might therefore be possible. The aim of our study was to verify if the conversion from a T.I.D. to a B.I.D. regimen affected the efficacy and safety of gabapentin therapy. Out of 171 patients treated with add-on gabapentin, we selected 29 stable responders, who were followed for three months with a T.I.D. schedule and then switched to B.I.D. regimen for further three months. Seizure number, side-effects and trough plasma levels of gabapentin were collected during both periods. Gabapentin mean dose was 2117.2 mg/day. Mean number of seizures/months was: 4.2 at baseline, 1.0 during the T.I.D., and 0.9 during the B.I.D. period. Mean trough plasma level of gabapentin was 5.9 microgram/ml during the T.I.D. and 5.2 microgram/ml during the B.I.D. period. Twelve side-effects were reported by 11 patients during the T.I.D. and 6 by 5 patients during the B.I.D. period., sedation and vertigo were the most frequent in both. Results of our study suggest that gabapentin can be administered safely and effectively either with a T.I.D. and a B.I.D. regimen.

Determination of fosinopril in pharmaceutical formulations containing hydrochlorothiazide by multiwavelength UV spectrophotometry.

A sensitive, simple, rapid and precise method for the simultaneous determination of fosinopril (FOS) and hydrochlorothiazide (HCT) in pharmaceutical formulations is presented. These active ingredients are extracted in aqueous solution and measured by multiwavelength UV spectrophotometry using the program QUEST. HCT acts as an internal standard to verify the accuracy of the analysis. Some aspects of the chemical, spectroscopic and thermoanalytical behaviour of FOS are also reported.

Liquid chromatographic determination of acyclovir.

An easy and precise HPLC method was developed to determine acyclovir in liophilized vials and ointments. The described procedure detects guanine which can be present in raw material as a synthetic contaminant or a degradation product. The method proved to be simple and accurate.

Hemodynamic status following regional and general anesthesia for carotid endarterectomy.

We prospectively studied 23 patients undergoing carotid endarterectomy under regional (n = 13) or general (n = 10) anesthesia to determine the hemodynamic basis of increased frequency in the need for postoperative vasopressor support when regional anesthesia was used. Anesthesia and postoperative care were conducted without reference to hemodynamic data from pulmonary artery catheterization. Although mean arterial pressure was similar in the two groups postoperatively, 11 of the 13 patients undergoing regional anesthesia and 3 of the 10 patients undergoing general anesthesia required phenylephrine postoperatively. No patient required therapy postoperatively to reduce a systolic pressure exceeding 160 mm Hg. Mean arterial pressure remained below the preoperative baseline value in both groups (p < 0.05 with general anesthesia; p = 0.06 with regional anesthesia) during follow-up. In the general anesthesia group, systemic vascular resistance declined significantly below baseline (p < 0.05) following the operation, accompanied by a decline in mean arterial pressure (p < 0.05) and a higher cardiac output. Intraoperative fluid requirements were greater during general anesthesia than during regional anesthesia (p < 0.01). Pulmonary artery occlusion pressure was lower postoperatively than at baseline in both groups (p < 0.05). Pulmonary artery occlusion pressure was higher in the general anesthesia group despite the greater use of phenylephrine in the regional anesthesia group.

The effects of regional and general anesthesia on blood pressure control after carotid endarterectomy.

We retrospectively reviewed the influence of preoperative blood pressure control and regional vs. general anesthetic techniques on the incidence of intraoperative and postoperative (recovery room and intensive care unit) hypotension and hypertension in 249 carotid endarterectomy patients. Preoperative blood pressure was classified as uncontrolled hypertension (systolic blood pressure >/= 170 mm Hg and/or diastolic blood pressure >/= 95 mm Hg), controlled hypertension (blood pressure <170/95 mm Hg on chronic antihypertensive therapy), or normotension (blood pressure <170/95 mm Hg without antihypertensive therapy). Hypotension, as defined by the requirement for vasopressor administration to maintain a systolic blood pressure of at least 120 mm Hg, occurred more frequently after regional than after general anesthesia (p < 0.05). Postoperative hypertension was defined as a systolic blood pressure >/= 200 mm Hg and/or a diastolic blood pressure >/= 110 mm Hg in the recovery room or in the Intensive Care Unit. Preoperative hypertension was not associated with acute postoperative hypertension in the intensive care unit in either the regional anesthesia (n = 190) or the general anesthesia (n = 59) groups, although with either type of anesthesia, preoperative hypertension was associated with an increased incidence of hypertension in the recovery room (p < 0.01 regional; p < 0.005 general).

Implications of nimodipine prophylaxis of cerebral vasospasm on anesthetic management during intracranial aneurysm clipping.

Nimodipine, a calcium entry blocking agent similar in structure to nifedipine but with selective cerebrovascular dilating effects, has potential use in the therapy and prevention of cerebral vasospasm after intracranial hemorrhage. The authors summarize the effects of calcium entry blockers, review the pharmacology of nimodipine, and discuss both the known and possible interactions of oral nimodipine with physical and pharmacological interventions that neuroanesthesiologists employ for patients with cerebral vasospasm during craniotomy for aneurysm clipping. In a series of 26 patients undergoing aneurysm clipping, the authors found that intraoperative blood pressure tended to be reduced by nimodipine. Although the number of patients was limited by the fact that they were enrolled in a multi-center nimodipine aneurysm study and thus had to meet the criteria for that study, it is concluded that prophylaxis of cerebral vasospasm with nimodipine in patients with ruptured intracranial aneurysm results only in a favorable tendency toward lower systemic blood pressure during craniotomy.