Factors influencing cortical silent period: optimized stimulus location, intensity and muscle contraction

Inhibitory silent period (SP) is a transient suppression of voluntary muscle activity after depolarization of representative motor neuronal populations following transcranial magnetic stimulation (TMS). Our aim was to evaluate and present an optimal protocol for the measurement of SP by (1) determining the impact of muscle activation level and stimulus intensity (SI) on the duration of SP, and, (2) studying the relationship between motor evoked potential (MEP) and SP, using targeted stimulus delivery. Single magnetic pulses were focused on the optimal representation area of the thenar musculature on primary motor cortex. We utilized real-time 3D-positioning of TMS-evoked electric field on anatomical structures derived from individual MR-images. The SI varied from 80% to 120% of individual resting motor threshold (MT). Muscle activation levels varied from 20% to 80% of the maximal voluntary contraction (MVC). Contralateral SP lengthened significantly with increasing SI independent of target muscle activation. The peak amplitude of the MEP was affected by SI and force. Latency and duration of the MEP were practically unaffected by SI or force. Focal stimulation at 110-120% MT and approximately 50% MVC (with only negligible need for control) provides most stable and informative SP. MEP should be included in SP as the error from marking the onset diminishes. This study provides a guideline for the consistent measurement of SP, which is applicable when using navigated or traditional TMS.     

Prednisolone and valaciclovir in Bell's palsy: a randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Previous trials of corticosteroid or antiviral treatments for Bell's palsy have been underpowered or have had insufficient follow-up. The aim of this study was to compare the short-term and long-term effects of prednisolone and valaciclovir in the recovery of the affected facial nerve in a large number of patients. METHODS: In this randomised, double-blind, placebo-controlled, multicentre trial, patients aged 18 to 75 years who sought care directly or were referred from emergency departments or general practitioners within 72 h of onset of acute, unilateral, peripheral facial palsy, between May, 2001, and September, 2006, were assessed. Patients were randomly assigned in permuted blocks of eight to receive placebo plus placebo; 60 mg prednisolone per day for 5 days then reduced by 10 mg per day (for a total treatment time of 10 days) plus placebo; 1000 mg valaciclovir three times per day for 7 days plus placebo; or prednisolone (10 days) plus valaciclovir (7 days). Follow-up was for 12 months. The primary outcome event was time to complete recovery of facial function, as assessed with a regional Sunnybrook scale score of 100 points. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT00510263. FINDINGS: Of 839 patients who were randomly assigned, 829 were included in the modified intention-to-treat analysis: 206 received placebo plus placebo, 210 prednisolone plus placebo, 207 valaciclovir plus placebo, and 206 prednisolone plus valaciclovir. Time to recovery was significantly shorter in the 416 patients who received prednisolone compared with the 413 patients who did not (hazard ratio 1.40, 95% CI 1.18 to 1.64; p<0.0001). There was no difference in time to recovery between the 413 patients treated with valaciclovir and the 416 patients who did not receive valaciclovir (1.01, 0.85 to 1.19; p=0.90). The number of patients with adverse events was similar in all treatment arms. INTERPRETATION: Prednisolone shortened the time to complete recovery in patients with Bell's palsy, whereas valaciclovir did not affect facial recovery.     

Subarachnoid hemorrhage in the subacute stage: elevated apparent diffusion coefficient in normal-appearing brain tissue after treatment

PURPOSE: To prospectively evaluate whether subarachnoid hemorrhage (SAH) is associated with a change in the apparent diffusion coefficient (ADC) in normal-appearing brain parenchyma. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for all patient and volunteer studies. One hundred patients (48 men, 52 women; mean age, 52 years +/- 12 [standard deviation]) with aneurysmal SAH underwent conventional and diffusion-weighted magnetic resonance (MR) imaging at a mean of 9 days +/- 3 after SAH to evaluate possible lesions caused by SAH, treatment of SAH, and vasospasm. Aneurysms were treated surgically (n = 70) or endovascularly (n = 30) before MR imaging. Diffusion-weighted MR imaging was performed at 1-year follow-up in 30 patients (10 men, 20 women; mean age, 51 years +/- 11). Thirty healthy age-matched volunteers (11 men, 19 women; mean age, 54 years +/- 16) underwent MR imaging with an identical protocol. ADC values were measured bilaterally in the gray and white matter (parietal, frontal, temporal, occipital lobes; cerebellum; caudate nucleus; lentiform nucleus; thalamus; and pons) that appeared normal on T2-weighted and diffusion-weighted MR images. Linear mixed model was used for comparison of ADC values of supratentorial gray matter and white matter; general linear regression analysis was used for comparison of ADC values of cerebellum and pons. RESULTS: In patients with SAH, the ADC values in normal-appearing white matter, with a single exception in the frontal lobe (P = .091), were significantly higher than they were in healthy volunteers (P /= .121). CONCLUSION: SAH and its treatment may cause global mild vasogenic edema in white matter and deep gray matter that is undetectable on T2-weighted and diffusion-weighted MR images but is detectable by measuring the ADC value in the subacute stage of SAH.     

Single-dose pegfilgrastim is comparable to daily filgrastim in mobilizing peripheral blood stem cells: a case-matched study in patients with lymphoproliferative malignancies

Pegfilgrastim (PEGFIL) has been found to be comparable to daily filgrastim (FIL) in managing chemotherapy-induced neutropenia. In the present study, we evaluated the ability of PEGFIL to mobilize stem cells in 38 consecutive patients with lymphoproliferative diseases (multiple myeloma, n = 18; lymphomas, n = 15; chronic lymphocytic leukemia, n = 5). Patients were mobilized using PEGFIL (6–18 mg as a single dose) during 2005–2006; 32 then received high-dose chemotherapy followed by autologous stem cell transplantation. PEGFIL-mobilized patients were matched by age, disease, and treatment line at a ratio of 1:2 to historical FIL-mobilized controls. The primary study endpoint was the blood CD34⁺ concentration at onset of leukapheresis. Leukapheresis began a median of 10 days from the beginning of mobilization chemotherapy in both groups. At the onset of leukapheresis, median blood CD34⁺ cell counts did not differ significantly in the FIL group compared with the PEGFIL group (79 × 10⁶/L vs 64 × 10⁶/L, respectively; p = 0.44). In the different disease categories, the respective CD34⁺ cell counts after FIL and PEGFIL mobilization were 72 × 10⁶/L vs 123 × 10⁶/L (p = 0.08) in myeloma, 51 × 10⁶/L vs 62 × 10⁶/L (p = 0.6) in lymphomas, and 27 × 10⁶/L vs 30 × 10⁶/L (p = 0.62) in CLL, respectively. The target CD34⁺ cell yield was harvested with one leukapheresis in 53% of PEGFIL-mobilized patients. Engraftment after autografting did not differ significantly in the two groups. Stem cell mobilization with a single dose of PEGFIL was, therefore, comparable to that achieved using daily FIL in patients with lymphoproliferative diseases. PEGFIL is a more practical way to mobilize stem cells than daily FIL.     

Sex, Age, and Tissue Specific Accumulation of Eight Metals, Arsenic, and Selenium in the European Hedgehog (Erinaceus europaeus)

Many insectivores have been shown to be sensitive to heavy metals and therefore suitable for biomonitoring purposes. In Finland, the hibernation period of the European hedgehog (Erinaceus europaeus) is long, and during hibernation the stress caused by environmental toxins may be crucial. Concentrations of cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), arsenic (As), and selenium (Se) were measured in a population of hedgehogs in the town of Joensuu in eastern Finland during the summers of 2004 and 2005. The analyzed tissues were kidney, liver, hair, and spine. The sampled hedgehogs (n = 65) were mainly road-killed animals. As expected, the concentrations of heavy metals were low because the hedgehogs were living in a comparatively unpolluted area. Significant increases with age were found in Cd concentrations (kidney, liver, and spine) and some essential elements (Se in spine, kidney, and liver; Mo in kidney and liver; Cu in spine; Fe in liver; and Mn in spine). Age accumulation and correlations between Se and Cd and between Mo and Cd may indicate the protective roles of Se and Mo against Cd toxicity in hedgehogs, in which Cd is already at comparatively low concentrations. Sex had no significant effect on concentrations of the elements studied. In conclusion, age is an important parameter to be taken into account when studying heavy-metal concentrations in hedgehogs and other insectivores.     

Nitric oxide metabolites in cervical fluid during pregnancy: further evidence for the role of cervical nitric oxide in cervical ripening

OBJECTIVE: Cervical tissue expresses all the isoenzymes of nitric oxide synthase. We studied the concentrations of nitric oxide metabolites in the cervical fluid in nonpregnant (n = 11) and pregnant women (n = 106). STUDY DESIGN: Cervical fluid was collected into a Dacron polyester swab, and nitric oxide metabolites were eluted into physiologic saline solution, which was assayed for nitric oxide metabolites with the Griess reaction. The detection limit of the method is 0.2 micromol/L. RESULTS: Cervical fluid nitric oxide metabolite was detectable in 46% of nonpregnant women (median, <0.2 micromol/L; 95% CI, 0-49), in 63% of women in early pregnancy (median, 11 micromol/L; 95% CI, 0-23) and in 82% of women in late pregnancy (median, 128 micromol/L; 95% CI, 21-276). In late pregnancy, the cervical fluid nitric oxide metabolite level was higher in women with Bishop score of > or =6 (median, 163 micromol/L; 95% CI, 105-276) than in women with Bishop score of <6 (median, 86 micromol/L; 95% CI, 21-99). Cervical fluid nitric oxide metabolite concentration before the onset of labor in parous women (median, 97 micromol/L; 95% CI, 78-283) was higher (P =.008) than that in nulliparous women (median, 28 micromol/L; 95% CI, 0-95). Cervical fluid nitric oxide metabolites before the initiation of labor (median, 33 micromol/L; 95% CI, 0-95) rose to 3.5-fold (median, 115 micromol/L; 95% CI, 78-284) after the commencement of uterine contractions and showed a significant relationship to Bishop score (r = 0.39, P =.01). Cervical fluid nitric oxide metabolite concentrations were not relative to simultaneous plasma nitric oxide metabolite levels (n = 41 women, r = 0.14, P =.41). Rupture of fetal membranes tended to decrease cervical fluid nitric oxide metabolite levels, whereas gentle cervical manipulation elevated it 6.6-fold in 1 minute. The administration of glyceryl trinitrate (0.5 mg, nitric oxide donor) intracervically resulted in a significant rise in the cervical fluid nitric oxide metabolite level in 2 minutes. CONCLUSION: Cervical fluid nitric oxide metabolite level rises after cervical ripening, nitric oxide donor administration, or cervical manipulation, which supports a role for cervical nitric oxide in cervical ripening.