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Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). Methods: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. Results: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain—either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)—a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). Conclusion: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2–3 months of treatment. [ABSTRACT FROM AUTHOR]

Preventing panel members from attriting is a fundamental challenge for panel surveys. Research has shown that response behavior in earlier waves (response or nonresponse) is a good predictor of panelists' response behavior in upcoming waves. However, response behavior can be described in greater detail by considering the time until the response is returned. In the present study, we investigated whether respondents who habitually return their survey late and respondents who switch between early and late response in multiple waves are more likely to attrit from a panel. Using data from the GESIS Panel, we found that later response is related to a higher likelihood of attrition (AME = 0.087) and that response-time stability is related to a lower likelihood of attrition (AME = −0.013). Our models predicted most cases of attrition; thus, survey practitioners could potentially predict future attriters by applying these models to their own data. [ABSTRACT FROM AUTHOR]

Introduction/Aims: The A‐wave is a late response related either to demyelination or early axonal regeneration. It may be helpful in the evaluation of some peripheral neuropathies. In leprosy, previous studies suggested that A‐waves could be a neurophysiological marker of pain in patients during reactions. Herein we have attempted to further assess the profile and clinical correlates of A‐waves by exploring a large leprosy cohort. Methods: Between 2015 and 2018, 63 patients with leprosy (47 men and 16 women) had A‐waves in nerve conduction studies and were included in this study. We included patients regardless of whether they were experiencing leprosy reactions or not. We then compared clinical features in nerves with and without A‐waves. Results: The mean age of study participants was 46.5 ± 12.3 years and most had borderline leprosy. From this cohort, we assessed separately 83 motor nerves that demonstrated A‐waves (group A+) and 29 motor nerves that did not demonstrate A‐waves (group A−). Neuropathic pain (NP) was found in 66 of 83 nerves in group A+, but only 5 of 29 in group A− (79.5 vs 17.2%, P <.001). In contrast, no significant between‐group difference emerged regarding presence of reactions, sensory function (based on Semmes‐Weinstein evaluations), or muscle strength. A‐waves were found in nerves with neuropathic pain experiencing (39 of 66 = 59%) or not experiencing (27 of 66 = 41%) leprosy reactions. Discussion: These results show that A‐waves are associated with neuropathic pain in leprosy patients, regardless of the nerves affected and the immune status (in reaction or not). [ABSTRACT FROM AUTHOR]

Introduction: In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. Materials and methods: In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan–Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). Results: Sixty-one out of one hundred seventy-six (34.7%) patients showed a sustained increase and 86/176 (48.8%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95% CI 0.22–0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95% CI 0.30–0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95% CI 0.78–2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95% CI 0.38–4.05; P = 0.68). Conclusion: Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression. [ABSTRACT FROM AUTHOR]

Loss or rearrangement of genetic information can result from incorrect responses to DNA double strand breaks (DSBs). The cellular responses to DSBs encompass a range of highly coordinated events designed to detect and respond appropriately to the damage, thereby preserving genomic integrity. In analogy with events occurring during viral infection, we appropriate the terms Immediate-Early, Early, and Late to describe the pre-repair responses to DSBs. A distinguishing feature of the Immediate-Early response is that the large protein condensates that form during the Early and Late response and are resolved upon repair, termed foci, are not visible. The Immediate-Early response encompasses initial lesion sensing, involving poly (ADP-ribose) polymerases (PARPs), KU70/80, and MRN, as well as rapid repair by so-called ‘fast-kinetic’ canonical non-homologous end joining (cNHEJ). Initial binding of PARPs and the KU70/80 complex to breaks appears to be mutually exclusive at easily ligatable DSBs that are repaired efficiently by fast-kinetic cNHEJ; a process that is PARP-, ATM-, 53BP1-, Artemis-, and resection-independent. However, at more complex breaks requiring processing, the Immediate-Early response involving PARPs and the ensuing highly dynamic PARylation (polyADP ribosylation) of many substrates may aid recruitment of both KU70/80 and MRN to DSBs. Complex DSBs rely upon the Early response, largely defined by ATM-dependent focal recruitment of many signalling molecules into large condensates, and regulated by complex chromatin dynamics. Finally, the Late response integrates information from cell cycle phase, chromatin context, and type of DSB to determine appropriate pathway choice. Critical to pathway choice is the recruitment of p53 binding protein 1 (53BP1) and breast cancer associated 1 (BRCA1). However, additional factors recruited throughout the DSB response also impact upon pathway choice, although these remain to be fully characterised. The Late response somehow channels DSBs into the appropriate high-fidelity repair pathway, typically either ‘slow-kinetic’ cNHEJ or homologous recombination (HR). Loss of specific components of the DSB repair machinery results in cells utilising remaining factors to effect repair, but often at the cost of increased mutagenesis. Here we discuss the complex regulation of the Immediate-Early, Early, and Late responses to DSBs proceeding repair itself.

Loss or rearrangement of genetic information can result from incorrect responses to DNA double strand breaks (DSBs). The cellular responses to DSBs encompass a range of highly coordinated events designed to detect and respond appropriately to the damage, thereby preserving genomic integrity. In analogy with events occurring during viral infection, we appropriate the terms Immediate-Early, Early, and Late to describe the pre-repair responses to DSBs. A distinguishing feature of the Immediate-Early response is that the large protein condensates that form during the Early and Late response and are resolved upon repair, termed foci, are not visible. The Immediate-Early response encompasses initial lesion sensing, involving poly (ADP-ribose) polymerases (PARPs), KU70/80, and MRN, as well as rapid repair by so-called 'fast-kinetic' canonical non-homologous end joining (cNHEJ). Initial binding of PARPs and the KU70/80 complex to breaks appears to be mutually exclusive at easily ligatable DSBs that are repaired efficiently by fast-kinetic cNHEJ; a process that is PARP-, ATM-, 53BP1-, Artemis-, and resection-independent. However, at more complex breaks requiring processing, the Immediate-Early response involving PARPs and the ensuing highly dynamic PARylation (polyADP ribosylation) of many substrates may aid recruitment of both KU70/80 and MRN to DSBs. Complex DSBs rely upon the Early response, largely defined by ATM-dependent focal recruitment of many signalling molecules into large condensates, and regulated by complex chromatin dynamics. Finally, the Late response integrates information from cell cycle phase, chromatin context, and type of DSB to determine appropriate pathway choice. Critical to pathway choice is the recruitment of p53 binding protein 1 (53BP1) and breast cancer associated 1 (BRCA1). However, additional factors recruited throughout the DSB response also impact upon pathway choice, although these remain to be fully characterised. The Late response somehow channels DSBs into the appropriate high-fidelity repair pathway, typically either 'slow-kinetic' cNHEJ or homologous recombination (HR). Loss of specific components of the DSB repair machinery results in cells utilising remaining factors to effect repair, but often at the cost of increased mutagenesis. Here we discuss the complex regulation of the Immediate-Early, Early, and Late responses to DSBs proceeding repair itself. [ABSTRACT FROM AUTHOR]

Deciding when and how to change treatment in patients with major depressive disorder who have inadequate response to initial antidepressant therapy is an important everyday clinical question. Here, we ask whether an early change of approach is superior to a delayed change. We consider the recommendations provided by recent guidelines, examine the evidence behind this guidance and suggest a decision tree to clarify treatment options and timing. Both the early and late-change strategies may have their place in clinical practice. However, we take the view that an earlier than currently usual change in antidepressant treatment should be considered more frequently in cases of non-response. Specific studies are needed to identify and to better understand predictors of early and late response. [ABSTRACT FROM AUTHOR]

This year's Annual Review Issue of The Journal of Pathology contains 18 invited reviews on current research areas in pathology. The subject areas reflect the broad range of topics covered by the journal and this year encompass the development and application of software in digital histopathology, implementation of biomarkers in pathology practice; genetics and epigenetics, and stromal influences in disease. The reviews are authored by experts in their field and provide comprehensive updates in the chosen areas, in which there has been considerable recent progress in our understanding of disease. [ABSTRACT FROM AUTHOR]

Aim: To evaluate outcomes of early dose optimization of golimumab in ulcerative colitis (UC) patients with inadequate response to golimumab induction treatment. Methods: This observational, multicenter, cohort study included patients with moderate-to-severe active UC and with inadequate response to subcutaneous golimumab induction doses, in whom weight-based golimumab maintenance dose (European labeling) of 50 mg every 4 weeks (q4wk) was optimized before week 14 to 100 mg q4wk. At week 14, we assessed clinical response and remission using the partial Mayo score. In the long term we evaluate the cumulative probabilities of golimumab failure-free survival and colectomy-free survival. Results: A total of 209 patients who received golimumab induction doses were eligible. Of these, 151 patients (72.2%) weighing less than 80 kg were assigned to a golimumab maintenance dose of 50 mg q4wk. Twenty-four patients (15.9% [12.5% overall]), in whom scheduled doses of 50 mg q4wk were optimized to 100 mg q4wk before week 14, compose the study population. At week 14, 16 patients (66.7%, 95% CI 45.7-87.6) had clinical response, of these 12 were corticosteroid free. Four patients (16.7%) achieved corticosteroid-free remission. After a median follow-up of 12 months (IQR 10-22), 13 patients (54.2%) maintained clinical benefit. Thirteen of 16 patients (81.2%) with clinical response at week 14 maintained clinical benefit at last follow-up. All patients avoided colectomy. In none of the patients was golimumab dose de-escalated. There were no adverse events leading to golimumab withdrawal. Conclusion: Early optimization of golimumab dose induces clinical response at week 14 in two thirds of UC patients and leads to long-term clinical benefit in over half of patients. [ABSTRACT FROM AUTHOR]

Objective: This paper prospectively evaluates the long-term followup [mean +- standard deviation (SD) duration: 89.7+-19.4 months] data of 15 patients (13 females and 2 males) with refractory symptomatic immune thrombocytopenia (ITP) treated with rituximab. Materials and Methods: Rituximab was administered at 375 mg/m2 weekly for a total of 4 doses. Complete response (CR) was defined as a platelet count of ≥100,000/mm3 and partial response (PR) as a platelet count of ≥30,000/mm3 but less than 100,000/mm3. Early response (ER) and late response (LR) were defined as response within 42 days and after 42 days of initiation of rituximab therapy, respectively. Sustained response (SR) was defined as response lasting for at least 6 months. Results: Mean age (+-SD) at the start of rituximab was 46.6+-11.3 years. Mean platelet count (+-SD) prior to rituximab treatment was 17,400+-8878/mm3. The mean time (+-SD) between rituximab therapy and response to rituximab in early responders and late responders was 1.8+-1.3 weeks and 10+-2.8 weeks, respectively. Mean durations (+-SD) of ER and LR were 51+-47.2 months and 6+-4.2 months, respectively. Seven of the 15 patients (46.7%) showed an initial response to rituximab (5 ER and 2 LR). The rate of SR over 6 months was 26.7% (4/15). Among the responders to rituximab, 3 (3/7, 42.9%) maintained their response 1 year after rituximab treatment and 2 (2/7, 28.6%) had ongoing response 5 years after initiation of rituximab. Two of the 7 patients (28.6%) still maintained their response 98 months after initiation of rituximab. All 5 initial responders with subsequent relapse achieved response from subsequent treatment modalities (3 CR, 2 PR). Conclusion: Our data confirm, over a long period of observation, that rituximab is safe and effective in the management of patients with chronic refractory primary ITP.

Introduction A-waves, which are observed following the M-wave during motor nerve conduction studies ( NCS), are late responses that are frequently found in many types of neurogenic disorders. However, A-waves are also common in healthy individuals, where their significance remains unclear. The aim of this study was to examine whether the occurrence of A-waves does in fact represent an increased risk for the future development of changes upon NCS or needle electromyography ( EMG) in the corresponding nerve. Methods Nerve conduction studies/needle electromyography findings at control examination were evaluated in relation to the occurrence of initial A-waves in 327 individuals who had undergone repeated NCS/ EMG examination and exhibited normal initial findings, with or without the occurrence of A-waves as the only acceptable abnormality. Results The odds ratio, which reflects the predictive power of the occurrence of A-waves at the initial testing for the development of an abnormality (neuropathy or radiculopathy) at the follow-up examination, ranged from 2.7 ( p = .041) in the tibial nerve and 3.9 ( p = .034) in peroneal one, to 30.0 ( p = .002) in the ulnar nerve. Conclusions A-waves constitute an initial abnormality in all nerves, and they may be predictive for the future development of broader NCS/ EMG abnormalities in the corresponding nerve. [ABSTRACT FROM AUTHOR]

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Abstract: Objectives: To ascertain the practical electrodiagnostic value of F-waves in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: We evaluated the diagnostic utility of F-waves in 18 prospectively-recruited patients with typical CIDP. Minimum/maximum/mean F-wave latencies, F-wave chronodispersion and F-wave persistence, were determined in median/ulnar/fibular/tibial nerves in patients and compared to controls with axonal neuropathy. Results: All latencies were significantly more delayed in CIDP patients. F-wave chronodispersion was significantly greater in median and ulnar nerves and F-wave persistence significantly more reduced in tibial nerves in CIDP patients. Use of these supplementary F-wave parameters was of value in identifying CIDP nerves. However F-wave studies were only of additional benefit to other demyelinating parameters in about 15% of all studied CIDP nerves. Conclusions: F-waves may be diagnostically helpful in CIDP in a minority of nerves without other nerve conduction abnormalities. Analysis of F-wave chronodispersion in upper limb nerves and possibly of F-wave persistence in tibial nerves, may add value to basic minimum F-wave latency studies. Significance: These results suggest F-wave analysis may not need to be systematic, for all nerves, in patients with suspected CIDP, especially those intolerant to electrical stimulation. Chronodispersion and persistence may be helpful parameters to consider in addition to minimum latency. [Copyright &y& Elsevier]

Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300 mg per day) due to intolerance, in comparison to optimal-dose imatinib (≥300 mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420 days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720 days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose. [ABSTRACT FROM AUTHOR]

The article discusses the possibility of using electrophysiological findings that may be used to predict response to intravenous immunoglobulin (IVIg) in patients with lower motor neuron (LMN) syndromes without multifocal conduction block (MCB). 9 patients were involved in the study in which results were measured using electrophysiological means. Results revealed that the presence of abnormal A waves may indicate the presence of IVIg-responsive LMN syndromes despite the absence of a conduction block.

Eur J Clin Invest 2010; 40 (6): 566–569 Background The inhibitory effect of corticosteroids (CS) on the secretions of cysteinyl-leukotrienes (Cys-LTs) in asthma is controversial. The aim of this study was to evaluate the effect of CS on allergen-induced increase in urinary leukotriene E4 (uLTE4) during early (EAR) and late (LAR) asthmatic responses in mild untreated asthmatics. Material and methods Nine subjects with mild untreated allergic asthma performed two allergen challenges, after 1-week treatment with beclomethasone dipropionate (BDP, 500 μg b.i.d) or placebo. Forced Expiratory Volume in one second 1 (FEV1) was monitored to assess EAR and LAR, and uLTE4 was measured before and during EAR and LAR. Results After placebo, uLTE4 increased significantly during EAR, but not during and after LAR, in comparison with baseline values. Beclomethasone dipropionate induced a significant attenuation of the uLTE4 increase during EAR, in comparison with placebo, in association with a good protection of LAR ( P = 0·002) and a mild protection of EAR ( P = 0·07). Conclusions Beclomethasone dipropionate blunts the early increase in uLTE4 excretion due to allergen challenge, in association with a significant effect on the severity of LAR. These data support the hypothesis that inhaled CS may inhibit the allergen-induced release of cys-LTs in asthma. [ABSTRACT FROM AUTHOR]

Abstract: Allergen inhalation by sensitized asthmatics induces an IgE and mast cell dependent bronchoconstriction and a Th2-dependent inflammatory airway reaction, mucus hypersecretion and airway hyperreactivity. The link between T cells and bronchoconstriction remains controversial. Here we analyzed allergen-induced changes in airway tone in ovalbumin-sensitized mice with established allergic airway inflammation. Inhalation of nebulized ovalbumin elicited a dose-dependent and allergen-specific increase in airway resistance and bronchial tone with a concomitant increase of lymphocytes and eosinophils in bronchoalveolar lavage fluid. A Th2 pattern of cytokine expression and increased mRNA expression of MCP-1, RANTES and VCAM-1 were demonstrated. Anti-CD4 monoclonal antibody treatment prior to provocation decreased IL-13 and VCAM-1 mRNA expression and abolished the increase in bronchial tone and the inflammatory response. We conclude that allergen inhalation in sensitized mice induces airway narrowing similar to the late asthmatic reactions in humans and that this phenomenon is based on activation of CD4+ T cells. [Copyright &y& Elsevier]

Abstract: Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs. [Copyright &y& Elsevier]

Early asthmatic responses (EAR) and late asthmatic responses (LAR) to allergen are induced by the local release of a series of bronchoconstrictor mediators, including leukotrienes and histamine. Both anti-leukotrienes and other anti-asthma drugs, such as inhaled glucocorticoids, have been shown to reduce both EAR and LAR. The aim of the present study was to directly compare the effects of regular treatment with an oral anti-leukotriene, montelukast (Mont; 10 mg once daily, for 8 days), and an inhaled glucocorticoid [fluticasone propionate (FP) 250 μg twice daily for 8 days] on the EAR and LAR to an inhaled allergen challenge. Patients with a documented EAR and LAR at a screening visit were randomized to these treatments, or placebo, in a double-blind, double-dummy, crossover fashion. Allergen challenge at a dose causing both an EAR and LAR was given on the eighth day of treatment. The maximum fall in FEV1 during the EAR was 17.8% during placebo treatment, 8.3% during Mont and 16.3% during FP (P < 0.05 for Montvsplacebo). The maximum fall during the EAR was 13.8% during placebo treatment, 11.8% during Mont and 2% during FP treatment (P < 0.05 for FPvsplacebo and FPvsMont). PC20 methacholine was significantly higher 24 h after allergen challenge during FP-treatment compared with Mont (P < 0.05). Both montelukast and fluticasone reduced the relative amount of sputum eosinophils after allergen compared with placebo treatment. This study shows that anti-leukotrienes are effective to attenuate the EAR, whereas inhaled glucocorticoids are more effective than anti-leukotrienes in attenuating the EARs and improves bronchial hyperresponsiveness to a greater extent. In conclusion, inhaled glucocorticoids have overall greater efficacy than oral anti-leukotrienes to attenuate allergen-induced airway responses in mild asthmatic patients. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures. [Copyright &y& Elsevier]

Abnormal electrophysiological findings may be delayed in the Guillain-Barré syndrome (GBS). In this study, conducted in 29 GBS patients, 23 patients (group 1) fulfilled the electrodiagnostic criteria for GBS [1]at the time of initial investigation, performed on average 22.3 days after onset of symptoms; whereas the 6 patients (group 2) who did not fulfil the criteria were first seen earlier, on average after 9.7 days. During the initial nerve conduction studies, numerous late responses, distinct from F waves, were observed in 26 of the 29 patients (90%), that is in 20 patients of group 1, and in all patients of group 2. Most of these responses, if not all, were indirect discharges (iDs) caused by proximal re-excitation on motor axons. If the iDs had been included in the electrodiagnostic criteria of GBS, all the patients of this series would have been diagnosed at the initial electrophysiological examination. We conclude that iDs occur frequently in GBS and are observed early in the disease. We recommend adding the presence of multiple iDs to the classical electrodiagnostic criteria of GBS. [ABSTRACT FROM AUTHOR]

We challenged 30 pollen-sensitive volunteers with allergen, recorded Symptoms and signs over a. 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment with the glucocorticosteroid budesonide (200 μg twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage. These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72% reduction; P < 0.01), a moderate effect on discharge (37% reduction; P < 0.01), and a slight effect on blockage (17% reduction of nasal inspiratory peak flow rate; P < 0.02). The degree of inhibition of the rechallenge response was similar to the effect on the initial early response. The effect on the late response was very pronounced for all symptoms and signs (97% reduction of sneezes, 76% reduction of nose-blowings, 96% reduction of blockage; F<0.01). In conclusion, we found it difficult in the individual subject to identify a well-defined late symptom response by criteria similar to those employed to characterize the late response in the bronchi. The effect of budesonide was more marked on sneezing than on blockage, and the drug was considerably more effective on the late response than on the early response. [ABSTRACT FROM AUTHOR]