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BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.
Genetic components of human pain sensitivity: a protocol for a genome-wide association study of experimental pain in healthy volunteers
<jats:sec><jats:title>Introduction</jats:title><jats:p>Pain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>A GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated.</jats:p></jats:sec><jats:sec><jats:title>Ethics and dissemination</jats:title><jats:p>This study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01–2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences.</jats:p></jats:sec>
International prospective observational study on intracranial pressure in intensive care (ICU): the SYNAPSE-ICU study protocol
<jats:sec><jats:title>Introduction</jats:title><jats:p>Intracranial pressure (ICP) monitoring is commonly used in neurocritical care patients with acute brain injury (ABI). Practice about indications and use of ICP monitoring in patients with ABI remains, however, highly variable in high-income countries, while data on ICP monitoring in low and middle-income countries are scarce or inconsistent. The aim of the SYNAPSE-ICU study is to describe current practices of ICP monitoring using a worldwide sample and to quantify practice variations in ICP monitoring and management in neurocritical care ABI patients.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>The SYNAPSE-ICU study is a large international, prospective, observational cohort study. From March 2018 to March 2019, all patients fulfilling the following inclusion criteria will be recruited: age >18 years; diagnosis of ABI due to primary haemorrhagic stroke (subarachnoid haemorrhage or intracranial haemorrhage) or traumatic brain injury; Glasgow Coma Score (GCS) with no eye opening (Eyes response=1) and Motor score ≤5 (not following commands) at ICU admission, or neuro-worsening within the first 48 hours with no eye opening and a Motor score decreased to ≤5. Data related to clinical examination (GCS, pupil size and reactivity, Richmond Agitation-Sedation Scale score, neuroimaging) and to ICP interventions (Therapy Intensity Levels) will be recorded on admission, and at day 1, 3 and 7. The Glasgow Outcome Scale Extended (GOSE) will be collected at discharge from ICU and from hospital and at 6-month follow-up. The impact of ICP monitoring and ICP-driven therapy on GOSE will be analysed at both patient and ICU level.</jats:p></jats:sec><jats:sec><jats:title>Ethics and dissemination</jats:title><jats:p>The study has been approved by the Ethics Committee ‘Brianza’ at the Azienda Socio Sanitaria Territoriale (ASST)-Monza (approval date: 21 November 2017). Each National Coordinator will notify the relevant ethics committee, in compliance with the local legislation and rules. Data will be made available to the scientific community by means of abstracts submitted to the European Society of Intensive Care Medicine annual conference and by scientific reports and original articles submitted to peer-reviewed journals.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="NCT03257904" ext-link-type="clintrialgov" specific-use="clinicaltrial results">NCT03257904</jats:ext-link>.</jats:p></jats:sec>
Blocking tactile input to one finger using anaesthetic enhances touch perception and learning in other fingers.
Brain plasticity is a key mechanism for learning and recovery. A striking example of plasticity in the adult brain occurs following input loss, for example, following amputation, whereby the deprived zone is "invaded" by new representations. Although it has long been assumed that such reorganization leads to functional benefits for the invading representation, the behavioral evidence is controversial. Here, we investigate whether a temporary period of somatosensory input loss to one finger, induced by anesthetic block, is sufficient to cause improvements in touch perception ("direct" effects of deafferentation). Further, we determine whether this deprivation can improve touch perception by enhancing sensory learning processes, for example, by training ("interactive" effects). Importantly, we explore whether direct and interactive effects of deprivation are dissociable by directly comparing their effects on touch perception. Using psychophysical thresholds, we found brief deprivation alone caused improvements in tactile perception of a finger adjacent to the blocked finger but not to non-neighboring fingers. Two additional groups underwent minimal tactile training to one finger either during anesthetic block of the neighboring finger or a sham block with saline. Deprivation significantly enhanced the effects of tactile perceptual training, causing greater learning transfer compared with sham block. That is, following deafferentation and training, learning gains were seen in fingers normally outside the boundaries of topographic transfer of tactile perceptual learning. Our results demonstrate that sensory deprivation can improve perceptual abilities, both directly and interactively, when combined with sensory learning. This dissociation provides novel opportunities for future clinical interventions to improve sensation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Hippocampal-prefrontal coherence mediates working memory and selective attention at distinct frequency bands and provides a causal link between schizophrenia and its risk gene GRIA1.
Increased fronto-temporal theta coherence and failure of its stimulus-specific modulation have been reported in schizophrenia, but the psychological correlates and underlying neural mechanisms remain elusive. Mice lacking the putative schizophrenia risk gene GRIA1 (Gria1-/-), which encodes GLUA1, show strongly impaired spatial working memory and elevated selective attention owing to a deficit in stimulus-specific short-term habituation. A failure of short-term habituation has been suggested to cause an aberrant assignment of salience and thereby psychosis in schizophrenia. We recorded hippocampal-prefrontal coherence while assessing spatial working memory and short-term habituation in these animals, wildtype (WT) controls, and Gria1-/- mice in which GLUA1 expression was restored in hippocampal subfields CA2 and CA3. We found that beta (20-30 Hz) and low-gamma (30-48 Hz) frequency coherence could predict working memory performance, whereas-surprisingly-theta (6-12 Hz) coherence was unrelated to performance and largely unaffected by genotype in this task. In contrast, in novel environments, theta coherence specifically tracked exploration-related attention in WT mice, but was strongly elevated and unmodulated in Gria1-knockouts, thereby correlating with impaired short-term habituation. Strikingly, reintroduction of GLUA1 selectively into CA2/CA3 restored abnormal short-term habituation, theta coherence, and hippocampal and prefrontal theta oscillations. Although local oscillations and coherence in other frequency bands (beta, gamma), and theta-gamma cross-frequency coupling also showed dependence on GLUA1, none of them correlated with short-term habituation. Therefore, sustained elevation of hippocampal-prefrontal theta coherence may underlie a failure in regulating novelty-related selective attention leading to aberrant salience, and thereby represents a mechanistic link between GRIA1 and schizophrenia.
OBJECTIVE: Since use of diffusion-weighted imaging (DWI) positivity in the "tissue-based" definition of stroke in patients with a clinical TIA is supported by the high associated 90-day risk of recurrent stroke, we aimed to determine long-term prognostic significance, stratified by etiologic subtype, and whether the same tissue-based distinction is predictive in minor strokes. METHODS: Consecutive eligible patients with TIA or minor stroke (NIH Stroke Scale [NIHSS] ≤3) in the population-based Oxford Vascular Study underwent brain MRI at baseline. Stroke risk on 10-year follow-up was stratified by NIHSS (0/1 vs 2/3) and Trial of Org 10172 in Acute Stroke Treatment classification of the initial event. RESULTS: Among 1,033 patients (633 TIA; 400 minor stroke), 248 (24.0%) had acute lesions on DWI (13.9% of TIAs; 40.0% of minor strokes). A positive DWI was associated with an increased 10-year risk of recurrent ischemic stroke after an index TIA (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.28-5.54, p = 0.009) or a stroke with NIHSS 0-1 (3.03, 1.29-7.08, p = 0.011), but not after a stroke with NIHSS 2-3 (0.70, 0.24-2.10, p = 0.53). Ischemic stroke risk after DWI-positive TIA was at least equivalent to that after DWI-negative stroke (1.81, 0.82-4.00, p = 0.14). Among all patients, DWI positivity was most predictive of 10-year risk after cryptogenic events (4.68, 1.70-12.92, p = 0.003). CONCLUSION: DWI positivity is associated with an increased long-term risk of recurrent stroke after TIA and minor stroke, supporting a tissue-based definition of minor stroke as well as TIA. Prognostic value is greatest after cryptogenic events.