Brain imaging abnormalities and outcome after acute ischaemic stroke: the ENCHANTED trial

alkiviadis.1961 shared this article with you from Inoreader Brain imaging abnormalities and outcome after acute ischaemic stroke: the ENCHANTED trial Via Journal of Neurology, Neurosurgery & Psychiatry current issue Objective To test the hypothesis that imaging signs of 'brain frailty' and acute ischaemia predict clinical outcomes and symptomatic intracranial haemorrhage (sICH) after thrombolysis for acute ischaemic stroke (AIS) in the alteplase dose arm of ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy (ENCHANTED). Methods Blinded assessors coded baseline images for acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions; and hyperattenuated arteries) and pre-existing changes (atrophy, leucoaraiosis and old ischaemic lesions). Logistic regression models assessed associations between imaging features and death at 7 and 90 days; good recovery (modified Rankin Scale scores 0–2 at 90 days) and sICH. Data are reported with adjusted ORs and 95% CIs. Results 2916 patients (67±13 years, National Institutes of Health Stroke Scale 8 (5–14)) were included. Visible ischaemic lesions, severe hypoattenuation, large ischaemic lesion, swelling and hyperattenuated arteries were associated with 7-day death (OR (95% CI): 1.52 (1.06 to 2.18); 1.51 (1.01 to 2.18); 2.67 (1.52 to 4.71); 1.49 (1.03 to 2.14) and 2.17 (1.48 to 3.18)) and inversely with good outcome. Severe atrophy was inversely associated with 7-day death (0.52 (0.29 to 0.96)). Atrophy (1.52 (1.08 to 2.15)) and severe leucoaraiosis (1.74 (1.20 to 2.54)) were associated with 90-day death. Hyperattenuated arteries were associated with sICH (1.71 (1.01 to 2.89)). No imaging features modified the effect of alteplase dose. Conclusions Non-expert-defined brain imaging signs of brain frailty and acute ischaemia contribute to the prognosis of thrombolysis-treated AIS patients for sICH and mortality. However, these imaging features showed no interaction with alteplase dose. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Epilepsy, an orphan disorder within the neurodevelopmental family

alkiviadis.1961 shared this article with you from Inoreader Epilepsy, an orphan disorder within the neurodevelopmental family Via Journal of Neurology, Neurosurgery & Psychiatry current issue In 1997, the neurologist Rajendra Kale stated in the British Medical Journal 'The history of epilepsy can be summarised as 4000 years of ignorance, superstition, and stigma followed by 100 years of knowledge, superstition, and stigma'. Epilepsy remains an orphan disorder, in so much that it remains ostracised from the family of neurodevelopmental disorders (NDDs). The NDDs primarily refer to intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), c ommunication disorders, specific learning disorders and motor disorders such as tics/Tourette. The Diagnostic and Statistical Manuel of Mental Disorders fifth edition (DSM V) description emphasises that NDDs typically have a childhood onset, with manifestations in early period as developmental deficits. Epilepsy and epileptic encephalopathy are not listed under NDDs, but epilepsy in particular genetic epilepsy is a remarkably common comorbidity of NDDs. Significantly higher epilepsy prevalence is observed in ID (22.5%), ASD (20%) and ADHD (15%) than... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Recognising hemihypomimia as a mimic of 'facial weakness

alkiviadis.1961 shared this article with you from Inoreader Recognising hemihypomimia as a mimic of 'facial weakness Via Journal of Neurology, Neurosurgery & Psychiatry current issue Case descriptions Patient A is a 69-year-old man with a 5-year history of progressive right hand then leg tremor, stiffness and slowness with recent diagnosis of Parkinson's disease (PD) 3 months prior to this encounter. Examination demonstrated unilateral right-sided facial droop at rest largely sparing the upper face and with accompanying decreased right lower facial muscle activation. Unified Parkinson's Disease Rating Scale motor examination score (UPDRS-III) was 26. UPDRS-III facial expression subscore had decre ased from 2 to 1 since starting carbidopa/levodopa 50–200 three times daily 3 months prior. Similarly, patient B is a 77-year-old woman with a 3-year history of tremor starting in her left hand and a diagnosis of PD since 2017. Examination demonstrated resting unilateral left-sided facial droop involving both the upper and lower face with associated upper-worse-than-lower facial asymmetry. UPDRS-III score was 24 including a UPDRS facial expression score of 1. She has been treated with ropinirole... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer

alkiviadis.1961 shared this article with you from Inoreader Isaacs syndrome: the frontier of neurology, psychiatry, immunology and cancer Via Journal of Neurology, Neurosurgery & Psychiatry current issue A syndrome of continuous muscle-fibre activity Authors: Isaacs H Year published: 1961 Number of times cited: 480 Evolution of Isaacs syndrome from case studies that described continuous ectopic activity through to an understanding as a multisystem autoimmune condition Six decades ago, Dr Hyam Isaacs reported a new clinical syndrome in the Journal of Neurology, Neurosurgery and Psychiatry.1 Isaacs used the term 'syndrome of continuous muscle-fibre activity ' or the more descriptive 'armadillo disease' for the condition which now has become known as Isaacs syndrome or acquired autoimmune neuromyotonia. In his landmark series, Isaacs described a phenotype of progressive muscle stiffness, with widespread fasciculation leading to weakness. A key finding was continuous muscle activity on electromyography, occurring at rest and unaffected by local nerve blockade. The original report also detailed a number of unsuccessful treatment approaches, as well as an astonishing improvement produced by sodium diphenyl... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis

alkiviadis.1961 shared this article with you from Inoreader Cognition and behaviour in frontotemporal dementia with and without amyotrophic lateral sclerosis Via Journal of Neurology, Neurosurgery & Psychiatry current issue Objective The precise relationship between frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is incompletely understood. The association has been described as a continuum, yet data suggest that this may be an oversimplification. Direct comparisons between patients who have behavioural variant FTD (bvFTD) with and without ALS are rare. This prospective comparative study aimed to determine whether there are phenotypic differences in cognition and behaviour between patients with FTD-ALS and bvFTD alone. Methods Patients with bvFTD or FTD-ALS and healthy controls underwent neuropsychological testing, focusing on language, executive functions and social cognition. Behavioural change was measured through caregiver interview. Blood samples were screened for known FTD genes. Results 23 bvFTD, 20 FTD-ALS and 30 controls participated. On cognitive tests, highly significant differences were elicited between patients and controls, confirming the tests' sensitivities to FTD. bvFTD and FTD-ALS groups performed similarly, although with slightly greater difficulty in patients with ALS-FTD on category fluency and a sentence-ordering task that assesses grammar production. Patients with bvFTD demonstrated more widespread behavioural change, with more frequent disinhibition, impulsivity, loss of empathy and repetitive behaviours. Behaviour in FTD-ALS was dominated by apathy. The C9ORF72 repeat expansion was associated with poorer performance on language-related tasks. Conclusions Differences were elicited in cognition and behaviour between bvFTD and FTD-ALS, and patients carrying the C9ORF72 repeat expansion. The findings, which raise the possibility of phenotypic variation between bvFTD and FTD-ALS, have clinical implications for early detection of FTD-ALS and theoretical implications for the nature of the relationship between FTD and ALS. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Vaccines, Vol. 8, Pages 689: Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC

alkiviadis.1961 shared this article with you from Inoreader Vaccines, Vol. 8, Pages 689: Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC Via Vaccines Vaccines, Vol. 8, Pages 689: Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC Vaccines doi: 10.3390/vaccines8040689 Authors: Shushan Harutyunyan Irene Neuhauser Alexandra Mayer Michael Aichinger Valéria Szijártó Gábor Nagy Eszter Nagy Petra Girardi Frank J. Malinoski Tamás Henics Shigella spp. and enterotoxigenic Escherichia coli (ETEC) remain the two leading bacterial causes of diarrheal diseases worldwide. Attempts to develop preventive vaccines against Shigella and ETEC have not yet been successful. The major challenge for a broad Shigella vaccine is the serotype-specific immune response to the otherwise protective LPS O-antigen. ETEC vaccines mainly rely on the heat-labile enterotoxin (LT), while heat-stable toxin (ST) has also been shown to be an important virulence factor. Methods: We constructed a combined Shigella and ETEC vaccine (ShigETEC) based on a live attenuated Shigella strain rendered rough and non-invasive with heterologous expression of two ETEC antigens, LTB and a detoxified version of ST (STN12S). This new vaccine strain was characterized and tested for immunogenicity in relevant animal models. Results: Immunization with ShigETEC resulted in serotype independent protection in the mouse lung shigellosis model and induced high titer IgG and IgA antibodies against bacterial lysates, and anti-ETEC toxin antibodies with neutralizing capacity. Conclusions: ShigETEC is a promising oral vaccine candidate against Shigella and ETEC infections and currently in Phase 1 testing. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Removing the legal barriers to treating the excruciating pain of cluster headaches

alkiviadis.1961 shared this article with you from Inoreader Removing the legal barriers to treating the excruciating pain of cluster headaches Via Journal of Medical Ethics blog By Jonathan Leighton. There is nothing worse than extreme pain and suffering. Patients experiencing unbearable pain may take their lives to escape it. The highest priority of medicine and of society in general – the issue with the most urgent call to action – is arguably to alleviate such suffering. Although the ethical framework I propose is explicitly centred on suffering, relieving extreme suffering is a high priority according to most mainstream ethical frameworks. Laws that prevent doctors from treating patients in extreme pain with effective medicines, or that threaten patients seeking to relieve extreme pain with criminal prosecution, are ethically unjustifiable. Rather incredibly, this is currently the case for cluster headaches, recognised as one of the most excruciating conditions known to medicine. Rated significantly more painful that migraines, kidney stones or childbirth, cluster attacks can occur many times during the day and night, last an hour or longer, and recur daily for months or even years without a break. Needless to say, these attacks can destroy patients' lives. How is this situation possible? And how can we change it? Currently, there is no medication that adequately treats cluster headaches. Verapamil can reduce the frequency of attacks but usually does not prevent entire cycles, and it can have cardiovascular side effects. Sumatriptan injected subcutaneously can usually abort attacks quickly, but because of cardiovascular side effects there are limits to its use. Increased usage appears to cause rebound attacks, and it also does not work for all patients. High-flow oxygen can usually abort attacks within 15 minutes, but again, it doesn't work for all patients, and it doesn't prevent attacks from happening. But it is now clear that several psychedelic substances of the indoleamine chemical family can have dramatic effects in aborting and preventing attacks and even entire cycles. They include psilocybin, found in psychedelic mushrooms, as well as LSD, DMT, found in ayahuasca, and 5-MeO-DALT. Although a few randomised controlled trials are now underway, there is already a wealth of evidence for efficacy, particularly for psilocybin. This evidence comes from scientifically conducted patient surveys and a large number of independent patient reports in cluster headache support groups and elsewhere. Although it is hard to offer precise figures, in a policy paper we just published we write that it is vanishingly improbable that the dramatic effect observed independently by so many patients was due to chance or artefact. From a safety perspective, psilocybin mushrooms and LSD have been evaluated as among the least harmful of recreational drugs – much less so than alcohol – and psilocybin has a long history of use. Furthermore, they have often been found to be effective in treating cluster headaches with just a few, often sub-hallucinogenic doses. Given how devastating cluster headaches are, it would be essential to make these substances available to patients even if there were doubts about their efficacy. Yet in most countries these substances cannot be prescribed by doctors. They are also illegal to purchase and possess, making it difficult for patients to access them, forcing those who can to use substances of uncertain purity and quality, reducing the availability of reliable information on how to use them effectively, and causing patients to live in fear of prosecution. The root of the problem lies in the decades-old war on drugs. This was based on an exaggerated perception of the risk of many psychoactive substances, and on the misguided belief that a heavy-handed criminal justice approach to drug policy is better than a health-centred one. As a result, the barriers are higher to having psychoactive substances approved for medical use. Meanwhile, patients in agony are not informed about promising therapeutic options or are left scrambling to navigate legal and logistical obstacles. As we argue in our policy paper, titled "Legalising Access to Psilocybin to End the Agony of Cluster Headaches", governments can dramatically improve the quality of life for many of their citizens with cluster headaches, with little or no additional cost or risk, by removing the legal barriers to accessing psilocybin and related compounds for therapeutic purposes. In particular: Existing regulations must be modified to allow doctors to prescribe currently restricted indoleamines such as psilocybin, LSD, DMT and 5-MeO-DALT to patients with cluster headaches, and to ensure that these substances can be readily produced or imported for such medical use. We also recommend that existing regulations be modified to ensure that patients with a cluster headache diagnosis who purchase or possess small amounts of psychoactive substances, or who purchase and use grow kits for psilocybin-containing mushrooms, for personal therapeutic use, cannot be legally prevented from doing so or be charged with a crime or offence. Finally, a shift to a drug policy based on harm reduction and general decriminalisation/legalisation is an available policy option that would also reduce many of the legal and practical barriers to self-treatment by cluster headache patients. While cluster headaches represent a particularly urgent case, these arguments have broader relevance. We advocate for a society where all intense pain and suffering is accorded the priority it deserves, and governmental policy-making is grounded in these ethical considerations. Author: Jonathan Leighton Affiliations: Executive Director, Organisation for the Prevention of Intense Suffering (OPIS) Competing interests:  None Social media accounts of post author: https://www.facebook.com/jonathan.leighton.01, https://twitter.com/JonLeighton1 The post Removing the legal barriers to treating the excruciating pain of cluster headaches appeared first on Journal of Medical Ethics blog. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Implantable Bladder Wrap for Improved Urinary Control

alkiviadis.1961 shared this article with you from Inoreader Implantable Bladder Wrap for Improved Urinary Control Via Medgadget Researchers at Penn State have developed an implantable device that coils around the bladder to detect when the bladder is full and assist with emptying it by contracting on-demand. The device is intended to treat underactive bladder, a condition in which incomplete bladder emptying leads to irregular and uncomfortable urination. "Researchers have been interested in studying urinary control for a while because a lot of diseases and conditions are related to this," said Larry Cheng, a researcher involved in the study. "There are two conditions in particular that researchers have been studying. The first condition is to force the urine out of the bladder when the muscle might be in a diseased state so that it really can't provide enough force to get the urine out. The second is an overactive bladder, in which an individual experiences the sudden or frequent tendency to urinate, which is related to urinary incontinence." In the case of underactive bladder, this is not only inconvenient, but in certain cases can lead to urinary retention and serious damage to the kidneys if urine backs up and is forced into them. Current treatments for underactive bladder include drug therapy, surgery or self-catheterization, which present various drawbacks ranging from limited efficacy, side-effects, pain, and inconvenience.   To address this, the Penn State researchers have designed a new implantable device that can mechanically assist with emptying the bladder. The device is a polymer wrap that encircles the bladder and can expand and contract as the bladder fills and empties. It also contains sensors that can detect when the bladder is full and needs to be emptied. The device can then send a signal to an electric thread which begins contracting, providing mechanical assistance in emptying the bladder. Interestingly, because of its unique serpentine shape, the wrap does not require glue or sutures to remain in place, which makes it easier to implant. "With the serpentine design built into the structure, we can stretch it to a much bigger geometry," said Cheng. "So, if we stretch that serpentine wrap, which is placed around and against the bladder, it would provide a sufficient force to hold the electronic thread with the sensors in place so that it won't be able to slip off." Open access study in Science Advances: Expandable and implantable bioelectronic complex for analyzing and regulating real-time activity of the urinary bladder Via: Penn State View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Determining dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralisation test in children in Cebu, Philippines: a prospective population-based study

alkiviadis.1961 shared this article with you from Inoreader [Articles] Determining dengue virus serostatus by indirect IgG ELISA compared with focus reduction neutralisation test in children in Cebu, Philippines: a prospective population-based study Via The Lancet Global Health Most children (89·3%) assessed in our study and eligible to participate in the mass dengue vaccination campaign were seropositive for previous dengue virus infection. Compared with FRNT, ELISA had high sensitivity and specificity (>90%), but the false-negative and false-positive rates makes the test suboptimal for prevaccination screening. Individuals who are falsely identified as seropositive by dengue IgG ELISA and then vaccinated might be at risk of developing severe disease during a subsequent exposure to wild-type dengue virus. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life

alkiviadis.1961 shared this article with you from Inoreader Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life Via Nature Neuroscience - Issue - nature.com science feeds Nature Neuroscience, Published online: 16 November 2020; doi:10.1038/s41593-020-00737-w Uhlmann et al. show that the preclinical phase of Alzheimer's disease may in fact be a relatively late manifestation of a much earlier pathogenic and targetable process of seed formation and propagation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production

alkiviadis.1961 shared this article with you from Inoreader Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H<sub>2</sub>O<sub>2</sub><sup>−</sup> production Via Nature Neuroscience - Issue - nature.com science feeds Nature Neuroscience, Published online: 16 November 2020; doi:10.1038/s41593-020-00735-y Chun et al. find that a severe model of reactive astrocytes overproduces hydrogen peroxide, leading to the development of Alzheimer's disease-like pathologies, including neurodegeneration, tauopathy and memory impairment. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.