On February 24, 2022, Russia launched a full-scale invasion of Ukraine that dominated headlines around the world. Millions of Ukrainians would flee the country, and a third of the population would be ...displaced. In the days following the invasion, Swedish migration expert Gregg Bucken-Knapp sent text messages to his Ukrainian colleagues, offering support and assistance. These were their responses. In a series of graphic vignettes, Messages from Ukraine takes the words of Ukrainian migration professionals and transforms them into snapshots of how war affects the lives of everyday people: those who are forced to flee home and seek safety elsewhere, those who choose to stay and volunteer or fight, those who witness events unfolding from afar, and those who find themselves trapped in cities under siege. Messages from Ukraine captures a moment in time to tell a timeless story about war, displacement, determination, and resilience. Proceeds from the sale of Messages from Ukraine will go to the Canada-Ukraine Foundation, a national charitable foundation that provides humanitarian aid to the people of Ukraine.
The war in Ukraine has altered the course of global history. These authors explore how.When Vladimir Putin's forces sought to conquer Ukraine in February 2022, they did more than threaten the ...survival of a vulnerable democracy. The invasion unleashed a crisis that has changed the course of world affairs. This conflict has reshaped alliances, deepened global cleavages, and caused economic disruptions that continue to reverberate around the globe. It has initiated the first great-power nuclear crisis in decades and raised fundamental questions about the sources of national power and military might in the modern age. The outcome of the conflict will profoundly influence the international balance of power, the relationship between democracies and autocracies, and the rules that govern global affairs. In War in Ukraine, Hal Brands brings together an all-star cast of analysts to assess the conflict's origins, course, and implications and to offer their appraisals of one of the most geopolitically consequential crises of the early twenty-first century. Essays cover topics including the twists and turns of the war itself, the successes and failures of US strategy, the impact of sanctions, the future of Russia and its partnership with China, and more.Contributors: Anne Applebaum, Joshua Baker, Alexander Bick, Hal Brands, Daniel Drezner, Peter Feaver, Lawrence Freedman, Francis Gavin, Brian Hart, William Inboden, Andrea Kendall-Taylor, Michael Kimmage, Michael Kofman, Stephen Kotkin, Mark Leonard, Bonny Lin, Thomas Mahnken, Dara Massicot, Michael McFaul, Robert Person, Kori Schake, and Ashley Tellis.
BackgroundHow do we show that neurological services and neurological practice are safe? We aimed to identify the range of safety practices in neurology, develop a means of measuring safety practice ...activity at individual, service and national levels, assess safety culture across UK neuroscience centres and create benchmarks to allow future comparison of safety practice. We intend that this will provide information for service improvement and individual revalidation.MethodsItems assessing safety practice were collated from medical literature and direct experience of ABN Quality and Service Committee members. These were combined into a pilot survey for distribution to ABN Advisory Groups and ABN Committee members.Results18 questions on individual practice and 15 service-level questions were identified for the pilot. Results of the pilot will be presented and delegates will be asked for feedback during the meeting on the safety questions and their use in appraisal and revalidation.ConclusionA suite of individual metrics can be combined to evidence safety practice at a personal and service level in neurology.
RG6102 is a bispecific 2+1 monoclonal antibody (mAb) under development for the treatment of Alz- heimer’s disease (AD). It combines the anti-amyloid beta antibody gantenerumab with a transferrin ...receptor 1-binding “Brain Shuttle” module, enabling active receptor-mediated transport across the blood–brain barrier.In preclinical studies, RG6102 has shown superior distribution, target engagement and amyloid plaque clearance compared with gantenerumab. In a human Phase Ia study, there was a markedly increased cerebrospinal fluid (CSF)/plasma ratio for RG6102 compared with typical mAbs.Brainshuttle AD is a 28-week, randomised, global, multicentre, double-blind, placebo-controlled, parallel- group Phase Ib/IIa study evaluating the safety, tolerability, immunogenicity and pharmacokinetics/phar- macodynamics (PK/PD) of RG6102. Multiple-ascending intravenous doses of RG6102 are administered every 4 weeks to patients with prodromal or mild-to-moderate AD. The study consists of a screening period, a double-blind treatment period and a safety follow-up period.The primary objective is to evaluate the safety and tolerability of RG6102. Secondary outcome measures include the change from baseline in brain amyloid load, plasma and CSF concentration of RG6102 and incidence of anti-drug antibodies to RG6102. Exploratory endpoints include the clinical effect of multiple doses of RG6102 on clinical outcome measures and on various PD biomarkers.Recruitment for Brainshuttle AD is currently ongoing.
West is best – a strongman with numb feet Edwards, Marc; Powell, Robert
Journal of neurology, neurosurgery and psychiatry,
09/2022, Letnik:
93, Številka:
9
Journal Article
Recenzirano
A 64-year-old post office worker presented with several years of progressive unsteadiness and tingling sensation in his feet. He was an enthusiastic bodybuilder and had been regularly taking anabolic ...steroids since his 20s.On examination he had a broad based gait and Romberg’s test was positive. There was mild dysarthria, dysmetria and an intention tremor. There was wasting evident in his right hand related to a known right ulnar neuropathy. Power was full throughout all limbs but reflexes were reduced. Pin-prick sensation was reduced to the knees and proprioception and vibratory sense were reduced distally.Neuroimaging revealed cerebellar atrophy and nerve conduction studies an axonal peripheral neuropa- thy. On further questioning the patient disclosed his dietary regime of 4 cans of blended tuna daily for the past 25 years. Mercury levels were significantly raised at 256nmol/l (normal range <25nmol/l). He was advised to stop eating tuna and was prescribed dimercaptosuccinic acid. The level subsequently dropped to 48nmol/l.Chronic mercury toxicity can present in a variety of ways due to its deposition in different organs (kidneys, liver, brain). In this case, excessive exposure to organic mercury in tuna fish led to a peripheral neuropathy and cerebellar ataxia.
RationaleFenfluramine substantially reduces rates of sudden unexplained death in epilepsy (SUDEP) in Dravet syndrome (Cross JH et al, AES 2020). Fenfluramine reduces respiratory arrest in the DBA/1 ...SUDEP mouse model (Tupal and Faingold, Epilepsia. 2019). Spreading depolarisation (SD) is a pathophysiologic event linked to cardiorespiratory collapse in SUDEP models. We report that fenfluramine inhibits SD, and explore its potential inhibitory mechanisms.MethodsWe examined the effects of fenfluramine on SD evoked by KCl or oxygen glucose deprivation (OGD) in cortical brain slices of adult C57Bl/6 mice. We also measured the effect on GABAAR-mediated inhibitory postsynaptic currents (sIPSC) in vitro.ResultsFenfluramine increased the threshold for SD events at clinically relevant concentration ranges (~10 µM). Blocking GABAARs with gabazine did not fully occlude SD inhibition by fenfluramine, suggesting that GABAAR potentiation is not involved in the inhibitory SD mechanism of fenfluramine.ConclusionOur results demonstrate that fenfluramine directly inhibits SD generation without acting via a neurovascular mechanism suggesting that SD inhibition could account for the decrease in expected rates of SUDEP in patients treated with fenfluramine.
ObjectivesCalcitonin gene-related peptide (CGRP) antagonists are recommended by NICE as 4th line migraine preventive treatment. We report the frequency and preventive treatment patterns of migraine ...in the UK, focusing on adult patients who cease ≥3 oral preventive medications.MethodsStudy populations were retrieved from the Clinical Practice Research Datalink GOLD database (study period: 19/09/2012−01/01/2020; inclusion criteria: ≥12 months follow-up, current-in-dataset, adult on 01/01/2020). Patients who used ≥1 oral preventive medication with ≥3-year follow-up after first pre- scription were considered preventive users; medication/class cessation was defined as cessation with no evidence of restart within 6 months from end-of-supply date.ResultsOn 01/01/2020, 30.5/1,000 (n=81,190/2,664,306, 95% CI 30.3–30.7) of study population had ≥1 migraine codes recorded over the study period. 42% of patients were preventive users. Of these, 10% had ≥3 preventive medication cessations, and 8% had ≥3 preventive medication class cessations. Patients with ≥3 preventive medication cessations were mostly female (83%), mean age was 46 years and 22% had a referral to a neurologist during the study period.ConclusionsA considerable proportion of patients with migraine cease ≥3 lines of oral preventive medi- cation, pointing to the need for additional therapeutic options.
IntroductionSporadic CJD (sCJD) is universally fatal. While median survival is 5 months, there is consider- able heterogeneity with some surviving weeks while others survive several months or years. ...We sought to evaluate characteristics influencing disease duration, and the performance of latest diagnostic criteria incorporating cortical ribboning on MRI brain and the RT-QuIC assay.Methods501 autopsy-confirmed cases from surveillance centres in the UK, France, Germany and Italy were stratified into short (<75 days), typical (75-222 days) and long (>222 days) survival groups. We evaluated clinical features, investigation results, and diagnostic criteria classification.ResultsShort survival was associated with male sex (p=0.02) and older age (p=0.004). Prion protein gene codon 129 polymorphism status greatly influenced duration (p=<0.001, with longest survival in methionine- valine heterozygotes). Extrapyramidal features were most frequent in long survivors (p=0.04). EEG and 14-3-3 were most sensitive with short survival (p<0.001), RT-QuIC with typical survival (p=0.03) and MRI sen- sitivity did not vary (p=0.4). Previous diagnostic criteria lacked sensitivity in long survivors (p=0.001) while updated criteria were equivalent between groups (p=0.19): sensitivity for long survivors increased 27.7%.ConclusionsThis study demonstrates important factors influencing survival and associated phenotypes. The latest diagnostic criteria for sCJD have significantly enhanced diagnosis in long survivors.
078 Bruns syndrome – broadening the phenotype Seddigh, Arshia; Mollan, Susan; Samarasekera, Shanika ...
Journal of neurology, neurosurgery and psychiatry,
09/2022, Letnik:
93, Številka:
9
Journal Article
Recenzirano
We present a 50-year-old lady with 6-months’ history of episodes of feeling weak with legs giving way triggered by sudden change of position or head-turning and no loss of consciousness. She had left ...tinnitus for years and one year worsening migraines with fortification spectra, visual blurring, and vertigo. ENT made a diagnosis of vestibular migraines.Her neurological examination was normal and attempted provocation of attacks with sudden changes in position and Dix-Hallpike was unsuccessful. Brain MRI revealed a large lesion obstructing foramina of Luschka-Magendie giving rise to obstructive hydrocephalus.Neuro-ophthalmology review showed bilateral papilledema and no evidence of Parinaud’s syndrome (no convergence retraction nystagmus or tectal pupils). Tumour biomarkers (bHCG-AFP-AlkPh-LDH) and body CT scan were normal. She underwent urgent CSF diversion. MDTs confirmed radiological diagnosis of epidermoid cyst awaiting debulking.Episodic headaches/vertigo with head-turning are described in Bruns syndrome manifesting as abrupt headaches, vertigo, vomiting provoked by changes in head position due to intermittent obstructive hydrocephalous (mass lesion and ball-valve mechanism). We propose patient’s acute episodes of lower limb weakness were similar phenomenon highlighting importance of imaging in stereotypical attacks after triggers.
Visual deterioration in Idiopathic Intracranial Hypertension (IIH) warrants surgical intervention. All patients with IIH admitted to St. George’s, London for 10-years from 2010 were identified and ...those with shunts were analyzed retrospectively. Of 1234 IIH patients, 27 had shunts, 12/27 were aged 19-30 and 24 were females. The most common indication for a shunt was quantifiable visual impairment (52%). Majority had lumboperitoneal shunts (67%). The average length of stay was 16 days (2SD+/-8 days). In the first 3 years, neurologists were not involved in the care of 11/27 patients but all since. The number of shunts per year peaked at 6 in 2013 and is now 1-2. At first follow-up, vision and headache improved in 84% and 85% of patients, respectively. 40% had recurrence of symptoms despite a functioning shunt due to coexisting migraine (36%), functional neurological disorder (9%) or both (18%). The most common complication was shunt obstruction (single-revision; 30%; multiple-revisions; 19%), followed by low-pressure symptoms (26%), requiring readmissions in 81% of patients. Shunting is not without risks but is currently indicated in those with deteriorating visual function; hence, the decision to proceed with shunting in IIH should be made with vigilance in accordance with the 2018 consensus guidelines.
