Hejlesendam9879

There are increasing reports of myasthenia gravis (MG) following oncological treatment with immune checkpoint inhibitors (ICIs).

A 66-year-old man with stage 3A lung adenocarcinoma was treated with second weekly infusions of durvalumab, a programmed cell death ligand-1 inhibitor, at a dose of 10 mg/kg. After the fourth infusion, he developed diplopia, dyspnoea and constitutional symptoms including headache, weakness and anorexia. 1 month later, he developed dysphagia and dysphonia. Examination showed proximal limb weakness with fatigability. An ice pack test was positive. Blood tests revealed a raised creatine kinase and positive PM-Scl75 antibody. Antititin antibody was strongly positive in the serum and cerebrospinal fluid. Antibodies for acetylcholinesterase receptor and antimuscle-specific kinase were negative. Electromyography showed myopathic changes. The patient was treated with steroids, pyridostigmine, mycophenolate mofetil and intravenous immunoglobulin. Eight weeks after treatment initiation ptosis, eye movements and limb strength were markedly improved and repeat creatine kinase was normal.

Clinicians using ICIs should have a high index of suspicion for ICI-induced MG and concurrent myositis as disease can be severe and is associated with high mortality rates.

Clinicians using ICIs should have a high index of suspicion for ICI-induced MG and concurrent myositis as disease can be severe and is associated with high mortality rates.

Huntington disease (HD) is a genetically inherited neurodegenerative disorder that classically involves a trinucleotide CAG repeat expansion on chromosome 4, with 36 repeats or greater being disease identifying. It generally presents between the age of 30 and 40 years old and is characterised by severe caudate/striatum degeneration with huntingtin protein aggregation. We present here the case of a patient in her early 80s who presented with 5-year history of worsening chorea and family history of HD but an intermediate length CAG expansion.

Genetic testing of CAG repeats on chromosome 4. Postmortem brain tissue was obtained and stained using immunohistochemistry for amyloid-beta, tau and glial fibrillary acidic protein (GFAP). Sections from the caudate/putamen were also analysed by p62 immunofluorescence. All sections were reviewed by trained neuropathologists.

On genetic testing the patient was found to have a 28 CAG repeat on the longest expansion. buy Natural Product Library Microscopic analysis revealed significant neuronal atrophy in the caudate and putamen with gliosis. Immunofluorescent staining demonstrated minimal intranuclear p62 inclusions suggesting little huntingtin aggregation present. Furthermore, there was significant amyloid-beta pathology (Thal-IV stage) and tau involvement in the medial temporal lobe (Braak stage II).

This case provides clinical and pathological evidence to support an emerging clinical entity involving HD presentation in late age with an intermediate CAG repeat.

This case provides clinical and pathological evidence to support an emerging clinical entity involving HD presentation in late age with an intermediate CAG repeat.

Remote ischaemic preconditioning (RIPC) is the exposure of body parts to brief periods of circulatory occlusion and reperfusion. Recent studies have also shown that RIPC can improve exercise performance in healthy individuals.

This study aimed to assess the effect of RIPC on walking in people with multiple sclerosis (MS).

This was a double-blind randomised controlled clinical trial. We used three cycles of RIPC delivered by occluding the upper arm with a blood pressure (BP) cuff inflated to a pressure of 30 mm Hg above the systolic BP. In patients in the sham intervention group, the BP cuff was inflated only to 30 mm Hg below diastolic BP. Outcome measures included the Six-Minute Walk Test (6MWT), gait speed, the Borg rate of perceived exertion (RPE) scale, the tolerability of the RIPC using a Numerical Rating Scale for discomfort from 0 to 10, and adverse events. We identified responders meeting the minimal clinically important difference (MCID) established in the literature in each group.

Seventy-five participants completed the study (RIPC 38 and Sham 37). The distance walked during the 6MWT improved by 1.9% in the sham group and 5.7% in the RIPC group (p=0.012). The number of responders meeting MCID criteria in the RIPC group was significantly greater compared with the sham intervention group. No serious adverse events occurred.

Single cycle of RIPC resulted in immediate improvement in walking distances during 6MWT in people with MS.

NCT03153553.

NCT03153553.

Spasticity is a complex and common condition but there is a lack of 'real-world' data on goal setting and spasticity treatment, as well as identifying those features that might be associated with goal achievement. Our aim was to provide such data.

Prospective attenders at a multi-disciplinary spasticity clinic over 2 years followed for consecutive appointments. Patient demographics and doses of botulinum toxin injected were documented. Main outcome was achievement of a primary goal but secondary goals were also recorded. Independent variables were examined for association to the outcome.

A total of 606 goals were set in 224 patients. The majority (75.2%) were achieved with similar levels across active (72.5%), passive (75.7%) and pain (78.6%) goals. However, in terms of the primary goal, active primary goals were achieved less frequently (59.7%) than non-active primary goal (74.2%). A logistic regression confirmed that this was the only independent variable associated with primary goal achievement. The r treatment factors are associated with outcome prediction. Further work needs to identify features that may predict successful outcome.Nucleosynthetic isotope anomalies show that the first few million years of solar system history were characterized by two distinct cosmochemical reservoirs, CC (carbonaceous chondrites and related differentiated meteorites) and NC (the terrestrial planets and all other groups of chondrites and differentiated meteorites), widely interpreted to correspond to the outer and inner solar system, respectively. At some point, however, bulk CC and NC materials became mixed, and several dynamical models offer explanations for how and when this occurred. We use xenoliths of CC materials in polymict ureilite (NC) breccias to test the applicability of such models. Polymict ureilites represent regolith on ureilitic asteroids but contain carbonaceous chondrite-like xenoliths. We present the first 54Cr isotope data for such clasts, which, combined with oxygen and hydrogen isotopes, show that they are unique CC materials that became mixed with NC materials in these breccias. It has been suggested that such xenoliths were implanted into ureilites by outer solar system bodies migrating into the inner solar system during the gaseous disk phase ~3-5 Myr after CAI, as in the "Grand Tack" model.