bluuebunny/crossref_metadata_2025 huggingface dataset:
A narrative review of prehospital hemorrhagic shock treatment with non‐blood product medications
Authors: Knight Caleb D. , Bebarta Vikhyat , Meledeo Michael A. , Ross Evan , Wu Xiaowu , Bynum James , Schauer Steven , Getz Todd , April Michael
Published: March 2023

Background

Hemorrhagic shock remains a leading cause of death in both military and civilian trauma casualties. While standard of care involves blood product administration, maintaining normothermia, and restoring hemostatic function, alternative strategies to treat severe hemorrhage at or near the point of injury are needed. We reviewed adjunct solutions for managing severe hemorrhage in the prehospital environment.

Methods

We performed a literature review by searching PubMed with a combination of several keywords. Additional pertinent studies were identified by crossreferencing primary articles. Clinical experience of each author was also considered.

Results

We identified several promising antishock therapies that can be utilized in the prehospital setting: ethinyl estradiol sulfate (EES), polyethylene glycol 20,000 (PEG20K), C1 esterase inhibitors (e.g. Berinert, Cinryze), cyclosporin A, niacin, bortezomib, rosiglitazone, icatibant, diazoxide, and valproic acid (VPA).

Conclusion

Several studies show promising adjunct treatment options in the management of severe prehospital hemorrhage. While some are rarely used, many others are readily available and commonly utilized for other indications. This suggests the potential for future use in resourcelimited settings. Human studies and case reports supporting their use are currently lacking.
Observations on Harmony, Voice-leading, and "Idea" in Schoenberg's Piano Piece Op. 11 No. 1
Authors: Väisälä Olli
Published: March 2023

This analysis of Schoenberg's Op. 11 No. 1 demonstrates ways in which two register-sensitive principles of harmony and voice-leading shed new light on its pitch organization.
 The 11-vs-1 principle posits a distinction in harmonic stability between the registrally ordered
intervals 11 and 1 (hereafter roi-11 and roi-1). This is manifest both in local relationships that suggest functional consonance and dissonance and in the large-scale emergence of a "group dissonance," i. e., the temporary predominance of roi-1 in marking the climactic high point
of tensions.
 The proximity principle distinguishes between the functions of "stepwise" and larger horizontal intervals. Whereas the former serve a purely horizontal function in voice-leading connectives, the latter imply arpeggiation. This distinction helps to reveal connections
between prominent harmonies and linear frameworks, concerning in particular horizontalizations of two referential harmonies—the first and last block chords—and their changing relationships. [...]
Form-Functional Ambivalence in Performance: The Third Movement of Beethoven's "Hammerklavier" Sonata in Recordings by Gulda, Brendel, and other Pianists
Authors: Utz Christian
Published: March 2023

Generalized theories of formal functions have yet to adequately capture the temporal experience of musical form. Recent research into musical performance suggests that sounded interpretation may generate temporal formal functions of its own. This thesis is elaborated through a discussion
of Friedrich Gulda's and Alfred Brendel's contrary readings of Beethoven's Adagio sostenuto, the third movement of the "Hammerklavier" Sonata Op. 106, within a corpus of 27 analyzed recordings of this movement between 1936 and 2021. Both Brendel and Gulda were in contact with post-Schoenbergian
methods of musical analysis in Vienna around 1950. A review of Erwin Ratz's analysis of Op. 106, iii and the recordings' differing temporal designs demonstrate the conflict between an architectural conception of the movement, in which caesuras are strengthened, and a process-like interpretation
that sustains the impression of continuity and flow across the sections by means of superordinate tempo progressions. This tension between interpretations is superimposed onto the specific formal ambiguity of this movement, which oscillates between sonata and variation form. To incorporate
such dimensions of sounded interpretation more consistently into form-analytical methods, a music-theoretical "quantum theory" is required that respects the basic ambivalence of formal function in performed time.
Untangling TMS‐EEG responses caused by TMS versus sensory input using optimized sham control and GABAergic challenge
Authors: Gordon Pedro C. , Song Yu Fei , Jovellar D. Blair , Rostami Maryam , Belardinelli Paolo , Ziemann Ulf
Published: March 2023

The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) elegantly probes the excitability and connectivity of the human brain. However, TMS‐EEG signals inevitably also contain sensory‐evoked responses caused by TMS‐associated auditory and somatosensory inputs, constituting a substantial confounding factor. Here we applied our recently established optimized SHAM protocol (Gordon et al., Neuroimage 2021:118708) to disentangle TMS‐EEG responses caused by TMS vs. sensory input. One unresolved question is whether these responses superimpose without relevant interaction, a requirement for their disaggregation by the optimized SHAM approach. We applied in 20 healthy subjects a pharmacological intervention using a single oral dose of 20 mg of diazepam, a positive modulator of GABAA receptors. Diazepam decreased the amplitudes of the P60 and P150 components specifically in the ACTIVE TMS and/or the ACTIVE TMS minus SHAM conditions but not in the SHAM condition, pointing to a response caused by TMS. In contrast, diazepam suppressed the amplitude of the N100 component indiscriminately in the ACTIVE TMS and SHAM conditions but not in the ACTIVE TMS minus SHAM condition, pointing to a response caused by sensory input. Moreover, diazepam suppressed the beta‐band response observed in the motor cortex specifically after ACTIVE TMS and ACTIVE TMS minus SHAM. These findings demonstrate a lack of interaction of TMS‐EEG responses caused by TMS vs. sensory input and validate optimized SHAM‐controlled TMS‐EEG as an appropriate approach to untangle these TMS‐EEG responses. This knowledge will enable the proficient use of TMS‐EEG to probe the physiology of the human cortex.

image

Key points

Optimized SHAM disentangles TMS‐EEG responses caused by TMS vs. sensory input.

Diazepam differentially modulates TMS‐EEG responses caused by TMS vs. sensory input.

Diazepam modulation of P60 and P150 indicate TMS‐EEG responses caused by TMS.

Diazepam modulation of N100 indicate a TMS‐EEG response caused by sensory input.
Ca2+ signals in pancreatic acinar cells in response to physiological stimulation in vivo
Authors: Takano Takahiro , Yule David I.
Published: March 2023

The exocrine pancreas secretes fluid and digestive enzymes in response to parasympathetic release of acetylcholine (ACh) via the vagus nerve and the gut hormone cholecystokinin (CCK). Both secretion of fluid and exocytosis of secretory granules containing enzymes and zymogens are dependent on an increase in the cytosolic [Ca2+] in acinar cells. It is thought that the specific spatiotemporal characteristics of the Ca2+ signals are fundamental for appropriate secretion and that these properties are disrupted in disease states in the pancreas. While extensive research has been performed to characterize Ca2+ signalling in acinar cells, this has exclusively been achieved in ex vivo preparations of exocrine cells, where it is difficult to mimic physiological conditions. Here we have developed a method to optically observe pancreatic acinar Ca2+ signals in vivo using a genetically expressed Ca2+ indicator and imaged with multi‐photon microscopy in live animals. In vivo, acinar cells exhibited baseline activity in fasted animals, which was dependent on CCK1 receptors (CCK1Rs). Both stimulation of intrinsic nervous input and administration of systemic CCK induced oscillatory activity in a proportion of the cells, but the maximum frequencies were vastly different. Upon feeding, oscillatory activity was also observed, which was dependent on CCK1Rs. No evidence of a vago‐vagal reflex mediating the effects of CCK was observed. Our in vivo method revealed the spatial and temporal profile of physiologically evoked Ca2+ signals, which will provide new insights into future studies of the mechanisms underlying exocrine physiology and that are disrupted in pathological conditions.

image

Key points

In the exocrine pancreas, the spatiotemporal properties of Ca2+ signals are fundamentally important for the appropriate stimulation of secretion by the neurotransmitter acetylcholine and gut hormone cholecystokinin.

These characteristics were previously defined in ex vivo studies. Here we report the spatiotemporal characteristics of Ca2+ signals in vivo in response to physiological stimulation in a mouse engineered to express a Ca2+ indicator in acinar cells.

Specific Ca2+ ‘signatures’ probably important for stimulating secretion are evoked in vivo in fasted animals, by feeding, neural stimulation and cholecystokinin administration.

The Ca2+ signals are probably the result of the direct action of ACh and CCK on acinar cells and not indirectly through a vago‐vagal reflex.
“We’re All the Same and We Love Football.” Experiences of Players and Facilitators Regarding a Collaborative, Inclusive Football Program Between Academy and Special Olympics Footballers
Authors: Fothergill Melissa A. , Baik Danna , Slater Hannah M. , Graham Pamela L.
Published: March 2023

This study provides insight into an inclusive program between Special Olympics (SO) and academy football (soccer) players in the United Kingdom from the perspectives of players and facilitators. Qualitative focus groups were conducted across 30 participants (six facilitators, 14 Premier League academy players, and 10 SO players). Focus groups compared stakeholders’ experiences of participating in a season-long inclusive football program. Three overarching higher order themes were generated, which highlighted positive outcomes from taking part. SO players provided endorsement for developing friendships and improving football skills, whereas academy players cited the positive impact that SO players had on their mood and motivation. Facilitators reflected on positive player outcomes and subsequent accomplishments. Overall, the findings indicated that this shared experience had psychosocial and football-specific benefits for everyone who participated. Facilitators indicated that these benefits could transition into everyday life but noted that there needs to be further considerations for future programs.
Training Quality—What Is It and How Can We Improve It?
Authors: Bucher Sandbakk Silvana , Walther Jacob , Solli Guro Strøm , Tønnessen Espen , Haugen Thomas
Published: March 2023

Purpose: The concept of training quality reflects that the effect of training is dependent on more than the mere product of training load (eg, duration, intensity, frequency). The aims of this commentary are to (1) propose a practice-oriented framework to describe training quality and its general and context-dependent characteristics and (2) discuss how athletes and coaches can work to improve training quality. Conclusions: Training quality can be viewed from different perspectives. The holistic dimension includes the entire training process (goal setting, gap analysis, application of training principles and methods, etc), while a narrower dimension encompasses the specific training sessions and how they are executed in relation to the intended purpose. To capture the varying contexts, we define training quality as the degree of excellence related to how the training process or training sessions are executed to optimize adaptations and, thereby, improve overall performance. Although training quality is challenging to quantify, we argue that identification and assessment of quality indicators will increase our scientific understanding and consequently help coaches and athletes to improve training quality. We propose that the physical, technical, and psychological factors of training quality can be improved through an individualized learning process of systematic planning, execution, and debriefing. However, assessment tools should be identified and scientifically validated across different training sessions and sports. We encourage further interventions to improve training quality.
A Protocol for a Local Community Monitoring and Feedback System for Physical Activity in Organized Group Settings for Children
Authors: Essay Ann M. , Schenkelberg Michaela A. , Von Seggern Mary J. , Rosen Marisa S. , Schlechter Chelsey R. , Rosenkranz Richard R. , Dzewaltowski David A.
Published: March 2023

Background: Communities are wellness landscapes of geospatially and temporally bound settings where children spend their time. Improving population physical activity (PA) requires investigating available community settings for children, such as classrooms and sport teams, and the dynamic social interactions producing PA. This protocol describes a multiscale community wellness landscape monitoring and feedback system of adult-led organized group settings and PA outcomes for children. Methods: The data system assessed organized groups for third- through sixth-grade children in 2 rural communities within seasons (fall 2018–2019). Within each season, groups were identified, sampled, and recruited. Sampled group meetings were assessed for children’s PA (accelerometry) and meeting routines (video observation). A data processing protocol time-segmented data into meetings and meeting routines into smaller units (sessions). A purpose code was assigned to each meeting (eg, classroom, sport) and session (eg, academic, PA). Group accelerometer data were paired with the coded segments. Multiscale metrics (season, meeting, and session) were generated and provided to the communities in tailored reports. Results: A total of 94 groups were recruited, and 73 groups with 1302 participants were included in the data system. Data were collected from 213 meetings and 844 sessions. Most participants (83.1%) consented to link their accelerometer data with demographic data from school enrollment records. Conclusions: The community data system identified available organized group settings for children and collected video and PA data from these settings. Incorporating setting data into local data systems provides detailed accounts of whole-of-community PA social systems to inform population health improvement efforts.
The Köhler Motivation Gain Effect With Exercise Tasks: A Meta-Analysis
Authors: Samendinger Stephen , Hill Christopher R. , Ahn Soyeon , Feltz Deborah L.
Published: March 2023

The purpose of this meta-analysis was to examine the Köhler motivation effect in partnered dyads (conjunctive task structure) during exercise. This preregistered meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included 19 (total sample size N = 1,912) primary, peer-reviewed research articles that have reported the effectiveness of the Köhler effect paradigm (with a no-partner control condition) in exercise tasks on the outcome variable of intensity or persistence of effort. The overall motivation gain effect was statistically significant, (SE = 0.12), suggesting a significantly higher performance gain in conjunctive partnered exercise groups compared with individual exercise. The large effect was moderated by the performance-dependent variable (persistence and intensity), mean participant age, and exercise partner type (human and software generated). There appears to be strong support for the Köhler motivation gain paradigm as a potential to help individuals improve their effort in exercise settings.
The Transformation of Taiwanese Women’s Physical Education in Schools During the Japanese Colonial Period (1895–1945)
Authors: Chin Hsiang-Pin , Lee Ping-Chao
Published: March 2023

This study explores the development of women’s physical education (PE) in Taiwanese schools during the Japanese colonial period. It seeks to understand how Japanese colonizers cultivated and shaped Taiwanese women’s bodies through PE in schools. First, Japanese colonizers faced the challenge of dismantling footbinding customs when implementing women’s PE and body engineering policies. However, when women were liberated from footbinding and the concept of natural feet emerged among the population, women’s PE came out of the shadow of footbinding. Second, as the natural feet generation arose, Taiwanese women started participating in physical activities and competitive sports while still abiding by the canons of the “Japanese woman.” Third, during the Pacific War, improving one’s physique and developing PE policies became part of a national defense strategy and the main focus in the process of producing imperial citizens. The body was given different meanings, yet its control and standardization were omnipresent under colonial governance.
“Star Maker”: George Powles, McClymonds High School, and the Youth of West Oakland
Authors: Wiggins David K.
Published: March 2023

This article assesses the life and career of George Powles, a legendary White youth sport and high school coach from Oakland, California. Born in 1910, Powles guided local American Legion, Babe Ruth, and Connie Mack baseball teams to various state, regional, and national titles and coached a plethora of outstanding athletes first at McClymonds High School, a predominantly Black institution in West Oakland and then later at Skyline High School, a predominantly White institution at the crest of the Oakland foothills, who would go onto legendary careers in professional sport. Among those he coached were iconic African American athletes who realized lasting fame for both their accomplishments on the playing field and involvement in the larger civil rights movement. Included among these athletes was Bill Russell, the Hall of Fame basketball player who led the University of San Francisco to successive National Collegiate Athletic Association national titles and the Boston Celtics to multiple National Basketball Association championships; Frank Robinson, the Hall of Fame baseball player and first African American to manage a Major League baseball team; Vada Pinson, the outstanding outfielder who played multiple years of Major League baseball; and Curt Flood, the gold-glove winning outfielder who famously challenged baseball’s reserve clause. In the end, Powles was a coach who served as an important mentor of Black athletes and believed strongly in sports power to bridge racial differences and instill important values and develop character among youth from all walks of life and cultural and socio-economic backgrounds.
Change in renal function associated with drug treatment in heart failure: national guidance
Authors: Clark Andrew L , Kalra Paul R , Petrie Mark C , Mark Patrick B , Tomlinson Laurie A , Tomson Charles RV
Published: March 2023

Inhibitors of the renin–angiotensin–aldosterone (RAAS) system are cornerstones of the management of patients with heart failure with reduced left ventricular ejection fraction (HFrEF). However, RAAS inhibitors may cause decline in renal function and/or hyperkalaemia, particularly during initiation and titration, intercurrent illness and during worsening of heart failure. There is very little evidence from clinical trials to guide the management of renal dysfunction. The Renal Association and British Society for Heart Failure have collaborated to describe the interactions between heart failure, RAAS inhibitors and renal dysfunction and give clear guidance on the use of RAAS inhibitors in patients with HFrEF. During initiation and titration of RAAS inhibitors, testing renal function is mandatory; a decline in renal function of 30% or more can be acceptable. During intercurrent illness, there is no evidence that stopping RAAS inhibitor is beneficial, but if potassium rises above 6.0 mmol/L, or creatinine rises more than 30%, RAAS inhibitors should be temporarily withheld. In patients with fluid retention, high doses of diuretic are needed and a decline in renal function is not an indication to reduce diuretic dose: if the patient remains congested, more diuretics are required. If a patient is hypovolaemic, diuretics should be stopped or withheld temporarily. Towards end of life, consider stopping RAAS inhibitors. RAAS inhibition has no known prognostic benefit in heart failure with preserved ejection fraction. Efforts should be made to initiate, titrate and maintain patients with HFrEF on RAAS inhibitor treatment, whether during intercurrent illness or worsening heart failure.
A 63-year-old woman with multiple secondary tumours
Authors: Muresan Ioana Danuta , Agoston-Coldea Lucia , Dumitrascu Dan Lucian
Published: March 2023

Clinical introduction

A 63-year-old woman recently diagnosed with lung metastasis, after routine chest radiography, was admitted to our hospital for unspecified symptoms, such as dyspnoea on minimal exertion and dry cough. Physical examination showed uncommon signs. The electrocardiogram showed sinus rhythm and incomplete left bundle branch block. Thoracic CT scan revealed bilateral lung and pleural metastases and pelvic CT showed a right femoral bone mass. Transthoracic echocardiography revealed a heterogeneous mass, lateral to the right ventricle, with pericardial effusion. Further, cardiac MRI (cMRI) was performed (figure 1A,B). Diagnosis was completed with an ultrasound-guided biopsy and histopathological examination (figure 1C,D).

Figure 1

(A,B) Cardiac MRI: asterisk is suggestive of fluid and the white arrow indicates fibrous encapsulation by LGE, (C) H&E stain:white arrow indicating a tumoral cell with atypical mitosis and (D) immunohistochemical staining for smooth muscle actin antibody.

Question

Which of the following is the most likely diagnosis?

Pericardial lymphoma.

Pericardial leiomyosarcoma.

Pericardial cyst.

Secondary malignant cardiac tumour.

Pericardial teratoma.
11.15 MS incidence rates vary threefold by health board in scotland, persistently
Authors: Kearns Patrick , Connick Peter , Paton Martin , O’Neill Martin , O’Riordan Jonathon , McDonald James , Colville Shuna , Ascherio Alberto , MacDougall Niall , Chandran Siddharthan
Published: March 2023

Fifteen regional studies of multiple sclerosis rates have been published in Scotland; spanning some six decades and surveying prevalence, mortality and hospital admissions. However, only one national study has attempted to compare regional rates (using admissions data).

We used the Scottish Multiple Sclerosis Register to investigate incidence rates (IR). We present crude and age-adjusted IRs, cumulative incidences, and the sex ratio of cases and rates, for all regions of Scotland: 01/01/2010 to 31/12/2017.

The overall IR for Scotland was 8.76/100,000 person-years (standardized: 8.54), which is high, but likely a conservative estimate of the total burden, including only definite cases. The female-male ratio was 2.3. Regional rates and sex ratios varied significantly – up to threefold – between Health Boards (p<10–13), well correlated with the 1997–2009 admissions data (r=0.85, p<0.001). Significant variation was observed on the mainland, not just on the islands. Lifetime risk ranged from 19.9/1000 for females in Orkney to 1.6/1000 for males in the Borders.

This study is the first attempt to analyse the patterns of incidence for the whole of Scotland from prospectively collected data and benefits from a high level of completeness and ascertainment. The wide variation in incidence rates and sex-ratios is unexplained.
12.15 Variation in neurology training: experiences from sites across the UK
Authors: Shribman Samuel , Alexander Sian , Zarkali Angelika , Warner Thomas T , Pereira Anthony , Hughes Tom , Mummery Catherine J
Published: March 2023

There is little evidence-based consensus on how to approach, structure or deliver neurology training. The General Medical Council conducts a National Trainee Survey in the UK on an annual basis and, while the results suggest significant variation in the quality of neurology training, they do not provide an explanation for this variation. In order to better understand how to train a neurologist we used the National Trainee Survey to identify four of the highest and lowest performing sites for neurology training across the UK and visited them to conduct semi-structured interviews with groups of trainees and, separately, local trainers. We identified common themes between the two groups of sites across a range of different aspects of neurology training. These included supervision, competency-based training, clinic attendance, subspecialty exposure, local teaching programmes and the educational culture within departments. Here, we present our findings, including case studies from top performing sites, and provide recommendations with specific examples for how to train a neurologist.
100 Progressive MRI and EEG changes in a patient with Creutzfeldt-Jakob disease
Authors: Johnson Naomi , Thura Myat , Tun Shwe , Mowafi Walied
Published: March 2023

We report the case of a 56 year old male, presenting approximately 6 weeks after his first symptoms of Sporadic Creutzfeldt-Jakob Disease. The patient demonstrated classical magnetic resonance imaging (MRI) and electroencephalographic (EEG) changes reflecting clinical progression.

Creutzfeldt-Jakob Disease was suspected and later confirmed by positive biochemical markers approximately 10 days after presentation; including positive protein 14-3-3, S-100b and positive rtQUIC assay.

Serial MRI and EEG findings correlated with clinical symptoms witnessed on presentation (nystagmus, mild myoclonus and lability of mood) and disease progression through to coma before death

MRI changes were seen as initial localised cortical ribboning progressing to more widespread ribboning and areas of high signal in the basal ganglia (striatum). This correlated with the findings on his earliest EEG of periodic frontal and right side dominant sharp waves, to the last EEG showing more widespread periodic sharp waves.

MRI and EEG findings are discussed as well as differentials that may appear with similar MRI findings.

The presentation provides an accessible learning case for neurologist, neuro-radiologists and neurophysiologists at all levels.
104 Utility and incidental findings on CT chest, abdomen and pelvis scans in neurology patients
Authors: Monaghan Ian , Fernandes Peter
Published: March 2023

CT scanning of the chest, abdomen and pelvis (CT-CAP) is often used by neurologists to identify underlying disease processes such as malignancy or sarcoidosis. However, the utility of CT-CAP, and the rate of incidental findings, remains uncertain.

This retrospective study investigated all CT-CAP requests by the neurology department in Edinburgh over a 5-year period (n=261), combining CT-CAP reports with electronic patient records. Incidental findings were classified by need for further investigations. Category 1 findings required further investigations (e.g. pulmonary nodule >4 mm). Category 2 findings required extra tests depending on clinical context (e.g. dilated biliary tract; liver function and surgical history determining need for further investigations). Category 3 findings did not require further investigations (e.g. simple diverticular disease).

20% (n=51) of CT-CAP scans were reported as showing an underlying malignancy, with half (n=26) confirmed as cancer by subsequent investigations. CT-CAP identified three cases of sarcoidosis and one of tuberculosis. There were 191 category 3 incidental findings, 57 category 2 incidental findings, and 27 category 1 findings.

Overall, CT-CAP shows an underlying cause of neurology symptoms in 11.5% of cases. The proportion of patients needing further tests due to category 1 or concerning category 2 incidental findings (12/57) was higher at 14.9%.
107 Secondary intracranial hypertension in nephropathic cystinosis
Authors: Harijanto Chloe , Pegg Emily , Biswas Sumito , Lavin Tim
Published: March 2023

A 21-year-old woman presented with bilateral papilloedema and a 2-week history of high-pressure headaches. Medical history was remarkable for Infantile Cystinosis and a renal transplant.

Her Body Mass Index was 26.7 kg/m2. Visual acuity (VA) was 6/12 in the left eye and 6/6 in the right. Cerebrospinal Fluid (CSF) opening pressure was 30cmH20 in the left decubitus position.

Following lumbar puncture and Acetazolamide 250 mg bd, VA improved but the latter was stopped due to renal side effects. She was asymptomatic on Topiramate 50 mg bd. VA was 6/6 bilaterally, with decreased optic disc swelling on Optical Coherence Tomography and a normal CSF opening pressure.

Discussion

Infantile Cystinosis is a rare autosomal recessive lysosomal storage disease where multisystem accumulation of cysteine leads to renal failure, hypothyroidism and corneal deposits.

Intracranial Hypertension occurs in around 5% of patients with cystinosis (Dogulu 2004). Meningeal cysteine accumulation could reduce CSF absorption by the arachnoid villi. Other risk factors include renal transplant and immunosuppressant therapy.

Neurologists should be aware of this rare but important complication of cystinosis. Low dose topiramate demonstrated benefit here and lacks the diuretic effects of acetazolamide. Early shunting or optic nerve decompression should be considered in severe cases.
108 Audit of the management of idiopathic intracranial hypertension in the context of new consensus guidelines
Authors: Katanga Jessica , Nitkunan Arani
Published: March 2023

Consensus guidelines were published for the first time in 2018 on the management of Idiopathic Intracranial Hypertension – a condition with an age and gender adjusted annual incidence of 2.4 per 100,000 and increasing. An audit was conducted across two sites - St George’s Hospital and Croydon University Hospital. Data was extracted on all patients admitted in 2017 with ICD code G93.2 and then those 16 or under, those who did not have IIH at the index event/it wasn’t their primary diagnosis and those with incomplete notes were excluded. The resultant cohort was 19 women, mean age 26.9 and mean BMI of 31.8. The quality standard for having lumbar puncture (100%), having brain imaging (100%), opening pressure recorded (100%) and brain imaging within 24 hours (84%) was achieved. Brain imaging performed within 48 hours was achieved in 53% due to delay in obtaining venography. Documentation of risk of teratogenicity, potential side effects and BMI was poor. Although the guidelines suggest venography within 48 hours, this would not be an easy target to meet and we would suggest that this is only needed for patients whose acuities/fields are affected, not female and not overweight.
111 An audit of headache referrals from primary care, and subsequent management in the outpatient clinic
Authors: Fernandes Linford , Tanti Matthew , Randall Marc , Cosgrove Jeremy
Published: March 2023

Background

Headache is the most common reason for referral to a neurology outpatient clinic but many headaches can be managed in primary care.

Methods

We audited 100 consecutive headache referrals against Leeds Teaching Hospitals NHS Trust (LTHT) referral criteria and the Neuro Network Vanguard (NNV) headache pathway.

Results

The mean age was 41 years (range 16 -90), 67% were female and 31% had previously seen a neurologist for headaches. Referrals were appropriate in 44% and 49% according to LTHT and NNV guidelines, respectively. Migraine was the suspected diagnosis in 50% of referrals - half of these tried two or more preventative medications. The clinic consultations of 89 of the 100 referrals were reviewed: 72% were diagnosed with migraine (of which 53% were chronic). Following consultation, migraine was the final diagnosis in 49% of referrals that proposed an alternative diagnosis; 9% referred as suspected migraine received a different diagnosis.

Conclusion

Less than half of the referrals received were appropriate according to LTHT and NNV criteria. Migraine was the major referral reason and ultimate diagnosis. Empowering primary care to manage migraine is an urgent local priority and may reflect a national issue.
112 Spontaneous intracranial hypotension presenting as postural head tremor and gait ataxia
Authors: Bangalore Priyadarshini , Jadun Changez , Davies Brenden , Abraham Roby
Published: March 2023

We present a 65 year old lady with 30 year history of chronic daily headache without postural changes after a road traffic accident presented with three months history of postural head and upper limb tremor, progressive ataxia, dizziness, mild confusion and few falls. She had worsening of epilepsy with partial status prompting acute hospital admission. Symptoms exacerbated on standing and she preferred lying down most of the time. Previous history of temporal lobe epilepsy and Anterior Cervical Decompression and Fusion.

Examination: She had a head tremor which exaggerated on upright posture along with truncal ataxia, gait ataxia and dysmetria bilaterally. Head and upper limb tremor improved on lying down position without any change to her headache. She did not have any other pyramidal or extrapyramidal features. Increasing Lamotrigine dosage and adding Levetiracetam helped control seizures.

CT head and two MRI head scan showed radiological features of low CSF pressure syndrome. There were small bilateral subdural hygromas, uniform meningeal enhancement thought the cranium extending to cervical spinal cord dura, and dural-venous-sinus engorgement. MRI spine did not show any CSF leak. CSF opening pressure was 12.0 cm of H20 with normal constituents.

A blind blood patch was performed with excellent outcome, her postural tremors, chronic headache and gait ataxia improved when reviewed at week one.

Low CSF pressure syndrome presenting as Movement disorder is rare and recognising atypical presentation is cardinal.
113 Incidence of migraine and treatment patterns in UK primary care
Authors: Yelland Eleanor , Ghosh Rebecca , Murray-Thomas Tarita , Williams Alison , Hacking Victoria
Published: March 2023

Objectives

To estimate the incidence of migraine and describe treatment patterns for an indicative year.

Methods

Patients ≥18 years old in the Clinical Practice Research Datalink with an incident diagnosis of migraine between 01/04/2007–31/07/2017. The incidence of migraine was estimated. Treatment groups were categorised as none, acute only, prophylactic only, acute and prophylactic. 12-month treatment patterns amongst patients initiating prophylactic treatment with amitriptyline, propranolol or topiramate were classified as continuous use, augmentation, switching or discontinuation. Treatment adherence was defined as medication possession ratio (MPR); patients were ‘adherent’ if their MPR was ≥0.80.

Results

89,442 patients with incident migraine were included. Mean age at diagnosis was 40 years [SD 15]; 76.6% were females. The cumulative incidence of migraine rate was 25.8/10,000 person-years [95%CI: 25.6–26.0]. 86.7% of patients received prophylactic and/or acute treatment; 37.6% and 20.1% had received ≥2 and ≥3 prophylactic treatments, respectively.

1,636 patients initiated prophylactic treatment in 2015. Propranolol (47.8%) and amitriptyline (47.4%) were most commonly prescribed. Although 80–85% of patients were adherent while on treatment, only 20–30% continued treatment up to 12 months.

Conclusions

Migraine treatment remains a challenge. Most patients receive one or more pharmacotherapies but the majority discontinue prophylactic treatment within 12 months of initiation.
115 Economic burden among migraine patients: United Kingdom perspective
Authors: Martelletti Paolo , Schwedt Todd , Lanteri-Minet Michel , Diener Hans-Christoph , Torre Elena Ruiz de la , Craven Audrey , Evans Simon , Walsh Donna , Dumas Paula , Laflamme Annik
Published: March 2023

Objectives

As part of the worldwide My Migraine Voice survey, this study evaluated the real-world healthcare resource utilization (HRU) and impact on work and activity impairment among people living with migraine in the United Kingdom (UK).

Methods

An analysis was conducted using UK subset data from My Migraine Voice survey: a worldwide, cross-sectional, online study including respondents (≥18 years), with ≥4 monthly migraine days, with 90% having used preventive migraine treatment in the preceding three months. HRU (Emergency room [ER] visits and hospitalisations) and impact of migraine on work and daily activities were evaluated and compared amongst different preventive treatment failure (TF) patient subgroups.

Results

Of the 690 respondents, 17% had visited ER (average 2.8 times/year), and 13% were hospitalised (average 3.0 days). Participants reported 13% missed working time (absenteeism), 52% reduction in productivity (presenteeism), and 58% reduction in both overall work productivity and daily activities due to migraine in last 7-days. HRU, absenteeism and presenteeism was higher in those with ≥2 TF vs patients with no TF.

Conclusion

This study demonstrates the burden among patients with migraine in terms of HRU, work productivity loss, and activity impairment. The impact is increased in patients who have had ≥2 preventive treatment failures.
119 Double jeopardy or VOMIT syndrome in trigeminal autonomic cephalalgias
Authors: Thaller Mark , Davies MB
Published: March 2023

This is a rare presentation of a cluster-like headaches which poses diagnostic and management dilemmas in light of two secondary headache pathologies being identified.

A female in her seventies presented with a 12 month history of worsening intensity and frequency left-side locked, excruciating, searing and stabbing craniofacial pain with associated eye watering and orbital oedema. Duration was 1–2 hours up to 4 times per week. There was never more than 3 weeks between attacks and was pain free in-between. There was a long term milder infrequent but similar headache and migraine with aura in her twenties reported.

The atypical features (older age of onset, female, frequency and limited autonomic features) as well as pattern change and lack of remission triggered further investigation. Her MRI head showed both a left cavernous sinus aneurysm and a pituitary adenoma.

Both cavernous sinus aneurysm and pituitary pathologies have individually been shown to ‘mimic’ cluster headache but dual pathology hasn’t been reported. Several authors suggest screening for pituitary pathology in patients with TACs and others for vascular lesions. However this can add an additional management dilemma when the case could be a Victim of Modern Imaging Technology (VOMIT) (incidentalomas).
14.57 Expanding the phenotypic spectrum of PSP: Findings from the PROSPECT-UK study
Authors: Jabbari Edwin , Woodside John , Costantini Alyssa , Lees Andrew , Morris Huw ,   on behalf of the PROSPECT-UK consortium
Published: March 2023

Background

Progressive supranuclear palsy (PSP) is a common cause of atypical parkinsonism.

Objective

To study the genetic and clinico-pathological profile of various PSP phenotypes using patient data from the PROSPECT-UK study.

Methods

Clinical data from PSP patients in the PROSPECT-UK study was analysed to assess the rates of various PSP phenotypes, as defined by the 2017 Movement Disorder Society diagnostic criteria. A subset of patients are currently undergoing 5 year longitudinal follow-up, including genetics, video clinical assessments and post-mortem confirmation of diagnosis.

Results

We have established a cohort of 345 patients with PSP. The longitudinal sub-cohort consists of 100 PSP patients: 58 patients with classical Richardson’s syndrome (RS) and 42 patients with a variety of non-RS presentations including PSP-Parkinsonism and Pure Akinesia with Gait Freezing. We found significant differences in the mean disease duration of deceased RS and non-RS cases (5.6 vs 9.2 years) but similar rates of PSP pathology in cases (n=28) with post-mortem confirmation (94% and 100%). Our PROSPECT-UK data has contributed to a GWAS which identified that common variation at the TRIM11 locus determined PSP phenotype (Jabbari et al 2018). In addition, we have identified 1 case with a MAPT L284R mutation and 1 case with genetic and biochemically confirmed Niemann-Pick type C disease.

Conclusions

The PROSPECT-UK study has furthered our knowledge on the clinical profile of PSP and the biological determinants which drive phenotypic variation.
127 Audit of poor response to botulinum toxin in cervical dystonia
Authors: Tucker Harry , Osei-Poku Foster , Ashton Diane , Lally Rachael , Alty Jane , Kobylecki Christopher
Published: March 2023

Background

Botulinum toxin (BoNT) is an effective first-line treatment for cervical dystonia. However, secondary non responsiveness to BoNT treatment remains a key reason for a discontinuation rate of 20%.

In 2016 the British Neurotoxin Network (BNN) published recommendations for the management of cervical dystonia patients with poor response to BoNT treatment.

Aims

To compare management of patients with secondary non responsiveness in two regional neuroscience centres with the BNN guidelines.

Methods

We retrospectively analysed 68 patients with cervical dystonia who met criteria for secondary non responsiveness to BoNT-A treatment.

Results

Suboptimal response to BoNT-A was recorded in 37 patients (54%), whilst 31 (46%) had no therapeutic response.

In the ‘suboptimal response’ group, 21 (57%) had a subsequent good therapeutic response with adjustment of dose, muscle selection and injection technique and continued BoNT-A treatment. Of the remainder, 6 (38%) were switched to BoNT-B and 7 (44%) were referred for Deep Brain Stimulation surgery.

In the ‘no response’ group 6 patients (19%) had a good therapeutic response with adjustments of dose, muscle selection and injection technique and continued BoNT-A treatment. In this group 22 patients (71%) were assessed for BoNT-A resistance, which was confirmed in 8 (36%).

Conclusion

Our audit shows the importance of careful assessment of patients with cervical dystonia presenting with secondary non-reponsiveness to BoNT-A therapy. The BNN recommendations provide a useful framework for improving dystonia treatment.
128 Efficacy and safety of deep brain stimulation in Parkinson’s disease: systematic review and meta-analysis
Authors: Bratsos Sosipatros , Karponis Dimitrios , Saleh Sohag
Published: March 2023

Background

Deep brain stimulation (DBS) is a neurosurgical procedure indicated in patients with advanced Parkinson’s disease (PD). This systematic review and meta-analysis aimed to investigate the efficacy and safety of DBS in comparison to best medical therapy (BMT) in the treatment of PD.

Methods

A systematic search was performed in Medline, Embase and Central. Randomised controlled trials (RCTs) comparing DBS to BMT in PD patients were included. Outcome measures were impairment/disability (UPDRS), quality of life (PDQ-39), levodopa equivalent dose (LED) and rates of serious adverse events (SAE).

Results

Eight eligible RCTs (n=1189) were included in the meta-analysis. Regarding efficacy outcomes, there were significant improvements in UPDRS, PDQ-39 and LED in favour of DBS (P<0.00001). The risk of SAE was significantly higher in the DBS group (P=0.005), as was the total number of SAE (P<0.0018).

Conclusions

Overall, DBS was found superior to BMT at improving impairment/disability, quality of life and reducing medication doses, but these benefits need to be weighed against the higher risk of SAE.
136 Mitochondrial biomarkers in parkinson’s disease
Authors: Davis Ryan L , Wong Siew L , Carling Phillipa J , Payne Thomas , Sue Carolyn M , Bandmann Oliver
Published: March 2023

Background

There is strong evidence of mitochondrial dysfunction in both familial and sporadic Parkinson’s disease (PD). A biomarker reliably identifying mitochondrial dysfunction would be particularly important for future stratified/personalized medicine trials in Parkinson’s disease. A previous comparison of serum biomarkers in mitochondrial disease established that serum growth differentiation factor 15 (GDF-15) outperforms fibroblast growth factor-21 (FGF-21) and distinguishes patients with mitochondrial diseases from those without them.

Objective

To systematically assess GDF-15, FGF-21 and mitochondrial DNA copy number (mtDNA) levels in the serum of patients with sporadic PD and controls to determine their utility as a suitable mitochondrial biomarker panel for PD.

Methods

120 patients with PD and 102 age-matched controls were recruited from a single centre. GDF-15, FGF-21 and mtDNA copy number were quantified using previously established assays.

Results

FGF-21 concentrations did not significantly differ between groups. GDF-15 serum levels were significantly raised in late onset PD compared to controls and early onset PD. There was no difference in mtDNA between groups. None of the biomarkers tested showed a significant association with disease following multivariate logistic regression analysis.

Conclusion

Serum FGF-21, GDF-15 and blood mtDNA could not accurately differentiate between PD and controls when assessed as candidate biomarkers.
137 Usability testing of a non-motor symptom app in PD
Authors: Dominey Thea , Mullin Stephen , Edwards Emma , Whipps John , Whipps Sue , Carroll Camille
Published: March 2023

Background

Non-motor symptoms (NMS) are a significant cause of morbidity in Parkinson’s, with major impact on quality of life. There is an urgent need to empower people with Parkinson’s (PwP) to self-manage NMS, and facilitate timely intervention. A mobile application (NMS Assist) was developed, which enables regular assessment of NMS and provides self-help information in the form of animations.

Aim

To evaluate key areas for NMS Assist design improvement.

Method

PwP and carers were recruited from local Parkinson’s UK groups. NMS Assist user journeys were designed and carried out, filmed with ‘Mr Tappy’, using ‘think aloud’ methodology. Satisfaction was evaluated by the System Usability Scale (SUS).

Results

13 Participants were recruited (PwP, n=9 and carers, n=4) with varying age, cognition, disease severity and smartphone experience. Amendment need was identified in three key areas: navigation, content and accessibility. There was no difference in SUS ratings between experienced and never smartphone users. However, the experienced group had a significantly higher error free task completion rate than never users (p=.01).

Conclusions

Refinements to NMS Assist design have been identified and implemented to improve its usability. The effectiveness of these interventions will be tested in future rounds of usability testing, leading to in-service evaluation.