Subspecialty preferences among Neurologists of the future.

INTRODUCTION: In the era of neurological subspecialization, most neurologists will have a field of specialist interest. The aim of this cross-sectional multi-national study was to identify the key areas of interest among trainees or junior specialists, assess the potential influence of an interest in research, and consider the results in light of population needs. METHODS: A total of 300 residents and junior neurologists who received a bursary to attend the European Academy of Neurology conference were invited to participate in this study. Demographic and work-related characteristics, as well as main subspecialty of choice were examined via an anonymous electronic questionnaire. Participants holding a higher degree (PhD/MD) or working in research posts were considered research oriented. RESULTS: In total, 191 Neurologists in training or junior specialists responded (response rate 63.7%). Full data were available for 187 participants (59.4% females). The study sample had a mean age of 30.5±3.4 years (range 25 - 45). The most popular subspecialty was movement disorders (18.2%), followed by multiple sclerosis (11.2%) and epilepsy (10.2%). This did not differ significantly between the participants who were or were not research-oriented. CONCLUSIONS: There is a potential mismatch between the interests of trainees, and the future needs of the populations they serve, which it is important to identify for workforce planning

Clinical Non-Motor Phenotyping of Black and Asian Minority Ethnic Compared to White Individuals with Parkinson's Disease Living in the United Kingdom

BACKGROUND: Ethnic phenotypic differences in Parkinson's disease (PD) are important to understand the heterogeneity of PD and develop biomarkers and clinical trials. OBJECTIVE: To investigate (i) whether there are non-motor symptoms (NMS)-and comorbidity-based phenotypic differences between Black, Asian and Minority Ethnic (BAME) and White PD patients and (ii) whether clinically available biomarkers may help differentiate and explain the diversity. METHODS: This is a multicentre (four sites, London), real-life, cross-sectional study including PD patients of BAME or White ethnicity. The primary outcome was a detailed NMS assessment, additional measurements included disease and motor stage, comorbidity, sociodemographic parameters and brain MRI imaging. RESULTS: 271 PD patients (54 Asian, 71 Black, and 146 White) were included balanced for age, gender, and disease severity (HY). Black patients had a shorter disease duration compared to White and Asian populations. The SCOPA-Motor activities of daily living scores as well as the NMSS scores were significantly higher in both Black (total score and domain "miscellaneous") and Asian (total score and domains "sleep/fatigue", mood/apathy" and perception/hallucinations) than White individuals. Both BAME populations had higher prevalence of arterial hypertension, and the Black population had a higher prevalence of diabetes mellitus. Brain MRI revealed a greater severity of white matter changes in Black compared to the White and Asian cohorts. CONCLUSION: These findings suggest differences in phenotype of PD in BAME populations with greater burden of NMS and motor disability and a higher rate of cardiovascular comorbidities

King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation

Pain is a key unmet need and a major aspect of non‐motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross‐sectional, open, multicenter, one‐point‐in‐time evaluation with retest study of the first PD‐specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0‐3) multiplied by frequency (0‐4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy‐eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29‐85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non‐PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser‐Mayer‐Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item‐total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD‐Motor, Non‐Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD. © 2015 International Parkinson and Movement Disorder Societ

Treatment of Nonmotor Symptoms in Parkinson's Disease

Nonmotor symptoms (NMS) are integral to Parkinson's disease (PD) and the management can often be challenging. In spite of the growing evidence that NMS have a key impact on the quality of life of patients and caregivers, most clinical trials still focus on motor symptoms as primary outcomes. As a consequence strong evidence-based treatment recommendations for NMS occurring in PD are spare. In this chapter, the current data addressing the treatment of major NMS such as sleep, cognitive and autonomic dysfunction, and depression and anxiety are described

Dietary Variations in a Multiethnic Parkinson’s Disease Cohort and Possible Influences on Nonmotor Aspects: A Cross-Sectional Multicentre Study

Dietary habits may differ between Parkinson’s disease (PD) patients of different ethnicities. The primary aim of this cross-sectional analysis was to compare dietary habits in a multiethnic PD population and investigate potential nonmotor differences. All patients completed a dietary habits questionnaire. Besides basic demographics, patients’ motor involvement (Hoehn and Yahr (HY)) and nonmotor symptoms (Nonmotor Symptoms Scale; Hospital Anxiety and Depression Scale) were assessed. 139 PD patients were included (mean age 66.8 ± 11.6 years; 61.2% male; mean disease duration 6.2 ± 5.2 years; median HY 3): 47.5% were White, 24.5% Asian, and 28.0% Black African and Caribbean (BAC). We found dietary differences between the groups, including a greater frequency of vegetarians and greater consumption of cumin, turmeric, and cinnamon as well as lower consumption of beef in Asian patients than in White and BAC and greater consumption of chili than in White patients and higher consumption of pork in White than Asian and BAC patients. There were no significant differences in dietary supplement consumption after correction for multiple comparisons. None of the dietary factors examined were associated with differences in nonmotor symptoms. Diet and supplement use vary in PD patients across ethnicities, this is both a problem and opportunity for nutritional medicine research. These data support the importance of considering ethnic diversity as part of recruitment strategy in nutrition and clinical studies

Non-motor predictors of 36-month quality of life after subthalamic stimulation in Parkinson disease.

To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy

Relationship between distal radius fracture malunion and arm-related disability: A prospective population-based cohort study with 1-year follow-up

<p>Abstract</p> <p>Background</p> <p>Distal radius fracture is a common injury and may result in substantial dysfunction and pain. The purpose was to investigate the relationship between distal radius fracture malunion and arm-related disability.</p> <p>Methods</p> <p>The prospective population-based cohort study included 143 consecutive patients above 18 years with an acute distal radius fracture treated with closed reduction and either cast (55 patients) or external and/or percutaneous pin fixation (88 patients). The patients were evaluated with the disabilities of the arm, shoulder and hand (DASH) questionnaire at baseline (concerning disabilities before fracture) and one year after fracture. The 1-year follow-up included the SF-12 health status questionnaire and clinical and radiographic examinations. Patients were classified into three hypothesized severity categories based on fracture malunion; no malunion, malunion involving either dorsal tilt (>10 degrees) or ulnar variance (≥1 mm), and combined malunion involving both dorsal tilt and ulnar variance. Multivariate regression analyses were performed to determine the relationship between the 1-year DASH score and malunion and the relative risk (RR) of obtaining DASH score ≥15 and the number needed to harm (NNH) were calculated.</p> <p>Results</p> <p>The mean DASH score at one year after fracture was significantly higher by a minimum of 10 points with each malunion severity category. The RR for persistent disability was 2.5 if the fracture healed with malunion involving either dorsal tilt or ulnar variance and 3.7 if the fracture healed with combined malunion. The NNH was 2.5 (95% CI 1.8-5.4). Malunion had a statistically significant relationship with worse SF-12 score (physical health) and grip strength.</p> <p>Conclusion</p> <p>Malunion after distal radius fracture was associated with higher arm-related disability regardless of age.</p

Treatment of post-traumatic degenerative changes of the radio-carpal and distal radio-ulnar joints by combining radius, scaphoid, and lunate (RSL) fusion with ulnar head replacement

Distal radial fractures are a common type of fracture. In the case of intra-articular fractures, they often result in post-traumatic arthrosis. The objective of this study is to describe a novel alternative to the established salvage techniques for the treatment of post-traumatic arthrosis of the radio-carpal and distal radio-ulnar joints (DRUJ). Six patients with radio-carpal and DRUJ arthrosis were treated with a combined radius, scaphoid, and lunate (RSL) arthrodesis and as a Herbert ulnar head prosthesis. Follow-up consisted of both radiographic and functional assessments. Functional measurements were noted both pre- and postoperatively. No non-union or pseudoarthrosis was seen; neither did any of the ulnar head prostheses show loosening. Clinical examination showed an improvement in strength, pain, and range of movement, as well as a decrease in disability. Combining RSL arthrodesis with a Herbert ulnar head prosthesis, which deals with pain while retaining partial wrist movement, can be an alternative to established salvage procedures

Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin

Abstract Background One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity. Methods RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined. Results These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines. Conclusion The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic

EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic

Background and purpose The recent SARS‐CoV‐2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast‐evolving pandemic, evidence‐based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID‐19. Methods A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co‐chairs rated importance on a five‐point Likert scale. Results were graded by importance and reported as consensus statements. Results In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty‐nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co‐chairs of 29 SPs. Whilst general recommendations related to prevention of COVID‐19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. Conclusion This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID‐19 pandemic that provides immediate guidance for neurologists. In this fast‐evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges