Misfolded α-Synuclein in Cerebrospinal Fluid of Contact Sport Athletes

Background

Misfolded α-synuclein in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) can be detected using the real-time quaking-induced conversion (RT-QuIC) technique in cerebrospinal fluid (CSF).

Objectives

The objectives are (1) to examine misfolded CSF α-synuclein incidence, and (2) to compare clinical presentation, sports history, brain volumes, and RT-QuIC α-synuclein positivity in former athletes.

Methods

Thirty former athletes with magnetic resonance imaging, neuropsychological testing, and CSF analyzed for phosphorylated tau 181 (p-tau), total tau (t-tau), amyloid-β 42 (Aβ42), and neurofilament light chain (NfL). CSF α-synuclein was detected using RT-QuIC.

Results

Six (20%) former athletes were α-synuclein positive. α-Synuclein positive athletes were similar to α-synuclein negative athletes on demographics, sports history, clinical features, CSF p-tau, t-tau, Aβ42, and NfL; however, had lower grey matter volumes in the right inferior orbitofrontal, right anterior insula and right olfactory cortices.

Conclusions

α-Synuclein RT-QuIC analysis of CSF may be useful as a prodromal biofluid marker of PD and DLB. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.     

Covid-19 pandemic and asthma: What did we learn?

This review addresses some of the major lessons we have learnt regarding asthma and the covid-19 pandemic, including susceptibility to SARS-CoV-2 infection and severe covid-19, potentially protective factors, comparison to other respiratory infections, changes in healthcare behaviour from the perspective of patients and clinicians, medications to treat or prevent covid-19, and post-covid syndrome.     

Perioperative intravenous lidocaine use in children

Perioperative pain management impacts patient morbidity, quality of life, and hospitalization cost. In children, it impacts not only the child, but the whole family. Adjuncts for improved perioperative analgesia continue to be sought to minimize adverse side effects associated with opioids and for those in whom regional or neuraxial anesthesia is not suitable. The use of ketamine and alpha agonists may be useful in these settings but have noted adverse effects including hallucinations, hemodynamic instability, and excessive sedation. One alternative is intravenous lidocaine. Despite its off-label use, intravenous lidocaine has demonstrated anti-neuropathic, anti-hyperalgesic, and anti-inflammatory actions and is an emerging technique. Multiple studies in adults have demonstrated beneficial effects of perioperative intravenous lidocaine including improved perioperative analgesia with reduced postoperative opioid use, improved gastrointestinal function, earlier mobilization, and reduction in hospital length of stay. Despite the limited pediatric literature, some of these findings have been replicated. Large-scale trials providing evidence for the pediatric pharmacokinetics and high-quality safety data with respect to intravenous lidocaine are still however lacking. To date, dose ranges studied in the pediatric population have not been associated with serious side effects and current data suggests perioperative intravenous lidocaine in a subgroup of pediatric surgical patients seems well-tolerated and beneficial.     

Informing youth-centred opioid agonist treatment: Findings from a retrospective chart review of youths' characteristics and patterns of opioid agonist treatment engagement in a novel integrated youth services program

Aim

Youth ages 12–24 account for approximately 20% of overdoses and yet are poorly reached by opioid agonist treatment (OAT), the most widely recommended treatment for opioid use disorder (OUD). This study contributes to understanding this critical gap by describing youths' patterns of OAT engagement at a novel integrated youth-specific OAT program.

Methods

A retrospective chart review was carried out on electronic medical records of n = 23 youth with OUD accessing a community-based integrated youth services (IYS) centre. Data abstraction focused on four domains: sociodemographic, social determinants of health, patterns of OAT engagement, and other services utilized.

Results

Youths' mean age was 22.6 years (SD = 2.1), with a mean age of first opioid use of 17.4 (SD = 2.7). Youth reported extensive histories of adverse childhood experiences, concurrent mental and physical health complications, and poly-substance use. All youth were offered OAT and 83% initiated treatment with buprenorphine/naloxone, methadone, or slow-release oral morphine. Among those initiating OAT, 42.1% were considered stable on OAT.

Conclusions

To our knowledge, this is the first empirical study to describe youths' OAT engagement in an integrated youth-specific OAT program. Our findings demonstrated that a high proportion of youth with OUD initiated OAT in this novel program with varying degrees of OAT stability. These findings can be used to inform the development and implementation of youth-specific and integrated OAT. To account for the novelty of this area of study and small sample sizes, future collaborative efforts across IYS initiatives should be considered, including mixed method approaches to understand outcomes and experiences.     

Review: Short bowel syndrome in infancy: recent advances and practical management

Short bowel syndrome (SBS) is a rare condition characterised by extensive loss of intestinal mass secondary to congenital or acquired disease. The outcomes are determined by dependency on parenteral nutrition (PN), its possible complications and factors that influence intestinal adaptation. In order to achieve the best results, patients should be managed by a specialised multidisciplinary team with the aims of promoting growth and development, stimulating intestinal adaptation and preventing possible complications. This involves timely surgical management aimed at rescuing maximum bowel length and eventually re-establishing intestinal continuity where appropriate. A combination of enteral and parenteral nutrition needs to be targeted towards maintaining a balance between fulfilling the nutritional and metabolic needs of the child while preventing or at least minimising potential complications. Enteral nutrition and establishment of oral feeding play a fundamental role in stimulating bowel adaptation and promoting enteral autonomy. Other measures to promote enteral autonomy include the chyme recycling in patients where bowel is not in continuity, autologous gastrointestinal reconstruction and pharmacological treatments, including promising new therapies like teduglutide. Strategies such as lipid reduction, changing the type of lipid emulsion and cycling PN are associated with a reduction in the rates of intestinal failure–associated liver disease. Even though vast improvements have been made in the surgical and medical management of SBS, there is still lack of consensus in many aspects and collaboration is essential.     

First case of desmosterolosis diagnosed by prenatal whole exome sequencing

Desmosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis resulting in multiple congenital abnormalities and syndromic intellectual disability. It is caused by defects in DHCR24, the gene encoding 3-β-hydroxysterol-24-reductase (24-dehydrocholesterol reductase), which acts in conversion of cholesterol precursor desmosterol, hence resulting in elevated plasma desmosterol levels. To date, desmosterolosis has been reported in 10 patients. Here we report an eleventh patient with desmosterolosis, and the first one to be diagnosed antenatally. Diagnosis was made on whole exome sequencing after amniocentesis due to complex antenatal abnormalities including cerebellar hypoplasia, microgyria, aortic stenosis, and renal tract abnormalities. Sterol quantitation was subsequently done postnatally, which supported the diagnosis. Although the nonspecific features make desmosterolosis difficult to suspect, we demonstrate that disorders of cholesterol synthesis can be considered as a differential diagnosis antenatally.