Ethnic background and distribution of clinical phenotypes in patients with probable progressive supranuclear palsy.

BACKGROUND: Progressive Supranuclear Palsy (PSP) is a sporadic neurodegenerative disease without a clear geographic prevalence. Cohorts studied in the UK and India showed no higher prevalence of atypical parkinsonism in South Asian patients. We describe the ethnic and racial background of PSP patients in the Greater Toronto Area (GTA), Canada. METHODS: A prospective observational study of patients with clinically probable PSP evaluated at the dedicated Rossy PSP program. Demographic and clinical data were collected at baseline including PSP phenotype. Results were compared with the latest demographic information from the greater Toronto area. RESULTS: Of the 197 patients screened, 135 had probable PSP and resided within the GTA. The mean age at visit was 71.1 years, disease duration 4.4 years, and disease severity moderate. Compared to our catchment area, there was a higher proportion of patients with a South Asian origin and a lower proportion of patients from East and Southeastern Asia and Africa. A secondary analysis using population census data limited to individuals greater than 65 confirmed the significantly higher representation of South Asians in our clinic but found no differences for other racial and ethnic origins. CONCLUSION: Evaluation of this Toronto cohort found a greater than expected proportion of affected individuals with South Asian ethnic and racial origin. Despite limitations, our results suggest the possibility of a racial and ethnic predisposition to PSP. Further studies are needed to confirm and to address potential associated risk factors, and genome-environmental interactions.

Investigating differences in young- and late-onset progressive supranuclear palsy.

BACKGROUND: The impact of age of onset on the presentation of progressive supranuclear palsy phenotypes is not well studied. We hypothesized that there is difference in presentation and phenotype between young- and late-onset PSP. OBJECTIVES: Our aim was to compare phenotypes and rate of change in disability between young-onset PSP (YOPSP) and late-onset PSP (LOPSP). METHODS: Retrospective data of patients seen in the Rossy PSP Centre from March 2014 to April 2022 with clinical diagnosis of PSP as per the MDS 2017 diagnostic criteria were examined. We used cut-off age of 65 years to categorize the patients into YOPSP and LOPSP. We compared the prevalence of phenotypes, presenting symptoms, and MDS core criteria between the two groups. The severity of disease between the two groups was measured using PSP-RS. RESULTS: We found 107 patients with clinical diagnosis of PSP as per MDS criteria, a third were defined as YOPSP. PSP speech/language (SL) phenotype was more prevalent in YOPSP (18% vs 0%, p < 0.001). Aphasia was significantly higher in YOPSP (16% vs 1.4%, p = 0.03). The speech and language dysfunction (C1) core criteria were more prevalent in YOPSP (33.3% vs 12.2%, p = 0.05). Longitudinal analysis of PSP-RS showed worsening of bulbar total score at 6 months in YOPSP (t (38) = 2.87; p = 0.05). CONCLUSION: Our study revealed that YOPSP are more likely to present with a speech and language variant. Our results highlight that age of onset may predict PSP phenotypes, which holds both clinical and prognostic importance.

Unanticipated consequences of COVID-19 pandemic policies on pediatric acute appendicitis surgery.

BACKGROUND: Global pandemics may limit access to specialized care, delaying diagnosis and treatment of common acute surgical diseases. We analyzed the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on acute appendicitis at an urban tertiary care center. We hypothesize that pandemics are associated with delayed presentation and worsened clinical sequelae, specifically, higher incidences of perforation in children. METHODS: We retrospectively assessed patients admitted to our institution with acute appendicitis in pre-pandemic control (February 2018-June 2019) and COVID-19 (February 2020-June 2021) cohorts. Primary outcomes included complicated appendicitis rates (perforation/abscess/bowel obstruction), COVID-19 status, complications and travel distance to our institution. 1107 patients met inclusion criteria: 491 (44.4%) during the control period and 616 (55.6%) in the COVID-19 cohort. Statistical analysis involved t-tests, contingency tables and logistic regression modelling for key variables. RESULTS: A larger proportion of complicated appendicitis occurred during COVID-19 compared to controls (28.3% vs 38.8%, p < 0.001). Symptom duration at presentation and length of stay were not significantly different. Duration of antibiotic treatment, surgery length, readmission rate and travel distances were significantly higher during COVID-19. The pre-pandemic cohort had a significantly younger age distribution. CONCLUSION: Pediatric appendicitis was significantly impacted during COVID-19, demonstrated by increased rates of complicated appendicitis, surgery duration and antibiotic duration. This may be an unintended secondary consequence of patients avoiding healthcare facilities for non-pandemic related illnesses or lockdown policies. Government policies directing all provincial pediatric appendicitis cases to pediatric institutions increased travel distances for our patients and had unanticipated consequences and resource requirements on tertiary healthcare. LEVEL OF EVIDENCE: Level III for "Treatment Studies".

The Rossy Progressive Supranuclear Palsy Centre: Creation and Initial Experience.

OBJECTIVE: To describe the development and initial experience of a clinical research program in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in Canada: The Rossy PSP Centre, to share the data acquisition tools adopted, and to report preliminary results. METHODS: Extensive demographic and longitudinal clinical information is collected every 6 months using standardized forms. Biofluids are collected for biobanking and genetic analysis, and many patients are enrolled in neuroimaging research protocols. Brain donation is an important component of the program, and standardized processing protocols have been established, including very short death to autopsy times in patients undergoing medical assistance in dying. RESULTS: Between Oct 2019 and Dec 2021, 132 patients were screened, 91 fulfilling criteria for PSP and 19 for CBS; age 71 years; 41% female; duration 5 years, age-of-onset 66 years. The most common symptoms at onset were postural instability and falls (45%), cognitive-behavioral changes (22%), and Parkinsonism (9%). The predominant clinical phenotype was Richardson syndrome (82%). Levodopa and amantadine resulted in partial and short-lasting benefit. CONCLUSIONS: The Rossy PSP Centre has been established to advance clinical and basic research in PSP and related tauopathies. The extent of the clinical data collected permits deep phenotyping of patients and allows for future clinical and basic research. Preliminary results showed expected distribution of phenotypes, demographics, and response to symptomatic treatments in our cohort. Longitudinal data will provide insight into the early diagnosis and management of PSP. Future steps include enrollment of patients in earlier stages, development of biomarkers, and fast-tracking well-characterized patients into clinical trials.