This presentation will enable the learner to:

1. 1. Discuss MADD as a mitochondrial and lipid storage disease

2. 2. Recognize the myopathology of MADD

To estimate the minimum prevalence of adult hereditary ataxias (HA) and spastic paraplegias (HSP) in Eastern Quebec and to evaluate the proportion of associated mutations in identified genes.

We conducted a descriptive cross-sectional study of patients who met clinical criteria for the diagnosis of HA (n = 241) and HSP (n = 115) in the East of the Quebec province between January 2007 and July 2019. The primary outcome was the prevalence per 100,000 persons with a 95% confidence interval (CI). The secondary outcome was the frequency of mutations identified by targeted next-generation sequencing (NGS) approach. Minimum carrier frequency for identified variants was calculated based on allele frequency values and the Hardy–Weinberg (HW) equation.

The minimum prevalence of HA in Eastern Quebec was estimated at 6.47/100 000 [95% CI; 6.44–6.51]; divided into 3.73/100 000 for autosomal recessive (AR) ataxias and 2.67/100 000 for autosomal dominant (AD) ataxias. The minimum prevalence of HSP was 4.17/100 000 [95% CI; 4.14–4.2]; with 2.05/100 000 for AD-HSP and 2.12/100 000 for AR-HSP. In total, 52.4% of patients had a confirmed genetic diagnosis. AR cerebellar ataxia type 1 (2.67/100 000) and AD spastic paraplegia SPG4 (1.18/100 000) were the most prevalent disorders identified. Mutations were identified in 23 genes and molecular alterations in 7 trinucleotides repeats expansion; the most common mutations were c.15705–12 A > G in SYNE1 and c.1529C > T (p.A510V) in SPG7.

We described the minimum prevalence of genetically defined adult HA and HSP in Eastern Quebec. This study provides a framework for international comparisons and service planning.

This presentation will enable the learner to:

Classify tau-immunopositive astrocytic inclusions characteristic of ARTAG

1. 1. Describe neuropathological components of CTE

2. 2. Identify CTE and cortical ARTAG in a case series

• Describe the value of segmentation in image analysis

• Define the role of feature analysis such as t-SNE in high dimensionality histopathology data

Venolymphatic malformations are rare benign vascular lesions of the head and neck. Sclerotherapy has become the first-line therapy of these lesions with bleomycin being a sclerosing agent commonly used.

To perform a systematic review of the published literature to synthesize evidence on the safety and efficacy of bleomycin for the treatment of head and neck venolymphatic malformations.

A systematic review of the literature (January 1995–May 2019) was performed in PubMed, Embase, and Cochrane Library databases to identify studies on sclerotherapy of venolymphatic malformations of the head and neck.

A total of 32 studies with participants met the inclusion criteria among which 1121 patients were included in the systematic review.

Two reviewers independently screened and extracted data and assessed the risk of bias. The primary outcome was the subjective or objective reduction of lesion size as well as minor and major complications.

The bleomycin/pingyangmycin sclerotherapy achieved subjective or objective lesion size reduction in 96.3% (95% CI 94.1%–98.5%) of patients. Minor complications were observed in 16.2% and major complications in 1.1%.

Bleomycin is a highly effective treatment of venolymphatic malformations of the head and neck with a low rate of major adverse events. This study represents an update on the “available” evidence, but only low-to-moderate quality studies were available.

This study reviewed 32 studies performed in different parts of the world, but there was heterogeneity of the study designs and interventions.

Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death.

We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM.

Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02).

We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Embolic ischemic strokes cause significant mortality and morbidity worldwide. It has been proposed that some of these strokes are due to unstable carotid plaques with intraplaque hemorrhage (IPH) but a low overall degree of stenosis. Our aim was to test a fat-saturated T1-weighted (T1WI) black-blood sequence on MRI for the detection of IPH in symptomatic individuals and to quantify the relation between IPH, severity of stenoses, and ischemic brain lesions.

Sixty-two patients were examined by 3T MRI. Sequences included brain diffusion-weighted imaging (DWI) as well as 3D turbo spin echo (TSE) fat-saturated black-blood T1 of the carotid bifurcations, to detect IPH as a focal intraplaque hyperintensity. Both carotid arteries were analyzed in each patient. The North American Symptomatic Carotid Endarterectomy Trial scale was used for quantification of stenosis degree.

Thirty-six out of 62 patients (mean age, 74) showed brain ischemia on DWI. Fifteen of these 36 patients (42%) had associated ipsilateral IPH at the carotid bifurcation or the proximal internal carotid artery. Mean degree of stenosis in this group was 50%. In 21 patients with ischemia without IPH, the mean degree of stenosis was 44%.

MRI with 3D TSE fat-saturated black-blood T1 technique is a safe, reliable, and noninvasive tool for the detection of IPH. A high percentage (42%) of ischemic events in patients with low- to moderate-degree stenosis were associated with IPH, an easily detectable imaging biomarker of plaque vulnerability. The ability to confirm IPH by MRI may help stratify patients into different risk and treatment groups in the future.

Microelectrode recordings (MERs) are used during deep brain stimulation surgery (DBS) to optimize patient outcomes and provide a unique method of collecting data regarding neurological conditions. However, MERs can be affected by anesthetics such as dexmedetomidine. Little is known about the effects of dexmedetomidine (DEX) on the globus pallidus interna (GPi), a common target for DBS. The primary aim of this study is to investigate the hypothesis that DEX is associated with alterations in GPi MERs.

We conducted a retrospective analysis comparing MERs from patients with Parkinson’s disease (PD) and dystonia who underwent insertion of DBS of the GPi under DEX sedation with those who went through the same procedure without DEX (No DEX).

Firing rates for GPi neurons in the DEX group were lower (57.44 ± 2.04; mean ± SEM, n = 163 cells) than the No DEX group (69.53 ± 2.06, n = 112 cells, P < 0.0001). Overall, DEX was associated with a greater proportion of GPi cells classified as firing in bursty pattern compared to our No DEX group. (29.41%, n = 153 vs 14.81%, n = 108, P = 0.008). This effect was present for both PD and dystonia patients who underwent the procedure. High doses of DEX were associated with lower firing rates than low doses.

Our results suggest that DEX is associated with a decrease in GPi firing rates and are associated with an increase in burstiness. Furthermore, these effects are similar between dystonia and PD patients. Lastly, the effects of DEX may differ between high doses and low doses.

This presentation will enable the learner to:

1. 1. Describe the clinicopathologic features of a nodding syndrome.

2. 2. Compare the pathology of NS to ALS/PDC and related disease

Patients with sellar masses undergoing transsphenoidal surgery (TSS) frequently develop endocrine dysfunction; therefore, in-hospital endocrinology consultation (IHEC) is recommended. However, we wondered whether routine endocrinology assessment of all TSS patients is always necessary.

We developed an IHEC Physician’s Guide to identify patients who would require peri-operative IHEC. An analysis of all patients undergoing TSS for a sellar mass over a 4-year period was conducted to assess the predictive value of the IHEC Physician’s Guide in identifying patients who required IHEC.

A total of 116 patients underwent TSS; 24 required IHEC. As expected, the risk of endocrine complications requiring peri-operative endocrine management was significantly higher in the IHEC group versus no-IHEC group (96% vs. 1%; p < 0.001). The negative predictive value of the IHEC Physician’s Guide in identifying patients who did not require IHEC was 0.99 (95% CI 0.9409–0.9997); Fisher’s exact test, p < 0.001), meaning that the IHEC Physician’s Guide successfully identified all but one patient who truly required IHEC.

Results from our study show that most patients do not need IHEC after TSS and that those patients requiring IHEC can be reliably predicted at surgery by using a simple IHEC Physician’s Guide.

Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality in critically ill patients. Pre-hospital care and transportation time may impact their outcomes.

Using the British Columbia Trauma Registry, we included 2,860 adult (≥18 years) patients with severe TBI (abbreviated injury scale head score ≥4), who were admitted to an intensive care unit (ICU) in a centre with neurosurgical services from January 1, 2000 to March 31, 2013. We evaluated the impact of transportation time (time of injury to time of arrival at a neurosurgical trauma centre) on in-hospital mortality and discharge disposition, adjusting for age, sex, year of injury, injury severity score (ISS), revised trauma score at the scene, location of injury, socio-economic status and direct versus indirect transfer.

Patients had a median age of 43 years (interquartile range [IQR] 26–59) and 676 (23.6%) were female. They had a median ISS of 33 (IQR 26–43). Median transportation time was 80 minutes (IQR 40–315). ICU and hospital length of stay were 6 days (IQR 2–12) and 20 days (IQR 7–42), respectively. Six hundred and ninety-six (24.3%) patients died in hospital. After adjustment, there was no significant impact of transportation time on in-hospital mortality (odds ratio 0.98, 95% confidence interval 0.95–1.01). There was also no significant effect on discharge disposition.

No association was found between pre-hospital transportation time and in-hospital mortality in critically ill patients with severe TBI.

Older persons with parkinsonism (PWP) are at high risk for hospitalization and adverse outcomes. Few effective strategies exist to prevent Emergency Department (ED) visits and hospitalization. The interdisciplinary Geriatrics Clinic for Parkinson’s (“our clinic”) was founded to address the complexity of parkinsonism in older patients, supported by a pharmacist-led telephone intervention (TI) service. Our primary objective was to study whether TI could avert ED visits in older PWP.

Using a prospective, observational cohort, we collected data from all calls in 2016, including who initiated and reasons for the calls, patient demographics, number of comorbidities and medications, diagnoses, duration of disease, and intervention provided. Calls with intention to visit ED were classified as “crisis calls”. Outcome of whether patients visited ED was collected within 1 week, and user satisfaction by anonymous survey within 3 weeks.

We received 337 calls concerning 114 patients, of which 82 (24%) were “crisis calls”. Eighty-one percent of calls were initiated by caregivers. Ninety-three percent of “crisis calls” resolved without ED visit after TI. The main reasons for “crisis calls” were non-motor symptoms (NMS) (39%), adverse drug effects (ADE) (29%), and motor symptoms (18%). Ninety-seven percent of callers were satisfied with the TI.

Pharmacist-led TI in a Geriatrics Clinic for Parkinson’s was effective in preventing ED visits in a population of older PWP, with high user satisfaction. Most calls were initiated by caregivers. Main reasons for crisis calls were NMS and ADE. These factors should be considered in care planning for older PWP.

Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not.

Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003–0.040 Hz), low (0.040–0.150 Hz), and high-frequency (0.15–0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics.

We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not.

A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.

To compare long-term survival of Parkinson’s disease (PD) patients with deep brain stimulation (DBS) to matched controls, and examine whether DBS was associated with differences in injurious falls, long-term care, and home care.

Using administrative health data (Ontario, Canada), we examined DBS outcomes within a cohort of individuals diagnosed with PD between 1997 and 2012. Patients receiving DBS were matched with non-DBS controls by age, sex, PD diagnosis date, time with PD, and a propensity score. Survival between groups was compared using the log-rank test and marginal Cox proportional hazards regression. Cumulative incidence function curves and marginal subdistribution hazard models were used to assess effects of DBS on falls, long-term care admission, and home care use, with death as a competing risk.

There were 260 DBS recipients matched with 551 controls. Patients undergoing DBS did not experience a significant survival advantage compared to controls (log-rank test p = 0.50; HR: 0.89, 95% CI: 0.65–1.22). Among patients <65 years of age, DBS recipients had a significantly reduced risk of death (HR: 0.49, 95% CI: 0.28–0.84). Patients receiving DBS were more likely than controls to receive care for falls (HR: 1.56, 95% CI: 1.19–2.05) and home care (HR: 1.59, 95% CI: 1.32–1.90), while long-term care admission was similar between groups.

Receiving DBS may increase survival for younger PD patients who undergo DBS. Future studies should examine whether survival benefits may be attributed to effects on PD or the absence of comorbidities that influence mortality.

• Summarize the current state and driving forces behind commercial and non-commercial scientific publishing in neuropathology.

• Describe the advantages and challenges of a non-commercial publishing platform for neuropathology.

This presentation will enable the learner to:

Recognize key anatomic divisions of the amygdala

1. 1. Describe how different neurodegenerative diseases affect the amygdala

2. 2. Consider how anatomic specificity of protein aggregation is important in the classification of neurodegenerative diseases