Baseline Neurological Morbidity Assessment in Adult Patients with Sickle Cell Disease : The Montreal Brain-SCD Cohort
Authors: Charles Chrystelle , Bereznyakova Olena , Jacquin Gregory , Bergeron Jade , Hafsaoui Amer Yassine , Fraile Valerie , Van Synghel Nancy , Arethuse Anais Elodie , Kazadi Costa , St-Onge Jonathan , Desforges Sara-Maude , Pouliot Olivier , Georges Phalica , Desmarais Philippe , Stapf Christian , Forte Stephanie 
Published: December 2024

Background

Individuals with sickle cell disease (SCD) are at a high risk of symptomatic stroke, vascular brain lesions, and cognitive impairment. Although these neurovascular complications are well documented in children, data in contemporary cohorts of adults remain limited. In addition, the effect of disease modifying interventions on the outcome of neurovascular complications over the lifespan are unknown. Since 2021, a multidisciplinary neurology-hematology clinic has been established at the Centre Hospitalier de l'Université de Montréal (CHUM). The primary aim of this study is to describe the study entry prevalence of symptomatic stroke and of any cognitive impairment in the Montreal-Brain-SCD cohort. The secondary aim is to measure the effect of the specialized clinic on diagnosis of cognitive comorbidities.

Methods

This prospective study is conducted at the CHUM with the ultimate goal of creating a database of all patients followed as part of the Montréal-Brain-SCD cohort. We present the baseline characteristics at study inclusion. The local ethics committee approved the project and patients signed informed consent. Participants, aged ≥18 of all genotypes (HbSS, HbS β°/β+-thalassemia, HbSC), were included if they had ≥1 visit between September 2021 and June 2024. Symptomatic stroke was defined as any cerebral infarction or intracranial hemorrhage on brain imaging with a corresponding focal neurological deficit or symptomatology. The diagnosis of cognitive disorder (major and mild) was defined according to the International Society of Vascular Behavioral and Cognitive Disorders (VasCog). Attention disorder broadly included difficulties with attention and formal diagnosis of attention deficit disorder (ADD).

Findings

A total of 292 adults with SCD were included. The median age was 32 years (18-79), 167 (57%) were female. The genotype distribution was 142 (48%) individuals with the SS/Sβ0 genotype, 122 (42%) of the SC genotype, and 28 (10%) of the Sβ+. Overall, 182 patients (62%) received hydroxyurea treatment, while 58 (20%) were on chronic transfusions. Both therapies were administered concurrently to 17 patients (6%).

Prior to the first assessment at the specialized clinic, the prevalences were: 12 patients (4%) had a confirmed history of prior stroke during their lifetime, 4 (1%) had a diagnosis of major cognitive disorder (MCD), none of mild cognitive disorder and 15 (5%) of ADD.

After a first visit at the clinic, the number of confirmed cases of MCD increased significantly from 4 (1%) to 15 (5%) (Fisher exact test, p-value &lt;0.001), with one patient in whom the diagnosis was revised from MCD to intellectual deficiency. Mild cognitive disorder was diagnosed in 17 (6%).

Before the assessment, attention disorder was diagnosed in 15 (5%). However, after further assessment, 8 diagnoses were retracted, with one modified to mild cognitive disorder, and 33 new diagnoses were made. As a result, a significantly higher proportion of patients had a diagnosis of attention disorder (40, 14%) (χ2 = 11.746, p-value &lt; 0.001).

The prevalence of confirmed stroke increased with age, with 0/109 (0%) in the 18-29 age group, 3/89 (3%) in the 30-39 age group, 5/51 (10%) in the 40-49 age group, 2/31 (7%) in the 50-59 age group and 2/12 (17%) in the ≥60 age group.

The prevalence of MCD also increased with age, with 9/280 (3%) in the 18-59 age groups and 6/12 (50%) in the ≥60 age group.

However, the overall prevalence of attention disorder in the cohort decreased with age, with 18/109 (17%) in the 18-29 age group, 11/89 (12%) in the 30-39 age group, 9/51 (18%) in the 40-49 age group, 2/31 (7%) in the 50-59 age group and 0/12 (0%) in the ≥60 age group.

Our analyses revealed a significant association between prior stroke and any diagnosis of cognitive disorder (Fisher exact test, p-value = 0.001).

Interpretation

This study carried out in an adult cohort of SCD patients revealed a high proportion of stroke and cognitive disorders. These results underline the need for a thorough neurological assessment in individuals with SCD, revealing an initial underdiagnosis of cognitive and attentional disorders. This highlights the neurocognitive vulnerability of this population, notably in those with a previous stroke. A prospective study of neurological complications affecting adult patients with SCD is ongoing.