International Stroke Conference
January 24–26

Deepak Gulati, MD

Stroke is a leading cause of morbidity and mortality among children with sickle cell disease. It was an interesting discussion by national and international speakers during one of the dedicated sessions at ISC 2018 on epidemiology of stroke, genetics, use of transcranial Doppler and hydroxyurea trial in sickle cell disease. Sickle cell disease is an inherited monogenetic disorder with a polygenic phenotype. Stroke affects 10–30% of children with sickle cell disease.

Dr. Rufus Akinyemi, MBBS, from the University of Ibadan in Nigeria, provided an update on the epidemiology of stroke in Africa. Non-communicable diseases contribute as much as 80% to medical admissions in some African hospitals. There are numerous studies providing varying number for stroke prevalence in Africa, ranging from 58 to 1,331/100,000. In one of the studies (Interstroke study), the one-month case fatality rate for stroke was 22% in Africa. Hemorrhagic strokes are reported to be more common in Africa. There has also been observed a relationship between HIV infection and stroke, but the pathogenesis is not entirely clear. One of the major concerns is the gaps in the stroke knowledge in health care workers and treatment choice influenced by cultural and religious beliefs. Because of various challenges, no study fulfilled the criteria for an excellent stroke incidence study. The relatively few stroke epidemiology studies in Africa have significant methodological flaws. ARISES (African Rigorous Innovative Stroke Surveillance) aims to conduct a 3-year surveillance of stroke cases in selected urban and rural sites in Nigeria, which have an existing demographic surveillance system. There is a great need for rigorous and reliable data to inform implementation efforts for prevention and control of stroke in Africa.

Several haplotypes exist with varying expression of . Dr. Hyacinth I. Hyacinth from Emory University provided an overview of genetics of sickle cell disease and stroke. 39% of children with sickle cell disease will develop silent cerebral infarct by age 20. Several candidate genes have been identified as modifiers of stroke susceptibility in SCD, including VCAM1 gene, alpha-thalassemia, TNF-alpha, Interleukin-6 G-174C, and angiotensinogen gene (GT-repeat) polymorphisms. One of the meta-analyses of genome-wide association studies identifies three variants associated with ischemic stroke in African Americans: 1) Between HNF1A and HNFA1-AS1 and coronary artery disease, 2) SFXN4 (exonic TG deletion) and macrocytic anemia, and 3) TMEM108 (TAA deletion) and cognitive function. There are many challenges of conducting stroke genetics studies in people of African ancestry like small sample size, heterogeneity of African genome, issues with replication and limited resources. Stroke is a major cardiovascular health consequence among people of African ancestry.

The Stroke Prevention Trial in SCA (STOP 1995-2000) showed that children with abnormal TCD who receive regular (about monthly) blood transfusions have a 90% lower risk of stroke. The STOP II (2000-2005) trial showed a high rate of TCD reversion back to high risk (>200cm/s), (one stroke vs. ten in control group) after the transfusion therapy is safely withdrawn. Dr. Foad Abdallah from Cairo University discussed the role of TCD in sickle cell disease and their experience in Egypt. The study from Egypt included 83 children with SCD including SS and S/beta thalassemia with age ranging from 2 to 18 years. Normal TCD findings were noticed in 79.5% of patients, whereas high-risk findings were noticed in 8.4%. Logistic regression analysis confirmed that the blood transfusion and hydroxyurea dose are inversely related to abnormal TCD findings.

There was another interesting presentation by Dr. Michael DeBaun from Vanderbilt University on a hydroxyurea trial among indigenous Africans and African Americans. The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Nigeria, >50% are born with sickle cell anemia and approximately 50% of the children with strokes will have recurrent stroke within two years (without treatment). A feasibility trial, SPIN trial, was conducted to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal TCD findings in Nigeria, which showed positive results in terms of recruitment, enrollment, adherence and acceptability to both children and parents with no increase in death or significant comorbidity. This led to another currently ongoing study, the SPRINT study — Moderate Dose Hydroxyurea for Secondary Stroke Prevention in Children With Sickle Cell Disease in Sub-Saharan Africa, as a result of unbelievably extensive efforts by Dr. DeBaun and his team members in collaboration with Kano, Nigeria. The strength of the efforts is reflected in a statement by Dr. DeBaun: “Takes a village to prevent strokes in children with sickle cell anemia.”

During one of the poster sessions at ISC 2018, SIREN study (Stroke Investigative Research and Educational Network) investigators interpreted that cardiometabolic factors are the key determinants of stroke risk among young Africans. Hemorrhagic stroke frequency is particularly striking in this population. This study included adults >18years with CT/MRI confirmed stroke.

Given the high incidence and prevalence of stroke in general in Africa, as well as in association with sickle cell disease, there seems to be a strong need for preventive and therapeutic interventions, which should be evidence-based and culturally tailored.