Abstract
In the Cooperative Study of Sickle Cell Disease the incidence of stroke in SCD-SS was estimated to be 0.61 per 100 patient-years. Since that study, the use of transcranial Doppler ultrasonography (TCD) has become routine to detect children at high risk of stroke and regular transfusions have been shown to reduce the risk of stroke by over 95% in those with abnormal TCD studies. The impact of TCD screening on the overall incidence of stroke in children with SCD has not been studied extensively. We sought to determine the impact of our TCD screening and treatment protocol on the incidence of first stroke in a cohort of children followed at our Sickle Cell Center. Routine TCD screening was instituted at our Center in Oct, 1998. Our protocol includes annual TCD studies for children with normal TCD results (<170 cm/s), repeat study every 3 to 6 months in those with conditional results (170–199 cm/s), and within 1–4 weeks for children with abnormal results (≥200 cm/s). Chronic transfusion therapy is recommended for patients with confirmed abnormal TCD velocities. In the current study, the rate of stroke in the 8-y period prior to TCD screening (Sept 1, 1990-Aug 31, 1998 – Pre-TCD) was compared to the rate in the 8-y period after TCD screening began (Sept 1, 1998 – Aug 31, 2006 – Post TCD). Eligible subjects were patients less than 22 years old with a diagnosis of SCD-SS or SCD-Sβ0-thalassemia. Subjects with a history of stroke prior to Sept, 1990 or before enrollment in our Center were excluded. Cases of stroke or other neurological event were identified from our clinical database. The study neurologist reviewed all clinical data and radiological studies for each neurological event and classified events into one of the following categories:
overt stroke - ischemic (neurological deficit conforming to a vascular territory with neuroimaging studies corresponding to the clinical deficit) or hemorrhagic not overt stroke (other neurological event), and indeterminate.
Incidence rates for stroke were calculated and compared between the Pre and Post TCD groups using a test of binomial proportions. Subjects were followed until they had a stroke or neurological event, turned 22 years old, the end of the 8-y period or until the last clinic date. The pre-TCD group included 475 children with a total follow-up time of 3,137 person-years. Twenty-one patients had overt stroke, 3 had other neurologic events (1-seizure, 1-transient ischemic attack/syncope, 1-behavioral changes) and 2 were indeterminate. The post-TCD group included 530 children with 3,578 person-years follow-up. Two patients had overt stroke, 6 had other neurological events [1-diffuse encephalopathy with viral syndrome, 1-febrile seizure, 3-dizzy and/or syncope (one with hgb=2.7), 1-headache with <30 min arm/leg weakness – all with acute punctate infarcts whose location did not correspond to clinical presentation], and 1 was indeterminate. The incidence of overt stroke in the pre-TCD period was 0.67 per 100 person-years, compared with an incidence of 0.06 per 100 person-years in the post-TCD period (p < 0.001). The first stroke case in the post-TCD period was a 3.4 year-old with ACA velocities > 200 cm/s but no abnormal velocities in the ICA/MCA and the second occurred in a 1.2 year-old, prior to the age that screening is started. Thus, our TCD screening and treatment program has been successful in reducing the rate of first overt stroke, although small vessel ischemia, particularly in the setting of an additional insult such as severe anemia, may not be prevented. Further modifications such as the addition of ACA velocity to treatment criteria, earlier screening, or the addition of other neuroimaging studies might further reduce the risk of first stroke.
Evaluation of Technical Issues in a Pilot Multicenter Newborn Screening Program for Sickle Cell Disease