No abstract

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Cré teil newborn SCA cohort (n ‫؍‬ 217 SS/ S␤ 0 ), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigengenoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L ؋ 10 9 /L increase, 95% CI 1.000-1.006; P ‫؍‬ .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P ‫؍‬ .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention. (Blood. 2011;117(4):1130-1140)

Stroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD).

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.

Neural diseases are often associated with respiratory muscle disorders. Assessment of the motor pathway from the central nervous system to the diaphragm is therefore highly clinically relevant from a diagnosis and follow-up point of view. Cortical magnetic stimulation (CxMS) combined with surface diaphragm electromyogram (EMGdi) has to date been limited in this application by the need of an underlying voluntary contraction to obtain a diaphragm response (facilitation). This study was performed to verify this point with high-powered stimulators and to describe the pattern of diaphragm response to CxMS. In nine subjects, EMGdi was compared with EMG of the abductor pollicis brevis (APB). CxMS was applied on relaxed muscles. The effects of its decreasing intensity and those of a voluntary contraction were studied. In three subjects, transdiaphragmatic pressure was also measured. CxMS consistently provoked a contraction of the relaxed diaphragm (16.06 +/- 0.64 ms, mean +/- SD). Decreasing stimulation intensity decreased the amplitude and increased the latency of this response. Underlying contractions had opposite effects. Respective behaviors of the diaphragm and APB were similar. It is concluded that CxMS gives access to central motor conduction to the diaphragm without the need for subject cooperation.