Objectives • Definition of silent strokes • Epidemiology • Mimics of silent strokes • Silent Infarct Transfusion Trial
Definition of Silent Strokes •
•
CSSCD – Increased signal on T2 weighted image on MRI with no history of a focal neurologic deficits SIT Trial – T2 weighted image on MRI with no history of a focal neurologic deficit and a normal neurologic examination by a pediatric neurologist Glauser et al. (J Child Neurol 1995; 10:88-92
Silent Infarct Mimics on MRI • Terminal Zones of Myelination • Virchow Robbins Spaces • Periventricular Leukomalacia
What is the prevalence of silent cerebral infarcts?
Prevalence of Silent Cerebral Infarcts at Institutions who Performed Surveillance MRI Examinations Reference
Number of Silent Cerebral Infarcts
Total Number of Patients
Prevalence
95% Confidence Interval
Pegelow, 2002
58
266
21.8%
16.8-26.8
Bernaudin, 2000
23
155
15%
9.4-20.6
Kirkham, 2000
16
64
25%
14.4-35.6
SIT
137
386
35%
31-40
Morbidity of Silent Cerebral Infarcts • Global IQ and specific cognitive domains scores are lower than children with SCA and normal MRIs •
Pediatrics. 1996; 97: 864-70
•
Neurology 1998; 50:1678-1682
• The rate of grade failure is twice that of children with normal MRIs and five times higher than sibling control •
Neurology 2001; 56(8):1109-1111.
• Lesion volume influences the magnitude of global IQ loss in silent cerebral infarcts •
J of Child Neurology 2002; 17:891-895
Silent Strokes Are Morbid, But Are They Progressive?
Patients with Silent Strokes and No Treatment Blood 2002; 99:3014-8
n=248 Mean age of first MRI = 8.3 years Mean follow up to second MRI= 5.2 years
Why Choose Blood Transfusion Therapy and How Effective Would You Expect Blood To Be?
Absolute and Relative Risk Reduction of Neurologic Progression in Patients with Sickle Cell Anemia Receiving Blood Transfusion Therapy
Primary Stroke Prevention with an Elevated TCD Measurement
Secondary Prevention of Stroke Two Years After Initial Stroke
Rate of Stroke Without Transfusion Therapy
Rate of Stroke With Transfusion Therapy
Absolute Risk Reduction
Relative Risk Reduction
14.9%
1.6%
13%
89%
50%
8%
42%
84%
Outcome at 36 Months for Subjects With and Without Silent Infarcts
Arch Neurol 2001 Dec;58(12):2017-21
Values
Benefits Reduced Rate of Strokes Pain ACS
Burden Blood transfusion/monthly Viral infection Excessive iron stores Direct and indirect costs
Primary Hypothesis: Prophylactic blood transfusion therapy in children with silent cerebral infarcts will result in at least 86% reduction in the proportion of patients with clinically evident strokes or new or progressive silent cerebral infarcts
• • •
24 clinical sites (Canada, UK and France) Statistical and Imaging Core Center 6.5 year study
Genetic Repository • DNA will be collected on 1880 study participants and stored at Johns Hopkins – Linked clinical database with biologic repository – Unique opportunity to study a large, well characterized patients with and without a single outcome (silent strokes) – Opportunities for studying genetic modifiers
Patient’s Origin Frequency United States United Kingdom Africa France Caribbean Unknown N = 351
286 27 15 15 2 3
% 81.48 7.69 8.55 4.25 0.57 0.85
Patient’s Race Frequency
%
Black
337
96.01
Asian
1
0.28
White
2
0.57
Other
11
3.13
N = 351
722 patients 6 through 12 years of age with hemoglobin SS or SB° and no history of stroke were approached to participate in the study 336 children declined to participate in the study
386 accepted screening
137 children had a positive MRI 4 children had a TCD > transfusion threshold
249 children had a negative MRI
133 children had a TCD < transfusion threshold
55 children were randomized and agreed to allocation
typically include fever, fatigue, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. The disease is transmitted by the ...
Feb 10, 2005 - SCD be screened by TCD to identify those at high risk for stroke [7]. ... questions remain unresolved: how long should transfu- sion therapy be ...
Aug 18, 2008 - The title. Copyright. American Association for the Advancement of ..... Dashed entries indicate no detectable levels of bacteria in blood. wt, wild ...
pediatric cAVM on the basis of the results reported in the literature and ... Table 1. Cerebral topography in 49 pediatric AVMs. Topography. Number. Frequency.
The main statistical procedure was repeated-measures analysis of variance (ANOVA) ..... this precise instruction was used when explaining the nature of the task to the subjects. .... Quarterly Journal of Experimental Psychology', 4, 11â26.
Jan 14, 1993 - entire pathway was initially illuminated, and with each successive button .... software, and the patients with Parkinson's disease who gave so freely of their time. 1 ... Critical analysis of the disability in. Parkinson's disease.
Goonhilly, Angleterre, UK. Câble : Sea-Me-We ... Sennen Cove, Angleterre, UK. Câble : ..... servers are placed under maximum security, it is all the more difficult ...
Silent Night. Open D Tuning n= D o= A p= F# q= D r= A s= D. Capo. 1 fret. :34 c. 1 ! ! hold and let all notes ring...... B. B ! B. &. 3. B ! B. %. 1. AD ! ! B. B ! B. &. B.
Page 79. Ehrlichia Coinfection Exacerbates Lyme Disease. 1. Thomas V, Anguita J, Barthold SW, Fikrig E. Coinfection with Borrelia burgdorferi and the agent of ...
of gaze); (e) on visual pursuit of a moving target, including convergence; ... oculocephalic maneuver with visual fixation (with the patient fixating a visual target.
cal direction (Fig 2, 3). The smooth pursuit movement was found to be saccadic or stepwise in six of 18 patients examined for the horizontal direction and in 12 of ...
Oct 30, 2010 - teristics of gait variability in PD on and off medication under single and dual task conditions. Fifty people with PD were assessed twice at home ...
In normal subjects target movement in a regular pattern enables predictive tracking ... In some circumstances the eye or limb may actually precede the target. In.
tion of EMG parameters associated with control of movement distance during fast ..... ber of bursts between female controls and male controls. (t[12]. 1.0; P. 0.32).
The effects of advance information on movement planning in parkinsonism were ... subjects to initiate movement on the basis of advance information, although such ..... Also shown in Table 2 are the 'specification times' for each of the three ...
Membrane-associated guanylate kinase-like proteins. ... Inflammation . ... lated by several intrinsic signaling pathways, including those involving calcium ... all cell types in the brain but failed to penetrate into the ..... Chemical lesion of the
