close

Вход

Забыли?

вход по аккаунту

?

Central nervous system abnormalities in asymptomatic young patients with S-thalassemia.

код для вставкиСкачать
Central Nervous System Abnormalities in
Asymptomatic Young Patients with
S␤-Thalassemia
Dimitrios I. Zafeiriou, MD, PhD,1 Mara Prengler, MD,2 Nikos Gombakis, MD, PhD,1
Konsantinos Kouskouras, MD, PhD,3 Marina Economou, MD,1 Achileas Kardoulas, MD,1
Chaido Tsantali, MD, PhD,1 Athanasios Dimitriadis, MD, PhD,3 Miranta Athanasiou, MD, PhD,1
and Fenella J. Kirkham, MB, BChir2,4
Twenty-one children and young adults with sickle/␤-thalassemia without overt stroke were examined with magnetic resonance
imaging and angiography (MRA), transcranial Doppler (TCD), visual (VEP) and median nerve somatosensory (SEP)–evoked
potential recordings, and neuropsychological testing (Wechsler Intelligence Scale [WISC-III]). Eight (38%) had silent infarction in the parietooccipital cortex, deep white matter, or basal ganglia, including two of three with previous seizures. Of 17
undergoing TCD, none had maximum middle cerebral artery (MCA) velocities greater than 126cm/sec, but 9 were abnormal,
with low velocities and difficulty in tracking the MCA and/or asymmetry. Three patients had abnormal MRA, one of whom
also had silent infarction. One patient had pathological VEP recordings, whereas all SEP recordings were normal. WISC-III
was performed in all 11 children, 4 with silent infarction: all but 1 had IQ scores greater than 85 (mean, 97.7; standard
deviation, 14.2). We conclude that Greek children and young adults with S␤-thalassemia and no history of clinical stroke have
TCD abnormalities and silent infarction similar to those reported in children and adolescents with sickle cell anemia, but
cognitive function is not necessarily compromised. International collaboration is needed to establish the risk factors for central
nervous system sequelae in patients with sickle cell disease, including S␤-thalassemia, leading to evidence-based prevention.
Ann Neurol 2004;55:835– 839
Cerebral infarction is a major source of disability in children with sickle cell disease (SCD). Up to 25% of patients with homozygous sickle cell anemia (SCA, hemoglobin [Hb]SS) experience stroke, with the peak incidence
in midchildhood,1 and more than 20% have silent infarction on magnetic resonance imaging (MRI) by adolescence,2 in association with cognitive difficulties3–5 affecting school performance,6 and an increase in new overt
and silent infarction at follow-up.2 Asymptomatic cerebrovascular disease may be detected using MR angiography (MRA)7 or transcranial Doppler (TCD).8 Chronic
transfusion decreases the incidence of new silent infarcts9
and strokes10 in children with SCA and elevated cerebral
arterial blood flow velocities, but there are few data on the
prevalence of silent infarction or elevated velocities in the
other sickle hemoglobinopathies.
Sickle ␤-thalassemia (S␤-thalassemia) is relatively
more common in the Mediterranean because of the
high prevalence of ␤-thalassemia genes11 and is classified as ␤0 and ␤⫹ genotypes according to the presence
and quantity of hemoglobin A. Patients with the ␤⫹
type I genotype have 3 to 5% HbA, those with the ␤⫹
type II genotype, the most common in Greece, have 6
to 14% HbA, and those with the ␤⫹ type III genotype
have 15 to 25% HbA. Patients with the S␤0 genotype
have no HbA but 15 to 25% HbF with normal or
slightly reduced HbA2 and run a clinical course similar
to patients with SCA.12
Silent infarction has been documented in patients with
S␤-thalassemia2,13–15 but any relation to cognitive outcome or the presence of cerebrovascular disease has not
been examined. Subtle abnormalities also might be shown
using neurophysiological techniques, such as evoked potentials. To determine the presence and extent of central
nervous system abnormalities in children and adolescents
with S␤-thalassemia, we examined 21 patients with neuroimaging, neurophysiological, and neuropsychological
methods.
From the 1First Pediatric Clinic, Aristotle University of Thessaloniki, Greece;2Institute of Child Health, University College London, London, United Kingdom;3Department of Radiology, Aristotle University of Thessaloniki, Thessaloniki, Greece; and
4
Department of Child Health, Southampton University Hospitals
NHS Trust, Southampton, United Kingdom.
Published online May 3, 2004, in Wiley InterScience
(www.interscience.wiley.com). DOI: 10.1002/ana.20104
Patients and Methods
Approximately 60 patients with S␤-thalassemia were treated in
Thessaloniki, of whom 21 children and adolescents (19 with
Address correspondence to Dr Zafeiriou, First Department of Pediatrics, Aristotle University of Thessaloniki, Egnatia St. 106, 54622
Thessaloniki, Greece. E-mail:jeff@med.auth.gr
Received Oct 16, 2003, and in revised form Mar 8, 2004. Accepted
for publication Mar 9, 2004.
© 2004 American Neurological Association
Published by Wiley-Liss, Inc., through Wiley Subscription Services
835
S␤⫹-thalassemia [7 SS␤I, 9 S␤II, 3 S␤III] and 2 with S␤0thalassemia; mean age, 14.9 ⫾ 3.9 years; 11 boys) were prospectively examined with MRI, MRA, TCD, visual (VEP), median
nerve somatosensory (SEP)–evoked potential recordings, and
neuropsychological testing (Wechsler Intelligence Scale [WISCIII]). Brainstem auditory-evoked potentials already have been reported.16 All children (⬍16 years) known to the service were
included and 10 older patients were randomly selected. None of
the patients had undergone transfusion. None of the patients
had a history of contraception, migraine, hypertension, or clinical stroke, although three had a history of seizures. Formal neurological evaluation was normal in all.
Magnetic Resonance
All MRI procedures were performed using a 1.5T Magnetom
machine with a standard Siemens head coil. T1-weighted
and turbo spin-echo MRI sets were acquired in the transverse
plane with, respectively, the following parameters: TR/TE ⫽
654/20 milliseconds and TR/TE ⫽ 2,347/80 milliseconds.
MRA was performed using a time-of-flight sequence to obtain spoiled gradient-echo images of the brain in the transverse plane at 64 section levels with the following parameters: TR/TE ⫽ 31/8.3 milliseconds. All MRI and MRA
films were reviewed by a neuroradiologist (K.K.) and a child
neurologist (D.I.Z.) using a standardized reporting form. In
cases in which there were discrepancies in the interpretation,
a second neuroradiologist (A.D.) and a second child neurologist (F.J.K.) were used to reach a consensus. An infarct was
defined as an area of abnormally increased signal intensity on
T2-weighted images (not including myelin delay, linear
perivascular spaces of Virchow-Robin, and focal heterotopias). MRA was classified as abnormal if marked stenosis or
occlusion of a major vessel was apparent.
Transcranial Doppler
Nonimaging TCD (2MHz probe; Nicolet EME, Kleinostheim, Germany) was used by M.P. to insonate the distal internal carotid (ICA), middle (MCA), anterior (ACA), posterior
cerebral (PCA) and basilar arteries using a previously described
protocol.8,17 Detection of arterial abnormality by TCD ultrasonography in the S␤-thalassemia patients was based on criteria drawn from the literature on normal children and young
adults compared with patients with SCD and arteriographic
abnormalities.8,17–21 In addition to Adams and colleagues’ criteria for the detection of stenosis,8 with velocities greater than
170cm/sec defined as abnormal, the cutoff for the lower limit
of normal for MCA mean velocity was defined as 50cm/sec,
because this value was ⫺2 SD for MCA velocity (mean, 90 ⫾
20cm/sec) in an unselected control population of African children aged 7 to 14 years,20 and the mean MCA velocity for
adults without SCD aged less than 30 years of age was 70 ⫾
16cm/sec (range, 54 – 86cm/sec).21 In a series of normal children, asymmetry between right and left MCA velocities was
not greater than 15%.19 TCD therefore was defined as abnormal if one or more of the following findings were present: (1)
MCA ratio (lowest: highest) velocity less than 0.518; (2) ACA:
MCA mean velocity ratio greater than 1.218; (3) mean MCA
velocity greater than 170cm/sec8; (4) mean MCA velocity less
than 50cm/sec20,21; (5) asymmetry of greater than 15% between maximum right and left velocities.19
836
Annals of Neurology
Vol 55
No 6
June 2004
Evoked Potentials
Pattern-reversal VEP and SEP were recorded as previously
described.22 Control data for VEP were obtained from 20
normal subjects of a similar age range and for SEP from 20
normal subjects of a similar height range. Abnormalities in
EPs were defined as those with latencies two or more standard deviations from the norm in a given patient (compared
with controls) and did not necessarily reflect abnormalities of
the whole group of S␤-thalassemia patients tested.
Psychometric Testing
Psychometric testing was performed by using the Wechsler Intelligence Scale for Children–third edition (Greek standardization)23 for all subjects between 6 years and 16 years. The examiner was aware that the subjects had S␤-thalassemia and were
participating in a study; however, he was unaware of specific
imaging or other study results. Anthropometric (birthweight,
height, and weight centiles),24 social (father’s occupation, number of older siblings), and infant feeding (breastfeeding, bottle)25
data were obtained from the patients’ records.
Results
Magnetic Resonance
The overall prevalence of silent infarcts was 8 of 21
(38%) or 4 of 11 of the children (36%). Two of three
patients with a history of seizures had silent infarcts. The
lesions were located in the periventicular and/or subcortical white matter in six patients, in the parietooccipital
cortex in four patients, and in the basal ganglia in two
patients (Table 1); five had bilateral infarcts. Three patients had abnormal MRA; one also had silent infarction. There was no significant difference between patients with infarcts and those without for sex, history of
seizures ( p ⫽ 0.66 and p ⫽ 0.53, respectively; Fisher’s
exact test), mean age (17.4 ⫾ 3.6 vs 18 ⫾ 3.7), fetal Hb
(13.8 ⫾ 12.2 vs 8.9 ⫾ 5.4), mean hematocrit (28.9 ⫾
3.4 vs 29.6 ⫾ 2.4), and mean Hb (9.2 ⫾ 1.3 vs 8.5 ⫾
0.84; p ⫽ 0.58, p ⫽ 0.32, p ⫽ 0.74, p ⫽ 0.85, respectively; independent sample t test).
Transcranial Doppler
TCD was undertaken in 17 of the patients (16 with
S␤⫹-thalassemia [7 S␤I, 8 S␤II, 1 S␤III, and one with
S␤0-thalassemia]; 9 male patients; mean age, 14.8 ⫾
3.6 years). Nine had abnormal TCD findings characterized by lowest to highest MCA ratio less than 0.5
(unilateral, n ⫽ 3; bilateral, n ⫽ 4) and/or asymmetry
between MCA velocities greater than 15% (n ⫽ 4)
and/or unilateral (n ⫽ 3) mean MCA velocities less
than 50cm/sec. The mean of the highest MCA velocities of the series was 62.1 ⫾ 46.1cm/sec. Nine of the
17 patients who had TCD performed had abnormal
neuroimaging; MRI was abnormal in seven patients
and MRA in another two (see Table 1). Abnormal
TCD was not significantly associated with abnormal
MRI (Fisher’s exact test, p ⫽ 0.15) or MRA (Fisher’s
exact test, p ⫽ 0.74).
Table 1. Results of Transcranial Doppler Ultrasonography, MRI, and MRA and Neuropsychology (WISC-III) in 21 Children and
Young Adults with S␤-thalassemiaa
Case
No.
Transcranial
Doppler
Ultrasound
Genotype
Sex
Age
Hb
Ht
1
2
B⫹ type II
B0
M
M
7
7
8.1
8.0
26.0
25.0
Normal
Not done
3
4
5
B0
␤⫹ type II
␤⫹ type II
M
F
F
10
11
12
8.3
8.8
9.5
25.8
27.3
28.2
5 (18%)
R1
L 1, R 1; 5 (28%)
6
7
B⫹ type I
B⫹ type I
M
F
12
13
8.4
8.4
26.0
25.4
Normal
R 1, L 1
8
9
B⫹ type I
␤⫹ type II
M
M
13
14
7.6
8.6
29.3
27.2
Normal
Normal
10
11
12
13
14
15
B⫹
␤⫹
␤⫹
␤⫹
␤⫹
B⫹
F
F
M
F
F
F
15
16
17
17
18
18
10.2
9.0
7.8
7.7
7.4
8.8
31.0
28.0
25.0
23.4
24.3
27.0
16
␤⫹ type I
M
18
10.3
31.2
Not done
L 4; 5 (85%)
L1
L1
Normal
R 1; L 1, 4; 5
(28%)
Normal
17
␤⫹ type II
M
18
11.8
36.2
Normal
R middle cerebral
artery stenosis
Normal
type
type
type
type
type
type
III
II
II
II
I
III
⫹
MRA
Normal
R supraclinoid
carotid artery
stenosis
Normal
Normal
Normal
Normal
R supraclinoid
carotid artery
stenosis
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Normal
18
19
20
␤ type I
␤⫹ type II
␤⫹ type I
M
F
F
18
18
20
8.9
10.2
9.4
29.4
32.3
28.5
L 1, 4; R 1
Not done
Normal
Normal
Normal
Normal
21
B⫹ type III
M
20
10.7
33.6
Not done
Normal
MRI
FS-IQ
V-IQ
PF-IQ
Normal
R parietal
75
107
76
101
80
112
Normal
Normal
R parietooccipital and L
subcortical
L and R periventricular
Normal
99
108
99
90
107
96
109
107
102
92
93
90
98
96
90
L periventricular
R lentiform nucleus, L
internal capsule, R
parietooccipital
Normal
Normal
Normal
Normal
Normal
R lentiform nucleus and
L subcortical frontal
Normal
96
103
101
108
90
97
108
91
ND
ND
ND
ND
99
91
ND
ND
ND
ND
116
93
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
L centrum semiovale and
frontal horn
Normal
Normal
L parietooccipital and R
periventricular
Normal
(1) MCA ratio (lowest:highest) velocity ⬍0.5; (2) ACA:MCA mean velocity ratio ⬎1.2; (3) mean MCA velocity ⬎170cm/sec; (4) mean MCA
velocity ⬍50cm/sec; (5) asymmetry of ⬎15% between maximum right and left velocities.
a
MRA ⫽ magnetic resonance angiography; MRI ⫽ magnetic resonance imaging; ND ⫽ not determined; PF-IQ ⫽ performance IQ; V-IQ ⫽
verbal IQ; FSP-IQ ⫽ full-scale IQ.
Evoked Potentials
One patient had a pathological VEP recording with an
increased P100 cortical latency on the right side; the
same patient had left-sided periventricular white matter
lesions on MRI. All participants had normal median
nerve SEP recordings. Control data for VEP and median nerve SEP recordings are given in Table 2.
Psychometry
WISC-III testing was performed only in the 11 patients younger than the upper age limit for this test. All
fathers were employed (one manual worker, one carpenter, three salesmen, three farmers, two office workers, and one with a small business). Ten had one older
sibling and one had three. None had a low birthweight
or birth head circumference or were below the third
percentile for height or weight. Six were breastfed and
six had used bottles as infants.
All but one patient (who had a normal MRI) had
IQ scores within the reference range (⬎85; mean,
97.7; SD, 14.2). There was no statistical difference between age or verbal performance or total IQ score and
the presence of silent infarcts on MRI ( p ⫽ 0.307,
p ⫽ 0.973, p ⫽ 0.533, and p ⫽ 0.575, respectively,
independent sample t test).
Discussion
In this study, we found TCD, MRI, and MRA abnormalities in a group of neurologically normal children and
adolescents with S␤-thalassemia with no history of overt
stroke. For TCD, MRI, and MRA, 9 of 17 (53%), 8 of
21 (38%), and 3 of 21 (14%) were abnormal respectively,
although the relatively low number of patients means that
Table 2. Control Data for Evoked Potentials (milliseconds)
VEP
P100
SEP
N9
N20
105.0 ⫾ 4.7
9.2 ⫾ 0.9
16.8 ⫾ 1.6
VEP ⫽ visual-evoked potentials; SEP ⫽ median nerve somatosensory–evoked potentials; P100 ⫽ cortical latency P100; N9 ⫽ latency at Erb’s point; N20 ⫽ cortical latency.
Zafeiriou et al: CNS Abnormalities in S␤-Thalassemia
837
Table 3. Full-scale, Verbal and Performance IQ on the
WISC-III in 11 Children with S␤-Thalassemia Aged Younger
than 16 Years.
Measure
No. of patients
Mean
SD
Median
Range
Full-scale
Verbal
Performance
11
97.4
9.7
99
75–108
11
96.1
9.1
98
76–108
11
99.3
11.0
97
80–116
WISC-II ⫽ Wechsler Intelligence Scale; SD ⫽ standard deviation.
this is only an estimate of frequency. Silent stroke appears
to be particularly common in adolescents with S␤thalassemia. However, despite the long TE, which might
have led to artefactual turbulence in these anemic patients,
only three had stenosis diagnosed on MRA, and no child
had high ICA/MCA velocities suggestive of severe stenosis, suggesting that basal cerebral artery pathology is rare
in older children and young adults with S␤-thalassemia in
Greece. In addition, in contrast with patients with SCA in
the United States and Northern Europe, only one child
had low IQ. Visual function has not been documented
extensively in SCD, although visual loss is a wellrecognized complication; one of our asymptomatic patients had abnormal VEPs.
Symptomatic or silent infarcts in patients are wellrecognized complications of SCA,1,2 but there are few
data in other hemoglobinopathies, such as ␤-thalassemia26
and S␤-thalassemia.1,13 Overt stroke has been reported
in up to 10% of patients with S␤-thalassemia,14,27 although perhaps less commonly than in patients with
homozygous SCA,28 but our data suggest that the
prevalence of silent stroke may be higher by the late
teens. Half of an Italian series of patients with S␤thalassemia aged younger than 50 years had asymptomatic brain damage on MRI,13 unrelated to age or hemoglobin level, but associated with the number of
crises per year. Pegelow and colleagues2 found that 5 of
29 patients (3 with S␤⫹ and 2 with S␤0-thalassemia)
in the cooperative study of SCD had silent infarction
on baseline MRI (17.2% prevalence). In the French
cohort,14 3 of 11 patients with S␤-thalassemia had silent stroke, but data on associations with TCD, psychometry, and risk factors were not analyzed separately.
In our study, the percentage of patients with silent
infarcts was lower than the only previous study13 dealing specifically with patients affected with S␤thalassemia, perhaps because of a higher proportion of
S␤0-thalassemia in the Italian study or the younger age
of our patients. The incidence may increase with age,13
in agreement with data from a group of 10 younger
London children with S␤-thalassemia in whom MR
scans were performed at a median age of 10 (range,
4 –15) years; only the child with the overt stroke had
838
Annals of Neurology
Vol 55
No 6
June 2004
an abnormal MRI, and only this child and one other
had abnormal MRA (F.J. Kirkham, unpublished data).
Interestingly, in our study, asymptomatic brain damage was located in the parietooccipital cortex, a typical
location for infarction secondary to sinovenous thrombosis,29 as well as in the deep white matter (which may
infarct after thrombosis in the deep venous sinuses),
and basal ganglia as previously described in SCA. Sinovenous thrombosis has been described in SCD29 –31
and thalassemia,29 although until recently the diagnosis
often was made postmortem31 and may be difficult
even when MR venography is performed during acute
neurological presentations.29 In the previous study involving 25 patients with S␤-thalassemia,13 only one
had a parietal infarct; vascular imaging was not reported. However, parietal and thalamic silent lesions,
often associated with sinovenous thrombosis, were
common in patients with SCA in the cooperative study
of SCD.32 The possibility that silent infarction associated with hemoglobinopathies is secondary to venous
as well as arterial disease merits further investigation.
The prognostic value of TCD in patients with SCA is
well established,8,18 but there are relatively few data on
TCD in asymptomatic patients with S␤-thalassemia. Of
10 patients in the London cohort,27 only one with an
overt stroke had a definitely abnormal TCD, with an
MCA ratio (lowest:highest) velocity of less than 0.5.
Most other studies2,8,14,15,33 have included S␤0thalassemia patients without giving further details. Our
patients commonly had minor abnormalities, of uncertain cause and significance, on TCD, and the highest
ICA/MCA velocity was 126cm/sec,8,18 within a reference range for an anemic population.20 Low velocity on
TCD appears to be associated with white matter hyperintensities in elderly adults.34 In this study, the presence
of a low velocity, asymmetry, or difficulty in tracking
the MCA on TCD was not significantly associated with
abnormal neuroimaging (MRI or MRA). However, because of the low number of patients, further studies
looking at the relationship between abnormal neuroimaging and TCD are required.
In neuropsychological studies, patients with S␤thalassemia have been specifically excluded,5 because
low numbers precluded statistical analysis and there are
very few data on cognitive performance in this condition. These data from Thessaloniki suggest that most
of the children have an IQ within the reference range,
whether or not they had silent infarction. Interestingly,
for six unselected London children with S␤-thalassemia
without overt or covert stroke (mean age, 8.4 ⫾ 3
years), the mean full-scale IQ was 82.7 ⫾ 10.2. This
discrepancy suggests that there may be an important
environmental component to the cognitive outcome in
SCD, perhaps related to diet,24,35 in addition to the
effect of brain pathology. Because this might be an important target for intervention, further studies that in-
clude data on important covariables such as nutrition,
growth, schooling, socioeconomic status, maternal IQ,
and family composition are needed.
We conclude that children and adolescents with S␤thalassemia and no history of clinical stroke commonly
have silent infarction and TCD abnormalities. Compared
with children and adolescents with SCA, high ICA/MCA
velocities appear to be rare; silent infarction may be more
common but is not necessarily associated with cognitive
dysfunction. Larger studies are needed to establish protocols for therapeutic intervention to prevent central nervous system sequelae in patients with S␤-thalassemia.
Dr Kirkham was funded by the Wellcome Trust and Action Research
We gratefully thank E. Koronaki and E. Mousafiropoulou for their
help in the psychometric and neurophysiological evaluation of the
patients, respectively.
References
1. Ohene-Frempong K, Weiner S, Sleeper L, et al. Cerebrovascular accidents in sickle cell disease. Rate and risk factors. Blood
1998;91:288 –294.
2. Pegelow CH, Macklin EA, Moser FG, et al. Longitudinal
changes in brain magnetic resonance imaging findings in children with sickle cell disease. Blood 2002;99:3014 –3018
3. De Baun M, Schatz J, Siegel M, et al. Cognitive screening examinations for silent cerebral infarcts in sickle cell disease. Neurology 1998;50:1678 –1682.
4. Watkins K, Hewes D, Connelly A, et al. Cognitive deficits associated with frontal lobe infarction in children with sickle cell
disease. Dev Med Child Neurol 1998;40:536 –543.
5. Wang W, Enos L, Gallagher D, et al. Neurophysiologic performance in school-aged children with sickle cell disease: a report
from the Cooperative Study of Sickle Cell Disease. J Pediatr
2001;139:391–397.
6. Schatz J, Brown RT, Pascual JM, et al. Poor school and cognitive functioning with silent cerebral infarcts and sickle cell
disease. Neurology 2001;56:1109 –1111.
7. Kandeel AY, Zimmerman RA, Ohene-Frempong K. Comparison of magnetic resonance angiography and conventional angiography in sickle cell disease: clinical significance and reliability. Neuroradiology 1996;38:409 – 416.
8. Adams RJ, McKie V, Carl EM, et al. Long-term stroke risk in
children with sickle cell disease screened with transcranial
Doppler. Ann Neurol 1997;42:699 –704.
9. Pegelow CH, Wang W, Granger S, et al. STOP Trial. Silent
infarcts in children with sickle cell anemia and abnormal cerebral artery velocity. Arch Neurol 2001;58:2017–2021.
10. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke
by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl
J Med 1998;339:5–11.
11. Christakis J, Vavatsi N, Hassapopoulou H, et al. A comparison
of sickle cell syndromes in Northern Greece. Br J Haematol
1991;77:386 –391.
12. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell
disease. Life expectancy and risk factors for early death. N Engl
J Med 1994;330:1639 –1644.
13. Manfre L, Giarratano E, Maggio A, et al. MR imaging of the
brain: findings in asymptomatic patients with thalassemia intermedia and sickle cell-thalassemia disease. Am J Roentgenol
1999;173:1477–1480
14. Bernaudin F, Verlhac S, Freard C, et al. Multicenter prospective study of children with sickle cell disease: radiographic and
psychometric correlation. J Child Neurol 2000;15:333–343.
15. Malouf A, Hamrick-Turner J, Doherty M, et al. Implementation of the STOP Protocol for stroke prevention in sickle cell
anemia by using duplex power Doppler imaging. Radiology
2001;219:359 –365.
16. Koussi A, Zafeiriou DI, Kontzoglou G, et al. Hearing loss in
children with sickle cell disease. Acta Otorhinolaryngol Belg
2001;55:235–239
17. Kirkham FJ, Calamante F, Bynevelt M, et al. Perfusion magnetic resonance abnormalities in patients with sickle cell disease.
Ann Neurol 2001;49:477– 485.
18. Adams RJ, Nichols FT, Figueroa R, et al. Transcranial Doppler
correlation with cerebral angiography in sickle cell disease.
Stroke 1992;23:1073–1077.
19. Bode H, Wais U. Age dependence of flow velocities in basal
cerebral arteries. Arch Dis Child 1998;63:606 – 611.
20. Newton CR, Marsh K, Peshu N, Kirkham FJ. Perturbations of
cerebral hemodynamics in Kenyans with cerebral malaria. Pediatr Neurol 1996;15:41– 49.
21. Ringelstein EB. Transcranial Doppler monitoring. In: Aaslid R, ed.
Transcranial Doppler sonography. Wien: Springer, 1986:147–163.
22. Zafeiriou DI, Kousi A, Tsantali CT, et al. Neurophysiologic
evaluation of long-term desferrioxamine therapy in betathalassemia patients. Pediatr Neurol 1998:420 – 424.
23. Georgas DD, Paraskevopoulos IN, Bezebegis IG, Giannitsas
ND. Wechsler Intelligence Scale for Children–III–Manual.
Greek edition. Athens: Hellenic Letters, 1997.
24. Knight S, Singhal A, Thomas P, Serjeant G. Factors associated
with lowered intelligence in homozygous sickle cell disease.
Arch Dis Child 1995;73:316 –320
25. Gale CR, Martyn C. Breastfeeding, dummy use and adult intelligence. Lancet 1996;347:1072–1075.
26. Incorpora G, Di Gregorio F, Romeo MA, et al. Focal neurological deficits in children with ␤-thalassemia major. Neuropediatrics 1999;30:45– 48.
27. Kirkham FJ, Hewes DKM, Prengler M, et al. Nocturnal hypoxaemia predicts CNS events in sickle cell disease. Lancet
2001;357:1656 –1659.
28. Driscoll MC, Hurlet A, Styles L, et al. Stroke risk in siblings
with sickle cell anemia. Blood 2003;101:2401–2404.
29. Sébire G, Tabarki B, Saunders DE, et al. Venous sinus thrombosis in children. Eur J Paediatr Neurol 2003;7:263.
30. van Mierlo TD, van den Berg HM, Nievelstein RAJ, Braun
KPJ. An unconscious girl with sickle cell disease. Lancet 2003;
361:136.
31. Garcia JH. Thromosis of cranial veins and sinuses: brain parenchymal effects. In: Cerebral sinus thrombosis: experimental and
clinical aspects. Einhäupl K, Kempski O, Baethmann A, eds.
New York: Plenum Press, 1990.
32. Moser FG, Miller ST, Bello JA, et al. The spectrum of brain MR
abnormalities in sickle-cell disease: a report from the co-operative
study of sickle cell disease. Am J Neuroradiol 1996;17:965–972.
33. Wang W, Gallagher D, Pegelow C, et al. Multicenter comparison of magnetic resonance imaging and transcranial Doppler
ultrasonography in the evaluation of the central nervous system
in children with sickle cell disease. J Pediatr Hematol Oncol
2000;22:335–339.
34. Tzourio C, Levy C, Dufouil C, et al. Low cerebral blood flow
velocity and risk of white matter hyperintensities. Ann Neurol
2001;49:411– 414.
35. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003;348:2599 –2608.
Zafeiriou et al: CNS Abnormalities in S␤-Thalassemia
839
Документ
Категория
Без категории
Просмотров
7
Размер файла
76 Кб
Теги
young, central, patients, nervous, abnormalities, system, asymptomatic, thalassemia
1/--страниц
Пожаловаться на содержимое документа