J Mol Neurosci (2013) 50:311–313
DOI 10.1007/s12031-013-9967-x

Sickle Cell Disease with Double Stroke in a Moroccan Family
Khalil Hamzi & Afaf Ben Itto & Zineb Jouhadi &
Ilham Slassi & Sellama Nadifi

Received: 15 December 2012 / Accepted: 14 January 2013 / Published online: 23 January 2013
# Springer Science+Business Media New York 2013

Abstract The sickle-cell disease is a group of chronic hemolytic diseases which associates three types of injuries:
severe anemia, severe infections, and ischemic vasoocclusive crisis that are secondary to conflicts between
small vessels and red blood cells too deformable. Thus,
organic various complications may arise. Its prevalence in
Europe is estimated to be about 1/150 and reaches15% in
the Mediterranean areas. Clinical manifestations vary widely from one person to another and from one moment to
another. In addition to anemia and bacterial infections,
vaso-occlusive crisis may manifest by focal ischemia. In
the long term, the VOC may compromise the function of a
particular tissue or organ. The transmission is autosomal
recessive. The sickle-cell diseases are determined by combinations of two abnormal alleles of beta globin gene including at least one which carries the mutation beta 6 glu-val
(Hb S). We report the case of a girl aged 11 years, who
presented two strokes in the interval of 8 months, which
manifested by a complete right hemiplegia and aphasia
confirmed by head CT scan; the electrophoresis of the
hemoglobin and the molecular test had confirmed the diagnosis of sickle-cell disease, and we were allowed to spread
better reflection on the prevention of stroke, which remains
a frequent and serious complication of sickle-cell disease.

Sickle-cell disease is known in Africa as a disease that would
cause arthritic pain, fever, jaundice, and early death (Howard
and Pearson 1976). The sickle-cell diseases are chronic hemolytic diseases likely to cause three types of acute injuries:
severe anemia, severe bacterial infections, and ischemic vasoocclusive crisis that are secondary to conflicts between small
vessels and red blood cells which are too deformable. Thus,
organic various complications may arise (Platt et al. 1994). Its
prevalence in Europe is estimated at about 1/150 and reaches
15 % in the Mediterranean countries (Moukarzel et al. 2000).
Children with sickle disease are at high risk for ischemic
stroke and transient ischemic attacks, usually secondary to
intracranial arteriopathy involving the terminal internal carotid
and proximal middle cerebral and anterior cerebral arteries,
which may be diagnosed using transcranial Doppler ultrasound or magnetic resonance angiography. Stroke occurs in
7–13 % of children with sickle-cell anemia (hemoglobin SS)
and can lead to motor disability, neuropsychological impairment, and death. Transcranial Doppler ultrasonography can
identify children with sickle-cell anemia who are at elevated
risk of stroke and may benefit from chronic transfusions
(Mazumdar and Heeney 2007).

Keywords Sickle-cell disease . Ischemic vaso-occlusive
crisis . Cerebral stroke

Case Report

K. Hamzi (*) : S. Nadifi
Laboratory of Human Genetics, Faculty of Medicine,
University Hospital, Casablanca, Morocco
e-mail: khalil.hamzi@gmail.com
A. B. Itto : Z. Jouhadi
Pediatrics Department, University Hospital, Casablanca, Morocco
I. Slassi
Neurology Department, University Hospital, Casablanca, Morocco

Introduction

We report the case of a girl aged of 11 years, the last in a
family of four (Fig. 1), with no familial clinical history, who
was received for an acute clinical neurological impairment
associated to fever and vomiting. Clinical examination
showed a 39 °C temperature, a 13/15 GCS (Glasgow score),
a right hemiplegia with aphasia with a muscular force scored
to 1/5. The clinical history noted a similar episode 8 months
before, involving the same body side, related to a leftextended stroke that was confirmed by brain CT (Fig. 2)

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J Mol Neurosci (2013) 50:311–313

Fig. 1 The pedigree presenting the Family of S.S. (II4)

and the symptomatology decreased gradually, since the patient was attending physiotherapy sessions. We realized an
emergency CT brain scan that showed the same lesions as in
the first episode. Unfortunately, we could not perform an
angio-CT scan at the moment. Considering the recurrence of
brain stroke in a child, we performed the systematic laboratory exams. Consequently, we could diagnose a sickle-cell
disease on basis of Hb electrophoresis and PCR, which
showed HbS in the homozygous state. The child was treated
by blood transfusion, and clinical, biological, and radiological controls have been introduced as preventive measures
for other crises.
Before this clinical vaso-occlusive crisis has been confirmed by brain CT (Fig. 3), a diagnosis of sickle-cell
disease has been discussed and confirmed by Hb electrophoresis and PCR, which showed HbS in the homozygous
state. The child was treated by blood transfusion, and clinical, biological, and radiological controls have been introduced as preventive measures for other crises.

Fig. 2 CT scan of brain in the first attack showing left frontal, parietal,
and temporal stroke

Fig. 3 CT scan of brain in the second attack showing left frontal,
parietal, and temporal stroke

Discussion
Clusters of sickled erythrocytes in small vessels cause
microinfarctions that produce cumulative damage to the
bone, heart, liver, spleen, and lung. This same mechanism is thought to cause small-vessel cerebral infarcts.
Several studies have shown evidence for congestion,
dilation, and obliteration of small vessels by sickled cells
(Greer and Schotland 1962). Another neuropathologic
report shows similar pathologic changes and adds the
notion that cumulative ischemic damage, even in the
absence of clinical symptoms, is associated with the
cognitive decline that might be seen in sickle-cell
patients (Koshy et al. 1990). Rothman et al. (Rothman
et al. 1986) show in their series that small-vessel infarction is also secondary to proximal large-vessel disease. A
proximal large-vessel occlusion can cause slowed circulation and local hypoxia that, together with other factors,
promote sickling inside small vessels and eventual infarct. A large-vessel vasculopathy that involves the circle
of Willis and the internal carotid artery (ICA) bifurcation
area is a predominant cause for stroke in sickle-cell
disease (Merkel et al. 1978). Intimal hyperplasia has been
described as a common finding in large vessels with
evidence of thrombi causing total or partial occlusion of
these vessels. At present, the most favored pathophysiologic theory for the intimal changes is primary injury to
the endothelial cells (Hess et al. 1991). Several possible
sources of injury to the endothelium include the following: The adhesion of erythrocytes to the endothelial
surface: It is believed that cells that have abnormal form,
although not completely sickled, are the most prone to
adhere to the endothelium (Mohandas et al. 1985).

J Mol Neurosci (2013) 50:311–313

Hemodynamic factors: The area of the most common
intimal change is in the supraclinoid portion of the ICA
(Hess et al. 1991). Stehbens et al. suggests that intimal
pads located in bifurcation areas in the cerebral vasculature are prone to intimal proliferation and red blood cell
breakdown products; a possible mechanism is the effect
of products such as endothelial-derived relaxing factor
from lysed cells (Hess et al. 1991). In our case, the
occurrence of two stroke attack even under treatment
and control maybe can be explained by the presence of
a genetic predisposition to stroke specially with The
MTHFR C677T polymorphism associated with higher
risk of stroke, particularly in the low folate status resulting in high homocysteine levels, and the ACE deletion
polymorphism, strongly associated with high ACE plasma level. These two polymorphisms are common in the
Moroccan population (26.4 % for T allele and 76.6 % for
D allele) (Thierry et al. 2009). It can be also caused by a
context of vascular cerebral malformation, which can be
proven by an angio-CT scan, or better, an angio-MRI.

Conclusion
Vaso-occlusive crisis is a well known complication of
sickle-cell disease, but we rarely think of it to be the cause
of an acute neurological impairment. But because the cerebral strokes are rare in children, we should think of it even if
the neurological symptoms are isolated.
Acknowledgments We are deeply grateful to the patient’s family for
their invaluable collaboration to this study. We are also grateful to Prof.

313
Ana Bersano, stroke expert from the Institute of Medical Genetics,
Milan, Italy, for article reviewing.

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