Sickle cell disease with double stroke in a moroccan family

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 he- molytic diseases which associates three types of injuries:

severe anemia, severe infections, and ischemic vaso- occlusive 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 wide- ly 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 combi- nations of two abnormal alleles of beta globin gene includ- ing 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 diag- nosis 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.

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

Introduction

Sickle-cell disease is known in Africa as a disease that would cause arthritic pain, fever, jaundice, and early death (Howard and Pearson1976). The sickle-cell diseases are chronic he- molytic diseases likely to cause three types of acute injuries:

severe anemia, severe bacterial infections, and ischemic vaso- occlusive 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 ultra- sound or magnetic resonance angiography. Stroke occurs in 7–13 % of children with sickle-cell anemia (hemoglobin SS) and can lead to motor disability, neuropsychological impair- ment, 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 Heeney2007).

Case Report

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 left- extended stroke that was confirmed by brain CT (Fig. 2) K. Hamzi (*)

:

Laboratory of Human Genetics, Faculty of Medicine, University Hospital, Casablanca, Morocco

e-mail: khalil.hamzi@gmail.com A. B. Itto

:

Pediatrics Department, University Hospital, Casablanca, Morocco I. Slassi

Neurology Department, University Hospital, Casablanca, Morocco J Mol Neurosci (2013) 50:311–313

DOI 10.1007/s12031-013-9967-x

and the symptomatology decreased gradually, since the pa- tient 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 labora- tory 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 radiolog- ical controls have been introduced as preventive measures for other crises.

Before this clinical vaso-occlusive crisis has been con- firmed by brain CT (Fig. 3), a diagnosis of sickle-cell disease has been discussed and confirmed by Hb electro- phoresis and PCR, which showed HbS in the homozygous state. The child was treated by blood transfusion, and clin- ical, biological, and radiological controls have been intro- duced as preventive measures for other crises.

Discussion

Clusters of sickled erythrocytes in small vessels cause microinfarctions that produce cumulative damage to the bone, heart, liver, spleen, and lung. This same mecha- nism 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 infarc- tion is also secondary to proximal large-vessel disease. A proximal large-vessel occlusion can cause slowed circu- lation and local hypoxia that, together with other factors, promote sickling inside small vessels and eventual in- farct. 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 pathophysio- logic 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 follow- ing: 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).

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

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

312 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 vascula- ture 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 result- ing in high homocysteine levels, and the ACE deletion polymorphism, strongly associated with high ACE plas- ma 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 cere- bral 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.

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

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