Twenty-nine (n=29) studies were selected (The flow chart is shown in Figure 1). Based on study type: Full original papers (n=13), conference abstracts (n=6), medical thesis (n=10). By locations: Rabat (n=5), Casablanca (n=7), Casablanca and Rabat (n=1), Marrakech (n=7), Fez (n=8), and Meknes (n=1). According to the study design: (n=15) were retrospective case series, (n = 8) were prospective case series, (n=1) were prospective cross sectional study, and (n = 5) were prospective case-control studies. According to the age of the target population of the selected studies, (n = 25) studies targeted all ages combined (Greater than 15 years old) and (n = 4) studies focused on the young population (15 - 45 years old). All studies were hospital series.
The Kappa statistical coefficient (κ=0.64). The Quality Rating of "case series",
"cas-control» and «cross-sectional» studies were considered "good" with an average score of 7.5/9 (the results of the methodological evaluation of case series studies are shown in Table 1).
3.1 Mean age and sex ratio of patients with ischemic stroke in Morocco
Twenty-three studies focusing on IS in all age groups revealed an average age ranging from 49 ± 15.2 to 67.3 ± 9.9 years old. Thus, the average age is listed in the fifth and sixth decade [13-35]. However, two studies did not specify the average age of patients. The first study was conducted by Chraa (2010), just reporting that the age was below 45 years old in 36% of cases and more than 45 years old in 64% of cases, and the second by Bourazza et al (2013) indicated an age between the two extremes of 24 and 104 years old [36, 37].
As for the sex ratio (n = 13), studies revealed a male predominance with a ratio ranging between 1.23 and 3.45 [16-19, 22, 24-28, 33, 37, 38]. A ratio of 1 has been reported only in (n = 3) studies [23, 33, 34]. Similarly, a slight female predominance with a ratio between 0.7 and 0.9 was reported in (n = 9) studies [13, 15, 20-22, 30, 31, 35, 36].
Concerning IS in early adulthood, four studies (n=4) included patients aged between 15 and 45 years old. The first was the study by Mbagui (2009) with an age ranging between 15 and 45 years old, the second of Ibouajbane (2014) between 16 and 45, the third of Chraa et al (2014) et al with an age between 18 and 45 and the fourth of Allaoui et al (2018) which included all patients admitted to internal medicine under the age of 45 [39-43].
According to the studies of IS in young people, the average age ranged from 28.3 ± 4.2 to 39 years old (Extremes: 16-45 years old) [39-43].
Concerning the sex-ratio of IS in young cases, (n=2) studies reported values less than 1. The first is the one by Ibouajbane (2014) with a clear female predominance (sex -ratio of 0.4) [39], and the second one was performed by Allaoui et al (2018) showing a slight female predominance with a sex ratio of 0.7 [43].
Male predominance was described by Chraa et al (2014) with a sex ratio of 1.4 [40]. In addition, the Mbagui (2009) study did not show any significant difference between the two genders [42].
3.2 Risk factors for ischemic stroke in Morocco according to the selected studies
Studies included in the present critical review of the literature have revealed several risk factors associated to cerebral ischemia in the local populations of interest. Indeed, high blood pressure (HBP), diabetes, smoking and heart disease were the four main risk factors listed and are as follows: HBP was reported in (n = 20) studies (31 to 65.4%) [13-16, 18-23, 25, 26, 28-30, 32-34, 36, 38], diabetes in (n = 20) studies (12- 41.8%) [13-16, 18-23, 25, 26, 28-30, 32-34, 36, 38], cardiac diseases in 14 studies (7- 44.3%) [13-15, 18, 20-23, 28-30, 32, 36, 38], atrial fibrillation as associated heart disease was specified in 9 studies (2,5-22%), and smoking in (n = 19) studies (4- 41.8%) [13-15, 18-23, 25, 26, 28-30, 32-34, 36, 38].
In addition to these risk factors, other risk factors have been reported, such as dyslipidemia in (n = 16) studies (0-61.8%) [13-16, 18-20, 22, 23, 25, 28-30, 32, 36, 38], obesity in (n = 6) studies (10.7-26.1%) [13, 18, 19, 28, 32, 36], the notion of an previous stroke was noted in (n = 10) hospital series (5-26.6%) [13, 14, 22, 23, 28-30, 32, 35, 36], alcoholism in (n = 10) studies [13-15, 20, 22, 26, 32-35], oral contraception in (n = 3) studies (6.6-12.2%) [15, 35, 36], and migraine in a single study at 6.5% [36].
Concerning the young population, the reported risk factors were smoking in (n = 4) studies (5-40.6%) [39-42], HBP in (n = 4) studies (8% - 49.2%) [39-43], oral contraception in (n = 4) studies (12-31.2%) [39-43], cardiac diseases only by Chraa et al (2014) with a percentage of 17.9% [40], diabetes in (n = 4) studies (7.5-13.2%) [39-43], migraine in (n = 4) studies (1.5-24%) [39-43], dyslipidemia in (n = 3) studies (0-15.3%) [39, 40, 42], alcoholism in (n = 3) studies (5-8%) [39, 40, 42], obesity only (n = 1) by the study of Ibouajbane (2014) with a percentage of 2.5% [39], previous strokes history in (n = 2) studies by Chraa et al (2014) and by Ibouajbane (2014) with a percentage of 2.3% and 2.5%, respectively [39, 40], the first-degree family history of stroke was reported in a single study by Allaoui et al (2018) with a percentage of 25% [43] and pregnancy was reported as key risk factor in (n = 2) studies, conducted by Mbagui (2009) and Chraa et al (2014) with percentages of 0.9% and 1.5% respectively [40, 42] (The results are detailed in Table 2.1 and Table 2.2).
3.3 Genetic risk factors for ischemic stroke in Moroccan studies
The present systematic review includes only (n=5) studies focusing on the genetic factors associated with IS in Morocco.
The first study by They et al (2011) suggested that the MTHFR C677T variant could be a determinant of the atherothrombotic event of IS in Morocco [33]. The same team, They et al (2013) demonstrated an interaction between MTHFR C677TT and F2 20210GA polymorphisms linked to an increased risk of IS [32]. The third study by Diakite et al (2014) suggesting another statistically significant association between G894T polymorphism at the level of eNOS gene and IS in the recessive, dominant and additive models [27].
In addition, another genetic study by Diakite et al (2015) evaluated the association of the FVF C2491T mutation with the risk of IS, suggesting that carriers of the mutated T allele were associated with a high risk of IS. But this risk was 8.95 times higher when the subject had the TT genotype (P <0.0001) and 4.08 times higher with the CT genotype, and they concluded that the FVF C2491T mutation could be a genetic risk factor for IS in the Moroccan population [25].
The fourth genetic research was conducted by Diakite et al (2016) on T-1131C APOA5 polymorphism and has observed a modest risk of IS with CC and C alleles. In addition, the same study explored also the risk of IS related to SG13S114 ALOX5AP showed a significant association with TT and T alleles. Despite the reduced sample size, variants of T-1131C APOA5 and SG13S114 could be considered as an independent genetic risk factor IS in the Moroccan population [26]. Furthermore, the fifth study by Balar (2014), showed that MTHFR gene (patients with MTHFR CT/ TT patients without CT/TT) and other factors (sex, age, HBP, diabetes, smoking, alcoholism, dyslipidemia) did not revealed significant correlation [16]. (Results are detailed in Table 3)
3.4 TOAST etiological classification of ischemic stroke in Moroccan studies
The most prominent etiology is atherosclerosis of large arteries according to (n = 16) studies (16-57.8%) [15, 17, 18, 22, 23, 25-33, 35, 36]. The cardioembolic origin comes second in (n = 17) studies (8.8-50%) [15, 17, 18, 20, 22, 23, 25-33, 35, 36], undetermined causes were present in (n = 12) studies (5.5-34%) [15, 17, 18, 22, 23, 28-30, 32, 33, 35, 36], lacunar ischemic stroke was reported in (n = 12) studies (0-39%) [17, 18, 23, 25-28, 30, 32, 33, 35, 36] and other identified causes are recorded in (n = 13) studies (0-27.4%] [15, 17, 22, 23, 25-27, 29, 30, 32, 33, 35, 36].
Concerning the etiological category "Other identified causes", five studies have specified the pathologies involved in the ontogeny and the occurrence of ischemic stroke conditions [22, 29, 30, 32, 36]. The first study was performed by Chraa (2010), and has reported 14 cases of syphilitic arteritis, 12 cases related to disorders of clotting factors, 5 cases of arterial dissection, 4 cases of systemic diseases, 4 cases of migraine, 1 case of chemotherapy, and 1 case of human immunodeficiency virus . The second study was conducted by Chtau (2012) and has revealed that 2% of all cases were related to arterial dissections. The third was done by Rachdi (2012) and has reported 1 case of Vaquez disease. The fourth study by Saraya (2013), revealed 1 case of polycythemia, 1 case with interhemispheric Meningioma, a toxic IS after Cannabis consumption, and an IS after cerebral angiography as part of the assessment of a C3 Neuroma. The last study was conducted by Rachdi (2015) and showed that 5% of all cases were related to carotid stenosis when it was greater than 50%. However, six other studies did not the “other identified causes” [15, 25-27, 33, 35].
With respect to the young population (15-45 years old), the undetermined causes were identified in four studies. The first study was by Mbagui (2009) with a percentage of 29% [42]. The second by Chraa et al (2014) with a percentage of 40.6% [40]. The third by Ibouajbane (2014), 55% of all cases were linked to undetermined causes [39]. Finally, Allaoui et al (2018) reported a percentage of 24% [43].
The IS of cardioembolic origin was also highlighted in four studies; the first study was performed by Mbagui (2009) and reported a percentage of 21.5% [42]. The second by Ibouajbane (2014) showing a percentage of 15% [39]. Interestingly, the third study was by Chraa et al (2014) revealing that 33.6% of all cases were present with cardioembolic source [40]. The fourth study by Allaoui et al (2018) reported a percentage of 4% [43].
As for the other determinant causes, they were identified in (n = 4) studies (Mbagui, 2009; Chraa et al., 2014; Ibouajbane, 2014; Allaoui et al., 2018) with 21.5%, 14.1%, 15% and 72% respectively [39, 40, 42, 43].
Concerning the details on the etiological class "other specific causes", four studies specified the causes involved in the occurrence of IS in young population. The first by Mbagui (2009) highlighted the implication of blood diseases, vasculitis, oral contraception and carotid dissections with percentages of 35%, 25% (2 cases of Behcet, 1 case of Takayashu, 2 cases of undetermined vasculitis), and 15%, respectively. In addition, 1 case of sneddon syndrome, and 1 post-partum cases were reported [42].
The second by Ibouajbane (2014), angiitis accounted for 5% of cases, hematological disorders for 5% of the cases, one case was observed during pregnancy and especially during the sixth month, and thrombophlebitis in another case [39]. The third by Chraa et al (2014), described 11 cases of syphilis, 3 cases of carotid dissections, 2 cases of coagulation protein deficiency (C), 1 case of sneddon syndrome, and 1 case of anti-phospholipids’ antibody syndrome [40].
The fourth study by Allaoui et al (2018) described a percentage of determinate causes of 72%. The etiologies in this study were dominated by systemic lupus (32%) associated with antiphospholipid syndrome (80%), Behcet's disease (16%), Takayasu's disease (12%) [43].
With respect to atherosclerosis of large arteries, it has been reported in (n = 3) studies; Chraa et al (2014), Ibouajbane (2014) and Mbagui (2009) with proportions respectively of 11.7%, 12.5% and 25.8% [39, 40, 42]. Lacunar IS was found in (n = 2) studies, including Mbagui (2009) and Ibouajbane (2014) with ratios of 2.1 and 2.5%, respectively [39, 42]. The Allaoui et al study (2018), TOAST III (lacunary) patients were 73% smokers, 8% had type II diabetes and / or High blood pressure, and 12% had oestroprogestative contraception at the time of diagnosis [43]. (Results are detailed in Table 4)
3.5 Prehospital delay in patients with ischemic stroke in Morocco
Since the notion of time is crucial in the management of cerebral ischemia, (n=5) studies evaluated the prehospital delay, which consists of the time extending between the time of the symptoms onset and the patient arrival to the emergency department of the different hospital structures [15, 28, 30, 31, 35]. In this perspective, a minimum prehospital average delay was 26 hours [Extremes: 15 Minutes- 8 months] according to the study by Azdad (2012) [15] and a maximum mean prehospital delay 61.9 hours [Extreme: 0.5 hour-216 hours] which was listed in the Yonmadji (2016) study [35]. (The results are detailed in Table 5)
Concerning the consultation period of young patients, It was assessed in two studies [39, 42]. Mbagui (2009) and Ibouajbane studies (2014) reported 134.4 hours and 342 hours respectively [39, 42]. Moreover, the Allaoui et al (2018) showed that the delay between the onset of symptoms and the performance of the first cerebral imaging exceeded 12 hours in 100% of cases [43]. No study investigated the factors influencing the consultation and admission time of patients with IS.
3.6 The percentage of patients with thrombolyzed ischemic stroke in Morocco
Four studies conducted at the neurology department of the University Hospital Hassan II of Fez, focused on the thrombolysis management. The proportion of thrombolysed patients ranged from 1.8% in the Azdad study (2012) [15] to 2.9% in the Rachdi (2015) study [30]. In addition, two studies by Yonmadji (2016) and Daouda et al (2018) revealed two medium proportions of thrombolysed patients of 1.94% and 2.8% respectively [24, 35].
3.7 Mortality in the acute phase and mortality in the chronic phase (3 months) in Morocco
Six studies have reported the mortality rates in the acute phase, ranging from 3% in the Yonmadji (2016) study to 13% for the Chraa (2010) study. In addition, four studies by Saraya (2013), Rhissassi et al (2010), Chtaou (2016) and Azdad (2012) have revealed intermediate values of 5.8%, 9.9%, 10% and 10.8% respectively [15, 23, 31, 32, 35, 36].
The rate of mortality after 3 months onset of the disease was reported in seven studies. Three studies by Bendriss et al (2012), Rachdi (2015), and Hadi (2018) reported respectively the mortality rates of 5.4%, 10%, and 8%. Four studies by Daouda et al (2018), Yonmadji (2016), Chtaou (2016), and Rachdi (2012), respectively reported mortality rates of 4.3%, 21.7%, 29%, and 32.5% in IS treated with thrombolysis [18, 23, 24, 28-30, 35].
The mortality during the acute phase in the young population, was indicated in (n = 3) studies. The first from Ibouajbane (2014) stated a mortality rate of 0% [39], the second by Mbagui (2009) at 1.1% [42] and the third by Chraa et al (2014) with a mortality rate of 16.4% [40].
For the mortality after three months, no study was dedicated to elucidating this parameter.