The clinical presentation of MS has a wide range of variability which makes it more difficult to reach a confident clinical diagnosis. In the current study, as regards the clinical presentation of MS, the most frequent presenting symptoms overall were motor symptoms (64.6%) (Table 1). This was consistent with studies carried out in KSA (61.8%) , Jordan (30.8%) , and Dubai (72.8%)  where motor symptoms were the most frequently encountered presenting symptoms of MS patients. In partial agreement with our findings in Iran, it was found that motor manifestations followed by sensory and then visual symptoms was the order of frequently presenting MS manifestations . On the other hand, sensory impairment was the most frequent presenting symptom in Kuwait (49.2%) and Qatar (33.3%) [18, 19]. On the contrary, an earlier study in India found that visual symptoms (58%) were more frequent than motor symptoms among Indian MS patients .
The proportion of patients with no (6.3%) or incomplete (64.6%) recovery from the first insult (Table 1) was higher than that reported in Europe among French patients (17%) . Higher levels of no or incomplete recovery after the first relapse among our patients may be attributed to the lack of awareness of MS symptoms and consequent delay in diagnosis and delay in treatment.
Fatigue is one of the main causes of impaired quality of life among MS patients . Fatigue is also among the most common symptoms, reported by at least 75% of MS patients at some point in the disease course . Similarly, 79.2% of patients in the present study reported a subjective sense of fatigue along the course of disease (Table 2). Although bladder manifestations are one of the most well-known symptoms of MS, with more than 90% of patients with MS experiencing bladder symptoms 10 years after disease onset , in the current study, only 47.9% of the sample had bladder symptoms (Table 2). This low rate might be explained by the variable duration of illness among MS patients (the mean duration of MS in our study was 5.2±4.8 years with a range 0.5–19 years) and low rate of spinal cord involvement in our sample (10/48=20.8%) together with the partial nature of spinal cord MS pathology.
It has been reported that HLA-G polymorphism has a potential contribution to MS susceptibility . Group of studies have investigated the possible relation between variable HLA-G genetic polymorphisms and MS [4, 5, 26]. HLA-G expression in MS patients is enhanced on CSF macrophages, monocytes, microglia, and endothelial cells at sites of demyelination . It was reported that the 14-bp DEL/ + 3142 G combined genotypic frequency was related significantly to MS risk . To the best of our knowledge, there are no available data regarding this issue for Egyptian patients with MS.
The present study showed no significant difference between patients and controls regarding genotypic and allelic frequencies of 14-bp INS/DEL polymorphism reflecting an insignificant risk of this polymorphism to MS susceptibility (P=0.305) (Table 3). Similarly, a study from Tunisia demonstrated that there was a lack of association between the 14-bp INS/DEL polymorphism and the risk of having MS . Moreover, Kroner and colleagues studied three polymorphic sites in the HLA-G genetic site including the 14-bp INS/DEL polymorphism and found no relation between any of these three polymorphisms and MS in the German population . Furthermore, a meta-analysis was carried out to find the link between the 14-bp INS/DEL polymorphism and various autoimmune diseases. It concluded that this polymorphism is not linked to MS and rheumatoid arthritis, but associated with several other autoimmune diseases such as systemic lupus erythematosus and Crohn’s disease. This finding suggests that this genetic polymorphism functionality is disease dependent. Thus, HLA-G 14-bp INS/DEL polymorphism is not a usual genetic factor for different autoimmune disorders but other various pathogenic mechanisms are linked to the emergence of polygenetic autoimmune disorders .
On the other hand, an Iranian study demonstrated that HLA-G 14-bp insertion/deletion polymorphism could be a risk factor for MS susceptibility .
The controversy between studies of HLA-G 14-bp INS/DEL polymorphism could be attributed to variance in sample sizes, the ethnic groups, and methods used in different studies besides variable environmental factors. This leads to a suggestion that other different HLA-G polymorphic sites may work together to affect HLA-G expression in MS.
However, Fredj and his colleagues found that 14-bp DEL/ + 3142 G haplotype combined genotype (+3142 G another studied polymorphic site) had significantly increased frequency in MS patients compared to controls .
Wisniewski and coauthors when evaluating the -725C > G > T, -716T > G, and 14-bp INS/DEL HLA-G polymorphisms in MS have found that the -725G/-716T/14-bp DEL haplotype may be a susceptibility factor to this disease in the Polish population . This confirms that the MS risk susceptibility may be not linked to a single allele but may depend on the combination of different polymorphic genetic sites.
The current study found no association between the 14-bp INS/DEL polymorphism genotypes and clinical characteristics or disease disability of MS patients assessed by EDSS (Table 4). Similarly, Fredj and his colleagues reported that the 14-bp INS/DEL polymorphism genotype had no effect on the initiation of the disease . Furthermore, previous studies found no association between HLA-G 14-bp INS/DEL gene polymorphism and the severity of MS [4, 25, 28]. On the other hand, it has been reported that MS patients with 14-bp INS/INS and 14-bp INS/DEL genotypes are more early disease onset compared to patients with 14-bp DEL/DEL genotype . However, in the current study, patients with 14-bp INS/INS and 14-bp INS/DEL genotypes tend to have a later age of MS onset (Table 4) but the difference was insignificant.
Taken together, the results of this study emphasize that the HLA-G 14-bp INS/DEL polymorphism alone does not affect MS susceptibility. This means that other polymorphic genetic sites may have an important role in the regulation of the risk of developing MS. Thus, it can be confirmed that different polymorphic sites interact to modulate the HLA-G role in MS. Therefore, a more extensive research is needed to better clarify the interactive relation between the 14-bp INS/DEL polymorphism, other HLA-G polymorphic sites, and MS. Moreover, further investigations are needed to evaluate detailed HLA-G polymorphisms and transcription and translation rate of the HLA-G gene under different pathological and normal conditions.