|Year : 2023 | Volume
| Issue : 1 | Page : 86
Demographic and clinical characteristics of familial and sporadic multiple sclerosis patients
Shahrzad Mokhtari1, Shakiba Houshi2, Omid Mirmosayyeb3, Mahdi Barzegar1, Alireza Afshari-Safavi4, Majid Ghasemi1, Vahid Shaygannejad1
1 School of Medicine, Najafabad Branch, Islamic Azad University, Isfahan, Iran
2 School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Neurology, School of Medicine, Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Biostatistics and Epidemiology, Faculty of Health, North Khorasan University of Medical Sciences, Bojnurd, Iran
|Date of Submission||27-May-2022|
|Date of Acceptance||17-May-2023|
|Date of Web Publication||22-Jun-2023|
Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Hezar Jerib Avenue, JM76 + 5M3, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, immune-mediated disease of the central nervous system. It is still unestablished whether heredity correlates with the disease's progression and severity. Methods: This study includes the patients with MS seen in the MS clinic of Kashani Hospital, affiliated with Isfahan University of Medical Sciences, from January 2019 to January 2020. We gathered data regarding the demographic and clinical characteristics, such as type of disease and family history of MS. Patients were grouped based on having relatives with MS. We compared demographic and clinical characteristics between those with a family history of MS (familial MS: FMS) and those without a family history of MS (sporadic MS: SMS). Results: We included 2,929 MS patients, 523 (17.2%) with FMS and 2,406 (82.8%) with SMS. Patients with FMS were found to have active lesions in the thoracic spine more frequently than those with SMS (P = 0.022). We also found differences in the distribution of gender (P = 0.036) and the frequency of having active brain lesions (P = .024) among patients with FMS and SMS. No difference was found between the demographic/clinical characteristics and the number of affected relatives in the family. Conclusions: Significant differences were found among different groups of patients in terms of demographical and clinical characteristics.
Keywords: Familial multiple sclerosis, magnetic resonance imaging, multiple sclerosis
|How to cite this article:|
Mokhtari S, Houshi S, Mirmosayyeb O, Barzegar M, Afshari-Safavi A, Ghasemi M, Shaygannejad V. Demographic and clinical characteristics of familial and sporadic multiple sclerosis patients. Int J Prev Med 2023;14:86
|How to cite this URL:|
Mokhtari S, Houshi S, Mirmosayyeb O, Barzegar M, Afshari-Safavi A, Ghasemi M, Shaygannejad V. Demographic and clinical characteristics of familial and sporadic multiple sclerosis patients. Int J Prev Med [serial online] 2023 [cited 2023 Sep 27];14:86. Available from: https://www.ijpvmjournal.net/text.asp?2023/14/1/86/379410
| Introduction|| |
Multiple sclerosis (MS) is a chronic, inflammatory, immune-mediated disease of the central nervous system, which causes demyelination and may contribute to neurodegeneration., MS is estimated to affect approximately 2.5 million people worldwide, 1 per 1,000 individuals in the United States and 1.62 per 1,000 individuals in Iran. The prevalence of MS is believed to be rising in several regions around the world. MS affects young people and women more frequently and is known as one of the common causes of disability.,
Although most MS cases are sporadic, studies have shown that nearly 20% of patients with MS have a family history of MS,, pointing to a possible contribution of genetic factors in the disease development. So far, more than 100 genes have been suggested to be associated with MS. Recent studies have shown different alleles that are seen more often in patients with MS, including HLA-DR2, HLA-DRw6, HLA-DR3, HLA-DR2, and HLA-DRB1*15. On the other hand, some genes are shown to have a protective effect against MS or found less often in patients with MS, including DR4 and HLA-DR9.,,,,,
Familial MS (FMS) is defined as having at least one first-degree, second-degree, or third-degree relative diagnosed with MS. The prevalence of FMS is higher in the areas with a higher prevalence of MS. FMS incidence is found to be higher among first-degree and second-degree relatives. For instance, if first-degree relatives have MS, the relative risk of developing MS is found to be 9.2 higher than the general population, and this risk is up to 3.2 times higher for individuals with a second-degree relative with MS. Additionally, FMS is more prevalent among twins, with 31-fold increased risk of developing MS in the other twins.
It is still unestablished whether heredity affects the progression and severity of the disease. Although some studies noted that heredity increases the likelihood of disease progression (but not the severity), there are still insufficient data to determine whether FMS has a different disease course compared to sporadic MS (SMS). This study aims to look into this question by evaluating patients with FMS and their disease course.
| Materials and Methods|| |
This study deploys a cross-sectional design using the MS database of the MS clinic in Kashani Hospital, affiliated with Isfahan University of Medical Sciences. We included patients who visited the clinic from January 2019 to January 2020 and were diagnosed with MS. The patients were diagnosed with MS by two neurologists based on the 2017 revised McDonald criteria. The regional bioethics committee of Isfahan University of Medical Sciences approved the study, and all participants signed a written informed consent prior to their enrollment in the study.
We gathered data regarding the demographic and clinical characteristics of study participants, including age, sex, alcohol consumption, smoking, occupation, level of education, disease-modifying drugs, course and type of disease (e.g., relapsing-remitting MS, progressive MS, clinically isolated syndrome), current and early symptoms (e.g., visual, sensory, motor, brainstem, and cerebellar), physical comorbidity, psychological comorbidity, other autoimmune diseases, active brain lesion, active cervical lesion, active thoracic spine lesion, brain atrophy, longitudinally extensive transverse myelitis, consanguinity, and family history of MS. We used 1.5 T magnetic resonance imaging (MRI) to report brain and spinal findings. Active lesions were discovered through the initial MRI of patients, and an MRI-based method was used to evaluate brain atrophy. Moreover, we evaluated the level of disability in all study participants using the extended disability status scale (EDSS). EDSS is an approach to quantify disability in MS and to monitor gradual changes in the course of disability. The score ranges from 0 to 10, with higher values representing higher levels of disability. To find cases with FMS, we looked for the status of MS in the first-degree, second-degree, and third-degree relatives. In this study, first-degree relatives are parents, siblings, and offspring; second-degree relatives are grandparents, uncles, aunts, and grandchildren; and third-degree relatives are nephews and offspring of grandchildren. We divided patients into two groups with and without a family history of MS to compare demographic and clinical characteristics between them. Different comparisons are made: the comparison between FMS and SMS, the comparison based on the degree of relatives, the comparison based on the number of MS patients in the family, and the comparison between MS patients and their relatives who are MS patients to highlight the factors that significantly contribute to the disease.
Descriptive statistics are reported as mean and standard deviation for continuous variables with a normal distribution, median and interquartile range for variables with non-normal distribution, and frequency (percentage) for categorical variables. We used the independent sample t-test, the nonparametric Mann-Whitney test, and the Kruskal-Wallis test to compare variables of interest between two groups. Additionally, for the categorical variables, we used the Chi-square test. In this study, we set the level of significance at 0.05 while performing two-tailed tests. All statistical analysis procedures were performed using IBM SPSS Statistics (version 18).
| Results|| |
Our final sample consisted of 2,929 patients with MS, including 523 (17.9%) cases with FMS and 2,406 (82.8%) cases with SMS. [Table 1] shows the comparison of demographic and clinical characteristics between patients with FMS and SMS. We found no statistically significant difference in the average age of patients with FMS (38.41 ± 9.55) and SMS (38.18 ± 9.80; P = 0.628). Similarly, we found no statistically significant difference between the two groups regarding gender (P = 0.283), first measured EDSS score (P = .508), and MS type (P = .142).
|Table 1: Demographic and clinical characteristics of familial MS compared to sporadic MS patients|
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Sensory symptoms were the most common symptoms among both groups (35.7% of patients with FMS 32.0% of those with SMS). Visual symptoms were the second most common symptoms among both groups (27.5% of cases with FMS and 30.1% of those with SMS). There was no statistically significant difference between the two groups in terms of the first symptoms (P = 0.692). Moreover, 39.0% of patients with FMS and 37.7% of patients with SMS had physical comorbidities (P = 0.584). There was no statistically significant difference in the number of cases with active brain lesions and cervical lesions between the two groups (P =.104 and P =.728, respectively). However, the number of cases with thoracic spine lesions was higher among patients with FMS (0.8%) compared to patients with SMS (0.1%) (P =.022).
[Table 2] shows the breakdown of FMS cases with regards to the degree of relatives with MS in comparison to patients with SMS. Overall, there were 159, 83, 220, and 61 patients with first-degree, second-degree, third-degree, and multiple-degree FMS, respectively. There were more women among patients with a second-degree relative with MS compared to other groups of FMS (P = 0.036). Moreover, fewer patients with a third-degree relative with MS had active brain lesions (P = 0.024). We found no difference regarding other clinical and demographic features between various groups of patients with FMS.
|Table 2: Demographic and clinical characteristics of familial MS categorized based on the degree of familial MS|
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[Table 3] presents the demographic and clinical characteristics of patients with FMS broken down by the number of relatives with MS. We grouped patients with FMS into three groups: patients with one affected relative, patients with two affected relatives, and patients with three or more affected relatives. We found no statistically significant difference in the demographic/clinical characteristics between these groups.
|Table 3: Demographic and clinical characteristics of familial MS, categorized based on the number of affected relatives in the family|
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Finally, we performed an analysis to compare the demographic and clinical characteristics of patients with MS and their affected relatives [Table 4]. We divided patients into three groups based on the degree of relatives affected with MS. Among patients with a second-degree relative with MS, current EDSS scores were higher among the relatives (P = 0.036). Moreover, among patients with a third-degree relative with MS, the distribution of the first clinical symptom was different between patients with MS and their relatives (P = 0.015).
|Table 4: Comparison between demographic and clinical characteristics of patients and those of patients' relatives|
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| Discussion|| |
In the present study, we looked for differences in clinical and demographic characteristics of patients with FMS and those with SMS.
In our group of patients with MS, nearly 18% had FMS. Previous studies in Isfahan, Iran, have reported the frequency of FMS from 10% to 20.1%.,, Moreover, among the 2,516 patients with MS in Saudi Arabia, 12.8% had a familial history of MS. In a larger study in Tehran, Iran, of 21,580 cases with MS, 13.04% were FMS. Furthermore, a recent study in Northwest Iran reported 13.9% of patients with MS had a family history of MS. While there are some inconsistencies in the frequency of FMS reported in different studies, the numbers are in a close range. The observed differences could be due to different sampling methods and study designs.
We found no difference in the age of onset between patients with FMS and SMS. A study conducted in Abu Dhabi showed that the age at disease onset is not associated with the FMS. Additionally, similar results were found among Lithuanian patients. Conversely, the age at onset was slightly higher among patients with SMS in a large study on 21,580 patients with MS conducted in Tehran, Iran. The observed difference could be due to the much larger sample size in the study conducted in Tehran, although another study showed that the age at disease onset does not contribute to FMS in older patients, while it contributes to FMS in younger patients.
We found no sufficient evidence indicating that the two groups are different regarding the EDSS scores. Similar results were reported among 318 patients with MS with 22% of FMS prevalence. On the contrary, in a study among 104 patients with MS, EDSS scores both at the time of diagnosis and the present time were higher among individuals with FMS. Moreover, the distribution of gender was found to have no association with the type of MS (familial/sporadic) in our study. This finding is in accordance with previous studies.,
We found no difference in the first symptom between patients with FMS and SMS. Similarly, among 384 patients with MS in Greece, findings indicated that the type of MS is not different between cases with FMS and SMS. Additionally, a study in Argentina showed that among a total of 1,333 patients with MS, the type of MS is distributed among cases with FMS and SMS in a similar manner. Our findings are consistent with the previous studies in terms of the first symptom.
Our results showed that there are no differences in physical comorbidities, psychological comorbidities, autoimmune diseases, active brain lesions, and active cervical lesions between the two groups of FMS and SMS. Similar findings were reported in a study done in Greece except for the frequency of active cervical lesions among cases with FMS with a first-degree relative. Brain lesions are reported to be more common among patients with FMS when first-degree FMS is concerned. Additionally, in our study, unlike previous studies, active thoracic spine lesions were more frequent among patients with FMS. Regarding consanguinity, a study showed that it is more frequent among patients with FMS. However, our observations are more aligned with the study by Ceccarelli et al., in which the frequency of consanguinity was similar among cases with FMS and SMS.
In a case-control study by Katsavos et al. in 2018, 102 patients with FMS and 282 with SMS were compared for age of onset, with FMS cases showing a significantly younger age of onset. Furthermore, the distribution of MRI lesions between FMS and SMS patients differed significantly between the two groups. In the former group, there were fewer subcortical lesions, perhaps fewer brainstem lesions, and more cervical cord lesions than those in the latter group (the latter corresponded to the degree of Genetic burden (GB), which could be expressed as the proximity of the relative affected).
With respect to the degrees of relatives with MS, our observations aligned with the literature in certain areas, while different outcomes were observed in other areas. Specifically, we found that age at onset is not associated with the degree of FMS. Our findings are different from those of previous studies reported by Steenhof et al. Conversely, researchers reported that the gender of patients is not correlated with the degree of FMS, while we found more female cases among patients with FMS with a second-degree relative. Additionally, we found that physical comorbidities and active brain lesions are seen more frequently among patients with FMS with first-degree or second-degree relatives. However, other researchers indicated no association between active brain/cerebellar lesion and the degree of FMS, although they reported a correlation between the active cervical lesion and the degree of FMS.
In the analysis of the number of affected relatives in the family, we found no correlation between this number and the demographic and clinical characteristics of patients with FMS. Finally, we investigated the differences between FMS patients' demographic and clinical characteristics and those of their families. Concerning the first-degree relatives, the demographic and clinical characteristics of patients with MS were observed not to be different from those of their first-degree relatives. Comparing the demographic and clinical characteristics of the second-degree relatives with those of the patients resulted in discovering statistically significant differences between them in terms of the current EDSS score. The same comparison between the third-degree relatives and the patients revealed that statistically, significantly different first symptoms appear in patients than in their third-degree relatives.
This study contains certain limitations. First, our sample was selected from the central part of Iran, limiting the generalizability of the results to other populations. Additionally, the clinical features we recorded were not containing all the features reported previously in the literature. A more rigorous data gathering can improve the results. However, in spite of the limitations, this study performed a comprehensive set of analyses on a relatively large sample of patients with MS.
| Conclusion|| |
Patients with FMS tend to have different MS types compared to patients with SMS. Additionally, these individuals have a significantly lower prevalence of active thoracic spine lesions. Comparison of patients with different degrees of FMS revealed that the degree of FMS has an association with the gender of patients, physical comorbidities, and active brain lesions. Furthermore, comparing the demographic and clinical characteristics of the second-degree relatives with those of the patients resulted in discovering a statistically significant difference between them in terms of the current EDSS score.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]