Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the ...literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS.
The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice.
The revised International Pediatric MS group diagnostic criteria improved the accuracy of diagnosis. Identification of red flags and mimickers (e.g. acute disseminated encephalomyelitis and neuromyelitis optica) are vital before establishing a definitive diagnosis. Possible etiology and mechanisms including both environmental and genetic risk factors are highlighted. Pediatric MS patients tend to have active inflammatory disease course with a tendency to have brainstem / cerebellar presentations at onset. Due to efficient repair mechanisms at early life, pediatric MS patients tend to have longer time to reach EDSS 6 but reach it at earlier age. Although no therapeutic randomized clinical trials were conducted in pediatric cohorts, open-label multi-center studies reported efficacy and safety results with beta interferons, glatiramer acetate and natalizumab in similar adult cohorts. Several randomized clinical trials assessing the efficacy and safety of oral disease-modifying therapies are ongoing in pediatric MS patients.
Pediatric MS has been increasingly recognized to have a more inflammatory course with frequent infratentorial presentations at onset, which would have important implications in the future management of pediatric cohorts while awaiting the results of ongoing clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Coronavirus disease-19 is caused by the severe acute respiratory syndrome coronavirus 2 Headache is a common symptom during and after Coronavirus disease-19. We aimed to study headache ...character in relation to COVID-19.
Methods
This was a cross-sectional study. Patients who had Coronavirus disease-19, confirmed by reverse transcription polymerase chain reaction technique and presented to the headache clinic within 3 months after the onset of infections were identified to the study. Study included patients diagnosed as primary headache disorders according to The International Classification of Headache Disorders, 3rd edition. Participants were grouped into categories according to having previous or de novo headache. Descriptive data, paired sample
t
-test and the chi-squared test (
X
2
) were used for statistical analyses of the data.
Results
A total of 121 patients were included in this study. Their mean age was 35.29 + 9.54 and most of them were females (83.5%). Prior to Coronavirus disease-19 infections, 78 (64.5%) had migraine and 11(9.1%) experienced a tension-type headache while 32 (26.4) reported de novo headache post Coronavirus disease-19. Patient had significant increase in headache days 11.09 ± 8.45 post Coronavirus disease-19 compared with 8.66 ± 7.49 headache days before Coronavirus disease-19 infection (
p
< 0.006). Post Coronavirus disease-19, the usage of analgesic increased significantly by the patient with migraine (2.31 ± 1.65 vs 3.05 ± 2.09,
p
= 0.002) while the patient with tension type headache had statistically significant increase in severity (5.556 ± 1.86 vs 7 ± 2.25,
p
= 0.033) and frequency (7 ± 6.29 vs 12.72 ± 7.96,
p
= 0.006) of headache attacks. Bi-frontal and temporal headache are the most reported (40.6% each) headache site among de novo headache group. Patients younger than 40 years had longer duration of the headache attack (18.50 ± 16.44 vs 5.5 ± 9.07,
p
= 0.045) post COVID-19. Male patients compared to females (8.66 ± 1.15 versus 5.93 ± 2.01
p
= 0.04) had more severe headache post Coronavirus disease-19. De novo headache resolved within 1 month in most of patients (65.3%).
Conclusion
Primary headache get worse after Coronavirus disease-19. De novo primary headache is frequent post Coronavirus disease-19 and resolve within 1 month. Headaches related to Coronavirus disease-19 are severe, present as migraine phenotype. Young male patients with Coronavirus disease-19 tend to have worse headache.
Multiple sclerosis (MS) is a complex, neurodegenerative chronic disorder. Circulating diagnostic biomarkers for MS have remained elusive, and those proposed so far have limited sensitivity and ...specificity to MS. Plasma-circulating microRNAs (miRNAs) have advantageous biochemical and physiological attributes that can be utilized in clinical testing and disease monitoring. MS miRNA expression microarray datasets analysis resulted in four candidate miRNAs that were assessed for their expression in a separate MS case-control study. Only miR-24-3p was downregulated in all MS patients compared to healthy controls. MiR-484 was significantly upregulated in relapsing-remitting MS (RRMS) patients compared to healthy controls. Mir-146-5p and miR-484 were significantly downregulated in secondary-progressive MS (SPMS) compared to RRMS. MiR-484 downregulation was associated with worsening disability and increased lipocalin-2 levels. Mir-342-3p and miR-24-3p downregulation were associated with increased semaphorin-3A levels in MS and RRMS patients. In conclusion, mir-24-3p downregulation is diagnostic of MS, and mir-484 upregulation and downregulation are potential biomarkers for RRMS and SPMS conversion, respectively. The differential expression of miR-146a-3p in MS subtypes suggests its potential as an SPMS transition biomarker. The association of downregulated mir-24-3p and mir-484 with increased neurodegeneration biomarkers suggests they play a role in MS pathogenesis and neurodegeneration.
•Mir-24-3p is downregulated in MS and is associated with increased semaphorin 3A.•Mir-484 is upregulated in RRMS and downregulated in SPMS.•Mir-484 downregulation associated with increased disability and lipocalin 2 levels.•Downregulation of miR-146-3p expression is specific to SPMS.
Published natural history data on late-onset of multiple sclerosis are limited. We aimed to assess the risk of attaining EDSS 6.0 among patients with late-onset (> 40 years) MS (LOMS) and young-onset ...(18-40 years) MS (YOMS).
This cross-sectional cohort study was conducted to identify LOMS and YOMS patients' with relapsing remitting course at MS diagnosis. Time (years) to reach sustained EDSS 6.0 was compared between LOMS and AOMS patients. Cox proportional hazards model was used to evaluate the demographic and clinical predictors of time to EDSS 6.0 in these cohorts.
LOMS and YOMS cohorts comprised 99 (10.7%) and 804 (89.3%) patients respectively. Spinal cord presentation at MS onset was more common among LOMS patients (46.5% vs. 32.3%). The proportions of LOMS and YOMS patients reaching EDSS 6.0 during the follow-up period were 19.2% and 15.7% respectively. In multivariable Cox proportional hazards model, older age at MS onset (adjusted hazard ratio (aHR) = 3.96; 95% CI: 2.14-7.32; p < 0.001), male gender (aHR = 1.85; 95% CI: 1.22-2.81; p = 0.004) and spinal cord presentation at onset (aHR = 1.47; 95% CI: 0.98-2.21; p = 0.062) were significantly associated with shorter time to EDSS 6.0.
LOMS patients attained EDSS 6.0 in a significantly shorter period that was influenced by male gender and spinal cord presentation at MS onset.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple Sclerosis (MS) is a complex chronic neurodegenerative disorder resulting from an autoimmune reaction against myelin. So far, many genetic variants have been reported to associate with MS ...risk however their association is inconsistent across different populations. Here we investigated the association of the most consistently reported genetic MS risk variants in the Kuwaiti MS population in a case-control study designs. Of the 94 reported MS risk variants four variants showed MS risk association in Arabs exome analysis (EVI5 rs11808092 p = 0.0002; TNFRSF1A rs1800693 p = 0.00003; MTHFR rs1801131 p = 0.038; and CD58 rs1414273 p = 0.00007). Replication analysis in Kuwaiti MS cases and healthy controls confirmed EVI5 rs11808092A (OR: 1.6, 95%CI: 1.19-2.16, p = 0.002) and MTHFR rs1801131G (OR: 1.79, 95%CI: 1.3-2.36, p = 0.001) as MS risk genetic factors, while TNFRSF1A rs1800693C had a marginal MS risk association (OR: 1.36, 95%CI: 1.04-1.78, p = 0.025) in the Kuwaiti population. CD58 rs1414273 did not sustain risk association (p = 0.37). In conclusion, EVI5 rs11808092A, TNFRSF1A rs1800693C and MTHFR rs1801131G are MS risk factors in the Kuwaiti population. Further investigations into their roles in MS pathogenesis and progression are merited.
It has been reasoned that stressful life events tend to alter immune function thereby increasing the susceptibility to autoimmune diseases including multiple sclerosis (MS). Using the database of ...Kuwait National MS Registry, this quasi-experimental study assessed the impact of the first Gulf War (Iraqi invasion of Kuwait in 1990) on MS risk in Kuwait.
MS incidence data from 1980 to 2019 were obtained from the Kuwait National MS Registry. Annual age-standardized incidence rates (ASIRs) (per 10
person-years) were computed using the World Standard Population as a reference. Interrupted time series analysis with the option of autoregressive order (1) was used to evaluate the impact of the first Gulf War on MS risk by treating 1990 as an intervention year.
Estimated baseline annual ASIR (per 10
person-years) was 0.38 (95% CI: -1.02, 1.78; p = 0.587). MS ASIRs (per 10
person-years) tended to increase significantly every year prior to 1990 by 0.45 (ASIR per 10
person-years = 0.45; 95% CI: 0.15, 0.76; p = 0.005). During the first year of the first Gulf War, there seemed to be a non-significant increase (step change) in ASIRs (per 10
person-years) of MS (ASIR per 10
person-years = 0.85; 95% CI: - 5.16, 6.86; p = 0.775) followed by a non-significant increase in the annual trend in MS ASIRs per 10
person-years (relative to the preintervention trend i.e., the difference between the pre-first Gulf War versus the post-first Gulf War trends) by 0.65 (ASIR per 10
person-years = 0.65; 95% CI: - 0.22, 1.52; p = 0.138). However, a postestimation measure of the post-first Gulf War trend was statistically significant (ASIR per 10
person-years = 1.10; 95% CI: 0.40, 1.80; p = 0.003), which implies that the post-first Gulf War trend in the annual ASIRs (per 10
person-years) inclined to be the same as was the pre-first Gulf War (i.e., counterfactual of the pre-first Gulf War trend in annual ASIRs (per 10
person-years) as if no first Gulf War took place).The Durbin-Watson test statistic (d = 1.89) showed almost non-significant autocorrelations across the time series observations on ASIRs (per 10
person-years).
This study suggests that the first Gulf War was not significantly associated with the increasing trend in MS risk at population level in Kuwait neither with any short-term change nor with secular trend. Future studies may consider confirming the role of conflict-related stress or other stressful life events in potential exacerbation of MS risk along with unraveling biologically plausible mechanistic pathways.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Discontinuation of injectable disease-modifying therapy (DMT) for multiple sclerosis (MS) after a long period of relapse freedom is frequently considered, but data on post-cessation disease course ...are lacking.
(1) To compare time to first relapse and disability progression among 'DMT stoppers' and propensity-score matched 'DMT stayers' in the MSBase Registry; (2) To identify predictors of time to first relapse and disability progression in DMT stoppers.
Inclusion criteria for DMT stoppers were: age ≥18 years; no relapses for ≥5 years at DMT discontinuation; follow-up for ≥3 years after stopping DMT; not restarting DMT for ≥3 months after discontinuation. DMT stayers were required to have no relapses for ≥5 years at baseline, and were propensity-score matched to stoppers for age, sex, disability (Expanded Disability Status Score), disease duration and time on treatment. Relapse and disability progression events in matched stoppers and stayers were compared using a marginal Cox model. Predictors of first relapse and disability progression among DMT stoppers were investigated using a Cox proportional hazards model.
Time to first relapse among 485 DMT stoppers and 854 stayers was similar (adjusted HR, aHR=1.07, 95% CI 0.84 to 1.37; p=0.584), while time to confirmed disability progression was significantly shorter among DMT stoppers than stayers (aHR=1.47, 95% CI 1.18 to 1.84, p=0.001). The difference in hazards of progression was due mainly to patients who had not experienced disability progression in the prebaseline treatment period.
Patients with MS who discontinued injectable DMT after a long period of relapse freedom had a similar relapse rate as propensity score-matched patients who continued on DMT, but higher hazard for disability progression.
Genetic and environmental factors seem to have etiologic roles in multiple sclerosis (MS). Kuwait is regarded as medium to high risk country for MS. However, there is a paucity of published data on ...the risk factors for MS in Kuwait. Therefore, this matched case-control study examined the association between various factors including family history, stressful life events, exposure to tobacco smoke, vaccination history, comorbidities and MS risk in Kuwait.
Confirmed 110 MS cases and age (± 5 years), gender and nationality matched controls (1:1) were enrolled. A pre-tested structured questionnaire was used to collect the data through face-to-face interviews both from cases and controls. Conditional logistic regression was used to analyze the data.
Among both cases and controls, majority were Kuwaiti (82.7%), and female (76.4%). Multivariable model showed that cases compared to controls were significantly more likely to have had a family history of MS (adjusted matched odds ratio (mOR
) = 5.1; 95% CI: 2.1-12.4; p < 0.001) or less likely to have been vaccinated against influenza A and B viruses before MS onset (mOR
= 0.4; 95% CI: 0.2-0.8; p = 0.010). None of the other variables considered were significantly related to MS status in this study.
Family history of MS had significantly direct, whereas, vaccination against influenza A and B viruses had inverse associations with MS status. Future studies may contemplate to verify the observed results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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