Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging.
We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data ...to reveal disability markers after 8.2±2.2 years of follow-up.
Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed.
CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group.
The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Fingolimod withdrawal may trigger the return of pretreatment disease activity. It is difficult to identify patients at risk of disease reactivation. We compared the demographic and ...clinical features of patients experiencing severe disease reactivation (SDR) after fingolimod cessation with those of patients who did not.
METHODS:All patients who commenced fingolimod and who continued therapy for at least 6 months were included. The demographic and clinical features of the 2 groups (SDR vs. no SDR) were assessed.
RESULTS:Forty-four of 303 patients discontinued fingolimod for various reasons. Among these, 31 fulfilled our inclusion criteria and 8 (25.8%) exhibited SDR after drug cessation. The mean time for SDR was 2.6 months (range, 2 to 3 mo). The annualized relapse rate before fingolimod therapy was higher in the SDR than in the non-SDR group (1.59 vs. 0.81) (P=0.018). Although statistical significance was not attained, the mean Expanded Disability Status Scale score at the time of fingolimod cessation was higher in the non-SDR than in the SDR group (2.5 vs. 1.12) (P=0.074).
CONCLUSIONS:SDR may develop within the first 3 months after cessation of fingolimod. Patients with higher annualized relapse rates and lower Expanded Disability Status Scale scores before commencing fingolimod treatment were more likely to exhibit SDR.
Many multiple sclerosis (MS)-associated common risk variants as well as candidate low-frequency and rare variants have been identified; however, approximately half of MS heritability remains ...unexplained. We studied seven multiplex MS families, six of which with parental consanguinity, to identify genetic factors that increase MS risk. Candidate genomic regions were identified through linkage analysis and homozygosity mapping, and fully penetrant, rare, and low-frequency variants were detected by exome sequencing. Weighted sum score and polygenic risk score (PRS) analyses were conducted in MS families (24 affected, 17 unaffected), 23 sporadic MS cases, 63 individuals in 19 non-MS control families, and 1272 independent, ancestry-matched controls. We found that familial MS cases had a significantly higher common risk variation burden compared with population controls and control families. Sporadic MS cases tended to have a higher PRS compared with familial MS cases, suggesting the presence of a higher rare risk variation burden in the families. In line with this, score distributions among affected and unaffected family members within individual families showed that known susceptibility alleles can explain disease development in some high-risk multiplex families, while in others, additional genetic contributors increase MS risk.
Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet’s syndrome (BS) and familial Mediterranean fever (FMF) is ...limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (
p
< 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.
Amaç: Bu çalışmada parenkimal tutulumu olan Nöro-Behçet hastalarında kognitif bozukluk sıklığını ve paternini değerlendirmeyi amaçladık.
Gereç ve Yöntem: Çalışmaya Cerrahpaşa Tıp Fakültesi Nöroloji ...Anabilim dalından takipli ve Cerrahpaşa Nörobehçet tanı kriterlerini dolduran 40 hasta dahil edildi. Olguların nörokognitif fonksiyonları seçici hatırlama testi, PASAT, görsel bellek testi, sembol sayı modaliteleri testi ve kelime akıcılığı testlerinden oluşan Brief Repeatable Battery of Neuropsychological Tests (BRB-N) ile değerlendirildi. Elde edilen sonuçlar daha önce normatif data oluşturulmak üzere kullanılan sağlıklı grup ile kıyaslandı.
Bulgular: Hasta grubun ortalama hastalık yaşı 39.48±10.66 idi ve Behçet tanısından ortalama 3.3 yıl sonra Nöro-Behçet hastalığı tanısı almışlardı. Erkek hakimiyeti mevcuttu. Hasta grubun tüm nöropsikolojik test sonuçları sağlıklılara kıyasla bozulmuştu. %60 hastada dikkati sürdürmede bozulma, %55 hastada görsel hafızada etkilenme, %45 hastada yürütücü işlevlerde etkilenme, %23.5 hastada sözel hafızada etkilenme saptandı.
Sonuç: Her iki hastadan birinde kognitif bozukluk tespit edildi. Gözlenen bu etkilenme sıklık sırasına göre dikkat, görsel hafıza ve yürütücü işlevlerdeydi. Bu yüksek prevelanstan dolayı Nörobehçet hastalarının klinik takibinde kognitif fonksiyonlar göz önünde bulundurulmalıdır.
OBJECTIVE:We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed.
METHODS:Patients whose common immunosuppressive ...medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis.
RESULTS:Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0–7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0–180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0–180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0–7.0; median duration 39.0 months, range 16.0–104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation.
CONCLUSION:We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome.
CLASSIFICATION OF EVIDENCE:This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability.
Purpose: Despite its implications for quality of life, temperament, and character in multiple sclerosis are underexplored. We aimed to explore temperament and character traits, their association with ...clinical characteristics, and explore the factors that impact depression in patients with relapsing-remitting multiple sclerosis (RRMS).Material and Methods: This cross-sectional study enrolled 67 patients (male/female=12/55) (median age=30 (18-53)) and 50 age-and gender-matched healthy controls (HCs) (male/female=16/34) (median age= 26.5 (18-60)) using a convenience sampling method. Temperament and Character Inventory, Beck Depression and Beck Anxiety Inventories, and Structured Clinical Interview for DSM-Axis I Disorders-SCID-I were applied. Results: In the patient group there were 45 MS patients with no psychiatric comorbidity (MSN) and 22 MS patients with psychiatric comorbidity (MSP). Higher self-forgetfulness was observed in the MSP group compared with MSN and HC groups. MSP and MSN demonstrated higher total harm avoidance than HCs. MSP group showed lower total self-directedness compared with HCs. While EDSS, duration of disease, or the number of relapses did not impact depression scores; higher anxiety (Β=0.416) and lower purposefulness (Β=-1.565) significantly impacted them (R2=.50, F=32.459). Conclusion: Temperament and character differences were observed in patients with and without psychiatric comorbidity. Higher anxiety levels and the difficulty to establish and attain meaningful goals may relate to higher depression levels. Future studies with larger samples examining coping, health behaviors, and resilience as potential mediators or moderators between self-forgetfulness and psychiatric disorders may aid in defining interventions for psychiatric disorders. Adequate treatment of anxiety symptoms and addressing purposefulness are potential targets for planning behavioral interventions.
Amaç: Yaşam kalitesi üzerindeki etkilerine rağmen, multipl sklerozda mizaç ve karakter yeterince araştırılmamıştır. Mizaç ve karakter boyutlarını, i, bunların klinik özelliklerle ilişkisini ve depresyon şiddetini etkileyen faktörleri tekrarlayan ve düzelen multiple skleroz (TDMS) hastalarında incelemeyi amaçladık. Gereç ve Yöntem: Bu kesitsel çalışmaya, elverişli örnekleme yöntemiyle 67 hasta (erkek/kadın=12/55) (medyan yaş=30 (18-53)) ve yaş ve cinsiyet açısından eşleştirilmiş 50 sağlıklı kontrol (SK) (erkek/kadın=16/34) (medyan yaş= 26.5 (18-60)) alındı. Mizaç ve Karakter Envanteri, Beck Depresyon ve Beck Anksiyete Envanterleri, DSM-Eksen I Bozuklukları için Yapılandırılmış Klinik Görüşme uygulandı. Bulgular: Hasta grubu içinde, psikiyatrik komorbiditesi olan 45 (MSP), psikiyatrik komorbiditesi olmayan (MSO) 22 hasta bulunuyordu. MSP grubu, MSO grubuna ve SK’lere göre daha yüksek kendilik kaybı gösterdi. MSP grubu ve MSO grubu toplam zarardan kaçınma puanları SK’lere kıyasla yüksekti. Toplam kendini yönetme puanları MSP grubunda SK’lerden düşüktü. EDSS, hastalık süresi, toplam nüks sayısı depresyon şiddetini etkilemezken; yüksek anksiyete (Β=0,416) ve düşük amaçlılık düzeyleri (Β=-1,565) depresyon düzeyini anlamlı derecede etkilemekteydi (R2=0.50, F=32.459). Sonuç: Komorbid psikiyatrik bozukluğu olan ve olmayan hastalar arasında mizaç ve karakter özellikleri açısından farklılıklar gözlendi. Artmış anksiyete düzeyleri; anlamlı hedefler belirleme ve bunlara ulaşmada güçlük, artmış depresyon düzeyleriyle ilişkili olabilir. Gelecek çalışmalar, daha geniş örneklemlerde, baş etme, sağlık davranışları ve dayanıklılığın kendilik kaybı ve psikiyatrik bozukluklar arasındaki aracı ve düzenleyici rolünü inceleyerek, psikiyatrik bozukluklara yönelik müdahalelerin tanımlanmasına yardımcı olabilir. Anksiyete belirtilerinin etkin tedavisi ve yaşam amaçlarının ele alınması, davranışsal müdahalelerin planlanması için olası hedeflerdir.
Background Multiple sclerosis (MS) has a complex pathophysiology, variable clinical presentation, and unpredictable prognosis; understanding the underlying mechanisms requires combinatorial ...approaches that warrant the integration of diverse molecular omics data. Methods Here, we combined genomic and proteomic data of the same individuals among a Turkish MS patient group to search for biologically important networks. We previously identified differentially-expressed proteins by cerebrospinal fluid proteome analysis of 179 MS patients and 42 non-MS controls. Among this study group, 11 unrelated MS patients and 60 independent, healthy controls were subjected to whole-genome SNP genotyping, and genome-wide associations were assessed. Pathway enrichment analyses of MS-associated SNPs and differentially-expressed proteins were conducted using the functional enrichment tool, PANOGA. Results Nine shared pathways were detected between the genomic and proteomic datasets after merging and clustering the enriched pathways. Complement and coagulation cascade was the most significantly associated pathway (hsa04610, P=6.96x10.sup.-30 ). Other pathways involved in neurological or immunological mechanisms included adherens junctions (hsa04520, P=6.64x10.sup.-25 ), pathogenic Escherichia coli infection (hsa05130, P=9.03x10.sup.-14 ), prion diseases (hsa05020, P=5.13x10.sup.-13 ). Conclusion We conclude that integrating multiple datasets of the same patients helps reducing false negative and positive results of genome-wide SNP associations and highlights the most prominent cellular players among the complex pathophysiological mechanisms.
Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and ...course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Behçet’s Syndrome (BS) is a multi-system, vascular-inflammatory disease of unknown origin, involving the nervous system in a subgroup of patients. The growing clinical and imaging evidence suggests ...that primary neurological involvement in BS may be subclassified into two major forms: the first one, which is seen in the majority of patients, may be characterized as a vascular-inflammatory central nervous system (CNS) disease, with focal or multifocal parenchymal involvement mostly presenting with a subacute brainstem syndrome and hemiparesis; the other, which has few symptoms and a better neurological prognosis, may be caused by isolated cerebral venous sinus thrombosis and intracranial hypertension. These two types rarely occur in the same individual, and their pathogenesis is likely to be different. Isolated behavioral syndromes and peripheral nervous system involvement are rare, whereas a nonstructural vascular type headache is relatively common and independent from neurological involvement. Neurologic complications secondary to systemic involvement of BS such as cerebral emboli from cardiac complications of BS and increased intracranial pressure due to superior vena cava syndrome, as well as neurologic complications related to BS treatments such as CNS neurotoxicity with cyclosporine and peripheral neuropathy with the use of thalidomide or colchisin are considered as secondary neurological complications of this syndrome. As the neurological involvement in this syndrome is so heterogeneous, it is difficult to predict its course and prognosis, and response to treatment. Currently, treatment options are limited to attack and symptomatic therapies with no evidence for the efficacy of any long term preventive treatment.
PDF
