Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant-Our Experience and Systematic Review of the Literature.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.

Cervical Artery Dissections-A Demographical Analysis of Risk Factors, Clinical Characteristics Treatment Procedures, and Outcomes-A Single Centre Study of 54 Consecutive Cases.

Cervical artery dissections (CAD) are a common cause of ischemic cerebrovascular events among the younger and middle-aged population. Altogether, CAD counts for up to 15% of all causes of stroke in patients aged 50 or younger. Among the known etiological causes, especially addressing the younger population with mechanical traumas and whiplash injuries are regarded as the main culprits. However, cases of spontaneous dissection are also widespread, with risk factors such as hypertension, migraine, and lifestyle factors increasing the risk of occurrence. Clinically, the symptoms associated with a cerebrovascular event caused by CADs are highly variable and can be classified as either compressive symptoms (such as Horner's syndrome and cervical pain) or stroke syndromes attributable to cerebral ischemia. Therefore, establishing an early diagnosis might be particularly challenging as it requires particular attention and quick clinical reasoning when interviewing the patient. With these certain particularities, our main focus was to conduct a prospective study involving up to 54 patients who were diagnosed with CAD in our clinical facility between January 2015 and December 2022, with the focus of assessing certain individual parameters attributable to each patient and their influence and prognosis value for their short and long term evolution. An important emphasis was placed on parameters such as topographical localization, clinical presentation, severity of the questioned cerebrovascular event, outcomes, and causative factors. Statistical validity tools were applied when possible.