Co-incident primary progressive multiple sclerosis and hereditary spastic paraplegia (SPG4) - a case report.

The cause of progressive disability in Primary Progressive Multiple Sclerosis (PPMS) is unknown. Pathogenic genes have been described in some MS cases that may contribute to progressive disability, independent of immune - mediated mechanisms (Jia et al., 2018). The autosomal dominant SPG4 (Spastin) mutation is the most common genotype in Hereditary Spastic Paraplegia (Solowska and Baas, 2015) and has been found in some patients with Relapsing Remitting Multiple Sclerosis (Mead et al., 2001, Yazici et al., 2013). Here, we describe the novel association of PPMS and the SPG4 (Spastin) mutation, in a patient with a family history of Hereditary Spastic Paraplegia, and discuss the therapeutic implications. While this single case report cannot discrimiate between simple co-occurence and the possibility of a pathogenic association, our report invites larger scale investigation.

Senescence and Inflammatory Markers for Predicting Clinical Progression in Parkinson's Disease: The ICICLE-PD Study.

BACKGROUND: Cognitive decline is a frequent complication of Parkinson's disease (PD) and the identification of predictive biomarkers for it would help in its management. OBJECTIVE: Our aim was to analyse whether senescence markers (telomere length, p16 and p21) or their change over time could help to better predict cognitive and motor progression of newly diagnosed PD patients. We also compared these senescence markers to previously analysed markers of inflammation for the same purpose. METHODS: This study examined the association of blood-derived markers of cell senescence and inflammation with motor and cognitive function over time in an incident PD cohort (the ICICLE-PD study). Participants (154 newly diagnosed PD patients and 99 controls) underwent physical and cognitive assessments over 36 months of follow up. Mean leukocyte telomere length and the expression of senescence markers p21 and p16 were measured at two time points (baseline and 18 months). Additionally, we selected five inflammatory markers from existing baseline data. RESULTS: We found that PD patients had shorter telomeres at baseline and 18 months compared to age-matched healthy controls which also correlated to dementia at 36 months. Baseline p16 levels were associated with faster rates of motor and cognitive decline over 36 months in PD cases, while a simple inflammatory summary score at baseline best predicted cognitive score over this same time period in PD patients. CONCLUSION: Our study suggests that both inflammatory and senescence markers (p16) are valuable predictors of clinical progression in PD patients.