Background Multiple Sclerosis typically presents in the third and fourth decades of life and was initially thought not to develop after the age of 50. However, onset after this age is now increasingly recognised. Differentiation of late–onset MS (LOMS) from other age–associated conditions presents a unique diagnostic challenge, and robust epidemiological studies examining long–term outcome in LOMS are lacking. Clearer understanding of LOMS presentation and outcome may facilitate diagnosis and optimise management. In this study we have examined disease presentation, paraclinical investigations and long–term outcome in a population–based cohort of LOMS patients in south–east Wales.

Methods Patients with disease onset at age >49 were identified from a regional MS database, comprising records from 3048 patients, of whom 2654 have MS and 2063 have prospective datasets. Medical notes of LOMS patients were reviewed to ascertain differential diagnoses considered at first presentation. LOMS was compared to adult onset MS (AOMS) using Student's t–test and chi–squared testing for demographic features, and Kaplan–Meier survival analysis to compare time to EDSS 4.0, 6.0 and 8.0. Statistical analyses were performed in SPSS v21.

Results 132 (5.2%) patients had LOMS (age range 50–72). LOMS patients were less likely to be female (57.6% versus 70.4% in AOMS, p=0.003). Primary progressive disease was more common in LOMS (47% versus 8.5%, p<0.0001).

Time from first symptoms to diagnosis was significantly shorter in LOMS patients (2.7 years (standard deviation 2.6) versus 4.6 years (SD 6.3) in AOMS). LOMS patients were more likely to be OCB negative (22.5% vs. 15.7%, p=0.03). Of 44 patients that had spinal MRI, 30 (68.1%) had inflammatory spinal cord lesions.

In 42.3% of LOMS no alternative diagnosis was likely, and diagnosis of MS was made more rapidly than patients with a differential diagnosis (1.8 versus 3.2 years, p=0.005). The most frequent differential diagnoses were cerebrovascular disease (16.2%), degenerative spinal disease (8.1%) and motor neurone disease (6.3%).

At onset, sensory (p=0.003) and cerebellar (p=0.03) symptoms were more common in LOMS, and optic neuritis in AOMS (p<0.001). Annualised relapse rates in the first ten years of disease were lower than in AOMS: 0.17 versus 0.30 (p<0.0001). LOMS patients reached disability milestones faster (EDSS 4:4.8y vs. 15.5y, p<0.001; EDSS 6:5.7y vs. 20.4y, p<0.001; EDSS 8:16.8y vs. 39.0y, p<0.001) but did so between 5.5y and 11.2y older than AOMS.

Conclusions Presentation of MS in older adults is often atypical, with sensorimotor and cerebellar symptoms constituting the predominant clinical syndrome, negative investigations including OCBs, fewer relapses and earlier progression of disability. This may make diagnosis of LOMS problematic. Once LOMS is established, disability progresses more rapidly than in younger onset patients. Although at present there are no effective treatments for progressive neurodegeneration in MS, it is important to identify this group of patients who are likely to require greater input from MS services, and who may benefit from early treatments for progression of disease in the future.