Persons with suspicious onset of multiple sclerosis but with undetermined diagnosis had persistent lower cognition and reduced quality of life.

Backgound: Differential diagnosis of multiple sclerosis (MS) includes a variety of disorders and misdiagnosis is common.

Objective: To follow-up persons with suspected onset of MS but in whom the diagnostic investigation was negative.

Methods: In a prospective study including 271 persons with clinical features of suspected MS onset, 136 persons were diagnosed with MS or clinically isolated syndrome (PwMS), 46 had other disorders, and 89 persons had a negative diagnostic work-up, i.e. persons with undetermined diagnosis (PwUD). They underwent diagnostic reassessment, and those who remained without a diagnosis were investigated for signs of pathology including cognitive tests and assessments of quality of life (QoL). Results were compared with those of PwMS and 24 age and sex matched healthy controls (HC).

Results: After reassement 55 (20%) persons still had undetermined diagnosis (PwUD). They had similar age and gender distribution as PwMS. In 76% of PwUD, the suspected clinical onset included sensory symptoms. PwUD and PwMS scored similarly in cognitive tests and QoL but significantly lower than HC. At 3 years follow-up, PwMS and PwUD improved in most test parameters, but PwUD scored lower than PwMS in cognition.

Conclusion: PwUD constituted the dominating differential diagnosis in persons with suspected clinical onset of MS. QoL and cognition were comparable with those of PwMS but significantly lower than in HC.