Psychotic symptoms prior or concomitant to diagnosis of multiple sclerosis: a systematic review of case reports and case series.

Objective: We aimed to examine the clinical features of psychotic symptoms preceding or concomitant to multiple sclerosis (MS) diagnosis.

Method: From the 1st to 10th of January 2020 a systematic review was conducted through an electronic search of different databases. Results were limited to English, French, German, Italian and Spanish language articles.

Results: We identified 599 titles, and included 32 cases from case-report and case series. One case report from our department was added. The mean age of first psychiatric symptoms was 25.8 ± 10.2 years, the mean age of MS diagnosis was 31.2 ± 10.7 years and the mean delay until MS diagnosis was 2.7 ± 3 years. Most reported symptoms were delusions (81%), auditory hallucinations (59%) and visual hallucinations (50%). Upon the MS diagnosis, immunosuppressive therapy was significantly more effective for psychotic symptoms than antipsychotics (OR = 9.0; 95%CI: 2.15-37; p = 0.002). Diffuse periventricular lesions were found in 95.6% of cases, with mostly temporal or frontal predominant lesions. In cases affected by predominant temporal lesions, 83% of cases presented visual hallucinations (p < 0.05).

Conclusion: Poor response or resistance to antipsychotics treatment should alert clinicians on the need to consider a differential diagnosis. Considering the impact of delay in MS diagnosis further research regarding this subject is warranted.KEY POINTSInsight into the occurrence of psychotic symptoms in multiple sclerosis (MS) is mainly limited to case reports and case series.Delay in MS management between initial psychotic symptoms and the MS diagnosis is 2.73 ± 3 years and 0.8 ± 1.2 years for patients presenting a first episode of psychosis.The resistance and poor response to antipsychotics found in most cases (75%) were associated with an excellent improvement (95%) of both psychiatric and neurologic symptoms with corticosteroids.Prospective studies are needed to investigate the spectrum of psychosis in MS.