Psychotic symptoms in multiple sclerosis (MS) have been infrequently studied, despite the existence of numerous case reports showing inconsistent findings. Our aim was to assess the timing of psychosis onset and examine its characteristics in MS cases.

We conducted a systematic review and meta-analysis according to PRISMA 2020. We searched for case reports and case series of psychosis in MS on MEDLINE through PubMed, Google Scholar, Web of Science, and Cochrane. SPSS 26 was used to perform the data analysis.

Overall, 43 cases were reviewed. Bipolar disorder and schizophrenia (SCZ) were the most frequently observed types. Psychosis was often present before or at the time of MS diagnosis. For patients with prior psychosis before MS diagnosis, those with SCZ were less likely to develop neurologic symptoms compared to those with other psychosis types. Polymorphic delusions were significantly associated with psychosis onset either after or concurrently with MS. Extensive periventricular white matter lesions, cerebellar peduncles, and cerebellar lesions were significantly associated with the onset of psychosis following MS diagnosis. Resistant-treatment psychosis occurred in 59.4% of cases. A favorable outcome was significantly more common in patients with relapsing-remitting MS compared to those with other forms of MS.

Our study highlights the importance of considering MS in patients with psychoses, especially those with SCZ or treatment-resistant psychosis. Some white matter lesions may trigger psychosis after MS diagnosis. While managing psychosis in MS can be challenging, MS-specific treatments have proven effective.

Jean-Martin Charcot (1825-1893) showed little interest in mental disorders, the domain of nineteenth-century alienists. But hallucinations are not confined to the field of psychiatry, and Charcot, who had once tested the hallucinogenic effects of hashish in his youth, went on to describe hallucinations in the course of various neurological conditions as just another semiological element. Most of his or his disciples' writings on hallucinations can be found in his work on hysteria. Hallucinations and delusions were part of "grand hysteria" and occurred at the end of the attack (third or fourth phase). Hypnosis or chemical agents could also induce hallucinations. Charcot and his disciples did not go so far as to emphasize the importance of hallucinations when they evoked past trauma, especially sexual trauma. Charcot's materialistic orientation led him and his disciples-especially D. M. Bourneville (1840-1909), G. Gilles de la Tourette (1857-1904), and the neurologist and artist P. Richer (1849-1833)-to seek hysteria in artistic representations of "possessed women" and in the visions of nuns and mystics. Finally, Charcot recognized the importance of hallucinations in neurological semiology, by means of precise and relevant observations scattered throughout his work. Preoccupied with linking hysteria to neurology, Charcot only scratched the surface of the possible significance of hallucinations in this context, paving the way for the work of his students Pierre Janet (1859-1947) and Sigmund Freud (1856-1939).

Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.

Neuropsychiatric abnormalities may be broadly divided in two categories: disorders of mood, affect, and behavior and abnormalities affecting cognition. Among these conditions, clinical depression, anxiety and neurocognitive disorders are the most common in multiple sclerosis (MS), with a substantial impact on patients' quality of life and adherence to treatments. Such manifestations may occur from the earliest phases of the disease but become more frequent in MS patients with a progressive disease course and more severe clinical disability. Although the pathogenesis of these neuropsychiatric manifestations has not been fully defined yet, brain structural and functional abnormalities, consistently observed with magnetic resonance imaging (MRI), together with genetic and immunologic factors, have been suggested to be key players. Even though the detrimental clinical impact of such manifestations in MS patients is a matter of crucial importance, at present, they are often overlooked in the clinical setting. Moreover, the efficacy of pharmacologic and non-pharmacologic approaches for their amelioration has been poorly investigated, with the majority of studies showing marginal or no beneficial effect of different therapeutic approaches, possibly due to the presence of multiple and heterogeneous underlying pathological mechanisms and intrinsic methodological limitations. A better evaluation of these manifestations in the clinical setting and improvements in the understanding of their pathophysiology may offer the potential to develop tools for differentiating these mechanisms in individual patients and ultimately provide a principled basis for treatment selection. This review provides an updated overview regarding the pathophysiology of the most common neuropsychiatric symptoms in MS, the clinical and MRI characteristics that have been associated with mood disorders (i.e., depression and anxiety) and cognitive impairment, and the treatment approaches currently available or under investigation.

In recent years, epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis. The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis (MS) later in life. It is well known that the immune system plays an important role in the etiopathogenesis of both disorders. Immune disturbances may be similar or very different in terms of different types of immune responses, disturbed myelination, and/or immunogenetic predispositions. A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity. In this review article, we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities. In addition, we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered, especially in the treatment of psychosis that coexists with MS. Autoimmune disorders could precipitate psychotic symptoms, and in this context, autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.

The article presents a clinical observation of a schizophrenia-like disorder in a patient with multiple sclerosis (MS). The patient had highly active MS with a relapsing course, the diagnosis was made based on the McDonald 2017 criteria. During the course of a demyelinating disease of the nervous system, the patient developed an episode of psychotic disorders with symptoms of mutism, hallucinations, delusions and impaired thinking, which was quickly stopped in stationary conditions. This case is of particular interest to neurologists and psychiatrists, since psychotic disorders occur in MS patients and cause difficulties in diagnosis and treatment.