A 2026 case report from Japan describes a woman in her 50s who was diagnosed with multiple sclerosis (MS) about 31 years after psychosis began. The report examines whether MS may have contributed to unusually difficult-to-treat psychiatric and cognitive symptoms.
The researchers did not conclude that MS caused her schizophrenia. They described the relationship as associative and said their proposed contribution of MS to treatment resistance remains a hypothesis.
How the MS diagnosis emerged
The woman first began feeling watched and developed persecutory delusions shortly after entering university. She later left university. A local clinic diagnosed atypical psychosis three years afterward, but she stopped follow-up without medication and remained untreated for about 13 years.
Fifteen years before the MS diagnosis, she was hospitalized with hallucinations and delusions and diagnosed with schizophrenia. Over the following years, several medicines—including haloperidol, zotepine, injectable paliperidone, olanzapine, lithium and valproic acid—did not adequately or durably control her symptoms.
Neurological events eventually added to the clinical picture. Ten years before the MS diagnosis, she developed left-sided facial weakness. An MRI showed no lesions at that time, and the weakness cleared with steroids. Four years before diagnosis, involuntary tongue and neck movements were identified as drug-induced dystonia.
In the year before the MS diagnosis, an MRI showed a white-matter lesion near the brain’s right lateral ventricle. A follow-up scan about 10 months later showed a new nearby lesion. A few months later, right-sided facial weakness and a new active brainstem lesion appeared. MRI findings and oligoclonal bands in cerebrospinal fluid led to the MS diagnosis.
Psychiatric symptoms did not follow the same course
Before the diagnosis, the patient’s Positive and Negative Syndrome Scale score rose from 68 in May to 84 in August. Her positive symptoms, including delusions, rose from 14 to 20.
High-dose intravenous steroids were stopped on the second day after she became severely agitated, experienced hallucinations and attempted self-harm. The treatment did not improve her psychosis.
After treatment with ofatumumab, she had no further MS relapses or new neurological problems during follow-up. Her persecutory delusions and emotional ups and downs continued, however. Clozapine improved her emotional instability or mood swings, but her delusions persisted. The report described the responses to ofatumumab and clozapine in words rather than follow-up symptom scores.
Why the researchers considered a possible connection
MS is an autoimmune disease in which the immune system attacks myelin in the brain and spinal cord. Lesions can appear as bright spots on MRI, often in white matter. The condition may involve weakness, numbness, vision problems, walking difficulties, depression, fatigue, and memory or thinking problems. Psychosis is less common.
A 2015 systematic review cited estimates of psychotic symptoms among people with MS ranging from 2% to 3% and 4.3% in population-based studies. The report also noted that psychosis associated with MS is not necessarily the same as schizophrenia in its symptoms, course or treatment response.
The researchers pointed to several features that shaped their hypothesis: the timing of the neurological findings, unusually severe attention and executive-function deficits, and biological findings reported in earlier research. Cognitive testing found that the patient’s attention and processing speed, as well as executive function, were significantly lower than average for people with schizophrenia her age.
They also cited a genetic study involving more than 20,000 people that identified risk regions shared by MS and schizophrenia. In addition, a postmortem study of brain tissue from 25 people with schizophrenia found unusually high aquaporin-4 gene activity in three people, whose differing genes were enriched in an MS-related pathway. Those genetic and postmortem findings came from other people, not from the patient in this case.
What the case can—and cannot—show
The report cannot establish when the patient’s MS began. No brain scan was performed when her psychosis started, and an MRI 10 years before the MS diagnosis was clear.
It also cannot show that MS caused her psychosis or treatment resistance, how often the two conditions occur together, or whether MS treatment improves psychiatric symptoms. Attention and executive difficulties are common in schizophrenia and cannot independently indicate MS.
The researchers acknowledged that decades of illness, repeated relapses and years of medication may also have contributed to treatment resistance. The symptom timeline was a clinician’s retrospective sketch rather than a series of continuously measured data.
The case’s main significance is therefore observational: it documents MS diagnosed in a person with long-standing treatment-resistant schizophrenia and raises questions about how neurological disease, cognition and psychiatric symptoms may overlap. It does not replace the separate diagnostic and treatment considerations for either condition.
AI tools were used to assist with the preparation of this article under our editorial standards.
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