Nightmares as harbingers? Neuropsychiatric symptoms in autoimmune diseases

Inflammation and cytokines can affect the brain and cause symptoms such as intense nightmares in neuropsychiatric lupus.

Can often-overlooked CNS symptoms be early signs?

Neuropsychiatric symptoms, for example, are more common than previously thought in lupus patients

There is growing evidence of a link between peripheral inflammatory processes and a cascade that can lead to neuroinflammation.4 Increased nightmares and hallucinations (also known as daymares or strange daytime perceptions) can herald autoimmune diseases such as systemic lupus erythematosus (SLE), according to an international team led by researchers from the University of Cambridge and King's College London.5

In a survey of 676 SLE patients and 400 clinicians on 29 neurological and psychological symptoms, they found that dream sleep was increasingly disturbed in three out of five SLE patients, with one-third of those affected experiencing this symptom more than a year before the onset of lupus disease. Such nightmares were the most common neuropsychiatric symptom and were described as vivid and particularly frightening (being attacked, trapped, crushed, or falling). One in three additional patients surveyed with other rheumatological diseases also complained of increased nightmares.3,5

Nearly one in four SLE patients reported hallucinations, although in the majority of patients (85%) these only occurred around the onset of the disease or later.

Nightmares and disturbed sleep patterns could be a reflection of increased cerebral arousal related to the immunological inflammation in SLE, the study authors suggest. Patients with neuropsychiatric lupus may also experience epileptic seizures.1 Their hypothesis is consistent with research suggesting that neuropsychiatric lupus is associated with the formation of autoantibodies and cytokines in the central nervous system, as well as a disruption of the blood-brain barrier. This is also consistent with the fact that, for example, nightmares often subside when the SLE flare-up is treated.1

“I feel like Alice in Wonderland...”

A lack of awareness of these connections has a major impact on those affected, their families, and medical providers. Patients who suffer from nightmares and hallucinations are hesitant to disclose this to their doctors because they have never connected them to disease flare-ups.5 "Both patients and physicians tend to avoid discussing psychological and neurological symptoms, especially if they don't understand them as part of an autoimmune disease," says lead author Dr. Melanie Sloan.5

The researchers found that using the term "daymares" (strange daydreams) instead of the stigmatized word "hallucinations" often triggered an "aha" moment in patients. One patient described seeing various things, as if waking up from a dream he no longer remembered. He felt as disoriented as Alice in Wonderland. "When you said the word 'daydream,' it immediately made sense; it's not necessarily frightening..."5

The difficulty with neuropsychiatric lupus, according to the researchers, is that it must be diagnosed clinically. Brain scans and cerebrospinal fluid analyses are often unremarkable and therefore not diagnostic.1 Reports from misdiagnosed patients demonstrate the importance of considering an autoimmune disease such as lupus when changes in REM sleep are observed. Many were initially hospitalized and treated with antipsychotics for psychotic episodes, borderline symptoms, or suicidal thoughts—early signs of a lupus flare that were often not correctly diagnosed until months later. With the underlying rheumatological disease controlled, the psychiatric symptoms soon subsided.5

What about other rheumatological diseases?

Several of the researchers were also involved in the data-rich INSPIRE study – an investigation into the frequency and impact of neuropsychiatric symptoms in rheumatic patients. Similar to the SLE study above, a surprising frequency and range of hidden psychological symptoms also emerged in the context of other systemic autoimmune diseases (SARDs). The study included 1,853 patients (with SLE, inflammatory arthritis, vasculitis, SS, PMR, UCTD, myositis, and SSc), 463 control subjects, and 289 physicians who cared for them. Fifty-five percent of SARD patients reported currently suffering from depression, and 57 percent reported anxiety.2

An important message from this study: 74% of patients reported never/very rarely being asked about these symptoms in the clinic. More than 50% of SARD patients had never/very rarely reported their psychological symptoms to clinicians, a proportion that was greatly underestimated by clinicians (<10%).2

There appears to be a self-reinforcing cycle whereby neuropsychiatric symptoms are under-recognized in clinical practice and research, under-reported in clinical trial results, and rarely, if ever, included in SARD criteria/guidelines.1 Most research projects over the past century have not focused on patient experience, explains Dr. Sloan.

The link between brain inflammation and mental health

In the coming years, studies could help better understand the interrelated causes and effects of these relationships. There is also growing evidence that a psychiatric illness, an infection, or a stressful life event can induce dysregulation of the immune system and thus promote the onset or flare-up of an autoimmune disease. Such a neuropsychiatric prodrome is associated with many diseases, including multiple sclerosis, various dementia syndromes, and Parkinson's disease.1

Sources
  1. Lupus & Nightmares. The Rheumatologist https://www.the-rheumatologist.org/article/lupus-nightmares/.
  2. Sloan, M. et al. Prevalence and identification of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases: an international mixed methods study. Rheumatology 63, 1259–1272 (2024).
  3. Sloan, M. et al. Neuropsychiatric prodromes and symptom timings in relation to disease onset and/or flares in SLE: results from the mixed methods international INSPIRE study. eClinicalMedicine 73, (2024).
  4. Kölliker-Frers, R. et al. Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell Interactions in Health and Disease. Mediators Inflamm 2021, 9999146 (2021).
  5. “I feel like I’m Alice in Wonderland”: nightmares and ‘daymares’ could be early warning signs of autoimmune disease | University of Cambridge. https://www.cam.ac.uk/research/news/autoimmune-disease-symptoms-nightmares-daymares-hallucinations (2024). letzter Zugriff auf Websites: 18.02.24