People with MS can report alterations of consciousness, self-perception, and reality testing. Among these neuropsychiatric phenomena, dissociative states—ranging from transient feelings of unreality to chronic depersonalisation-derealization disorder (DPDR) and non-epileptic seizures (NES) - can occur in pwMS and are often undiagnosed.
PwMS have an elevated risk of experiencing dissociative phenomena arising from lesions in the temporal and parietal lobes, which can disrupt neural networks responsible for embodied self-awareness (organic dissociation). Psychogenic dissociative states can also occur as a result of the psychological trauma of diagnosis and the high prevalence of comorbid post-traumatic stress disorder (PTSD) in pwMS. Finally, dissociated states can be induced by pharmacological interventions, particularly high-dose corticosteroids and psychoactive symptomatic treatments (iatrogenic dissociation).
As you know, the prevalence of psychiatric comorbidities in MS is high, with depression and anxiety affecting up to 50% of pwMS. Dissociation is typically defined as a disruption in the integration of consciousness, memory, identity, emotion, perception, body representation, motor control, and behaviour. The most frequently reported dissociative symptoms in the MS population fall under the spectrum of depersonalization-derealisation.
Depersonalisation (the fragmentation of self)
Depersonalization is characterised by a persistent or recurring feeling of being detached from one’s own body or mental processes. PwMS describe this as feeling like an “outside observer” of their life, or as if they are an automaton or “robot” with no control over their speech or actions. In MS, depersonalisation is associated with parietal lobe lesions or spinal cord damage, which disrupts joint position and proprioceptive feedback. PwMS may experience their limbs as “alien” or not belonging to them. Please note that this is not a delusion, as reality testing remains intact, but rather a sensory failure in which the “body schema” (the brain’s internal map of your body) no longer matches the physical body. A patient may see their hand move and intellectually know it is theirs, but lack the subjective feeling of agency or ownership over the movement.
Derealisation (the distortion of the world)
Derealisation involves a subjective sense of detachment from the surroundings. The external world may appear foggy, dreamlike, lifeless, colourless, or artificially two-dimensional. Objects may appear distorted in size or shape; macropsia is when things appear prominent, and micropsia is when they are small. With derealisation, sounds may seem muted or distant. For pwMS, derealisation is frequently exacerbated by sensory deficits. Optic neuritis, a common initial presentation of MS, causes visual blurring, colour desaturation, and visual field defects. When the brain receives degraded visual input, it struggles to construct a vivid, “real-feeling” model of the environment, which can lead to a secondary sense of derealisation. It never ceases to amaze me how often pwMS who have optic neuritis complain of weird visual symptoms. I am sure many of you can relate to this.
Vestibular dysfunction (vertigo) is often associated with derealisation, as a mismatch between visual and vestibular signals can cause pwMS to feel disoriented.
Non-epileptic seizures (NES)
NES, also referred to as dissociative seizures, represents one behavioural manifestation of dissociation. These events resemble epileptic seizures — involving convulsive movements, apparent loss of consciousness, and stiffening of the body — but are not caused by abnormal neuronal discharges on EEG. Instead, these non-epileptiform attacks are psychological and are thought to be a mechanism for managing distress or trauma. The relationship between MS and PNES is complicated by the fact that MS patients are also at a higher risk for epilepsy due to cortical pathology. MRI studies suggest that lesions in the right hemisphere and the frontal lobes may predispose the brain to the generation of non-epileptic seizures.
Dissociative amnesia and brain fog
Dissociative amnesia is the inability to recall important personal information, usually of a traumatic or stressful nature, that is inconsistent with ordinary forgetting. In MS, this poses a diagnostic challenge due to the high prevalence of cognitive dysfunction that affects processing speed and working memory. In a study differentiating organic memory loss from dissociative amnesia in MS, it was found that self-reported memory problems were significantly associated with high levels of dissociation and emotional distress (anxiety), but not with objective performance on neuropsychological tests (see paper below). This implies that what many pwMS experience as “memory loss” is often a failure of attention due to a mild dissociative state or emotional preoccupation, rather than a structural deficit in memory formation or hippocampal function.
Dissociative identity disorder (DID)
While rare, cases of DID, characterised by the presence of two or more distinct personality states, have been documented in pwMS. These cases typically have childhood trauma, which predisposes the individual to develop dissociation, with the onset of MS acting as a further stressor that may destabilise the identity systems. Other symptoms of DID can include functional weakness and sensory loss, which can mimic MS relapses, leading to potential misdiagnoses.
Mechanisms
Unlike dissociative disorders in the general psychiatric population, which are primarily conceptualised as psychogenic, dissociation in MS often has a neuroanatomical correlate. The MS disease processes of demyelination, axonal transection, and grey matter involvement disrupt brain functional connectivity, leading to disconnection syndromes in which the disruption of white matter tracts isolates cortical regions from one another, preventing the integration of sensation, emotion, and cognition into a conscious experience.
The temporal lobes play a central role in memory encoding, emotional processing, and the integration of auditory and visual inputs. Lesions in these areas are associated with psychiatric manifestations in MS, including psychosis and dissociation. The temporal lobe also houses the amygdala (emotion) and the hippocampus (memory). Demyelination in the white matter tracts connecting these limbic structures to the frontal cortex (uncinate fasciculus) or to sensory cortices can disrupt the emotional content of an experience.
When a pwMS perceives a familiar object or person, the visual cortex sends data to the limbic system to retrieve the associated emotional resonance (e.g., warmth, recognition). If MS lesions sever this connection, the pwMS perceives the object accurately but feels no emotional familiarity with it. This mismatch, i.e. recognition without feeling, is the core of derealisation and the “jamais vu” phenomenon (the strange feeling that a familiar situation, word, or place is suddenly unfamiliar and new) often reported in temporal lobe disorders.
Temporal lobe epilepsy (TLE)
MS plaques in the temporal cortex can act as epileptogenic foci. Even in the absence of overt convulsions, erratic electrical activity in the temporal lobes can induce “dreamy states,” profound déjà vu, or feelings of unreality that mimic the aura of TLE. Symptoms of depersonalisation disorder overlap with those experienced in TLE, particularly regarding anomalous body experiences and memory distortions. A case report of a pwMS detailed first-episode psychosis and paranoia directly linked to acute lesions in the temporal lobe. His symptoms, including auditory hallucinations and persecutory delusions (”they are out to get me”), abated with treatment of the MS flare, confirming the organic origin of the dissociative state (Yadav & Zigmond. Temporal lobe lesions and psychosis in multiple sclerosis. BMJ Case Rep. 2010 Oct 12;2010:bcr0120102651).
Parietal lobe
The parietal lobe is responsible for integrating sensory information to form a single perception (cognition) and constructing a spatial coordinate system to represent the world around us. The brain maintains an internal model of the body, or “body schema,” constantly updated by sensory inputs from the spinal cord. MS lesions in the parietal lobe or the posterior columns of the spinal cord deprive the brain of this data.
When the brain ceases to receive reliable input from a limb, it may “dissociate” that body part from the self-image. This can manifest as asomatognosia (the inability to recognise parts of one’s own body), somatoparaphrenia (the delusion that a limb belongs to someone else) and/or depersonalisation (a generalised feeling that one’s physical form is merely a vessel or a machine, distinct from the observing self).
The temporoparietal junction (TPJ) is a hub for integrating vestibular (balance), visual, and somatosensory signals to locate the self in space. Electrical stimulation of the TPJ has been shown to induce out-of-body experiences. In MS, lesions affecting the TPJ or the brainstem vestibular pathways can trigger these dissociative events. The pwMS may feel they are floating above their body or viewing themselves from a third-person perspective. This is often precipitated by vestibular dysfunction; studies indicate a correlation between vestibular disease and derealisation, as the brain attempts to reconcile conflicting spatial data.
Occipital lobe
Lesions in the occipital lobes or the optic radiations can lead to complex visual distortions that can trigger derealisation. Alice in Wonderland Syndrome is a perceptual distortion in which objects appear much smaller (micropsia) or much larger (macropsia) than they actually are. This can occur in MS when lesions involve the visual association areas. PwMS can experience two-dimensional vision; they report that the world appears “flat,” like a painted backdrop. This loss of depth perception contributes to the feeling of living in a movie or a simulation, a feature of derealisation.
Clinico-radiological paradox
The clinico-radiological paradox refers to the discrepancy between the number and volume of MS lesions seen on MRI and a patient’s level of physical disability. Some pwMS possess a massive burden of brain lesions yet maintain relatively preserved motor function (low EDSS scores). While these patients may appear physically “fine,” the “silent” lesions in associative cortices (frontal, parietal, temporal) may disrupt high-order cognitive and emotional networks. This group may be at high risk for subjective dissociation—feeling internally fragmented or cognitively detached—while objective observers (and disability scales) fail to register any deficit. These hidden symptoms can further exacerbate the patient’s sense of isolation and unreality.
Trauma-related aetiologies
While focal MS lesions provide the “hardware failure” that enables dissociation, psychological factors often provide the “software trigger.” MS is an inherently traumatic, chronic, and unpredictable condition that requires psychological adjustment. Receiving a diagnosis of MS should be classified as a medical trauma. Many pwMS fulfil the diagnostic criteria for having PTSD explicitly related to their MS diagnosis and prognosis. I have discussed this issue before on MS-Selfie (please see, ‘How common is post-traumatic stress disorder in people with MS?’, 4-Sept-2021). The onset of a chronic, incurable, and potentially disabling neurological condition affects one’s fundamental assumptions of invulnerability and future planning. In the face of this existential threat, dissociation serves as an adaptive defence mechanism — a “mental flight” when physical flight is impossible. By detaching from the reality of the diagnosis, the pwMS attempt to shield themselves from overwhelming anxiety and grief. I know this sounds dramatic, but it represents one model for why pwMS develop dissociative disorders.
We know that the diagnostic MS journey often involves invasive procedures (lumbar punctures), frightening MRI experiences (claustrophobia), and hospitalisations. These repeated exposures to threat and a feeling of helplessness can induce a state of chronic hyperarousal and subsequent dissociation, consistent with the dissociative subtype of PTSD.
Question: I would be interested to know if any of you have been diagnosed with the dissociative subtype of PTSD?
Childhood trauma
Research has demonstrated the relationship between childhood trauma, dissociation, and possibly the development of MS. Severe stress, neglect, or abuse in childhood permanently dysregulates the hypothalamic-pituitary-adrenal (HPA) axis. This results in a chronic pro-inflammatory state and altered cortisol responses, which may increase biological susceptibility to developing MS later in life. Large-scale cohort studies indicate that women who experienced childhood abuse are significantly more likely to develop MS in the future (see Rehan et al. Association of adverse childhood experiences with adulthood multiple sclerosis: A systematic review of observational studies. Brain Behav. 2023 Jun;13(6):e3024).
Iatrogenic causes
The management of MS involves disease-modifying therapies (DMTs) and corticosteroids for acute relapse management. Many of these agents have significant neuropsychiatric side effects that can mimic, induce, or exacerbate dissociative states. High-dose intravenous methylprednisolone (IVMP) (e.g., 1000mg daily for 3-5 days) is the standard of care for speeding up the recovery from acute MS relapses. It is well-documented to cause acute psychiatric disturbances. Psychiatric adverse effects occur in a large number of patients treated with corticosteroids and are typically dependent on dose. Symptoms often begin with insomnia and euphoria but can progress to severe mood lability, anxiety, and frank dissociation and delirium. Patients may experience a “steroid high” followed by a crash into depression, or develop acute psychosis with hallucinations and confusion. Corticosteroids enhance dopamine activity. They may cause acute, reversible reductions in hippocampal volume. The effect of corticosteroids on the brain presumably decouples the patient from reality, leading to a temporary dissociative or psychotic state that resolves upon tapering the medication.
Interferon-beta has a longstanding association with depression and anxiety. Interferons are cytokines that induce a pro-inflammatory response similar to “sickness behaviour,” which includes social withdrawal, fatigue, and anhedonia. They may also decrease serotonin levels in the brain. While direct dissociation is less common, the severe anxiety and depression induced by interferons presumably lower the threshold for stress-induced depersonalization.
Natalizumab is a highly effective monoclonal antibody, but it carries specific risks. The “crap gap” often reported as a “wearing off” effect in the week preceding the next infusion can be characterised by intensifying fatigue, cognitive fog, and mood instability, which can manifest as a feeling of detachment or unreality. The most severe risk associated with natalizumab is progressive multifocal leukoencephalopathy (PML). PML causes extensive, rapid demyelination that can lead to confusion, personality changes, and cognitive decline. These symptoms can be misinterpreted as psychiatric dissociation or dementia in the early stages.
Fingolimod, an S1P modulator, has been associated with posterior reversible encephalopathy syndrome (PRES). This condition involves vasogenic oedema in the posterior brain regions (parietal/occipital lobes). It presents with acute confusion, visual changes, headaches, and altered consciousness—a constellation of symptoms that could mimic derealisation and dissociation.
Abrupt withdrawal of baclofen and tizanidine, which are used for spasticity, can cause severe delirium, hallucinations, and dissociation. Similarly, gabapentin and pregabalin, which are often used in pwMS to manage neuropathic pain, can cause sedation and cognitive clouding (”zombie-like” feeling) that contributes to depersonalisation.
Diagnosis
Diagnosing a dissociative state in an MS patient requires the exclusion of organic mimics before attributing symptoms to a purely psychogenic cause. A diagnostic algorithm should do the following:
* Rule out an MS relapse: any new onset of psychiatric or dissociative symptoms warrants an MRI with gadolinium. New lesions in the temporal, parietal, or frontal lobes can directly cause these symptoms.
* Rule out infection (delirium): Urinary Tract Infections (UTIs) are extremely common in MS and are the leading cause of acute confusional states (delirium) that can mimic dissociation. A urinalysis and work-up for other infections is mandatory.
* Medication review: assess for recent steroid use, anticholinergic burden (bladder meds), or withdrawal from muscle relaxants (baclofen and tizanidine).48
* Neuro-otological examination: assess for nystagmus and vestibular dysfunction. Treating vertigo may resolve the derealisation.
* Psychological screening: Your HCP can use the Dissociative Experiences Scale (DES) or the Dissociative Disorders Interview Schedule (DDIS) to quantify symptom severity. PwMS generally score in the normal range on the DES unless they have comorbid DID or PTSD, but helping to differentiate organic from psychiatric dissociation is difficult. It may require a referral to a neuropsychiatrist. MS-related cog-fog or cognitive impairment is characterised by slowed processing speed, word-finding difficulties, and fatigue. Patients try to engage but fail.
* In comparison, dissociation is characterised by a subjective sense of detachment (”I am not here”). Patients may have preserved processing speed but feel emotionally disconnected. As noted above, MS cog-fog often contains a dissociative component driven by anxiety. Treating the anxiety usually clears the “cog-fog” more effectively than cognitive rehabilitation alone.
Management
Managing dissociative states in MS requires a dual approach: treating MS, i.e. a biological approach, and using psychological strategies.
Pharmacological Management
The primary prevention of organic dissociation is preventing new lesion formation. High-efficacy DMTs are the best way to preserve brain volume and connectivity. Psychotropics such as SSRIs (e.g., fluoxetine, sertraline) can help manage the anxiety and depression that underlie DPDR. They may also help with MS-related fatigue. Antipsychotics (e.g., quetiapine, olanzapine) may be rarely indicated for managing steroid-induced psychosis or organic paranoia related to temporal lobe lesions. Lamotrigine and other anticonvulsants can be used for both seizures and depersonalization; they are particularly beneficial in patients with temporal lobe pathology.
Psychotherapeutic interventions
Cognitive behavioural therapy (CBT) is the gold standard for treating DPDR. It helps patients reframe the terrifying sensation of “going crazy” or “disappearing” as a harmless, albeit distressing, symptom of anxiety or the disease. This reduces the catastrophic thinking that perpetuates the dissociation.
Eye Movement desensitisation and reprocessing (EMDR) can be effective for MS-related PTSD (medical trauma) or childhood trauma. However, standard EMDR can be overwhelming for patients with dissociation. I have read that protocols can be modified (e.g., “titrated” EMDR) to prevent flooding the patient with traumatic memories before they have stabilisation skills. I have no personal experience with EMDR, but it is available via some NHS psychiatric services.
Grounding and mindfulness are techniques that anchor the patient in the present moment (e.g., holding an ice cube, describing the environment) and help manage acute episodes of derealisation. Mindfulness-based stress reduction (MBSR) has shown efficacy in improving quality of life and reducing depressive symptoms in people with multiple sclerosis (pwMS.
Vestibular rehabilitation should be offered to pwMS where derealization is driven by vertigo, and physical therapy to improve balance and gaze stability can directly reduce the feeling of unreality.
I am writing this newsletter as this is one of the stops on my MS-Selfie Self-Management tube map (version 9.0) that I have not covered before.
This newsletter will form one of the sections in the chapter on psychiatric manifestations of MS, with a link to one of the hidden symptoms of MS. This is yet another MS-related group of symptoms that is probably neglected in routine MS neurological practice and may fall through the cracks.
Questions: Have any of you experienced dissociative symptoms? Did you bring this up with your HCPs? How was it handled? I.e., were you investigated, diagnosed appropriately, and offered treatment for your symptoms? Or is this issue new to you, i.e. is this the first time you have heard about dissociative symptoms being linked to having MS?
Paper
Multiple sclerosis (MS) patients’ self-reported cognitive difficulties do not typically correlate well with objective neuropsychological assessment. The relationship between self-reported memory, dissociation, emotional problems, and objective cognitive functioning was examined in 79 MS patients. Increased self-reported memory problems were significantly associated with higher levels of normative dissociation. Self-reported memory problems were also associated with more reports of depression, anxiety, and neuroticism. Consistent with expectations, self-reported memory was not significantly associated with performance on any of the neuropsychological variables. The present study then evaluated a theoretical causal model with normative dissociation mediating the relationship between emotional problems and perceived cognitive problems. Increased depression, anxiety, and neuroticism were all significantly correlated with more dissociative cognitive failures, which, in turn, were strongly associated with perceived memory problems. Findings have significant theoretical implications for understanding the relationship between perceived and objective cognitive difficulties. Findings are also clinically relevant and suggest that dissociative experiences should be evaluated when MS patients report memory problems.
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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have any problems, please tell your healthcare professional, who can help you.
