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Cognition and mental health

Dissociative states and MS

This MS-related group of symptoms is probably neglected in routine MS neurological practice and may fall through the cracks.

Key points

  • Dissociative states in people with MS may arise for different reasons: organic (resulting from damage to the temporal and parietal lobes), psychogenic (following psychological trauma) or iatrogenic (induced by drug treatments).
  • Such states range from transient feelings of unreality to recurring episodes of depersonalisation and/or derealisation. Other presentations may also occur.
  • Depersonalisation feels like being detached from one’s own body or thoughts, feeling like an ‘outside observer’ of one’s life.
  • Derealisation feels like being detached from the external world, which may appear foggy, dreamlike, lifeless or two-dimensional.
  • In MS, dissociation often has a physical (organic) basis in the brain. This article explores the specific effects of damage to each of the four lobes of the human brain.
  • Managing dissociative states in MS requires a dual approach: biological (treating the underlying MS disease) and psychological.
  • To differentiate between physical and psychological causes, doctors must consider the possibility of an MS relapse, an infection or the effects of an MS-related treatment. Checks for balance, hearing and psychological screening are also needed.

Causes and range of dissociative states

People with MS have an elevated risk of experiencing dissociative phenomena that give rise to alterations of consciousness, self-perception and reality testing (being able to assess what is real versus what is imagined). These dissociative states − ranging from transient feelings of unreality to chronic depersonalisation−derealisation disorder (DPDR) and non-epileptic seizures − are often undiagnosed. They may arise for different reasons.

  • Organic dissociation results from damage(lesions)to the temporal and parietal lobes, which can disrupt neural networks responsible for ‘embodied self-awareness’ (the constant experience of oneself through physical sensations, emotions and bodily signals).
  • Psychogenic dissociative states can occur in people with MS following the psychological trauma of diagnosis and the high prevalence of comorbid post-traumatic stress disorder (PTSD).
  • Iatrogenic dissociative states can be induced by drug treatments, particularly high-dose corticosteroids and psychoactive symptomatic treatments.

Dissociation is typically characterised by disruption in the normal 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 depersonalisation−derealisation.

Depersonalisation (the fragmentation of self)

Depersonalisation is characterised by a persistent or recurring feeling of being detached from one’s own body or thoughts. People with MS describe this as feeling like an ‘outside observer’ of their life, like watching oneself in a movie, or like a ‘robot’ with no control over their speech or actions. In MS, depersonalisation is associated with damage to the parietal lobe or the spinal cord – areas that help the brain detect body position and movement (proprioception). People with damage to these areas may feel as though a limb does not belong to them. This is not a delusion, because the person may see their limb move and intellectually know it is theirs. Rather, it is a sensory problem with the ‘body schema’ (the brain’s internal map of your body), that no longer matches your physical body.

Derealisation (the distortion of the world)

Derealisation involves a feeling of being detached from your surroundings. The external world may appear foggy, dreamlike, lifeless, colourless or artificially two-dimensional. Objects may appear distorted in size or shape; sounds may seem muted or distant. Derealisation is often worsened by sensory problems in people with MS (affecting sight, sound, touch, taste, smell or movement). Optic neuritis, a common early sign of MS, causes visual blurring, reduced colour intensity and visual field defects (gaps); see Colour vision and Driving at night. When the brain receives unclear visual input, it struggles to construct a vivid, real-feeling model of the environment, which can lead to a secondary sense of derealisation.

Problems with balance (vestibular dysfunction, leading to vertigo, dizziness and gait instability) are often associated with derealisation; conflicting signals from the eyes and inner ear can cause people with MS to feel disoriented. 

Non-epileptic seizures

Non-epileptic seizures, also referred to as dissociative seizures, resemble epileptic seizures − involving convulsive movements, apparent loss of consciousness and stiffening of the body. However, they are not caused by abnormal electrical activity in the brain (usually visible on an electroencephalogram) but are psychological, most likely a mechanism for managing distress or trauma. Care is needed to determine the correct cause in each individual because people with MS are actually at increased risk for epilepsy due to brain lesions. Studies of magnetic resonance imaging (MRI) scans suggest that damage in the right brain hemisphere or the frontal lobes may increase the risk of non-epileptic seizures.

Dissociative amnesia and brain fog

Dissociative amnesia is the inability to recall important personal information, far beyond ordinary forgetting. It is usually related to stress or trauma. In MS, this poses a diagnostic challenge because many patients already experience cognitive dysfunction that affects processing speed and working memory. A study differentiating organic (‘true’) memory loss from dissociative amnesia in MS found that people who reported memory problems often had high levels of dissociation and anxiety but did not show major problems on formal memory testing.1 This implies that the ‘memory loss’ experienced by many people with MS may be an attention problem due to a mild dissociative state or emotional overload, rather than a result of permanent damage to memory structures in the brain.

Dissociative identity disorder

While rare, cases of dissociative identity disorder (DID) have been reported in people with MS. DID is characterised by the presence of two or more distinct personality states. Affected individuals typically have experienced childhood trauma, which makes them more prone to develop dissociation. A diagnosis of MS acts as a further stressor that challenges their sense of identity. Other symptoms of DID may include physical weakness and sensory loss, which can mimic an MS relapse and lead to misdiagnosis. 

Underlying disease processes in MS

In the general psychiatric population, dissociative disorders are usually regarded as psychological in origin. In MS, however, dissociation often has a physical basis in the brain. MS damages myelin (the protective covering of nerve fibres), severs nerve connections and affects grey matter, all of which disrupts communication between different brain regions. When these connections are broken, the brain cannot integrate sensation, emotion and thought into a conscious experience.

Structure of the brain

Structure of the brain, showing the left and right cerebral hemispheres (left) and the four lobes (frontal, parietal, temporal and occipital; right) in each cerebral hemisphere. Each individual lobe has particular key roles; however, they do not function in isolation but as part of a wider system of neural networks. From Gemini Pro.

Temporal lobe

The temporal lobes play a central role in processing memory and emotions as well as in combining auditory and visual information. MS-related damage in these areas is associated with psychiatric symptoms, including psychosis and dissociation. The temporal lobe also houses the limbic system, comprising the amygdala (which processes emotion) and the hippocampus (which supports memory). If there is damage to the white matter pathways between the limbic system and the frontal cortex (a region known as the uncinate fasciculus) or to sensory regions, the emotional content of experiences can be lost. For example, when a person with MS sees a familiar object or person, the visual cortex sends information to the limbic system, thus activating the appropriate emotional response (e.g. warmth, recognition). If MS disrupts this connection, the person may recognise the object but feel no emotional familiarity. This mismatch, i.e. recognition without feeling, is central to derealisation and to the jamais vu phenomenon (the strange feeling that something familiar is suddenly unfamiliar or new) that is often reported in temporal lobe disorders.

sagittal

A sagittal (longitudinal) view of the human brain showing the interconnected network of the limbic system, a key regulator of emotion, memory and spatial navigation. From Gemini Pro 3.0.

Temporal lobe epilepsy

MS lesions in the temporal lobe can sometimes trigger epileptic activity. Even in the absence of full-blown convulsions, abnormal electrical activity there can cause ‘dreamy states,’ profound déjà vu or feelings of unreality similar to the warning phase (aura) of temporal lobe epilepsy. Symptoms of depersonalisation disorder overlap with those experienced in temporal lobe epilepsy, particularly unusual body experiences and memory distortions.

Parietal lobe

The parietal lobe combines sensory information from different sources to form a single perception (cognition) and helps the brain build a map of the body and the world around us. The brain constantly updates this map, or ‘body schema’, using signals from the spinal cord. MS lesions in the parietal lobe or spinal cord can interrupt this information and deprive the brain of body map data.

When the brain ceases to receive reliable input from a limb, because of MS-related damage, it may ‘dissociate’ that body part from its self-image. This can manifest as:

  • asomatognosia (the inability to recognise a part of one’s own body)
  • somatoparaphrenia (the delusion that a limb belongs to someone else)
  • depersonalisation (see above).

Temporoparietal junction

The temporoparietal junction, where the temporal and parietal lobes meet, is a hub for integrating balance, visual and somatosensory signals to locate the ‘self’ in space. Electrical stimulation of this area can cause out-of-body experiences. In MS, lesions affecting the temporoparietal junction or the balance pathways in the brainstem can trigger dissociative events (for example, a feeling of floating above one’s body or viewing oneself from outside. These episodes are often linked to balance problems, suggesting that the brain is trying to make sense of conflicting signals.

Occipital lobe

The occipital lobe is the main visual processing centre of the brain. Damage in this region or in visual pathways can lead to complex visual distortions that trigger derealisation. ‘Alice in Wonderland Syndrome’ is a perceptual distortion in which objects appear much smaller (micropsia) or much larger (macropsia) than they really are. When damage from MS affects the visual association areas, vision may appear two-dimensional, with the world looking ‘flat’ or like a painted backdrop. This loss of depth perception contributes to the feeling of living in a movie or a simulation.

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 people with MS have extensive brain lesions but relatively normal movement and minimal disability scores. While these patients may appear physically ‘fine’, lesions in high-level areas of the cortex (frontal, parietal and temporal lobes) can disrupt cognitive and emotional networks.  Such individuals may be at high risk for subjective dissociation − feeling fragmented or cognitively detached − while objective observers (and disability scales) fail to register any deficit. These hidden symptoms can worsen the patient’s sense of isolation and unreality.

Trauma-related causes

Receiving a diagnosis of MS

While localised MS lesions create the ‘hardware failure’ in the brain that enables dissociation, psychological factors often provide the ‘software trigger’. Receiving a diagnosis of MS may be considered a medical trauma, often involving invasive procedures (lumbar punctures), frightening MRI experiences (claustrophobia) and hospitalisations. These repeated exposures to threat and a feeling of helplessness and vulnerability can induce a state of chronic hyperarousal and subsequent dissociation, consistent with the dissociative subtype of PTSD. Many people with MS meet the diagnostic criteria for PTSD specifically related to their MS diagnosis and outlook (please see, How common is post-traumatic stress disorder in people with MS?). Developing an ongoing, incurable and potentially disabling neurological condition can shatter one’s expectations for the future. By detaching from the reality of their diagnosis, people with MS may attempt to shield themselves from overwhelming anxiety and grief. Dissociation serves as an adaptive defence mechanism – a ‘mental flight’ when physical flight is impossible. This sounds dramatic, but it may explain why some people with MS develop dissociative disorders. 

Childhood trauma

Research has demonstrated a potential relationship between childhood trauma, dissociation and the development of MS. Severe stress, neglect or abuse in childhood permanently dysregulates the hypothalamic−pituitary−adrenal axis (a system that is crucial for the body’s stress management). It consists of three organs that each release hormones to eventually raise cortisol levels in the body. This results in a chronic proinflammatory 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.2

Treatment-related 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.

Corticosteroids. High doses of the intravenous corticosteroid methylprednisolone (e.g. 1000 mg daily for 3−5 days) are the standard of care for speeding up the recovery from acute MS relapses. It is known to cause acute psychiatric adverse effects in many patients (dependent on the corticosteroid 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; some develop acute psychosis with hallucinations and confusion. Corticosteroids enhance dopamine activity. They may cause acute, reversible reductions in hippocampal volume. Their effect on the brain presumably decouples the patient from reality, leading to a temporary dissociative or psychotic state that resolves upon tapering the steroid dosage.

Interferon-beta has a longstanding association with depression and anxiety. Interferons are cytokines that induce a proinflammatory response similar to ‘sickness behaviour,’ which includes social withdrawal, fatigue and anhedonia (inability to feel pleasure in activities that are usually considered to be pleasurable). 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 the onset of stress-induced depersonalisation.

Natalizumab is a highly effective monoclonal antibody, but it carries specific risks. The ‘wearing off’ effect in the week preceding the next infusion can be characterised by intensifying fatigue, cognitive fog and mood instability, which may manifest as a feeling of detachment or unreality.  The most severe risk associated with natalizumab is progressive multifocal leukoencephalopathy; this 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. This condition involves swelling in the posterior brain regions (parietal/occipital lobes) caused by leakage of fluid from capillaries. It presents with acute confusion, visual changes, headaches and altered consciousness − a constellation of symptoms that could mimic derealisation and dissociation.

Symptomatic treatments. 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 people with MS to manage neuropathic pain, can cause sedation and cognitive clouding (‘zombie-like’ feeling) that contribute to depersonalisation.

Diagnosis

When someone with MS develops dissociative symptoms, doctors must first rule out physical (organic) causes before assuming the problem is purely psychological. A diagnostic algorithm should do the following.

1. Rule out an MS relapse
Any new onset of psychiatric or dissociative symptoms warrants an MRI scan with gadolinium. New lesions in the temporal, parietal or frontal lobes can directly cause these symptoms.

2. Rule out infection
Urinary tract infections are extremely common in MS and are the leading cause of acute confusional states (delirium) that can mimic dissociation. A urinalysis and a workup for other infections are mandatory.

3. Review medication
Assess for recent steroid use, cumulative damage from anticholinergic drugs (e.g. for bladder dysfunction) or withdrawal from muscle relaxants (baclofen and tizanidine).

4. Check balance and hearing
‘Neuro-otological examination’ is a specialised assessment for dizziness, vertigo, hearing loss and balance disorders. Checking for nystagmus (uncontrollable eye movements) helps to diagnose balance disorders. Treating vertigo may resolve the derealisation.

5. Carry out psychological screening
Your health professional can use the Dissociative Experiences Scale (DES-II) or the Dissociative Disorders Interview Schedule to quantify symptom severity. People with MS generally score in the normal range on DES-II unless they have comorbid DID or PTSD.

Differentiating organic from psychiatric dissociation is difficult. It may require referral to a neuropsychiatrist. MS-related brain fog or cognitive impairment with an organic basis is characterised by slowed processing speed, word-finding difficulties and fatigue. Patients try to engage but fail. In comparison, psychiatric 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: biological (i.e. treating the underlying MS disease) and psychological. 

Drug treatments

The primary prevention of organic dissociation involves preventing new lesion formation. High-efficacy DMTs are the best way to preserve brain volume and connectivity. Psychotropics such as selective serotonin reuptake inhibitors (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 (e.g. carbamazepine and oxcarbazepine) can be used to treat both seizures and depersonalisation; they are particularly beneficial in patients with temporal lobe pathology. 

Psychological interventions

Cognitive behavioural therapy 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. Modified (e.g. ‘titrated’) EMDR protocols can prevent flooding the patient with traumatic memories before they have stabilisation skills. EMDR is available via some UK NHS psychiatric services. 

Grounding and mindfulness techniques (e.g. holding an ice cube, describing the environment) anchor the patient in the present moment and help them to manage acute episodes of derealisation. Mindfulness-based stress reduction has shown efficacy in improving the quality of life and reducing depressive symptoms in people with MS.

Vestibular rehabilitation therapy (VRT) is a specialised, exercise-based physical therapy designed to reduce vertigo, dizziness and imbalance. It should be offered to people with MS where derealisation is driven by vertigo. VRT helps the brain compensate for inner-ear deficits through personalised exercises that focus on gaze stabilisation, balance training and habituation. Physical therapy to improve balance and gaze stability can directly reduce the feeling of unreality. 

Conclusions

To self-manage dissociative states effectively, individuals with MS can proactively apply several key principles highlighted above. During acute episodes of derealisation or dissociation, employing practical grounding and mindfulness techniques – such as holding an ice cube or actively describing the immediate environment – can serve as vital tools to anchor oneself in the present moment. Furthermore, individuals can apply cognitive behavioural principles by ‘reframing’ their experiences. Recognising that terrifying feelings of ‘disappearing’ or ‘going crazy’ are often harmless symptoms of anxiety or the disease itself can help reduce the catastrophic thinking that perpetuates dissociation.

Effective self-management also involves staying vigilant about physical triggers (e.g. monitoring for signs of urinary tract infections or medication side effects) and pursuing targeted physical interventions, such as vestibular rehabilitation exercises, if feelings of unreality are driven by dizziness and balance issues. By combining these practical coping strategies with a clear understanding of the biological and psychological origins of their symptoms, individuals with MS can regain a sense of control and significantly reduce the impact of dissociative states on their daily lives.

References

  1. Bruce J, et al. Self-reported memory problems in multiple sclerosis: influence of psychiatric status and normative dissociative experiences. Arch Clin Neuropsychol 2010;25:39–48.
  2. Rehan ST, et al. Association of adverse childhood experiences with adulthood multiple sclerosis: A systematic review of observational studies. Brain Behav 2023;13:e3024.
Bladder and bowel, Intimate issues

Intimate issues: bladder dysfunction

Bladder dysfunction in people with MS is a sign of early damage, particularly to the spinal cord, and an early indication of a poor prognosis. Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? Here, I explain why I take bladder problems seriously and their implications for MS management.

Key points

  • Urinary hesitancy, urgency, frequency and incontinence, including at night, are bladder problems that affect many people with MS and cause significant frustration and anxiety.
  • A range of drug-based treatments, behavioural techniques and specialist physical interventions can help people with MS to manage bladder dysfunction and achieve adequate control.
  • However, the bladder pathways will probably continue to be affected in the long term due to the development of new lesions or the expansion of old lesions.
  • Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress.
  • I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.
  • Lifestyle approaches, such as avoiding smoking and reducing alcohol and caffeine consumption, should help to reduce bladder symptoms. Pelvic floor exercises are also important.
  • Dehydration is not a good way to control your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms.

Causes and significance of bladder dysfunction

Bladder dysfunction is the most common symptomatic problem I encounter in an MS clinic, affecting more than 50% of people with MS. It is one of the signs of early damage, particularly spinal cord damage, and an early indication of a poor prognosis. It therefore has important implications for treatment: if you have early bladder symptoms, you may want to take a more effective therapy early on rather than starting on a less effective DMT and waiting to see how you respond. It is best to maximise your chances of responding to treatment by opting for a highly efficacious therapy first-line. I call this ‘flipping the pyramid’.

Infections, both viral and bacterial, are a known trigger of relapse in MS. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce UTIs. You can read more about managing  UTIs here.

Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? The bladder is a complicated organ with several neurological components that need to be coordinated. The descending nerve fibres that travel from the brain to the lower segments of the spinal cord are very long and have the greatest chance of being damaged by MS lesions in their path down to the bladder centre in the sacral area of the lower spinal cord. Therefore, any progressive or worsening MS damage is likely to manifest with bladder dysfunction early on.

The detrusor (or balloon) muscles and the sphincter (or valve) need to coordinate their action to enable normal bladder function. When the bladder is filling, the detrusor muscle relaxes to allow the bladder to expand and the sphincter contracts to keep the urine in the bladder. The opposite occurs when you pass urine; the sphincter opens and the detrusor contracts to empty the bladder.

Common MS-related bladder problems

Hesitancy

Urinary hesitancy occurs when the function of the detrusor and sphincter muscles is not coordinated: you try to pass urine, but the bladder sphincter won’t open. Hesitancy may be intermittent; if you try again later, the bladder will open, allowing you to pass urine. Conversely, the sphincter may close as you pass urine, which breaks up the urine stream or prevents complete bladder emptying; this can cause dribbling. The medical term for incoordination of the bladder muscles is dyssynergia or, more correctly, detrusor-sphincter-dyssynergia (DSD). People with MS find urinary hesitancy and its unpredictability very frustrating.

The drug treatment for DSD includes alpha-blockers (prazosin, indoramin, tamsulosin, alfuzosin, doxazosin and terazosin). Other strategies include small bladder stimulators or vibrators that are placed over the pubic area and work by blocking signals that inhibit the sphincters. The vibrators work in some people with MS and may help relax the sphincter.

Trying to relax when passing urine can help to improve hesitancy. The sound of running water, for example from a tap, may trigger the relaxation of the sphincter. Simulating this in public toilets may not be possible. Some people with MS find pressing on the lower abdomen helps. If all else fails, intermittent self-catheterisation (ISC) may be the only option to manage urinary hesitancy (see below).

Frequency and urgency

In MS the commonest bladder problem is spasticity, or irritability, of the detrusor muscle. The detrusor can’t relax, which prevents the bladder from filling to its maximum capacity. Frequent spasms of the detrusor muscle tell the brain that the bladder is full and you need to pass urine. This causes frequency, i.e. the need to use the toilet many times during the day and night. Frequency often accompanies the symptom of urgency, the need to get to the toilet as quickly as possible to prevent incontinence. 

When urgency is a problem, distraction techniques such as breathing exercises and mental tricks (e.g. counting) may be helpful. If urinary frequency is your main problem, you might try to retrain your bladder by holding on for as long as you can each time before passing urine. The aim is to train the detrusor muscle to expand more to hold on for longer when you need the toilet. These behavioural techniques rarely work for long; MS is a relapsing and/or progressive disease, and the bladder pathways will likely continue to be affected due to the development of new lesions or the expansion of old lesions.

Incontinence

Incontinence occurs when you lose the ability to suppress or ignore the signals from the detrusor muscle with the result that the sphincter relaxes or opens as part of a spinal cord reflex. We typically treat this problem with anticholinergic drugs, e.g. oxybutynin, solifenacin or tolterodine. The older generation anticholinergics such as oxybutynin cross the blood ̶ brain barrier and enter the brain, where they can exacerbate cognitive problems in people with MS. The commonest side effect of anticholinergics is dryness of the mouth; they can also worsen constipation. People with MS must be warned about the risk that anticholinergics will relax the bladder too much and precipitate urinary retention; the solution to urinary retention is ISC. 

The good news is that we now have a relatively new muscle relaxant, mirabegron (Betmiga), which activates the β3 adrenergic receptor in the detrusor muscle. I am increasingly using mirabegron to avoid the side effects (particularly cognitive issues) associated with anticholinergics. The main side effect of mirabegron is that it tends to increase your blood pressure.

Nocturia

Nocturia means you need to get up frequently at night to pass urine. If nocturia is your main bladder problem, using agents to concentrate the urine at night might help. A hormone called DDAVP works on the kidneys to reduce urine production; it is available as a nasal spray or tablets (Desmotabs or Desmospray). DDAVP should only be taken once a day, to avoid continuous water retention by the kidneys; this presents as swelling of the feet and reduces the salt or sodium levels in your blood, which can be dangerous. You therefore need to have your sodium levels checked about 4 ̶ 6 weeks after starting DDAVP therapy. 

Second-line treatments for bladder problems

If you fail to respond to anticholinergics, mirabegron and/or behavioural techniques, you need a bladder scan to see if you have a raised residual volume (the amount of urine left after you have emptied your bladder). If the residual volume is greater than 80 ̶ 100mL you may need to consider intermittent self-catheterisation (ISC). Some continence advisors act at the 80 mL threshold, and others at the 100 mL threshold, when recommending ISC.

Intermittent self-catheterisation

ISC serves two purposes. It increases your functional residual bladder volume, allowing more storage space for urine, which reduces frequency and urgency. This can help if you need to travel some distance or to join in a social activity without having to pass urine. It also helps to reduce nocturia, which in turn improves sleep and possibly MS-related daytime fatigue.

ISC also removes urine from the bladder. The residual urine acts as a culture medium for bacteria; by clearing your bladder you can prevent bladder infections. Conversely, if you don’t do the ISC technique correctly you can introduce bacteria into the bladder that then cause infections.

Botox

Botox injection into the detrusor muscle is increasingly used as a treatment for bladder dysfunction, in conjunction with ISC. Botox paralyses the muscle, turning it into a flaccid bag for urine storage. The surgical techniques that were previously used to remove the nerve supply to the bladder (which had the same effect as Botox) are now rarely used.

Percutaneous tibial nerve stimulation 

Percutaneous (or posterior) tibial nerve stimulation is a form of neuromodulation that can help with impaired bladder function and may improve urinary urgency, urinary frequency and urge incontinence. It is offered as a treatment in specialist neuro-urology units.

Permanent catheterisation

If all else fails, some people with MS may need to be permanently catheterised. This can be done via the urethra or the lower abdominal wall; the latter is called a suprapubic catheter. Being permanently catheterised sounds drastic, but this significantly improves the quality of life in some people with MS. Allowing bladder dysfunction to control your life can result in social isolation and constant anxiety about being incontinent in public. With the above-mentioned strategies, adequate bladder control should be the norm in MS.

In my experience, the biggest hurdle to achieving adequate bladder control is when people with MS assume their bladder symptoms are part of the disease and resign themselves to living with them. Such patients may start using continence pads as if this is normal or inevitable for someone living with MS. This is not normal; incontinence can lead to skin rashes and pressure sores. Please don’t accept this as the norm or something you must live with. If you have problems, tell your MS nurse or neurologist; they can help you.

Anatomy of the human urinary bladder; reproduced from Wikipedia, created by U.S. National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program.

Lifestyle factors that impact your bladder

Smoking, alcohol and caffeine

Nicotine irritates the bladder. If you are a smoker, then stopping smoking may significantly improve your bladder symptoms. Similarly, reducing alcohol and caffeine consumption may help; these agents are diuretics and cause the kidneys to make more urine.

Pelvic floor exercises

One of the treatments recommended to all patients with bladder problems is pelvic floor exercises. These are also important for managing bowel and/or sexual problems. For detailed guidance on incorporating these into your daily life, please see pelvic floor training post.

Avoiding dehydration

Try to anticipate times when urinary frequency and urgency will be most inconvenient; reducing the amount you drink beforehand may help. For example, don’t drink too much for 2 ̶ 3 hours before you go out. After you have finished passing urine, go back to the toilet again after a few minutes to try to pass some more urine. This is called the double micturition technique, which aims to ensure the bladder is emptied completely. However, do not reduce your total fluid intake to less than 1.5 litres each day.

Dehydration is not a good way to control your bladder symptoms. The issue of people with MS dehydrating themselves to manage their bladder problems was highlighted as early as the 1960s by Professor Bryan Matthews, a neurologist in Oxford, in his textbook on MS.

When researching the topic in the 1990s, it became clear to me that people with MS with severe disability were most likely to have bladder dysfunction and were chronically dehydrating themselves to manage urinary frequency, urgency and nocturia. Studies showed that a high urinary concentration of creatinine, a waste product that the kidneys filter out of the blood through the urine, correlated with increased disability levels. Urine containing myelin basic protein-like material (MBPLM), an indicator of myelin damage in MS, was also shown to correlate with disability. It is dehydration that causes higher levels of MBPLM and creatinine in the urine, indicating that dehydration is associated with disability.1 

A more recent paper from researchers in the Southampton group described the same findings, that urinary tract symptoms are very common in people with progressive MS and are associated with inadequate hydration.2

Despite highlighting the issue of chronic dehydration in MS over the years, it remains a persistent problem. My message is clear: don’t use dehydration to manage your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms. Some potential effects of chronic dehydration are listed in the box below.

  1. Physical performance: Dehydration can decrease physical endurance, cause muscle cramps and exacerbate or cause fatigue. This can affect overall physical performance and make everyday tasks more challenging.
  2. Cognitive function: Dehydration has been linked to cognitive impairment, including issues with concentration, alertness and short-term memory. Prolonged dehydration may even contribute to long-term cognitive decline.
  3. Mood and mental health: Studies have shown that dehydration can affect mood and contribute to increased feelings of anxiety and irritability. In severe cases, it can even lead to symptoms resembling depression.
  4. Kidney function: Chronic dehydration can put a strain on the kidneys, potentially leading to the formation of kidney stones and urinary tract infections. It can impair the kidneys’ ability to effectively filter waste from the blood. It also makes you more susceptible to the side effects of non-steroidal anti-inflammatory medications.
  5. Digestive problems: Dehydration can lead to constipation and other digestive issues. It may also contribute to an increased risk of developing peptic ulcers and acid reflux.
  6. Skin health: Inadequate hydration can lead to dry, flaky skin and exacerbate conditions such as eczema and psoriasis. Proper hydration is essential for maintaining overall skin health and elasticity.
  7. Heat-related illnesses: Dehydration reduces your body’s ability to regulate temperature, increasing the risk of heat exhaustion and heat stroke, particularly in hot and humid conditions. Please remember that people with MS, particularly those with more advanced MS, may already have a problem with thermoregulation.

In conclusion

I advise using a holistic approach to managing urinary symptoms, in addition to medication or other aids where recommended. Please review the questions below to check whether you are optimising your self-management.

  • Have you deconditioned your bladder because you are not training yourself to resist emptying it whenever you get the urge to pass urine? The bladder is a muscle that needs to be trained.
  • Have you tried peripherally acting anticholinergics or mirabegron?
  • Have you had a post-micturition bladder scan to see if you are emptying your bladder?
  • Do you need to use intermittent self-catheterisation to increase your functional bladder volume?
  • Do you have a chronic low-grade urinary tract infection? Are you performing regular urine dipstick testing (see post on UTIs and dipstick testing)?
  • Do you have bladder stones?
  • Have you tried DDAVP (Desmotabs or Desmospray) to help concentrate your urine without dehydrating yourself?
  • Are you avoiding bladder irritants or stimulants such as caffeine and nicotine?
  • Are you doing your pelvic floor exercises? If you are a post-menopausal woman, have you tried HRT (hormone replacement therapy)? Pelvic floor tone and bladder function often improve on HRT. 

References

  1. Giovannoni G, et al. Urinary myelin basic protein-like material as a correlate of the progression of multiple sclerosis. Ann Neurol 1996;40:128 ̶ 9.
  2. Kaninia S, et al. Dehydration associates with lower urinary tract symptoms in progressive multiple sclerosis. Eur J Neurol 2024;31: e16175.
Fatigue and insomnia, Sleep disorders

Fatigue in MS – a disabling symptom

Fatigue in MS is common, but it is often not investigated or managed properly. This post highlights the complexity of MS-related fatigue and explains why and how to manage it holistically. 

Key points

  • The different mechanisms underlying MS-related fatigue are explained.
  • The MS disease process, the burden of living with MS, and other factors such as drug side effects, comorbidities and lifestyle choices may all contribute to fatigue in MS.
  • Practical guidance is provided on managing many aspects of MS-related fatigue, using a holistic and systematic approach.
  • Not all fatigue is MS-related; it is important to ascertain if your fatigue could be due to another disease process.

Fatigue is one of the most disabling of all the symptoms of MS. It is the symptom that over 50% of people with MS would most like to be rid of. MS-related fatigue has several underlying mechanisms.

Fatigue caused by MS disease processes

Inflammation in the brain

Inflammatory mediators or cytokines associated with MS – in particular, interleukin-1 (IL-1) and TNF-alpha – trigger ‘sickness behaviour’. This is the response to inflammation that forces us to rest and sleep so that our body can recover. Sickness behaviour is also the body’s response to a viral infection such as flu; in fact, many people with MS describe their fatigue as being like the fatigue they experience with flu. 

Sickness behaviour from an evolutionary perspective is well conserved and occurs in most animals. This type of fatigue needs to be managed by switching off ongoing inflammation in the brain. Many people with MS who take a highly effective DMT report feeling much better and free from fatigue and/or brain fog. This is why recent-onset fatigue that cannot be explained by other factors (see below) may indicate MS disease activity. At present, fatigue on its own does not constitute a relapse.

Many patients with MS who have had COVID-19 tell me that MS-related cog-fog and fatigue feel like the cog-fog and fatigue of COVID-19 and long-COVID. As many as one in four people with long-COVID experience cog-fog, which includes problems in attention, language fluency, processing speed, executive function, and memory: these are the same problems that affect people with MS. 

Cog-fog related to MS and to COVID-19 could be linked to the same inflammatory mechanisms. This syndrome of systemic inflammation causing profound fatigue and cog-fog is not new. Some people with MS who have a systemic infection take weeks or months to return to normal; some patients with more advanced MS never return to their original baseline. This is why, as part of the holistic management of MS, we need to treat and prevent systemic infections as best we can.

The overlap between COVID-19 and MS-related cog-fog raises the question whether both are due to viral infections. There is some evidence of recent Epstein-Barr virus (EBV) reactivation in patients with long-COVID,1 suggesting that the EBV rather than the SARS-CoV-2 may be causing long-COVID symptoms. This is important because chronic EBV infection has been associated with chronic fatigue syndrome. It has also been suggested that chemo-brain is due to similar mechanisms, i.e. chemotherapy triggers CNS inflammation, which causes cog-fog.

Neural plasticity

When parts of the brain are damaged by MS, other areas are co-opted to help take over, or supplement, the function of the damaged area. In other words, people with MS use more brain power than people without MS to complete the same task. This usually manifests as mental fatigue and is why people with MS have difficulty concentrating for prolonged periods and multitasking. At present we have no specific treatment for this type of fatigue, but some patients find amantadine or modafinil helpful. There is also some emerging evidence that fampridine may help with cognitive fatigue. However, preventing damage in the first place should prevent this type of fatigue.

Exercise-related conduction block

Damage to axons that conduct electrical impulses is the reason why people with MS notice their legs getting weaker or another neurological symptom getting worse with exercise. We think this is due to demyelinated or remyelinated axons failing to conduct electrical impulses when they become exhausted. Exercise-induced fatigue is probably the same as temperature-related fatigue; a rise in body temperature also causes vulnerable axons to block and stop conducting. To deal with this type of fatigue we need therapies to promote remyelination and to increase conduction. These types of fatigue are treated by rest, cooling and possibly drugs such as fampridine that improve conduction. At the heart of this type of fatigue is localised energy failure.

Fatigue from living with MS symptoms

Temperature sensitivity

Many people with MS are temperature sensitive. Typically, high temperatures worsen fatigue, but low temperatures also affect some patients. Many people with MS manipulate their behaviour to avoid hot or cold environments. Some find it helpful to use cooling suits, but these are costly and are not covered by NHS funding. Cold or ice baths, swimming and air conditioning can all help with temperature-related fatigue.

Case example

One of my patients had a walk-in butcher’s fridge installed in her house, and she spends 30 minutes there 4 ̶ 5 times a day to manage her fatigue. She is a wheelchair user, and she sits in her wheelchair in the fridge.

Menstrual and menopausal fatigue

Menstrual (or catamenial) fatigue is a form of temperature-related fatigue that occurs in women during the second half of the menstrual cycle when their body temperature increases. It responds to paracetamol and to non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen. Fatigue is a common symptom of menopause too; some women with MS who are menopausal and have fatigue find hormone replacement therapy helpful. 

Whether or not men go through a ‘menopause’ is a moot point. Testosterone levels do drop with age, however, and some male patients find that testosterone replacement therapy helps their MS-related fatigue. In the UK, the indications for testosterone replacement therapy are very well defined and do not include MS-related fatigue, so most people with MS who want to try this therapy need to pay for a private prescription.

Bladder problems

Intermittent waking due to bladder problems may result in fatigue from disrupted sleep. Bladder problems may also contribute to insomnia, with the affected individual needing to visit the bathroom frequently and unable to relax into sleep. For detailed guidance on managing bladder problems, particularly at night, please see the bladder and bowel section of the website, particularly the article on nocturia.  

Insomnia due to pain and discomfort

Other disease-related factors that contribute to fatigue include insomnia from pain, discomfort of being unable to turn in bed and restless legs syndrome (RLS). RLS is common in people with MS, affects sleep quality and is associated with poor cognition. For detailed guidance on managing these MS symptoms, please see the post entitled Sleep disrupted by pain and discomfort.  

A case scenario

“A 28-year-old woman with early relapsing ̶ remitting MS, on glatiramer acetate, and little overt neurological impairment suffers from severe fatigue, which is worse during the latter half of her menstrual cycle. She has recently split up with her long-term partner because of the impact her symptoms have had on her relationship. She has also had to stop working as a bank clerk because of her fatigue.”

Prof G’s response
This patient needs to be examined and will need an MRI and a lumbar puncture to measure her spinal fluid neurofilament levels. If she has evident inflammatory disease activity, her DMT will need to be switched. She needs a full medical assessment, which includes a screen for comorbidities.

The patient complains of cognitive fatigue and, despite not having much physical disability, she was found to have a high brain MS lesion load and noticeable brain volume loss. A formal neuropsychological assessment to establish if she has cognitive impairment would allow her to be referred to a cognitive rehabilitation programme; this can target specific areas to help her cope with her cognitive deficits.

To combat fatigue during her menstrual cycle, this patient did well on naproxen, which is longer acting than ibuprofen and paracetamol. Naproxen only needs to be taken during the second half of her cycle. She was screened for poor sleep hygiene, and she volunteered intermittent early morning waking due to bladder problems and anxiety. Both would need to be addressed as part of her fatigue management programme.

It was clear that the patient had both depression and anxiety, which were related to the impact of MS on her occupational and social functioning. This must be managed with cognitive behavioural therapy (CBT), mindfulness and an exercise programme. If this approach is not helpful, then I would suggest the judicious use of an antidepressant and, failing this, a referral to a psychiatrist and/or psychologist.

Fatigue resulting from other factors

Comorbidities and other diseases

Comorbidities and other diseases related to MS can cause fatigue and should be screened for. These include infections (see above). In people with more advanced MS, the urinary tract is most often affected, but other sites of infection include the sinuses, teeth, lungs, skin (intertrigo and pressure sores) and bowels.

Fatigue is common with thyroid disease; an underactive thyroid gland (hypothyroidism) and an overactive gland (hyperthyroidism, or thyrotoxicosis) cause fatigue. Diabetes, other endocrine (hormonal) problems, anaemia and heart, kidney, liver or lung diseases all cause fatigue.

Side effects of drugs

Fatigue is a common side effect of many medications, particularly drugs that cause sedation and some DMTs. Flu-like side effects from interferon-beta, for example, may make fatigue worse. Anticholinergics and antispasticity drugs are sedating, blunt cognition and may worsen MS-related fatigue. If you have fatigue, therefore, it is important to review your medications. MS is associated with polypharmacy, but some of the medications that cause or exacerbate fatigue can be reduced in dose, stopped or potentially replaced with alternatives that don’t exacerbate fatigue.

Lack of sleep and/or sleep disorders

Poor sleep means you feel tired in the morning. Most people with MS have poor sleep hygiene and almost half have an actual sleep disorder. A clue to this is how you feel in the morning and whether you have excessive daytime sleepiness. If you wake up in the morning and don’t feel refreshed and/or you fall asleep frequently during the day, you need a formal sleep assessment. You can complete the Epworth Sleepiness Scale online to see if you have a problem.

Depression and anxiety

Fatigue is a common symptom of depression and anxiety. Of the many online screening tools for depression and anxiety, the best one to use if you have MS is probably the Hospital Anxiety and Depression Scale (HADS). 

Obesity

Being overweight requires additional energy to perform physical tasks, and obesity itself causes fatigue. Recently an association has been found between obesity and depression. Obesity also predisposes you to sleep disorders; obese people with MS are more likely to have obstructive sleep apnoea. For all these reasons you should engage with lifestyle and wellness programmes to manage obesity and fatigue. 

Deconditioning

Deconditioning is simply the term we use for being unfit. If you are unfit, performing a demanding physical task makes you tired. Deconditioning is treated with exercise, which paradoxically can reduce fatigue. Patients may claim that exercising makes their fatigue worse. Yes, that does happen, but if you persevere and get fitter your fatigue often improves. The important thing is to start a graded exercise programme and build up slowly. Exercise does some incredible things to the brain, many of which explain why it is effective at treating not only fatigue but also depression and anxiety. Exercise is a form of ‘disease-modifying therapy’ and hence everyone with MS should be participating in an exercise programme. 

Poor nutrition and ‘food coma’

Some people with MS are anorexic and eat very poorly; as a result, they have little energy. Although this is quite rare, I have had a few such patients over the years. Similarly, overnutrition may have the same effect. Some of the hormones your gut produces cause you to feel tired and want to sleep; this is the so-called siesta effect (also referred to as food coma or postprandial hypersomnolence). Reducing the size of your meals and changing your eating behaviour may improve this. Postprandial hypersomnolence has two components.

  1. A state of perceived low energy related to activation of the parasympathetic nervous system (which is part of the autonomic nervous system) in response to expansion of the stomach and duodenum from a meal. In general, the parasympathetic nervous system slows everything down. 
  2. A specific state of sleepiness triggered by the hormone cholecystokinin that helps digest food and regulate appetite. It is released in response to eating and to changes in the firing and activation of specific brain regions. The coupling, or interaction, of digestion and the brain is referred to as ‘neurohormonal modulation of sleep’ and it underlies the reflexes responsible for postprandial hypersomnolence. There is therefore a well-studied biological reason why we feel sleepy after eating a meal. 

Managing food coma – practical tips

The first patient who alerted me to the problem of food coma in MS was so affected by postprandial hypersomnolence that she now eats only one meal a day, late in the evening. She can then ‘crash’ and go to sleep about an hour after eating. She needs to be functional during the day but cannot do her professional work if she eats anything substantial during working hours because of her overwhelming desire to sleep. She has tried caffeine, modafinil and amantadine to counteract postprandial hypersomnolence, but all these substances had only a small effect.

Other patients reporting postprandial hypersomnolence derive some benefit from the judicious use of stimulants. You can start by self-medicating with caffeine, but this may have the drawback of worsening your bladder function. Please note, however, that it is not advisable to take stimulants later than about 3 pm or 4 pm because they have a long half-life and can cause insomnia.

Some patients find carbohydrate-rich foods particularly potent at inducing ‘food coma’. Indeed, glucose-induced insulin secretion is one of the drivers of this behavioural response. This may be why people who fast or eat very low-carbohydrate or ketogenic diets describe heightened alertness and an ability to concentrate for long periods. Another option is to reduce your meal size: instead of large meals, try eating multiple small snacks during the day.

Exercise has helped some patients deal with postprandial hypersomnolence. I am not sure exactly how exercise works – possibly by lowering glucose and insulin levels and improving insulin sensitivity. The latter will reduce hyperinsulinaemia, which not only causes postprandial hypersomnolence but is an important driver and component of metabolic syndrome and obesity.

Postprandial hypersomnolence will be worse if you already suffer from a sleep disorder and excessive daytime sleepiness. Most people with MS have a sleep disorder, so there is little point in focusing on postprandial hypersomnolence and ignoring the elephant in the room.

Using your energy effectively

One strategy to manage MS-related fatigue is to imagine your energy levels as a battery, i.e. you have only so much energy in the day. People with MS have smaller batteries than people without MS and therefore need to plan their day and activities to maximise their use of energy. For example, if you do something tiring in the morning, you should rest in the afternoon to conserve energy for evening activities. Similarly, if you find some activities very tiring, such as taking a hot shower or bath, plan to do this in the evening before bed.

Conclusion

It is apparent from this discussion that fatigue in MS is more complex than we realise. So be careful, or at least wary, if your neurologist simply wants to reach for the prescription pad to get you out of the consultation room. Any MS-related symptoms that can affect sleep need to be managed accordingly. Like other MS-related problems, a holistic and systematic approach is needed to manage and treat MS-related fatigue correctly. Not all fatigue is MS-related. This is why it is important to take a step backwards and ask yourself if your fatigue could be due to another disease process.

Reference

  1. Gold JE et al. Investigation of long COVID prevalence and its relationship to Epstein-Barr virus reactivation. Pathogens 2021;10:763.