Tag Archives: cognitive changes

MS and bipolar disorder: understanding the link

22/02/2026 Gavin Giovannoni

The association between multiple sclerosis (MS) and depression is well-established. Are people with MS also at risk of developing bipolar disorder?

Key points

Bipolar disorder is significantly more common in people with MS than in the general population.
This is not merely a byproduct of the stress of chronic illness; it also has to do with changes in the brain, caused by MS, that affect mood as well as physical function.
Mood symptoms may be caused by MS lesions, disease-related inflammation, or medications (steroids in particular).
Differentiating ‘primary’ (organic) mania from ‘secondary’ (MS-related) mania is crucial to ensure the correct diagnosis and treatment.
Key features that distinguish MS-related mania from organic mania include:
- Late onset, often after age 35–40 years, or onset associated with MS disease progression
- Weak or absent family history of bipolar disorder
- Lack of response to standard treatments for bipolar disorder
Treatment for people with MS who experience bipolar disorder is available and effective. With coordinated care, they can successfully manage their symptoms.

MS affects movement, sensation and other bodily functions, but it also impacts the brain systems involved in thinking, emotions and behaviour. Here, I discuss the relationship between MS and bipolar disorder, a mental health condition that causes episodes of unusually high mood (mania or hypomania) and low mood (depression). Bipolar disorder has received less attention than depression in people with MS, despite its substantial effect on quality of life, treatment adherence and prognosis.

For some people with MS, symptoms of bipolar disorder appear for the first time as their disease develops. In others, existing mood symptoms may be made worse by inflammation, brain lesions or medications used to treat MS. This article explains why bipolar symptoms occur in MS, how they may present, how they can be recognised early and how they can be effectively managed.

How common is bipolar disorder in MS?

Research consistently shows that bipolar disorder is more common in people with MS than in the general population. In the general population, bipolar disorder affects roughly 1–2.4% of people. In MS, studies report current and lifetime prevalence rates of about 3% and 8%, respectively. This means people with MS have approximately double or even treble the usual risk.

Importantly, this increased risk is not simply because people with MS interact with healthcare systems more frequently than the general population, which increases the likelihood of mental health conditions being detected (we call this the ‘admission rate’ bias). Nor is it merely a byproduct of the stress of chronic illness (which might explain depression). Large studies that compare people with MS to similar individuals without MS still show a higher rate of bipolar disorder in the MS group. This suggests the association is real and probably related to changes in the brain caused by MS.

What factors cause MS-related mania?

Researchers believe there are three main mechanisms that drive cognitive and behavioural changes in MS; they can occur alone or together.

MS lesions that affect mood-regulating circuits
inflammation and immune changes
treatment-related factors.

Understanding these mechanisms allows clinicians to distinguish MS-related mania from ‘primary’ (organic) psychiatric illness and to deliver appropriate management.

MS lesions that affect mood-regulating circuits

This mechanism disrupts the ‘hardware’ that controls mood. MS causes inflammation and lesions (scarring) in the brain. Areas that are especially important for controlling emotions and behaviour include:

the right orbitofrontal cortex (OFC) – involved in regulating social behaviour, judgement and impulse control
the temporal lobes – important for memory and emotional processing
the white-matter pathways that connect these regions with deeper emotional and reward centres such as the amygdala and thalamus.

If MS lesions interfere with these circuits, the balance between emotional impulses and rational control can be disrupted. This may lead to behaviours that are characteristic of mania, including disinhibition (reduced ‘internal brakes’), uncontrolled emotions, euphoria (unusually elevated mood) and impulsivity. This pattern is sometimes called secondary mania (mania caused directly by a brain condition such as MS).

There is evidence that right-sided frontal or temporal injury leads to mania-like behaviours in other conditions (e.g. stroke, traumatic brain injury, tumours).

Understanding right- and left-sided brain functions

Consistent with literature on secondary mania from stroke or tumours, MS-associated mania is most often associated with right-sided brain lesions. The right hemisphere is dominant for processing negative emotions and withdrawal behaviours, while the left hemisphere processes positive emotions and approach behaviours. A lesion in the right hemisphere may impair the processing of negative emotions, leading to an unopposed ‘positive’ or euphoric affect (‘highs’) driven by the intact left hemisphere.

Inflammation and immune changes

During MS relapses or periods of immune activation, inflammatory molecules disrupt how brain cells communicate (think of it as a disruption to the brain’s ‘software’). One important system involved is the kynurenine pathway, which controls how the body uses tryptophan (an amino acid essential for the creation of compounds such as serotonin and melatonin).

Inflammation increases the activity of an enzyme called indoleamine 2,3-dioxygenase. This shifts tryptophan away from serotonin production towards production of quinolinic acid, a substance that overly stimulates nerve cells through NMDA receptors (N-methyl-D-aspartate receptors). This ‘excitatory overload’ can lead to symptoms like those seen in primary mania, such as agitation, mood instability, sleep disturbance and racing thoughts.

The kynurenine pathway in inflammation-induced pathology of the central nervous system. Activation of IDO in peripheral immune cells (e.g. macrophages) or in the brain leads to production of kynurenine. This is converted to kynurenic acid in astrocytes and to quinolinic acid in microglia. Kynurenic acid can block the release of glutamate and dopamine, contributing to cognitive dysfunction. Quinolinic acid, by contrast, can increase glutamate release, which contributes to neurodegeneration. Figure modified from Haroon et al.

3-HAO, 3-hydroxy-anthranilic acid oxygenase; IDO, indoleamine-2,3-dioxygenase; KAT II, kynurenine aminotransferase II; KMO, kynurenine-3-monooxygenase; NMDA, N-methyl-D-aspartate.

This pathway is one of the clearest biochemical links between MS inflammation and bipolar-type symptoms.

Treatment-related factors

Some medications used in MS influence mood and may contribute to manic symptoms.

Steroids

High-dose intravenous methylprednisolone, typically 1000 mg/day for 3–5 days, is the most common cause of drug-induced mania in MS. Up to 12% of people treated with corticosteroids experience symptoms of mania, and nearly 65% of those with psychiatric side effects present with a mix of mania and psychosis.

A history of prior steroid-induced mood changes, female sex, older age and higher steroid doses increase risk. Steroid-induced mania typically appears 3 − 4 days after starting treatment (median 11 days in some studies) and may involve:

severe insomnia
pressured speech
irritability or agitation
grandiosity
psychosis in severe cases.

Symptoms usually resolve when the dose is tapered (within roughly 3 weeks), but they can persist longer in individuals with underlying bipolar disorder. I therefore try to avoid treating MS relapses with steroids. However, this is not always possible.

Other agents that may cause mania

Amantadine, used for fatigue, can trigger mania in susceptible individuals.
Modafinil and methylphenidate, also used for fatigue, have been linked to sudden switching between manic and depressive symptoms.
Cannabinoids may destabilise mood or cognition.
Interferons more commonly cause depression than mania, but irritability, aggression and mania have been reported. The risk of new psychiatric symptoms is low, and patients with stable mood disorders can usually tolerate interferons with careful monitoring.
Fingolimod is linked to mood changes; severe rebound inflammatory activity after discontinuation could theoretically trigger mania.

Diagnosis of MS-related mania

Distinguishing between primary bipolar disorder, secondary MS-related mania and steroid-induced mania can be difficult. Accurate diagnosis is essential for effective management, as treatment for one form may exacerbate another. Below are some of the ‘atypical’ features of MS-related mania that deviate from classic bipolar disorder.

Late onset of symptoms

Primary bipolar disorder usually begins in adolescence or early adulthood. In contrast, secondary mania associated with MS can appear later, often after age 35–40 or during disease progression. A manic or psychotic episode may sometimes be the first manifestation of MS, occurring months or years before a neurological diagnosis.

Mania coinciding with an MS relapse

A sudden change in mood, sleep or behaviour that coincides with new neurological symptoms (e.g. numbness, vision changes, weakness) may indicate that inflammation or new lesions are affecting mood circuits. There may also be evidence of disease progression from MRI scans.

Weak family history

Primary bipolar disorder often runs in families; the absence of a family history suggests a secondary cause (i.e. MS-related pathology).

Disproportionate cognitive decline

Impulse control and executive functions, such as planning, organising and paying attention, are impaired – possibly reflecting frontal lobe involvement.

Mania as an MS relapse

A minority of patients present with isolated psychiatric symptoms (mania, psychosis, delirium) as the only manifestation of a relapse. MRI often reveals new frontal or temporal lesions, even when motor or sensory signs are absent.

Lack of response to standard treatments

Failure to respond to standard mood stabilisers, or paradoxical worsening with antidepressants, warrants a re-evaluation for organic causes.

Genetic considerations

Is the risk solely environmental (inflammation/lesions), or do MS and bipolar disorder share a genetic root? The Major Histocompatibility Complex (MHC) on chromosome 6 is the primary genetic risk factor for MS (specifically the HLA-DRB1*15:01 allele). Interestingly, Genome-Wide Association Studies have suggested that the MHC region is also involved in bipolar disorder and schizophrenia.
There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

Management

Treatment of MS-related mania depends on the cause.

Steroid-induced mania

If steroids triggered the symptoms, the steroids should be tapered or discontinued if safe.
Short-term antipsychotic medications, such as quetiapine, olanzapine or risperidone, can help stabilise mania symptoms. Quetiapine has the added benefit of aiding sleep, which is commonly disrupted in people with MS. Use of low-dose benzodiazepines during the steroid course can help to reduce the insomnia that often precedes or triggers mania.

Mania caused by MS inflammation

If mania is part of an organic, MS relapse, treating the inflammation is important. High-dose steroids may then be necessary, even though they can in other circumstances cause mania.
This crucial distinction underscores the need for close coordination between neurology and psychiatry.

Mood swings

Lithium is still the gold standard mood stabiliser and is generally safe for psychiatric management in MS. The anticonvulsants valproate, lamotrigine and carbamazepine are useful alternatives in people with MS; they treat both the mania and other MS-related comorbidities, such as neuropathic pain and trigeminal neuralgia.

Managing future steroid treatment

People with a known history of bipolar disorder or steroid-induced instability may benefit from:

starting a low-dose mood stabiliser (e.g. lithium) before the steroid course
adding an antipsychotic temporarily (e.g. olanzapine)
using sleep support (e.g. low-dose benzodiazepines) to prevent insomnia (a common trigger for mania).

Long-term management

Any MS patient presenting with new-onset mania requires a comprehensive workup, including MRI (to check for new frontal/temporal lesions) and a review of recent medication changes, rather than a direct referral to psychiatry. Ongoing coordination between neurologists and psychiatrists is, however, essential. A neurologist might misinterpret mania as ‘euphoria’ related to frontal lobe damage (pseudobulbar affect), while a psychiatrist might miss the neurological signs of an MS relapse that is driving the mood change. Screening tools (e.g. Mood Disorder Questionnaire) may help identify individuals at higher risk but should not replace clinical judgement.

Recognising the distinguishing features of MS-related mania allows clinicians to intervene promptly, reduce misdiagnosis and optimise care. With integrated neurological and psychiatric management, most people with MS experiencing bipolar symptoms can achieve stable, effective control of their mood and maintain a high quality of life.

Reference

Haroon, E et al. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology Rev; 2011:1–26.

Cognition and mental health

Mental ill-health in MS: prevalence and causes

08/02/2026 Gavin Giovannoni

It is now well established that the burden of MS extends far beyond the purely neurological problems to include mental health.

Key points

Many patients with MS experience both anxiety and depression.
Other emotional and behavioural changes associated with MS include cognitive changes, apathy, inappropriate laughing and crying, euphoria, mania and bipolar disorder.
Physical symptoms like fatigue, sleep disturbances, concentration difficulties, numbness, tingling and dizziness may occur both in MS and in anxiety states, complicating diagnosis.
Unless severe anxiety symptoms are formally diagnosed as an anxiety disorder, individuals miss out on targeted treatments.
There is growing evidence that MS-related emotional changes are not necessarily a psychological consequence of living with a disability.
- They may have a biological origin related to structural damage in the brain, caused by the MS disease process.
- Brain imaging techniques that measure activity reveal how these brain networks function in real time.
Emotional changes sometimes occur as a side effect of medications used in the management of MS, including steroids used to treat MS relapses..

Background and introduction

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease of the central nervous system (CNS) that is typically defined by its physical manifestations, such as motor weakness, sensory disturbances and fatigue. However, the burden of MS extends far beyond the purely neurological problems to include cognitive changes and mental health disorders such as anxiety, depression, apathy, mania and uncontrolled laughter and crying.

Anxiety and depression in people with MS

Among the most prevalent mental health problems in MS is anxiety, a condition that for many years was overshadowed by the clinical and research focus on depression. Anxiety is not a secondary issue but a core component of the disease experience for many people with MS. Anxiety and depression in MS are closely related, with many patients experiencing both simultaneously. Indeed, the presence of depression in people with MS is a strong predictor of the future development of anxiety, and vice versa. Both conditions share common underlying psychological risk factors such as avoidant coping styles and low optimism as well as unhealthy behaviours like smoking or lack of exercise.

Many large-scale studies have shown that anxiety is more prevalent in the MS population than in the general population. Two meta-analyses published in 2017 and 2023 assessed more than 50 published studies; based on pooled results, they estimated that 22% and 36%, respectively, of people with MS experienced anxiety.^1,2 The prevalence rates for depressive disorders in people with MS are about 20−30%. Further research, utilising the UK MS Register, suggests that more than half (54%) of the 4000 patients recorded in the database have experienced clinically significant anxiety and 47% have experienced depression.³

The proportions of people with different levels of anxiety (normal, mild, moderate or severe) and who have a depression score of 8 or above (N = 1961). Data from UK MS Register.³

The proportions of people with different levels of depression (normal, mild, moderate or severe) and who have an anxiety score of 8 or above (N = 2268). Data from UK MS Register.³

By contrast, the lifetime prevalence of any anxiety disorder in the general population in the USA is around 29% (though the prevalence at a specific point in time is lower). Anxiety is also significantly more prevalent in MS than in many other chronic neurological conditions, suggesting a relationship that may be specific to the pathophysiology or lived experience of MS.

Psychiatric symptoms versus psychiatric disorders

A critical nuance in understanding the epidemiology of anxiety in MS lies in the distinction between clinically significant anxiety symptoms and formally diagnosed anxiety disorders. The two are related but not interchangeable, and the disparity between their prevalence rates reveals a crucial aspect of the clinical challenge. The 2017 meta-analysis that found a 22% prevalence for anxiety disorders also found a substantially higher (34%) prevalence of clinically significant anxiety symptoms.This discrepancy indicates that for every ten patients who meet the formal diagnostic criteria for a specific anxiety disorder, such as generalised anxiety disorder (GAD) or panic disorder, there are approximately 15 patients who experience a level of anxiety that is severe enough to cause distress and impair functioning but is not formally identified and diagnosed in a clinical setting. The result is that these individuals miss out on targeted interventions such as specific psychotherapies or drug treatment that they might otherwise receive.

This large population of symptomatic but undiagnosed individuals may exist for several reasons. First, there is considerable symptom overlap between anxiety and MS itself. Physical symptoms like fatigue, sleep disturbances, concentration difficulties, numbness, tingling and dizziness can be manifestations of either MS or an anxiety state, creating a diagnostic challenge for clinicians and confusion for people with MS. Second, both patients and clinicians may view anxiety as an ’understandable’ or ’normal’ psychological reaction to living with a chronic, unpredictable illness, rather than as a distinct, treatable clinical entity. Finally, the historical research emphasis on depression may have led to less routine screening for anxiety in clinical practice. As an MSologist, it is also essential to differentiate formal depressive disorders from clinically significant depressive symptoms, which are much commoner than disorders.

Among those who do meet the criteria for a formal disorder, GAD appears to be the most prevalent, followed by panic disorder and obsessive-compulsive disorder. Recognising the full spectrum of anxiety, from subclinical symptoms to formal disorders, is essential for developing effective screening protocols and ensuring that all people with MS experiencing anxiety receive appropriate care (see article on management of mental ill-health in MS).

Other emotional and behavioural changes

MS impairs neuropsychiatric function (the interplay between neurological and psychological functioning) in a similar manner to its effects on other neurological functions. Living with MS can result in personality changes and subsequent relationship problems.

Cognitive changes

Cognitive impairment (i.e. dysfunction), particularly slowed information processing speed, is a common, well-documented and debilitating feature of MS. Anxiety has a demonstrably detrimental effect on cognitive domains that are often already compromised in MS, such as attention and executive functions.

Apathy

Apathy, characterised by profound loss of interest, blunted affect and reduced motivation, is also common in MS, particularly advanced MS. It is often misdiagnosed as depression. Apathy is not merely a component of low mood but is linked to executive dysfunction. Predictors identified include depressive symptoms, poor global quality of life, and poor attention and information processing speeds, probably due to MS lesions in the frontal lobe.

Inappropriate laughing and crying

Pathological laughing and crying, also known as pseudobulbar affect (PBA), are common but under-recognised and undertreated symptoms of MS that can be highly distressing and embarrassing for the patient and their relatives. The sudden, involuntary and explosive expressions of laughter or crying characteristic of PBA are often disproportionate or unrelated to the individual’s underlying emotional state.PBA is also associated with cognitive and mood problems, though the sudden and disproportionate emotional reactivity differentiates it from depression. The clinical presentation is due to frontal lobe or brainstem damage resulting from MS, which disrupts motor control pathways for emotional expression.

Rare affective changes

Euphoria and mania are relatively uncommon in people with MS but are often triggered by high-dose steroids used to treat MS relapses.

Bipolar disorder is significantly more common in people with MS than in the general population; please see the separate post/chapter on this. The diagnosis must be made and treated by psychiatrists and involves lifelong therapy.

The biological basis of mental illness in MS

MS-related emotional and mood changes are not necessarily a consequence of disability; they are often intrinsic to the MS disease process. This was recognised by the French neurologist Charcot, who, in 1877, noted pathological laughing, weeping, euphoria and depression in his patients who had MS.

Anxiety as a manifestation of MS pathology

While the psychological stress of living with a chronic illness contributes to anxiety in MS, there is growing evidence that anxiety is not solely a reactive or psychological phenomenon. The same autoimmune attack that damages myelin and axons, leading to physical disability, also targets and disrupts the complex neural circuits responsible for mood regulation, threat perception and emotional processing.

Neuroinflammation and demyelination (damage to nerve insulation) are directly implicated in the development of anxiety and other psychiatric disorders. MS lesions are not confined to areas of the brain responsible for motor and sensory function but also occur within the networks that govern emotion and mood.

Structural and functional brain changes

Research has shown that people with MS can develop gradual grey matter loss in brain regions involved in emotion and motivation, particularly the limbic system and the basal ganglia. The limbic system includes the hippocampus, amygdala and cingulate cortex, and it plays a central role in processing emotions. Changes in the shape of the hippocampus have also been observed.

Primary components of the limbic system. Modified from Encyclopaedia Britannica Inc.

These structural changes are thought to contribute to the development of mood and anxiety problems in MS. When MS-related inflammation, demyelination (damage to nerve insulation) or atrophy affects these areas, the brain’s ability to regulate fear and emotional responses can be disrupted. This creates a biological vulnerability to anxiety. From a structural perspective, therefore, anxiety in MS can be viewed as a direct consequence of neurological damage, in the same way that damage to the optic nerve causes visual impairment, or damage to the spinal cord leads to motor weakness.

In people with MS, depressive symptoms are consistently correlated with the volume of lesions in the brain and the degree of damage to connections between the cortex and subcortex. Neuroimaging studies show an association between depression and damage in the frontal and temporal areas of the cortex. In contrast, PBA is associated with lesions in the brainstem.

Brain imaging techniques that measure activity, such as functional MRI (fMRI), help to explain how these structural changes translate into anxiety symptoms. Rather than only showing where structural damage exists, fMRI studies reveal how brain networks function in real time. One key process identified in anxious people with MS is ‘fear overgeneralisation’. This occurs when the brain reacts to safe or neutral situations as if they were dangerous. For example, an individual learns to associate a specific signal (e.g. a picture of a circle) with a negative outcome (e.g. a mild electric shock). Anxious individuals tend to ’overgeneralise’ this fear, responding with fear to a similar but harmless signal (e.g. an oval), thus expanding their perception of danger in everyday life.

fMRI studies show that this process mainly involves the hippocampus (which is responsible for comparing incoming new experiences with ‘learned’ memories of danger) and the anterior insula (which plays a key role in generating the physical and emotional feeling of fear). In MS patients with anxiety, the physical pathways connecting these two regions are often disrupted, so that accurate information from the hippocampus is less effectively communicated to the anterior insula. As a result, the anterior insula may generate strong fear responses even when a situation is only mildly threatening or even safe.

fMRI studies have also revealed that many MS patients exhibit greater brain responses or increased recruitment of key emotional regions (e.g. prefrontal cortex and amygdala) compared to healthy controls. This likely reflects compensatory mechanisms the brain deploys to limit the clinical expression of emotional symptoms. The damaged MS brain tries to cope.

Neurological versus psychological causes

MS can trigger primary psychopathology as a result of demyelination and damage to specific functional circuits within the brain, as described above.It can be challenging to differentiate primary organic issues from reactive psychological problems, which is why people with MS may be referred for psychiatric assessments.

I have, however, also seen patients in whom the initial symptoms were psychiatric, e.g. depression or (rarely) mania, but who were later found to have MS. The link between MS-related CNS damage and emotional symptoms is based on lesion location and lesion burden. For example, MS patients with lesions affecting the functional parts of the brain (rather than the connecting structures) exhibit a higher burden of emotional symptoms than those with lesions confined to the spinal cord. Our emotions are part of brain function in a similar way to motor function. Therefore, it is not surprising that MS impacts emotions.

Lesion location and emotional symptoms

The evidence for a direct correlation between lesion location and anxiety is inconsistent. Some researchers suggest that, unlike depression, anxiety in MS may be driven more by psychosocial pressures and the psychological reaction to the illness rather than by focal brain damage.This discrepancy does not necessarily invalidate the biological basis of anxiety in MS. It may be that anxiety is related to more diffuse or subtle pathological changes, such as microstructural damage in white matter tracts or widespread neuroinflammation, that are not easily captured by conventional MRI lesion analysis. It is also possible that the broad distribution of the brain’s anxiety circuits means that damage to any number of different locations could produce a similar clinical outcome, making it difficult to pinpoint a single ’anxiety-causing’ lesion location.

Other contributing factors

Emotional changes may occur as a side effect of medications used in the management of MS, including certain disease-modifying therapies. People with MS are also susceptible to the effects of the menopause, seasonal affective disorder and comorbidities associated with depression and anxiety, such as alcohol and other substance misuse disorders. It is advisable, therefore, to have a complete assessment before having a mood disorder labelled as being due to MS.

Anxiety in MS may also be caused by high-dose corticosteroids, which are the standard treatment for MS relapses. Steroids have significant neuropsychiatric side effects, including anxiety, mania, insomnia and psychosis.For someone with MS already dealing with the stress of a relapse, the addition of steroid-induced anxiety can be particularly distressing.

‘Prodromal’ MS and psychiatric symptoms

Psychiatric comorbidities, such as anxiety and depression, have historically been viewed as consequences that follow the diagnosis of MS. Recent research, however, points to the existence of an ‘MS prodrome’, during which anxiety and depression occur years before the first classical neurological event.⁴ Increased rates of anxiety are a significant feature of this prodromal phase, suggesting that anxiety and/or depression may be early signs of MS, not merely a consequence. This body of recent research supports the idea that psychiatric symptoms in MS have a biological origin. This is most likely driven by the same low-level, diffuse neuroinflammatory and neurodegenerative processes that are smouldering away in the CNS long before the first eloquent MS lesion.

References

Boeschoten, RE et al. Prevalence of depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. J Neurol Sci 2017;372:331−341.
Zhang X et al. The prevalence and risk factors of anxiety in multiple sclerosis: A systematic review and meta-analysis. Front Neurosci 2023;17:1120541.
Jones KH, et al. A large-scale study of anxiety and depression in people with multiple sclerosis: a survey via the web portal of the UK MS Register. PLoS ONE 2012;7:e41910.
Ruiz-Algueró, M et al. Health care use before multiple sclerosis symptom onset. JAMA Netw Open 2025;8:e2524635.