A Case of Bipolar Disorder due to Multiple Sclerosis with Episodes of Mania : Malaysian Journal of Psychiatry

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Case Report

A Case of Bipolar Disorder due to Multiple Sclerosis with Episodes of Mania

Xin, Gan Ning1,2,; Yee, Kenny Ong Kheng1; Kiat, Ang Jin2

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Malaysian Journal of Psychiatry 31(2):p 92-95, Jul–Dec 2022. | DOI: 10.4103/mjp.mjp_19_22
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Bipolar and related disorders are common and disabling psychiatric conditions characterized by recurrent episodes of elevated mood (manic or hypomanic) and depressive episodes, coupled with changes in activity or energy levels.[1,2] A large number of substances of abuse, some prescribed medications, and several medical conditions can induce manic-like phenomena. Multiple sclerosis (MS) is an example of the above medical conditions.[2] Early detection of the symptoms, accurate diagnosis, and prompt treatment are important to facilitate rapid stabilization and full symptomatic remission with restoration of premorbid functioning.

MS is an idiopathic inflammatory demyelinating illness which is characterized by neurodegeneration and neuroinflammation. It is autoimmune in origin with diverse neurological sequelae such as demyelination and degenerative axonal loss throughout the white matter, except the peripheral nerves.[3]

Multiple demyelinating lesions of the brainstem, optic nerves, cerebellum, and spinal cord can be found in MS. The disease is presented with variable neurological signs that correlate with the distribution of plaques.[4]

MS can result in “secondary” mania. Although the pathogenesis is likely to be different, both mania and MS are associated with white matter changes on magnetic resonance imaging (MRI).[5] Nevertheless, mania can also be medication-induced or idiopathic such as due to steroids, dantrolene, baclofen, and tizanidine or even due to illicit drugs use. A thorough evaluation that includes history-taking, full neurological examination, neuroimaging, and other relevant tests is crucial to differentiate secondary mania from primary mania. Common treatment regimen if steroids can induce mania, thus complicating the diagnostic process.

This case report highlights the development of manic symptoms in a patient with MS.


Miss. C, a 16-year-old teenage girl with a background history of childhood bronchial asthma, was diagnosed with relapsing–remitting MS (aggressive disease) since the 12 years of age. She had eight relapses in the first 2 years of illness, complicated with left optic neuritis and generalized tonic–clonic seizure. Miss C experienced multiple neurological complaints at different sites in each relapse such as headache, dizziness, blurred vision, unsteady gait with lower limb weakness, and loss of hand function. She was first referred for psychiatric assessment in August 2019 when she was presented with manic symptoms for 2 years that were worsened over 2 months, evidenced by persistent elated mood with irritability, increased energy level, talkativeness, racing thoughts, distractibility, overfriendliness, sexually disinhibition, spending spree, and grandiosity. These symptoms worsened during each relapse of MS. Some residual manic symptoms of elated mood and overfriendliness were present in between the relapses. There were perceptual disturbances such as auditory, visual, and olfactory hallucinations in April and October 2018 during her second and fourth relapses, respectively. She had significant academic and social functional deterioration. Her mother stopped her from schooling after her school teacher complained that she hugged a male student in school due to sexual disinhibition. Miss C had not experienced any depressive episode.

Miss C was the only child in her adopted family who did not know her biological family’s mental health history. Her birth history was normal, and her developmental milestones were appropriate to age. Miss C was a child with easy temperament and was brought up in a caring but rather permissive and overprotective family. There was no feature suggestive of autistic spectrum disorder, attention-deficit hyperactive disorder, separation anxiety, or learning disability. She excelled in her studies till she fell ill at 12 years old. There was no history of smoking or substance use. She was an introvert premorbidly.

Mental state examination revealed a teenage girl with overfamiliarity and distractibility. She had increased tone and amount in her speech but no pressured speech. Her mood was described as “very happy” with the mood score of 10/10. Her effect was elated but appropriate to her thought. Her flow of thoughts was increased. Miss C had inflated self-esteem with grandiosity. Cognitive deficits such as impaired attention and concentration, impaired abstract thinking, and social and personal judgment with partial insight were found. Physical examinations revealed cerebellar signs such as broad base gait, ataxia, and left-sided dysmetria with bilateral relative afferent pupillary defect.

Various investigations were done. Serum rheumatoid factor, antinuclear antibody test, antiaquaporin 4 test, and antimyelin oligodendrocyte glycoprotein antibody were all negative. MRI brain and spine contrast revealed a demyelinating disease. The latest MRI on January 2019 showed new lesion at the left frontal region [Figure 1]. Frontal lobe assessment showed deficits in lexical fluency and similarities test with signs of executive dysfunction.

Figure 1:
New left frontal lobe lesion (periventricular region) seen in magnetic resonance imaging in January 2019

Miss C was managed aggressively by the treating team with parenteral immunoglobulin, methylprednisolone, or interferon followed by oral prednisolone. Her manic symptoms flared up during each MS relapse and resolved after its treatment. Miss C was started on risperidone 2 mg daily, and she responded to it. Her adherence to the treatment was poor; thus, symptoms reoccurred. Since 1.5 years ago, Miss C was started on rituximab therapy 6 monthly, and no relapse was reported since then. Her parents informed that 1–2 weeks before rituximab treatment, she would appear to be more irritable and laugh excessively at times.


Comprehensive physical and psychiatric evaluations which consisted of thorough history taking, mental state and physical examinations, neuropsychiatric assessment, and relevant biopsychosocial investigations were crucial to ascertain the diagnosis, thus guide the future management plan. The temporal relationship between manic episodes and the course of the MS should be reviewed. Patten and Neutel highlighted the important association of corticosteroid-induced adverse psychiatric effects in MS patients such as depressive, manic, and mixed features, psychotic disorders, and delirium.[6]

Miss C was diagnosed to have bipolar disorder due to MS with episodes of mania. She had manic episodes during each MS relapse and resolved following treatment for MS. A left frontal lobe new plaque lesion was found in her most recent MRI brain. There was evidence from her history, physical examination, and laboratory findings that her manic manifestations and cognitive deficits were in consequence of her MS. Thus, we did not entertain a separate diagnosis of primary psychiatric disorder. It was unlikely a medication-induced mood disorder as Miss C’s manic symptoms developed before the use of steroid in MS treatment, and they did not develop after the exposure of steroids.

Neuropsychiatric symptoms are not uncommon in patients with MS, and they can be divided into cognitive and behavioral types.[7] Miss C complained of poor attention and concentration with the difficulty to understand what had been taught by her teachers in class. She was once an excellent student, but she could no longer cope with her studies. She dropped from second rank in her class to second last in her class. Her cognitive impairment had significant negative impact onto her academic functioning.

The prevalence of cognitive deficit of MS is 40%–65% that impairs the occupational and social functions, independently of the degree of physical disability.[8] The cognitive impairment varies between those who are affected based on the location of lesions that include forgetfulness, emotional changes, or personality changes slow in thought process, as well as are unable to manipulate information. Besides, intelligence quotient can decline in patients with MS.[9] The common cognitive symptoms such as deficits in executive functioning, complex attention, information processing, long-term memory, and processing speed may adversely affect the patients’ ability to participate fully in society, run a household, and maintain employment and thus detrimental to their quality of life.[10]

In a case series done by et al., three cases of MS and bipolar disorder were reported and they discussed possible etiological hypothesis and treatment options. One patient was presented with high-dose corticosteroid-induced mania, and one patient presented with new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients required antipsychotic treatment. Based on the lesions in the MRI, it was suggested the possible implication of local MS -related brain damage to development of psychiatric manifestations in patients.[11]

The association of steroid treatment and mania is clinically relevant. Up to one-third of patients who use steroids may have mild-to-moderate mania.[4] Steroids are addictive substances. It can later cause increased anger, arousal, irritability, hostility, anxiety, somatization, and depression, especially when steroids are stopped.[7] In acute exacerbation of MS, high dose of methylprednisolone followed by oral prednisolone was commonly used. This can perpetuate or induce mania and even psychosis. Since Miss C was put on rituximab, third-line treatment for MS according to the Malaysia Clinical Practice Guideline, she had no MS relapse and subsequently no manic episode.[12]

In short, there are several potential reasons for the relationship between affective disorder and MS: (1) The mood disorder could be a psychological reaction to the diagnosis and chronicity of the disease; (2) affective illness and MS may share a common neurologic substrate; (3) a disorder of immune function or infectious agent can be common to both disorders; and (4) high-dose steroids use in the treatment may induce affective symptoms. High prevalence of mood disturbance in MS patients may contribute to higher morbidity. Thus, early detection of mood disorder is important. Currently, there is no specific treatment guideline for mood disorder secondary to MS. Based on the current Canadian Clinical Guidelines, general principles for managing bipolar disorder also apply to children and adolescents,[13] but they are more susceptible to metabolic side effects, especially when atypical antipsychotic is used like in this case, risperidone.[14] Specific and definitive management for the mood disorder is needed since the prevalence of affective disorder is high in MS. Future research and clinical guidelines should focus on this area.

Ethical Statement

A written informed consent was obtained from the patient’s mother and her details were kept anonymous. This report had met the ethical guideline and legal requirements in Malaysia.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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Bipolar disorder; frontal lobe deficits; mania secondary to general medical condition; multiple sclerosis; secondary mania; steroid-induced mania

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