Emotional disturbances are highly prevalent with an early onset in patients with multiple sclerosis (MS) [
A 39-year-old man, with no family medical history, was followed up since 1992 at the age of 20 for bipolar disorder with mainly manic fits. He was treated with a mood stabilizer (lithium carbonate). In October 2003, he presented a decrease in visual acuity that resolved spontaneously after 15 days. In September 2004, he reported paresthesia and weakness of the left side of the body associated with urinary incontinence. The symptoms regressed after a five-day course of intravenous methylprednisolone (1 g per day). Neurological examination revealed a left hemiparesis and left pyramidal syndrome. Cerebrospinal MRI showed multiple T2-weighted hyperintense lesions in periventricular white matter and in corpus callosum, as well as the cervical spine at C2 and C3 (Figure
Axial cerebral T2-weighted image showing multiple lesions in periventricular and subcortical white matter. Dawson’s finger (arrow) is a characteristic finding in multiple sclerosis.
A 38-year-old woman, with a family history of bipolar disorder in a maternal uncle, has been followed up since the age of 20 for manic depressive psychosis with mainly manic episodes. A mood stabilizer treatment was prescribed (lithium carbonate). She consulted in 2005 about an episode of weakness of both lower limbs. She reported a similar episode in 2004 that resolved spontaneously after a few days. Neurological examination revealed a quadripyramidal syndrome with right kinetic cerebellar syndrome. Cerebrospinal MRI displayed multiple ovoid and confluent T2 hyperintense lesions in periventricular and semioval white matter and a cervical lesion at the level of C6. No gadolinium-enhanced lesions were identified. Serological tests for syphilis, hepatitis B and C, and HIV, inflammatory tests, and anti-nuclear antibodies were negative. The diagnosis of clinically definite MS was made. On follow-up, she presented one motor fit per year and was treated with high doses of methylprednisolone in each episode. The last fit was in June 2010. She consulted about an episode of weakness of both lower limbs. A three-day course of high doses of intravenous methylprednisolone was prescribed. Two days later, she presented a manic fit requiring hospitalization in a psychiatric department. Cerebrospinal MRI showed no new lesions. The patient was treated with atypical antipsychotics (olanzapine) associated with lithium carbonate with resolution of the manic episode.
A 23-year-old woman, with a family history of bipolar disorder in a sister, had no past personal history. In April 2005, she presented clumsiness in the right side of her body that completely regressed after two months. In February 2007, she reported weakness in her left hemibody with blurred vision, completely regressed after one month. In November 2008, the patient was hospitalized for a motor deficiency in the right hemibody associated with diplopia and bladder dysfunction. Neurological examination showed right hemiparesis with quadripyramidal syndrome and static and kinetic cerebellar syndrome. Cerebral MRI revealed multiple T2 hyperintense lesions in periventricular and subcortical “white matter”, mainly in frontal and temporal lobes, right cerebellar peduncle, and corpus callosum and two cervical lesions at the level of C2 and C3. Analysis of the cerebrospinal fluid (CSF) detected the presence of oligoclonal bands. The diagnosis of relapsing-remitting MS was confirmed according to McDonald criteria. The patient received a 5-day course of intravenous methylprednisolone (1 g per day). Six months later, the patient developed psychiatric symptoms with irritability, frequent crying, social withdrawal, and insomnia. She has not consulted and received no treatment. A few months later, the clinical picture changed spontaneously and the patient was hospitalized for a manic episode with euphoria, grandiosity, hyperactivity, and reduced need to sleep. Neurological examination was normal. Cerebral MRI showed a right orbitofrontal active lesion with gadolinium enhancement (Figure
Axial cerebral T1-weighted image revealing a right orbitofrontal active lesion with gadolinium enhancement (arrow).
The first case report describes a man with a long term history of bipolar disorder who developed MS. In this case, the most likely hypothesis advanced to explain this comorbidity would be a casual association. In fact, MS is a relatively rare disease with an estimated prevalence in Tunisia of 20.1 per 100,000 inhabitants [
The second case report illustrates the occurrence of a manic episode following high doses of methylprednisolone. Corticosteroids have long been implicated in the precipitation of the onset of certain psychiatric symptoms. The most common adverse effects of short-term corticosteroid therapy are mood disorder, euphoria, and hypomania. Conversely, long-term therapy tends to induce depressive symptoms [
Although research of the etiopathogenesis of the association between MS and bipolar disorder is still limited, a common genetic susceptibility to both diseases was discussed. In a series of 56 patients, Schiffer et al. noted a higher frequency of the HLA-DR2 and -DR3 haplotype and a decrease in the frequency of HLA-DR1 and -DR4 in patients with both MS and bipolar disorder with a family history of affective disorders [
The manic symptoms may also be related to white matter lesions location [
Bipolar disorder in MS patients is usually treated in the same way as in the general population. A treatment with mood stabilizers (sodium valproate, carbamazepine, and lithium) associated with atypical antipsychotics is generally effective on manic fits. This was the case in our three patients. The use of lithium must be with caution in patients with sphincter disorders since they tend to reduce their fluid intake and may thus have high serum levels of lithium approaching toxic doses [
Interferon beta (IFN-
These three case reports highlighted the possible association between MS and bipolar disorder, an association that is still not well studied. We conclude that interferon beta treatments are well tolerated while high dose corticosteroids may induce manic fits. MS and bipolar association may be due to local MS-related brain damage or due to common genetic vulnerability. More studies focusing on specific response to treatment and genetic susceptibility are mandatory.
The authors declare that there is no conflict of interests regarding the publication of this paper.