When The Immune System Attacks the Brain – Case Files of a Young Female with Mania
There is increasing evidence of the emerging link between Autoimmunity and Psychiatric Disorders. [Kayser and Dalmau, 2011].
This case is one of several that provides further compelling evidence for the role of autoimmune mechanisms in the pathogenesis of psychiatric disorders and the need for vigilance for autoimmunity in psychiatric practice. [Rege S & Hodgkinson S, 2014]
A 21-year-old female of Maltese background presented with a first episode of mania and was initiated on Risperidone and Sodium Valproate. The dose was increased to a dose of 4 mg /day of Risperidone and 1500 mg /day of Sodium Valproate with minimal response.
Two of the main aspects of the presentation pointing towards atypicality were fluctuating cognition and significant short-term memory dysfunction. Also, the absence of a family history of psychiatric disorder, drug use and a viral prodrome two weeks prior raised the suspicion of a possible organic cause.
Organic Screen revealed the following
- Antinuclear antibodies (ANA) 1:640 (Homogenous and Nucleolar type) ( Normal< 1:80)
- DsDNA: 17 ( Normal<4)
- No electrolyte or metabolic abnormalities
- Negative anti-thyroid antibodies and normal Thyroid function tests
- Negative anti-phospholipid antibodies
- Normal ESR and CRP
- MRI, SPECT, and PET brain normal
- CT and US pelvis was normal
- There is a high association of a specific type of encephalitis called Anti-NMDA encephalitis with Ovarian Teratomas.
- MRI T2 white matter hyperintensities and SPECT perfusion deficits are found in autoimmune encephalitis and Neuropsychiatric Lupus.
THE ROLE OF ELECTROENCEPHALOGRAM (EEG)
The first EEG showed non-specific slow-wave abnormalities bifrontally with no epileptiform patterns.
- Abnormal slow waves can point towards an organic cause.
The above pattern was not considered significant or definitive of an organic cause. Hence another sleep-deprived EEG was obtained.
The sleep-deprived EEG showed an abnormal EEG due to ‘the presence of generalised slow wave activity’.
- A sleep-deprived EEG can exacerbate underlying pathology if present.
HOW WAS THE PATIENT TREATED?
The atypical clinical picture, abnormal serology and EEG pointed strongly to the possibility of autoimmune encephalitis. The referral to the rheumatology team did not offer any input as the presentation was deemed ‘psychiatric’. [Read autoimmune encephalitis masquerading as psychiatric disorders]
An empirical trial of Methylprednisone (1g/day for five days) was instituted in collaboration with a neuroimmunologist. The patient responded dramatically within three days and showed a marked
improvement in her mental state.
She was then transitioned to 1 mg/kg/day of prednisone in two divided doses. Prednisone was gradually ceased over two weeks which resulted in a relapse two weeks later.
A Trial of Intravenous Gamma Globulin (IV IGG) was unsuccessful. Plasmapheresis was trialled with good response in 2 days.
She was discharged on Mycophenolate 1 g BD which was changed after two months to Azathioprine 100 mg daily.
The psychiatric medication was reduced and ceased. The patient remained in complete remission for six months and was maintained on a low dose of Azathioprine 25 mg BD. Azathioprine was also further reduced and ceased, and the patient remained in remission for a further eight months on no medication. No further admissions occurred during this period.
WHAT DID WE FIND?
The poor response to psychotropics, followed by a good response to immunosuppressants, the presence of antineuronal antibodies indicates immune dysfunction and is consistent with synaptic encephalitis. The antineuronal antibodies were not in a pattern previously known.
TAKE HOME MESSAGES
- Neuropsychiatric Systemic Lupus Erythematosus and Anti-NMDA Encephalitis are significant differentials for the psychiatrist to consider when suspecting organic etiologies in psychiatric disorders, particularly psychosis. For a summary of these conditions and how to suspect them in clinical practice click here.
- Seventy-five percent (75%) of anti-NMDA encephalitis cases initially present to psychiatrists and milder cases (formes frustes) may be missed due to the absence of overt neurological symptomatology. Learn more about neuroinflammation.
- Case reports are often written in a straightforward manner, but the difficulties in diagnosis or management due to decision-making errors or biases are not highlighted. This case posed a significant challenge as there is a distinct gap in collaboration between medical specialities. In this case, the specialities of immunology, neurology, psychiatry and rheumatology. The real message is for doctors to keep an open mind and show a genuine sense of curiosity in problem-solving.