A Summary of 3 Important Autoimmune Neuropsychiatric Disorders for Psychiatrists – Dr Sanil Rege
Dr. Sanil Rege is a Consultant Psychiatrist and founder of Psych Scene (a platform to enhance psychiatry education) and Vita Healthcare, providing high-quality mental health care services to the public. He is a Fellow of the Royal Australian and New Zealand College of Psychiatrists and Member of the Royal College of Psychiatrists (UK). His clinical and research interests include psychosis, depression, anxiety, post-traumatic stress disorders, and personality disorders.
Evidence actually suggests that there is a lot of inflammation in bipolar disorder.
There are clear abnormalities and imbalance between pro-inflammatory and anti-inflammatory cytokines (in bipolar disorder).
Encephalitis is a very prominent disorder and something that we should be highly vigilant for.
What we do know is that thyroid-autoimmunity is an independent risk factor for bipolar disorder with no association with lithium exposure and may serve as an endophenotype for bipolar disorder.
Increased autoantibody production, increased ANA and autoimmune processes precede the onset of bipolar disorder.
Dr. Sanil Rege begins with an overview of immune dysregulation in bipolar disorder and the role of cytokines in inflammation.
Neuropsychiatric Systematic Lupus Erythematosus (NPSLE):
- Common symptoms are: cognitive dysfunction (75-80%), mood disorders (69-74%), headache (39-61%), seizures (8-18%), cerebrovascular disease (2-8%), psychosis (3-5%)
- Neither a normal ESR nor negative serology excludes CNS lupus
- A subset of the anti-DNA antibody is known to cross-react with the NR2 glutamate receptor
- Elevated antibodies to the NR2 subunit of the glutamate receptor in the acute phase of mania but not at follow up
- Antineuronal antibodies in NPSLE recognize the NR2A and the NR2B subunits of the NMDA receptor, which are highly concentrated in the hippocampus
- MHC region of chromosome 6 implicated in bipolar disorder and a range of autoimmune disorder, especially SLE
White matter lesions in the periventricular area in a patient with lupus presenting with a mood disorder. These lesions are not specific to lupus. Learn more about white matter hyperintensities.
SPECT perfusion defects in a lupus patient:
Pathogenesis of NPSLE:
The antibodies result in the formation of immune complexes which in turn lead to alterations in serotonin, noradrenaline and HPA axis.
Encephalopathy associated with Synaptic Antibodies:
- Antibodies: Anti-NMDA, AMPA, Ma, Hu, GABA, VGKC, Caspr2
- Clinical presentation: Psychosis, memory deficits, confusion, dyskinesia, seizures, autonomic instability
- Diverse psychiatric symptoms: irritability, hallucinations, personality changes, cognitive dysfunction, sleep disturbances
- EEG: Non-specific slow, disorganized activity, sometimes with seizure activity
- MRI: T2 or FLAIR signal in medical temporal lobes (15%); Normal in >50%
- Anti NMDA encephalitis has a strong association with an ovarian teratoma – Over 50% of cases are not associated with neoplasm
- 75-80% make a full or substantial recovery
Encephalopathy Associated with Autoimmune Thyroiditis (EAAT):
- Also known as Hashimoto’s encephalopathy
- Misdiagnosis is common: differentials include viral encephalitis, CJD, migraine, Alzheimer’s and Lewy body dementia, psychosis and delirium
- Common clinical features: cognitive dysfunction and behavioral changes, fluctuating symptoms, transient aphasia, tremor, myoclonus, ataxia, seizures, sleep disturbance, headache (50%) and psychosis (25%)
- Diffuse increase signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the cerebral white matter
- Anti TPO, Anti Thyroglobulin, ANA, Raised ESR and Elevated LFT’s
- Generalized slowing/FIRDA/focal slow waves/epileptiform discharges
- Good response to steroids
Take-home messages from Steroid Responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT):
- The presence of thyroid antibodies in serum, not the level, was the clinically relevant issue, indicating that SREAT should be considered in patients with encephalopathy even if thyroid antibody levels are only mildly elevated (Castillo et al., 2006)
- SREAT should be considered in patients with encephalopathy regardless of whether they are euthyroid or mildly hypothyroid (Castillo et al., 2006)
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- La Cava A, Matarese G. The weight of leptin in immunity. Nat Rev Immunol. 2004;4(5):371-9.
- Brietzke E, Stertz L, Fernandes BS, et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116(3):214-217.
- Rege, S., & Hodgkinson, S. J. (2013). Immune dysregulation and autoimmunity in bipolar disorder: synthesis of the evidence and its clinical application. Australian & New Zealand Journal of Psychiatry, 47(12), 1136-1151.