What are the neurological presentations of TR (thyroid receptor) antibody?

From the Guidelines

TR antibody neuro presentation is most commonly associated with NMDAR-Ab encephalitis, which typically presents with psychiatric symptoms, memory deficits, seizures, movement disorders, autonomic instability, and decreased level of consciousness, as reported in the study by 1.

Key Clinical Features

• Psychiatric symptoms, such as psychosis and anxiety
• Memory deficits and cognitive impairment
• Seizures, including faciobrachial dystonic seizures
• Movement disorders, such as dyskinesia and rigidity
• Autonomic instability, including dysautonomia and hyperthermia
• Decreased level of consciousness, ranging from lethargy to coma

Diagnosis and Treatment

• Diagnosis is based on clinical presentation, MRI findings, and detection of NMDAR antibodies in serum or CSF
• First-line treatment includes immunotherapy with IV methylprednisolone, oral prednisone, and IV immunoglobulin or plasma exchange, as described in the study by 1
• If a tumor is detected, particularly ovarian teratoma in females or testicular teratoma in males, surgical removal is essential
• Second-line treatments include rituximab and cyclophosphamide for patients who do not respond to first-line therapy

Prognosis and Outcome

• Recovery can take months to years, with 75-80% of patients achieving good outcomes, as reported in the study by 1
• Early treatment initiation improves prognosis, but approximately 12-25% of patients may relapse, necessitating long-term immunosuppression
• The pathophysiology involves antibodies targeting NMDA receptors, causing receptor internalization and disrupting glutamatergic transmission in the brain, which explains the diverse neurological and psychiatric manifestations, as described in the study by 1

From the Research

TR Antibody Neuro Presentation

• The detection of autoantibodies in suspected autoimmune encephalitis can be done through various methods, including indirect immunohistochemistry and cell-based assays 2.
• Onconeuronal antibodies are well-established biomarkers for paraneoplastic neurological syndromes (PNS) and may serve as specific tumor markers 2.
• Anti-neuronal surface antibodies are sensitive and specific biomarkers for autoimmune encephalitis, and their identification requires the use of test methods that allow the recognition of conformation-dependent epitopes 2.
• Tissue-based assays can detect most of the currently known neuronal surface antibodies and thus enable broad screening of biological samples 2.
• In patients with peripheral neuropathy, the screening may be expanded to teased nerve fibers to identify antibodies against the node of Ranvier, which can help identify a novel subgroup of peripheral autoimmune neuropathies 2.

Diagnostic Value and Limitations

• The recommended procedure to detect onconeuronal antibodies is a combination of indirect immunohistochemistry on fixed rodent cerebellum and confirmation of the specificity by line assays 2.
• Simplification of this approach by only using line assays with recombinant proteins bears the risk of missing antibody-positive samples 2.
• Antibody screening assays represent promising avenues of research to improve the diagnostic yield of current assays for antibody-associated autoimmune encephalitis 2.
• Ordering practices for suspected autoimmune encephalitis and paraneoplastic disorders are suboptimal, with frequent overlapping antibody panel evaluations and non-paired serum/CSF samples 3.
• Repeat autoantibody testing is a commonplace practice, yet it yields novel information in only a minority of cases, and these new results are often clinically irrelevant 3.

Treatment and Management

• Myasthenia gravis is an autoimmune disorder of the neuromuscular junction, and treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation 4, 5, 6.
• Azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America, and their comparative effectiveness has been evaluated in a prospective cohort study 4.
• The choice of medication, dose, and follow-up intervals should be determined by treating clinicians, and outcome measures and adverse events should be recorded at each visit 4.
• Therapies for myasthenia gravis include symptomatic and immunosuppressive/immunomodulatory treatment, and options for immunosuppression include corticosteroids, azathioprine, mycophenolate mofetil, and others 5, 6.