Psychiatric symptoms sent her down an autoimmune path. MELAS was the real diagnosis.

A sudden decline

In March 2024, a 46-year-old man was admitted to a local hospital. One month after a respiratory illness, he had developed progressive hearing loss and expressive aphasia. Initial brain MRI showed hyperintensities in the temporal lobes, leading doctors to suspect viral encephalitis. Despite being treated with antiviral and antibiotic medications, his condition worsened as psychiatric symptoms emerged.

The psychiatric and neurological turn

The man was transferred to a tertiary care center on March 15. On his fifth day there, he developed convulsive status epilepticus, requiring intubation and mechanical ventilation. Doctors noted he was apathetic and poorly cooperative with examinations. He was treated with diazepam and levetiracetam for seizures. Clinical records noted a body mass index of 17.3 kg/m² and a history of chronic, unevaluated headaches.

The autoimmune hunt

Tests for infections like HIV and syphilis were negative. However, a comprehensive autoimmune encephalitis panel returned a positive result for anti-glial fibrillary acidic protein (GFAP) antibodies in both his blood and spinal fluid, with a titer of 1:32. Based on this and MRI findings showing cortical swelling, the initial working diagnosis was set as autoimmune encephalitis.

The patient was treated with aggressive immunotherapy, including intravenous immunoglobulin, high-dose methylprednisolone, and cyclophosphamide. Despite these treatments, he remained somnolent with minimal responsiveness. Follow-up scans showed the disease was spreading to his thalamus and occipital lobe.

The genetic reality

While the medical team navigated the autoimmune findings, a deeper clinical history suggested a different path. The man’s sister and son had both died at age three from unknown causes, and his mother suffered from the same chronic headaches he did. Genetic testing eventually revealed the m.3243 A > G mutation in the MT-TL1 gene with 11.91% heteroplasmy.

The true diagnosis was MELAS syndrome—a maternally inherited mitochondrial disorder. The positive anti-GFAP antibodies, which initially pointed toward a primary autoimmune disease, were likely a secondary response to the extensive brain tissue damage caused by the mitochondrial crisis.

Outcome

Once the genetic diagnosis was confirmed, the patient was started on mitochondrial supplements, including coenzyme Q10 and L-arginine. However, the secondary autoimmune treatments had failed to stop the progression. His neurological status continued to decline, and he died approximately three months after his symptoms first appeared.