Overlapping cortical presentations in MELAS, CAA-ri, and Anti-GABA_A receptor encephalitis: a case series

Background Seizures may occur in a broad spectrum of neurological disorders with heterogeneous etiologies. Rare neurological diseases involving cortical lesions may present with overlapping clinical symptoms and neuroimaging findings, thereby posing substantial diagnostic challenges. Case presentation We retrospectively analyzed three patients with rare neurological disorders admitted to Sanbo Brain Hospital, Capital Medical University. The final diagnoses were mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), cerebral amyloid angiopathy-related inflammation (CAA-ri), and anti-gamma-aminobutyric acid type A receptor (anti-GABA_A receptor) encephalitis. The patient with MELAS presented with seizures, headache, psychiatric symptoms, and cognitive impairment. Brain magnetic resonance imaging showed migratory cortical lesions that were not restricted to vascular territories, magnetic resonance spectroscopy demonstrated an elevated lactate peak, and genetic testing identified the mitochondrial MT-TL1 m.3243A>G mutation. The patient with CAA-ri presented with recurrent seizures and mild cognitive impairment. Neuroimaging revealed asymmetric cortical and subcortical inflammatory edema involving multiple lobes, which improved markedly after immunotherapy, and genetic testing detected a heterozygous pathogenic APP variant. The patient with anti-GABA_A receptor encephalitis predominantly presented with psychiatric symptoms and movement disorders without seizures. Brain magnetic resonance imaging demonstrated extensive confluent cortical and subcortical lesions, and anti-GABA_A receptor antibodies were detected in both serum and cerebrospinal fluid. Conclusions MELAS, CAA-ri, and anti-GABA_A receptor encephalitis may show overlapping clinical and neuroimaging features, but several findings are helpful for differential diagnosis. Migratory cortical lesions with elevated lactate levels suggest MELAS, asymmetric steroid-responsive cortical and subcortical edema supports CAA-ri, and extensive cortical-subcortical lesions combined with positive neuronal antibodies favor autoimmune encephalitis. A multimodal diagnostic approach integrating neuroimaging, electrophysiology, genetic testing, and antibody assays is essential for accurate diagnosis and timely treatment of these uncommon neurological disorders.