Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders

A previously healthy 44-year-old woman presented with subacute psychiatric disturbance with no fever or seizures. A, Bilateral and asymmetric hyperintensity was observed on an axial FLAIR image in the enlarged amygdalae and hippocampi (asterisks), predominantly on the left side. B, A faint ill-defined enhancement of the left hippocampus was documented on an axial T1 postcontrast image (arrowheads). Autoimmune encephalitis was considered, and the presence of anti–N-methyl-D-aspartate receptor autoantibodies was confirmed. C and D, Imaging follow-up revealed signal abnormalities and atrophy on FLAIR that involved the hippocampus, amygdala, parahippocampal gyrus, and left insula (arrowheads), compatible with severe sequelae.

A 22-year-old man with Hodgkin lymphoma presented with acute onset of short-term memory loss and mental confusion. A, An evident hyperintensity and subtle enlargement of the right hippocampus and amygdala were noticed on an axial FLAIR image (arrow). B, No parenchymal enhancement was observed (arrowhead). In addition to the fact that CNS involvement is not expected in Hodgkin lymphoma, a lack of enhancement is not the expected imaging pattern. After the patient did not respond to antiviral treatment, PLE was considered. The findings fulfilled the criteria for Ophelia syndrome, which consists in an interval of <4 years between the onset of neuropsychiatric disturbance and the diagnosis of the Hodgkin lymphoma, exclusion of other cancer-related complications, and evidence of hippocampal abnormalities on MR imaging.

A 38-year-old woman presented with personality and behavioral changes associated with progressive drug-resistant epilepsy. Memory testing revealed an anterograde episodic memory disorder, and electroencephalography showed TL epileptiform discharges. A, A selective hyperintensity in the hippocampi that extended to the amygdalae bilaterally was noticed on an axial FLAIR image, predominantly on the left side (arrow). B, Imaging follow-up revealed bilateral hippocampal sclerosis, which is shown in a coronal FLAIR image (arrowheads). Whole-body PET/CT and pelvic sonography were unremarkable (not shown). Autoimmune encephalitis was suggested, and a high titer of GAD65 antibodies was confirmed.

A healthy 46-year-old woman presented with an acute onset of psychiatric disturbance and hyponatremia. A, Bilateral hyperintensity and mild enlargement were noticed on an axial FLAIR image in both hippocampi and amygdalae. B, No abnormal restricted diffusion was observed on DWI. The final diagnosis was anti-VGKC encephalitis. Restricted diffusion may occur in approximately 50% of patients at this phase and is usually restricted to the limbic system. The presence of faciobrachial dystonic or tonic seizures, hyponatremia, and unremarkable CSF in the setting of LE should raise concern that anti-LGI1 encephalitis is present.

A 47-year-old man with HSE. A, Bilateral symmetric cortical swelling and hyperintensity on axial FLAIR were observed in the anteromedial TLs (arrows) and also affected the insular cortex and rectus gyri (arrowhead). B, Restricted diffusion was documented in the same areas on DWI (asterisks). Bilateral and usually asymmetric involvement of the limbic system sparing the basal ganglia in the setting of acute LE should raise concerns for HSE. The presence of hemorrhagic foci and gyriform enhancement are also of diagnostic value in more-advanced disease. C, A similar pattern with bilateral asymmetrical involvement of the anteromedial TLs (arrows) on coronal FLAIR was observed in addition to the extensive white matter changes (arrowheads) in a 59-year-old man with progressive dementia who was later diagnosed with neurosyphilis.

A previously healthy 67-year-old man presented with a transient isolated episode of partial complex seizures and dysphasia. A, A cortical abnormality that involved the lateral aspect of the left TL (asterisk) and a subtle hyperintensity on coronal T2 were noticed in the ipsilateral hippocampus. B, Restricted diffusion on DWI was visible in the same areas (arrowhead), and a diagnosis of postictal edema was considered. C, After 2 months and a worsening of the clinical manifestations, a necrotic mass in the left TL (arrow) was observed on a T1 postcontrast image. A diagnosis of glioblastoma was confirmed after surgery. High-grade gliomas can manifest early as ill-defined lesions that usually have restricted diffusion and involve the cortex with a lack of a mass effect. Follow-up imaging and advanced imaging techniques are crucial for making the diagnosis.

A 15-month-old child presented with a prolonged generalized tonic-clonic seizure episode. A, Extensive hyperintensity on an axial FLAIR image that involves the cortex and the white matter of the right TL (asterisk) indicated postictal edema. B, Comparative FLAIR imaging results on follow-up after 6 months are consistent with right mesial temporal sclerosis (arrowhead) in this patient who developed chronic epilepsy.

A 45-year-old woman presented with strokelike episodes associated with fluctuating and progressive cognitive impairment. Severe atrophy and bilateral hyperintensity in the hippocampi (arrowheads) along with mild cortical atrophy and scattered white matter changes were observed on a coronal FLAIR image. Although the patient had euthyroid status, she presented with high titers of serum antithyroperoxidase (490 U/mL; reference value, <60 U/mL). After excluding other causes, the diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis was considered.