Limbic Encephalitis: A Double Hit

History and Physical

A 4-year-old right-handed boy presented to the emergency department with fever, twitching of the left side of his face, and altered sensorium for two days. On day one, he complained of an altered sensation on the left side of his face that lasted for 30 minutes. This was followed by multiple episodes of focal-onset motor seizures affecting the left face. Subsequently, he became lethargic and confused. There was no relevant family history. His perinatal history was normal and he attained age-appropriate developmental milestones. Immunizations were up to date. He had a prior history of febrile seizures at one year of age.

Physical examination showed a fever of 101°F and a Glasgow Coma score of 11. Neurological examination demonstrated neck stiffness, left hemiparesis (3/5), brisk deep tendon reflexes, and extensor plantar response bilaterally. Due to the history of acute febrile encephalopathy with left hemiparesis, he was admitted for suspicion of CNS infection and started on empirical intravenous acyclovir, ceftriaxone, and antiseizure medications. He showed improvement after one week of treatment.

In the third week of illness, he developed new-onset generalized hyperkinetic movement disorder, insomnia, and behavioral problems, without fever or seizures at this time.

Diagnostic Workup

Brain MRI with contrast showed diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) hyperintense signal in the bilateral thalami, insulae, insular and perirolandic cortex, and white matter ( Fig. 37.1 ). There was no associated contrast enhancement or susceptibility.

A panel shows three brain M R I at the top and three M R I at the bottom with sagittal, axial, and coronal views with white matter signal changes. The section A shows a sagittal T1 view with the corpus callosum and brainstem. Section B shows an axial T2 view with hyperintense signal in the periventricular white matter. Section C shows an axial T2 view at the level of the orbits and brainstem. Section D shows a coronal F L A I R view with signal changes in the splenium of the corpus callosum and surrounding white matter. Section E shows an axial T1 post contrast view with enhancement at the posterior white matter. Section F shows a coronal T1 post contrast view with enhancement in the splenium and adjacent regions. — Fig. 37.1

Follow-up MRI in the third week showed development of gliosis in the previously affected areas, without new lesions identified ( Fig. 37.2 ).

A panel shows two brain M R I at the top and two M R I at the bottom with sagittal, axial, and coronal sections with noticeable structural variations. The section A shows a sagittal T1 view with clear delineation of the corpus callosum, ventricles, and brainstem. Section B shows an axial T1 view with symmetric ventricles and bright signal in the posterior periventricular area. Section C shows a coronal F L A I R view with prominent lateral ventricles and hyperintense signal in the surrounding white matter. Section D shows an axial T1 view with enlarged lateral ventricles and preserved cortical structures. — Fig. 37.2

Hematological and biochemical testing were normal. Cerebrospinal fluid examination (CSF) showed 10 cells (lymphocytes), glucose 80 mg/dL, protein 48 mg/dL, and sterile culture. Serum antibodies for dengue, scrub typhus, and Japanese encephalitis (JE) were negative. Herpes virus DNA was detected in the CSF by PCR. Due to the onset of new neurological symptoms in the second week of illness, CSF was collected and sent for anti-N-methyl-D-aspartate (NMDA) receptor antibodies showing an elevated titer ( Fig. 37.3 ).

A brain M R I panel of an infant presents axial T1 and T2 sections with visible white matter and brainstem changes. The section A shows a T2 axial view with symmetric bright signal areas near the lateral ventricles and cerebellar peduncles. section B shows another T2 axial view with hyperintense signal in the white matter surrounding the fourth ventricle and cerebellum. Section C shows a T1 post contrast axial view with visible enhancement in the brainstem and cranial nerves. Section D shows a T1 post contrast axial view highlighting symmetric enhancement along the base of the brain and cranial nerves. — Fig. 37.3

Clinical Differential Diagnoses

Acute encephalitis syndrome (AES) is characterized by acute onset of fever, change in mental status lasting for more than 24 hours (lethargy, personality change, disorientation, inability to talk, alteration in sleep-wake cycle, or coma), and new-onset seizures. Common causes of AES include herpesviruses, enteroviruses, paramyxoviruses, and influenza viruses. There is clinical overlap in presentation, so CSF viral serology or DNA/RNA testing is required for confirmation. Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic encephalitis in children worldwide. In adolescents and young adults, this is related to reactivation of latent oropharyngeally transmitted herpesvirus in the trigeminal nerve, while neonates can present with more widespread brain infection due to vertical transmission during birth.

Limbic encephalitis can be seen with parainfectious conditions, demyelinating diseases, cytokine exacerbation causing acute leukoencephalopathy, and autoimmune conditions such as anti-NMDA receptor encephalitis.

Rarely, metabolic disorders such as uremia, hepatic failure, and urea cycle defects can cause similar symptoms.

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