History and Physical
A 9-year-old previously healthy boy presented with personality changes, fatigue, right facial weakness, drooling, and dysarthria over the course of 2 weeks. He became withdrawn and less interactive with his family. He did not have any recent illnesses, vaccination, travel, or insect bites. Upon presentation, he was perseverative, dysarthric, and had mild right facial droop with tongue deviation to the right. He also had right pronator drift, right upper extremity ataxia, and mild difficulty with tandem gait.
Diagnostic Workup
Brain MRI was significant for multifocal T2/FLAIR hyperintensities involving the bilateral frontotemporal lobes, particularly the inferior frontal lobes, mesial temporal lobes, and insulae ( Fig. 54.1 ). There was no restricted diffusion, hemorrhage, or abnormal enhancement. Cranial nerves were normal.
Limbic encephalitis. Brain MRI, axial FLAIR, shows multifocal hyperintensities involving the (A) left frontal lobe, (B) right insula, and (C) bilateral mesial temporal lobes. Follow-up MRI shows decreased signal abnormalities with development of atrophy in the (D) insulae, (E) hippocampi and temporal lobes. FLAIR , Fluid-attenuated inversion recovery.
HSV encephalitis. MRI brain, (A) axial FLAIR, (B) T2, and (C) DWI show hyperintense signal in the left hippocampus. DWI , Diffusion-weighted imaging; FLAIR , fluid-attenuated inversion recovery.
Within 24 hours the patient developed hypotonia, worsening distal weakness (left greater than right), areflexia in all extremities, and diffuse pain. Blood testing for metabolic/endocrine abnormalities and serum inflammatory markers was unrevealing, aside from mildly elevated ESR. Autoimmune encephalitis and meningitis/encephalitis panels were negative. Rheumatologic testing showed positive antinuclear antibody (ANA) (titer 1:80). EBV, mycoplasma, and CMV IgG were positive, with negative IgM. CSF at presentation was significant for 23 WBCs (90% lymphocytes), with normal protein and glucose. Neopterin and IgG index were elevated and oligoclonal bands were positive. MOG and AQP-4 antibodies were negative. CT chest, abdomen, and pelvis did not reveal any evidence of malignancy. Over the subsequent 3 days, a sensory level was identified around T5 to T8. He was treated with IV methylprednisolone for 5 days, started on IVIG for 2 days with clinical improvement, then discharged on daily prednisone.
Repeat MRI 1 month later revealed decreased T2/FLAIR hyperintensities, with corresponding volume loss of the temporal lobes. He ultimately developed seizures with EEG significant for left temporal notched slowing, for which he was started on oxcarbazepine with good control. At 3-month follow up, his residual deficits were mild intrinsic hand weakness, mild decreased sensation to temperature in the lower extremities, hyperreflexia, and bilateral ankle clonus.
Clinical Differential Diagnoses
Rapidly progressive mental status changes and cranial nerve deficits can be seen in infectious, rheumatologic, and autoimmune processes.
CNS infections include Lyme, Powassan, syphilis, HIV, HSV, varicella zoster, EBV, CMV, HHV-6, arbovirus, and fungi such as histoplasma and aspergillus.
Rheumatologic processes include Sjogren’s disease, CNS lupus, sarcoidosis, and neuro-Behcet’s.
Autoimmune encephalitides, such as limbic encephalitis and NMDAR receptor (NMDAR) encephalitis, can present with subacute changes in mental status. NMDAR encephalitis is more likely to be associated with speech dysfunction, seizures, movement disorders, and dysautonomia. Limbic encephalitis can be associated with several specific antibodies, including LGI1, GABA B R, AMPAR, CASPR2, Hu, Ma2, and GAD. Both limbic encephalitis and NMDAR encephalitis may be associated with paraneoplastic processes, such as ovarian or testicular teratoma.
Imaging Differential Diagnoses
T2/FLAIR hyperintensities of the mesial temporal lobes can be seen in multiple conditions. The differential diagnosis includes infectious, metabolic, vascular, neoplastic/paraneoplastic, and autoimmune disorders.
HSV classically causes T2/FLAIR hyperintensities in the mesial temporal lobes as well as insulae, cingulate gyri, and frontal lobes with sparing of the lentiform nuclei ( Fig. 54.2 ). DWI and SWI can be helpful for early detection of restricted diffusion and hemorrhage.
Congenital CMV can also yield bilateral temporal lobe signal abnormalities with white matter changes, temporal lobe cysts, and periventricular calcifications ( Fig. 54.3 ), but typically presents at birth with chronic symptoms. Other infectious etiologies include varicella, tuberculosis, and neurosyphilis.
