What is the management approach for a patient with a low-density lesion in the temporal lobes?

Management of Low-Density Temporal Lobe Lesions

The immediate priority is to obtain MRI with specific epilepsy protocols to characterize the lesion and determine if this represents herpes simplex encephalitis (requiring urgent acyclovir), mesial temporal sclerosis, a low-grade epilepsy-associated tumor, or another etiology—each requiring distinct management pathways. 1, 2

Initial Diagnostic Approach

Urgent Considerations: Rule Out Herpes Simplex Encephalitis

• Bilateral temporal lobe involvement with low-density lesions is nearly pathognomonic for herpes simplex encephalitis (HSE), which represents a medical emergency requiring immediate empiric acyclovir treatment. 1

• HSE typically presents with fever, hemicranial headache, language and behavioral abnormalities, memory impairment, and seizures. 1

• MRI reveals temporal and/or inferior frontal lobe edema with high signal intensity on FLAIR and T2-weighted images; more than 90% of HSE cases documented by CSF PCR show MRI abnormalities. 1

• CSF PCR for HSV-1 and HSV-2 has 95% sensitivity and 99% specificity and should be obtained immediately if HSE is suspected. 1

• CT findings in HSE show low-density lesions in the deep temporal lobe, with contrast enhancement present in patients examined within 78 days of symptom onset. 3

MRI Protocol Requirements

• MRI is the imaging study of choice and must include thin coronal slices (3 mm) perpendicular to the long axis of the hippocampus, high-resolution 3-D T1-weighted gradient echo sequences with 1-mm isotropic voxels, and coronal T2 and coronal/axial FLAIR sequences. 1, 2

• These sequences assess for hippocampal signal abnormality, atrophy, loss of internal structure (mesial temporal sclerosis), and malformations of cortical development including focal cortical dysplasia. 1

• Intravenous contrast is not routinely necessary but should be used when images without contrast are insufficient or if neoplasm or inflammatory conditions are suspected. 1

• Diffusion-weighted imaging is superior to conventional MRI for detecting early signal abnormalities in viral encephalitis. 1

Differential Diagnosis Framework

Mesial Temporal Sclerosis (MTS)

• MTS is the most common cause of temporal lobe seizures and presents as hippocampal atrophy with increased T2/FLAIR signal. 1, 2

• MRI shows sensitivity of 84% for MTS, significantly higher than CT (62%). 2

• Patients typically present with medically refractory complex partial seizures with or without secondary generalization. 2

• FDG-PET demonstrates glucose hypometabolism in the affected temporal lobe with sensitivity of 63-67% when MRI is normal or nonspecific. 2

Low-Grade Epilepsy-Associated Tumors

• Dysembryoplastic neuroepithelial tumors (DNETs) are indolent tumors with benign pathology that remain clinically stable over many years. 1

• DNETs typically present in children and young adults with long-standing, medically intractable epilepsy. 1

• Patients with DNET have normal life expectancy and should not undergo postoperative chemotherapy or radiotherapy. 1

• Cortical dysplasia is present adjacent to DNETs in approximately 70-83% of cases, which has implications for surgical planning. 1

Other Etiologies

• CT alone is often insufficient, as it has difficulty differentiating cystic from solid lesions and neoplastic from non-neoplastic pathology based on imaging features alone. 4

• Flavivirus encephalitis (West Nile, Japanese encephalitis) and Eastern equine encephalitis can show mixed intensity or hypodense lesions in the thalamus, basal ganglia, and midbrain on T1-weighted images. 1

Management Based on Etiology

If Herpes Simplex Encephalitis

• Initiate acyclovir immediately (B-III recommendation) without waiting for confirmatory testing if clinical suspicion is high. 1

• Obtain CSF for HSV PCR, but do not delay treatment. 1

• Monitor for complications including cerebral edema, hemorrhage, and seizures. 1

If Mesial Temporal Sclerosis with Medically Refractory Epilepsy

• The standard trial of medical management is 2 years, but earlier surgical intervention is reasonable when multiple appropriate antiepileptic drugs fail to establish control. 1, 2

• Complete surgical resection of the epileptogenic region via temporal lobectomy is the treatment of choice for medically refractory MTS, with extended resection showing higher success rates and low morbidity compared to lesionectomy alone. 1, 2

• Temporal lobectomy demonstrates better seizure outcomes than lesionectomy in multiple studies. 1, 2

• Incomplete resection significantly increases the risk of seizure recurrence and need for reoperation. 1, 2

• Duration of epilepsy prior to resection does not affect epilepsy outcome, so surgery should not be delayed once the decision is made. 1, 2

If DNET or Low-Grade Tumor

• Complete excision of the DNET together with a rim of surrounding dysplastic brain is the most efficient surgical approach given higher success rates and low morbidity. 1

• Resection of dysplastic brain in addition to the DNET leads to better long-term seizure control, as cortical dysplasia is present in 70-83% of cases. 1

• Residual tumor is a risk factor for seizure recurrence at long-term follow-up, making complete resection critical. 1

• Temporal lobectomy leads to better seizure outcomes than lesionectomy alone (86.6% Engel Class I vs. 69%). 1

• Recurrences after complete surgical resection have not been described, and even following partial resection, progressive disease is not typically observed. 1

Advanced Functional Imaging

When to Consider FDG-PET

• FDG-PET should be obtained when MRI is normal or shows nonspecific findings, with sensitivity of 63-67% for detecting metabolic abnormalities in temporal lobe epilepsy. 2

• In extra-temporal lobe epilepsy, FDG-PET sensitivity is approximately 55% overall but reaches 80% in presurgical settings when combined with visual and quantification tools. 1

• Focal hypometabolism on PET is a significant positive indicator of postoperative seizure freedom. 1

• Concordance between multiple diagnostic modalities (MRI, EEG, PET, SPECT) is associated with better surgical outcomes. 2

Ictal and Interictal SPECT

• Ictal SPECT demonstrates hyperperfusion of the epileptogenic region during seizures, while interictal SPECT shows hypoperfusion. 2

• Subtraction ictal SPECT co-registered to MRI (SISCOM) improves sensitivity and specificity of seizure-related perfusion networks. 2

Critical Pitfalls to Avoid

• Never delay empiric acyclovir if herpes simplex encephalitis is in the differential—bilateral temporal involvement is nearly pathognomonic and mortality is high without treatment. 1

• Do not rely on CT alone for characterization, as it cannot reliably differentiate cystic from solid or neoplastic from non-neoplastic lesions. 4

• Incomplete surgical resection dramatically increases seizure recurrence rates—complete removal of both the lesion and surrounding dysplastic cortex is essential. 1, 2

• Do not assume unilateral temporal lesions will cause significant semantic memory deficits—bilateral anterior temporal pathology is typically required for central semantic impairment. 5

• Avoid performing only lesionectomy when temporal lobectomy is feasible, as extended resection provides superior seizure outcomes. 1