Diagnostic Value of the "Insular Knife-Cut" Sign in Patients With Suspected Herpes Simplex Virus Encephalitis

The "insular knife-cut" sign is a sharp demarcation between hyperintense insular lesions on fluid-attenuated inversion recovery axial images and the basal ganglia, detected on brain MRI. This sign has been associated with herpes simplex virus encephalitis (HSVE); however, its specificity remains unknown. We assessed the frequency and specificity of the insular knife-cut sign in a real-life cohort of patients with suspected HSVE.

We retrospectively identified patients admitted for suspected HSVE over the past 10 years at three Neurology Units in Italy. Inclusion criteria were cerebrospinal fluid (CSF) tested for HSV-1/2 PCR and acute brain MRI available.

A total of 188 patients were included: HSVE, 44; alternative diagnoses, 144 (autoimmune encephalitis, 51; infectious encephalitis, 22; other acute encephalopathies, 71). The insular knife-cut sign was present on the initial brain MRI in 23/44 (52.3%) HSVE patients and 1/144 (0.7%) patients with alternative diagnoses (p < 0.001). The specificity and sensitivity of the sign were 99.3% (95% CI, 96-100) and 52% (95% CI, 38-66), respectively. In eight HSVE patients, the insular knife-cut sign appeared on subsequent MRIs obtained acutely, raising the sensitivity to 70.5% (95% CI, 56-82). On multivariate regression, the insular knife-cut sign was the strongest independent predictor (odds ratio [95% CI]) of HSVE (68.9 [11.42-415.54]), followed by temporal pole involvement (8.44 [2.06-34.6]), and CSF pleocytosis (6 [1.7-21.18]).

In patients with suspected encephalitis, the insular knife-cut sign on MRI strongly predicts a diagnosis of HSVE. Its detection should prompt consideration of HSVE, even when other diagnostic tests are equivocal/unavailable.