Diagnostic Value of the 'Insular Knife-Cut' Sign in Suspected Herpes Simplex Virus Encephalitis
Sofia Marini1, Maria Luisa Usai2, Silvia Falso1, Davide Turilli2, Pietro Zara2, Pietro Businaro3, Martina Marini1, Giovanni Sotgiu2, Matteo Paoletti3, Salvatore Masala2, Anna Picchiecchio3, Mariangela Puci2, Sabrine Othmani2, Giacomo Greco3, Rossella Meloni2, Matteo Gastaldi3, Paolo Solla2, Raffaele Iorio1, Elia Sechi2
1Catholic University of the Sacred Heart, 2University of Sassari, 3IRCCS Mondino Foundation
Objective:

To assess the frequency and specificity of the insular knife-cut sign in patients with suspected herpes simplex virus encephalitis (HSVE).

Background:
The "insular knife-cut" sign, a sharp demarcation between FLAIR insular abnormalities and the basal ganglia on axial images, has been associated with HSVE, though its specificity remains unclear.
Design/Methods:
We retrospectively identified patients admitted for suspected HSVE over the past ten years at three Neurology Units in Italy. Inclusion criteria were: 1) CSF tested for HSV-1/2 PCR as part of the diagnostic work-up; and 2) acute brain MRI available. Brain MRIs were reviewed by two investigators in each center blinded to the final diagnosis, to determine the presence of the insular knife-cut sign.
Results:

A total of 188 patients were included: HSVE, 44; alternative diagnoses, 144 (autoimmune/paraneoplastic encephalitis, 51; infectious encephalitis, 22; acute encephalopathies of other etiologies, 71). The two groups were similar in (median [range]) age at symptoms onset (66 [56-73] vs 64 [52-74] years) and days from onset to the first brain MRI (5 [4-9] vs 4.5 [1-13]).The insular knife-cut sign was present on the initial brain MRI in 23/43 (53%) HSVE patients and 1/95 (1%) 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). In eight HSVE patients, the insular knife-cut sign appeared on subsequent MRIs, raising the sensitivity to 70.45% (95%CI, 56-82). Multivariate regression identified the insular knife-cut sign as the strongest independent predictor of HSVE (OR:42.4, 95%CI, 7.3-486.4), followed by temporal pole involvement (OR:12.86, 95%CI, 3.7-54.6), abnormal brain MRI (OR:7.4, 95%CI, 1.6-34.3), and CSF pleocytosis (OR:4.9, 95%CI, 1.4-19.4).

Conclusions:

The insular knife-cut sign is a common and highly specific MRI finding in patients with HSVE. Its detection in clinical practice might aid HSVE diagnosis and treatment, especially when other tests are equivocal/unavailable.

10.1212/WNL.0000000000210507
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