ArticleBMC neurology2025
Diagnostic performance of "pons chocolate chip sign" in heterozygous HTRA1-related cerebral small vessel disease.
Article in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
background and purposeHeterozygous HTRA1-related cerebral small vessel disease (hHTRA1-CSVD) presents diagnostic challenges due to its clinical and imaging similarities with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and sporadic cerebral small vessel disease (CSVD). Recently, the "chocolate chip sign" around the midbrain has been proposed as a potential imaging marker for hHTRA1-CSVD. However, the diagnostic value of similar findings around the pons remains unclear. This study aims to assess the diagnostic performance of the "pons chocolate chip sign" in distinguishing hHTRA1-CSVD from CADASIL and sporadic CSVD. MATERIALS AND
methodsThis cross-sectional study included seven patients with hHTRA1-CSVD, twenty-seven patients with CADASIL and twelve patients with sporadic CSVD. All participants underwent 7.0T magnetic resonance imaging (MRI). The "pons chocolate chip sign" was defined as round or ovoid hypointense dots (≥ 2 mm in diameter) surrounding the pons on T2*-weighted gradient echo images. The number of chocolate chips was independently assessed by two blinded neurologists. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, with genetic diagnosis as the gold standard.
resultsThe "pons chocolate chip sign" was found in 5/7 patients with hHTRA1-CSVD, compared to 2/27 in CADASIL and 0/12 in sporadic CSVD. ROC analysis revealed that it exhibited good discriminatory capability for hHTRA1-CSVD (area under the curve [AUC] = 0.84, 95% confidence interval [CI]: 0.63-1.00, P = 0.004). At an optimal cutoff of chocolate chips ≥ 1, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Youden index were 71.42%, 94.87%, 71.42%, 94.87%, and 0.66, respectively. When the cutoff was increased to ≥ 3 chocolate chips, the specificity improved further, reaching 100%.
conclusionsThe "pons chocolate chip sign" demonstrates high specificity for hHTRA1-CSVD and good discriminatory performance in differentiating hHTRA1-CSVD from CADASIL and sporadic CSVD.
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