Background: Bone or cartilage anomalies with affection of brain supplying arteries are a potential structural cause for ischemic stroke. In the following, we termed this entity bony stroke. Due to rarity of their description, there is no standardized workup and therapy for bony strokes. Methods: Retrospectively, we extracted diagnostic and therapeutic workup of all patients considered to have had a bony stroke between January 2017 to March 2022 at our comprehensive care center. Results: In total, 6 patients classified as a bony stroke were identified among 4200 acute patients with ischemic stroke treated during the study period. Each patient had recurrent ischemic strokes in the dependent vascular territory before diagnosis. Diagnosis was achieved by a combination of imaging devices, including sonography, computed tomography, and magnetic resonance imaging. In addition to conventional static imaging, the application of dynamic imaging modalities with the patients’ head in rotation or reclination confirmed a vessel affection following head movements in 3 patients (50%). Treatment options were interdisciplinary assessed and included the following: conservative treatment (n=1), endovascular stenting (n=2) or occlusion (n=2), surgical removal of bone/ cartilage (n=2), and surgical bypass treatment (n=1). In follow-up (mean 11.7 months), no patient experienced further ischemia. Conclusions: As a differential diagnosis, bony strokes may be considered in patients with recurrent ischemic stroke of unknown cause in one dependent vascular territory. Interdisciplinary evaluation and treatment may eliminate risk of stroke recurrence.

Background and Purpose Mechanical thrombectomy (MT) is standard care for patients suffering from an ischemic stroke due to a large vessel occlusion. Immediate and follow‐up transcranial ultrasound examinations after MT were shown to have a diagnostic benefit. However, it is unclear whether repeated extracranial ultrasound after MT has an additional diagnostic yield, that is, depicts new findings. Methods Retrospectively, from our prospective database we identified all patients after MT who presented for a follow‐up examination between January 2017 and March 2020 and who had received an ultrasound examination after MT and at follow‐up. Clinical data were extracted from our database. Ultrasound images of all patients were revisited to identify new findings at follow‐up compared to examination after MT. Results Ninety‐one patients were identified appropriate for further analysis, with a mean age of 67.8 ± 16 years. Median National Institute of Health Stroke Scale at admission was 11 ± 8.5 points. At baseline ultrasound, 18 patients (19.8%) had no atherosclerotic alterations and 73 patients (82.2%) had a plaque burden of ≥1 plaque. During follow‐up, in 5 patients (5.5%) a pathological finding presented in first examination evolved dynamically, that is, normalized. Vessel status of all other patients was stable, especially, in no patient a new relevant pathological finding occurred. Conclusions Although sonographic normalization of pathologic findings was observed, pathologic new findings were not detected during follow‐up. This study provides first data for a discussion of the role of ultrasound in a structured stroke care after MT. However, larger studies are required to improve the understanding.

With great interest, we read the research article by Park et al 1 reporting pathogenic or likely pathogenic variants according to American College of Medical Genetics and Genomics (ACMG) guidelines in 1 of 15 examined stroke genes in 12.7% of their Korean cohort of juvenile stroke. The authors classify them as "clinically relevant genetic variants" (CRGVs) but do not necessarily claim causality. In this context, we would like to discuss the clinical interpretation of genetic variants and the implementation of the umbrella term CRGV, with 3 considerations.First, Park et al describe heterozygous variants in CBS and ABCC6 as CRGVs. Whereas biallelic pathogenic variants account for autosomal recessive homocystinuria and pseudoxanthoma elasticum, monoallelic variants can represent risk alleles in ischemic stroke. 2 Such risk alleles in disease-causing genes are not necessarily causative, and the clinical impact on individuals is unclear. Beyond that, variant classification can lead to conflicting results in different sources; the variants c.*38G > A and c.1990C > T in ABCC6 are classified as pathogenic by Park et al, but mostly as likely benign on ClinVar (IDs 433370, 433252).Second, Park et al detect the p.Arg4810Lys variant in RNF213 in 5.7% of patients. RNF213 constitutes a susceptibility gene of moyamoya disease (MMD). The variant is currently not deemed to be causative of MMD, and European guidelines do not recommend testing in clinical routine. 3 Susceptibility genes should be differentiated from disease-causing genes, and application of ACMG guidelines is recommended for genes causing monogenic disorders only. 4 The authors nicely illustrate that only a quarter of patients with this variant show features of MMD and discuss an association of this variant with intracranial artery stenosis. They state that clinical implications of the variant have to be explored.Third, pathogenic variants in NOTCH3 are present in 15 of the Korean patients; however, 11 patients do not show imaging features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and penetrance of the variants remains undetermined. Park et al highlight that NOTCH3 variants may have incomplete penetrance and therefore pathogenic variants may not be clinically relevant.Concluding, we would like to emphasize the benefits of a precise genetic classification, which differentiates highly penetrant pathogenic variants associated with monogenic diseases from variants that serve as risk alleles in both disease-causing and susceptibility genes. This is relevant not only in juvenile stroke but also in other neurological diseases with monogenic forms as well as genetic risk factors, for example, amyotrophic lateral sclerosis and Parkinson disease. Applying this classification in German juvenile ischemic stroke patients, we detected a monogenic disease in 2.9% (CADASIL, Fabry disease) and variants in genes associated with an increased risk of stroke in another 2.9% (RNF213, ABCC6, PROS1). 5