Dimethyl Fumarate Mediates Sustained Vascular Smooth Muscle Cell Remodeling in a Mouse Model of Cerebral Aneurysm.

Cerebral aneurysms (CA) are a type of vascular disease that causes significant morbidity and mortality with rupture. Dysfunction of the vascular smooth muscle cells (VSMCs) from circle of Willis (CoW) vessels mediates CA formation, as they are the major cell type of the arterial wall and play a role in maintaining vessel integrity. Dimethyl fumarate (DMF), a first-line oral treatment for relapsing-remitting multiple sclerosis, has been shown to inhibit VSMC proliferation and reduce CA formation in a mouse model. Potential unwanted side effects of DMF on VSMC function have not been investigated yet. The present study characterizes the impact of DMF on VSMC using single-cell RNA-sequencing (scRNA-seq) in CoW vessels following CA induction and further explores its role in mitochondrial function using in vitro VSMC cultures. Two weeks of DMF treatment following CA induction impaired the transcription of the glutathione redox system and downregulated mitochondrial respiration genes in VSMCs. In vitro, DMF treatment increased lactate formation and enhanced the mitochondrial production of reactive oxygen species (ROS). These effects rendered VSMCs vulnerable to oxidative stress and led to mitochondrial dysfunction and enhancement of apoptosis. Taken together, our data support the concept that the DMF-mediated antiproliferative effect on VSMCs is linked to disturbed antioxidative functions resulting in altered mitochondrial metabolism. This negative impact of DMF treatment on VSMCs may be linked to preexisting alterations of cerebrovascular function due to renal hypertension. Therefore, before severe adverse effects emerge, it would be clinically relevant to develop indices or biomarkers linked to this disturbed antioxidative function to monitor patients undergoing DMF treatment.

Prevalence, Laterality, and Classification of Ossified Petroclival Ligaments: An Anatomical and Histological Study With Application to Skull Base Surgery.

Background The petroclival ligament (PL) forms the roof of Dorello's canal (DC). In humans, partial and complete ossification of this ligament have been reported. When completely ossified, DC is transformed into a bony foramen for the abducens nerve and accompanying vascular structures. As this osteological finding might have an impact on skull base surgery, this anatomical study was performed. Methodology Using 100 adult human skulls, the presence of an ossified PL was noted and classified. The diameter of the resultant bony foramen and laterality were documented. Additionally, PL was evaluated histologically in 10 heads. Results Overall, 8% of the sides were found to have partial or complete ossification of the PL. Partial ossification (type I) was noted on 3% of the sides. Completely ossified PL was identified on 5% of the sides. Some ossified ligaments (2.5%) were seen as an ossified bridge (type II), and others (2.5%) were converted into small foramina (type III). Three skulls (3%) were found to have a completely ossified ligament bilaterally. The mean diameter of the underlying DC was 0.8 mm. Partially ossified ligaments were statistically more likely to be on the right sides, and the diameter of the underlying DC was statistically smaller in type III. Histologically, the PL was found to have bone within it on three skull sides. Conclusions An ossified ligament can be found on imaging of the skull base. Moreover, during surgical approaches to the petroclival region and, specifically, DC, skull base surgeons should be cognizant of this anatomical variation.

Granular Foveolae in the Groove of the Sigmoid Sinus: An Anatomical Study.

Background Granular foveolae in the groove of the sigmoid sinus have rarely been reported in the literature compared to numerous published reports on the granular foveolae near the superior sagittal sinus and its sulcus on the internal aspect of the calvaria. The present study was performed to better elucidate their prevalence and locations. Materials and methods One hundred and ten adult dry skulls (220 sides) were analyzed for the presence of granular foveolae within the groove of the sigmoid sinus. The exact position of the foveolae was documented, and the diameter of the granular foveola was measured. Results Granular foveolae were found in the groove of the sigmoid sinus on 3.6% of the sides. These were at or within a mean of 1.3 cm inferior to the transverse-sigmoid junction. When a mastoid foramen was noted in the groove, it was always located inferior to the granular foveolae when present. The mean diameters of the granular foveolae of the left groove of the sigmoid sinus were 2.8 mm and 4 mm for the right grooves. The mean depth of the granular foveolae in the left groove of the sigmoid sinus was 2.7 mm and 3.5 mm for the right grooves. Granular foveolae were statistically larger and deeper on the right versus left sides (p<0.05). Conclusions Granular foveolae of the groove of the sigmoid sinus were identified most commonly on the right sides and 3.6% on all sides. If identified on medical imaging, these uncommon structures at the skull base should be considered normal anatomical variations.

Morphology of the groove of the inferior petrosal sinus: application to better understanding variations and surgery of the skull base.

Although adequate venous drainage from the cranium is imperative for maintaining normal intracranial pressure, the bony anatomy surrounding the inferior petrosal sinus and the potential for a compressive canal or tunnel has, to our knowledge, not been previously investigated. One hundred adult human skulls (200 sides) were observed and documented for the presence or absence of an inferior petrosal groove or canal. Measurements were made and a classification developed to help better understand their anatomy and discuss it in future reports. We identified an inferior petrosal sinus groove (IPSG) in the majority of specimens. The IPSG began anteriorly where the apex of the petrous part of the temporal bone articulated with the sphenoid part of the clivus, traveled posteriorly, in a slight medial to lateral course, primarily just medial to the petro-occipital fissure, and ended at the anteromedial aspect of the jugular foramen. When the IPSGs were grouped into five types. In type I specimens, no IPSG was identified (10.0%), in type II specimens, a partial IPSG was identified (6.5%), in type III specimens, a complete IPSG (80.0%) was identified, in type IV specimens, a partial IPS tunnel was identified (2.5%), and in type V specimens, a complete tunnel (1.0%) was identified. An improved knowledge of the bony pathways that the intracranial dural venous sinuses take as they exit the cranium is clinically useful. Radiological interpretation of such bony landmarks might improve patient diagnoses and surgically, such anatomy could decrease patient morbidity during approaches to the posterior cranial fossa.

Prevalence of Petrooccipital Fissure Fusion: Osteological Study with Application to Approaches to the Skull Base and Imaging Interpretation.

INTRODUCTION: The petrooccipital fissure (POF) has relevance to skull base approaches, various tumors and craniosynostoses, and some cases of age-related hearing loss. However, the prevalence of fusion and classification of such is rarely found in the extant medical literature. METHODS: One-hundred and 10 dry human skulls (220 sides) were used for this study. The skulls were evaluated for fusion of the POF. Both the endocranial and exocranial aspects of the POF were analyzed. A classification scheme was developed to better describe the location of POF fusion. RESULTS: A fused POF was identified on 36 sides (16.4%) and commonly found bilaterally (11%). Of these, 30 sides (83.3%) were completely fused (type I) and 6 sides (2.7%) were partially fused (types II and III). For the partially fused fissures, the fused part was on all but 2 sides with the most anterior portion of the petrous part of the temporal bone and adjacent clivus (type II). For the 2 sides (both right sides), the fusion was more posteriorly located between the petrous part of the temporal bone and lateral clivus (type III). Fusion of the POF was more often found in specimens with a partially or fully ossified petroclival ligament. Completely fused POF was positively correlated to sides with an intrajugular bony septum. CONCLUSIONS: A POF fusion was relatively common and associated with an ossified petroclival ligament and intrajugular bony septation. Such a prevalence is important for clinicians and skull base surgeons interpreting imaging of the skull base.