Assessing donor-recipient arterial pressure dynamics in STA-MCA bypass for moyamoya disease.

BACKGROUND: In bypass surgery for moyamoya disease (MMD), the superficial temporal artery's (STA) pressure needs to surpass that of the cortical M4 recipient of the middle cerebral artery (MCA), boosting cerebral blood flow into the MCA and enhancing cerebral circulation. This study investigates the STA-MCA arterial pressure parameters and gradients during bypass surgery, aiming to deepen our understanding of hemodynamic shifts pre- and post-operation. METHODS: DSA imaging data were prospectively collected from patients diagnosed with bilateral MMD who underwent STA-MCA bypass surgery between 2022 and 2023 and stratified according to the Suzuki stage. The mean arterial pressure (MAP) of the donor and recipient arteries was directly measured during the STA-MCA bypass procedure, and these data were statistically analyzed and evaluated. RESULTS: Among 48 MMD patients, Suzuki grading revealed that 43.8% were in early stages (II and III), while 56.2% were in advanced stages (IV, V, and VI). Predominantly, 77.1% presented with ischemic-type MMD and 22.9% with hemorrhagic type. Pre-bypass assessments showed that 62.5% exhibited antegrade blood flow direction, and 37.5% had retrograde. The mean recipient artery pressure was 35.0 ± 2.3 mmHg, with a mean donor-recipient pressure gradient (δP) of 46.4 ± 2.5 mmHg between donor and recipient arteries. Post-bypass, mean recipient artery pressure increased to 73.3 ± 1.6 mmHg. No significant correlation (r = 0.18, P = 0.21) was noted between δP and Suzuki staging. CONCLUSION: Our study elucidated that cerebral blood pressure significantly decreases beyond the moyamoya network at the distal M4 segment. Furthermore, we observed bidirectional flow in MCA territories and a significant positive pressure gradient between the STA and M4 segments. The lack of correlation between Suzuki stages and M4 pressures indicates that angiographic severity may not reflect hemodynamic conditions before surgery, highlighting the need for customized surgical approaches.

Mammalian IRE1α dynamically and functionally coalesces with stress granules.

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

Mea6/cTAGE5 cooperates with TRAPPC12 to regulate PTN secretion and white matter development.

Mutations of TRAPPC12 are associated with progressive childhood encephalopathy including abnormal white matter. However, the underlying pathogenesis is still unclear. Here, we found that Trappc12 deficiency in CG4 and oligodendrocyte progenitor cells (OPCs) affects their differentiation and maturation. In addition, TRAPPC12 interacts with Mea6/cTAGE5, and Mea6/cTAGE5 ablation in OPCs affects their proliferation and differentiation, leading to marked hypomyelination, compromised synaptic functionality, and aberrant behaviors in mice. We reveal that TRAPPC12 is associated with COPII components at ER exit site, and Mea6/cTAGE5 cKO disrupts the trafficking pathway by affecting the distribution and/or expression of TRAPPC12, SEC13, SEC31A, and SAR1. Moreover, we observed marked disturbances in the secretion of pleiotrophin (PTN) in Mea6-deficient OPCs. Notably, exogenous PTN supplementation ameliorated the differentiation deficits of these OPCs. Collectively, our findings indicate that the association between TRAPPC12 and MEA6 is important for cargo trafficking and white matter development.

Geometric constraint-triggered collagen expression mediates bacterial-host adhesion.

Cells living in geometrically confined microenvironments are ubiquitous in various physiological processes, e.g., wound closure. However, it remains unclear whether and how spatially geometric constraints on host cells regulate bacteria-host interactions. Here, we reveal that interactions between bacteria and spatially constrained cell monolayers exhibit strong spatial heterogeneity, and that bacteria tend to adhere to these cells near the outer edges of confined monolayers. The bacterial adhesion force near the edges of the micropatterned monolayers is up to 75 nN, which is ~3 times higher than that at the centers, depending on the underlying substrate rigidities. Single-cell RNA sequencing experiments indicate that spatially heterogeneous expression of collagen IV with significant edge effects is responsible for the location-dependent bacterial adhesion. Finally, we show that collagen IV inhibitors can potentially be utilized as adjuvants to reduce bacterial adhesion and thus markedly enhance the efficacy of antibiotics, as demonstrated in animal experiments.

The Salmonella Typhimurium Effector SpvB Subverts Host Membrane Trafficking by Targeting Clathrin and AP-1.

Salmonella enterica, the etiological agent of gastrointestinal and systemic diseases, translocates a plethora of virulence factors through its type III secretion systems to host cells during infection. Among them, SpvB has been reported to harbor an ADP-ribosyltransferase domain in its C terminus, which destabilizes host cytoskeleton by modifying actin. However, whether this effector targets other host factors as well as the function of its N terminus still remains to be determined. Here, we found that SpvB targets clathrin and its adaptor AP-1 (adaptor protein 1) via interactions with its N-terminal domain. Notably, our data suggest that SpvB-clathrin/AP-1 associations disrupt clathrin-mediated endocytosis and protein secretion pathway as well. In addition, knocking down of AP-1 promotes Salmonella intracellular survival and proliferation in host cells.

The Treatment Outcomes of Radiotherapy and Surgical Treatment for Patients with Cavernous Sinus Hemangioma: A Meta-Analysis.

OBJECTIVE: Cavernous sinus hemangiomas (CSHs) are infrequent benign neoplasms. This meta-analysis was conducted with the objective of examining the prognostic outcomes of surgical interventions and radiotherapy (RT) in patients diagnosed with CSHs. METHODS: A comprehensive literature search was performed across PubMed, Embase, and Web of Science databases, with traceability up to June 22, 2021. The evaluation of continuous variables was conducted by applying the weighted mean difference (WMD) and 95% confidence interval. A one-arm meta-analysis was used to scrutinize the tumor control rate, clinical improvement rate, recovery rates of abducens nerve palsy and visual disturbance, total resection rate, and the incidence rate of permanent nerve palsy post-treatment. RESULTS: In total, 29 articles were incorporated into the meta-analysis. Post-RT for CSHs, a significant reduction in tumor volume was observed (WMD [95% confidence interval] = -17.16 [-21.52, -12.80] cm3). The tumor control rate, clinical improvement rate, recovery rate of abducens nerve palsy, and the recovery rate of visual disturbance were 97.1% (92.9, 99.7), 91.9% (82.3, 98.5), 95.6% (83.2, 100.0), and 86.3% (65.0, 99.5), respectively. Following surgical treatment, the total resection rate, mean intraoperative blood loss, recovery rate of visual disturbance, incidence rate of permanent nerve palsy, and recovery rate of abducens nerve palsy were 73.2% (57.1, 86.9), 971.17 mL (584.07, 1358.27), 66.4% (32.4, 0.942), 16.0% (4.6, 31.1), and 70.6% (51.0, 87.7), respectively. Notably, the recovery rate of abducens nerve palsy post-RT was markedly higher than postsurgical treatment. CONCLUSIONS: The results of this meta-analysis underscore that RT is an effective and safe treatment modality for CSHs. Furthermore, the prognostic outcomes of RT demonstrated superiority over surgical intervention.

The protocol of tagging endogenous proteins with fluorescent tags using CRISPR-Cas9 genome editing.

The currently widely used CRISPR-Cas9 genome editing technology enables the editing of target genes (knock-out or knock-in) with high accuracy and efficiency. Guided by the small guide RNA, the Cas9 nuclease induces a DNA double-strand break at the targeted genomic locus. The DNA double-strand break can be repaired by the homology-directed repair pathway in the presence of a repair template. With the repair template containing the coding sequence of a fluorescent tag, the targeted gene can be inserted with the sequence of a fluorescent tag at the designed position. The genome editing mediated labeling of endogenous proteins with fluorescent tags avoids the potential artifacts caused by gene overexpression and substantially improves the reproductivity of imaging experiments. This protocol focuses on creating mammalian cell lines with endogenous proteins tagged with fluorescent proteins or self-labeling protein tags using CRISPR-Cas9 genome editing.

Structure and dynamics of the EGFR/HER2 heterodimer.

HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex.

Rationalized deep learning super-resolution microscopy for sustained live imaging of rapid subcellular processes.

The goal when imaging bioprocesses with optical microscopy is to acquire the most spatiotemporal information with the least invasiveness. Deep neural networks have substantially improved optical microscopy, including image super-resolution and restoration, but still have substantial potential for artifacts. In this study, we developed rationalized deep learning (rDL) for structured illumination microscopy and lattice light sheet microscopy (LLSM) by incorporating prior knowledge of illumination patterns and, thereby, rationally guiding the network to denoise raw images. Here we demonstrate that rDL structured illumination microscopy eliminates spectral bias-induced resolution degradation and reduces model uncertainty by five-fold, improving the super-resolution information by more than ten-fold over other computational approaches. Moreover, rDL applied to LLSM enables self-supervised training by using the spatial or temporal continuity of noisy data itself, yielding results similar to those of supervised methods. We demonstrate the utility of rDL by imaging the rapid kinetics of motile cilia, nucleolar protein condensation during light-sensitive mitosis and long-term interactions between membranous and membrane-less organelles.

Cavernoma-Associated Epilepsy Within the Mesial Temporal Lobe: Surgical Management and Seizure Outcome.

OBJECTIVE: We sought to explore a treatment protocol for patients with mesial temporal cerebral cavernoma (MTC)-associated epilepsy. METHODS: All MTC-associated epilepsy patients admitted to our center between January 2005 and December 2013 were analyzed. Seizure outcome for each presurgical epilepsy type was reported. The modified Engel classification was used to assess outcome. The neurologic outcome was scored by the modified Rankin Scale. RESULTS: Fifty-three patients admitted to the center were seen by a functional electrocortigraphy (ECoG group) or vascular (non-ECoG group) neurosurgery team. There were 21 patients with drug-resistant epilepsy (DRE), 20 patients with chronic epilepsy (CE), and 12 patients with sporadic epilepsy (SE). The neurovascular team treated 37 (69.8%) patients, and the ECoG group treated 16 (30.2%) patients. All patients underwent a mean follow-up of 106.5 ± 29.1 months. Almost all SE patients (11/12, 91.7%) in both teams achieved seizure-free status at follow-up. In the CE group, the long-term seizure-free probability among patients in the ECoG and non-ECoG groups was (66.7%) and (52.9%), respectively. DRE patients in the ECoG group had a lower seizure relapse rate after surgery than those who underwent non-ECoG surgery (P = 0.042). Fifty-two patients (98.1%) complained of postsurgery memory loss. Seizure outcome in the first postoperative year was a reasonable predictor of long-term outcome. CONCLUSIONS: A comprehensive preoperative and intraoperative assessment could help the patient with MTC-associated epilepsy choose a suitable surgical time and maximize the benefit between seizure control and cognition protection. The characters of intraoperative ECoG and postoperative seizure outcome at 1-year follow-up can predict a long-term epilepsy prognosis.

Inherited nuclear pore substructures template post-mitotic pore assembly.

Nuclear envelope assembly during late mitosis includes rapid formation of several thousand complete nuclear pore complexes (NPCs). This efficient use of NPC components (nucleoporins or "NUPs") is essential for ensuring immediate nucleocytoplasmic communication in each daughter cell. We show that octameric subassemblies of outer and inner nuclear pore rings remain intact in the mitotic endoplasmic reticulum (ER) after NPC disassembly during prophase. These "inherited" subassemblies then incorporate into NPCs during post-mitotic pore formation. We further show that the stable subassemblies persist through multiple rounds of cell division and the accompanying rounds of NPC mitotic disassembly and post-mitotic assembly. De novo formation of NPCs from newly synthesized NUPs during interphase will then have a distinct initiation mechanism. We postulate that a yet-to-be-identified modification marks and "immortalizes" one or more components of the specific octameric outer and inner ring subcomplexes that then template post-mitotic NPC assembly during subsequent cell cycles.

The ZAR1 resistosome is a calcium-permeable channel triggering plant immune signaling.

Nucleotide-binding, leucine-rich repeat receptors (NLRs) are major immune receptors in plants and animals. Upon activation, the Arabidopsis NLR protein ZAR1 forms a pentameric resistosome in vitro and triggers immune responses and cell death in plants. In this study, we employed single-molecule imaging to show that the activated ZAR1 protein can form pentameric complexes in the plasma membrane. The ZAR1 resistosome displayed ion channel activity in Xenopus oocytes in a manner dependent on a conserved acidic residue Glu11 situated in the channel pore. Pre-assembled ZAR1 resistosome was readily incorporated into planar lipid-bilayers and displayed calcium-permeable cation-selective channel activity. Furthermore, we show that activation of ZAR1 in the plant cell led to Glu11-dependent Ca2+ influx, perturbation of subcellular structures, production of reactive oxygen species, and cell death. The results thus support that the ZAR1 resistosome acts as a calcium-permeable cation channel to trigger immunity and cell death.

Tracking Calcium Dynamics and Immune Surveillance at the Choroid Plexus Blood-Cerebrospinal Fluid Interface.

The choroid plexus (ChP) epithelium is a source of secreted signaling factors in cerebrospinal fluid (CSF) and a key barrier between blood and brain. Here, we develop imaging tools to interrogate these functions in adult lateral ventricle ChP in whole-mount explants and in awake mice. By imaging epithelial cells in intact ChP explants, we observed calcium activity and secretory events that increased in frequency following delivery of serotonergic agonists. Using chronic two-photon imaging in awake mice, we observed spontaneous subcellular calcium events as well as strong agonist-evoked calcium activation and cytoplasmic secretion into CSF. Three-dimensional imaging of motility and mobility of multiple types of ChP immune cells at baseline and following immune challenge or focal injury revealed a range of surveillance and defensive behaviors. Together, these tools should help illuminate the diverse functions of this understudied body-brain interface.

Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic.

Clathrin-coated vesicles lose their clathrin lattice within seconds of pinching off, through the action of the Hsc70 "uncoating ATPase." The J- and PTEN-like domain-containing proteins, auxilin 1 (Aux1) and auxilin 2 (GAK), recruit Hsc70. The PTEN-like domain has no phosphatase activity, but it can recognize phosphatidylinositol phosphate head groups. Aux1 and GAK appear on coated vesicles in successive transient bursts, immediately after dynamin-mediated membrane scission has released the vesicle from the plasma membrane. These bursts contain a very small number of auxilins, and even four to six molecules are sufficient to mediate uncoating. In contrast, we could not detect auxilins in abortive pits or at any time during coated pit assembly. We previously showed that clathrin-coated vesicles have a dynamic phosphoinositide landscape, and we have proposed that lipid head group recognition might determine the timing of Aux1 and GAK appearance. The differential recruitment of Aux1 and GAK correlates with temporal variations in phosphoinositide composition, consistent with a lipid-switch timing mechanism.

Quantitative Characterization of the Membrane Dynamics of Newly Delivered TGF-ß Receptors by Single-Molecule Imaging.

The dynamics and stoichiometry of receptors newly delivered on the plasma membrane play a vital role in cell signal transduction, yet knowledge of this process is limited because of the lack of suitable analytical methods. Here we developed a new strategy that combines single-molecule imaging (SMI) and fluorescence recovery after photobleaching (FRAP), named FRAP-SMI, to monitor and quantify individual newly delivered and inserted transmembrane receptors on plasma membranes of living cells. Transforming-growth-factor-ß type II receptor (TßRII), a typical serine/threoninekinase receptor, was studied with this method. We first eliminated the fluorescence signals from the pre-existing EGFP-labeled TßRII molecules on the plasma membrane, and then we recorded the individual newly appeared TßRII-GFP by total-internal-reflection fluorescence imaging. The fluorescence-intensity distributions, photobleaching steps, and diffusion rates of the single TßRII-GFP molecules were analyzed. We reported, for the first time, that TßRII was transported to the plasma membrane mainly in the monomeric form in both resting and TGF-ß1stimulated cells. This strongly supported our former discovery that TßRII could exist as a monomer on the cell membrane. We also found that ligand stimulation resulted in enhanced delivery rates and prolonged membrane-association times for the TßRII molecules. On the basis of these observations, we proposed a mechanism of TGF-ß1-induced TßRII dimerization for receptor activation. Our method provides a useful tool for the real-time quantification of the spatial arrangement, mobility, and oligomerization of cell-surface proteins in living cells, thus providing a better understanding of cell signaling.

Mitochondria are transported along microtubules in membrane nanotubes to rescue distressed cardiomyocytes from apoptosis.

Membrane nanotubes (MNTs) act as "highways" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs); however, the elucidation of the underlying mechanism and pathophysiological significance of this transfer requires additional study. In this study, we determined that the mean movement velocity of mitochondria in MNTs between CMs and MFs was approximately 17.5 ± 2.1 nm/s. Meanwhile, treatment with microtubule polymerisation inhibitors nocodazole or colcemid in cell culture decreased mitochondrial velocity, and knockdown of the microtubule motor protein kinesin family member 5B (KIF5B) led to a similar effect, indicating that mitochondrial movement was dependent on microtubules and the motor protein KIF5B. Furthermore, we showed that hypoxia/reoxygenation-induced CM apoptosis was attenuated by coculture with intact or hypoxia/reoxygenation-treated MFs, which transferred mitochondria to CMs. This rescue was prevented either by separating the cells using Transwell culture or by impairing mitochondrial transfer with nocodazole or colcemid treatment. In conclusion, as a novel means of intercellular communication, MNTs rescue distressed CMs from apoptosis by transporting mitochondria along microtubules via KIF5B.

Preliminary Exploration of the Diagnosis and Treatment of Skull-Based Chondromyxoid Fibromas.

BACKGROUND: Chondromyxoid fibromas (CMFs) are benign tumors that occur rarely in the skull base. OBJECTIVE: To conduct a preliminary exploration of the diagnosis and treatment of cranial CMFs. METHODS: A retrospective analysis of 19 cases of CMFs in the base of the skull between 2009 and 2014 in our hospital was conducted. The clinical manifestations, imaging characteristics, pathology, treatment strategies, and outcomes were examined. RESULTS: The study cohort included 7 women (36.8%) and 12 men (63.2%), and symptom duration ranged from 1 mo to 5 yr. Of the 19 intracranial CMF cases examined, 15 (78.9%) conformed with the diagnostic criteria for extracranial CMF. Resection operations yielded subtotal removal of 13 tumors (68.4%) and partial removal of 6 tumors (31.6%). Postoperative pathological analysis demonstrated that the tumors were characterized by spindle-shaped or stellate cells arranged in a myxoid matrix without mitoses or permeation. Follow-up (range 2-7.3 yr; mean, 4.4 ± 1.7 yr) revealed that symptoms improved postoperatively in 15 cases (78.9%), were maintained in 2 cases (10.5%), and worsened in 2 cases (10.5%). Imaging follow-up revealed that residual tumors were stable in 18 cases (94.7%) and enlarged in 1 case (5.3%). CONCLUSION: An accurate diagnosis should involve comprehensive consideration of clinical, radiological, and pathological features. The treatment strategy for CMFs consists of maximizing tumor removal while protecting adjacent key structures. Postoperative stereotactic radiotherapy is appropriate for residual tumors.

Dynamics of phosphoinositide conversion in clathrin-mediated endocytic traffic.

Vesicular carriers transport proteins and lipids from one organelle to another, recognizing specific identifiers for the donor and acceptor membranes. Two important identifiers are phosphoinositides and GTP-bound GTPases, which provide well-defined but mutable labels. Phosphatidylinositol and its phosphorylated derivatives are present on the cytosolic faces of most cellular membranes. Reversible phosphorylation of its headgroup produces seven distinct phosphoinositides. In endocytic traffic, phosphatidylinositol-4,5-biphosphate marks the plasma membrane, and phosphatidylinositol-3-phosphate and phosphatidylinositol-4-phosphate mark distinct endosomal compartments. It is unknown what sequence of changes in lipid content confers on the vesicles their distinct identity at each intermediate step. Here we describe 'coincidence-detecting' sensors that selectively report the phosphoinositide composition of clathrin-associated structures, and the use of these sensors to follow the dynamics of phosphoinositide conversion during endocytosis. The membrane of an assembling coated pit, in equilibrium with the surrounding plasma membrane, contains phosphatidylinositol-4,5-biphosphate and a smaller amount of phosphatidylinositol-4-phosphate. Closure of the vesicle interrupts free exchange with the plasma membrane. A substantial burst of phosphatidylinositol-4-phosphate immediately after budding coincides with a burst of phosphatidylinositol-3-phosphate, distinct from any later encounter with the phosphatidylinositol-3-phosphate pool in early endosomes; phosphatidylinositol-3,4-biphosphate and the GTPase Rab5 then appear and remain as the uncoating vesicles mature into Rab5-positive endocytic intermediates. Our observations show that a cascade of molecular conversions, made possible by the separation of a vesicle from its parent membrane, can label membrane-traffic intermediates and determine their destinations.

Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-ß first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-ß along filopodia. Arp2/3 and integrin-ß then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-ß, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-ß and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

Long-Term Outcomes of Surgical Treatment in 181 Patients with Supratentorial Cerebral Cavernous Malformation-Associated Epilepsy.

OBJECTIVE: To evaluate the efficacy of surgery as a treatment for supratentorial cerebral cavernous malformation-associated epilepsy (SCCMAE) and determine the factors that influence outcomes. METHODS: During the 5-year period from 2005 to 2009, this study included 181 consecutive patients who were diagnosed with SCCMAE and surgically treated in a single institution. Each patient was followed up for at least 5 years postoperatively. A time-to-event analysis was performed using Kaplan-Meier curves and Cox regression models to evaluate the associated risk factors. RESULTS: The age at seizure onset was 30.6 ± 14.3 years, and the age at the time of surgery was 33.4 ± 14.6 years. The female/male ratio was 0.81:1. The mean diameter of the cerebral cavernous malformations (CCMs) was 2.0 cm. For CCMs involving eloquent brain areas, the CCM was removed with (in 14 cases) or without (in 28 lesions) the peripheral hemosiderin. None of the patients had long-term neurologic disabilities. An Engel class I outcome was achieved in 89.0%, 83.4%, 81.8%, and 80.1% of the patients after 6 months, 1 year, 2.5 years, and 5-years of follow-up, respectively. In patients who were class I after 1 year, the prevalence of seizure remission 5 years postoperatively was 96.0% (95% confidence interval, 94.4%-97.6%). CONCLUSIONS: This study supports the efficacy of using surgery to treat SCCMAE. A shorter duration of preoperative epilepsy was associated with better seizure control after surgery, and patient status at the 1-year follow-up was a reliable indicator of long-term Engel class I epilepsy control.