Chronobiological Spatial Clusters of Cortical Regions in the Human Brain.

PURPOSE: We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs). METHODS: High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us. RESULTS: We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2). CONCLUSIONS: This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.

Dimensional changes of the gingival tissues induced by clear aligners and fixed orthodontic appliances: A retrospective study.

OBJECTIVE: The aim of this study was to evaluate gingival tissue adaption induced by orthodontic tooth movement, in terms of clinical crown height (i.e., attachment loss), and thickness of the keratinized gingiva at the margin level. METHODS: Pre- and post-treatment intraoral models/scans of 100 orthodontically treated patients (50 treated with clear aligners and 50 treated with fixed appliance) were acquired. Models were digitally scanned. Each couple of pre- and post-treatment scans were superimposed using the Compare© software (Medit spa, Seoul, Republic of Korea) taking the same reference landmarks in all cases, that were the palatal rugae for the upper arch, and the labial median frenulum for the lower arch. Only teeth that had undergone vestibulo-palatal (or vice versa) movement, greater than 1 mm were included in the analyses. The change from pre-treatment to post-treatment, in the clinical crown height and thickness of the keratinized gingiva at the margin level were digitally measured and compared between the two groups. Statistical analysis included paired t-tests, and unpaired t-tests with significance set at p<0.05. RESULTS: There was a statistically significant change in clinical crown height and gingival thickness in both groups. However, a clinically relevant attachment loss was found only within the fixed appliance group. Whereas, regarding the change in gingival thickness, there was no clinically relevant changes between the two groups. CONCLUSIONS: Orthodontic tooth movement with fixed appliance is associated to a clinically relevant attachment loss. Clear aligners seem to be associated with a more discrete attachment loss than the one observed with fixed appliances. CLINICAL RELEVANCE: Orthodontists should pay attention and monitoring the clinical crown height (i.e., attachment loss) during orthodontic movement, mostly when using fixed appliances.

Investigation of the extent of post-extraction bone contraction and remodeling after 4 months. A prospective pilot study.

OBJECTIVES: To investigate the correlation between the serum levels of 25(OH)D and the resorption of the alveolar bone walls and regeneration of the alveolar space after tooth extraction. METHODS: 14 adults in need of extraction of hopeless teeth were enrolled. An intraoral digital impression was performed, and each patient was tested to assess serum vitamin D levels. Subsequently, extraction of teeth and contextual guided bone regeneration was performed using porcine origin graft material and a resorbable collagen membrane to covert the defect. After 4 months, an impression was taken, and the model was scanned using a professional scanner for lab. At the same time, a cone beam computed tomography was performed to plan implant insertion through fully digital computer guided surgery. Bone was collected to perform histological and histomorphometric analysis. Pre and postoperative scans were compared using a specific software to estimate the volumetric changes. Tests were applied to investigate the relationship between the different predictor variables and the outcome variables. RESULTS: 14 patients were divided in 3 groups depending on the serum Vit-D levels, identifying three ranges corresponding to low (lower than 20), medium (between 20 and 30), and optimal vitamin D levels (higher than 30). Volumetric contraction after extraction was observed for all patients, without any significant difference between the groups. Focusing on the post-extraction regeneration, patients belonging to the group with lower levels of Vit-D displayed lower and more disorganized levels of bone. Immunohistochemistry analysis showed that Col1A1 and Osteocalcin had no physiological alteration. Osteopontin could be identified near the external surface of bone tissue granules. Runx2 signals were detected near the margins of bone trabeculae. CONCLUSIONS: Serum vit-D levels do not appear to influence the extent of post-extraction bone contraction; on the contrary, they seem to influence the post-extraction regeneration. CLINICAL SIGNIFICANCE: Vit D serum levels may influence the regenerative aspect during post-extraction turn-over. This might suggest controlling and (in case of low levels) recommend Vit D supplement in the patient diet in case of extraction.

Effects of the intraoral scanner and implant library on the trueness of digital impressions in the full-arch implant scan: A comparative in vitro study.

OBJECTIVE: To evaluate the effect of intraoral scanners (IOSs) and implant libraries (ILs) on the trueness of digital impressions for the fabrication of implant-supported full-arch (FA) prostheses. METHODS: A stone cast of an edentulous maxilla with 6 implant analogues and cylindrical scanbodies (IPD ProCam®, Matarò, Barcelona, Spain) was probed using a coordinate measuring machine to capture a reference model (RM). The cast was mounted on a mannequin and scanned with 3 different IOSs (iTERO Element 5D Plus®, Align Technologies, San José, CA, USA; IS 3800®, Dexis, Quackertown, PN, USA; and i-700®, Medit, Seoul, South Korea). Ten scans were performed by an experienced operator using each IOS, first capturing only the occlusal surfaces, then the buccal and finally the palatal surfaces (less than 45 s per scan). In each scan, the meshes of the SBs were replaced by the corresponding IL file, with and without increment, to obtain the best correction for the mesh growth. The positions of the SBs in each file were compared with those in the RM, to evaluate the linear and cross distances between them. The final outcome was the trueness of the different IOSs, evaluating the effect of using different ILs on the quality of the impressions. RESULTS: Significant differences were found between the different IOS scans and the RM, and among the different IOSs, in the different segments. The correction of the mesh growth through incremental ILs did not affect the final trueness of the IOS scans. CONCLUSIONS: Different levels of trueness were found among the IOSs evaluated, in the different scan segments, but with the cylindrical SBs used herein, the correction of the mesh growth with incremental ILs did not affect the final quality of the digital impressions. STATEMENT OF CLINICAL RELEVANCE: There are still errors with IOS in the FA impressions. IOS have an effect on the quality of the digital impressions, and apparently the library has not, with purely cylindrical SBs: further studies are needed to confirm this aspect.

Impact of seizure onset zone and intracranial electroencephalography ictal characteristics on epilepsy surgery outcomes in tuberous sclerosis complex.

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1-3 was defined as good and 4-6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort.

High-gamma modulation language mapping and cognitive outcomes after epilepsy surgery.

OBJECTIVE: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high-gamma power modulations (HGM) during a visual naming task, although these sites were found language-negative on standard-of-care electrical stimulation mapping (ESM). METHODS: In drug-resistant epilepsy patients who underwent resection/ablation after stereo-electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1-year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming-related HGM. The analyses were adjusted for 1-year seizure freedom, operated hemispheres, and the volumes of surgical lesions. RESULTS: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [ß] = -.10), working memory (ß = -.10), VLI (ß = -.14), and letter-word identification (LWI; ß = -.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (ß = -.31), story memory immediate (ß = -.27), verbal learning recognition (ß = -.18), LWI (ß = -.16), spelling (ß = -.49), and passage comprehension (ß = -.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. SIGNIFICANCE: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.

Implant placement using mixed reality-based dynamic navigation: A proof of concept.

OBJECTIVES: To present the first clinical application of a novel mixed reality-based dynamic navigation (MR-DN) system in the rehabilitation of a single tooth gap. METHODS: The protocol consisted of the following: (1) three-dimensional patient data acquisition using intraoral scanning (IOS) and cone-beam computed tomography (CBCT), (2) implant planning using guided surgery software, (3) holography-guided implant placement using the novel MR-DN system (ANNA®, MARS Dental, Haifa, Israel) and (4) placement accuracy verification. RESULTS: The novel MR-DN system was safe and time-efficient, as the surgery took 30 min from anaesthesia to suturing. The accuracy of implant placement was high with minimal deviations recorded in the three planes of space compared to the presurgical planning: the error at the entry point planar distance (XY) was 0.381 mm, and the entry point planar distance (Z) was 0.173 mm, for a 3D entry point distance (En) of 0.417 mm. A 3D apex deviation (An) of 0.193 mm was registered, with an angle difference of 1.852° Conclusions: This proof-of-concept study demonstrated the clinical feasibility of MR-DN for guided implant placement in single tooth gaps. Further clinical studies on a large sample of patients are needed to confirm these positive preliminary results. Statement of clinical relevance: The use of MR-DN can change the perspectives of guided dental implant surgery as a possible alternative to the classic static and dynamic guided surgical techniques for the rehabilitation of single tooth gaps.

Infection rates during eras of intrathecal antibiotic use followed by antibiotic-impregnated catheter use in prevention of cerebrospinal fluid shunt infection.

OBJECTIVE: The Hydrocephalus Clinical Research Network (HCRN) implemented a perioperative infection prevention bundle for all CSF shunt surgeries in 2007 that included the relatively unproven technique of intrathecal instillation of the broad-spectrum antibiotics vancomycin and gentamicin into the shunt. In the meantime, the field debated the use of antibiotic-impregnated catheter (AIC) shunt tubing using clindamycin and rifampin, an increasingly widespread, but expensive and controversial, technique. It is unknown whether there were changes in infecting organisms associated with the use of these techniques during CSF shunt surgery at the hospital level. Key comparison periods include during the use of intrathecal antibiotics (period 1 from June 1, 2007, to December 31, 2011, at HCRN hospitals) and AIC (period 2 from January 1, 2012, to December 31, 2015, at HCRN as well as increasing over time at non-HCRN hospitals) and only standard use of routine prophylactic antibiotics (period 1 at non-HCRN hospitals). The aim of this study was to examine rates of CSF shunt surgery-related infections from 2007 to 2012 at the hospital level, including HCRN and non-HCRN hospitals, with a focus on infections with gram-negative organisms. METHODS: The authors conducted a retrospective observational cohort study at 6 children's hospitals with enrollment from 2007 to 2012 and surveillance through 2015. Bimonthly rates of shunt surgery-related infections were summarized to produce an overall hospital-specific time series, as well as by HCRN/non-HCRN status. An interrupted time series analysis was performed to assess the impact of change in HCRN perioperative infection prevention bundle on overall bimonthly infection rates. Quarterly rates of gram-negative shunt surgery-related infections were summarized to produce an overall hospital-specific time series. RESULTS: The overall bimonthly CSF shunt infection rate over time did not change significantly from 2007 to 2012. There was no difference in the trajectory of infection rates between HCRN and non-HCRN hospitals during the entire study period. No change in distributions of gram-negative organism infections was observed in hospitals from 2007 to 2015. CONCLUSIONS: There were no differences observed in hospital-level infection rates for low-risk patients undergoing CSF shunt surgery. This included analyses based on participation in the HCRN network, given their regular use of intrathecal antibiotics in period 1 and a focus on gram-negative infections with increasing adoption of AICs in period 2.

Novel AI-based automated virtual implant placement: Artificial versus human intelligence.

OBJECTIVES: To assess quality, clinical acceptance, time-efficiency, and consistency of a novel artificial intelligence (AI)-driven tool for automated presurgical implant planning for single tooth replacement, compared to a human intelligence (HI)-based approach. MATERIALS AND METHODS: To validate a novel AI-driven implant placement tool, a dataset of 10 time-matching cone beam computed tomography (CBCT) scans and intra-oral scans (IOS) previously acquired for single mandibular molar/premolar implant placement was included. An AI pre-trained model for implant planning was compared to human expert-based planning, followed by the export, evaluation and comparison of two generic implants-AI-generated and human-generated-for each case. The quality of both approaches was assessed by 12 calibrated dentists through blinded observations using a visual analogue scale (VAS), while clinical acceptance was evaluated through an AI versus HI battle (Turing test). Subsequently, time efficiency and consistency were evaluated and compared between both planning methods. RESULTS: Overall, 360 observations were gathered, with 240 dedicated to VAS, of which 95 % (AI) and 96 % (HI) required no major, clinically relevant corrections. In the AI versus HI Turing test (120 observations), 4 cases had matching judgments for AI and HI, with AI favoured in 3 and HI in 3. Additionally, AI completed planning more than twice as fast as HI, taking only 198 ± 33 s compared to 435 ± 92 s (p < 0.05). Furthermore, AI demonstrated higher consistency with zero-degree median surface deviation (MSD) compared to HI (MSD=0.3 ± 0.17 mm). CONCLUSION: AI demonstrated expert-quality and clinically acceptable single-implant planning, proving to be more time-efficient and consistent than the HI-based approach. CLINICAL SIGNIFICANCE: Presurgical implant planning often requires multidisciplinary collaboration between highly experienced specialists, which can be complex, cumbersome and time-consuming. However, AI-driven implant planning has the potential to allow clinically acceptable planning, significantly more time-efficient and consistent than the human expert.

White matter characteristics in children with cerebral palsy prior to selective dorsal rhizotomy: a multicenter diffusion tensor imaging study.

OBJECTIVE: The aims of this study were to 1) assess and quantify white matter (WM) microstructural characteristics derived from diffusion tensor imaging (DTI) in children with cerebral palsy (CP) prior to selective dorsal rhizotomy (SDR), and 2) investigate potential associations between WM diffusion properties and gross motor function and spasticity in children with spastic CP who underwent SDR. METHODS: This study is a multisite study based on DT images acquired prior to SDR as well as postoperative outcome data. DTI data collected from two sites were harmonized using the ComBat approach to minimize intersite scanner difference. The DTI abnormalities between children with spastic CP and controls were analyzed and correlated with the severity of impaired mobility based on the Gross Motor Function Classification System (GMFCS). The improvement in gross motor function and spasticity after SDR surgery was assessed utilizing the Gross Motor Function Measure-66 (GMFM-66), the Modified Tardieu Scale (MTS), and the modified Ashworth scale (MAS). Alterations in these outcome measures were quantified in association with DTI abnormalities. RESULTS: Significant DTI alterations, including lower fractional anisotropy (FA) in the genu of the corpus callosum (gCC) and higher mean diffusivity (MD) in the gCC and posterior limb of the internal capsule (PLIC), were found in children in the SDR group when compared with the age-matched control group (all p < 0.05). Greater DTI alterations (FA in gCC and MD in gCC and PLIC) were associated with lower mobility levels as determined based on GMFCS level (p < 0.05). The pre- to post-SDR improvement in motor function based on GMFM-66 was statistically significant (p = 0.006 and 0.002 at 6-month and 12-month follow-ups, respectively). The SDR efficacy was also identified as improving spasticity in lower-extremity muscle groups assessed with the MTS and MAS. Partial correlation analysis presented a significant association between pre- to post-SDR MTS alteration and DTI abnormalities. CONCLUSIONS: The findings in the present study provided initial quantitative evidence to establish the WM microstructural characteristics in children with spastic CP prior to SDR surgery. The study generated data for the association between baseline DTI characteristics and mobility in children with CP prior to SDR surgery. The study also demonstrated SDR efficacy in improving motor function and spasticity based on the GMFM-66, MTS, and MAS, respectively, in association with DTI data.

Artificial intelligence and mixed reality for dental implant planning: A technical note.

AIM: The aim of this work is to present a new protocol for implant surgical planning which involves the combined use of artificial intelligence (AI) and mixed reality (MR). METHODS: This protocol involves the acquisition of three-dimensional (3D) patient data through intraoral scanning (IOS) and cone beam computed tomography (CBCT). These data are loaded into AI software which automatically segments and aligns the patient's 3D models. These 3D models are loaded into MR software and used for planning implant surgery through holography. The files are then exported and used to design surgical guides via open-source software, which are 3D printed and used to prepare the implant sites through static computer-assisted implant surgery (s-CAIS). The case is finalized prosthetically through a fully digital protocol. The accuracy of implant positioning is verified by comparing the planned position with the actual position of the implants after surgery. RESULTS: As a proof of principle, the present protocol seems to be to be reliable and efficient when used for planning simple cases of s-CAIS in partially edentulous patients. The clinician can plan the implants in an authentic 3D environment without using any radiology-guided surgery software. The precision of implant placement seems clinically acceptable, with minor deviations. CONCLUSIONS: The present study suggests that AI and MR technologies can be successfully used in s-CAIS for an authentic 3D planning. Further clinical studies are needed to validate this protocol.

3D-printed short-span hybrid composite implant-supported restorations fabricated through tilting stereolithography: A retrospective clinical study on 85 patients with 1 year of follow-up.

PURPOSE: To report the clinical results obtained with fixed short-span (single crowns [SCs] and fixed partial prostheses [FPPs]) implant-supported hybrid composite restorations fabricated through tilting stereolithography (TSLA). METHODS: This retrospective clinical study included 85 patients who had been restored with 95 fixed short-span implant-supported hybrid composite (Irix Max®, DWS Systems) restorations (70 SCs and 25 FPPs up to three units) fabricated with TSLA. The full-digital model-free workflow was based on intraoral implant scanning, computer-assisted design (CAD) and 3D printing using TSLA (Dfab®, DWS Systems). The primary outcomes were the marginal adaptation, the quality of the occlusal and interproximal contact points, and the chromatic integration of the restorations, assessed independently by two experienced operators (a prosthodontist and a periodontist). A score from 1 to 5 (with 5 as the highest value, 4 for satisfactory quality, 3 for acceptable quality, and 2 and 1 as the lowest values, expressing unsatisfactory quality) was assigned by each operator to each restoration at delivery. The secondary outcomes were the survival and success of the restorations at the 1-year follow-up. The restoration was defined as successful in the absence of any complications throughout the follow-up period. A statistical analysis was conducted. RESULTS: For the quality of the marginal closure and occlusal and interproximal contact points, the 3D-printed hybrid composite restorations scored highly; the aesthetic integration was satisfactory. One year after placement, all restorations survived, with a low incidence (4.2 % overall, 5.7 % SCs) of complications (two abutment screw loosenings, two decementation of the restorations, and one upper portion of the hybrid abutment decemented from the titanium base), for a success rate of 95.8 %. CONCLUSIONS: Within the limits of this study (retrospective design, follow-up limited to 1 year from the delivery, and only cemented restorations included) fixed short-span implant-supported hybrid composite crowns and bridges fabricated through TSLA were clinically precise, presenting a low incidence of complications at 1 year. STATEMENT OF CLINICAL RELEVANCE: The use of TSLA printing technology can open new perspectives for the treatment of small edentulous gaps with definitive implant-supported prosthetic restorations.

Emotional facial expression and perioral motor functions of the human auditory cortex.

OBJECTIVE: We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements. METHODS: In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation. RESULTS: Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri. CONCLUSIONS: Multimodal data suggests that TTG+ may participate in auditory-motor integration. SIGNIFICANCE: TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse.

Accuracy of implant placement using a mixed reality-based dynamic navigation system versus static computer-assisted and freehand surgery: An in Vitro study.

PURPOSE: This in vitro study aimed to compare the accuracy of dental implant placement in partially edentulous maxillary models using a mixed reality-based dynamic navigation (MR-DN) system to conventional static computer-assisted implant surgery (s-CAIS) and a freehand (FH) method. METHODS: Forty-five partially edentulous models (with teeth missing in positions #15, #16 and #25) were assigned to three groups (15 per group). The same experienced operator performed the model surgeries using an MR-DN system (group 1), s-CAIS (group 2) and FH (group 3). In total, 135 dental implants were placed (45 per group). The primary outcomes were the linear coronal deviation (entry error; En), apical deviation (apex error; Ap), XY and Z deviations, and angular deviation (An) between the planned and actual (post-surgery) position of the implants in the models. These deviations were computed as the distances between the stereolithographic (STL) files for the planned implants and placed implants captured with an intraoral scanner. RESULTS: Across the three implant sites, the MR-DN system was significantly more accurate than the FH method (in XY, Z, En, Ap and An) and s-CAIS (in Z, Ap and An), respectively. However, S-CAIS was more accurate than MR-DN in XY, and no difference was found between MR-DN and s-CAIS in En. CONCLUSIONS: Within the limits of this study (in vitro design, only partially edentulous models), implant placement accuracy with MR-DN was superior to that of FH and similar to that of s-CAIS. STATEMENT OF CLINICAL RELEVANCE: In vitro, MR-DN showed greater accuracy in implant positioning than FH, and similar accuracy to s-CAIS: it could, therefore, represent a new option for the surgeon. However, clinical studies are needed to determine the feasibility of MR-DN.

Antibiotic impregnated catheters and intrathecal antibiotics for CSF shunt infection prevention in children undergoing low-risk CSF shunt surgery.

BACKGROUND: Cerebrospinal fluid (CSF) shunts allow children with hydrocephalus to survive and avoid brain injury (J Neurosurg 107:345-57, 2007; Childs Nerv Syst 12:192-9, 1996). The Hydrocephalus Clinical Research Network implemented non-randomized quality improvement protocols that were shown to decrease infection rates compared to pre-operative prophylactic intravenous antibiotics alone (standard care): initially with intrathecal (IT) antibiotics between 2007-2009 (J Neurosurg Pediatr 8:22-9, 2011), followed by antibiotic impregnated catheters (AIC) in 2012-2013 (J Neurosurg Pediatr 17:391-6, 2016). No large scale studies have compared infection prevention between the techniques in children. Our objectives were to compare the risk of infection following the use of IT antibiotics, AIC, and standard care during low-risk CSF shunt surgery (i.e., initial CSF shunt placement and revisions) in children. METHODS: A retrospective observational cohort study at 6 tertiary care children's hospitals was conducted using Pediatric Health Information System + (PHIS +) data augmented with manual chart review. The study population included children ≤ 18 years who underwent initial shunt placement between 01/2007 and 12/2012. Infection and subsequent CSF shunt surgery data were collected through 12/2015. Propensity score adjustment for regression analysis was developed based on site, procedure type, and year; surgeon was treated as a random effect. RESULTS: A total of 1723 children underwent initial shunt placement between 2007-2012, with 1371 subsequent shunt revisions and 138 shunt infections. Propensity adjusted regression demonstrated no statistically significant difference in odds of shunt infection between IT antibiotics (OR 1.22, 95% CI 0.82-1.81, p = 0.3) and AICs (OR 0.91, 95% CI 0.56-1.49, p = 0.7) compared to standard care. CONCLUSION: In a large, observational multicenter cohort, IT antibiotics and AICs do not confer a statistically significant risk reduction compared to standard care for pediatric patients undergoing low-risk (i.e., initial or revision) shunt surgeries.

The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.

OBJECTIVE: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS: The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS: Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p > 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p < 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p < 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle < 125° (p = 0.02), and occipital condyle-C2 sagittal vertical alignment (C-C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS: The authors' results indicate that the occipital condyle-atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.

MRI and pathology comparisons in Rasmussen's encephalitis: a multi-institutional examination of hemispherotomy outcomes relative to imaging and histological severity.

PURPOSE: Rasmussen encephalitis (RE) is a very rare chronic neurological disorder of unilateral inflammation of the cerebral cortex. Hemispherotomy provides the best chance at achieving seizure freedom in RE patients, but with significant risks and variable long-term outcomes. The goal of this study is to utilize our multicenter pediatric cohort to characterize if differences in pathology and/or imaging characterization of RE may provide a window into post-operative seizure outcomes, which in turn could guide decision-making for parents and healthcare providers. METHODS: This multi-institutional retrospective review of medical record, imaging, and pathology samples was approved by each individual institution's review board. Data was collected from all known pediatric cases of peri-insular functional hemispherotomy from the earliest available electronic medical records. Mean follow-up time was 4.9 years. Clinical outcomes were measured by last follow-up visit using both Engel and ILAE scoring systems. Relationships between categorical and continuous variables were analyzed with Pearson correlation values. RESULTS: Twenty-seven patients met study criteria. No statistically significant correlations existed between patient imaging and pathology data. Pathology stage, MRI brain imaging stages, and a combined assessment of pathology and imaging stages showed no statistically significant correlation to post-operative seizure freedom rates. Hemispherectomy Outcome Prediction Scale scoring demonstrated seizure freedom in only 71% of patients receiving a score of 1 and 36% of patients receiving a score of 2 which were substantially lower than predicted. CONCLUSIONS: Our analysis did not find evidence for either independent or combined analysis of imaging and pathology staging being predictive for post peri-insular hemispherotomy seizure outcomes, prompting the need for other biomarkers to be explored. Our data stands in contrast to the recently proposed Hemispherectomy Outcome Prediction Scale and does not externally validate this metric for an RE cohort.

Early Identification of Candidates for Epilepsy Surgery: A Multicenter, Machine Learning, Prospective Validation Study.

BACKGROUND AND OBJECTIVES: Epilepsy surgery is often delayed. We previously developed machine learning (ML) models to identify candidates for resective epilepsy surgery earlier in the disease course. In this study, we report the prospective validation. METHODS: In this multicenter, prospective, longitudinal cohort study, random forest models were validated at a pediatric epilepsy center consisting of 2 hospitals and 14 outpatient neurology clinic sites and an adult epilepsy center with 2 hospitals and 27 outpatient neurology clinic sites. The models used neurology visit notes, EEG and MRI reports, visit patterns, hospitalizations, and medication, laboratory, and procedure orders to identify candidates for surgery. The models were trained on historical data up to May 10, 2019. Patients with an ICD-10 diagnosis of epilepsy who visited from May 11, 2019, to May 10, 2020, were screened by the algorithm and assigned surgical candidacy scores. The primary outcome was area under the curve (AUC), which was calculated by comparing scores from patients who underwent epilepsy surgery before November 10, 2020, against scores from nonsurgical patients. Nonsurgical patients' charts were reviewed to determine whether patients with high scores were more likely to be missed surgical candidates. Delay to surgery was defined as the time between the first visit that a surgical candidate was identified by the algorithm and the date of the surgery. RESULTS: A total of 5,285 pediatric and 5,782 adult patients were included to train the ML algorithms. During the study period, 41 children and 23 adults underwent resective epilepsy surgery. In the pediatric cohort, AUC was 0.91 (95% CI 0.87-0.94), positive predictive value (PPV) was 0.08 (0.05-0.10), and negative predictive value (NPV) was 1.00 (0.99-1.00). In the adult cohort, AUC was 0.91 (0.86-0.97), PPV was 0.07 (0.04-0.11), and NPV was 1.00 (0.99-1.00). The models first identified patients at a median of 2.1 years (interquartile range [IQR]: 1.2-4.9 years, maximum: 11.1 years) before their surgery and 1.3 years (IQR: 0.3-4.0 years, maximum: 10.1 years) before their presurgical evaluations. DISCUSSION: ML algorithms can identify surgical candidates earlier in the disease course. Even at specialized epilepsy centers, there is room to shorten the time to surgery. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that a machine learning algorithm can accurately distinguish patients with epilepsy who require resective surgery from those who do not.

Utilization trends in cerebrospinal fluid shunt infection prevention techniques in the United States from 2007 to 2015.

OBJECTIVE: The objective of this study was to describe trends in the utilization of infection prevention techniques (standard care, intrathecal [IT] antibiotics, antibiotic-impregnated catheters [AICs], and combination of IT antibiotics and AICs) among participating hospitals over time. METHODS: This retrospective cohort study at six large children's hospitals between 2007 and 2015 included children ≤ 18 years of age who underwent initial shunt placement between 2007 and 2012. Pediatric Health Information System + (PHIS+) data were augmented with chart review data for all shunt surgeries that occurred prior to the first shunt infection. The Pearson chi-square test was used to test for differences in outcomes. RESULTS: In total, 1723 eligible children had initial shunt placement between 2007 and 2012, with 3094 shunt surgeries through 2015. Differences were noted between hospitals in gestational age, etiology of hydrocephalus, and race and ethnicity, but not sex, weight at surgery, and previous surgeries. Utilization of infection prevention techniques varied across participating hospitals. Hydrocephalus Clinical Research Network hospitals used more IT antibiotics in 2007-2011; after 2012, increasing adoption of AICs was observed in most hospitals. CONCLUSIONS: A consistent trend of decreasing IT antibiotic use and increased AIC utilization was observed after 2012, except for hospital B, which consistently used AICs.

Application of the virtual-fit method for fixed complete denture cases designed on intraoral scans: Effect of cement spacing.

OBJECTIVES: To validate the virtual-fit alignment, analyze the impact of cement spacing on internal/marginal gaps, and correlate results with conventional trueness measures. METHODS: Four dental abutment models were scanned using an industrial reference scanner (one time each), Emerald S (three times each), and Medit i700 (three times each) intraoral scanners (IOS). On each IOS scan (n = 24), three complete-arch fixed frameworks were designed with 70 or 140 µm cement space with no marginal space (groups 70 and 140) and 70 µm with an additional 20 µm space, including the margin (group 70+20). Two types of alignment were performed by GOM Inspect software. The reference and IOS scans were aligned through a conventional iterative closest point algorithm (ICP) where the penetration of the two scans was permitted into each other (conventional trueness method). Second, the computer-aided designs were superimposed with the reference scan also using an ICP, but preventing the design from virtual penetration into the model (virtual-fit method). The virtual-fit algorithm was validated by non-penetration alignment of the designs with the IOS scans. Internal and marginal gap was measured between the design and the abutments. The difference between spacing groups was compared by Friedman's test. A statistical correlation (Spearman's Rho Test) was computed between the measured gaps and the conventional trueness method. A significant difference was accepted at p<0.05 after the Bonferroni correction. RESULTS: The gaps deviated from the set cement space by 3-13 µm on IOS scans (validation of virtual-fit algorithm). The internal gap of the design on the reference scan was not affected by cement spacing (Emerald S, p = 0.779; Medit i700, p = 0.205). The marginal gap in groups 70 and 70+20 was significantly lower than in group 140 in Emerald S (p<0.05). In Medit i700, it was lower in the 70+20 group than in the group 70 (p<0.01) and in the group 140 (p<0.05). Some Medit i700 scans exhibited high marginal gaps within group 70 but not in groups 70 and 140. The measured gaps correlated significantly (r = 0.51-0.81, p<0.05-0.001) with the conventional trueness but were 2.6-4.6 times higher (p<0.001). CONCLUSION: Virtual-fit alignment can simulate restoration seating. A 20 µm marginal and 90 µm internal spacing could compensate for scan errors up to several hundred micrometers. However, 140 µm internal spacing is counterproductive. The conventional trueness method could only partially predict framework misfit. CLINICAL SIGNIFICANCE: The virtual-fit method can provide clinically interpretable data for intraoral scanners. Emerald S and Medit i700 intraoral scanners are suitable for fabricating complete-arch fixed tooth-supported prostheses. In addition, a slight elevation of spacing at the margin could compensate for moderate inaccuracies in a scan.