Smart Spine Implants.

Smart spine implants promise to stimulate healing and provide objective information about healing progression. The ability of implants to accelerate healing and provide objective data could help guide postoperative care, foster better outcomes, and reduce complications. Real-time monitoring, remote control and programming, and data analytics are actively being developed and translated into clinical practice. This article discusses advances in smart spinal implant technology and how they may aid patients and surgeons.

Management of mild degenerative cervical myelopathy and asymptomatic spinal cord compression: an international survey.

STUDY DESIGN: Cross-sectional survey. OBJECTIVE: Currently there is limited evidence and guidance on the management of mild degenerative cervical myelopathy (DCM) and asymptomatic spinal cord compression (ASCC). Anecdotal evidence suggest variance in clinical practice. The objectives of this study were to assess current practice and to quantify the variability in clinical practice. METHODS: Spinal surgeons and some additional health professionals completed a web-based survey distributed by email to members of AO Spine and the Cervical Spine Research Society (CSRS) North American Society. Questions captured experience with DCM, frequency of DCM patient encounters, and standard of practice in the assessment of DCM. Further questions assessed the definition and management of mild DCM, and the management of ASCC. RESULTS: A total of 699 respondents, mostly surgeons, completed the survey. Every world region was represented in the responses. Half (50.1%, n = 359) had greater than 10 years of professional experience with DCM. For mild DCM, standardised follow-up for non-operative patients was reported by 488 respondents (69.5%). Follow-up included a heterogeneous mix of investigations, most often at 6-month intervals (32.9%, n = 158). There was some inconsistency regarding which clinical features would cause a surgeon to counsel a patient towards surgery. Practice for ASCC aligned closely with mild DCM. Finally, there were some contradictory definitions of mild DCM provided in the form of free text. CONCLUSIONS: Professionals typically offer outpatient follow up for patients with mild DCM and/or asymptomatic ASCC. However, what this constitutes varies widely. Further research is needed to define best practice and support patient care.

Toward Shared Decision-Making in Degenerative Cervical Myelopathy: Protocol for a Mixed Methods Study.

BACKGROUND: Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. OBJECTIVE: The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. METHODS: Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. RESULTS: Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. CONCLUSIONS: This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46809.

A scoping review of information provided within degenerative cervical myelopathy education resources: Towards enhancing shared decision making.

BACKGROUND: Degenerative cervical myelopathy (DCM) is a chronic neurological condition estimated to affect 1 in 50 adults. Due to its diverse impact, trajectory and management options, patient-centred care and shared decision making are essential. In this scoping review, we aim to explore whether information needs in DCM are currently being met in available DCM educational resources. This forms part of a larger Myelopathy.org project to promote shared decision making in DCM. METHODS: A search was completed encompassing MEDLINE, Embase and grey literature. Resources relevant to DCM were compiled for analysis. Resources were grouped into 5 information types: scientific literature, videos, organisations, health education websites and patient information leaflets. Resources were then further arranged into a hierarchical framework of domains and subdomains, formed through inductive analysis. Frequency statistics were employed to capture relative popularity as a surrogate marker of potential significance. RESULTS: Of 2674 resources, 150 information resources addressing DCM were identified: 115 scientific literature resources, 28 videos, 5 resources from health organisations and 2 resources from health education websites. Surgical management was the domain with the largest number of resources (66.7%, 100/150). The domain with the second largest number of resources was clinical presentation and natural history (28.7%, 43/150). Most resources (83.3%, 125/150) were designed for professionals. A minority (11.3% 17/150) were written for a lay audience or for a combined audience (3.3%, 5/150). CONCLUSION: Educational resources for DCM are largely directed at professionals and focus on surgical management. This is at odds with the needs of stakeholders in a lifelong condition that is often managed without surgery, highlighting an unmet educational need.

Spontaneous postpartum lateral rectus haemorrhage.

A postpartum woman presented with sudden-onset left eyelid swelling and severe pain. Clinical examination revealed left exophthalmos and ophthalmoplegia with marked resistance to retropulsion of the left globe. The patient was not able to perceive light in the affected left eye and a relative afferent pupillary defect was present. CT orbits showed an enhancing lesion in the left retrobulbar space, suggestive of a lateral rectus haemorrhage. An emergency left lateral canthotomy and inferior cantholysis was performed. A day later, an MRI showed expansion of the left lateral rectus with significant mass effect on the globe. As the visual acuity remained reduced at counting fingers and there was a persistent relative afferent pupillary defect (RAPD), an exploratory orbitotomy and haematoma evacuation was performed. Three days postoperatively, the visual acuity had returned to 6/6. Eye movements normalised within 2 weeks and follow-up imaging revealed near complete resolution of the haematoma.

Improving Awareness Could Transform Outcomes in Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 1].

STUDY DESIGN: Literature Review (Narrative). OBJECTIVE: To introduce the number one research priority for Degenerative Cervical Myelopathy (DCM): Raising Awareness. METHODS: Raising awareness has been recognized by AO Spine RECODE-DCM as the number one research priority. This article reviews the evidence that awareness is low, the potential drivers, and why this must be addressed. Case studies of success from other diseases are also reviewed, drawing potential parallels and opportunities for DCM. RESULTS: DCM may affect as many as 1 in 50 adults, yet few will receive a diagnosis and those that do will wait many years for it. This leads to poorer outcomes from surgery and greater disability. DCM is rarely featured in healthcare professional training programs and has received relatively little research funding (<2% of Amyotrophic Lateral Sclerosis or Multiple Sclerosis over the last 25 years). The transformation of stroke and acute coronary syndrome services, from a position of best supportive care with occasional surgery over 50 years ago, to avoidable disability today, represents transferable examples of success and potential opportunities for DCM. Central to this is raising awareness. CONCLUSION: Despite the devastating burden on the patient, recognition across research, clinical practice, and healthcare policy are limited. DCM represents a significant unmet need that must become an international public health priority.

Matrix Mechanotransduction via Yes-Associated Protein in Human Lamina Cribrosa Cells in Glaucoma.

Purpose: Extracellular matrix stiffening is characteristic of both aging and glaucoma, and acts as a promoter and perpetuator of pathological fibrotic remodeling. Here, we investigate the role of a mechanosensitive transcriptional coactivator, Yes-associated protein (YAP), a downstream effector of multiple signaling pathways, in lamina cribrosa (LC) cell activation to a profibrotic, glaucomatous state. Methods: LC cells isolated from glaucomatous human donor eyes (GLC; n = 3) were compared to LC cells from age-matched nonglaucomatous controls (NLC; n = 3) to determine differential YAP expression, protein levels, and proliferation rates. NLC cells were then cultured on soft (4 kPa), and stiff (100 kPa), collagen-1 coated polyacrylamide hydrogel substrates. Quantitative real-time RT-PCR, immunoblotting, and immunofluorescence microscopy were used to measure the expression, activity, and subcellular location of YAP and its downstream targets, respectively. Proliferation rates were examined in NLC and GLC cells by methyl thiazolyl tetrazolium salt assays, across a range of incrementally increased substrate stiffness. Endpoints were examined in the presence or absence of a YAP inhibitor, verteporfin (2 µM). Results: GLC cells show significantly (P < 0.05) increased YAP gene expression and total-YAP protein compared to NLC cells, with significantly increased proliferation. YAP regulation is mechanosensitive, because NLC cells cultured on pathomimetic, stiff substrates (100 kPa) show significantly upregulated YAP gene and protein expression, increased YAP phosphorylation at tyrosine 357, reduced YAP phosphorylation at serine 127, increased nuclear pooling, and increased transcriptional target, connective tissue growth factor. Accordingly, myofibroblastic markers, α-smooth muscle actin (α-SMA) and collagen type I, alpha 1 (Col1A1) are increased. Proliferation rates are elevated on 50 kPa substrates and tissue culture plastic. Verteporfin treatment significantly inhibits YAP-mediated cellular activation and proliferation despite a stiffened microenvironment. Conclusions: These data demonstrate how YAP plays a pivotal role in LC cells adopting a profibrotic and proliferative phenotype in response to the stiffened LC present in aging and glaucoma. YAP provides an attractive and novel therapeutic target, and its inhibition via verteporfin warrants further clinical investigation.

A prospective multi-center study comparing the complication profile of modest systemic hypothermia versus normothermia for acute cervical spinal cord injury.

STUDY DESIGN: Prospective multi-center trial. OBJECTIVES: To characterize the complication profile associated with modest systemic hypothermia after acute cervical SCI in a prospective multi-center study. SETTING: Five trauma centers in the United States. METHODS: We analyzed data from a prospective, multi-center trial on the use of modest systemic hypothermia for acute cervical SCI. Patients with acute cervical SCI were assigned to receive modest systemic hypothermia (33 C) or standard of care medical treatment. Patients in the hypothermia group were cooled to 33 C and maintained at the target temperature for 48 h. Complication profile and the rate of complications within the first 6 weeks after injury were compared between the two groups. Multiple regression analysis was performed to determine risk factors for complications after injury. RESULTS: Fifty patients (hypothermia: 27, control: 23) were analyzed for this study. Median age was significantly lower in the hypothermia arm (39 vs 59 years, p = 0.02). Respiratory complications were the most common (hypothermia: 55.6% vs control: 52.2%, p = 0.81). The rate of deep vein thrombosis was not significantly different between the two groups (hypothermia: 14.8% vs control 17.4%, p = 0.71). The rate of complications was not statistically different between the two groups. CONCLUSION: In this prospective multi-center controlled trial, preliminary data show that modest systemic hypothermia was not associated with increased risk of complications within the first 6 weeks after acute cervical SCI. TRIAL INFORMATION: The study is registered on clinicaltrials.gov NCT02991690. University of Miami IRB (Central IRB) approval No.: 20160758. Emory University IRB #IRB00093786.

Historical perspectives, challenges, and future directions of implantable brain-computer interfaces for sensorimotor applications.

Almost 100 years ago experiments involving electrically stimulating and recording from the brain and the body launched new discoveries and debates on how electricity, movement, and thoughts are related. Decades later the development of brain-computer interface technology began, which now targets a wide range of applications. Potential uses include augmentative communication for locked-in patients and restoring sensorimotor function in those who are battling disease or have suffered traumatic injury. Technical and surgical challenges still surround the development of brain-computer technology, however, before it can be widely deployed. In this review we explore these challenges, historical perspectives, and the remarkable achievements of clinical study participants who have bravely forged new paths for future beneficiaries.

Prolonged phenanthrene exposure reduces cardiac function but fails to mount a significant oxidative stress response in the signal crayfish (Pacifastacus leniusculus).

Crustaceans are important ecosystem bio-indicators but their response to pollutants such as polyaromatic hydrocarbons (PAHs) remains understudied, particularly in freshwater habitats. Here we investigated the effect of phenanthrene (at 0.5, 1.0 and 1.5 mg L-1), a 3-ringed PAH associated with petroleum-based aquatic pollution on survival, in vivo and in situ cardiac performance, the oxidative stress response and the tissue burden in the signal crayfish (Pacifastacus leniusculus). Non-invasive sensors were used to monitor heart rate during exposure. Phenanthrene reduced maximum attainable heart rate in the latter half (days 8-15) of the exposure period but had no impact on routine heart rate. At the end of the 15-day exposure period, the electrical activity of the semi-isolated in situ crayfish heart was assessed and significant prolongation of the QT interval of the electrocardiogram was observed. Enzyme pathways associated with oxidative stress (superoxide dismutase and total oxyradical scavenging capacity) were also assessed after 15 days of phenanthrene exposure in gill, hepatopancreas and skeletal muscle; the results suggest limited induction of protective antioxidant pathways. Lastly, we report that 15 days exposure caused a dose-dependent increase in phenanthrene in hepatopancreas and heart tissues which was associated with reduced survivability. To our knowledge, this study is the first to provide such a thorough understanding of the impact of phenanthrene on a crustacean.

The role of lamina cribrosa tissue stiffness and fibrosis as fundamental biomechanical drivers of pathological glaucoma cupping.

The primary biomechanical driver of pathological glaucomatous cupping remains unknown. Finite element modeling indicates that stress and strain play key roles. In this article, primarily a review, we utilize known biomechanical data and currently unpublished results from our lab to propose a three-stage, tissue stiffness-based model to explain glaucomatous cupping occurring at variable levels of translaminar pressure (TLP). In stage 1, a short-term increase in TLP gradient induces a transient increase in lamina cribrosa (LC) strain. Beyond a critical level of strain, the tissue stiffness rises steeply provoking cellular responses via integrin-mediated mechanotransduction. This early mechanoprotective cellular contraction reduces strain, which reduces tissue stiffness by return of the posteriorly deflected LC to baseline. In stage 2 a prolonged period of TLP increase elicits extracellular matrix (ECM) production leading to fibrosis, increasing baseline tissue stiffness and strain and diminishing the contractile ability/ability to return to the baseline LC position. This is supported by our three-dimensional collagen contraction assays, which show significantly reduced capacity to contract in glaucoma compared with normal LC cells. Second, 15% cyclic strain in LC cells over 24 h elicits a typical increase in ECM profibrotic genes in normal LC cells but a highly blunted response in glaucoma LC cells. Stage 3 is characterized by persistent fibrosis causing further stiffening and inducing a feed-forward ECM production cycle. Repeated cycles of increased strain and stiffness with profibrotic ECM deposition prevent optic nerve head (ONH) recoil from the new deflected position. This incremental maladaptive modeling leads to pathological ONH cupping.

PI3K-Yap activity drives cortical gyrification and hydrocephalus in mice.

Mechanisms driving the initiation of brain folding are incompletely understood. We have previously characterized mouse models recapitulating human PIK3CA-related brain overgrowth, epilepsy, dysplastic gyrification and hydrocephalus (Roy et al., 2015). Using the same, highly regulatable brain-specific model, here we report PI3K-dependent mechanisms underlying gyrification of the normally smooth mouse cortex, and hydrocephalus. We demonstrate that a brief embryonic Pik3ca activation was sufficient to drive subtle changes in apical cell adhesion and subcellular Yap translocation, causing focal proliferation and subsequent initiation of the stereotypic 'gyrification sequence', seen in naturally gyrencephalic mammals. Treatment with verteporfin, a nuclear Yap inhibitor, restored apical surface integrity, normalized proliferation, attenuated gyrification and rescued the associated hydrocephalus, highlighting the interrelated role of regulated PI3K-Yap signaling in normal neural-ependymal development. Our data defines apical cell-adhesion as the earliest known substrate for cortical gyrification. In addition, our preclinical results support the testing of Yap-related small-molecule therapeutics for developmental hydrocephalus.

Maximising Refractive Outcomes with an Extended Depth of Focus IOL.

OBJECTIVE: To assess the impact of the magnitude of preoperative and postoperative corneal astigmatism on refractive outcomes in patients undergoing cataract surgery or lens exchange with an extended depth of focus intraocular lens. To compare visual outcomes of steep and temporal on-axis corneal incisions. SETTING: Department of Ophthalmology, Blackrock Clinic, Dublin, Ireland. DESIGN: Prospective cohort analysis. METHODS: Fifty-three consecutive adult patients (94 eyes) undergoing routine phacoemulsification with Symfony IOL implantation were analysed. Exclusion criteria: targets for mini-monovision, incomplete data, other ocular pathology. Data were prospectively collected on pre- and postoperative refraction, keratometry, distance vision, near vision, surgical wound site and Surgically Induced Astigmatism (SIA). RESULTS: The average postoperative monocular Uncorrected Distance and Near visual acuities (UDVA and UNVA) were 0.12 LogMAR (± 0.1) (6/7.5+1) and 0.34 LogMAR (± 0.09) respectively. The average binocular UDVA and UNVA were 0.05 (± 0.07) and 0.29 LogMAR (± 0.06) respectively. Low levels of preoperative corneal astigmatism (0-0.99 D) were associated with better LogMAR UDVA and UNVA when compared with higher levels (> 0.99 D): 0.11 (CI 0.103-0.107) vs. 0.206 (CI 0.122-0.290) (p =0.015, CI 95%) and 0.33 (CI 0.316 - 0.356) vs. 0.39 (CI 0.34-0.43) (p =0.034, CI 95%) respectively. When patients with steep on-axis corneal incisions were compared with temporal on-axis corneal incisions, no difference was detected in visual outcome or SIA. CONCLUSION: The Symfony IOL is an effective surgical means of addressing presbyopia and reducing postoperative spectacle dependence. We stress caution when offering potential spectacle independence for patients with over 1D of preoperative corneal astigmatism as these patients achieve statistically significantly inferior and less predictable visual results.

Fractional anisotropy to quantify cervical spondylotic myelopathy severity.

BACKGROUND: A number of clinical tools exist for measuring the severity of cervical spondylotic myelopathy (CSM). Several studies have recently described the use of non-invasive imaging biomarkers to assess severity of disease. These imaging markers may provide an additional tool to measure disease progression and represent a surrogate marker of response to therapy. Correlating these imaging biomarkers with clinical quantitative measures is critical for accurate therapeutic stratification and quantification of axonal injury. METHODS: Fourteen patients and seven healthy control subjects were enrolled. Patients were classified as mildly (7) or moderately (7) impaired based on Modified Japanese Orthopedic Association Scale. All patients underwent diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) analyses. In addition to standard neurological examination, all participants underwent 30-m Walking Test, 9-hole Peg Test (9HPT), grip strength, key pinch, and vibration sensation thresholds in the index finger and great toe. Differences in assessment scores between controls, mild and moderate CSM patients were correlated with DTI and DBSI derived fractional anisotropy (FA). RESULTS: Clinically, 30-meter walking times were significantly longer in the moderately impaired group than in the control group. Maximum 9HPT times were significantly longer in both the mildly and moderately impaired groups as compared to normal controls. Scores on great toe vibration sensation thresholds were lower in the mildly impaired and moderately impaired groups as compared to controls. We found no clear evidence for any differences in minimum grip strength, minimum key pinch, or index finger vibration sensation thresholds. There were moderately strong associations between DTI and DBSI FA values and 30-meter walking times and 9HPT. CONCLUSIONS: The 30-m Walking Test and 9HPT were both moderately to strongly associated with DTI/DBSI FA values. FA may represent an additional measure to help differentiate and stratify patients with mild or moderate CSM.

Spinal Cord Injury Disrupts Resting-State Networks in the Human Brain.

Despite 253,000 spinal cord injury (SCI) patients in the United States, little is known about how SCI affects brain networks. Spinal MRI provides only structural information with no insight into functional connectivity. Resting-state functional MRI (RS-fMRI) quantifies network connectivity through the identification of resting-state networks (RSNs) and allows detection of functionally relevant changes during disease. Given the robust network of spinal cord afferents to the brain, we hypothesized that SCI produces meaningful changes in brain RSNs. RS-fMRIs and functional assessments were performed on 10 SCI subjects. Blood oxygen-dependent RS-fMRI sequences were acquired. Seed-based correlation mapping was performed using five RSNs: default-mode (DMN), dorsal-attention (DAN), salience (SAL), control (CON), and somatomotor (SMN). RSNs were compared with normal control subjects using false-discovery rate-corrected two way t tests. SCI reduced brain network connectivity within the SAL, SMN, and DMN and disrupted anti-correlated connectivity between CON and SMN. When divided into separate cohorts, complete but not incomplete SCI disrupted connectivity within SAL, DAN, SMN and DMN and between CON and SMN. Finally, connectivity changed over time after SCI: the primary motor cortex decreased connectivity with the primary somatosensory cortex, the visual cortex decreased connectivity with the primary motor cortex, and the visual cortex decreased connectivity with the sensory parietal cortex. These unique findings demonstrate the functional network plasticity that occurs in the brain as a result of injury to the spinal cord. Connectivity changes after SCI may serve as biomarkers to predict functional recovery following an SCI and guide future therapy.

Diffusion Assessment of Cortical Changes, Induced by Traumatic Spinal Cord Injury.

Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm known as Diffusion Basis Spectrum Imaging (DBSI) has been proposed to more accurately delineate white matter injury. The objective of this study was to investigate whether DTI/DBSI changes that extend to level of the cerebral peduncle and internal capsule following a SCI could be correlated with clinical function. A prospective non-randomized cohort of 23 patients with chronic spinal cord injuries and 17 control subjects underwent cranial diffusion weighted imaging, followed by whole brain DTI and DBSI computations. Region-based analyses were performed on cerebral peduncle and internal capsule. Three subgroups of patients were included in the region-based analysis. Tract-Based Spatial Statistics (TBSS) was also applied to allow whole-brain white matter analysis between controls and all patients. Functional assessments were made using International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) as modified by the American Spinal Injury Association (ASIA) Scale. Whole brain white matter analysis using TBSS finds no statistical difference between controls and all patients. Only cervical ASIA A/B patients in cerebral peduncle showed differences from controls in DTI and DBSI results with region-based analysis. Cervical ASIA A/B SCI patients had higher levels of axonal injury and edema/tissue loss as measured by DBSI at the level of the cerebral peduncle. DTI Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD) was able to detect differences in cervical ASIA A/B patients, but were non-specific to pathologies. Increased water fraction indicated by DBSI non-restricted isotropic diffusion fraction in the cerebral peduncle, explains the simultaneously increased DTI AD and DTI RD values. Our results further demonstrate the utility of DTI to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss. Our results suggest a preservation of axonal integrity at the cortical level and has implications for future regenerative clinical trials.

Bioresorbable silicon electronic sensors for the brain.

Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.

Dural arteriovenous fistula-induced thalamic dementia: report of 4 cases.

Nonhemorrhagic neurological deficits are underrecognized symptoms of intracranial dural arteriovenous fistulas (dAVFs) having cortical venous drainage. These symptoms are the consequence of cortical venous hypertension and portend a clinical course with increased risk of neurological morbidity and mortality. One rarely documented and easily misinterpreted type of nonhemorrhagic neurological deficit is progressive dementia, which can result from venous hypertension in the cortex or in bilateral thalami. The latter, which is due to dAVF drainage into the deep venous system, is the less common of these 2 dementia syndromes. Herein, the authors report 4 cases of dAVF with venous drainage into the vein of Galen causing bithalamic edema and rapidly progressive dementia. Two patients were treated successfully with endovascular embolization, and the other 2 patients were treated successfully with endovascular embolization followed by surgery. The radiographic abnormalities and presenting symptoms rapidly resolved after dAVF obliteration in all 4 cases. Detailed descriptions of these 4 cases are presented along with a critical review of 15 previously reported cases. In our analysis of these 19 published cases, the following were emphasized: 1) the clinical and radiographic differences between dAVF-induced thalamic versus cortical dementia syndromes; 2) the differential diagnosis and necessary radiographic workup for patients presenting with a rapidly progressive thalamic dementia syndrome; 3) the frequency at which delays in diagnosis occurred and potentially dangerous and avoidable diagnostic procedures were used; and 4) the rapidity and completeness of symptom resolution following dAVF treatment.

Radiation Therapy for Residual or Recurrent Atypical Meningioma: The Effects of Modality, Timing, and Tumor Pathology on Long-Term Outcomes.

BACKGROUND: Optimal use of stereotactic radiosurgery (SRS) vs external beam radiation therapy (EBRT) for treatment of residual/recurrent atypical meningioma is unclear. OBJECTIVE: To analyze features associated with progression after radiation therapy. METHODS: Fifty radiation-naive patients who received SRS or EBRT for residual and/or recurrent atypical meningioma were examined for predictors of progression using Cox regression and Kaplan-Meier analyses. RESULTS: Thirty-two patients (64%) received adjuvant radiation after subtotal resection, 12 patients (24%) received salvage radiation after progression following subtotal resection, and 6 patients (12%) received salvage radiation after recurrence following gross total resection. Twenty-one patients (42%) received SRS (median 18 Gy), and 7 (33%) had tumor progression. Twenty-nine patients (58%) received EBRT (median 54 Gy), and 13 (45%) had tumor progression. Whereas tumor volume (P = .53), SRS vs EBRT (P = .45), and adjuvant vs salvage (P = .34) were not associated with progression after radiation therapy, spontaneous necrosis (hazard ratio [HR] = 82.3, P < .001), embolization necrosis (HR = 15.6, P = .03), and brain invasion (HR = 3.8, P = .008) predicted progression in univariate and multivariate analyses. Tumors treated with SRS/EBRT had 2- and 5-year actuarial locoregional control rates of 91%/88% and 71%/69%, respectively. Tumors with spontaneous necrosis, embolization necrosis, and no necrosis had 2- and 5-year locoregional control rates of 76%, 92%, and 100% and 36%, 73%, and 100%, respectively (P < .001). CONCLUSION: This study suggests that necrosis may be a negative predictor of radiation response regardless of radiation timing or modality. ABBREVIATIONS: AM, atypical meningiomaEBRT, external beam radiation therapyGTR, gross total resectionLC, locoregional controlOS, overall survivalPOE, preoperative embolizationRT, radiation therapySRS, stereotactic radiosurgerySTR, subtotal resection.

Magnetic Resonance Imaging Biomarker of Axon Loss Reflects Cervical Spondylotic Myelopathy Severity.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: In this study, we employed diffusion basis spectrum imaging (DBSI) to quantitatively assess axon/myelin injury, cellular inflammation, and axonal loss of cervical spondylotic myelopathy (CSM) spinal cords. SUMMARY OF BACKGROUND DATA: A major shortcoming in the management of CSM is the lack of an effective diagnostic approach to stratify treatments and to predict outcomes. No current clinical diagnostic imaging approach is capable of accurately reflecting underlying spinal cord pathologies. METHODS: Seven patients with mild (mJOA ≥15), five patients with moderate (14≥mJOA ≥11), and two patients with severe (mJOA <11) CSM were prospectively enrolled. Given the low number of severe patients, moderate and severe patients were combined for comparison with seven age-matched controls and statistical analysis. We employed the newly developed DBSI to quantitatively measure axon and myelin injury, cellular inflammation, and axonal loss. RESULTS: Median DBSI-inflammation volume is similar in control (266 µL) and mild CSM (171 µL) subjects, with a significant overlap of the middle 50% of observations (quartile 3 - quartile 1). This was in contrast to moderate CSM subjects that had higher DBSI-inflammation volumes (382 µL; P = 0.033). DBSI-axon volume shows a strong correlation with clinical measures (r = 0.79 and 0.87, P = 1.9 x 10-5 and 2 x 10-4 for mJOA and MDI, respectively). In addition to axon and myelin injury, our findings suggest that both inflammation and axon loss contribute to neurological impairment. Most strikingly, DBSI-derived axon volume declines as severity of impairment increases. CONCLUSION: DBSI-quantified axonal loss may be an imaging biomarker to predict functional recovery following decompression in CSM. Our results demonstrate an increase of about 60% in the odds of impairment relative to the control for each decrease of 100 µL in axon volume. LEVEL OF EVIDENCE: 3.