Aperiodic neural activity is a biomarker for depression severity.

A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain - a surgical setting providing exquisite temporal and spatial sensitivity to detect this relationship in a difficult-to-measure brain area, the ventromedial prefrontal cortex (VMPFC). The aperiodic slope of the power spectral density captures the balance of activity across all frequency bands and is construed as a putative proxy for excitatory/inhibitory balance in the brain. This study demonstrates how shifts in aperiodic slope correlate with depression severity in a clinical trial of deep brain stimulation for treatment-resistant depression (TRD). The correlation between depression severity scores and aperiodic slope is significant in N=5 subjects, indicating that flatter (less negative) slopes correspond to reduced depression severity, especially in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient response to MDD treatment, facilitating individualized therapies in both intracranial and non-invasive monitoring scenarios.

Default mode network spatio-temporal electrophysiological signature and causal role in creativity.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. It subserves self-referential thinking, recollection of the past, mind wandering, and creativity. Knowledge about the electrophysiology underlying DMN activity is scarce, due to the difficulty to simultaneously record from multiple distant cortical areas with commonly-used techniques. The present study employs stereo-electroencephalography depth electrodes in 13 human patients undergoing monitoring for epilepsy, obtaining high spatiotemporal resolution neural recordings across multiple canonical DMN regions. Our results offer a rare insight into the temporal evolution and spatial origin of theta (4-8Hz) and gamma signals (30-70Hz) during two DMN-associated higher cognitive functions: mind-wandering and alternate uses. During the performance of these tasks, DMN activity is defined by a specific pattern of decreased theta coupled with increased gamma power. Critically, creativity and mind wandering engage the DMN with different dynamics: creativity recruits the DMN strongly during the covert search of ideas, while mind wandering displays the strongest modulation of DMN during the later recall of the train of thoughts. Theta band power modulations, predominantly occurring during mind wandering, do not show a predominant spatial origin within the DMN. In contrast, gamma power effects were similar for mind wandering and creativity and more strongly associated to lateral temporal nodes. Interfering with DMN activity through direct cortical stimulation within several DMN nodes caused a decrease in creativity, specifically reducing the originality of the alternate uses, without affecting creative fluency or mind wandering. These results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in creative thinking. Our findings shed light on the neural constructs supporting creative cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Spinal and Paraspinal Plexiform Neurofibromas in Patients with Neurofibromatosis Type 1: A Novel Scoring System for Radiological-Clinical Correlation.

BACKGROUND AND PURPOSE: Neurofibromatosis type 1 is a common tumor predisposition syndrome. The aim of this study was to characterize the radiologic presentation of patients with neurofibromatosis type 1 with widespread spinal disease and to correlate it to clinical presentation and outcome. MATERIALS AND METHODS: We conducted a historical cohort study of adult patients with neurofibromatosis type 1 with spinal involvement. Longitudinal clinical evaluation included pain and neurologic deficits. Radiologically, spinal involvement was classified according to a novel classification system, and a radiologic risk score was calculated. RESULTS: Two hundred fifty-seven adult patients with neurofibromatosis type 1 are followed in our center. Thirty-four of these patients qualified for inclusion in this study. Three independent factors were found to be associated with increased risk for neurologic deficit: 1) bilateral tumors at the same level in the cervical region that approximated each other, 2) paraspinal tumors at the lumbar region, and 3) intradural lesions. On the basis of these factors, we calculated a combined risk score for neurologic deficits for each patient. We found a clear correlation between patient status and the calculated radiologic risk score. Patients with neurologic deficits were found to have a higher risk score (9 ± 8.3) than patients without neurologic deficits (2.5 ± 2.9, P < .05). Patients who progressed during the follow-up period had significantly higher scores at presentation than patients with stable conditions (9.9 ± 8.73 versus 3.9 ± 5.3, respectively; P < .05). CONCLUSIONS: In this series, neurologic deficit is correlated with tumor burden and subtype. We found no direct correlation with tumor burden and pain. Our novel radiologic classification scoring system may be used to predict increased risk for neurologic morbidity.

Management of post-neurosurgical meningitis: narrative review.

BACKGROUND: Infections complicating neurosurgery pose unacceptable mortality and morbidity. AIMS: To summarize what is known about the epidemiology, diagnosis and treatment of post-neurosurgical meningitis (PNM). SOURCES: PubMed, references of identified studies and reviews, and personal experience when evidence was lacking. CONTENT: The incidence and pathogen distribution of PNM is highly variable. A shift towards Gram-negative bacteria has been observed with use of antibiotic prophylaxis and antibiotic-coated devices directed mainly against Gram-positive bacteria. However, knowledge of the local epidemiology is necessary to treat PNM. The diagnosis of PNM is difficult because, unlike community-acquired meningitis, symptoms are less specific; patients are ill at baseline and many neurosurgical conditions mimic meningitis and cause cerebrospinal fluid (CSF) abnormalities. Pivotal CSF findings for diagnosis of PNM are the CSF glucose, CSF lactate and Gram stain. CSF leucocyte counts are not specific in PNM. Current diagnostic capabilities leave a non-negligible category of patients with microbiologically negative, uncertain diagnosis of PNM. There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement. Some data point to a potential benefit of IV/IT antibiotic treatment, mainly for PNM caused by carbapenem-resistant Gram-negative bacteria. Carbapenem-colistin combination therapy is suggested for PNM caused by carbapenem-resistant Gram-negative bacteria with a carbapenem MIC ≤8 mg/L. IMPLICATIONS: Guiding the optimal management of PNM will necessitate collaborative multicentre efforts and unique study designs.

Risk factors associated with death or neurological deterioration among patients with Gram-negative postneurosurgical meningitis.

In a retrospective cohort of 115 patients with Gram-negative postneurosurgical meningitis, factors associated with 30-day mortality or neurological deterioration on multivariate analysis included days from admission to meningitis (OR 1.05 per day, 95% CI 1.02-1.09), decreased level of consciousness (OR 2.69, 95% CI 0.99-7.31), blood glucose level >180 mg/dL (OR 3.70, 95% CI 1.27-10.77), higher creatinine level (OR 4.07 per 1 mg/dL, 95% CI 1.50-11.08), and cerebrospinal fluid glucose <50 mg/dL (OR 5.02, 95% CI 1.71-14.77) at diagnosis. A predictive score triaged patients into three groups with low (4/44, 9.1%), intermediate (16/38, 42.1%) and high (22/33, 66.7%) unfavourable outcome rates. Validation on a different group of 36 patients with Gram-negative postneurosurgical meningitis was acceptable.

Intrathecal or intraventricular therapy for post-neurosurgical Gram-negative meningitis: matched cohort study.

Gram-negative post-operative meningitis due to carbapenem-resistant bacteria (CR-GNPOM) is a dire complication of neurosurgical procedures. We performed a nested propensity-matched historical cohort study aimed at examining the possible benefit of intrathecal or intraventricular (IT/IV) antibiotic treatment for CR-GNPOM. We included consecutive adults with GNPOM in two centres between 2005 and 2014. Patients receiving combined systemic and IT/IV treatment were matched to patients receiving systemic treatment only. Matching was done based on the propensity of the patients to receive IT/IV treatment. We compared patient groups with 30-day mortality defined as the primary outcome. The cohort included 95 patients with GNPOM. Of them, 37 received IT/IV therapy in addition to systemic treatment (22 with colistin and 15 with amikacin), mostly as initial therapy, through indwelling cerebrospinal fluid drains. Variables associated with IT/IV therapy in the propensity score included no previous neurosurgery, time from admission to meningitis, presence of a urinary catheter and GNPOM caused by carbapenem-resistant Gram-negative bacteria. Following propensity matching, 23 patients given IT/IV therapy and 27 controls were analysed. Mortality was significantly lower with IT/IV therapy: 2/23 (8.7%) versus 9/27 (33.3%), propensity-adjusted OR 0.19, 95% CI 0.04-0.99. Death or neurological deterioration at 30 days, 14-day and in-hospital mortality were lower with IT/IV therapy (OR <0.4 for all) without statistically significant differences. Among patients discharged alive, those receiving IT/IV therapy did not experience more neurological deterioration. Serious adverse events with IT/IV therapy were not documented. Our results support the early use of IT antibiotic treatment for CR-GNPOM when a delivery method is available.

Tumor burden evaluation in NF1 patients with plexiform neurofibromas in daily clinical practice.

BACKGROUND: Existing volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as they require delineation of PN boundaries, a procedure that is not practical in the typical clinical setting. The aim of this study is to assess the Plexiform Neurofibroma Instant Segmentation Tool (PNist), a novel semi-automated segmentation program that we developed for PN delineation in a clinical context. PNist was designed to greatly simplify volumetric assessment of PNs through use of an intuitive user interface while providing objectively consistent results with minimal interobserver and intraobserver variabilities in reasonable time. MATERIALS AND METHODS: PNs were measured in 30 magnetic resonance imaging (MRI) scans from 12 patients with neurofibromatosis 1. Volumetric measurements were performed using PNist and compared to a standard semi-automated volumetric method (Analyze 9.0). RESULTS: High correlation was detected between PNist and the semi-automated method (R(2) = 0.996), with a mean volume overlap error of 9.54 % and low intraobserver and interobserver variabilities. The segmentation time required for PNist was 60 % of the time required for Analyze 9.0 (360 versus 900 s, respectively). PNist was also reliable when assessing changes in tumor size over time, compared to the existing commercial method. CONCLUSIONS: Our study suggests that the new PNist method is accurate, intuitive, and less time consuming for PN segmentation compared to existing commercial volumetric methods. The workflow is simple and user-friendly, making it an important clinical tool to be used by radiologists, neurologists and neurosurgeons on a daily basis, helping them deal with the complex task of evaluating PN burden and progression.

Optic nerve sheath diameter on MR imaging: establishment of norms and comparison of pediatric patients with idiopathic intracranial hypertension with healthy controls.

BACKGROUND AND PURPOSE: IIH is a disorder associated with increased intracranial pressure with no clinical, laboratory, or radiologic evidence of an intracranial space-occupying lesion. The aim of this study was to establish ONSD standards of healthy pediatric subjects and compare the normal measurements with those of patients with IIH. MATERIALS AND METHODS: One hundred fifteen MR imaging studies of children 4 months to 17 years of age were blinded and reviewed by a pediatric neuroradiologist. A total of 230 optic nerves were measured. Eighty-six MR imaging examinations were performed in apparently healthy subjects. This control group included subjects who underwent MR imaging for various reasons, and their MR imaging findings were interpreted as normal. Twenty-nine MR imaging examinations were performed in patients with documented IIH. The ONSD was measured 1 cm anterior to the optic foramina on an axial T2 sequence. For statistical analysis, both patients and controls were stratified into 4 age groups (I, 0-3 years; II, 3-6 years; III, 6-12 years; IV, 12-18 years). RESULTS: The mean ONSD of the control group in all age groups (I, 3.1 mm; II, 3.41 mm; III, 3.55 mm; IV, 3.56 mm) was significantly smaller than the mean ONSD of patients (I, 4.35 mm; II, 4.37 mm; III, 4.25 mm; IV, 4.69 mm). A positive correlation between age and ONSD (r = 0.414, P < .01) was found in the control group. CONCLUSIONS: According to our study, in pediatric patients with IIH, the ONSD is significantly larger than that in healthy controls regardless of age group and sex. This measurement might prove to be an auxiliary tool in the diagnosis of increased intracranial pressure in pediatric patients.

Automatic segmentation, internal classification, and follow-up of optic pathway gliomas in MRI.

This paper presents an automatic method for the segmentation, internal classification and follow-up of optic pathway gliomas (OPGs) from multi-sequence MRI datasets. Our method starts with the automatic localization of the OPG and its core with an anatomical atlas followed by a binary voxel classification with a probabilistic tissue model whose parameters are estimated from the MR images. The method effectively incorporates prior location, tissue characteristics, and intensity information for the delineation of the OPG boundaries in a consistent and repeatable manner. Internal classification of the segmented OPG volume is then obtained with a robust method that overcomes grey-level differences between learning and testing datasets. Experimental results on 25 datasets yield a mean surface distance error of 0.73 mm as compared to manual segmentation by experienced radiologists. Our method exhibits reliable performance in OPG growth follow-up MR studies, which are crucial for monitoring disease progression. To the best of our knowledge, this is the first method that addresses automatic segmentation, internal classification, and follow-up of OPG.