Widespread, depth-dependent cortical microstructure alterations in pediatric focal epilepsy.

OBJECTIVE: Tissue abnormalities in focal epilepsy may extend beyond the presumed focus. The underlying pathophysiology of these broader changes is unclear, and it is not known whether they result from ongoing disease processes or treatment-related side effects, or whether they emerge earlier. Few studies have focused on the period of onset for most focal epilepsies, childhood. Fewer still have utilized quantitative magnetic resonance imaging (MRI), which may provide a more sensitive and interpretable measure of tissue microstructural change. Here, we aimed to determine common spatial modes of changes in cortical architecture in children with heterogeneous drug-resistant focal epilepsy and, secondarily, whether changes were related to disease severity. METHODS: To assess cortical microstructure, quantitative T1 and T2 relaxometry (qT1 and qT2) was measured in 43 children with drug-resistant focal epilepsy (age range = 4-18 years) and 46 typically developing children (age range = 2-18 years). We assessed depth-dependent qT1 and qT2 values across the neocortex, as well as their gradient of change across cortical depths. We also determined whether global changes seen in group analyses were driven by focal pathologies in individual patients. Finally, as a proof-of-concept, we trained a classifier using qT1 and qT2 gradient maps from patients with radiologically defined abnormalities (MRI positive) and healthy controls, and tested whether this could classify patients without reported radiological abnormalities (MRI negative). RESULTS: We uncovered depth-dependent qT1 and qT2 increases in widespread cortical areas in patients, likely representing microstructural alterations in myelin or gliosis. Changes did not correlate with disease severity measures, suggesting they may represent antecedent neurobiological alterations. Using a classifier trained with MRI-positive patients and controls, sensitivity was 71.4% at 89.4% specificity on held-out MRI-negative patients. SIGNIFICANCE: These findings suggest the presence of a potential imaging endophenotype of focal epilepsy, detectable irrespective of radiologically identified abnormalities.

Pharmacist-led medication review in a residential in-reach service leads to deprescribing.

OBJECTIVE: To examine the effect of a pharmacist-led medication review on deprescribing medications in a Residential In-Reach (RIR) service which provides acute care substitution to residential aged care residents. METHODS: A pre-post observational study was conducted. Patient characteristics and admission and discharge medications were collected over two 3-month phases before (prephase) and after (postphase) the introduction of a pharmacist who performed a comprehensive medication review and provided deprescribing recommendations. The Screening Tool of Older Persons' Prescriptions (STOPP) version 2 was used to identify potentially inappropriate medications (PIMs). The Drug Burden Index (DBI) was used to measure cumulative anticholinergic and sedative medication burden. Outcome of deprescribing was measured by the reduction in the number of PIMs, DBI scores and proportion of polypharmacy from admission to discharge. RESULTS: The prephase included 59 patients (mean age 87.3 years, 63% female), and the postphase included 88 patients (mean age 87.3 years, 63% female). There was a significant reduction in the mean number of PIMs (pre +0.05 ± 2.59 vs. post -0.78 ± 2.32, p = 0.04) and median DBI (pre -0.004 ± 0.17 vs. post -0.07 ± 0.2, p = 0.03) in postphase compared to prephase. The proportion of polypharmacy at discharge was reduced in the postphase (pre-100% vs. post-90%, p = 0.01). The most deprescribed PIMs as measured by STOPP in postphase were drugs without indication, cardiovascular system drugs and gastrointestinal system drugs. CONCLUSIONS: The introduction of a pharmacist-led medication review in RIR service was associated with a significant reduction in the mean number of PIMs, median DBI and polypharmacy. Future studies are needed to determine whether deprescription is sustained to examine correlations to long-term patient outcomes.

In vivo T1 mapping of neonatal brain tissue at 64 mT.

PURPOSE: Ultralow-field (ULF) point-of-care MRI systems allow image acquisition without interrupting medical provision, with neonatal clinical care being an important potential application. The ability to measure neonatal brain tissue T1 is a key enabling technology for subsequent structural image contrast optimization, as well as being a potential biomarker for brain development. Here we describe an optimized strategy for neonatal T1 mapping at ULF. METHODS: Examinations were performed on a 64-mT portable MRI system. A phantom validation experiment was performed, and a total of 33 in vivo exams were acquired from 28 neonates with postmenstrual age ranging from 31+4 to 49+0  weeks. Multiple inversion-recovery turbo spin-echo sequences were acquired with differing inversion and repetition times. An analysis pipeline incorporating inter-sequence motion correction generated proton density and T1 maps. Regions of interest were placed in the cerebral deep gray matter, frontal white matter, and cerebellum. Weighted linear regression was used to predict T1 as a function of postmenstrual age. RESULTS: Reduction of T1 with postmenstrual age is observed in all measured brain tissue; the change in T1 per week and 95% confidence intervals is given by dT1  = -21 ms/week [-25, -16] (cerebellum), dT1  = -14 ms/week [-18, -10] (deep gray matter), and dT1  = -35 ms/week [-45, -25] (white matter). CONCLUSION: Neonatal T1 values at ULF are shorter than those previously described at standard clinical field strengths, but longer than those of adults at ULF. T1 reduces with postmenstrual age and is therefore a candidate biomarker for perinatal brain development.

The Developing Human Connectome Project Neonatal Data Release.

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed.

Neurogenic Bladder and Urodynamic Outcomes in Patients with Spinal Cord Myelopathy.

BACKGROUND: Urodynamics (UDs) are routine in traumatic spinal cord injury (SCI), but there are few reports regarding nontraumatic spinal cord myelopathy (SCM) patients. PURPOSE: To describe the neurogenic bladder and UD outcomes in SCM patients and determine whether the UD recommendations result in clinically important changes to bladder management. METHODS: This retrospective case study examined a series of SCM patients admitted to a spinal rehabilitation service who underwent UDs between January 1, 2000 and June 30, 2010. RESULTS: Sixty-five UD tests were performed a median of 7 months post SCM. Most (n = 34; 57%) patients were male, and the median age was 60 years. Most patients (n = 46; 77%) were paraplegic and were continent of urine (n = 38; 58%). Thirty-five (46%) patients voided on sensation, 26 (40%) performed intermittent self-catheterization, and 9 (14%) had an indwelling catheter. The most common UD finding was overactive detrusor with no dysynergia (n = 31; 48%), followed by overactive detrusor with sphincter dysynergia (n = 16; 25%) and detrusor areflexia/underactive (n = 12; 18%). Key UD findings were median cystometric capacity 414 mL (interquartile range [IQR], 300-590), median maximum detrusor contraction 49.5 cmH2O (IQR, 25-85), and median residual volume post voiding 100 mL (IQR, 5-200). The recommendations for changes to bladder management following UDs resulted in clinically important changes to existing strategies in 57 studies (88%). CONCLUSIONS: Future studies should ascertain whether our screening protocol is appropriate, and a longer-term follow-up should examine the relationship between UD recommendations and prevention of complications.