MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused by the epigenetic de-repression of the DUX4 gene, a transcription factor normally repressed in skeletal muscle. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle magnetic resonance imaging (MRI) changes is crucial both to understand disease mechanisms and for the design of future clinical trials. Here, we performed MRIs of the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely accessible muscles.

Laser Ablation Therapy for Pediatric Patients with Intracranial Lesions in Eloquent Areas.

Background: Laser interstitial thermal therapy (LITT) is an alternative, less-invasive, and, in some circumstances, effective treatment for patients with intracranial pathology including epilepsy and some tumors. For intracranial lesions in eloquent areas, resection by conventional craniotomy proves often to be a challenge, including in the care of pediatric patients. Herein, we reviewed our experience with magnetic resonance imaging (MRI)-guided LITT as treatment for pediatric patients with intracranial lesions in eloquent areas and evaluate neurologic function and clinical outcomes.

Changes in resting-state connectivity in pediatric temporal lobe epilepsy.

OBJECTIVE Functional connectivity magnetic resonance imaging (fcMRI) is a form of fMRI that allows for analysis of blood oxygen level-dependent signal changes within a task-free, resting paradigm. This technique has been shown to have efficacy in evaluating network connectivity changes with epilepsy. Presurgical data from patients with unilateral temporal lobe epilepsy were evaluated using the fcMRI technique to define connectivity changes within and between the diseased and healthy temporal lobes using a within-subjects design.

Geometric morphometrics reveal altered corpus callosum shape in pyridoxine-dependent epilepsy.

Objective: To evaluate the features and maturational changes in overall callosal shape in patients with pyridoxine-dependent epilepsy (PDE).

Methods: Measurements were conducted through landmark-based geometric morphometrics applied on cerebral MRIs of patients with PDE and age-matched control subjects. The outline of the corpus callosum was manually traced in the midsagittal plane.

Preservation of electrophysiological functional connectivity after partial corpus callosotomy: case report.

Prior studies of functional connectivity following callosotomy have disagreed in the observed effects on interhemispheric functional connectivity. These connectivity studies, in multiple electrophysiological methods and functional MRI, have found conflicting reductions in connectivity or patterns resembling typical individuals. The authors examined a case of partial anterior corpus callosum connection, where pairs of bilateral electrocorticographic electrodes had been placed over homologous regions in the left and right hemispheres.

MRI change metrics of facioscapulohumeral muscular dystrophy: Stir and T1.

Introduction: MRI evaluation in facioscapulohumeral muscular dystrophy (FSHD) demonstrates fatty replacement and inflammation/edema in muscle. Our previous work demonstrated short T1 inversion recovery (STIR)-hyperintense (STIR+) signal in muscle 2 years before fatty replacement. We evaluated leg muscle STIR changes and fatty replacement within 14 months.

A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD).

Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts.

Corpus Callosum Diffusion and Connectivity Features in High Functioning Subjects With Pyridoxine-Dependent Epilepsy.

Background: In this observational study, white matter structure, functional magnetic resonance imaging (fMRI) task-based responses, and functional connectivity were assessed in four subjects with high functioning pyridoxine-dependent epilepsy and age-matched control subjects.

Methods: Four male subjects with pyridoxine-dependent epilepsy (mean age 31 years 8 months, standard deviation 12 years 3 months) and age-matched control subjects (32 years 4 months, standard deviation 13 years) were recruited to participate in the study. Diffusion tensor data were collected and postprocessed in Functional Magnetic Resonance Imaging of the Brain Software Library to quantify corpus callosum tracts as a means to assess white matter structure.

Callosal alterations in pyridoxine-dependent epilepsy.

Aim: While there have been isolated reports of callosal morphology differences in pyridoxine-dependent epilepsy (PDE), a rare autosomal disorder caused by ALDH7A1 gene mutations, no study has systematically evaluated callosal features in a large sample of patients. This study sought to overcome this knowledge gap.

Method: Spanning a wide age range from birth to 48 years, corpus callosum morphology and cross-sectional cerebral area were measured in 30 individuals with PDE (12 males, 18 females, median age 3.

Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model.

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle.

Metaphyseal and diaphyseal bone loss in the tibia following transient muscle paralysis are spatiotemporally distinct resorption events.

When the skeleton is catabolically challenged, there is great variability in the timing and extent of bone resorption observed at cancellous and cortical bone sites. It remains unclear whether this resorptive heterogeneity, which is often evident within a single bone, arises from increased permissiveness of specific sites to bone resorption or localized resorptive events of varied robustness. To explore this question, we used the mouse model of calf paralysis induced bone loss, which results in metaphyseal and diaphyseal bone resorption of different timing and magnitude.

Tissue localization during resective epilepsy surgery.

Object: Imaging-guided surgery (IGS) systems are widely used in neurosurgical practice. During epilepsy surgery, the authors routinely use IGS landmarks to localize intracranial electrodes and/or specific brain regions. The authors have developed a technique to coregister these landmarks with pre- and postoperative scans and the Montreal Neurological Institute (MNI) standard space brain MRI to allow 1) localization and identification of tissue anatomy; and 2) identification of Brodmann areas (BAs) of the tissue resected during epilepsy surgery.

Longitudinal features of STIR bright signal in FSHD.

Introduction: Magnetic resonance imaging of muscle shows short tau-inversion recovery (STIR) brightness in autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1) suggestive of active inflammation/injury. We measured the longitudinal stability/progression of this potential disease biomarker.

Methods: Nine subjects underwent calf MRI imaging over 2 years.

Multimodality localization of the sensorimotor cortex in pediatric patients undergoing epilepsy surgery.

Object: The gold-standard method for determining cortical functional organization in the context of neurosurgical intervention is electrical cortical stimulation (ECS), which disrupts normal cortical function to evoke movement. This technique is imprecise, however, as motor responses are not limited to the precentral gyrus. Electrical cortical stimulation also can trigger seizures, is not always tolerated, and is often unsuccessful, especially in children.

Control of bone resorption in mice by Schnurri-3.

Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover.

The magnetic resonance imaging spectrum of facioscapulohumeral muscular dystrophy.

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is associated with a repeat contraction in the D4Z4 gene locus on chromosome 4q35. We used a one-step quantitative magnetic resonance imaging (MRI) method to evaluate muscle, edema, and fat in patients spanning the range of severity.

Methods: Fifteen patients with FSHD were compared with 10 healthy subjects using non-negative linear least-squares fitting of 32-echo relaxation data (T2).

Skeletal muscle edema in muscular dystrophy: clinical and diagnostic implications.

Muscle degeneration in muscular dystrophies often includes a period of edema before fatty replacement of muscle tissue. Magnetic resonance imaging (MRI) has been used successfully to characterize muscle and fat patterns in several types of muscular dystrophies. Recent MRI techniques enable characterization of edema in tissues.

Transient muscle paralysis degrades bone via rapid osteoclastogenesis.

A unilateral injection of botulinum toxin A (BTxA) in the calf induces paralysis and profound loss of ipsalateral trabecular bone within days. However, the cellular mechanism underlying acute muscle paralysis-induced bone loss (MPIBL) is poorly understood. We hypothesized that MPIBL arises via rapid and extensive osteoclastogenesis.

Freehand placement of depth electrodes using electromagnetic frameless stereotactic guidance.

The presurgical evaluation of patients with epilepsy often requires an intracranial study in which both subdural grid electrodes and depth electrodes are needed. Performing a craniotomy for grid placement with a stereotactic frame in place can be problematic, especially in young children, leading some surgeons to consider frameless stereotaxy for such surgery. The authors report on the use of a system that uses electromagnetic impulses to track the tip of the depth electrode.

Cortical bone resorption following muscle paralysis is spatially heterogeneous.

Mechanical loading of the skeleton, as induced by muscle function during activity, plays a critical role in maintaining bone homeostasis. It is not understood, however, whether diminished loading (and thus diminished mechanical stimuli) directly mediates the bone resorption that is associated with disuse. Our group has recently developed a murine model in which we have observed rapid and profound bone loss in the tibia following transient paralysis of the calf muscles.

Transient muscle paralysis disrupts bone homeostasis by rapid degradation of bone morphology.

We have previously shown that transient paralysis of murine hindlimb muscles causes profound degradation of both trabecular and cortical bone in the adjacent skeleton within 3 weeks. Morphologically, the acute loss of bone tissue appeared to arise primarily due to osteoclastic bone resorption. Given that the loss of muscle function in this model is transient, we speculated that the stimulus for osteoclastic activation would be rapid and morphologic evidence of bone resorption would appear before 21 days.

RAD001 (Everolimus) inhibits growth of prostate cancer in the bone and the inhibitory effects are increased by combination with docetaxel and zoledronic acid.

Introduction: mTOR activity is increased in advanced prostate cancer (CaP) as a result of a high rate of PTEN mutations. RAD001 (Everolimus) is a new orally available mTOR inhibitor. The objective of our study was to evaluate the effects of RAD001 on the growth of CaP in the bone, both alone and in combination with docetaxel and zoledronic acid.