Motion Characteristics of the Functional Spinal Unit During Lumbar Disc Injection (Discography) Including Comparison Between Normal and Degenerative Levels.

OBJECTIVE: While provocation lumbar discography has been used to identify discs responsible for low back pain, the biomechanical effects of disc injection have received little attention. The purpose of this study was to assess the motion of the functional spinal unit including the endplate and facet/pedicle region during disc injection including comparison between normal and degenerative discs. SUBJECTS: Subjects represent 91 consecutive patients referred for discography with chronic low back pain. METHODS: Lateral projection vertebral motion was retrospectively analyzed at 232 levels (normal: 76 [32.8%], degenerative: 156 [67.2%]). Pre- and postinjection fluoroscopic images were size scaled, and lower endplates were superimposed on separate PowerPoint images. Upper endplate and facet/pedicle motion was separately and independently analyzed on toggled PowerPoint images, subjectively graded as prominent, intermediate, questionable/uncertain, or no motion. Disc morphology was graded using the anteroposterior/lateral postinjection disc appearance (Adams criteria). RESULTS: Prominent or intermediate endplate and facet/pedicle motion was identified at most lumbar levels with substantial overall agreement (degenerative: κ = 0.93, 95% confidence intervals [CI] = 0.87-1.00; normal: κ = 0.80, 95% CI = 0.61-1.00). Degenerative levels were strongly associated with a lower degree of endplate and facet/pedicle motion compared with normal: ("prominent" motion grade: endplate: 61% [95/156] vs 89% [68/76], P < 0.001; facet/pedicle: 60% [93/156] vs 88% [67/76], P < 0.001). CONCLUSION: Disc injection expands the disc space inducing endplate motion, pedicle motion, and facet translation in almost all normal and most degenerate levels. Disc injection therefore biomechanically "provokes" the entire functional spinal unit. When provoked pain is encountered during lumbar discography, contribution from the associated facet joint and myotendinous insertions should be considered.

GluN2A NMDA Receptor Enhancement Improves Brain Oscillations, Synchrony, and Cognitive Functions in Dravet Syndrome and Alzheimer's Disease Models.

NMDA receptors (NMDARs) play subunit-specific roles in synaptic function and are implicated in neuropsychiatric and neurodegenerative disorders. However, the in vivo consequences and therapeutic potential of pharmacologically enhancing NMDAR function via allosteric modulation are largely unknown. We examine the in vivo effects of GNE-0723, a positive allosteric modulator of GluN2A-subunit-containing NMDARs, on brain network and cognitive functions in mouse models of Dravet syndrome (DS) and Alzheimer's disease (AD). GNE-0723 use dependently potentiates synaptic NMDA receptor currents and reduces brain oscillation power with a predominant effect on low-frequency (12-20 Hz) oscillations. Interestingly, DS and AD mouse models display aberrant low-frequency oscillatory power that is tightly correlated with network hypersynchrony. GNE-0723 treatment reduces aberrant low-frequency oscillations and epileptiform discharges and improves cognitive functions in DS and AD mouse models. GluN2A-subunit-containing NMDAR enhancers may have therapeutic benefits in brain disorders with network hypersynchrony and cognitive impairments.

Imaging Review of Common and Rare Causes of Stroke in Children.

Vascular injury is increasingly recognized as an important cause of mortality and morbidity in children (29 days to 18 years of age). Since vascular brain injury in children appears to be less common than in adults, the index of suspicion for vascular brain injury is usually lower. In this review article, we describe frequent and rare conditions underlying pediatric stroke including cardioembolic, viral, autoimmune, post-traumatic, and genetic etiologies. Furthermore, we provide a neuroimaging correlate for clinical mimics of pediatric stroke. This review highlights the role of multimodal noninvasive neuroimaging in the early diagnosis of pediatric stroke, providing a problem-solving approach to the differential diagnosis for the neuroradiologist, emergency room physician, and neurologist.

Nonaneurysmal Subarachnoid Hemorrhage in Sickle Cell Disease: Description of a Case and a Review of the Literature.

Descriptions of the natural history of cerebrovascular complications of sickle cell disease (SCD) characterize ischemic stroke as common during childhood and hemorrhagic stroke as more common in adulthood. Childhood ischemic stroke is attributed to vasculopathy with moyamoya syndrome. Hemorrhagic stroke is commonly attributed to aneurysms accompanying HbSS cerebral vasculopathy in SCD. However, a growing body of literature highlights multiple contributing factors to hemorrhagic stroke in children. Primary hemorrhagic stroke is one of the most devastating neurological complications of SCD. We describe the case of an 18-year-old female affected by HbSS genotype SCD presenting with reversible cerebral vasoconstriction syndrome (RCVS) as well as features of posterior reversible encephalopathy syndrome and convexity subarachnoid hemorrhage (SAH) after transfusion of red blood cells. We reviewed the existing literature dealing with SCD, blood transfusion, and hemorrhagic strokes. To our knowledge, this case presentation is unique with convexity SAH predominantly attributable to a RCVS spectrum disorder occurring in the setting of a recent blood transfusion in an adolescent female with SCD. As this case illustrates, neurological deterioration accompanied by intracranial hemorrhage in children and young adults with SCD after blood transfusion should raise suspicion for RCVS as part of a complex cerebral vasculopathy. A better understanding of the risk factors leading to hemorrhagic stroke may help prevent this severe complication in subjects with SCD. Neuroimaging including angiography in these subjects may enable prompt diagnosis and management.

Nav1.1-Overexpressing Interneuron Transplants Restore Brain Rhythms and Cognition in a Mouse Model of Alzheimer's Disease.

Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.

In Vivo Demonstration of Traumatic Rupture of the Bridging Veins in Abusive Head Trauma.

OBJECTIVE: In victims of abusive head trauma, bridging vein thrombosis is a common finding on magnetic resonance imaging. We aimed to evaluate the utility of high-resolution coronal susceptibility-weighted imaging (SWI) in depicting bridging vein thrombosis as well as to verify the morphology of the bridging vein thrombosis on axial SWI. We additionally analyzed the correlations between bridging vein thrombosis or bridging vein deformation and other magnetic resonance imaging findings that often occur in association with abusive head trauma. METHODS: Seventeen patients with abusive head trauma were retrospectively evaluated for the presence of thrombosis on axial SWI. The affected veins were localized on coronal SWI, and the strength of association between the presence of bridging vein thrombosis on axial versus high-resolution coronal SWI was determined. RESULTS: Of 11 patients identified with thrombosis on axial SWI, high-resolution coronal SWI verified bridging vein thrombosis in four individuals (36%). The previously reported "tadpole sign" on axial images did not predict bridging vein thrombosis on coronal SWI (odds ratio = 0.3 [0.02, 5.01], P = 0.538). Volumetric coronal SWI disclosed additional irregularities of the bridging vein walls which was associated with the presence of subdural hematoma on magnetic resonance imaging (P = 0.03), suggesting traumatic injury. CONCLUSION: Coronal SWI confirmed thrombosis of the bridging veins only in a minority of cases. Diffusely irregular contours of the veins observed on high-resolution coronal SWI was a major finding in our study. Disruption of the normal anatomy of the bridging veins in abusive head trauma further supports the traumatic nature of the disease.

Nuclear pore complex remodeling by p75(NTR) cleavage controls TGF-ß signaling and astrocyte functions.

Astrocytes modulate neuronal activity and inhibit regeneration. We show that cleaved p75 neurotrophin receptor (p75(NTR)) is a component of the nuclear pore complex (NPC) required for glial scar formation and reduced gamma oscillations in mice via regulation of transforming growth factor (TGF)-ß signaling. Cleaved p75(NTR) interacts with nucleoporins to promote Smad2 nucleocytoplasmic shuttling. Thus, NPC remodeling by regulated intramembrane cleavage of p75(NTR) controls astrocyte-neuronal communication in response to profibrotic factors.