Secondary self-injurious behavior (SSIB) is underreported and predominantly not associated with suicide. In both adults and children, SSIB can cause intractable self-harm and is associated with a ...variety of clinical disorders, particularly those involving dysfunctional motor control.
We performed a literature review evaluating the clinical efficacy of deep-brain stimulation (DBS) as modulating SSIB observations and review current progress in preclinical SSIB animal studies.
Neuromodulation is an effective therapeutic option for several movement disorders. Interestingly, this approach is emerging as a potentially effective treatment for movement disorder-associated SSIB (secondary); however, it is important to understand the neuroanatomy, clinical appraisal, and outcome data when considering surgical therapy for SSIB.
The current review examines the literature encompassing animal models and human case studies while identifying existing hypotheses from cytoarchitectonic-based targeting to neurotransmitter-based pathways. This review also highlights the need for awareness of an underrecognized pathology that may be amenable to DBS.
Gamma-secretase cleavage is the final enzymatic step generating beta-amyloid via intramembranous cleavage of the amyloid precursor protein (APP). Presenilin (PS), initially identified as a gene in ...which mutations account for the vast majority of early-onset autosomal dominant Alzheimer's disease, is a major component of gamma-secretase. Enzymatic activity also depends on nicastrin, Aph-1, and Pen-2. We propose a model in which gamma-secretase components assemble, interact with substrates initially at a docking site, and then cleave and release substrates. To test this model, we developed a novel morphological technique on the basis of advanced fluorescence microscopy methods, fluorescence lifetime imaging microscopy (FLIM). FLIM allows us to examine protein-protein "proximity" in intact cells. We show that, although the strongest colocalization of APP and PS1 is in the perinuclear area, the strongest interactions detected by FLIM are at or near the cell surface. We also found that APP-PS1 interactions occur even when gamma-secretase inhibitors or "dominant-negative" PS1 mutations are used to block gamma-secretase activity. Finally, using nicastrin RNA interference, we demonstrate that nicastrin is critical for APP association with PS1. We interpret these results to suggest that there is a noncatalytic docking site closely associated with PS1-gamma-secretase.
Review of the articles.
The objective of this study was to review all articles related to spinal instability to determine a consensus statement for a contemporary, practical definition applicable to ...thoracolumbar injuries.
Traumatic fractures of the thoracolumbar spine are common. These injuries can result in neurological deficits, disability, deformity, pain, and represent a great economic burden to society. The determination of spinal instability is an important task for spine surgeons, as treatment strategies rely heavily on this assessment. However, a clinically applicable definition of spinal stability remains elusive.
A review of the Medline database between 1930 and 2014 was performed limited to papers in English. Spinal instability, thoracolumbar, and spinal stability were used as search terms. Case reports were excluded. We reviewed listed references from pertinent search results and located relevant manuscripts from these lists as well.
The search produced a total of 694 published articles. Twenty-five articles were eligible after abstract screening and underwent full review. A definition for spinal instability was described in only 4 of them. Definitions were primarily based on biomechanical and classification studies. No definitive parameters were outlined to define stability.
Thirty-six years after White and Panjabi's original definition of instability, and many classification schemes later, there remains no practical and meaningful definition for spinal instability in thoracolumbar trauma. Surgeon expertise and experience remains an important factor in stability determination. We propose that, at an initial assessment, a distinction should be made between immediate and delayed instability. This designation should better guide surgeons in decision making and patient counseling.
Laboratory of Neural Control, Section on Developmental Neurobiology, National Institutes of Health, Bethesda, Maryland
Submitted 6 September 2004;
accepted in final form 21 October 2004
Calcium ...imaging of neural network function has been limited by the extent of tissue labeled or the time taken for labeling. We now describe the use of electroporationan established technique for transfecting cells with genesto load neurons with calcium-sensitive dyes in the isolated spinal cord of the neonatal mouse in vitro. The dyes were injected subdurally, intravascularly, or into the central canal. This technique results in rapid and extensive labeling of neurons and their processes at all depths of the spinal cord, over a rostrocaudal extent determined by the position and size of the electrodes. Our results suggest that vascular distribution of the dye is involved in all three types of injections. Electroporation disrupts local reflex and network function only transiently ( 1 h), after which time they recover. We describe applications of the method to image activity of neuronal populations and individual neurons during antidromic, reflex, and locomotor-like behaviors. We show that these different motor behaviors are characterized by distinct patterns of activation among the labeled populations of cells.
Address for reprint requests and other correspondence: A. Bonnot, Lab. of Neural Control, Section on Developmental Neurobiology, NINDS, NIH, 35 Convent Dr., Rm. 3C1010, Bethesda, MD 20892 (E-mail: bonnota{at}ninds.nih.gov )
Current methods for myelin staining in tissue sections include both histological and immunohistochemical techniques. Fluorescence immunohistochemistry, which uses antibodies against myelin components ...such as myelin basic protein, is often used because of the convenience for multiple labeling. To facilitate studies on myelin, this paper describes a quick and easy method for direct myelin staining in rodent and human tissues using novel near-infrared myelin (NIM) dyes that are comparable to other well-characterized histochemical reagents. The near-infrared fluorescence spectra of these probes allow fluorescent staining of tissue sections in multiple channels using visible light fluorophores commonly used in immunocytochemistry. These dyes have been used successfully to detect normal myelin structure and myelin loss in a mouse model of demyelination disease.
During clathrin‐mediated endocytosis, the GTPase dynamin promotes formation of clathrin‐coated vesicles, but its mode of action is unresolved. We provide evidence that a switch in three functional ...states of dynamin (dimers, tetramers, rings/spirals) coordinates its GTPase cycle. Dimers exhibit negative cooperativity whereas tetramers exhibit positive cooperativity with respect to GTP. Our study identifies tetramers as the kinetically most stable GTP‐bound conformation of dynamin, which is required to promote further assembly into higher order structures such as rings or spirals. In addition, using fluorescence lifetime imaging microscopy, we show that interactions between dynamin and auxilin in cells are GTP‐, endocytosis‐ and tetramer‐dependent. Furthermore, we show that the cochaperone activity of auxilin is required for constriction of clathrin‐coated pits, the same early step in endocytosis known to be regulated by the lifetime of dynamin:GTP. Together, our findings support the model that the GTP‐bound conformation of dynamin tetramers stimulates formation of constricted coated pits at the plasma membrane by regulating the chaperone activity of hsc70/auxilin.
Review of the articles.
The objective of this study was to review all articles related to spinal instability to determine a consensus statement for a contemporary, practical definition applicable to ...thoracolumbar injuries.
Traumatic fractures of the thoracolumbar spine are common. These injuries can result in neurological deficits, disability, deformity, pain, and represent a great economic burden to society. The determination of spinal instability is an important task for spine surgeons, as treatment strategies rely heavily on this assessment. However, a clinically applicable definition of spinal stability remains elusive.
A review of the Medline database between 1930 and 2014 was performed limited to papers in English. Spinal instability, thoracolumbar, and spinal stability were used as search terms. Case reports were excluded. We reviewed listed references from pertinent search results and located relevant manuscripts from these lists as well.
The search produced a total of 694 published articles. Twenty-five articles were eligible after abstract screening and underwent full review. A definition for spinal instability was described in only 4 of them. Definitions were primarily based on biomechanical and classification studies. No definitive parameters were outlined to define stability.
Thirty-six years after White and Panjabi's original definition of instability, and many classification schemes later, there remains no practical and meaningful definition for spinal instability in thoracolumbar trauma. Surgeon expertise and experience remains an important factor in stability determination. We propose that, at an initial assessment, a distinction should be made between immediate and delayed instability. This designation should better guide surgeons in decision making and patient counseling.
Introduction
Freehand techniques for thoracic pedicle screw placement have gained popularity as they reduce intraoperative radiation exposure and overall operative time. The goal of this work is to ...present our technique as well as systematically and comprehensively review the published literature on this topic.
Material and Methods
A PubMed search from 2001 to 2014 was performed, focusing on clinical studies that describe technical aspects of freehand thoracic pedicle screw placement. Cadaveric studies were excluded.
Results
The search yielded 15 studies and, of those, only 5 described technical aspects of thoracic screw placement. Definitive entry points were represented in four studies, and in one study entry point varied by a thoracic level. There were no definitive guidelines for sagittal or an axial trajectory with an exception of a one study in which sagittal trajectory was based on suboptimally visualized endplate. In our technique, we identified a uniform entry point for each thoracic level that is 3 mm caudal to the junction of the transverse process and the lateral margin of the superior articulating process. The sagittal trajectory is orthogonal to the dorsal curvature of the corresponding spine.
Conclusion
Freehand thoracic pedicle screw placement is safe and effective based on published reports in the literature. Few studies, however, detail the technique and provide meaningful instructions for trainees. We are hopeful that precise parameters that rely on less variability in entry point and trajectories will facilitate trainee education.
Abstract Objective The anatomic area delineated medially by the lateral part of the L4-L5 vertebral bodies, distally by the anterior-superior surface of the sacral wing, and laterally by an imaginary ...line joining the base of the L4 transverse process to the proximal part of the sacroiliac joint, is of particular interest to spine surgeons. We are referring to this area as the lumbo-sacro-iliac triangle (LSIT); knowledge of LSIT anatomy is necessary during approaches for L5 vertebral and sacral fractures, sacral and iliac tumors, and extraforaminal decompression of the L5 nerve roots. Methods We performed an anatomic dissection of the LSIT in three embalmed cadavers (six triangles), from an anterior and posterior approach. Results We identified three key tissue planes: the neurological plexus plane, constituted by L4 and L5 nerve roots; an intermediate level constituted by the ileosacral tunnel; and posteriorly, by the lumbosacral ligament, and the posterior muscular plane. Conclusion Improving anatomic knowledge of the LSIT may help surgeons decrease the risk of possible complications. When LSIT pathology is present, a lateral approach corresponding to the tip of the L4 transverse process, medially, is suggested to decrease the risk of vessel and nerve root damage.
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