This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Background: Pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) has been identified recently as the major disease protein in amyotrophic lateral sclerosis (ALS), and in frontotemporal lobar degeneration with ubiquitinated inclusions, with or without motor neuron disease, but the distribution of TDP-43 pathology in ALS may be more widespread than previously described. Objective:To determine the extent of TDP-43 pathology in the central nervous systems of patients with clinically confirmed and autopsy confirmed diagnoses of ALS.Design: Performance of an immunohistochemical wholecentral nervous system scan for evidence of pathological TDP-43 in ALS patients.Setting: An academic medical center. Participants:We included 31 patients with clinically and pathologically confirmed ALS and 8 control participants. Main Outcome Measures:Immunohistochemistry and double-labeling immunofluorescence to assess the frequency and severity of TDP-43 pathology.Results: In addition to the stereotypical involvement of upper and lower motor neurons, neuronal and glial TDP-43 pathology was present in multiple areas of the central nervous systems of ALS patients, including in the nigro-striatal system, the neocortical and allocortical areas, and the cerebellum, but not in those of the controls.Conclusions: These findings suggest that ALS does not selectively affect only the pyramidal motor system, but rather is a multisystem neurodegenerative TDP-43 proteinopathy. Neurol. 2008;65(5):636-641 Arch

To determine the extent of transactivation response DNA-binding protein with a molecular weight of 43 kDa ) pathology in the central nervous system of patients with clinically and autopsyconfirmed diagnoses of frontotemporal lobar degeneration with and without motor neuron disease and amyotrophic lateral sclerosis with and without cognitive impairment.Design: Performance of immunohistochemical wholecentral nervous system scans for evidence of pathological TDP-43 and retrospective clinical medical record review.Setting: An academic medical center.Participants: We included 64 patients with clinically and pathologically confirmed frontotemporal lobar degeneration with ubiquitinated inclusions with or without motor neuron disease and amyotrophic lateral sclerosis with or without cognitive impairment.Main Outcome Measure: Neuronal and glial TDP-43 pathology.Results: We found evidence of neuronal and glial TDP-43 pathology in all disease groups throughout the neuraxis, albeit with variations in the frequency, morphology, and distribution of TDP-43 lesions. Moreover, the major clinical manifestations (eg, cognitive impairments, motor neuron signs, extrapyramidal symptoms, neuropsychiatric features) were reflected by the predominant distribution and burden of TDP-43 pathology. Conclusion:These findings strongly suggest that amyotrophic lateral sclerosis, frontotemporal lobar degeneration with amyotrophic lateral sclerosis or motor neuron disease, and frontotemporal lobar degeneration with ubiquitinated inclusions are different manifestations of a multiple-system TDP-43 proteinopathy linked to similar mechanisms of neurodegeneration.

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Recently, TDP-43, a 43 kDa nuclear TAR DNA-binding protein, was identified as the major disease protein in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), FTLD-U with motor neuron disease (FTLD-MND), and amyotrophic lateral sclerosis. To date, TDP-43 pathology in sporadic FTLD-MND has been reported only in select central nervous system areas. However, this distribution of lesions is insufficient to explain all clinical signs of FTLD-MND and the extent of TDP-43 pathology, throughout the brain, remains unknown. Therefore, as a pilot study, we performed an immunohistochemical whole brain scan of two cases diagnosed clinically as FTLD-MND and two control subjects. We found evidence of both neuronal and glial TDP-43 pathology in multiple brain areas including the nigro-striatal system, neo- and allocortical brain areas, with varying frequency, morphology, and degree, and nowhere in control tissue. The finding of a distinct cytopathological profile consisting of a cell nucleus devoid of endogenous TDP-43 staining coupled with diffuse/granular cytoplasmic staining ("pre-inclusion") was prominent in a couple of brain areas. These pre-inclusions were not or only weakly ubiquitin-immunoreactive. While the findings of severe involvement of extracortical or extrapyramidal areas are strongly suggestive for FTLD-MND being a TDP-43 multisystem proteinopathy rather than a disease predominantly affecting the cortex and spinal cord, more detailed clinicopathological studies of larger cohorts are needed to fully elucidate the distribution and severity of pathological TDP-43 in this disease.

Neurons in the human medial temporal lobe (MTL) that are selective for the identity of specific people are classically thought to encode identity invariant to visual features. However, it remains largely unknown how visual information from higher visual cortex is translated into a semantic representation of an individual person. Here, we show that some MTL neurons are selective to multiple different face identities on the basis of shared features that form clusters in the representation of a deep neural network trained to recognize faces. Contrary to prevailing views, we find that these neurons represent an individual’s face with feature-based encoding, rather than through association with concepts. The response of feature neurons did not depend on face identity nor face familiarity, and the region of feature space to which they are tuned predicted their response to new face stimuli. Our results provide critical evidence bridging the perception-driven representation of facial features in the higher visual cortex and the memory-driven representation of semantics in the MTL, which may form the basis for declarative memory.

Robot-assisted stereotactic neurosurgery is an emerging technology with a growing range of applications. The ROSA system is a robotic stereotactic system that has been shown to be accurate in laboratory studies and large case series. The goal of this study was to examine the accuracy of the ROSA across different registration methods as well as different clinical applications. Sixteen patients with one hundred and seventeen stereotactic trajectories were examined. Accuracy was compared by measuring the distance between the trajectory target and the actual termination of the device as determined by imaging. Entry error and angular deviation were also measured. Variables included bone fiducials vs. laser facial scanning, the clinical indication for stereotactic surgery, and the effect of lead deflection on accuracy. Bone fiducials did not offer an accuracy benefit over laser facial scanning (mean target error 4.5-3.9 mm, p = 0.34) in these clinical scenarios. Laser interstitial thermal therapy, responsive neurostimulation, and stereo electroencephalography were equally accurate when placed by the ROSA (mean target error 4.4-4.3-4.0 mm, respectively, p = 0.69). Deflection did not affect lead accuracy (mean target error 4.4-3.9 mm, p = 0.11). Similar results are seen for entry error and angular deviation. ROSA is a highly accurate stereotactic system. Laser facial scanning provides the same accuracy as bone fiducials in these stereotactic applications. The ROSA is equally accurate across a wide spectrum of applications. The ROSA is effective at limiting lead deflection, and when it does occur, it does not impact target accuracy in a significant way.

The obese population is particularly challenging to the spine surgeon in all phases of care. A narrative literature review was performed to review difficulties in spine surgery on the obese patient population and techniques for mitigation. We specifically aimed to assess several topics with regard to this population: patient selection and preoperative care; intraoperative and surgical techniques; and postoperative care, outcomes, and complications. The literature review demonstrated that obese patients are at increased surgical risk with spine surgery due to a variety of factors at all stages of intervention. Preoperatively, obese patients have worse outcomes with physical therapy and present technical difficulties for injections. Transport to a hospital, imaging, resuscitation, and intubation are all challenged by increased body habitus. Intraoperatively, obese patients have increased operative times, blood loss, surgical site infections, and nerve palsies. Patient positioning and intraoperative imaging may be limited. Surgery itself may be technically challenging due to body habitus and minimally invasive techniques are becoming more prevalent in this population. Postoperatively, several studies demonstrate that obese patients have inferior outcomes compared with nonobese counterparts. Patient selection is a key for elective interventions, and appropriate infrastructure aids in the ultimate outcomes for both elective and nonelective surgical treatments. Overall, obese patients present several challenges to the spine surgeon, and certain precautions can be undertaken preoperatively, intraoperatively, and postoperatively to mitigate the associated risks to optimize outcomes.