Journal Scan

Journal Scan — This Month in Other Journals, May 2019

May 2019 (9 papers)

1. Ebeling PR, Akesson K, Bauer DC, et al. The Efficacy and Safety of Vertebral Augmentation: A Second ASBMR Task Force Report. J Bone Miner Res. 2019;34(1):3-21. doi:10.1002/jbmr.3653.

Two placebo-controlled trials of percutaneous vertebroplasty published in 2009 questioned the value of this procedure, and an additional three trials, all in participants with acute symptoms (for up to 9 weeks), have now confirmed the findings of these earlier trials. No placebo-controlled trials of balloon kyphoplasty have been performed and evidence of the value of this procedure is reliant on low quality evidence from trials that have compared kyphoplasty with usual care or head-to-head comparisons with vertebroplasty. In addition, there have been few trials of other nonpharmacological approaches to reduce pain in patients with vertebral fractures.

The American Society for Bone and Mineral Research (ASBMR) leadership charged this Task Force to address key questions on the efficacy and safety of vertebral augmentation and other nonpharmacological approaches for the treatment of pain after VF. This report details the findings and recommendations of this Task Force.

For patients with acutely painful VF, percutaneous vertebroplasty provides no demonstrable clinically significant benefit over placebo. Results did not differ according to duration of pain. There is also insufficient evidence to support kyphoplasty over nonsurgical management, percutaneous vertebroplasty, vertebral body stenting, or KIVA®. There is limited evidence to determine the risk of incident VF or serious adverse effects (AE) related to either percutaneous vertebroplasty or kyphoplasty. No recommendation can be made about harms, but they cannot be excluded.

For patients with painful VF, it is unclear whether spinal bracing improves physical function, disability, or quality of life. Exercise may improve mobility and may reduce pain and fear of falling but does not reduce falls or fractures in individuals with VF. General and intervention-specific research …

Journal Scan — This Month in Other Journals, April 2019

1. Solomon AJ, Naismith RT, Cross AH. Misdiagnosis of multiple sclerosis. Neurology. 2019;92(1):26-33. doi:10.1212/WNL.0000000000006583.

The expert panel that formulated the 2017 McDonald criteria acknowledged that the current criteria “were not developed to differentiate MS from other conditions” but rather to facilitate earlier diagnosis of MS in patients presenting with typical demyelinating syndromes. The use of McDonald criteria in atypical syndromes, or any clinical presentations other than optic neuritis, brainstem/cerebellar syndromes, or transverse myelitis, diminishes accuracy.

In patients with a history of migraine, vascular risk factors, or examination findings suggestive of a functional neurologic disorder who fulfill McDonald criteria, evaluation for CSF OCB or spinal cord lesions should be pursued to support the diagnosis of MS. MRI criteria using a lesion threshold of 6 mm may improve specificity for MS in atypical syndromes and older patients, as even healthy controls can have T2 abnormalities in the 2–4 mm range. The identification of callosal lesions may help to differentiate MRI demyelination from vascular changes. The diagnosis of MS, especially in atypical syndromes, should not rely on questionable spinal cord lesions observed only on sagittal view. Lesions should be confirmed on axial images and on at least 2 different MRI sequences (such as proton density, T2, or short tau inversion recovery). In equivocal cases, repeat imaging may be necessary to confirm a spinal cord lesion. Repeating CSF evaluation may also be prudent in patients with atypical or challenging syndromes.

Recommendations for prevention of multiple sclerosis misdiagnosis when applying 2017 McDonald criteria:

MRI lesions and their characteristics:
1. Juxtacortical lesions must abut the cortex, without intervening white matter
2. Periventricular lesions must abut the ventricles, without intervening white matter
3. Lesions should be 3 mm or larger in diameter
4. Small punctate lesions should not be used to fulfill MRI criteria
4. Use …

Journal Scan — This Month in Other Journals, March 2019

1. Fox MD. Mapping Symptoms to Brain Networks with the Human Connectome. N Engl J Med. 2018;379(23):2237-2245. doi:10.1056/NEJMra1706158.

Single-lesion analysis has been the foundation of clinical neurology and the basis for localization of most neurologic symptoms and behaviors. The traditional neurologic approach to localization of brain function has been by the identification of focal areas of damage, (for example- stroke) that correspond to a symptom or sign, such as paralysis.

It has become apparent that lesion-based localization is sometimes flawed because similar symptoms can result from lesions in different brain locations. For example, most lesions that disrupt language are located outside the left frontal cortex, most lesions that disrupt memory are located outside the hippocampus, and lesions that disrupt social behavior are frequently outside the frontal cortex. Even when the locations of lesions overlap between patients with the same symptom, the site of overlap may not conform to conventional ideas about the function of that part of the brain. For example, brain-stem lesions that cause visual hallucinations overlap in the midbrain and medial thalamus, but these locations have no clear role in vision or visual imagery. The relationship between symptoms and lesion location is therefore not straightforward.

Lesion-based localization is also limited by the fact that many complex symptoms occur in patients without overt brain lesions. Common neurobehavioral and psychiatric conditions, such as delirium, amnesia, autism, and schizophrenia, occur in patients with no obvious brain lesions.

If a complex behavior requires integrated function of multiple connected brain regions, lesions in any of these regions can disrupt behavior and lead to similar symptoms. For example, complex problem solving requires coordinated function of frontal and parietal regions, and lesions in either location degrade performance. Similarly, damage to the connection between regions can cause complex “disconnection” syndromes, while the cortical regions required …

Journal Scan – This Month in Other Journals, February 2019

1. Gallina P, Lastrucci G, Caini S, Lorenzo N Di, Porfirio B, Scollato A. Accuracy and safety of 1-day external lumbar drainage of CSF for shunt selection in patients with idiopathic normal pressure hydrocephalus. J Neurosurg. 2018:1-7. doi:10.3171/2018.6.JNS18400.

Cerebrospinal fluid shunting is the treatment of choice for idiopathic normal pressure hydrocephalus (iNPH) with a 75%–82% rate of successful outcome and 11% risk of serious adverse events. Not all patients diagnosed with iNPH are likely to benefit from shunt, and preoperative “supplemental prognostic tests” with intracranial pressure recording or CSF infusion/subtraction are recommended. External lumbar drainage (ELD) of CSF has gained wide acceptance among neurosurgeons as the best predictor of successful shunt surgery. The hypothesis underlying ELD is that prolonged drainage of a relatively large amount of CSF, more than with the spinal tap test, mimics a shunt effect.

Three to five days of external lumbar drainage of CSF is a test for ventriculoperitoneal shunt (VPS) selection in idiopathic normal pressure hydrocephalus. The accuracy and complication rates of a shorter (1-day) ELD procedure were analyzed.

Of 93 patients who underwent 1-day ELD, 3 did not complete the procedure. Of the remaining 90 patients, 2 experienced transient nerve root irritation. Twenty-four patients had negative test outcomes and 66 had positive test outcomes. Nine negative-outcome patients had intraprocedural headache, which showed 37.5% sensitivity and 100% specificity as predictors of negative 1-day ELD outcome. Sixty-eight patients (6 with negative and 62 with positive outcomes) underwent VPS insertion, which was successful in 0 and 58 patients, respectively, at 1-month follow-up.

They conclude that one-day ELD is a reliable tool in iNPH management, with low complication risk and short trial duration. The test is very consistent in predicting who will have a positive outcome with VPS placement, given the high chance of successful outcome at …

Journal Scan – This Month in Other Journals, January 2019

1.) Zanier, E. R., Bertani, I., Sammali, E., Pischiutta, F., Chiaravalloti, M. A., Vegliante, G., … Chiesa, R. (2018). Induction of a transmissible tau pathology by traumatic brain injury. Brain, 2685–2699. https://doi.org/10.1093/brain/awy193

Traumatic brain injury is a risk factor for subsequent neurodegenerative disease, including chronic traumatic encephalopathy, a tauopathy mostly associated with repetitive concussion and blast, but not well recognized as a consequence of severe traumatic brain injury. The authors show that a single severe brain trauma is associated with the emergence of widespread hyperphosphorylated tau pathology in a proportion of humans surviving late after injury. In parallel experimental studies, in a model of severe traumatic brain injury in wild-type mice, they found progressive and widespread tau pathology, replicating the findings in humans. Scary part: Brain homogenates from these mice, when inoculated into the hippocampus and overlying cerebral cortex of naïve mice, induced widespread tau pathology, synaptic loss, and persistent memory deficits. The observation that TBI-induced tau pathology can be transmitted between wild-type mice and can cause persistent memory deficits satisfies the main requirement for a toxic, bona fide prion.

These results indicate that tau prions are generated in TBI, providing a mechanistic explanation for how a biomechanical insult might trigger self-sustained neurodegeneration. They also conclude that the demonstration of tau prions in human TBI will urgently require studies to determine whether neurosurgical intervention in such patients should conform to well established precautions for transmission of prion disease, as suggested by the Centers for Disease Control for CJD.
8 Figures

2.) Trapp, B. D., Vignos, M., Dudman, J., Chang, A., Fisher, E., Staugaitis, S. M., … Rudick, R. A. (2018). Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. The Lancet Neurology, 17(10), 870–884.
https://doi.org/10.1016/S1474-4422(18)30245-X

Brains and spinal cords were removed at autopsy from patients, …

Journal Scan – This Month in Other Journals, December 2018

1. Zanier, E. R., Bertani, I., Sammali, E., Pischiutta, F., Chiaravalloti, M. A., Vegliante, G., … Chiesa, R. (2018). Induction of a transmissible tau pathology by traumatic brain injury. Brain, 2685–2699. https://doi.org/10.1093/brain/awy193

Traumatic brain injury is a risk factor for subsequent neurodegenerative disease, including chronic traumatic encephalopathy, a tauopathy mostly associated with repetitive concussion and blast, but not well recognized as a consequence of severe traumatic brain injury. The authors show that a single severe brain trauma is associated with the emergence of widespread hyperphosphorylated tau pathology in a proportion of humans surviving late after injury. In parallel experimental studies, in a model of severe traumatic brain injury in wild-type mice, they found progressive and widespread tau pathology, replicating the findings in humans. Scary part: Brain homogenates from these mice, when inoculated into the hippocampus and overlying cerebral cortex of naïve mice, induced widespread tau pathology, synaptic loss, and persistent memory deficits. The observation that TBI-induced tau pathology can be transmitted between wild-type mice and can cause persistent memory deficits satisfies the main requirement for a toxic, bona fide prion.

These results indicate that tau prions are generated in TBI, providing a mechanistic explanation for how a biomechanical insult might trigger self-sustained neurodegeneration. They also conclude that the demonstration of tau prions in human TBI will urgently require studies to determine whether neurosurgical intervention in such patients should conform to well established precautions for transmission of prion disease, as suggested by the Centers for Disease Control for CJD.
8 Figures

2. Trapp, B. D., Vignos, M., Dudman, J., Chang, A., Fisher, E., Staugaitis, S. M., … Rudick, R. A. (2018). Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. The Lancet Neurology, 17(10), 870–884. https://doi.org/10.1016/S1474-4422(18)30245-X

Brains and spinal cords were removed at autopsy from patients, …

Journal Scan – This Month in Other Journals, November 2018


1. Absinta, M., Ha, S.-K., Nair, G., Sati, P., Luciano, N. J., Palisoc, M., … Reich, D. S. (2017). Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. ELife, 6, 1–15. https://doi.org/10.7554/eLife.29738

Previous investigators have described the existence of a network of true lymphatic vessels within the mammalian dura that runs alongside blood vessels, such as the superior sagittal and transverse sinuses. The dural lymphatic vessels display typical immuno-histochemical markers that identify lymphatic vessels elsewhere in the body. They provide an alternate conduit for drainage of immune cells and CSF from the brain, beyond previously described pathways of flow: via arachnoid granulations into the dural venous sinuses, and via the cribriform plate into the ethmoid region. Recent studies which are based on injections of fluorescent tracers and in vivo microscopy, indicate that the dural system may be substantially more important for drainage of macromolecules and immune cells than previously realized.

The authors, using high-resolution T2-FLAIR and T1-weighted black-blood MRI images, obtained after the intravenous injection of gadobutrol, were able to visualize the collection of interstitial gadolinium within dural lymphatic vessels (maximum apparent diameter ~1 mm) in 5/5 human healthy volunteers and 3/3 common marmoset monkeys. Their results suggest that in the dura, similar to many other organs throughout the body, small intravascular molecules extravasate into the interstitium and then, under a hydrostatic pressure gradient, collect into lymphatic capillaries through a loose lymphatic endothelium.

Meningeal lymphatics were also assessed using a second gadolinium-based contrast agent, gadofosveset (trade names Vasovist, Ablavar), a blood-pool contrast agent. Gadofosveset binds reversibly to serum albumin, increasing its molecular weight from 0.9 to 67 kDa. Under physiological conditions, albumin has a low transcapillary exchange rate into the interstitial compartment, estimated to be on the order of 5% per hour, which explains …

Journal Scan – This Month in Other Journals, October 2018

1.Yue, Q., Yu, Y., Shi, Z., Wang, Y., Zhu, W., Du, Z., … Mao, Y. (2018). Prediction of BRAF mutation status of craniopharyngioma using magnetic resonance imaging features. Journal of Neurosurgery, 129(1), 27–34. https://doi.org/10.3171/2017.4.JNS163113

Classically, craniopharyngiomas are divided into 2 histological subtypes: squamous-papillary and adamantinous. The squamous-papillary craniopharyngiomas arise from squamous-cell nests formed by metaplastic cells of the pars tuberalis of the adenohypophysis and are characterized by well-differentiated, nonkeratinizing squamous epithelium and little adhesion to surrounding tissues. In contrast, the adamantinous craniopharyngiomas originate from cell remnants of the craniopharyngeal duct and are characterized by multicystic components, nodules containing wet keratin, and invasion into the brain parenchyma. Despite this histopathologic difference, no obvious difference in the recurrence rate, postoperative outcome, or mortality has been discovered between the 2 subtypes.

The BRAF protein is from the RAF kinase family and regulates cell growth through the mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) signaling pathway. Its mutations, among which V600E is the most common, are discovered in a variety of tumors and are considered to promote tumor progression as oncogenic drivers.

BRAF is the most widely studied molecular characteristic of craniopharyngioma,
and its V600E mutation is present in nearly all squamous-papillary craniopharyngiomas. Treatment with inhibitors targeting the BRAF V600E mutation, which has exhibited satisfactory efficacy for several malignancies, has been recently reported to be associated with shrinkage of recurrent craniopharyngiomas. If primary craniopharyngiomas could be diagnosed as BRAF V600E mutated via noninvasive methods, the inhibitors might serve as first-line treatment instead of surgery, or at least partially reduce the tumor size to facilitate subsequent surgery. Moreover, a precise pretreatment diagnosis of BRAF V600E–mutated craniopharyngioma is necessary for further clinical trials to assess the inhibitors’ efficacy in a larger population.

In this study, eight of the 52 patients had BRAF-mutated craniopharyngiomas, and the remaining …

Journal Scan – This Month in Other Journals, September 2018

 

Kermany, D. S., Goldbaum, M., Cai, W., Valentim, C. C. S., Liang, H., Baxter, S. L., … Zhang, K. (2018). Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning. Cell, 172(5), 1122–1124.e9. https://doi.org/10.1016/j.cell.2018.02.010

 

Ting, D. S. W., Liu, Y., Burlina, P., Xu, X., Bressler, N. M., & Wong, T. Y. (2018). AI for medical imaging goes deep. Nature Medicine, 24(5), 539–540. https://doi.org/10.1038/s41591-018-0029-3

Deep learning is a form of AI which is designed to mimic the layers of neurons in the human brain to process and extract information, allowing computers to learn without being explicitly programmed. This technique has been used to detect diseases, including retinal diseases, TB from chest radiographs and malignant melanoma from skin images. In the February issue in Cell, Kermany et al. present an AI approach for detecting several medical conditions, including diabetic macular edema (DME), choroidal neovascularization (CNV), drusen and pediatric pneumonia, from patient images, with promising diagnostic performance.

Transfer learning is a method for building an AI system using convolutional networks that have already been pretrained using a large data set in the public domain. Transfer learning allows the knowledge gained during the training process to recognize animals in images to be used in recognizing retinal diseases from optical coherence tomography (OCT) images. A ConvNet consists of multiple layers of “neurons” with trainable weights that are thus able to learn features and patterns. In medical imaging, many publicly available ConvNet models (VGGNet, ResNet, Inception V3 and DenseNet) have been used.

In this study, the authors trained the deep learning framework on 37,000 images of CNV, ∼ 11,000 images of DME, ∼ 9,000 images of drusen and ∼ 51,000 images from unaffected individuals using Inception V3; images were obtained from 4,686 individuals in total. This was followed by validation on 1,000 images, consisting …

Journal Scan – This Month in Other Journals, August 2018

Burkhardt BW, Simgen A, Wagenpfeil G, Reith W, Oertel JM. Adjacent Segment Degeneration After Anterior Cervical Discectomy and Fusion With an Autologous Iliac Crest Graft: A Magnetic Resonance Imaging Study of 59 Patients With a Mean Follow-up of 27 Years. Neurosurgery. 2018;82(6):799-807. doi:10.1093/neuros/nyx304.

Despite the high surgical acceptance of ACDF, it is associated with several disadvantages. One of those is the acceleration of adjacent segment degeneration (ASD). Adjacent segment degeneration might become a symptomatic condition that requires repeat surgery. The literature presents 2 different opinions on the development of adjacent segment degeneration. One supports the hypothesis that ASD is the result of a physiological process of degeneration. Other authors believe that fusion increases the stress and strain at the 2 adjacent segments and thereby accelerate segmental degeneration.

This study reports the evaluation of MRI findings of disc degeneration of 59 (36 male, 23 female) patients who underwent ACDF. The mean follow-up was 27 yr (18-45 yr). Besides measuring the disc height, a 5-step grading system (segmental degeneration index [SDI]) including disc signal intensity, anterior and posterior disc protrusion, narrowing of the disc space, and foraminal stenosis was used to assess the grade of adjacent and adjoining segments.

The authors state that the present study is unique and presents 2 important aspects. This is the first study that assessed the grade of degeneration of the 2 segments that are located cranial and caudal to the fused level (adjacent segments) using MRI with a follow-up of 27 yr. Secondly, this study assessed and compared the grade of degeneration of the first and second segments, which are located cranial to the cranial adjacent segment (cranial adjoining segments) and located caudal to the caudal adjacent segment (caudal adjoining segments). Depending on the location of the initial fusion, 2 adjacent segments (1 cranial and 1 …