1. Song J, Kadaba P, Kravitz A, et al. Multiparametric MRI for early identification of therapeutic response in recurrent glioblastoma treated with immune checkpoint inhibitors. Neuro Oncol 2020;22:1658–66
Immune checkpoint inhibitors (ICIs) such as the charmingly named programmed cell death 1 (PD-1) inhibitors are being used to treat various solid tumors, including melanoma and non-small-cell lung cancer. The use of immune checkpoint inhibitors in clinical trials for GBM have revealed mixed results. Treatment with immune checkpoint inhibitors can lead to T-cell proliferation and production of cytokines with an associated inflammatory response. This inflammatory response can change the blood–brain barrier permeability and result in contrast extravasation and be a major diagnostic challenge on conventional MRI, mimicking imaging appearance of tumor progression with increased enhancement and FLAIR changes, commonly referred to as pseudoprogression. The ambiguities related to interpretation of brain tumor imaging with immunotherapy on conventional brain MRI within the first 6 months of treatment has been acknowledged and reflected in recently updated modified Response Assessment in Neuro-Oncology (RANO) criteria.
In this study, a single total dose of gadobenate dimeglumine contrast medium (0.1 mmol/ kg of body weight) was used for both DCE and DSC perfusion imaging, with 40% of the contrast volume used for DCE imaging and the remaining 60% of contrast volume injected for DSC perfusion. During an 8-minute interval between DCE and DSC, axial T2-weighted and T1-weighted contrast-enhanced images were obtained.
Out of 19 patients who met inclusion criteria and follow-up, 12 were determined to have tumor progression, while 7 had treatment response after 6 months of Immune checkpoint inhibitors treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC. Interval change in rCBV, Ktrans, Vp (plasma volume), and Ve (extravascular extracellular space volume) were not indicative of treatment response within 6 months.
In conclusion, they found that similar to cytotoxic treatment, treatment response following immune checkpoint inhibitors can be depicted by interval increase in ADC values. In fact, ADC was the only imaging parameter that changed favorably in 6/7 patients and unfavorably (interval decrease) in 11/12 patients following ICI treatment.
4 figures, 2 tables including MR images
2. Kaelberer MM, Rupprecht LE, Liu WW, et al. Neuropod cells: the emerging biology of gut-brain sensory transduction. Annu Rev Neurosci 2020;43:337–53
The focus of this review is on gut sensory epithelial cells capable of synapsing with nerves. Although gut sensory epithelial cells include enteroendocrine cells, the term neuropod cell was coined in 2018 to distinguish those that are capable of forming synapses (Kaelberer et al. 2018). Neuropod cells were first uncovered when Bohórquez et al. (2015) discovered that enteroendocrine cells form synapses with nerves in the mucosa of the murine small intestine and colon. The existence of these synapses has since been confirmed by other studies (Bellono et al. 2017, Lu et al. 2019). In 2018, Kaelberer et al. (2018) revealed that neuropod cells synapse with neurons of the vagal nodose to transduce a sense from gut to brain. They do so in milliseconds, using glutamate as a neurotransmitter. This discovery sparked a new area of exploration in sensory neurobiology: the field of gut-brain sensory transduction.
A variety of gut sensors are discussed, including various nutrients, mechanical, and bacterial.
2 figures, no imaging
3. Raudner M, Schreiner MM, Hilbert T, et al. Clinical implementation of accelerated T2 mapping: quantitative magnetic resonance imaging as a biomarker for annular tear and lumbar disc herniation. Eur Radiol 2020 Dec 3. Available from: http://link.springer.com/10.1007/s00330-020-07538-6
The aim of this study was (A) to investigate whether GRAPPATINI can be used in direct comparison with T2 maps reconstructed from a conventional 2D multi-echo spin-echo (MESE) sequence dataset, (B) to discriminate between different degeneration states, reflected by Pfirrmann classifications, (C) to differentiate discs with and without herniation, and (D) to distinguish between discs with and without annular tear.
GRAPPATINI combines “model-based accelerated relaxometry by iterative non-linear inversion” (MARTINI) and “generalized auto-calibrating partial parallel acquisition” (GRAPPA).
Fifty-eight individuals were prospectively examined at 3 T. This cohort study consisted of 19 patients, 20 rowers, and 19 volunteers. GRAPPATINI was conducted with the same parameters as a conventional 2D multi-echo spin-echo (MESE) sequence in 02:27 min instead of 13:18 min. Additional T2 maps were calculated after discarding the first echo (T2-WO1ST) and only using even echoes (T2-EVEN).
The authors data show that GRAPPATINI is capable of significantly shortening the acquisition time needed for accurate T2 mapping from 13:18 to 2:27 min while maintaining the known advantages of quantitatively reflecting the most common disc pathologies. T2-GRAPPATINI of the nucleus pulposus showed an AUC comparable to the other methods when assessing discs with neither bulging nor herniation present. The same was true when assessing discs for bulging. Additionally, T2- GRAPPATINI showed the only significant difference in the posterior annular region for healthy discs compared to discs with herniation present.
3 figures, 2 tables with MR images
4. Brooks M, Dower A, Abdul Jalil MF, et al. Radiological predictors of recurrent lumbar disc herniation: a systematic review and meta-analysis. J Neurosurg Spine 2020 Nov 27;1–11. Available from: https://thejns.org/view/journals/j-neurosurg-spine/aop/article-10.3171-2020.6.SPINE20598/article-10.3171-2020.6.SPINE20598.xml
Lumbar discectomy for the management of lumbar radiculopathy is a commonly performed procedure with generally excellent patient outcomes. However, recurrent lumbar disc herniation (rLDH) remains one of the most common complications of the procedure, often necessitating repeat surgery. rLDH is known to be influenced by a variety of factors, and in this systematic review the authors aimed to explore the radiological predictors of recurrence.
In total, 1626 reported studies were screened, with 23 being included in this review, of which 13 were appropriate for meta-analysis. Three factors, namely disc height index, Modic changes, and sagittal range of motion, were determined to be significantly correlated with an increased rate of recurrent lumbar disc herniation.
Modic changes in the disc endplate are also associated with early signs of disc degeneration. In particular, type 1 changes were found to be significantly correlated with a higher recurrence rate of 62% compared with 12.3% in the nonrecurrent group. This finding is thought to be due to the biomechanical instability that is associated with type 1 changes. This biomechanical instability is due to the nature of the endplate changes, wherein type 1 changes are associated with an underlying inflammatory process, while type 2 changes are associated with a more stable and unchanging process. In agreement with this hypothesis, the authors determined that type 1 Modic endplate changes were the most significant factor for developing rLDH following discectomy.
7 figures, 1 table with many forest plots
5. Takai K, Endo T, Yasuhara T, et al. Neurosurgical versus endovascular treatment of spinal dural arteriovenous fistulas: a multicenter study of 195 patients. J Neurosurg Spine 2020 Nov 13;1–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33186917
Consecutive patients with dAVFs in the thoracic and lumbosacral regions who were treated with neurosurgery and/or endovascular embolization between 2009 and 2018 were included. Data from 199 consecutive patients with thoracic and lumbosacral spinal dAVFs were collected from 18 centers. Angiographic and clinical findings, the rate of initial treatment failure or recurrence by procedures, risk factors for treatment failure, complications, and neurological outcomes were statistically analyzed.
Spinal dAVFs were frequently detected in the thoracic region (81%), fed by a single feeder (86%), and shunted into an intradural vein via the dura mater. The fistulous connection between the feeder(s) and intradural vein was located at a single spinal level in 195 patients (98%) and at 2 independent levels in 4 patients (2%). Among the neurosurgical (n = 145), and endovascular (n = 50) treatment groups of single dAVFs (n = 195), the rate of initial treatment failure or recurrence was significantly higher in the index endovascular treatment group (0.68% and 36%). A multivariate analysis identified endovascular treatment as an independent risk factor with significantly higher odds of initial treatment failure or recurrence. The rate of complications did not significantly differ between the two treatment groups (4.1% for neurosurgical vs 4.0% for endovascular treatment).
They conclude that neurosurgery is still the gold standard for patients with spinal dAVFs because neurosurgery via limited laminectomy was found to be superior to endovascular embolization as a primary treatment for complete obliteration of the fistula.
2 figures, 4 tables, no imaging
6. Dubey D, Wilson MR, Clarkson B, et al. Expanded clinical phenotype, oncological associations, and immunopathologic insights of paraneoplastic Kelch-like protein-11 encephalitis. JAMA Neurol 2020;77:1420. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2769014
Many neural autoantibody biomarkers of paraneoplastic encephalitis have been defined in the past decade, and new autoantibodies continue to be discovered. Many serve as biomarkers for specific cancer types. In 2019, the authors described the index case of a new paraneoplastic autoimmune Kelch-like protein-11 (KLHL11) encephalitis associated with seminoma and summarized clinical findings for 12 additional cases. The 26 additional patients they report here provide a more comprehensive overview of the clinical phenotype, its initial presentation, neurologic findings, oncologic associations, and disability outcomes.
All patients (including 13 previously reported) were male, and their median age was 46 years. In 28 of 39 cases, the predominant clinical presentation was paraneoplastic rhomboencephalitis (brainstem encephalitis and/or cerebellitis); 5 presented with a combination of paraneoplastic rhombencephalitis and limbic encephalitis; and 6 presented with only limbic encephalitis. Most patients presented with gait instability (n = 32; 82%) and diplopia (n = 22; 56%). Vertigo (n = 21; 54%), hearing loss (n = 15; 39%), and tinnitus (n = 14; 36%) were a common and distinctive clinical symptom among patients with autoimmune KLHL11 encephalitis.
Twenty-eight patients (76%) had T2/FLAIR hyperintensity (temporal lobe, n = 12; cerebellum, n = 9; brainstem, n = 3; and diencephalon, n = 3). One patient had midbrain T2 hyperintensity on brain MRI along with bilaterally symmetric T2 signal abnormality involving central gray structures extending to the upper thoracic spinal cord. Three patients had gadolinium enhancement on MRI (temporal lobe, n = 2; and midbrain and lumbosacral roots, n = 1).
Before a paraneoplastic etiology was considered, 21 patients (54%) were assigned varied alternative diagnosis, including infectious encephalitis (n = 6; Whipple disease in 4), brain tumor (n = 3), alcoholic cerebellar degeneration (n = 2), multiple sclerosis (n = 2), medication toxicity (n = 1), Wernicke encephalopathy (n = 1), neurosarcoidosis (n = 1), ischemic stroke (n = 1), Alzheimer disease (n = 1), frontotemporal degeneration/ amyotrophic lateral sclerosis (n = 1), benign paroxysmal positional vertigo (n = 1), and functional neurological disorder (n = 1).
Testicular cancer was diagnosed in most patients who had follow-up information (n = 13 of 20; 65%) after their physicians were informed about the high frequency of testicular cancer association in patients whose serum was scored positive for the immunostaining pattern. Only 25% of cases were noted to improve neurologically following cancer treatment and/or immunotherapy.
4 figures, 1 table, with MR images
7. Lundy P, Domino J, Ryken T, et al. The role of imaging for the management of newly diagnosed glioblastoma in adults: a systematic review and evidence-based clinical practice guideline update. J Neurooncol 2020;150:95–120. Available from: https://doi.org/10.1007/s11060-020-03597-3
The evidence-based clinical practice guideline taskforce members, the Joint Tumor Section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) have prioritized an update of the guidelines for management of newly diagnosed glioblastoma (GBM). The writers represent a multi-disciplinary panel of clinical experts encompassing neurosurgery, neuro-oncology, and radiation oncology. Together, they were recruited to develop this update on the evidence-based practice guidelines for newly diagnosed glioblastoma (GBM) in adults.
The 4493 citations were manually reviewed by the team with specific inclusion and exclusion criteria. 27 publications met the eligibility criteria. These papers were subdivided into publications that answered the specific imaging questions of diagnostic specificity (13), prognosis (8), and methods that suggest correlation between imaging and molecular tumor subtype.
To summarize this gigantic literature review, for patients with a suspected GBM, it is a class II recommendation that the minimum MRI exam should be an anatomic exam with both T2 weighted, FLAIR and pre- and post-gadolinium contrast enhanced T1 weighted imaging. With respect to prognostication, several class III series support the addition of diffusion and perfusion weighted MR imaging in the assessment of suspected GBM, for the purposes of distinguishing GBM from other tumor types (e.g., primary CNS lymphoma or metastases). There is also class III evidence to support magnetic resonance spectroscopy and nuclear medicine (PET 18F-FDG and 11CMET) may provide additional support for the diagnosis of GBM. Likewise, several class III studies have evaluated the use of imaging modalities to predict the molecular profile of GBM. At this time there is still insufficient data to make clear recommendations regarding the role of imaging for the prognostic stratification or prediction of molecular characteristics of tumors.
8. Shankar GM, Van Beaver LA, Choi BD, et al. Survival after surgery for renal cell carcinoma metastatic to the spine: impact of modern systemic therapies on outcomes. Neurosurgery 2020;87:1174–80
The authors identified 78 patients with metastatic RCC in whom instrumented stabilization was performed in 79% and postoperative stereotactic radiosurgery was performed in 41% of patients. Of patients presenting with weakness or myelopathy, 93% noted postoperative improvement and 78% reported improvement in radicular and axial paraspinal pain severity. Increased overall survival (OS) 913 days vs 222 days following surgery was noted in patients who received postoperative systemic therapy a median of 80 days following the surgical intervention.
At the time of intervention for spine metastasis, a total of 38 (49%) patients had received or were receiving systemic therapy with 28 (36%) patients receiving tyrosine kinase inhibitors (TKI), 3 (1%) receiving IL-2, 5 (6%) patients receiving an mTOR inhibitor, and 2 (3%) receiving an immune checkpoint inhibitor. Given the potential concerns for the effect of tyrosine kinase inhibitors on wound healing, alternative systemic therapies of mTOR inhibitors and immunotherapy provide reasonable options in the perioperative setting.
Surgical intervention for metastatic RCC of the vertebral column has a notable risk profile; however, the survival benefit associated with the inclusion of postoperative systemic therapies is an important consideration in the multimodal perioperative management of this patient population.
3 figures, 1 table, no imaging
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