1. Kamagata K, Andica C, Takabayashi K, et al. Association of MRI Indices of Glymphatic System With Amyloid Deposition and Cognition in Mild Cognitive Impairment and Alzheimer Disease. Neurology. 2022;99(24):e2648-60. doi:10.1212/WNL.0000000000201300
According to the glymphatic hypothesis, subarachnoid CSF enters the brain’s interstitial space from the periarterial space through the AQP4 channel expressed in the astrocyte end-feet and then mixes with the interstitial fluid (ISF) and waste solutes in the brain. The resulting CSF/ISF exchange and waste products, such as Aβ, are then drained out of the brain by the perivenous efflux pathway. Recent studies have demonstrated the possibility of measuring glymphatic functions using MRI, with most of them being MRI tracer–based studies using a gadolinium-based contrast agent (GBCA). Both intrathecal and intravenous GBCA administration are relatively invasive. Promising MRI-based noninvasive methods that do not require MRI tracers, namely, perivascular space (PVS) volumetry, calculation of the fractional volume of free water (FW) in brain parenchyma (i.e., brain ISF) from a bitensor diffusion tensor imaging (DTI) model, and calculation of the diffusivity along the PVS (ALPS) index, were recently introduced for the indirect evaluation of perivascular network activity.
Elevated WM FW has been reported in patients with Alzheimer disease, suggesting the stagnation of fluid drainage caused by glymphatic dysfunction. Using DTI, Taoka et al. proposed the ALPS index, which is calculated from the diffusivity along the deep medullary vein at the level of the lateral ventricle body, as a measure of perivascular clearance activity in the human brain.
In this study, MRI measures including perivascular space (PVS) volume fraction (PVSVF), fractional volume of free water in white matter (FW-WM), and index of diffusivity along the perivascular space (ALPS index) of patients with MCI, those with AD, and healthy controls from the Alzheimer’s Disease Neuroimaging Initiative database were compared. MRI measures were also correlated with the levels of CSF biomarkers, PET SUVR, and cognitive score in the combined subcohort of patients with MCI and AD.
36 patients with AD, 44 patients with MCI, and 31 healthy controls were analyzed. Patients with AD had significantly higher total, WM, and basal ganglia perivascular space volume fraction and fractional volume of free water in white matter and a lower ALPS index than healthy controls. Meanwhile, the MCI group only showed significantly higher total and WM PVSVF.
They conclude that changes in PVS-related MRI parameters occur in MCI and AD, possibly due to impairment of the glymphatic system. They report the associations between MRI parameters and Aβ deposition, neuronal change, and cognitive impairment in AD.
Lots of caveats with this paper, including that the ALPS index cannot evaluate whole brain glymphatic function. It is based on the orthogonal geometric relationship between projection and association fibers and medullary arteries and veins in the lateral ventricle body. Therefore, the ALPS can only be evaluated at the level of the lateral ventricle body. The ALPS index does not exclusively measure the diffusivity of the perivenous space around the deep medullary vein—that is, it is also influenced by the surrounding white matter microstructure included in the ROI.
5 figures and 1 table
2. Zhang JK, Jayasekera D, Song C, et al. Diffusion Basis Spectrum Imaging Provides Insights Into Cervical Spondylotic Myelopathy Pathology. Neurosurgery. 2023;92(1):102-109. doi:10.1227/neu.0000000000002183
Diffusion basis spectrum imaging (DBSI) is a noninvasive quantitative imaging modality that may improve understanding of cervical spondylotic myelopathy (CSM) pathology through detailed evaluations of spinal cord microstructural compartments.
A single-center prospective cohort study enrolled 50 patients with CSM and 20 controls from 2018 to 2020. All patients underwent clinical evaluation and diffusion weighted MRI, followed by diffusion tensor imaging and DBSI analyses. Diffusion weighted MRI metrics assessed white matter integrity by fractional anisotropy, axial diffusivity, radial diffusivity, and fiber fraction. In addition, DBSI further evaluates extra axonal changes by isotropic restricted and nonrestricted fraction. Including an intra axonal diffusion compartment, DBSI improves estimations of axonal injury through intra-axonal axial diffusivity. Patients were categorized into mild, moderate, and severe CSM using modified Japanese Orthopedic Association classifications. Imaging parameters were compared among patient groups using independent samples t tests and ANOVA.
Diffusion tensor imaging and DBSI fractional anisotropy, axial diffusivity, and radial diffusivity were significantly different between control and patients with CSM. DBSI fiber fraction, restricted fraction, and nonrestricted fraction were significantly different between groups. DBSI intra-axonal axial diffusivity was lower in mild compared with moderate and severe CSM.
The authors state that the results highlight the ability of DBSI to provide more granular assessments of white matter tract integrity and support its application as a noninvasive imaging biomarker of CSM disease severity and a potential predictor of postoperative improvement.
4 figures and 1 table. Interesting, but very early data. I would have liked to see some routine MR imaging correlations with the diffusion metrics.
3. Andersen BM, Reardon DA. Immunotherapy approaches for adult glioma: knowledge gained from recent clinical trials. Curr Opin Neurol. 2022;35(6):803-813. doi:10.1097/wco.0000000000001118
Despite the widespread success of therapies targeting the T-cell checkpoints programmed-death 1 and cytotoxic T lymphocyte antigen 4 in other malignancies, recent phase III trials in glioblastoma confirm the lack of efficacy of anti-programmed-death 1 monotherapy in more than 90% of patients. Vaccination approaches remain under investigation for high-grade glioma and have shown activity in some low-grade glioma patients. Chimeric antigen receptor T cells now feature a new generation of products engineered to potentially withstand glucocorticoid therapy. Oncolytic viral therapies have similarly advanced in sophistication, with drug-sensitive gene expression and tumor-selective modifications. Combinations of therapies hold promise for overcoming the numerous mechanisms of immune suppression in glioma.
As the complex interplay of glioma-associated immune cells comes into focus, clinical trials will likely also increase in complexity. Although many approaches hold promise in our ability to eradicate glioma through activation of an immune response, success in further combination clinical trials will require careful selection of drug combinations, the timing of drug administration, treatment and dose combinations, tumor tissue-based immune analysis, cooperation with various drug developers, and additional safety evaluation.
1 table
4. el Naamani K, Saad H, Chen CJ, et al. Comparison of Flow-Redirection Endoluminal Device and Pipeline Embolization Device in the Treatment of Intracerebral Aneurysms. Neurosurgery. 2023;92(1):118-124. doi:10.1227/neu.0000000000002148
The use of flow diverters for treating intracranial aneurysms has been widely used in the past decade; however, data comparing pipeline embolization device (PED; Medtronic Inc) and flow-redirection endoluminal device (FRED; MicroVention) in the treatment of intracranial aneurysms remain scarce.
This is a single-center retrospective review of aneurysms treated with PED and FRED devices. Patients treated with PED or FRED were included. Cases requiring multiple or adjunctive devices were excluded. Primary outcome was complete aneurysm occlusion at 6 months. Secondary outcomes included good functional outcome, need for retreatment, and any complication.
The study cohort comprised 150 patients, including 35 aneurysms treated with FRED and 115 treated with PED. Aneurysm characteristics including location and size were comparable between the 2 cohorts. 6-month complete occlusion rate was significantly higher in the PED cohort (74.7% vs 51.5%) but lost significance after inverse probability weights. Patients in the PED cohort were associated with higher rates of periprocedural complications (3.5% vs 0%), and the rate of in-stent stenosis was approximately double in the FRED cohort.
Compared with PED, FRED offers modest 6 months occlusion rates, which may be due to aneurysmal and baseline patient characteristics differences between both cohorts. Although not significant, FRED was associated with a higher complication rate mostly because of in-stent stenosis. Additional studies with longer follow-up durations should be conducted to further evaluate FRED thrombogenicity and efficacy.
2 tables and 4 figures, with catheter angios
5. Salem MM, Srinivasan VM, Tonetti DA, et al. Microsurgical Obliteration of Craniocervical Junction Dural Arteriovenous Fistulas: Multicenter Experience. Neurosurgery. 2023;92(1):205-212. doi:10.1227/neu.0000000000002196
Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports.
Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021). Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%.
They conclude that craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point.
5 figures, 4 tables including catheter angio, intraop photos and intraoperative indocyanine green images.
6. Fusini F, Girardo M, Aprato A, et al. Percutaneous Cement Discoplasty in Degenerative Spinal Disease: Systematic Review of Indications, Clinical Outcomes, and Complications. World Neurosurg. 2022;168:219-226. doi:10.1016/j.wneu.2022.10.008
Percutaneous cement discoplasty (PCD) is a minimally invasive surgical technique that hopes to improve stability by injecting bone cement into a severely degenerated disc. This procedure is intended to decrease spinal instability in advanced disc degeneration and seems to show promising results in the short and middle term. The procedure was developed as an alternative interbody spacer option in patients unsuitable for conventional surgery. The principle of PCD is based on vertebral segment instability, where disc degeneration causes spondylolisthesis with a reduced neuroforamen area.
Despite the spread of this technique, the real benefit of this technique is unclear, with little evidence regarding postoperative outcomes at longer follow-up, actual hospital stay, complications, and reoperation after PCD.
In this systematic review, a total of 7639 documents was retrieved from the databases search. After duplication removal and title/abstract screening, a total of 15 articles was selected. According to inclusion and exclusion criteria, 5 full text articles were included in the review.
All included studies were case series with a retrospective study design. The level of evidence for included articles was IV. A total of 25 major complications (requiring surgical intervention or long-term intravenous therapy) were collected: 9 cases of radiculopathy due to cement leakage or disc extrusion or persistent radiculopathy, 3 cases of deep infection, 5 cases of pain recurrence at a different level, 5 persistent pain after procedure needing fusion surgery, 2 adjacent vertebral fractures requiring vertebroplasty, and 1 case of deep vein thrombosis.
The methodologic quality of the articles included showed a poor Methodological index for nonrandomized studies score (median 9, range 6 11). The prospective collection of data and calculation of sample size, appropriate follow-up, and unbiased endpoint assessment were the parameters with lower scores.
Safe to say we don’t really know if this is effective given the quality of evidence and limited literature.
2 tables, no images.
7. Koch G, Casula EP, Bonnì S, et al. Precuneus magnetic stimulation for Alzheimer’s disease: a randomized, sham-controlled trial. Brain. 2022;145(11):3776-3786. doi:10.1093/brain/awac285
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a non-invasive therapeutic strategy in the battle against Alzheimer’s disease. Alzheimer’s disease patients primarily show alterations of the default mode network for which the precuneus is a key node. Here, the authors hypothesized that targeting the precuneus with TMS represents a promising strategy to slow down cognitive and functional decline in Alzheimer’s disease patients.
They performed a randomized, double-blind, sham-controlled, phase 2, 24-week trial to determine the safety and efficacy of precuneus stimulation in patients with mild-to-moderate Alzheimer’s disease. Fifty Alzheimer’s disease patients were randomly assigned in a 1:1 ratio to either receive precuneus or sham rTMS (mean age 73.7 years; 52% female). The trial included a 24-week treatment, with a 2-week intensive course in which rTMS (or sham) was applied daily five times per week, followed by a 22-week maintenance phase in which stimulation was applied once weekly. The Clinical Dementia Rating Scale–Sum of Boxes was selected as the primary outcome measure, in which post-treatment scores were compared to baseline. Secondary outcomes included score changes in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, Mini-Mental State Examination and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale. Moreover, single-pulse TMS in combination with EEG was used to assess neurophysiological changes in precuneus cortical excitability and oscillatory activity.
The findings show that patients that received precuneus repetitive magnetic stimulation presented a stable performance of the Clinical Dementia Rating Scale–Sum of Boxes score, whereas patients treated with sham showed a worsening of their score. Compared with the sham stimulation, patients in the precuneus stimulation group also showed also significantly better performances for the secondary outcome measures, including the Alzheimer’s Disease Assessment Scale–Cognitive Subscale, Mini-Mental State Examination and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale. Neurophysiological results showed that precuneus cortical excitability remained unchanged after 24 weeks in the precuneus stimulation group, whereas it was significantly reduced in the sham group. Finally, they found an enhancement of local gamma oscillations in the group treated with precuneus stimulation but not in patients treated with sham. They conclude that 24 weeks of precuneus rTMS may slow down cognitive and functional decline in Alzheimer’s disease. Repetitive TMS targeting the default mode network could represent a novel therapeutic approach in Alzheimer’s disease patients.
5 figures, 2 tables
8. Mair G, White P, Bath PM, et al. External Validation of e-ASPECTS Software for Interpreting Brain CT in Stroke. Ann Neurol. 2022;92(6):943-957. doi:10.1002/ana.26495
The purpose of this study was to test e-ASPECTS software in patients with stroke. Marketed as a decision support tool, e-ASPECTS may detect features of ischemia or hemorrhage on computed tomography (CT) imaging and quantify ischemic extent using Alberta Stroke Program Early CT Score (ASPECTS).
Using CT from 9 stroke studies, the authors compared software with masked experts. As per indications for software use, they assessed e-ASPECTS results for patients with/without middle cerebral artery (MCA) ischemia but no other cause of stroke. In an analysis outside the intended use of the software, they enriched their dataset with non-MCA ischemia, hemorrhage, and mimics to simulate a representative “front door” hospital population. With final diagnosis as the reference standard, they tested the diagnostic accuracy of e-ASPECTS for identifying stroke features (ischemia, hyperattenuated arteries, and hemorrhage) in the representative population. The authors included 4,100 patients. Final diagnosis was ischemia (78%), hemorrhage (14%), or mimic (8%). From 3,035 CTs with expert-rated ASPECTS, most (2084/3035, 69%) e-ASPECTS results were within one point of experts. In the representative population, the diagnostic accuracy of e-ASPECTS was 71% for detecting ischemic features, 85% (83–86%) for hemorrhage. Software identified more false positive ischemia (12% vs 2%) and hemorrhage (14% vs <1%) than experts.
In conclusion, on independent testing, e-ASPECTS provided moderate agreement with experts and overcalled stroke features. Therefore, future prospective trials testing impacts of artificial intelligence (AI) software on patient care and outcome are required before widespread implementation of stroke decision-support software.
4 figures, 4 tables…no imaging.
The American Society of Neuroradiology is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Visit the ASNR Education Connection website to claim CME credit for this podcast.
