1. Requena M, Olivé-Gadea M, Muchada M, et al. Direct to angiography suite without stopping for computed tomography imaging for patients with acute stroke: a randomized clinical trial. JAMA Neurol 2021;78:1099–107
Direct transfer to angiography suite (DTAS)
Door-to-puncture [DTP]) time
Despite the efforts dedicated to reduce DTP times, published registries and clinical trials have shown the difficulties in decreasing DTP time below 60 minutes, a target that has been set by expert consensus. The HERMES meta-analysis reported DTP times ranging from 81 minutes for transferred patients to 116 minutes for patients directly admitted to an endovascular center. Research assessing optimized workflows has led to a newly proposed paradigm in the acute treatment of patients with severe stroke: direct transfer to angiography suite (DTAS). Protocols for DTAS were simultaneously designed in several centers mirroring the ST-segment elevation myocardial infarction strategy of bypassing the emergency department and conventional imaging. On arrival at the angiography suite, the use of flat-panel computed tomography (FPCT) enables the ruling out of either an intracranial hemorrhage (ICH) or a large established infarct. In addition, LVO can be diagnosed with a flat-panel angiography system immediately before arterial puncture or directly with initial diagnostic angiography. Regardless of the protocol details, DTAS has been consistently shown to be effective in decreasing DTP time to as low as 16 minutes without safety concerns. The effect of DTAS on long-term functional outcomes varies between published nonrandomized studies and is still unclear.
The study was an investigator-initiated, single-center, evaluator-blinded randomized clinical trial. Of 466 consecutive patients with acute stroke screened, 174 with suspected LVO acute stroke within 6 hours of symptom onset were included.
Patients were randomly assigned (1:1) to follow either DTAS (89 patients) or conventional workflow (85 patients received direct transfer to computed tomographic imaging, with usual imaging performed and EVT indication decided) to assess the indication of EVT.
Mean onset-to-door time was 228.0 minutes, and their median admission National Institutes of Health Stroke Scale score was 18. In the modified intention-to-treat population, EVT was performed for all 74 patients in the DTAS group and for 64 patients (87.7%) in the conventional workflow group. The DTAS protocol decreased the median door–to–arterial puncture time (18 minutes vs 42 minutes and door-to-reperfusion time (57 minutes vs 84 minutes). The DTAS protocol decreased the severity of disability across the range of the mRS (modified Rankin Scale).
DTAS protocol was safe and led to improved clinical outcomes compared with the DTCT protocol. The DTAS protocol decreased in-hospital delays, achieving shorter times from hospital admission to treatment onset and to reperfusion, which were associated with a significant shift toward better outcomes across the spectrum of disability.
2 figures, 3 tables
2. Manzano GS, McEntire CRS, Martinez-Lage M, et al. Acute disseminated encephalomyelitis and acute hemorrhagic leukoencephalitis following COVID-19. Neurol Neuroimmunol Neuroinflamm 2021;8:e1080
Patients with a history of COVID-19 infection were included if their reports provided adequate detail to confirm a diagnosis of ADEM or AHLE by virtue of clinical features, radiographic abnormalities, and histopathologic findings. Cases purported to be secondary to vaccination against COVID-19 or occurring in the context of a preexisting relapsing CNS demyelinating disease were excluded. Case reports and series were identified via PubMed on May 17, 2021, and 4 additional cases from the authors’ hospital files supplemented the systematic review of the literature.
Forty-six patients (28 men, median age 49.5 years, 1/3 >50 years old) were analyzed, derived from 26 case reports or series originating from 8 countries alongside 4 patient cases from the authors’ hospital files. COVID-19 infection was laboratory confirmed in 91% of cases, and infection severity necessitated intensive care in 67%. ADEM occurred in 31 cases, whereas AHLE occurred in 15, with a median presenting nadir modified Rankin Scale score of 5 (bedridden). Anti-MOG seropositivity was rare (1/15 patients tested). Noninflammatory CSF was present in 30%. Hemorrhage on brain MRI was identified in 42%. Seventy percent received immunomodulatory treatments, most commonly steroids, IV immunoglobulins, or plasmapheresis. The final mRS score was ≥4 in 64% of patients with adequate follow-up information, including 32% who died.
In contrast to ADEM cases from the prepandemic era, reported post–COVID-19 ADEM and AHLE cases were often advanced in age at onset, experienced severe antecedent infection, displayed an unusually high rate of hemorrhage on neuroimaging, morbidity with ADEM was high despite the use of standard ADEM treatments, and mortality was common even with relatively short follow-up.
3 figures, 4 tables including MR and histology
3. Bathla G, Abdel-Wahed L, Agarwal A, et al. Vascular involvement in neurosarcoidosis. Neurol Neuroimmunol Neuroinflamm 2021;8:e1063
A total of 13 consecutive patients with NS underwent VWI. Images were analyzed by 2 neuroradiologists in consensus. The assessment included segment-wise evaluation of larger and medium-sized vessels (internal carotid artery, M1-M3 middle cerebral artery; A1-A3 anterior cerebral artery; V4 segments of vertebral arteries; basilar artery; and P1-P3 posterior cerebral artery), lenticulostriate perforator vessels, and medullary and deep cerebral veins. Cortical veins were not assessed due to flow-related artifacts. Brain biopsy findings were available in 6 cases and were also reviewed.
Mean patient age was 54.9 years (33–71 years) with an M:F of 8:5. Mean duration between initial diagnosis and VWI study was 18 months. Overall, 9/13 (69%) patients had vascular abnormalities. Circumferential large vessel enhancement was seen in 3/13 (23%) patients, whereas perforator vessel involvement was seen in 6/13 (46%) patients. Medullary and deep vein involvement was also seen in 6/13 patients. In addition, 7/13 (54%) patients had microhemorrhages in susceptibility-weighted imaging, and 4/13 (31%) had chronic infarcts.
This study, although performed on a small patient cohort, provides insights into the spectrum of vascular involvement in patients with NS using dedicated VWI-MRI. The authors state that the findings support prior observations that cerebrovascular manifestations are likely more common than previously realized and involve both arterial and venous structures, similar to primary angiitis of the CNS. This is also supported by the review of brain histopathology slides, which were available in 6/13 patients with NS.
3 figures including MR, 2 tables
4. Metz I, Gavrilova RH, Weigand SD, et al. Magnetic resonance imaging correlates of multiple sclerosis immunopathological patterns. Ann Neurol 2021;90:440–54
Multiple sclerosis (MS) is an inflammatory demyelinating disease with unknown etiology and a considerable heterogeneity regarding clinical characteristics, therapeutic response, and MR features. Furthermore, histological analysis reveals substantial differences when comparing lesions from different patients. Although all lesions show the common characteristics of demyelination, inflammation, axonal damage, and astrocytic gliosis, major histological differences can be found, allowing their classification into 3 main immunopathological patterns of active demyelination (patterns I–III). Immunopatterns among early active MS lesions have been shown to be consistent within an individual over space and time. These patterns suggest different mechanisms of lesion development. Patterns I and II are typically sharply demarcated, and all myelin proteins are lost to an equal extent. However, only pattern II lesions are associated with immunoglobulins and complement deposited along myelin sheaths and present within macrophages, suggesting an antibody- and complement-mediated mechanism of demyelination. In contrast, pattern III lesions are characterized by an ill-defined lesion edge, the presence of apoptotic oligodendrocytes, and a preferential loss of myelin-associated glycoprotein (MAG) compared to other myelin proteins. MAG is located in distal oligodendrocyte processes, and its loss is considered to be a marker of metabolically stressed oligodendrocytes. Changes observed in pattern III lesions suggest oligodendrocyte damage preceding demyelination. Thus far, these immunopathological patterns can only be diagnosed by histology. The MRI correlates are unknown.
The authors evaluated in an international collaborative retrospective cohort study the MRI lesion characteristics of 789 conventional prebiopsy and follow-up MRIs in relation to their histopathologically classified immunopathological patterns (n = 161 subjects) and lesion edge features (n = 112).
A strong association of a ringlike enhancement and a hypointense T2-weighted (T2w) rim with patterns I and II, but not pattern III, was observed. Only a fraction of pattern III patients showed a ringlike enhancement, and this was always atypical. Ringlike enhancement and T2w rims colocalized, and ringlike enhancement showed a strong association with macrophage rims as shown by histology.
In conclusion, the authors compared the MRI characteristics of 161 patients who were classified according to their immunopathological patterns by histology and found that the majority of pattern I and pattern II patients but only a minority of pattern III patients showed ring enhancing lesions. In addition, ring enhancing lesions of pattern III patients did not reveal a smooth-contoured, thin, and regular ring or arc as was typical for pattern I and II patients. Instead, when present at all, they were atypical rings such as irregularly thick rings and arcs. In addition, 2 patients showed concentric rings that indicate Balo’s concentric sclerosis. It is known that Balo’s concentric sclerosis lesions are pattern III lesions, and they could confirm this in the current study.
3 tables, 5 figures including MR and path
5. Chen CJ, Ding D, Lee CC, et al. Stereotactic radiosurgery with versus without embolization for brain arteriovenous malformations. Neurosurgery 2021;88:313–21
Conventional stereotactic radiosurgery (SRS) delivered in a single session struggles to successfully treat large (diameter > 3 cm or volume > 12 ml) brain arteriovenous malformations (AVMs). Endovascular embolization has been used as a neoadjuvant intervention to render large nidi more amenable to SRS and target high-risk AVM-associated features, such as arterial aneurysms and high-flow intranidal arteriovenous fistulas. However, the role of upfront AVM embolization has come under scrutiny due to accumulating evidence of its potentially deleterious effect on obliteration rates after SRS. The etiology of lower post-SRS obliteration rates in embolized AVMs has been purported to stem from the physical properties of ethylene vinyl alcohol copolymer (Onyx, Medtronic Neurovascular), the most frequently used embolysate in contemporary neurointerventional procedures. However, previous studies that analyzed the effect of prior embolization on AVM SRS outcomes failed to account for the baseline nidal dimensions and angioarchitectural features before embolization. This represents a fundamental flaw that pervades the available literature pertaining to the relationship between prior Onyx embolization and post-SRS outcomes. The aim of this multicenter, retrospective matched cohort study is to compare the outcomes of SRS with versus without neoadjuvant Onyx embolization using de novo characteristics of the pre-embolized nidus.
The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively) and cumulative probabilities at 3, 4, 5, and 6 years of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively.
Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration.
Although the present study does not deem Onyx embolization detrimental to AVM SRS outcomes, the authors also failed to show a discrete benefit from the combination of both AVM therapies. Nevertheless, they believe that pre-SRS AVM embolization with Onyx will retain a role in the treatment of carefully selected patients. Specifically, targeted embolization of a large AVM with multiple compartments could simplify its morphology to facilitate treatment of the residual nidus with single-session SRS, thereby averting staged SRS approaches that can require longer implementation periods. Embolization can also eliminate AVM-associated arterial aneurysms that, left untreated, can elevate the risk of post-SRS hemorrhage. Lastly, endovascular occlusion can manage high-flow intranidal arteriovenous shunts, which are relatively radioresistant.
5 tables, 2 figures, no imaging
6. Rich CW, Fasano RE, Isbaine F, et al. MRI-guided stereotactic laser corpus callosotomy for epilepsy: distinct methods and outcomes. J Neurosurg 2021;135:770–82
SLCC = stereotactic laser corpus callosotomy
Several small series have described stereotactic MRI-guided laser interstitial thermal therapy for partial callosotomy of astatic and generalized tonic-clonic (GTC) seizures, especially in association with Lennox-Gastaut (Len nox Gas Ta) syndrome. Larger case series and comparison of distinct stereotactic methods for stereotactic laser corpus callosotomy (SLCC), however, are currently lacking. The objective of this study was to report seizure outcomes in a series of adult patients with epilepsy following anterior, posterior, and complete SLCC procedures and to compare the results achieved with a frameless stereotactic surgical robot versus direct MRI guidance frames.
Thirteen patients underwent 15 SLCC procedures. The median age at surgery was 29 years (range 20–49 years), the median duration of epilepsy was 21 years (range 9–48 years), and median post ablation follow-up was 20 months (range 4–44 months). Ten patients underwent anterior SLCC with a median 73% (range 33%–80%) midsagittal length of callosum acutely ablated. Following anterior SLCC, 6 of 10 patients achieved meaningful (> 50%) reduction of target seizures. Four patients underwent posterior (completion) SLCC following prior anterior callosotomy, and 1 patient underwent complete SLCC as a single procedure; 3 of these 5 patients experienced meaningful reduction of target seizures. Overall, 8 of 10 patients in whom astatic seizures were targeted and treated by anterior and/or posterior SLCC experienced meaningful improvement. SLCC procedures with direct MRI guidance (n = 7) versus a frameless surgical robot (n = 8) yielded median radial accuracies of 1.1 mm versus 2.4 mm. The most serious adverse event was a clinically significant intraparenchymal hemorrhage in a patient who underwent the robotic technique.
They conclude that SLCC provides seizure outcomes comparable to open surgery outcomes reported in the literature. Direct MRI guidance is more accurate, which has the potential to reduce the risks of SLCC.
4 tables, 4 figures
7. Gassert FT, Kufner A, Gassert FG, et al. MR-based proton density fat fraction (PDFF) of the vertebral bone marrow differentiates between patients with and without osteoporotic vertebral fractures. Osteoporos Int 2021 Sep 18. [Epub ahead of print]. Available from: https://doi.org/10.1007/s00198-021-06147-3
Of the 52 study patients, 32 presented with vertebral fractures of the lumbar spine (66.4 ± 14.4 years, 62.5% women; acute low-energy osteoporotic/osteopenic vertebral fractures, N = 25; acute high-energy traumatic vertebral fractures, N = 7). These patients were frequency matched for age and sex to patients without vertebral fractures (N = 20, 69.3 ± 10.1 years, 70.0% women). Trabecular bone mineral density (BMD) values were derived from quantitative computed tomography. Chemical shift encoding-based water-fat MRI of the lumbar spine was performed, and proton density fat fraction maps were calculated. Associations between fracture status and proton density fat fraction were assessed using multivariable linear regression models.
Over all patients, mean proton density fat fraction and trabecular BMD correlated significantly. In the osteoporotic/ osteopenic group, those patients with osteoporotic/osteopenic fractures had a significantly higher PDFF than those without osteoporotic fractures after adjusting for age, sex, weight, height, and trabecular BMD although trabecular BMD values showed no significant difference between the subgroups. For the differentiation of patients with and without vertebral fractures in the osteoporotic/osteopenic subgroup using mean proton density fat fraction, an area under the receiver operating characteristic (ROC) curve (AUC) of 0.88 was assessed.
The authors conclude that the bone marrow proton density fat fraction measurements derived from chemical shift encoding-based water fat separation have the potential to differentiate between osteoporotic/osteopenic patients with and without vertebral fractures, suggesting that PDFF may be a useful tool for fracture risk assessment. The PDFF differences remained significant even when adjusting for age, sex, height, weight, and trabecular BMD using a multivariable linear regression model. Moreover, the mean PDFF assessed in vertebral bodies may provide radiation-free information on bone stability, additionally to BMD.
4 figures with MR
8. Funaba M, Imajo Y, Suzuki H, et al. The associations between radiological and neurological findings of degenerative cervical myelopathy: radiological analysis based on kinematic CT myelography and evoked potentials of the spinal cord. J Neurosurg Spine 2021;35:308–19. Available from: https://thejns.org/view/journals/j-neurosurg-spine/35/3/article-p308.xml
One hundred twenty-one patients with DCM were enrolled. The Japanese Orthopaedic Association (JOA) score, radiological parameters, MRI and kinematic CT myelography (CTM) parameters, and the affected spinal level (according to multimodal spinal cord evoked potential examinations) were assessed. Kinematic CTM was conducted with neutral positioning or at maximal extension or flexion of the cervical spine. The cross-sectional area (CSA) of the spinal cord, dynamic change in the CSA, C2–7 range of motion, and C2–7 angle were measured. The associations between radiological parameters and hyperreflexia, the Hoffmann reflex (finger flexor reflex), the Babinski sign, and positional sense were analyzed via multiple logistic regression analysis.
In univariate analyses, the upper- and lower-limb JOA scores were found to be significantly associated with a positive Hoffmann reflex and a positive Babinski sign, respectively. In the multivariate analysis, a positive Hoffmann reflex was associated with a higher MRI grade and a responsible level other than C6–7. A small cross-sectional area during flexion was found to be significantly associated with a positive Babinski sign. The presence of ossification of the posterior longitudinal ligament and a larger C2–7 angle during flexion were significantly associated with abnormal great toe proprioception (GTP).
This study found that the Hoffmann reflex is associated with chronic and severe spinal cord compression but not the dynamic factors. The Babinski sign is associated with severe spinal cord compression during neck flexion. The GTP is associated with large cervical lordosis.
Neurological examination is essential in the diagnosis of patients with DCM. Considering the findings of this study will help to explain the existence of individual differences in neurological findings and will lead to a more appropriate assessment. The authors believe that it is preferable to conduct kinematic imaging evaluation as extensively as possible before making a diagnosis and planning surgical procedures. First, although the role of the Hoffmann reflex in the diagnosis of DCM is well established, it can yield a false-positive result, and thus it is necessary to confirm the consistency of the reflex with the signal intensity of the spinal cord on MRI and the level of spinal cord compression on kinematic imaging for improved diagnostic accuracy. Second, in patients with a positive Babinski sign, the authors recommend conducting radiological imaging during neck flexion, considering the involvement of spinal cord compression factors.
5 tables, 4 figures with MR and CTM
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