1. Alomari S, Lubelski D, Sacino AN, et al. Does myelopathy increase the morbidity and mortality of elective single-level anterior cervical discectomy and fusion? An updated propensity-matched analysis of 3938 patients from the American College of Surgeons National Surgical Quality Improvement Program database. Neurosurgery 2021;89:109–15

This present study used the American College of Surgeon National Surgical Quality Improvement Program (ACS-NSQIP) database to examine the effect of myelopathy on early morbidity and mortality after elective single-level ACDF. They employed a propensity score matching analysis to minimize the effects of any preoperative characteristic differences between the 2 cohorts. The authors hypothesized that patients undergoing ACDF for myelopathy versus radiculopathy would be significantly associated with worse postoperative outcomes.

Twenty percent of the cohort was myelopathic. These patients were significantly older, had more comorbidities, more likely to be functionally dependent, and to undergo emergency surgery when compared to the nonmyelopathic cohort. When 1969 myelopathic patients were 1:1 propensity matched with non-myelopathic patients, there was no difference between the myelopathic and nonmyelopathic patients in incidence of postoperative intensive care unit admission or death. Patients in the myelopathic group were significantly more likely to have a nonhome discharge and less likely to be discharged on the first postoperative day. Myelopathic patients had a higher rate of return to operating room within the same admission (2.2%) as well as a higher unplanned readmission rate (4.2%). The total operation time (143 min) and average length of hospital stay (52 h) were significantly higher in the myelopathic group when compared to the nonmyelopathic group (117 min) and (33 h), respectively.

Patients with myelopathy who undergo elective single-level ACDF have higher risks of several perioperative events including longer operative time, longer hospital stay, higher return to operating room, and unplanned readmission rates, when compared to nonmyelopathic patients.

The authors used the most recent data from the ACS-NSQIP database (2016-2018), using a larger cohort of patients and a strict propensity score matching method, which allows for strict control of baseline heterogeneity between the cohorts and thus, leading to more valid results. This type of analysis also accounts for some of the limitations of previous studies. In contrast to prior studies, their analysis revealed no significant association between myelopathy and mortality for those undergoing elective single-level ACDF.

5 tables, no imaging

2. Sarraj A, Grotta J, Albers GW, et al. Clinical and neuroimaging outcomes of direct thrombectomy vs bridging therapy in large vessel occlusion. Neurology 2021;96:e2839–53

Despite the fact that >80% of the participants in pivotal EVT trials received IV tPA before EVT and that current international recommendations advocate IV thrombolysis (IVT) before the initiation of EVT for all eligible patients with LVO (Class of Recommendation I, Level of Evidence IA), concerns have been raised regarding the utility of tPA pretreatment for patients with LVO who have been selected for EVT.

The arguments in favor of direct EVT (dEVT) include the potential delay in EVT initiation with tPA pretreatment, the low overall recanalization rates with IV tPA before thrombectomy, increased thrombus fragility and migration with increased risk of distal emboli, increased risk for systemic and hemorrhagic complications with bridging therapy (BT; IVT plus EVT), and the increased costs of tPA administration.

Arguments in favor of IVT before EVT include the potential for early reperfusion that was observed in 7% to 8% of patients in early-window EVT trials, thrombus softening and facilitation of successful reperfusion, the potential role of IV tPA in patients who do not achieve successful reperfusion with EVT, and the effect on distal residual occlusions after EVT.

In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke [SELECT]), patients with anterior circulation large vessel occlusion (LVO) presenting to EVT capable centers within 4.5 hours from last known well were stratified into bridging therapy (BT) vs dEVT. The primary outcome was 90-day functional independence (modified Rankin Scale [mRS] score 0–2). Secondary outcomes included a shift across 90-day mRS grades, mortality, and symptomatic intracranial hemorrhage. The authors also performed subgroup analyses according to initial presentation to EVT-capable center (direct vs transfer), stroke severity, and baseline infarct core volume.

BT appears to be associated with better clinical outcomes, especially with milder NIHSS scores, smaller presentation core volumes, and those who were “dripped and shipped.” They did not observe any potential benefit of BT in patients with more severe strokes.

Patients presenting with baseline ischemic core volume of <50 cm3 treated with BT had significantly higher rates and likelihood of 90-day functional independence (BT 61.9% vs dEVT 46.4%) compared to patients receiving dEVT; this association was not evident in patients presenting with ischemic core volume of ≥50 cm3 (BT 26% vs dEVT 25%).

They observed no difference in other efficacy or safety outcomes, including the risk of symptomatic or asymptomatic ICH and neurologic worsening. In addition, IVT was not associated with delays in EVT because the median times from hospital arrival to groin puncture were similar in the 2 groups. They also detected an interaction that may modify the beneficial effect of BT compared to dEVT in patients with LVO. More specifically, BT appears to be more effective in patients with LVO with mild or moderate baseline stroke severity (NIHSS scores <15 points) who were transfers to EVT centers and those with smaller infarct core volume.

3 tables, 4 figures, no imaging

3. Fabritius MP, Tiedt S, Puhr-Westerheide D, et al. Computed tomography perfusion deficit volumes predict functional outcome in patients with basilar artery occlusion. Stroke 2021;52:2016–23

Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation ASPECTS on noncontrast CT, CTA source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps.

Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, NIH Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation ASPECTS, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome. In multivariate analyses, Basilar artery CTA score, posterior-circulation ASPECTS and perfusion deficit volumes on all CTP maps remained as independent outcome predictors. Cerebral blood flow deficit volume yielded the best performance for the classification of good clinical outcome with an area under the curve of 0.92.

Quantitative perfusion parameters, especially perfusion deficit volumes, presented excellent performance in outcome prediction in BAO patients after EVT and outperformed clinical parameters or traditional scores on CTA-SI and noncontrast CT in this cohort.

2 figures, 3 tables with imaging

4. Chen BS, Meyer BI, Saindane AM, et al. Prevalence of incidentally detected signs of intracranial hypertension on magnetic resonance imaging and their association with papilledema. JAMA Neurol 2021;78:718–25. Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2778357

The authors examined the prevalence of MRI signs of IH among consecutive outpatients undergoing brain MRI for any clinical indication and to explore their association with papilledema. This prospective cross-sectional study of outpatients undergoing brain MRI at 1 outpatient imaging facility was conducted between August 1, 2019, and March 31, 2020, with ocular fundus photographs taken concurrently. Radiographic images from consecutive adult patients who were undergoing brain MRI and able to participate in fundus photography were analyzed for MRI signs of IH.

Evaluation included prevalence of MRI signs of IH and prevalence of papilledema detected on ocular fundus photographs. Radiographic signs of IH included empty sella, optic nerve head protrusion, posterior scleral flattening, increased perioptic cerebrospinal fluid, optic nerve tortuosity, enlarged Meckel caves, cephaloceles, cerebellar tonsillar descent, and bilateral transverse venous sinus stenosis.

Among the 296 patients included in the study, the median age was 49.5 years, and 188 patients (63.5%) were female. The most common indication for MRI was surveillance of a brain neoplasm (82 patients). Investigations of headaches (26 patients [8.8%]) and disorders of intracranial pressure (4 patients [1.4%]) were uncommon. At least 1 radiographic sign of IH was present in 145 patients (49.0%). Among 296 total study patients, 98 patients (33.1%) had empty sella, 47 patients (15.9%) had enlarged Meckel caves, 32 patients (10.8%) had increased perioptic cerebrospinal fluid, 23 patients (7.8%) had optic nerve tortuosity, 2 patients (0.7%) had scleral flattening, and 4 patients (1.4%) had cephaloceles. Bilateral transverse venous sinus stenosis was present in 6 of 198 patients (3.0%). Five patients (1.7%) had papilledema.

Compared with patients without papilledema, those with papilledema had a significantly higher body mass index and history of IIH, in addition to an increased prevalence of empty sella, optic nerve tortuosity, and transverse venous sinus stenosis detected on MRI. The prevalence of papilledema increased from 2.8% among patients with at least 1 MRI sign of IH to 40.0% among patients with 4 or more MRI signs of IH.

They conclude that MRI signs of IH were common among patients undergoing brain MRI in this study but rarely associated with papilledema. The management of patients with incidentally detected signs of IH likely does not require systematic lumbar puncture unless concerning symptoms or papilledema are present.

1 figure with IH examples, 4 tables

5. Egger P, Evangelista GG, Koch PJ, et al. Disconnectomics of the rich club impacts motor recovery after stroke. Stroke 2021;52:2115–24

Structural brain networks possess a few hubs, which are not only highly connected to the rest of the brain but are also highly connected to each other. These hubs, which form a rich-club, play a central role in global brain organization. To investigate whether the concept of rich-club sheds new light on post-stroke recovery, the authors applied a novel network-theoretical quantification of lesions to patients with stroke and compared the outcomes with what lesion size alone would indicate.

Whole-brain structural networks of 73 patients with ischemic stroke were reconstructed using diffusion-weighted imaging data. Disconnectomes, a new type of network analyses, were constructed using only those fibers that pass through the lesion.

The authors considered the same set of nodes as found by van den Heuvel and Sporns to form the rich-club, namely the bilateral precuneus, superior frontal cortex, superior parietal cortex, hippocampus, putamen, and thalamus. They also added the brain stem and bilateral cerebellum, due to their highly connected natures.

Conclusions from their results are 3-fold. First, lesion volume is not the main factor in determining the likelihood of a patient with stroke having good recovery; the specifics of the lesion profile (disconnectome) matter. Second, the integrity of the rich-club may be the key in facilitating natural recovery. Finally, smaller lesions that focus on the rich club may lead to equally poor or worse recovery compared with larger lesions, which are more diffuse. Their results provide the first network-theoretical lesion profiling based on the disconnectome and its derived metrics L1 and L1RC .

6 figures

6. Carpenter K, Decater T, Iwanaga J, et al. Revisiting the vertebral venous plexus–a comprehensive review of the literature. World Neurosurg 2021;145:381–95. Available from: https://doi.org/10.1016/j.wneu.2020.10.004

The VVP can be classified into 3 separate plexuses in accordance with the location of the plexus as well as in which plane they course. The 3 divisions include the internal VVP (IVVP) (with anterior and posterior parts), the external VVP (EVVP) (with anterior and posterior parts), and the basivertebral veins. The IVVP lies within the spinal canal but external to the dura and courses longitudinally from the cranial vault to the sacrum. The EVVP surrounds the vertebral column and similar to the IVVP courses longitudinally from the cranial vault to the sacrum. Contrary to the IVVP and EVVP, the basivertebral veins run horizontally and lie within the vertebrae.

The valveless nature of the VVP allows for both forward and backward flow of blood. Groen not only confirmed the lack of valves within the VVP but also noted the connections between the VVP and the cranial sinuses, the subcutaneous cranial veins, the intercostal veins, and the sacral venous plexus, creating a widespread open communication network between the intracranial, intrathoracic, and intra-abdominal veins. The ability of the VVP to have retrograde and bidirectional flow is a critical distinction between the CSVS and the systemic venous system. The systemic venous system contains valves that force blood to move in 1 direction toward the heart, whereas the bidirectional flow of the CSVS does not function to return blood to the heart. This has been described of the CSVS as having an “ebb-and-flow” system with a predominantly linear and bidirectional nature.

6 figures

7. Berg D, Borghammer P, Fereshtehnejad SM, et al. Prodromal Parkinson disease subtypes — key to understanding heterogeneity. Nat Rev Neurol 2021;17:349–61. Available from: http://dx.doi.org/10.1038/s41582-021-00486-9

The prodromal phase is defined by the emergence of observable signs or symptoms of neurodegeneration. Markers of the prodromal phase include REM sleep behaviour disorder (RBD), olfactory loss, autonomic dysfunction, depression (with or without comorbid anxiety), mild motor signs, and pathological imaging markers of the presynaptic dopaminergic system and the cardiac sympathetic system. These markers have predictive value for clinical PD, although their specificity varies considerably.

The initial pathological aggregation and propagation of α-synuclein can occur in the brain or the periphery, and this observation has led to the hypothesis that PD comprises two overall subtypes: a body-first (or bottom-up) subtype, in which α-synuclein pathology originates in the autonomic and enteric nervous system and invades the CNS via the vagus nerve and sympathetic connectome, and a brain-first (top-down) subtype, in which pathology arises in the brain itself, most often in the limbic system or sometimes secondary to entry via the olfactory bulb, and descends through the brainstem and into the periphery. These subtypes align well with data from post-mortem studies and established neuropathological staging systems in PD and DLB. Post-mortem studies have identified two overarching profiles of Lewy pathology in the brain of patients with PD or DLB: a brainstem-predominant pattern of α-synuclein pathology that hypothetically corresponds with the body-first subtype, and a limbic predominant pattern that corresponds with the brain-first subtype.

In this framework, premotor REM sleep behaviour disorder is tightly linked to the body-first type, since ascending α-synuclein pathology affects pontine structures before the nigral dopamine neurons. By contrast, patients with the brain-first subtype usually do not have RBD when motor symptoms emerge.

Patients with iRBD and patients with de novo PD and premotor RBD follow the expected body-first trajectory, characterized by initial loss of cardiac sympathetic innervation and intestinal parasympathetic innervation followed by damage to the nigrostriatal dopamine system. By contrast, patients with de novo PD but no REM sleep behaviour disorder follow the opposite trajectory: initial loss of the nigrostriatal dopamine innervation but relatively intact sympathetic and parasympathetic innervation.

Imaging can be used to detect involvement of the peripheral autonomic nervous system, which is unique to Lewy body disorders among the neurodegenerative diseases. 123I-MIBG scintigraphy has demonstrated that marked cardiac sympathetic denervation is nearly ubiquitous among patients with iRBD. By contrast, MIBG scans are normal in 40–50% of patients with de novo PD. These findings suggest that patients with prodromal PD but without REM sleep behaviour disorder mostly have intact cardiac innervation. Studies of the parasympathetic innervation of the colon with 11C-donepezil PET and CT produced similar findings: in patients with de novo PD and REM sleep behaviour disorder and patients with iRBD the colonic PET signal is markedly reduced compared with that in healthy controls, whereas findings in patients with de novo PD but no REM sleep behaviour disorder are similar to those in controls.

3 figures with PET and MIBG imaging

8. Starmans NLP, van Dijk MR, Kappelle LJ, et al. Sneddon syndrome: a comprehensive clinical review of 53 patients. J Neurol 2021;268:2450–57. Available from: https://doi.org/10.1007/s00415-021-10407-x

After exclusion of more common causes of stroke, livedo reticularis may be a clue to the etiology of ischemic stroke, leading to a diagnosis of Sneddon syndrome (SS). It is a rare disorder, which predominantly affects young women. SS may involve various other organ systems, including the heart, blood vessels and kidneys, and may also cause thrombotic and obstetric complications. Common neurological manifestations are ischemic or hemorrhagic stroke, transient ischaemic attack (TIA), cognitive impairment, headache and epilepsy.

SS is considered to be a non-inflammatory thrombotic vasculopathy that involves the small- and medium-sized arteries of the skin. Various theories about the aetiology of this disorder have been proposed, but no consensus has been reached. At present, 2 groups of patients can be differentiated: those with and those without antiphospholipid antibodies (APL). APL-positive patients can also be diagnosed with the antiphospholipid syndrome (APS), which has overlapping features with SS. However, the presence of livedo reticularis is not required for a diagnosis of APS.

Consecutive patients, diagnosed with SS between 1996 and 2017, were retrospectively reviewed for their demographic, neurological, dermatological, cardiac and extracerebral vascular features. Diagnosis of SS was made only if other causes of stroke were excluded. Patients with and without APL were included and compared for their clinical features.

Fifty-three patients (79% female) were included, of whom 14 patients were APL-positive. Median age at diagnosis was 40 years. Approximately 60% of the patients had ≥ 3 cardiovascular risk factors. There were 129 previous vascular events (66 ischaemic strokes, 62 TIAs and 1 amaurosis fugax) during a median period of 2 years between the first event and diagnosis of SS. Skin biopsy was positive for SS in 29 patients (67%), mostly showing a thickened vessel wall with neovascularization in the deep dermis. After a median follow-up of 28 months, 4 patients, either on antiplatelet or oral anticoagulation therapy, had a recurrent stroke.

SS predominantly affects young women with a relatively large number of cardiovascular risk factors. Clinical features of SS are comparable across different studies. The authors found no differences in the main clinical features between APL positive and APL-negative patients.

5 tables, no imaging

9. Cicone F, Carideo L, Scaringi C, et al. Long-term metabolic evolution of brain metastases with suspected radiation necrosis following stereotactic radiosurgery: longitudinal assessment by F-DOPA PET. Neuro Oncol 2021;23:1024–34

The evolution of radiation necrosis (RN) varies depending on the combination of radionecrotic tissue and active tumor cells. In this study, the authors characterized the long-term metabolic evolution of RN by sequential PET/ CT imaging with F-DOPA in patients with brain metastases following stereotactic radiosurgery (SRS). Thirty consecutive patients with 34 suspected radionecrotic brain metastases following SRS repeated F-DOPA PET/CT every 6 months or yearly in addition to standard MRI monitoring. Diagnoses of local progression (LP) or RN were confirmed histologically or by clinical follow-up. Semi-quantitative parameters of F-DOPA uptake were extracted at different time points, and their diagnostic performances were compared with those of corresponding contrast-enhanced MRI.

The authors state that these results clearly show that F-DOPA PET is a highly reliable method for assessing the metabolic evolution of RN over time, which can be used to inform the referring clinicians on when a treatment should be initiated. Longitudinal assessment by F-DOPA PET enables the analysis of intrapatient variations of uptake measures, which proved to be robust indicators of lesions’ outcome in addition to conventional static semi-quantitative evaluation.

This suggests that asymptomatic, contrast enhancing lesions that do not shrink, or even enlarge, over time, may continue to be observed without any need of further treatments when associated with F-DOPA uptake values suggestive of RN. Conversely, the authors recommend a closer monitoring for lesions whose uptake values exceed “safety” uptake thresholds (eg, rSUV around 1.9–2.0). If symptoms develop, these lesions should be promptly referred for surgery to avoid the complications associated with the long-term use of high dose of steroids.

2 tables, 4 figures, 1 with 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.

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