Reperfusion strategies in stroke with medium-to-distal vessel occlusion: a prospective observational study.

INTRODUCTION: Medium vessel occlusion (MeVO) accounts for 30% of acute ischemic stroke cases. The risk/benefit profile of endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or the combination of the two (bridging therapy (BT)) is still unclear in MeVO. Here, we compare reperfusion strategies in MeVO for clinical and radiological outcomes. METHODS: This prospective single center study enrolled consecutive patients with AIS due to primary MeVO undergoing IVT, EVT, or BT at a comprehensive stroke center. Primary outcome was good functional status, defined as modified Rankin Scale (mRS) 0-2 at 3-month follow-up. Additional outcomes included mortality, successful recanalization, defined as mTICI ≥ 2b, stroke severity at discharge, and symptomatic intracerebral hemorrhage (sICH) according to SITS-MOST criteria. Logistic regression was modeled to define independent predictors of the primary outcome. RESULTS: Overall, 180 consecutive people were enrolled (IVT = 59, EVT = 38, BT = 83), mean age 75. BT emerged as independent predictor of primary outcome (OR = 2.76, 95% CI = 1.08-7.07) together with age (OR = 0.94, 95% CI = 0.9-0.97) and baseline NIHSS (OR = 0.88, 95% CI = 0.81-0.95). BT associated with a 20% relative increase in successful recanalization compared to EVT (74.4 vs 56.4%, p = 0.049). Rates of sICH (1.1%) and procedural complications (vasospasm 4.1%, SAH in 1.7%) were very low, with no difference across groups. DISCUSSION: BT may carry a higher chance of good functional outcome compared to EVT/IVT only in people with AIS due to MeVO, with marginally higher rates of successful recanalization. Randomized trials are needed to define optimal treatment tailoring for MeVO.

Pragmatic computerised perfusion diagnostics for non-convulsive status epilepticus: a prospective observational study.

BACKGROUND: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow. METHODS: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard. RESULTS: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1). CONCLUSION: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes.

Progressive multifocal leukoencephalopathy in multiple myeloma: a case report of a patient with SARS-CoV-2 infection and an updated systematic literature review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the human polyomavirus 2 (HPyV-2, previously known as JCV) in immunosuppressed individuals. Few cases of PML have been described in multiple myeloma (MM) patients. METHODS: We described a case of PML in a patient with MM with fatal worsening that occurred during SARS-CoV-2 infection. We also performed a literature review to update the 16 cases series of MM patients with PML already collected until April 2020. RESULTS: A 79-year-old female patient with refractory IgA lambda MM in Pomalidomide- Cyclophosphamide-Dexamethasone regimen developed gradual lower limbs and left arm paresis along with a decreased consciousness 3.5 years after the MM diagnosis. Symptoms developed shortly after the recognition of hypogammaglobulinemia. After SARS-CoV-2 infection, her neurological status quickly worsened until she deceased. MRI features and JCV-positive PCR on CSF confirmed the PML diagnosis. Our literature review adds sixteen clinical cases of PML in MM published between May 2020 and March 2023 to the 16 cases already collected in the previously published review by Koutsavlis. DISCUSSION: PML has been increasingly described in MM patients. It remains questionable if the HPyV-2 reactivation is determined by the severity of MM itself, by the effect of drugs or by a combination of both. SARS-CoV-2 infection may have a role in worsening PML in affected patients.

Carotid free-floating thrombus in COVID-19: a cerebrovascular disorder of cytokine storm-related immunothrombosis.

BACKGROUNDS: Several neurological manifestations, including stroke, have been reported in COVID-19 patients. The putative role of the COVID-19-related hyperinflammatory state in cerebrovascular disorders remains unclear. METHODS: From March 2020 to September 2021, we searched for patients who exhibited an ischemic stroke related to carotid free-floating thrombus (CFFT) to investigate its incidence and relationship with COVID-19. RESULTS: Of 853 ischemic strokes referred to our Stroke Centre during the study period, 5.7% (n = 49) were positive for SARS-CoV-2. Six had CFFT, of which two tested positive for SARS-CoV-2 (2/49 = 4.1%), and four did not (4/802 = 0.5%). The former were two middle-aged men suffering from COVID-19 pneumonia. Floating thrombi were promptly extracted by endarterectomy and endovascular thrombectomy, respectively, with no early and long-term complications. Notably, our COVID-19 patients exhibited little or no atherosclerosis burden on CT angiography, markedly elevated D-dimer levels, and extensive thrombus length. CONCLUSIONS: COVID-19-induced immunothrombosis possibly played a significant pathogenic role in CFFT.

Hyperperfusion Tmax mapping for nonconvulsive status epilepticus in the acute setting: A pilot case-control study.

OBJECTIVE: Nonconvulsive status epilepticus (NCSE) is misdiagnosed in >50% of cases in the emergency department. Computed tomographic perfusion (CTP) has been implemented in the hyperacute setting to detect seizure-induced hyperperfusion. However, the diagnostic value of CTP is limited by the lack of thresholds for hyperperfusion and high interrater variability. This pilot case-control study aims at identifying the diagnostic value of reverse Tmax (rTmax) in differentiating NCSE from acute ischemic stroke in the hyperacute setting. METHODS: We enrolled patients with NCSE (Salzburg criteria-based diagnosis) and stroke cases 1:1 matched for clinical features and time of presentation. CTP standard maps (mean transit time [MTT]-cerebral blood volume-cerebral blood flow [CBF]) and rTmax maps were elaborated and rated by two experts in CTP blinded to the final diagnosis. Hyperperfusion was adjudicated for standard CTP maps as an increase in CBF and a decrease in MTT, and for rTmax as the presence of a black area on 3-, 2-, and 1-s threshold maps. Cronbach alpha was used for interrater agreement; receiver operating curve analysis was run to measure accuracy with area under the curve. RESULTS: Overall, 34 patients were included (17 NCSE, 17 stroke; time from onset to imaging = 2 h for both groups). People with NCSE were older and more frequently had a history of epilepsy. NCSE patients had hyperperfusion on rTmax maps in 11 of 17 cases versus zero of 17 in stroke. Intra- and interrater reliability was higher for rTmax than for standard CTP maps (κ = 1 vs. κ = .6). rTmax was 82% (95%CI = 67-97%) accurate in predicting NCSE versus stroke in the hyperacute setting. Agreement between neuroimaging and electroencephalography (EEG) was limited at a hemispheric level for standard CTP maps, whereas rTMax had agreement with EEG largely reaching the sublobar level. SIGNIFICANCE: rTmax mapping might represent a reliable tool to spot NCSE-induced hyperperfusion with a threshold-based reproducible approach. Further studies are needed for validation and implementation in the differential diagnosis of focal neurological deficit in the hyperacute setting.

Predictive value of Tmax perfusion maps on final core in acute ischemic stroke: an observational single-center study.

PURPOSE: To assess utility of computed tomography perfusion (CTP) protocols for selection of patients with acute ischemic stroke (AIS) for reperfusive treatments and compare the diagnostic accuracy (ACC) in predicting follow-up infarction, using time-to-maximum (Tmax) maps. METHODS: We retrospectively reviewed consecutive AIS patients evaluated for reperfusive treatments at comprehensive stroke center, employing a multimodal computed tomography. To assess prognostic accuracy of CTP summary maps in predicting final infarct area (FIA) in AIS patients, we assumed the best correlation between non-viable tissue (NVT) and FIA in early and fully recanalized patients and/or in patients with favorable clinical response (FCR). On the other hand, the tissue at risk (TAR) should better correlate with FIA in untreated patients and in treatment failure. RESULTS: We enrolled 158 patients, for which CTP maps with Tmax thresholds of 9.5 s and 16 s, presented sensitivity of 82.5%, specificity of 74.6%, and ACC of 75.9%. In patients selected for perfusion deficit in anterior circulation territory, CTP-Tmax > 16 s has proven relatively reliable to identify NVT in FCR patients, with a tendency to overestimate NVT. Similarly, CTP-Tmax > 9.5 s was reliable for TAR, but it was overestimated comparing to FIA, in patients with unfavorable outcomes. CONCLUSIONS: In our experience, Tmax thresholds have proven sufficiently reliable to identify global hypoperfusion, with tendency to overestimate both NVT and TAR, not yielding satisfactory differentiation between true penumbra and benign oligoemia. In particular, the overestimation of NVT could have serious consequences in not selecting potential candidates for a reperfusion treatment.