Vagus nerve dysfunction in the post-COVID-19 condition: a pilot cross-sectional study.

OBJECTIVES: The post-COVID-19 condition (PCC) is a disabling syndrome affecting at least 5%-10% of subjects who survive COVID-19. SARS-CoV-2 mediated vagus nerve dysfunction could explain some PCC symptoms, such as dysphonia, dysphagia, dyspnea, dizziness, tachycardia, orthostatic hypotension, gastrointestinal disturbances, or neurocognitive complaints. METHODS: We performed a cross-sectional pilot study in subjects with PCC with symptoms suggesting vagus nerve dysfunction (n = 30) and compared them with subjects fully recovered from acute COVID-19 (n = 14) and with individuals never infected (n = 16). We evaluated the structure and function of the vagus nerve and respiratory muscles. RESULTS: Participants were mostly women (24 of 30, 80%), and the median age was 44 years (interquartile range [IQR] 35-51 years). Their most prevalent symptoms were cognitive dysfunction 25 of 30 (83%), dyspnea 24 of 30 (80%), and tachycardia 24 of 30 (80%). Compared with COVID-19-recovered and uninfected controls, respectively, subjects with PCC were more likely to show thickening and hyperechogenic vagus nerve in neck ultrasounds (cross-sectional area [CSA] [mean ± standard deviation]: 2.4 ± 0.97mm2 vs. 2 ± 0.52mm2 vs. 1.9 ± 0.73 mm2; p 0.08), reduced esophageal-gastric-intestinal peristalsis (34% vs. 0% vs. 21%; p 0.02), gastroesophageal reflux (34% vs. 19% vs. 7%; p 0.13), and hiatal hernia (25% vs. 0% vs. 7%; p 0.05). Subjects with PCC showed flattening hemidiaphragms (47% vs. 6% vs. 14%; p 0.007), and reductions in maximum inspiratory pressure (62% vs. 6% vs. 17%; p ≤ 0.001), indicating respiratory muscle weakness. The latter findings suggest additional involvement of the phrenic nerve. DISCUSSION: Vagus and phrenic nerve dysfunction contribute to the complex and multifactorial pathophysiology of PCC.

CT Assessment of Otic Capsule Bone Density in Paget's Disease of the Temporal Bone and Its Relationship With Hearing Loss.

OBJECTIVES: To study computed tomography findings in Paget's disease of temporal bone (PDTB) and analyze the relations between otic capsule bone mineral density values measured in Hounsfield Units (HU) and hearing loss (HL). STUDY DESIGN: Observational case-control study. SETTING: Tertiary referral center. PATIENTS: Radiographically confirmed PDTB cases and control group. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Hearing thresholds and computed tomography bone density values. RESULTS: Twenty-three ears in the case group (PDTB) and 27 control ears were included. In the PDTB group, HL was found in 87% of the ears (43% mixed) and an air-conduction threshold of 50.7 dB (SD = 19.8). In the control group, 48% of the ears showed HL (7% mixed) and an air-conduction threshold of 34.5 dB (SD = 20.6) was found; the difference was statistically significant (p < 0.05). Measurements of bone density (HU) in the otic capsule (regions of interest [ROI] 1 and 2) and in the petrous bone (ROI 3) were significantly lower (p < 0.05) in the PDTB group than in controls.The PDTB group presented a significant association between otic capsule bone density in ROI 1 and mean otic capsule density with air and bone-conduction thresholds (p < 0.05). In controls, no association was observed between any density value and audiometric thresholds. CONCLUSION: PDTB patients showed more frequent HL, lower thresholds, and a higher proportion of mixed HL than controls. Bone density (HU) was decreased in all ROIs in PDTB patients in comparison with controls. Bone density in the otic capsule was associated with HL in PDTB patients, but no association was observed between bone density and HL in controls.

Validation of shunt dependency prediction scores after aneurysmal spontaneous subarachnoid hemorrhage.

BACKGROUND: Currently available scores for predicting shunt dependency after aneurysmal spontaneous subarachnoid hemorrhage (aSAH) are limited and not widely accepted. The key purpose of this study was to validate a recently created score for shunt dependency in aSAH (SDASH) in an independent population of aSAH patients. We compared this new SDASH score based on a combination of the Hunt and Hess grade, Barrow Neurological Institute (BNI) score, and the presence or not of acute hydrocephalus with other published predictive scores. METHODS: The SDASH score, Hijdra score, BNI grading system, chronic hydrocephalus ensuing from SAH score (CHESS), Graeb score, and modified Graeb score (mGS) were calculated for a cohort of aSAH patients. Logistic regression analysis was used to determine the reliability of the SDASH score, and the area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to assess the discriminative ability of the model. RESULTS: In 214 patients with aSAH, 40 (18.7%) developed shunt-dependent hydrocephalus (SDHC). The AUC for the SDASH score was 0.816. The SDASH score reliably predicted SDHC in aSAH (odds ratio: 2.93, 95% CI: 1.99-4.31; p < 0.001) with no statistically significant differences being found between the SDASH score and the CHESS score (AUC: 0.816), radiological-based Graeb score (AUC: 0.742), or modified Graeb score (AUC: 0.741). However, the Hijdra score (AUC: 0.673) and BNI grading system (AUC: 0.616) showed lower predictive values than the SDASH score. CONCLUSIONS: Our findings support the ability of the SDASH score to predict shunt dependency after SAH in a population independent to that used to develop the score. The SDASH score may aid in the early management of hydrocephalus in aSAH, and it does not differ greatly from other predictive scores.

Deep Learning Based Software to Identify Large Vessel Occlusion on Noncontrast Computed Tomography.

BACKGROUND AND PURPOSE: Reliable recognition of large vessel occlusion (LVO) on noncontrast computed tomography (NCCT) may accelerate identification of endovascular treatment candidates. We aim to validate a machine learning algorithm (MethinksLVO) to identify LVO on NCCT. METHODS: Patients with suspected acute stroke who underwent NCCT and computed tomography angiography (CTA) were included. Software detection of LVO (MethinksLVO) on NCCT was tested against the CTA readings of 2 experienced radiologists (NR-CTA). We used a deep learning algorithm to identify clot signs on NCCT. The software image output trained a binary classifier to determine LVO on NCCT. We studied software accuracy when adding National Institutes of Health Stroke Scale and time from onset to the model (MethinksLVO+). RESULTS: From 1453 patients, 823 (57%) had LVO by NR-CTA. The area under the curve for the identification of LVO with MethinksLVO was 0.87 (sensitivity: 83%, specificity: 71%, positive predictive value: 79%, negative predictive value: 76%) and improved to 0.91 with MethinksLVO+ (sensitivity: 83%, specificity: 85%, positive predictive value: 88%, negative predictive value: 79%). CONCLUSIONS: In patients with suspected acute stroke, MethinksLVO software can rapidly and reliably predict LVO. MethinksLVO could reduce the need to perform CTA, generate alarms, and increase the efficiency of patient transfers in stroke networks.

Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke.

Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS). Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P = .007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials.

BACKGROUND: Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement. OBJECTIVE: To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality. METHODS: Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated. RESULTS: Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively). CONCLUSIONS: In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

Post-Operative Localization of Deep Brain Stimulation Electrodes in the Subthalamus Using Transcranial Sonography.

OBJECTIVES: The correct positioning of deep brain stimulation electrodes determines the success of surgery. In this study, we attempt to validate transcranial sonography (TCS) as a method for early postoperative confirmation of electrode location in the subthalamic nucleus (STN). MATERIALS AND METHODS: Nineteen patients diagnosed with Parkinson's disease were enrolled in the study. Postoperative TCS was applied to measure the distance between the implanted electrodes and the third ventricle in the axial plane. Whether the electrodes were positioned within or outside the substantia nigra (SN) was evaluated through measurements in the coronal plane. The obtained metrics through TCS were compared with those from postoperative computed tomography (CT) and magnetic resonance imaging (MRI). RESULTS: A statistically significant correlation between distances from electrode to third ventricle by TCS and CT/MRI (r = 0.75, p < 0.01) was observed. Distances from third ventricle to electrodes tips were different when sonographically they showed to be inside or outside the SN (p < 0.01). A cut-off value of 8.85mm in these distances was the most sensitive (100%) and specific (90.5%) to predict if electrodes were positioned inside the SN (CI 95% 0.81-10.30, p = 0.001). CONCLUSIONS: Transcranial sonography is a useful technique to reliably identify targeted positioning of deep brain stimulation electrodes in or out of the SN.

Validation of the new Graded Prognostic Assessment scale for brain metastases: a multicenter prospective study.

BACKGROUND: Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. METHODS: A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months. RESULTS: During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. CONCLUSIONS: Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

Value of bone SPECT-CT to predict chronic pain relief after percutaneous vertebroplasty in vertebral fractures.

BACKGROUND CONTEXT: Longer life span has resulted in increased risk of vertebral osteoporotic fractures. Among minimally invasive procedures, percutaneous vertebroplasty (PV) has shown excellent results in the treatment of chronic vertebral pain. The role of preintervention bone single photon emission computed tomography-computed tomography (SPECT-CT) has not been clearly established for the management of these patients. PURPOSE: To determine the value of bone SPECT-CT in patient selection, treatment planning, and prediction of response to PV. A comparison with magnetic resonance imaging (MRI) was also aimed. STUDY DESIGN: Prospective consecutive series. PATIENT SAMPLE: We studied the performance of bone SPECT-CT on 33 consecutive patients with chronic pain because of vertebral fracture intended for PV. OUTCOME MEASURES: Improvement of clinical status was based on comparison of preprocedure and postprocedure outcome measurements of pain, mobility, and analgesic use. METHODS: Bone SPECT was done using a dual-detector variable-angle gamma camera coupled with a two-slice CT scanner (Symbia T2 System; Siemens, Munich, Germany). Magnetic resonance imaging was done using a magnet of 1.5 T (Giroscan System ACS NT Intera; Philips, Amsterdam, The Netherlands). RESULTS: Of the 33 patients, 24 finally underwent PV. Positive SPECT-CT images predicted clinical improvement in 91% (21 of 23) of them. Agreement between SPECT-CT and MRI was 80% (20 of 25). Single photon emission computed tomography-computed tomography images showed an alternative cause of pain in some cases, such as new fractures or multiple coexisting fractures, persisting bone remodeling in a previous cemented vertebra, and facet or discal degenerative disease. Single photon emission computed tomography-computed tomography was mandatory in eight patients that could no receive MRI, all of whom improved after PV. CONCLUSIONS: Positive bone SPECT-CT seems a good predictor of postprocedural response. It also adds valuable information as to the cause of back pain and facilitates complete patient evaluation in patients that can not receive MRI.

Biological signatures of brain damage associated with high serum ferritin levels in patients with acute ischemic stroke and thrombolytic treatment.

BACKGROUND AND PURPOSE: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. METHODS: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. RESULTS: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p < 0.001) levels at baseline, and with glutamate (r = 0.57, p < 0.001), interleukin-6 (r = 0.49, p < 0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. CONCLUSIONS: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research.

Prognostic value of CT in the early assessment of patients with acute pancreatitis.

OBJECTIVE: This study investigates the prognostic value of early CT in acute pancreatitis, the role of pancreatic necrosis as a indicator of prognosis, and the need for the routine use of IV iodinated contrast material in early CT to assess prognosis in these patients. MATERIALS AND METHODS: We conducted a retrospective review of 148 patients who underwent unenhanced and contrast-enhanced helical CT within 72 hr after onset of symptoms of a first episode of acute pancreatitis. Patients were classified by CT grade and grouped into two categories (mild: grades A, B, C; and severe: grades D and E) that were correlated with complications and death. In the grades including patients with pancreatic necrosis, it was also correlated with complications and death. RESULTS: All complications (n = 15) and deaths (n = 4) occurred in patients with a CT grade of severe disease; differences as compared with mild grade were significant (p < 0.001 and p < 0.03, respectively). CT grade had a sensitivity and specificity of 100% and 61.6%, respectively, for predicting morbidity and 100% and 56.9% for predicting mortality. The 13 patients with necrosis were all in the severe group (p < 0.001). Necrosis detection on early CT had a sensitivity and specificity of 53.3% and 90.2%, respectively, for predicting morbidity and 75% and 83.8% for mortality. CONCLUSION: Early unenhanced CT alone was a good indicator of severity of acute pancreatitis in our selected population. CT grade was sensitive for predicting outcome in acute pancreatitis. Pancreatic necrosis, estimated on early, contrast-enhanced CT and seen only in patients having severe disease, was a specific predictor of morbidity and mortality. These findings lead us to suggest that the use of iodinated contrast material to assess necrosis can be reserved for only those patients classified as having severe disease on unenhanced CT.

Replacement lipomatosis related to renal tuberculosis: imaging findings in one case.

Replacement lipomatosis of the kidney in a case of long-standing renal tuberculosis is reported. The radiologic and pathologic findings are described and the differential diagnosis is discussed. A hypothesis is given to explain the association of renal tuberculosis and replacement lipomatosis of the kidney.