Early isolated subarachnoid hemorrhage versus hemorrhagic infarction in cerebral venous thrombosis.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare cerebral vascular disease, the presentation of which is highly variable clinically and radiologically. A recent study demonstrated that isolated subarachnoid hemorrhage (iSAH) in CVT is not as rare as thought previously and may have a good prognostic significance. Hemorrhagic venous infarction, however, is an indicator of an unfavorable outcome. We therefore hypothesized that patients who initially suffered iSAH would have a better clinical outcome than those who suffered hemorrhagic cerebral infarction. PATIENTS AND METHODS: We selected patients hospitalized due to CVT, who presented either with isolated SAH or cerebral hemorrhagic infarction at admission or during the following 24 hours: 23 (10 men) aged 22-73 years. The data were extracted from hospital admission records, our computer data system, and the hospital radiological database. RESULTS: The iSAH group consisted of 8 (6 men) aged 49.3 ± 16.2 and the hemorrhagic infarction group included 15 (4 men) aged 47.9 ± 16.8. Despite having a significantly greater number of thrombosed venous sinuses/deep veins (Mann-Whitney Rank Sum Test, p = 0.002), the isolated SAH group had a significantly better outcome on its modified Rankin Score (mRs) than the hemorrhagic infarction group (Mann-Whitney Rank Sum Test, p = 0.026). Additional variables of significant impact were edema formation (p = 0.004) and sulcal obliteration (p = 0.014). CONCLUSIONS: The patients who suffer iSAH initially had a significantly better outcome prognosis than the hemorrhagic infarction patients, despite the greater number of thrombosed sinuses/veins in the iSAH group. A possible explanation might include patent superficial cerebral communicating veins.

Invasive sinus aspergillosis with mycotic aneurysm of the vertebral artery and subarachnoid hemorrhage - Case report.

Invasive sinus aspergillosis is a rare life-threatening condition usually found in immunocompromised patients. The fungus spreads from paranasal sinuses into the central nervous system by direct extension or through blood vessels. Perineural spread is an uncommon mechanism of spread in invasive aspergillosis. A mycotic aneurysm is a dangerous complication of invasive sinus aspergillosis because of its insidious development and is often diagnosed only post-mortem after causing fatal intracranial hemorrhage. Intracranial vascular complications of invasive sinus aspergillosis require prompt recognition and treatment and should always be considered when a diagnosis of CNS aspergillosis is made. We present a case of invasive sinus aspergillosis in an apparently immunocompetent patient that manifested with a brain abscess, perineural spread of the infection, and mycotic aneurysm of the vertebral artery with subsequent rupture and fatal subarachnoid hemorrhage. This case highlights the possibility of perineural spread and hemorrhagic complications in invasive cerebral aspergillosis.

Revascularization outcomes following acute ischemic stroke in patients taking direct oral anticoagulants: a single hospital cohort study.

Successful revascularization therapy is of paramount importance in patients suffering acute ischemic stroke (AIS). However, there is currently only limited evidence on revascularization outcomes for patients suffering AIS while treated with direct oral anticoagulants (DOACs). The aim of our study was to determine the efficacy and safety of intravenous thrombolysis (IVT) and mechanical reperfusion (MeR) in AIS patients taking DOACs, and compare them to randomized clinical trials (RCTs), which included patients without DOAC treatment. In an observational cohort study, we analyzed clinical and radiological outcomes following AIS for all consecutive patients on DOAC therapy treated by IVT or MeR, between 2013 and 2019, at the University Medical Center Ljubljana. Patients in the IVT group were on dabigatran treatment and have received idarucizumab as a reversal agent prior to IVT. Patients in the MeR group had a large vessel occlusion. The primary outcome of the study was efficiency, defined as significant improvement after recanalization (National Institutes of Health Stroke Scale (NIHSS) score improvement of ≥8 points after 24 h and modified Rankin Scale (mRS) ≤2 after 3 months) and safety, defined as occurrence of symptomatic intracerebral hemorrhage (SICH) and mortality. Fifty-one DOAC-treated patients with AIS were included. Nineteen dabigatran-treated patients received IVT after reversal by idarucizumab. Thirty-two patients with a large vessel occlusion (12 on dabigatran, 12 on rivaroxaban, and 8 on apixaban) received MeR. Median NIHSS at admission was 9 in the IVT group and 17 in the MeR group. A significant clinical improvement, 24 h after revascularization (median improvement of NIHSS ≥8), occurred in 84% of patients treated with IVT and 25% of patients treated with MeR. A favorable functional outcome after 3 months (modified Rankin Scale (mRS) ≤2) occurred in 84 % of patients treated with IVT and 44% of patients treated with MeR. SICH occurred in one patient (5%) in the IVT group, and in two patients (6%) in the MeR group. In summary, in our observational study of DOAC-treated AIS patients, the level of IVT efficiency was substantially better than in the RCTs. At the same time, the results of MeR treatment were on the same level as in non-DOAC AIS patients included in the RCTs. The observed safety of IVT and MeR treatment was similar to the RCTs. We propose that thrombi in patients on dabigatran may have increased susceptibility to IVT, thereby allowing for better clinical results.

Infarct-core CT perfusion parameters in predicting post-thrombolysis hemorrhagic transformation of acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis (IVT) is the method of choice in reperfusion treatment of patients with signs and symptoms of acute ischemic stroke (AIS) lasting less than 4.5 hours. Hemorrhagic transformation (HT) of acute ischemic stroke is a serious complication of IVT and occurs in 4.5-68.0% of clinical cases. The aim of our study was to determine the infarct core CT perfusion parameter (CTPP) most predictive of HT. PATIENTS AND METHODS: Seventy-five patients with AIS who had undergone CT perfusion (CTP) imaging and were treated with IVT were enrolled in this retrospective study. Patients with and without HT after IVT were defined as cases and controls, respectively. Controls were found by matching for time from AIS symptom onset to IVT ± 0.5 h. The following CTPPs were measured: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), relative CBF (rCBF) and relative CBV (rCBV). Receiver operating characteristic analysis curves of significant CTPPs determined cut-off values that best predict HT. RESULTS: There was a significant difference between cases and controls for CBF (p = 0.004), CBV (p = 0.009), rCBF (p < 0.001) and rCBV (p = 0.001). Receiver operating characteristic analysis revealed that rCBF < 4.5% of the contralateral mean (area under the curve = 0.736) allowed prediction of HT with a sensitivity of 71.0% and specificity of 52.5%. CONCLUSIONS: CTP imaging has a considerable role in HT prediction, assisting in selection of patients that are likely to benefit from IVT. rCBF proved to have the highest HT predictive value.

Dynamic Susceptibility Contrast Enhanced (DSC) MRI Perfusion and Plasma Cytokine Levels in Patients after Tonic-clonic Seizures.

BACKGROUND: Inflammatory events in brain parenchyma and glial tissue are involved in epileptogenesis. Blood concentration of cytokines is shown to be elevated after tonic-clonic seizures. As a result of inflammation, blood-brain barrier leakage occurs. This can be documented by imaging techniques, such is dynamic susceptibility contrast enhanced (DSC) MRI perfusion. Our aim was to check for postictal brain inflammation by studying DSC MRI perfusion and plasma level of cytokines. We looked for correlations between number and type of introducing seizures, postictal plasma level of cytokines and parameters of DSC MRI perfusion. Furthermore, we looked for correlation of those parameters and course of the disease over one year follow up. PATIENTS AND METHODS: We prospectively enrolled 30 patients, 8-24 hours after single or repeated tonic-clonic seizures. RESULTS: 25 of them had normal perfusion parameters, while 5 had hyperperfusion. Patients with hyperperfusion were tested again, 3 months later. Two of 5 had hyperperfusion also on control measurements. Number of index seizures negatively correlated with concentration of proinflammatory cytokines IL-10, IFN-ϒ and TNF-α in a whole cohort. In patients with hyperperfusion, there were significantly lower concentrations of antiinflammatory cytokine IL-4 and higher concentrations of proinflammatory TNF-a. CONCLUSIONS: Long lasting blood- brain barrier disruption may be crucial for epileptogenesis in selected patients.

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

INTRODUCTION: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear. METHODS: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics. After the traditional diagnostic workup, diagnostic confidence of AD pathology (DCAD) was estimated by the physicians in charge. The latter were provided with the results of automated hippocampal volumetry in standardized format and DCAD was reassessed. RESULTS: An increment of one interquartile range in hippocampal volume was associated with a mean change of DCAD of -8.0% (95% credible interval: [-11.5, -5.0]). Automated hippocampal volumetry showed a statistically significant impact on DCAD beyond the contributions of neuropsychology, 18F-fluorodeoxyglucose positron emission tomography/single-photon emission computed tomography, and cerebrospinal fluid markers (-8.5, CrI: [-11.5, -5.6]; -14.1, CrI: [-19.3, -8.8]; -10.6, CrI: [-14.6, -6.1], respectively). DISCUSSION: There is a measurable effect of hippocampal volume on DCAD even when used on top of the traditional diagnostic workup.

Non-contrast computed tomography in the diagnosis of cerebral venous sinus thrombosis.

BACKGROUND: The aim of the study was to investigate the sensitivity and specificity of non-contrast computed tomography (NCCT) in the diagnosis of cerebral venous sinus thrombosis (CVST). Methods. Screening our neurological department database, we identified 53 patients who were admitted to neurological emergency department with clinical signs of CVST. Two independent observers assessed the NCCT scans for the presence of CVST. CT venography and/or MR venography were used as a reference standard. Interobserver agreement between the two readers was assessed using Kappa statistic. Attenuation inside the cerebral venous sinuses was measured and compared between the patient and the control group. RESULTS: CVST was confirmed in 13 patients. Sensitivity and specificity of NCCT for overall presence of CVST were 100% and 83%, respectively, with Kappa value of 0.72 (a good agreement between observers). The attenuation values between CVST patients and control group were significantly different (73.4 ± 14.12 HU vs. 58.1 ± 7.58 HU; p = 0.000). The ROC analysis showed an area under the curve (AUC) of 0.916 (95% CI, 0.827 - 1.00) and an optimal cutoff value of 64 HU, leading to a sensitivity of 85% and specificity of 87%. CONCLUSIONS: NCCT as a first-line investigation has a high value for diagnosis of CVST in the emergency setting. The additional measurement of the sinus attenuation may improve the diagnostic value of the examination.

The presence of cerebral and/or systemic endothelial dysfunction in patients with leukoaraiosis--a case control pilot study.

BACKGROUND: In spite of high prevalence and clinical relevance of leukoaraiosis (LA), its pathophysiology is still incompletely understood. Theories of ischaemic genesis and a leaky blood-brain barrier are contradictory yet could share a common denominator-endothelial dysfunction (cerebral, systemic or both), which has not been studied thoroughly in LA. METHODS: Thirty patients with LA (58 years (SD 7)) and 30 gender- and age-matched controls without LA (55 years (SD 6)) were recruited. The vascular risk factors (VRF) were identical in both groups. Cerebral endothelial function was determined by cerebrovascular reactivity to L-arginine (CVR). Systemic endothelial function was determined by flow-mediated dilatation (FMD) of the brachial artery after hyperaemia. All participants underwent a brain MRI to search for radiological signs of LA that was classified according to the Fazekas score. Linear regression was used to explore the correlation between CVR and FMD in patients with LA. A 95 % confidence interval was used. For any statistical test used in the study, p ≤ 0.050 was regarded as statistically significant. RESULTS: We found a marked and significant decrease in both CVR (9.6 % (SD 3.2) vs. 15.8 % (SD 6.1), p < 0.001) and FMD (4.8 % (SD 3.1) vs. 7.4 % (SD 3.8), p = 0.004) in LA patients compared to controls. Both CVR (7.4 % (SD 3.1) vs. 12.2 % (SD 2.6), p = 0.001) and FMD (3.0 % (SD 2.2) vs. 6.4 % (SD 3.1), p = 0.011) were significantly decreased in LA subgroup Fazekas 3 compared to subgroup Fazekas 1. CVR and FMD significantly positively correlated (b = 0.192, 95 % CI = 0.031-0.354, p = 0.02). CONCLUSIONS: The results of our pilot study suggest that patients with LA have a significant impairment of both cerebral and systemic endothelial function that is larger than could be expected based on present VRF. Endothelial dysfunction increases in parallel with LA severity and correlates between cerebral and systemic arterial territory. Overall, our results suggest a so far unknown "intrinsic" generalised endothelial dysfunction in patients with LA that could be involved in LA pathophysiology. This interesting issue needs to be confirmed in larger samples since it could help better understand the mechanisms underlying LA.

Blood-brain barrier permeability imaging using perfusion computed tomography.

BACKGROUND: The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases. CONCLUSIONS: Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging.

Artery of Percheron infarction: review of literature with a case report.

BACKGROUND: Clinical features indicating an ischemic infarction in the territory of posterior cerebral circulation require a comprehensive radiologic examination, which is best achieved by a multi-modality imaging approach (computed tomography [CT], CT-perfusion, computed tomography angiography [CTA], magnetic resonance imaging [MRI] and diffusion weighted imaging [DWI]). The diagnosis of an acute ischemic infarction, where the damage of brain tissue may still be reversible, enables selection of appropriate treatment and contributes to a more favourable outcome. For these reasons it is essential to recognize common neurovascular variants in the territory of the posterior cerebral circulation, one of which is the artery of Percheron. CASE REPORT: A 69 year-old woman, last seen awake 10 hours earlier, presented with two typical clinical features of the artery of Percheron infarction, which were vertical gaze palsy and coma. Brain CT and CTA of neck and intracranial arteries upon arrival were interpreted as normal. A new brain CT scan performed 24 hours later revealed hypodensity in the medial parts of thalami. Other imaging modalities were not performed, due to the presumption that the window for the application of effective therapy was over. The diagnosis of an artery of Percheron infarction was therefore made retrospectively with the re-examination of the CTA of neck and intracranial arteries. CONCLUSIONS: A multi-modality imaging approach is necessary in every patient with suspicion of the posterior circulation infarction immediately after the onset of symptoms, especially in cases where primary imaging modalities are unremarkable and clinical features are severe, where follow-up examinations are indicated.

Analysis of risk factors for perifocal oedema after endovascular embolization of unruptured intracranial arterial aneurysms.

BACKGROUND: Endovascular embolization is a treatment of choice for the management of unruptured intracranial aneurysms, but sometimes is complicated with perianeurysmal oedema. The aim of our study was to establish incidence and outcomes of perianeurysmal oedema after endovascular coiling of unruptured intracranial aneurysms, and to reveal possible risk factors for development of this potentially serious complication. METHODS: In total 119 adult patients with endovascular embolization of unruptured intracranial aneurysm (performed at Department for Interventional Neuroradiology, Clinical Center, Kragujevac, Serbia) were included in our study. The embolizations were made by electrolite-detachable platinum coils: pure platinum, hydrophilic and combination of platinum and hydrophilic coils. Primary outcome variable was perianeurysmal oedema visualized by magnetic resonance imaging (MRI) 7, 30 and 90 days after the embolization. RESULTS: The perianurysmal oedema appeared in 47.6% of patients treated with hydrophilic coils, in 21.6% of patients treated with platinum coils, and in 53.8% of those treated with mixed type of the coils. The multivariate logistic regression showed that variables associated with occurrence of perianeurysmal oedema are volume of the aneurysm, hypertension, diabetes and smoking habit. Hypertension is the most important independent predictor of the perianeurysmal oedema, followed by smoking and diabetes. CONCLUSIONS: The results of our study suggest that older patients with larger unruptured intracranial aneurysms, who suffer from diabetes mellitus and hypertension, and have the smoking habit, are under much higher risk of having perianeurysmal oedema after endovascular coiling.

Pretreatment perfusion CT and CT volumetry in squamous cell carcinoma of the head and neck region.

PURPOSE: Perfusion computed tomography imaging (PCT) is a robust, reproducible, widely accessible non-invasive method. The objective of our study was to assess whether prospectively collected pretreatment PCT parameters and volumetric measurements of locoregionally advanced squamous cell carcinoma (SCCA) of the oral cavity, oropharynx and hypopharynx could predict the response to concomitant chemoradiotherapy with cisplatin Methods: Pretreatment contrast enhanced PCT was performed in 30 patients. Radiologic response criteria (RECIST) were used to evaluate tumor response. The correlation and predictive value of baseline PCT parameters and tumor volume were examined by using the Student's t-test, Pearson's correlation coefficient and receiver operating characteristic (ROC) curves. RESULTS: Baseline tumor volume, blood volume (BV) and blood flow (BF) were significantly higher in responders than in non-responders. Permeability surface (PS) did not show any significant difference between the two groups. Pretreatment tumor volume correlated with baseline BV (r=-0.4; p=0.01). Pretreatment tumor volume had 100% sensitivity and specificity (p=0.0001) and BV and BF also showed satisfactory sensitivity and specificity (100% and 65%, p=0.0002; 78% and 80.2%, p=0.01, respectively) for prediction of tumor response to concomitant chemoradiotherapy with cisplatin. CONCLUSION: Baseline BV, BF and tumor volume values were significantly different between responders and non-responders and could predict response to concomitant chemoradiotherapy with cisplatin in locoregionally advanced SCCA.

Role of perfusion computed tomography in assessing submandibular gland radiochemotherapy-induced injury.

OBJECTIVE: We aimed to detect changes in the volume and perfusion parameters of the submandibular glands during and after radiochemotherapy. STUDY DESIGN: Twelve patients underwent computed tomography (CT) and perfusion CT before radiochemotherapy, after 40 Gy, after 70 Gy, and 3 months after radiochemotherapy. Submandibular gland volume, blood volume, permeability surface area product, and blood flow were quantified. RESULTS: Submandibular gland volumes during and after therapy were significantly lower compared with the baseline value (P < .001). Blood volume, blood flow, and permeability surface area product values showed statistically significant reduction during and 3 months after therapy. A significant linear correlation was found between changes in submandibular gland volume and of the perfusion parameter blood volume in the period between baseline and 3 months after therapy (P = .012; RP = -0.697). CONCLUSIONS: Changes in submandibular gland volume and dynamics of perfusion parameters imply that radiation-induced injury of submandibular glands develops early during radiochemotherapy.

Imaging findings in bisphosphonate-induced osteonecrosis of the jaws.

BACKGROUND: Bisphosphonates are drugs used in the treatment of lytic bone metastases, multiple myeloma, hypercalcemia of malignant origin, osteoporosis, and diseases such as Paget's disease. Recently osteonecrosis of the jaw has been associated with the use of bisphosphonates. This study describes the imaging findings of bisphosphonate-associated osteonecrosis of the jaws. PATIENTS AND METHODS: Eleven patients, receiving bisphosphonate medication for approximately 28 months, with pain on affected side, nonhealing extraction sockets, purulent discharge and swelling in soft tissue were examined. Imaging consisted of non-contrast enhanced CT and contrast enhanced MRI. All patients underwent surgery of affected bone and histology confirmed osteonecrosis. RESULTS: CT scan showed osteolytic and sclerotic lesions with cortical bone destruction in all patients. The osteonecrosis was identified as delimited focal lesions with reduction of the signal on T1- weighted imaging and T2- weighted imaging. All the patients had soft-tissue involvement with enhancement in orbicular, buccinator muscle of the mouth or masticator space and adenopathy in submandibular and jugular digastric chain. CONCLUSIONS: Bisphosphonate related osteonecrosis of the jaw presents a variety of imaging findings that help to determine the extent of the disease and track the progression, however they are not specific for this disease.

Radiosensitivity of squamous cell carcinoma metastases to the neck assessed by immunocytochemical profiling of fine-needle aspiration biopsy cell specimens: a pilot study.

PURPOSE: To assess radiosensitivity of neck metastases of squamous cell carcinoma of the head and neck (SCCHN) by immunocytochemical profiling of fine-needle aspiration biopsy (FNAB) cell specimens. PATIENTS AND METHODS: Immunocytochemical reactions to p53, cyclin D1, stefin A and Ki-67 were determined in FNAB cell samples of neck metastases from 21 patients treated with concomitant chemoradiotherapy and correlated to clinical characteristics and response to therapy. RESULTS: Six (28.6%), eight (38.1%), 15 (71.4%) and nine (42.9%) FNAB cell samples were classified as p53, cyclin D1, stefin A and Ki-67 positive, respectively. Statistically significant predictors of favorable nodal response to chemoradiation were p53 (P=0.025) and cyclin D1 (cytoplasmic fraction, P=0.048) negativity and Ki-67 positivity (P=0.045). Regional recurrence correlated with low Ki-67 immunoreactivity. A favorable profile of cyclin D1 and Ki-67 (one or both of the two) further improved the predictive strength of these markers. CONCLUSIONS: FNAB is a non-invasive, simple and cheap procedure, which could serve simultaneously for diagnostic purposes and for radiosensitivity testing. Immunocytochemical determination of cyclin D1 and Ki-67 in FNAB cell samples from neck metastases of SCCHN seems to be a valuable marker for predicting regional response to radiotherapy and might assist when deciding on appropriate primary therapy.