Enhanced external counter pulsation therapy in patients with symptomatic and severe intracranial steno-occlusive disease: a randomized clinical trial protocol.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03921827.

Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning.

PURPOSE: To conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning. METHODS: We acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images. At each count level, patches extracted from 23 pairs of SD/SLD PET images were used to train three IQT models - global linear, single tree, and random forest regressions with cubic patch sizes of 3 and 5 voxels. The models were then used to estimate SD images from LD images at each count level for 10 unseen subjects. Lesion-detection task was carried out on matched lesion-present and lesion-absent images. RESULTS: LD PET-CT protocol yielded lesion detectability with sensitivity of 0.98 and specificity of 1. Random forest algorithm with cubic patch size of 5 allowed further 11.7% reduction in the effective PETCT dose without compromising lesion detectability, but underestimated SUV by 30%. CONCLUSION: LD PET-CT protocol was validated for lesion detection using ALD PET scans. Substantial image quality improvement or additional dose reduction while preserving clinical values can be achieved using machine learning methods though SUV quantification may be biased and adjustment of our research protocol is required for clinical use.

Reversal of the reversed 'Robin Hood syndrome' after superficial temporal-Middle cerebral artery bypass for severe intracranial stenosis.

Background: Intracranial arterial stenosis is a common cause of ischemic stroke. Recent attempts with intracranial stenting and superficial temporal-middle cerebral artery (STA-MCA) bypass failed to show benefit. Perhaps, better strategies are needed for selecting suitable patients. Acetazolamide-challenged single photon emission computed tomography (SPECT) can demonstrate reversed Robin Hood syndrome (RRHS) due to intracranial steal phenomenon and identify high-risk patients.Methods: We describe the clinical and SPECT findings of RRHS.Results: In our patient with severe and symptomatic severe stenosis of the right MCA, STA-MCA bypass resulted in complete resolution of RRHS.Conclusion: STA-MCA bypass surgery should be considered a possible option in patients with severe stenosis of intracranial internal carotid artery or MCA in carefully selected patients.

Rationale and design of a randomized trial of early intensive blood pressure lowering on cerebral perfusion parameters in thrombolysed acute ischemic stroke patients.

BACKGROUND AND RATIONALE: Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow (CBF) and functional in AIS patients treated with intravenous thrombolysis. METHODS: In a randomized controlled trial, 54 thrombolysed AIS patients with a systolic BP of 160 to 180 mm Hg will be randomized to early intensive BP lowering (systolic target range 140-160 mm Hg) or guideline-based BP management (systolic range 160-180 mm Hg) during first 72-hours using primarily intravenous labetalol. We hypothesize that early intensive BP lowering will not reduce CBF by 20% and/or increase the volume of hypoperfused tissue by >20% on computed tomographic perfusion. Clinical outcome will be assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome vs scores 2-6 as dead or dependent) at 90 days. Other outcome would be symptomatic intracerebral hemorrhage. The trial is registered at ClinicalTrials.gov, NCT03443596. CONCLUSION: This randomized study will provide important information about the physiological effects of BP reduction on cerebral perfusion after intravenous thrombolysis in AIS.

Impact of Image Reconstruction Settings on Texture Features in 18F-FDG PET.

UNLABELLED: Evaluation of tumor heterogeneity based on texture parameters has recently attracted much interest in the PET imaging community. However, the impact of reconstruction settings on texture parameters is unclear, especially relating to time-of-flight and point-spread function modeling. Their effects on 55 texture features (TFs) and 6 features based on first-order statistics (FOS) were investigated. Standardized uptake value (SUV) measures were also evaluated as peak SUV (SUVpeak), maximum SUV, and mean SUV (SUVmean). METHODS: This study retrospectively recruited 20 patients with lesions in the lung who underwent whole-body (18)F-FDG PET/CT. The coefficient of variation (COV) of each feature across different reconstructions was calculated. RESULTS: SUVpeak, SUVmean, 18 TFs, and 1 FOS were the most robust (COV ≤ 5%) whereas skewness, cluster shade, and zone percentage were the least robust (COV > 20%) with respect to reconstruction algorithms using default settings. Heterogeneity parameters had different sensitivities to iteration number. Twenty-four parameters including SUVpeak and SUVmean exhibited variation with a COV less than 5%; 28 parameters, including maximum SUV, showed variation with a COV in the range of 5%-10%. In addition, skewness, cluster shade, and zone percentage were the most sensitive to iteration number. In terms of sensitivity to full width at half maximum (FWHM), 15 TFs and 1 FOS had the best performance with a COV less than 5%, whereas SUVpeak and SUVmean had a COV between 5% and 10%. Grid size had the largest impact on image features, which was demonstrated by only 11 features, including SUVpeak and SUVmean, having a COV less than 10%. CONCLUSION: Different image features have different sensitivities to reconstruction settings. Iteration number and FWHM of the gaussian filter have a similar impact on the image features. Grid size has a larger impact on the features than iteration number and FWHM. The features that exhibited large variations such as skewness in FOS, cluster shade, and zone percentage should be used with caution. The entropy in FOS, difference entropy, inverse difference normalized, inverse difference moment normalized, low gray-level run emphasis, high gray-level run emphasis, and low gray-level zone emphasis are the most robust features.

Improvement in cerebral hemodynamic parameters and outcomes after superficial temporal artery-middle cerebral artery bypass in patients with severe stenoocclusive disease of the intracranial internal carotid or middle cerebral arteries.

OBJECT: Both the older and the recent extracranial-intracranial (EC-IC) bypass trials for symptomatic carotid occlusion failed to demonstrate a reduction in stroke recurrence. However, the role of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in patients with symptomatic intracranial stenoocclusive disease has been rarely evaluated. The authors evaluated serial changes in various cerebral hemodynamic parameters in patients with severe stenoocclusive disease of the intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) and impaired cerebral vasodilatory reserve (CVR), treated by STA-MCA bypass surgery or medical treatment. METHODS: Patients with severe stenoocclusive disease of the intracranial ICA or MCA underwent transcranial Doppler (TCD) ultrasonography and CVR assessment using the breath-holding index (BHI). Patients with impaired BHI (< 0.69) were further evaluated with acetazolamide-challenge technitium-99m hexamethylpropyleneamine oxime ((99m)Tc HMPAO) SPECT. STA-MCA bypass surgery was offered to patients with impaired CVR on SPECT. All patients underwent TCD and SPECT at 4 ± 1 months and were followed up for cerebral ischemic events. RESULTS: A total of 112 patients were included. This total included 73 men, and the mean age of the entire study population was 56 years (range 23-78 years). (99m)Tc HMPAO SPECT demonstrated impaired CVR in 77 patients (69%). Of these 77 patients, 46 underwent STA-MCA bypass while 31 received best medical treatment. TCD and acetazolamide-challenge (99m)Tc HMPAO SPECT repeated at 4 ± 1 months showed significant improvement in the STA-MCA bypass group. During a mean follow-up of 34 months (range 18-39 months), only 6 (13%) of 46 patients in the bypass group developed cerebral ischemic events, as compared with 14 (45%) of 31 patients receiving medical therapy (absolute risk reduction 32%, p = 0.008). CONCLUSIONS: STA-MCA bypass surgery in carefully selected patients with symptomatic severe intracranial stenoocclusive disease of the intracranial ICA or MCA results in significant improvement in hemodynamic parameters and reduction in stroke recurrence.

Plaque Inflammation Imaging in Severe Carotid Stenosis and Recurrent Cerebral Ischemia.

A strong relationship exists between the severity of carotid stenosis and early stroke risk. Inflammation is believed to be an important event for atherosclerotic plaque destabilization and subsequent thromboembolism. (18)F-FDG can image atherosclerotic inflammation, providing information about plaque biology, which may serve as a useful biomarker for the assessment of early stroke risk.

Changes in cerebral hemodynamic and cognitive parameters after external carotid-internal carotid bypass surgery in patients with severe steno-occlusive disease: a pilot study.

BACKGROUND: The direct impact of external carotid-internal carotid (EC-IC) bypass surgery on cognition of patients with severe steno-occlusive disease of internal carotid (ICA) or middle cerebral artery (MCA) is unknown. In this pilot study, we evaluated changes in cerebral hemodynamic and cognition in these patients. METHODS: Patients with severe steno-occlusive disease and impaired cerebral vasodilatory reserve (CVR) with transcranial Doppler (TCD) breath holding index (BHI) and acetazolamide-challenged HMPAO-Single Photon Emission Tomographic (SPECT) imaging were offered EC-IC bypass surgery. CVR and cognitive performance using a formal neuropsychological battery were evaluated before and 3-6 months after surgery. RESULTS: Nine patients and 9 matched controls were recruited. Significant CVR improvement from TCD-BHI [median 0 (Inter-quartile range IQR 0.45) to 1.10 (IQR 0.73), p<0.001] and SPECT (p<0.001) was observed in surgery patients. EC-IC bypass patients had significant improvement in verbal memory (p=0.037) and executive function (p=0.043) and a trend of improvement in visual memory (p=0.052) compared to controls. CONCLUSION: EC-IC bypass surgery in carefully selected patients could improve cerebral hemodynamics and verbal memory and executive function.

Persistence of hyperdense middle cerebral artery sign on follow-up CT scan after intravenous thrombolysis is associated with poor outcome.

BACKGROUND: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months. METHODS: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0-1) and poor (mRS score 2-6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows. RESULTS: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19-92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4-32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151-1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666-0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991-11.333, p = 0.039) were associated with poor outcome at 3 months. CONCLUSION: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome.

Chronic brainstem ischemia in subclavian steal syndrome.

Subclavian steal syndrome is usually an incidental finding and rarely causes vertebrobasilar ischemia. We present a 58-year-old man who, over six months, experienced progressive slowing in both talking and walking. Cervical duplex sonography revealed severe stenosis of the right subclavian artery; fixed retrograde flow was noted in the right vertebral artery on transcranial Doppler. The hyperemia-ischemia cuff test resulted in considerable reduction in flow velocities in both posterior cerebral arteries. We attributed his slowness to chronic vertebrobasilar ischemia and surgical revascularization was performed. His symptoms subsided immediately after surgery. The improved perfusion in the posterior circulation was demonstrated on technetium-99 hexamethylpropyleneamine oxime single photon-emission CT. Early diagnosis and prompt treatment resulted in an improved quality of life.

Role of Multimodal Evaluation of Cerebral Hemodynamics in Selecting Patients with Symptomatic Carotid or Middle Cerebral Artery Steno-occlusive Disease for Revascularization.

BACKGROUND: The circle of Willis provides collateral pathways to perfuse the affected vascular territories in patients with severe stenoocclusive disease of major arteries. The collateral perfusion may become insufficient in certain physiological circumstances due to failed vasodilatory reserve and intracranial steal phenomenon, so-called 'Reversed-Robinhood syndrome'. We evaluated cerebral hemodynamics and vasodilatory reserve in patients with symptomatic distal internal carotid (ICA) or middle cerebral artery (MCA) severe steno-occlusive disease. METHODS: Diagnostic transcranial Doppler (TCD) and TCD-monitoring with voluntary breath-holding according to a standard scanning protocol were performed in patients with severe ICA or MCA steno-occlusive disease. The steal phenomenon was detected as transient, spontaneous, or vasodilatory stimuli-induced velocity reductions in affected arteries at the time of velocity increase in normal vessels. Patients with exhausted vasomotor reactivity and intracranial steal phenomenon during breath-holding were further evaluated by (99)technetium(m)-hexamethyl propylene amine oxime single photon emission computed tomography (HMPAO-SPECT) with acetazolamide challenge. RESULTS: Sixteen patients (age 27-74 years, 11 men) fulfilled our TCD criteria for exhausted vasomotor reactivity and intracranial steal phenomenon during the standard vasomotor testing by breath holding. Acetazolamide-challenged HMPAO-SPECT demonstrated significant hypoperfusion in 12 patients in affected arterial territories, suggestive of failed vasodilatory reserve. A breath-holding index of ≤0.3 on TCD was associated with an abnormal HMPAO-SPECT with acetazolamide challenge. TCD findings of a breath holding index of ≤0.3 and intracranial steal during the procedure were determinants of a significant abnormality on HMPAO-SPECT with acetazolamide challenge. CONCLUSION: Multimodal evaluation of cerebral hemodynamics in symptomatic patients with severe steno-occlusive disease of the ICA or MCA is helpful in the identification and quantification of failed vasodilatory reserve. This approach may be useful in selecting patients for possible revascularization procedures.

Epidermoid cyst of anterior fontanelle with clear contents.

BACKGROUND: Epidermal inclusion cysts very rarely occur in the midline in the area of the anterior fontanelle. CASE DESCRIPTION: We report the second case of epidermal inclusion cysts in the midline in the area of the anterior fontanelle in world literature of a 7-month female infant who presented with a slow-growing soft mass located in the midline over the vertex of the head. CONCLUSION: These lesions with clear contents can have all the features of encephalocele on clinical examination, and imaging will show the exact location, but histopathology will confirm the diagnosis.

Application of a plain abdominal radiograph transition zone (PARTZ) in Hirschsprung's disease.

BACKGROUND: A standard contrast enema for Hirschsprung's disease can sometimes be inconclusive in delineating a transition zone especially in neonates and infants. The aim of this study was to determine the utility and diagnostic accuracy of a plain abdominal radiograph transition zone (PARTZ) in predicting the level of aganglionosis. METHODS: A prospective observational study of neonates and infants with biopsy proven Hirschsprung's disease was carried out from March 2004 through March 2006. All patients underwent a plain abdominal radiograph and a contrast enema followed by a rectal biopsy. The transition zone on a plain radiograph (PARTZ) and contrast enema (CETZ) were compared with operative and pathology reports. Results were analyzed by chi square test and expressed as their p values and 95% confidence intervals. RESULTS: PARTZ and CETZ suggestive of Hirschsprung's disease was seen in 24(89%) and 18(67%) patients respectively. The PARTZ and CETZ matched with the pathologic level of transition zone in 22(92%) and 13(72%) patients, p = 0.001, 95% CI (-1.87 to -0.79). In the 9 (33%) patients in whom contrast enema failed to reveal a transition zone, PARTZ was seen in 6/9(66%) patients and correlated with the pathological level of aganglionosis in 4/6(67%) patients, p = 0.001 95% CI (-1.87 to -0.79). The overall accuracy of PARTZ and CETZ was 96% and 84% respectively, p = 0.008, 95% CI (-6.09 to -3.6). CONCLUSION: A plain abdominal radiographic transition zone is reliable in predicting the level of transition zone in cases of inconclusive contrast enema. It may be particularly helpful developing countries where laparoscopic techniques are not available to accurately identify the transition zone.

Incidence of megaloblastic anaemia and its correction in leishmaniasis--a prospective study at BPKIHS hospital, Nepal.

Fifty (50) cases of Leishmaniasis were included in a prospective study after making the diagnosis based on the demonstration of L D Bodies on bone marrow aspirate. Hemoglobin (Hb) and total leucocyte count (TLC) were less than 10 gm/dl and 4000 per/ml respectively in 22 out of 50 cases. Among 50 cases, 30 showed macrocytic red cell and hypersegmented neutrophils on peripheral blood smear as features of megaloblastic anemia. Out of 30 cases of leishmaniasis with megaloblastic anemia, 10 cases showed decreased reticulocyte count. Bone marrow aspiration cytology showed megaloblastic maturation in erythroid series and giant metamyelocytes in myeloid series in all 30 cases of leishmaniasis with megaloblastic changes. Bone marrow iron was also increased in these cases. However megakaryocyte was normal in all. Among 30 cases of leishmaniasis with megaloblastic changes, 15 cases were treated with sodium antimony gluconate (SAG) only and other 15 with SAG, folic acid and Vit. B12. Rest 20 cases of leishmaniasis without megaloblastic changes were also treated with SAG only. After treatment with SAG alone as well as with SAG, folic acid and vit. B12, hemoglobin and TLC improved in all 50 cases. Of 15 cases of leishmaniasis with megaloblastic changes, who were treated with SAG, folic acid and vit. B12, the reticulocyte count reached at peak on the 7th day and normalized at the end of 4th week. Red blood cells (RBC) also became normocytic normochromic and neutrophils became normal on peripheral blood smear. But no change was observed in reticulocyte count, RBC and white blood cell (WBC) morphology on peripheral blood smear in cases of leishmaniasis without megaloblastic changes and other 15 cases of leishmaniasis with megaloblastic changes, who received SAG only.

Tuberculous splenic abscess--a case report and review of literature.

Splenic abscess due to tuberculosis is a rare condition and is mostly diagnosed in immuno-compromised hosts. A case of tuberculous splenic abscess detected incidentally after splenectomy without any underlying disease is reported in an immuno-competent patient.