Hagen Kunte

Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas.

Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1‐regulated NCCa‐ATP channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT.

Morphometric and volumetric MRI changes in idiopathic intracranial hypertension

Objective We aimed at validating established imaging features of idiopathic intracranial hypertension (IIH) by using state-of-the-art MR imaging together with advanced post-processing techniques and correlated imaging findings to clinical scores. Methods Twenty-five IIH patients as well as age-, sex- and body mass index (BMI)-matched controls underwent high-resolution T1w and T2w MR imaging in a 1.5 T scanner, followed by assessment of optic nerve sheaths, pituitary gland, ventricles and Meckels cave. Imaging findings were correlated with cerebrospinal fluid (CSF) opening pressures and clinical symptom scores of visual disturbances (visual field defects or enlarged blind spot), headache, tinnitus (pulsatile and non-pulsatile) and vertigo. CSF as well as ventricle volumes were determined by using an automated MRI volumetry algorithm. Results So-called ‘empty sella’ and optic nerve sheath distension were identified as reliable imaging signs in IIH. Posterior globe flattening turned out as a highly specific but not very sensitive sign. No abnormalities of the lateral ventricles were observed. These morphometric results could be confirmed using MR volumetry (VBM). Clinical symptoms did not correlate with an increase in lumbar opening pressure. Conclusions Our study results indicate that lateral ventricle size is not affected in IIH. In contrast, abnormalities of the pituitary gland and optic nerve sheath were reliable diagnostic signs for IIH.

Markers of instability in high-risk carotid plaques are reduced by statins.

BACKGROUND Macrophage infiltration and expression of matrix metalloproteinase-9 (MMP-9) are markers of high-risk atherosclerotic carotid plaques and strong indicators of plaque instability. Use of statins is associated with a decreased risk of stroke and reportedly improves stability of atherosclerotic plaques, but available data addressing the mechanism of this effect are conflicting. METHODS We retrospectively analyzed data from 94 consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy. Excised plaques underwent systematic quantitative immunohistochemical analysis to determine the percentage of macrophage area and the percentage of MMP-9 area. Associations between percentage of macrophage area and percentage of MMP-9 area and use of statins and cerebrovascular disease were examined by univariate and multivariate analysis. RESULTS We found significantly higher values of percentage of macrophage area and of MMP-9 area in recently symptomatic (n = 26) compared with asymptomatic (n = 68) internal carotid artery stenoses: median (IQR) percentage of macrophage area was 2.29 (1.53-4.129) vs 0.53 (0.27-0.96) and percentage of MMP-9 area was 0.61 (0.36-0.89) vs 0.08 (0.02-0.27; both P < .0005). Patients treated with statins (n = 49) showed lower percentage values of macrophage area and MMP-9 area than untreated patients: the percentage of macrophage area was 0.54 (0.31-1.18) vs 1.03 (0.57-2.08; P = .01) and percentage of MMP-9 area was 0.06 (0.02-0.22) vs 0.36 (0.16-0.62; P < .0005). These associations between statin treatment and percentages of macrophage area and MMP-9 area did not change after controlling for symptomatic cerebrovascular disease and the effects of other potential confounders in multivariable analysis. CONCLUSIONS Our results confirm the value of percentage of macrophage area and percentage of MMP-9 area as markers of plaque instability and provide further evidence to support the hypothesis that statins reduce inflammatory responses and thereby stabilize carotid atherosclerotic plaques.

Optic nerve head quantification in idiopathic intracranial hypertension by spectral domain OCT.

Objective To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumbar punctures and could therefore ease monitoring of treatment or disease progression.

Olfactory dysfunction in patients with idiopathic intracranial hypertension

Objective: Although accumulating evidence suggests that a malfunction of the CSF system in idiopathic intracranial hypertension (IIH) may give rise to olfactory dysfunction, little objective knowledge is available at present about the olfactory capacity of patients with this condition. Methods: Seventeen patients with IIH and 17 age- and sex-matched controls were included. The extended Sniffin’ Sticks procedure was used to test odor threshold, discrimination, and identification (TDI). Results: Median (interquartile range) values of the composite TDI score (29 [26.5–35.5] vs 35 [34–37], p = 0.003) were reduced in patients with IIH. Furthermore, Spearman correlation revealed reduced TDI values in patients with a recent clinical deterioration of IIH (r = 0.66, p = 0.004). Conclusions: Our pilot study provides new evidence that olfaction is impaired in patients with IIH, especially in those who have been newly diagnosed or who have experienced a recent clinical deterioration.

Structural Olfactory Nerve Changes in Patients Suffering from Idiopathic Intracranial Hypertension

Background Complications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure (ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the other side, there is growing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbed in cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested in the past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changes of the olfactory nerve system can be detected in patients with IIH. Methodology/Principal Findings Twenty-three patients with IIH and 23 matched controls were included. Olfactory bulb volume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values of total OBV (128.7±38.4 vs. 130.0±32.6 mm3, p=0.90) and mean OS depth (8.5±1.2 vs. 8.6±1.1 mm, p=0.91) were similar in both groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r=0.53, p<0.01). In untreated symptomatic patients (n=7), the effect was greater (r=0.76, p<0.05). Patients who suffered from IIH for less than one year (n=8), total OBV was significantly smaller than in matched controls (116.6±24.3 vs. 149.3±22.2 mm3, p=0.01). IIH patients with visual disturbances (n=21) revealed a lower OS depth than patients without (8.3±0.9 vs. 10.8±1.0 mm, p<0.01). Conclusions/Significance The results suggest that morphological changes of the olfactory nerve system could be present in IIH patients at an early stage of disease.

Differences in carotid plaque content of macrophages, T cells and MMP-9 between patients with embolic and hemodynamic cerebral ischemia due to symptomatic carotid stenosis

BACKGROUND Cerebral ischemia in patients with carotid artery atherosclerosis is most often caused by thromboembolism, while hemodynamic stroke mechanism is rare. Differences in plaque inflammation according to stroke mechanism are an understudied issue. The purpose of this pilot study was to compare carotid plaque inflammation in patients with thromboembolic and hemodynamic cerebral ischemia. METHODS We included 6 patients with hemodynamic and 27 with embolic cerebral ischemia who had carotid endarterectomy (CEA). We compared plaque morphology markers (macrophages, T cells, MMP-9, plaque rupture, surface thrombus, intraplaque hemorrhage, lipid core) between patients with hemodynamic and embolic cerebral ischemia and assessed vascular events and deaths during the first year post CEA. RESULTS Compared to patients with hemodynamic mechanism, those with embolic mechanism showed a higher median (interquartile range) content of T cells/mm(2) [49.66 (21.26-71.39) vs. 10.28 (7.05-13.87); P=0.0005] and higher median total percentages of macrophage area [2.81% (1.69-4.09) vs. 0.99% (0.57-1.50); P=0.003] and MMP-9 area [0.63% (0.42-1.01) vs. 0.25% (0.05-0.45); P=0.007]. Signs of plaque instability such as plaque rupture, surface thrombus and intraplaque hemorrhage showed a tendency to be more pronounced in patients with thromboembolism. The incidences of vascular events and the survival rates in the first year after CEA were similar in the two groups. CONCLUSIONS Major differences in plaques related to stroke mechanism were found in patients with symptomatic carotid stenosis. However, further investigations are necessary to validate our results. Identification of stroke mechanism may improve risk stratification and could help to identify the most suitable secondary stroke prevention strategy.

Longitudinal Testing of Olfactory and Gustatory Function in Patients with Multiple Sclerosis

Background The aim of the study was to investigate changes of the olfactory and gustatory capacity in patients with multiple sclerosis (MS). Methodology 20 MS patients were tested longitudinally for 3 years after initial testing. The Threshold Discrimination Identification test (TDI) was used for subjective olfactometry. Objective olfactometry was performed by registering olfactory evoked potentials (OEP) by EEG. The Taste Strip Test (TST) was used for gustatory testing. Results 45% of the patients showed olfactory dysfunction in the follow-up TDI test and 50% showed delayed OEP´s. 20% of the patients showed gustatory dysfunction on follow-up visit. The patients showed mild disease activity with 0,3 ± 0,5 relapses over the testing period and no significant change of their olfactory and gustatory capacity. The olfactory capacity for the discrimination of odors correlated inversely with the number of relapses (r = -0.5, p ≤ 0.05). The patients were aware of their olfactory deficit. Conclusions Olfactory and gustatory dysfunction is a symptom in MS patients and may be a useful parameter to estimate disease progression in MS patients. As the discrimination of odors is processed in higher central regions of the central nervous system (CNS), the results suggest that olfactory dysfunction could be due to CNS damage.

Identification of neovascularization by contrast–enhanced ultrasound to detect unstable carotid stenosis

Background Plaque neovascularization accompanies local inflammation and critically contributes to plaque instability. Correct identification of intraplaque neovascularization by contrast–enhanced ultrasound (CEUS) may provide an additional risk marker in carotid stenosis. This pilot study investigates the correlation between histological evaluation of carotid plaque specimens and pre-surgery CEUS to identify neovascularization. Methods 17 patients with high-grade internal carotid artery (ICA) stenosis were studied. CEUS was performed in all patients shortly before carotid endarterectomy. Neovascularization, infiltration of T cells and macrophages along with intraplaque hemorrhage were studied in excised plaques by immunohistochemistry. Ultrasound-based four-level and two-level classification systems for neovascularization were used. CEUS findings were compared with histological findings. Results Scores on the CEUS-based four-level and two-level classifications were robustly correlated with the density of intraplaque vessels (r = 0.635, p = 0.006 and r = 0.578, p = 0.015, respectively). Histological evaluation of regions with strong and prolonged intraplaque enhancement typically showed strong intraplaque neovascularization in conjunction with acute intraplaque hemorrhage. Moreover, higher grades of intraplaque neovascularization as determined by ultrasound were associated with a higher percentage of macrophage-rich areas. Conclusion CEUS is a technique well suited to gauge the degree of neovascularization of carotid plaques. Future research will have to define the reliability and validity of CEUS in everyday clinical practice. Further, our study suggests that CEUS may also be useful to pick up features of vulnerable plaques such as acute intraplaque hemorrhages.

Contrast-enhanced ultrasound and detection of carotid plaque neovascularization

A 62-year-old man was admitted after recurrent transient left-sided weakness and sensory loss. Ultrasound (US) examination revealed a 70% narrowing of the right proximal internal carotid artery (ICA). Contrast-enhanced US suggested plaque neovascularization (figure, A). Carotid endarterectomy of the right ICA was performed. Immunohistochemistry of the specimen showed, corresponding to the US findings, extensive plaque neovascularization associated with dense macrophage infiltration (figure, B, C). Plaque neovascularization is associated with inflammation and plaque progression.1 The detection of plaque neovascularization by contrast-enhanced US could give further evidence of plaque vulnerability, but further study is needed to determine its value.