Anastasios Chatzikonstantinou

Features of acute DWI abnormalities related to status epilepticus.

We analyzed the phenomenon of transient regional diffusion-weighted MRI (DWI) hyperintensity in a series of status epilepticus (SE) patients with respect to seizure type, epileptogenic lesions and EEG findings. A prospective series of 54 patients (30 men, 24 women, mean age 61.5 years) admitted with SE was analyzed with regard to clinical semiology, EEG and MRI findings including DWI and EEG recordings in the acute peri-ictal phase. DWI abnormalities occurred most frequently in patients with complex-partial SE (27/50%) and generalized SE (18/33.3%). Forty patients (74.1%) had symptomatic, 13/24.1% cryptogenic and 1/1.9% idiopathic epilepsies. On DWI, the hippocampus was affected in 37/68.5% cases, often in combination with other brain areas (15/40.5%), in particular the pulvinar was affected in 14/25.9% patients. Bilateral DWI changes were found in 8/14.8% patients. No correlation with a specific seizure type was observed. In 21/38.9%, DWI changes were ipsilateral to the epileptogenic brain lesion (p<0.001) and in 5/9.3% contralateral, whereas in the majority of patients, either bilateral changes or no specific epileptogenic lesion were found. EEG abnormalities correlated with lateralization of DWI abnormalities in 44/81.5% (p<0.001). The most common localization of DWI abnormalities associated with ictal activity was the hippocampus and the pulvinar. Combined DWI-MRI and EEG analysis provides clues to seizure localization and propagation, as well as to identify brain structures affected by continuous or frequent ictal activity. This large series of patients with different features (SE type and cause, various epileptogenic lesions) demonstrates the heterogeneity of the phenomenon of peri-ictal DWI changes.

CT Angiography of the Aorta Is Superior to Transesophageal Echocardiography for Determining Stroke Subtypes in Patients with Cryptogenic Ischemic Stroke

Background: The etiology of ischemic strokes remains cryptogenic in about one third of patients, even after extensive workup in specialized centers. Atherosclerotic plaques in the aorta can cause thromboembolic events but are often overlooked. They can elude standard identification by transesophageal echocardiography (TEE), which is invasive or at best uncomfortable for many patients. CT angiography (CTA) can be used as an alternative or in addition to TEE if this technique fails to visualize every part of the aorta and in particular the aortic arch. Methods: We prospectively studied 64 patients (47 men, age 60 ± 13 years) classified as having cryptogenic stroke after standard and full workup [including brain MRI and 24-hour electrocardiogram (ECG)] with ECG-triggered CTA of the aorta in search of plaques and compared the results with those of TEE. Investigators were blinded to the results of both techniques. Plaques were graded on CTA according to their presence (0 = not present; 1 = mild; 2 = severe) and degree of calcification (1a or 2a = noncalcified; 1b or 2b = calcified). Associations with risk factors and infarct localization were also assessed. Results: Only 21 of 64 patients (32.8%) had aortic plaques identified by TEE, compared to 43 of 64 (67.2%) with CTA (p < 0.05). The plaque localization was as follows (TEE vs. CTA): ascending aorta, 10 vs. 20 (p < 0.05); aortic arch, 10 vs. 40 (p < 0.05), and descending aorta, 20 vs. 34 (p < 0.05). Grade 1 plaques were most commonly found in the aortic arch (25; 39%), while grade 2 plaques were most often detected in the aortic arch (15; 23.4%) and the descending aorta (14; 21.9%). There was no significant correlation between plaque location, infarct territory or vascular risk profile, except for hypertension (p = 0.003), which was significantly associated with the presence of plaques. Conclusions: CTA identifies more plaques throughout the aortic arch and around the origins of the major cerebral arteries in particular compared to TEE. These may represent potential embolic sources of acute ischemic stroke. Better plaque detection may have an impact on the best available secondary prevention regimen in individual patients if proximal embolic sources are suspected.

Brain imaging in patients with transient ischemic attack: a comparison of computed tomography and magnetic resonance imaging.

Background: Brain imaging in stroke aims at the detection of the relevant ischemic tissue pathology. Cranial computed tomography (CT) is frequently used in patients with transient ischemic attack (TIA) but no data is available on how it directly compares to magnetic resonance imaging (MRI). Methods: We compared detection of acute ischemic lesions on CT and MRI in 215 consecutive TIA patients who underwent brain imaging with either CT (n = 161) or MRI (n = 54). An MRI was performed within 24 h in all patients who had CT initially. Results: An initial assessment with CT revealed no acute pathology in 154 (95.7%) and possible acute infarction in 7 (4.3%) patients. The acute infarct on CT was confirmed by diffusion-weighted imaging (DWI) in only 2 cases (28.6%). DWI detected an acute infarct in 50 of the 154 patients with normal baseline CT (32.5%). Among 54 patients without baseline CT, DWI showed acute ischemic lesions in 19 (35.2%). The ischemic lesions had a median volume of 0.87 cm3 (range: 0.08–15.61), and the lesion pattern provided clues to the underlying etiology in 13.7%. Conclusion: Acute MRI is advantageous over CT to confirm the probable ischemic nature and to identify the etiology in TIA patients.

Transient Ischemic Attack Patients with Fluctuations Are at Highest Risk for Early Stroke

Background: The management and risk of early stroke are unclear in patients with fluctuating neurological symptoms. We aimed to evaluate the clinical course of these patients presenting within 24 h after onset of acute cerebral ischemia symptoms. Methods: All patients with transient ischemic signs/symptoms consecutively admitted to our Emergency Stroke Unit were recruited. Patients were neurologically examined and underwent prompt CCT plus MRI imaging for visualization of early signs of ischemia. Results: Among 122 patients, 84 (69%) had single symptoms, 33 (27%) showed rapidly relapsing and remitting symptoms – in 5 cases (4%) symptom duration could not reliably be assessed. 11/122 (9%) suffered a stroke during hospitalization. ABCD2 scores did not predict early strokes: 2/11 (18.2%) were in the ‘lower risk’, 7/11 (63.6%) in the ‘moderate risk’ and only 2/11 (18.2%) in the ‘high risk’ group (p = 0.103). 3/11 patients (27.3%) revealed lesions in neuroimaging, but surprisingly 8/11 (72.7%, p = 0.132) did not. However, patients with fluctuations in neurological status were significantly more likely to suffer a stroke: 9/122 versus 2/122 with stable symptoms (p < 0.05). Patients with small vessel disease were common in all (53/ 122; 43.4%) and within those who suffered an early stroke (6/11; 54.5%). Conclusions: Patients with unstable transient ischemic attacks immediately after onset of clinical symptoms are at high risk for subsequent stroke – they may benefit from Stroke Unit management and potential early thrombolysis once they develop strokes.

Successive affection of bilateral temporomesial structures in a case of non-paraneoplastic limbic encephalitis demonstrated by serial MRI and FDG-PET

Sirs, Non-paraneoplastic limbic encephalitis (NPLE) often results in an unfavorable clinical course with progressive neuropsychological deficits and epileptic seizures despite treatment [1–3]. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDGPET) and antibodies against voltage-gated potassium channels (VGKC-Ab) are helpful in monitoring the course of the disease [3–5]. We present a follow-up of a NPLE patient over a 3-year period with successive affection of bilateral temporomesial structures. A 67-year-old man with no relevant medical history presented with recurrent episodes of visual hallucinations, memory impairment, disorientation and myoclonic jerks. Neurological examination was unremarkable; however neuropsychological testing revealed severe verbal (shortterm) memory, speech fluency and visual recognition deficits. EEG showed an intermittent theta-focus as well as intermittent right temporal ictal rhythmic activity. On MRI hyperintensity and diffuse swelling of the right hippocampus on T2and diffusion-weighted (DWI) images was found. FDG-PET revealed right temporomesial hypermetabolism and bilateral hypometabolism in the temporal lobes (Fig. 2a). There were no signs of tumor in the wholebody PET examination. CSF (including virological analysis) was normal except for elevated VGKC-Ab levels ([9085 pM, controls \100 pM). Thyroid function and autoantibodies tests were negative. The diagnosis of NPLE was made and methylprednisolone (MP; 4000 mg i.v. over 5 days) as well as gabapentin treatment was initiated. Figure 1 shows the course of the disease, examination results and therapeutic management. Three months later, the patient presented with a deterioration of symptoms. MRI showed an atrophy of the right hippocampus, with mild residual T2-hyperintensity. FDGPET showed left temporal hypermetabolism and a right temporomesial ‘‘cold’’ lesion (Fig. 2b). VGKC-Ab were still elevated ([8067 pM). Treatment with MP (5000 mg i.v. over 5 days) was started again. Six months later he was re-admitted with progressive memory impairment, confirmed by neuropsychological examination. Now on MRI, left hippocampal edema was found and FDG-PET demonstrated severe hypometabolism in both temporomesial regions. After 2 months of stable condition, there was once again neuropsychological deterioration. There were no significant changes on MRI compared to the previous examinations and the FDG-PET showed left temporomesial hypometabolism. IV immunoglobulin therapy (150 g over 3 days) was applied. Two and 4 months later MRI and FDG-PET findings remained unchanged. VGCK-Ab levels were almost normal. Memory impairment had temporarily deteriorated before improving again, this time under immunosuppressive treatment with azathioprine (100 mg/ d). At the last two visits (after 2 and 3.5 years) the patient was seizure-free under gabapentin and showed an improvement of his cognitive functions under azathioprine treatment. MRI showed left hippocampal atrophy and FDG-PET hypometabolism in both temporomesial areas (Fig. 2c). A neoplasm was excluded by repeated wholebody PET examinations. In NPLE, neuropsychological deficits often remain or deteriorate even if seizures are controlled and immunosuppressive treatment is applied. In our case, disease A. Chatzikonstantinou (&) K. Szabo C. Ottomeyer R. Kern M. G. Hennerici Department of Neurology, Universitatsklinikum Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany e-mail: chatziko@neuro.ma.uni-heidelberg.de

Noise reduction and image quality improvement of low dose and ultra low dose brain perfusion CT by HYPR-LR processing.

Purpose To evaluate image quality and signal characteristics of brain perfusion CT (BPCT) obtained by low-dose (LD) and ultra-low-dose (ULD) protocols with and without post-processing by highly constrained back-projection (HYPR)–local reconstruction (LR) technique. Methods and Materials Simultaneous BPCTs were acquired in 8 patients on a dual-source-CT by applying LD (80 kV,200 mAs,14×1.2 mm) on tube A and ULD (80 kV,30 mAs,14×1.2 mm) on tube B. Image data from both tubes was reconstructed with identical parameters and post-processed using the HYPR-LR. Correlation coefficients between mean and maximum (MAX) attenuation values within corresponding ROIs, area under attenuation curve (AUC), and signal to noise ratio (SNR) of brain parenchyma were assessed. Subjective image quality was assessed on a 5-point scale by two blinded observers (1:excellent, 5:non-diagnostic). Results Radiation dose of ULD was more than six times lower compared to LD. SNR was improved by HYPR: ULD vs. ULD+HYPR: 1.9±0.3 vs. 8.4±1.7, LD vs. LD+HYPR: 5.0±0.7 vs. 13.4±2.4 (both p<0.0001). There was a good correlation between the original datasets and the HYPR-LR post-processed datasets: r = 0.848 for ULD and ULD+HYPR and r = 0.933 for LD and LD+HYPR (p<0.0001 for both). The mean values of the HYPR-LR post-processed ULD dataset correlated better with the standard LD dataset (r = 0.672) than unprocessed ULD (r = 0.542), but both correlations were significant (p<0.0001). There was no significant difference in AUC or MAX. Image quality was rated excellent (1.3) in LD+HYPR and non-diagnostic (5.0) in ULD. LD and ULD+HYPR images had moderate image quality (3.3 and 2.7). Conclusion SNR and image quality of ULD-BPCT can be improved to a level similar to LD-BPCT when using HYPR-LR without distorting attenuation measurements. This can be used to substantially reduce radiation dose. Alternatively, LD images can be improved by HYPR-LR to higher diagnostic quality.

Asymptomatic and Symptomatic Carotid Stenosis: An Obsolete Classification?

Since many years, clinical decisions about the management of patients with carotid stenosis have been based on the distinction between “asymptomatic” and “symptomatic” presentations. This was also reflected by the design of previous studies on the surgical versus conservative treatment and of current studies on interventional treatment versus surgery. Both terms, however, only address different phases of activity of the one and the same condition and blur the significant message that carotid stenosis is a most important marker of systemic atherosclerosis, which is accompanied by a much higher risk of cardiovascular events rather than stroke. As a consequence, early diagnosis and followup during best medical treatment, life-style management, regular cardiovascular assessment, and good control of all vascular risk factors should be recommended in all patients with carotid stenosis—whether identified in the long-lasting “silent” or short-lasting “vulnerable” period lasting only a few weeks after cerebral ischemia. Patients in this short time window benefit from additional carotid intervention, under the condition of an individually favorable benefit-risk ratio (“individual vulnerability”).

Coexisting large and small vessel disease in patients with ischemic stroke of undetermined cause

Background and Purpose: Large artery atherosclerosis (LAA) and small vessel disease (SVD) share common risk factors for stroke. We aimed at investigating the association of SVD with cerebral LAA as well as with atherosclerosis in patients with stroke likely to originate from aortic plaques. Methods: We investigated 71 consecutive patients (48 men, mean age 64.2 ± 13 years) with ischemic stroke of undetermined cause according to the ASCO classification, who received ECG-triggered CT angiography for best available atherosclerotic plaque detection in the aorta. Results: Aortic atherosclerotic plaques were detected in 54 patients (76.1%). The presence of SVD significantly correlated with the presence of aortic plaques (p < 0.001), as well as LAA (p < 0.001) and risk factors such as arterial hypertension (p = 0.032) and diabetes mellitus (p = 0.017). Conclusions: Aortic plaques are common in patients with stroke of undetermined cause. If so, SVD and LAA are often coexisting, which demonstrates the close link of macro- and microangiopathy, at least in cases of severe risk factors of atherosclerosis.

Cerebral microbleeds are uncommon in ischemic stroke associated with nonvalvular atrial fibrillation.

Patients with cardioembolic ischemic stroke from nonvalvular atrial fibrillation (NVAF) are candidates for long‐term anticoagulation. This study examines the prevalence of cerebral microbleeds (MBs) in stroke patients with NVAF.

Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies

BACKGROUND Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. METHODS We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. FINDINGS In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1-7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8-5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6-8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). INTERPRETATION Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. FUNDING Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Koreas Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.