Alex Förster

Gender Differences in Acute Ischemic Stroke: Etiology, Stroke Patterns and Response to Thrombolysis

Background and Purpose— Differences between women and men in relation to stroke are increasingly being recognized. Methods— From July 2004 until June 2007, 237 acute ischemic stroke (AIS) patients were treated with recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of women were compared to those of men. Results— Of 237 AIS patients (mean age 70.7 years), 111 (46.8%) were women and 126 (53.2%) were men. Women were older (P=0.001), but history of hyperlipidemia (P=0.03), smoking (P=0.03), and coronary heart disease (P<0.001) was less frequent than in men. Internal carotid artery disease occurred more often in men (P=0.02), whereas atrial fibrillation was observed more often in women (P=0.002). In men borderzone/small embolic and lacunar stroke was found more frequently (39.7 versus 27.2%), whereas women showed a higher percentage of large territorial stroke (72.8 versus 60.3%, P=0.09). Baseline National Institute of Health Stroke Scale scores (12.5 versus 11.3), NIHSS score at discharge (11.0 versus 9.5), 3-month-outcome modified Rankin Scale score, thrombolysis-related (17.1% versus 13.5%) or independent complications (32.4% versus 30.2%), and mortality after 3 months (13.5% versus 9.5%) were similar. Conclusion— Differences of stroke lesion patterns in genders are paralleled by differences in etiology and risk factor profiles (women, cardioembolism; men, large and small vessel disease). Baseline characteristics, rates of rtPA-related and independent complications, as well as clinical outcomes were not different between women and men with AIS.

Hippocampal Lesion Patterns in Acute Posterior Cerebral Artery Stroke. Clinical and MRI Findings

Background and Purpose— Reports of ischemic stroke affecting the hippocampus are rare. In this study we used diffusion-weighted MRI (DWI) to characterize patients with posterior circulation stroke involving the hippocampus. Methods— Fifty-seven consecutive acute stroke patients with hippocampal infarct (HI) on DWI were analyzed with regard to clinical features and ischemic lesion patterns. The last 20 of these underwent additional neuropsychological testing of short-term, working, and episodic long-term memory. Results— We found unilateral HI in 54 and bilateral HI in 3 patients. Visual analysis identified 4 patterns of DWI lesion affecting (1) the complete hippocampus (15/60), (2) the lateral (19/60) or (3) dorsal (22/60) parts of the hippocampal body and tail, and (4) circumscribed lesions in the lateral hippocampus (4/60), corresponding well to hippocampal vascular anatomy. In all cases DWI showed further ischemic lesions in the posterior circulation. Symptoms from lesions outside the hippocampus were the common leading clinical signs. Whereas mnestic deficits were prominent in only 11/57 patients, neuropsychological examination in 20 patients showed deficits of verbal episodic long-term memory in left and of nonverbal episodic long-term memory in right HI. Conclusion— Several phenotypic lesion patterns can be distinguished in HI that usually occur as part of multifocal PCA ischemia. A careful neuropsychological examination is necessary to detect resulting memory deficits.

Diffusion-weighted imaging for the differential diagnosis of disorders affecting the hippocampus

Background: The human hippocampus can be affected in a large variety of very different neurological diseases, of which acute ischemic stroke, transient global amnesia, epilepsy, and limbic encephalitis are the most common. Less frequent etiologies include various infections and encephalopathy of different origins. Clinical presentation notably comprises confusional state, altered vigilance, memory deficits of various extent and seizures. While in hypoxic or hypoglycemic encephalopathy, clinical presentation and surrounding circumstances provide some clues to reach the correct diagnosis, in the above-listed more common disorders, signs and symptoms might overlap, making the differential diagnosis difficult. This review presents recent studies using the diffusion-weighted imaging (DWI) technique in diseases involving the hippocampus. Methods: References for the review were identified through searches of PubMed from 1965 to January 2011. Only papers published in English were reviewed. Full articles were obtained and references were checked for additional material where appropriate. Results: All pathologies affecting the hippocampus are associated with distinct lesion patterns on magnetic resonance imaging, and especially DWI has the ability to demonstrate even minute and transient hippocampal lesions. In acute ischemic stroke in the posterior cerebral artery territory, involvement of the hippocampal formation occurs in four distinct patterns on DWI that can be easily differentiated and correspond to the known vascular anatomy of the hippocampus. In the subacute phase after transient global amnesia (TGA), dot-like hyperintense lesions are regularly found in the lateral aspect of the hippocampus on DWI. The DWI lesions described after prolonged seizures or status epilepticus include unilateral or bilateral hippocampal, thalamic, and cortical lesions of various extent, not restricted to vascular territories. In limbic encephalitis, DWI lesions are only infrequently found and usually affect the hippocampus, uncus and amygdala. Furthermore, in some rare cases DWI lesions of different etiology may coexist. Conclusion: In patients with diseases affecting the hippocampus, DWI appears to be useful in differentiating between underlying pathologies and may facilitate a definite diagnosis conducive to an optimal treatment. With a careful clinical examination, experience with the interpretation of DWI findings and knowledge of associated phenomena, it is indeed possible to differentiate between ischemic, ictal, metabolic, and TGA-associated findings.

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.

Reduced Diffusion in a Subset of Acute MS Lesions: A Serial Multiparametric MRI Study

BACKGROUND AND PURPOSE: MRI studies have focused on newly developing MS lesions to characterize the early pathology of the disease. DWI is highly sensitive to acute and chronic tissue changes in MS. We characterized the development of acute MS lesions by using DWI in a multiparametric MRI protocol. MATERIALS AND METHODS: Seventy-two consecutive patients presenting with a new symptom with definite MS or a CIS suggestive of central nervous system demyelination were screened with MRI. Patients who showed an acute MRI lesion with a reduction of ADC were studied with serial MRI for up to 4 months after presentation. RESULTS: Ten of 72 screened patients who showed a lesion with a reduced ADC were each examined 4–7 times, resulting in 52 examinations in total. We identified a characteristic sequence of signal-intensity changes: 1) days 0–7: slight T2 hyperintensity and prominent ADC reduction (maximum, −66%), faint or no enhancement on postcontrast T1-weighted images; 2) days 7–10: prominent T2 hyperintensity and contrast enhancement, ADC normalization/pseudonormalization; 3) up to 4 weeks: elevated ADC values, prominent enhancement on postcontrast images; 4) after 4 weeks: partial reversibility of T2 hyperintensity, ADC elevation, and resolution of contrast enhancement. CONCLUSIONS: In a subgroup of patients with MS presenting soon after new symptom onset, a transient reduction of the ADC delineated a short and very early phase of MS lesion evolution. Subsequent pseudonormalization of the ADC occurred along with signs of the development of vasogenic edema.

Mechanisms of Disease: pathophysiological concepts of stroke in hemodynamic risk zones|[mdash]|do hypoperfusion and embolism interact?

The pathophysiology of cerebral ischemia in the borderzones between the large cerebral arteries has been the topic of considerable debate since this disease entity was defined in the first half of the twentieth century. Hemodynamic failure and microembolization were two seemingly mutually exclusive pathophysiological concepts that were proposed to explain the phenomenon of borderzone infarction in patients with arterial occlusive disease. Sufficient evidence has now accumulated, however, to indicate that borderzone infarcts are in fact caused by an interaction between hypoperfusion and microembolization. In this Review, we summarize the historical background of borderzone infarction and current knowledge regarding the various possible pathophysiological concepts. We present a representative survey of publications from the 1950s to the present day, starting with early autopsy-based studies, followed by later anatomical and in vitro studies, as well as CT-based and MRI-based investigations. The clinical symptoms of borderzone infarction and the possibility of a clinical distinction between borderzone and territorial infarcts are discussed. In addition, we consider techniques to localize hemodynamic risk zones in patients with arterial occlusive disease, such as perfusion-weighted MRI, and techniques to identify a hemodynamic component of stroke, such as investigation of the cerebrovascular reserve capacity with transcranial Doppler ultrasound.

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.

Thrombolysis in posterior circulation stroke: stroke subtypes and patterns, complications and outcome.

Background: Patients with posterior circulation stroke (PCS) were underrepresented in or even excluded from the large clinical trials investigating acute therapy with thrombolysis. Therefore, the knowledge about potential benefits and risks of thrombolysis in PCS is sparse. Methods: From July 2004 until June 2007, 237 stroke patients were treated with thrombolysis within 3 h after onset of symptoms in our stroke unit. Baseline characteristics, etiology, CT/MRI stroke patterns, clinical outcome, and complications of patients with PCS were compared to those with anterior circulation stroke (ACS). Results: There were 30 patients in the PCS group; 198 had ACS. In the PCS group, less patients had a history of prior stroke (0/30 vs. 31/198 (15.7%), p = 0.02) and less were treated with platelet inhibitors (6/30 (20.0%) vs. 83/198 (41.9%), p = 0.02). Onset to treatment time was higher in the PCS group (156.2 ± 23.2 vs. 141.1 ± 30.7, p = 0.01). Small vessel disease occurred more often in PCS patients (10/30 (33.3%) vs. 12/198 (6.1%), p < 0.001), whereas stroke of undetermined cause was less frequent (5/30 (16.7%) vs. 75/198 (37.9%), p = 0.02). Correspondingly, PCS patients had more lacunar (13/30 (43.3%) vs. 15/198 (7.3%), p < 0.001) strokes on CT/MRI. Patients with PCS had significantly lower median NIHSS scores after 2 and 24 h, whereas the median NIHSS and mRS scores at discharge as well as the mRS score at the 3-month follow-up, although still lower, did not differ significantly between both groups. Outcome was similar with regard to complications and mortality. Conclusions: Patients with PCS have a higher rate of small vessel disease and lacunar stroke. In terms of potential benefits and risks of thrombolysis, we could demonstrate no significant differences between PCS and ACS. Acute PCS patients should be diagnosed and treated with the same elaborateness as ACS patients.

Comparison of Fenestra LC, ExiTron nano 6000, and ExiTron nano 12000 for micro-CT imaging of liver and spleen in mice.

RATIONALE AND OBJECTIVES The purpose of this study was to compare different contrast agents for longitudinal liver and spleen imaging in a mouse model of liver metastasis. MATERIALS AND METHODS Mice developing liver metastases underwent longitudinal micro-computed tomography imaging after injection of Fenestra LC, ExiTron nano 6000, or ExiTron nano 12000. Elimination times and contrast enhancement of liver and spleen were compared. RESULTS For all contrast agents, liver contrast peaked at approximately 4 hours and spleen contrast at 48 hours postinjection. A single dose of 100 μL of ExiTron nano 6000 or 12000 resulted in longstanding enhancement of liver and spleen tissue for longer than 3 weeks, whereas repeated injections of 400 μL of Fenestra LC were required to retain contrast at acceptable levels and allowed imaging of the liver/spleen for up to 2 and 9 days, respectively. CONCLUSION Both ExiTron nano agents provide longer and stronger contrast enhancement of liver and spleen compared to Fenestra LC, and they do so at a 75% lower injection volume in mice.

MR Imaging-Guided Intravenous Thrombolysis in Posterior Cerebral Artery Stroke

SUMMARY: PCA stroke was under-represented in or excluded from the clinical trials examining thrombolysis based on the PWI-DWI mismatch concept. We present 6 patients with PCA stroke treated with thrombolysis in an extended time window by using MR imaging criteria. Symptoms included aphasia, sensorimotor hemiparesis, hemineglect, and homonymous hemianopia. Initial MR imaging demonstrated circumscribed ischemic lesions in the thalamus or hippocampus; MR angiography showed PCA occlusion with corresponding hypoperfusion. Follow-up MR imaging showed partial/complete recanalization in 4 patients with minor infarction growth, while in 1 patient, PCA occlusion persisted, resulting in a large PCA infarction. Three patients improved within 2 hours; at discharge, homonymous hemianopia had resolved in 3 patients. At 3-month follow-up, 4 patients had an mRS score of 0 or 1. These results support the approach to treat patients with PCA stroke with thrombolysis based on the mismatch concept. Because rehabilitation options for hemianopia are limited, thrombolysis may enhance the chance of a favorable outcome.