Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine Aura: An Observational Study.

BACKGROUND: Changes in cerebral perfusion during migraine with aura (MA) have been assessed mainly using dynamic susceptibility contrast (DSC) magnetic resonance perfusion imaging. A contrast agent-free method to assess these changes would be desirable. We assessed changes in cerebral perfusion during MA using arterial spin labeling (ASL) perfusion magnetic resonance imaging. METHODS: We investigated 4 patients with a standardized protocol including ASL perfusion imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow-up. Semiquantitative evaluation was done using a region of interest (ROI) within hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were calculated. DSC imaging was done at initial time points and compared visually with ASL findings. RESULTS: In all patients, regional perfusion changes were detected in the acute phase. These abnormalities did not respect the boundaries of major cerebral vascular territories but overlapped onto adjoining regions. During MA, adjacent hypoperfused and hyperperfused areas were found, whereas during headache, regional hyperperfusion only was observed. Perfusion abnormalities normalized on follow-up. CONCLUSIONS: ASL perfusion imaging is a contrast agent-free method suitable for assessment of reversible perfusion changes during or immediately after MA.

Prediction of Early Reperfusion From Repeated Arterial Spin Labeling Perfusion Magnetic Resonance Imaging During Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: There are few in vivo data on the pathophysiology of reperfusion during systemic thrombolysis. We monitored the time course of cerebral perfusion changes in patients during thrombolysis with repeated arterial spin labeling perfusion magnetic resonance imaging. METHODS: Ten patients with proximal arterial occlusion within 4.5 hours after symptom onset were prospectively enrolled. All patients received intravenous thrombolysis during the magnetic resonance imaging examination. Repeated arterial spin labeling perfusion images were acquired during the 60-minute therapy and at follow-up after 24 to 72 hours. Clinical data, magnetic resonance imaging features, and cerebral perfusion changes were analyzed. RESULTS: Before thrombolysis, arterial spin labeling hypoperfusion and fluid-attenuation inversion recovery vascular hyperintensity in the territory of the occluded arteries were observed in all patients. In 5 patients, extensive arterial transit artifacts (ATA) developed in the hypoperfused area. The ATA corresponded with fluid-attenuation inversion recovery vascular hyperintensities. All 5 patients who developed extensive ATA in the hypoperfused area had complete reperfusion after thrombolysis, whereas the 5 without extensive ATA showed no or only partial reperfusion (P<0.01). The development of ATA preceded the normalization of tissue perfusion. CONCLUSIONS: The development of ATA during thrombolysis is associated with early reperfusion after thrombolysis. arterial spin labeling assessment during intravenous thrombolysis has the potential to guide subsequent therapeutic strategies in patients with acute stroke.

Heterogeneity of acute multiple sclerosis lesions on sodium (23Na) MRI.

BACKGROUND: Advanced magnetic resonance imaging (MRI) techniques provide a window into pathological processes in multiple sclerosis (MS). Nevertheless, to date only few studies have performed sodium MRI in MS. OBJECTIVES: We analysed total sodium concentration (TSC) in hyperacute, acute and chronic lesions in MS with (23)Na MRI. METHODS: (23)Na MRI and (1)H MRI were performed in 65 MS patients and 10 healthy controls (HC). Mean TSC was quantified in all MS lesions with a diameter of >5 mm and in the normal appearing white and grey matter (NAWM, NAGM). RESULTS: TSC in the NAWM and the NAGM of MS patients was significantly higher compared to HC (WM: 37.51 ± 2.65 mM versus 35.17 ± 3.40 mM; GM: 43.64 ± 2.75 mM versus 40.09 ± 4.64 mM). Acute and chronic MS lesions showed elevated TSC levels of different extent (contrast-enhancing lesions (49.07 ± 6.99 mM), T1 hypointense lesions (45.06 ± 6.26 mM) and remaining T1 isointense lesions (39.88 ± 5.54 mM)). However, non-enhancing hyperacute lesions with a reduced apparent diffusion coefficient showed a TSC comparable to the NAWM (37.22 ± 4.62 mM). CONCLUSIONS: TSC is not only a sensitive marker of the severity of chronic tissue abnormalities in MS but is also highly sensitive to opening of the blood-brain barrier and vasogenic tissue oedema in contrast-enhancing lesions.

True Effects or Bias? MMP-2 and MMP-9 Serum Concentrations after Acute Stroke.

BACKGROUND: Average serum matrix metalloproteinase (MMP) concentrations in patients with acute stroke have shown to be varying across studies. Possibly, next to true effects, other factors may influence MMP levels. The aim of this study was to investigate the dynamics of these enzymes in repeated measurements in the acute post-stroke period, in respect to different stroke etiologies, and highlight potential sources for variability. METHODS: Serum in 233 patients with acute ischemic or hemorrhagic stroke (stroke cohort; SC) was ascertained within 24 h after onset and then 1, 3 and 7 days thereafter. One hundred five controls (control cohort; Co) were recruited. Multi-variable adjustment was carried out using salient extraneous covariates including stroke etiology, clinical severity and lesion size next to a set of routine laboratory parameters. RESULTS: Unadjusted SC MMP-2 concentrations are significantly lower (SC 165.4, 95% CI 158.5-172.4; Co 203.7 ng/ml, 95% CI 190.7-216.5; p < 0.001) and MMP-9 concentrations significantly higher than in controls (SC 608.5 ng/ml, 95% CI 555.3-661.8; Co 475.6 ng/ml, 95% CI 413.6-537.6; p < 0.001). Adjustment mitigates associations between MMP concentrations and stroke etiology, clinical severity, lesion size or differences in temporal profile shown present without adjustment. Salient covariates absorb much of the effect: age, leukocyte count and albumin concentrations are associated significantly with MMP-2 concentrations; only leukocyte count is significantly associated with MMP-9. CONCLUSIONS: Concentrations of MMP-2 and MMP-9 in serum in humans measured after acute stroke are potentially influenced by extraneous covariates rather than being directly associated with characteristics of the underlying stroke.

Acute Stroke Syndromes with Isolated Hypoperfusion on MRI - A Clinical and MRI Study.

BACKGROUND: Acute stroke syndromes with negative diffusion-weighted imaging (DWI) but extensive perfusion deficits are rare and constitute a diagnostic challenge due to different operational definitions of penumbral hypoperfusion in acute stroke patients based on MRI criteria. METHODS: MR profiles of 19 patients presenting with acute stroke syndromes with negative DWI in the presence of an extensive area of hypoperfusion on time-to-peak (TTP) maps of dynamic susceptibility contrast perfusion-weighted imaging (PWI) were analysed. DWI and PWI lesions were quantified and interpreted with regard to the clinical course. RESULTS: Despite the large area of abnormal perfusion on TTP maps, the clinical course was benign (median National Institute of Health Stroke Scale 2 at admission, 0 at discharge). The volume of hypoperfused tissue was significantly smaller on postprocessed TTP maps with a TTP delay of >4 s than on unprocessed TTP maps with manual contrast adjustment. Semiquantitatively assessed TTP lesion volume was associated with the presence of DWI lesions on follow-up. CONCLUSION: TTP maps are highly sensitive to demonstrate even small-scale perfusion abnormalities. The additional information from TTP delay thresholds indicates critically reduced perfusion and appears to be a good prognostic indicator in combination with MR angiography and symptomatology.

Transient global amnesia in legal proceedings.

Transient global amnesia (TGA) is a neurological disorder characterized by an acute onset of severe anterograde amnesia. While retrograde amnesia may be present-although to a lesser extent-patients have no further cognitive disturbances or neurological signs. These symptoms resolve fully within several hours leaving a permanent memory gap for the duration of the episode and do not lead to long-term neurological deficits. In addition to well-defined clinical diagnostic criteria, in up to 80 % of patients, small, point-shaped lesions in the hippocampus are detected 24-48 h after symptom onset on diffusion-weighted magnetic resonance images. Despite several etiological hypotheses, to date, there is no scientific proof for the etiology of TGA or the small hippocampal lesions. Interestingly, in a large number of cases, an emotionally or physically straining event precipitates the onset of TGA, suggesting a stress-related mechanism. We report two cases of TGA occurring in legally relevant settings: affecting the victim of brutal burglary and the key witness in a murder trial. In the context of forensic medicine, the knowledge of this disorder and recognition of its typical features are essential.

Cerebrospinal fluid pleocytosis in multiple sclerosis patients with lesions showing reduced diffusion.

In multiple sclerosis (MS) occasionally acute lesions show a reduced apparent diffusion coefficient (ADC) on magnetic resonance imaging (MRI); however, the underlying mechanism of this phenomenon is not known. We compared cerebrospinal fluid (CSF) findings with diffusion MRI signal characteristics of acute lesions in 25 patients with MS or a clinically isolated syndrome (CIS) later confirmed as MS. In nine of 25 patients investigated between days 1 and 4 after symptom onset, a reduced intralesional ADC value (-15% to -51%) was accompanied by a marked CSF pleocytosis (11-46 leukocytes/µl). Our results suggest that ADC reduction in acute MS lesions is a phenomenon that is possibly related to an aggressive inflammatory milieu as indirectly indicated by CSF pleocytosis. Furthermore, the ADC reduction and CSF pleocytosis were observed only early after symptom onset, which suggests that both are typically early and transient phenomena.

Multimodal assessment of optokinetic visual stimulation response in migraine with aura.

OBJECTIVE: This study aimed to assess activation patterns and the hemodynamic response to optokinetic stimulation in migraine with aura patients compared with controls. BACKGROUND: It has been proposed that altered visual motion processing in striate and extrastriate visual areas is present in migraine patients and might play a role in the pathophysiology of the disease. Besides activating a large visual network, optokinetic stimulation in particular has been shown to provoke symptoms associated with migraine. METHODS: In this study, we examined the response to visual stimulation in 18 migraine with aura patients compared with 18 healthy controls by using functional magnetic resonance imaging and functional transcranial Doppler, thereby assessing the activation pattern of the visual areas (V1-V5) as well as the vasomotor reactivity of the posterior cerebral artery. For stimulation, we used a vertically rotating optokinetic drum with complex colored figures. RESULTS: Group analysis of migraineurs with aura vs controls revealed different activation patterns in functional magnetic resonance imaging: attenuation of the physiological right lateralization with a significantly increased activation in the left V5 complex, the left area V3, and the right V5 complex. Analysis of the visually evoked flow response of the cerebral blood flow velocity in the posterior cerebral artery showed a larger side-difference of the offset latency (P < .05) and a reduced steepness of the decreasing slope on the left side (P < .05). CONCLUSION: Combining examinations with a good structural (functional magnetic resonance imaging) and temporal (functional transcranial Doppler) resolution is a novel approach to migraine pathophysiology. Our findings of an altered pattern of activation by optokinetic visual stimulation with hyperresponsiveness in visual areas activated by motion perception (V5 and V3) further strengthen the concept of an interictal motion-processing deficit in migraine. This is complemented by the slower restitution of the visually evoked flow response after stimulus offset in migraine with aura patients.

Protocol: Prospective evaluation of feasibility, added value and satisfaction of remote digital self-assessment for mild cognitive impairment in routine care with the neotivCare app.

INTRODUCTION: Timely diagnosis of mild cognitive impairment (MCI) in Alzheimer's disease is crucial for early interventions, but its implementation is often challenging due to the complexity and time burden of required cognitive assessments. To address these challenges, the usability of new unsupervised digital remote assessment tools needs to be validated in a care context. METHODS AND ANALYSIS: This multicentric healthcare research evaluation survey, re.cogni.ze, aims to evaluate physician satisfaction with a remote digital assessment solution (neotivCare) in primary and specialised routine care in Germany. Over a period of 22 months, physicians in different regions of Germany will recommend the application (app) to approximately 1000 patients for a 12-week self-assessment of cognition. The primary endpoint is the evaluation of physicians' and patients' overall satisfaction with neotivCare and with neuropsychological questionnaires/standard procedures using a Likert scale, while secondary endpoints include user-friendliness, qualitative assessment of acceptance and potential improvements on medical routine services. The study also aims to evaluate the proportion of physicians or patients attributing added value to neotivCare compared with standard paper-pencil tests. The study results will provide insights into the feasibility, efficiency and acceptance of new digital tools for MCI diagnosis in routine care. The re.cogni.ze survey will thus provide proof-of-concept information for the implementation of remote digital cognitive assessment apps for MCI into medical routine care. ETHICS AND DISSEMINATION: This study was approved by the ethics committee of the State Medical Association (Landesärztekammer) Baden-Württemberg, (F-2021-161) as the leading committee and nine ethics committees local to the participating healthcare professionals (Lower Saxony, North Rhine, Westphalia-Lippe, Hesse, Bremen, Berlin, University of Göttingen, Charite, University of Rostock). The results can be shared (upon reasonable quest) to improve routine clinical processes and holistic approaches.

Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data.

BACKGROUND AND PURPOSE: The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. METHODS: We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. RESULTS: We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register. CONCLUSIONS: Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

Cerebral network disruption as a possible mechanism for impaired recovery after acute pontine stroke.

BACKGROUND: Recovery from stroke is presumed to be a function of a widespread cerebral network. Chronic white matter lesions (WML) have been proposed to be a predictor of poor outcome after acute stroke. We tested the hypothesis that the extent of WML has an effect on functional recovery in acute pontine stroke by disrupting the integrity of the supratentorial cerebral network. METHODS: Seventeen patients with acute unilateral pontine stroke who had received a standardized stroke workup and additional diffusion tensor imaging (DTI) were studied. After grading the extent of WML according to the Fazekas scale and semiautomated lesion volume calculation, we compared patients with acute pontine infarction and advanced WML to those with absent or minimal WML regarding baseline characteristics, stroke subtype and clinical outcome. In addition, we used tract-based spatial statistics for voxel-wise analysis of the DTI-derived parameter fractional anisotropy in the white matter tracts. RESULTS: The volume of WML ranged between 0.1 and 42.1 cm³ (mean = 15.9) and was graded as follows: 0 in 5.9%, 1 in 35.3%, 2 in 41.2% and 3 in 17.6%. Both patients with Fazekas grades 2-3 (p = 0.014) as well as those with larger WML volumes (p = 0.037) had severer functional deficits at the 3-month follow-up. White matter tracts displaying a significant decrease in fractional anisotropy values were the corpus callosum, the anterior thalamic radiation and the inferior fronto-occipital fasciculus. CONCLUSIONS: Chronic WML contribute to a less favorable clinical outcome after pontine stroke depending on (1) the extent of pre-existing WML and (2) the degree of disruption of cerebral connectivity as indicated by reduced tissue integrity in the white matter not affected by WML as detected by DTI and tract-based spatial statistics.

Recent advances in magnetic resonance imaging in posterior circulation stroke: implications for diagnosis and prognosis.

OPINION STATEMENT: For some time, posterior circulation stroke has been neglected in diagnostic and therapeutic studies for various reasons, such as minor incidence compared to anterior circulation stroke or anatomical and vascular characteristics. This changed at least partly when the New England Medical Center (NEMC) Posterior Circulation Registry was initiated, and now the number of publications concerning posterior circulation stroke is continuously increasing. Whether the differences outweigh the similarities between posterior and anterior circulation stroke remains open to debate, but both are the subject of intensive investigations. In this article, we review the most recent literature on different MRI techniques, such as diffusion-weighted and diffusion tensor imaging (DWI and DTI), perfusion-weighted imaging (PWI), vascular imaging, and susceptibility weighted imaging (SWI), in posterior circulation stroke and discuss their diagnostic and prognostic impact as well as general implications for acute treatment.

Exploring joint patterns of brain structure and function in inflammatory bowel diseases using multimodal data fusion.

BACKGROUND: A growing number of neuroimaging studies suggest distinct neural changes in inflammatory bowel diseases (IBDs). Whether such changes may show similar spatial patterns across distinct neural features within and between specific IBD is unclear. To address this question, we used multivariate multimodal data fusion analysis to investigate structure/function modulation in remitted patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Patients with IBD (n = 46; n = 31 with CD, n = 15 with UC) in stable remission and 17 healthy controls (HC) underwent structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI) as well as cognitive testing. Anxiety, depression, and fatigue were assessed using self-rating questionnaires. sMRI data were analyzed via voxel-based morphometry (VBM) and rs-fMRI data via amplitude of low-frequency fluctuations (ALFFs) and regional homogeneity (ReHo). Detection of cross-information between VBM, ALFF, and ReHo was conducted by means of a joint independent component analysis (jICA), followed by group-inference statistics. KEY RESULTS: Joint independent component analysis detected structural alterations in middle frontal and temporal regions (VBM), and functional changes in the superior frontal gyrus (ReHo) and the medial as well as inferior frontal, inferior temporal, rectal, and subcallosal gyrus (ALFF). One joint component of extracted features of the three modalities differed significantly between IBD patients and controls (p = 0.03), and most distinctly between HC and patients with UC. CONCLUSIONS AND INFERENCES: Using a multivariate data fusion technique, this study provides further evidence to brain alterations in IBD. The data suggest distinct neural differences between CD and UC, particularly in frontotemporal regions.

Dynamic susceptibility contrast perfusion MRI identifies persistent vessel pathology in acute pontine stroke.

BACKGROUND: In large territorial stroke of the anterior and the posterior circulation, the extent of affected tissue can be characterized by the demonstration of vessel occlusion on MR angiography (MRA), while the extent of hypoperfusion can be shown on dynamic susceptibility contrast perfusion-weighted MRI (PWI). The ability of MRA and conventional MRI sequences to demonstrate branches of the basilar artery (BA) is very limited. This study analyzes the value of the combined use of diffusion-weighted MRI (DWI), MRA and PWI in acute pontine stroke. METHODS: A series of 24 consecutive patients with acute pontine stroke received an extensive MRI stroke workup including DWI, PWI and MRA. RESULTS: In 11/24 patients visual analysis of PWI demonstrated persisting hypoperfusion, and in 1/24 patients indication of hyperperfusion was found. Vessel abnormalities were seen in 19/24 patients (15/24 hypoplastic vertebral artery, 9/24 stenosis or occlusion of the BA, 1/20 ectatic BA). Persistent pontine hypoperfusion was more frequently associated with BA pathology (9/11 vs. 1/13, p = 0.001), large-vessel disease (8/11 vs. 1/13; p = 0.001) and a more pronounced clinical deficit (NIHSS score on day 1: 7 vs. 3, p = 0.01). CONCLUSIONS: In pontine ischemia areas of hypoperfusion can be identified due to the strong contrast induced by ischemia on PWI and can be easily related to DWI lesion size. This is of use particularly as small vessels are frequently missed by MRA and occlusion of the BA can be better characterized with the help of PWI.

Diffusion-weighted MRI in transient global amnesia and its diagnostic implications.

OBJECTIVE: To analyze how the evidence of hippocampal diffusion-weighted imaging (DWI) lesions may support the clinical diagnosis of transient global amnesia (TGA). METHODS: In this retrospective observational study, 390 consecutive patients with isolated TGA were analyzed, who were evaluated at our institution between July 1999 and August 2018. The size, location, and number of lesions and time-dependent lesion detectability were examined. The incidence of DWI lesions was reviewed with regard to different levels of clinical diagnostic certainty upon presentation to the emergency department. RESULTS: Hippocampal DWI lesions were detected in 272 (70.6%) patients with TGA, with a mean of 1.05 ± 0.98 (range 0-6) and a mean lesion size of 4.01 ± 1.22 mm (range 1.7-8.6 mm). In the subgroups of lower diagnostic certainty (amnesia witnessed by layperson or self-reported amnestic gap), DWI was helpful in supporting the diagnosis of TGA in 76 (69.1%) patients. In 187 patients with information about the exact onset, DWI lesions were analyzed in relation to latency between onset and MRI. Lesions could be detected at all time points and up to 6 days after symptom onset in individual patients; the highest rate of DWI-positive MRI (93%) was in the 12-24 hours time window. CONCLUSION: MRI findings can support the diagnosis of TGA and may be particularly valuable in situations of low clinical certainty. DWI-ideally performed with a minimum delay of 20 hours after onset-should therefore be considered a useful adjunct to the diagnosis of TGA.

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. CONCLUSIONS: 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.

Selective disruption of hippocampus-mediated recognition memory processes after episodes of transient global amnesia.

Transient global amnesia (TGA) is characterized by the abrupt onset of severe amnesia without concomitant focal neurological symptoms. Recent studies revealed that small and punctate MR-signal diffusion-weighted imaging (DWI) lesions can be found within the hippocampus of TGA patients during the post-acute phase. On the basis of dual-process models of recognition memory, the present study examined the hypothesis that hippocampal dysfunction as suggested by these DWI lesions disrupts hippocampus-mediated recollection in patients with TGA, whereas familiarity-based recognition memory that is assumed to be supported by extra-hippocampal brain regions should be unaffected. We administered a recognition memory task for faces and words to eleven TGA patients during the post-acute phase and to eleven matched controls. Receiver operating characteristics (ROCs) were obtained in order to derive estimates of familiarity and recollection by applying a formal dual-process model of recognition memory. Analyses of ROC curves revealed a disruption of recollection in TGA patients' memory for words [t(20)=2.70, p<.05], but no difference in familiarity-based recognition memory between patients and controls [t(20)=-1.10, p=.284]. Post hoc analyses indicated that the deficit in recollection is more pronounced in TGA patients who show visible hippocampal lesions on diffusion-weighted MR imaging compared to those without detectable hippocampal lesions. In conclusion, consistent with recent neuroanatomical dual-process models of recognition memory, hippocampal dysfunction in patients with TGA is associated with a selective effect on specific recognition memory subprocesses.

TIMP-2 gene polymorphism is associated with intracerebral hemorrhage.

BACKGROUND: Both ischemic stroke and intracerebral hemorrhage are associated with altered expression and activation of matrix metalloproteinases (MMPs). Particularly relevant are MMP-2 and MMP-9. This proteolytic effect is dampened by tissue inhibitors of metalloproteinases (TIMPs). TIMP-2 is an important endogenous inhibitor of MMP-2. Alterations in the TIMP-2 gene expression may contribute to the incidence of ischemic stroke and intracerebral hemorrhage. METHODS: TIMP-2 gene SNP -261G/A was genotyped from sequentially recruited stroke patients (n = 356, f/m 151/205, mean age 68.2 years, range 19-100 years) and gender and age matched controls (n = 253, f/m 114/139, mean age 68.5 years, range 32-92 years). The SNP -261G/A was detected after gene sequencing of 95 patients and controls. Furthermore, in a subgroup of 93 patients the serum levels of TIMP-2 were measured during the first 7 days after stroke onset and compared to the genotype. RESULTS: SNP -261G/A in the TIMP-2 gene shows an allele frequency of approximately 39.14%. Homozygosity for allele A is associated significantly with the development of ICH (p = 0.025, OR = 2.020, CI = 1.115-3.661) as compared to heterozygosity and homozygosity for allele G (recessive genotypic model). Concordantly, the serum levels of TIMP-2 showed a nonsignificant decreases, depending on the genotype (p = 0.111). CONCLUSION: We investigated a SNP 261 base pairs upstream of the start codon in exon 1 of TIMP-2. Our data suggest that carriers of homozygosity for allele A are at increased risk of developing intracerebral hemorrhage.

Enhanced cortisol secretion in acute transient global amnesia.

INTRODUCTION: Stress-related transient inhibition of memory formation in the hippocampus has been hypothesized as one of the underlying pathomechanisms of transient global amnesia (TGA). TGA episodes, during which patients cannot encode and recall new information (anterograde amnesia affecting episodic long-term memory), are frequently preceded by a psychologically or physically stressful event. METHODS: We measured salivary cortisol during acute TGA in 14 patients, as well as cortisol day-profiles and the effect of experimental exposure to stress (using the socially evaluated cold pressor test) on cortisol levels during the subacute phase. We assessed psychiatric comorbidity as well as depression, trait anxiety and chronic stress. These findings were compared with data of 20 healthy controls. FINDINGS: Nine patients reported a precipitating stressor and all 14 developed typical hippocampal lesions on follow-up MRI. During TGA, salivary cortisol levels were more than 3-fold higher compared to time-matched day levels. While there was no difference in mean cortisol levels of the diurnal rhythm, we found a significant interaction between groups during experimental stress exposure (p = 0.049) with the TGA group revealing a higher cortisol increase. The TGA group reported higher levels of depressive symptomatology (CES-D) and higher scores of chronic stress (TICS) compared with the control group and there was a significant correlation between cortisol increase during TGA and the results of self-rating according to the CES-D (r = 0.615; p = 0.004), as well as to the STAI (r = 0.702; p = 0.001). CONCLUSION: Our findings of enhanced secretion of cortisol in acute TGA patients correlating with symptoms of depression and anxiety and a persisting hyperreactivity to experimental stress in the subacute phase support the hypothesis that stress might be significant for the pathogenesis of TGA.

Resting-state connectivity alterations during transient global amnesia.

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.