When Atrial Fibrillation Meets Cerebral Amyloid Angiopathy: Current Evidence and Strategies.

Non-valvular atrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) are two common diseases in elderly populations. Despite the effectiveness of oral anticoagulant therapy in cardioembolic stroke prevention, intracranial hemorrhage represents the most serious complication of these therapies. Cerebral amyloid angiopathy is one of the main risk factors for spontaneous intracranial bleeding, and this risk is highly increased by age and concomitant antithrombotic therapies. Cerebral amyloid angiopathy can be silent for years and then manifest with clinical features simulating TIA (TIA-mimics) or stroke in AF patients, pushing clinicians to rapidly start VKAs or DOACs, thus increasing the risk of intracranial bleeding if the diagnosis of CAA was unknown. Because the cerebral amyloid angiopathy is easily diagnosed with non-contrast MRI, suspecting the disease can avoid catastrophic complications. In this review, we will provide physicians managing anticoagulant therapies with key tips to familiarize themselves with cerebral amyloid angiopathy, with a focus on the possible clinical presentations and on the diagnostic criteria.

Focal bilateral motor seizures precipitated by abrupt cessation of chronic lormetazepam abuse and amitriptyline overdose.

We report the case of an adult psychiatric patient who developed new-onset focal bilateral motor seizures (FBMS) in the context of a severe benzodiazepine withdrawal syndrome. The patient was forced to interrupt chronic lormetazepam abuse and overdosed on amitriptyline (800 mg in an oral solution) before the onset of seizures. Typical signs of amitriptyline intoxication such as sedation and anticholinergic effects were not observed. Video-EEG recordings revealed a stereotypical ictal motor pattern with asymmetric tonic posturing and bilateral clonic movements of the upper limbs, but there were no abnormalities identified by EEG. Seizures recurred multiple times per day but resolved simultaneously when withdrawal symptomatology subsided eight days after onset. Nonepileptic seizures (NES) were considered in the differential diagnosis because of the patient's psychiatric history including preserved awareness during the bilateral convulsions, the absence of postictal confusion, and normal EEG. The present case indicates that FBMS may occur during benzodiazepine withdrawal in patients who overdosed on amitriptyline. The diagnosis may be challenging as FBMS may mimic NES in the absence of abnormal neurophysiologic findings. This may be especially challenging in patients with an underlying psychiatric disease.

Left Atrial Appendage Occlusion in High Bleeding Risk Patients.

OBJECTIVES: The aim of this study was to investigate the outcomes of left atrial appendage occlusion (LAAO) in high bleeding risk patients suffering atrial fibrillation (AF) and to analyze the different antithrombotic therapies following the intervention. BACKGROUND METHODS: This monocentric study included 68 patients with nonvalvular AF with an absolute contraindication to OAT or at high bleeding risk. Follow-up was done with a clinical visit at 3-6-12 months. RESULTS: Successful LAAO was achieved in 67/68 patients. At discharge, 32/68 patients were on dual antiplatelet therapy (APT), 34/68 were without any antithrombotic therapy or with a single antiplatelet drug, and 2/68 were on anticoagulant therapy. At three-month follow-up visit, 73.6% of the patients did not receive dual APT, of whom 14.7% had no thrombotic therapy and 58.9% were on single antiplatelet therapy. During a follow-up of 1.4 ± 0.9 years, 3/62 patients had late adverse effects (2 device-related thrombus without clinical consequences and 1 extracranial bleeding). The device-related thrombosis was not related to the antithrombotic therapy. CONCLUSIONS: LAAO is feasible and safe and prevents stroke in patients with AF with contraindication to oral anticoagulant therapy. After LAAO, single antiplatelet therapy seems to be a safe alternative to dual antiplatelet therapy, especially in patients at high bleeding risk. No benefit has been observed with dual APT.

[Cerebral amyloid angiopathy and atrial fibrillation: a dangerous union]. / Angiopatia amiloide cerebrale e fibrillazione atriale: un pericoloso connubio.

Intracranial hemorrhage (ICH) is the major complication of oral anticoagulant therapy. Cerebral amyloid angiopathy (CAA) is an age-related disease characterized by the pathological deposition of ß-amyloid protein in leptomeningeal and cortical cerebral vessels. Such vascular alterations expose to the risk of spontaneous vascular rupture. The main clinical manifestations are represented by ICH, cognitive decline and transient focal neurological episodes (TFNE). In the patient subgroup with TFNE, a misdiagnosis with transient ischemic attack may have catastrophic consequences, resulting in a significant increase in the risk of spontaneous ICH within weeks after clinical onset, with potentially devastating consequences if anticoagulant therapy is started.The prevention of bleeding complications related to CAA is based on disease knowledge. This is particularly relevant because non-pharmacological treatment options, including percutaneous left atrial appendage occlusion, are emerging as an alternative to traditional anticoagulant therapies in patients at high bleeding risk.

Restoring consciousness with vagus nerve stimulation.

Patients lying in a vegetative state present severe impairments of consciousness [1] caused by lesions in the cortex, the brainstem, the thalamus and the white matter [2]. There is agreement that this condition may involve disconnections in long-range cortico-cortical and thalamo-cortical pathways [3]. Hence, in the vegetative state cortical activity is 'deafferented' from subcortical modulation and/or principally disrupted between fronto-parietal regions. Some patients in a vegetative state recover while others persistently remain in such a state. The neural signature of spontaneous recovery is linked to increased thalamo-cortical activity and improved fronto-parietal functional connectivity [3]. The likelihood of consciousness recovery depends on the extent of brain damage and patients' etiology, but after one year of unresponsive behavior, chances become low [1]. There is thus a need to explore novel ways of repairing lost consciousness. Here we report beneficial effects of vagus nerve stimulation on consciousness level of a single patient in a vegetative state, including improved behavioral responsiveness and enhanced brain connectivity patterns.

Pseudotumoral presentation of cerebral amyloid angiopathy-related inflammation.

OBJECTIVE: To identify the clinical and radiologic features that should raise suspicion for the pseudotumoral presentation of cerebral amyloid angiopathy-related inflammation (CAA-I). METHODS: We retrospectively reviewed the characteristics of 5 newly diagnosed and 23 previously reported patients in whom the CAA-I imaging findings were initially interpreted as CNS neoplasms. RESULTS: Most cases (85%) occurred in patients >60 years old. The clinical characteristics at presentation included subacute cognitive decline (50%), confusion (32%), focal deficits (32%), seizures (25%), and headaches (21%). Brain MRI demonstrated infiltrative white matter lesions that exhibited a loco-regional mass effect without parenchymal enhancement (93%). In general, these findings were interpreted as low-grade glioma or lymphoma. Eighteen patients (64%) underwent a biopsy, which was nondiagnostic in 4 patients (14%), and 6 patients (21%) underwent a surgical resection. The primary reason for the misinterpretation of the imaging findings was the absence of T2*-weighted gradient recalled echo (T2*-GRE) sequences on initial imaging (89%). When subsequently performed (39%), the T2*-GRE sequences demonstrated multiple characteristic cortical and subcortical microhemorrhages in all cases. Perfusion MRI and magnetic resonance spectroscopy (MRS), which were performed on a subset of patients, indicated markedly reduced relative cerebral blood flow and a normal metabolic ratio. CONCLUSION: The identification of one or several nonenhancing space-occupying lesions, especially in elderly patients presenting with cognitive impairment, should raise suspicion for the pseudotumoral presentation of CAA-I and lead to T2*-GRE sequences. Perfusion MRI and MRS appear to be useful techniques for the differential diagnosis of this entity.

Early Blood Brain Barrier Changes in Acute Ischemic Stroke: A Sequential MRI Study.

BACKGROUND AND PURPOSE: We sought to identify MRI factors associated with BBB changes at the acute stage of ischemic stroke. METHODS: We analyzed BBB changes on admission and within 3 hours after the first scan. BBB changes was defined as the presence of leptomeningeal and parenchymal contrast enhancement on T1-weighted imaging. Tmax , CBV, and DWI lesion volume were assessed on baseline MRI. Clinical and MRI factors associated with BBB changes were assessed by univariate and multivariate logistic regressions analyses. RESULTS: Forty-four patients were included. BBB changes on baseline MRI was observed in 2 of 44 patients (3%). BBB disruption on H3-MRI was present in 19 of 44 patients (43%). Hemodynamic status and baseline ischemic core size were not different between patients with or without BBB changes. BBB alteration on H3 MRI was strongly associated with FLAIR MRI sequence positivity, 16/19 patients (83%) P = .001. CONCLUSION: BBB changes are exceptional during the first 3 hours after stroke onset. Delayed BBB alteration was associated with FLAIR positivity mainly reflecting vasogenic edema.

Theta signal as the neural signature of social exclusion.

The feeling of being excluded from a social interaction triggers social pain, a sensation as intense as actual physical pain. Little is known about the neurophysiological underpinnings of social pain. We addressed this issue using intracranial electroencephalography in 15 patients performing a ball game where inclusion and exclusion blocks were alternated. Time-frequency analyses showed an increase in power of theta-band oscillations during exclusion in the anterior insula (AI) and posterior insula, the subgenual anterior cingulate cortex (sACC), and the fusiform "face area" (FFA). Interestingly, the AI showed an initial fast response to exclusion but the signal rapidly faded out. Activity in the sACC gradually increased and remained significant thereafter. This suggests that the AI may signal social pain by detecting emotional distress caused by the exclusion, whereas the sACC may be linked to the learning aspects of social pain. Theta activity in the FFA was time-locked to the observation of a player poised to exclude the participant, suggesting that the FFA encodes the social value of faces. Taken together, our findings suggest that theta activity represents the neural signature of social pain. The time course of this signal varies across regions important for processing emotional features linked to social information.

Objective response to radiation therapy and long-term survival of patients with WHO grade II astrocytic gliomas with known LOH 1p/19q status.

BACKGROUND: WHO grade II gliomas are often approached by radiation therapy (RT). However, little is known about tumor response and its potential impact on long-term survival. PATIENTS AND METHODS: Patients subjected to RT were selected from the own database of WHO grade II gliomas diagnosed between 1991 and 2000. The volumetric tumor response after RT was assessed based on magnetic resonance imaging and graded according to standard criteria as complete, partial (PR, >or= 50%), or minor (MR, 25% to <50%). RESULTS: There were 24 astrocytomas and three oligoastrocytomas. 21 patients (78%) were dead at follow-up (mean survival 74 months). None of the patients had chemotherapy. Objective response occurred in 14 patients (52%, five PR and nine MR) but was not associated with overall survival. The vast majority of the tumors had no loss of heterozygosity (LOH) 1p and/or 19q (86%). CONCLUSION: Approximately 50% of patients with astrocytic WHO grade II gliomas respond to RT despite the absence of LOH for 1p/19q. The potential predictive factors for response and the impact of response on overall survival remain unclear.

Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy.

PURPOSE: This study was conducted to elucidate the impact of loss of heterozygosity (LOH) for chromosomes 1p36 and 19q13 on the overall survival of patients with diffusely infiltrating WHO grade 2 gliomas treated without chemotherapy. PATIENTS AND METHODS: We assessed the LOH status of tumors from patients harboring WHO grade 2 gliomas diagnosed between 1991 and 2000. Patients were either followed after initial biopsy or treated by surgery and/or radiation therapy (RT). Overall survival, time to malignant transformation, and progression-free survival were last updated as of March 2005. RESULTS: Of a total of 79 patients, LOH 1p36 and LOH 19q13 could be assessed in 67 and 66 patients, respectively. The median follow-up after diagnosis was 6 years. Loss of either 1p or 19q, in particular codeletion(s) at both loci, was found to positively impact on both overall survival (log-rank P < .01), progression-free survival, and survival without malignant transformation (P < .05). Tumor volume (P < .0001), neurologic deficits at diagnosis (P < .01), involvement of more than one lobe (P < .01), and absence of an oligodendroglial component (P < .05) were also predictors of shorter overall survival. The extent of surgery was similar in patients with or without LOH 1p and/or 19q; RT was more frequently resorted to for patients without than for patients with LOH 1p/19q (30% v 60%). CONCLUSION: The presence of LOH on either 1p36 or 19q13, and in particular codeletion of both loci is a strong, nontreatment-related, prognostic factor for overall survival in patients with diffusely infiltrating WHO grade 2 gliomas.