Incidence of silent cerebral infarctions after catheter ablation of atrial fibrillation utilizing the second-generation cryoballoon.

AIMS: Pulmonary vein (PV) isolation (PVI) utilizing a cryoballoon (CB) has become one of the standard therapeutic options for atrial fibrillation (AF). However, it connotes a potential risk of cerebral ischaemic events (CIEs). This study aimed to clarify the prevalence of CIEs after PVI using second-generation CBs assessed by magnetic resonance imaging (MRI) of the brain. METHODS AND RESULTS: This prospective observational study consisted of 160 patients that underwent PVI with second-generation CBs for drug-refractory AF. Irrigated radiofrequency (RF) ablation for 'touch-up' procedures was utilized when conduction gaps between the left atrium (LA) and PVs were found after the CB application. Radiofrequency linear ablation was added in select patients. Cerebral MRI and neurological examinations were performed on the day following the ablation procedure. The MRI depicted micro-cerebral infarctions in 43 patients (26.9%, 1.49 lesions per case). All patients were free from symptomatic focal neurological deficits. Touch up ablation was required for the PVI establishment in 35 patients (21.9%). Linear ablation was performed in 59 patients (36.9%). Additional RF ablation within the LA was an independent risk of CIEs in the uni- and multivariate analyses. When the analyses were limited to patients who had undergone only CB ablation, CIEs were found in 12 of 66 patients (18.2%). CONCLUSION: Pulmonary vein isolation utilizing second-generation CBs carries a negligible risk of symptomatic CIEs; however, it includes a comparable risk of asymptomatic CIEs as in the previous similar reports using the first-generation CB. Radiofrequency applications in addition to the CB within the LA were the only predictor of this adverse effect.

A Score for Predicting Paroxysmal Atrial Fibrillation in Acute Stroke Patients: iPAB Score.

BACKGROUND: Detection of paroxysmal atrial fibrillation (PAF) after a stroke is challenging. The purpose of this study was to develop a clinical score to predict PAF in a cohort of acute ischemic stroke patients prospectively and to validate it in an independent cohort. METHODS: Consecutive acute ischemic stroke patients without permanent atrial fibrillation were enrolled in a derivation sample (n = 294) or a validation sample (n = 155). We developed a score for predicting PAF by independent risk factors derived from a logistic regression analysis of the derivation cohort and validated the score in the external cohort. RESULTS: Multivariate analysis in the derivation cohort identified 3 variables independently associated with PAF. We calculated a score from these variables (history of arrhythmia or antiarrhythmic agent use [yes, 3 points], left atrial dilation [≥40 mm, 1 point], brain natriuretic peptide [BNP, ≥50 pg/mL, 1 point; ≥90 pg/mL, 2 points; ≥150 pg/ml, 3 points], total score, 0-7). The iPAB score (identified by past history of arrhythmia or antiarrhythmic agent use, atrial dilation, and BNP elevation) predicted PAF in the derivation (c statistic, .90) and validation (.94) cohorts at levels statistically superior to other biomarkers and clinical scores. For a total score 2 or more, the sensitivity and specificity were 93% and 71%, respectively. For a total score of 4 or more, the corresponding values were 60% and 95%. CONCLUSIONS: Our prospective study suggests that this simple risk score superior to other scores help clinicians predict PAF or identify good candidates for further evaluation to detect PAF.

Three-layered structure shared between Lewy bodies and lewy neurites-three-dimensional reconstruction of triple-labeled sections.

Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD). Although LBs and LNs, frequently coexistent, share some histological properties, their appearances are quite different under conventional two-dimensional observation. In order to clarify how these apparently different structures (LBs and LNs) are related during their formation, we performed three-dimensional observation on post-mortem brainstem tissues with PD. Sixty-microm thick floating sections were multi-immunofluorolabeled for alpha-synuclein (alphaS), ubiquitin (Ub) and neurofilament (NF). Serial confocal images were reconstructed with software. External three-dimensional configuration of LBs, double-labeled for alphaS and NF, exhibited frequent continuity with LNs (70%). Internally, alphaS and Ub formed the three-dimensional concentric inner layers and NF rimmed these inner layers. This layered structure was shared among spherical LBs, rod-shaped LNs and even convoluted forms of LBs/LNs. Furthermore, each layer exhibited continuity without interruption even in the convoluted form and around its junction to spherical LBs. This three-layered structure shared among various Lewy pathologies and their layered continuity on three-dimensional basis favor the hypothesis that LNs evolve into LBs. Besides progression from pale bodies to LBs, structural evolution from LNs into LBs may provide an alternative explanation for the variability of alphaS deposits and their interrelation.

[Bilateral medial medullary infarction presented with monoplegia of the lower limb, followed by paraplegia and finally by tetraplegia].

A 69-year-old Japanese man suddenly developed monoplegia of left lower extremity, followed by paraplegia and finally by tetraplegia. MRI revealed an infarction in bilateral medial medulla extending from the cervicomedullary junction up to the upper limit of the medulla. Both hypoglossal nerve palsy and sensory disturbance were absent. At the pyramidal decussation, fibers to the lower extremities cross caudal to the fibers going to the upper extremities, therefore right below the decussation, fibers to the lower extremities run medial side of the fibers to the upper extremities, but later the former run lateral side of the latter. In this patient, the authors considered that the lesion initially damaged the pyramidal decussation at a slightly lower level, involving the tract to left lower extremity, and then extended to right lower extremity, to the left upper extremity, finally to the right upper extremity. Bilateral medial medullary infarction must be considered in the clinical course seen as in this patient.

Pale neurites, premature α-synuclein aggregates with centripetal extension from axon collaterals.

Progressive aggregation of α-synuclein (αS) from pale bodies (PBs) and extension from Lewy neurites (LNs) are candidate mechanisms for Lewy body (LB) formation. To identify how aggregation of αS is related to its extension along neurites, 60-µm-thick brainstem sections of Parkinson disease (PD) patients were prepared for three-dimensional (3D) reconstruction of αS-positive neurites with neurofilament (NF) and thiazin red (TR), a fluorochrome with an affinity to solid aggregates. This demonstrated 3D layering of αS surrounded by NF with the aggregates probed by TR in the center, corresponding to the eosinophilic core of mature LBs. This eosinophilic/TR-positive profile, characteristically absent in PBs, premature counterpart of LBs, was similarly absent in some LNs. We would like to refer these premature LNs as "pale neurites" (PNs). Their premature nature was evidenced by 3D fluoroprofiling with quantum dots (QDs) and subsequent electron microscopic identification (3D-oriented immunoelectron microscopy) as loosely packed αS (QDs)-positive filaments. Quantification of LNs, frequently extended around branching axons, demonstrated that LNs are initiated at axon collaterals to extend centripetally into proximal segments. This branching-oriented extension of αS is related to its selective predisposition to systems with highly divergent axons, preferentially affected in PD, which may explain barely somatotopic manifestations of PD.

Degeneration of cardiac sympathetic nerve can occur in multiple system atrophy.

Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [(123)I] MIBG myocardial scintigraphy, a sensitive biological marker for Parkinson's disease (PD), is related to cardiac sympathetic denervation in patients with PD. A slight decrease in cardiac uptake of MIBG has also been reported in some patients with multiple system atrophy (MSA). However, the pathophysiological mechanism accounting for the slight decrease in MIBG uptake in MSA remains to be elucidated. For confirmation, we examined cardiac tissue and sympathetic ganglia from patients with MSA. We immunohistochemically examined each specimen of 15 patients with MSA together with 10 control subjects using antibodies against tyrosine hydroxylase (TH) and neurofilament (NF). The number of TH-immunoreactive nerve fibers in the epicardium was preserved in 8 of 15 patients with MSA as well as in 10 control subjects. The number of TH-immunoreactive, but not of NF-immunoreactive nerve fibers in the epicardium was mildly or moderately decreased in six patients with MSA, of whom four showed a decrease of TH immunoreactivity in the neuronal somata in the sympathetic ganglia. Moreover, TH- and NF-immunoreactive nerve fibers almost entirely disappeared in the heart of one patient with MSA, in whom Lewy body pathology was present in the sympathetic ganglia. These findings suggest that mild degeneration of the cardiac sympathetic nerve can occur in MSA which is closely related to the pathological change of neurons in the sympathetic ganglia, accounting for the slight decrease in cardiac uptake of MIBG. Moreover, concurrent Lewy body pathology in the sympathetic ganglia might accelerate cardiac sympathetic denervation even in MSA.