Juan M. Racosta

Atrial Fibrillation Detected after Acute Ischemic Stroke: Evidence Supporting the Neurogenic Hypothesis

BACKGROUNDnIt is unknown whether atrial fibrillation (AF) detected after acute ischemic stroke is caused by neurogenic or cardiogenic mechanisms. Based on the potential damage to the autonomic nervous system, neurogenic mechanisms could be implicated in the pathophysiology of newly diagnosed AF. To test this hypothesis, we developed a mechanistic approach by comparing a prespecified set of indicators in acute ischemic stroke patients with newly diagnosed AF, known AF, and sinus rhythm.nnnMETHODSnWe prospectively assessed every acute ischemic stroke patient undergoing continuous electrocardiographic monitoring from 2008 through 2011. We compared newly diagnosed AF, known AF, and sinus rhythm patients by using 20 indicators grouped in 4 domains: vascular risk factors, underlying cardiac disease, burden of neurological injury, and in-hospital outcome.nnnRESULTSnWe studied 275 acute ischemic stroke patients, 23 with newly diagnosed AF, 64 with known AF, and 188 with sinus rhythm. Patients with newly diagnosed AF had a lower proportion of left atrial enlargement (60.9% versus 91.2%, P=.001), a smaller left atrial area (22.0 versus 26.0 cm2, P=.021), and a higher frequency of insular involvement (30.4% versus 9.5%, P=.017) than participants with known AF. Compared with patients in sinus rhythm, those with newly diagnosed AF had a higher proportion of brain infarcts of 15 mm or more (60.9% versus 37.2%, P=.029) and a higher frequency of insular involvement (30.4% versus 7.3%, P<.001).nnnCONCLUSIONSnThe low frequency of underlying cardiac disease and the strikingly high proportion of concurrent strategic insular infarctions in patients with newly diagnosed AF provide additional evidence supporting the role of neurogenic mechanisms in a subset of AF detected after acute ischemic stroke.

School performance as a marker of cognitive decline prior to diagnosis of multiple sclerosis

Background: For many years, cognitive impairment has been established as a well-known symptom of multiple sclerosis. Moreover, we know that it was present even at the beginning of the disease. Objective: In this case-control study, we decided to evaluate whether there is an impairment of cognitive functions even before onset in those patients who will eventually suffer from multiple sclerosis. Methods: We evaluated the overall school performance, and particularly school performance in math and language in a group of patients who would later develop the disease and we compared our findings with a control group. Results: We found that school performance was poorer in subjects who were to become patients. And we found that the later the start of the first symptom, the better the qualifications. Conclusion: Testing a premorbid cognitive deficit by a validated indirect evaluation method allowed us to verify that there was evidence of neurological compromise even before a clinical diagnosis or the completion of the first magnetic resonance imaging in patients who would then suffer from multiple sclerosis.

Subcutaneous vs. Intravenous Immunoglobulin for Chronic Autoimmune Neuropathies: A Meta-analysis

Introduction: High‐dose intravenous immunoglobulin (IVIg) is an evidence‐based treatment for multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). Recently, subcutaneous immunoglobulin (SC‐Ig) has received increasing attention. Methods: We performed a meta‐analysis of reports of efficacy and safety of SC‐Ig versus IVIg for inflammatory demyelinating polyneuropathies. Results: A total of 8 studies comprising 138 patients (50 with MMN and 88 with chronic CIDP) were included in the meta‐analysis. There were no significant differences in muscle strength outcomes in MMN and CIDP with Sc‐Ig (MMN: effect size [ES] = 0.65, 95% confidence interval [CI] = ‐0.31‐1.61; CIDP: ES = 0.84, 95% CI = ‐0.01‐1.69). Additionally SC‐Ig had a 28% reduction in relative risk (RR) of moderate and/or systemic adverse effects (95% CI = 0.11‐0.76). Conclusions: The efficacy of SC‐Ig is similar to IVIg for CIDP and MMN and has a significant safety profile. Muscle Nerve 55: 802–809, 2017

Newly diagnosed atrial fibrillation linked to wake-up stroke and TIA: Hypothetical implications

Background: Based on the higher frequency of paroxysmal atrial fibrillation during night and early morning hours, we sought to analyze the association between newly diagnosed atrial fibrillation and wake-up ischemic cerebrovascular events. Methods: We prospectively assessed every acute ischemic stroke and TIA patient admitted to our hospital between 2008 and 2011. We used a forward step-by-step multiple logistic regression analysis to assess the relationship between newly diagnosed atrial fibrillation and wake-up ischemic stroke or TIA, after adjusting for significant covariates. Results: The study population comprised 356 patients, 274 (77.0%) with a diagnosis of acute ischemic stroke and 82 (23.0%) with TIA. A total of 41 (11.5%) of these events occurred during night sleep. A newly diagnosed atrial fibrillation was detected in 27 patients of 272 without known atrial fibrillation (9.9%). We found an independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA (odds ratio 3.6, 95% confidence interval 1.2–7.7, p = 0.019). Conclusions: The odds of detecting a newly diagnosed atrial fibrillation were 3-fold higher among wake-up cerebrovascular events than among non–wake-up events. The significance of this independent association between newly diagnosed atrial fibrillation and wake-up ischemic stroke and TIA and the role of other comorbidities should be investigated in future studies.

Autonomic dysfunction, immune regulation, and multiple sclerosis

ObjectiveTo review existing evidence regarding interactions between the autonomic nervous system and the immune system functions in multiple sclerosis.MethodsWe reviewed the literature regarding new insights linking autonomic dysfunction to immune deregulation in multiple sclerosis, with particular focus on the specific influence of sympathetic and parasympathetic dysfunction on inflammatory and neurodegenerative processes.ResultsAutonomic dysfunction is common in multiple sclerosis, representing a significant cause of disability. Several connections between pathologic immune pathways and the autonomic nervous system function were found.ConclusionsAutonomic dysfunction may enhance inflammatory and neurodegenerative pathways that are of major importance in multiple sclerosis. Autonomic dysfunction can present with highly variable manifestations. Sympathetic and parasympathetic dysfunction displays different patterns in multiple sclerosis, with specific impact on inflammation and neurodegeneration.

Cardiovascular autonomic dysfunction in multiple sclerosis: a meta-analysis.

BACKGROUND AND OBJECTIVEnThe definition of cardiovascular autonomic dysfunction in patients with multiple sclerosis is controversial. Thus, its true prevalence is unknown. We performed a systematic review and meta-analysis to compare the proportion of patients with multiple sclerosis that would be diagnosed with cardiovascular dysautonomia using a definition of at least one abnormal cardiac autonomic test vs. at least two abnormal studies.nnnMETHODSnWe searched PubMed, Embase, and Scopus from 1980 to December 2013 for publications reporting abnormal autonomic tests in patients with multiple sclerosis. We performed random-effects meta-analyses for calculating the proportion of patients diagnosed with autonomic dysfunction with both definitions.nnnRESULTSnWe included 16 studies comprising 611 patients with multiple sclerosis, assessing ≥3 cardiovascular autonomic tests. The proportion of patients with autonomic dysfunction was two-fold higher (p=0.006) when using the definition of only one abnormal autonomic test (42.1%) compared to that using at least two abnormal results (18.8%).nnnCONCLUSIONSnWe found a wide variation in the proportion of patients with multiple sclerosis diagnosed with cardiovascular dysautonomia by using the two definitions. Consensus is needed to define autonomic dysfunction in patients with multiple sclerosis. In the meantime, we encourage investigators to report results using both thresholds.

Autonomic dysfunction in multiple sclerosis

Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

The Role of Autonomic Dysregulation from Pathophysiology to Therapeutics ofMultiple Sclerosis: A Putative Novel Treatment Target?

Autonomic Nervous System (ANS) dysfunction (AuD) is a common cause of disability in people living with nMultiple Sclerosis (MS), but clinical manifestations are heterogeneous and therapeutic options are lacking. AuD is nimplicated as having a possible role in the regulation of inflammation and neurodegeneration. Hence, treatments nwith drugs that affect the ANS may have an impact in the inflammatory and neurodegenerative processes intrinsic to nMS, resulting in an intriguing and potentially significant novel therapeutic consideration. Additionally, just alike npatients with most other chronic diseases, MS patients often are exposed to a broad range of treatments both ndisease-specific and due to complications or co-morbidities. Considering them into an integrated context affords the nopportunity to understand and exploit their therapeutic potential.

Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE): A Translational, Integrated, and Transdisciplinary Approach

BACKGROUNDnIt has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart.nnnMETHODSnThe Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke.nnnCONCLUSIONSnPARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Autonomic function and brain volume

ObjectiveThe aim of this study is to review the evidence on the role of the autonomic nervous system as a determinant of brain volume. Brain volume measures have gained increasing attention given its biological importance, particularly as a measurement of neurodegeneration.MethodsUsing an integrative approach, we reviewed publications addressing the anatomical and physiological characteristics of brain autonomic innervation focusing on evidence from diverse clinical populations with respect to brain volume.ResultsMultiple mechanisms contribute to changes in brain volume. Autonomic influence on cerebral blood volume is of significant interest.ConclusionWe suggest a role for the autonomic innervation of brain vessels in fluctuations of cerebral blood volume. Further investigation in several clinical populations including multiple sclerosis is warranted to understand the specific role of parenchyma versus blood vessels changes on final brain volume.