Cardiovascular autonomic dysfunction after stroke.

Strokes are the paradigmatic example of the sudden impairment of the cerebral regulation of cardiac autonomic regulation. Although several aspects of dysautonomic cardiovascular regulation post stroke remain unanswered, there has been a wealth of research in this area in the last decade. In this article, we present a state-of-the-art review on the anatomical and functional organization of cardiovascular autonomic regulation, and the pathophysiology, incidence, time course, diagnosis, clinical aspects, prognosis, and management of post-stroke cardiovascular autonomic dysfunction.

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

BACKGROUND: It 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. METHODS: The 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. CONCLUSIONS: PARADISE 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.

Subcutaneous versus 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.

Autonomic function and brain volume.

OBJECTIVE: The 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. METHODS: Using 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. RESULTS: Multiple mechanisms contribute to changes in brain volume. Autonomic influence on cerebral blood volume is of significant interest. CONCLUSION: We 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.

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.

Screening of major depression in epilepsy: the Neurologic Depression Disorders Inventory in Epilepsy-Spanish version (Argentina).

OBJECTIVES: To validate and translate the English version of the Neurologic Depression Disorders Inventory in Epilepsy (NDDI-E) into Spanish as a screening instrument for major depressive episodes (MDE) for patients with epilepsy from Argentina and Uruguay. METHODS: One hundred fifty-five consecutive outpatients with epilepsy participated in this study. The module of MDE of the MINI International Neuropsychiatric Instrument (MINI Plus version) was used as the gold standard against which the translated version of the NDDI-E was validated. RESULTS: Among the 155 patients, 25 (16%) met Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) criteria for MDE according to the MINI. With a total score of >15, The NDDI-E identified MDE with an 80% sensitivity, 90% specificity, 60% positive predictive value, and 95.5% negative predictive value. SIGNIFICANCE: These data indicate that the Spanish version of the NDDI-E can reliably identify MDE in patients with epilepsy from Argentina and Uruguay.

Self-reported cognitive function mediates the relationship between employment status and cognitive functioning in persons with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is common in people with MS (PwMS). Evidence is lacking for the self-reported CI's mediation effect on employment status and objective cognitive performance. Self-reported CI was found to be unreliable and seemed to be more associated with depression rather than formal cognitive performance. We hypothesized that the link between subjective and objective assessments of cognitive functions, mood, and employment status may be more complex in PwMS than previously reported. OBJECTIVE: The aims of this study are the following: (Romero-Pinel et al., 2022) to determine whether employment status could affect performance in cognitive function testing and (Rao et al., 1991) whether their relationship may be mediated by self-reported CI; and (Deluca et al., 2013) to determine whether self-reported depression interacts with self-reported CI in influencing performance in various cognitive domains in PwMS. METHODOLOGY: A retrospective study was performed involving PwMS who completed the self-report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale-depression scale (HADS-D), Minimal Assessment of Cognitive Function in MS (MACFIMS) and had data regarding employment status. Included PwMS were classified as employed or unemployed. A structural equation modeling (SEM) approach was taken due to the advantage of examining multiple cognitive outcomes simultaneously while accounting for shared associations. First, a latent factor of memory and executive functioning modeled the error-free associations between both factors and a processing speed task (SDMT). Next, the model tested for the indirect effect of self-reported cognition (MSNQ) on employment status differences in each outcome (memory, speed, and executive functioning). Finally, we tested interactions between MSNQ and HADS-D on each of the outcomes. RESULTS: We included 590 PwMS: 72.5% female, mean age 44.2 years (SD = 10.5), mean disease duration 8.6 years (SD 9.0). The majority (n = 455, 77.1%) had relapsing MS; 357 (60.5%) were employed. About half (n = 301, 51%) did not report CI on the MSNQ; of those, 213 (70.8%) were employed. The mean MSNQ for employed PwMS was 24.5 (SD = 10.7) and 29.8 (SD = 11.2) for unemployed PwMS. Employed PwMS had significantly better memory (ß = .16, p < .05), executive functioning (ß = .25, p < .05), and processing speed (ß = .22, p < .05). MSNQ partially indirectly mediated the effect of employment status on memory (Δß = .03, p < .05) and executive functioning (Δß = .03, p < .05) and processing speed (Δß = .04, p < .05), indicating that self-report CI partially explains the influence of employment status on these cognitive domains. The association between MSNQ with both memory and executive functioning was moderated by depression, meaning that in PwMS with high HADS-D scores, MSNQ was more strongly related to worse memory and executive functioning. The final model was an acceptable fit to the data (χ2(87) = 465.07, p < .05; CFI = .90, RMSEA = .08, 90% CI [.06, .09], SRMR = .05) explaining 41.20%, 38.50% and 33.40% of the variability in memory, executive functioning, and processing speed, respectively. CONCLUSION: Self-reported CI partially explains the associations between employment status and objective cognitive assessment in PwMS. Depression may moderate the relationship between self-reported cognitive assessment and objective cognitive performance. Thus, employment status and mood may guide the interpretation of self-reported CI.

Atrial fibrillation detected after acute ischemic stroke: evidence supporting the neurogenic hypothesis.

BACKGROUND: It 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. METHODS: We 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. RESULTS: We 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). CONCLUSIONS: The 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.

Identifying specific myelopathy etiologies in the evaluation of suspected myelitis: A retrospective analysis.

BACKGROUND: Myelopathies require prompt etiologic diagnosis. We aimed to identify a specific myelopathy diagnosis in cases of suspected myelitis to highlight clinicoradiologic differences. METHODS: In this retrospective, single-centre cohort of subjects with suspected myelitis referred to London Multiple Sclerosis (MS) Clinic between 2006 and 2021, we identified those with MS and reviewed the remaining charts for etiologic diagnosis based on clinical, serologic, and imaging details. RESULTS: Of 333 included subjects, 318/333 (95.5%) received an etiologic diagnosis. Most (274/333, 82%) had MS or clinically isolated syndrome. Spinal cord infarction (n = 10) was the commonest non-inflammatory myelitis mimic characterized by hyperacute decline (n = 10/10, 100%), antecedent claudication (n = 2/10, 20%), axial owl/snake eye (n = 7/9, 77%) and sagittal pencillike (n = 8/9, 89%) MRI patterns, vertebral artery occlusion/stenosis (n = 4/10, 40%), and concurrent acute cerebral infarct (n = 3/9, 33%). Longitudinal lesions were frequent in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD) (n = 7/7, 100%) and myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) (n = 6/7, 86%), accompanied by bright spotty (n = 5/7, 71%) and central-grey-restricted (n = 4/7, 57%) T2-lesions on axial sequences, respectively. Leptomeningeal (n = 4/4, 100%), dorsal subpial (n = 4/4, 100%) enhancement, and positive body PET/CT (n = 4/4, 100%) aided the diagnosis of sarcoidosis. Spondylotic myelopathies had chronic sensorimotor presentations (n = 4/6, 67%) with relative bladder sparing (n = 5/6, 83%), localizable to sites of disc herniation (n = 6/6, 100%). Metabolic myelopathies showed dorsal column or inverted 'V' sign (n = 2/3, 67%) MRI T2-abnormality with B12 deficiency. CONCLUSIONS: Although no single feature reliably confirms or refutes a specific myelopathy diagnosis, this study highlights patterns that narrow the differential diagnosis of myelitis and facilitate early recognition of mimics.

Does multilingualism act as a protective factor (cognitive reserve) against cognitive impairment in multiple sclerosis?: A retrospective cohort study.

BACKGROUND: Cognitive impairment (CI) is common in multiple sclerosis (MS), affecting half of persons with MS (PwMS). Cognitive reserve has been associated with delaying the onset and slowing the progression of CI in PwMS. Multilingualism has been demonstrated to be a protective factor against CI in Alzheimer's disease (AD) but has never been studied in PwMS. OBJECTIVE: To explore if multilingualism is a protective factor against CI in PwMS. METHODS: This is a retrospective cohort study of PwMS aged 18-59, with a confirmed diagnosis of relapsing MS, fluent in English, who completed the Minimal Assessment of Cognitive Function in MS (MACFIMS) at the London (ON) MS Clinic. Any PwMS with a history of dementia or developmental delay, daily marijuana use, a major psychiatric disorder, or less than grade 9 education was excluded. We focused on the Brief Visuospatial Memory Test (BVMTR), immediate recall (-IR) and delayed recall (-DR) as it would be the least affected by language, as well as the Symbol Digit Modalities Test (SDMT), as information processing speed is the most commonly affected domain in PwMS. One-way ANOVA was used to compare raw scores on the BVMTR and SDMT between groups (uni- vs. multillingual), while chi-square was used to compare impairment on BVMTR and SDMT between groups. RESULTS: The cohort consisted of 678 subjects. The mean age was 39.7 (± 9.6) years with 501 (73.9 %) females (sex at birth), the mean duration of disease of 5.9 (± 6.9) years, and mean years of education was 13.9 (±2.2). The majority of subjects (563, 83 %) were unilingual and (115, 17 %) were multilingual; 102 subjects were bilingual and 13 subjects fluent in ≥ three languages. English was the first language was in most of subjects (614, 90.6 %). There was no significant difference on the BVMTR-IR scores (p = 0.189) or BVMTR-DR (p = 0.096) between groups. Similarly, there was no difference in the number of subjects impaired on the BVMTR-IR (X2 (1, N = 678) = 3.167, p = 0.057) or BVMT-DR between groups (X2 (1, N = 678) = 2.996, p = 0.083). Further, there was no significant difference on the SDMT (p = 0.506) between groups, or in number of subjects impaired on the SDMT between groups (X2 (1, N = 678) = 1.023, p = 0.312). CONCLUSION: This study shows that multilingualism does not have a protective effect against CI in PwMS and does not play a role in enriching the cognitive reserve, in contrast to studies in AD. This difference may be explained by a different underlying pathological mechanism in these diseases and warrants further study.

Comparison of Heart Rate Variability Parameters to the Autonomic Reflex Screen in Postural Orthostatic Tachycardia Syndrome and Neurogenic Orthostatic Hypotension.

PURPOSE: The clinical significance of heart rate variability (HRV) in the context of autonomic dysfunction continues to be a matter of debate. Therefore, the purpose of the current study was to investigate the clinical relevance of HRV in the context of autonomic dysfunction. METHODS: Heart rate variability data from 225 volunteers consisting of controls (n = 166) and patients with mild (n = 25) and severe (n = 34) autonomic dysfunction were retrospectively analyzed. Time and frequency parameters were correlated against baseline and standardized tests of autonomic function. RESULTS: During baseline, resting HR was negatively correlated with time (SD of all normal RR interval, r = -0.511; RMSSD, r = -0.585; pNN50, r = -0.545) and frequency (low-frequency, r = -0.362; high-frequency, r = -0.421) parameters (P < 0.01). Resting systolic blood pressure demonstrated similar significant correlations (P < 0.01). During head-up tilt, SD of all normal RR intervals was positively correlated with [INCREMENT]HR and change in systolic blood pressure (r = 0.340; r = 0.538, respectively; P < 0.01). Similarly, low-frequency, high-frequency, and low-frequency/high-frequency ratios were correlated with [INCREMENT]HR (r = 0.422, r = 0.176, r = 0.470) and change in systolic blood pressure (r = 0.451, r = 0.407, and r = 0.185) (P < 0.01). Time parameters (SD of all normal RR intervals, RMSSD, and pNN50) were all significantly correlated with deep breathing (r = 0.600; r = 0.556; r = 0.516; P < 0.01, respectively). Low-frequency and high-frequency power were also correlated (r = 0.596; r = 0.580, respectively) (P < 0.01). CONCLUSIONS: Time and frequency parameters showed significant negative correlations with baseline hemodynamics. During a test of sympathetic activation and parasympathetic withdrawal, this relationship shifted to reveal significant positive correlations between HRV parameters and hemodynamics. Last, during a test of parasympathetic activation, there were significant positive correlations with cardiovagally mediated HRV parameters. Overall, these results suggest broader clinical relevance for HRV parameters within the spectrum of autonomic functioning.

Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.

PURPOSE: The clinical significance of heart rate variability in the context of autonomic dysfunction continues to be a matter of debate. A consensus is lacking on the best heart rate variability measures for clinical purposes. Therefore, the purpose of this study was to investigate the utility of heart rate variability parameters in healthy versus autonomic dysfunction. METHODS: Healthy young (n = 134), healthy older (n = 32), and patients with mild (postural tachycardia syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34) autonomic dysfunction were included. Time and frequency parameters during baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB) were compared. RESULTS: Cardiovagal time parameters were significantly reduced during HUT in healthy young and postural tachycardia syndrome (P < 0.001). Healthy young had significantly higher time parameters during baseline, HUT, and HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate (HR) (61.4 ± 9.0 bpm vs. 76.8 ± 13.6 bpm; P < 0.001) and a smaller [INCREMENT]HR during HUT (32.8 ± 10.5 bpm vs. 44.4 ± 13.3 bpm; P < 0.001). Time parameters increased in young and postural tachycardia syndrome during HRDB, which was characterized by a nonsignificant difference in [INCREMENT]HR between both groups. Time parameters were significantly higher in healthy old versus neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During HUT, only the SD of all normal RR intervals remained significantly higher. Heart rate changes corroborated these findings. Resting HR was significantly lower in healthy older (62.6 ± 11.0 bpm vs. 70.7 ± 12.4 bpm), and [INCREMENT]HR during HRDB was significantly higher (15.9 ± 9.2 bpm vs. 3.9 ± 4.2 bpm; P < 0.001). During HUT, [INCREMENT]HR showed no significant differences. CONCLUSIONS: Time domain parameters of heart rate variability have a greater utility than frequency parameters in clinical autonomic disorders.

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.