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.

Evidence of Impaired Cerebellar Connectivity at Rest and During Autonomic Maneuvers in Patients with Autonomic Failure.

The objective of the current study was to investigate whether patients with neurogenic orthostatic hypotension (NOH) secondary to autonomic failure have impaired functional connectivity between the cerebellum and central autonomic structures during autonomic challenges. Fifteen healthy controls (61 ± 14 years) and 15 NOH patients (67 ± 6 years; p = 0.12) completed the following tasks during a functional brain MRI: (1) 5 min of rest, (2) 5 min of lower-body negative pressure (LBNP) performed at - 35 mmHg, and (3) Three, 15-s Valsalva maneuvers (VM) at 40 mmHg. Functional connectivity (Conn Toolbox V18) between central autonomic structures and discrete cerebellar regions involved in cardiovascular autonomic control, including the vermis and posterior cerebellum, was assessed using a regions-of-interest approach during rest, LBNP and VM. Functional connectivity was contrasted between controls and patients with autonomic failure. At rest, controls had significantly more intra-cerebellar connectivity and more connectivity between cerebellar lobule 9 and key central autonomic structures, including: bilateral anterior insula (TR-value: 4.84; TL-value: 4.51), anterior cingulate cortex (T-value: 3.41) and bilateral thalamus (TR-value: 3.95; TL-value: 4.51). During autonomic maneuvers, controls showed significantly more connectivity between cardiovascular cerebellar regions (lobule 9 and anterior vermis) and important autonomic regulatory sites, including the brainstem, hippocampus and cingulate: vermis-brainstem (T-value: 4.31), lobule 9-brainstem (TR-value, 5.29; TL-value, 4.53), vermis-hippocampus (T-value, 4.63), and vermis-cingulate (T-value, 4.18). Anatomical and functional studies in animals and humans substantiate a significant role for the cerebellum in cardiovascular autonomic control during postural adjustments. In the current study, patients with NOH related to autonomic failure showed evidence of reduced connectivity between cardiovascular cerebellar regions and several important central autonomic structures, including the brainstem. The cerebellum is an established structure in cardiovascular autonomic control; therefore, evidence of impaired cerebellar connectivity to other autonomic structures may further contribute to the inability to properly regulate blood pressure during postural changes in NOH patients.

The Orthostatic Discriminant and Severity Scale (ODSS): an assessment of orthostatic intolerance.

PURPOSE: To assess the ability of the Orthostatic Discriminant and Severity Scale (ODSS) to distinguish symptoms of orthostatic intolerance from non-orthostatic symptoms. METHODS: Clinical evaluations and questionnaire responses were collected in 73 healthy controls and 132 patients referred to the Autonomic Disorders Clinic from September 1, 2016, through April 30, 2018, for queries regarding autonomic dysfunction. A receiver operating characteristic (ROC) curve analysis was used to interpret sensitivity and specificity and to determine cutoff scores for symptom assessment. Inter-item reliability was assessed using Cronbach's alpha. To calculate positive and negative predictive powers, patient data were collected in a single-blinded fashion where the researcher collecting questionnaire data was blinded to the clinical evaluation and diagnosis. Predictive powers were calculated using a chi-squared cross-tabulation. RESULTS: The orthostatic and non-orthostatic symptoms scores produced ROC curves with an area under the curve of 0.89 and 0.79, respectively. The orthostatic scores yielded a positive and negative predictive power value of 73% and 81%, respectively. Combined, the ODSS identified patients with and without orthostatic symptoms with an overall accuracy of 76%. The reliability of the ODSS was significant, with a Cronbach's alpha of 0.88, and all dichotomous items were deemed worthy of retention following an inter-item reliability assessment. CONCLUSIONS: The ODSS demonstrated a strong ability to distinguish patients with and without orthostatic intolerance and demonstrated sensitivity and specificity equivalent to that of other standardized measures. Overall, the ODSS produces symptom scores that are both reliable and useful for both research and clinical practice.

Nerve dysfunction leads to muscle morphological abnormalities in chronic inflammatory demyelinating polyneuropathy assessed by MRI.

Neuropathic features of chronic inflammatory demyelinating polyneuropathy (CIDP) have been well documented, however very little is known about the implication of this neuropathy on skeletal muscle, and whether nerve lesions in CIDP lead to uniform disruptions in skeletal muscles. In this study, we assessed the triceps surae complex, using magnetic resonance imaging (MRI) in a group (n = 10) of CIDP patients compared with a healthy age-matched control group (n = 9). MRI (T1 and T2) of the leg musculature as well as plantar flexion strength measurements were obtained from both groups. CIDP patients compared with controls had ∼28% lower plantar flexion strength and ∼19% less total muscle volume (T1) of the triceps surae. When strength was normalized to fat corrected triceps surae volume CIDP patients were ∼30% weaker than controls. Relaxation times from the T2 scans were significantly longer in CIDP with the soleus, medial head of gastrocnemius and lateral head of gastrocnemius showing ∼37%, ∼38% and ∼26% longer relaxation times, respectively. CIDP patients were significantly weaker compared to controls and despite normalizing strength to total triceps surae contractile tissue volume this difference remained. CIDP patients had significantly longer T2 times, reflecting increased noncontractile tissue infiltration. These results indicate reduced muscle quantity and quality as a result of alterations in axonal function. Furthermore, when present study results are considered together with a prior report on the anterior compartment (Gilmore et al. 2016, Muscle Nerve 3:413-420), it is clear that both anterior and posterior leg compartments are affected similarly in CIDP despite different terminal nerve innervation and functional properties. Clin. Anat. 32:77-84, 2019. © 2019 Wiley Periodicals, Inc.

Initial validation of symptom scores derived from the orthostatic discriminant and severity scale.

OBJECTIVE: To develop a scale to quantify and discriminate orthostatic from non-orthostatic symptoms. In the current study, we present validation and reliability of orthostatic and non-orthostatic symptom scores taken from the orthostatic discriminate and severity scale (ODSS). METHODS: Validity and reliability were assessed in participants with and without orthostatic intolerance. Convergent validity was assessed by correlating symptoms scores with previously validated tools [autonomic symptom profile (ASP) and the orthostatic hypotension questionnaire (OHQ)]. Clinical validity was assessed by correlating scores against standardized autonomic testing. Test-retest reliability was calculated using an intra-class correlation coefficient. RESULTS: Convergent validity: orthostatic (OS) and non-orthostatic (NS) symptom scores from 77 controls and 67 patients with orthostatic intolerance were highly correlated with both the orthostatic intolerance index of the ASP (OS: r = 0.903; NS: r = 0.651; p < 0.001) and the composite score of the OHQ: (OS: r = 0.800; NS: r = 0.574; p < 0.001). Clinical validity: symptom scores were significantly correlated with the total composite autonomic severity score (OS: r = 0.458; NS: r = 0.315; p < 0.001), and the systolic blood pressure change during head-up tilt (OS: r = - 0.445; NS: r = - 0.354; p < 0.001). In addition, patients with orthostatic intolerance had significantly higher symptom scores compared to controls (OS: 66.5 ± 18.1 vs. 17.4 ± 12.9; NS: 19.9 ± 11.3 vs. 10.2 ± 6.8; p < 0.001, respectively). Test-retest reliability: Both orthostatic and non-orthostatic symptom scores were highly reliable (OS: r = 0.956 and NS: r = 0.574, respectively; p < 0.001) with an internal consistency of 0.978 and 0.729, respectively. INTERPRETATION: Our initial results demonstrate that the ODSS is capable of producing valid and reliable orthostatic and non-orthostatic symptom scores. Further studies are ongoing to test sensitivity, specificity and symptom severity.

An updated normative data set from the autonomic reflex screen representative of Southwestern Ontario.

In evaluating autonomic dysfunction, the autonomic reflex screen (ARS) is an established set of standardized tests to evaluate the presence and severity of autonomic dysfunction. Our laboratory previously reported normative data on 121 healthy individuals; however, the sample size in older individuals was reduced compared with other age groups. Therefore, the objective of the current study was to provide updated normative values representative of young, middle-aged, and older individuals from Southwestern Ontario. Two hundred and fifty-two healthy individuals completed quantitative sudomotor axon reflex testing, heart rate responses to deep breathing (HRDB), and Valsalva maneuver using standard protocols of the ARS. All 4 sweat sites demonstrated a significant effect of sex (p < 0.001). In addition, the proximal leg, distal leg, and foot were all significantly affected by age (p < 0.001). Cardiovagal parameters, measured via HRDB and Valsalva ratio revealed a significant regression with age (p < 0.001). These results show similar trends with previously reported normative data sets. All normative data as a function of age and sex, where appropriate, are expressed as percentiles (2.5th, 5th, 95th, 97.5th). The current study provides updated normative data describing autonomic functioning in healthy individuals obtained from the sudomotor and cardiovagal components of the ARS.

Reductions in muscle quality and quantity in chronic inflammatory demyelinating polyneuropathy patients assessed by magnetic resonance imaging.

INTRODUCTION: Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but this has not been explored. METHODS: Twelve patients with CIDP (mean age 61 years) and 10 age-matched (mean age 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. RESULTS: Isometric strength was 36% lower in CIDP patients compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ∼17% compared with controls, and non-contractile tissue volume was ∼58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ∼29% and ∼18% lower, respectively, in CIDP patients. DISCUSSION: These results provide insight into the structural integrity of muscle contractile proteins and pathologic changes to whole-muscle tissue composition that contribute to impaired muscle function in CIDP. Muscle Nerve 58: 396-401, 2018.

Role of melatonin in blood pressure regulation: An adjunct anti-hypertensive agent.

Cardiovascular diseases account for approximately one-third of all deaths each year. Of this, hypertension accounts for approximately 9.4 million deaths. Melatonin, the primary circadian hormone, has been substantiated as an effective and safe adjunct anti-hypertensive agent. In support of this, melatonin receptors have been identified within the central and peripheral nervous system, as well as the cardiovascular system, including various vascular tissues. Therefore, it is not surprising that recent research has emerged highlighting a key role of melatonin in autonomic regulation of blood pressure. In animals, pinealectomies elicit peripheral vasoconstriction and hypertension. In studies involving humans, both healthy controls and patient populations of essential and nocturnal hypertension, melatonin administration demonstrates significant hypotensive effects that yield clinically significant results. However, the precise mechanism by which melatonin elicits its hypotensive effects in humans require further investigation. This review focuses on melatonin, its role within the cardiovascular system and the emerging implications for its use as an anti-hypertensive agent. Additionally, this review will discuss the current thinking on potential mechanisms behind the hypotensive effects of melatonin including: endothelium-dependent vasodilation, anti-oxidant defence mechanisms and sympatho-vagal autonomic regulation.

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.

Electrophysiological and neuromuscular stability of persons with chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We assessed motor unit (MU) properties and neuromuscular stability in the tibialis anterior (TA) of chronic inflammatory demyelinating polyneuropathy (CIDP) patients using decomposition-based quantitative electromyography. METHODS: Dorsiflexion strength was assessed, and surface and concentric needle electromyography were sampled from the TA. Estimates of MU numbers were derived using decomposition-based quantitative electromyography and spike-triggered averaging. Neuromuscular transmission stability was assessed from concentric needle-detected MU potentials. RESULTS: CIDP patients had 43% lower compound muscle action potential amplitude than controls, and despite near-maximum voluntary activation, were 37% weaker. CIDP had 27% fewer functioning MUs in the TA, and had 90% and 44% higher jiggle and jitter values, respectively compared with controls. CONCLUSIONS: CIDP had lower strength and compound muscle action potential values, moderately fewer numbers of MUs, and significant neuromuscular instability compared with controls. Thus, in addition to muscle atrophy, voluntary weakness is also due to limitations of peripheral neural transmission consistent with demyelination. Muscle Nerve 56: 413-420, 2017.

Palliative Care Discussions in Multiple System Atrophy: A Retrospective Review.

OBJECTIVE: Multiple system atrophy (MSA) is an incurable neurodegenerative illness in which progressive symptoms, including stridor and acute laryngeal obstruction, occur. Advanced care planning and palliative care discussions in people living with MSA are not well defined. The aim of the present study is to evaluate advanced care planning and current practices in palliative care in MSA to identify opportunities for improving quality of care. METHODS: The study is a retrospective chart review assessing the focus and timing of palliative care discussions in people living with MSA. Some 22 charts were reviewed. RESULTS: A total of 22 patients were included. The most common symptoms were parkinsonism, orthostatic hypotension, GI/GU dysfunction, ataxia and gait impairment. Six patients had stridor. Of the palliative care discussions that took place, the most common topics were diagnosis, symptoms or symptom management, and prognosis. In the majority of patients who died and who had a do-not-attempt-resuscitation order, discussions surrounding resuscitation and goals of care took place only hours before death. CONCLUSIONS: There is no standard approach to advanced care planning and palliative care discussions in people living with MSA. We propose a framework to guide advanced care planning and palliative care discussions in MSA.

The utility of Valsalva maneuver in the diagnoses of orthostatic disorders.

The objective of this study was to assess hemodynamic responses and baroreflex sensitivity (BRS) indexes during Valsalva maneuver (VM) and head-up tilt (HUT) testing in orthostatic intolerance (OI). Patients with neurogenic orthostatic hypotension (NOH, n = 26), postural tachycardia syndrome (n = 26) and symptomatic OI (n = 14) were compared with healthy population (control, n = 107) and inappropriate sinus tachycardia (n = 7). Hemodynamic assessment included patterning and quantification with vagal and adrenergic BRS (BRSa/BRSa1). In NOH, cardiovagal systolic blood pressure (SBP) decrements in VM and HUT were correlated (r = 0.660, P < 0.001); a "V" pattern of VM indicated α-BRSa failure. Yet BRSa1 did not reveal changes vs. control (P > 0.05) or was not applicable in 60% of NOH. In symptomatic OI, compared with control, cardiovagal SBP decrements were larger (P < 0.05); higher BRSa1 contradicted higher adrenergic index (Composite Autonomic Severity Score). Overshoot in phase IV dipped below baseline or dropped ≥ 10 mmHg over 8 s in postural tachycardia syndrome ("N" pattern), but by 3 s in inappropriate sinus tachycardia ("M" pattern). Visualization of distinct VM patterns allows primary evaluation of autonomic dysfunction and differentiation of the various forms of OI. BRSa1 evaluation is compromised by pathological SBP patterns. VM patterning is a valuable nonpostural supplement to HUT capable of detecting and differentiating OI.

Reduced skeletal muscle quantity and quality in patients with diabetic polyneuropathy assessed by magnetic resonance imaging.

INTRODUCTION: The aim of this study was to determine whether diabetic polyneuropathy (DPN) is associated with reduced muscle quality using MRI. METHODS: MRIs of the tibialis anterior (TA) muscle were recorded from 9 individuals (5 men) with DPN (∼65 years) and 8 (4 men) age- and gender-matched controls. A magnetization transfer ratio (MTR) and T2 relaxation times of the TA were calculated. RESULTS: Despite equal voluntary activation, the DPN group was ∼37% weaker than controls, with a significantly lower proportion (∼8%) of contractile tissue and lower MTR (0.28 ± 0.03 vs. 0.32 ± 0.02 percent units). T2 relaxation time was significantly longer in the DPN group (77 ± 16 ms) compared with controls (63 ± 6 ms). CONCLUSIONS: These findings indicate a reduction in the structural integrity and myocellular protein density in the TA of those with DPN. Thus, muscle weakness in DPN is likely due to both a loss of muscle mass and a reduction in contractile quality.

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.

Autonomic dysfunction, immune regulation, and multiple sclerosis.

OBJECTIVE: To review existing evidence regarding interactions between the autonomic nervous system and the immune system functions in multiple sclerosis. METHODS: We 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. RESULTS: Autonomic 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. CONCLUSIONS: Autonomic 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.

A practical guide to the treatment of neurogenic orthostatic hypotension.

Neurogenic orthostatic hypotension (NOH) is a debilitating condition associated with many central and peripheral neurological disorders. It has a complex pathophysiology and variable clinical presentation, which makes diagnosis and treatment difficult. Neurogenic orthostatic hypotension is often confused with other disorders of orthostatic intolerance, hypovolemic states and systemic conditions. Diagnosis is usually made by an autonomic specialist following characteristic responses to head-up tilt. Symptom control can be achieved through a combination of patient education, nonpharmacologic and pharmacologic therapy. The purpose of this review is to provide the clinician with a practical approach to the diagnosis and management of NOH.

A prospective study of excessive postural heart rate change on head-up tilt.

PURPOSE: Healthy subjects with asymptomatic postural tachycardia (≥30 bpm) at baseline were evaluated over a 1-year period to determine whether they developed orthostatic symptoms. METHODS: Subjects were evaluated at baseline and at 1 year using the autonomic reflex screen and autonomic symptom profile (ASP). RESULTS: Heart rate increment on HUT did not differ at baseline (40.6 ± 7.5 bpm) or at 1 year (37.1 ± 11.1 bpm; n = 26; p > 0.05). Orthostatic symptoms measured by the ASP did not reveal significant orthostatic dysfunction throughout follow-up (baseline, 7.88 ± 7.61; 1 year, 9.04 ± 6.64; n = 26; p > 0.05). The ten autonomic domains of the ASP did not reveal a change in autonomic symptoms from baseline (13.56 ± 13.66) to 1-year follow-up (15.12 ± 11.62; n = 26; p > 0.05). Cardiovagal function was unchanged between baseline and follow-up for both heart rate variability to deep breathing (baseline, 23.9 ± 11.6 bpm; 1 year, 23.0 ± 9.3 bpm; n = 26; p > 0.05) and Valsalva ratio (baseline, 2.16 ± 0.39; 1 year, 2.15 ± 0.33; n = 26; p > 0.05). CONCLUSIONS: These findings further argue that heart rate criteria (≥30 bpm) for Postural Tachycardia Syndrome (POTS) are not appropriate in younger individuals and higher postural heart rates do not predispose individuals to the development of POTS.

Motor unit loss and weakness in association with diabetic neuropathy in humans.

INTRODUCTION: Diabetes mellitus can be associated with peripheral neuropathy which may affect numbers of functioning motor units (MUs) of limb muscles. Direct quantitative assessment of MU numbers and muscle strength have not been performed in humans. We compared the estimated number of MUs of individuals with diabetic polyneuropathy (DPN) versus controls. METHODS: Patients with signs/symptoms of DPN were studied using decomposition-enhanced quantitative electromyography of the tibialis anterior (TA). Motor unit number estimates were derived from this analysis. RESULTS: Dorsiflexion strength was ∼60% less in DPN than controls (P < 0.05). Additionally, the estimated number of functioning TA MUs was ∼60% fewer in patients with DM (∼46) versus controls (∼111) (P < 0.05). CONCLUSIONS: These data directly measure MU loss associated with DPN in a proximal muscle in humans. It remains to be determined whether quantifying MU loss has clinical utility in monitoring the progression or management of DPN.

Nocturnal deterioration after ischemic stroke and autonomic dysfunction: hypothesis and implications.

BACKGROUND: A significant number of patients admitted to hospital after acute ischemic stroke deteriorate clinically. Deterioration is generally noted within the first 48 h after stroke onset. The mechanisms leading to this deterioration are not fully understood. SUMMARY: One potential cause of this deterioration may be altered or impaired autonomic function. We expect the hemodynamic changes regulated by the autonomic nervous system that are dysregulated after stroke to be exaggerated during sleep, resulting in arrhythmia and blood pressure fluctuations in these patients. Such physiological changes could result in worsening the overall outcome of the ischemic stroke patient or in sudden death. Therefore, it is necessary to summarize yet unrelated observations and hypothesize on their individual effects and interactions as they relate to poststroke deterioration. KEY MESSAGES: If the hypothesis is correct that dysautonomia occurs to the degree that it affects clinical outcomes negatively, this would have important implications for the prevention of neurological deterioration and sudden death after ischemic stroke.