Abstract Purpose Syncope is a common cause of hospitalization in the US. The main objective of this study is to determine the incidence and mortality rates when patients are admitted with a principle ...diagnosis of syncope. Methods An observational cross-sectional study included patients with the principle diagnosis of syncope identified from the National Inpatient Sample database for the years 2000-2005. Incidence rate of syncope was adjusted according to the US Census data. In-hospital mortality and its predictors were identified by a logistic regression analysis, and Cochran-Armitage test was used for trend analysis. Results After data cleansing, 305,932 patients were included in the analysis. Adjusted incidence rate of syncope varied between 0.80 and 0.93 per 1000 person-years and was unchanged over the years included in the analysis. Overall mortality rate is 0.28%, a trend that has not changed over the years ( P = 0.07). The odds ratio (OR) of death increased with age, becoming more prominent after age 40 years. Hospital mortality is higher in men (OR 1.49; 95% confidence interval CI, 1.30-1.71) and in patients with higher comorbidity index (OR 1.39; 95% CI, 1.20-1.62) for moderate, and (OR 4.14; 95% CI, 3.05-5.61) for severe comorbidity index. The median cost of hospitalization is $8579, which increased by 3- to 11-fold if patients had a cardiac pacemaker or implantable cardioverter-defibrillator. Conclusions Syncope remains a common cause of hospital admission. The hospital mortality rate for syncope is low. A better definition and a nationally implemented care path for syncope diagnosis could provide a substantial cost savings.
Background. Fatigue is often the primary complaint of children with functional gastrointestinal disorders (FGDI) and other chronic overlapping pain disorders (COPC). The basis for this symptom ...remains unknown. We evaluated mitochondrial function in the white blood cells of these patients. Methods. This prospective Children’s Wisconsin IRB approved study recruited subjects aging 10–18 years from pediatric neurogastroenterology clinics and healthy comparison subjects (HC). Environmental and oxidative stressors can damage the mitochondrial respiratory chain. The known low-grade inflammation in COPC could, therefore, impact the respiratory chain and theoretically account for the disabling fatigue so often voiced by patients. Mitochondrial energy generation can be easily measured in peripheral mononuclear cells (PMC) as a general marker by the Seahorse XF96 Extracellular Flux Analyzer. We measured 5 parameters of oxygen consumption using this methodology: basal respiration (BR), ATP linked oxygen consumption (ATP-LC), maximal oxygen consumption rate (max R), spare respiratory capacity (SRC), and extracellular acidification rate (ECAR), which reflect non-electron chain energy generation through glycolysis. In health, we expect high ATP linked respiration, high reserve capacity, low proton leak, and low non-mitochondrial respiration. In disease, the proton leak typically increases, ATP demand increases, and there is decreased reserve capacity with increased non-mitochondrial respiration. Findings and clinical data were compared to healthy control subjects using a Mann–Whitney test for skewed variables, Fisher’s exact test for dichotomous variables, and regression tree for association with functional outcome (functional disability inventory, FDI). Results. 19 HC and 31 COPC showed no statistically significant difference in age. FGID, orthostatic intolerance, migraine, sleep disturbance, and chronic fatigue were present in the majority of COPC subjects. BR, ECAR, and ATP-LC rates were lower in the COPC group. The low BR and ATP-LC suggest that mitochondria are stressed with decreased ability to produce ATP. Tree analysis selected SRC as the best predictor of functional disability: patients with SRC >150 had a greater FDI (more disability) compared to patients with SRC <=150, p-value = 0.021. Conclusion. Subjects with COPC have reduced mitochondrial capacity to produce ATP. Predisposing genetic factors or reversible acquired changes may be responsible. A higher SRC best predicts disability. Since a higher SRC is typically associated with more mitochondrial reserve, the SRC may indicate an underutilized available energy supply related to inactivity, or a “brake” on mitochondrial function. Prospective longitudinal studies can likely discern whether these findings represent deconditioning, true mitochondrial dysfunction, or both.
Although cyclic vomiting syndrome (CVS) is associated with migraine, and migraine in turn is associated with orthostatic tachycardia, few studies have explored the association of CVS and autonomic ...dysfunction. We describe the results of autonomic testing in 6 children with characteristic CVS.
All patients fully met the established criteria for the diagnosis of CVS, were well hydrated, and were beyond their episode of vomiting. We performed 3 tests of cardiovascular function and 1 sudomotor test, using standard previously published methods.
The findings were surprisingly uniform, with normal cardiovascular responses to deep breathing and to the Valsalva maneuver in all patients, a significant increase in heart rate (>30 beats per minute) with tilt testing, and a vasodepressor tendency in 2 patients. Interestingly, abdominal pain occurred at blood pressure nadir in both these patients and in a third patient without the vasodepressor findings but who described syncope clinically. Sudomotor test results were abnormal in all 6 patients, with reduced responses in 5 of 6 and exaggerated responses in the 6th. All 6 patients reported a personal or family history of migraine headaches.
CVS is associated with remarkably uniform primarily sympathetic autonomic dysfunction, affecting mainly the vasomotor and sudomotor systems, and compatible with an underlying autonomic neuropathy. The occurrence of symptoms during tilt testing in half the patients suggests that these findings may play a true pathophysiologic role. A vagally modulated sympathetic effect is postulated as the best mechanistic model to account for all current physiologic data on cyclic vomiting and gastroparesis.
Multiple system atrophy (MSA) is an adult-onset, rapidly progressive neurodegenerative syndrome. The diagnosis of MSA is primarily clinical. Neurophysiologic studies can provide important clues to ...the diagnosis of MSA and differentiate it from other neurodegenerative diseases especially when the clinical picture is unclear. This chapter reviews common and less common neurophysiological studies useful in the diagnosis of MSA.
Abstract Background Clinicians depend on history given by the patients when considering the diagnosis of orthostatic hypotension. Methods Patients with a decrease in systolic blood pressure more than ...60 mm Hg from baseline during a head-up tilt table test were included. They were classified according to their symptoms during the head-up tilt table test. Localization of the cause of orthostatic hypotension was sought in each of these groups. Results Eighty-eight (43%) patients had typical symptoms, 49 (24%) had atypical symptoms, and 68 (33%) were asymptomatic. The average decrease in systolic blood pressure was 88 mm Hg, 87.5 mm Hg, and 89.8 mm Hg in the typical, atypical, and asymptomatic groups, respectively ( P = .81). Patients reported severe dizziness with a similar frequency as lower extremity discomfort. Backache and headache also were common atypical complaints. Patients with peripheral cause of dysautonomia were able to sustain the longest upright position during the head-up tilt table test (21 minutes, compared with central dysautonomia 15 minutes) ( P = .005). There was no correlation between the cause of dysautonomia and the occurrence of symptoms during the head-up tilt table test ( P = .58). Conclusion A third of the patients with severe orthostatic hypotension are completely asymptomatic during the head-up tilt table test, and another quarter have atypical complaints that would not lead physicians toward the diagnosis of orthostatic hypotension. These findings suggest that they might not provide adequate information in diagnosing profound orthostatic hypotension in a subset of patients with this disorder.
Abstract only Introduction Acute ischemic stroke varies in presentation, and it is crucial to quickly identify patients presenting with stroke for timely intervention. Secondary movement disorders ...occurring after a delayed period following ischemic stroke have been well‐documented, though rare. Holmes tremor specifically has been described as a delayed result of ischemic infarction involving subcortical structures such as mollaret triangle, thalamus, and basal ganglia. However, it is novel for frontal cortical infarcts to present with acute‐onset contralateral limb tremor, especially as an isolated symptom. Our case suggests a “secondary insult” involving the frontal cortex can disinhibit the motor pathway that leads to tremor in preexisting midbrain and thalamic lesions. We present a 67‐year‐old male with acute onset, constant, rhythmic tremor in the setting of acute ischemic frontal cortical infarction. Methods n/a, case report Results A 67‐year‐old male with medical history of pineal gland cyst status‐post shunt placement and hypertension who presented for evaluation of acute onset right upper extremity rhythmic tremor that started 24 hours prior. He did not have any associated weakness, numbness, vision changes, nausea, or vomiting. He had never had this tremor before. Neurologic examination was significant for a 4.0 Hz rhythmic resting tremor that was present throughout exam and was non‐distractible. This tremor remained consistent even with kinetic movements and postures. Electroencephalogram (EEG) was performed STAT during this tremor and was not based in seizure. Non‐contrast head computerized tomography (CT) was negative for any acute hemorrhage or intracranial pathology. CT angiogram head and neck showed left internal carotid artery (ICA) long segment tapered occlusion from the proximal cervical ICA to the distal petrous segment, likely dissection of undetermined chronicity. Magnetic resonance imaging (MRI) Brain with and without contrast was significant for acute punctate foci involving the precentral cortex of the left frontal lobe consistent with acute ischemic infarction. Encephalomalacia was also present involving the bilateral posterior thalami and left midbrain chronic ischemic infarctions. This suggests the tremor was caused by disinhibition of the motor pathway from the ischemic insult to the frontal cortex, as he had pre‐existing asymptomatic ischemic insult to the typical structures known to cause this tremor. He was outside of the Tenecteplase window and was given a load of Aspirin followed by aspirin 81 mg daily. He was trialed on propranolol for treatment of symptomatic tremor however this was discontinued before discharge as it was ineffective and patient preferred to hold off on other treatments. He is now awaiting outpatient Neurology follow up. Conclusion This case suggests that acute onset Holmes tremor can be the sole presenting sign in acute ischemic frontal cortical infarction. The pre‐existing asymptomatic infarctions in the midbrain and thalamus also support that a “second hit” located in the frontal cortex can disinhibit the motor pathway between the cortex and rubral tract. This is important as Holmes tremor is more commonly known to be from a mechanism of damage to the red nucleus or thalamic structures in a delayed manner, typically at least two weeks after stroke. This knowledge will help identify rare strokes in a timely manner.
Summary Background No available treatments slow or halt progression of multiple system atrophy, which is a rare, progressive, fatal neurological disorder. In a mouse model of multiple system atrophy, ...rifampicin inhibited formation of α-synuclein fibrils, the neuropathological hallmark of the disease. We aimed to assess the safety and efficacy of rifampicin in patients with multiple system atrophy. Methods In this randomised, double-blind, placebo-controlled trial we recruited participants aged 30–80 years with possible or probable multiple system atrophy from ten US medical centres. Eligible participants were randomly assigned (1:1) via computer-generated permuted block randomisation to rifampicin 300 mg twice daily or matching placebo (50 mg riboflavin capsules), stratified by subtype (parkinsonian vs cerebellar), with a block size of four. The primary outcome was rate of change (slope analysis) from baseline to 12 months in Unified Multiple System Atrophy Rating Scale (UMSARS) I score, analysed in all participants with at least one post-baseline measurement. This study is registered with ClinicalTrials.gov , number NCT01287221. Findings Between April 22, 2011, and April 19, 2012, we randomly assigned 100 participants (50 to rifampicin and 50 to placebo). Four participants in the rifampicin group and five in the placebo group withdrew from study prematurely. Results of the preplanned interim analysis (n=15 in each group) of the primary endpoint showed that futility criteria had been met, and the trial was stopped (the mean rate of change slope analysis of UMSARS I score was 0·62 points SD 0·85 per month in the rifampicin group vs 0·47 points 0·48 per month in the placebo group; futility p=0·032; efficacy p=0·76). At the time of study termination, 49 participants in the rifampicin group and 50 in the placebo group had follow-up data and were included in the final analysis. The primary endpoint was 0·5 points (SD 0·7) per month for rifampicin and 0·5 points (0·5) per month for placebo (difference 0·0, 95% CI −0·24 to 0·24; p=0·82). Three (6%) of 50 participants in the rifampicin group and 12 (24%) of 50 in the placebo group had one or more serious adverse events; none was thought to be related to treatment. Interpretation Our results show that rifampicin does not slow or halt progression of multiple system atrophy. Despite the negative result, the trial does provide information that could be useful in the design of future studies assessing potential disease modifying therapies in patients with multiple system atrophy. Funding National Institutes of Health, Mayo Clinic Center for Translational Science Activities, and Mayo Funds.
Purpose Interstitial cystitis/bladder pain syndrome and myofascial pelvic pain are frequently comorbid chronic pelvic pain disorders. Differences in bladder function between interstitial ...cystitis/bladder pain syndrome and myofascial pelvic pain suggest that efferent autonomic function may differentiate these syndromes. Heart rate variability, defined as the difference in duration of successive heartbeats, serves as an index of autonomic function by measuring its ability to modify heart rate in response to neurophysiological changes. High frequency heart rate variability was used as a reflection of more rapid vagally mediated (parasympathetic) changes. Low frequency heart rate variability signified slower fluctuations related to the baroreflex and sympathetic outflow. Materials and Methods Heart rate variability was derived by autoregressive frequency analysis of the continuous electrocardiogram recording of heart rate with the subject supine for 10 minutes, tilted 70 degrees with the head up for 30 minutes and supine again for 10 minutes. This institutional review board approved study included 105 female subjects, including 32 who were healthy, and 26 with interstitial cystitis/bladder pain syndrome, 12 with myofascial pelvic pain and 35 with interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Results In all positions healthy controls had higher high frequency heart rate variability than women with interstitial cystitis/bladder pain syndrome and interstitial cystitis/bladder pain syndrome plus myofascial pelvic pain. Subjects with myofascial pelvic pain were similar to controls with greater high frequency heart rate variability at baseline (supine 1) and in upright positions than subjects with interstitial cystitis/bladder pain syndrome. Differences in low frequency heart rate variability were less evident while low-to-high frequency ratio differences appeared to be driven by the high frequency heart rate variability component. Conclusions Subjects with interstitial cystitis/bladder pain syndrome had diminished vagal activity and a shift toward sympathetic nervous system dominance. Overall these data support the hypothesis that changes in autonomic function occur in interstitial cystitis/bladder pain syndrome but not in myofascial pelvic pain. These changes may result from interstitial cystitis/bladder pain syndrome or contribute to its pathophysiology through abnormal self-regulatory function.
Abstract Background There are conflicting opinions on whether postural tachycardia syndrome predisposes to syncope. We investigated this relationship by comparing the frequency of syncope in postural ...tachycardia syndrome and orthostatic hypotension. Methods We queried our autonomic laboratory database of 3700 patients. Orthostatic hypotension and postural tachycardia syndrome were defined in standard fashion, except that postural tachycardia syndrome required the presence of orthostatic symptoms and a further increase in heart rate beyond 10 minutes. Syncope was defined as an abrupt decrease in blood pressure and often, heart rate, requiring termination of the tilt study. Statistical analysis utilized Fisher's exact test and Student's t test, as appropriate. Results Of 810 patients referred for postural tachycardia syndrome, 185 met criteria while another 328 patients had orthostatic hypotension. Of the postural tachycardia syndrome patients, 38% had syncope on head-up tilt, compared with only 22% of those with orthostatic hypotension ( P <.0001). In the postural tachycardia group, syncope on head-up tilt was associated with a clinical history of syncope in 90%, whereas absence of syncope on head-up tilt was associated with a clinical history of syncope in 30% ( P <.0001). In contrast, syncope on head-up tilt did not bear any relationship to clinical history of syncope in the orthostatic hypotension group (41% vs 36%; P = .49). Conclusion Our results demonstrate that syncope (both tilt table and clinical) occurs far more commonly in patients who have postural tachycardia syndrome than in patients with orthostatic hypotension. These findings suggest that one should be clinically aware of the high risk of syncope in patients with postural tachycardia syndrome, and the low-pressure baroreceptor system that is implicated in postural tachycardia syndrome might confer more sensitivity to syncope than the high pressure system implicated in orthostatic hypotension.
Objective To determine if children with benign joint hypermobility (BJH) syndrome and chronic functional pain disorders have more autonomic dysfunction. Study design Retrospective chart review study ...of pediatric patients seen in the pediatric neurogastroenterology and autonomic clinic who underwent autonomic testing and had either a Beighton score of ≥6 and met Brighton criteria for BJH (with BJH) or a score of ≤2 (no BJH). Results Twenty-one female subjects (10 without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by genetics consultation. We evaluated for postural tachycardia syndrome, syncope, orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as well as baseline heart rate, peak heart rate in first 10 minutes of head up tilt ( P = .35 and P = .61, respectively), and sudomotor index (suggestive of autonomic neuropathy) ( P = .58), showed differences between the groups. Age of onset of symptoms was also similar ( P = .61) (BJH vs without BJH: median range:15.6 years 12.9-17.5 vs 15.4 years 11.1-18.2). There was no difference between groups in complaints of migraine, chronic nausea, chronic fatigue, lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep, irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal pain, constipation, or fibromyalgia. Conclusions Children with chronic functional pain disorders and BJH have autonomic testing findings and comorbid features compared with a similar cohort of subjects without BJH, suggesting that BJH is not the driver of the autonomic and comorbid disorders.
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