Performance of the COMPASS-31 questionnaire with regard to autonomic nervous system testing results and medication use: a prospective study in a real-life setting.

The aim of this study was to investigate the performance of the Composite Autonomic System Score-31 (COMPASS-31) questionnaire in a real-life setting in consecutive patients referred to the laboratory for objective testing of the autonomic nervous system (ANS), with the hypothesis that COMPASS-31 results differ depending on medications and findings of the tilt table test results. One hundred seventy-one consecutive patients (125 females, mean age 41.5 ± 19.3) referred for testing of the ANS were enrolled. Before testing, all patients completed the recently validated Croatian version of COMPASS-31. The following data were systematically collected for all patients: age, sex, diagnoses, and medications. Results of COMPASS-31 were significantly higher in patients taking medications with a known influence on the ANS (p < 0.001). Patients with postural orthostatic tachycardia had significantly higher orthostatic intolerance and vasomotor domains of COMPASS-31 (p = 0.048 and p = 0.022, respectively). Patients with a cardiovagal score ≥ 1 had a significantly higher vasomotor domain of COMPASS-31 compared to patients with normal results of ANS tests (p = 0.030). These findings suggest the COMPASS-31 might be a valuable screening tool for autonomic dysfunctions, as it is associated with impaired ANS tests, but usage of medications that modify the ANS should always be taken into account.

Minimal ensemble based on subset selection using ECG to diagnose categories of CAN.

BACKGROUND AND OBJECTIVE: Early diagnosis of cardiac autonomic neuropathy (CAN) is critical for reversing or decreasing its progression and prevent complications. Diagnostic accuracy or precision is one of the core requirements of CAN detection. As the standard Ewing battery tests suffer from a number of shortcomings, research in automating and improving the early detection of CAN has recently received serious attention in identifying additional clinical variables and designing advanced ensembles of classifiers to improve the accuracy or precision of CAN diagnostics. Although large ensembles are commonly proposed for the automated diagnosis of CAN, large ensembles are characterized by slow processing speed and computational complexity. This paper applies ECG features and proposes a new ensemble-based approach for diagnosis of CAN progression. METHODS: We introduce a Minimal Ensemble Based On Subset Selection (MEBOSS) for the diagnosis of all categories of CAN including early, definite and atypical CAN. MEBOSS is based on a novel multi-tier architecture applying classifier subset selection as well as the training subset selection during several steps of its operation. Our experiments determined the diagnostic accuracy or precision obtained in 5 × 2 cross-validation for various options employed in MEBOSS and other classification systems. RESULTS: The experiments demonstrate the operation of the MEBOSS procedure invoking the most effective classifiers available in the open source software environment SageMath. The results of our experiments show that for the large DiabHealth database of CAN related parameters MEBOSS outperformed other classification systems available in SageMath and achieved 94% to 97% precision in 5 × 2 cross-validation correctly distinguishing any two CAN categories to a maximum of five categorizations including control, early, definite, severe and atypical CAN. CONCLUSIONS: These results show that MEBOSS architecture is effective and can be recommended for practical implementations in systems for the diagnosis of CAN progression.

Autonomic Neuropathy.

Autonomic nerve fibers are affected in most generalized peripheral neuropathies. Although this involvement is often mild or subclinical, there are a group of peripheral neuropathies in which the small or unmyelinated fibers are selectively or prominently targeted. These include the autonomic neuropathies associated with diabetes and amyloid, immune-mediated autonomic neuropathies including those associated with a paraneoplastic syndrome, inherited autonomic neuropathies, autonomic neuropathies associated with infectious diseases, and toxic autonomic neuropathies. The presenting features include impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor function. The accurate diagnosis of the autonomic neuropathies has been enhanced by the availability of physiological tests that measure autonomic function, and more recently, structural studies of the autonomic cutaneous innervation. With the help of these investigations and the judicious use of laboratory testing, many autonomic neuropathies can be accurately diagnosed and their clinical progression monitored.

Clinical classification and neuro-vestibular evaluation in chronic dizziness.

OBJECTIVE: This study attempts to clarify the clinical characteristics of chronic dizziness and its relationships with specific vestibular, oculomotor, autonomic and psychiatric dysfunctions. METHODS: 73 Patients with idiopathic chronic dizziness were recruited and classified based on history taking and clinical examination into the following four clinical subgroups; vestibular migraine (VM), dysautonomia, psychogenic, and unspecified groups. They were also evaluated using oculomotor, otolithic and autonomic function tests, and psychologic investigation. RESULTS: Patients in the VM group showed a high proportion of abnormality on smooth pursuit and otolithic function testing compared to the other groups. The dysautonomia group revealed significant abnormalities in sympathetic and cardiovagal autonomic function, while the psychogenic group had a high frequency of abnormality in sympathetic autonomic testing and in Beck's anxiety inventory scale. The unspecified group showed abnormalities on saccade, smooth pursuit and autonomic function testing. CONCLUSIONS: Clinical classification of patients with chronic dizziness was relevant and they showed a correlation with disease-specific abnormal results in oculomotor, otolithic, autonomic function and psychology testing. SIGNIFICANCE: Appropriate diagnostic investigation based on precise clinical diagnosis of chronic dizziness reduces the need for extensive laboratory testing, neuroimaging, and other low-yield tests.

Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria.

A syndrome of paroxysmal, episodic sympathetic hyperactivity after acquired brain injury has been recognized for almost 60 years. This project sought to simplify the confused nomenclature for the condition (>31 eponyms) and simplify the nine overlapping sets of diagnostic criteria. A consensus-developed questionnaire based on a systematic review of the literature was circulated to a widely representative, international expert group utilizing a Delphi approach. Diagnostic criteria were dropped if group consensus failed to agree on their relative importance, with a goal of reaching a Cronbach α of 0.8 (suitable for research purposes). The resulting criteria were combined into an assessment measure for clinical and research settings. The consensus group recommend that the term "paroxysmal sympathetic hyperactivity" replace previous terms to describe the "syndrome, recognised in a subgroup of survivors of severe acquired brain injury, of simultaneous, paroxysmal transient increases in sympathetic [elevated heart rate, blood pressure, respiratory rate, temperature, sweating] and motor [posturing] activity." An 11 point probabilistic diagnostic scale was developed with reference to published criteria, yielding an acceptable Cronbach α of 0.8. These 11 items were proceduralized and combined with a symptom severity index to produce a diagnostic tool for use with adults (the paroxysmal sympathetic hyperactivity assessment measure [PSH-AM]). Development of a pediatric version of the scale and further research into the validity of the PSH-AM is recommended. The consensus position builds on previous literature to establish diagnostic definitions and criteria, an important move to standardize research and management of this condition.

Long-term results of endoscopic sympathetic block using the Lin-Telaranta classification.

BACKGROUND: Endoscopic thoracic sympathectomy has been used successfully in the treatment of blushing, excessive sweating, and social phobia. However, the adverse effects of endoscopic thoracic sympathectomy are more severe and frequent than the adverse effects of endoscopic sympathetic block (ESB). The use of different blocking levels for different indications in ESB according to the Lin-Telaranta classification further decreases the postoperative adverse effects. However, there are few data on the long-term results of ESB performed using the Lin-Telaranta classification. METHODS: Ninety-five patients (55 men, 40 women) were interviewed by before the surgery using our routine questionnaire, and the same questionnaire was answered postoperatively by the patients. In addition, a long-term follow-up questionnaire was sent to all patients whose address was known. Forty-seven patients (24 men, 23 women) answered to this questionnaire. The Davidson brief social phobia scale and the Liebowitz quality of life scale were used. Patients were divided to 3 categories: category 1, patients with sweating problems; category 2, patients with blushing; and category 3, and patients with symptoms other than sweating or blushing. RESULTS: Among patients in category 1, social phobia decreased from 12.43 to 6.71 (p = 0.004), in category 2 from 13.97 to 7.69 (p < 0.001), and in category 3 from 13.18 to 9.64 (p = 0.007) during long-term follow-up. Among patients with severe sweating problems preoperatively, sweating decreased from 2.50 to 1.29 (p = 0.003) among patients in category 1 and from 1.86 to 1.16 (p < 0.001) among patients in category 2. Among patients with unbearable blushing, blushing decreased from 4 to 1.80 (p < 0.001). CONCLUSIONS: Patients got a clear help from ESB performed using the Lin-Telaranta classification to treat blushing, excessive sweating, and social phobia with and without physical symptoms. In addition, compensatory sweating increased only slightly.

Genetic autonomic disorders.

Genetic disorders affecting the autonomic nervous system can result in abnormal development of the nervous system or they can be caused by neurotransmitter imbalance, an ion-channel disturbance or by storage of deleterious material. The symptoms indicating autonomic dysfunction, however, will depend upon whether the genetic lesion has disrupted peripheral or central autonomic centers or both. Because the autonomic nervous system is pervasive and affects every organ system in the body, autonomic dysfunction will result in impaired homeostasis and symptoms will vary. The possibility of genetic confirmation by molecular testing for specific diagnosis is increasing but treatments tend to remain only supportive and directed toward particular symptoms.

[Vagotonía. The medical thesis of Salvador Zubirán]. / Vagotonía. La tesis recepcional de Salvador Zubirán.

Salvador Zubirán submitted his thesis for his MD degree in 1923. This thesis falls within the context of the new Mexican physiological medicine and denotes the visionary character of its author. Zubirán appears here as the introducer in Mexico of the physiopharmacological approach in autonomic nervous system disorders.

Funções autonômica cardíaca e mecânica ventricular na cardiopatia chagásica crônica assintomática / Cardiac autonomic and ventricular mechanical functions in asymptomatic chronic chagasic cardiomyopathy

FUNDAMENTO: A associação das funções autonômica cardíaca e ventricular sisto-diastólica variavelmente alteradas ainda é controversa e pouco explorada na cardiopatia chagásica crônica. OBJETIVO: Avaliar em que extensão as funções autonômica cardíaca e mecânica ventricular estão alteradas e se ambas estão relacionadas na cardiopatia chagásica assintomática. MÉTODOS: EM 13 cardiopatas chagásicos assintomáticos e 15 indivíduos normais (grupo controle), foram avaliadas e correlacionadas a modulação autonômica da variabilidade da frequência cardíaca durante cinco minutos, nos domínios temporal e espectral, nas posições supina e ortostática, e a função ventricular com base em variáveis morfofuncionais Doppler ecocardiográficas. A análise estatística empregou o teste de Mann-Whitney e a correlação de Spearman. RESULTADOS: Em ambas as posições, os índices temporais (p = 0,0004-0,01) e as áreas espectrais total (p = 0,0007-0,005) e absoluta, de baixa e alta frequências (p = 0,0001-0,002), mostraram-se menores no grupo chagásico. O balanço vagossimpático mostrou-se semelhante em ambas as posturas (p = 0,43-0,89). As variáveis ecocardiográficas não diferiram entre os grupos (p = 0,13-0,82), exceto o diâmetro sistólico final do ventrículo esquerdo que se mostrou maior (p = 0,04), correlacionando-se diretamente com os reduzidos índices da modulação autonômica global (p = 0,01-0,04) e parassimpática (p = 0,002-0,01), nos pacientes chagásicos, em posição ortostática. CONCLUSÃO: AS DEpressões simpática e parassimpática com balanço preservado associaram-se apenas a um indicador de disfunção ventricular. Isso sugere que a disfunção autonômica cardíaca pode preceder e ser independentemente mais severa que a disfunção ventricular, não havendo associação causal entre ambos os distúrbios na cardiopatia chagásica crônica.

BACKGROUND: The association of variably altered cardiac autonomic and ventricular systolic and diastolic functions is still controversial and little explored in chronic Chagas' disease. OBJECTIVE: To evaluate the extent to which cardiac autonomic and mechanical ventricular functions are altered and whether they are associated in asymptomatic chagasic cardiomyopathy. METHODS: A total of 13 patients with asymptomatic chagasic cardiomyopathy and 15 normal subjects (control group) were evaluated and the autonomic modulation of heart rate variability for five minutes, in the temporal and spectral domains, in the supine and orthostatic positions, as well as ventricular function based on morphological-functional variables obtained by Doppler echocardiography were correlated. Statistical analysis used the Mann-Whitney test and Spearman's correlation. RESULTS: In both positions, the temporal index (p = 0.0004 to 0.01) and total (p = 0.0007-0.005) and absolute spectral areas, of low and high frequencies (p = 0.0001 to 0.002), were lower in the chagasic group. The vagal-sympathetic balance was similar in both positions (p = 0.43 to 0.89). The echocardiographic variables did not differ between groups (p = 0.13 to 0.82), except the left ventricular end-systolic diameter, which was larger (p = 0.04) and correlated directly with reduced rates of global (p = 0.01 to 0.04) and parasympathetic (p = 0.002 to 0.01) autonomic modulation in patients with Chagas disease in the orthostatic position. CONCLUSION: The sympathetic and parasympathetic depressions with preserved balance were associated with only one ventricular dysfunction indicator. This suggests that cardiac autonomic dysfunction may precede and be independently more severe than ventricular dysfunction, with no causal association between both disorders in chronic chagasic cardiomyopathy.

Cardiac autonomic and ventricular mechanical functions in asymptomatic chronic chagasic cardiomyopathy.

BACKGROUND: The association of variably altered cardiac autonomic and ventricular systolic and diastolic functions is still controversial and little explored in chronic Chagas' disease. OBJECTIVE: To evaluate the extent to which cardiac autonomic and mechanical ventricular functions are altered and whether they are associated in asymptomatic chagasic cardiomyopathy. METHODS: A total of 13 patients with asymptomatic chagasic cardiomyopathy and 15 normal subjects (control group) were evaluated and the autonomic modulation of heart rate variability for five minutes, in the temporal and spectral domains, in the supine and orthostatic positions, as well as ventricular function based on morphological-functional variables obtained by Doppler echocardiography were correlated. Statistical analysis used the Mann-Whitney test and Spearman's correlation. RESULTS: In both positions, the temporal index (p = 0.0004 to 0.01) and total (p = 0.0007-0.005) and absolute spectral areas, of low and high frequencies (p = 0.0001 to 0.002), were lower in the chagasic group. The vagal-sympathetic balance was similar in both positions (p = 0.43 to 0.89). The echocardiographic variables did not differ between groups (p = 0.13 to 0.82), except the left ventricular end-systolic diameter, which was larger (p = 0.04) and correlated directly with reduced rates of global (p = 0.01 to 0.04) and parasympathetic (p = 0.002 to 0.01) autonomic modulation in patients with Chagas disease in the orthostatic position. CONCLUSION: The sympathetic and parasympathetic depressions with preserved balance were associated with only one ventricular dysfunction indicator. This suggests that cardiac autonomic dysfunction may precede and be independently more severe than ventricular dysfunction, with no causal association between both disorders in chronic chagasic cardiomyopathy.

Diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) affects each tissue, organ, system and the whole body, and presents with a diverse clinical picture. Originating from endocrine factors, this neurological disease may cause symptoms, whose differential diagnosis needs a good knowledge of the whole internal medicine. DAN is strongly involved in the development of diabetic foot, ulceration and amputation. The life threatening consequences of cardiac and patient-frustrating sequels of other types of DAN is more difficult to estimate. In this chapter the different clinical aspects of DAN will be discussed, according to the involved system--cardiovascular, gastrointestinal, genitourinary, sudomotor and pupillary dysfunctions and the unawareness and unresponsiveness to hypoglycaemia. The diagnostic tests for DAN are more complicated and time consuming, compared with the somatic tools. There is a need for simple devices and methods for evaluation of autonomic functions in the everyday clinical practice. Tight glycaemic control is the cornerstone of the prevention, progression and retardation of DAN. An effective broad-spectrum pathogenetic treatment of neural deterioration remains to be established. In most cases symptomatic drugs are the treatment of choice.

Rigorously defined hemicrania continua presenting bilaterally.

BACKGROUND: Hemicrania continua (HC) is a headache syndrome characterized by continuous, unilateral head pain, autonomic features, and a complete therapeutic response to indomethacin. Although HC is classified as a unique entity among primary headache disorders, it clearly shares features with other primary headaches, including trigeminal autonomic cephalalgias, and chronic daily headaches, such as chronic migraine and chronic tension-type headache. In addition, the diagnosis is often delayed secondary to a relatively low incidence and the occurrence of some phenotypic variability as found in previous case series. CASE: A 62-year-old woman presented with 5 months of unremitting, bilateral headache with significant autonomic symptoms during exacerbations of pain. Neurological examination and imaging studies were normal. After failure to respond to numerous previous therapeutic medicines and interventions, she experienced complete resolution following administration of indomethacin and eventual remission on sustained treatment. CONCLUSION: This case demonstrates that hemicrania continua with requisite autonomic features can occur in a purely bilateral form. Although the definitive aspects of HC continue to evolve, a bilateral headache meeting the current criteria warrants a therapeutic trial of indomethacin.

A review of paroxysmal sympathetic hyperactivity after acquired brain injury.

Severe excessive autonomic overactivity occurs in a subgroup of people surviving acquired brain injury, the majority of whom show paroxysmal sympathetic and motor overactivity. Delayed recognition of paroxysmal sympathetic hyperactivity (PSH) after brain injury may increase morbidity and long-term disability. Despite its significant clinical impact, the scientific literature on this syndrome is confusing; there is no consensus on nomenclature, etiological information for diagnoses preceding the condition is poorly understood, and the evidence base underpinning our knowledge of the pathophysiology and management strategies is largely anecdotal. This systematic literature review identified 2 separate categories of paroxysmal autonomic overactivity, 1 characterized by relatively pure sympathetic overactivity and another group of disorders with mixed parasympathetic/sympathetic features. The PSH group comprised 349 reported cases, with 79.4% resulting from traumatic brain injury (TBI), 9.7% from hypoxia, and 5.4% from cerebrovascular accident. Although TBI is the dominant causative etiology, there was some suggestion that the true incidence of the condition is highest following cerebral hypoxia. In total, 31 different terms were identified for the condition. Although the most common term in the literature was dysautonomia, the consistency of sympathetic clinical features suggests that a more specific term should be used. The findings of this review suggest that PSH be adopted as a more clinically relevant and appropriate term. The review highlights major problems regarding conceptual definitions, diagnostic criteria, and nomenclature. Consensus on these issues is recommended as an essential basis for further research in the area.

Comorbid health conditions in women with syncope.

OBJECTIVE: We determine the comorbid conditions associated with syncope in women. In addition, we hypothesize a higher proportion of autonomic comorbid conditions during the female reproductive age. METHODS: We identified a cohort of patients admitted to US hospitals with the principal diagnosis of syncope. We compare patient demographics stratified by gender as well as syncope associated comorbidities. We compared these comorbidities in female of reproductive age (15-45) to men as control. RESULTS: From a total sample of 305,932, females constituted 56.7% (n = 173,434). Females were slightly older (mean age 70.9 +/- 17.9 vs. 66.7 +/- 17.3; P < 0.0001); with similar racial distribution (white 57.8 vs. 57.5%), and similar length of hospital stay (mean 2.66 +/- 2.63 vs. 2.68 +/- 2.72 days; P > 0.05). Females had higher proportion of migraine (1.65 vs. 1.29%; odds ratio 'OR' 1.29; 95% confidence interval 'CI' 1.21, 1.36); chronic fatigue syndrome (1.73 vs. 1.3%; OR 1.32; 95% CI 1.25, 1.4); gastroparesis (0.2 vs. 0.12%; OR 1.64; 95% CI 1.35, 1.98); interstitial cystitis (0.07 vs. 0.01%; OR 7.44; 95% CI 4.10, 13.5); and postural tachycardia syndrome (0.49 vs. 0.44%; OR 1.1; 95% CI 1.001, 1.23). Orthostatic hypotension was not different between the groups (P = 0.24). When the sample was stratified by age category, the odds ratio for gastroparesis, orthostatic hypotension, and postural tachycardia syndrome was increased (P < 0.05). INTERPRETATION: A higher proportion of autonomic dysfunction was present in women compared to men. In addition, these comorbid autonomic conditions were especially prominent during the female reproductive age.

Nonmotor fluctuations in Parkinson's disease: clinical spectrum and classification.

UNLABELLED: The majority of patients with Parkinson's disease (PD) on levodopa (LD) treatment usually experience motor fluctuations (MFs) within several years of initiation of treatment. Besides the classic MFs, many nonmotor fluctuations (NMFs) may occur in PD. NMFs appear both in the "on" state and "off" state. However, the clinical spectrum and the frequency of these symptoms are not well recognized. NMFs are usually mild and less disabling than MFs but sometimes can lead to unnecessary tests and therapies. NMFs occurring in association with the "on" state are better known and therefore more frequently diagnosed than those occurring in the "off" state. NMFs can be classified into three groups: autonomic, cognitive/psychiatric, and sensory. They include gastrointestinal and urinary symptoms, drenching sweats, temperature and blood-pressure changes, depression, anxiety, hallucinations, hypomania, moaning/screaming, confusion, cognitive dysfunction, sexual deviations and dopamine dysregulation syndrome (DDS), pain, akathisia, internal tremor, numbness/parasthesia, and dyspnea. CONCLUSION: Recognition of NMFs may prevent unnecessary diagnostic tests and may lead to treatment modifications aimed to minimize their occurrence.

Other autonomic neuropathies associated with ganglionic antibody.

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders.

Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and adult epilepsies: a consensus view.

PURPOSE: To discuss and propose a definition of autonomic status epilepticus (SE), describe its clinical and EEG features, and review what is known about its epidemiology, pathophysiology, differential diagnosis, and management. METHODS: An international consortium of established researchers in the field was identified from their published work, agreed the purpose of the project, searched the literature, and, by use of e-mail communication, agreed the consensus document. RESULTS: Autonomic SE is a condition lasting at least 30 min and characterized by epileptic activity causing altered autonomic function of any type at seizure onset or in which manifestations consistent with altered autonomic function are prominent (quantitatively dominant or clinically important) even if not present at seizure onset. It is best described, and probably most commonly encountered in children, with Panayiotopoulos syndrome. However, it also occurs in children with symptomatic epilepsies and, exceptionally, in adults. Its pathogenesis and most appropriate management are poorly understood. CONCLUSIONS: It is hoped that this document will help clinical recognition of Autonomic SE, reduce misdiagnosis, and promote further interest and studies into what has been a relatively neglected area.