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.

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.

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.

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.

[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.

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.

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.

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.

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 peripheral neuropathy.

The autonomic neuropathies are a group of disorders in which the small, lightly myelinated and unmyelinated autonomic nerve fibres are selectively targeted. Autonomic features, which involve the cardiovascular, gastrointestinal, urogenital, sudomotor, and pupillomotor systems, occur in varying combination in these disorders. Diabetes is the most common cause of autonomic neuropathy in more developed countries. Autonomic neuropathies can also occur as a result of amyloid deposition, after acute infection, as part of a paraneoplastic syndrome, and after exposure to neurotoxins including therapeutic drugs. Certain antibodies (eg, anti-Hu and those directed against neuronal nicotinic acetylcholine receptor) are associated with autonomic signs and symptoms. There are several familial autonomic neuropathies with autosomal dominant, autosomal recessive, or X-linked patterns of inheritance. Autonomic dysfunction can occur in association with specific infections. The availability of sensitive and reproducible measures of autonomic function has improved physicians' ability to diagnose these disorders.

An electrophysiological approach to the evaluation of regional sympathetic dysfunction: a proposed classification.

BACKGROUND: The importance to physicians of maintaining a level of understanding of illnesses and their treatment continues to reveal itself in a most striking fashion when it comes to the progressive interest recently directed to disorders of the autonomic nervous system (ANS). In particular, the relevance to pain practitioners of disease states which directly involve the sympathetic portion of the ANS has increased markedly following the international renaming of reflex sympathetic dystrophy (RSD) and causalgia to complex regional pain syndrome (CRPS) Type I and Type II respectively, as well as sympathetically maintained pain (SMP). Subsequently it has become better understood that many other forms of neuropathic pain also demonstrate local abnormalities of the sympathetic nervous supply to the skin within the painful territory, thereby increasing the diagnostic value of these (often subtle) cutaneous clinical signs. OBJECTIVES: The objectives of this presentation include (a) a concise review of laboratory tests that are currently used in the evaluation of the autonomic nervous system, (b) a discussion of those procedures that were developed for the assessment of sympathetic sudomotor function, (c) a review of the anatomic pathways subserving those electrophysiological methods for sudomotor testing, and (d) the current diagnostic classification for regional abnormalities of sympathetic sudomotor dysfunction. METHODS: Methods used in the preparation of this article have included a review of (a) historic clinical and laboratory articles (or translations thereof) regarding the medical importance of disorders of the autonomic nervous system, dating back to more than 155 years ago (b) anatomic and electrophysiological basis for electroneurodiagnostic sudomotor testing, and (c) the author's proposal for a diagnostic classification of regional sympathetic sudomotor dysfunction.

Spectrum of autonomic cardiovascular neuropathy in diabetes.

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.

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.

Neuroaxonal and dendritic dystrophy in diabetic autonomic neuropathy. Classification and topographic distribution in the BB-rat.

Autonomic diabetic neuropathy in sympathetic nerves is characterized by the progressive development of an axonopathy and dystrophic changes. In the present study the dystrophic changes occurring in the diabetic BB-rat were further characterized. Based on their ultrastructural composition, they could be divided into five types; tubulovesicular (Tv), layered membrane (Lm), neurofilamentous (Nf), membranous body (Mb) and large branching tubular (Bt) types. The relative frequencies of the various types changed during the course of diabetes, with the Mb type being most frequent during the early course of the neuropathy, whereas the Tv and Nf types were more common during the late stage. The Mb and Tv types commonly terminated in growth cones and filopodia in the mesenteric nerve. The Nf type was common in proximal axons, dendrites and postganglionic perikarya, whereas the Bt type was only found in postganglionic dendrites. The chronologic development and topographic distribution of the various types of dystrophic changes suggest a diversified pathogenesis of these pathologic structures.

Diabetic neuropathies: features and mechanisms.

Diabetic neuropathies include both focal neuropathies and diffuse polyneuropathy. Polyneuropathy, the most common of the diabetic neuropathies excluding focal entrapment, has not yet been explained by a single disease mechanism despite intensive investigation. A number of abnormalities appear to cascade into a 'vicious cycle' of progressive microvascular disease associated with motor, sensory and autonomic fiber loss. These abnormalities include excessive polyol (sugar alcohol) flux through the aldose reductase pathway, functional and structural alterations of nerve microvessels, nerve and ganglia hypoxia, oxidative stress, nonspecific glycosylation of axon and microvessel proteins, and impairment in the elaboration of trophic factors critical for peripheral nerves and their ganglia. While an initiating role for nerve ischemia in the development of polyneuropathy has been proposed, the evidence for it can be questioned. The role of sensory and autonomic ganglia in the development of polyneuropathy has had relatively less attention despite the possibility that they may be vulnerable to a variety of insults, particularly neurotrophin deficiency. Superimposed on the deficits of polyneuropathy is the failure of diabetic nerves to regenerate as effectively as nondiabetics. Polyneuropathy has not yet yielded to specific forms of treatment but a variety of new trials addressing plausible hypotheses have been initiated. This review will summarize some of the clinical, pathological and experimental work applied toward understanding human diabetic neuropathy and will emphasize ideas on pathogenesis.

Dysautonomia with acute sensory motor neuropathy. A new classification of acute autonomic neuropathy.

OBJECTIVES: To characterize the dysautonomia associated with acute sensory motor neuropathy and to discuss the classification of acute autonomic neuropathy. DESIGN: Case series. METHODS: Sympathetic skin response. Local sweat response to acetylcholine. Norepinephrine infusion test and acetylcholinesterase histochemistry of sural nerve biopsy specimens in addition to making conventional analyses of myelinated and unmyelinated fibers. RESULTS: In 12 patients with chronic neuropathy, acetylcholinesterase-positive fiber density and plantar sympathetic skin response size were well correlated, but in the two patients with acute autonomic sensory and motor neuropathy, there were discrepancies, acetylcholinesterase-positive fiber density being well preserved and sympathetic skin responses being absent. Histologic and electrophysiologic results indicated primary demyelination of the myelinated fibers. In contrast, previous studies of acute autonomic sensory and motor neuropathy reported dysfunction of the sympathetic postganglionic fibers and axonopathic change in myelinated fibers, poor recovery from dysautonomia. CONCLUSIONS: Dysautonomia with acute idiopathic neuropathy can be divided into two categories--postganglionic axonopathic and preganglionic demyelinating types of the sympathetic efferent pathways. The recovery from dysautonomia produced by the former lesion is poor, but recovery is better for that produced by the latter lesion.

Autonomic neuropathy, II: Specific peripheral neuropathies.

Autonomic dysfunction is a common complication of peripheral neuropathies. It is often of little clinical importance, but some conditions may cause profound disturbance of autonomic function. These conditions include acute dysautonomia, diabetes, primary and familial amyloidosis, Guillain-Barré syndrome, porphyria, and some inherited neuropathies. A wide range of neuropathies are associated with lesser degrees of autonomic dysfunction. These include hereditary neuropathies, and neuropathies associated with metabolic disturbances, alcohol abuse, malignancy, medications, infections, and connective tissue disorders.

Phenomenology of simple partial seizures.

Based on a sample of 325 inpatients we present the subjective experiences during simple partial seizures. In a majority of cases, auras comprised composed forms of different symptomatic qualities. We describe rules which seem to govern sequences of aura phenomena. Autonomous and vestibular sensations were shown to have preceding positions related to others, olfactory and gustatory sensations preferred a following position. The tentative explanation of the findings favours the idea of heterogeneity rather than the concept of a focal discharge in a simple partial seizures.

Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications.

The diagnosis of chronic fatigue syndrome (CFS) is based on patient history and treatment on cognitive behavior therapy and graded exercise. There is increasing evidence that dysautonomia occurs in CFS manifest primarily as disordered regulation of cardiovascular responses to stress. We impart our experience relating to diagnosis, monitoring, and treatment of CFS based on identification and management of dysautonomia. Recently proposed methods for assessment of the cardiovascular reactivity, the 'hemodynamic instability score' (HIS) and the 'Fractal and Recurrence Analysis-based Score' (FRAS), served for this purpose. On HUTT, a particular dysautonomia is revealed in CFS patients that differ from dysautonomia in several other disorders. This distinct abnormality in CFS can be identified by HIS >-0.98 (sensitivity 84.5% and specificity 85.1%) and FRAS > +0.22 (sensitivity 70% and specificity 88%). Therefore, the HIS and FRAS may be used, in the appropriate clinical context, to support the diagnosis of CFS, which until now, could only be subjectively inferred. A pilot study suggested that midodrine treatment, directed at the autonomic nervous system in CFS, results first in correction of dysautonomia followed by improvement of fatigue. This finding implies that dysautonomia is pivotal in the pathophysiology CFS, at least in a large part of the patients, and that manipulating the autonomic nervous system may be effective in the treatment of CFS.

Classification of autonomic disorders.

Recent advances in our understanding of the pathophysiology of cardiovascular regulation and the metabolism of catecholamines have enabled us to develop an improved system of classification of autonomic disorders. Patients with autonomic impairment, clinically unassociated with other neurological abnormalities, are considered to have the Bradbury-Eggleston syndrome (idiopathic orthostatic hypotension, pure autonomic failure). Individuals whose autonomic failure is accompanied by degeneration in other neurological systems are classified as having the Shy-Drager syndrome (multiple system atrophy with autonomic failure). Patients in whom a deficiency of the enzyme dopamine-beta-hydroxylase is present from birth have many features suggestive of the Bradbury-Eggleston syndrome but manifest normal sweating and biochemically have an elevated plasma and urinary dopamine level. Recognition of these individuals is of particular importance because they are uniquely responsive to treatment with oral dihydroxyphenylserine (L-DOPS). A fourth disorder is baroreflex failure; this disorder is usually due to surgery, trauma, radiation or other injury to the ninth or tenth cranial nerves or the medullary nuclei which their fibers innervate. Patients with baroreflex failure have oscillations between hypertension and hypotension, but these alterations are poorly correlated with posture. Very high levels of plasma norepinephrine are found during the hypertensive phase of baroreflex failure. Baroreflex failure is generally responsive to treatment with clonidine. In conclusion, the diagnosis and therapy of autonomic disorders has improved due to the more precise taxonomy now current.