Guillermo A. Suarez

The Autonomic Symptom Profile A new instrument to assess autonomic symptoms

Objective: To develop a new specific instrument called the Autonomic Symptom Profile to measure autonomic symptoms and test its validity. Background: Measuring symptoms is important in the evaluation of quality of life outcomes. There is no validated, self-completed questionnaire on the symptoms of patients with autonomic disorders. Methods: The questionnaire is 169 items concerning different aspects of autonomic symptoms. The Composite Autonomic Symptom Scale (COMPASS) with item-weighting was established; higher scores indicate more or worse symptoms. Autonomic function tests were performed to generate the Composite Autonomic Scoring Scale (CASS) and to quantify autonomic deficits. We compared the results of the COMPASS with the CASS derived from the Autonomic Reflex Screen to evaluate validity. Results: The instrument was tested in 41 healthy controls (mean age 46.6 years), 33 patients with nonautonomic peripheral neuropathies (mean age 59.5 years), and 39 patients with autonomic failure (mean age 61.1 years). COMPASS scores correlated well with the CASS, demonstrating an acceptable level of content and criterion validity. The mean (±SD) overall COMPASS score was 9.8 (±9) in controls, 25.9 (±17.9) in the patients with nonautonomic peripheral neuropathies, and 52.3 (±24.2) in the autonomic failure group. Scores of symptoms of orthostatic intolerance and secretomotor dysfunction best predicted the CASS on multiple stepwise regression analysis. Conclusions: We describe a questionnaire that measures autonomic symptoms and present evidence for its validity. The instrument shows promise in assessing autonomic symptoms in clinical trials and epidemiologic studies.

Idiopathic autonomic neuropathy Clinical, neurophysiologie, and follow‐up studies on 27 patients

We evaluated the natural history, electrophysiologic characteristics, spectrum of autonomic involvement, pathology, and laboratory features in 27 patients with idiopathic autonomic neuropathy who were followed up for a mean of 32 months. The typical features of idiopathic autonomic neuropathy include the absence of an associated disease, frequent history of preceding infection, and acute or subacute onset with a monophasic course. The spectrum of autonomic involvement ranges from panautonomic to selective adrenergic or cholinergic failure. There is infrequent involvement of somatic nerve fibers as assessed by routine nerve conduction studies. Pathologic features include the presence of a small inflammatory mononuclear cell infiltrate in the epineurium. Recovery tends to be gradual and frequently incomplete. The acute onset, frequent antecedent viral infection, selectivity of involvement by fiber type and autonomic level, and presence of perivascular mononuclear cell infiltration suggest that the underlying mechanism is likely to be immune-mediated. These observations may justify plasma exchange or other immunosuppressive modalities as early therapeutic intervention in patients with progressive disability.

Prospective Evaluation of Clinical Characteristics of Orthostatic Hypotension

OBJECTIVE To undertake a prospective study of the clinical characteristics of orthostatic intolerant patients referred to the Mayo Autonomic Reflex Laboratory with suspected orthostatic hypotension (OH). DESIGN Autonomic function tests were performed to quantify the severity of sudomotor, adrenergic, and cardiovagal failure and generate a composite autonomic symptom score (CASS). CASS was related to a symptom score, which was derived from the frequency of orthostatic intolerance and syncope and the standing time until occurrence of symptoms. RESULTS Three groups were defined by their response to a tilt study: group I, 90 patients with symptomatic OH, mean age, 63.6 years; group II, 60 patients who had symptoms without OH, mean age, 48.9 years; and group III, 5 patients with asymptomatic OH, mean age, 68.0 years. Group I had a significantly higher CASS (P < 0.001) than did those without OH. Further analysis was done on the 90 patients in group I. The most common symptoms were lightheadedness, weakness, impaired cognition, visual blurring, tremulousness, and vertigo. The most common aggravating factors were prolonged standing, exercise, warming, and eating. Most patients (75%) could stand for less than 5 minutes before symptoms occurred. Symptoms regressed significantly with CASS but not with the tilt grade. CONCLUSION Patients with generalized autonomic failure have a recognizable pattern of symptoms and aggravating factors that relate, albeit imperfectly, to the severity of autonomic failure.

The dropped head syndrome

We describe four patients with a neuromuscular syndrome characterized by relatively isolated neck extensor weakness. EMG and muscle biopsies suggest a restrictive noninflammatory myopathy predominantly affecting the cervical paraspinal muscles.

Immune brachial plexus neuropathy Suggestive evidence for an inflammatory-immune pathogenesis

We report brachial plexus biopsy findings from two Australian and two American patients with brachial plexus neuropathy.There were florid multifocal mononuclear inflammatory cell infiltrates. Present evidence suggests that these brachial neuropathies have an immune basis. NEUROLOGY 1996;46: 559-561

Autonomic dysfunction in peripheral nerve disease

Autonomic neuropathies are inherited or acquired neuropathies in which autonomic nerve fibers are selectively or disproportionately affected. Generally, sympathetic and parasympathetic fibers are both affected but there are exceptions. Acquired cases can be autoimmune; due to diabetes, amyloidosis, drugs, or toxins; or idiopathic. Autoimmune autonomic neuropathy is often subacute, sometimes associated with a neoplasm, and associated with high titers of antibody to ganglionic nicotinic acetylcholine receptor in about half of the severe cases. The molecular basis of inherited autonomic neuropathies is better known, including recent identification of the loci and genes of hereditary sensory and autonomic neuropathies types I, III, and IV. The inherited amyloid neuropathies are due to mutations of three proteins: transthyretin, apolipoprotein A1, and gelsolin. Non‐invasive autonomic testing complements clinical and electrophysiological characterization of the autonomic neuropathies. Muscle Nerve 27: 646–661, 2003

Polyneuropathy associated with monoclonal gammopathy of undetermined significance: Further evidence that IgM‐MGUS neuropathies are different than IgG‐MGUS

We evaluated the clinical characteristics and electromyographic features of 39 patients with monoclonal gammopathy of undetermined significance (MGUS) and neuropathy. Twenty-three patients had a monoclonal IgM protein, 13 had an IgG, and three had an IgA. In 15 patients of the IgM group, the M protein reacted with myelin-associated glycoprotein (MAG). Comparing IgM-MGUS and IgG-MGUS neuropathies, we found the following differences: (1) There was a statistically significant higher frequency of sensory loss in the IgM group. (2) Nine attributes of nerve conduction abnormality were statistically worse in the IgM group, with slowing of conduction velocities and prolonged distal latencies. (3) The frequency of monoclonal IgM was overrepresented in the MGUS neuropathy group. In general, the clinical and electrophysiologic features of the IgM-MGUS MAG-reactive group were not significantly different than the MAG-nonreactive group. Our cases are similar to those previously reported and suggest that monoclonal IgM-MGUS should be separated conceptually from monoclonal IgG neuropathies.

Sudden cardiac death in diabetes mellitus: risk factors in the Rochester diabetic neuropathy study

Objectives: To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS) Methods: Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death. Results: 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease. Conclusions: Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

Comparison of the postural tachycardia syndrome (POTS) with orthostatic hypotension due to autonomic failure

Postural tachycardia syndrome (POTS) is characterized by orthostatic dizziness, tremulousness, tachycardia and variable blood pressure changes. Since some POTS patients have a marked reduction in pulse pressure on standing, a major mechanism of their symptoms might be venous pooling. We therefore studied the cardiovascular response to head-up tilt, Valsalva maneuver and deep breathing in: control subjects (n = 11; F = 8; M = 3; 39.2 +/- 14.4 years); patients with orthostatic hypotension secondary to autonomic failure (n = 11; F = 9; M = 2; 61.7 +/- 13.0 years), and patients with POTS (n = 15); F = 13; M = 2; 32.3 +/- 10.6 years). Blood pressure was measured with a Finapres, and cardiac output, stroke volume, end-diastolic volume and thoracic impedance (TFI) were measured by thoracic electrical bioimpedance. During tilt (in contrast to patients with orthostatic hypotensiom), patients with POTS had excessive tachycardia (P < 0.001), a normal to excessive total peripheral resistance increase, and an exaggerated decrease in stroke volume (P < 0.001) and end-diastolic volume (P < 0.001). These findings suggest that sympathetic arteriolar function remains relatively intact but that sympathetic venomotor function is selectively impaired. These findings may have significant implications for the treatment of patients with POTS.

COMPASS 31: a refined and abbreviated Composite Autonomic Symptom Score.

OBJECTIVE To develop a concise and statistically robust instrument to assess autonomic symptoms that provides clinically relevant scores of autonomic symptom severity based on the well-established 169-item Autonomic Symptom Profile (ASP) and its validated 84-question scoring instrument, the Composite Autonomic Symptom Score (COMPASS). PATIENTS AND METHODS We assessed the internal consistency of COMPASS using Cronbach α coefficients based on the ASP of 405 healthy control subjects recruited and seen in the Mayo Clinic Autonomic Disorders Center between March 1, 1995, and March 31, 2010. Applying a simplified scoring algorithm, we then used exploratory factor analysis with orthogonal rotation and eigenvalue calculations to extract internally consistent domains and to reduce dimensionality. This analysis was followed by expert revisions to eliminate redundant content and to retain clinically important questions and final assessment of the new instrument. RESULTS The new simplified scoring algorithm alone resulted in higher Cronbach α values in all domains. Factor analysis revealed 7 domains with a total of 54 questions retained. Expert revisions resulted in further reduction of questions and domains with a remaining total of 31 questions in 6 domains (COMPASS 31). Measures of internal consistency were much improved compared to those for COMPASS. Following appropriate weighting, this instrument provides an autonomic symptom score from 0 to 100. CONCLUSION COMPASS 31 is a refined, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original ASP and COMPASS, applies a much simplified scoring algorithm, and is suitable for widespread use in autonomic research and practice.