Autonomic Peripheral Neuropathies: Clinical Presentation, Diagnosis, and Treatment.[Review]. Journal of Clinical Neuromuscular Disease. 2(3):147-157, March 2001.
Autonomic neuropathy, I. Clinical features, investigation, pathophysiology, and treatment. [Review]. Journal of the Neurological Sciences. 137(2):79-88, 1996 May.
Autonomic neuropathy, II: Specific peripheral neuropathies. [Review].Journal of the Neurological Sciences. 138(1-2):1-13, 1996 Jun.
Orthostatic intolerance. A historical introduction to the pathophysiological mechanisms. [Review]. American Journal of the Medical Sciences. 317(2):78-87, 1999 Feb.
Orthostatic hypotension, 2001. [Review]. Cardiology in Review. 9(6):339-47, 2001 Nov-Dec.
Orthostatic Intolerance: A Disorder of Young Women.Obstetrical & Gynecological Survey. 55(4):251-259, April 2000.
Orthostatic Hypotension in Pediatrics.[Review]. Heart Disease. 4(1):33-39, January/February 2002.
Autonomic dysfunction in movement disorders. [Review]. Current Opinion in Neurology. 14(4):505-11, 2001 Aug.
Dysfunction of the autonomic nervous system is an under-recognised but important aspect of the aetiological and clinical manifestation of primary degenerative dysautonomias such as multiple system atrophy (MSA) and Parkinson's disease (PD). Although the clinical presentation of dysautonomia in these two disorders may overlap, yet pathological and in vivo imaging studies suggest considerable differences. Functional imaging studies suggest that selective cardiac sympathetic denervation may occur early in PD but not in other parkinsonian syndromes. The clinical implication of this apparently disease specific peripheral dysautonomia is unknown and would be the subject of much interest in future years. Dysautonomia in degenerative disorders also affect respiration, genitourinary function and sleep. Sleep related disorders such as rapid eye movement behaviour disorder and urinary voiding dysfunction appear to precede the development of PD related symptoms while patients with sporadic ataxia have been shown to progress to develop MSA. Dysautonomia has also been recognised in other movement disorders, examples being the combination of dystonia and complex regional pain syndrome with elevated HLA-DR13 and late onset Huntington's disease presenting with dominant parkinsonism and minimal chorea. These studies have helped progress in various diagnostic and management parameters in relation to autonomic dysfunction and movement disorders.
Autonomic control of cardiovascular function: clinical evaluation in health and disease. [Review]. Journal of Clinical Pharmacology. 34(5):363-74, 1994 May.
Autonomic assessment of cardiovascular disease. [Review]. Hospital Medicine (London). 59(9):714-8, 1998 Sep.
Autonomic Peripheral Neuropathies: Clinical Presentation, Diagnosis, and Treatment.[Review]. Journal of Clinical Neuromuscular Disease. 2(3):147-157, March 2001.
Blood pressure and heart rate variability in autonomic disorders: a critical review. [Review]. Clinical Autonomic Research. 6(3):171-82, 1996 Jun.
Heart Rate Variability. Annals of Internal Medicine. Volume 118(6) 15 March 1993 pp 436-447
Biochemical and pharmacologic assessment of autonomic function. [Review]. Advances in Neurology. 69:373-6, 1996.
Catecholamines: the cardiovascular and neuroendocrine system. [Review]. European Heart Journal. 19 Suppl F:F2-6, 1998 Jun
Autonomic Tone as a Cardiovascular Risk Factor: The Dangers of Chronic Fight or Flight.[Review]. Mayo Clinic Proceedings. 77(1):45-54, January 2002.
Autonomic nervous function assessment using thermal reactivity of microcirculation. [Review]. Clinical Neurophysiology. 111(10):1880-8, 2000 Oct.
Assessment of orthostatic blood pressure: measurement technique and clinical applications. [Review]. Southern Medical Journal. 92(2):167-73, 1999 Feb.
Is undetected autonomic dysfunction responsible for sudden death in Type 1 diabetes mellitus? The 'dead in bed' syndrome revisited. Diabetic Medicine. 16(8):626-31, 1999 Aug.
the 'dead in bed' syndrome probably occurs in Type 1 diabetic persons with early autonomic neuropathy, resulting in relative sympathetic overactivity. In such persons, risks of ventricular dysrhythmias will be compounded by nocturnal hypoglycaemia, which may be associated with an increase in the electrocardiographic Q-T interval, and Q-T dispersion. This could lead to the observed sudden death in undisturbed beds. Further research in this area is urgently needed, in particular into the possible protective use of drugs that modulate the autonomic nervous system
Exercise and autonomic function.[Review] Coronary Artery Disease. 11(2):129-135, March 2000.
Aerobic exercise training can increase activity of the parasympathetic nervous system and decrease sympathetic activity. Conversely, it is well-documented that cardiac disease is often characterized by attenuated parasympathetic activity and heightened sympathetic tone. A correlation between autonomic disequilibrium and disease has led to the hypothesis that exercise training, as a therapy that restores the autonomic nervous system towards normal function, may be associated with, and possibly responsible for, outcome improvements in various populations. This is merely one of the many benefits that is conferred by chronic exercise training and reviewed in this issue.
Arrhythmias and the autonomic nervous system. [Review]. Journal of Cardiovascular Risk. 1(4):322-31, 1994 Dec.
Differentiation in the angiotensin II receptor 1 blocker class on autonomic function. [Review]. Current Hypertension Reports. 3 Suppl 1:S17-23, 2001 Sep.
Autonomic function is disordered in cardiovascular disease states such as chronic heart failure (CHF) and hypertension. Interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) may potentially occur at a number of sites. These include central sites (eg, rostral ventrolateral medulla), at the level of baroreflex control, and at the sympathetic prejunctional angiotensin II receptor 1 (AT(1)) receptor, which is facilitatory for norepinephrine release from the sympathetic nerve terminal. Therefore, drugs that block the RAAS may be expected to improve autonomic dysfunction in cardiovascular disease states. In order to test the hypothesis that RAAS inhibition directly reduces SNS activity, a pithed rat model of sympathetic stimulation has been established. In this model, an increase in frequency of stimulation results in a pressor response that is sympathetically mediated and highly reproducible. This pressor response is enhanced in the presence of angiotensin II and is reduced in the presence of nonselective AIIRAs that block both AT(1) and AT(2) receptor subtypes (eg, saralasin). AT(1)-selective antagonists have also been studied in this model, at pharmacologically relevant doses. In one such study, only the AT(1) blocker eprosartan reduced sympathetically stimulated increases in blood pressure, whereas comparable doses of losartan, valsartan, and irbesartan did not. The reason(s) for the differences between eprosartan and other agents of this class on sympathetic modulation are not clear, but may relate to the chemical structure of the drug (a non- biphenyl tetrazole structure that is chemically distinct from the structure of other AIIRAs), receptor binding characteristics (competitive), or unique effects on presynaptic AT(1) receptors.
Special feature for the Olympics: effects of exercise on the immune system: overtraining effects on immunity and performance in athletes. [Review]. Immunology & Cell Biology. 78(5):502-9, 2000 Oct.
Overtraining is a process of excessive exercise training in high-performance athletes that may lead to overtraining syndrome. Overtraining syndrome is a neuroendocrine disorder characterized by poor performance in competition, inability to maintain training loads, persistent fatigue, reduced catecholamine excretion, frequent illness, disturbed sleep and alterations in mood state. Although high-performance athletes are generally not clinically immune deficient, there is evidence that several immune parameters are suppressed during prolonged periods of intense exercise training. These include decreases in neutrophil function, serum and salivary immunoglobulin concentrations and natural killer cell number and possibly cytotoxic activity in peripheral blood. Moreover, the incidence of symptoms of upper respiratory tract infection increases during periods of endurance training. However, all of these changes appear to result from prolonged periods of intense exercise training, rather than from the effects of overtraining syndrome itself. At present, there is no single objective marker to identify overtraining syndrome. It is best identified by a combination of markers, such as decreases in urinary norepinephrine output, maximal heart rate and blood lactate levels, impaired sport performance and work output at 110% of individual anaerobic threshold, and daily self-analysis by the athlete (e.g. high fatigue and stress ratings). The mechanisms underlying overtraining syndrome have not been clearly identified, but are likely to involve autonomic dysfunction and possibly increased cytokine production resulting from the physical stress of intense daily training with inadequate recovery
Autonomic dysfunction in movement disorders.[Review]. Current Opinion in Neurology. 14(4):505-511, August 2001.
Dysfunction of the autonomic nervous system is an under-recognised but important aspect of the aetiological and clinical manifestation of primary degenerative dysautonomias such as multiple system atrophy (MSA) and Parkinson's disease (PD). Although the clinical presentation of dysautonomia in these two disorders may overlap, yet pathological and in vivo imaging studies suggest considerable differences. Functional imaging studies suggest that selective cardiac sympathetic denervation may occur early in PD but not in other parkinsonian syndromes. The clinical implication of this apparently disease specific peripheral dysautonomia is unknown and would be the subject of much interest in future years. Dysautonomia in degenerative disorders also affect respiration, genitourinary function and sleep. Sleep related disorders such as rapid eye movement behaviour disorder and urinary voiding dysfunction appear to precede the development of PD related symptoms while patients with sporadic ataxia have been shown to progress to develop MSA. Dysautonomia has also been recognised in other movement disorders, examples being the combination of dystonia and complex regional pain syndrome with elevated HLA-DR13 and late onset Huntington's disease presenting with dominant parkinsonism and minimal chorea. These studies have helped progress in various diagnostic and management parameters in relation to autonomic dysfunction and movement disorders.
Role of neurotransmitter autoantibodies in the pathogenesis of chagasic peripheral dysautonomia. [Review]. Annals of the New York Academy of Sciences. 917:273-80, 2000.
Chagas' disease is caused by a parasite, Trypanosoma cruzi, which is widely distributed in South and Central America. Dysautonomias, derangements of sympathetic and parasympathetic nervous system function, are seen fairly often during the chronic course of Chagas' disease. Many infected subjects developed, in the course of the disease, neurogenic cardiomyopathy or digestive damage. Our investigations show the existence of circulating antibodies in Chagas' disease that bind to beta-adrenergic and muscarinic cholinergic receptor (mAChR). The neurotransmitter receptor-autoantibody interaction triggers in the cells intracellular signal transductions that alter the physiological behavior of the target organs, leading to tissue damage. Moreover, the deposit of autoantibodies behaving as agonists induces desensitization and/or down regulation of the receptors. This in turn can lead to a progressive blockade of them with sympathetic and parasympathetic denervation. Using synthetic peptides for immunoblotting and enzyme immunoassay, we demonstrated that these autoantibodies reacted against the second extracellular loop of the human heart beta 1 adrenoceptor and M2 cholinoceptor. Also, the corresponding affinity-purified antipeptide antibodies displayed an agonist-like activity associated with specific receptor activation. A strong association between circulating antipeptide M2 mAChR autoantibodies and the presence of patients' low heart rate variability index, bradycardia and cardiac or esophageal autonomic dysfunction in chronic chagasic patients was verified. This fact make these antipeptide antibodies a proper marker of cardiac neuromyopathy and achalasia.
The autonomic nervous system in functional bowel disorders. [Review]. Canadian Journal of Gastroenterology. 13 Suppl A:15A-17A, 1999 Mar.
Communications along the brain-gut axis involve neural pathways as well as immune and endocrine mechanisms. The two branches of the autonomic nervous system are integrated anatomically and functionally with visceral sensory pathways, and are responsible for the homeostatic regulation of gut function. The autonomic nervous system is also a major mediator of the visceral response to central influences such as psychological stress. As defined, functional disorders comprise a constellation of symptoms, some of which suggest the presence of altered perception, while other symptoms point to disordered gastrointestinal function as the cause of the symptoms. A growing number of reports have demonstrated disordered autonomic function in subgroups of functional bowel patients. While a number of different methods were used to assess autonomic function, the reports point to a generally decreased vagal (parasympathetic) outflow or increased sympathetic activity in conditions usually associated with slow or decreased gastrointestinal motility, while other studies found either an increased cholinergic activity or a decreased sympathetic activity in patients with symptoms compatible with an increased motor activity. Under certain conditions, altered autonomic balance (including low vagal tone and increased sympathetic activity) may alter visceral perception. Autonomic dysfunction may also represent the physiological pathway accounting for many of the extraintestinal symptoms seen in irritable bowel syndrome patients and some of the frequent gastrointestinal complaints reported by patients with disorders such as chronic fatigue and fibromyalgia
Transthyretin related familial amyloid polyneuropathy. Current Opinion in Neurology. 13(5):569-573, October 2000.
Familial amyloid polyneuropathy (FAP) applies to a group of dominantly inherited severe diseases with endoneurial and polyvisceral deposition of amyloidosis. The transthyretin, essentially produced by the liver, is the main protein involved in FAP. Up to 80 different mutations of the transthyretin gene are identified, many of them being associated with small fibres sensory-motor and autonomic polyneuropathy and/or cardiomyopathy. Variable age of onset, clinical expression and penetrance are largely reported. However, phenotypic-genotypic correlations remain unclear and the genetic or environmental modifying factors are unknown. The liver transplantation is proposed as a curative treatment of FAP resulting in an improvement of the general condition and a stabilization of the neuropathy, in a majority of patients. At present, the ratio benefit/risk seems acceptable when the procedure is performed early in the course of the disease.
New trends in the treatment of orthostatic hypotension. [Review]. Current Hypertension Reports. 3(3):216-26, 2001 Jun.
Nonpharmacologic and pharmacologic treatment can significantly attenuate the symptoms of orthostatic hypotension. Some of the interventions that are used to treat orthostatic hypotension have been known for decades. However, several new treatment strategies have been developed in recent years. New knowledge about the pathophysiology of orthostatic syndromes has been gathered that will strongly influence the way treatments are tailored to individual patients. For example, patients with and without residual autonomic function exhibit differential responses to certain treatments. A large subgroup of patients with severe autonomic failure show a profound pressor response to water drinking. This simple effect can be exploited to treat orthostatic and postprandial hypotension in some patients. New bioengineering technologies that attempt to replicate normal baroreflex mechanisms may become available for selected patients with central autonomic dysfunction.
The treatment of autonomic dysfunction. [Review]. Journal of Clinical Neurophysiology. 10(1):61-82, 1993 Jan.
Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs.
Neurally Mediated Syncope and Syncope Due to Autonomic Failure: Differences and Similarities. Journal of Clinical Neurophysiology. Neurocardiogenic Syncope. 14(3):183-196, May 1997.
Abnormalities in autonomic cardiovascular control can impair blood supply to the brain and produce syncope in two different disorders: autonomic failure and neurally mediated syncope. In autonomic failure, sympathetic efferent activity is chronically impaired so that vasoconstriction is deficient, upon standing blood pressure always falls (i.e., orthostatic hypotension), and syncope or presyncope occurs. Conversely, in neurally mediated syncope, the failure of sympathetic efferent casoconstrictor traffic (and hypotension) occurs episodically and in response to a trigger. Between syncopal episodes, patients with neurally mediated syncope have normal blood pressure and orthostatic tolerance. This article reviews the characteristics of autonomic failure and describes in more detail the pathophysiology, diagnosis, and treatment of neurally mediated syncope.
Autonomic dysfunction in uremia. [Review]. American Journal of Kidney Diseases. 38(4 Suppl 1):S118-21, 2001 Oct.
Asthma, asthma medication and autonomic nervous system dysfunction. [Review]. Clinical Physiology. 21(2):260-9, 2001 Mar.
Autonomic dysfunction and the gastrointestinal tract. [Review]. Clinical Autonomic Research. 9(2):75-81, 1999 Apr.
Autonomic dysfunction in chronic liver disease. [Review]. Clinical Autonomic Research. 3(4):227-31, 1993 Aug.
Chronic liver disease is accompanied by a number of circulatory changes including impairment of cardiovascular autonomic reflexes. This occurs irrespective of the aetiology of liver disease, increases in prevalence and severity with worsening hepatic function, and is related at least in part to an autonomic neuropathy. Parasympathetic abnormalities predominate and, although largely subclinical, they may play a role in the altered fluid homeostasis and neurohumoral disturbances associated with cirrhosis. On prospective follow up, the presence of autonomic impairment was associated with a five-fold increased mortality, largely from sepsis and variceal haemorrhage. Defective responses to such stressful events as a result of an afferent defect could possibly explain these findings. Further studies are required to evaluate the natural history of this complication, and determine if it is reversible with improvement in hepatic function or after liver transplantation.
Mitral prolapse. A heart anomaly in a clinical neuroendocrine context. [Review]. Minerva Cardioangiologica. 48(6):161-8, 2000 Jun.
Mitral valve prolapse was identified as a separate nosological entity by Barlow in 1963. A characteristic of this cardiac anomaly is blood reflux into the left atrium during the systole owing to the lack of adhesion between valve flaps. The presence of symptoms linked to neuroendocrine dysfunctions or to the autonomic nervous system lead to the onset of the pathology known as mitral valve prolapse syndrome (MVPs). It is usually diagnosed by chance in asymptomatic patients during routine tests. MVPs includes complex alterations to the neurovegetative system and a high clinical incidence of neuropsychiatric symptoms, like anxiety and panic attacks. A neuroendocrine mechanism thought to underlie panic attacks was recently proposed based on a biological model. In general, the cardiovascular anomaly manifested by patients with MVPs could be defined in neuroendocrine-constitutional terms.